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  • 1
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    German Medical Science; Düsseldorf, Köln
    In:  Kooperative Versorgung - Vernetzte Forschung - Ubiquitäre Information; 49. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 19. Jahrestagung der Schweizerischen Gesellschaft für Medizinische Informatik (SGMI) und Jahrestagung 2004 des Arbeitskreises Medizinische Informatik (ÖAKMI) der Österreichischen Computer Gesellschaft (OCG) und der Österreichischen Gesellschaft für Biomedizinische Technik (ÖGBMT); 20040926-20040930; Innsbruck; DOC04gmds009 /20040914/
    Publication Date: 2004-09-14
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    Keywords: CELLS ; ENDOTHELIAL-CELLS ; EXPRESSION ; Germany ; IN-VIVO ; PATHWAY ; SYSTEM ; SYSTEMS ; liver ; EFFICIENCY ; MICE ; ACTIVATION ; IFN-GAMMA ; INDUCTION ; ANTIGEN ; ANTIGENS ; DENDRITIC CELLS ; T-CELL ; T-CELLS ; TOLERANCE ; BONE-MARROW ; MATURATION ; knockout ; MOUSE ; LINE ; DEGRADATION ; IMMUNITY ; NAIVE ; CYTOTOXICITY ; CROSS-PRESENTATION ; endothelial cells ; PH ; development ; KNOCKOUT MICE ; CYTOKINE PRODUCTION ; CELL TOLERANCE ; dendritic cell ; INDUCE ; T cell tolerance ; KUPFFER CELLS ; ADOPTIVE TRANSFER ; CD8 T cell tolerance ; ENDOTOXIN ; oral tolerance ; scavenger endothelial cells
    Abstract: After ingestion, oral antigens distribute systemically and provoke T cell stimulation outside the gastrointestinal tract. Within the liver, scavenger liver simisoidal endothelial cells (LSEC) eliminate blood-borne antigens and induce T cell tolerance. Here we investigated whether LSEC contribute to oral tolerance. Oral antigens were efficiently cross-presented on H-2k(b) by LSEC to naive CD8 T cells. Cross-presentation efficiency in LSEC but not dendritic cells was increased by antigen-exposure to heat or low pH. Mechanistically, cross-presentation in LSEC requires endosomal maturation, involves hsc73 and proteasomal degradation. H-2k(b)-restricted cross-presentation of oral antigens by LSEC in vivo induced CD8 T cell priming and led to development of CD8 T cell tolerance in two independent experimental systems. Adoptive transfer of LSEC from mice fed with antigen (ovalbumin) into RAG2(-/-) knockout mice, previously reconstituted with naive ovalbumin-specific CD8 T cells, prevented development of specific cytotoxicity and expression of IFN-gamma in CD8 T cells. Using a new transgenic mouse line expressing H-2k(b) only on endothelial cells, we have demonstrated that oral antigen administration leads to tolerance in H-2K(b)-restricted CD8 T cells. Collectively, our data demonstrate a participation of the liver, in particular scavenger LSEC, in development of CD8 T cell tolerance towards oral antigens
    Type of Publication: Journal article published
    PubMed ID: 16163670
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  • 3
    Keywords: MOLECULE ; CHROMATIN ; CRYSTAL-STRUCTURE ; FLUORESCENCE ; ANGSTROM RESOLUTION ; COMPACTION ; RESONANCE ENERGY-TRANSFER ; CORE PARTICLE ; ACCESSIBILITY ; CONFORMATIONAL DYNAMICS
    Abstract: Opening of the nucleosome structure is essential for accessing genomic DNA. To study the mechanism of this process, we monitor the distance between various fluorescently labeled positions on mononucleosomes by single-molecule Forster resonance energy transfer (FRET). Here, we compare nucleosomes reconstituted from recombinant mouse, Xenopus, and yeast histones. As DNA sequences we compared, the effect of 5S rDNA, MMTV-B sequence, and Widom 601 DNA. The stability, as measured by the salt concentration at the opening transition midpoint, is lowest for yeast, followed by Xenopus and mouse. The 601 DNA sequence builds much more stable nucleosomes and the distribution of FRET efficiencies is narrower than for those reconstituted on 5S rDNA or MMTV-B sequences. The opening pathway through an intermediate state, as found for Xenopus histones, could be verified for the mouse and yeast systems and for the different DNA sequences, suggesting a general mechanism for accessing nucleosomal DNA. (c) 2013 International Society for Advancement of Cytometry.
