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Sample records for leber neugeborener schweine

  1. LEBER'S DISEASE. CLINICAL CASE

    Directory of Open Access Journals (Sweden)

    N. N. Maslova

    2013-01-01

    Full Text Available Violation of visual functions and oculomotor frustration develop at 90% of patients with MS. More than a half of patients are transferred by the numerous recurrence of an optical neuritis which is coming to an end with a partial atrophy of optic nerve. For well-timed purpose of pathogenetic treatment differential diagnostics with other diseases, being accompanied an atrophy of an optic nerve, in particular with Leber's disease. 

  2. Kombinierte Leber- Dünndarmtransplantation

    OpenAIRE

    Thorwarth, Wolf Michael

    2002-01-01

    Nach Transplantation moduliert die Leber nicht nur die Immunantwort des Empfängers gegenüber ihr selbst, sondern übt auch auf mittransplantierte Organe einen protektiven Effekt aus. Dieses Phänomen wurde in der vorliegenden Arbeit an dem hoch immunogenen Dünndarm untersucht. Diese Studie war dabei nicht nur unter immunologischen Gesichtspunkten von Bedeutung. So stellt die simultane Leber- / Dünndarmtransplantation für Patienten, die an einer Leberzirrhose infolge eines Kurzdarmsyndrom leiden...

  3. Hopp, hopp, hopp im Schweinsgalopp? Klauen- und Gliedmaßengesundheit beim Schwein

    OpenAIRE

    Leeb, Christine; Bernardi, Florian; Winckler, Christoph

    2009-01-01

    Immer wieder kommen aus der Praxis Anfragen, über Lahmheitbeim Schwein zu berichten, auch ein Klauenpflegekurs wurde bereits durchgeführt, um akute Probleme lösen zu können. Doch was sind die Ursachen für Lahmheiten beim Schwein? Dieser Beitrag soll nicht nur die klinischen Symptome aufzählen und rasche Lösungen vermitteln (die es selten gibt), sondern Fragen stellen und zum selbst Beobachten und Nachdenken anregen. Dazu wird vom Wildschwein ausgehend das Normalverhalten betrac...

  4. Leber-opticusatrofie; een mitochondriaal overervende ziekte

    NARCIS (Netherlands)

    Oostra, R. J.; Bolhuis, P. A.; Wijburg, F. A.; Bleeker-Wagemakers, E. M.

    1995-01-01

    Leber hereditary optic neuropathy (LHON) is a heritable disorder, clinically characterized by rapidly progressive loss of central vision due to severe bilateral optic atrophy. The disease predominantly occurs in men. The clinical picture shows marked interpersonal variation. Recently it has been

  5. MRI in Leber's hereditary optic neuropathy

    DEFF Research Database (Denmark)

    Matthews, Lucy; Enzinger, Christian; Fazekas, Franz

    2015-01-01

    BACKGROUND: Leber's hereditary optic neuropathy (LHON) and a multiple sclerosis (MS)-like illness appear to coexist 50 times more frequently than would be expected by chance. This association of LHON and MS (LMS) raises an important question about whether there could be a common pathophysiological...

  6. Genetics Home Reference: Leber congenital amaurosis

    Science.gov (United States)

    ... correlations with genotypes, gene therapy trials update, and future directions. J AAPOS. 2009 Dec;13(6):587-92. doi: 10.1016/j.jaapos.2009.10.004. Review. Citation on PubMed Cremers FP, van den Hurk JA, den Hollander AI. Molecular genetics of Leber congenital amaurosis. Hum Mol ...

  7. Genetic analysis of a consanguineous Pakistani family with Leber ...

    Indian Academy of Sciences (India)

    2014-08-01

    Aug 1, 2014 ... RESEARCH NOTE. Genetic analysis of a consanguineous Pakistani family with Leber .... representation of the deleterious mutation at genomic and protein level. ... In the last couple of years, numerous mutations in. GUCY2D ...

  8. Leber's Hereditary Optic Neuropathy: A Case Report

    Directory of Open Access Journals (Sweden)

    Chi-Wu Chang

    2003-10-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited mitochondrial disease that primarily affects the optic nerve, causing bilateral vision loss in juveniles and young adults. A 12-year-old boy had complained of blurred vision in both eyes for more than 1 year. His best-corrected visual acuity was 0.08 in the right eye and 0.1 in the left. Ophthalmologic examination showed bilateral optic disc hyperemia and margin blurring, peripapillary telangiectasis, and a relative afferent pupil defect in his right eye. Fluorescein angiography showed no stain or leakage around the optic disc in the late phase. Visual field analysis showed central scotoma in the left eye and a near-total defect in the right. Upon examination of the patient's mitochondrial DNA, a point mutation at nucleotide position 11778 was found, and the diagnosis of LHON was confirmed. Coenzyme Q10 was used to treat the patient.

  9. 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.

  10. 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

  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

    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

  12. On the many faces of Leber hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, R. J.; Tijmes, N. T.; Cobben, J. M.; Bolhuis, P. A.; van Nesselrooij, B. P.; Houtman, W. A.; de Kok-Nazaruk, M. M.; Bleeker-Wagemakers, E. M.

    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

  13. 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

  14. 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…

  15. Characterization and comparative analysis of the genome of Puccinia sorghi Schwein, the causal agent of maize common rust.

    Science.gov (United States)

    Rochi, Lucia; Diéguez, María José; Burguener, Germán; Darino, Martín Alejandro; Pergolesi, María Fernanda; Ingala, Lorena Romina; Cuyeu, Alba Romina; Turjanski, Adrián; Kreff, Enrique Domingo; Sacco, Francisco

    2018-03-01

    Rust fungi are one of the most devastating pathogens of crop plants. The biotrophic fungus Puccinia sorghi Schwein (Ps) is responsible for maize common rust, an endemic disease of maize (Zea mays L.) in Argentina that causes significant yield losses in corn production. In spite of this, the Ps genomic sequence was not available. We used Illumina sequencing to rapidly produce the 99.6Mbdraft genome sequence of Ps race RO10H11247, derived from a single-uredinial isolate from infected maize leaves collected in the Argentine Corn Belt Region during 2010. High quality reads were obtained from 200bppaired-end and 5000bpmate-paired libraries and assembled in 15,722 scaffolds. A pipeline which combined an ab initio program with homology-based models and homology to in planta enriched ESTs from four cereal pathogenic fungus (the three sequenced wheat rusts and Ustilago maydis) was used to identify 21,087 putative coding sequences, of which 1599 might be part of the Ps RO10H11247 secretome. Among the 458 highly conserved protein families from the euKaryotic Orthologous Groups (KOG) that occur in a wide range of eukaryotic organisms, 97.5% have at least one member with high homology in the Ps assembly (TBlastN, E-value⩽e-10) covering more than 50% of the length of the KOG protein. Comparative studies with the three sequenced wheat rust fungus, and microsynteny analysis involving Puccinia striiformis f. sp. tritici (Pst, wheat stripe rust fungus), support the quality achieved. The results presented here show the effectiveness of the Illumina strategy for sequencing dikaryotic genomes of non-model organisms and provides reliable DNA sequence information for genomic studies, including pathogenic mechanisms of this maize fungus and molecular marker design. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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    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.

  17. Increased Mortality and Comorbidity Associated With Leber's Hereditary Optic Neuropathy

    DEFF Research Database (Denmark)

    Vestergaard, Nanna; Rosenberg, Thomas; Torp-Pedersen, Christian

    2017-01-01

    Purpose: Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease in which optic neuropathy is considered a key feature. Several other manifestations of LHON have been reported; however, only little is known of their incidence and the life expectancy in LHON patients. Methods...... patients (RR: 4.26, 95% CI: 1.91-9.48; P neuropathy, and alcohol-related disorders. Conclusions: The manifestation of LHON was associated...

  18. 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.

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

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    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

  20. 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

    2016-11-01

    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 2cumulated = 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

  1. 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

  2. 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

  3. Mitochondrial DNA analysis as a diagnostic tool in singleton cases of Leber's hereditary optic neuropathy

    NARCIS (Netherlands)

    Oostra, R. J.; Bolhuis, P. A.; Bleeker-Wagemakers, E. M.

    1993-01-01

    Leber's hereditary optic neuropathy (LHON) is characterized by subacute loss of central vision due to bilateral optic nerve atrophy accompanied by several nonspecific clinical findings. The only pathognomonic feature is its strictly maternal inheritance. It was therefore impossible to establish the

  4. Magnetic resonance elastography of the liver; Magnetresonanzelastographie der Leber

    Energy Technology Data Exchange (ETDEWEB)

    Sack, I.; Fischer, T.; Thomas, A. [Charite-Universitaetsmedizin Berlin, Campus Charite Mitte, Institut fuer Radiologie, Berlin (Germany); Braun, J. [Charite-Universitaetsmedizin Berlin, Campus Benjamin Franklin, Institut fuer Medizinische Informatik, Berlin (Germany)

    2012-08-15

    The early detection of liver fibrosis remains a major challenge in medical imaging. Nowadays staging of liver fibrosis is not a task for radiological examinations and the gold standard is liver puncture. Elastography is sensitive to the mechanical properties of soft tissues and in the liver stiffness is highly correlated to the degree of fibrosis. In magnetic resonance imaging elastography (MRE) time-harmonic vibrations are induced in the liver and encoded by motion-sensitive phase-contrast sequences. Viscoelastic constants are recovered from the obtained wave images and displayed by so-called elastograms. The MRE procedure is able to discriminate low grades of fibrosis (F0-F1) from medium and severe fibrosis (F2-F4) with a diagnostic accuracy (AUROC) of 0.92. Currently, MRE is the most sensitive imaging modality for the noninvasive staging of liver fibrosis. Current technical developments of MRE may further improve the accuracy of the method towards a new gold standard for noninvasive staging of fibrosis by radiologists. (orig.) [German] Die Leberfibrose laesst sich nichtinvasiv und bildgestuetzt nur schwer von normal gesundem Gewebe unterscheiden. Morphologische Kenngroessen geben kaum Aufschluss ueber das Vorliegen einer Leberfibrose, insbesondere der Schweregrad der Erkrankung kann nicht sicher beurteilt werden. Diagnose und Graduierung der Leberfibrose sind derzeit keine Aufgabenstellungen der Radiologie, als Goldstandard gilt die Leberpunktion. Die Elastographie ist sensitiv auf Veraenderungen mechanischer Eigenschaften eines Organs. In der Leber korreliert der Fibrosegrad mit der Steifigkeit. Die Elastographie in der MRT (MRE) nutzt harmonische Schwingungen, welche ueber bewegungssensitive Phasenkontrastaufnahmetechniken kodiert werden. Aus den aufgenommenen Wellenbildern koennen Karten viskoelastischer Kenngroessen berechnet werden. Auf dem derzeitigen Stand der Technik ist die MRE in der Lage, fruehe Fibrosegrade (F0-F1) von mittlerer und schwerer Fibrose

  5. Generation of patient-specific induced pluripotent stem cells from Leber's hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Huai-En Lu

    2018-04-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited mitochondrial disease caused by homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. In this report, we generated an induced pluripotent stem cell (iPSCs line, TVGH-iPSC-010-09, from the peripheral blood mononuclear cells of a female patient with Leber's hereditary optic neuropathy (LHON by using the Sendai-virus delivery system. The resulting iPSCs retained the disease-causing mitochondrial DNA mutation, expressed pluripotent markers and could differentiate into the three germ layers. We believe LHON patient-specific iPSCs provide a powerful in vitro model for evaluating the pathological phenotypes of the disease.

  6. Leber congenital amaurosis associated with optic disk neovascularization and vitreous hemorrhage.

    Science.gov (United States)

    Kurz, Daryl; Ciulla, Thomas A

    2003-05-01

    To report an unusual case of optic disk neovascularization and vitreous hemorrhage associated with Leber congenital amaurosis (LCA). Interventional case report. A 16-year-old Caucasian girl with a history of LCA presented with decreased vision in her left eye, diffuse retinal pigmentary abnormalities characteristic of LCA, and hemorrhage over the left optic disk and macula. Six months of follow-up revealed optic disk neovascularization. A small amount of neovascularization was noted in the right eye at 6 months. An extensive systemic evaluation indicated no other cause for the neovascularization. Panretinal photocoagulation was performed in both eyes, and subsequently the neovascularization regressed. Leber congenital amaurosis like retinitis pigmentosa, can rarely be associated with neovascularization of the disk, which is amenable to treatment with peripheral photocoagulation if it does not spontaneously regress.

  7. Messung der Respirationsverschiebung intraabdominaler Organe am Beispiel der Leber unter maschineller Ventilation

    OpenAIRE

    Olbrich, Bernhard

    2008-01-01

    Ziel dieser Arbeit ist es, die Bewegung intraabominaler Organe am Beispiel der Leber unter den Bedingungen maschineller Beatmung zu quantifizieren. Ein Messverfahren mit Hilfe eines elektromagnetischen Trackingsystems, wurde hierzu im Tierversuch neu entwickelt. Im Anschluss wurden die Messdaten mit Hilfe einer Explorativen Datenanalyse, validiert und ein einfaches Modell entwickelt, das die virtuelle Kompensation der Atemverschiebung ermöglicht. Zusätzlich wird eine praktische Anwendungsmögl...

  8. The Decrease in Mitochondrial DNA Mutation Load Parallels Visual Recovery in a Leber Hereditary Optic Neuropathy Patient

    Directory of Open Access Journals (Sweden)

    Sonia Emperador

    2018-02-01

    Full Text Available The onset of Leber hereditary optic neuropathy is relatively rare in childhood and, interestingly, the rate of spontaneous visual recovery is very high in this group of patients. Here, we report a child harboring a rare pathological mitochondrial DNA mutation, present in heteroplasmy, associated with the disease. A patient follow-up showed a rapid recovery of the vision accompanied by a decrease of the percentage of mutated mtDNA. A retrospective study on the age of recovery of all childhood-onset Leber hereditary optic neuropathy patients reported in the literature suggested that this process was probably related with pubertal changes.

  9. 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

  10. Brain white matter 1 H MRS in Leber optic neuropathy mutation carriers

    DEFF Research Database (Denmark)

    Ostojic, Jelena; Jancic, Jasna; Kozic, Dusko

    2009-01-01

    OBJECTIVE: This study was conducted in order to test the hypothesis that proton MR spectroscopic (1H MRS) profile of Leber's hereditary optic neuropathy (LHON) mutation carriers group (including both symptomatic and asymptomatic) differs from group of healthy individuals and to determine metabolite...... or ratio that contributes most to differentiation. PATIENTS AND METHODS: We performed single voxel 1H MRS in normal appearing white matter of eighteen LHON mtDNA mutation carriers bearing one of three LHON mtDNA point mutations and in fifty control subjects. RESULTS: ANOVA showed significant difference...

  11. Long-Term Effect of Gene Therapy on Leber's Congenital Amaurosis

    OpenAIRE

    Bainbridge, James W B; Mehat, Manjit S; Sundaram, Venki; Robbie, Scott J; Barker, Susie E; Ripamonti, Caterina; Georgiadis, Anastasios; Mowat, Freya M; Beattie, Stuart G; Gardner, Peter J; Feathers, Kecia L; Luong, Vy A; Yzer, Suzanne; Balaggan, Kamaljit; Viswanathan, Ananth

    2015-01-01

    Background Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. Methods We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, an...

  12. Leber hereditary optic neuropathy due to a new ND1 mutation

    DEFF Research Database (Denmark)

    Soldath, Patrick; Wegener, Marianne; Sander, Birgit

    2017-01-01

    We report a proband with Leber hereditary optic neuropathy (LHON), in whom we have identified a novel homoplasmic m.3,395A>G mutation in the ND1 gene. The mutation alters a highly conserved amino acid in codon 30 which previously has been associated with LHON and leads to a severe selective complex...... and is present in the early stage of the disease. Furthermore, evaluation of two unaffected mutation carriers disclosed asymptomatic borderline ganglion cell loss and thin pRNFL in one....

  13. 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.

  14. 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....

  15. Bilateral vision loss due to Leber's hereditary optic neuropathy after long-term alcohol, nicotine and drug abuse.

    Science.gov (United States)

    Maass, Johanna; Matthé, Egbert

    2018-04-01

    Leber's hereditary optic neuropathy is relatively rare, and no clinical pathognomonic signs exist. We present a rare case of bilateral vision loss of a patient with multiple drug abuse in the history. A 31-year-old man presented with a history of progressive, decreased vision in both eyes for 6 month. On examination, his visual acuity was hand motion in both eyes. Funduscopy demonstrated a temporal pallor of the optic disc. Goldmann visual field perimetry showed a crescent visual field in the right eye and a circular decrease to less than 50 ° in the left eye. Electroretinogram showed a scotopic b-wave amplitude reduction. Optical coherence tomographies, Heidelberg Retina tomography, visual evoked potentials, and magnetic resonance imaging with contrast as well as blood tests were normal. The patient reported to consume various kinds of drugs as well as recreational drug use and alcohol consumption since he was 16 years old. We started a hemodilution therapy, believing the patient suffered from a bilateral, toxic optic neuropathy due to his lifestyle. Laboratory results later on showed Leber's hereditary optic neuropathy. Leber's hereditary optic neuropathy is a rare disease without a typical, pathognomonic presentation. Even though the patient gave good reasons for a toxic optic neuropathy, one should never stop to test for other diseases.

  16. 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

  17. Cyclosporine A does not prevent second-eye involvement in Leber's hereditary optic neuropathy.

    Science.gov (United States)

    Leruez, Stéphanie; Verny, Christophe; Bonneau, Dominique; Procaccio, Vincent; Lenaers, Guy; Amati-Bonneau, Patrizia; Reynier, Pascal; Scherer, Clarisse; Prundean, Adriana; Orssaud, Christophe; Zanlonghi, Xavier; Rougier, Marie-Bénédicte; Tilikete, Caroline; Miléa, Dan

    2018-02-17

    Evaluation of the efficacy of oral cyclosporine A as a prophylactic agent in preventing second-eye involvement in Leber's hereditary optic neuropathy (LHON) in a prospective, open-label, non-randomized, multicenter pilot study. Only LHON patients aged 18 years or more, with confirmed primary mitochondrial DNA mutations and strictly unilateral optic neuropathy occurring within 6 months prior to enrolment, were included in the study. All these patients, receiving treatment with oral cyclosporine (Neoral®, Novartis) at 2.5 mg/kg/day, were examined at three-month intervals for a year. The primary endpoint was the best corrected visual acuity in the unaffected eye; the secondary endpoints were the best corrected visual acuity in the first eye affected, the mean visual field defect on automated perimetry, the thickness of the perifoveal retinal ganglion cell inner plexiform layer, and the thickness of the peripapillary retinal nerve fiber layer in both eyes. Among the 24 patients referred to our institution with genetically confirmed LHON, between July 2011 and April 2014, only five patients, four males and one female, fulfilled the inclusion criteria. Age at enrolment ranged from 19 to 42 years (mean: 27.2 years; median: 26 years), four patients harbored the m.11778G > A pathogenic variant, and one the m.14484 T > C pathogenic variant. The time-interval between the onset of symptoms and inclusion in the study ranged from 7 to 17 weeks (mean: 11.8 weeks; median: 9 weeks). Despite treatment with oral cyclosporine A, all patients eventually experienced bilateral eye involvement, occurring within 11-65 weeks after the initiation of treatment. Over the study time period, the average best corrected visual acuity worsened in the first eye affected; by the end of the study, both eyes were equally affected. Oral cyclosporine, at 2.5 mg/kg/day, did not prevent second-eye involvement in patients with strictly unilateral Leber's hereditary optic neuropathy

  18. 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

  19. 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.

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

    International Nuclear Information System (INIS)

    Zhao, Fuxin; Guan, Minqiang; Zhou, Xiangtian; Yuan, Meixia; Liang, Ming; Liu, Qi; Liu, Yan; Zhang, Yongmei; Yang, Li; Tong, Yi; Wei, Qi-Ping; Sun, Yan-Hong; Qu, Jia

    2009-01-01

    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.

  1. International Consensus Statement on the Clinical and Therapeutic Management of Leber Hereditary Optic Neuropathy.

    Science.gov (United States)

    Carelli, Valerio; Carbonelli, Michele; de Coo, Irenaeus F; Kawasaki, Aki; Klopstock, Thomas; Lagrèze, Wolf A; La Morgia, Chiara; Newman, Nancy J; Orssaud, Christophe; Pott, Jan Willem R; Sadun, Alfredo A; van Everdingen, Judith; Vignal-Clermont, Catherine; Votruba, Marcela; Yu-Wai-Man, Patrick; Barboni, Piero

    2017-12-01

    Leber hereditary optic neuropathy (LHON) is currently estimated as the most frequent mitochondrial disease (1 in 27,000-45,000). Its molecular pathogenesis and natural history is now fairly well understood. LHON also is the first mitochondrial disease for which a treatment has been approved (idebenone-Raxone, Santhera Pharmaceuticals) by the European Medicine Agency, under exceptional circumstances because of the rarity and severity of the disease. However, what remains unclear includes the optimal target population, timing, dose, and frequency of administration of idebenone in LHON due to lack of accepted definitions, criteria, and general guidelines for the clinical management of LHON. To address these issues, a consensus conference with a panel of experts from Europe and North America was held in Milan, Italy, in 2016. The intent was to provide expert consensus statements for the clinical and therapeutic management of LHON based on the currently available evidence. We report the conclusions of this conference, providing the guidelines for clinical and therapeutic management of LHON.

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

    International Nuclear Information System (INIS)

    Liang, Min; Guan, Minqiang; Zhao, Fuxing; Zhou, Xiangtian; Yuan, Meixia; Tong, Yi; Yang, Li; Wei, Qi-Ping; Sun, Yan-Hong; Lu, Fan; Qu, Jia

    2009-01-01

    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.

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

    OpenAIRE

    Barreda Gago, David; Gómez Ledesma, Isabel; Santiago Rodríguez, María de los Ángeles; Hernández Galilea, Emiliano

    2016-01-01

    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 ...

  4. Reversal of Blindness in Animal Models of Leber Congenital Amaurosis Using Optimized AAV2-mediated Gene Transfer

    OpenAIRE

    Bennicelli, Jeannette; Wright, John Fraser; Komaromy, Andras; Jacobs, Jonathan B; Hauck, Bernd; Zelenaia, Olga; Mingozzi, Federico; Hui, Daniel; Chung, Daniel; Rex, Tonia S; Wei, Zhangyong; Qu, Guang; Zhou, Shangzhen; Zeiss, Caroline; Arruda, Valder R

    2008-01-01

    We evaluated the safety and efficacy of an optimized adeno-associated virus (AAV; AAV2.RPE65) in animal models of the RPE65 form of Leber congenital amaurosis (LCA). Protein expression was optimized by addition of a modified Kozak sequence at the translational start site of hRPE65. Modifications in AAV production and delivery included use of a long stuffer sequence to prevent reverse packaging from the AAV inverted-terminal repeats, and co-injection with a surfactant. The latter allows consis...

  5. Effect of EPI-743 on the clinical course of the mitochondrial disease Leber hereditary optic neuropathy.

    Science.gov (United States)

    Sadun, Alfredo A; Chicani, Carlos Filipe; Ross-Cisneros, Fred N; Barboni, Piero; Thoolen, Martin; Shrader, William D; Kubis, Kenneth; Carelli, Valerio; Miller, Guy

    2012-03-01

    To evaluate the safety and efficacy of a new therapeutic agent, EPI-743, in Leber hereditary optic neuropathy (LHON) using standard clinical, anatomic, and functional visual outcome measures. Open-label clinical trial. University medical center. Patients  Five patients with genetically confirmed LHON with acute loss of vision were consecutively enrolled and treated with the experimental therapeutic agent EPI-743 within 90 days of conversion. Intervention  During the course of the study, 5 consecutive patients received EPI-743, by mouth, 3 times daily (100-400 mg per dose). Treatment effect was assessed by serial measurements of anatomic and functional visual indices over 6 to 18 months, including Snellen visual acuity, retinal nerve fiber layer thickness measured by optical coherence tomography, Humphrey visual fields (mean decibels and area with 1-log unit depression), and color vision. Treatment effect in this clinical proof of principle study was assessed by comparison of the prospective open-label treatment group with historical controls. Of 5 subjects treated with EPI-743, 4 demonstrated arrest of disease progression and reversal of visual loss. Two patients exhibited a total recovery of visual acuity. No drug-related adverse events were recorded. In a small open-label trial, EPI-743 arrested disease progression and reversed vision loss in all but 1 of the 5 consecutively treated patients with LHON. Given the known natural history of acute and rapid progression of LHON resulting in chronic and persistent bilateral blindness, these data suggest that the previously described irreversible priming to retinal ganglion cell loss may be reversed.

  6. Long-term effect of gene therapy on Leber's congenital amaurosis.

    Science.gov (United States)

    Bainbridge, James W B; Mehat, Manjit S; Sundaram, Venki; Robbie, Scott J; Barker, Susie E; Ripamonti, Caterina; Georgiadis, Anastasios; Mowat, Freya M; Beattie, Stuart G; Gardner, Peter J; Feathers, Kecia L; Luong, Vy A; Yzer, Suzanne; Balaggan, Kamaljit; Viswanathan, Ananth; de Ravel, Thomy J L; Casteels, Ingele; Holder, Graham E; Tyler, Nick; Fitzke, Fred W; Weleber, Richard G; Nardini, Marko; Moore, Anthony T; Thompson, Debra A; Petersen-Jones, Simon M; Michaelides, Michel; van den Born, L Ingeborgh; Stockman, Andrew; Smith, Alexander J; Rubin, Gary; Ali, Robin R

    2015-05-14

    Mutations in RPE65 cause Leber's congenital amaurosis, a progressive retinal degenerative disease that severely impairs sight in children. Gene therapy can result in modest improvements in night vision, but knowledge of its efficacy in humans is limited. We performed a phase 1-2 open-label trial involving 12 participants to evaluate the safety and efficacy of gene therapy with a recombinant adeno-associated virus 2/2 (rAAV2/2) vector carrying the RPE65 complementary DNA, and measured visual function over the course of 3 years. Four participants were administered a lower dose of the vector, and 8 were administered a higher dose. In a parallel study in dogs, we investigated the relationship among vector dose, visual function, and electroretinography (ERG) findings. Improvements in retinal sensitivity were evident, to varying extents, in six participants for up to 3 years, peaking at 6 to 12 months after treatment and then declining. No associated improvement in retinal function was detected by means of ERG. Three participants had intraocular inflammation, and two had clinically significant deterioration of visual acuity. The reduction in central retinal thickness varied among participants. In dogs, RPE65 gene therapy with the same vector at lower doses improved vision-guided behavior, but only higher doses resulted in improvements in retinal function that were detectable with the use of ERG. Gene therapy with rAAV2/2 RPE65 vector improved retinal sensitivity, albeit modestly and temporarily. Comparison with the results obtained in the dog model indicates that there is a species difference in the amount of RPE65 required to drive the visual cycle and that the demand for RPE65 in affected persons was not met to the extent required for a durable, robust effect. (Funded by the National Institute for Health Research and others; ClinicalTrials.gov number, NCT00643747.).

  7. 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

  8. The mitochondrial DNA mutation ND6*14,484C associated with leber hereditary optic neuropathy, leads to deficiency of complex I of the respiratory chain

    NARCIS (Netherlands)

    Oostra, R. J.; van Galen, M. J.; Bolhuis, P. A.; Bleeker-Wagemakers, E. M.; van den Bogert, C.

    1995-01-01

    The electron transfer activity of Complex I of the respiratory chain and Complex I-linked ATP synthesis were investigated in leukocytes of four males affected by Leber hereditary optic neuropathy and a mutation in the ND6 gene at nucleotide position 14,484 of mtDNA. The electron transfer activity in

  9. Clinical evaluation and mitochondrial DNA sequence analysis in three Chinese families with Leber's hereditary optic neuropathy

    International Nuclear Information System (INIS)

    Qian Yaping; Zhou Xiangtian; Hu Yongwu; Tong Yi; Li Ronghua; Lu Fan; Yang Huanming; Mo Junqin; Qu Jia; Guan Minxin

    2005-01-01

    We report here the clinical, genetic, and molecular characterization of three Chinese families (WZ4, WZ5, and WZ6) with Leber's hereditary optic neuropathy (LHON). Clinical and genetic evaluations revealed the variable severity and age-of-onset in visual impairment in these families. Penetrances of visual impairment in these Chinese families were 33.3%, 35.7%, and 35.5%, respectively, with an average 34.8%. Furthermore, the average age-at-onset in those Chinese families was 17, 20, and 18 years. In addition, the ratios between affected male and female matrilineal relatives in these Chinese families were 3:0, 1:1, and 1.2:1, respectively. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical G11778A mutation associated with LHON in many families. The fact that mtDNA of those pedigrees belonged to different haplogroups F1, D4, and M10 suggested that the G11778A mutation occurred sporadically and multiplied through evolution of the mtDNA in China. However, there was the absence of functionally significant mutations in tRNA and rRNAs or secondary LHON mutations in these Chinese families. The I187T mutation in the ND1, the S99A mutation in the A6, the V254I in CO3, and I58V in ND6 mutation, showing high evolutional conservation, may contribute to the phenotypic expression of the G11778A mutation in the WZ6 pedigree. By contrast, none of mtDNA variants are evolutionarily conserved and implicated to have significantly functional consequence in WZ4 and WZ5 pedigrees. Apparently, these variants do not have a potential modifying role in the development of visual impairment associated with G11778A mutation in those two families. Thus, nuclear modifier gene(s) or environmental factor(s) seem to account for the penetrance and expressivity of LHON in these three Chinese families carrying the G11778A mutation

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

    Science.gov (United States)

    Corton, Marta; Avila-Fernandez, Almudena; Vallespín, Elena; López-Molina, María Isabel; Almoguera, Berta; Martín-Garrido, Esther; Tatu, Sorina D; Khan, M Imran; Blanco-Kelly, Fiona; Riveiro-Alvarez, Rosa; Brión, María; García-Sandoval, Blanca; Cremers, Frans P M; Carracedo, Angel; Ayuso, Carmen

    2014-01-01

    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. Case series. A cohort of 217 unrelated Spanish families affected by autosomal recessive or isolated retinal dystrophy, that is, 79 families with LCA and 138 families with early-onset retinitis pigmentosa (EORP). A total of 100 healthy, unrelated Spanish individuals were screened as controls. High-resolution homozygosity mapping was performed in 44 patients with LCA using genome-wide single nucleotide polymorphism (SNP) microarrays. Direct sequencing of the LCA5 gene was performed in 5 patients who showed homozygous regions at chromosome 6 and in 173 unrelated individuals with LCA or EORP. The ophthalmic history of 8 patients carrying LCA5 mutations was reviewed and additional examinations were performed, including electroretinography (ERG), optical coherence tomography (OCT), and fundus photography. Single nucleotide polymorphism genotyping, identity-by-descent (IBD) regions, LCA5 mutations, best-corrected visual acuity, visual field assessments, fundus appearance, ERG, and OCT findings. Four novel and 2 previously reported LCA5 mutations have been identified in 6 unrelated families with LCA by homozygosity mapping or Sanger sequencing. Thus, LCA5 mutations have a frequency of 7.6% in the Spanish population. However, no LCA5 mutations were found in 138 patients with EORP. Although most of the identified LCA5 mutations led to a truncated protein, a likely pathogenic missense variant was identified for the first time as a cause of LCA, segregating in 2 families. We also have characterized a novel splicing site mutation at the RNA level, demonstrating that the mutant LCA5 transcript was absent in a patient. All patients carrying LCA5 mutations presented nystagmus, night blindness, and progressive loss of visual acuity and visual field leading to blindness toward the third decade of life. Fundoscopy

  11. 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

  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. MR of the liver in Wilson`s disease; MRT der Leber bei Morbus Wilson

    Energy Technology Data Exchange (ETDEWEB)

    Vogl, T.J. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Steiner, S. [Klinikum Grosshadern, Radiologische Klinik und Poliklinik, Univ. Muenchen (Germany); Hammerstingl, R. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Schwarz, S. [Klinikum Grosshadern, Neurologische Klinik, Univ. Muenchen (Germany); Kraft, E. [Klinikum Grosshadern, Neurologische Klinik, Univ. Muenchen (Germany); Weinzierl, M. [Klinikum Grosshadern, 2. Medizinische Klinik, Univ. Muenchen (Germany); Felix, R. [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany)

    1994-01-01

    To show that Wilson`s disease is one likely cause of multiple low-intensity nodules of the liver we obtained MR images in 16 patients with clinically and histopathologically confirmed Wilson`s disease. Corresponding to morphological changes MRI enabled the subdivision of the patients into two groups. Using a T{sub 2}-weighted spin-echo sequence (TR/TE=2000/45-90) liver parenchyma showed multiple tiny low-intensity-nodules surrounded by high-intensity septa in 10 out of 16 patients. 5 patients had also low-intensity nodules in T{sub 1}-weighted images (TR/TE=600/20). In patients of this group histopathology revealed liver cirrhosis (n=7) and fibrosis (n=2). Common feature of this patient group was marked inflammatory cell infiltration into fibrous septa, increase of copper concentration in liver parenchyma and distinct pathological changes of laboratory data. In the remaining 6 patients no pathological change of liver morphology was demonstrated by MRI corresponding to slight histopathological changes of parenchyma and normal laboratory data. As low-intensity nodules surrounded by high intensity septa can be demonstrated in patients with marked inflammatory infiltration of liver parenchyma MRI may help to define Wilson patients with poorer prognosis. In patients with low-intensity nodules of the liver and unknown cause of liver cirrhosis laboratory data and histopathology should be checked when searching for disorders of copper metabolism. (orig.) [Deutsch] Im Rahmen einer prospektiven Studie wurde die Leber bei 16 Patienten mit klinisch gesichertem Morbus Wilson magnetresonanztomographisch untersucht. Zum Einsatz kamen T{sub 1}- und T{sub 2}-gewichtete Spin-Echo-Sequenzen vor und nach Applikation von Gd-DTPA (0,1 mmol/kg KG). Anhand der MRT-Befunde konnten zwei unterschiedliche Patientenkollektive definiert werden. 10 Patienten wiesen in der T{sub 2}-gewichteten Sequenz hypointense Regeneratknoten auf und zeigten histopathologisch ausgepraegte Befunde einer

  14. Endometriosis of the liver: Findings in imaging diagnosis; Endometriose in der Leber: Befunde der bildgebenden Diagnostik

    Energy Technology Data Exchange (ETDEWEB)

    Nakanishi, K. [Inst. fuer Roentgendiagnostik, Zentralklinikum Augsburg (Germany); Bohndorf, K. [Inst. fuer Roentgendiagnostik, Zentralklinikum Augsburg (Germany); Lindemann, F. [2. Chirurgische Klinik, Zentralklinikum Augsburg (Germany); Leipprand, E. [Inst. fuer Pathologie, Zentralklinikum Augsburg (Germany)

    1994-10-01

    Endometriosis of the liver is an extremely rare disease. To our knowledge, no more than three such cases were so far mentioned in the relevant literature. Moreover, we understand that nmr findings to prove the presence of hepatic endometriosis have not yet been described. We consider nmr imaging to be a suitable tool to establish a presumptive, if not firm, diagnosis of hepatic endometriosis. A sign strongly suggestive of the disorder is the irregular pattern of blood constituents of different ages that can invariably be visualized using this method. Due to the great amounts of free methaemoglobin found in subacute haemorrhages in increase insignal intensity can be observed for T{sub 1}-weighted and T{sub 2}-weighted SE sequences. The residues of former bleedings into the stroma, which are histologically confirmed by haemosiderin deposits, account for the greatly diminished signal intensity in T{sub 1}-weighted images. An unusual finding here was the comparatively high signal intensity observed for T{sub 2}-weighted images in those areas, where signals were practically absent in T{sub 1}-weighted images. In our opinion, this can be explained by scattered subacute bleedings, which are probably too small in amount to produce signals in T{sub 1}-weighted pictures. (orig./MG) [Deutsch] Endometriosen in der Leber sind ein ungewoehnlicher Befund. In der Weltliteratur sind unseres Wissens nur drei Faelle belegt. MR-Befunde einer hepatischen Endometriose liegen unserer Kenntnis nach nicht vor. Die MR-Tomographie ist unseres Erachtens in der Lage, zumindest die Verdachtsdiagnose einer hepatischen Endometriose zu stellen. Diagnostisch wegweisend ist die irregulaere Anordnung von Blutbestandteilen unterschiedlichen Alters, die mittels der MRT sicher gelingt. Subakute Blutungen haben aufgrund des hohen Anteils an freiem Methaemoglobin eine hohe Signalintensitaet in T{sub 1}- und T{sub 2}-gewichteten SE-Sequenzen. Die auch histologisch nachweisbaren Haemosiderinablagerungen als

  15. 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.

  16. Autosomal-dominant Leber Congenital Amaurosis Caused by a Heterozygous CRX Mutation in a Father and Son.

    Science.gov (United States)

    Arcot Sadagopan, Karthikeyan; Battista, Robert; Keep, Rosanne B; Capasso, Jenina E; Levin, Alex V

    2015-06-01

    Leber congenital amaurosis (LCA) is most often an autosomal recessive disorder. We report a father and son with autosomal dominant LCA due to a mutation in the CRX gene. DNA screening using an allele specific assay of 90 of the most common LCA-causing variations in the coding sequences of AIPL1, CEP290, CRB1, CRX, GUCY2D, RDH12 and RPE65 was performed on the father. Automated DNA sequencing of his son examining exon 3 of the CRX gene was subsequently performed. Both father and son have a heterozygous single base pair deletion of an adenine at codon 153 in the coding sequence of the CRX gene resulting in a frameshift mutation. Mutations involving the CRX gene may demonstrate an autosomal dominant inheritance pattern for LCA.

  17. Whole-Exome Sequencing Identifies ALMS1, IQCB1, CNGA3, and MYO7A Mutations in Patients with Leber Congenital Amaurosis

    OpenAIRE

    Wang, Xia; Wang, Hui; Cao, Ming; Li, Zhe; Chen, Xianfeng; Patenia, Claire; Gore, Athurva; Abboud, Emad B.; Al-Rajhi, Ali A.; Lewis, Richard A.; Lupski, James R.; Mardon, Graeme; Zhang, Kun; Muzny, Donna; Gibbs, Richard A.

    2011-01-01

    It has been well documented that mutations in the same retinal disease gene can result in different clinical phenotypes due to difference in the mutant allele and/or genetic background. To evaluate this, a set of consanguineous patient families with Leber congenital amaurosis (LCA) that do not carry mutations in known LCA disease genes was characterized through homozygosity mapping followed by targeted exon/whole-exome sequencing to identify genetic variations. Among these families, a total o...

  18. 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.

  19. Reversal of blindness in animal models of leber congenital amaurosis using optimized AAV2-mediated gene transfer.

    Science.gov (United States)

    Bennicelli, Jeannette; Wright, John Fraser; Komaromy, Andras; Jacobs, Jonathan B; Hauck, Bernd; Zelenaia, Olga; Mingozzi, Federico; Hui, Daniel; Chung, Daniel; Rex, Tonia S; Wei, Zhangyong; Qu, Guang; Zhou, Shangzhen; Zeiss, Caroline; Arruda, Valder R; Acland, Gregory M; Dell'Osso, Lou F; High, Katherine A; Maguire, Albert M; Bennett, Jean

    2008-03-01

    We evaluated the safety and efficacy of an optimized adeno-associated virus (AAV; AAV2.RPE65) in animal models of the RPE65 form of Leber congenital amaurosis (LCA). Protein expression was optimized by addition of a modified Kozak sequence at the translational start site of hRPE65. Modifications in AAV production and delivery included use of a long stuffer sequence to prevent reverse packaging from the AAV inverted-terminal repeats, and co-injection with a surfactant. The latter allows consistent and predictable delivery of a given dose of vector. We observed improved electroretinograms (ERGs) and visual acuity in Rpe65 mutant mice. This has not been reported previously using AAV2 vectors. Subretinal delivery of 8.25 x 10(10) vector genomes in affected dogs was well tolerated both locally and systemically, and treated animals showed improved visual behavior and pupillary responses, and reduced nystagmus within 2 weeks of injection. ERG responses confirmed the reversal of visual deficit. Immunohistochemistry confirmed transduction of retinal pigment epithelium cells and there was minimal toxicity to the retina as judged by histopathologic analysis. The data demonstrate that AAV2.RPE65 delivers the RPE65 transgene efficiently and quickly to the appropriate target cells in vivo in animal models. This vector holds great promise for treatment of LCA due to RPE65 mutations.

  20. 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.

  1. 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.

  2. Leber's hereditary optic neuropathy is associated with the mitochondrial ND4 G11696A mutation in five Chinese families

    International Nuclear Information System (INIS)

    Zhou Xiangtian; Wei Qiping; Yang Li; Tong Yi; Zhao Fuxin; Lu Chunjie; Qian Yaping; Sun Yanghong; Lu Fan; Qu Jia; Guan Minxin

    2006-01-01

    We report here the clinical, genetic, and molecular characterization of five Chinese families with Leber's hereditary optic neuropathy (LHON). Clinical and genetic evaluations revealed the variable severity and age-of-onset in visual impairment in these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of the complete mitochondrial genomes in these pedigrees showed the distinct sets of mtDNA polymorphism, in addition to the identical ND4 G11696A mutation associated with LHON. Indeed, this mutation is present in homoplasmy only in the maternal lineage of those pedigrees but not other members of these families. In fact, the occurrence of the G11696A mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Furthermore, the N405D in the ND5 and G5820A in the tRNA Cys , showing high evolutional conservation, may contribute to the phenotypic expression of G11696A mutation in the WZ10 pedigree. However, there was the absence of functionally significant mtDNA mutations in other four Chinese pedigrees carrying the G11696A mutation. Therefore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic expression of the LHON-associated G11696A mutation in these Chinese pedigrees

  3. 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.

  4. Leber's hereditary optic neuropathy is associated with the mitochondrial ND6 T14484C mutation in three Chinese families

    International Nuclear Information System (INIS)

    Sun Yanhong; Wei Qiping; Zhou Xiangtian; Qian Yaping; Zhou Jian; Lu Fan; Qu Jia; Guan Minxin

    2006-01-01

    We report here the clinical, genetic, and molecular characterization of three Chinese families with maternally transmitted Leber's hereditary optic neuropathy (LHON). Clinical and genetic evaluations revealed the variable severity and age-of-onset in visual impairment in these families. In the affected matrilineal relatives, the loss of central vision is bilateral, the fellow eye becoming affected either simultaneously (45%) or sequentially (55%). The penetrances of vision loss in these pedigrees were 27%, 50%, and 60%, respectively. The age-at-onset of vision loss in these families was 14, 19, and 24 years, respectively. Furthermore, the ratios between affected male and female matrilineal relatives were 1:1, 1:1.2, and 1:2, respectively. Mutational analysis of mitochondrial DNA revealed the presence of homoplasmic ND6 T14484C mutation, which has been associated with LHON. The incomplete penetrance and phenotypic variability implicate the involvement of nuclear modifier gene(s), environmental factor(s) or mitochondrial haplotype(s) in the phenotypic expression of the LHON-associated T14484C mutation in these Chinese pedigrees

  5. 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.

  6. 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.

  7. Leber Congenital Amaurosis

    Science.gov (United States)

    ... Campaign to End Blindness Other Ways to Fight Blindness Corporate Support Volunteer Take Action You are here ... become narrow and constricted. A variety of pigmentary (color) changes can also occur in the retinal pigment ...

  8. Wolff-Parkinson-White syndrome and noncompaction in Leber's hereditary optic neuropathy due to the variant m.3460G>A.

    Science.gov (United States)

    Finsterer, Josef; Stollberger, Claudia; Gatterer, Edmund

    2018-05-01

    This report describes a 66-year-old Caucasian male who acutely developed severe, bilateral impairment of visual acuity at 24 years of age. Leber's hereditary optic neuropathy (LHON) was suspected but the diagnosis was not genetically confirmed until the age of 49 years when the primary LHON mutation m.3460G>A was detected. Since onset, visual acuity had slightly improved. The family history was positive for LHON (brother, two sisters of mother, female cousin) and genetically confirmed in his brother and one aunt. Since the age of 65 years, he had experienced recurrent vertigo. His cardiological history was positive for arterial hypertension, noncompaction, myocardial thickening, intermittent right bundle-branch-block (RBBB) and Wolff-Parkinson-White (WPW) syndrome. In addition to LHON, he presented with polyneuropathy, hyperCKaemia, carotid artery occlusion, and a history of stroke. Cardiological investigations at 66 years of age revealed mildly reduced systolic function, enlarged atria, and nonsustained ventricular tachycardias. He underwent an electrophysiological investigation, but radiofrequency ablation was ruled out due to a 'bizarre' cardiac conduction system. Instead, an implantable cardioverter defibrillator was proposed but refused by the patient. Since the vertigo did not resolve it was attributed to polyneuropathy. This case demonstrates that LHON may be associated with noncompaction, myocardial thickening, reduced systolic function, enlarged atria, RBBB, WPW syndrome and nonsustained ventricular tachycardias. WPW syndrome in LHON may require invasive antiarrhythmic treatment.

