72 results on '"Aumayr K"'
Search Results
2. REGULATORY T CELL THERAPY IMPROVES OUTCOME OF CHRONIC CTLA4IG THERAPY IN MURINE HEART TRANSPLANTATION: 049
- Author
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Schwarz, Ch., Mahr, B., Unger, L., Mayerhoffer, S., Pilat, N., Hock, K., Kristo, I., Aumayr, K., and Wekerle, Th.
- Published
- 2014
3. Hemodynamic Compromising Antibody Mediated Rejection (HCAMR) After Heart Transplantation (HTX).: Abstract# C1608
- Author
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Aliabadi, A., Uyanik-Uenal, K., Goekler, J., Wallner, S., Masseti, M., Aumayr, K., Fischer, G., Boehmig, G., Laufer, G., and Zuckermann, A.
- Published
- 2014
4. ANALYSIS OF STERNAL FORCE DISTRIBUTION DURING MEDIAN STERNOTOMY ON CORPSES: P5
- Author
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Aigner, P., Schlöglhofer, T., Eskandary, F., Gottardi, R., Aumayr, K., Laufer, G., and Schima, H.
- Published
- 2012
5. Myocardial lipofuscin-laden lysosomes contain the apoptosis marker caspase-cleaved cytokeratin-18
- Author
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Soleiman, A., Lukschal, A., Hacker, S., Aumayr, K., Hoetzenecker, K., Lichtenauer, M., Moser, B., Untersmayr, E., Horvat, R., and Ankersmit, H. J.
- Published
- 2008
6. Genome amplification and cellular senescence are hallmarks of human placenta development
- Author
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Xiaowei Zhu, airhofer M, ikula M, Robert Lindau, Martin Knöfler, Alexander E. Urban, Gerda Egger, Thomas Lendl, Roberta L. Hannibal, Philipp Velicky, Peter Haslinger, Jürgen Pollheimer, Clemens Röhrl, Aumayr K, Birgit Schütz, Beatrix Weil, Kerstin Plessl, Julie C. Baker, Jürgen Neesen, Jan Ernerudh, Sigrid Vondra, Gudrun Meinhardt, and Tamara Weiss
- Subjects
Embryology ,lcsh:QH426-470 ,Cellbiologi ,Maternal Health ,Placenta ,Primary Cell Culture ,Cellular senescence ,Genome amplification ,Biology ,Polyploidy ,Endometrium ,Pregnancy ,Cell Movement ,Cyclins ,Medicine and Health Sciences ,Decidua ,Genetics ,Humans ,Cell Cycle and Cell Division ,Cellular Senescence ,Cell Proliferation ,Mammalian Genomics ,Genome ,Uterus ,Cell Cycle ,Reproductive System ,Biology and Life Sciences ,Obstetrics and Gynecology ,Human placenta ,Cell Differentiation ,Cell Biology ,Genomics ,Cell Cycle Checkpoints ,Placentation ,Cell biology ,Trophoblasts ,Tetraploidy ,lcsh:Genetics ,Pregnancy Trimester, First ,Cell Processes ,Animal Genomics ,Women's Health ,Blastocysts ,Female ,Anatomy ,Departures from Diploidy ,Research Article ,Developmental Biology - Abstract
Genome amplification and cellular senescence are commonly associated with pathological processes. While physiological roles for polyploidization and senescence have been described in mouse development, controversy exists over their significance in humans. Here, we describe tetraploidization and senescence as phenomena of normal human placenta development. During pregnancy, placental extravillous trophoblasts (EVTs) invade the pregnant endometrium, termed decidua, to establish an adapted microenvironment required for the developing embryo. This process is critically dependent on continuous cell proliferation and differentiation, which is thought to follow the classical model of cell cycle arrest prior to terminal differentiation. Strikingly, flow cytometry and DNAseq revealed that EVT formation is accompanied with a genome-wide polyploidization, independent of mitotic cycles. DNA replication in these cells was analysed by a fluorescent cell-cycle indicator reporter system, cell cycle marker expression and EdU incorporation. Upon invasion into the decidua, EVTs widely lose their replicative potential and enter a senescent state characterized by high senescence-associated (SA) β-galactosidase activity, induction of a SA secretory phenotype as well as typical metabolic alterations. Furthermore, we show that the shift from endocycle-dependent genome amplification to growth arrest is disturbed in androgenic complete hydatidiform moles (CHM), a hyperplastic pregnancy disorder associated with increased risk of developing choriocarinoma. Senescence is decreased in CHM-EVTs, accompanied by exacerbated endoreduplication and hyperploidy. We propose induction of cellular senescence as a ploidy-limiting mechanism during normal human placentation and unravel a link between excessive polyploidization and reduced senescence in CHM., Author summary In tissues, cellular differentiation is normally associated with cell cycle arrest. However, in some cases differentiating cells continue their cyclic activity in the absence of cell division. This event, referred to as endoreduplication, leads to polyploidy, which means an increased number of chromosome sets per cell and has been demonstrated in rodent placental trophoblast giant cells (TGCs). However, it is unknown whether human placental trophoblasts also endoreduplicate their genome. To study this, we focused on extravillous trophoblasts (EVTs), a specific trophoblastic subtype that invades the uterus during pregnancy in order to control blood supply and nutrient transfer to the growing embryo. We show that initiation of EVT differentiation is characterized by induced endoreduplication leading to genomic tetraploidization. Different to TGCs, EVTs duplicate their genome in an even manner. Upon invasion into the uterus, EVTs stop their endoreduplicative cycle and undergo cellular senescence. We further show that EVTs of hyperplastic complete hydatidiform mole (CHM) placentas, a genetic pregnancy disorder, are characterized by exacerbated endoreduplication, a greater DNA content and reduced signs for senescence. In summary, we propose senescence as a ploidy limiting factor during placental development and describe its suppression in hyperploid CHM-EVTs.
- Published
- 2018
7. Comparative Analysis of the Impact of Stenotic Microvasculopathy on Survival After Heart Transplantation in Two Major European Transplant Centers
- Author
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Aumayr, K., primary, Ullrich, R., additional, Zuckermann, A., additional, and Wassilew, K., additional
- Published
- 2015
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- View/download PDF
8. Comparative Analysis of Distribution of Acute Cellular Rejection and Antibody-Mediated Rejection With Emphasis on Time After Heart Transplantation in Two European Transplant Centers
- Author
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Wassilew, K., primary, Haberl, T., additional, Zuckermann, A., additional, and Aumayr, K., additional
- Published
- 2015
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- View/download PDF
9. Cardiac Post-Transplant Biopsy Tissue Processing and Reporting Protocols for Rejection: A Comparative Survey of Routine Practice Across Three European Centres
- Author
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Chaturvedi, A., primary, Aumayr, K., additional, and Wassilew, K., additional
- Published
- 2015
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- View/download PDF
10. Hemodynamic Compromising Antibody Mediated Rejection (HC-AMR) After Heart Transplantation (HTX).
- Author
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Aliabadi, A., primary, Uyanik-Uenal, K., additional, Goekler, J., additional, Wallner, S., additional, Masseti, M., additional, Aumayr, K., additional, Fischer, G., additional, Boehmig, G., additional, Laufer, G., additional, and Zuckermann, A., additional
- Published
- 2014
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11. Hemodynamic Compromising Antibody Mediated Rejection (HC-AMR) After Heart Transplantation
- Author
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Aliabadi, A.Z., primary, Groemmer, M., additional, Uyanik-Uenal, K., additional, Gökler, J., additional, Wallner, S., additional, Masseti, M., additional, Aumayr, K., additional, Fischer, G., additional, Boehmig, G., additional, Laufer, G., additional, and Zuckermann, A.O., additional
- Published
- 2014
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12. The new St Thomas' Hospital polarized cardioplegia: improved efficacy of myocardial protection in pigs on CPB
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Santer, D., primary, Dietl, W., additional, Trescher, K., additional, Kreibich, M., additional, Dzilic, E., additional, Nagel, F., additional, Hallström, S., additional, Aumayr, K., additional, Fallouh, H., additional, Chambers, D.J., additional, and Podesser, B.K., additional
- Published
- 2014
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13. Long term results in salivary gland adenoid cystic carcinoma (SACC)
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Poeschl, P.W., primary, Seemann, R., additional, Czembirek, C., additional, Wiener, C., additional, Thurnher, D., additional, Aumayr, K., additional, and Ewers, R., additional
- Published
- 2013
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14. P16INK4aImmunohistochemistry for Detection of Human Papilloma Virus-Associated Penile Squamous Cell Carcinoma is Superior toin-SituHybridization
- Author
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Aumayr, K., primary, Susani, M., additional, Horvat, R., additional, Wrba, F., additional, Mazal, P., additional, Klatte, T., additional, Koller, A., additional, Neudert, B., additional, and Haitel, A., additional
- Published
- 2013
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15. Effects of thoracic spreader shape on the sternal force distribution during median sternotomy
- Author
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Aigner, P, primary, Eskandary, F, additional, Schlöglhofer, T, additional, Gottardi, R, additional, Aumayr, K, additional, Laufer, G, additional, and Schima, H, additional
- Published
- 2013
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16. Thermal Effects of Diagnostic Ultrasound in an Anthropomorphic Skull Model
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Vyskocil, E., additional, Pfaffenberger, S., additional, Kollmann, C., additional, Gleiss, A., additional, Nawratil, G., additional, Kastl, S., additional, Unger, E., additional, Aumayr, K., additional, Schuhfried, O., additional, Huber, K., additional, Wojta, J., additional, and Gottsauner-Wolf, M., additional
- Published
- 2012
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17. Do elevated levels of interleukin-6 activated through PICSO intervention promote structural regeneration in heart failure patients?
