TY - THES A1 - Kurz, Antje T1 - Hemmung des PI3K-Signalweges im Ovarialkarzinom T1 - Anti-tumour activity of phosphoinositide-3-kinase antagonist AEZS-126 in models of ovarian cancer N2 - Störungen des PI3K-AKT-Signalweges treten besonders häufig in Endometrium und Ovarialkarzinomen auf. Ursache kann eine Überaktivierung von Wachstumsfaktor-Rezeptoren, Mutationen oder der Funktionsverlust von PTEN sein, was zu einer Störung der Regulation und damit zu einer Überaktivierung des PI3K-AKTSignalweges führt und so das Einleiten autophagischer Prozesse verhindert. Hierauf kommt es zu unkontrollierter Zellvermehrung, welche zur Tumorentstehung und Tumorprogression beiträgt [12][23]. Die in dieser Arbeit durchgeführten Untersuchungen konnten zeigen, dass die Hemmung des PI3K-AKT-Signalweges durch den PI3K-Inhibitor AEZS-126 erfolgversprechende antiproliferative Effekte in in vitro-Modellen des Ovarialkarzinoms zeigte. In vitro konnte die niedermolekulare Pyridopyrazin-Verbindung AEZS-126 das Wachstum und die Progression von Zellen der parentalen Ovarialkarzinom-Zelllinie A2780, der daraus abgeleiteten cis-Platin-resistenten Tochterzelllinie Acis2780 und der aus einem Ovar-Adenokarzinom gewonnenen Zelllinie SKOV-3 signifikant hemmen. In Vitalitätsassays ermittelte IC50-Werte lagen im mikromolaren Bereich und zeigten konzentrationsabhängige Antitumor-Effekte. Neben den AEZS-126-abhängigen Effekten wurde auch die Wirksamkeit des mTOR-Inhibitors Rapamycin auf die Zelllinien A2780 und Acis2780 untersucht. Es zeigten sich ebenfalls konzentrationsabhängige antiproliferative Effekte. Durch die Kombination der beiden Inhibitoren AEZS-126 und Rapamycin konnte zusätzlich eine gesteigerte Wirksamkeit gegen die Tumorzellen erzielt werden und synergistische Effekte traten auf. ImWestern-Blot konnte nach Inkubation der Ovarialkarzinomzelllinien mit AEZS-126 durch den Einsatz von AEZS-126 eine verminderte Expression von pAKT nachgewiesen werden, welche insbesondere bei den cis-Platin-resistenten Acis2780-Zellen durch die Kombination mit Rapamycin noch verstärkt wurde. Durch FACS-Analysen konnte gezeigt werden, dass die Ovarialkarzinomzellen durch die Behandlung mit AEZS-126 im Wachstum gehemmt werden und unabhängig von ihrer Zellzyklusphase in den Zelltod geführt werden können. So zeigte sich in den Zellzyklusanalysen eine konzentrationsabhängige Verschiebung der Zellzahl von der G0/G1-Phase in die sub-G0-Phase, welche die Population der toten Zellen darstellt. Eine Spezifizierung des Zelltod-Mechanismuses erfolgte einerseits durch Annexin-V-FITC-FACS-Analysen und andererseits durch Vitalitätsassays mit Koinkubation von AEZS-126 mit dem Caspase-Inhibitor zVAD-fmk, dem Nekroptose-Inhibitor Necrostatin-1 und dem Nekrose-Inhibitor Necrox-2. Aus diesen Untersuchungen ging klar hervor, dass AEZS-126 in den Zelllinien A2780, Acis2780 und SKOV-3 Nekroptose induziert. Rapamycin alleine zeigte sowohl apoptotische als auch nekrotische Wirkmechanismen. Die Kombination der beiden Inhibitoren AEZS-126 und Rapamycin führte zu einer synergistischen Wirkverstärkung, was sich in einem verstärkten Absterben der Zellen schon bei geringeren eingesetzten Konzentrationen der beiden Inhibitoren zeigte. Auch hier traten hauptsächlich nekrotische Effekte auf. Von besonderem Interesse war die Interaktion von Ovarialkarzinomzellen (A2780, Acis2780), die mit AEZS-126 vorbehandelt worden waren, mit Zellen des Immunsystems. So konnte gezeigt werden, dass AEZS-126 eine verbesserte Zelllyse der Tumorzellen durch NK-Zellen ermöglicht. Zusätzlich konnten die cis-Platin-resistenten Acis2780-Zellen durch Vorbehandlung mit entsprechende Konzentrationen des PI3KInhibitors in vergleichbarem Ausmaß wie die parentalen A2780-Zellen für die Lyse durch NK-Zellen zugänglich gemacht werden. AEZS-126 scheint auf Grund dieser Ergebnisse und der schon nachgewiesenen guten antiproliferativen Wirkung von AEZS-126 auf verschiedene Zelllinien ein geeigneter Kandidat für weiterführende in vivo-Versuche zu sein. Zusätzlich sollte erwogen werden, neben der Inhibiton des PI3K-AKT-Signalweges eine zeitgleiche Hemmung des Ras-Raf-MEK-ERK-Signalweges in Betracht zu ziehen. Durch die Interaktionen der beiden Signalwege könnte es sonst bei der Inaktivierung des einen zur Aktivierung des anderen Signalweges kommen [143]. Durch eine Überexpression von pAKT durch eine PTEN-Mutation kommt es beispielsweise zur Inaktivierung von Ras und der darauf folgenden Signalkaskade, während ein erhöhtes Expressionsniveau an pAKT im PI3K-AKT-Signalweg zu einer Aktivierung von mTOR und damit zur Hemmung autophagischer Prozesse führt [23]. So kann die Phosphorylierung des Proteins p70S6K, dem Schlüsselmolekül zwischen den beiden Signalwegen, welches mTOR nachgeschaltet ist, durch Rapamycin gehemmt werden und damit zu einer erhöhten Aktivierung von AKT und ERK führen [143]. Durch die Kombinationsbehandlung mit Inhibitoren des PI3K-AKT-Signalweges, die an verschiedenen Stellen der Signalkaskade angreifen, kann, wie in dieser Arbeit gezeigt wurde, die Antitumorwirkung verstärkt werden. Die in dieser Arbeit untersuchten Inhibitoren AEZS-126 und Rapamycin zeigten bei den parentalen Ovarialkarzinom- zellen A2780 und den cis-Platin-resistenten Acis2780-Zellen in der Kombinationsbehandlung synergistische Effekte und führten schon bei geringen Konzentrationen zu verstärkter antiproliferativer Wirksamkeit. Aus den erzielten Ergebnissen geht hervor, dass die Kombinationsbehandlung mit AEZS-126 und Rapamycin geeignet wäre, in in vivo-Experimenten weiter untersucht zu werden. N2 - Purpose Platinum resistance is the most crucial problem for treatment of ovarian cancer. There is a clinical need for new treatment strategies which overcome platinum resistance. Recently high level of AKT was shown to be involved in platinum resistance and furthermore in resistance against Natural-killer (NK)-cell mediated killing in ovarian cancer. Methods Here, we investigate the ability of the PI3K/AKT inhibitor AEZS-126 alone and in combination with rapamycin to