  9. Only male matrilineal relatives with Leber's hereditary optic neuropathy in a large Chinese family carrying the mitochondrial DNA G11778A mutation

    International Nuclear Information System (INIS)

    Qu Jia; Li Ronghua; Tong Yi; Hu Yongwu; Zhou Xiangtian; Qian Yaping; Lu Fan; Guan Minxin

    2005-01-01

    We report here the characterization of a five-generation large Chinese family with Leber's hereditary optic neuropathy (LHON). Very strikingly, six affected individuals of 38 matrilineal relatives (17 females/21 males) are exclusively males in this Chinese family. These matrilineal relatives in this family exhibited late-onset/progressive visual impairment with a wide range of severity, ranging from blindness to normal vision. The age of onset in visual impairment varies from 17 to 30 years. Sequence analysis of the complete mitochondrial genome in this pedigree revealed the presence of the G11778A mutation in ND4 gene and 29 other variants. This mitochondrial genome belongs to the Southern Chinese haplogroup B5b. We showed that the G11778A mutation is present at near homoplasmy in matrilineal relatives of this Chinese family but not in 164 Chinese controls. Incomplete penetrance of LHON in this family indicates the involvement of modulatory factors in the phenotypic expression of visual dysfunction associated with the G11778A mutation. However, none of other mtDNA variants are evolutionarily conserved and implicated to have significantly functional consequence. Thus, nuclear modifier gene(s) or environmental factor(s) seem to account for the penetrance and phenotypic variability of LHON in this Chinese family carrying the G11778A mutation

  10. Veno-occlusive liver disease after infradiaphragmatic total lymphoid irradiation. A rare complication; Die Venenverschlusskrankheit der Leber nach infradiaphragmaler total lymphatischer Bestrahlung. Eine seltene Nebenwirkung

    Energy Technology Data Exchange (ETDEWEB)

    Bischof, M.; Zierhut, D.; Gutwein, S.; Wannenmacher, M. [Heidelberg Univ. (DE.) Abt. fuer Klinische Radiologie - Schwerpunkt Strahlentherapie; Hansmann, J. [Heidelberg Univ. (DE.) Abt. fuer Radiologische Diagnostik; Stremmel, W.; Mueller, M. [Heidelberg Univ. (DE). Abt. Innere Medizin 4 (Schwerpunkt Gastroenterologie)

    2001-06-01

    -jaehrigen Patienten mit einem zentrozytisch-zentroblastischen Non-Hodgkin-Lymphom, Stadium IA (Lokalisation: Linke Leiste) wurde die gesamte Abdomen- und Beckenregion ('abdominelles Bad') bestrahlt. Bei einer woechentlichen Fraktionierung von fuenfmal 1,5 Gy wurde eine Gesamtdosis von 30 Gy appliziert. Zum Schutz der Risikoorgane wurden Nierenbloecke nach 13,5 Gy und Leberbloecke nach 25 Gy eingesetzt. Waehrend der letzten beiden Therapietage kam es zur Verschlechterung des Allgemeinzustandes des Patienten mit Gewichtszunahme, Vergroesserung des Bauchumfanges, Dyspnoe und einem Anstieg der Leberwerte. Die weiterfuehrende Diagnostik ergab eine Hepatosplenomegalie mit ausgepraegter Aszitesbildung und einen erhoehten portosystemischen Druckgradienten. Im Leberbiopsat wurde eine Venenverschlusskrankheit gefunden. Innerhalb 1 Woche nach Anlage eines transjungulaeren intrahepatischen portosystemischen Stent-Shunts (TIPSS), Vollheparinisierung und unter Diuretikagabe war der Patient beschwerdefrei. Die Leberwerte sind im Normbereich. Schlussfolgerung: Die Venenverschlusskrankheit der Leber (VOD) ist eine sehr seltene Nebenwirkung bei der abdominellen Bestrahlung nicht vorbehandelter follikulaerer Keimzentrumslymphome. Bei Oberbauchbeschwerden, Anstieg der Leberenzyme sowie Aszitesbildung, insbesondere in einem Zeitraum von bis zu 4 Monaten nach Therapieabschluss, muss an diese Komplikation gedacht werden. Genese, Diagnostik und Therapie der Venenverschlusskrankheit der Leber werden im Literaturueberblick praesentiert. (orig.)

  11. The background of mitochondrial DNA haplogroup J increases the sensitivity of Leber's hereditary optic neuropathy cells to 2,5-hexanedione toxicity.

    Directory of Open Access Journals (Sweden)

    Anna Ghelli

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited blinding disease due to mitochondrial DNA (mtDNA point mutations in complex I subunit genes, whose incomplete penetrance has been attributed to both genetic and environmental factors. Indeed, the mtDNA background defined as haplogroup J is known to increase the penetrance of the 11778/ND4 and 14484/ND6 mutations. Recently it was also documented that the professional exposure to n-hexane might act as an exogenous trigger for LHON. Therefore, we here investigate the effect of the n-hexane neurotoxic metabolite 2,5-hexanedione (2,5-HD on cell viability and mitochondrial function of different cell models (cybrids and fibroblasts carrying the LHON mutations on different mtDNA haplogroups. The viability of control and LHON cybrids and fibroblasts, whose mtDNAs were completely sequenced, was assessed using the MTT assay. Mitochondrial ATP synthesis rate driven by complex I substrates was determined with the luciferine/luciferase method. Incubation with 2,5-HD caused the maximal loss of viability in control and LHON cells. The toxic effect of this compound was similar in control cells irrespective of the mtDNA background. On the contrary, sensitivity to 2,5-HD induced cell death was greatly increased in LHON cells carrying the 11778/ND4 or the 14484/ND6 mutation on haplogroup J, whereas the 11778/ND4 mutation in association with haplogroups U and H significantly improved cell survival. The 11778/ND4 mutation on haplogroup U was also more resistant to inhibition of complex I dependent ATP synthesis by 2,5-HD. In conclusion, this study shows that mtDNA haplogroups modulate the response of LHON cells to 2,5-HD. In particular, haplogroup J makes cells more sensitive to its toxic effect. This is the first evidence that an mtDNA background plays a role by interacting with an environmental factor and that 2,5-HD may be a risk element for visual loss in LHON. This proof of principle has broad

  12. Results at 2 Years after Gene Therapy for RPE65-Deficient Leber Congenital Amaurosis and Severe Early-Childhood-Onset Retinal Dystrophy.

    Science.gov (United States)

    Weleber, Richard G; Pennesi, Mark E; Wilson, David J; Kaushal, Shalesh; Erker, Laura R; Jensen, Lauren; McBride, Maureen T; Flotte, Terence R; Humphries, Margaret; Calcedo, Roberto; Hauswirth, William W; Chulay, Jeffrey D; Stout, J Timothy

    2016-07-01

    To provide an initial assessment of the safety of a recombinant adeno-associated virus vector expressing RPE65 (rAAV2-CB-hRPE65) in adults and children with retinal degeneration caused by RPE65 mutations. Nonrandomized, multicenter clinical trial. Eight adults and 4 children, 6 to 39 years of age, with Leber congenital amaurosis (LCA) or severe early-childhood-onset retinal degeneration (SECORD). Patients received a subretinal injection of rAAV2-CB-hRPE65 in the poorer-seeing eye, at either of 2 dose levels, and were followed up for 2 years after treatment. The primary safety measures were ocular and nonocular adverse events. Exploratory efficacy measures included changes in best-corrected visual acuity (BCVA), static perimetry central 30° visual field hill of vision (V30) and total visual field hill of vision (VTOT), kinetic perimetry visual field area, and responses to a quality-of-life questionnaire. All patients tolerated subretinal injections and there were no treatment-related serious adverse events. Common adverse events were those associated with the surgical procedure and included subconjunctival hemorrhage in 8 patients and ocular hyperemia in 5 patients. In the treated eye, BCVA increased in 5 patients, V30 increased in 6 patients, VTOT increased in 5 patients, and kinetic visual field area improved in 3 patients. One subject showed a decrease in BCVA and 2 patients showed a decrease in kinetic visual field area. Treatment with rAAV2-CB-hRPE65 was not associated with serious adverse events, and improvement in 1 or more measures of visual function was observed in 9 of 12 patients. The greatest improvements in visual acuity were observed in younger patients with better baseline visual acuity. Evaluation of more patients and a longer duration of follow-up will be needed to determine the rate of uncommon or rare side effects or safety concerns. Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  13. 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

  14. The coexistence of mitochondrial ND6 T14484C and 12S rRNA A1555G mutations in a Chinese family with Leber's hereditary optic neuropathy and hearing loss

    International Nuclear Information System (INIS)

    Wei Qiping; Zhou Xiangtian; Yang Li; Sun Yanhong; Zhou Jian; Li Guang; Jiang, Robert; Lu Fan; Qu Jia; Guan Minxin

    2007-01-01

    We report here the clinical, genetic and molecular characterization of one three-generation Han Chinese family with Leber's hereditary optic neuropathy (LHON) and hearing loss. Four of 14 matrilineal relatives exhibited the moderate central vision loss at the average age of 12.5 years. Of these, one subject exhibited both LHON and mild hearing impairment. Sequence analysis of the complete mitochondrial genomes in the pedigree showed the presence of homoplasmic LHON-associated ND6 T14484C mutation, deafness-associated 12S rRNA A1555 mutation and 47 other variants belonging to Eastern Asian haplogroup H2. None of other mitochondrial variants was evolutionarily conserved and functional significance. Therefore, the coexistence of the A1555G mutation and T14484C mutations in this Chinese family indicate that the A1555G mutation may play a synergistic role in the phenotypic manifestation of LHON associated ND6 T14484C mutation. However, the incomplete penetrance of vision and hearing loss suggests the involvement of nuclear modifier genes and environmental factors in the phenotypic expression of these mtDNA mutations

  15. Caracterización molecular de las formas precoces de distrofia de retina recesivas y esporádicas en población española: amaurosis congénita de Leber y Retinosis pigmentaria de inicio precoz

    OpenAIRE

    Tatu, Sorina Daniela

    2016-01-01

    Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 27-01-2016 Esta tesis tiene embargado el acceso al texto completo hasta 27-07-2017 Las distrofias hereditarias de la retina (DR) son un conjunto de trastornos que se producen por una degeneración primaria y progresiva de fotorreceptores. Entre ellas, la amaurosis congénita de Leber (LCA) representa la forma más precoz y severa, ocasionando ...

  16. VIBE with parallel acquisition technique - a novel approach to dynamic contrast-enhanced MR imaging of the liver; VIBE mit paralleler Akquisitionstechnik - eine neue Moeglichkeit der dynamischen kontrastverstaerkten MRT der Leber

    Energy Technology Data Exchange (ETDEWEB)

    Dobritz, M.; Radkow, T.; Bautz, W.; Fellner, F.A. [Inst. fuer Diagnostische Radiologie, Friedrich-Alexander-Univ. Erlangen-Nuernberg (Germany); Nittka, M. [Siemens Medical Solutions, Erlangen (Germany)

    2002-06-01

    Purpose: The VIBE (volume interpolated breath-hold examination) sequence in combination with parallel acquisition technique (iPAT: integrated parallel acquisition technique) allows dynamic contrast-enhanced MRI of the liver with high temporal and spatial resolution. The aim of this study was to obtain first clinical experience with this technique for the detection and characterization of focal liver lesions. Materials and Methods: We examined 10 consecutive patients using a 1.5 T MR system (gradient field strength 30 mT/m) with a phased-array coil combination. Following sequences- were acquired: T{sub 2}-w TSE and T{sub 1}-w FLASH, after administration of gadolinium, 6 VIBE sequences with iPAT (TR/TE/matrix/partition thickness/time of acquisition: 6.2 ms/ 3.2 ms/256 x 192/4 mm/13 s), as well as T{sub 1}-weighted FLASH with fat saturation. Two observers evaluated the different sequences concerning the number of lesions and their dignity. Following lesions were found: hepatocellular carcinoma (5 patients), hemangioma (2), metastasis (1), cyst (1), adenoma (1). Results: The VIBE sequences were superior for the detection of lesions with arterial hyperperfusion with a total of 33 focal lesions. 21 lesions were found with T{sub 2}-w TSE and 20 with plain T{sub 1}-weighted FLASH. Diagnostic accuracy increased with the VIBE sequence in comparison to the other sequences. Conclusion: VIBE with iPAT allows MR imaging of the liver with high spatial and temporal resolution providing dynamic contrast-enhanced information about the whole liver. This may lead to improved detection of liver lesions, especially hepatocellular carcinoma. (orig.) [German] Ziel: Die VIBE-Sequenz (Volume Interpolated Breath-hold Examination) in Kombination mit paralleler Bildgebung (iPAT) ermoeglicht eine dynamische kontrastmittel-gestuetzte Untersuchung der Leber in hoher zeitlicher und oertlicher Aufloesung. Ziel war es, erste klinische Erfahrungen mit dieser Technik in der Detektion fokaler

  17. Fermentation instead of animal feeding; In den Fermenter statt in den Magen des Schweins

    Energy Technology Data Exchange (ETDEWEB)

    Brombach, T.

    2008-07-01

    Since 2006, Germany has prohibited the feeding of class K3 waste food from gastronomy, canteens and the food industry to pigs. Fermentation is a creative solution. In Haid on the Schwaebische Alb mountain range, two creative waste managers developed a plant for power generation from fat and used oils. (orig.)

  18. Verbraucherstudie zum Thema dänische männliche, nicht kastrierte Schweine

    DEFF Research Database (Denmark)

    Godt, Jannik; Kristensen, Kai; Poulsen, Carsten Stig

    1996-01-01

    Former studies of the unpleasant odour of meat from certain uncastrated male pigs have been based mainly on evaluations made by trained sensory panellists. This study analyses the effect of the two dominating male pig odour components, skatole and androstenone, on the evaluation of eating quality...... made in-home by consumers, thus bringing the analysis out of the laboratory and into the market place. The vast majority of the population of uncastrated male pigs have low concentrations of skatole and androstenone. The cutlets that were evaluated in this study were selected from uncastrated male pigs...

  19. Genetics Home Reference: Leber hereditary optic neuropathy

    Science.gov (United States)

    ... the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within ... in mtDNA . Because egg cells, but not sperm cells, ... mtDNA mutations from their mother. These disorders can appear in every generation of ...

  20. Rasterelektronenmikroskopische und immunhistochemische Untersuchungen am Eileiter vom Schwein während Zyklus und Trächtigkeit

    OpenAIRE

    Mayer, Judith

    2008-01-01

    In der vorliegenden Arbeit wurden zum einen mit Hilfe des Rasterelektronenmikroskops die morphologischen Veränderungen des Eileiterepithels und zum anderen die Expression hypophysärer wachstums- und proliferationsfördernder Hormone und ihrer Rezeptoren immunhistochemisch und mit der Reverse Transkriptase (RT)-PCR sowohl im Verlauf des Zyklus als auch der Trächtigkeit analysiert. Hierfür wurden, von 24 Schweinen der Deutschen Landrasse, die drei Abschnitte des Eileiters (Infundibulum, Ampulle,...

  1. PEX1 deficiency presenting as Leber congenital amaurosis

    NARCIS (Netherlands)

    Michelakakis, Helen M.; Zafeiriou, Dimitrios I.; Moraitou, Marina S.; Gootjes, Jeannette; Wanders, Ronald J. A.

    2004-01-01

    Peroxisome biogenesis disorders result from defects in peroxin proteins involved in peroxisomal matrix and membrane protein import. Peroxins are encoded in peroxin protein genes; to date, the PEX genes responsible for all 12 peroxisome biogenesis disorders complementation groups are known. Peroxin

  2. Liver: radiological methods supplementary; Radiologische Diagnostik der Leber

    Energy Technology Data Exchange (ETDEWEB)

    Delorme, S. [Deutsches Krebsforschungszentrum, Heidelberg (Germany). Abt. Onkologische Diagnostik und Therapie

    2000-10-01

    Highly specific methods are required for the diagnostic workup of focal hepatic lesions, since benign circumscribed liver changes are very common. Although cross-sectional imaging techniques have a high diagnostic accuracy, radionuclide imaging techniques such as colloid, red blood cell, or hepatobiliary scan are commonly performed when a benign lesion is assumed since these permit a definite diagnosis with high specificity. The diagnosis of a primary or secondary malignant liver tumor, however, usually relies on radiological imaging techniques along, supported by needle biopsy. Whether positron emission tomography as a primary or supplementary diagnostic tool will have a role in the routine staging of malignant tumors remains to be determined. (orig.) [German] Die Abklaerung umschriebener Leberveraenderungen erfordert den Einsatz von Methoden hoher Spezifitaet, da die Praevalenz benigner, fokaler Laesionen sehr hoch ist. Hierfuer sind radiologische Schnittbildtechniken grundsaetzlich gut geeignet. Wenn aufgrund der sonographischen, computertomographischen oder magnetresonanztomographischen Befunde eine gutartige Laesion anzunehmen ist, werden jedoch haeufig ergaenzend die Kolloiderythrozyten- oder hepatobiliaere Szintigraphie - ggf. in Kombination - eingesetzt, da hiermit rasch eine abschliessende Diagnose mit hoher Spezifitaet gestellt werden kann. Bei malignen primaeren oder sekundaeren Lebertumoren hingegen werden nuklearmedizinische Zusatzuntersuchungen seltener angefordert, da der radiologische Befund, ggf. gestuetzt durch eine Ultraschall- oder CT-gezielte Biopsie, eine Diagnose in den meisten Faellen erlaubt. Inwieweit sich der primaere oder ergaenzende Einsatz der Positronenemissionstomographie im Vergleich zu radiologischen Schnittbildtechniken beim Staging boesartiger Tumoren bewaehrt, ist noch nicht abschliessend geklaert. (orig.)

  3. Antiretroviral therapy-induced Leber's hereditary optic neuropathy

    African Journals Online (AJOL)

    2014-06-01

    Jun 1, 2014 ... Optic neuropathy in HIV-infected patients results from the HIV ... individuals was triggered by NRTI drugs lamivudine and tenofovir when ... in disseminated tuberculosis where its prolonged use over ... Fungal: cryptococcal meningitis .... Genetic testing of LHON by polymerase chain reaction and restriction.

  4. Memorias de alemanes en España durante la Guerra de la Independencia : la estancia de Philipp Schwein en la isla Cabrera

    Directory of Open Access Journals (Sweden)

    Hiltrud Friederrich-Stegmann

    2003-01-01

    Full Text Available El presente artículo tiene tres objetivos principales. Primero, da una información general de las memorias de alemanes participantes en la Guerra de la Independencia, junto con una relación bibliográfica, añadida como apéndice. En segundo lugar, da a conocer el autor alemán Johann Christian Mámpel que en seis libros, publicados anónimamente, cuenta las guerras napoleónicas desde el punto de vista del soldado raso, del Feldjáger. A Goetfie le gustó tanto esta obra que escribió el prólogo. Finalmente, el estudio incluye dos traducciones, la de un episodio del tercer tomo, que Mámpel dedica a la estancia de un compañero de guerra como prisionero en la desierta isla de Cabrera, y también la de la introducción de Goethe al mismo tomo con sus reflexiones sobre este asunto.The present article has three main objects. Firstly, it gives a general view of the memoirs written by Germán participants in the Spanish War of Independence, including an appendix with a related bibliography. Secondly, it introduces the German author Johann Christian Mámpel, who wrote six books, anonimously published, about the Napoleonic Wars from the point of view of the prívate soldier, the Feldjáger. Goethe was so impressed by it, that he wrote the prologue. Finally, the study includes two translations: an episode of the third volume, which Mámpel dedicates to a fellow soldier, who was a prisoner of war on the desert island of Cabrera, and also Goethe's introduction to the same volume with his reflections about this event.

  5. Novel compound heterozygous NMNAT1 variants associated with Leber congenital amaurosis

    DEFF Research Database (Denmark)

    Siemiatkowska, Anna M; van den Born, L Ingeborgh; van Genderen, Maria M

    2014-01-01

    , were screened in 532 additional patients with retinal dystrophies. This cohort encompassed 108 persons with isolated or autosomal recessive cone-rod dystrophy (CRD), 271 with isolated or autosomal recessive retinitis pigmentosa (RP), and 49 with autosomal dominant RP, as well as 104 persons with LCA...... and associated phenotypes in different types of inherited retinal dystrophies. METHODS: DNA samples of 161 patients with LCA without genetic diagnosis were analyzed for variants in NMNAT1 using Sanger sequencing. Variants in exon 5 of NMNAT1, which harbors the majority of the previously identified mutations...

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

    OpenAIRE

    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.

    2013-01-01

    The first retinal gene therapy in human blindness from RPE65 mutations has focused on safety and efficacy, as defined by improved vision. The disease component not studied, however, has been the fate of photoreceptors in this progressive retinal degeneration. We show that gene therapy improves vision for at least 3 y, but photoreceptor degeneration progresses unabated in humans. In the canine model, the same result occurs when treatment is at the disease stage equivalent to humans. The study ...

  7. Radiofrequency of the liver. An update; Radiofrequenzablation der Leber. Eine aktuelle Uebersicht

    Energy Technology Data Exchange (ETDEWEB)

    Bangard, Christopher [Universitaetsklinikum Koeln (Germany). Inst. und Poliklinik fuer Radiologische Diagnostik

    2011-08-15

    The impact of radiofrequency ablation (RFA) as a local ablative tumor therapy is increasing. Randomized trials justify RFA for small hepatocellular carcinoma (HCC) (single tumor {<=} 5 cm or three or less tumors {<=} 3 cm). Surgical resection still remains the gold standard for resectable colorectal liver metastases (CRLM). Several single center trials demonstrate improved patient survival by RFA and justify RFA for non-resectable CRLM. Local recurrence increases significantly with tumor diameters > 3 cm. There is insufficient evidence at this time to resolve the issue of optimal approach for treatment of CRLM. Technical development of the electrode design, improved ablation algorithms, and simplification of the exact electrode placement by new real-time fusion techniques of pre-interventional CT or MRT images with intra-interventional ultrasound have the potential to reduce the variable and sometimes high rate of local tumor recurrence. The clinical impact of immunological aspects following RFA with regard to patient survival and local tumor recurrence remains unclear. (orig.)

  8. NMR imaging of the liver. Diagnostics, differential diagnostics, therapeutic approaches; MRT der Leber. Diagnostik, Differenzialdiagnostik, Therapieansaetze

    Energy Technology Data Exchange (ETDEWEB)

    Fischbach, Frank; Fischbach, Katharina [Universitaetsklinikum Magdeburg A.oe.R. (Germany). Klinik fuer Radiologie und Nuklearmedizin

    2017-03-01

    The book on NMR imaging of the liver covers the following issues: Fundamentals of NMR imaging, T1-weighted imaging; T2-weighted imaging, diffusion-weighted imaging, cavernous hemangioma, focal nodular hyperplasy; hepatocellular adenoma, hepatocellulas carcinoma, cholangiocellular carcinoma, hepatic metastases.

  9. Bioinformatische Analyse und funktionelle Charakterisierung von strukturellen Genvarianten in ADME-Genen in humaner Leber

    OpenAIRE

    Tremmel, Roman

    2016-01-01

    Die Pharmakogenetik beschreibt die Untersuchung von interindividuellen genetischen Unterschieden, welche die Wirkung von Medikamenten und die Reaktion auf xenobioti-sche Substanzen beeinflussen. Ein Großteil dieser Variabilität beruht auf Unterschieden im hepatischen Arzneimittelmetabolismus. Die daran beteiligten Enzyme, Transporter und Rezeptoren sind in die Prozesse der Absorption, der Distribution, des Metabolismus und der Exkretion involviert und werden als ADME-Gengruppe zusammengefasst...

  10. 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

    a national register of hereditary eye diseases at the National Eye Clinic (NEC), a tertiary low vision rehabilitation center for the entire Danish population. The assembling of LHON pedigrees was based on the reconstruction of published families and newly diagnosed cases from 1980 to 2012 identified...... in the files of NEC. Genealogic follow-up on the maternal ancestry of all affected individuals was performed to identify a possible relation to an already known maternal line. A full genotypic characterization of the nation-based LHON cohort is provided. RESULTS: Forty different lines were identified....... 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...

  11. Linkage studies and mutation analysis of the PDEB gene in 23 families with Leber congenital amaurosis

    DEFF Research Database (Denmark)

    Riess, O; Weber, B; Nørremølle, Anne

    1992-01-01

    as to whether mutations in the human PDEB gene might cause LCA. We have previously cloned and characterized the human homologue of the mouse Pdeb gene and have mapped it to chromosome 4p16.3. In this study, a total of 23 LCA families of various ethnic backgrounds have been investigated. Linkage analysis using...

  12. Optical coherence tomography angiography changes in radial peripapillary capillaries in Leber hereditary optic neuropathy

    Directory of Open Access Journals (Sweden)

    Mitsuhiro Matsuzaki

    2018-03-01

    Conclusions and importance: Optical coherence tomography angiography showed LHON from the presymptomatic stage. The results indicate that temporal RPC defects and RFT thinning start to spread once the pseudoedema begins to resolve.

  13. CT and MRI of the liver: when, what, why?; CT und MRT der Leber: wann, was, warum

    Energy Technology Data Exchange (ETDEWEB)

    Budjan, J.; Schoenberg, S.O.; Attenberger, U.I. [Medizinische Fakultaet Mannheim der Universitaet Heidelberg, Institut fuer Klinische Radiologie und Nuklearmedizin, Universitaetsmedizin Mannheim, Mannheim (Germany)

    2017-05-15

    The detection and differential diagnostic clarification of liver pathologies play an important role in almost all medical disciplines. Because of its superior soft tissue contrast, the availability of liver-specific contrast agents and functional techniques, magnetic resonance imaging (MRI) is the method of choice for the diagnostics of focal and diffuse liver pathologies. In addition to its superior detection and differentiation capabilities, MRI can provide prognostic information and enable early assessment of the therapy response for malignant liver lesions using functional techniques, especially diffusion imaging. Computed tomography (CT) is the imaging method of choice for the detection of traumatic liver injury. Despite the increasing availability of functional techniques in CT, MRI remains the overall modality of choice in liver imaging. (orig.) [German] Die Detektion und die differenzialdiagnostische Abklaerung von Leberpathologien spielen in nahezu allen medizinischen Disziplinen eine bedeutende Rolle. Ihre Vorteile in Hinblick auf Weichteilkontrast, die Verfuegbarkeit leberspezifischer Kontrastmittel und funktionelle Techniken machen die MRT zum bildgebenden Verfahren der Wahl fuer die gezielte Abklaerung fokaler oder diffuser Leberpathologien. Neben hoeheren Detektionsraten und besseren Differenzierungsmoeglichkeiten stehen in der MRT funktionelle Techniken - insbesondere die Diffusionsbildgebung - zur Verfuegung, die eine Prognoseabschaetzung und die fruehe Beurteilung von Therapieansprechen bei malignen Leberlaesionen erlauben. Die CT ist bei der Detektion traumatischer Leberverletzungen Bildgebungsverfahren der Wahl; trotz der auch in der CT zunehmend verfuegbaren funktionellen Techniken bleibt die MRT in der Leberbildgebung weiterhin ueberlegen. (orig.)

  14. Prognostic impact of hepatobiliary scintigraphy in diagnosis and postoperative follow-up of newborns with biliary atresia; Prognostische Wertigkeit der hepatobiliaeren Funktionszintigraphie in Diagnostik und Nachsorge der Gallengangsatresie

    Energy Technology Data Exchange (ETDEWEB)

    Rossmueller, B.; Porn, U.; Dresel, S.; Hahn, K. [Muenchen Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Schuster, T. [Muenchen Univ. (Germany). Kinderchirurgische Klinik; Lang, T. [Muenchen Univ. (Germany). Kinderklinik

    2000-01-01

    Aim: To investigate the prognostic relevance of hepatobiliary scintigraphy (HBS) in newborns suffering from biliary atresia (BA) for establishing the primary diagnosis and in the postoperative follow-up after portoenterostomy (Kasai). Methods: Twenty newborns with direct hyperbilirubinemia and 6 children after operative treatment of BA (Kasai) underwent HBS with Tc-99m-DEIDA. In patients without intestinal drainage, hepatocellular extraction was estimated visually and calculated semiquantitatively by means of liver/heart-ratio 5 min p.i. Results: 10/20 patients with hyperbilirubinemia did not display biliary drainage; 6 had BA, 3 intrahepatic hypoplasia, and one showed a bile plug syndrom. 4/6 with BA but none of the 4 children with diagnoses other than BA presented with a good extraction. All of the 4 children with BA, who had either pre- or postoperatively a bad extraction, needed liver transplantation due to liver failure. Both of the two newborns with BA and favourable outcome after Kasai had a good extraction in the preoperative HBS and demonstrated good intestinal drainage in the postoperative scan. Conclusion: HBS rules out BA with high accuracy by demonstrating drainage of bile into the intestine. In newborns without drainage a good extraction favours the diagnosis of BA. In newborns with BA a bad extraction seems to indicate a poor postoperative prognosis after Kasai operation. HBS might therefore help to select those children who will not benefit from portoenterostomy. Postoperatively, HBS can easily and quickly confirm the successful hepatobiliary anastomosis by demonstrating biliary drainage into the intestine. (orig.) [German] Ziel der Studie war es, die diagnostische Wertigkeit und die prognostische Aussagekraft der hepatobiliaeren Funktionsszintigraphie (HB-FS) in der Primaerdiagnostik der Gallengangsatresie (GG-Atresie) und bei postoperativen Kontrollen nach Portoenterostomie (Kasai-OP) zu ueberpruefen. Methoden: 20 Neugeborene (Alter: 3-119 d) mit

  15. 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

    by targeted segment sequencing of 61 regions in 14 causative genes was performed. Subsequently, exome sequencing was undertaken in the proband, unaffected consanguineous parents and two unaffected siblings. Bioinformatic analysis used two independent pipelines, BWA-GATK and SOAP, followed by Annovar and Snp...

  16. Morphological aspects of liver CT in patients with HIV infections. CT-morphologische Aspekte der Leber bei Patienten mit HIV-Infektion

    Energy Technology Data Exchange (ETDEWEB)

    Schedel, H [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Wicht, L [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Roegler, G [2. Medizinische Klinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Langer, R [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany); Felix, R [Strahlenklinik und Poliklinik, Universitaetsklinikum Rudolf Virchow, Freie Univ. Berlin (Germany)

    1994-07-01

    CT examinations of the liver in HIV-infected patients show more frequent pathological findings. The extended spectrum of differential diagnosis and atypical manifestations of disorders in immunodeficient patients needs to be considered in the interpretation of CT scans. Difficulties in the differential diagnosis of focal hepatic lesions in HIV-infected patients are demonstrated in the following. Besides the relatively common findings in HIV-infection such as hepato- or hepatosplenomegalia, lymphoma, and inflammatory changes of the bowel an infection with Cryptococcus neoformans, hepatitis, and local steatosis of the liver are discussed as the rare causes for suspect computertomographic findings in the live of HIV-infected patients. The examinations were obtained consecutively in 76 HIV-infected patients during abdominal CT staging. (orig.)

  17. Radiation sensitivity and the acute and chronical radiation injury of the liver. Strahlenempfindlichkeit und die akute und chronische Strahlenschaedigung der Leber

    Energy Technology Data Exchange (ETDEWEB)

    Lesch, R [Freiburg Univ. (Germany, F.R.). Abt. Experimentelle Pathologie

    1976-01-01

    The extended German version of the contribution 'Radiation-induced injury of the liver' from the manual of experimental pharmacology, volume XVI, part 5 (p. 227-304), Springer Verlag, Berlin-Heidelberg-New York 1976, is dealt with here. Following a brief presentation of the radiation-induced change of the human liver by external and internal radiation source, experimental results in the latter case of the radiation effect on the regeneration behaviour of the liver particularly regarding the nucleic acid synthesis are indicated especially using findings after thorotrast application. Furthermore, effects on the metabolic activities and on the liver function with combined radiation drug application on test animals is shown.

  18. Noninvasive MRI-based liver iron quantification. Methodic approaches, practical applicability and significance; Nicht invasive MRT-basierte Bestimmung des Leber-Eisen-Gehalts. Methodische Ansaetze, Anwendbarkeit in der Praxis und Aussagekraft

    Energy Technology Data Exchange (ETDEWEB)

    Wunderlich, A.P. [Universitaetsklinikum Ulm (Germany). Section for Experimental Radiology; Universitaetsklinikum Ulm (Germany). Clinic for Diagnostic and Interventional Radiology; Cario, H. [Universitaetsklinikum Ulm (Germany). Dept. of Pediatrics and Adolescent Medicine; Juchems, M.S. [Konstanz Hospital (Germany). Diagnostic and Interventional Radiology; Beer, M.; Schmidt, S.A. [Universitaetsklinikum Ulm (Germany). Clinic for Diagnostic and Interventional Radiology

    2016-11-15

    Due to the dependence of transverse relaxation times T{sub 2} and T{sub 2}* on tissue iron content, MRI offers different options for the determination of iron concentration. These are the time-consuming spin-echo sequence as well as the gradient-echo sequence. For the latter, several data analysis approaches have been proposed, with different requirements for acquisition and post-processing: the mathematically challenging R{sub 2}* analysis and the signal-intensity ratio method with its high demand on the signal homogeneity of MR images. Furthermore, special procedures currently under evaluation are presented as future prospects: quantitative susceptibility imaging, as a third approach for analyzing gradient echo data, and multi-contrast spin-echo using repeated refocusing pulses. MR theory, as far as needed for understanding the methods, is briefly depicted.

  19. Multivariable analysis of clinical influence factors on liver enhancement of Gd-EOB-DTPA-enhanced 3T MRI; Multivariable Analyse klinischer Einflussfaktoren auf die Signalintensitaet bei Gd-EOB-DTPA 3T-MRT der Leber

    Energy Technology Data Exchange (ETDEWEB)

    Verloh, N.; Haimerl, M.; Stroszczynski, C.; Fellner, C.; Wiggermann, P. [University Hospital Regensburg (Germany). Dept. of Radiology; Zeman, F. [University Hospital Regensburg (Germany). Center for Clinical Trials; Teufel, A. [University Hospital Regensburg (Germany). Dept. of Gastroenterology; Lang, S. [University Hospital Regensburg (Germany). Dept. of Surgery

    2015-01-15

    The purpose of this study was to identify clinical factors influencing Gd-EOB-DTPA liver uptake in patients with healthy liver parenchyma. A total of 124 patients underwent contrast-enhanced MRI with a hepatocyte-specific contrast agent at 3T. T1-weighted volume interpolated breath-hold examination (VIBE) sequences with fat suppression were acquired before and 20 minutes after contrast injection. The relative enhancement (RE) between plain and contrast-enhanced signal intensity was calculated. Simple and multiple linear regression analyses were performed to evaluate clinical factors influencing the relative enhancement. Patients were subdivided into three groups according to their relative liver enhancement (HRE, RE ≥ 100 %; MRE, 100 % > RE > 50 %; NRE, RE ≤ 50 %) and were analyzed according to the relevant risk factors. Simple regression analyses revealed patient age, transaminases (AST, ALT, GGT), liver, spleen and delta-liver volume (the difference between the volumetrically measured liver volume and the estimated liver volume based on body weight) as significant factors influencing relative enhancement. In the multiple analysis the transaminase AST, spleen and delta liver volume remained significant factors influencing relative enhancement. Delta liver volume showed a significant difference between all analyzed groups. Liver enhancement in the hepatobiliary phase depends on a variety of factors. Body weight-adapted administration of Gd-EOB-DTPA may lead to inadequate liver enhancement after 20 minutes especially when the actual liver volume differs from the expected volume.

  20. Incidental findings of liver, biliary system, pancreas and spleen in asymptomatic patients. Assessment and management recommendations; Zufallsbefunde von Leber, Gallensystem, Pankreas und Milz bei asymptomatischen Patienten. Bewertung und Managementempfehlung

    Energy Technology Data Exchange (ETDEWEB)

    Scharitzer, M.; Tamandl, D.; Ba-Ssalamah, A. [Medizinische Universitaet Wien, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Wien (Austria)

    2017-04-15

    The increased use of highly developed imaging procedures, such as multidetector-row computed tomography and magnetic resonance imaging has led to a substantial increase of asymptomatic and unexpected findings. Abdominal CT investigations are particularly affected with a large number of incidental findings. This valuable diagnostic procedure also entails the risk of complex and cost-intensive subsequent investigations with partly invasive procedures. For this reason radiologists are more often confronted with the difficult task of correctly assessing these lesions, to decide on the need for additional investigations and to inform the patient in detail about the clinical relevance. The aims of this article are to describe the most common abdominal incidentalomas, to assist with the interpretation and differential diagnosis and to give recommendations for further management. (orig.) [German] Die vermehrte Verwendung hoch entwickelter bildgebender Verfahren wie Multidetektorcomputertomographie und Magnetresonanztomographie hat zu einer betraechtlichen Zunahme asymptomatischer und unerwarteter Befunde gefuehrt. Besonders betroffen sind abdominelle CT-Untersuchungen mit einer Vielzahl inzidenteller Befunde. Dieses wertvolle Diagnoseverfahren birgt auch die Gefahr aufwendiger und auch kostenintensiver Folgeuntersuchungen mit z. T. invasiven Verfahren. Vor diesem Hintergrund stellt sich fuer den Radiologen immer haeufiger die schwierige Aufgabe, diese Laesionen korrekt einzuschaetzen, ueber die Notwendigkeit einer weiteren Abklaerung zu entscheiden und den Patienten umfassend ueber die klinische Relevanz zu informieren. Das Ziel dieses Artikels ist es, die am haeufigsten vorkommenden abdominellen Zufallsbefunde zu beschreiben sowie Hilfestellung bei ihrer Interpretation und Differenzialdiagnose mit Empfehlungen fuer das weitere Management zu geben. (orig.)

  1. Ätiologie und Prävalenz permanenter kindlicher Hörstörungen in Deutschland

    OpenAIRE

    Spormann-Lagodzinski, ME; Nubel, K; König, O; Gross, M; Gross, M

    2003-01-01

    Permanente Hörstörungen bei Kindern haben in den letzten Jahren bezüglich Ätiologie und Prävalenz einen deutlichen Wandel erlebt. In den westlichen Industrienationen ist sie auf 1 bis 3 pro 1.000 Neugeborene gesunken. Nach Ergebnissen des Deutschen Zentralregisters für kindliche Hörstörungen (DZH) liegt die Prävalenz in Deutschland bei ca. 1,2:1.000. Von 6.200 ausgewerteten Datensätzen des DZH haben 36% aller permanenten Hörstörungen eine (vermutlich oder gesichert) genetische Ursache, 18% si...

  2. Hongos tremeloides (Heterobasidiomycetes de la Reserva de la Biosfera de Calakmul, Campeche, México Tremelloid fungi (Heterobasidiomycetes from Calakmul Biosphere Reserve, Campeche, Mexico

    Directory of Open Access Journals (Sweden)

    Sigfrido Sierra

    2012-03-01

    Full Text Available Se registran 7 especies de hongos tremeloides de la Reserva de la Biosfera de Calakmul: Auricularia cornea Ehrenb., A. delicata (Fr. Henn., A. mesenterica (Dicks. Pers., Dacryopinax elegans (Berk. et M.A. Curtis G.W. Martin, D. spathularia (Schwein. G.W. Martin, Tremella wrightii Berk. et M.A. Curtis y Tremelloscypha gelatinosa (Murrill Oberw. et K. Wells. Todas son registros nuevos para la reserva. Auricularia cornea y T. gelatinosa son nuevos registros para el estado de Campeche.Seven species of tremelloid fungi are recorded from Calakmul Biosphere Reserve: Auricularia cornea Ehrenb., A. delicata (Fr. Henn., A. mesenterica (Dicks. Pers., Dacryopinax elegans (Berk. et M.A. Curtis G.W. Martin, D. spathularia (Schwein. G.W. Martin, Tremella wrightii Berk. et M.A. Curtis and Tremelloscypha gelatinosa (Murrill Oberw. et K. Wells. All are new records for the reserve. Auricularia cornea and T. gelatinosa are new records for Campeche state.

  3. Measuring the Foundation of Homeland Security

    Science.gov (United States)

    2007-03-01

    Pirak Kevin Eack Susan Pyle Chuck Eaneff Joseph Saitta Susan Fernandez Shelly Schechter Helen Fitzpatrick Rick Schwein Jay...multiple disciplines. The scope of this literature review is to cast a broad net and then narrow to specific literature related to Homeland Security...Suez Canal. His successes as a planner, diplomat and promoter made him the most celebrated man in Europe. Because of these successes, De Lesseps

  4. Isolation und Charakterisierung retroviraler Partikel und Proteine zur Untersuchung immunsuppressiver Effekte

    OpenAIRE

    Pietsch, Heiko

    2016-01-01

    Obgleich auf dem Gebiet der Transplantationsmedizin in jüngster Zeit beachtliche Fortschritte erzielt worden sind, ist der Mangel an Organspendern ein fortbestehendes Problem. Im Rahmen der Xenotransplantation können Schweine als Spender zur Transplantation von Zellen oder Organen beim Menschen dienen. Um die Sicherheit der Xenotransplantation zu gewährleisten, ist sowohl die Entwicklung sensitiver Nachweismethoden als auch die Einschätzung des Gefahrenpotentials durch eine Infektion für den ...

  5. Glaucoma

    Medline Plus

    Full Text Available ... Diabetic Eye Disease Education Program Glaucoma Education Program Low Vision Education Program Hispanic/Latino Program Vision and ... Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish ...

  6. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Diabetic Eye Disease Education Program Glaucoma Education Program Low Vision Education Program Hispanic/Latino Program Vision and ... Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish ...

  7. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Diabetic Eye Disease Education Program Glaucoma Education Program Low Vision Education Program Hispanic/Latino Program Vision and Aging ... Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos ...

  8. Glaucoma

    Medline Plus

    Full Text Available ... Diabetic Eye Disease Education Program Glaucoma Education Program Low Vision Education Program Hispanic/Latino Program Vision and Aging ... Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos ...

  9. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Amblyopia Embedded ...

  10. Glaucoma

    Medline Plus

    Full Text Available ... Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube Videos: Glaucoma Embedded ...

  11. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Vision Education Program Hispanic/Latino Program Vision and Aging Program African American Program Training and Jobs Fellowships ... Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive ...

  12. Glaucoma

    Medline Plus

    Full Text Available ... Vision Education Program Hispanic/Latino Program Vision and Aging Program African American Program Training and Jobs Fellowships ... Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive ...

  13. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Education Program (NEHEP) Diabetic Eye Disease Education Program Glaucoma Education Program Low Vision Education Program Hispanic/Latino ... Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision ...

  14. Retinitis Pigmentosa

    Science.gov (United States)

    ... Linked Retinoschisis (XLRS) X-Linked Retinitis Pigmentosa (XLRP) Usher Syndrome Other Retinal Diseases Glossary News & Research News & Research ... degenerate. Forms of RP and related diseases include Usher syndrome, Leber congenital amaurosis, and Bardet-Biedl syndrome, among ...

  15. Glaucoma

    Medline Plus

    Full Text Available ... Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity ...

  16. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity ...