- Author
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Wadowski, P, primary, Andreas, M, additional, Khazen, C, additional, Vukovich, T, additional, Aumayr, K, additional, Jusic, A, additional, Milasinovic, D, additional, and Mohl, W, additional
- Published
- 2012
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18. (881) - Comparative Analysis of Distribution of Acute Cellular Rejection and Antibody-Mediated Rejection With Emphasis on Time After Heart Transplantation in Two European Transplant Centers
- Author
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Wassilew, K., Haberl, T., Zuckermann, A., and Aumayr, K.
- Published
- 2015
- Full Text
- View/download PDF
19. (882) - Cardiac Post-Transplant Biopsy Tissue Processing and Reporting Protocols for Rejection: A Comparative Survey of Routine Practice Across Three European Centres
- Author
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Chaturvedi, A., Aumayr, K., and Wassilew, K.
- Published
- 2015
- Full Text
- View/download PDF
20. (876) - Comparative Analysis of the Impact of Stenotic Microvasculopathy on Survival After Heart Transplantation in Two Major European Transplant Centers
- Author
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Aumayr, K., Ullrich, R., Zuckermann, A., and Wassilew, K.
- Published
- 2015
- Full Text
- View/download PDF
21. (467) - Hemodynamic Compromising Antibody Mediated Rejection (HC-AMR) After Heart Transplantation
- Author
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Aliabadi, A.Z., Groemmer, M., Uyanik-Uenal, K., Gökler, J., Wallner, S., Masseti, M., Aumayr, K., Fischer, G., Boehmig, G., Laufer, G., and Zuckermann, A.O.
- Published
- 2014
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- View/download PDF
22. P16INK4A IMMUNOHISTOCHEMISTRY FOR DETECTION OF HUMAN PAPILLOMA VIRUS-ASSOCIATED PENILE SQUAMOUS CELL CARCINOMA IS SUPERIOR TO IN-SITU HYBRIDIZATION.
- Author
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AUMAYR, K., SUSANI, M., HORVAT, R., WRBA, F., MAZAL, P., KLATTE, T., KOLLER, A., NEUDERT, B., and HAITEL, A.
- Published
- 2013
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23. P16INK4aImmunohistochemistry for Detection of Human Papilloma Virus-Associated Penile Squamous Cell Carcinoma is Superior to in-SituHybridization
- Author
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Aumayr, K., Susani, M., Horvat, R., Wrba, F., Mazal, P., Klatte, T., Koller, A., Neudert, B., and Haitel, A.
- Abstract
We evaluated p16INK4aas a reliable option to detect human papilloma virus (HPV) DNA in penile tumor specimens. Formalin-fixed paraffin embedded samples of 26 patients with penile cancer and another 18 cases with non-tumorigenic lesions were stained by three different widely used commercially available chromogenic in-situhybridization assays high-risk HPV CISH Y1443 (Genpoint, DAKO), pan HPV CISH Y1404 (Genpoint, DAKO), INFORM HPV III (Ventana, Tucson, Arizona) and p16INK4aimmunohistochemistry, then compared to the known gold standard polymerase chain reaction detecting HPV 16, 18, 31, and 33. Immunoreactivity for p16INK4awas evaluated by using a 4-tiered (0, 1, 2, and 3) pattern based system. 19 cases were positive for p16INK4a, 13 of which showed a continuous transepithelial staining (pattern 3). Pan HPV ISH showed positivity in 9 cases, high-risk HPV ISH in 7 cases and INFORM HPVIII ISH in 7 cases. p16INK4aIHC pattern 3 versus pattern 0, 1 and 2 exhibited a specificity and positive predictive value of 100%, with a sensitivity and negative predictive value of 72% and 62%, respectively, which was much better than all HPV in-situhybridization methods referred to polymerase chain reaction. p16INK4aseems to be a superior marker for the detection of HPV-associated penile squamous cell carcinoma compared to CISH tests, but is not recommend for the detection of non-tumorigenic lesions, where PCR should be used for the initial assessment.
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- 2013
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24. Staying on track - Keeping things running in a high-end scientific imaging core facility.
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Renaud O, Aulner N, Salles A, Halidi N, Brunstein M, Mallet A, Aumayr K, Terjung S, Levy D, Lippens S, Verbavatz JM, Heuser T, Santarella-Mellwig R, Tinevez JY, Woller T, Botzki A, Cawthorne C, and Munck S
- Subjects
- Biological Science Disciplines methods
- Abstract
Modern life science research is a collaborative effort. Few research groups can single-handedly support the necessary equipment, expertise and personnel needed for the ever-expanding portfolio of technologies that are required across multiple disciplines in today's life science endeavours. Thus, research institutes are increasingly setting up scientific core facilities to provide access and specialised support for cutting-edge technologies. Maintaining the momentum needed to carry out leading research while ensuring high-quality daily operations is an ongoing challenge, regardless of the resources allocated to establish such facilities. Here, we outline and discuss the range of activities required to keep things running once a scientific imaging core facility has been established. These include managing a wide range of equipment and users, handling repairs and service contracts, planning for equipment upgrades, renewals, or decommissioning, and continuously upskilling while balancing innovation and consolidation., (© 2024 The Authors. Journal of Microscopy published by John Wiley & Sons Ltd on behalf of Royal Microscopical Society.)
- Published
- 2024
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25. QUAREP-LiMi: A community-driven initiative to establish guidelines for quality assessment and reproducibility for instruments and images in light microscopy.
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Nelson G, Boehm U, Bagley S, Bajcsy P, Bischof J, Brown CM, Dauphin A, Dobbie IM, Eriksson JE, Faklaris O, Fernandez-Rodriguez J, Ferrand A, Gelman L, Gheisari A, Hartmann H, Kukat C, Laude A, Mitkovski M, Munck S, North AJ, Rasse TM, Resch-Genger U, Schuetz LC, Seitz A, Strambio-De-Castillia C, Swedlow JR, Alexopoulos I, Aumayr K, Avilov S, Bakker GJ, Bammann RR, Bassi A, Beckert H, Beer S, Belyaev Y, Bierwagen J, Birngruber KA, Bosch M, Breitlow J, Cameron LA, Chalfoun J, Chambers JJ, Chen CL, Conde-Sousa E, Corbett AD, Cordelieres FP, Nery ED, Dietzel R, Eismann F, Fazeli E, Felscher A, Fried H, Gaudreault N, Goh WI, Guilbert T, Hadleigh R, Hemmerich P, Holst GA, Itano MS, Jaffe CB, Jambor HK, Jarvis SC, Keppler A, Kirchenbuechler D, Kirchner M, Kobayashi N, Krens G, Kunis S, Lacoste J, Marcello M, Martins GG, Metcalf DJ, Mitchell CA, Moore J, Mueller T, Nelson MS, Ogg S, Onami S, Palmer AL, Paul-Gilloteaux P, Pimentel JA, Plantard L, Podder S, Rexhepaj E, Royon A, Saari MA, Schapman D, Schoonderwoert V, Schroth-Diez B, Schwartz S, Shaw M, Spitaler M, Stoeckl MT, Sudar D, Teillon J, Terjung S, Thuenauer R, Wilms CD, Wright GD, and Nitschke R
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- Reference Standards, Reproducibility of Results, Microscopy
- Abstract
A modern day light microscope has evolved from a tool devoted to making primarily empirical observations to what is now a sophisticated , quantitative device that is an integral part of both physical and life science research. Nowadays, microscopes are found in nearly every experimental laboratory. However, despite their prevalent use in capturing and quantifying scientific phenomena, neither a thorough understanding of the principles underlying quantitative imaging techniques nor appropriate knowledge of how to calibrate, operate and maintain microscopes can be taken for granted. This is clearly demonstrated by the well-documented and widespread difficulties that are routinely encountered in evaluating acquired data and reproducing scientific experiments. Indeed, studies have shown that more than 70% of researchers have tried and failed to repeat another scientist's experiments, while more than half have even failed to reproduce their own experiments. One factor behind the reproducibility crisis of experiments published in scientific journals is the frequent underreporting of imaging methods caused by a lack of awareness and/or a lack of knowledge of the applied technique. Whereas quality control procedures for some methods used in biomedical research, such as genomics (e.g. DNA sequencing, RNA-seq) or cytometry, have been introduced (e.g. ENCODE), this issue has not been tackled for optical microscopy instrumentation and images. Although many calibration standards and protocols have been published, there is a lack of awareness and agreement on common standards and guidelines for quality assessment and reproducibility. In April 2020, the QUality Assessment and REProducibility for instruments and images in Light Microscopy (QUAREP-LiMi) initiative was formed. This initiative comprises imaging scientists from academia and industry who share a common interest in achieving a better understanding of the performance and limitations of microscopes and improved quality control (QC) in light microscopy. The ultimate goal of the QUAREP-LiMi initiative is to establish a set of common QC standards, guidelines, metadata models and tools, including detailed protocols, with the ultimate aim of improving reproducible advances in scientific research. This White Paper (1) summarizes the major obstacles identified in the field that motivated the launch of the QUAREP-LiMi initiative; (2) identifies the urgent need to address these obstacles in a grassroots manner, through a community of stakeholders including, researchers, imaging scientists, bioimage analysts, bioimage informatics developers, corporate partners, funding agencies, standards organizations, scientific publishers and observers of such; (3) outlines the current actions of the QUAREP-LiMi initiative and (4) proposes future steps that can be taken to improve the dissemination and acceptance of the proposed guidelines to manage QC. To summarize, the principal goal of the QUAREP-LiMi initiative is to improve the overall quality and reproducibility of light microscope image data by introducing broadly accepted standard practices and accurately captured image data metrics., (© 2021 The Authors. Journal of Microscopy published by JohnWiley & Sons Ltd on behalf of Royal Microscopical Society.)