selectively target ovarian cancer cell proliferation and survival in vitro by MTT-assays and FACS based analysis. Furthermore the mechanism of cytotoxicity is analysed by FACS based assays. The NK-killing efficiency of ovarian cancer cells with and without pre-treatment with AEZS-126 was analysed. Results AEZS-126 showed good anti-tumour activity in in vitro models of ovarian cancer. Main mechanism of cytotoxicity seems to be necroptosis which could be abrogated by co-incubation with necrostatin-1. Furthermore pre-treatment of platinum resistant cells with AEZS-126 resulted in an increased accessibility of these tumour cells for killing by NK-cells. Conclusion We demonstrated the highly efficient anti-tumour activity of AEZS-126 in in vitro models of ovarian cancer. Due to the good anti-tumour activity and the expected increase in NK-cell mediated killing even of platinum resistant tumour cells, AEZS-126 seems to be a promising candidate for clinical testing in ovarian cancer. KW - pi3k-signalweg KW - Hemmung KW - PI3K-Signalweg KW - Ovarialkarzinom Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-103872 ER - TY - THES A1 - Wieching, Anna T1 - Pandemische Influenza A (H1N1) 2009- assoziierte Hospitalisationen bei Kindern und Jugendlichen im Raum Würzburg, Bayern T1 - Pandemic Influenza A (H1N1) 2009- associated paediatric hospitalisations in Würzburg, Bavaria N2 - Influenza gehört zu den häufigsten respiratorischen Erkrankungen im Kindesalter. Auf Grund der raschen weltweiten Verbreitung des im Frühjahr 2009 neu aufgetretenen pandemischen Influenza A (H1N1) 2009- Virus rief die Weltgesundheitsorganisation (WHO) am 11. Juni 2009 die höchste Pandemiestufe aus. Ziel der vorliegenden Studie war es, alle hospitalisierten Kinder < 18 Jahren im Raum Würzburg mit laborchemischem Nachweis von pandemischer Influenza A (H1N1) 2009 (PIA) zu erfassen und den klinischen Verlauf sowie die aufgetretenen Komplikationen zu beschreiben. Weiterhin wurde die PIA-assoziierte Hospitalisations-Inzidenz für das Haupteinzugsgebiet der Kliniken für verschiedene Altersgruppen berechnet und mit Hospitalisations-Inzidenzen für saisonale Influenza der Saisons 2006/2007 bis 2008/2009 verglichen. Im Zeitraum von Juli 2009 bis März 2010 waren 94 Kinder < 18 Jahren (62% männlich) mit einer PIA-Infektion in stationärer Behandlung. Das Alter der Patienten lag im Median bei 7,1 Jahren (IQR: 3-12 Jahre). Eine Vorerkrankung bestand bei 40 Kindern (43%), wobei hier Adipositas (n=12, 30% der 40 Patienten mit Grunderkrankung), Asthma bronchiale (n=10, 25%) und neurologische Erkrankungen (n=8, 20%) am häufigsten waren. Die häufigsten Symptome bei stationärer Aufnahme waren Husten (n=75, 80% der 94 Patienten), Fieber (n=73, 78%) und Rhinitis (n=48, 51%). Eine Komplikation der PIA trat bei 37 Kindern (39%) auf, am häufigsten war eine Infektion der unteren Luftwege. Sechzehn Kinder (17%) benötigten eine Sauerstoffsupplementierung und drei Kinder (3%) wurden maschinell beatmet. Sechs Kinder (6%) wurden intensivstationär behandelt. Lediglich 3 Kinder (3%) waren gegen PIA und eines (1%) gegen saisonale Influenza geimpft. Die geschätzte Hospitalisations-Inzidenz im Würzburger Raum lag bei 118/100.000 für Kinder unter 18 Jahren und war am höchsten für Kinder unter einem Jahr (242/100.000). Die Hospitalisations-Inzidenz für saisonale Influenza A für Kinder unter 18 Jahren war in den drei vorhergehenden Saisons 2006/2007, 2007/2008 und 2008/2009 mit 41-97/100.000 niedriger als für PIA. Neben den 94 ambulant erworbenen Infektionen traten sieben nosokomiale Infektionen auf. Hierunter war ein Todesfall bei einem 16-jährigen Mädchen mit schweren Grunderkrankungen zu verzeichnen. Trotz der hohen Hospitalisierungs-Inzidenz verlief der überwiegende Anteil an PIA-assoziierten Hospitalisierungen ohne schwere Komplikationen. Kinder mit einer Grunderkrankung waren häufiger von einer Komplikation der PIA betroffen und nur ein geringer Anteil dieser Patienten war gegen Influenza geimpft, obwohl eine explizite Impfempfehlung der Ständigen Impfkommission am Robert Koch-Institut für diese Patientengruppe besteht. Höhere Durchimpfungsraten sind notwendig, um die Krankheitslast und das Auftreten von Komplikationen zu reduzieren. Derzeit wird daher die Einführung einer generellen Empfehlung der Impfung gegen Influenza für Kinder diskutiert. N2 - Influenza is one of the most frequent respiratoric diseases in childhood. Because of the rapid and worldwide spreading of the new 2009 pandemic influenza A (H1N1) (PIA) virus the World Health Organisation (WHO) announced the highest level of pandemic on 11th June 2009. The aims of our study were to identify all hospitalised children <18 years of age with laboratory-confirmed PIA in the region of Wuerzburg and to describe the clinical characteristics and complications. Furthermore, PIA-associated hospitalisation-incidences for different age groups were calculated and compared with hospitalisation-incidences for seasonal influenza A of the seasons 2006/2007 to 2008/2009. Between July 2009 and March 2010, we counted 94 PIA- associated hospitalisations (62% males) in children < 18 years of age. The median age was 7.1 years (IQR: 3-12 years). Underlying diseases were documented in 40 (43%) children; obesity (n = 12, 30% of all 94 children), asthma (n = 10, 25%) and neurologic disorders (n = 8, 20%) were the most frequently reported. The most frequent symptoms at admission to hospital were cough (n=75, 80%), fever (n=73, 78%) and rhinorrhoe (n=48, 51%). Complications occured in 37 children (39%); mainly infections of the lower respiratory tract. Sixteen (17%) children received oxygen supplementation, three (3%) children required mechanical ventilation and six (6%) children were admitted to an intensive care unit. Only 3 children (3%) were vaccinated against PIA and one child (1%) against seasonal influenza. Estimated hospitalisation incidence for PIA in children < 18 years of age was 118/100.000 and was highest for children < 1 year of age (242/100.000). The