  17. Is the propagation speed of ultrasound in human organs a diagnostic parameter for tissue characterization? Evaluation using the liver parenchyma in children and adolescents as an example; Die Schallleitgeschwindigkeit im menschlichen Gewebe. Ein diagnostisch verwertbarer Parameter? Evaluation am Beispiel der Leber bei Kindern und Jugendlichen

    Energy Technology Data Exchange (ETDEWEB)

    Born, M. [Bonn Univ. (Germany). Radiologische Klinik - Kinderradiologie; Franke, I. [Bonn Univ. (Germany). Kinderklinik

    2011-09-15

    New sonographic machines permit the measurement of the propagation speed of ultrasound (PSU) in humans. The liver seems to be an appropriate organ for examining whether the PSU may be used as a diagnostic parameter for tissue characterization since the liver is easily accessible to sonography and its variable content of fat impacts the PSU. Purpose: To determine whether there is a measurable correlation between obesity and PSU in the liver. Methods: In 69 children and adolescents, the PSU in the liver was measured sonographically and correlated to BMI, age, size and weight of the children. Results: A strong correlation was found between the PSU in the liver and the BMI. The PSU was significantly lower in obese children (1507 m/s) than in children with normal body weight (1564 m/s). Conclusion: PSU seems to be promising as an additional diagnostic parameter for characterizing liver tissue. Further evaluation is necessary. (orig.)

  18. Fusariosis de la espiga del trigo : dinámica del inóculo de Fusarium graminearum ante un manejo sustentable

    OpenAIRE

    Mourelos, Cecilia Alejandra

    2015-01-01

    Mourelos, C. A. (2015). Fusariosis de la espiga del trigo: Dinámica del inóculo de Fusarium graminearum ante un manejo sustentable. (Tesis de doctorado). Universidad Nacional de Quilmes, Bernal, Argentina. La fusariosis de la espiga de trigo (FET) es una de las enfermedades fúngicas más importantes del cultivo de trigo y de otros cereales en la Argentina. En el país, la enfermedad es causada principalmente por Fusarium graminearum Schwabe [teleomorfo Gibberella zeae (Schwein.) Petch]. Esta...

  19. Metabolismus des tabakspezifischen Nitrosamins N'-Nitrosonornicotin in Gewebeschnitten von Mäusen, Ratten und Menschen sowie Möglichkeiten der Hemmung durch Nicotin, Cotinin und Phenethylisothiocyanat

    OpenAIRE

    Lassnack, Bettina

    2005-01-01

    Das Ziel dieser Arbeit war es, speziesspezifische Unterschiede in der Metabolisierung des tabakspezifischen Nitrosamins N'-Nitrosonornicotin (NNN) in den Organen Lunge und Leber von Mäusen, Ratten und Mensch zu untersuchen. Gewebeschnitte von Lunge und Leber der Maus, Ratte und des Menschen wurden unter identischen Versuchsbedingungen mit [5-3H]-NNN sechs Stunden inkubiert. Es kamen je 8 Konzentrationen von 0,001 bis 1,2 µM zum Einsatz. Bei Maus und Ratte wurden pro Konzentration die Schnitte...

  20. A De Novo Mutation in Causes Generalized Dystonia in 2 Unrelated Children

    Directory of Open Access Journals (Sweden)

    Yasemin Gulcan Kurt MD

    2016-03-01

    Full Text Available Dystonia is often associated with the symmetrical basal ganglia lesions of Leigh syndrome. However, it has also been associated with mitochondrial ND mutations, with or without Leber hereditary optic neuropathy. The m.14459G>A mutation in ND6 causes dystonia with or without familial Leber hereditary optic neuropathy. We report heteroplasmic 14459G>A mutations in 2 unrelated children with nonmaternally inherited generalized dystonia and showing bilateral magnetic resonance imaging lesions in nucleus pallidus and putamen. Both children have reached their teenage years, and they are intellectually active, despite their motor problems.

  1. [Progress in research on pathogenic genes and gene therapy for inherited retinal diseases].

    Science.gov (United States)

    Zhu, Ling; Cao, Cong; Sun, Jiji; Gao, Tao; Liang, Xiaoyang; Nie, Zhipeng; Ji, Yanchun; Jiang, Pingping; Guan, Minxin

    2017-02-10

    Inherited retinal diseases (IRDs), including retinitis pigmentosa, Usher syndrome, Cone-Rod degenerations, inherited macular dystrophy, Leber's congenital amaurosis, Leber's hereditary optic neuropathy are the most common and severe types of hereditary ocular diseases. So far more than 200 pathogenic genes have been identified. With the growing knowledge of the genetics and mechanisms of IRDs, a number of gene therapeutic strategies have been developed in the laboratory or even entered clinical trials. Here the progress of IRD research on the pathogenic genes and therapeutic strategies, particularly gene therapy, are reviewed.

  2. Simultaneous Mutation Detection in 90 Retinal Disease Genes in Multiple Patients Using a Custom-designed 300-kb Retinal Resequencing Chip

    NARCIS (Netherlands)

    Booij, Judith C.; Bakker, Arne 1; Kulumbetova, Jamilia; Moutaoukil, Youssef; Smeets, Bert; Verheij, Joke; Kroes, Hester Y.; Klaver, Caroline C. W.; van Schooneveld, Mary; Bergen, Arthur A. B.; Florijn, Ralph J.

    Purpose: To develop a high-throughput, cost-effective diagnostic strategy for the identification of known and new mutations in 90 retinal disease genes. Design: Evidence-based study. Participants: Sixty patients with a variety of retinal disorders, including Leber's congenital amaurosis, ocular

  3. Targeted ablation of Crb2 in photoreceptor cells induces retinitis pigmentosa

    NARCIS (Netherlands)

    Alves, Celso Henrique; Pellissier, Lucie P; Vos, Rogier M; Garcia Garrido, Marina; Sothilingam, Vithiyanjali; Seide, Christina; Beck, Susanne C; Klooster, J.; Furukawa, Takahisa; Flannery, John G; Verhaagen, J.; Seeliger, Mathias W; Wijnholds, J.

    2014-01-01

    In humans, the Crumbs homolog-1 (CRB1) gene is mutated in autosomal recessive Leber congenital amaurosis and early-onset retinitis pigmentosa. In mammals, the Crumbs family is composed of: CRB1, CRB2, CRB3A and CRB3B. Recently, we showed that removal of mouse Crb2 from retinal progenitor cells, and

  4. Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa

    NARCIS (Netherlands)

    Booij, J. C.; Florijn, R. J.; ten Brink, J. B.; Loves, W.; Meire, F.; van Schooneveld, M. J.; de Jong, P. T. V. M.; Bergen, A. A. B.

    2005-01-01

    OBJECTIVE: To identify mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. METHODS: Mutation analysis was carried out in a group of 35 unrelated patients with juvenile autosomal recessive retinitis pigmentosa (ARRP), Leber's congenital

  5. Tailored Communication to Enhance Adaptation Across the Breast Cancer Spectrum

    Science.gov (United States)

    2007-10-01

    Manager Geary, Shannon Health Educator Gillespie, Kathleen Research Study Assistant Ginsberg, Barbara Assistant Director Glenn, Melanie Project...Kandadai, Venk Student Intern Kimenour, James Unit Aide Klein , Margaret Health Educator II LaMonica, Stephen Project Manager Leber, Elva Health Educator

  6. Idebenone increases mitochondrial complex I activity in fibroblasts from LHON patients while producing contradictory effects on respiration

    DEFF Research Database (Denmark)

    Angebault, Claire; Gueguen, Naig; Desquiret-Dumas, Valerie

    2011-01-01

    ABSTRACT: BACKGROUND: Leber's hereditary optic neuropathy (LHON) is caused by mutations in the complex I subunits of the respiratory chain. Although patients have been treated with idebenone since 1992, the efficacy of the drug is still a matter of debate. Methods: We evaluated the effect...

  7. Stem Cell Ophthalmology Treatment Study II

    Science.gov (United States)

    2018-02-01

    Retinal Disease; Age-Related Macular Degeneration; Retinitis Pigmentosa; Stargardt Disease; Optic Neuropathy; Nonarteritic Ischemic Optic Neuropathy; Optic Atrophy; Optic Nerve Disease; Glaucoma; Leber Hereditary Optic Neuropathy; Blindness; Vision Loss Night; Vision Loss Partial; Vision, Low; Retinopathy; Maculopathy; Macular Degeneration; Retina Atrophy

  8. No evidence of association between optic neuritis and secondary LHON mtDNA mutations in patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Andalib, Sasan; Talebi, Mahnaz; Sakhinia, Ebrahim

    2017-01-01

    Leber's Hereditary Optic Neuropathy (LHON) shares features with Multiple Sclerosis (MS). Both diseases develop optic lesions. Frequent secondary LHON mutations in MS patients may explain the optic damage. Here, we tested the hypothesis that secondary LHON mutations are associated with optic...

  9. Journal of Genetics | Indian Academy of Sciences

    Indian Academy of Sciences (India)

    Genetic analysis of a consanguineous Pakistani family with Leber congenital amaurosis identifies a novel mutation in GUCY2D gene. Muzammil Ahmad Khan Verena Rupp Muhammad Ayaz Khan Muhammad Pervaiz Khan Muhammad Ansar Christian Windpassinger. Research Note Volume 93 Issue 2 August 2014 pp ...

  10. Glaucoma

    Medline Plus

    Full Text Available ... Macular Degeneration Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube ...

  11. NEI You Tube Videos: Amblyopia

    Medline Plus

    Full Text Available ... Macular Degeneration Amblyopia Animations Blindness Cataract Convergence Insufficiency Diabetic Eye Disease Dilated Eye Exam Dry Eye For Kids Glaucoma Healthy Vision Tips Leber Congenital Amaurosis Low Vision Refractive Errors Retinopathy of Prematurity Science Spanish Videos Webinars NEI YouTube ...

  12. Temporal constraints on visual perception

    DEFF Research Database (Denmark)

    Nielsen, Simon

    be triggered by attention capture to the first target (Folk, Leber & Egeth, 2008) and that if making the first target easier to perceive increases its saliency this may increase the attentional blink (Chua, 2005). This thesis examines the attention capture hypothesis with focus on empirical investigations...

  13. CRB2 acts as a modifying factor of CRB1-related retinal dystrophies in mice

    NARCIS (Netherlands)

    Pellissier, L.P.; Lundvig, D.M.S.; Tanimoto, N.; Klooster, J.; Vos, R.M.; Richard, F.; Sothilingam, V.; Garrido, M. Garcia; Bivic, A. le; Seeliger, M.W.; Wijnholds, J.

    2014-01-01

    Mutations in the CRB1 gene lead to retinal dystrophies ranging from Leber congenital amaurosis (LCA) to early-onset retinitis pigmentosa (RP), due to developmental defects or loss of adhesion between photoreceptors and Muller glia cells, respectively. Whereas over 150 mutations have been found, no

  14. CRB2 acts as a modifying factor of CRB1-related retinal dystrophies in mice

    NARCIS (Netherlands)

    Pellissier, Lucie P; Lundvig, Ditte M S; Tanimoto, Naoyuki; Klooster, J.; Vos, Rogier M; Richard, Fabrice; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Le Bivic, André; Seeliger, Mathias W; Wijnholds, J.

    2014-01-01

    Mutations in the CRB1 gene lead to retinal dystrophies ranging from Leber congenital amaurosis (LCA) to early-onset retinitis pigmentosa (RP), due to developmental defects or loss of adhesion between photoreceptors and Müller glia cells, respectively. Whereas over 150 mutations have been found, no

  15. Some Boletes of Thailand

    Directory of Open Access Journals (Sweden)

    Te-chato, S.

    2007-05-01

    Full Text Available The objective of this study was to collect and identify some Boletes of Thailand. Through periodical excursions in woodland area in the north, northeast and south of Thailand, and regular visits to markets inthe areas during 1995-2005, 20 species of Boletes were collected and identified. These were Boletellus ananas (M.A.Curtis Murrill, Boletellus emodensis (Berk. Singer, Boletellus sp. 1, Boletellus sp. 2, Boletellus sp. 3,Boletinus sp., Boletus griseipurpureus Corner, Boletus bicolor Peck, Boletus nanus (Massee. Singer, Boletus sp. 1, Boletus sp. 2, Boletus sp. 3, Heimiella retispora (Pat. & C.F. Baker Boedijn, Phlebopus colossus (R.Heim Singer, Phylloporus pelletieri (Lev. Quel., Pulveroboletus ravenelii (Berk. & M.A.Curtis Murrill, Pulveroboletus sp., Strobilomyces confusus Singer, Strobilomyces floccopus (Vahl P. Karst., and Tylopilusalbo - ater (Schwein Murrill.

  16. Melanopsin retinal ganglion cells are resistant to neurodegeneration in mitochondrial optic neuropathies

    DEFF Research Database (Denmark)

    La Morgia, C; Ross-Cisneros, F.N.; Sadun, A.A.

    2010-01-01

    Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retinal...... ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex...... subjects as in controls, indicating that the retinohypothalamic tract is sufficiently preserved to drive light information detected by melanopsin retinal ganglion cells. We then investigated the histology of post-mortem eyes from two patients with Leber hereditary optic neuropathy and one case...

  17. Possible use of wild-living rats (Rattus norvegicus) as bioindicators for heavy metal pollution. Part I. Sex and age-related quantification of Al, As, Cd, Co, Cu, Mn, Ni, Pb, Sr, Ti, Tl and Zn in liver, heart, lung, kidney, muscle, brain and bones, and the establishment of distribution patterns; Untersuchungen zur Eignung wildlebender Wanderratten (Rattus norvegicus) als Indikatoren der Schwermetallbelastung. T. I. Alters- und geschlechtsspezifische Quantifizierung der Verteilung von Al, As, Cd, Co, Cu, Mn, Ni, Pb, Sr, Ti, Tl und Zn in den Organen Herz, Leber, Lunge, Niere, Muskulatur, Gehirn und Knochen

    Energy Technology Data Exchange (ETDEWEB)

    Wuenschmann, S. [Internationales Hochschulinstitut Zittau (Germany). Lehrstuhl fuer Umweltverfahrenstechnik; Hochschule fuer Technik, Wirtschaft und Sozialwesen Zittau/Goerlitz (FH), Zittau (Germany). Fachbereich Mathematik/Naturwissenschaften; Oehlmann, J. [J. W. Goethe-Univ. Frankfurt, Zoologisches Inst., Frankfurt/M. (Germany); Delakowitz, B. [Hochschule fuer Technik, Wirtschaft und Sozialwesen Zittau/Goerlitz (FH), Zittau (Germany). Fachbereich Mathematik/Naturwissenschaften; Markert, B. [Internationales Hochschulinstitut Zittau (Germany). Lehrstuhl fuer Umweltverfahrenstechnik

    2001-07-01

    The objective of the current attempt was to investigate the suitability of wild-living rats (Rattus norvegicus) as a passive bioindicator using quantitative determinations of 12 chemical elements in different organs taken from rats which were caught in the Zoological Garden of Zittau. Aside from the determinations of so-called background levels, the focus of interest was with accumulations of certain elements within the organs depending on either sex or age of the rats. There were different affinities of the elements towards certain organs. Because of apparent sex and age-related differences in element concentrations and accumulation features, a well-planned sampling strategy for the use of rats as possible passive bioindicators is indeed required. The consideration of element distribution patterns within the organ system of Rattus norvegicus (based on body burden calculations (in part 2 of this work)) allows an effective use of the rat for purposes of integrative monitoring. (orig.) [German] Durch die Quantifizierung von 12 chemischen Elementen im Organsystem von wildlebenden Ratten (Rattus norvegicus) aus dem Tierpark Zittau (Sachsen) sollte die Eignung dieser Spezies als passiver Bioindikator untersucht werden. Neben der Ermittlung von sogenannten Hintergrundkonzentrationen standen insbesondere Fragen zur geschlechts- und altersspezifischen Akkumulation einzelner Elemente im Organsystem von Rattus norvegicus im Vordergrund. Spezifisch zeigten dabei einzelne Elemente unterschiedliche Affinitaeten zu den entsprechenden Geweben und Organen. Insbesondere die hierbei ermittelten geschlechts- und altersspezifischen Charakteristika einzelner Elemente macht eine detaillierte Ausarbeitung einer Beprobungsstrategie fuer den spaeteren Einsatz als passiver Bioindikator zwingend. Unter Beruecksichtigung des durch die Berechnung des Body Burden (Koerperlast) im 2. Teil der Arbeit ermittelten typischen Verteilungsmusters einzelner Elemente ist Rattus norvegicus zum integrativen Monitoringeinsatz praedestiniert. (orig.)

  18. Die Wirkung von Desacetylcefotaxin, einem Metaboliten von Cefotaxim, in vitro und auf die experimentelle Infektion mit Escherichia coli

    OpenAIRE

    Wirbelauer, J.; Hof, H.; Hacker, Jörg

    2009-01-01

    Die MHK-Werte von Desacetylcefotaxim gegen verschiedene, z. T. ampicillinresistente Stämme von Escherichia coH, die mit Hilfe einer Agardilutionsmethode erhoben wurden, waren höher als die von Cefotaxim und Ceftriaxon, jedoch niedriger als die von Cefoxitin. In einem Modell der systemischen Infektion der Maus mit einem plasmidtragenden, betalactamaseproduzierenden Stamm von E. coli führte die Therapie mit Desacetylcefotaxim zu einer starken Reduktion der Keime pro Leber. Im Vergleich zur Ther...

  19. Inherited Retinal Degenerative Disease Registry

    Science.gov (United States)

    2017-09-13

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  20. Untersuchungen zur Expansion, funktionellen Charakterisierung und kontinuierlichen Bereitstellung von Hepatocyten für die Anwendung in bioartifiziellen Leberunterstützungssystemen

    OpenAIRE

    Iding, Kai

    2001-01-01

    Der vollständige Funktionsverlust der Leber kann in der modernen Medizin bisher nur durch den Austausch des funktionsuntüchtigen gegen ein gesundes Organ, d.h. durch eine Lebertransplantation behandelt werden. Da es jedoch weit mehr transplantationsbedürftige Patienten gibt als geeignete Spenderorgane zur Verfügung stehen, gibt es weltweite Anstrengungen zur Entwicklung alternativer Behandlungsmethoden. Nach bisherigem wissenschaftlichen Erkenntnisstand ist die bioartifizielle Leberunterst...

  1. Defizienz der c-Jun n-terminalen Kinase und das metabolische Syndrom

    OpenAIRE

    Haß, Tim Frederick

    2009-01-01

    Auswirkungen eines JNK2/3 Doppelknockout im Mausmodel im Hinblick auf das Metabolische Syndrom. Die untersuchten Parameter waren u. a. Gewichtsentwicklung, Fettzellgröße, Stoffwechsel des Fettgewebes und der Leber. Effects of the double knockout of JNK2 and JNK3 in mice with regards to the metabolic syndrome. Analysis of weight, fat cell size and metabolism of liver and fat tissue.

  2. Moose von Inselbergen in Benin

    OpenAIRE

    Frahm, Jan-Peter; Porembski, Stefan

    1998-01-01

    Acht Leber- und zehn Laubmoosarten werden von Inselbergen aus Benin angegeben. Fünf der Lebermoose (Acrolejeunea emergens, Riccia atropurpurea, R. congoana, R. discolor, R. moenkemeyeri) und alle Laubmoose (Archidium ohioense, Brachymenium acuminatum, B. exile, Bryum arachnoideum, B. argenteum, Bryum deperssum, Garckea moenkemeyeri, Hyophila involuta, Philonotis mniobryoides und Weissia cf. edentula) werden neu für Benin angegeben. Eight liverworts and ten mosses are reported from inselber...

  3. Prenatal, transplacental uptake of polychlorinated biphenyls and hexachlorobenzene in humans. Pt. 3.. Personal characteristics (gestational age, birth weight, maternal age, smoking habits of the parents) and geographic differences; Praenatale, transplazentare Uebertragung von polychlorierten Biphenylen und Hexachlorbenzol beim Menschen. T. 3. Personenbezogene Einflussfaktoren (Gestationsalter, Geburtsgewicht, muetterliches Alter, Tabakkonsum der Eltern) und geographische Unterschiede

    Energy Technology Data Exchange (ETDEWEB)

    Lackmann, G.M. [Duesseldorf Univ. (Germany). Zentrum fuer Kinderheilkunde

    2001-07-01

    untersuchen. Methode: Es wurde von insgesamt 200 gesunden, reifen Neugeborenen, die 1998 entweder in Fulda oder in Duesseldorf geboren wurden, eine Nabelschnurprobe gewonnen. Die Eltern aller Kinder waren dabei zeitlebens in der betreffenden Stadt ansaessig und niemals beruflich oder akzidentell hohen PCB- oder HCB-Belastungen ausgesetzt. Das Serum wurde umgehend bei -20 C tiefgefroren; die Analysen wurden geschlossen und verblindet 1999 durchgefuehrt. Dabei wurden die sechs PCB-Kongenere 28, 52, 101, 138, 153 und 180 sowie HCB kapillar-gaschromatographisch mit ECD-Detektion bestimmt. Ergebnisse: Im Gesamtkollektiv (n = 199) - ein Kind wurde wegen ungewoehnlich hoher PCB-Konzentrationen von der Auswertung ausgeschlossen - fanden wir eine signifikante Korrelation zwischen der Schwangerschaftsdauer sowie dem muetterlichen Alter und der praenatalen Schadstoffakkumulation, wobei Kinder der 42. SSW um den Faktor 3,5 hoehere PCB-Konzentrationen aufwiesen, als Kinder der 38. SSW, und Neugeborene einer 50-jaehrigen Frau bis 500% hoehere PCB-Werte, als Kinder einer 20-jaehrigen Mutter (p < 0,0001). Ein Zusammenhang zum Geburtsgewicht bestand nicht. Ausserdem konnten wir zeigen, dass Neugeborene aktiv rauchender Muetter signifikant hoehere PCB- und HCB-Konzentrationen aufwiesen, als Kinder passiv oder nicht rauchender Muetter. Es bestand kein Unterschied in der praenatalen PCB-Akkumulation zwischen den Kindern aus Fulda und denen aus Duesseldorf, waehrend letztere um 62% hoehere HCB-Werte aufwiesen. (orig.)

  4. On-line Processing of German Number-marked Relative Clauses in the Visual-world Paradigm

    Directory of Open Access Journals (Sweden)

    Anne Adelt

    2014-04-01

    (3 Filler: Wo ist das Schwein mit dem Ballon? (Where is the pig with the balloon? All sentences are randomized and presented auditorily. Simultaneously, colored illustrations of animals performing an action are shown on a computer screen (see Figure 1. Participants have to identify via button press (left/right the target animal to which the question refers. During this task, eye movements are collected as an on-line measure of sentence processing. Off-line comprehension is measured in terms of accuracy of target identification. Ten IWAs with sentence comprehension deficits and 30 healthy controls are tested. Discussion Following Burchert et al. (2003, we expect the IWA’s off-line comprehension of SRCs and ORCs to be at chance level, while controls make hardly any errors. In the on-line data, the number of fixations to the target picture are supposed to increase only at the verb or shortly after the sentence offset, since disambiguation occurs sentence finally at the verb. Controls are expected to show faster or longer fixations to the target in SRCs compared to ORCs (Caplan et al., 2007. In line with Hanne, Sekerina, Vasishth, Burchert, and De Bleser (2011, IWA’s fixations to the target should not differ qualitatively from those of controls, at least for correct responses, but eye gaze patterns may be delayed. Data collection and analysis is still ongoing. Results will be ready by October and presented and discussed at the Academy of Aphasia conference.

  5. Mycobiota of rape seeds in Romania. I. Identification of mycobiota associated with rape seeds from different areas of Romania

    Directory of Open Access Journals (Sweden)

    Tatiana-Eugenia Şesan

    2013-12-01

    Full Text Available The spectrum of fungal diversity associated with rape seeds belonging to 33 cultivars (Alaska, Astrada, Astrid, Atlantic, Betty, Champlein, Chayenne, Dexter, Digger, Elvis, Eurowest, Finesse, Herkules, Hydromel, Hydromel-MA, Ladoga, anitoba, Masa Rom, Milena, Mohican, Montego, Nectar, Ontario, Orkan, Perla (4 lots, Remy, Robust, Rodeo, Saphir, Tiger, Tiger CBC Lot ROM06-121-110, Triangle, Valesca, Vectra and 2 hybrids (H-90-20-83, H-90-21-83 has been established by samples’ macroscopical and microscopical analizying, during 2006-2008, for the first time in Romania. The Ulster method on malt-agar and PDA culture media has been used, evaluating the percentage of fungal taxons present on/in rape seeds. The most important pathogenic fungi identified were: Sclerotinia sclerotiorum (Lib. de Bary, Botrytis cinerea Pers., Rhizoctonia solani Kühn, Alternaria brassicae (Berk. Sacc., A. brassicicola (Schwein. Wiltshire and Fusarium spp. Also, a large quantities of some saprophytic fungi, as Alternaria, Cladosporium, Aspergillus, Penicillium, Rhizopus have been recorded. These ones have been affected the health condition of rape seeds, suppressing their germination and other vital phenomena. Among potential antagonistic fungi the following genera have been isolated: Chaetomium (0-4%, Trichoderma (0-10%, Aspergillus (0-14%, Penicillium (0-100%. Some correlations and comparisons have been established between fungal diversity, their provenience, cultivars, culture media (Malt-Agar/MA, Potato-Dextrose-Agar/PDA used. It has been evaluated the behaviour of rape cultivars and hybrids towards the main rape seed pathogens.

  6. Neuropathies optiques héréditaires

    DEFF Research Database (Denmark)

    Milea, D; Verny, C

    2012-01-01

    Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy...... and autosomal dominant optic atrophy) are very different in their clinical presentation and their genetic transmission, leading however to a common, non-specific optic nerve atrophy. Beyond the optic atrophy-related visual loss, which is the clinical hallmark of this group of diseases, other associated...

  7. Investor Outlook: Focus on Upcoming LCA2 Gene Therapy Phase III Results.

    Science.gov (United States)

    Schimmer, Joshua; Breazzano, Steven

    2015-09-01

    Investor interest in gene therapy has increased substantially over the past few years, and the next major catalyst for the field is likely to be Spark Therapeutics's phase III trial for the treatment of visual impairment caused by RPE65 gene mutations (often referred to as Leber congenital amaurosis type 2, or LCA2, but may include other retinal disorders). Analysis of the approach from the basic genetics, underlying visual mechanisms, clinical data, and commercialization considerations helps frame investor expectations and the potential implications for the broader field.

  8. Treatment strategies for inherited optic neuropathies: past, present and future

    OpenAIRE

    Yu-Wai-Man, P; Votruba, M; Moore, A T; Chinnery, P F

    2014-01-01

    Bilateral visual loss secondary to inherited optic neuropathies is an important cause of registrable blindness among children and young adults. The two prototypal disorders seen in clinical practice are Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). About 90% of LHON cases are due to one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A, and m.14484T>C, which affect critical complex I subunits of the mitochondrial respiratory chain...

  9. Osseous abnormalities and CT findings in stueve-wiedemann-syndrome (SWS); Ossaere Manifestationen und CT-Befunde bei der seltenen Skelettdysplasie Stueve-Wiedemann (SWS)

    Energy Technology Data Exchange (ETDEWEB)

    Langer, R. [UAE University, Dept. of Radiology, Al Ain (United Arab Emirates); Al-Gazali, L. [UAE University, Dept. of Paediatrics (United Arab Emirates); Haas, D. [FMHS - UAE Univ. and Tawam Hospital - Dept. of Radiology (United Arab Emirates); Raupp, P.; Varady, E. [Dept. of Paediatrics Al Ain (United Arab Emirates)

    2004-02-01

    -Wiedemann-Syndrom (SWS) werden anhand des eigenen Patientenkollektives analysiert. Methode: Bei 16 dysmorphen, kleinwuechsigen Neugeborenen wurden zur Klassifizierung der Dysplasie Thorax- und Skelettaufnahmen sowie in einem Fall erstmalig eine CT des Gesichtsschaedels durchgefuehrt. Die Diagnose eines SWS konnte nach Korrelation der klinischen und radiologischen Befunde frueh gestellt werden. Bei vier ueberlebenden Patienten erfolgten radiologische Verlaufskontrollen. Ergebnisse: Alle Neugeborene mit SWS wiesen Kleinwuchs, eine Mittelgesichtshypoplasie, verkruemmte lange Roehrenknochen mit Betonung der unteren Extremitaeten, dreieckige kortikale diaphysaere Sklerosen an den Konkavseiten der Verbiegungen und erweiterte Metaphysen mit abnormer Trabekelstruktur auf. Vier ueberlebende Patienten zeigten bei radiologischen Verlaufskontrollen progrediente Verkruemmungen der unteren Extremitaeten und zunehmende metaphysaere Entkalkungen. Schlussfolgerungen: Die Diagnose des seltenen SWS kann wegen der charakteristischen Roentgenveraenderungen bereits frueh postpartal gestellt werden. Hierzu ist eine gute Kooperation zwischen Radiologen, Klinikern und Genetikern erforderlich. Neben dem meist frueh letalen Verlauf gibt es auch selten Faelle, die die Neugeborenenperiode ueberleben. (orig.)

  10. Gene therapy and genome surgery in the retina.

    Science.gov (United States)

    DiCarlo, James E; Mahajan, Vinit B; Tsang, Stephen H

    2018-06-01

    Precision medicine seeks to treat disease with molecular specificity. Advances in genome sequence analysis, gene delivery, and genome surgery have allowed clinician-scientists to treat genetic conditions at the level of their pathology. As a result, progress in treating retinal disease using genetic tools has advanced tremendously over the past several decades. Breakthroughs in gene delivery vectors, both viral and nonviral, have allowed the delivery of genetic payloads in preclinical models of retinal disorders and have paved the way for numerous successful clinical trials. Moreover, the adaptation of CRISPR-Cas systems for genome engineering have enabled the correction of both recessive and dominant pathogenic alleles, expanding the disease-modifying power of gene therapies. Here, we highlight the translational progress of gene therapy and genome editing of several retinal disorders, including RPE65-, CEP290-, and GUY2D-associated Leber congenital amaurosis, as well as choroideremia, achromatopsia, Mer tyrosine kinase- (MERTK-) and RPGR X-linked retinitis pigmentosa, Usher syndrome, neovascular age-related macular degeneration, X-linked retinoschisis, Stargardt disease, and Leber hereditary optic neuropathy.

  11. Gene therapy for inherited retinal and optic nerve degenerations.

    Science.gov (United States)

    Moore, Nicholas A; Morral, Nuria; Ciulla, Thomas A; Bracha, Peter

    2018-01-01

    The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity. Areas covered: This review covers Leber's congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, Stargardt disease, Leber's hereditary optic neuropathy, Achromatopsia, and X-linked retinoschisis. Expert opinion: Despite great potential, gene therapy for IRD raises many questions, including the potential for less invasive intravitreal versus subretinal delivery, efficacy, safety, and longevity of response, as well as acceptance of novel study endpoints by regulatory bodies, patients, clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will require widespread genetic screening to identify and diagnose patients based on genotype instead of phenotype.

  12. [Gene Therapy for Inherited RETINAL AND OPTIC NERVE Disorders: Current Knowledge].

    Science.gov (United States)

    Ďuďáková, Ľ; Kousal, B; Kolářová, H; Hlavatá, L; Lišková, P

    The aim of this review is to provide a comprehensive summary of current gene therapy clinical trials for monogenic and optic nerve disorders.The number of genes for which gene-based therapies are being developed is growing. At the time of writing this review gene-based clinical trials have been registered for Leber congenital amaurosis 2 (LCA2), retinitis pigmentosa 38, Usher syndrome 1B, Stargardt disease, choroideremia, achromatopsia, Leber hereditary optic neuropathy (LHON) and X-linked retinoschisis. Apart from RPE65 gene therapy for LCA2 and MT-ND4 for LHON which has reached phase III, all other trials are in investigation phase I and II, i.e. testing the efficacy and safety.Because of the relatively easy accessibility of the retina and its ease of visualization which allows monitoring of efficacy, gene-based therapies for inherited retinal disorders represent a very promising treatment option. With the development of novel therapeutic approaches, the importance of establishing not only clinical but also molecular genetic diagnosis is obvious.Key words: gene therapy, monogenic retinal diseases, optic nerve atrophy, mitochondrial disease.

  13. Analysis of Genetic Mutations in a Cohort of Hereditary Optic Neuropathy in Shanghai, China.

    Science.gov (United States)

    Gan, Dekang; Li, Mengwei; Wu, Jihong; Sun, Xinghuai; Tian, Guohong

    2017-01-01

    To evaluate the clinical classification and characteristics of hereditary optic neuropathy patients in a single center in China. Retrospective case study. Patients diagnosed with hereditary optic neuropathy between January 2014 and December 2015 in the neuro-ophthalmology division in Shanghai Eye and ENT Hospital of Fudan University were recruited. Clinical features as well as visual field, brain/orbital MRI, and spectrum domain optical coherence tomography (SD-OCT) were analyzed. Eighty-two patients diagnosed by gene test were evaluated, including 66 males and 16 females. The mean age of the patients was 19.4 years (range, 5-46 years). A total of 158 eyes were analyzed, including 6 unilateral, 61 bilateral, and 15 sequential. The median duration of the disease was 0.5 year (range, 0.1-20 years). Genetic test identified 68 patients with Leber hereditary optic neuropathy, 9 with dominant optic neuropathy, and 2 with a Wolfram gene mutation. There was also one case of hereditary spastic paraplegia, spinocerebellar ataxia, and polymicrogyria with optic nerve atrophy, respectively. Leber hereditary optic neuropathy is the most common detected type of hereditary optic neuropathy in Shanghai, China. The detection of other autosomal mutations in hereditary optic neuropathy is limited by the currently available technique.

  14. Modern magnetic resonance imaging of the liver; Modernes MR-Protokoll fuer die Leberbildgebung

    Energy Technology Data Exchange (ETDEWEB)

    Hedderich, D.M.; Maintz, D.; Persigehl, T. [Universitaetsklinikum Koeln, Institut fuer Diagnostische und Interventionelle Radiologie, Koeln (Germany); Weiss, K. [Universitaetsklinikum Koeln, Institut fuer Diagnostische und Interventionelle Radiologie, Koeln (Germany); Philips Healthcare Deutschland, Hamburg (Germany)

    2015-12-15

    Magnetic resonance imaging (MRI) of the liver has become an essential tool in the radiological diagnostics of both focal and diffuse diseases of the liver and is subject to constant change due to technological progress. Recently, important improvements could be achieved by innovations regarding MR hardware, sequences and postprocessing methods. The diagnostic spectrum of MRI could be broadened particularly due to new examination sequences, while at the same time scanning time could be shortened and image quality has been improved. The aim of this article is to explain both the technological background and the clinical application of recent MR sequence developments and to present the scope of a modern MRI protocol for the liver. (orig.) [German] Die Magnetresonanztomographie (MRT) der Leber ist in der radiologischen Diagnostik fokaler und diffuser Lebererkrankungen fest etabliert und untersteht einem steten Wandel durch den fortwaehrenden technischen Fortschritt. Durch Neuerungen bei der Hardware, den Sequenzen und der Bildnachverarbeitung konnten in den letzten Jahren deutliche Fortschritte erzielt werden. Insbesondere auf dem Gebiet der Untersuchungssequenzen kam es zu Entwicklungen, die das diagnostische Spektrum der MRT erweiterten, zu einer Verkuerzung der Scanzeit fuehrten und zu einer Verbesserung der Bildqualitaet beitrugen. Gegenstand dieses Artikels ist es, den technischen Hintergrund und die klinische Anwendung neuerer Sequenztechniken zu erklaeren und so die Moeglichkeiten und den Umfang eines modernen MRT-Untersuchungsprotokolls fuer die Leber darzustellen. (orig.)

  15. Progress toward the maintenance and repair of degenerating retinal circuitry.

    Science.gov (United States)

    Vugler, Anthony A

    2010-01-01

    Retinal diseases such as age-related macular degeneration and retinitis pigmentosa remain major causes of severe vision loss in humans. Clinical trials for treatment of retinal degenerations are underway and advancements in our understanding of retinal biology in health/disease have implications for novel therapies. A review of retinal biology is used to inform a discussion of current strategies to maintain/repair neural circuitry in age-related macular degeneration, retinitis pigmentosa, and Type 2 Leber congenital amaurosis. In age-related macular degeneration/retinitis pigmentosa, a progressive loss of rods/cones results in corruption of bipolar cell circuitry, although retinal output neurons/photoreceptive melanopsin cells survive. Visual function can be stabilized/enhanced after treatment in age-related macular degeneration, but in advanced degenerations, reorganization of retinal circuitry may preclude attempts to restore cone function. In Type 2 Leber congenital amaurosis, useful vision can be restored by gene therapy where central cones survive. Remarkable progress has been made in restoring vision to rodents using light-responsive ion channels inserted into bipolar cells/retinal ganglion cells. Advances in genetic, cellular, and prosthetic therapies show varying degrees of promise for treating retinal degenerations. While functional benefits can be obtained after early therapeutic interventions, efforts should be made to minimize circuitry changes as soon as possible after rod/cone loss. Advances in retinal anatomy/physiology and genetic technologies should allow refinement of future reparative strategies.

  16. The potentials of spiral CT for detection of focal liver lesions; Moeglichkeiten der Spiral-CT zur Diagnostik fokaler Leberlaesionen

    Energy Technology Data Exchange (ETDEWEB)

    Helmberger, H. [Technische Univ. Muenchen, Klinikum rechts der Iser, Inst. fuer Roentgendiagnostik (Germany); Kersting-Sommerhoff, B. [Technische Univ. Muenchen, Klinikum rechts der Iser, Inst. fuer Roentgendiagnostik (Germany); Lenz, M. [Technische Univ. Muenchen, Klinikum rechts der Iser, Inst. fuer Roentgendiagnostik (Germany); Kirsten, R. [Technische Univ. Muenchen, Klinikum rechts der Iser, Inst. fuer Roentgendiagnostik (Germany); Bautz, W. [Technische Univ. Muenchen, Klinikum rechts der Iser, Inst. fuer Roentgendiagnostik (Germany)

    1996-03-01

    Spiral CT currently is the modality of choice for all aspects of diagnostic evaluation of the liver. Optimal selection of treatment should be based inter alia on the findings obtained by spiral CT with arterial application of contrast medium, as for example S-CTA (primary liver tumors), or S-CTAP (secondary liver tumors). Ultrasonography is the major supplementing modality. In the near future, MR imaging applying liver-specific contrast-enhancing agents is expected to become an important competing technique, and further developments of interest in diagnostic imaging of the liver are in the offing: it is not yet known which technique will be the modality of choice at the onset of the 21st century. (orig.) [Deutsch] Die Spiral-CT ist zur Zeit das empfehlenswerte Verfahren fuer alle Fragen der Leberdiagnostik. Zur optimalen praetherapeutischen Beurteilung der Leber sollte die Spiral-CT mit arterieller Kontrastmittelapplikation als S-CTA (primaere Lebertumoren) bzw. S-CTAP (sekundaere Lebertumoren) durchgefuehrt werden. Der US kommt ein Stellenwert als ergaenzende Methode zu. In Zukunft wird die MRT mit leberspezifischen Kontrastmitteln ein konkurrierendes Verfahren zur Spiral-CT darstellen, wobei eine weitere interessante Entwicklung auf dem Gebiet der hepatischen Bildgebung zu erwarten ist: Das diagnostische Verfahren der Wahl fuer die Leber zu Beginn des 21. Jahrhunderts ist noch nicht definiert. (orig.)

  17. Hepatotoxicity after liver irradiation in children and adolescents. Results from the RiSK

    Energy Technology Data Exchange (ETDEWEB)

    Roesler, Pascal; Christiansen, Hans [Medical School Hannover, Department of Radiotherapy and Special Oncology, Hannover (Germany); Kortmann, Rolf-Dieter [University of Leipzig, Department of Radiotherapy, Leipzig (Germany); Martini, Carmen [University Hospital of Freiburg, Department of Radiotherapy, Freiburg im Breisgau (Germany); Matuschek, Christiane [Heinrich-Heine University of Duesseldorf, Department of Radiotherapy, Medical Faculty, Duesseldorf (Germany); Meyer, Frank [Hospital Augsburg, Department of Radiotherapy, Augsburg (Germany); Ruebe, Christian [University Hospital of Homburg/Saar, Department of Radiotherapy, Homburg/Saar (Germany); Langer, Thorsten [University Hospital of Schleswig-Holstein, Department of Pediatrics, Pediatric Oncology, Campus Luebeck (Germany); Koch, Raphael [University of Muenster, Institute of Biostatistics and Clinical Research, Muenster (Germany); Eich, Hans Theodor; Willich, Normann [University Hospital of Muenster, Department of Radiotherapy, Muenster (Germany); Steinmann, Diana [Medical School Hannover, Department of Radiotherapy and Special Oncology, Hannover (Germany); University Hospital of Muenster, Department of Radiotherapy, Muenster (Germany)

    2015-05-01

    offers the option of increasing these conservative doses if tumor control is necessary. (orig.) [German] Ziel dieser Auswertung war die Bewertung der akuten und spaeten bestrahlungsassoziierten Hepatotoxizitaet im Kindes- und Jugendalter unter Beruecksichtigung der Dosis-Volumen-Effekte und der Leberfunktion. Seit 2001 werden in Deutschland bestrahlte Kinder und Jugendliche prospektiv im ''Register zur Erfassung von Spaetfolgen nach Strahlentherapie im Kindes- und Jugendalter (RiSK)'' mit Hilfe standardisierter Frageboegen dokumentiert. Die Toxizitaet wurde nach den Kriterien der Radiation Therapy Oncology Group (RTOG) graduiert. Bis April 2012 wurden 1392 Kinder und Jugendliche aus 62 Strahlentherapiezentren erfasst. Davon wurden 216 Patienten an der Leber bestrahlt (medianes Alter 9 Jahre, Spanne 1-18 Jahre, 70 Ganzkoerperbestrahlungen [TBI]). Von 75 % der Patienten ohne TBI lagen uns Angaben zur akuten Toxizitaet der Leber vor: 24 Patienten mit Grad 1-4 (Grad 1, 2 und 4 traten bei jeweils 20, 3 und1 Patienten auf), darunter 5 Patienten mit simultaner hepatotoxischer Chemotherapie. Eine maximale Spaettoxizitaet ≥ 0 (465 Frageboegen von 216 Patienten, medianes Follow-up 2 Jahre, maximaler Grad der Toxizitaet im zeitlichen Verlauf) trat bei 18 Patienten auf (15 mit Grad 1, 2 mit Grad 2 und 1 Patient mit Grad 3), darunter waren 3 Patienten (17 %) mit TBI. Eine simultane Chemotherapie erhielten 28 % der Patienten. In der multivariaten Analyse zeigten die Volumen-Dosis-Beziehungen keine statistisch auffaelligen Effekte hinsichtlich akuter oder chronischer Toxizitaet. Nach der Bestrahlung verschiedener abdomineller und thorakaler Tumoren entwickelten Kinder eine nur geringe Lebertoxizitaet. Aufgrund der niedrigen Strahlendosen an der Leber (mediane Leberdosis: 5 Gy) und der konsekutiv geringen beobachteten Toxizitaeten konnten Toxizitaetskurven der Dosis-Leber-Volumen nicht etabliert werden. Diese Befunde spiegeln die vorsichtige Einstellung der

  18. Interrelationships between different generations of interconnected tillers of Cares bigelowii

    International Nuclear Information System (INIS)

    Jonsdottir, I.S.; Callaghan, T.V.