- Published
- 2021
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26. St Thomas' Hospital polarizing blood cardioplegia improves hemodynamic recovery in a porcine model of cardiopulmonary bypass.
- Author
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Santer D, Kramer A, Kiss A, Aumayr K, Hackl M, Heber S, Chambers DJ, Hallström S, and Podesser BK
- Subjects
- Animals, Bicarbonates pharmacology, Biomarkers blood, Calcium Chloride pharmacology, Creatine Kinase, MB Form blood, Energy Metabolism drug effects, Female, Magnesium pharmacology, MicroRNAs metabolism, Models, Animal, Myocardium metabolism, Myocardium pathology, Potassium Chloride pharmacology, Recovery of Function, Sodium Chloride pharmacology, Sus scrofa, Time Factors, Cardioplegic Solutions pharmacology, Cardiopulmonary Bypass adverse effects, Circulatory Arrest, Deep Hypothermia Induced adverse effects, Hemodynamics drug effects, Ventricular Function, Left drug effects
- Abstract
Objective: Cardiac surgery demands highly effective cardioprotective regimens. We previously demonstrated improved cardioprotection with "polarized" compared with "depolarized" arrest. This study uses a clinically relevant porcine model of cardiopulmonary bypass to compare the efficacy of blood-based St Thomas' Hospital polarizing cardioplegia (STH-Pol-B) with blood-based St Thomas' Hospital hyperkalemic cardioplegia (STH2-B)., Methods: Pigs were monitored and subjected to normothermic cardiopulmonary bypass, cardiac arrest via antegrade cold (4°C) blood cardioplegia (STH2-B, control group: n = 6 or STH-Pol-B, study group: n = 7), and global ischemia (60 minutes) followed by on-pump reperfusion (60 minutes) and subsequent off-pump reperfusion (90 minutes). At termination, tissue samples were taken for analysis of high-energy phosphates, ultrastructure, and microRNAs. The primary endpoint of this study was creatine kinase-muscle/brain release during reperfusion., Results: Creatine kinase-muscle/brain was comparable in both groups. After pigs were weaned from cardiopulmonary bypass, hemodynamic parameters such as mean arterial pressure (P = .007), left ventricular systolic pressure (P < .001), external heart work (P = .012), stroke volume (P = .015), as well as dp/dt
max (P = .027), were improved with polarizing cardioplegia. Wedge pressure was significantly lower in the study group (P < .01). Energy charge was comparable between groups. MicroRNA-708-5p was significantly lower (P = .019) and microRNA-122 expression significantly (P = .046) greater in STH-Pol-B hearts., Conclusions: Polarized cardiac arrest offers similar myocardial protection and enhances functional recovery in a porcine model of cardiopulmonary bypass. Differential expression of microRNAs may indicate possible new ischemia-reperfusion markers. These results confirm the noninferiority and potential of polarized versus depolarized arrest., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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27. Genome amplification and cellular senescence are hallmarks of human placenta development.
- Author
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Velicky P, Meinhardt G, Plessl K, Vondra S, Weiss T, Haslinger P, Lendl T, Aumayr K, Mairhofer M, Zhu X, Schütz B, Hannibal RL, Lindau R, Weil B, Ernerudh J, Neesen J, Egger G, Mikula M, Röhrl C, Urban AE, Baker J, Knöfler M, and Pollheimer J
- Subjects
- Cell Cycle, Cell Cycle Checkpoints, Cell Differentiation, Cell Movement, Cell Proliferation, Endometrium cytology, Female, Genome physiology, Humans, Placentation genetics, Placentation physiology, Polyploidy, Pregnancy, Pregnancy Trimester, First, Primary Cell Culture, Tetraploidy, Trophoblasts metabolism, Cellular Senescence physiology, Placenta metabolism, Placenta physiology
- Abstract
Genome amplification and cellular senescence are commonly associated with pathological processes. While physiological roles for polyploidization and senescence have been described in mouse development, controversy exists over their significance in humans. Here, we describe tetraploidization and senescence as phenomena of normal human placenta development. During pregnancy, placental extravillous trophoblasts (EVTs) invade the pregnant endometrium, termed decidua, to establish an adapted microenvironment required for the developing embryo. This process is critically dependent on continuous cell proliferation and differentiation, which is thought to follow the classical model of cell cycle arrest prior to terminal differentiation. Strikingly, flow cytometry and DNAseq revealed that EVT formation is accompanied with a genome-wide polyploidization, independent of mitotic cycles. DNA replication in these cells was analysed by a fluorescent cell-cycle indicator reporter system, cell cycle marker expression and EdU incorporation. Upon invasion into the decidua, EVTs widely lose their replicative potential and enter a senescent state characterized by high senescence-associated (SA) β-galactosidase activity, induction of a SA secretory phenotype as well as typical metabolic alterations. Furthermore, we show that the shift from endocycle-dependent genome amplification to growth arrest is disturbed in androgenic complete hydatidiform moles (CHM), a hyperplastic pregnancy disorder associated with increased risk of developing choriocarinoma. Senescence is decreased in CHM-EVTs, accompanied by exacerbated endoreduplication and hyperploidy. We propose induction of cellular senescence as a ploidy-limiting mechanism during normal human placentation and unravel a link between excessive polyploidization and reduced senescence in CHM., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2018
- Full Text
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28. HER2 and TOP2A Gene Amplification and Protein Expression in Upper Tract Urothelial Carcinomas.
- Author
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Aumayr K, Klatte T, Neudert B, Birner P, Shariat S, Schmidinger M, Susani M, and Haitel A
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- Adult, Aged, Aged, 80 and over, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Female, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Humans, Male, Middle Aged, Prognosis, Retrospective Studies, Urologic Neoplasms pathology, DNA Topoisomerases, Type II genetics, DNA Topoisomerases, Type II metabolism, Gene Amplification, Poly-ADP-Ribose Binding Proteins genetics, Poly-ADP-Ribose Binding Proteins metabolism, Receptor, ErbB-2 genetics, Receptor, ErbB-2 metabolism, Urologic Neoplasms genetics, Urologic Neoplasms metabolism
- Abstract
HER2, a potential target for therapy, has been described to be amplified in urothelial carcinomas. As the topoisomerase II alpha (TOP2A) gene is located close to the HER2 gene on chromosome 17q12-q21, it is frequently either co-amplified or deleted with HER2 amplification. The purpose of this study was to assess the impact HER2 and TOP2A gene amplification as well as protein expression on outcomes of upper tract urothelial carcinoma (UTUC). HER2 and TOP2A gene amplification and protein expression were assessed in 81 patients with radical nephroureterectomy for UTUC. Immunohistochemistry and chromogenic in-situ hybridization was performed on formalin-fixed, paraffin-embedded samples. HER2 protein expression was observed in 27/81 (33%) cases, of which 8 cases exhibited amplification of HER2. One of them had an additional polysomy 17, whereas 6/67 HER2 non-amplified cases revealed a polysomy 17. Coamplification of HER2 and TOP2A was found in 4 cases, whereas 3 cases showed only HER2 amplification and 20 cases only TOP2A amplification. HER2 IHC overexpression was associated with higher-grade tumors (p = 0.001), non-organ confined carcinomas (p = 0.017), HER2 amplification (p < 0.00001) and TOP2A amplification (p = 0.016). HER2 amplification was association with higher tumor grade (p = 0.001) and lymphnode metastasis (p = 0.003). TOP2A IHC positivity was significantly associated with higher tumor grade (p = 0.0004), TOP2A amplification (p = 0.0003), polysomy 17 (p = 0.035) and HER2 IHC overexpression (p = 0.28), whereas all categories of tumor stage and HER2 amplification remained not related. TOP2A amplification was significantly more frequent in tumors with higher grade, higher tumor stage, polysomy 17 and distant metastasis (p = 0.015; p = 0.042; p = 0.032; p = 0.011), respectively. In univariate analyses HER2 IHC positivity, TOP2A amplification, and polysomy 17 were associated with poor clinical outcome after surgery. HER2 IHC overexpression and TOP2A amplification are associated with features of biologically aggressive UTUC. Overexpression and/or amplification of HER2 and TOP2A could help identify patients who may benefit from targeted therapy.
- Published
- 2018
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29. Cardiac extracellular matrix is associated with adverse outcome in patients with chronic heart failure.