hospitalisation incidences during the seasons of 2006/2007 to 2008/2009 were lower (41-97/100.000) compared with PIA-associated hospitalisation incidences. Apart from 94 community acquired PIA-infections, 7 nosocomial infections occured, including one fatality (16 year-old girl with severe underlying diseases). Despite the high hospitalisation incidence, most PIA-associated hospitalisations demonstrated a benign course of disease. Children with underlying diseases were more frequently affected by complications of PIA and only a few of them were vaccinated against influenza, despite the recommendation from the Standing Vaccination Commission of the Robert Koch Institute. Higher vaccination coverage rates are necessary to reduce the disease burden of influenza and the number of complications. For this reason the implementation of a general recommendation of vaccination against influenza for children is currently discussed. KW - Schweineinfluenza KW - Grippe KW - Pandemische Influenza A Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119041 ER - TY - JOUR A1 - Isaias, Ioannis Ugo A1 - Dipaola, Mariangela A1 - Michi, Marlies A1 - Marzegan, Alberto A1 - Volkmann, Jens A1 - Rodocanachi Roidi, Mariana L. A1 - Frigo, Carlo Albino A1 - Cavallari, Paolo T1 - Gait Initiation in Children with Rett Syndrome JF - PLoS ONE N2 - Rett syndrome is an X-linked neurodevelopmental condition mainly characterized by loss of spoken language and a regression of purposeful hand use, with the development of distinctive hand stereotypies, and gait abnormalities. Gait initiation is the transition from quiet stance to steady-state condition of walking. The associated motor program seems to be centrally mediated and includes preparatory adjustments prior to any apparent voluntary movement of the lower limbs. Anticipatory postural adjustments contribute to postural stability and to create the propulsive forces necessary to reach steady-state gait at a predefined velocity and may be indicative of the effectiveness of the feedforward control of gait. In this study, we examined anticipatory postural adjustments associated with gait initiation in eleven girls with Rett syndrome and ten healthy subjects. Muscle activity (tibialis anterior and soleus muscles), ground reaction forces and body kinematic were recorded. Children with Rett syndrome showed a distinctive impairment in temporal organization of all phases of the anticipatory postural adjustments. The lack of appropriate temporal scaling resulted in a diminished impulse to move forward, documented by an impairment in several parameters describing the efficiency of gait start: length and velocity of the first step, magnitude and orientation of centre of pressure-centre of mass vector at the instant of (swing-)toe off. These findings were related to an abnormal muscular activation pattern mainly characterized by a disruption of the synergistic activity of antagonistic pairs of postural muscles. This study showed that girls with Rett syndrome lack accurate tuning of feedforward control of gait. KW - syndrome KW - ankles   KW - biological locomotion KW - kinematics KW - rett KW - soleus muscles KW - walking KW - velocity KW - children Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119789 SN - 1932-6203 VL - 9 IS - 4 ER - TY - JOUR A1 - Häusler, Sebastian F. M. A1 - del Barrio, Itsaso Montalbán A1 - Diessner, Joachim A1 - Stein, Roland G. A1 - Strohschein, Jenny A1 - Hönig, Arnd A1 - Dietl, Johannes A1 - Wischhusen, Jörg T1 - Anti-CD39 and anti-CD73 antibodies A1 and 7G2 improve targeted therapy in ovarian cancer by blocking adenosine-dependent immune evasion JF - American Journal of Translational Research N2 - The ectonucleotidases CD39 and CD73 degrade ATP to adenosine which inhibits immune responses via the \(A_{2A}\) adenosine receptor (ADORA2A) on T and NK cells. The current study investigates the potential therapeutic use of the specific anti CD39- and anti CD73-antibodies A1 (CD39) and 7G2 (CD73) as these two ectonucleotidases are overexpressed in ovarian cancer (OvCA). As expected, NK cell cytotoxicity against the human ovarian cancer cell lines OAW-42 or SK-OV-3 was significantly increased in the presence of A1 or 7G2 antibody. While this might partly be due to antibody-dependent cell-mediated cytotoxicity, a luciferase-dependent assay for quantifying biologically active adenosine further showed that A1 and 7G2 can inhibit CD39 and CD73-dependent adenosine-generation. In turn, the reduction in adenosine levels achieved by addition of A1 and 7G2 to OAW-42 or SK-OV-3 cells was found to de-inhibit the proliferation of \(CD4^+\) T cells in coculture with OvCA cells. Likewise, blocking of CD39 and CD73 on OvCA cells via A1 and 7G2 led to an increased cytotoxicity of alloreactive primed T cells. Thus, antibodies like A1 and 7G2 could improve targeted therapy in ovarian cancer not only by specifically labeling overexpressed antigens but also by blocking adenosine-dependent immune evasion in this immunogenic malignancy. KW - ovarian cancer KW - immune escape KW - adenosine KW - CD39 KW - CD73 Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-120016 SN - 1943-8141 VL - 6 IS - 2 ER - TY - JOUR A1 - Dempfle, Astrid A1 - Herpertz-Dahlmann, Beate A1 - Timmesfeld, Nina A1 - Schwarte, Reinhild A1 - Egberts, Karin M. A1 - Pfeiffer, Ernst A1 - Fleischhaker, Christian A1 - Wewetzer, Christoph A1 - Bühren, Katharina T1 - Predictors of the resumption of menses in adolescent anorexia nervosa JF - BMC Psychiatry N2 - Background: The resumption of menses is an important indicator of recovery in anorexia nervosa (AN). Patients with early-onset AN are at particularly great risk of suffering from the long-term physical and psychological consequences of persistent gonadal dysfunction. However, the clinical variables that predict the recovery of menstrual function during weight gain in AN remain poorly understood. The aim of this study was to investigate the impact of several clinical parameters on the resumption of menses in