    1988-01-01

    (1) The interrelationships between tiller generations of Carex bigelowii Torr. ex Schwein were investigated at two subarctic sites by labelling young tiller modules with 14 C and detecting its translocation, and by severing modules at increasing distances from the youngest tiller generation. Tiller survival, regeneration and physiological continuity were all measured. All of the investigations were on systems produced by vegetative proliferation and subsequent fragmentation: recruitment from seedlings was not observed. (2) 14 C-assimilates were translocated through the rhizome system, from the one to two years old assimilating tillers into the roots and rhizomes of nine to eleven years old tillers with only below-ground organs remaining. This shows that the roots and rhizomers of the numerous interconnected old non-assimilating tillers were alive and that their roots were probably still functioning. (3) The severing-experiment showed that the few assimilating young tiller generations were to some extent dependent on the old below-ground, non-assimilating tiller generations for their survival, growth and reproduction. Water and nutrients are probably the forms of subsidy. (4) The minimum size of a succesful physiologically functional unit was around five interconnected tiller generations. The maximum size could not be determined. (5) Apical dominance effects were detected within the rhizome system. The rhizomes keep a reserve of dormant buds. When the connection between tiller generations was severed, buds on the old rhizomes, which had been dormant for several years, developed into new tillers. These tillers were characterized by having only short rhizomes and they produced green leaves in the first season of growth. (6) The integrated system of old and young tiller generations, together with a spatial network of modules controlled by apical dominance, provide Carex bigelowii with mechanisms for locating and exploiting favorable patches in a nutrient poor, but

  19. Functional magnetic resonance imaging (fMRI) for fetal oxygenation during maternal hypoxia: initial results

    Energy Technology Data Exchange (ETDEWEB)

    Wedegaertner, U.; Adam, G. [Abt. fuer Diagnostische und Interventionelle Radiologie, Klinik und Poliklinik fuer Radiologie, UKE Hamburg (Germany); Tchirikov, M.; Schroeder, H. [Abt. fuer experimentelle Gynaekologie der Universitaetsfrauenklinik, Klinik und Poliklinik fuer Frauenheilkunde, UKE, Hamburg (Germany); Koch, M. [Klinik und Poliklinik fuer Neurologie, UKE Hamburg (Germany)

    2002-06-01

    Purpose: To investigate the potential of fMRI to measure changes in fetal tissue oxygenation during acute maternal hypoxia in fetal lambs. Material and Methods: Two ewes carrying singleton fetuses (gestational age 125 and 131 days) underwent MR imaging under inhalation anesthesia. BOLD imaging of the fetal brain, liver and myocardium was performed during acute maternal hypoxia (oxygen replaced by N{sub 2}O). Maternal oxygen saturation and heart rate were monitored by a pulse-oxymeter attached to the maternal tongue. Results: Changes of fetal tissue oxygenation during maternal hypoxia were clearly visible with BOLD MRI. Signal intensity decreases were more distinct in liver and heart ({proportional_to}40%) from control than in the fetal brain ({proportional_to}10%). Conclusions: fMRI is a promising diagnostic tool to determine fetal tissue oxygenation and may open new opportunities in monitoring fetal well being in high risk pregnancies complicated by uteroplacentar insufficiency. Different signal changes in liver/heart and brain may reflect a centralization of the fetal blood flow. (orig.) [German] Ziel: Untersuchung des Potentiales der funktionellen MRT (BOLD) in der Darstellung von Veraenderungen in der Sauerstoffsaettigung fetaler Gewebe waehrend akuter materner Hypoxie bei fetalen Laemmern. Material und Methoden: Die MR-Untersuchung wurde an zwei Mutterschafen mit 125 und 131 Tage alten Feten in Inhalationsnarkose durchgefuehrt. Die BOLD Messungen von fetaler Leber, Myokard und Gehirn erfolgten waehrend einer akuten Hypoxiephase des Muttertieres, in der Sauerstoff durch N{sub 2}O ersetzt wurde. Die materne Sauerstoffsaettigung und Herzfrequenz wurde durch ein Pulsoxymeter ueberwacht. Ergebnisse: Aenderungen der fetalen Gewebsoxygenierung waehrend einer akuten Hypoxiephase der Mutter waren mit der BOLD-MR-Bildgebung deutlich darstellbar. In der fetalen Leber und dem Myokard zeigte sich ein staerkerer Signalabfall um ca. 40% von den Kontrollwerten als im fetalen

  20. Value of magnetic resonance imaging in diffuse liver diseases; Stellenwert der MRT bei diffusen Lebererkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Schramm, N.; D' Anastasi, M.; Reiser, M.F.; Zech, C.J. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany)

    2012-08-15

    Diffuse liver diseases show an increasing prevalence. The diagnostic gold standard of liver biopsy has several disadvantages. There is a clinical demand for non-invasive imaging-based techniques to qualitatively and quantitatively evaluate the entire liver. Ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) are routinely used. Steatosis: chemical shift and frequency selective imaging, MR spectroscopy (MRS). Hemochromatosis: MR-based iron quantification. Fibrosis: MR elastography, diffusion, intravoxel incoherent motion (IVIM) and MR perfusion. T1-weighted in and opposed phase imaging is the clinically most frequently used MR technique to noninvasively detect and quantify steatosis. New methods for quantification that are not influenced by confounders like iron overload are under investigation. The most sensitive method to measure the fat content of the liver is MRS. As data acquisition and analysis remain complex and there is no whole organ coverage, MRS of the liver is not a routine method. With an optimized protocol incorporating T2* sequences, MRI is the modality of choice to quantify iron overload in hemochromatosis. Standard MR sequences cannot depict early stages of liver fibrosis. Advanced MR techniques (e.g. elastography, diffusion, IVIM and perfusion) for noninvasive assessment of liver fibrosis appear promising but their role has to be further investigated. (orig.) [German] Die Praevalenz diffuser Lebererkrankungen nimmt zu. Der klinische Goldstandard, die Leberbiopsie, hat zahlreiche Nachteile. Es besteht ein Bedarf an bildgebenden Verfahren zur nichtinvasiven qualitativen und quantitativen Beurteilung der gesamten Leber bei diesen Erkrankungen. Hier sind Ultraschall, CT und MRT zu nennen. Steatosis: Chemical-shift- und frequenzselektive Bildgebung, MR-Spektroskopie (MRS) zur Fettquantifizierung. Haemochromatose: MR-basierte Eisenquantifizierung. Fibrose: MR-Elastographie, Diffusion, ''intravoxel incoherent motion

  1. Molecular screening of 980 cases of suspected hereditary optic neuropathy with a report on 77 novel OPA1 mutations

    DEFF Research Database (Denmark)

    Ferré, Marc; Bonneau, Dominique; Milea, Dan

    2009-01-01

    We report the results of molecular screening in 980 patients carried out as part of their work-up for suspected hereditary optic neuropathies. All the patients were investigated for Leber's hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (ADOA), by searching for the ten...... and OPA3 mutations in cases of suspected hereditary optic neuropathy, even in absence of a family history of the disease....... novel OPA1 mutations reported here. The statistical analysis of this large set of mutations has led us to propose a diagnostic strategy that should help with the molecular work-up of optic neuropathies. Our results highlight the importance of investigating LHON-causing mtDNA mutations as well as OPA1...

  2. Potential of Gene Editing and Induced Pluripotent Stem Cells (iPSCs) in Treatment of Retinal Diseases.

    Science.gov (United States)

    Chuang, Katherine; Fields, Mark A; Del Priore, Lucian V

    2017-12-01

    The advent of gene editing has introduced the ability to make changes to the genome of cells, thus allowing for correction of genetic mutations in patients with monogenic diseases. Retinal diseases are particularly suitable for the application of this new technology because many retinal diseases, such as Stargardt disease, retinitis pigmentosa (RP), and Leber congenital amaurosis (LCA), are monogenic. Moreover, gene delivery techniques such as the use of adeno-associated virus (AAV) vectors have been optimized for intraocular use, and phase III trials are well underway to treat LCA, a severe form of inherited retinal degeneration, with gene therapy. This review focuses on the use of gene editing techniques and another relatively recent advent, induced pluripotent stem cells (iPSCs), and their potential for the study and treatment of retinal disease. Investment in these technologies, including overcoming challenges such as off-target mutations and low transplanted cell integration, may allow for future treatment of many debilitating inherited retinal diseases.

  3. Applications of CRISPR/Cas9 in retinal degenerative diseases

    Science.gov (United States)

    Peng, Ying-Qian; Tang, Luo-Sheng; Yoshida, Shigeo; Zhou, Ye-Di

    2017-01-01

    Gene therapy is a potentially effective treatment for retinal degenerative diseases. Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has been developed as a new genome-editing tool in ophthalmic studies. Recent advances in researches showed that CRISPR/Cas9 has been applied in generating animal models as well as gene therapy in vivo of retinitis pigmentosa (RP) and leber congenital amaurosis (LCA). It has also been shown as a potential attempt for clinic by combining with other technologies such as adeno-associated virus (AAV) and induced pluripotent stem cells (iPSCs). In this review, we highlight the main points of further prospect of using CRISPR/Cas9 in targeting retinal degeneration. We also emphasize the potential applications of this technique in treating retinal degenerative diseases. PMID:28503441

  4. Oestrogen, ocular function and low-level vision: a review.

    Science.gov (United States)

    Hutchinson, Claire V; Walker, James A; Davidson, Colin

    2014-11-01

    Over the past 10 years, a literature has emerged concerning the sex steroid hormone oestrogen and its role in human vision. Herein, we review evidence that oestrogen (oestradiol) levels may significantly affect ocular function and low-level vision, particularly in older females. In doing so, we have examined a number of vision-related disorders including dry eye, cataract, increased intraocular pressure, glaucoma, age-related macular degeneration and Leber's hereditary optic neuropathy. In each case, we have found oestrogen, or lack thereof, to have a role. We have also included discussion of how oestrogen-related pharmacological treatments for menopause and breast cancer can impact the pathology of the eye and a number of psychophysical aspects of vision. Finally, we have reviewed oestrogen's pharmacology and suggest potential mechanisms underlying its beneficial effects, with particular emphasis on anti-apoptotic and vascular effects. © 2014 Society for Endocrinology.

  5. Exercise Intolerance and Myoglobinuria Associated with a Novel Maternally Inherited MT-ND1 Mutation

    DEFF Research Database (Denmark)

    Rafiq, Jabin; Duno, Morten; Østergaard, Elsebet

    2016-01-01

    The most common clinical phenotype caused by a mtDNA mutation in complex I of the mitochondrial respiratory chain is Leber hereditary optic neuropathy. We report a family with a novel maternally inherited homoplasmic mtDNA m.4087A>G mutation in the ND1 gene (MT-ND1) associated with isolated...... myopathy, recurrent episodes of myoglobinuria, and rhabdomyolysis. DNA from blood in seven family members and muscle from four family members were PCR amplified and sequenced directly and assessed for the m.4087A>G variation in MT-ND1. Mitochondrial enzyme activity in all muscle biopsies was measured. PCR...... myoglobinuria is a rare phenotype of mitochondrial myopathies. We report this phenotype in a family affected by a novel homoplasmic mutation in MT-ND1. It is the first time such a phenotype has been associated with complex I gene mutations and a homoplasmic mutation of mtDNA....

  6. Temporal constraints on visual perception: A psychophysical investigation of the relation between attention capture and the attentional blink

    DEFF Research Database (Denmark)

    Nielsen, Simon

    in processing targets, which effectively causes a perceptual bottleneck (Chun & Potter, 1995). According to bottleneck models, making the first target easier to perceive should improve processing in the bottleneck and reduce the attentional blink. However, recent studies suggest that an attentional blink may...... is often reduced in the first half second. This phenomenon is known as the attentional blink (Raymond, Shapiro & Arnell, 1992) and as suggests by the name is assumed to pertain to how fast attention can be reallocated. Bottleneck models suggest that the attentional blink is caused by limited capacity...... be triggered by attention capture to the first object (Folk, Leber & Egeth, 2008) and that if making the first target easier to perceive increase its saliency this may increase the attentional blink (Chua, 2005). This thesis examines the attention capture hypothesis with focus on empirical investigations...

  7. Genetics for the ophthalmologist

    Directory of Open Access Journals (Sweden)

    Karthikeyan A Sadagopan

    2012-01-01

    Full Text Available The eye has played a major role in human genomics including gene therapy. It is the fourth most common organ system after integument (skin, hair and nails, nervous system, and musculoskeletal system to be involved in genetic disorders. The eye is involved in single gene disorders and those caused by multifactorial etiology. Retinoblastoma was the first human cancer gene to be cloned. Leber hereditary optic neuropathy was the first mitochondrial disorder described. X-Linked red-green color deficiency was the first X-linked disorder described. The eye, unlike any other body organ, allows directly visualization of genetic phenomena such as skewed X-inactivation in the fundus of a female carrier of ocular albinism. Basic concepts of genetics and their application to clinical ophthalmological practice are important not only in making a precise diagnosis and appropriate referral, but also in management and genetic counseling.

  8. Investor Outlook: Significance of the Positive LCA2 Gene Therapy Phase III Results.

    Science.gov (United States)

    Schimmer, Joshua; Breazzano, Steven

    2015-12-01

    Spark Therapeutics recently reported positive phase III results for SPK-RPE65 targeting the treatment of visual impairment caused by RPE65 gene mutations (often referred to as Leber congenital amaurosis type 2, or LCA2, but may include other retinal disorders), marking an important inflection point for the field of gene therapy. The results highlight the ability to successfully design and execute a randomized trial of a gene therapy and also reinforce the potentially predictive nature of early preclinical and clinical data. The results are expected to pave the way for the first approved gene therapy product in the United States and should sustain investor interest and confidence in gene therapy for many approaches, including retina targeting and beyond.

  9. Pupillometric evaluation of the melanopsin containing retinal ganglion cells in mitochondrial and non-mitochondrial optic neuropathies

    DEFF Research Database (Denmark)

    Ba-Ali, Shakoor; Lund-Andersen, Henrik

    2017-01-01

    of pupillary light reflex is primarily driven by the ipRGCs. Optic neuropathies i.e. Leber hereditary optic neuropathy (LHON), autosomal dominant optic atrophy (ADOA), nonarteritic anterior ischemic optic neuropathy (NAION), glaucoma, optic neuritis and idiopathic intracranial hypertension (IIH) are among...... the diseases, which have been subject to pupillometric studies. The ipRGCs are differentially affected in these various optic neuropathies. In mitochondrial optic neuropathies, the ipRGCs are protected against degeneration, whereas in glaucoma, NAION, optic neuritis and IIH the ipRGCs are damaged. Here, we...... will review the results of pupillometric, histopathological and animal studies evaluating the ipRGCs in mitochondrial and non-mitochondrial optic neuropathies....

  10. Improvement and decline in vision with gene therapy in childhood blindness.

    Science.gov (United States)

    Jacobson, Samuel G; Cideciyan, Artur V; Roman, Alejandro J; Sumaroka, Alexander; Schwartz, Sharon B; Heon, Elise; Hauswirth, William W

    2015-05-14

    Retinal gene therapy for Leber's congenital amaurosis, an autosomal recessive childhood blindness, has been widely considered to be safe and efficacious. Three years after therapy, improvement in vision was maintained, but the rate of loss of photoreceptors in the treated retina was the same as that in the untreated retina. Here we describe long-term follow-up data from three treated patients. Topographic maps of visual sensitivity in treated regions, nearly 6 years after therapy for two of the patients and 4.5 years after therapy for the third patient, indicate progressive diminution of the areas of improved vision. (Funded by the National Eye Institute; ClinicalTrials.gov number, NCT00481546.).

  11. Using Stem Cells to Model Diseases of the Outer Retina

    Directory of Open Access Journals (Sweden)

    Camille Yvon

    2015-01-01

    Full Text Available Retinal degeneration arises from the loss of photoreceptors or retinal pigment epithelium (RPE. It is one of the leading causes of irreversible blindness worldwide with limited effective treatment options. Generation of induced pluripotent stem cell (IPSC-derived retinal cells and tissues from individuals with retinal degeneration is a rapidly evolving technology that holds a great potential for its use in disease modelling. IPSCs provide an ideal platform to investigate normal and pathological retinogenesis, but also deliver a valuable source of retinal cell types for drug screening and cell therapy. In this review, we will provide some examples of the ways in which IPSCs have been used to model diseases of the outer retina including retinitis pigmentosa (RP, Usher syndrome (USH, Leber congenital amaurosis (LCA, gyrate atrophy (GA, juvenile neuronal ceroid lipofuscinosis (NCL, Best vitelliform macular dystrophy (BVMD and age related macular degeneration (AMD.

  12. Gait rehabilitation in a patient affected with Charcot-Marie-Tooth disease associated with pyramidal and cerebellar features and blindness.

    Science.gov (United States)

    Vinci, Paolo

    2003-05-01

    Charcot-Marie-Tooth (CMT) disease, an inherited neuropathy characterized by length-dependent degeneration of the motor and sensory nerve fibers with consequent distal muscle atrophy and sensory reduction, can be associated with symptoms and signs of involvement of the central nervous system and/or cranial nerves. We present a patient with relatively severe CMT, cerebellar ataxia, pyramidal involvement, and blindness due to Leber's hereditary optic neuropathy. The patient presented with poor standing and gait, with consequent severe disability. Factors responsible for the patient's functional impairment (plantarflexor failure, footdrop, foot rotation, knee flexor contracture, poor proprioception, cerebellar dysfunction, spastic paraparesis, blindness) were identified and addressed by a rehabilitation management, which included, as a main intervention, ankle stabilization by drop-foot boots instead of ankle-foot orthoses. Improved balance and independent ambulation resulted from rehabilitation.

  13. Melanopsin-expressing retinal ganglion cells are resistant to cell injury, but not always.

    Science.gov (United States)

    Georg, Birgitte; Ghelli, Anna; Giordano, Carla; Ross-Cisneros, Fred N; Sadun, Alfredo A; Carelli, Valerio; Hannibal, Jens; La Morgia, Chiara

    2017-09-01

    Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive RGCs deputed to non-image forming functions of the eye such as synchronization of circadian rhythms to light-dark cycle. These cells are characterized by unique electrophysiological, anatomical and biochemical properties and are usually more resistant than conventional RGCs to different insults, such as axotomy and different paradigms of stress. We also demonstrated that these cells are relatively spared compared to conventional RGCs in mitochondrial optic neuropathies (Leber's hereditary optic neuropathy and Dominant Optic Atrophy). However, these cells are affected in other neurodegenerative conditions, such as glaucoma and Alzheimer's disease. We here review the current evidences that may underlie this dichotomy. We also present our unpublished data on cell experiments demonstrating that melanopsin itself does not explain the robustness of these cells and some preliminary data on immunohistochemical assessment of mitochondria in mRGCs. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  14. Regenerative Medicine: Solution in Sight.

    Science.gov (United States)

    Wang, Qingjie; Stern, Jeffrey H; Temple, Sally

    2016-01-01

    The retina, like other central nervous system tissues, has poor regenerative properties in humans. Therefore, diseases that cause retinal cell loss, such as Age-related macular degeneration (AMD), retinitis pigmentosa (RP), Leber congenital amaurosis, Usher syndrome, glaucoma, and diabetic retinopathy, typically result in permanent visual impairment. Stem cell technologies have revolutionized our ability to produce neural cells in abundant supply. Much stem cell research effort is focused on producing the required cell types for cell replacement, or to generate disease-in-a-dish models to elucidate novel disease mechanisms for therapeutic development. Here we review the recent advances in stem cell studies relevant to producing RPE and retinal cells, and highlight future directions.

  15. Using Stem Cells to Model Diseases of the Outer Retina.

    Science.gov (United States)

    Yvon, Camille; Ramsden, Conor M; Lane, Amelia; Powner, Michael B; da Cruz, Lyndon; Coffey, Peter J; Carr, Amanda-Jayne F

    2015-01-01

    Retinal degeneration arises from the loss of photoreceptors or retinal pigment epithelium (RPE). It is one of the leading causes of irreversible blindness worldwide with limited effective treatment options. Generation of induced pluripotent stem cell (IPSC)-derived retinal cells and tissues from individuals with retinal degeneration is a rapidly evolving technology that holds a great potential for its use in disease modelling. IPSCs provide an ideal platform to investigate normal and pathological retinogenesis, but also deliver a valuable source of retinal cell types for drug screening and cell therapy. In this review, we will provide some examples of the ways in which IPSCs have been used to model diseases of the outer retina including retinitis pigmentosa (RP), Usher syndrome (USH), Leber congenital amaurosis (LCA), gyrate atrophy (GA), juvenile neuronal ceroid lipofuscinosis (NCL), Best vitelliform macular dystrophy (BVMD) and age related macular degeneration (AMD).

  16. Radiological interventional procedures for the acute abdomen; Radiologisch-interventionelle Massnahmen beim akuten Abdomen

    Energy Technology Data Exchange (ETDEWEB)

    Trumm, C.; Hoffmann, R.T.; Reiser, M.F. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Institut fuer Klinische Radiologie, Muenchen (Germany)

    2010-03-15

    In patients with acute thrombo-embolic occlusion of the superior mesenteric artery, catheter-assisted thrombolytic therapy represents a procedure of increasing importance in addition to surgery and intensive care treatment. The thrombolytic drugs utilized for this purpose are urokinase, streptokinase and recombinant tissue plasminogen activator (rtPA). Therapeutic embolization is predominantly used in the treatment of arterial bleeding from the gastro-intestinal tract, the liver, the intestines (due to an aneurysm or vascular malformation) and in bleeding from intestinal anastomoses. Polyvinyl alcohol particles, embospheres, gelfoam and microcoils can be utilized as embolic agents. Percutaneous transhepatic cholangiodrainage and stent implantation are applied in patients with biliary obstructions caused by inoperable tumors of the gall bladder or bile ducts, of the pancreatic head or duodenum and by metastases located in the liver parenchyma or hepatic hilum. Image-guided percutaneous drainage is a valuable option in the management of abscesses in the peritoneal cavity; less common indications are lymphoceles, biliomas, urinomas, hematomas, necrosis and pseudocysts. (orig.) [German] Die kathetergestuetzte thrombolytische Therapie stellt im Kontext einer chirurgischen und intensivmedizinischen Versorgung von Patienten mit thrombembolisch bedingter mesenterialer Ischaemie ein unterstuetzendes Behandlungsverfahren von zunehmender Bedeutung dar. Als thrombolytische Agenzien werden Urokinase, Streptokinase und der rekombinante Gewebeplasminogenaktivator (rtPA) verwendet. Die therapeutische Embolisation kommt neben der endoskopischen und chirurgischen Blutungsstillung bei arteriellen Blutungen im Gastrointestinaltrakt, aus der Leber, im Darm (als Folge eines Aneurysmas oder einer vaskulaeren Malformation) sowie bei blutenden intestinalen Anastomosen zum Einsatz. Zur Embolisation koennen Polyvinylalkoholpartikel, Embosphaeren, Gelfoam oder Mikrocoils verwendet werden. Die

  17. [Preimplantation genetic diagnosis and monogenic inherited eye diseases].

    Science.gov (United States)

    Hlavatá, L; Ďuďáková, Ľ; Trková, M; Soldátová, I; Skalická, P; Kousal, B; Lišková, P

    Preimplantation genetic diagnosis (PGD) is an established application of genetic testing in the context of in vitro fertilization. PGD is an alternative method to prenatal diagnosis which aims to prevent the transmission of an inherited disorder to the progeny by implanting only embryos that do not carry genetic predisposition for a particular disease. The aim of this study is to provide an overview of eye disorders for which PGD has been carried out. The European literature search focused on best practices, ethical issues, risks and results of PGD for inherited eye disorders. PGD is performed for a number of ocular disorders; a prerequisite for its application is however, the knowledge of a disease-causing mutation(s). The main advantage of this method is that the couple is not exposed to a decision of whether or not to undergo an abortion. Qualified counselling must be provided prior to the PGD in order to completely understand the risk of disability in any child conceived, consequences of disease manifestation, and advantages as well as limitations of this method. In the group of non-syndromic eye diseases and diseases in which ocular findings dominate, PGD has been performed in European countries for aniridia, choroideremia, congenital fibrosis of extraocular muscles, Leber congenital amaurosis, ocular albinism, retinitis pigmentosa, X-linked retinoschisis, Stargardt disease, blepharophimosis-ptosis-inverse epicanthus syndrome and retinoblastoma. Sexing for X-linked or mitochondrial diseases has been carried out for blue cone monochromatism, choroideremia, familial exudative vitreoretinopathy, Leber hereditary optic neuropathy, macular dystrophy (not further specified), Norrie disease, X-linked congenital stationary night blindness, X-linked retinoschisis and nystagmus (not further specified). In recent years, there has been an increase in potential to use PGD. The spectrum of diseases for this method has widened to include severe inherited eye diseases

  18. [Molecular genetics of pigmentary retinopathies: identification of mutations in CHM, RDS, RHO, RPE65, USH2A and XLRS1 genes].

    Science.gov (United States)

    Hamel, C P; Griffoin, J M; Bazalgette, C; Lasquellec, L; Duval, P A; Bareil, C; Beaufrère, L; Bonnet, S; Eliaou, C; Marlhens, F; Schmitt-Bernard, C F; Tuffery, S; Claustres, M; Arnaud, B

    2000-12-01

    To evaluate the occurrence and inheritance of various types of pigmentary retinopathy in patients followed at the outpatient clinic in the university hospital, Montpellier, France. To characterize genes and mutations causing these conditions. Ophthalmic examination and various visual tests were performed. Mutations were sought from genomic DNA by PCR amplification of exons associated with single-strand conformation analysis and/or direct sequencing. Among 315 patients over an 8-year period, cases of retinitis pigmentosa (63.2%), Usher's syndrome (10.2%), Stargardt's disease (5.4%), choroideremia (3.2%), Leber's congenital amaurosis (3.2%), congenital stationary night blindness (2.9%), cone dystrophy (2.5%), dominant optic atrophy (1.9%), X-linked juvenile retinoschisis (1.6%), Best's disease (1.6%), and others (4.3%) were diagnosed. In retinitis pigmentosa, inheritance could be determined in 54.2% of the cases including dominant autosomic (26.6%), recessive autosomic (22.6%), and X-linked cases (5%) while it could not be confirmed in 45.7% of the cases (simplex cases in the majority). For the 6 examined genes, mutations were found in 22 out of 182 propositus (12.1%). Analysis of phenotype-genotype correlations indicates that in retinitis pigmentosa, RDS is more frequently associated with macular involvement and retinal flecks, RHO with regional disease, and RPE65 with the great severity of the disease with some cases of Leber's congenital amaurosis. Identification of genes may help in diagnosis and in genetic counseling, especially in simplex cases with retinitis pigmentosa. In this latter condition, molecular diagnosis will be necessary to rationalize future treatments.

  19. Diffuse and vascular hepatic diseases; Diffuse und vaskulaere Lebererkrankungen

    Energy Technology Data Exchange (ETDEWEB)

    Kreimeyer, S.; Grenacher, L. [Universitaetsklinikum Heidelberg, Abteilung Diagnostische und Interventionelle Radiologie, Heidelberg (Germany)

    2011-08-15

    In addition to focal liver lesions, diffuse and vascular disorders of the liver represent a wide spectrum of liver diseases which are from the radiological point of view often difficult or nearly impossible to diagnose. Classical diagnostic methods are computed tomography and magnetic resonance imaging in addition to ultrasound. Diffuse parenchymal damage caused by diseases of various etiologies is therefore difficult to evaluate because it often lacks characteristic morphological features. For hepatic steatosis, hemochromatosis/siderosis as an example of a diffuse storage disease and sarcoidosis and candidiasis as infectious/inflammatory diseases, an image-based diagnosis is appropriate in some cases. For most diffuse liver diseases, however only nonspecific changes are visualized. Vascular pathologies of the liver, such as the Budd-Chiari syndrome and portal vein thrombosis, however, can usually be diagnosed very clearly using radiology and there is also a very effective interventional radiological treatment. Chronic diseases very often culminate in liver cirrhosis which is highly associated with an increased risk of liver cancer. (orig.) [German] Neben den fokalen Leberlaesionen stellen diffuse und vaskulaere Lebererkrankungen ein weites Spektrum an Erkrankungen der Leber dar, die radiologisch oft schwer oder gar nicht diagnostizierbar sind. Klassische diagnostische Verfahren sind dabei neben dem Ultraschall die Computertomographie und die Magnetresonanztomographie. Diffuse Parenchymschaeden, bedingt durch Erkrankungen unterschiedlichster Aetiologie, sind deshalb schwierig evaluierbar, weil haeufig charakteristische bildmorphologische Merkmale fehlen. Die Steatosis hepatis, die Haemochromatose/Siderose als Beispiel der Speicherkrankheiten sowie die Sarkoidose und die Candidose als infektioes-entzuendliche Erkrankungen sind einer bildbasierten Diagnosestellung z. T. zugaenglich, bei den meisten diffusen Lebererkrankungen jedoch zeigen sich lediglich unspezifische

  20. [ERG diagnosis and differential diagnosis: results of examination over 6 years].

    Science.gov (United States)

    Stemeyer, G; Stähli, P

    1996-05-01

    This study reviews the patient material first from the point of view of referral diagnosis. Secondly, we focus on difficulties in selective differential diagnoses. 1501 patients underwent electroretinographic (ERG) testing from 1989 to 1994, amounting to 1815 ERG recordings, including follow-up examinations. The technique applied is full-field, single flash ERG with selective stimulation of the rod- and of the cone-systems. In 3.8% (57 cases) the ERG was performed under general anesthesia in outpatients. Tapetoretinal degenerations, toxic retinal side effects, inflammatory disease and ocular trauma represented, in this order, the major groups of referral diagnoses aside from unclear visual loss. The documentation or the exclusion of tapetoretinal degeneration represented the largest share (57%) of the application of the diagnostic procedure. 171 cases of isolated retinitis pigmentosa (RP) and 33 cases of syndromic RP were identified. Frequent and rare diagnostic entities and their differential diagnoses within this group are discussed. Inevitably, a number of diagnostic decisions remain problematic, in particular at the first examination. These diagnostic difficulties are addressed also and include the differentiation between RP sine pigmento and congenital amaurosis Leber in infants, RP with macular involvement vs. cone-rod degeneration, unilateral RP vs. postinflammatory conditions, and progressive cone dystrophy vs. achromatopsia, cone-rod degeneration or Stargardt's disease. Frequent and meaningful indications for ERG recording and difficult diagnostic decisions arise from this review of a relatively large group of patients. A number of diagnoses can hardly, if not at all be established without ERG testing. These include retinal cause of visual loss in infants, congenital amaurosis Leber, RP sine pigmento, early stages of RP, carrier status in XL RP and in choroideremia, progressive cone dystrophy, toxic retinopathy without fundus changes, retinal involvement

  1. Classificação diagnóstica dos portadores de doenças degenerativas de retina, integrantes dos grupos Retina São Paulo e Retina Vale do Paraíba Diagnostic classification of retinal degenerative diseases São Paulo and Vale Retina groups

    Directory of Open Access Journals (Sweden)

    Nichard Unonius

    2003-08-01

    Full Text Available OBJETIVO:Organizar um banco de dados regional de todos os indivíduos portadores de doenças degenerativas da retina, com o objetivo de classificar cada paciente de acordo com o tipo de distrofia e padrão de herança. MÉTODOS: Durante o encontro do Grupo Retina São Paulo no dia 5 de maio de 2001, duzentas e quarenta e três pessoas foram registradas, sendo que parte forneceu dados de antecedentes oculares, pessoais e familiares e árvore genealógica. Noventa e três pacientes foram questionados quanto a idade, origem, tipo de distrofia, história familiar e árvore genealógica, tipo de herança, outras anomalias sistêmicas e exames complementares. Foram classificados quanto ao diagnóstico e padrão de herança. RESULTADOS: Dos duzentos e quarenta e três pacientes registrados, as distrofias encontradas foram retinose pigmentária, doença de Stargardt, síndrome de Usher, amaurose congênita de Leber e coroideremia. Quanto à divisão por doença dos 93 pacientes argüidos, havia 62 pacientes com retinose pigmentária, 13 com doença de Stargardt, 13 com síndrome de Usher, três com amaurose congênita de Leber e dois com coroideremia. Dos pacientes com retinose pigmentária, o padrão de herança detectado foi autossômico dominante em quatro casos (7%, autossômico recessivo em vinte casos (32%, ligado ao cromossomo X recessivo em sete casos (11%, caso isolado em vinte e nove (47% e padrão indeterminado em dois (3%. Para a doença de Stargardt três indivíduos (23% seguiam o padrão de herança autossômico recessivo e dez (77% eram casos isolados. Dos treze pacientes com síndrome de Usher, oito (61,5% apresentavam herança autossômica recessiva, quatro (31% eram casos isolados e um (7,5% tinha o padrão de herança indeterminado. Os dois pacientes com coroideremia seguiam o padrão de herança ligado ao X recessivo. Para amaurose congênita de Leber, um paciente (33,5% tinha padrão autossômico recessivo de herança e dois (66

  2. Prevention, screening and therapy of thyroid diseases and their cost-effectiveness; Praevention, Screening und Therapie gutartiger Schilddruesenerkrankungen unter dem Aspekt von Kosten und Nutzen

    Energy Technology Data Exchange (ETDEWEB)

    Dietlein, M.; Moka, D.; Schmidt, M.; Theissen, P.; Schicha, H. [Koeln Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin

    2003-10-01

    60%. (orig.) [German] Kosten/Nutzenanalysen in Bezug auf gutartige Schilddruesenerkrankungen sind in der Literatur unterrepraesentiert. Insbesondere die Erhebung eines Geldwertes pro gewonnenem Lebensjahr gestaltet sich methodisch schwierig: Der Nutzen praeventiver Massnahmen ist weit in die Zukunft verlagert. Der Einfluss einer unbehandelten Schilddruesenerkrankung auf die Lebenszeit wird ebenfalls erst durch einen langfristigen Horizont und dann eher epidemiologisch als individuell zu erfassen sein. Als Prophylaxe (primaere Praevention) sind Programme zum Ausgleich des Iodmangels sowie die Aufklaerung ueber den negativen Einfluss des Rauchens auf die Entwicklung einer Struma oder eines M. Basedows aus entscheidungstheoretischer Sicht sehr kosteneffektiv. Screening-Programme (sekundaere Praevention) werden fuer die Parameter TSH, Calcium und Calcitonin diskutiert. Eine besonders guenstige Kosten-Effektivitaet des TSH-Screenings ist in besonderen Lebensphasen (Neugeborene, Schwangerschaft, postpartal, hoeheres Alter, stationaerer Patient mit akuter Erkrankung) und bei definierten Vorbefunden (TSH>2mU/l, TPO-Antikoerper) aus klinisch-epidemiologischer Sicht zu erwarten, ohne dass hierzu gesonderte gesundheitsoekonomische Berechnungen vorgelegt wurden. Andererseits konnte die Kosten-Effektivitaet eines generellen TSH-Screening ab dem 35. Lebensjahr in einer qualitativ hochwertigen gesundheitsoekonomischen Studie bereits belegt werden. Die Therapiestrategien bei gutartigen Schilddruesenerkrankungen (tertiaere Praevention) zielen auf eine Minimierung sekundaerer Krankheitsfolgen (Vorhofflimmern, Myokardinfarkt, Herztod) und iatrogener Nebenwirkungen. Beispiele fuer eine solche tertiaere Praevention sind die definitive Therapie (Radioiodtherapie) der Immunhyperthyreose M. Basedow bei unguenstigen initialen Praedikatoren fuer eine Rezidivhyperthyreose, die Radioiodtherapie der latenten Hyperthyreose sowie die Radioiodtherapie der grossvolumigen Struma bei aelteren oder

  3. Molecular tagging of a novel rust resistance gene R(12) in sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Gong, L; Hulke, B S; Gulya, T J; Markell, S G; Qi, L L

    2013-01-01

    Sunflower production in North America has recently suffered economic losses in yield and seed quality from sunflower rust (Puccinia helianthi Schwein.) because of the increasing incidence and lack of resistance to new rust races. RHA 464, a newly released sunflower male fertility restorer line, is resistant to both of the most predominant and most virulent rust races identified in the Northern Great Plains of the USA. The gene conditioning rust resistance in RHA 464 originated from wild Helianthus annuus L., but has not been molecularly marked or determined to be independent from other rust loci. The objectives of this study are to identify molecular markers linked to the rust resistance gene and to investigate the allelism of this gene with the unmapped rust resistance genes present in HA-R6, HA-R8 and RHA 397. Virulence phenotypes of seedlings for the F(2) population and F(2:3) families suggested that a single dominant gene confers rust resistance in RHA 464, and this gene was designated as R(12). Bulked segregant analysis identified ten markers polymorphic between resistant and susceptible bulks. In subsequent genetic mapping, the ten markers covered 33.4 cM of genetic distance on linkage group 11 of sunflower. A co-dominant marker CRT275-11 is the closest marker distal to R(12) with a genetic distance of 1.0 cM, while ZVG53, a dominant marker linked in the repulsion phase, is proximal to R(12) with a genetic distance of 9.6 cM. The allelism test demonstrated that R(12) is not allelic to the rust resistance genes in HA-R6, HA-R8 and RHA 397, and it is also not linked to any previously mapped rust resistance genes. Discovery of the R(12) novel rust resistance locus in sunflower and associated markers will potentially support the molecular marker-assisted introgression and pyramiding of R(12) into sunflower breeding lines.

  4. Cholecystokinin like immunoreactivity in the brains of young Meishan and Duroc pigs(4).

    Science.gov (United States)

    Elmquist, J K; Ross, L R; Hsu, W; Rothschild, M F; Jacobson, C D

    1993-01-12

    Cholecystokinin (CCK), a peptide found in both the gastrointestinal tract and brain, has been shown to be involved in the control of feed intake in a variety of animals including the pig. Chinese breeds of pigs such as the Meishan are noted for slow growth and heavy adipose deposition. In this study we have described the regional cholecystokinin-like immunoreactivity (CCK-IR) concentrations in the brain of young Duroc and Meishan pigs utilizing radioimmunoassay. Brains of days 1, 10, and 20 postnatal pigs from each breed were examined. The CCK-IR increased with age in all three areas examined (cortex, medulla, and hypothalamus). The cortical concentrations rose significantly from days 1 to 10 and from days 10 to 20. The levels in the hypothalamus and medulla increased significantly between days 1 and 20. There were no statistically significant differences in CCK-IR between the breeds at any of the three ages examined. Our results indicate that a rise in CCK-IR in the regions of the brain involved in the control of feed intake may parallel the ability of the young pigs to assimilate nutrients from a solid diet. ZUSAMMENFASSUNG: Cholecystokinin-ähnliche Immunreaktivität in den Gehirnen junger Meishan- und Durocschweine Das Peptid Cholecystokinin (CCK) wird im Gastrointestinaltrakt und im Gehirn gefunden und beeinflußt Futteraufnahme in einer Reihe von Tieren einschließlich Schwein. Chinesische Rassen wie Meishan sind wegen ihres langsamen Wachstums und der starken Fettablagerung bekannt. In dieser Studie beschreiben wir regionale Cholecystokinin-ähnliche Immunreaktivitäts-(CCK-IR)Konzentrationen im Gehirn junger Duroc- und Meishantiere, mittels Radioimmunassay bestimmt. Gehirne von 1, 10 und 20 Tage alten Ferkeln jeder Rasse wurden untersucht. CCK-IR nahm mit dem Alter in allen drei untersuchten Organen zu (Kortex, Medulla und Hypothalamus). Die kortikalen Spiegel stiegen vom Tag 1 bis 10 und vom Tag 10 bis 20 signifikant, die des Hypothalamus und der Medulla

  5. MR imaging in congenital complicated anterior body wall defects; MRT von komplizierten angeborenen Bauchwanddefekten

    Energy Technology Data Exchange (ETDEWEB)

    Hoermann, M.; Scharitzer, M. [Universitaetsklinik fuer Radiodiagnostik, AKH-Wien (Austria); Pumberger, W. [Universitaetsklinik fuer Kinderchirurgie, AKH-Wien (Austria); Patzak, B. [Pathologisch-anatomisches Museum im Narrenturm, AKH-Wien (Austria)

    2003-04-01

    Introduction: Aim of this study was to estimate the value of postmortem MR imaging in evaluation of specimen with congenital anterior body wall defects of the museum of pathologic-anatomy. Material and Methods: We examined 19 specimen with a 1.5 Tesla unit by using T{sub 1}- and T{sub 2}-weighted sagittal and coronal sequences. In some specimen additional axial T{sub 2}-weighted images were obtained. We evaluated the site of the bowel, the liver, the heart and presence of associated disorders. Results: The bowels were completely intraabdominal, in two specimen, completely extraabdominal in 12 specimen and in 5 specimen intra- and extraabdominal. The liver was in two specimen completely extraabdominal/in 12 completely intracorporal, and in 5 specimen intra- and extraabdominal. In 5 cases the heart was located extraanatomically. In 12 specimen we found disorders of the spine and the extremities. Congenital disorders of the kidneys were found in 6 specimen. Conclusion: MR imaging is of great value in the assessment of congenital anterior body wall defects. In the light of ultrafast sequences the role of fetal MR imaging in the evaluation of congenital body wall defects may be mandatory in the future. (orig.) [German] Einleitung: Wir nutzten die Sammlung des pathologisch-anatomischen Museums in Wien, um die Wertigkeit der MRT zur Beschreibung von angeborenen vorderen Bauchwanddefekten und deren assoziierten Erkrankungen zu bestimmen. Material und Methode: Wir untersuchten 19 Exponate mit einem 1,5-Tesla-Geraet unter Verwendung von sagittalen und koronalen T{sub 1}- und T{sub 2}-gewichteten Sequenzen. Ausgewertet wurden die Lage des Darmes, der Leber, des Herzens und assoziierte Missbildungen. Ergebnisse: Der Darm lag in zwei Faellen intraabdominal, zur Gaenze extraabdominal in 12 Faellen, intra- und extraabdominal in 5 Faellen. Die Leber war in zwei Exponaten zur Gaenze extraabdominal, in 5 intra- und extraabdominal und in 12 Exponaten intraabdominal. Assoziiert waren

  6. Development of biotest assays using cell cultures from fish for the demonstration of lethal and sublethal damage to organisms due to environmental pollutants in water. Cellular biomarkers in fish cell cultures; Entwicklung von Biotestverfahren mit Zellkulturen aus Fischen zum Nachweis letaler und subletaler Schaeden von Organismen durch Umweltschadstoffe im Wasser. Zellulaere Biomarker in Fischzellkulturen

    Energy Technology Data Exchange (ETDEWEB)

    Braunbeck, T [Heidelberg Univ. (Germany). Zoologisches Inst. 1

    1994-06-01

    Methoden zum Nachweis des (oeko-)toxikologischen Potential von Schadstoffen dar. In allen Experimenten konnten klare Zeit-Wirkungs- und Dosis-Wirkungs-Beziehungen aufgestellt werden. Isolierte Hepatocyten aus der Leber der Regebogenforelle reagieren empfindlicher als die parallel untersuchten permanenten Zellinien R1 und RTG-2. In Cytotoxizitaetstests mit den bibrocytischen Fischzellinien R1 und RTG-2 aus der Leber bzw. der Gonade der Regenbogenforelle wurden fuer verschiedene organische Schadstoffe und organische und anorganische Schwermetallverbindungen Cytotoxizitaetsdaten erhoben. Diese Erkenntnisse wurden einem Konzept fuer den Einsatz von mehrstugigen Zelltests zur Abschaetzung des oekotoxikologischen Potentials von Umweltschadstoffen zugrunde gelegt, das hier vorgestellt wird. (orig./VHE)

  7. Possible use of wild-living rats (Rattus norvegicus) as bioindicators for heavy metal pollution. Part 2. Body burden calculations for identification of depot compartments; Untersuchungen zur Eignung wildlebender Wanderratten (Rattus norvegicus) als Indikatoren der Schwermetallbelastung. Teil 2. Die Berechnung der Koerperlast zur Identifikation von Depotkompartimenten

    Energy Technology Data Exchange (ETDEWEB)

    Wuenschmann, S. [Internationales Hochschulinstitut Zittau, Lehrstuhl Umweltverfahrenstechnik, Zittau (Germany); Hochschule Zittau/Goerlitz, Fachbereich Mathematik/Naturwissenschaften, Zittau (Germany); Oehlmann, J. [J.W. Goethe-Univ. Frankfurt, Zoologisches Inst., Frankfurt/M. (Germany); Delakowitz, B. [Hochschule Zittau/Goerlitz, Fachbereich Mathematik/Naturwissenschaften, Zittau (Germany); Markert, B. [Internationales Hochschulinstitut Zittau, Lehrstuhl Umweltverfahrenstechnik, Zittau (Germany)

    2002-07-01

    aufzuzeigen. Geschlechts- und altersspezifische Affinitaetsunterschiede und Organe und Gewebe, die sich aufgrund spezifischen Schwermetallakkumulation fuer das Monitoring bestehender Belastungen eignen, werden beschrieben. Als bevorzugte Depotkompartimente wurden Leber und Niere fuer die Schwermetalle Cu, Mn, Cd (adult) und Tl identifiziert, waehrend sich die Elemente Ni, Sr, Pb (adult) und Ti als knochenaffine Elemente zeigten. Co und Zn wiesen eine vergleichbar hohe Affinitaet zu den Geweben der Leber und Knochen auf. Des weiteren konnten hohe geschlechtsspezifische Verteilungsunterschiede der Schwermetalle Cd und Pb bei juvenilen Ratten und auch im Vergleich zu den adulten Tieren aufgezeigt werden. Zusammenfassend ist festzustellen, dass die Verteilung der untersuchten Elemente im Organismus der wildlebenden Ratte (Freilandbedingungen) mit der relativen Verteilung im menschlichen Organismus weitgehend identisch ist; lediglich fuer Nickel wurden Abweichungen ermittelt. (orig.)