- Author
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Duca F, Zotter-Tufaro C, Kammerlander AA, Panzenböck A, Aschauer S, Dalos D, Köll B, Börries B, Agis H, Kain R, Aumayr K, Klinglmüller F, Mascherbauer J, and Bonderman D
- Subjects
- Aged, Atrial Pressure, Chronic Disease, Echocardiography, Doppler, Female, Heart Failure diagnostic imaging, Heart Failure mortality, Heart Failure physiopathology, Hospitalization, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Mortality, Prognosis, Pulmonary Wedge Pressure, Stroke Volume, Extracellular Matrix pathology, Heart Failure pathology, Heart Ventricles pathology, Myocardium pathology
- Abstract
Aims: Accumulation of extracellular matrix (ECM) is known to play a crucial role in the pathophysiology of heart failure (HF). However, its prognostic relevance is poorly investigated., Methods and Results: A total of 73 HF patients who underwent LV endomyocardial biopsy were enrolled in our study. ECM area was quantified by TissueFAXS and ImageJ software. Patients were followed-up at 6-month intervals. The study endpoint was defined as hospitalization for a cardiac reason and/or cardiac death. Furthermore, the influence of the ECM on invasively measured haemodynamic parameters was tested. During a median follow-up period of 9.0 months, 34 patients (46.6%) reached the combined endpoint. Median ECM area was 30.5%. Patients with ECM area ≥30.5% experienced significantly more events (67.6% vs. 25.0%, P < 0.001) in comparison with patients with an ECM area <30.5%. ECM area was independently associated with outcome in the total HF cohort [hazard ratio (HR) 1.041, 95% confidence interval (CI) 1.017-1.066, P = 0.001] as well as in HF patients with preserved (HR 1.079, 95% CI 1.001-1.163, P =0 .046) or reduced ejection fraction (HR 1.149, 95% CI 1.036-1.275, P = 0.009). Positive correlations were found between ECM area and LV end-diastolic pressure (P = 0.021, R = 0.303), pulmonary artery wedge pressure (P = 0.042, R = 0.249), mean pulmonary arterial pressure (P = 0.035, R = 0.258), as well as right atrial pressure (P = 0.003, R = 0.353)., Conclusion: ECM area within the LV myocardium correlates with left and right heart haemodynamics and is associated with clinical course in various non-ischaemic HF types., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)
- Published
- 2017
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30. Effects of angiotensin-converting-enzyme inhibitor therapy on the regulation of the plasma and cardiac tissue renin-angiotensin system in heart transplant patients.
- Author
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Kovarik JJ, Kopecky C, Antlanger M, Domenig O, Kaltenecker CC, Werzowa J, Hecking M, Mahr S, Grömmer M, Wallner C, Aumayr K, Kain R, Zuckermann A, Poglitsch M, and Säemann MD
- Subjects
- Aged, Austria, Biopsy, Needle, Cross-Sectional Studies, Echocardiography, Female, Follow-Up Studies, Graft Survival, Heart Failure diagnostic imaging, Heart Failure surgery, Heart Transplantation adverse effects, Humans, Immunohistochemistry, Male, Middle Aged, Reference Values, Risk Assessment, Role, Treatment Outcome, Angiotensin-Converting Enzyme Inhibitors administration & dosage, Graft Rejection prevention & control, Heart Failure blood, Heart Transplantation methods, Renin-Angiotensin System drug effects
- Abstract
Background: Angiotensin-converting enzyme (ACE) inhibitors (ACEis) are beneficial in patients with heart failure, yet their role after heart transplantation (HTx) remains ambiguous. Particularly, the effects of ACEis on plasma and cardiac metabolites of the "classical" and "alternative" renin-angiotensin system (RAS) in HTx patients are unknown., Methods: This cross-sectional study used a novel mass spectrometry-based approach to analyze plasma and tissue RAS regulation in homogenates of heart biopsy specimens from 10 stable HTx patients without RAS blockade and in 15 patients with ACEi therapy. Angiotensin (Ang) levels in plasma and Ang formation rates in biopsy tissue homogenates were measured., Results: Plasma Ang II formation is exclusively ACE dependent, whereas cardiac Ang II formation is primarily chymase dependent in HTx patients. ACEi therapy substantially increased plasma Ang-(1-7), the key effector of the alternative RAS, leaving plasma Ang II largely intact. Importantly, neprilysin and prolyl-carboxypeptidase but not angiotensin converting enzyme 2 are essential for cardiac tissue Ang-(1-7) formation., Conclusion: ACE is the key enzyme for the generation of plasma Ang II, whereas chymase is responsible for cardiac tissue production of Ang II. Furthermore, our findings reveal that neprilysin and prolyl-carboxypeptidase are the essential cardiac enzymes for the alternative RAS after HTx. These novel insights into the versatile regulation of the RAS in HTx patients might affect future therapeutic avenues, such as chymase and neprilysin inhibition, beyond classical Ang II blockade., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
- Published
- 2017
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31. Overexpression of DCLK1 is predictive for recurrent disease in major salivary gland malignancies.
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Kadletz L, Aumayr K, Heiduschka G, Schneider S, Enzenhofer E, and Lill C
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- Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma metabolism, Carcinoma mortality, Carcinoma pathology, Disease-Free Survival, Doublecortin-Like Kinases, Female, Humans, Immunohistochemistry, Lymphatic Metastasis, Male, Middle Aged, Neoplasm Recurrence, Local pathology, Prognosis, Retrospective Studies, Salivary Gland Neoplasms mortality, Salivary Gland Neoplasms pathology, Young Adult, Biomarkers, Tumor metabolism, Intracellular Signaling Peptides and Proteins metabolism, Neoplasm Recurrence, Local metabolism, Protein Serine-Threonine Kinases metabolism, Salivary Gland Neoplasms metabolism
- Abstract
Salivary gland carcinomas are a rare malignancy. Therefore, little is known about biomarkers and cancer stem cells in salivary gland malignancies. Double cortin-like kinase 1 (DCLK1) is a promising therapeutic target and cancer stem cell marker, predominantly investigated in pancreatic and colorectal cancer. The purpose of this study was to investigate the expression of DCLK1 in major and minor salivary gland carcinomas and its influence on survival. We examined a total of 80 patients with major or minor salivary gland cancer in this retrospective study. Immunohistochemistry with anti-DCLK1 antibody was applied to assess the expression of DCLK1. Moreover, we evaluated the impact of DCLK1 on overall and disease-free survival. DCLK1 expression could be detected in 66.3 % of all examined cases. Overexpression of DCLK1 was associated with reduced overall and disease-free survival in patients with major salivary gland cancer. Disease-free survival reached statistical significance (p = 0.0107). However, expression of DCLK1 had no influence on survival in patients with minor salivary gland cancer. Since treatment of recurrent disease in oncologic patients is utterly challenging, DCLK1 may be a promising prognostic biomarker that helps to identify patients with a high risk for recurrence of major salivary gland carcinoma.
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- 2017
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32. Influence of antithymocyte globulin treatment of brain-dead organ donor on inflammatory response in cardiac grafts: an experimental study in mice.
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Kremer J, Muschitz GK, Aumayr K, Moser P, Szabo G, Weymann A, Zuckermann A, and Podesser BK
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- Animals, Brain Death, Cytokines metabolism, Enzyme-Linked Immunosorbent Assay, Female, Immunohistochemistry, Interleukin-2 metabolism, Interleukin-6 metabolism, Mice, Random Allocation, Tissue Donors, Antilymphocyte Serum therapeutic use, Heart Failure surgery, Heart Transplantation, Inflammation metabolism, Myocardium metabolism
- Abstract
The expression of proinflammatory cytokines in donor hearts after antithymocyte globulin (ATG) treatment given prior to organ removal was evaluated to analyze changes in inflammatory response. Adult female OF-1 mice were randomized into brain death (BD) groups (BD Control, BD ATG) with or without treatment, and Controls (Control, ATG). BD induction was performed through gradual inflation of an intracranial positioned balloon catheter. At the end of a 6-h observation period, ATG (1 mg/kg BW) was given intravenously. After 45 min, the donor hearts were removed. Proinflammatory markers IL-2 and IL-6 were examined using ELISA and immunohistochemistry staining. After single administration of ATG, the inflammatory reaction in the myocardium showed a significant reduction in IL-2 expression (BD Control vs. BD ATG, P = 0.033). Our investigation showed expected increase in proinflammatory mediators after BD. This increase was abolished by single infusion of ATG, indicated by significant reduction in IL-2 levels in the myocardium. We observed a reduction of IL-6 deposition in media cells in ATG-treated specimens. Further research is necessary to evaluate the role of ATG in donor management considering a potentially positive effect of ATG on IL-2-directed inflammatory response and possible reduction of IL-6-mediated vascular changes., (© 2016 Steunstichting ESOT.)
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- 2016
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33. The prognostic significance of β-catenin, cyclin D1 and PIN1 in minor salivary gland carcinoma: β-catenin predicts overall survival.
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Schneider S, Thurnher D, Seemann R, Brunner M, Kadletz L, Ghanim B, Aumayr K, Heiduschka G, and Lill C
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- Austria, Biomarkers, Tumor metabolism, Female, Humans, Male, Middle Aged, Outcome Assessment, Health Care, Predictive Value of Tests, Prognosis, Retrospective Studies, Statistics as Topic, Survival Analysis, Carcinoma, Adenoid Cystic metabolism, Carcinoma, Adenoid Cystic pathology, Cyclin D1 metabolism, NIMA-Interacting Peptidylprolyl Isomerase metabolism, Salivary Gland Neoplasms metabolism, Salivary Gland Neoplasms pathology, Salivary Glands, Minor pathology, beta Catenin metabolism
- Abstract
Minor salivary gland carcinoma is a rare and heterogeneous type of cancer. Molecular prognostic and predictive markers are sparse. The aim of this study was to identify new prognostic and predictive markers in minor salivary gland carcinoma. 50 tissue samples of carcinomas of the minor salivary glands (adenoid cystic carcinoma n = 23, mucoepidermoid carcinoma n = 12, adenocarcinoma n = 10, carcinoma ex pleomorphic adenoma n = 2, salivary duct carcinoma n = 1, clear cell carcinoma n = 1, basal cell carcinoma n = 1) were immunohistochemically stained for β-catenin, cyclin D1 and PIN1. Expression patterns were analyzed and correlated to clinical outcome of 37 patients with complete clinical data. High expression of membranous β-catenin was linked to significantly better overall survival in patients with adenoid cystic carcinoma (log rank test, χ (2) = 13.3, p = .00397, Bonferroni corrected p = .024). PIN1 and cyclin D1 did not show any significant correlation to patients' clinical outcome. Expression of β-catenin in adenoid cystic carcinoma of the minor salivary glands significantly correlates with better overall survival. Hence, evaluation of β-catenin might serve as a clinical prognostic marker.