first-onset adolescent AN in a large, well-characterized, homogenous sample that was followed-up for 12 months. Methods: A total of 172 female adolescent patients with first-onset AN according to DSM-IV criteria were recruited for inclusion in a randomized, multi-center, German clinical trial. Menstrual status and clinical variables (i.e., premorbid body mass index (BMI), age at onset, duration of illness, duration of hospital treatment, achievement of target weight at discharge, and BMI) were assessed at the time of admission to or discharge from hospital treatment and at a 12-month follow-up. Based on German reference data, we calculated the percentage of expected body weight (%EBW), BMI percentile, and BMI standard deviation score (BMI-SDS) for all time points to investigate the relationship between different weight measurements and resumption of menses. Results: Forty-seven percent of the patients spontaneously began menstruating during the follow-up period. %EBW at the 12-month follow-up was strongly correlated with the resumption of menses. The absence of menarche before admission, a higher premorbid BMI, discharge below target weight, and a longer duration of hospital treatment were the most relevant prognostic factors for continued amenorrhea. Conclusions: The recovery of menstrual function in adolescent patients with AN should be a major treatment goal to prevent severe long-term physical and psychological sequelae. Patients with premenarchal onset of AN are at particular risk for protracted amenorrhea despite weight rehabilitation. Reaching and maintaining a target weight between the 15th and 20th BMI percentile is favorable for the resumption of menses within 12 months. Whether patients with a higher premorbid BMI may benefit from a higher target weight needs to be investigated in further studies. KW - girls KW - amenorrhea KW - brain KW - increases KW - return KW - menarche KW - target weight KW - adolescence anorexia nervosa KW - resumption of menses KW - recovery KW - ovarian function KW - weight gain KW - eating disorders KW - bone-mineral density KW - menstrual recovery KW - outcome KW - body mass index Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122106 VL - 13 IS - 308 ER - TY - JOUR A1 - Hedrich, Christian M. A1 - Hofmann, Sigrun R. A1 - Pablik, Jessica A1 - Morbach, Henner A1 - Girschick, Hermann J. T1 - Autoinflammatory bone disorders with special focus on chronic recurrent multifocal osteomyelitis (CRMO) JF - Pediatric Rheumatology N2 - Sterile bone inflammation is the hallmark of autoinflammatory bone disorders, including chronic nonbacterial osteomyelitis (CNO) with its most severe form chronic recurrent multifocal osteomyelitis (CRMO). Autoinflammatory osteopathies are the result of a dysregulated innate immune system, resulting in immune cell infiltration of the bone and subsequent osteoclast differentiation and activation. Interestingly, autoinflammatory bone disorders are associated with inflammation of the skin and/or the intestine. In several monogenic autoinflammatory bone disorders mutations in disease-causing genes have been reported. However, regardless of recent developments, the molecular pathogenesis of CNO/CRMO remains unclear. Here, we discuss the clinical presentation and molecular pathophysiology of human autoinflammatory osteopathies and animal models with special focus on CNO/CRMO. Treatment options in monogenic autoinflammatory bone disorders and CRMO will be illustrated. KW - bisphosphonate treatment KW - IL-10 expression KW - TNF-α KW - IL-10 KW - inflammation KW - bone KW - CRMO KW - CNO KW - DIRA KW - PAPA KW - Majeed-Syndrome KW - disease KW - deficiency KW - pediatric patients KW - treatment KW - TLR4 KW - PAPA syndrome KW - hypertrophic osteodystrophy KW - chronic nonbacterial osteomyelitis KW - congenital dyserythropoietic anemia Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125694 SN - 1546-0096 VL - 11 IS - 47 ER - TY - THES A1 - Hinderer, Kirsten T1 - Untersuchung der laryngealen Regelleistung in Form der Kurzzeitvariabilität der Grundfrequenz in vorsprachlichen Vokalisationen des 2. und 3. Lebensmonats von Säuglingen mit und ohne oro-faziale Spaltbildungen T1 - Analyses of spontaneous cries during the second and third month of life of 19 infants with cleft lip and palate compared to 24 non-cleft infants as a reference group N2 - Die vorliegende Arbeit analysiert vorsprachliche Lautäußerungen des zweiten und dritten Lebensmonates von 19 Säuglingen mit oro-fazialen Spaltbildungen und 24 gesunden Säuglingen als Referenzgruppe erstmalig unter dem Aspekt des Einflusses einer erfolgten kieferorthopädischen Frühbehandlung. Die Untersuchungen konzentrierten sich dabei auf die Grundfrequenz und die Länge der Einzelvokalisationen sowie auf verschiedene Stimmstabilitätsparameter (Jitter, Shimmer, PPQ). Für die Grundfrequenz der Lautäußerungen konnten weder deutliche Unterschiede zwischen Säuglingen mit oro-fazialen Spaltbildungen und den gesunden Gleichaltrigen festgestellt werden, noch konnte ein maßgeblicher Einfluss der Oberkieferplatte auf die mittlere Grundfrequenz vorsprachlicher Vokalisationen gezeigt werden. Die Tatsache, dass bei nahezu allen Analysen der Stimmstabilität ein positiver Effekt der Oberkieferplatte zu verzeichnen war, spricht stark dafür, dass sich diese kieferorthopädische Maßnahme positiv auf die Stabilität der Phonation auswirkt. Die hier durchgeführten Analysen zeigen vor allem signifikante Unterschiede zwischen der Kontrollgruppe und der Gruppe mit rechtsseitiger LKGS-Spalte. Inwieweit dieser Befund tatsächlich Bestand hat, müssen weiterführende Studien zeigen, in denen insbesondere ein stärkeres Augenmerk auf adäquate begleitende pädaudiologische Untersuchungen gelegt werden sollte. N2 - The present paper analyses spontaneous cries during the second and third month of life of 19 infants with cleft lip and palate compared to 24 non-cleft infants as a reference group. Research has been performed in the light of the influence of pre-orthodontic