  8. Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A

    International Nuclear Information System (INIS)

    Wang Huawei; Jia Xiaoyun; Ji Yanli; Kong Qingpeng; Zhang Qingjiong; Yao Yonggang; Zhang Yaping

    2008-01-01

    The penetrance of Leber's hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and nuclear genetic background, as well as environmental factors, have been reported to be involved in different affected pedigrees. Here we describe two large Chinese families that show a striking difference in the penetrance of LHON, in which 53.3% and 15.0% of members were affected (P < 0.02), respectively. Analysis of the complete mtDNA genome of the two families revealed the presence of the primary mutation G11778A and several other variants suggesting the same haplogroup status G2a. The family with higher penetrance contained a previously described secondary mutation G13708A, which presents a polymorphism in normal Chinese samples and does not affect in vivo mitochondrial oxidative metabolism as described in a previous study. Evolutionary analysis failed to indicate any putatively pathogenic mutation that cosegregated with G11778A in these two pedigrees. Our results suggest that the variable penetrance of LHON in the two Chinese families is independent of both their mtDNA haplotype background and a secondary mutation G13708A. As a result, it is likely that unknown nuclear gene involvement and/or other factors contribute to the strikingly different penetrance of LHON

  9. Clinical and molecular features of an infant patient affected by Leigh Disease associated to m.14459G > A mitochondrial DNA mutation: a case report

    Directory of Open Access Journals (Sweden)

    Moggio Maurizio

    2011-07-01

    Full Text Available Abstract Background Leigh Syndrome (LS is a severe neurodegenerative disorder characterized by bilateral symmetrical necrotic lesions in the basal ganglia and brainstem. Onset is in early infancy and prognosis is poor. Causative mutations have been disclosed in mitochondrial DNA and nuclear genes affecting respiratory chain subunits and assembly factors. Case presentation Here we report the clinical and molecular features of a 15-month-old female LS patient. Direct sequencing of her muscle-derived mtDNA revealed the presence of two apparently homoplasmic variants: the novel m.14792C > G and the already known m.14459G > A resulting in p.His16Asp change in cytochrome b (MT-CYB and p.Ala72Val substitution in ND6 subunit, respectively. The m.14459G > A was heteroplasmic in the mother's blood-derived DNA. Conclusions The m.14459G > A might lead to LS, complicated LS or Leber Optic Hereditary Neuropathy. A comprehensive re-evaluation of previously described 14459G > A-mutated patients does not explain this large clinical heterogeneity.

  10. Retrospective assessment of the most common mitochondrial DNA mutations in a large Hungarian cohort of suspect mitochondrial cases.

    Science.gov (United States)

    Remenyi, Viktoria; Inczedy-Farkas, Gabriella; Komlosi, Katalin; Horvath, Rita; Maasz, Anita; Janicsek, Ingrid; Pentelenyi, Klara; Gal, Aniko; Karcagi, Veronika; Melegh, Bela; Molnar, Maria Judit

    2015-08-01

    Prevalence estimations for mitochondrial disorders still vary widely and only few epidemiologic studies have been carried out so far. With the present work we aim to give a comprehensive overview about frequencies of the most common mitochondrial mutations in Hungarian patients. A total of 1328 patients were tested between 1999 and 2012. Among them, 882 were screened for the m.3243A > G, m.8344A > G, m.8993T > C/G mutations and deletions, 446 for LHON primary mutations. The mutation frequency in our cohort was 2.61% for the m.3243A > G, 1.47% for the m.8344A > G, 17.94% for Leber's Hereditary Optic Neuropathy (m.3460G > A, m.11778G > A, m.14484T > C) and 0.45% for the m.8993T > C/G substitutions. Single mtDNA deletions were detected in 14.97%, while multiple deletions in 6.01% of the cases. The mutation frequency in Hungarian patients suggestive of mitochondrial disease was similar to other Caucasian populations. Further retrospective studies of different populations are needed in order to accurately assess the importance of mitochondrial diseases and manage these patients.

  11. Preimplantation genetic diagnosis as a strategy to prevent having a child born with an heritable eye disease.

    Science.gov (United States)

    Yahalom, Claudia; Macarov, Michal; Lazer-Derbeko, Galit; Altarescu, Gheona; Imbar, Tal; Hyman, Jordana H; Eldar-Geva, Talia; Blumenfeld, Anat

    2018-05-21

    In developed countries, genetically inherited eye diseases are responsible for a high percentage of childhood visual impairment. We aim to report our experience using preimplantation genetic diagnostics (PGD) in order to avoid transmitting a genetic form of eye disease associated with childhood visual impairment and ocular cancer. Retrospective case series of women who underwent in vitro fertilization (IVF) and PGD due to a familial history of inherited eye disease and/or ocular cancer, in order to avoid having a child affected with the known familial disease. Each family underwent genetic testing in order to identify the underlying disease-causing mutation. IVF and PGD treatment were performed; unaffected embryos were implanted in their respective mothers. Thirty-five unrelated mothers underwent PGD, and the following hereditary conditions were identified in their families: albinism (10 families); retinitis pigmentosa (7 families); retinoblastoma (4 families); blue cone monochromatism, achromatopsia, and aniridia (2 families each); and Hermansky-Pudlak syndrome, Leber congenital amaurosis, Norrie disease, papillorenal syndrome, primary congenital cataract, congenital glaucoma, Usher syndrome type 1F, and microphthalmia with coloboma (1 family each). Following a total of 88 PGD cycles, 18 healthy (i.e., unaffected) children were born. Our findings underscore the importance an ophthalmologist plays in informing patients regarding the options now available for using prenatal and preimplantation genetic diagnosis to avoid having a child with a potentially devastating genetic form of eye disease or ocular cancer. This strategy is highly relevant, particularly given the limited options currently available for treating these conditions.

  12. Loss of Ikbkap Causes Slow, Progressive Retinal Degeneration in a Mouse Model of Familial Dysautonomia.

    Science.gov (United States)

    Ueki, Yumi; Ramirez, Grisela; Salcedo, Ernesto; Stabio, Maureen E; Lefcort, Frances

    2016-01-01

    Familial dysautonomia (FD) is an autosomal recessive congenital neuropathy that is caused by a mutation in the gene for inhibitor of kappa B kinase complex-associated protein ( IKBKAP ). Although FD patients suffer from multiple neuropathies, a major debilitation that affects their quality of life is progressive blindness. To determine the requirement for Ikbkap in the developing and adult retina, we generated Ikbkap conditional knockout (CKO) mice using a TUBA1a promoter-Cre ( Tα1-Cre ). In the retina, Tα1-Cre expression is detected predominantly in retinal ganglion cells (RGCs). At 6 months, significant loss of RGCs had occurred in the CKO retinas, with the greatest loss in the temporal retina, which is the same spatial phenotype observed in FD, Leber hereditary optic neuropathy, and dominant optic atrophy. Interestingly, the melanopsin-positive RGCs were resistant to degeneration. By 9 months, signs of photoreceptor degeneration were observed, which later progressed to panretinal degeneration, including RGC and photoreceptor loss, optic nerve thinning, Müller glial activation, and disruption of layers. Taking these results together, we conclude that although Ikbkap is not required for normal development of RGCs, its loss causes a slow, progressive RGC degeneration most severely in the temporal retina, which is later followed by indirect photoreceptor loss and complete retinal disorganization. This mouse model of FD is not only useful for identifying the mechanisms mediating retinal degeneration, but also provides a model system in which to attempt to test therapeutics that may mitigate the loss of vision in FD patients.

  13. Rescue of cell death and inflammation of a mouse model of complex 1-mediated vision loss by repurposed drug molecules.

    Science.gov (United States)

    Yu, Alfred K; Datta, Sandipan; McMackin, Marissa Z; Cortopassi, Gino A

    2017-12-15

    Inherited mitochondrial optic neuropathies, such as Leber's hereditary optic neuropathy (LHON) and Autosomal dominant optic atrophy (ADOA) are caused by mutant mitochondrial proteins that lead to defects in mitochondrial complex 1-driven ATP synthesis, and cause specific retinal ganglion cell (RGC) loss. Complex 1 defects also occur in patients with primary open angle glaucoma (POAG), in which there is specific RGC loss. The treatment of mitochondrial optic neuropathy in the US is only supportive. The Ndufs4 knockout (Ndufs4 KO) mouse is a mitochondrial complex 1-deficient model that leads to RGC loss and rapid vision loss and allows for streamlined testing of potential therapeutics. Preceding RGC loss in the Ndufs4 KO is the loss of starburst amacrine cells, which may be an important target in the mechanism of complex 1-deficient vision loss. Papaverine and zolpidem were recently shown to be protective of bioenergetic loss in cell models of optic neuropathy. Treatment of Ndufs4 KO mice with papaverine, zolpidem, and rapamycin-suppressed inflammation, prevented cell death, and protected from vision loss. Thus, in the Ndufs4 KO mouse model of mitochondrial optic neuropathy, papaverine and zolpidem provided significant protection from multiple pathophysiological features, and as approved drugs in wide human use could be considered for the novel indication of human optic neuropathy. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Retinal Diseases Caused by Mutations in Genes Not Specifically Associated with the Clinical Diagnosis.

    Directory of Open Access Journals (Sweden)

    Xia Wang

    Full Text Available When seeking a confirmed molecular diagnosis in the research setting, patients with one descriptive diagnosis of retinal disease could carry pathogenic variants in genes not specifically associated with that description. However, this event has not been evaluated systematically in clinical diagnostic laboratories that validate fully all target genes to minimize false negatives/positives.We performed targeted next-generation sequencing analysis on 207 ocular disease-related genes for 42 patients whose DNA had been tested negative for disease-specific panels of genes known to be associated with retinitis pigmentosa, Leber congenital amaurosis, or exudative vitreoretinopathy.Pathogenic variants, including single nucleotide variations and copy number variations, were identified in 9 patients, including 6 with variants in syndromic retinal disease genes and 3 whose molecular diagnosis could not be distinguished easily from their submitted clinical diagnosis, accounting for 21% (9/42 of the unsolved cases.Our study underscores the clinical and genetic heterogeneity of retinal disorders and provides valuable reference to estimate the fraction of clinical samples whose retinal disorders could be explained by genes not specifically associated with the corresponding clinical diagnosis. Our data suggest that sequencing a larger set of retinal disorder related genes can increase the molecular diagnostic yield, especially for clinically hard-to-distinguish cases.

  15. C2 Domains as Protein-Protein Interaction Modules in the Ciliary Transition Zone

    Directory of Open Access Journals (Sweden)

    Kim Remans

    2014-07-01

    Full Text Available RPGR-interacting protein 1 (RPGRIP1 is mutated in the eye disease Leber congenital amaurosis (LCA and its structural homolog, RPGRIP1-like (RPGRIP1L, is mutated in many different ciliopathies. Both are multidomain proteins that are predicted to interact with retinitis pigmentosa G-protein regulator (RPGR. RPGR is mutated in X-linked retinitis pigmentosa and is located in photoreceptors and primary cilia. We solved the crystal structure of the complex between the RPGR-interacting domain (RID of RPGRIP1 and RPGR and demonstrate that RPGRIP1L binds to RPGR similarly. RPGRIP1 binding to RPGR affects the interaction with PDEδ, the cargo shuttling factor for prenylated ciliary proteins. RPGRIP1-RID is a C2 domain with a canonical β sandwich structure that does not bind Ca2+ and/or phospholipids and thus constitutes a unique type of protein-protein interaction module. Judging from the large number of C2 domains in most of the ciliary transition zone proteins identified thus far, the structure presented here seems to constitute a cilia-specific module that is present in multiprotein transition zone complexes.

  16. Involvement of Endoplasmic Reticulum Stress in TULP1 Induced Retinal Degeneration.

    Directory of Open Access Journals (Sweden)

    Glenn P Lobo

    Full Text Available Inherited retinal disorders (IRDs result in severe visual impairments in children and adults. A challenge in the field of retinal degenerations is identifying mechanisms of photoreceptor cell death related to specific genetic mutations. Mutations in the gene TULP1 have been associated with two forms of IRDs, early-onset retinitis pigmentosa (RP and Leber congenital amaurosis (LCA. TULP1 is a cytoplasmic, membrane-associated protein shown to be involved in transportation of newly synthesized proteins destined for the outer segment compartment of photoreceptor cells; however, how mutant TULP1 causes cell death is not understood. In this study, we provide evidence that common missense mutations in TULP1 express as misfolded protein products that accumulate within the endoplasmic reticulum (ER causing prolonged ER stress. In an effort to maintain protein homeostasis, photoreceptor cells then activate the unfolded protein response (UPR complex. Our results indicate that the two major apoptotic arms of the UPR pathway, PERK and IRE1, are activated. Additionally, we show that retinas expressing mutant TULP1 significantly upregulate the expression of CHOP, a UPR signaling protein promoting apoptosis, and undergo photoreceptor cell death. Our study demonstrates that the ER-UPR, a known mechanism of apoptosis secondary to an overwhelming accumulation of misfolded protein, is involved in photoreceptor degeneration caused by missense mutations in TULP1. These observations suggest that modulating the UPR pathways might be a strategy for therapeutic intervention.

  17. Pharmacotherapy of retinal disease with visual cycle modulators.

    Science.gov (United States)

    Hussain, Rehan M; Gregori, Ninel Z; Ciulla, Thomas A; Lam, Byron L

    2018-04-01

    Pharmacotherapy with visual cycle modulators (VCMs) is under investigation for retinitis pigmentosa (RP), Leber congenital amaurosis (LCA), Stargardt macular dystrophy (SMD) and nonexudative age-related macular degeneration (AMD), all blinding diseases that lack effective treatment options. Areas covered: The authors review investigational VCMs, including oral retinoids, 9-cis-retinyl-acetate (zuretinol) and 9-cis-β-carotene, which restore 11-cis-retinal levels in RP and LCA caused by LRAT and RPE65 gene mutations, and may improve visual acuity and visual fields. Therapies for SMD aiming to decrease accumulation of toxic Vitamin A dimers and lipofuscin in the retina and retinal pigment epithelium (RPE) include C20-D3-vitamin A (ALK-001), isotretinoin, VM200, emixustat, and A1120. Mouse models of SMD show promising data for these treatments, though proof of efficacy in humans is currently lacking. Fenretinide and emixustat are investigational VCMs for dry AMD, though neither has been shown to reduce geographic atrophy or improve vision in human trials. A1120 prevents retinol transport into the RPE and may spare the side effects typically seen in VCMs (nyctalopia and chromatopsia) per mouse studies. Expert opinion: Oral VCMs may be feasible treatment options for degenerative retinal diseases based on pre-clinical and some early clinical studies. Further trials are warranted to assess their efficacy and safety in humans.

  18. Gene therapy for ocular diseases.

    Science.gov (United States)

    Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

    2011-05-01

    The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

  19. Republished review: Gene therapy for ocular diseases.

    Science.gov (United States)

    Liu, Melissa M; Tuo, Jingsheng; Chan, Chi-Chao

    2011-07-01

    The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.

  20. 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.

  1. Color coded duplex sonography. Interdisciplinary vascular ultrasonography; Farbkodierte Duplexsonographie. Interdisziplinaerer vaskulaerer Ultraschall

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    Kubale, R. [Institut fuer Radiologie, Sonographie und Nuklearmedizin, Pirmasens (Germany); Stiegler, H. [Staedtisches Krankenhaus Schwabing, Muenchen (Germany). 7. Medizinische Abt.

    2002-07-01

    An interdisciplinary team of experts impart the state of the art in color coded duplex sonography applied for examination of all anatomic areas. Detailed information is given for every vascular area, describing the examination procedure, possible origins of mistakes or faults, and means to avoid them. In addition to the classical applications, eg. for examination of the extra- and intracranial vessels, vessels of the limbs, visceral vessels and the vessels of liver and kidney, there are chapters devoted to: haemodialysis shunts, arteriovenous malformations, duplex sonography of the penis, tumor vascularisation. (orig./CB) [German] Ein interdisziplinaeres Autorenteam vermittelt Ihnen den State of the Art der FKDS fuer alle anatomischen Regionen. Fuer jede der Gefaessregionen werden detaillierte Angaben zum Untersuchungsablauf, zu moeglichen Fehlerquellen und zu deren Vermeidung geboten. Neben den klassischen Anwendungen bei der Untersuchung - der extra- und intrakraniellen Gefaesse, - der Extremitaetengefaesse, - der viszeralen Gefaesse sowie der Gefaesse von Niere und Leber finden Sie Kapitel zu den Themen: Haemodialyseshunt, arteriovenoese Malformationen, Duplexsonographie des Penis und Tumorvaskularisation. (orig./AJ)

  2. MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load

    Directory of Open Access Journals (Sweden)

    Yi Shiau Ng

    2018-04-01

    Full Text Available Mutations in the m.13094T>C MT-ND5 gene have been previously described in three cases of Leigh Syndrome (LS. In this retrospective, international cohort study we identified 20 clinically affected individuals (13 families and four asymptomatic carriers. Ten patients were deceased at the time of analysis (median age of death was 10 years (range: 5·4 months−37 years, IQR = 17·9 years. Nine patients manifested with LS, one with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS, and one with Leber hereditary optic neuropathy. The remaining nine patients presented with either overlapping syndromes or isolated neurological symptoms. Mitochondrial respiratory chain activity analysis was normal in five out of ten muscle biopsies. We confirmed maternal inheritance in six families, and demonstrated marked variability in tissue segregation, and phenotypic expression at relatively low blood mutant loads. Neuropathological studies of two patients manifesting with LS/MELAS showed prominent capillary proliferation, microvacuolation and severe neuronal cell loss in the brainstem and cerebellum, with conspicuous absence of basal ganglia involvement. These findings suggest that whole mtDNA genome sequencing should be considered in patients with suspected mitochondrial disease presenting with complex neurological manifestations, which would identify over 300 known pathogenic variants including the m.13094T>C. Keywords: Mitochondrial encephalomyopathy, Lactic acidosis and stroke-like episodes (MELAS, Leigh syndrome (LS, Mitochondrial DNA, Heteroplasmy, Neuropathology

  3. Intravitreal Injection of Splice-switching Oligonucleotides to Manipulate Splicing in Retinal Cells

    Directory of Open Access Journals (Sweden)

    Xavier Gérard

    2015-01-01

    Full Text Available Leber congenital amaurosis is a severe hereditary retinal dystrophy responsible for neonatal blindness. The most common disease-causing mutation (c.2991+1655A>G; 10–15% creates a strong splice donor site that leads to insertion of a cryptic exon encoding a premature stop codon. Recently, we reported that splice-switching oligonucleotides (SSO allow skipping of the mutant cryptic exon and the restoration of ciliation in fibroblasts of affected patients, supporting the feasibility of a SSO-mediated exon skipping strategy to correct the aberrant splicing. Here, we present data in the wild-type mouse, which demonstrate that intravitreal administration of 2’-OMePS-SSO allows selective alteration of Cep290 splicing in retinal cells, including photoreceptors as shown by successful alteration of Abca4 splicing using the same approach. We show that both SSOs and Cep290 skipped mRNA were detectable for at least 1 month and that intravitreal administration of oligonucleotides did not provoke any serious adverse event. These data suggest that intravitreal injections of SSO should be considered to bypass protein truncation resulting from the c.2991+1655A>G mutation as well as other truncating mutations in genes which like CEP290 or ABCA4 have a mRNA size that exceed cargo capacities of US Food and Drug Administration (FDA-approved adeno-associated virus (AAV-vectors, thus hampering gene augmentation therapy.

  4. Stereotactic body radiotherapy for liver tumors. Principles and practical guidelines of the DEGRO Working Group on Stereotactic Radiotherapy

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    Sterzing, Florian [Deutsches Krebsforschungszentrum (DKFZ), Klinische Kooperationseinheit Strahlentherapie, Heidelberg (Germany); Radiologische Universitaetsklinik, Abteilung fuer Radioonkologie und Strahlentherapie, Heidelberg (Germany); Brunner, Thomas B. [Universitaetsklinikum Freiburg, Klinik fuer Strahlenheilkunde, Radiologische Klinik, Freiburg (Germany); Ernst, Iris; Greve, Burkhard [Universitaetsklinikum Muenster, Klinik fuer Strahlentherapie - Radioonkologie, Muenster (Germany); Baus, Wolfgang W. [Universitaetsklinikum Koeln, Klinik und Poliklinik fuer Strahlentherapie, Koeln (Germany); Herfarth, Klaus [Radiologische Universitaetsklinik, Abteilung fuer Radioonkologie und Strahlentherapie, Heidelberg (Germany); Guckenberger, Matthias [UniversitaetsSpital Zuerich, Klinik fuer Radio-Onkologie, Zuerich (Switzerland)

    2014-10-15

    This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a practical guideline for safe and effective stereotactic body radiotherapy (SBRT) of liver tumors. The literature on the clinical evidence of SBRT for both primary liver tumors and liver metastases was reviewed and analyzed focusing on both physical requirements and special biological characteristics. Recommendations were developed for patient selection, imaging, planning, treatment delivery, motion management, dose reporting, and follow-up. Radiation dose constraints to critical organs at risk are provided. SBRT is a well-established treatment option for primary and secondary liver tumors associated with low morbidity. (orig.) [German] Die Arbeitsgruppe Stereotaxie der Deutschen Gesellschaft fuer Radioonkologie (DEGRO) legt hier eine Empfehlung zur sicheren und effektiven Durchfuehrung der SBRT von Lebertumoren vor. Eine Literaturrecherche zur Untersuchung der Evidenz der SBRT sowohl fuer primaere Lebertumore als auch fuer Lebermetastasen wurde durchgefuehrt. Auf dieser Basis werden Empfehlungen fuer technisch-physikalische Voraussetzungen wie auch fuer die taegliche Praxis der Leber-SBRT gegeben. Weiterhin werden radiobiologische Besonderheiten dieses Verfahrens dargestellt. Praktische Vorgaben werden fuer Patientenselektion, Bildgebung, Planung, Applikation, Bewegungsmanagement, Dosisdokumentation und Follow-up gegeben. Dosisempfehlungen fuer die kritischen Risikoorgane werden dargestellt. Die SBRT stellt eine etablierte Behandlungsmethode fuer primaere und sekundaere Lebertumore dar und ist mit niedriger Morbiditaet assoziiert. (orig.)

  5. Whole genome sequencing and bioinformatics analysis of two Egyptian genomes.

    Science.gov (United States)

    ElHefnawi, Mahmoud; Jeon, Sungwon; Bhak, Youngjune; ElFiky, Asmaa; Horaiz, Ahmed; Jun, JeHoon; Kim, Hyunho; Bhak, Jong

    2018-05-15

    We report two Egyptian male genomes (EGP1 and EGP2) sequenced at ~ 30× sequencing depths. EGP1 had 4.7 million variants, where 198,877 were novel variants while EGP2 had 209,109 novel variants out of 4.8 million variants. The mitochondrial haplogroup of the two individuals were identified to be H7b1 and L2a1c, respectively. We also identified the Y haplogroup of EGP1 (R1b) and EGP2 (J1a2a1a2 > P58 > FGC11). EGP1 had a mutation in the NADH gene of the mitochondrial genome ND4 (m.11778 G > A) that causes Leber's hereditary optic neuropathy. Some SNPs shared by the two genomes were associated with an increased level of cholesterol and triglycerides, probably related with Egyptians obesity. Comparison of these genomes with African and Western-Asian genomes can provide insights on Egyptian ancestry and genetic history. This resource can be used to further understand genomic diversity and functional classification of variants as well as human migration and evolution across Africa and Western-Asia. Copyright © 2017. Published by Elsevier B.V.

  6. Baseline demographics, clinical features, and treatment protocols of 240 patients with optic neuropathy: experiences from a neuro-ophthalmological clinic in the Aegean region of Turkey.

    Science.gov (United States)

    Karti, Omer; Karti, Dilek Top; Kilic, İlay Hilal; Gokcay, Figen; Celebisoy, Nese

    2017-12-19

    To analyze the demographic patterns, clinical characteristics, and treatment protocols of optic neuropathies. The hospital data of patients with optic neuropathy admitted to the Department of Neuro-ophthalmology in a tertiary referral center in Turkey between January 2010 to January 2017 were retrospectively analyzed. Demographic patterns, clinical features, treatment protocols, and the natural disease courses were assessed. The total number of patients with optic neuropathy seen over this period was 240, which consist of 43 with idiopathic optic neuritis (17.9%), 40 with multiple sclerosis-related optic neuritis (16.7%), 12 with chronic relapsing inflammatory optic neuritis (5.0%), 12 with atypical optic neuritis (5.0%), 11 with neuromyelitis optica spectrum disorders-related optic neuritis (4.6%), 90 with non-arteritic ischemic optic neuropathy (37.5%), 4 with arteritic ischemic optic neuropathy (1.7%), 10 with traumatic optic neuropathy (4.1%), 6 with compressive optic neuropathy (2.5%), and 12 with mitochondrial optic neuropathy [9 with toxic optic neuropathy (3.7%) and 3 with Leber's hereditary optic neuropathy (1.2%)]. There were 101 males (42%) and 139 females (58%). The mean age was 43.34 ± 15.86 years. This study reported the demographics, clinical characteristics, and treatment protocols of optic neuropathies in a neuro-ophthalmology specialty clinic at a tertiary referral center in Turkey during the past decade. The data may be useful in assessing the global status of optic neuropathies.

  7. [Eye and cat scratch disease: A case series].

    Science.gov (United States)

    Deschasse, C; Bielefeld, P; Muselier, A; Bour, J B; Besancenot, J F; Garcher, C C; Bron, A M

    2016-02-01

    Cat scratch disease is a pleiomorphic condition, sometimes with isolated ophthalmic involvement. We report the clinical observations of seven cases with ophthalmologic manifestations of cat scratch disease. There were seven patients, with a median age of 52 years, of whom five were women and three had unilateral involvement. Six exhibited Leber's stellate neuroretinitis, an incomplete syndrome in two cases, and one associated with chorioretinal foci. One patient had isolated retinal infiltrates. The diagnosis of cat scratch disease was confirmed by Bartonella henselae serology, positive in all cases. All patients received treatment with doxycycline. Ocular complications (with optic atrophy and macular retinal pigment epithelial changes) were noted in five cases. Ocular bartonellosis is an atypical clinical form. It requires a directed ancillary work-up with serology or PCR, which has the peculiarity of being highly specific if not very sensitive. Treatment is above all preventive. Antibiotics may be initiated. Cat scratch disease must be excluded in the work-up of posterior uveitis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Minisequencing mitochondrial DNA pathogenic mutations

    Directory of Open Access Journals (Sweden)

    Carracedo Ángel

    2008-04-01

    Full Text Available Abstract Background There are a number of well-known mutations responsible of common mitochondrial DNA (mtDNA diseases. In order to overcome technical problems related to the analysis of complete mtDNA genomes, a variety of different techniques have been proposed that allow the screening of coding region pathogenic mutations. Methods We here propose a minisequencing assay for the analysis of mtDNA mutations. In a single reaction, we interrogate a total of 25 pathogenic mutations distributed all around the whole mtDNA genome in a sample of patients suspected for mtDNA disease. Results We have detected 11 causal homoplasmic mutations in patients suspected for Leber disease, which were further confirmed by standard automatic sequencing. Mutations m.11778G>A and m.14484T>C occur at higher frequency than expected by change in the Galician (northwest Spain patients carrying haplogroup J lineages (Fisher's Exact test, P-value Conclusion We here developed a minisequencing genotyping method for the screening of the most common pathogenic mtDNA mutations which is simple, fast, and low-cost. The technique is robust and reproducible and can easily be implemented in standard clinical laboratories.

  9. Unique presentation of LHON/MELAS overlap syndrome caused by m.13046T>C in MTND5.

    Science.gov (United States)

    Kolarova, Hana; Liskova, Petra; Tesarova, Marketa; Kucerova Vidrova, Vendula; Forgac, Martin; Zamecnik, Josef; Hansikova, Hana; Honzik, Tomas

    2016-12-01

    Leber hereditary optic neuropathy (LHON) and mitochondrial encephalopathy, myopathy, lactic acidosis and stroke-like episodes (MELAS) syndromes are mitochondrially inherited disorders characterized by acute visual failure and variable multiorgan system presentation, respectively. A 12-year-old girl with otherwise unremarkable medical history presented with abrupt, painless loss of vision. Over the next few months, she developed moderate sensorineural hearing loss, vertigo, migraines, anhedonia and thyroiditis. Ocular examination confirmed bilateral optic nerve atrophy. Metabolic workup documented elevated cerebrospinal fluid lactate. Initial genetic analyses excluded the three most common LHON mutations. Subsequently, Sanger sequencing of the entire mitochondrial DNA (mtDNA) genome was performed. Whole mtDNA sequencing revealed a pathogenic heteroplasmic mutation m.13046T>C in MTND5 encoding the ND5 subunit of complex I. This particular variant has previously been described in a single case report of MELAS/Leigh syndrome (subacute necrotizing encephalopathy). Based on the constellation of clinical symptoms in our patient, we diagnose the condition as LHON/MELAS overlap syndrome. We describe a unique presentation of LHON/MELAS overlap syndrome resulting from a m.13046T>C mutation in a 12-year-old girl. In patients with sudden vision loss in which three of the most prevalent LHON mitochondrial mutations have been ruled out, molecular genetic examination should be extended to other mtDNA-encoded subunits of MTND5 complex I. Furthermore, atypical clinical presentations must be considered, even in well-described phenotypes.

  10. Vitamin A Derivatives as Treatment Options for Retinal Degenerative Diseases

    Directory of Open Access Journals (Sweden)

    Tadao Maeda

    2013-07-01

    Full Text Available The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT and retinal pigment epithelium-specific 65-kDa protein (RPE65 known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA and retinitis pigmentosa (RP. Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients.

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

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    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

  12. Homozygosity mapping and targeted sanger sequencing reveal genetic defects underlying inherited retinal disease in families from pakistan.

    Directory of Open Access Journals (Sweden)

    Maleeha Maria

    Full Text Available Homozygosity mapping has facilitated the identification of the genetic causes underlying inherited diseases, particularly in consanguineous families with multiple affected individuals. This knowledge has also resulted in a mutation dataset that can be used in a cost and time effective manner to screen frequent population-specific genetic variations associated with diseases such as inherited retinal disease (IRD.We genetically screened 13 families from a cohort of 81 Pakistani IRD families diagnosed with Leber congenital amaurosis (LCA, retinitis pigmentosa (RP, congenital stationary night blindness (CSNB, or cone dystrophy (CD. We employed genome-wide single nucleotide polymorphism (SNP array analysis to identify homozygous regions shared by affected individuals and performed Sanger sequencing of IRD-associated genes located in the sizeable homozygous regions. In addition, based on population specific mutation data we performed targeted Sanger sequencing (TSS of frequent variants in AIPL1, CEP290, CRB1, GUCY2D, LCA5, RPGRIP1 and TULP1, in probands from 28 LCA families.Homozygosity mapping and Sanger sequencing of IRD-associated genes revealed the underlying mutations in 10 families. TSS revealed causative variants in three families. In these 13 families four novel mutations were identified in CNGA1, CNGB1, GUCY2D, and RPGRIP1.Homozygosity mapping and TSS revealed the underlying genetic cause in 13 IRD families, which is useful for genetic counseling as well as therapeutic interventions that are likely to become available in the near future.

  13. Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

    Directory of Open Access Journals (Sweden)

    Isabella Bernardis

    2016-01-01

    Full Text Available To assess the clinical utility of targeted Next-Generation Sequencing (NGS for the diagnosis of Inherited Retinal Dystrophies (IRDs, a total of 109 subjects were enrolled in the study, including 88 IRD affected probands and 21 healthy relatives. Clinical diagnoses included Retinitis Pigmentosa (RP, Leber Congenital Amaurosis (LCA, Stargardt Disease (STGD, Best Macular Dystrophy (BMD, Usher Syndrome (USH, and other IRDs with undefined clinical diagnosis. Participants underwent a complete ophthalmologic examination followed by genetic counseling. A custom AmpliSeq™ panel of 72 IRD-related genes was designed for the analysis and tested using Ion semiconductor Next-Generation Sequencing (NGS. Potential disease-causing mutations were identified in 59.1% of probands, comprising mutations in 16 genes. The highest diagnostic yields were achieved for BMD, LCA, USH, and STGD patients, whereas RP confirmed its high genetic heterogeneity. Causative mutations were identified in 17.6% of probands with undefined diagnosis. Revision of the initial diagnosis was performed for 9.6% of genetically diagnosed patients. This study demonstrates that NGS represents a comprehensive cost-effective approach for IRDs molecular diagnosis. The identification of the genetic alterations underlying the phenotype enabled the clinicians to achieve a more accurate diagnosis. The results emphasize the importance of molecular diagnosis coupled with clinic information to unravel the extensive phenotypic heterogeneity of these diseases.

  14. Strikingly different penetrance of LHON in two Chinese families with primary mutation G11778A is independent of mtDNA haplogroup background and secondary mutation G13708A

    Energy Technology Data Exchange (ETDEWEB)

    Wang Huawei [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China)]|[Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming 650091 (China); Jia Xiaoyun; Ji Yanli [State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060 (China); Kong Qingpeng [State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223 (China); Zhang Qingjiong [State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060 (China)], E-mail: qingjiongzhang@yahoo.com; Yao Yonggang [Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223 (China)]|[State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223 (China)], E-mail: ygyaozh@yahoo.com; Zhang Yaping [Laboratory for Conservation and Utilization of Bio-resource, Yunnan University, Kunming 650091 (China)]|[State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223 (China)

    2008-08-25

    The penetrance of Leber's hereditary optic neuropathy (LHON) in families with primary mitochondrial DNA (mtDNA) mutations is very complex. Matrilineal and nuclear genetic background, as well as environmental factors, have been reported to be involved in different affected pedigrees. Here we describe two large Chinese families that show a striking difference in the penetrance of LHON, in which 53.3% and 15.0% of members were affected (P < 0.02), respectively. Analysis of the complete mtDNA genome of the two families revealed the presence of the primary mutation G11778A and several other variants suggesting the same haplogroup status G2a. The family with higher penetrance contained a previously described secondary mutation G13708A, which presents a polymorphism in normal Chinese samples and does not affect in vivo mitochondrial oxidative metabolism as described in a previous study. Evolutionary analysis failed to indicate any putatively pathogenic mutation that cosegregated with G11778A in these two pedigrees. Our results suggest that the variable penetrance of LHON in the two Chinese families is independent of both their mtDNA haplotype background and a secondary mutation G13708A. As a result, it is likely that unknown nuclear gene involvement and/or other factors contribute to the strikingly different penetrance of LHON.

  15. NMNAT1 variants cause cone and cone-rod dystrophy.

    Science.gov (United States)

    Nash, Benjamin M; Symes, Richard; Goel, Himanshu; Dinger, Marcel E; Bennetts, Bruce; Grigg, John R; Jamieson, Robyn V

    2018-03-01

    Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

  16. Optic nerve histopathology in a case of Wolfram Syndrome: a mitochondrial pattern of axonal loss.

    Science.gov (United States)

    Ross-Cisneros, Fred N; Pan, Billy X; Silva, Ruwan A; Miller, Neil R; Albini, Thomas A; Tranebjaerg, Lisbeth; Rendtorff, Nanna D; Lodahl, Marianne; Moraes-Filho, Milton N; Moraes, Milton N; Salomao, Solange R; Berezovsky, Adriana; Belfort, Rubens; Carelli, Valerio; Sadun, Alfredo A

    2013-11-01

    Mitochondrial dysfunction in Wolfram Syndrome (WS) is controversial and optic neuropathy, a cardinal clinical manifestation, is poorly characterized. We here describe the histopathological features in postmortem retinas and optic nerves (ONs) from one patient with WS, testing the hypothesis that mitochondrial dysfunction underlies the pathology. Eyes and retrobulbar ONs were obtained at autopsy from a WS patient, and compared with those of a Leber hereditary optic neuropathy (LHON) patient and one healthy control. Retinas were stained with hematoxylin & eosin for general morphology and ONs were immunostained for myelin basic protein (MBP). Immunostained ONs were examined in four "quadrants": superior, inferior, nasal, and temporal. The WS retinas displayed a severe loss of retinal ganglion cells in the macular region similar to the LHON retina, but not in the control. The WS ONs, immunostained for MBP, revealed a zone of degeneration in the temporal and inferior quadrants. This pattern was similar to that seen in the LHON ONs but not in the control. Thus, the WS patient displayed a distinct pattern of optic atrophy observed bilaterally in the temporal and inferior quadrants of the ONs. This arrangement of axonal degeneration, involving primarily the papillomacular bundle, closely resembled LHON and other mitochondrial optic neuropathies, supporting that mitochondrial dysfunction underlies its pathogenesis. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. The mitochondrial DNA 10197 G > A mutation causes MELAS/Leigh overlap syndrome presenting with acute auditory agnosia.

    Science.gov (United States)

    Leng, Yinglin; Liu, Yuhe; Fang, Xiaojing; Li, Yao; Yu, Lei; Yuan, Yun; Wang, Zhaoxia

    2015-04-01

    Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes/Leigh (MELAS/LS) overlap syndrome is a mitochondrial disorder subtype with clinical and magnetic resonance imaging (MRI) features that are characteristic of both MELAS and Leigh syndrome (LS). Here, we report an MELAS/LS case presenting with cortical deafness and seizures. Cranial MRI revealed multiple lesions involving bilateral temporal lobes, the basal ganglia and the brainstem, which conformed to neuroimaging features of both MELAS and LS. Whole mitochondrial DNA (mtDNA) sequencing and PCR-RFLP revealed a de novo heteroplasmic m.10197 G > A mutation in the NADH dehydrogenase subunit 3 gene (ND3), which was predicted to cause an alanine to threonine substitution at amino acid 47. Although the mtDNA m.10197 G > A mutation has been reported in association with LS, Leber hereditary optic neuropathy and dystonia, it has never been linked with MELAS/LS overlap syndrome. Our patient therefore expands the phenotypic spectrum of the mtDNA m.10197 G > A mutation.

  18. Individual differences in working memory capacity predict learned control over attentional capture.

    Science.gov (United States)

    Robison, Matthew K; Unsworth, Nash

    2017-11-01

    Although individual differences in working memory capacity (WMC) typically predict susceptibility to attentional capture in various paradigms (e.g., Stroop, antisaccade, flankers), it sometimes fails to correlate with the magnitude of attentional capture effects in visual search (e.g., Stokes, 2016), which is 1 of the most frequently studied tasks to study capture (Theeuwes, 2010). But some studies have shown that search modes can mitigate the effects of attentional capture (Leber & Egeth, 2006). Therefore, the present study examined whether or not the relationship between WMC and attentional capture changes as a function of the search modes available. In Experiment 1, WMC was unrelated to attentional capture, but only 1 search mode (singleton-detection) could be employed. In Experiment 2, greater WMC predicted smaller attentional capture effects, but only when multiple search modes (feature-search and singleton-detection) could be employed. Importantly this relationship was entirely independent of variation in attention control, which suggests that this effect is driven by WMC-related long-term memory differences (Cosman & Vecera, 2013a, 2013b). The present set of findings help to further our understanding of the nuanced ways in which memory and attention interact. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  19. Gene therapy: light is finally in the tunnel.

    Science.gov (United States)

    Cao, Huibi; Molday, Robert S; Hu, Jim

    2011-12-01

    After two decades of ups and downs, gene therapy has recently achieved a milestone in treating patients with Leber's congenital amaurosis (LCA). LCA is a group of inherited blinding diseases with retinal degeneration and severe vision loss in early infancy. Mutations in several genes, including RPE65, cause the disease. Using adeno-associated virus as a vector, three independent teams of investigators have recently shown that RPE65 can be delivered to retinal pigment epithelial cells of LCA patients by subretinal injections resulting in clinical benefits without side effects. However, considering the whole field of gene therapy, there are still major obstacles to clinical applications for other diseases. These obstacles include innate and immune barriers to vector delivery, toxicity of vectors and the lack of sustained therapeutic gene expression. Therefore, new strategies are needed to overcome these hurdles for achieving safe and effective gene therapy. In this article, we shall review the major advancements over the past two decades and, using lung gene therapy as an example, discuss the current obstacles and possible solutions to provide a roadmap for future gene therapy research.

  20. KMeyeDB: a graphical database of mutations in genes that cause eye diseases.

    Science.gov (United States)

    Kawamura, Takashi; Ohtsubo, Masafumi; Mitsuyama, Susumu; Ohno-Nakamura, Saho; Shimizu, Nobuyoshi; Minoshima, Shinsei

    2010-06-01

    KMeyeDB (http://mutview.dmb.med.keio.ac.jp/) is a database of human gene mutations that cause eye diseases. We have substantially enriched the amount of data in the database, which now contains information about the mutations of 167 human genes causing eye-related diseases including retinitis pigmentosa, cone-rod dystrophy, night blindness, Oguchi disease, Stargardt disease, macular degeneration, Leber congenital amaurosis, corneal dystrophy, cataract, glaucoma, retinoblastoma, Bardet-Biedl syndrome, and Usher syndrome. KMeyeDB is operated using the database software MutationView, which deals with various characters of mutations, gene structure, protein functional domains, and polymerase chain reaction (PCR) primers, as well as clinical data for each case. Users can access the database using an ordinary Internet browser with smooth user-interface, without user registration. The results are displayed on the graphical windows together with statistical calculations. All mutations and associated data have been collected from published articles. Careful data analysis with KMeyeDB revealed many interesting features regarding the mutations in 167 genes that cause 326 different types of eye diseases. Some genes are involved in multiple types of eye diseases, whereas several eye diseases are caused by different mutations in one gene.

  1. Assessment of different virus-mediated approaches for retinal gene therapy of Usher 1B.

    Science.gov (United States)

    Lopes, Vanda S; Diemer, Tanja; Williams, David S

    2014-01-01

    Usher syndrome type 1B, which is characterized by congenital deafness and progressive retinal degeneration, is caused by the loss of the function of MYO7A. Prevention of the retinal degeneration should be possible by delivering functional MYO7A to retinal cells. Although this approach has been used successfully in clinical trials for Leber congenital amaurosis (LCA2), it remains a challenge for Usher 1B because of the large size of the MYO7A cDNA. Different viral vectors have been tested for use in MYO7A gene therapy. Here, we review approaches with lentiviruses, which can accommodate larger genes, as well as attempts to use adeno-associated virus (AAV), which has a smaller packaging capacity. In conclusion, both types of viral vector appear to be effective. Despite concerns about the ability of lentiviruses to access the photoreceptor cells, a phenotype of the photoreceptors of Myo7a-mutant mice can be corrected. And although MYO7A cDNA is significantly larger than the nominal carrying capacity of AAV, AAV-MYO7A in single vectors also corrected Myo7a-mutant phenotypes in photoreceptor and RPE cells. Interestingly, however, a dual AAV vector approach was found to be much less effective.