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- 2016
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34. The nitric oxide donor, S-nitroso human serum albumin, as an adjunct to HTK-N cardioplegia improves protection during cardioplegic arrest after myocardial infarction in rats.
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Trescher K, Dzilic E, Kreibich M, Gasser H, Aumayr K, Kerjaschki D, Pelzmann B, Hallström S, and Podesser BK
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- Animals, Cardiac Output drug effects, Cardiac Output physiology, Cardioplegic Solutions pharmacology, Disease Models, Animal, Glucose pharmacology, Heart Arrest etiology, Male, Mannitol pharmacology, Myocardial Infarction complications, Myocardial Infarction physiopathology, Potassium Chloride pharmacology, Procaine pharmacology, Rats, Rats, Sprague-Dawley, Serum Albumin, Human, Treatment Outcome, Heart Arrest prevention & control, Heart Arrest, Induced methods, Myocardial Infarction therapy, Nitric Oxide Donors pharmacology, Nitroso Compounds pharmacology, Serum Albumin pharmacology
- Abstract
Objectives: Currently available cardioplegic solutions provide excellent protection in patients with normal surgical risk; in high-risk patients, however, such as in emergency coronary artery bypass surgery, there is still room for improvement. As most of the cardioplegic solutions primarily protect myocytes, the addition of substances for protection of the endothelium might improve their protective potential. The nitric oxide donor, S-nitroso human serum albumin (S-NO-HSA), which has been shown to prevent endothelial nitric oxide synthase uncoupling, was added to the newly developed histidine-tryptophan-ketoglutarat (HTK-N) cardioplegia in an isolated heart perfusion system after subjecting rats to acute myocardial infarction (MI) and reperfusion., Methods: In male Sprague-Dawley rats, acute MI was induced by ligation for 1 h of the anterior descending coronary artery. After 2 h of in vivo reperfusion hearts were evaluated on an isolated erythrocyte-perfused working heart model. Cold ischaemia (4°C) for 60 min was followed by 45 min of reperfusion. Cardiac arrest was induced either with HTK (n = 10), HTK-N (n = 10) or HTK-N + S-NO-HSA (n = 10). In one group (HTK-N + S-NO-HSA plus in vivo S-NO-HSA; n = 9) an additional in vivo infusion of S-NO-HSA was performed., Results: Post-ischaemic recovery of cardiac output (HTK: 77 ± 4%, HTK-N: 86 ± 7%, HTK-N + S-NO-HSA: 101 ± 5%, in vivo S-NO-HSA: 93 ± 8%), external heart work (HTK: 79 ± 5%, HTK-N: 83 ± 3%, HTK-N + S-NO-HSA: 101 ± 8%, in vivo S-NO-HSA: 109 ± 13%), coronary flow (HTK: 77 ± 4%, HTK-N: 94 ± 6%, HTK-N + S-NO-HSA: 118 ± 15%, in vivo S-NO-HSA: 113 ± 3.17%) [HTK-N + S-NO-HSA vs HTK P < 0.001; HTK-N + S-NO-HSA vs HTK-N P < 0.05] and left atrial diastolic pressure (HTK: 122 ± 31%, HTK-N: 159 ± 43%, HTK-N + S-NO-HSA: 88 ± 30, in vivo S-NO-HSA: 62 ± 10%) [HTK-N + S-NO-HSA vs HTK P < 0.05; in vivo S-NO-HSA vs HTK-N P < 0.05] were significantly improved in both S-NO-HSA-treated groups compared with HTK and HTK-N, respectively. This was accompanied by better preservation of high-energy phosphates (adenosine triphosphate; energy charge) and ultrastructural integrity on transmission electron microscopy. However, no additional benefit of in vivo S-NO-HSA infusion was observed., Conclusions: Addition of the NO donor, S-NO-HSA refines the concept of HTK-N cardioplegia in improving post-ischaemic myocardial perfusion. HTK-N with S-NO-HSA is a possible therapeutic option for patients who have to be operated on for acute MI., (© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
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- 2015
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35. Coronary Pan-Ischemia as a First Sign of a Fulminant Host-Versus-Graft Reaction Eight Years After Orthotopic Heart Transplantation.
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Kammler J, Blessberger H, Kypta A, Lichtenauer M, Nahler A, Lambert T, Aumayr K, Zuckermann A, and Steinwender C
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- Bradycardia diagnosis, Bradycardia etiology, Electrocardiography methods, Fatal Outcome, Female, Humans, Middle Aged, Myocardium pathology, Severity of Illness Index, Graft Rejection diagnosis, Graft Rejection pathology, Graft Rejection physiopathology, Heart Transplantation adverse effects, Myocardial Ischemia diagnosis, Myocardial Ischemia etiology, Myocardial Ischemia physiopathology, Postoperative Complications diagnosis, Postoperative Complications pathology, Postoperative Complications physiopathology
- Abstract
Acute graft rejection in patients after heart transplantation can cause arrhythmias and acute angina pectoris with electrocardiographic ST-segment elevation. We report a case of a 53-year old female patient who had undergone cardiac transplantation 8 years previously. She developed bradycardia with co-existent ST-segment elevation caused by a histologically proven acute graft rejection. After administration of methylprednisolone and immune absorption leading to initial clinical improvement, the patient died unexpectedly. The reasons remain unclear, but a degeneration of the conduction system as well as impaired blood flow in the right coronary caused by cellular and humoral rejection most likely have both contributed.
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- 2015
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36. Correlation of β-catenin, but not PIN1 and cyclin D1, overexpression with disease-free and overall survival in patients with cancer of the parotid gland.
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Lill C, Schneider S, Seemann R, Kadletz L, Aumayr K, Ghanim B, and Thurnher D
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- Adolescent, Adult, Aged, Aged, 80 and over, Carcinoma mortality, Carcinoma pathology, Disease-Free Survival, Female, Humans, Male, Middle Aged, NIMA-Interacting Peptidylprolyl Isomerase, Parotid Neoplasms pathology, Retrospective Studies, Survival Rate, Young Adult, Carcinoma metabolism, Cyclin D1 metabolism, Parotid Neoplasms metabolism, Parotid Neoplasms mortality, Peptidylprolyl Isomerase metabolism, beta Catenin metabolism
- Abstract
Background: Malignant tumors of the salivary glands comprise about 3% to 5% of all head and neck carcinomas. The purpose of our study was to find possible predictive and/or prognostic markers for parotid cancer., Methods: A total of 46 tissue samples of carcinomas of the parotid gland were immunohistochemically stained for ß-catenin, cyclin D1, and PIN1. The factors were analyzed regarding their prognostic value for disease-free and overall survival., Results: An overexpression of the cytoplasmatic ß-catenin was linked to a statistically significant worse outcome regarding disease-free (p = .0296) and overall survival (p = .0416). The 5-year overall survival was 83.9% in patients without and 0% in patients presenting with overexpression of cytoplasmatic ß-catenin. Additionally, Union Internationale Contre le Cancer (UICC) stage correlated with overall survival (p = .0306) and disease-free survival (DFS; p = .0473)., Conclusion: Multivariate analysis showed that overexpression of cytoplasmatic ß-catenin and the UICC stage are 2 independent prognostic markers for survival in patients with parotid cancer., (© 2014 Wiley Periodicals, Inc.)
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- 2015
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37. Interleukin-like epithelial-to-mesenchymal transition inducer activity is controlled by proteolytic processing and plasminogen-urokinase plasminogen activator receptor system-regulated secretion during breast cancer progression.
- Author
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Csiszar A, Kutay B, Wirth S, Schmidt U, Macho-Maschler S, Schreiber M, Alacakaptan M, Vogel GF, Aumayr K, Huber LA, and Beug H
- Subjects
- Animals, Breast Neoplasms mortality, Breast Neoplasms pathology, Cell Line, Tumor, Disease Progression, Epithelial-Mesenchymal Transition, Female, Fibrinolysin metabolism, Humans, Kaplan-Meier Estimate, Leukocyte Elastase metabolism, Lung Neoplasms mortality, Lung Neoplasms secondary, Mice, Nude, Neoplasm Transplantation, Plasma Kallikrein metabolism, Protein Processing, Post-Translational, Protein Transport, Proteolysis, Breast Neoplasms metabolism, Cytokines physiology, Lung Neoplasms metabolism, Neoplasm Proteins physiology, Receptors, Urokinase Plasminogen Activator metabolism
- Abstract
Introduction: Interleukin-like epithelial-to-mesenchymal transition inducer (ILEI) is an essential cytokine in tumor progression that is upregulated in several cancers, and its altered subcellular localization is a predictor of poor survival in human breast cancer. However, the regulation of ILEI activity and the molecular meaning of its altered localization remain elusive., Methods: The influence of serum withdrawal, broad-specificity protease inhibitors, different serine proteases and plasminogen depletion on the size and amount of the secreted ILEI protein was investigated by Western blot analysis of EpRas cells. Proteases with ILEI-processing capacity were identified by carrying out an in vitro cleavage assay. Murine mammary tumor and metastasis models of EpC40 and 4T1 cells overexpressing different mutant forms of ILEI were used-extended with in vivo aprotinin treatment for the inhibition of ILEI-processing proteases-to test the in vivo relevance of proteolytic cleavage. Stable knockdown of urokinase plasminogen activator receptor (uPAR) in EpRas cells was performed to investigate the involvement of uPAR in ILEI secretion. The subcellular localization of the ILEI protein in tumor cell lines was analyzed by immunofluorescence. Immunohistochemistry for ILEI localization and uPAR expression was performed on two human breast cancer arrays, and ILEI and uPAR scores were correlated with the metastasis-free survival of patients., Results: We demonstrate that secreted ILEI requires site-specific proteolytic maturation into its short form for its tumor-promoting function, which is executed by serine proteases, most efficiently by plasmin. Noncleaved ILEI is tethered to fibronectin-containing fibers of the extracellular matrix through a propeptide-dependent interaction. In addition to ILEI processing, plasmin rapidly increases ILEI secretion by mobilizing its intracellular protein pool in a uPAR-dependent manner. Elevated ILEI secretion correlates with an altered subcellular localization of the protein, most likely representing a shift into secretory vesicles. Moreover, altered subcellular ILEI localization strongly correlates with high tumor cell-associated uPAR protein expression, as well as with poor survival, in human breast cancer., Conclusions: Our findings point out extracellular serine proteases, in particular plasmin, and uPAR as valuable therapeutic targets against ILEI-driven tumor progression and emphasize the prognostic relevance of ILEI localization and a combined ILEI-uPAR marker analysis in human breast cancer.