    Type of Publication: Journal article published
    PubMed ID: 23843180
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  • 4
    Abstract: BACKGROUND AND PURPOSE: To internally and externally validate an atlas based automated segmentation (ABAS) in loco-regional radiation therapy of breast cancer. MATERIALS AND METHODS: Structures of 60 patients delineated according to the ESTRO consensus guideline were included in four categorized multi-atlas libraries using MIM Maestro software. These libraries were used for auto-segmentation in two different patient groups (50 patients from the local institution and 40 patients from other institutions). Dice Similarity Coefficient, Average Hausdorff Distance, difference in volume and time were computed to compare ABAS before and after correction against a gold standard manual segmentation (MS). RESULTS: ABAS reduced the time of MS before and after correction by 93% and 32%, respectively. ABAS showed high agreement for lung, heart, breast and humeral head, moderate agreement for chest wall and axillary nodal levels and poor agreement for interpectoral, internal mammary nodal regions and LADCA. Correcting ABAS significantly improved all the results. External validation of ABAS showed comparable results. CONCLUSIONS: ABAS is a clinically useful tool for segmenting structures in breast cancer loco-regional radiation therapy in a multi-institutional setting. However, manual correction of some structures is important before clinical use. The ABAS is now available for routine clinical use in Danish patients.
    Type of Publication: Journal article published
    PubMed ID: 27697296
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  • 5
    Keywords: THERAPY ; TRANSPLANTATION ; T-CELLS ; NK cells ; CANCER-PATIENTS ; GENE-EXPRESSION ANALYSIS ; PHASE-II ; ACUTE MYELOID-LEUKEMIA ; EX-VIVO EXPANSION ; LARGE-SCALE
    Abstract: BACKGROUND AIMS: Ex vivo expansion of natural killer (NK) cells is a strategy to produce large numbers of these effector cells for immunotherapy. However, the transfer of bench-top expansion protocols to clinically applicable methods is challenging for NK cell-based therapy because of regulatory aspects and scale-up issues. Therefore, we developed an automated, large-scale NK cell expansion process. METHODS: Enriched NK cells were expanded with interleukin-2 and irradiated clinical-grade Epstein-Barr virus-transformed lymphoblastoid feeder cells with the use of an automated system in comparison to manual expansion, and the cells were investigated for their functionality, phenotype and gene expression. RESULTS: Automated expansion resulted in a mean 850-fold expansion of NK cells by day 14, yielding 1.3 (+/-0.9) x 10(9) activated NK cells. Automatically and manually produced NK cells were comparable in target cell lysis, degranulation and production of interferon-gamma and tumor necrosis factor-alpha and had similar high levels of antibody-dependent cellular cytotoxicity against rituximab-treated leukemic cells. NK cells after automated or manual expansion showed similar gene expression and marker profiles. However, expanded NK cells differed significantly from primary NK cells including upregulation of the functional relevant molecules TRAIL and FasL and NK cell-activating receptors NKp30, NKG2D and DNAM-1. Neither automatically nor manually expanded NK cells showed reduced telomere length indicative of a conserved proliferative potential. CONCLUSIONS: We established an automated method to expand high numbers of clinical-grade NK cells with properties similar to their manually produced counterparts. This automated process represents a highly efficient tool to standardize NK cell processing for therapeutic applications.
    Type of Publication: Journal article published
    PubMed ID: 25881519
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  • 6
    Abstract: BACKGROUND AND PURPOSE: To report on a Quality assessment (QA) of Skagen Trial 1, exploring hypofractionation for breast cancer patients with indication for regional nodal radiotherapy. MATERIAL AND METHODS: Deviations from protocol regarding target volume delineations and dose parameters (Dmin, Dmax, D98%, D95% and D2%) from randomly selected dose plans were assessed. Target volume delineation according to ESTRO guidelines was obtained through atlas based automated segmentation and centrally approved as gold standard (GS). Dice similarity scores (DSC) with original delineations were measured. Dose parameters measured in the two delineations were reported to assess their dosimetric outcome. RESULTS: Assessment included 88 plans from 12 centres in 4 countries. DSC showed high agreement in contouring, 99% and 96% of the patients had a complete delineation of target volumes and organs at risk. No deviations in the dosimetric outcome were found in 76% of the patients, 82% and 95% of the patients had successful coverage of breast/chestwall and CTVn_L2-4-interpectoral. Dosimetric outcomes of original delineation and GS were comparable. CONCLUSIONS: QA showed high protocol compliance and adequate dose coverage in most patients. Inter-observer variability in contouring was low. Dose parameters were in harmony with protocol regardless original or GS segmentation.