  2. Effects of bone morphogenetic protein-2 on bone cells in primary culture: immunohistochemical and electronmicroscopical studies

    Energy Technology Data Exchange (ETDEWEB)

    Schmitz, I.; Prochnow, N.; Mueller, K.M. [Berufsgenossenschaftliche Kliniken Bergmannsheil, Bochum (Germany). Inst. fuer Pathologie; Wiemann, M.; Schirrmacher, K.; Bingmann, D. [Essen Univ. (Germany). Inst. fuer Physiologie; Sebald, W. [Wuerzburg Univ. (Germany). Inst. fuer Physiologische Chemie II

    2001-02-01

    was not changed after a 3 days lasting stimulation with BMP-2. (orig.) [German] Bone-morphogenetisches Protein 2 (BMP-2) foerdert Differenzierung und Wachstum in fast allen Geweben. Am bekanntesten ist seine stimulatorische Wirkung auf die Knochenneubildung. Daher ist es naheliegend, BMP-2 auch fuer eine beschleunigte Osteointegration von Implantaten einzusetzen. Zahlreiche Untersuchungen in vivo und an Zelllinien haben die Wirksamkeit von BMP-2 auf die Zellproliferation ergeben. Effekte von BMP-2 sind aber kaum in Primaerkulturen von Knochenzellen untersucht worden, in denen die Differenzierung von unterschiedlichen Zelltypen eher als in Zelllinien ueberprueft werden kann. Da solche Information aber eine Voraussetzung fuer das Verstaendnis und die Kontrolle von Zellreaktionen auf der Implantatoberflaeche sind, wurde in den vorliegenden Untersuchungen die Wirkung von BMP-2 (50 nM) auf Primaerkulturen geprueft, die aus Kalvarienbruchstuecken neugeborener Ratten gezuechtet wurden. Dabei wurden die Zellen fuer 3 oder 6 Tage mit BMP-2 stimuliert, das dem Naehrmedium zugesetzt war. Licht- und elektronenmikroskopische Untersuchungen zeigten, dass BMP-behandelte Zellen in der Aussprossungszone groesser und haeufiger spindelfoermig waren. Darueber hinaus hatten stimulierte Zellen mehr Nukleoli als die Kontrollzellen und ihr endoplasmatisches Retikulum war geweitet. Dennoch behielten die stimulierten Zellen Eigenschaften von Knochenzellen. Eine immunhistochemische Analyse zeigte, dass BMP-2 stimulierte Zellen die Aktivitaet ihrer alkalischen Phosphatase steigerten und weiterhin Kollagen Typ I sowie zu einem geringen Teil Kollagen Typ III sezernierten. Der Gehalt an Actin, Desmin und Vimentin war in BMP-stimulierten Kulturen kaum veraendert. Fibronektin-positive Strukturen erschienen weniger vernetzt. Die Osteocalcin-Verteilung bzw Faerbeintensitaet aendert sich nach BMP-Einwirkungen nicht ekennbar. Nach der Stimulation loesten sich vermehrt Zellen von den Deckglaeschen ab

  3. Genetics and mapping of the R₁₁ gene conferring resistance to recently emerged rust races, tightly linked to male fertility restoration, in sunflower (Helianthus annuus L.).

    Science.gov (United States)

    Qi, L L; Seiler, G J; Vick, B A; Gulya, T J

    2012-09-01

    Sunflower oil is one of the major sources of edible oil. As the second largest hybrid crop in the world, hybrid sunflowers are developed by using the PET1 cytoplasmic male sterility system that contributes to a 20 % yield advantage over the open-pollinated varieties. However, sunflower production in North America has recently been threatened by the evolution of new virulent pathotypes of sunflower rust caused by the fungus Puccinia helianthi Schwein. Rf ANN-1742, an 'HA 89' backcross restorer line derived from wild annual sunflower (Helianthus annuus L.), was identified as resistant to the newly emerged rust races. The aim of this study was to elucidate the inheritance of rust resistance and male fertility restoration and identify the chromosome location of the underlying genes in Rf ANN-1742. Chi-squared analysis of the segregation of rust response and male fertility in F(2) and F(3) populations revealed that both traits are controlled by single dominant genes, and that the rust resistance gene is closely linked to the restorer gene in the coupling phase. The two genes were designated as R ( 11 ) and Rf5, respectively. A set of 723 mapped SSR markers of sunflower was used to screen the polymorphism between HA 89 and the resistant plant. Bulked segregant analysis subsequently located R ( 11 ) on linkage group (LG) 13 of sunflower. Based on the SSR analyses of 192 F(2) individuals, R ( 11 ) and Rf5 both mapped to the lower end of LG13 at a genetic distance of 1.6 cM, and shared a common marker, ORS728, which was mapped 1.3 cM proximal to Rf5 and 0.3 cM distal to R ( 11 ) (Rf5/ORS728/R ( 11 )). Two additional SSRs were linked to Rf5 and R ( 11 ): ORS995 was 4.5 cM distal to Rf5 and ORS45 was 1.0 cM proximal to R ( 11 ). The advantage of such an introduced alien segment harboring two genes is its large phenotypic effect and simple inheritance, thereby facilitating their rapid deployment in sunflower breeding programs. Suppressed recombination was observed in LGs 2, 9

  4. Braille use among Norwegian children from 1967 to 2007: trends in the underlying causes.

    Science.gov (United States)

    Augestad, Liv Berit; Klingenberg, Oliv; Fosse, Per

    2012-08-01

    The aim of the study was to estimate the occurrence, diagnoses and time trends among Norwegian children that have received education in braille from 1967 to 2007. We used a retrospective population-based study design. The health care system is free for all inhabitants in Norway. We included all children that had received braille education the last four decades. From each student's record, we abstracted year born, country of birth, gender, year diagnosed, diagnosis, classification of visual impairment and type of reading media. We identified 287 children (137 girls and 150 boys) that had received braille education over the last 40 years. Of these, 262 (91.3%) children were born in Norway, 145 (53.7%) were diagnosed within the first year of life and 59 (20.6%) from age of one to five. The most frequent diagnoses were Retinopathy of Prematurity (ROP), Juvenile Ceroid Lipofuscinoses (JNCL), Lebers Congenital Amaurosis (LCA) and Retinitis Pigmentosa (RP). Among the children, 63% (N = 170) used braille only, 9% (N = 25) braille and print, but priority braille, and 27% (N = 73) braille and print, priority print. The number of children with ROP using braille had a peak in 1977, then the number declined. The number diagnosed with LCA increased from 1987 to 1992. The number of braille users among children diagnosed with JNCL tended to increase substantially after 1992. Braille education seemed to be dependent of trends in diagnoses as well as trends in recommendations from professional educators. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

  5. Dog as a model in studies on human hereditary diseases and their gene therapy.

    Science.gov (United States)

    Switonski, Marek

    2014-03-01

    During the last 15 years spectacular progress has been achieved in knowledge on the dog genome organization and the molecular background of hereditary diseases in this species. A majority of canine genetic diseases have their counterparts in humans and thus dogs are considered as a very important large animal model in human biomedicine. Among canine monogenic diseases with known causative gene mutations there are two large groups classified as retinal dystrophies and lysosomal storage diseases. Specific types of these diseases are usually diagnosed in a single or several breeds. A well known disorder, restricted to a single breed, is congenital stationary night blindness described in Briards. This disease is a counterpart of Leber amaurosis in children. On the other hand, one of the most common monogenic human diseases (Duchenne muscular dystrophy), has its canine counterparts in several breeds (e.g., the Golden retriever, Beagle and German short-haired pointer). For some of the canine diseases gene therapy strategy was successfully applied, e.g., for congenital stationary night blindness, rod-cone dystrophy and muccopolysaccharydoses type I, IIIB and VII. Since phenotypic variability between the breeds is exceptionally high, the dog is an interesting model to study the molecular background of congenital malformations (e.g., dwarfism and osteoporosis imperfecta). Also disorders of sexual development (DSD), especially testicular or ovotesticular DSD (78,XX; SRY-negative), which is widely distributed across dozens of breeds, are of particular interest. Studies on the genetic background of canine cancers, a major health problem in this species, are also quite advanced. On the other hand, genetic studies on canine counterparts of major human complex diseases (e.g., obesity, the metabolic syndrome and diabetes mellitus) are still in their infancy. Copyright © 2014 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish

  6. Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa.

    Science.gov (United States)

    Booij, J C; Florijn, R J; ten Brink, J B; Loves, W; Meire, F; van Schooneveld, M J; de Jong, P T V M; Bergen, A A B

    2005-11-01

    To identify mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. Mutation analysis was carried out in a group of 35 unrelated patients with juvenile autosomal recessive retinitis pigmentosa (ARRP), Leber's congenital amaurosis (LCA), or juvenile isolated retinitis pigmentosa (IRP), by denaturing high performance liquid chromatography followed by direct sequencing. All three groups of patients showed typical combinations of eye signs associated with retinitis pigmentosa: pale optic discs, narrow arterioles, pigmentary changes, and nystagmus. Mutations were found in 34% of in CRB1 (11%), GUCY2D (11%), RPE65 (6%), and RPGRIP1 (6%). Nine mutations are reported, including a new combination of two mutations in CRB1, and new mutations in GUCY2D and RPGRIP1. The new GUCY2D mutation (c.3283delC, p.Pro1069ArgfsX37) is the first pathological sequence change reported in the intracellular C-terminal domain of GUCY2D, and did not lead to the commonly associated LCA, but to a juvenile retinitis pigmentosa phenotype. The polymorphic nature of three previously described (pathological) sequence changes in AIPL1, CRB1, and RPGRIP1 was established. Seven new polymorphic changes, useful for further association studies, were found. New and previously described sequence changes were detected in retinitis pigmentosa in CRB1, GUCY2D, and RPGRIP1; and in LCA patients in CRB1, GUCY2D, and RPE65. These data, combined with previous reports, suggest that LCA and juvenile ARRP are closely related and belong to a continuous spectrum of juvenile retinitis pigmentosa.

  7. Side-effects and complications of intra-arterial tumour therapy - experience gained from 577 interventions; Nebenwirkungen und Komplikationen der intraarteriellen Tumortherapie - Erfahrungen aus 577 Interventionen

    Energy Technology Data Exchange (ETDEWEB)

    Goerich, J. [Radiologische Universitaetsklinik Ulm (Germany); Hasan, I. [Radiologische Universitaetsklinik Bonn (Germany); Sittek, H. [Radiologische Universitaetsklinik Bonn (Germany); Harder, T. [Radiologische Universitaetsklinik Bonn (Germany); Rieber, A. [Radiologische Universitaetsklinik Ulm (Germany); Hartlapp, H.J. [Medizinische Universitaetsklinik Bonn (Germany); Keilholz, U. [Heidelberg Univ. (Germany). Medizinische Klinik und Poliklinik; Kunze, V. [Radiologische Universitaetsklinik Ulm (Germany); Brado, M. [Radiologische Universitaetsklinik Heidelberg (Germany); Reiser, M. [Radiologische Universitaetsklinik Bonn (Germany); Brambs, H. [Radiologische Universitaetsklinik Ulm (Germany)

    1995-05-01

    305 bearers of different types of tumour went through a total of 577 cycles of intra-arterial therapy (287 perfusions, 290 embolizations). The treatments were carried out for pelvic, hepatic, renal and mammary tumours, for bone metastization, pulmonary carcinomas as well as tumours of the gastrointestinal tract or the extremities. Except for 105 cases, all patients had previously been subjected to surgery or radiotherapy to cure the disease now treated by the intra-arterial method. Systemic chemotherapy had been performed in 58% of the patients. The cytostatic and embolization drugs used varied according to tumour histology and vascularization. Serious complications occurred in 1-2% of the patients. They were observed to be two times more frequent for tumour embolization (1.4%) as compared to intra-arterial perfusion therapy (0.7%). An invariable use of refined methods like intraarterial computerized angiotomography to monitor perfusion and a choice of cytostatic drugs also based on anatomic determinants may further diminish the number of serious complications during perfusion therapy. (orig./VHE) [Deutsch] Bei 305 Patienten mit unterschiedlichen Tumorerkrankungen wurden insgesamt 577 intraarterielle Therapiezyklen (287 Perfusionen, 290 Embolisationen) durchgefuehrt. Behandlungsursache waren Tumoren des Beckens, der Leber, der Niere, der Mamma, Knochenmetastasen, Lungenkarzinome, gastrointestinale Tumoren und Extremitaetstumoren. Mit Ausnahme von 105 Patienten war der zur intraarteriellen Therapie anstehende Befund lokal operiert und/oder strahlentherapeutisch vorbehandelt worden. Einer systemischen Chemotherapie hatten sich 58% der Patienten unterzogen. In Abhaengigkeit von der Tumorhistologie und -vaskularisation wurden unterschiedliche Zytostatika verwendet. Die Rate an schweren Komplikationen betrug 2%. Bei der Tumorembolisation waren schwerwiegende Komplikationen mit 1,4% doppelt so haeufig wie bei der intraarteriellen Perfusionstherapie. Verbesserte

  8. Using CRISPR-Cas9 to Generate Gene-Corrected Autologous iPSCs for the Treatment of Inherited Retinal Degeneration.

    Science.gov (United States)

    Burnight, Erin R; Gupta, Manav; Wiley, Luke A; Anfinson, Kristin R; Tran, Audrey; Triboulet, Robinson; Hoffmann, Jeremy M; Klaahsen, Darcey L; Andorf, Jeaneen L; Jiao, Chunhua; Sohn, Elliott H; Adur, Malavika K; Ross, Jason W; Mullins, Robert F; Daley, George Q; Schlaeger, Thorsten M; Stone, Edwin M; Tucker, Budd A

    2017-09-06

    Patient-derived induced pluripotent stem cells (iPSCs) hold great promise for autologous cell replacement. However, for many inherited diseases, treatment will likely require genetic repair pre-transplantation. Genome editing technologies are useful for this application. The purpose of this study was to develop CRISPR-Cas9-mediated genome editing strategies to target and correct the three most common types of disease-causing variants in patient-derived iPSCs: (1) exonic, (2) deep intronic, and (3) dominant gain of function. We developed a homology-directed repair strategy targeting a homozygous Alu insertion in exon 9 of male germ cell-associated kinase (MAK) and demonstrated restoration of the retinal transcript and protein in patient cells. We generated a CRISPR-Cas9-mediated non-homologous end joining (NHEJ) approach to excise a major contributor to Leber congenital amaurosis, the IVS26 cryptic-splice mutation in CEP290, and demonstrated correction of the transcript and protein in patient iPSCs. Lastly, we designed allele-specific CRISPR guides that selectively target the mutant Pro23His rhodopsin (RHO) allele, which, following delivery to both patient iPSCs in vitro and pig retina in vivo, created a frameshift and premature stop that would prevent transcription of the disease-causing variant. The strategies developed in this study will prove useful for correcting a wide range of genetic variants in genes that cause inherited retinal degeneration. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  9. The medical management of high risk individuals. Experiences with persons exposed to chronic internal irradiation; Ueber den aerztlichen Umgang mit Hochrisikopersonen. Erfahrungen bei Personen mit chronischer interner Strahlenexposition

    Energy Technology Data Exchange (ETDEWEB)

    Kaick, G. van; Delorme, S. [Deutsches Krebsforschungszentrum, E010 - Radiologie, Heidelberg (Germany)

    2011-12-15

    The medical management and counseling of persons at high risk due to exposure to chemicals or radiation or due to personal disposition, present an additional challenge for physicians and especially radiologists involved. This article is based on own experiences with patients who had been exposed to Thorotrast. They had been injected with the contrast medium Thorotrast, which was in use world-wide until around 1950. Thorotrast caused a chronic alpha irradiation mainly of the liver (up to 0.4 Gy/a), spleen (1.2 Gy/a) and bone marrow (0.1 Gy/a). For the Thorotrast patients and their physicians the most worrying problem was the risk of primary malignant liver tumors which occurred in more than 20% of the exposed persons, i.e. 100 times more frequently than in a non-exposed control group. The medical and especially radiological experiences with the management of these patients summarize a general aspect of the problem and can be referred to when managing other high risk groups. (orig.) [German] Die aerztliche Fuehrung von Personen, die noch nicht erkrankt sind, aber ein deutlich hoeheres Risiko fuer bestimmte Tumorerkrankungen aufgrund exogener oder endogener Ursachen haben, stellt den Arzt und speziell den diagnostischen Radiologen vor neue Herausforderungen. Dem Beitrag zugrunde liegen die Erfahrungen bei der Betreuung und Beratung so genannter Thorotrastpatienten, d. h. Personen, die nach lange zurueckliegender (vor 1950) intravasaler Injektion eines weltweit eingesetzten Roentgenkontrastmittels zeitlebens einer Alphastrahlung v. a. der Leber (bis 0,4 Gy/a), der Milz (1,2 Gy/a) und des Knochenmarks (0,1 Gy/a) ausgesetzt waren. Fuer die Thorotrastpatienten und die Aerzte stand im Vordergrund die Sorge der Entstehung primaerer, maligner Lebertumoren, die bei mehr als 20% der Betroffenen und damit im Vergleich zu einer Kontrollgruppe 100-fach haeufiger auftraten. Die allgemeinen aerztlichen und speziell radiologischen Erfahrungen sind grundsaetzlicher Art und lassen

  10. The gene therapy revolution in ophthalmology.

    Science.gov (United States)

    Al-Saikhan, Fahad I

    2013-04-01

    The advances in gene therapy hold significant promise for the treatment of ophthalmic conditions. Several studies using animal models have been published. Animal models on retinitis pigmentosa, Leber's Congenital Amaurosis (LCA), and Stargardt disease have involved the use of adeno-associated virus (AAV) to deliver functional genes into mice and canines. Mice models have been used to show that a mutation in cGMP phosphodiesterase that results in retinitis pigmentosa can be corrected using rAAV vectors. Additionally, rAAV vectors have been successfully used to deliver ribozyme into mice with a subsequent improvement in autosomal dominant retinitis pigmentosa. By using dog models, researchers have made progress in studying X-linked retinitis pigmentosa which results from a RPGR gene mutation. Mouse and canine models have also been used in the study of LCA. The widely studied form of LCA is LCA2, resulting from a mutation in the gene RPE65. Mice and canines that were injected with normal copies of RPE65 gene showed signs such as improved retinal pigment epithelium transduction, visual acuity, and functional recovery. Studies on Stargardt disease have shown that mutations in the ABCA4 gene can be corrected with AAV vectors, or nanoparticles. Gene therapy for the treatment of red-green color blindness was successful in squirrel monkeys. Plans are at an advanced stage to begin clinical trials. Researchers have also proved that CD59 can be used with AMD. Gene therapy is also able to treat primary open angle glaucoma (POAG) in animal models, and studies show it is economically viable.

  11. Genetic testing for retinal dystrophies and dysfunctions: benefits, dilemmas and solutions.

    Science.gov (United States)

    Koenekoop, Robert K; Lopez, Irma; den Hollander, Anneke I; Allikmets, Rando; Cremers, Frans P M

    2007-07-01

    Human retinal dystrophies have unparalleled genetic and clinical diversity and are currently linked to more than 185 genetic loci. Genotyping is a crucial exercise, as human gene-specific clinical trials to study photoreceptor rescue are on their way. Testing confirms the diagnosis at the molecular level and allows for a more precise prognosis of the possible future clinical evolution. As treatments are gene-specific and the 'window of opportunity' is time-sensitive; accurate, rapid and cost-effective genetic testing will play an ever-increasing crucial role. The gold standard is sequencing but is fraught with excessive costs, time, manpower issues and finding non-pathogenic variants. Therefore, no centre offers testing of all currently 132 known genes. Several new micro-array technologies have emerged recently, that offer rapid, cost-effective and accurate genotyping. The new disease chips from Asper Ophthalmics (for Stargardt dystrophy, Leber congenital amaurosis [LCA], Usher syndromes and retinitis pigmentosa) offer an excellent first pass opportunity. All known mutations are placed on the chip and in 4 h a patient's DNA is screened. Identification rates (identifying at least one disease-associated mutation) are currently approximately 70% (Stargardt), approximately 60-70% (LCA) and approximately 45% (Usher syndrome subtype 1). This may be combined with genotype-phenotype correlations that suggest the causal gene from the clinical appearance (e.g. preserved para-arteriolar retinal pigment epithelium suggests the involvement of the CRB1 gene in LCA). As approximately 50% of the retinal dystrophy genes still await discovery, these technologies will improve dramatically as additional novel mutations are added. Genetic testing will then become standard practice to complement the ophthalmic evaluation.

  12. The Role of Gene Therapy in the Treatment of Retinal Diseases: A Review.

    Science.gov (United States)

    Campa, C; Gallenga, C E; Bolletta, E; Perri, P

    2017-01-01

    Gene therapy represents the therapeutic delivery of nucleic acid polymers into patient cells with the aim of treating an underlying disease. Over the past 2 decades this new therapy has made substantial progress owing to better understanding of the pathobiologic basis of various diseases coupled with growth of gene transfer biotechnologies. The eye, in particular, represents a suitable target for such therapy due to the immune privilege provided by the blood-ocular barrier, the ability to directly visualize, access and locally treat the cells and the minimal amount of vector needed given the size of this organ. It is not surprising therefore that several clinical trials are now ongoing in this field. The purpose of this review was to provide an update on gene therapy for retinal diseases, discussing differences in treatment strategies, vector designs and surgical techniques. Research was performed on PubMed, ClinicalTrials.gov, and Home Genetic Reference. We additionally utilized the internet database for genetics of retinal diseases, the portal for rare diseases and orphan drugs and the NCBI database Online Mendelian Inheritance in Man. No restriction was applied on the language of publications. We present the available results of current active clinical trials for inherited retinal disease such as Leber's congenital amaurosis type 2, choroideremia, Stargardt disease, achromatopsia and juvenile X-linked retinoschisis. We also illustrate a new approach of this therapy for the treatment of much more common ocular diseases such as age-related macular degeneration and diabetic retinopathy. Gene therapy represents an emerging and promising therapeutic approach for the treatment not only of rare inherited retinal diseases but also much more common retinal pathologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Lentiviral expression of retinal guanylate cyclase-1 (RetGC1 restores vision in an avian model of childhood blindness.

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    Melissa L Williams

    2006-06-01

    Full Text Available Leber congenital amaurosis (LCA is a genetically heterogeneous group of retinal diseases that cause congenital blindness in infants and children. Mutations in the GUCY2D gene that encodes retinal guanylate cyclase-1 (retGC1 were the first to be linked to this disease group (LCA type 1 [LCA1] and account for 10%-20% of LCA cases. These mutations disrupt synthesis of cGMP in photoreceptor cells, a key second messenger required for function of these cells. The GUCY1*B chicken, which carries a null mutation in the retGC1 gene, is blind at hatching and serves as an animal model for the study of LCA1 pathology and potential treatments in humans.A lentivirus-based gene transfer vector carrying the GUCY2D gene was developed and injected into early-stage GUCY1*B embryos to determine if photoreceptor function and sight could be restored to these animals. Like human LCA1, the avian disease shows early-onset blindness, but there is a window of opportunity for intervention. In both diseases there is a period of photoreceptor cell dysfunction that precedes retinal degeneration. Of seven treated animals, six exhibited sight as evidenced by robust optokinetic and volitional visual behaviors. Electroretinographic responses, absent in untreated animals, were partially restored in treated animals. Morphological analyses indicated there was slowing of the retinal degeneration.Blindness associated with loss of function of retGC1 in the GUCY1*B avian model of LCA1 can be reversed using viral vector-mediated gene transfer. Furthermore, this reversal can be achieved by restoring function to a relatively low percentage of retinal photoreceptors. These results represent a first step toward development of gene therapies for one of the more common forms of childhood blindness.

  14. Noninvasive, in vivo assessment of mouse retinal structure using optical coherence tomography.

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    M Dominik Fischer

    Full Text Available BACKGROUND: Optical coherence tomography (OCT is a novel method of retinal in vivo imaging. In this study, we assessed the potential of OCT to yield histology-analogue sections in mouse models of retinal degeneration. METHODOLOGY/PRINCIPAL FINDINGS: We achieved to adapt a commercial 3(rd generation OCT system to obtain and quantify high-resolution morphological sections of the mouse retina which so far required in vitro histology. OCT and histology were compared in models with developmental defects, light damage, and inherited retinal degenerations. In conditional knockout mice deficient in retinal retinoblastoma protein Rb, the gradient of Cre expression from center to periphery, leading to a gradual reduction of retinal thickness, was clearly visible and well topographically quantifiable. In Nrl knockout mice, the layer involvement in the formation of rosette-like structures was similarly clear as in histology. OCT examination of focal light damage, well demarcated by the autofluorescence pattern, revealed a practically complete loss of photoreceptors with preservation of inner retinal layers, but also more subtle changes like edema formation. In Crb1 knockout mice (a model for Leber's congenital amaurosis, retinal vessels slipping through the outer nuclear layer towards the retinal pigment epithelium (RPE due to the lack of adhesion in the subapical region of the photoreceptor inner segments could be well identified. CONCLUSIONS/SIGNIFICANCE: We found that with the OCT we were able to detect and analyze a wide range of mouse retinal pathology, and the results compared well to histological sections. In addition, the technique allows to follow individual animals over time, thereby reducing the numbers of study animals needed, and to assess dynamic processes like edema formation. The results clearly indicate that OCT has the potential to revolutionize the future design of respective short- and long-term studies, as well as the preclinical

  15. Distilling a Visual Network of Retinitis Pigmentosa Gene-Protein Interactions to Uncover New Disease Candidates.

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    Daniel Boloc

    Full Text Available Retinitis pigmentosa (RP is a highly heterogeneous genetic visual disorder with more than 70 known causative genes, some of them shared with other non-syndromic retinal dystrophies (e.g. Leber congenital amaurosis, LCA. The identification of RP genes has increased steadily during the last decade, and the 30% of the cases that still remain unassigned will soon decrease after the advent of exome/genome sequencing. A considerable amount of genetic and functional data on single RD genes and mutations has been gathered, but a comprehensive view of the RP genes and their interacting partners is still very fragmentary. This is the main gap that needs to be filled in order to understand how mutations relate to progressive blinding disorders and devise effective therapies.We have built an RP-specific network (RPGeNet by merging data from different sources: high-throughput data from BioGRID and STRING databases, manually curated data for interactions retrieved from iHOP, as well as interactions filtered out by syntactical parsing from up-to-date abstracts and full-text papers related to the RP research field. The paths emerging when known RP genes were used as baits over the whole interactome have been analysed, and the minimal number of connections among the RP genes and their close neighbors were distilled in order to simplify the search space.In contrast to the analysis of single isolated genes, finding the networks linking disease genes renders powerful etiopathological insights. We here provide an interactive interface, RPGeNet, for the molecular biologist to explore the network centered on the non-syndromic and syndromic RP and LCA causative genes. By integrating tissue-specific expression levels and phenotypic data on top of that network, a more comprehensive biological view will highlight key molecular players of retinal degeneration and unveil new RP disease candidates.

  16. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration.

    Science.gov (United States)

    Yang, Fan; Ma, Hongwei; Belcher, Joshua; Butler, Michael R; Redmond, T Michael; Boye, Sanford L; Hauswirth, William W; Ding, Xi-Qin

    2016-12-01

    Recent studies have implicated thyroid hormone (TH) signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we found that antithyroid treatment preserves cones. This work investigates the significance of targeting intracellular TH components locally in the retina. The cellular TH level is mainly regulated by deiodinase iodothyronine (DIO)-2 and -3. DIO2 converts thyroxine (T4) to triiodothyronine (T3), which binds to the TH receptor, whereas DIO3 degrades T3 and T4. We examined cone survival after overexpression of DIO3 and inhibition of DIO2 and demonstrated the benefits of these manipulations. Subretinal delivery of AAV5-IRBP/GNAT2-DIO3, which directs expression of human DIO3 specifically in cones, increased cone density by 30-40% in a Rpe65 -/- mouse model of Lebers congenital amaurosis (LCA) and in a Cpfl1 mouse with Pde6c defect model of achromatopsia, compared with their respective untreated controls. Intravitreal and topical delivery of the DIO2 inhibitor iopanoic acid also significantly improved cone survival in the LCA model mice. Moreover, the expression levels of DIO2 and Slc16a2 were significantly higher in the diseased retinas, suggesting locally elevated TH signaling. We show that targeting DIOs protects cones, and intracellular inhibition of TH components locally in the retina may represent a novel strategy for retinal degeneration management.-Yang, F., Ma, H., Belcher, J., Butler, M. R., Redmond, T. M., Boye, S. L., Hauswirth, W. W., Ding, X.-Q. Targeting iodothyronine deiodinases locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

  17. Genetic and Clinical Analyses of DOA and LHON in 304 Chinese Patients with Suspected Childhood-Onset Hereditary Optic Neuropathy.

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    Yadi Li

    Full Text Available Leber hereditary optic neuropathy (LHON and dominant optic atrophy (DOA, the most common forms of hereditary optic neuropathy, are easily confused, and it is difficult to distinguish one from the other in the clinic, especially in young children. The present study was designed to survey the mutation spectrum of common pathogenic genes (OPA1, OPA3 and mtDNA genes and to analyze the genotype-phenotype characteristics of Chinese patients with suspected childhood-onset hereditary optic neuropathy. Genomic DNA and clinical data were collected from 304 unrelated Chinese probands with suspected hereditary optic neuropathy with an age of onset below 14 years. Sanger sequencing was used to screen variants in the coding and adjacent regions of OPA1, OPA3 and the three primary LHON-related mutation sites in mitochondrial DNA (mtDNA (m.3460G>A, m.11778G>A and m.14484T>C. All patients underwent a complete ophthalmic examination and were compared with age-matched controls. We identified 89/304 (29.3% primary mtDNA mutations related to LHON in 304 probands, including 76 mutations at m.11778 (76/89, 85.4% of all mtDNA mutations, four at m.3460 (4/89, 4.5% and nine at m.14484 (9/89, 10.1%. This result was similar to the mutation frequency among Chinese patients with LHON of any age. Screening of OPA1 revealed 23 pathogenic variants, including 11 novel and 12 known pathogenic mutations. This study expanded the OPA1 mutation spectrum, and our results showed that OPA1 mutation is another common cause of childhood-onset hereditary optic neuropathy in Chinese pediatric patients, especially those with disease onset during preschool age.

  18. Treatment strategies for inherited optic neuropathies: past, present and future

    Science.gov (United States)

    Yu-Wai-Man, P; Votruba, M; Moore, A T; Chinnery, P F

    2014-01-01

    Bilateral visual loss secondary to inherited optic neuropathies is an important cause of registrable blindness among children and young adults. The two prototypal disorders seen in clinical practice are Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). About 90% of LHON cases are due to one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A, and m.14484T>C, which affect critical complex I subunits of the mitochondrial respiratory chain. The majority of patients with DOA harbour pathogenic mutations within OPA1, a nuclear gene that codes for a multifunctional inner mitochondrial membrane protein. Despite their contrasting genetic basis, LHON and DOA share overlapping pathological and clinical features that serve to highlight the striking tissue-specific vulnerability of the retinal ganglion cell (RGC) layer to disturbed mitochondrial function. In addition to severe visual loss secondary to progressive optic nerve degeneration, a subgroup of patients will also develop a more aggressive syndromic phenotype marked by significant neurological deficits. The management of LHON and DOA remains largely supportive, but major advances in our understanding of the mechanisms underpinning RGC loss in these two disorders are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process. In addition to neuroprotective strategies for rescuing RGCs from irreversible cell death, innovative in vitro fertilisation techniques are providing the tantalising prospect of preventing the germline transmission of pathogenic mtDNA mutations, eradicating in so doing the risk of disease in future generations. PMID:24603424

  19. Identification of a new human mtDNA polymorphism (A14290G in the NADH dehydrogenase subunit 6 gene

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    M. Houshmand

    2006-06-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited form of retinal ganglion cell degeneration leading to optic atrophy in young adults. Several mutations in different genes can cause LHON (heterogeneity. The ND6 gene is one of the mitochondrial genes that encodes subunit 6 of complex I of the respiratory chain. This gene is a hot spot gene. Fourteen Persian LHON patients were analyzed with single-strand conformational polymorphism and DNA sequencing techniques. None of these patients had four primary mutations, G3460A, G11788A, T14484C, and G14459A, related to this disease. We identified twelve nucleotide substitutions, G13702C, T13879C, T14110C, C14167T, G14199T, A14233G, G14272C, A14290G, G14365C, G14368C, T14766C, and T14798C. Eleven of twelve nucleotide substitutions had already been reported as polymorphism. One of the nucleotide substitutions (A14290G has not been reported. The A14290G nucleotide substitution does not change its amino acid (glutamic acid. We looked for base conservation using DNA star software (MEGALIGN program as a criterion for pathogenic or nonpathogenic nucleotide substitution in A14290G. The results of ND6 gene alignment in humans and in other species (mouse, cow, elegans worm, and Neurospora crassa mold revealed that the 14290th base was not conserved. Fifty normal controls were also investigated for this polymorphism in the Iranian population and two had A14290G polymorphism (4%. This study provides evidence that the mtDNA A14290G allele is a new nonpathogenic polymorphism. We suggest follow-up studies regarding this polymorphism in different populations.

  20. Autofluorescence Imaging With Near-Infrared Excitation:Normalization by Reflectance to Reduce Signal From Choroidal Fluorophores

    Science.gov (United States)

    Cideciyan, Artur V.; Swider, Malgorzata; Jacobson, Samuel G.

    2015-01-01

    Purpose. We previously developed reduced-illuminance autofluorescence imaging (RAFI) methods involving near-infrared (NIR) excitation to image melanin-based fluorophores and short-wavelength (SW) excitation to image lipofuscin-based flurophores. Here, we propose to normalize NIR-RAFI in order to increase the relative contribution of retinal pigment epithelium (RPE) fluorophores. Methods. Retinal imaging was performed with a standard protocol holding system parameters invariant in healthy subjects and in patients. Normalized NIR-RAFI was derived by dividing NIR-RAFI signal by NIR reflectance point-by-point after image registration. Results. Regions of RPE atrophy in Stargardt disease, AMD, retinitis pigmentosa, choroideremia, and Leber congenital amaurosis as defined by low signal on SW-RAFI could correspond to a wide range of signal on NIR-RAFI depending on the contribution from the choroidal component. Retinal pigment epithelium atrophy tended to always correspond to high signal on NIR reflectance. Normalizing NIR-RAFI reduced the choroidal component of the signal in regions of atrophy. Quantitative evaluation of RPE atrophy area showed no significant differences between SW-RAFI and normalized NIR-RAFI. Conclusions. Imaging of RPE atrophy using lipofuscin-based AF imaging has become the gold standard. However, this technique involves bright SW lights that are uncomfortable and may accelerate the rate of disease progression in vulnerable retinas. The NIR-RAFI method developed here is a melanin-based alternative that is not absorbed by opsins and bisretinoid moieties, and is comfortable to view. Further development of this method may result in a nonmydriatic and comfortable imaging method to quantify RPE atrophy extent and its expansion rate. PMID:26024124

  1. Liposomal nanoparticles encapsulating iloprost exhibit enhanced vasodilation in pulmonary arteries

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    Jain PP

    2014-07-01

    Full Text Available Pritesh P Jain,1 Regina Leber,1,2 Chandran Nagaraj,1 Gerd Leitinger,3 Bernhard Lehofer,4 Horst Olschewski,1,5 Andrea Olschewski,1,6 Ruth Prassl,1,4 Leigh M Marsh11Ludwig Boltzmann Institute for Lung Vascular Research, 2Biophysics Division, Institute of Molecular Biosciences, University of Graz, 3Research Unit Electron Microscopic Techniques, Institute of Cell Biology, Histology, and Embryology, 4Institute of Biophysics, 5Division of Pulmonology, Department of Internal Medicine, 6Department of Anesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, AustriaAbstract: Prostacyclin analogues are standard therapeutic options for vasoconstrictive diseases, including pulmonary hypertension and Raynaud’s phenomenon. Although effective, these treatment strategies are expensive and have several side effects. To improve drug efficiency, we tested liposomal nanoparticles as carrier systems. In this study, we synthesized liposomal nanoparticles tailored for the prostacyclin analogue iloprost and evaluated their pharmacologic efficacy on mouse intrapulmonary arteries, using a wire myograph. The use of cationic lipids, stearylamine, or 1,2-di-(9Z-octadecenoyl-3-trimethylammonium-propane (DOTAP in liposomes promoted iloprost encapsulation to at least 50%. The addition of cholesterol modestly reduced iloprost encapsulation. The liposomal nanoparticle formulations were tested for toxicity and pharmacologic efficacy in vivo and ex vivo, respectively. The liposomes did not affect the viability of human pulmonary artery smooth muscle cells. Compared with an equivalent concentration of free iloprost, four out of the six polymer-coated liposomal formulations exhibited significantly enhanced vasodilation of mouse pulmonary arteries. Iloprost that was encapsulated in liposomes containing the polymer polyethylene glycol exhibited concentration-dependent relaxation of arteries. Strikingly, half the concentration of iloprost in liposomes elicited

  2. Successful amelioration of mitochondrial optic neuropathy using the yeast NDI1 gene in a rat animal model.

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    Mathieu Marella

    2010-07-01

    Full Text Available Leber's hereditary optic neuropathy (LHON is a maternally inherited disorder with point mutations in mitochondrial DNA which result in loss of vision in young adults. The majority of mutations reported to date are within the genes encoding the subunits of the mitochondrial NADH-quinone oxidoreductase, complex I. Establishment of animal models of LHON should help elucidate mechanism of the disease and could be utilized for possible development of therapeutic strategies.We established a rat model which involves injection of rotenone-loaded microspheres into the optic layer of the rat superior colliculus. The animals exhibited the most common features of LHON. Visual loss was observed within 2 weeks of rotenone administration with no apparent effect on retinal ganglion cells. Death of retinal ganglion cells occurred at a later stage. Using our rat model, we investigated the effect of the yeast alternative NADH dehydrogenase, Ndi1. We were able to achieve efficient expression of the Ndi1 protein in the mitochondria of all regions of retinal ganglion cells and axons by delivering the NDI1 gene into the optical layer of the superior colliculus. Remarkably, even after the vision of the rats was severely impaired, treatment of the animals with the NDI1 gene led to a complete restoration of the vision to the normal level. Control groups that received either empty vector or the GFP gene had no effects.The present study reports successful manifestation of LHON-like symptoms in rats and demonstrates the potential of the NDI1 gene therapy on mitochondrial optic neuropathies. Our results indicate a window of opportunity for the gene therapy to be applied successfully after the onset of the disease symptoms.

  3. The Pathway From Genes to Gene Therapy in Glaucoma: A Review of Possibilities for Using Genes as Glaucoma Drugs.

    Science.gov (United States)

    Borrás, Teresa

    2017-01-01

    Treatment of diseases with gene therapy is advancing rapidly. The use of gene therapy has expanded from the original concept of re-placing the mutated gene causing the disease to the use of genes to con-trol nonphysiological levels of expression or to modify pathways known to affect the disease. Genes offer numerous advantages over conventional drugs. They have longer duration of action and are more specific. Genes can be delivered to the target site by naked DNA, cells, nonviral, and viral vectors. The enormous progress of the past decade in molecular bi-ology and delivery systems has provided ways for targeting genes to the intended cell/tissue and safe, long-term vectors. The eye is an ideal organ for gene therapy. It is easily accessible and it is an immune-privileged site. Currently, there are clinical trials for diseases affecting practically every tissue of the eye, including those to restore vision in patients with Leber congenital amaurosis. However, the number of eye trials compared with those for systemic diseases is quite low (1.8%). Nevertheless, judg-ing by the vast amount of ongoing preclinical studies, it is expected that such number will increase considerably in the near future. One area of great need for eye gene therapy is glaucoma, where a long-term gene drug would eliminate daily applications and compliance issues. Here, we review the current state of gene therapy for glaucoma and the possibilities for treating the trabecular meshwork to lower intraocular pressure and the retinal ganglion cells to protect them from neurodegeneration. Copyright© 2017 Asia-Pacific Academy of Ophthalmology.

  4. Application of a high-throughput genotyping method for loci exclusion in non-consanguineous Australian pedigrees with autosomal recessive retinitis pigmentosa.

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    Paterson, Rachel L; De Roach, John N; McLaren, Terri L; Hewitt, Alex W; Hoffmann, Ling; Lamey, Tina M

    2012-01-01

    Retinitis pigmentosa (RP) is the most common form of inherited blindness, caused by progressive degeneration of photoreceptor cells in the retina, and affects approximately 1 in 3,000 people. Over the past decade, significant progress has been made in gene therapy for RP and related diseases, making genetic characterization increasingly important. Recently, high-throughput technologies have provided an option for reasonably fast, cost-effective genetic characterization of autosomal recessive RP (arRP). The current study used a single nucleotide polymorphism (SNP) genotyping method to exclude up to 28 possible disease-causing genes in 31 non-consanguineous Australian families affected by arRP. DNA samples were collected from 59 individuals affected with arRP and 74 unaffected family members from 31 Australian families. Five to six SNPs were genotyped for 28 genes known to cause arRP or the related disease Leber congenital amaurosis (LCA). Cosegregation analyses were used to exclude possible causative genes from each of the 31 families. Bidirectional sequencing was used to identify disease-causing mutations in prioritized genes that were not excluded with cosegregation analyses. Two families were excluded from analysis due to identification of false paternity. An average of 28.9% of genes were excluded per family when only one affected individual was available, in contrast to an average of 71.4% or 89.8% of genes when either two, or three or more affected individuals were analyzed, respectively. A statistically significant relationship between the proportion of genes excluded and the number of affected individuals analyzed was identified using a multivariate regression model (pA) and USH2A in two families (c.2276 G>T). This study has shown that SNP genotyping cosegregation analysis can be successfully used to refine and expedite the genetic characterization of arRP in a non-consanguineous population; however, this method is effective only when DNA samples are

  5. [Diagnosis of mitochondrial disorders in children with next generation sequencing].

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    Liu, Zhimei; Fang, Fang; Ding, Changhong; Zhang, Weihua; Li, Jiuwei; Yang, Xinying; Wang, Xiaohui; Wu, Yun; Wang, Hongmei; Liu, Liying; Han, Tongli; Wang, Xu; Chen, Chunhong; Lyu, Junlan; Wu, Husheng

    2015-10-01

    To explore the application value of next generation sequencing (NGS) in the diagnosis of mitochondrial disorders. According to mitochondrial disease criteria, genomic DNA was extracted using standard procedure from peripheral venous blood of patients with suspected mitochondrial disease collected from neurological department of Beijing Children's Hospital Affiliated to Capital Medical University between October 2012 and February 2014. Targeted NGS to capture and sequence the entire mtDNA and exons of the 1 000 nuclear genes related to mitochondrial structure and function. Clinical data were collected from patients diagnosed at a molecular level, then clinical features and the relationship between genotype and phenotype were analyzed. Mutation was detected in 21 of 70 patients with suspected mitochondrial disease, in whom 10 harbored mtDNA mutation, while 11 nuclear DNA (nDNA) mutation. In 21 patients, 1 was diagnosed congenital myasthenic syndrome with episodic apnea due to CHAT gene p.I187T homozygous mutation, and 20 were diagnosed mitochondrial disease, in which 10 were Leigh syndrome, 4 were mitochondrial encephalomyopathy with lactic acidosis and stroke like episodes syndrome, 3 were Leber hereditary optic neuropathy (LHON) and LHON plus, 2 were mitochondrial DNA depletion syndrome and 1 was unknown. All the mtDNA mutations were point mutations, which contained A3243G, G3460A, G11778A, T14484C, T14502C and T14487C. Ten mitochondrial disease patients harbored homozygous or compound heterozygous mutations in 5 genes previously shown to cause disease: SURF1, PDHA1, NDUFV1, SUCLA2 and SUCLG1, which had 14 mutations, and 7 of the 14 mutations have not been reported. NGS has a certain application value in the diagnosis of mitochondrial diseases, especially in Leigh syndrome atypical mitochondrial syndrome and rare mitochondrial disorders.

  6. The Eye Drop Preservative Benzalkonium Chloride Potently Induces Mitochondrial Dysfunction and Preferentially Affects LHON Mutant Cells.

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    Datta, Sandipan; Baudouin, Christophe; Brignole-Baudouin, Francoise; Denoyer, Alexandre; Cortopassi, Gino A

    2017-04-01

    Benzalkonium chloride (BAK) is the most commonly used eye drop preservative. Benzalkonium chloride has been associated with toxic effects such as "dry eye" and trabecular meshwork degeneration, but the underlying biochemical mechanism of ocular toxicity by BAK is unclear. In this study, we propose a mechanistic basis for BAK's adverse effects. Mitochondrial O2 consumption rates of human corneal epithelial primary cells (HCEP), osteosarcoma cybrid cells carrying healthy (control) or Leber hereditary optic neuropathy (LHON) mutant mtDNA [11778(G>A)], were measured before and after acute treatment with BAK. Mitochondrial adenosine triphosphate (ATP) synthesis and cell viability were also measured in the BAK-treated control: LHON mutant and human-derived trabecular meshwork cells (HTM3). Benzalkonium chloride inhibited mitochondrial ATP (IC50, 5.3 μM) and O2 consumption (IC50, 10.9 μM) in a concentration-dependent manner, by directly targeting mitochondrial complex I. At its pharmaceutical concentrations (107-667 μM), BAK inhibited mitochondrial function >90%. In addition, BAK elicited concentration-dependent cytotoxicity to cybrid cells (IC50, 22.8 μM) and induced apoptosis in HTM3 cells at similar concentrations. Furthermore, we show that BAK directly inhibits mitochondrial O2 consumption in HCEP cells (IC50, 3.8 μM) at 50-fold lower concentrations than used in eye drops, and that cells bearing mitochondrial blindness (LHON) mutations are further sensitized to BAK's mitotoxic effect. Benzalkonium chloride inhibits mitochondria of human corneal epithelial cells and cells bearing LHON mutations at pharmacologically relevant concentrations, and we suggest this is the basis of BAK's ocular toxicity. Prescribing BAK-containing eye drops should be avoided in patients with mitochondrial deficiency, including LHON patients, LHON carriers, and possibly primary open-angle glaucoma patients.