treatment for the first time. Tests have been focused on fundamental frequency (F0), length of the infant cries and on different parameters of the F0 stability (Jitter, Shimmer, PPQ). No significant varieties have been found between infants with cleft lip and palate and the non-cleft contemporaries. A decisive impact of the intra-oral plate on fundamental frequency of pre-linguistic vocalization has not been found either. Almost all tests have shown a positive effect of the pre-orthodontic treatment on voice stability. This strongly suggests that the orthodontic measure has a favourable impact on the stability of Phonation. The current tests show significant differences in particular between the non-cleft group and the group with unilateral cleft lip and palate. Whether these findings will be confirmed or not has to be shown by future research that is preferably focused on appropriate paediatric audiology investigations / examinations. KW - Grundfrequenz KW - oro-faziale Spaltbildungen KW - cleft lip and palate KW - Jitter KW - PPQ KW - Stimmstabilität KW - Shimmer KW - kieferorthopädische Frühbehandlung KW - fundamental frequency KW - F0 stability KW - pre-orthodontic treatment Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-91423 ER - TY - THES A1 - Forstner, Maria Elisabeth T1 - Einfluss des transmembranen Hüllproteins des humanen endogenen Retrovirus K (HERV-K) auf die Zytokinproduktion humaner in-vitro kultivierter unreifer und reifer dendritischer Zellen T1 - Influence of the transmembrane envelope protein of human endogenous retrovirus K (HERV-K) on the cytokine production of human in vitro cultured immature and mature dendritic cells N2 - Bei der Implantation des Fetus in den Uterus und während der Schwangerschaft kommt es zu einer Interaktion fetaler Trophoblastzellen mit dem mütterlichen Immunsystem. Trotz vieler verschiedener Studien ist bis heute nicht grundlegend geklärt, welche Mechanismen zur immunologischen Akzeptanz des (semi-)allogenen Fetus durch die Mutter beitragen. Zur wechselseitigen Kommunikation zwischen Kind und Mutter tragen Zytokine bei, die von allen immunkompetenten Zellen sezerniert werden können und regulatorisch auf die Immunantwort wirken. Eine Störung im Gleichgewicht der Zytokine kann zu Aborten, Präeklampsie oder anderen Pathologien führen. Eine wichtige Quelle von Zytokinen stellen u.a. die reifen und unreifen dendritischen Zellen (DC), die in der humanen Dezidua nachgewiesen wurden, dar. DC übernehmen als effiziente Antigen präsentierende Zellen eine entscheidende Funktion im Immunsystem und können inflammatorische Immunantworten induzieren. Jedoch spielen sie auch eine wichtige Rolle bei der Vermittlung immunologischer Toleranz. Die menschliche Plazenta weist eine auffällig starke Expression verschiedener humaner endogener Retroviren (HERV) auf. Immunmodulierende Eigenschaften von HERV wurden bereits beschrieben, jedoch nicht die direkte Wirkung von HERV-Proteinen der Plazenta auf Zellen des Immunsystems. Im Rahmen der Arbeit sollte daher die Wirkung des Hüllproteins des HERV-K, das in den Zytotrophoblastenzellen und in den Zellen des extravillösen Trophoblasten nachgewiesen wurde, auf die Zytokinproduktion unreifer (iDC) und reifer DC (mDC) untersucht werden. Als Modellsystem wurden in-vitro aus Monozyten des peripheren Blutes differenzierte DC gewählt. Die DC wurden in unreifem und reifem Zustand mit unterschiedlichen Konzentrationen von HERV-K-Peptiden (rekombinante Proteine (TM05.04 und TM12.12) bzw. Peptide aus 22 Aminosäuren (K120 und K177)) behandelt. Untersucht wurden die Veränderungen der Zytokinspiegel in den Zellkulturüberständen mittels Cytometric Bead Assay und Durchflusszytometrie. Die Messungen zeigten z.T. signifikante Veränderungen der Zytokinproduktion. So wurde die TNF-α-Sekretion der mDC durch K120 und K177 signifikant vermindert. Dieselben Peptide supprimierten ebenfalls signifikant die IL-8-Sekretion der mDC. Jedoch kam es durch alle vier HERV-Peptide (bei drei Peptiden signifikant) zu einer Steigerung der IL-8-Produktion in den iDC. Auch IL-6 wurde von den iDC durch HERV-K mehrheitlich signifikant vermehrt ausgeschüttet. Bzgl. IL-6 ergaben sich jedoch keine signifikanten Veränderungen in den mDC. In allen Ansätzen kam es zu einer konzentrationsabhängigen Stimulation der Sekretion des immunsuppressiven IL-10 (bei je drei Peptiden signifikante Ergebnisse). Keine signifikanten Veränderungen ergaben sich für IL1-β und IL-4. Die Erkenntnis, dass die HERV-Peptide die Zytokinproduktion der DC z.T. signifikant modulieren und diese Veränderung in den unterschiedlichen Reifestadien der DC variieren, lässt vermuten, dass die in der humanen Plazenta exprimierten Proteine einen Einfluss auf den Verlauf einer Schwangerschaft nehmen. Bei einer Schwangerschaft sind extrem fein abgestimmte, komplexe Vorgänge, bei denen viele verschiedene Faktoren eine Rolle spielen, für einen Erfolg vonnöten. Eine Übertragung der in-vitro-Ergebnisse auf in-vivo-Zustände ist nicht leicht zu vollziehen. Die vorliegenden Ergebnisse sprechen jedoch für einen Einfluss des HERV-K auf die Kommunikation zwischen Fetus und Mutter. Inwiefern genau und wie wichtig bzw. essentiell die Expression der HERV-K-Peptide für einen physiologischen Verlauf der Schwangerschaft ist, ob sie einen Einfluss auf Pathologien während der Gestation hat und ob dem HERV-K eine Bedeutung in der humanen Evolution zukommt, kann mit dieser Arbeit nicht geklärt werden. Jedoch gibt diese Arbeit Anlass dafür, den Einfluss des HERV-K auf die menschliche Fortpflanzung weitergehend zu untersuchen. N2 - During the implantation of the fetus in the uterus and during pregnancy fetal trophoblast cells interact with the maternal immune system. Despite a multitude of studies, so far it is not completely clear, which mechanisms contribute to the immunological acceptance of the (semi)allogeneic fetus by the mother. Cytokines are vital to an intact communication between child and mother. They have a significant regulatory influence on the maternal immune