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- 2014
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38. A strand-specific switch in noncoding transcription switches the function of a Polycomb/Trithorax response element.
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Herzog VA, Lempradl A, Trupke J, Okulski H, Altmutter C, Ruge F, Boidol B, Kubicek S, Schmauss G, Aumayr K, Ruf M, Pospisilik A, Dimond A, Senergin HB, Vargas ML, Simon JA, and Ringrose L
- Subjects
- Animals, Base Sequence, Binding Sites, Chromatin genetics, DNA-Binding Proteins genetics, Drosophila melanogaster, Genome, Insect, Histone-Lysine N-Methyltransferase genetics, Molecular Sequence Data, Transcription Factors genetics, Chromosomal Proteins, Non-Histone genetics, Drosophila Proteins genetics, Genes, Switch, Polycomb-Group Proteins genetics, RNA, Untranslated, Response Elements, Transcription, Genetic
- Abstract
Polycomb/Trithorax response elements (PRE/TREs) can switch their function reversibly between silencing and activation by mechanisms that are poorly understood. Here we show that a switch in forward and reverse noncoding transcription from the Drosophila melanogaster vestigial (vg) PRE/TRE switches the status of the element between silencing (induced by the forward strand) and activation (induced by the reverse strand). In vitro, both noncoding RNAs inhibit PRC2 histone methyltransferase activity, but, in vivo, only the reverse strand binds PRC2. Overexpression of the reverse strand evicts PRC2 from chromatin and inhibits its enzymatic activity. We propose that the interaction of RNAs with PRC2 is differentially regulated in vivo, allowing regulated inhibition of local PRC2 activity. Genome-wide analysis shows that strand switching of noncoding RNAs occurs at several hundred Polycomb-binding sites in fly and vertebrate genomes. This work identifies a previously unreported and potentially widespread class of PRE/TREs that switch function by switching the direction of noncoding RNA transcription.
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- 2014
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39. Phosphorylation of STAT3 correlates with HER2 status, but not with survival in pancreatic ductal adenocarcinoma.
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Koperek O, Aumayr K, Schindl M, Werba G, Soleiman A, Schoppmann S, Sahora K, and Birner P
- Subjects
- Aged, Carcinoma, Pancreatic Ductal pathology, Female, Gene Amplification, Humans, Immunohistochemistry, In Situ Hybridization, Male, Middle Aged, Pancreatic Neoplasms pathology, Phosphorylation, Prognosis, Receptor, ErbB-2 genetics, Retrospective Studies, STAT3 Transcription Factor chemistry, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal metabolism, Genes, erbB-2, Pancreatic Neoplasms genetics, Pancreatic Neoplasms metabolism, Receptor, ErbB-2 metabolism, STAT3 Transcription Factor metabolism
- Abstract
Activation of signal-transcriptional factor signal transducer and activator of transcription 3 (STAT3) is associated with more aggressive behaviour in a variety of human malignancies. As selective STAT3 inhibitors exist, this protein might represent a novel therapeutic target. Although STAT3 seems to play an important role in progression of pancreatic ductal carcinoma (PDAC), only few data on this subject exist. The aim of our study was the investigation of STAT3 activation and its correlation with its possible regulator HER2. Expression of tyrosine-705 phosphorylated STAT3 (pSTAT3) was determined immunohistochemically in 79 PDACs. HER2 status assessed by immunohistochemistry and double colour silver in situ hybridization was available from a previous study. PSTAT3 expression was seen in 33 (41.8%) patients. Six patients were scored as HER2 positive having strong correlation with pSTAT3 expression (p = 0.004, Fisher's exact test). No association of pSTAT3 expression with patients' age, tumour staging and grading, perineural invasion of tumour cells or survival time was seen. pSTAT3 is frequently expressed in PDAC. Nevertheless, its immediate clinical relevance seems to be low. However, further research needs to determine whether STAT3 status in PDAC is predictive for the response to novel targeting therapies., (© 2013 APMIS. Published by John Wiley & Sons Ltd.)
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- 2014
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40. T-regulatory cell treatment prevents chronic rejection of heart allografts in a murine mixed chimerism model.
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Pilat N, Farkas AM, Mahr B, Schwarz C, Unger L, Hock K, Oberhuber R, Aumayr K, Wrba F, and Wekerle T
- Subjects
- Allografts, Animals, Chronic Disease, Female, Mice, Mice, Inbred Strains, Sirolimus pharmacology, Skin Transplantation, Transplantation Immunology immunology, Bone Marrow Transplantation, Heart Transplantation, T-Lymphocytes, Regulatory immunology, T-Lymphocytes, Regulatory transplantation, Transplantation Chimera immunology, Transplantation Tolerance immunology
- Abstract
Background: The mixed chimerism approach induces donor-specific tolerance in both pre-clinical models and clinical pilot trials. However, chronic rejection of heart allografts and acute rejection of skin allografts were observed in some chimeric animals despite persistent hematopoietic chimerism and tolerance toward donor antigens in vitro. We tested whether additional cell therapy with regulatory T cells (Tregs) is able to induce full immunologic tolerance and prevent chronic rejection., Methods: We recently developed a murine "Treg bone marrow (BM) transplantation (BMT) protocol" that is devoid of cytoreductive recipient pre-treatment. The protocol consists of a moderate dose of fully mismatched allogeneic donor BM under costimulation blockade, together with polyclonal recipient Tregs and rapamycin. Control groups received BMT under non-myeloablative irradiation and costimulation blockade without Treg therapy. Multilineage chimerism was followed by flow cytometry, and tolerance was assessed by donor-specific skin and heart allografts., Results: Durable multilineage chimerism and long-term donor skin and heart allograft survival were successfully achieved with both protocols. Notably, histologic examination of heart allografts at the end of follow-up revealed that chronic rejection is prevented only in chimeras induced with the Treg protocol., Conclusions: In a mouse model of mixed chimerism, additional Treg treatment at the time of BMT prevents chronic rejection of heart allografts. As the Treg-chimerism protocol also obviates the need for cytoreductive recipient treatment it improves both efficacy and safety over previous non-myeloablative mixed chimerism regimens. These results may significantly impact the development of protocols for tolerance induction in cardiac transplantation., (© 2014 International Society for Heart and Lung Transplantation Published by International Society for the Heart and Lung Transplantation All rights reserved.)
- Published
- 2014
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41. Known players, new interplay in atherogenesis: Chronic shear stress and carbamylated-LDL induce and modulate expression of atherogenic LR11 in human coronary artery endothelium.
- Author
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Bajari TM, Winnicki W, Gensberger ET, Scharrer SI, Regele H, Aumayr K, Kopecky C, Gmeiner BM, Hermann M, Zeillinger R, and Sengölge G
- Subjects
- Atherosclerosis genetics, Atherosclerosis pathology, Cell Movement, Cell Proliferation, Cells, Cultured, Coronary Artery Disease genetics, Coronary Artery Disease pathology, Coronary Vessels pathology, Culture Media, Conditioned metabolism, Endothelial Cells pathology, Enzyme Activation, Humans, Muscle, Smooth, Vascular metabolism, Myocytes, Smooth Muscle metabolism, Phosphorylation, Stress, Mechanical, Time Factors, p38 Mitogen-Activated Protein Kinases metabolism, Atherosclerosis metabolism, Coronary Artery Disease metabolism, Coronary Vessels metabolism, Endothelial Cells metabolism, LDL-Receptor Related Proteins metabolism, Lipoproteins, LDL metabolism, Mechanotransduction, Cellular, Membrane Transport Proteins metabolism
- Abstract
In this study we examined whether low-density lipoprotein (LDL) receptor family members represent a link between blood flow characteristics and modified low-density lipoproteins involved in endothelial injury, a pivotal factor in atherogenesis. We demonstrated the expression of pro-atherogenic LDL receptor relative (LR11) for the first time in human coronary artery endothelial cells (HCAEC) in vitro and in vivo. Next, LR11 expression and regulation were explored in HCAEC cultured conventionally or on the inner surface of hollow fiber capillaries under exposure to shear stress for 10 days in the presence or absence of LDL. There was no LR11 expression under static conditions. When exposed to chronic low shear stress (2.5 dynes/cm²) transmembrane and soluble endothelial-LR11 were detected in high levels irrespective of the type of LDL added (carbamylated or native). In contrast, chronic high shear stress (25 dynes/cm²) inhibited the LR11-inducing effect of LDL such that transmembrane and soluble LR11 expression became non-detectable with native LDL. Carbamylated LDL significantly counteracted this atheroprotective effect of high shear stress as shown by lower, yet sustained expression of soluble and transmembrane LR11. Oxidised LDL showed similar effects compared to carbamylated LDL but caused significantly lower LR11 expression under chronic high shear stress. Medium from HCAEC under LR11-inducing conditions enhanced vascular smooth muscle cell migration, which was abrogated by the anti-LR11 antibody. Expression of LR11 depended entirely on p38MAPK phosphorylation. We conclude that coronary endothelial LR11 expression modulated by LDL and chronic shear stress contributes to atherogenesis. LR11 and p38MAPK are potential targets for prevention of atherosclerosis.