  7. Bicistronic lentiviruses containing a viral 2A cleavage sequence reliably co-express two proteins and restore vision to an animal model of LCA1.

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    Jonathan D Verrier

    Full Text Available The disease processes underlying inherited retinal disease are complex and are not completely understood. Many of the corrective gene therapies designed to treat diseases linked to mutations in genes specifically expressed in photoreceptor cells restore function to these cells but fail to stop progression of the disease. There is growing consensus that effective treatments for these diseases will require delivery of multiple therapeutic proteins that will be selected to treat specific aspects of the disease process. The purpose of this study was to design a lentiviral transgene that reliably expresses all of the proteins it encodes and does so in a consistent manner among infected cells. We show, using both in vitro and in vivo analyses, that bicistronic lentiviral transgenes encoding two fluorescent proteins fused to a viral 2A-like cleavage peptide meet these expression criteria. To determine if this transgene design is suitable for therapeutic applications, we replaced one of the fluorescent protein genes with the gene encoding guanylate cyclase-1 (GC1 and delivered lentivirus carrying this transgene to the retinas of the GUCY1*B avian model of Leber congenital amaurosis-1 (LCA1. GUCY1*B chickens carry a null mutation in the GC1 gene that disrupts photoreceptor function and causes blindness at hatching, a phenotype that closely matches that observed in humans with LCA1. We found that treatment of these animals with the 2A lentivector encoding GC1 restored vision to these animals as evidenced by the presence of optokinetic reflexes. We conclude that 2A-like peptides, with proper optimization, can be successfully incorporated into therapeutic vectors designed to deliver multiple proteins to neural retinal. These results highlight the potential of this vector design to serve as a platform for the development of combination therapies designed to enhance or prolong the benefits of corrective gene therapies.

  8. Exome sequencing of index patients with retinal dystrophies as a tool for molecular diagnosis.

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    Marta Corton

    Full Text Available Retinal dystrophies (RD are a group of hereditary diseases that lead to debilitating visual impairment and are usually transmitted as a Mendelian trait. Pathogenic mutations can occur in any of the 100 or more disease genes identified so far, making molecular diagnosis a rather laborious process. In this work we explored the use of whole exome sequencing (WES as a tool for identification of RD mutations, with the aim of assessing its applicability in a diagnostic context.We ascertained 12 Spanish families with seemingly recessive RD. All of the index patients underwent mutational pre-screening by chip-based sequence hybridization and resulted to be negative for known RD mutations. With the exception of one pedigree, to simulate a standard diagnostic scenario we processed by WES only the DNA from the index patient of each family, followed by in silico data analysis. We successfully identified causative mutations in patients from 10 different families, which were later verified by Sanger sequencing and co-segregation analyses. Specifically, we detected pathogenic DNA variants (∼50% novel mutations in the genes RP1, USH2A, CNGB3, NMNAT1, CHM, and ABCA4, responsible for retinitis pigmentosa, Usher syndrome, achromatopsia, Leber congenital amaurosis, choroideremia, or recessive Stargardt/cone-rod dystrophy cases.Despite the absence of genetic information from other family members that could help excluding nonpathogenic DNA variants, we could detect causative mutations in a variety of genes known to represent a wide spectrum of clinical phenotypes in 83% of the patients analyzed. Considering the constant drop in costs for human exome sequencing and the relative simplicity of the analyses made, this technique could represent a valuable tool for molecular diagnostics or genetic research, even in cases for which no genotypes from family members are available.

  9. Dysregulated mitophagy and mitochondrial organization in optic atrophy due to OPA1 mutations.

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    Liao, Chunyan; Ashley, Neil; Diot, Alan; Morten, Karl; Phadwal, Kanchan; Williams, Andrew; Fearnley, Ian; Rosser, Lyndon; Lowndes, Jo; Fratter, Carl; Ferguson, David J P; Vay, Laura; Quaghebeur, Gerardine; Moroni, Isabella; Bianchi, Stefania; Lamperti, Costanza; Downes, Susan M; Sitarz, Kamil S; Flannery, Padraig J; Carver, Janet; Dombi, Eszter; East, Daniel; Laura, Matilde; Reilly, Mary M; Mortiboys, Heather; Prevo, Remko; Campanella, Michelangelo; Daniels, Matthew J; Zeviani, Massimo; Yu-Wai-Man, Patrick; Simon, Anna Katharina; Votruba, Marcela; Poulton, Joanna

    2017-01-10

    To investigate mitophagy in 5 patients with severe dominantly inherited optic atrophy (DOA), caused by depletion of OPA1 (a protein that is essential for mitochondrial fusion), compared with healthy controls. Patients with severe DOA (DOA plus) had peripheral neuropathy, cognitive regression, and epilepsy in addition to loss of vision. We quantified mitophagy in dermal fibroblasts, using 2 high throughput imaging systems, by visualizing colocalization of mitochondrial fragments with engulfing autophagosomes. Fibroblasts from 3 biallelic OPA1(-/-) patients with severe DOA had increased mitochondrial fragmentation and mitochondrial DNA (mtDNA)-depleted cells due to decreased levels of OPA1 protein. Similarly, in siRNA-treated control fibroblasts, profound OPA1 knockdown caused mitochondrial fragmentation, loss of mtDNA, impaired mitochondrial function, and mitochondrial mislocalization. Compared to controls, basal mitophagy (abundance of autophagosomes colocalizing with mitochondria) was increased in (1) biallelic patients, (2) monoallelic patients with DOA plus, and (3) OPA1 siRNA-treated control cultures. Mitophagic flux was also increased. Genetic knockdown of the mitophagy protein ATG7 confirmed this by eliminating differences between patient and control fibroblasts. We demonstrated increased mitophagy and excessive mitochondrial fragmentation in primary human cultures associated with DOA plus due to biallelic OPA1 mutations. We previously found that increased mitophagy (mitochondrial recycling) was associated with visual loss in another mitochondrial optic neuropathy, Leber hereditary optic neuropathy (LHON). Combined with our LHON findings, this implicates excessive mitochondrial fragmentation, dysregulated mitophagy, and impaired response to energetic stress in the pathogenesis of mitochondrial optic neuropathies, potentially linked with mitochondrial mislocalization and mtDNA depletion. Copyright © 2016 The Author(s). Published by Wolters Kluwer Health, Inc

  10. Treatment strategies for inherited optic neuropathies: past, present and future.

    Science.gov (United States)

    Yu-Wai-Man, P; Votruba, M; Moore, A T; Chinnery, P F

    2014-05-01

    Bilateral visual loss secondary to inherited optic neuropathies is an important cause of registrable blindness among children and young adults. The two prototypal disorders seen in clinical practice are Leber hereditary optic neuropathy (LHON) and autosomal dominant optic atrophy (DOA). About 90% of LHON cases are due to one of three mitochondrial DNA (mtDNA) point mutations: m.3460G>A, m.11778G>A, and m.14484T>C, which affect critical complex I subunits of the mitochondrial respiratory chain. The majority of patients with DOA harbour pathogenic mutations within OPA1, a nuclear gene that codes for a multifunctional inner mitochondrial membrane protein. Despite their contrasting genetic basis, LHON and DOA share overlapping pathological and clinical features that serve to highlight the striking tissue-specific vulnerability of the retinal ganglion cell (RGC) layer to disturbed mitochondrial function. In addition to severe visual loss secondary to progressive optic nerve degeneration, a subgroup of patients will also develop a more aggressive syndromic phenotype marked by significant neurological deficits. The management of LHON and DOA remains largely supportive, but major advances in our understanding of the mechanisms underpinning RGC loss in these two disorders are paving the way for novel forms of treatment aimed at halting or reversing visual deterioration at different stages of the disease process. In addition to neuroprotective strategies for rescuing RGCs from irreversible cell death, innovative in vitro fertilisation techniques are providing the tantalising prospect of preventing the germline transmission of pathogenic mtDNA mutations, eradicating in so doing the risk of disease in future generations.

  11. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration.

    Science.gov (United States)

    Ma, Hongwei; Yang, Fan; Butler, Michael R; Belcher, Joshua; Redmond, T Michael; Placzek, Andrew T; Scanlan, Thomas S; Ding, Xi-Qin

    2017-08-01

    Thyroid hormone (TH) signaling regulates cell proliferation, differentiation, and metabolism. Recent studies have implicated TH signaling in cone photoreceptor viability. Using mouse models of retinal degeneration, we demonstrated that antithyroid drug treatment and targeting iodothyronine deiodinases (DIOs) to suppress cellular tri-iodothyronine (T3) production or increase T3 degradation preserves cones. In this work, we investigated the effectiveness of inhibition of the TH receptor (TR). Two genes, THRA and THRB , encode TRs; THRB 2 has been associated with cone viability. Using TR antagonists and Thrb2 deletion, we examined the effects of TR inhibition. Systemic and ocular treatment with the TR antagonists NH-3 and 1-850 increased cone density by 30-40% in the Rpe65 -/- mouse model of Leber congenital amaurosis and reduced the number of TUNEL + cells. Cone survival was significantly improved in Rpe65 -/- and Cpfl1 (a model of achromatopsia with Pde6c defect) mice with Thrb2 deletion. Ventral cone density in Cpfl1/Thrb2 -/- and Rpe65 -/- / Thrb2 -/- mice was increased by 1- to 4-fold, compared with age-matched controls. Moreover, the expression levels of TR were significantly higher in the cone-degeneration retinas, suggesting locally elevated TR signaling. This work shows that the effects of antithyroid treatment or targeting DIOs were likely mediated by TRs and that suppressing TR protects cones. Our findings support the view that inhibition of TR locally in the retina is a therapeutic strategy for retinal degeneration management.-Ma, H., Yang, F., Butler, M. R., Belcher, J., Redmond, T. M., Placzek, A. T., Scanlan, T. S., Ding, X.-Q. Inhibition of thyroid hormone receptor locally in the retina is a therapeutic strategy for retinal degeneration. © FASEB.

  12. Investigations on the bioavailability of traffic-related platinum group elements (PGE) to the aquatic fauna with special consideration being given to palladium; Untersuchungen zur Bioverfuegbarkeit Kfz-emittierter Platingruppenelemente (PGE) fuer die aquatische Fauna unter besonderer Beruecksichtigung von Palladium

    Energy Technology Data Exchange (ETDEWEB)

    Sures, B.; Thielen, F.; Zimmermann, S. [Karlsruhe Univ. (T.H.) (Germany). Zoologisches Inst.

    2002-07-01

    The uptake and accumulation of the traffic-related platinum group elements (PGE) Pt, Pd and Rh by the aquatic fauna was investigated. Zebra mussels, eels and barbels were maintained in water containing either road dust or ground catalytic converter material. Following the exposure, samples of fish liver and kidney, as well as the soft tissues of the mussels, were analysed. Our results revealed that all three catalytic noble metals were accumulated by aquatic organisms. The highest bioavailability was found for Pd, followed by Pt and Rh. The concentration factor of Pd for Dreissena polymorpha was 5 times higher compared with Pb and only 6 times lower than the essential element Cu. With regard to the increasing emission of Pd the level of this metal has to be monitored very carefully in the environment. (orig.) [German] Die Aufnahme und Anreicherung der Kfz-buertigen Platingruppenelemente (PGE) Pt, Pd und Rh durch aquatische Tiere wurde an Dreikantmuscheln, Aalen und Barben untersucht. Hierzu wurden die Testorganismen in Wasser mit Strassenstaub einer stark befahrenen Strasse oder mit zerriebenem Autokatalysatormaterial ueber mehrere Wochen exponiert und anschliessend Leber und Niere der Fische sowie das Weichgewebe der Muscheln analysiert. Im Rahmen dieser Studien konnte nachgewiesen werden, dass alle drei Edelmetalle durch Fische wie durch Muscheln aufgenommen und angereichert werden. Fuer Pd fand sich die hoechste Bioverfuegbarkeit, gefolgt von Pt und Rh. Das Ausmass der Aufnahme von Pd durch Dreissena polymorpha war ca. 5fach hoeher als von Pb und 6fach niedriger verglichen mit dem essenziellen Element Cu. In Anbetracht der steigenden Emission von Pd sollte ein Umweltmonitoring die Verbreitung von Pd in der Umwelt klaeren. (orig.)

  13. Environmental medicine disaster - which medical knowledge is to be derived from their analysis? Pt. 3. Yusho (oil disease); Umweltmedizinische Katastrophen - Welche medizinischen Erkenntnisse bringt ihre Analyse. Teil 3. Yusho-Krankheit (Oelkrankheit)

    Energy Technology Data Exchange (ETDEWEB)

    Seidel, H.J.; Krefeldt, T. [Ulm Univ. (Germany). Inst. fuer Arbeits-, Sozial- und Umweltmedizin

    1999-02-01

    der Erhitzung, erheblich mit polychlorierten Dibenzofuranen und weiteren chlororganischen Verbindungen kontaminiert - die genaue chemische Analyse von Asservaten erfolgte wesentlich spaeter. Im Biomonitoring konnten die Kontaminanten im Blut, Fettgewebe und der Leber der betroffenen Personen festgestellt werden. Die Intoxikation erwies sich as teratogen und fetotoxisch, beim Mortalitaetsspektrum der erwachsenen Opfer fiel lediglich ein vermehrtes Auftreten von Lebertumoren auf. Der Vorfall gab in Japan den entscheidenen Anstoss, sich mit den vielfaeltig eingesetzten PCBs auch oekotoxikologisch zu befassen. Es enstanden umweltmedizinische Regelwerke, schliesslich wurde 1972 ein generelles PCB-Verbot ausgesprochen. (orig.)

  14. Incidence and significance of small focal liver lesions on MRI; Haeufigkeit und Bedeutung von kleinen fokalen Leberlaesionen in der MRT

    Energy Technology Data Exchange (ETDEWEB)

    Kreft, B.; Pauleit, D.; Bachmann, R.; Conrad, R.; Kraemer, A.; Schild, H.H. [Bonn Univ. (Germany). Radiologische Klinik

    2001-05-01

    Analysis of the frequency and significance of small focal liver lesions ({<=} 2 cm) detected on MRI in the presence or absence of a history of malignancy. Methods: 628 MRI examinations of the liver performed during 1994 - 1996 were evaluated. The inclusion criterion into the study was the detection of a focal liver lesion with a size {<=} 2 cm. The frequency, the size, the diagnostic proof, and the differential diagnosis of the focal liver lesions were analysed with regard to the patients history of a known malignant tumor. Results: Overall, 179 of the 628 patients (28.5%) had focal liver lesions {<=} 2 cm (n = 338). 58.9% of the lesions could be classified based upon follow-up studies by ultrasound, CT or MRI, or by biopsy. The remaining 41.1% of the lesions could not be classified due to the absence of follow-up examinations. 57.3% of all proven lesions were benign and 42.7% were malignant. A history of a malignant tumor was present in 76.7% of all patients with small liver lesions; however, lesions were benign in these patients in 50.6% of the cases. In patients with no known history of a malignancy, 75% of the lesions were benign and 25% were malignant. However, these malignant lesions were in 10/11 cases hepatocellular carcinomas in patients with liver cirrhosis. (orig.) [German] Analyse der Haeufigkeit und der Bedeutung von kleinen Leberlaesionen ({<=} 2 cm) in der MRT in Abhaengigkeit einer vorbestehenden Tumoranamnese. Methode: Es wurden insgesamt 628 MRT-Untersuchungen der Leber aus dem Zeitraum von 1994-1996 ausgewertet. Einschlusskriterium in die Studie war der Nachweis von Leberlaesionen mit einer Groe paragraph e {<=} 2 cm, wobei die Haeufigkeit, die Groe paragraph enverteilung, die Diagnosesicherung und die Differenzialdiagnose in Abhaengigkeit von der Anamnese einer Tumorerkrankung untersucht wurden. Ergebnisse: Insgesamt wiesen 179 der 628 Patienten (28,5%) fokale Leberlaesionen {<=} 2 cm (n = 338) auf. 58,9% der Laesionen konnten aufgrund von

  15. Abdominal polytrauma and parenchymal organs; Abdominelles Polytrauma und Parenchymorgane

    Energy Technology Data Exchange (ETDEWEB)

    Krestan, C.R. [Medizinische Universitaet Wien AKH, Abteilung fuer Allgemeine Radiologie und Kinderradiologie, Klinik fuer Radiologie und Nuklearmedizin, Wien (Austria)

    2014-09-15

    enormer Bedeutung fuer die Prognose und Therapie polytraumatisierter Patienten. Die Verletzungsmuster sind komplex und erfordern eine grosse Erfahrung, um sie in Minutenschnelle analysieren zu koennen. Im nachfolgenden Uebersichtsartikel werden die radiologische Diagnostik und die klinisch-radiologische Graduierung der Verletzungen von Milz, Leber, Pankreas und Nieren beschrieben. Es wird der Stellenwert der Ultraschalldiagnostik bei der Abklaerung von Polytraumapatienten beschrieben. Fuer die oben genannten Organe werden die wichtigsten traumaassoziierten Veraenderungen in der Computertomographie beschrieben und in Form praegnanter Fallbeispiele veranschaulicht. Ultraschallkontrastmittel koennen diagnostisch wertvolle Zusatzinformationen beim Focused-Assessment-Sonography-for-Trauma(FAST)-Scan der Parenchymorgane liefern. Die Computertomographie hat sich als bildgebendes Standardverfahren zur Abklaerung von Polytraumapatienten etabliert. Innovative organadaptierte Protokolle und Kontrastmittelapplikationen verbessern die diagnostische Treffsicherheit der Multidetektor(MD)-CT. Einsatz des FAST-Scans in Abstimmung mit den anderen klinischen Faechern des Traumateams als Screeningmethode. Die Anwendung der MDCT ist traumaabhaengig, und die Klassifizierung des Verletzungsgrads der parenchymatoesen Organe ist letztendlich fuer die weitere Therapie und Prognose entscheidend. (orig.)

  16. Local ablative radiotherapy of oligometastatic colorectal cancer; Moeglichkeiten der lokal-ablativen Bestrahlung (SBRT) bei metastasiertem kolorektalem Karzinom

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, C. [Universitaetsklinikum Hamburg-Eppendorf, Klinik fuer Strahlentherapie und Radioonkologie, Hamburg (Germany); Universitaetsklinikum Hamburg-Eppendorf, Ambulanzzentrum, Hamburg (Germany); Gauer, T. [Universitaetsklinikum Hamburg-Eppendorf, Klinik fuer Strahlentherapie und Radioonkologie, Hamburg (Germany)

    2017-02-15

    nur eingeschraenkt anwendbar. Die stereotaktische Bestrahlung ist eine strahlentherapeutische Technik, mit der in wenigen Sitzungen und sehr geringer Toxizitaet eine lang anhaltende Metastasenkontrolle erreicht werden kann. Was ist die Evidenz zur stereotaktischen Bestrahlung von Patienten mit metastasiertem kolorektalem Karzinom? Wie ist der Einfluss der SBRT auf die lokale Kontrolle von Leber- und Lungenmetastasen. Welche Nebenwirkungen koennen auftreten. Literatursuche nach prospektiven und retrospektiven Studien. Die stereotaktische Radiotherapie bei Patienten mit metastasiertem kolorektalem Karzinom ist eine valide Therapieoption und sollte in der klinischen Praxis als Alternative zur Metastasenchirurgie und anderen lokal ablativen Verfahren erwogen werden. (orig.)

  17. [Early therapeutic trials for retinitis pigmentosa].

    Science.gov (United States)

    Dufier, Jean-Louis

    2003-01-01

    Non syndromic forms of Retinitis Pigmentosa (RP) constitute a collection of clinically and genetically heterogeneous inherited retinal degenerative diseases. They are characterized by a bilateral progressive visual loss susceptible to cause blindness. These diseases are transmitted through pedigrees according to all known modes of inheritance. They are bilateral and usually start during infancy. However, very early clinical presentations exist, such as those observed in children affected by Leber Congenital Amaurosis, as well as late onset autosomal dominant forms of retinitis pigmentosa. The characteristic clinical aspect of the rod-cone RP dystrophies is marked by alterations of the peripheral retina associated with a night blindness and a progressive narrowing of the visual field. The ophthalmoscopic examination of RP patients commonly reveals thin retinal arteries and scattered pigmentary accumulations. In contrast, there are cone rod retinal dystrophies whose onset is marked by a decreased visual acuity before the appearance of any visual field alteration. Some forms of RPs display an ocular fundus devoid of any pigmentary alteration. Syndromic forms of RPs are not uncommon. The association of deafness with RP is detected in nearly 30% of the patients. Other associations with RP can include mental deficiency, facial dysmorphy, microcephaly, obesity, kidney deficiency, immune deficiencies, metabolic disorders. The existence of such syndromic forms of RP localizes RPs at the crossroad of several medical specialties. A long lasting collaboration between our department of ophthalmology and the department of medical genetics of the Necker-Sick Children Hospital has allowed us to establish numerous genotype-phenotype correlations, especially in LCA and Stargardt's disease. ABCR gene mutations cause Stargardt disease. ABCR mutations may also cause some types of Ages Related Macular Degenerations (AMD). Nowadays, there is no known efficient therapy available for

  18. Prescreening whole exome sequencing results from patients with retinal degeneration for variants in genes associated with retinal degeneration

    Directory of Open Access Journals (Sweden)

    Bryant L

    2017-12-01

    heterozygous mutation identified that would cause recessive disease and 13% had no obviously pathogenic variants and no family members available to perform segregation analysis. Eleven subjects are good candidates for novel gene discovery. Two de novo mutations were identified that resulted in dominant retinal degeneration.Conclusion: Whole exome sequencing allows for thorough genetic analysis of candidate genes as well as novel gene discovery. It allows for an unbiased analysis of genetic variants to reduce the chance that the pathogenic mutation will be missed due to incomplete or inaccurate family history or analysis at the early stage of a syndromic form of retinal degeneration. Keywords: retinal degeneration, genetic diagnosis, retinitis pigmentosa, Leber congenital amaurosis, cone–rod dystrophy, whole exome sequencing

  19. Intraoperative radiotherapy (IORT) for locally advanced or recurrent renal cell carcinoma; Intraoperative Radiotherapie (IORT) lokal ausgedehnter und rezidivierter Nierenzellkarzinome

    Energy Technology Data Exchange (ETDEWEB)

    Eble, M.J.; Wannenmacher, M. [Radiologische Klinik, Ruprecht-Karls-Univ. Heidelberg (Germany); Staehler, G. [Urologische Klinik, Ruprecht-Karls-Univ. Heidelberg (Germany)

    1998-01-01

    Mittel 11,5 Monaten an einer Fernmetastasierung (Lunge, Leber, Knochen, Mediastinum) verstorben. Das mittlere progressionsfreie Intervall betrug 6,4 Monate. Ein Patient verstarb an einem Zweikarzinom. Zwei Patienten leben mit Fernmetastasen. Alle Patienten waren zum Ende der Nachbeobachtung lokal tumorfrei. Das errechnete Vier-Jahres-Gesamt- und rezidivfreie Ueberleben betrug 47% bzw. 34%. Der postoperative Verlauf war bei drei Patienten beeintraechtigt (Abszess n=1, Bauchwandnahtdehiszenz n=2). Die gastrointestinale Toxizitaet der perkutanen Radiotherapie war gering. IORT-eigene Spaeteffekte wurden nicht beobachtet. (orig./MG)

  20. Mitochondrial optic neuropathies – Disease mechanisms and therapeutic strategies

    Science.gov (United States)

    Yu-Wai-Man, Patrick; Griffiths, Philip G.; Chinnery, Patrick F.

    2011-01-01

    Leber hereditary optic neuropathy (LHON) and autosomal-dominant optic atrophy (DOA) are the two most common inherited optic neuropathies in the general population. Both disorders share striking pathological similarities, marked by the selective loss of retinal ganglion cells (RGCs) and the early involvement of the papillomacular bundle. Three mitochondrial DNA (mtDNA) point mutations; m.3460G>A, m.11778G>A, and m.14484T>C account for over 90% of LHON cases, and in DOA, the majority of affected families harbour mutations in the OPA1 gene, which codes for a mitochondrial inner membrane protein. Optic nerve degeneration in LHON and DOA is therefore due to disturbed mitochondrial function and a predominantly complex I respiratory chain defect has been identified using both in vitro and in vivo biochemical assays. However, the trigger for RGC loss is much more complex than a simple bioenergetic crisis and other important disease mechanisms have emerged relating to mitochondrial network dynamics, mtDNA maintenance, axonal transport, and the involvement of the cytoskeleton in maintaining a differential mitochondrial gradient at sites such as the lamina cribosa. The downstream consequences of these mitochondrial disturbances are likely to be influenced by the local cellular milieu. The vulnerability of RGCs in LHON and DOA could derive not only from tissue-specific, genetically-determined biological factors, but also from an increased susceptibility to exogenous influences such as light exposure, smoking, and pharmacological agents with putative mitochondrial toxic effects. Our concept of inherited mitochondrial optic neuropathies has evolved over the past decade, with the observation that patients with LHON and DOA can manifest a much broader phenotypic spectrum than pure optic nerve involvement. Interestingly, these phenotypes are sometimes clinically indistinguishable from other neurodegenerative disorders such as Charcot-Marie-Tooth disease, hereditary spastic

  1. Profound vision loss impairs psychological well-being in young and middle-aged individuals.

    Science.gov (United States)

    Garcia, Giancarlo A; Khoshnevis, Matin; Gale, Jesse; Frousiakis, Starleen E; Hwang, Tiffany J; Poincenot, Lissa; Karanjia, Rustum; Baron, David; Sadun, Alfredo A

    2017-01-01

    The aim of this study was to evaluate the effects of profound vision loss on psychological well-being in adolescents, young adults, and middle-aged adults with regard to mood, interpersonal interactions, and career-related goals. In addition, we assessed the significance of the resources that may be used to enhance psychological well-being in cases of profound vision loss, and in particular, examined the utility of low vision aids and the role of the ophthalmologist as a provider of emotional support. A questionnaire was issued to individuals aged 13-65 years with profound vision loss resulting from Leber's hereditary optic neuropathy (LHON). Depression prevalence was evaluated with questions regarding major depressive disorder symptomatology. Participants appraised the effects of vision loss on their interpersonal interactions and career goals by providing an impact rating (IR) on a 21-point psychometric scale from -10 to +10. Social well-being index was defined as the average of interpersonal IR and career IR. Subjects were additionally asked about the use of low vision aids and sources of emotional support. A total of 103 participants (mean age =26.4±11.2 years at LHON diagnosis; mean ± standard deviation) completed the questionnaire. Nearly half (49.5%) met the depression criteria after vision loss. Negative impacts on interpersonal interactions (median IR = -5) and career goals (median IR = -6) were observed; both ratings were worse ( P negative interpersonal IR and career IR. Sixty-eight percent of subjects used electronic vision aids; controlling for age, social well-being index was higher among these individuals than for those who did not use electronic aids ( P =0.03). Over half of the participants (52.4%) asserted that they derived emotional support from their ophthalmologist. Profound vision loss in adolescents, young adults, and middle-aged adults is associated with significant negative psychological and psychosocial effects, which are influenced by

  2. Modern imaging of liver metastases; Moderne Bildgebung der Lebermetastasen

    Energy Technology Data Exchange (ETDEWEB)

    Breitenseher, J.; Pones, M.; Wengert, G.; Ba-Ssalamah, A. [Medizinische Universitaet Wien, Universitaetsklinik fuer Radiologie und Nuklearmedizin, Allgemeines Krankenhaus, Wien (Austria)

    2015-01-01

    The liver is the second most common location of metastases following the lymph nodes. The accurate characterization of focal liver lesions in oncology patients is especially important because of the high prevalence of benign liver lesions and the possibility of co-existing benign and malignant lesions. The exact interpretation of these lesions is crucial for therapeutic decisions and thus for the prognosis of the patient. It is essential to detect all focal liver lesions and to distinguish benign from malignant lesions, especially in the management of oncology patients. Numerous imaging modalities are available for these challenges in the daily routine. An extensive understanding of the advantages and limitations of the various imaging modalities and knowledge of the morphology and the typical and atypical appearances of the different metastases is important. This review explains the radiological criteria for various metastases in different modalities. To evaluate the individual prognosis and risk assessment preoperatively, functional imaging is necessary. These personalized pretherapeutic diagnostics are discussed. (orig.) [German] Die Leber stellt nach den Lymphknoten die zweithaeufigste Lokalisation von Metastasen dar. Aufgrund der hohen Praevalenz gutartiger Leberlaesionen ist die genaue Charakterisierung fokaler Leberlaesionen bei Patienten mit bekanntem Malignom besonders wichtig, da maligne und benigne Tumoren koexistieren koennen. Die eindeutige Zuordnung dieser Laesionen ist entscheidend fuer die Therapie und somit die Prognose des Patienten. Insbesondere fuer das Management onkologischer Patienten ist es daher essenziell, alle fokalen Leberlaesionen zu detektieren und zwischen benignen und malignen zu differenzieren. Um dieser Anforderung im radiologischen Alltag nachzukommen, stehen derzeit zahlreiche Bildgebungsmodalitaeten zur Verfuegung. Daher sind sowohl ein tiefgreifendes Verstaendnis der Vorteile und Limitationen der verschiedenen diagnostischen

  3. Introduction to genetics in ophthalmology, value of family studies

    Science.gov (United States)

    Ohba

    2000-05-01

    This paper reviews the author's personal experience with genetic eye diseases and discusses the significance of family studies in providing key information for the advancement of molecular research. Choroideremia: This disease has long been known as an X-linked progressive tapetoretinal degeneration, but it was first described in Japan in 1974 after finding asymptomatic fundus changes in heterozygous female carriers that are compatible with X chromosomal inactivation. Mutations in the disease-causing gene (REP-1) provide a clue to the diagnosis and pathophysiology of the disease.Leber's Hereditary Optic Neuropathy: The clinical expression is so variable among affected individuals and families that mild optic nerve disease of insidious onset should be differentiated from autosomal dominant optic atrophy. Molecular assessment of mitochondrial DNA leads to a definite diagnosis of the disease, but mitochondrial DNA mutations do not fully account for the clinical manifestation and phenotypic variability of the disease.Norrie Disease: This rare X-linked vitreoretinal dysplasia, characterized by congenital bilateral blindness, was documented in Japan some twenty years ago and the disease has been identified in four unrelated Japanese families. The disease, once diagnosed on the basis of elaborate clinical and familial studies, can now be defined by molecular assessment of the Norrie disease gene.Congenital Nystagmus: A four-generation family was described which presented with autosomal dominantly inherited congenital nystagmus, peripheral corneal opacity, and foveal hypoplasia without any iris tissue malformation. The diagnosis of this family was established by detection of a missense mutation in the paired domain of the PAX 6 gene, hence conforming to a forme fruste of congenital aniridia.Sorsby's Fundus Dystrophy: Two Japanese families with Sorsby's fundus dystrophy showed late-onset retinal dystrophy characterized by submacular hemorrhage and atrophy. Our patients

  4. [Introduction to genetics in ophthalmology. Value of family studies].

    Science.gov (United States)

    Ohba, N

    1999-12-01

    This paper reviews the author's personal experience with genetic eye diseases and discusses the significance of family studies in providing key information for the advancement of molecular research. CHOROIDEREMIA: This disease has long been known as an X-linked progressive tapetoretinal degeneration, but it was first described in Japan in 1974 after finding asymptomatic fundus changes in heterozygous female carriers that are compatible with X chromosomal inactivation. Mutations in the disease-causing gene (REP-1) provide a clue to the diagnosis and pathophysiology of the disease. LEBER'S HEREDITARY OPTIC NEUROPATHY: The clinical expression is so variable among affected individuals and families that mild optic nerve disease of insidious onset should be differentiated from autosomal dominant optic atrophy. Molecular assessment of mitochondrial DNA leads to a definite diagnosis of the disease, but mitochondrial DNA mutations do not fully account for the clinical manifestation and phenotypic variability of the disease. NORRIE DISEASE: This rare X-linked vitreoretinal dysplasia, characterized by congenital bilateral blindness, was documented in Japan some twenty years ago and the disease has been identified in four unrelated Japanese families. The disease, once diagnosed on the basis of elaborate clinical and familial studies, can now be defined by molecular assessment of the Norrie disease gene. CONGENITAL NYSTAGMUS: A four-generation family was described which presented with autosomal dominantly inherited congenital nystagmus, peripheral corneal opacity, and foveal hypoplasia without any iris tissue malformation. The diagnosis of this family was established by detection of a missense mutation in the paired domain of the PAX 6 gene, hence conforming to a forme fruste of congenital aniridia. SORSBY'S FUNDUS DYSTROPHY: Two Japanese families with Sorsby's fundus dystrophy showed late-onset retinal dystrophy characterized by submacular hemorrhage and atrophy. Our patients

  5. Epidemic optic neuropathy in Cuba. Eye findings.

    Science.gov (United States)

    Sadun, A A; Martone, J F; Muci-Mendoza, R; Reyes, L; DuBois, L; Silva, J C; Roman, G; Caballero, B

    1994-05-01

    To characterize and establish a clinical definition of the optic neuropathy that appeared in epidemic form in Cuba in 1992 and 1993. At the invitation of the Cuban Ministry of Health, Havana, members of ORBIS International and the Pan American Health Organization, assembled teams that traveled to Cuba in May 1993. We were initially briefed by Cuban national experts in the areas of virology, nutrition, toxicology, ophthalmology, neurology, and public health. We then examined 20 patients on our own. Thirteen of these patients underwent a comprehensive neuro-ophthalmologic examination, including neurologic examination, ophthalmologic examination, visual fields, optic nerve function studies, contrast sensitivity studies, and funduscopy. We returned 4 months later to perform an additional 12 comprehensive neuro-ophthalmologic and follow-up examinations. Only seven of the 13 patients who were alleged to have the optic form of the epidemic and who were rigorously and systematically examined on the first visit demonstrated a bilateral optic neuropathy. These seven patients had several features that included decreased visual acuity, poor color vision, central scotomas, decreased contrast sensitivity, saccadic eye movements, and most prominent and distinctive of all, nerve fiber layer wedge defects of the papillomacular bundle. Our clinical definition was then implemented by the Cuban ophthalmologists and epidemiologists. On returning 4 months later, we found that all newly presented patients were correctly diagnosed to have the epidemic disease. With the new case definition and the application of a few simple psychophysical tests, the false-positive rate of diagnosis became much lower. After vitamin therapy, we reexamined the patients seen on our initial visit, and all showed marked improvement. The Cuban epidemic was characterized by an optic neuropathy with features that were similar to those of tobacco/alcohol amblyopia and Leber's optic atrophy. Recent political

  6. TIPSS: 10 years of experience; TIPSS: 10 Jahre klinische Erfahrung

    Energy Technology Data Exchange (ETDEWEB)

    Richter, G.M.; Brado, M.; Simon, C.; Radeleff, B.; Kauffmann, G.W. [Heidelberg Univ. (Germany). Abt. Radiodiagnostik; Noeldge, G.; Scharf, J.; Hansmann, J.

    1998-04-01

    Purpose: To demonstrate and document 10 years of clinical experience gathered by us with TIPSS and to discuss achievements, problems and outlook. Results: Variceal filling was widely reduced by TIPSS, and significantly reduced portal liver perfusion as assessed morphologically and rheologically. However, there was an immediate onset of compensated liver perfusion by increased arterial inflow. Total liver perfusion did not change significantly. In TIPSS portal decompression was readily achieved, the portosystemic gradient dropping from an average of 24 mm Hg to 10.5 mm Hg. In our series we could not demonstrate an increased incidence of hepatic encephalopathy during the 30-day post-TIPSS period. Early mortality was 4% and early rebleeding rate 3%. The 12-month re-intervention rate based on an invasive portography follow-up protocol was 76%, and the 24-month re-intervention rate was 90%. The definite occlusion rate was below 5%. Beyond a follow-up time span of 24-months the necessity for re-intervention dropped significantly: Less than one-third of our patients required some sort of re-intervention. (orig./AJ) [Deutsch] Ziel: Darstellung der nach 10jaehriger klinischer Anwendung von TIPSS gewonnenen Erfahrungen unter Beruecksichtigung der technischen Grundlagen, der Veraenderungen in der Haemodynamik der Leber und der Langzeitergebnisse. Ergebnisse: TIPSS reduziert die Varizenfuellung und verringert morphologisch und haemodynamisch die portale Perfusion. Die Gesamtleberperfusion aendert sich nicht signifikant. Unter TIPSS kommt es zu einer unmittelbaren Zunahme der arteriellen Leberperfusion. Die portale Drucksenkung erfolgt von einem portosystemischen Mitteldruck von 24 mmHg auf 10,5 mmHg im Durchschnitt. Die spontane hepatische Enzephalopathierate von etwa 20% aendert sich durch TIPSS nicht wesentlich. Die Fruehletalitaet betraegt 4% und die Nachblutungsrate 3%. Insbesondere die Standardisierung von Indikationen und Kontraindikationen, des Punktionsbesteckes, der

  7. Radiofrequency ablation of liver metastases; Radiofrequenzablation von Lebermetastasen

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, P.L.; Clasen, S.; Schmidt, D.; Wiskirchen, J.; Tepe, G.; Claussen, C.D. [Abt. fuer Radiologische Diagnostik, Eberhard-Karls-Univ. Tuebingen (Germany); Boss, A. [Abt. fuer Radiologische Diagnostik, Eberhard-Karls-Univ. Tuebingen (Germany); Sektion fuer Experimentelle Radiologie der Abt. fuer Radiologische Diagnostik, Eberhard-Karls-Univ. Tuebingen (Germany); Gouttefangeas, C. [Abt. Immunologie des Inst. fuer Zellbiologie, Eberhard-Karls-Univ. Tuebingen (Germany); Burkart, C. [Zentrum fuer gastroenterologische Onkologie der Medizinischen Klinik, Eberhard-Karls-Univ. Tuebingen (Germany)

    2004-04-01

    The liver is the second only to lymph nodes as the most common site of metastatic disease irrespective of the primary tumor. Up to 50% of all patients with malignant diseases will develop liver metastases with a significant morbidity and mortality. Although the surgical resection leads to an improvement of the survival time, only approximately 20% of the patients are eligible for surgical intervention. Radiofrequency (RF) ablation represents one of the most important alternatives as well as complementary methods for the therapy of liver metastases. RF ablation can lead in a selected patient group to a palliation or to an increased life expectancy. RF ablation appears either safer (vs. cryotherapy) or easier (vs. laser) or more effective (percutaneous ethanol instillation [PEI]), transarterial chemoembolisation [TACE] in comparison with other minimal invasive procedures. RF ablation can be performed percutaneously, laparoscopically or intraoperatively and may be combined with chemotherapy as well as with surgical resection. Permanent technical improvements of RF systems, a better understanding of the underlying electrophysiological principles and an interdisciplinary approach will lead to a prognosis improvement in patients with liver metastases. (orig.) [German] Die Leber ist unabhaengig vom Primaertumor nach den Lymphknoten die zweithaeufigste Lokalisation von Metastasen. Bis zu 50% aller Patienten mit malignen Erkrankungen werden im Verlauf ihrer Erkrankung Lebermetastasen entwickeln, die mit einer signifikanten Morbiditaet und Mortalitaet verbunden sind. Obwohl die chirurgische Resektion zu einer verlaengerten Ueberlebenszeit fuehrt, sind nur ca. 20% der Patienten fuer einen chirurgischen Eingriff geeignet. Die Radiofrequenz-(RF-)Ablation stellt derzeit eine der effektivsten Alternativen und komplementaeren Methoden bei der Therapie von Lebermetastasen dar. In einem selektierten Patientengut fuehrt die RF-Ablation ueber den palliativen Einsatz hinaus zu einer

  8. Two novel mutations in the EYS gene are possible major causes of autosomal recessive retinitis pigmentosa in the Japanese population.