response. A disturbance in the balance of cytokines can lead to miscarriage, preeclampsia or other pathologies. Among others, an important source of cytokines are the mature and immature dendritic cells (DC), which were detected in the human decidua. DC have a crucial function in the immune system: They are efficient antigen presenting cells and are able to induce inflammatory immune responses. However, they also play an important role in the mediation of immunological tolerance. The human placenta shows a remarkably high expression of various human endogenous retroviruses (HERV). Immunomodulating properties of HERV have been described. The direct effect of placental HERV proteins on cells of the immune system, however, has not been analyzed yet. Hence this study examines the effect of the transmembrane envelope protein of HERV-K, which was detected in cytrophoblast and extravillous trophoblast cells, on the cytokine production of human immature (iDC) and mature (mDC) DC. The significant changes in cytokine release suggest that the expression of the HERV-K peptides have an influence on the course of human pregnancy. KW - Fetomaternal KW - Immunologie KW - Endogene Retroviren KW - Dendritische Zelle KW - Cytokine KW - Fetomaternale Immunologie KW - Plazenta KW - Dendritische Zellen KW - Humane endogene Retroviren KW - HERV-K KW - Fetomaternal immunology KW - Placenta KW - Human Endogenous Retrovirus - K KW - Dendritic cells Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-102506 ER - TY - JOUR A1 - Neubauer, Henning A1 - Wirth, Clemens A1 - Ruf, Katharina A1 - Hebestreit, Helge A1 - Beer, Meinrad T1 - Acute Muscle Trauma due to Overexercise in an Otherwise Healthy Patient with Cystic Fibrosis JF - Case Reports in Pediatrics N2 - Cystic fibrosis (CF) is one of the most common inherited diseases and is caused by mutations in the CFTR gene. Although the pulmonary and gastrointestinal manifestations of the disease remain in the focus of treatment, recent studies have shown expression of the CFTR gene product in skeletal muscle cells and observed altered intramuscular \(Ca^{2+}\) release dynamics in CFTR-deficient animal models. Physical exercise is beneficial for maintaining fitness and well-being in CF patients and constitutes one aspect of modern multimodal treatment, which has considerably increased life span and reduced morbidity. We report on a case of acute muscle trauma resulting from excessive dumbbell exercise in a young adult with cystic fibrosis and describe clinical, laboratory and imaging characteristics of acute exercise-induced muscle injury. KW - Cystic fibrosis Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123967 VL - 2012 IS - 527989 ER - TY - JOUR A1 - Otto, Wolfgang A1 - Rubenwolf, Peter C. A1 - Burger, Maximilian A1 - Fritsche, Hans-Martin A1 - Rößler, Wolfgang A1 - May, Matthias A1 - Hartmann, Arndt A1 - Hofstädter, Ferdinand A1 - Wieland, Wolf F. A1 - Denzinger, Stefan T1 - Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer JF - BMC Cancer N2 - Background: Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. Method: AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guerin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. Results: 59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 - 44.68; p=0.025). Conclusions: Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC. KW - urothelial bladder carcinoma KW - progression KW - transitional cell carcinoma KW - bacillus calmette guerin KW - water channels KW - follow up KW - in vitro KW - recurrence KW - growth KW - T1 KW - tumor KW - proliferation KW - stage pT1 KW - aquaporin 3 protein KW - immunohistochemistry Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135679 VL - 12 IS - 459 ER - TY - JOUR A1 - Bender, Stephan A1 - Resch, Franz A1 - Klein, Christoph A1 - Renner, Tobias A1 - Fallgatter, Andreas J. A1 - Weisbrod, Matthias A1 - Romanos, Marcel T1 - Influence of Stimulant Medication and Response Speed on Lateralization of Movement-Related Potentials in Attention-Deficit/Hyperactivity Disorder JF - PLoS One N2 - Background: Hyperactivity is one of the core symptoms in attention deficit hyperactivity disorder (ADHD). However, it remains unclear in which way the motor system itself and its development are affected by the disorder. Movement-related potentials (MRP) can separate different stages of movement execution, from the programming of a movement to motor post-processing and memory traces. Pre-movement MRP are absent or positive during early childhood and display a developmental increase of negativity. Methods: We examined the influences of response-speed, an indicator of the level of attention, and stimulant medication on lateralized MRP in 16 children with combined type ADHD compared to 20 matched healthy controls. Results: We detected a significantly diminished lateralisation of MRP over the pre-motor and primary motor cortex during movement execution (initial motor potential peak, iMP) in patients with ADHD. Fast reactions (indicating increased visuo-motor attention) led to increased lateralized negativity during movement execution only in healthy controls, while in children with ADHD faster reaction times were associated with more positive amplitudes. Even though stimulant medication had some effect on attenuating group differences in lateralized MRP, this effect was insufficient to normalize lateralized iMP amplitudes. Conclusions: A reduced focal (lateralized) motor cortex activation during the command to muscle contraction points towards an immature motor system and a maturation delay of the (pre-) motor cortex in children with ADHD. A delayed maturation of the neuronal circuitry, which involves primary motor cortex, may contribute to ADHD pathophysiology. KW - deficit-hyperactivity disorder KW - anticipatory mechanisms KW - motor preparation KW - TIC disorder KW - children KW - ADHD KW - methylphenidate KW - contingent negative-variation KW - continuous performance-test KW - slow cortical potentials Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135262 