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- 2014
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42. A dual role for autophagy in a murine model of lung cancer.
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Rao S, Tortola L, Perlot T, Wirnsberger G, Novatchkova M, Nitsch R, Sykacek P, Frank L, Schramek D, Komnenovic V, Sigl V, Aumayr K, Schmauss G, Fellner N, Handschuh S, Glösmann M, Pasierbek P, Schlederer M, Resch GP, Ma Y, Yang H, Popper H, Kenner L, Kroemer G, and Penninger JM
- Subjects
- Animals, Autophagy-Related Protein 5, Disease Progression, Female, Gene Deletion, Gene Expression Profiling, Male, Mice, Mice, Inbred BALB C, Microtubule-Associated Proteins genetics, Mutation genetics, T-Lymphocytes, Regulatory pathology, T-Lymphocytes, Regulatory physiology, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 physiology, Autophagy physiology, Disease Models, Animal, Lung Neoplasms pathology, Lung Neoplasms physiopathology, Microtubule-Associated Proteins physiology
- Abstract
Autophagy is a mechanism by which starving cells can control their energy requirements and metabolic states, thus facilitating the survival of cells in stressful environments, in particular in the pathogenesis of cancer. Here we report that tissue-specific inactivation of Atg5, essential for the formation of autophagosomes, markedly impairs the progression of KRas(G12D)-driven lung cancer, resulting in a significant survival advantage of tumour-bearing mice. Autophagy-defective lung cancers exhibit impaired mitochondrial energy homoeostasis, oxidative stress and a constitutively active DNA damage response. Genetic deletion of the tumour suppressor p53 reinstates cancer progression of autophagy-deficient tumours. Although there is improved survival, the onset of Atg5-mutant KRas(G12D)-driven lung tumours is markedly accelerated. Mechanistically, increased oncogenesis maps to regulatory T cells. These results demonstrate that, in KRas(G12D)-driven lung cancer, Atg5-regulated autophagy accelerates tumour progression; however, autophagy also represses early oncogenesis, suggesting a link between deregulated autophagy and regulatory T cell controlled anticancer immunity.
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- 2014
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43. HER2 gene amplification and protein expression in pancreatic ductal adenocarcinomas.
- Author
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Aumayr K, Soleiman A, Sahora K, Schindl M, Werba G, Schoppmann SF, and Birner P
- Subjects
- Aged, Carcinoma, Pancreatic Ductal mortality, Female, Gene Amplification, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, In Situ Hybridization, Male, Middle Aged, Pancreatic Neoplasms mortality, Receptor, ErbB-2 genetics, Silver, Survival Analysis, Tissue Array Analysis, Carcinoma, Pancreatic Ductal diagnosis, Pancreatic Neoplasms diagnosis, Receptor, ErbB-2 metabolism
- Abstract
Background: Despite advances in combination therapies, the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains extremely poor. Blocking of overexpressed HER2 oncogene improves survival in breast and gastroesophageal cancer and might be also a therapeutic option in PDAC. The purpose of this study was to evaluate HER2 gene amplification and protein expression in PDAC., Methods: HER2 protein expression was investigated using a FDA-approved antibody in 87 formalin-fixed and paraffin-embedded cases of PDAC with complete follow-up. HER2 gene amplification was assessed on tissue microarrays using dual color silver in situ hybridization (DISH)., Results: Generally, HER2 immunostaining showed considerable heterogeneity. In 19 cases, ≥10 of tumor cells showed some positive reaction. In no case, complete membranous staining was observed. Using the scoring system developed for assessment of HER2 status in gastroesophageal cancer, 9 cases showed positive immunohistologic staining (score 2+ to 3+). After performing DISH, 6 (7%) immunohistochemically 2+ or 3+ cases were found to have HER2 gene amplification, whereas none of these cases showed polyploidy. No association of HER2 status and clinicopathologic parameters or survival was observed (P>0.05)., Conclusions: HER2 is overexpressed in a subset of PDACs, identifying them as possible candidates for a targeted therapy. For assessment of HER2 status in PDAC, the scoring system originally developed for gastric cancer is recommend.
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- 2014
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44. Sternal force distribution during median sternotomy retraction.
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Aigner P, Eskandary F, Schlöglhofer T, Gottardi R, Aumayr K, Laufer G, and Schima H
- Subjects
- Aged, Cadaver, Equipment Design, Female, Fractures, Bone etiology, Humans, Male, Middle Aged, Sternotomy adverse effects, Sternum injuries, Stress, Mechanical, Transducers, Pressure, Sternotomy instrumentation, Sternum surgery, Surgical Instruments
- Abstract
Background: Median sternotomy is the access of choice in cardiac surgery. Sternal retractors exert significant forces on the thoracic cage and might cause considerable damage. The aim of this study was to determine the effects of retractor shape on local force distribution to obtain criteria for retractor design., Methods: Two types of sternal retractors (straight [SSR] and curved [CSR]) were equipped with force sensors. Force distribution, total force, and displacement were recorded to a spread width of 10 cm in 18 corpses (11 males and 7 females; age, 62 ± 12 years). Both retractors were used in alternating sequence in 4 iterations in every corpse. Data were compared with respect to the different retractor blade shapes., Results: Maximum total forces for full retraction of both retractors resulted in 349.4 ± 77.9 N. Force distribution during the first retraction for the cranial/median/caudal part of the sternum was 101.5 ± 43.9/29.1 ± 33.9/63.0 ± 31.4 N for the SSR and 38.7 ± 41.3/80.9 ± 64.5/34.0 ± 25.8 N for the CSR, respectively. During the 4 spreading cycles, the average force decreased from 224.6 ± 61.3 N in the first to 110.8 ± 39.8 N in the fourth iteration. The mean total force for the first retraction revealed 226.4 ± 71.9 N for the CSR and 222.8 ± 52.9 N for the SSR., Conclusions: The shape of sternal retractors considerably influences the force distribution on the sternal incision. In the SSR, forces on the cranial and caudal sternum are significantly higher than in the median section, whereas in the CSR, forces in the median section are highest., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)
- Published
- 2013
- Full Text
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45. Brain-wide 3D imaging of neuronal activity in Caenorhabditis elegans with sculpted light.
- Author
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Schrödel T, Prevedel R, Aumayr K, Zimmer M, and Vaziri A
- Subjects
- Animals, Animals, Genetically Modified, Behavior, Animal drug effects, Behavior, Animal radiation effects, Brain radiation effects, Calcium Signaling genetics, Equipment Design, Green Fluorescent Proteins genetics, Imaging, Three-Dimensional instrumentation, Lab-On-A-Chip Devices, Light, Microscopy, Fluorescence, Models, Neurological, Neural Pathways radiation effects, Neuroimaging, Neurons radiation effects, Oxygen pharmacology, Recombinant Fusion Proteins genetics, Stimulation, Chemical, Brain physiology, Caenorhabditis elegans genetics, Caenorhabditis elegans physiology, Imaging, Three-Dimensional methods, Neural Pathways physiology, Neurons physiology
- Abstract
Recent efforts in neuroscience research have been aimed at obtaining detailed anatomical neuronal wiring maps as well as information on how neurons in these networks engage in dynamic activities. Although the entire connectivity map of the nervous system of Caenorhabditis elegans has been known for more than 25 years, this knowledge has not been sufficient to predict all functional connections underlying behavior. To approach this goal, we developed a two-photon technique for brain-wide calcium imaging in C. elegans, using wide-field temporal focusing (WF-TeFo). Pivotal to our results was the use of a nuclear-localized, genetically encoded calcium indicator, NLS-GCaMP5K, that permits unambiguous discrimination of individual neurons within the densely packed head ganglia of C. elegans. We demonstrate near-simultaneous recording of activity of up to 70% of all head neurons. In combination with a lab-on-a-chip device for stimulus delivery, this method provides an enabling platform for establishing functional maps of neuronal networks.
- Published
- 2013
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46. P16INK4A immunohistochemistry for detection of human papilloma virus-associated penile squamous cell carcinoma is superior to in-situ hybridization.