    Type of Publication: Journal article published
    PubMed ID: 28351523
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  • 7
    Keywords: APOPTOSIS ; CELLS ; ENDOTHELIAL-CELLS ; tumor ; TUMOR-CELLS ; CELL ; Germany ; IN-VIVO ; VIVO ; SYSTEM ; liver ; MICE ; MECHANISM ; INDUCTION ; ANTIGEN ; ANTIGENS ; DENDRITIC CELLS ; T cell ; T cells ; T-CELLS ; TOLERANCE ; BONE-MARROW ; CANCER-CELLS ; NATURAL-KILLER-CELLS ; FRAGMENTS ; FAILURE ; ADAPTIVE IMMUNITY ; TUMOR CELLS ; ELIMINATION ; IMMUNE ESCAPE ; IMMUNE-SYSTEM ; ESCAPE ; CYTOKINE PRODUCTION ; TUMOR-CELL ; KUPFFER CELLS ; in vivo ; FRAGMENT ; CD8(+) T cell ; COLON-CARCINOMA CELLS ; liver sinusoidal endothelial cells ; NKT CELLS ; PERFORIN/GRANZYME PATHWAY ; sinusoidal endothelial cells
    Abstract: Development of tumor-specific T cell tolerance contributes to the failure of the immune system to eliminate tumor cells. Here we report that hematogenous dissemination of tumor cells followed by their elimination and local removal of apoptotic tumor cells in the liver leads to subsequent development of T cell tolerance towards antigens associated with apoptotic tumor cells. We provide evidence that liver sinusoidal. endothelial cells (LSEC) remove apoptotic cell fragments generated by induction of tumor cell apoptosis through hepatic NK1.1(+) cells. Antigen associated with apoptotic cell material is processed and cross-presented by LSEC to CD8(+) T cells, leading to induction of CD8(+) T cell tolerance. Adoptive transfer of LSEC isolated from mice challenged previously with tumor cells promotes development of CD8(+) T cell tolerance towards tumor-associated antigen in vivo. Our results indicate that hematogenous dissemination of tumor cells, followed by hepatic tumor cell elimination and local cross-presentation of apoptotic tumor cells by LSEC and subsequent CD8(+) T cell tolerance induction, represents a novel mechanism operative in tumor immune escape
    Type of Publication: Journal article published
    PubMed ID: 17039564
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  • 8
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  32. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie (DGPP); 20150924-20150927; Oldenburg; DOC62 /20150907/
    Publication Date: 2015-09-08
    Description: Hintergrund: Der Zusammenhang zwischen soziodemographischen und Lebensstil-Faktoren und der Sprechstimme ist bislang kaum in größeren populationsbasierten Studien untersucht worden. Ziel der vorliegenden Studie war es, die Auswirkungen von Alter, Geschlecht, sozioökonomischem Status (SES) sowie Rauchen auf das Sprechstimmumfangsprofil zu untersuchen.Material und Methoden: Im Rahmen der bevölkerungsbezogenen Studie für Erwachsene des Leipziger Forschungszentrums für Zivilisationserkrankungen (LIFE) mit insgesamt 10.000 zufällig ausgewählten Probanden wurde bei 2.446 Probanden ein Sprechstimmumfangsprofil gemessen (DIVAS Stimmanalyse von XION medical, Berlin). Für die Sprechstimme wurden vier Messintensitäten definiert: Leiseste Sprechstimme (I), Gesprächsstimme (II), Vortragsstimme (III) und Rufstimme (IV). Unter Verwendung eines Fragebogens wurde der sozioökonomische Status und Rauchstatus ermittelt. Die Assoziation der genannten Einflussgrößen mit der Sprechstimme wurde mithilfe multivariater Regressionsmodelle untersucht.Ergebnisse: Insgesamt flossen Daten von 1.301 weiblichen und 1.145 männlichen Probanden zwischen 40-79 Jahren in die Auswertung ein. GESCHLECHT: Die weibliche Sprechstimme liegt etwa sechs Halbtöne über der männlichen Sprechstimme. ALTER: Mit zunehmendem Alter zeigt sich bei den männlichen Probanden eine signifikante Frequenzerhöhung, für die weiblichen Probanden zeigt sich kein Zusammenhang zwischen Alter und Frequenz. Die Intensität steigt für beide Geschlechter für (I) bis (III). Für männliche Probanden sinkt die Intensität bei (IV). SES: Die Sprechstimmdynamik erhöht sich mit steigendem SES. RAUCHSTATUS: Es zeigen sich kaum Unterschiede zwischen Nichtrauchern und ehemaligen Rauchern. Aktuelle Raucher haben eine tiefere Stimme.Diskussion: Die mittlere Frequenzlage der weiblichen Sprechstimme ist tiefer als bisher in der Literatur beschrieben. Die Zunahme der Frequenz bei Männern mit dem Alter ist möglicherweise auf altersbedingte Umbauprozesse im Kehlkopf zurückzuführen. Eventuell haben Probanden mit einem hohen SES weniger Hemmungen in einer Messsituation ihre Stimmdynamik auszureizen. Die Effekte des Rauchens auf Frequenz und Intensität erscheinen reversibel.
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 9
    ISSN: 0168-9002
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 0304-3770
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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