VL - 7 IS - 6 ER - TY - JOUR A1 - Havik, Bjarte A1 - Degenhardt, Franziska A. A1 - Johansson, Stefan A1 - Fernandes, Carla P. D. A1 - Hinney, Anke A1 - Scherag, André A1 - Lybaek, Helle A1 - Djurovic, Srdjan A1 - Christoforou, Andrea A1 - Ersland, Kari M. A1 - Giddaluru, Sudheer A1 - O'Donovan, Michael C. A1 - Owen, Michael J. A1 - Craddock, Nick A1 - Mühleisen, Thomas W. A1 - Mattheisen, Manuel A1 - Schimmelmann, Benno G. A1 - Renner, Tobias A1 - Warnke, Andreas A1 - Herpertz-Dahlmann, Beate A1 - Sinzig, Judith A1 - Albayrak, Özgür A1 - Rietschel, Marcella A1 - Nöthen, Markus M. A1 - Bramham, Clive R. A1 - Werge, Thomas A1 - Hebebrand, Johannes A1 - Haavik, Jan A1 - Andreassen, Ole A. A1 - Cichon, Sven A1 - Steen, Vidar M. A1 - Le Hellard, Stephanie T1 - DCLK1 Variants Are Associated across Schizophrenia and Attention Deficit/Hyperactivity Disorder JF - PLoS One N2 - Doublecortin and calmodulin like kinase 1 (DCLK1) is implicated in synaptic plasticity and neurodevelopment. Genetic variants in DCLK1 are associated with cognitive traits, specifically verbal memory and general cognition. We investigated the role of DCLK1 variants in three psychiatric disorders that have neuro-cognitive dysfunctions: schizophrenia (SCZ), bipolar affective disorder (BP) and attention deficit/hyperactivity disorder (ADHD). We mined six genome wide association studies (GWASs) that were available publically or through collaboration; three for BP, two for SCZ and one for ADHD. We also genotyped the DCLK1 region in additional samples of cases with SCZ, BP or ADHD and controls that had not been whole-genome typed. In total, 9895 subjects were analysed, including 5308 normal controls and 4,587 patients (1,125 with SCZ, 2,496 with BP and 966 with ADHD). Several DCLK1 variants were associated with disease phenotypes in the different samples. The main effect was observed for rs7989807 in intron 3, which was strongly associated with SCZ alone and even more so when cases with SCZ and ADHD were combined (P-value = 4x10\(^{-5}\) and 4x10\(^{-6}\), respectively). Associations were also observed with additional markers in intron 3 (combination of SCZ, ADHD and BP), intron 19 (SCZ+BP) and the 3'UTR (SCZ+BP). Our results suggest that genetic variants in DCLK1 are associated with SCZ and, to a lesser extent, with ADHD and BP. Interestingly the association is strongest when SCZ and ADHD are considered together, suggesting common genetic susceptibility. Given that DCLK1 variants were previously found to be associated with cognitive traits, these results are consistent with the role of DCLK1 in neurodevelopment and synaptic plasticity. KW - psychosis KW - deficit hyperactivity disorder KW - genome-wide association KW - bipolar disorder KW - VAL66MET polymorphism KW - doublecortine-like KW - genes KW - kinase KW - BDNF KW - endophenotype Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135285 VL - 7 IS - 4 ER - TY - JOUR A1 - Neuhoff, Nina A1 - Bruder, Jennifer A1 - Bartling, Jürgen A1 - Warnke, Andreas A1 - Remschmidt, Helmut A1 - Müller-Myhsok, Bertram A1 - Schulte-Körne, Gerd T1 - Evidence for the Late MMN as a Neurophysiological Endophenotype for Dyslexia JF - PLoS One N2 - Dyslexia affects 5-10% of school-aged children and is therefore one of the most common learning disorders. Research on auditory event related potentials (AERP), particularly the mismatch negativity (MMN) component, has revealed anomalies in individuals with dyslexia to speech stimuli. Furthermore, candidate genes for this disorder were found through molecular genetic studies. A current challenge for dyslexia research is to understand the interaction between molecular genetics and brain function, and to promote the identification of relevant endophenotypes for dyslexia. The present study examines MMN, a neurophysiological correlate of speech perception, and its potential as an endophenotype for dyslexia in three groups of children. The first group of children was clinically diagnosed with dyslexia, whereas the second group of children was comprised of their siblings who had average reading and spelling skills and were therefore "unaffected'' despite having a genetic risk for dyslexia. The third group consisted of control children who were not related to the other groups and were also unaffected. In total, 225 children were included in the study. All children showed clear MMN activity to/da/-/ba/ contrasts that could be separated into three distinct MMN components. Whilst the first two MMN components did not differentiate the groups, the late MMN component (300-700 ms) revealed significant group differences. The mean area of the late MMN was attenuated in both the dyslexic children and their unaffected siblings in comparison to the control children. This finding is indicative of analogous alterations of neurophysiological processes in children with dyslexia and those with a genetic risk for dyslexia, without a manifestation of the disorder. The present results therefore further suggest that the late MMN might be a potential endophenotype for dyslexia. KW - processing deficits KW - children KW - event-related potentials KW - mismatch negativity mmn KW - developmental dyslexia KW - reading disability KW - auditory discrimination KW - susceptibility gene KW - speech perception KW - novelty detection Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133686 VL - 7 IS - 5 ER - TY - JOUR A1 - von Kries, Rüdiger A1 - Weiss, Susanne A1 - Falkenhorst, Gerhard A1 - Wirth, Stephan A1 - Kaiser, Petra A1 - Huppertz, Hans-Iko A1 - Tenenbaum, Tobias A1 - Schroten, Horst A1 - Streng, Andrea A1 - Liese, Johannes A1 - Shai, Sonu A1 - Niehues, Tim A1 - Girschick, Hermann A1 - Kuscher, Ellen A1 - Sauerbrey, Axel A1 - Peters, Jochen A1 - Wirsing von Koenig, Carl Heinz A1 - Rückinger, Simon A1 - Hampl, Walter A1 - Michel, Detlef A1 - Mertens, Thomas T1 - Post-Pandemic Seroprevalence of Pandemic Influenza A (H1N1) 2009 Infection (Swine Flu) among Children < 18 Years in Germany JF - PLoS