- Author
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Aumayr K, Susani M, Horvat R, Wrba F, Mazal P, Klatte T, Koller A, Neudert B, and Haitel A
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Squamous Cell chemistry, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell virology, Humans, Image Interpretation, Computer-Assisted, Male, Middle Aged, Papillomaviridae classification, Papillomavirus Infections complications, Papillomavirus Infections virology, Penile Neoplasms chemistry, Penile Neoplasms pathology, Penile Neoplasms virology, Polymerase Chain Reaction, Predictive Value of Tests, Biomarkers, Tumor analysis, Carcinoma, Squamous Cell diagnosis, Cyclin-Dependent Kinase Inhibitor p16 analysis, DNA, Viral analysis, Human Papillomavirus DNA Tests, Immunohistochemistry, In Situ Hybridization, Papillomaviridae genetics, Papillomavirus Infections diagnosis, Penile Neoplasms diagnosis
- Abstract
We evaluated p16INK4A as a reliable option to detect human papilloma virus (HPV) DNA in penile tumor specimens. Formalin-fixed paraffin embedded samples of 26 patients with penile cancer and another 18 cases with non-tumorigenic lesions were stained by three different widely used commercially available chromogenic in-situ hybridization assays high-risk HPV CISH Y1443 (Genpoint, DAKO), pan HPV CISH Y1404 (Genpoint, DAKO), INFORM HPV III (Ventana, Tucson, Arizona) and p16INK4A immunohistochemistry, then compared to the known gold standard polymerase chain reaction detecting HPV 16, 18, 31, and 33. Immunoreactivity for p16INK4A was evaluated by using a 4-tiered (0, 1, 2, and 3) pattern based system. 19 cases were positive for p16INK4A, 13 of which showed a continuous transepithelial staining (pattern 3). Pan HPV ISH showed positivity in 9 cases, high-risk HPV ISH in 7 cases and INFORM HPVIII ISH in 7 cases. p16INK4A IHC pattern 3 versus pattern 0, 1 and 2 exhibited a specificity and positive predictive value of 100 percent, with a sensitivity and negative predictive value of 72 and 62 percent, respectively, which was much better than all HPV in-situ hybridization methods referred to polymerase chain reaction. p16INK4A seems to be a superior marker for the detection of HPV-associated penile squamous cell carcinoma compared to CISH tests, but is not recommend for the detection of non-tumorigenic lesions, where PCR should be used for the initial assessment.
- Published
- 2013
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47. A new COL3A1 mutation in Ehlers-Danlos syndrome type IV.
- Author
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Eder J, Laccone F, Rohrbach M, Giunta C, Aumayr K, Reichel C, and Trautinger F
- Subjects
- Adult, Arterial Occlusive Diseases etiology, Biopsy, Ehlers-Danlos Syndrome complications, Ehlers-Danlos Syndrome pathology, Female, Humans, Peripheral Arterial Disease etiology, Skin pathology, Skin ultrastructure, Collagen Type III genetics, Ehlers-Danlos Syndrome genetics, Mutation genetics
- Abstract
The vascular type of the Ehlers-Danlos syndrome (Ehlers-Danlos syndrome type IV, EDS IV; OMIM #130050) is a rare connective tissue disorder with autosomal dominant transmission caused by mutations in the COL3A1 gene resulting in increased fragility of connective tissue with arterial, intestinal, and uterine ruptures and premature death. We present a 28-year-old female who in addition to typical EDS IV symptoms had severe peripheral artery occlusive disease (PAOD) and subtotal stenosis of the abdominal aorta. COL3A1 sequencing resulted in detection of an as yet undescribed mutation in exon 36 at position 2465 leading to a nucleotide replacement (c.2465G>C; p.G822A). Ultrastructural analysis of a skin biopsy revealed abnormal morphology and distribution of dermal collagen fibres. We conclude that PAOD is a possible manifestation of EDS IV and that further research is required to define its true prevalence among patients with EDS IV and its molecular pathology including genotype-phenotype correlation., (© 2013 John Wiley & Sons A/S.)
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- 2013
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48. 5-Methoxyleoligin, a lignan from Edelweiss, stimulates CYP26B1-dependent angiogenesis in vitro and induces arteriogenesis in infarcted rat hearts in vivo.
- Author
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Messner B, Kern J, Wiedemann D, Schwaiger S, Türkcan A, Ploner C, Trockenbacher A, Aumayr K, Bonaros N, Laufer G, Stuppner H, Untergasser G, and Bernhard D
- Subjects
- Animals, Arterioles enzymology, Arterioles growth & development, Arterioles pathology, Arterioles physiopathology, Chick Embryo, Coronary Circulation drug effects, Coronary Vessels enzymology, Coronary Vessels pathology, Coronary Vessels physiopathology, Disease Models, Animal, Human Umbilical Vein Endothelial Cells, Humans, Lignans chemistry, Male, Myocardium pathology, Rats, Rats, Wistar, Retinoic Acid 4-Hydroxylase, Ventricular Function, Left drug effects, Asteraceae chemistry, Cytochrome P-450 Enzyme System metabolism, Lignans pharmacology, Myocardial Infarction drug therapy, Myocardial Infarction enzymology, Myocardial Infarction pathology, Myocardial Infarction physiopathology, Myocardium enzymology, Neovascularization, Physiologic drug effects
- Abstract
Background: Insufficient angiogenesis and arteriogenesis in cardiac tissue after myocardial infarction (MI) is a significant factor hampering the functional recovery of the heart. To overcome this problem we screened for compounds capable of stimulating angiogenesis, and herein investigate the most active molecule, 5-Methoxyleoligin (5ML), in detail., Methods and Results: 5ML potently stimulated endothelial tube formation, angiogenic sprouting, and angiogenesis in a chicken chorioallantoic membrane assay. Further, microarray- and knock down- based analyses revealed that 5ML induces angiogenesis by upregulation of CYP26B1. In an in vivo rat MI model 5ML potently increased the number of arterioles in the peri-infarction and infarction area, reduced myocardial muscle loss, and led to a significant increase in LV function (plus 21% 28 days after MI)., Conclusion: The present study shows that 5ML induces CYP26B1-dependent angiogenesis in vitro, and arteriogenesis in vivo. Whether or not CYP26B1 is relevant for in vivo arteriogenesis is not clear at the moment. Importantly, 5ML-induced arteriogenesis in vivo makes the compound even more interesting for a post MI therapy. 5ML may constitute the first low molecular weight compound leading to an improvement of myocardial function after MI.
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- 2013
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49. Airn transcriptional overlap, but not its lncRNA products, induces imprinted Igf2r silencing.
- Author
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Latos PA, Pauler FM, Koerner MV, Şenergin HB, Hudson QJ, Stocsits RR, Allhoff W, Stricker SH, Klement RM, Warczok KE, Aumayr K, Pasierbek P, and Barlow DP
- Subjects
- Alternative Splicing, Animals, Cells, Cultured, Mice, Multigene Family, Promoter Regions, Genetic, RNA Polymerase II metabolism, RNA, Long Noncoding genetics, Gene Silencing, Genomic Imprinting, RNA, Long Noncoding metabolism, Receptor, IGF Type 2 genetics, Transcription, Genetic
- Abstract
Mammalian imprinted genes often cluster with long noncoding (lnc) RNAs. Three lncRNAs that induce parental-specific silencing show hallmarks indicating that their transcription is more important than their product. To test whether Airn transcription or product silences the Igf2r gene, we shortened the endogenous lncRNA to different lengths. The results excluded a role for spliced and unspliced Airn lncRNA products and for Airn nuclear size and location in silencing Igf2r. Instead, silencing only required Airn transcriptional overlap of the Igf2r promoter, which interferes with RNA polymerase II recruitment in the absence of repressive chromatin. Such a repressor function for lncRNA transcriptional overlap reveals a gene silencing mechanism that may be widespread in the mammalian genome, given the abundance of lncRNA transcripts.
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- 2012
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50. Quantification of extraprostatic perineural spread and its prognostic value in pT3a pN0 M0 R0 prostate cancer patients.
- Author
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Aumayr K, Breitegger M, Mazal PR, Koller A, Marberger M, Susani M, and Haitel A
- Subjects
- Biopsy, Disease-Free Survival, Humans, Male, Neoplasm Grading, Neoplasm Recurrence, Local epidemiology, Perineum innervation, Predictive Value of Tests, Prognosis, Proportional Hazards Models, Prostate innervation, Prostatectomy, Prostatic Neoplasms epidemiology, Prostatic Neoplasms surgery, Risk Factors, Neoplasm Invasiveness pathology, Neoplasm Recurrence, Local pathology, Perineum pathology, Prostate pathology, Prostatic Neoplasms pathology
- Abstract
Background: The prognostic relevance of the amount of extraprostatic cancer spread in nerves in prostate cancer patients is not well established., Methods: Eighty-eight patients were included in our study with pT3a pN0 M0 R0 prostate cancer treated with retropubic prostatectomy. Eighty-seven of them showed perineural invasion, 54 were confined to the prostate, 33 showed cancer spread in extraprostatic nerves, which was quantified by counting each transverse section of nerves infiltrated by cancer in totally embedded specimens. Biochemical relapse was established by serum PSA levels of ≥0.2 ng/ml as well as PSA ≥ 0.4 ng/ml and higher according to the EAU guidelines., Results: Extraprostatic but not intraprostatic perineural infiltration was significantly more often found in tumors of higher Gleason score. Intraprostatic number of infiltrated nerves (NIN) correlated with extraprostatic NIN. There was no association between extraprostatic or intraprostatic NIN and Gleason score, lymphatic, or blood vessel invasion. Extraprostatic neural infiltration in ≤10 nerves extended relapse free survival in univariate analysis for PSA 0.2 and 0.4 ng/ml (P = 0.002 and P < 0.000001, respectively) and remained significant in multivariate analysis for PSA 0.4 ng/ml (P = 0.039)., Conclusions: High amount of extraprostatic NIN correlates with tumor progression and seems to be an independent prognostic parameter., (Copyright © 2011 Wiley Periodicals, Inc.)
- Published
- 2011
- Full Text
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