    Directory of Open Access Journals (Sweden)

    Katsuhiro Hosono

    Full Text Available Retinitis pigmentosa (RP is a highly heterogeneous genetic disease including autosomal recessive (ar, autosomal dominant (ad, and X-linked inheritance. Recently, arRP has been associated with mutations in EYS (Eyes shut homolog, which is a major causative gene for this disease. This study was conducted to determine the spectrum and frequency of EYS mutations in 100 Japanese arRP patients. To determine the prevalence of EYS mutations, all EYS exons were screened for mutations by polymerase chain reaction amplification, and sequence analysis was performed. We detected 67 sequence alterations in EYS, of which 21 were novel. Of these, 7 were very likely pathogenic mutations, 6 were possible pathogenic mutations, and 54 were predicted non-pathogenic sequence alterations. The minimum observed prevalence of distinct EYS mutations in our study was 18% (18/100, comprising 9 patients with 2 very likely pathogenic mutations and the remaining 9 with only one such mutation. Among these mutations, 2 novel truncating mutations, c.4957_4958insA (p.S1653KfsX2 and c.8868C>A (p.Y2956X, were identified in 16 patients and accounted for 57.1% (20/35 alleles of the mutated alleles. Although these 2 truncating mutations were not detected in Japanese patients with adRP or Leber's congenital amaurosis, we detected them in Korean arRP patients. Similar to Japanese arRP results, the c.4957_4958insA mutation was more frequently detected than the c.8868C>A mutation. The 18% estimated prevalence of very likely pathogenic mutations in our study suggests a major involvement of EYS in the pathogenesis of arRP in the Japanese population. Mutation spectrum of EYS in 100 Japanese patients, including 13 distinct very likely and possible pathogenic mutations, was largely different from the previously reported spectrum in patients from non-Asian populations. Screening for c.4957_4958insA and c.8868C>A mutations in the EYS gene may therefore be very effective for the genetic testing

  9. Optic neuropathies--importance of spatial distribution of mitochondria as well as function.

    Science.gov (United States)

    Yu Wai Man, C Y; Chinnery, P F; Griffiths, P G

    2005-01-01

    Optic neuropathies such as Leber's hereditary optic neuropathy, dominant optic atrophy and toxic amblyopia are an important cause of irreversible visual failure. Although they are associated with a defect of mitochondrial energy production, their pathogenesis is poorly understood. A common feature to all these disorders is relatively selective degeneration of the papillomacular bundle of retinal ganglion cells resulting central or caecocentral visual field defects. The striking similarity in the pattern of clinical involvement seen with these disparate disorders suggests a common pathway in their aetiology. The existing hypothesis that the optic nerve head has higher energy demands than other tissues making it uniquely dependent on oxidative phosporylation is not satisfactory. First, other ocular tissues such as photoreceptors, which are more dependent on oxidative phosporylation are not affected. Second, other mitochondrial disorders, which have a greater impact on mitochondrial energy function, do not affect the optic nerve. The optic nerve head has certain unique ultra structural features. Ganglion cell axons exit the eye through a perforated collagen plate, the lamina cribrosa. There is a sharp discontinuity in the density of mitochondria at the optic nerve head, with a very high concentration in the prelaminar nerve fibre layer and low concentration behind the lamina. This has previously been attributed to a mechanical hold up of axoplasmic flow, which has itself been proposed as a factor in the pathogenesis of a number of optic neuropathies. More recent evidence shows that mitochondrial distribution reflects the different energy requirements of the unmyelinated prelaminar axons in comparison to the myelinated retrolaminar axons. The heterogeous distribution of mitochondria is actively maintained to support conduction through the optic nerve head. We propose that factors that disrupt the heterogeneous distribution of mitochondria can result in ganglion cell

  10. RETINOBASE: a web database, data mining and analysis platform for gene expression data on retina

    Directory of Open Access Journals (Sweden)

    Léveillard Thierry

    2008-05-01

    Full Text Available Abstract Background The retina is a multi-layered sensory tissue that lines the back of the eye and acts at the interface of input light and visual perception. Its main function is to capture photons and convert them into electrical impulses that travel along the optic nerve to the brain where they are turned into images. It consists of neurons, nourishing blood vessels and different cell types, of which neural cells predominate. Defects in any of these cells can lead to a variety of retinal diseases, including age-related macular degeneration, retinitis pigmentosa, Leber congenital amaurosis and glaucoma. Recent progress in genomics and microarray technology provides extensive opportunities to examine alterations in retinal gene expression profiles during development and diseases. However, there is no specific database that deals with retinal gene expression profiling. In this context we have built RETINOBASE, a dedicated microarray database for retina. Description RETINOBASE is a microarray relational database, analysis and visualization system that allows simple yet powerful queries to retrieve information about gene expression in retina. It provides access to gene expression meta-data and offers significant insights into gene networks in retina, resulting in better hypothesis framing for biological problems that can subsequently be tested in the laboratory. Public and proprietary data are automatically analyzed with 3 distinct methods, RMA, dChip and MAS5, then clustered using 2 different K-means and 1 mixture models method. Thus, RETINOBASE provides a framework to compare these methods and to optimize the retinal data analysis. RETINOBASE has three different modules, "Gene Information", "Raw Data System Analysis" and "Fold change system Analysis" that are interconnected in a relational schema, allowing efficient retrieval and cross comparison of data. Currently, RETINOBASE contains datasets from 28 different microarray experiments performed

  11. An analytical model for droplet separation in vane separators and measurements of grade efficiency and pressure drop

    International Nuclear Information System (INIS)

    Koopman, Hans K.; Köksoy, Çağatay; Ertunç, Özgür; Lienhart, Hermann; Hedwig, Heinz; Delgado, Antonio

    2014-01-01

    Highlights: • An analytical model for efficiency is extended with additional geometrical features. • A simplified and a novel vane separator design are investigated experimentally. • Experimental results are significantly affected by re-entrainment effects. • Outlet droplet size spectra are accurately predicted by the model. • The improved grade efficiency doubles the pressure drop. - Abstract: This study investigates the predictive power of analytical models for the droplet separation efficiency of vane separators and compares experimental results of two different vane separator geometries. The ability to predict the separation efficiency of vane separators simplifies their design process, especially when analytical research allows the identification of the most important physical and geometrical parameters and can quantify their contribution. In this paper, an extension of a classical analytical model for separation efficiency is proposed that accounts for the contributions provided by straight wall sections. The extension of the analytical model is benchmarked against experiments performed by Leber (2003) on a single stage straight vane separator. The model is in very reasonable agreement with the experimental values. Results from the analytical model are also compared with experiments performed on a vane separator of simplified geometry (VS-1). The experimental separation efficiencies, computed from the measured liquid mass balances, are significantly below the model predictions, which lie arbitrarily close to unity. This difference is attributed to re-entrainment through film detachment from the last stage of the vane separators. After adjustment for re-entrainment effects, by applying a cut-off filter to the outlet droplet size spectra, the experimental and theoretical outlet Sauter mean diameters show very good agreement. A novel vane separator geometry of patented design (VS-2) is also investigated, comparing experimental results with VS-1

  12. Osler's disease; Morbus Osler

    Energy Technology Data Exchange (ETDEWEB)

    Ahlhelm, F.; Mueller, U. [Kantonsspital Baden AG, Institut fuer Radiologie, Baden (Switzerland); Lieb, J. [Universitaetsspital Basel, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland); Schneider, G. [Universitaetskliniken des Saarlandes, Klinik fuer Diagnostische und Interventionelle Radiologie, Homburg/Saar (Germany); Ulmer, S. [Medizinisch-Radiologisches Institut, Zuerich (Switzerland)

    2013-12-15

    Osler's disease, also known as hereditary hemorrhagic telangiectasia (HHT) and Osler-Weber-Rendu syndrome, is an autosomal dominant disorder leading to abnormal blood vessel formation in the skin, mucous membranes and often in organs, such as the lungs, liver and brain (arteriovenous malformations AVM). Various types are known. Patients may present with epistaxis. Teleangiectasia can be identified by visual inspection during physical examination of the skin or oral cavity or by endoscopy. Diagnosis is made after clinical examination and genetic testing based on the Curacao criteria. Modern imaging modalities, such as computed tomography (CT) or magnetic resonance imaging (MRI) have become more important as they can depict the AVMs. Pulmonary AVMs can be depicted in CT imaging even without the use of a contrast agent while other locations including the central nervous system (CNS) usually require administration of contrast agents. Knowledge of possible clinical manifestations in various organs, possible complications and typical radiological presentation is mandatory to enable adequate therapy of these patients. Interventional procedures are becoming increasingly more important in the treatment of HHT patients. (orig.) [German] Der Mobus Osler (Synonyme: hereditaere haemorrhagische Teleangiektasie [HHT], Morbus Rendu-Osler-Weber) ist eine Multisystemerkrankung und gehoert zur Gruppe der vaskulaeren haemorrhagischen Erkrankungen. Bei der autosomal dominanten Erkrankung, die zu den haeufigsten Phakomatosen zaehlt, kann je nach Gendefekt zwischen verschiedenen Formen, die zu einer Stoerung der Blutgefaessbildung fuehren, unterschieden werden. Neben der genetischen Diagnostik und der klinischen Untersuchung sind bildgebende Verfahren entscheidend fuer die Diagnose. Klinisch stehen die Epistaxis, mukokutane Teleangiektasien und viszerale arteriovenoese Malformationen (AVM) v. a. in Lunge, Leber und Hirn sowie die Folgen dieser Gefaesspathologien wie z. B

  13. Distrofias retinianas da infância: análise retrospectiva Retinal dystrophies in childhood: retrospective analysis

    Directory of Open Access Journals (Sweden)

    Heloisa Andrade Maestrini

    2004-12-01

    Full Text Available OBJETIVOS: Descrever o quadro clínico e os resultados dos exames complementares dos pacientes portadores das seguintes distrofias retinianas: amaurose congênita de Leber (ACL, acromatopsia, distrofia de cones e distrofia mista, atendidos no Serviço de Visão Subnormal do Hospital São Geraldo da UFMG, no período de 1992 a 2003. MÉTODOS: Análise retrospectiva dos prontuários de 40 pacientes, sendo 10 portadores de ACL, 17 com acromatopsia, 6 com distrofia de cones e 7 com distrofia mista. RESULTADOS: A acuidade visual foi extremamente baixa na ACL, variando de 20/710 a percepção luminosa. Situou-se em torno de 20/200 na acromatopsia, 20/280 na distrofia de cones e 20/260 na mista. A alta hipermetropia foi o erro refracional mais comum na ACL, ao passo que a hipermetropia predominou na acromatopsia e na distrofia de cones e a miopia na mista. A fundoscopia mostrou-se alterada na maioria dos casos de ACL, distrofia de cones e distrofia mista e normal na maioria dos acromatas. A compressão óculo-digital e o enoftalmo foram exclusivos da ACL, ao passo que a fotofobia e a dificuldade na discriminação de cores predominaram nos outros grupos. O nistagmo e o estrabismo foram freqüentes em todos eles. O atraso no desenvolvimento neuro-psico-motor foi muito freqüente no grupo da ACL e quase ausente nos demais. A ACL apareceu associada a síndromes genéticas em 2 casos. Os sintomas da ACL e da acromatopsia se manifestaram ao nascimento ou no 1º ano de vida, ao passo que na distrofia de cones e na mista surgiram também em idades mais avançadas, porém não depois dos 10 anos. A consangüinidade e a história familiar positiva foram altamente prevalentes em todos os grupos. O ERG mostrou ausência de resposta na ACL, redução da resposta fotópica na acromatopsia e na distrofia de cones e redução difusa na mista. Os testes de visão de cores mostraram alterações principalmente na acromatopsia e na distrofia de cones. CONCLUSÕES: As

  14. Genetic analysis of maternal ability in Iberian pigs.

    Science.gov (United States)

    Rodriguez, C; Rodrigañez, J; Silio, L

    1994-01-12

    Analyse von Muttereigenschaften iberischer Schweine Ein praktisches Maß für Milchleistung von Sauen ist das Drei-Wochen-Wurfgewicht, das völlig von der Muttermilchleistung abhängt. Genetische Parameter für Geburtswurfgröße (LS) und Geburtswurfgewicht bei 21 Tagen (LW21) wurden mit DFREML von 4883 Würfen (2049 für LW21) geschätzt. Vorläufige Analysen zeigten vernachläßigbare maternale Wirkungen. Das Modell enthält fixe Wirkungen der Wurfperiode (86), Wurffolge (6) und Inzuchtkoeffizienten von Muttersau (Fd) und Wurf (F(1) ) als Ko-variable und dazu drei zufällige Wirkungen: additiv-genetischer Wert, permanenter Umwelteinfluß und der Rest, bei beiden Merkmalen. Heritabilität und Wiederholbarkeit wurden auf 0,064 und 0,126 (LS) und auf 0,163 und 0,270 (LW21) geschätzt. Genetische und phänotypische Korrelationen waren 0,214 bzw. 0,043. Inzuchtdepression pro 10 % für Fd bzw. Fl waren -0,15 bzw. -0,17 bei lebenden Ferkeln und -0,983 bzw. -1,023 Kg in Wurfgewicht. Wenn im Modell für LW21 Mutterinzucht und Zahl saugender Ferkel berücksichtigt wurde, waren die Heritabilitäts- und Wiederholbarkeitsschätzungen 0,243 und 0,431. Eine komplementäre Analyse wurde für Einzelgewichte bei 21 Tagen an 26206 Ferkel von 1317 Sauen durchgeführt. Das Modell enthält festgesetzte Wirkungen von Geschlecht, Wurfperiode, Wurffolge und Inzuchtkoeffizient von Mutter und Ferkel sowie vier zufällige Wirkungen: direkte und maternale Wirkungen, gemeinsame Umweltwirkungen und den Rest. Schätzwerte für Heritabilität, maternale Heritabilität und Wurfumwelt waren 0,019, 0,163 bzw. 0,128, was auf genetische Varianz bei Milchleistung iberischer Sauen hinweist. Die geschätzten Werte für Inzucht-depression für Drei-Wochen-Ferkelgewicht waren -0,072 und -0,098 pro 10% Inzuchtsteigerung von Muttersau und Wurf. RESUMEN: Análisis genético de la aptitud maternal en cerdos ibéricos Una medida práctica de la capacidad lechera de la cerda es el peso de la camada con tres semanas

  15. Metastases in patients with malignant melanoma despite of negative sentinel lymph node: has the concept to be changed?; Metastasierung beim malignen Melanom trotz histologisch negativem Sentinel Lymph Node: muss das Konzept in Frage gestellt werden?

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, M.; Dresel, S.; Tatsch, K.; Hahn, K. [Muenchen Univ. (Germany). Klinik und Poliklinik fuer Nuklearmedizin; Konz, B.; Schmid-Wendtner, M.H.; Sander, C.; Volkenandt, M. [Muenchen Univ. (Germany). Dermatologische Klinik und Poliklinik

    2000-11-01

    und des Abdomens, Roentgen-Thorax) erfolgte vierteljaehrlich. Ergebnisse: Trotz negativem SLN zeigten 8/162 Patienten nach einer Beobachtungszeit von 5/27 Monaten eine Metastasierung. Bei drei Patienten konnte eine Lymphknotenmetastasierung in der SLN-Region gesichert werden, bei einem Patienten liess sich der praeoperativ szintigraphisch markierte SLN intraoperativ nicht sicher mittels Sonde lokalisieren. Ein Patient zeigte Intransit- bzw. Hautmetastasen, bei einem weiteren zeigte sich ein Narbenrezidiv. In einem anderen Fall ist von einer mit dieser Methode nicht erfassbaren haematogenen Streuung (Leber) auszugehen. Bei einem weiteren Patienten lag die Metastasierung ausserhalb des durch diese Lokalisationsmethode erfassten lymphogenen Abflussgebietes (zervikal). Schlussfolgerung: In unserem Kollektiv zeigten 4,9% der Patienten trotz negativem SLN eine Metastasierung; demgegenueber finden sich in der Literatur Angaben bis zu 11% (Beobachtungszeitraum bis 35 Monate). Davon kam es lediglich bei 3 Patienten (1,9%) zu einer Melanomprogression in der SLN-Region. Unsere Daten unterstreichen, dass derzeit keine Notwendigkeit besteht das SLN-Konzept bei Patienten im klinischen Stadium I und II zu aendern. (orig.)

  16. Radiation-induced liver injury mimicking liver metastases on FDG-PET-CT after chemoradiotherapy for esophageal cancer. A retrospective study and literature review

    Energy Technology Data Exchange (ETDEWEB)

    Voncken, Francine E.M.; Aleman, Berthe M.P. [The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Radiation Oncology, Amsterdam (Netherlands); Dieren, Jolanda M. van [The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Gastroenterology, Amsterdam (Netherlands); Grootscholten, Cecile [The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Internal Medicine, Amsterdam (Netherlands); Lalezari, Ferry [The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Radiology, Amsterdam (Netherlands); Sandick, Johanna W. van [The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Surgery, Amsterdam (Netherlands); Steinberg, Jeffrey D.; Vegt, Erik [The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Department of Nuclear Medicine, Amsterdam (Netherlands)

    2018-02-15

    Praxis wird aber nach CRT ebenfalls eine fokale FDG-Aufnahme in der Leber beobachtet, die nicht durch Lebermetastasen erklaert werden kann. Dieser strahlungsinduzierte Leberschaden (RILI) kann ein ''Overstaging'' verursachen. In unserer Klinik wurde in den elektronischen Aufzeichnungen aus allen PET-CT-Scans zwischen 2006 und 2015 systematisch nach moeglichen Patienten mit RILI nach nCRT beim Oesophaguskarzinom gesucht. Zusaetzliche Daten ueber potenzielle Faelle wurden aus den elektronischen Patientenakten entnommen. Zudem wurde eine Literatursuche zu RILI durchgefuehrt. Insgesamt wurden 205 Patienten mit nCRT behandelt, von denen 6 Patienten mit lokal erhoehter FDG-Aufnahme im Lobus caudatus oder linken Lebersegment nach nCRT aufgrund eines Oesophaguskarzinoms identifiziert wurden. Keiner dieser Patienten hatte Anzeichen von Lebermetastasen bei zusaetzlicher Bildgebung, waehrend der Operation, bei Biopsie oder waehrend des Follow-up (Spanne 11-46 Monate). In unserem Institut betrug die Inzidenz von RILI nach nCRT beim Oesophaguskarzinom 3 %. In der Literatur wird ein RILI bei circa 8 % der Patienten waehrend dem Restaging beschrieben. FDG-avide Laesionen treten besonders im hohen Strahlendosisbereich auf, und dann in der Regel im Lobus caudatus oder linken Lebersegment. FDG-Akkumulationen im Lobus caudatus oder linken Lebersegment nach CRT im hohen Strahlendosisbereich koennen sowohl durch Metastasen als auch durch einen RILI verursacht werden. Differenzialdiagnostisch ist ein RILI mit zu erwaegen, um Fehlinterpretationen und ein Overstaging zu vermeiden. (orig.)

  17. First clinical experience with extended planning and navigation in an interventional MRI unit; Erste klinische Erfahrungen mit einer erweiterten Eingriffsplanung und Navigation am interventionellen MRT

    Energy Technology Data Exchange (ETDEWEB)

    Moche, M.; Schneider, J.P.; Schulz, T.; Voerkel, C.; Kahn, T.; Busse, H. [Klinik und Poliklinik fuer Diagnostische Radiologie, Universitaetsklinikum Leipzig (Germany); Schmitgen, A.; Bublat, M. [Fraunhofer-Inst. fuer Angewandte Informationstechnik, St. Augustin (Germany); Trantakis, C. [Klinik und Poliklinik fuer Neurochirurgie, Universitaetsklinikum Leipzig (Germany); Bennek, J. [Klinik und Poliklinik fuer Kinderchirurgie, Univ. Leipzig (Germany)

    2004-07-01

    -Datensaetze dienen der Eingriffsplanung. Der Informationsgehalt dieser Referenzdaten wird durch Ueberlagerung zusaetzlicher Bildmodalitaeten (u.a. fMRT, CT) und durch farbige Darstellung der Bereiche frueher und rascher Kontrastmittelaufnahme erhoeht. Mit Hilfe dieses Systems wurden innerhalb von 18 Monaten 123 Patienten operiert (Gehirn: 64, Nasennebenhoehle: 9, Mamma: 20, Leber: 17, Knochen: 9, Muskel: 4). Der durchschnittliche Zeitaufwand der 64 Hirnoperationen wurde mit dem von 36 Eingriffen mit herkoemmlicher Navigation verglichen. Ergebnisse: Im Vergleich zur schnellen, kontinuierlichen Bildgebung des MRT-Systems (0,25 Bilder/s) erlauben erst die hoehere Qualitaet sowie die Echtzeitdarstellung (4 Bilder/s) der aus dem 3-D-Referenzdatensatz rekonstruierten MR-Bilder eine angemessene Auge-Hand-Koordination. Patienten- bzw. Gewebeverlagerungen lassen sich fruehzeitig intraoperativ erkennen und die Navigation kann durch Aktualisierung der Referenzdaten sicher fortgefuehrt werden. Das System zeichnete sich durch eine hohe Stabilitaet, effiziente Systemintegration und einfache Bedienbarkeit aus. Die bildgestuetzten Hirnoperationen dauerten trotz zusaetzlicher, noch zu optimierender Arbeitsschritte nicht signifikant laenger. (orig.)

  18. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation.

    Directory of Open Access Journals (Sweden)

    Geoffrey K Aguirre

    2007-06-01

    Full Text Available RPE65 is an essential molecule in the retinoid-visual cycle, and RPE65 gene mutations cause the congenital human blindness known as Leber congenital amaurosis (LCA. Somatic gene therapy delivered to the retina of blind dogs with an RPE65 mutation dramatically restores retinal physiology and has sparked international interest in human treatment trials for this incurable disease. An unanswered question is how the visual cortex responds after prolonged sensory deprivation from retinal dysfunction. We therefore studied the cortex of RPE65-mutant dogs before and after retinal gene therapy. Then, we inquired whether there is visual pathway integrity and responsivity in adult humans with LCA due to RPE65 mutations (RPE65-LCA.RPE65-mutant dogs were studied with fMRI. Prior to therapy, retinal and subcortical responses to light were markedly diminished, and there were minimal cortical responses within the primary visual areas of the lateral gyrus (activation amplitude mean +/- standard deviation [SD] = 0.07% +/- 0.06% and volume = 1.3 +/- 0.6 cm(3. Following therapy, retinal and subcortical response restoration was accompanied by increased amplitude (0.18% +/- 0.06% and volume (8.2 +/- 0.8 cm(3 of activation within the lateral gyrus (p < 0.005 for both. Cortical recovery occurred rapidly (within a month of treatment and was persistent (as long as 2.5 y after treatment. Recovery was present even when treatment was provided as late as 1-4 y of age. Human RPE65-LCA patients (ages 18-23 y were studied with structural magnetic resonance imaging. Optic nerve diameter (3.2 +/- 0.5 mm was within the normal range (3.2 +/- 0.3 mm, and occipital cortical white matter density as judged by voxel-based morphometry was slightly but significantly altered (1.3 SD below control average, p = 0.005. Functional magnetic resonance imaging in human RPE65-LCA patients revealed cortical responses with a markedly diminished activation volume (8.8 +/- 1.2 cm(3 compared to controls

  19. Successful closure of persistent oro-cutaneous fistulas by injection of autologous adipose-derived stem cells: a case report [Erfolgreiche Behandlung persistierender oro-kutaner Fisteln durch Injektion mit autologen Fettstammzellen: ein Fallbericht

    Directory of Open Access Journals (Sweden)

    Föll, D. A.

    2013-07-01

    , die bisher nur in wenigen Studien klinisch zum Einsatz kam. In diesem Fallbericht schildern wir die Anwendung von konzentrierten, autologen Stammzellen aus Fettgewebe, wodurch zwei oro-kutane Fisteln zur Abheilung gebracht werden konnten.Fallbeschreibung: Eine 57-jährige, immunsupprimierte Leber- und Nierentransplantatempfängerin stellte sich mit einem tiefen mandibulären Weichteildefekt vor. Dieser resultierte aus der radikalen Entfernung und Bestrahlung eines von der Zungenbasis ausgehenden Plattenepithelkarzinoms. Im postoperativen Verlauf der Defektrekonstruktion, die mit einem freien Lappen durchgeführt wurde, bildeten sich zwei oro-kutane Fisteln. Da eine operative Revision zu keiner Heilung der Fisteln führte, wurde der Entschluss gefasst, autologe Stammzellen aus Fettgewebe um die Fisteln herum einzubringen. Die Stammzellen wurden mit Hilfe des Cytori Celution Systems extrahiert und in der gleichen Sitzung appliziert. Im postoperativen Verlauf kam es nach 4 Wochen zum vollständigen Verschluss der beiden Fisteln und bis zum aktuellen Zeitpunkt (6 Monate postoperativ trat kein Rezidiv auf.Fazit: Nach unserem Wissen ist dies die erste erfolgreiche Applikation von konzentrierten Stammzellen aus Fettgewebe zur Behandlung von oro-kutanen Fisteln. Dieser Fall zeigt, wie innovative Stammzelltherapie in Kombination mit gut etablierten chirurgischen Methoden in besonderen Fällen eine sinnvolle Therapiestrategie darstellen kann.

  20. Extrakorporale Stoßwellentherapie (ESWT aus orthopädischer und traumatologischer Sicht

    Directory of Open Access Journals (Sweden)

    Auersperg V

    2004-01-01

    :// www.ismst.com/quality_standards.htm geforderte Mindesttherapie vor ESWT erscheint sinnvoll, wird aber im Einzelfall bewertet werden müssen und ist subjektiv an die Patientenerfordernisse anzupassen. Wie bisher wird die Durchführung als ärztliche Tätigkeit betrachtet, das bedeutet, daß der Anwender auch entsprechend geschult sein muß. Einer der größten Vorteile der ESWT ist die geringe Rate an Nebenwirkungen, die meist harmlos sind, wenn die gewählte Energie nicht über die vorgeschlagenen Richtwerte der Firmen bzw. Gerätehersteller und ESWT-Gesellschaften geht. Als oberer Grenzwert wird derzeit 0,5 mJ/mm² EFD (Energieflußdichte angesehen. ● Eventuelle kurzzeitige mäßige Schmerzverstärkung ● Rötungen und Schwellungen ● Hämatome und petechiale Blutungen ● Kopfschmerzen und Kollapsneigung während der ESWT ● Kurzzeitige Hypästhesie Aufgrund fehlender Studien und mangelhafter Datenlage müssen derzeit folgende Kontraindikationen weiter gelten, obwohl wahrscheinlich einige in Zukunft relativiert werden könnten: ● Blutgerinnungspathologie (iatrogen oder kongenital ● Offene Epiphysenfugen im Fokus ● Schwangerschaft ● Parenchymatöses oder nervales Gewebe (Lunge, Leber, Hirn, Rückenmark etc. ● Akute Entzündung Man kann festhalten, daß die ESWT in den besprochenen Indikationen durch Studien der Klasse 1A (EBM-Kriterien ihre Wirksamkeit und Komplikationslosigkeit bewiesen hat. Auch wenn einzelne Studien die ESWT kontroversiell beurteilen, sind wir in Anbetracht der vielen positiven Anwendungsbeobachtungen und der geringen Nebenwirkungen der Ansicht, daß man die ESWT als Therapie zulassen und insbesondere nach erfolgloser konservativer Therapie einsetzen sollte, vor allem wenn man damit eine Operation verhindern kann.

  1. Dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Lenaers Guy

    2012-07-01

    Full Text Available Abstract Definition of the disease Dominant Optic Atrophy (DOA is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3 encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8 are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7 are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of

  2. Limited value of fluorine-18-fluorodeoxyglucose PET for the differential diagnosis of focal liver lesions in patients with chronic hepatitis C virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, O. [Frankfurt Univ. (Germany). Dept. of Nuclear Medicine]|[Frankfurt Univ. (Germany). 2. Dept. of Internal Medicine; Trojan, J.; Zeuzem, S. [Frankfurt Univ. (Germany). 2. Dept. of Internal Medicine; Baum, R.P. [Frankfurt Univ. (Germany). Dept. of Nuclear Medicine

    1998-12-31

    ueber einen moeglichen diagnostischen Zugewinn durch die Bestimmung des Glukosestoffwechsels mittels FDG-PET in der Evaluation fokaler Leberlaesionen bei Patienten mit chronischer Hepatitis C liegen nicht vor. Methoden: An 10 Patienten wurden nach Injektion von 370 MBq FDG-Ganzkoerper-PET sowie transmissionskorrigierte Regionalaufnahmen der Leber und SUV-Bestimmungen 60 Minuten nach i.v. Applikation von FDG durchgefuehrt. Parallel dazu erfolgten abdomineller Ultraschall, CT, Serum-anti-p53-Bestimmung sowie die histologische und p53-Antigen-immunhistochemische Aufarbeitung der fokalen Leberherde. Ergebnisse: Die histologische Untersuchung der sonographisch nachgewiesenen Leberherde ergab 5 HCC, 2 Lebermetastasen sowie 3 zirrhotische Regeneratknoten. Mit der FDG-PET konnten sowohl ein hepatisch metatasiertes Adeno-Ca des Rektums als auch 2/5 HCC detektiert werden. Alle benignen Leberlaesionen, jedoch auch 3 HCC und das hepatisch metastasierte Karzinoid waren dagegen nicht nachweisbar. Mit Ultraschall oder CT gelang der Nachweis saemtlicher intrahepatischer Prozesse. Beide Tumoren mit einer sehr starken Expression von p53 wiesen einen stark erhoehten Glukosemetabolismus auf. Schlussfolgerung: FDG-PET ist morphologischen bildgebenden Verfahren in der Detektion und der nichtinvasiven Differenzierung fokaler Leberlaesionen bei Patienten mit HCV unterlegen. Die nachgewiesene Beziehung zwischen der p53-Expression und dem SUV bedarf weiterer Untersuchungen. (orig.)

  3. Radiation exposure to the patient caused by single-photon transmission measurement for 3D whole-body PET; Die Strahlenexposition des Patienten durch die Einzelphotonen-Transmissionsmessung bei der PET

    Energy Technology Data Exchange (ETDEWEB)

    Schaefer, A.; Donsch, P.; Kirsch, C.M. [Universitaet des Saarlandes, Homburg/Saar (Germany). Abt. fuer Nuklearmedizin; Seifert, H. [Universitaet des Saarlandes, Homburg/Saar (Germany). Abt. Strahlentherapie der Radiologischen Klinik

    2000-11-01

    Patienten durch die Transmissionsmessung mittels Einzelphotonenquellen bei der PET. Material und Methode: Zwei Cs-137-Punktquellen (E{gamma}=662 keV, A=614 MBq) werden zur Transmissionsmessung im Einzelphotonenmodus an einem 3D-Scanner (ECAT ART) eingesetzt. Bei der Simulation einer Ganzkoerper-Transmission (axiale Laenge: 75 cm, 6 ueberlappende Bettpositionen), werden Dosismessungen mit Thermolumineszenzdosimetern unter Verwendung eines Thorax- und eines Abdomenphantoms durchgefuehrt. Aus den Messwerten wurde in Anlehnung an den Report Nr. 60 der ICRP die effektive Dosis fuer die Transmissionsmessung abgeschaetzt. Ergebnisse: Bei einer Gesamtaufnahmedauer von 360 min (60 min pro Bettposition) ergaben sich folgende Energiedosen: Oberflaeche (Xyphoid) 189 {mu}Gy, Herz 196 {mu}Gy, Lunge 234 {mu}Gy, BWS 240 {mu}Gy, Niere 207 {mu}Gy, Leber 204 {mu}Gy, Gonaden 205 {mu}Gy, Schilddruese 249 {mu}Gy und Blase 185 {mu}Gy, aus denen sich ein Konversionsfaktor von 1,7*10{sup -4} mSv/(h*MBq) errechnete. Die Abschaetzung der effektiven Dosis fuer den Patienten aufgrund einer Transmissionsmessung (Akquisitionszeit von 3,2 min pro Bettposition) ergab einen Wert von 11 {mu}Sv. Die Abschaetzung des Verhaeltnisses der Konversionsfaktoren durch Transmissionsmessung im Einzelphotonen- und im Koinzidenzmodus (zwei Ge-68/Ga-68-Linienquellen mit jeweils 40 MBq) ergab einen Wert von 0,18. Der Vergleich zwischen den effektiven Dosen durch die Transmission im Einzelphotonen-Modus und die Emission (bei Injektion von 250 MBq FDG) ergab ein Verhaeltnis von 2,3*10{sup -3}. Schlussfolgerung: Die Strahlenexposition der Patienten durch die Transmissionsmessung in der 3D-PET ist vernachlaessigbar gering. Sie wird durch die Verwendung der Einzelphotonenmethode mit kollimierten Punktquellen relativ hoher Aktivitaet im Vergleich zur Koinzidenzmethode mit nicht-kollimierten Linienquellen relativ niedriger Aktivitaet weiter reduziert. (orig.)

  4. Breathing-motion-compensated robotic guided stereotactic body radiation therapy. Patterns of failure analysis

    Energy Technology Data Exchange (ETDEWEB)

    Stera, Susanne; Imhoff, Detlef; Roedel, Claus [University Hospital Frankfurt, Department of Radiation Oncology, Frankfurt am Main (Germany); Balermpas, Panagiotis; Keller, Christian [University Hospital Frankfurt, Department of Radiation Oncology, Frankfurt am Main (Germany); Saphir Radiosurgery Center, Frankfurt (Germany); Chan, Mark K.H. [University Medical Center Schleswig-Holstein, Department of Radiation Oncology, Kiel (Germany); Huttenlocher, Stefan [Saphir Radiosurgery Center, Guestrow (Germany); Wurster, Stefan [Saphir Radiosurgery Center, Guestrow (Germany); University Medicine Greifswald, Department of Radiation Oncology, Greifswald (Germany); Rades, Dirk [University Medical Center Schleswig-Holstein, Department of Radiation Oncology, Luebeck (Germany); Dunst, Juergen [University Medical Center Schleswig-Holstein, Department of Radiation Oncology, Kiel (Germany); University Hospital Copenhagen, Department of Radiation Oncology, Copenhagen (Denmark); Hildebrandt, Guido [University Medicine Rostock, Department of Radiation Oncology, Rostock (Germany); Blanck, Oliver [Saphir Radiosurgery Center, Frankfurt (Germany); University Medical Center Schleswig-Holstein, Department of Radiation Oncology, Kiel (Germany); Saphir Radiosurgery Center, Guestrow (Germany)

    2018-02-15

    atembewegungskompensierter (EAK) stereotaktischer Koerperstammstrahlentherapie (SBRT) durch. Zwischen 2011 und 2016 wurden insgesamt 198 Patienten mit 280 Lungen-, Leber- und Abdominaltumoren mit EAK-SBRT behandelt. Das mediane makroskopische Tumorvolumen (GTV) lag bei 12,3 cm{sup 3} (0,1-372,0 cm{sup 3}). Die mediane mittlere GTV-BED{sub α/β=10} {sub Gy} lag bei 148,5 Gy{sub 10} (31,5-233,3 Gy{sub 10}; BED = biologisch effektive Dosis) und die verschriebene PTV-BED{sub α/β=10} {sub Gy} bei 89,7 Gy{sub 10} (28,8-151,2 Gy{sub 10}; PTV = Planungszielvolumen). Wir analysierten das Gesamtueberleben (GUe) und die lokale Kontrolle (LK) basierend auf verschiedenen Faktoren, einschliesslich BED mit α/β-Verhaeltnissen von 15 Gy (Lungenmetastasen), 21 Gy (primaere Lungentumoren) und 27 Gy (Lebermetastasen). Die mediane Nachbeobachtungszeit betrug 10,4 Monate (2,0-59,0 Monate). Die 2-Jahres-LK betrug 100 und 86,4 % fuer primaere Lungentumoren im Frueh- bzw. fortgeschrittenen Stadium, 100 % fuer Lungenmetastasen, 82,2 % fuer Lebermetastasen und 90 % fuer extrapulmonale, extrahepatische Metastasen. Die 2-Jahres-GUe-Rate ueber alle Patienten betrug 47,9 %. In der uni- und multivariaten Analyse wurde die LK vor allem durch eine zur ueblichen Praxis vergleichsweise niedrige PTV-Verschreibungsdosis (aequivalent zu 3-mal 12-13 Gy) sowie durch hoehere mittlere GTV-Dosen (aequivalent zu 3-mal 18 Gy) beeinflusst. Fuer ein hohes GUe waren ein hoher Karnofsky-Index (100 %), das Geschlecht (weiblich) und die SBRT ohne gleichzeitige Chemotherapie prognostisch signifikant. Grad-3-Nebenwirkungen waren selten (0,5 %). Die robotergefuehrte EAK-SBRT kann als eine sichere und wirksame Behandlung fuer solide Tumoren in beweglichen Organen angesehen werden. Fuer eine ausreichend hohe lokale Kontrollrate sind hohe mittlere GTV-Dosen erforderlich. Weitere prospektive Studien sind noetig, um diese Punkte zu evaluieren. (orig.)

  5. SPECT/CT for staging and treatment monitoring in oncology. Applications in differentiated thyroid cancer and liver tumors; SPECT/CT zum initialen Staging und Therapiemonitoring in der Onkologie. Indikationen beim differenzierten Schilddruesenkarzinom und bei Lebertumoren

    Energy Technology Data Exchange (ETDEWEB)

    Weber, K.; Berger, F.; Reiser, M.F. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Innenstadt, Institut fuer Klinische Radiologie, Muenchen (Germany); Mustafa, M.; Bartenstein, P.; Haug, A. [Klinikum der Ludwig-Maximilians-Universitaet Muenchen, Campus Grosshadern, Klinik und Poliklinik fuer Nuklearmedizin, Muenchen (Germany)

    2012-07-15

    Tumormarkers Thyreoglobulin, ergaenzt durch Radiojodganzkoerperszintigraphien im weiteren Follow-up bei besonderem Risikoprofil. Darstellung des durch die leberversorgenden Arterien versorgten Gebiets durch eine {sup 99m}Tc-MAA-Szintigraphie als Vorbereitung auf eine SIRT. ''Single photon emission computed tomography''/CT (SPECT/CT) der Hals- und Thoraxregion mit einer therapeutischen Aktivitaetsmenge Radiojod im Rahmen des postablativen Stagings. Darstellung der leberversorgenden Arterien mittels {sup 99m}Tc-MAA-SPECT/CT vor Beginn einer SIRT. Analyse und Quantifizierung des Speicherverhaltens der Lebertumoren, insbesondere im Vergleich zum Leberparenchym durch die SPECT/CT. Aufgrund der Kombination von funktioneller und morphologischer Information ist die SPECT/CT in der Lage, radiojodpositive Herde exakter morphologisch zu korrelieren, damit optimiertes Staging im Vergleich zur Ganzkoerperszintigraphie. Durch die zusaetzliche, von der SPECT/CT gebotene anatomische Information gelingt eine genauere Darstellung der arteriellen Versorgung der Leber sowie potenzieller Abstroeme der Mikrosphaeren in andere Organe. Darueber hinaus ermoeglicht die SPECT/CT eine Analyse und Quantifizierung des Speicherverhaltens der Lebertumoren. Verbessertes postablatives Staging bei Patienten mit differenziertem Schilddruesenkarzinom, insbesondere in Bezug auf das Auffinden von Lymphknotenmetastasen (LKM) im Vergleich zur ueblichen Radiojodganzkoerperszintigraphie. Verbesserte Planung und Durchfuehrung einer SIRT-Therapie bei Leberlaesionen; Optimierung der applizierten Dosis durch Einsatz der SPECT/CT. Integration der SPECT/CT in den klinischen Standard im Rahmen des postablativen Stagings bei Patienten mit DTC. Anwendung der SPECT/CT im Planungsprozess einer SIRT-Therapie sowie bei der Dosisberechnung. (orig.)

  6. Theme-Based Bidisciplinary Chemistry Laboratory Modules

    Science.gov (United States)

    Leber, Phyllis A.; Szczerbicki, Sandra K.

    1996-12-01

    .; Bell, C. E., Jr.; Clark, A. K. Organic Chemistry Laboratory; Saunders: Philadelphia, 1990; p 455. 4. Reference 3, pp 361-365. 5. Ballal, S.; Ellias, R.; Fluck, R.; Jameton, R.; Leber, P.; Lirio, R.; Salama, D. Plant Physiol. Biochem. 1993, 31, 249-255. 6. Venis, M. A.; Napier, R. M. Plant Growth Regulation 1991, 10, 329-340.

  7. The role of positron-emission-tomography (F-18-FDG-PET) in the staging and follow-up of lung cancer and in the evaluation of focal pulmonary abnormalities; Positronenemissionstomographie (PET) mit F-18-FDG in der Diagnostik des Bronchialkarzinoms und zur Dignitaetsabklaerung von pulmonalen Raumforderungen

    Energy Technology Data Exchange (ETDEWEB)

    Baum, R.P. [Zentralklinik Bad Berka (Germany). Klinik fuer Nuklearmedizin/PET-Zentrum; Bonnet, R.B. [Zentralklinik Bad Berka (Germany). Klinik fuer Pneumologie; Presselt, N. [Zentralklinik Bad Berka (Germany). Klinik fuer Thorax- und Gefaesschirurgie; Leonhardi, J. [Zentralklinik Bad Berka (Germany). Inst. fuer Bildgebende Diagnostik

    2001-04-01

    bronchial carcinomas (except for slowly growing neuroendocrine tumors like carcinoids which show rarely an increased FDG metabolism). The specificity of FDG-PET is in the range of >80%. (orig.) [German] Prospektive Studien zeigten im Direktvergleich von PET und Spiral-CT eine deutlich hoehere diagnostische Genauigkeit der PET im Lymphknotenstaging des Bronchialkarzinoms (insbesondere mediastinal, d.h. N2- oder N3-Befall). Mittels FDG-PET koennen auch normal grosse Lymphknoten (im CT<10 mm) als tumorbefallen charakterisiert werden (Upstaging). Andererseits kann die PET aufgrund der hoeheren Spezifitaet eine Metastasierung in computertomographisch vergroesserten Lymphknoten oftmals ausschliessen (Downstaging in bis zu 30% der untersuchten Patienten). Eine Aenderung des therapeutischen Prozedere durch die PET-Untersuchung ergab sich bei bis zu 30% aller Patienten und unter Einschluss der Fernmetastasen bei ueber 40% der untersuchten Patienten. Nebennierenmetastasen (Sensitivitaet 100%, Spezifitaet 80%), als auch Leber-, Knochen- und parenchymatoese Lungenmetastasen und abdominelle und zervikale Lymphknotenmetastasen werden mit hoher Sensitivitaet und Spezifitaet detektiert. Bei zerebralen Metastasen ist die MRT im Nachweis eindeutig ueberlegen, bei sehr kleinen Lungenlaesionen (<5 mm) ist die Spiral-CT sensitiver. Der Nachweis des lokalen Rezidivs eines zuvor operierten Lungenkarzinoms ist mit einer Sensitivitaet von 83-100% (Mittel 95%) und einer Spezifitaet von 62-100% (Mittel 81%) moeglich. Auch zur Therapiekontrolle ist die FDG-PET geeignet, da die Abnahme des Glukosemetabolismus mit dem Therapieerfolg korreliert. Problematisch sind inflammatorische Veraenderungen in den ersten Wochen nach Strahlentherapie ('Strahlenpneumonitis'), die ebenfalls zu einem gesteigerten Glukosemetabolismus fuehren koennen, weshalb ein groesserer Zeitabstand (mehrere Wochen bis Monate) nach Strahlentherapie sinnvoll ist. Die FDG-PET hat sich in der Differenzialdiagnostik von

  8. Factors of influence on body lead and cadmium levels in regions of Saxony Anhalt with different pollution levels, with special consideration to heavy metal uptake via household dust; Einflussfaktoren auf die innere Blei- und Cadmiumbelastung in unterschiedlich belasteten Regionen Sachsen-Anhalts unter besonderer Beruecksichtigung der Schwermetallaufnahme ueber den Hausstaub

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, I.

    2002-07-01

    - bzw. Cadmiumniederschlag im Hausstaub beeinflusst wird und ueberprueft, ob es eine zeitliche Veraenderung der inneren Belastung bei Kindern von 1992/93 nach 1998/99 gab. Zum Nachweis einer korporalen Belastung wurde in dieser Arbeit die Blutbleikonzentration verwendet. Der Bleiniederschlag im Hausstaub wurde am staerksten von der Wohnnaehe zu den Huetten beeinflusst und von Faktoren, die den Eintrag von bleihaltigem Staub in die Wohnung reflektieren. Auch auf die innere Belastung mit Blei wirkten sich v.a. das Wohnen in Emittentennaehe und bei Kindern zusaetzlich die damit verbundene Belastung des Hausstaubes sowie eine Staubaufwirbelung durch Haustiere aus. Des weiteren hatten Jungen deutlich erhoehte Werte. Waehrend bei Kindern Blei im Trinkwasser und eine Gartennutzung keinen nachweisbaren Effekt auf die innere Belastung hatten, spielten diese Faktoren sowie das Rauchen und die Freisetzung von Blei aus den Knochen nach der Menopause bei Frauen eine wichtige Rolle. Die innere Belastung mit Blei nahm bei Kindern zwischen 1992/93 und 1998/99 deutlich ab. Cadmium wird v.a. in der Niere und Leber gespeichert. Die Cadmiumkonzentration im Urin spiegelt die kumulative, lebenslange Exposition wider. Auch der Cadmiumniederschlag im Hausstaub wurde massgeblich durch das Wohnen in den belasteten Wohngebieten und durch den Eintrag von Cadmium in die Wohnung bestimmt. Die Hoehe des Cadmiumniederschlags spiegelte sich in der korporale Belastung der Kinder wider. Aeltere Kinder wiesen eine erhoehte innere Cadmiumbelastung auf. Die Cadmiumkonzentration im Urin nahm bei Kindern aus Hettstedt von 1992/93 nach 1998/99 deutlich ab. Bei Frauen erwies sich nur das Wohnen in der Belastungsregion Hettstedt als signifikanter Einflussfaktor auf die innere Belastung. Bei den untersuchten Kindern der Region Hettstedt kam es nur in wenigen Faellen zu einer Ueberschreitung der von der Kommission fuer ''Human-Biomonitoring'' des Umweltbundesamtes empfohlenen Werte. (orig.)

  9. Proceedings of the International Cancer Imaging Society (ICIS 16th Annual Teaching Course

    Directory of Open Access Journals (Sweden)

    Dow-Mu Koh

    2016-10-01

    oncologic practice: truths, tricks and tips M. Nazar, M. Wirtz, MD. Pascuzzi, F. Troncoso, F. Saguier, EP. Eyheremendy P21 Methotrexate-induced leukoencephalopathy in paediatric ALL Patients D.J. Quint, L. Dang, M. Carlson, S. Leber, F. Silverstein P22 Pitfalls in oncology CT reporting. A pictorial review R Rueben, S Viswanathan P23 Imaging of perineural extension in head and neck tumours B Nazir, TH Teo, JB Khoo P24 MRI findings of molecular subtypes of breast cancer: a pictorial primer K Sharma, N Gupta, B Mathew, T Jeyakumar, K Harkins P25 When cancer can’t wait! A pictorial review of oncological emergencies K Sharma, B Mathew, N Gupta, T Jeyakumar, S Joshua P26 MRI of pancreatic neuroendocrine tumours: an approach to interpretation D Christodoulou, S Gourtsoyianni, A Jacques, N Griffin, V Goh P27 Gynaecological cancers in pregnancy: a review of imaging CA Johnson, J Lee P28 Suspected paraneoplastic neurological syndromes - review of published recommendations to date, with proposed guideline/flowchart JA Goodfellow, AS Al-adhami, S Viswanathan P29 Multi-parametric MRI of the pelvis for suspected local recurrence of prostate cancer after radical prostatectomy R Bradley P30 Utilisation of PI-RADS version 2 in multi-parametric MRI of the prostate; 12-months experience R Bradley P31 Radiological assessment of the post-chemotherapy liver A Yong, S Jenkins, G Joseph P32 Skeletal staging with MRI in breast cancer – what the radiologist needs to know S Bhuva, K Partington P33 Perineural spread of lympoma: an educational review of an unusual distribution of disease CA Johnson, S Bhuva, M Subesinghe, N Taylor P34 Visually isoattenuating pancreatic adenocarcinoma. Diagnostic imaging tools. C Carrera, A Zanfardini, S De Luca, L Alarcón, V Blanchet, EP Eyheremendy P35 Imaging of larynx cancer: when is CT, MRI or FDG PET/CT the best test? K Cavanagh, E Lau