ONE N2 - Background: We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children. Methodology/Principal Findings: Eight pediatric hospitals distributed over Germany prospectively provided sera from in-or outpatients aged 1 to 17 years from April 1(st) to July 31(st) 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1-4 and 5-17 years the prevalence of HI titers (>= 1:10) was 27.1% (95% CI: 23.5-31.3) and 53.5% (95% CI: 50.9-56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3-30.5) in children aged 1-4 years and 48.0% (95% CI: 42.6-52.0) in 5-17 year old children. Of children with HI titers >= 1: 10, 25.5% (95% CI: 22.5-28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0-96.6) of the 5-17 year old but only 47.8% (95%-CI: 33.5-66.5) of the 1-4 year old children exhibited HI titers against influenza A virus (H1N1) 2009. Conclusion: Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5-17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03(B)-adjuvanted split virion vaccine need further scrutiny. KW - Hemagglutination inhibition KW - Vaccine KW - Age KW - Immunogenicity KW - Prevalence KW - Antibody KW - Viruses KW - England KW - Safety KW - Risk Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141698 VL - 6 IS - 9 ER - TY - JOUR A1 - Hamm, Henning A1 - Höger, Peter H T1 - Skin Tumors in Childhood JF - Deutsches Ärzteblatt International N2 - Background: Dermatologists, paediatricians, and general practitioners are often consulted by worried parents for the evaluation of a cutaneous tumor. Methods: Selective literature review. Results: Only 1-2% of skin tumors excised in children turn out to be malignant when examined histologically. Warning signs of malignancy include rapid growth, firm consistency, diameter exceeding 3 cm, ulceration, a non-movable mass, and presence in the neonatal period. The more common malignant skin tumors in adults-basal cell carcinoma, cutaneous squamous cell carcinoma, and melanoma-are very rare in childhood. Congenital melanocytic nevi and sebaceous nevi bear a lower malignant potential than previously believed; nevertheless, their excision is often indicated. A Spitz nevus can mimic a melanoma both clinically and histologically. Some benign skin tumors of childhood tend to regress spontaneously within a few years but may cause complications at particular locations and when multiple. For infantile hemangiomas requiring systemic treatment because of imminent obstruction or ulceration, propranolol seems to have a far more favorable risk-benefit ratio than corticosteroids. Conclusion: Physicians need specialized knowledge in order to decide whether a skin tumor in a child should be excised, non-surgically treated, or further evaluated, or whether it can be safely left untreated because of the likelihood of spontaneous remission. KW - congenital melanocytic nevi KW - mastocytosis KW - diagnosis KW - melanoma KW - children KW - lumps Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142402 VL - 108 IS - 20 ER - TY - JOUR A1 - Goepel, Johanna A1 - Biehl, Stefanie C. A1 - Kissler, Johanna A1 - Paul-Jordanov, Isabelle T1 - Pro- and antisaccades in children elicited by visual and acoustic targets - does modality matter? JF - BMC Pediatrics N2 - Background: Children are able to inhibit a prepotent reaction to suddenly arising visual stimuli, although this skill is not yet as pronounced as it is in adulthood. However, up to now the inhibition mechanism to acoustic stimuli has been scarcely investigated Methods: Reflexive (prosaccade) and inhibitory (antisaccade) responses to visual and acoustic targets were examined with an eye tracker system in 31 children between seven and twelve years of age using a gap-overlap task and two target eccentricities. Results: Acoustically cued saccades had longer reaction times than visually cued saccades. A gap effect (i.e., shorter reaction time in the gap than the overlap condition) was only found for visually elicited saccades, whereas an eccentricity effect (i.e., faster saccades to more laterally presented targets - 12 degrees vs. 6 degrees or rather 90 degrees vs. 45 degrees) was only present in the acoustic condition. Longer reaction times of antisaccades compared to prosaccades were found only in the visual task. Across both tasks the typical pattern of elevated error rates in the antisaccade condition was found. Antisaccade errors declined with age, indicating an ongoing development of inhibitory functions. Conclusions: The present results lay the ground for further studies of acoustically triggered saccades in typically as well as atypically developing children and it might thus be possible to upgrade physiological diagnostic tools. KW - Saccadic eye-movements KW - Auditory targets KW - Voluntary control KW - Task-performance KW - Latency KW - Prosaccade KW - Vergence KW - Stimuli KW - GAP Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141807 VL - 11 IS - 116 ER - TY - JOUR A1 - Reinards, THCM A1 - Albers, HM A1 - Brinkman, DMC A1 - Kamphuis, SSM A1 - van Rossum, MAJ A1 - Hoppenreijs, EPAH A1 - Girschick, HJ A1 - Wouters, C A1 - Saurenmann, RK A1 - Houwing-Duistermaat, JJ A1 - Toes, REM A1 - Huizinga, TWJ A1 - ten Cate, R A1 - Schilham, MW T1 - Association of the CCR5Δ32 variant with juvenile idiopathic arthritis in a meta-analysis JF - Pediatric Rheumatology N2 - No abstract available. KW - Pädiatrie KW - Rheumatologie Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133763 VL - 9 IS - Suppl. 1 ER - TY - JOUR A1 - Reinards, THCM A1 - Albers, HM A1 - Brinkman, DMC A1 - Kamphuis, SSM A1 - van Rossum, MAJ A1 - Hoppenreijs, EPAH A1 - Girschick, HJ A1 - Wouters, C A1 - Saurenmann, RK A1 - Houwing-Duistermaat, JJ A1 - Toes, REM A1 - Huizinga, TWJ A1 - ten Cate, R A1 - Schilham, MW T1 - Association of the CD226 (DNAM-1) Gly307Ser polymorphism with juvenile idiopathic arthritis JF - Pediatric Rheumatology N2 - No abstract available. KW - Pädiatrie KW - Rheumatologie Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133773 VL - 9 IS - Suppl. 1 ER -