The Experts below are selected from a list of 2553 Experts worldwide ranked by ideXlab platform
Attila Tárnok - One of the best experts on this subject based on the ideXlab platform.
-
Potential of a Cytomics Top-Down Strategy for Drug Discovery
Current medicinal chemistry, 2010Co-Authors: Attila Tárnok, Arkadiusz Pierzchalski, G. ValetAbstract:It takes about 10 to 15 years and roughly 800 mln $ to bring a new drug to the market. Only 10% of drug molecules entering clinical trials succeed and only 3 out of 10 drugs generate enough profit to pay back for the investment. Drug targets may be searched by hypothesis driven modeling of molecular networks within and between cells by systems biology. However, there is the potential to simplify the search for new drugs and drug targets by an initial top-down Cytomics phase. The Cytomics approach i) requires no detailed a-priori knowledge on mechanisms of drug activity or complex diseases, ii) is hypothesis driven for the investigated parameters (genome, transcriptome, proteome, metabolome a.o.) and iii) is hypothesis-free for data analysis. Moreover it iv) carries the potential to uncover unknown molecular interrelations as a prerequisite for later new hypothesis driven modeling and research strategies. A set of discriminatory parameter patterns (molecular hotspots) describing the cellular model (mechanism of drug action) can be identified by differential molecular cell phenotyping. Hereby, the immediate modeling of existing complexities by bottom-up oriented systems biology is avoided. The review focuses on the fast technological developments of molecular single cell analysis in recent years. They comprise a multitude of sensitive new molecular markers as well as various new image and flow cytometric high-content screening methods as facilitators of the Cytomics concept. New bioinformatic tools enable the extraction of relevant molecular hotspots in description of cellular models, being required for the subsequent molecular reverse engineering phase by systems biology.
-
Clinical applications of slide-based cytometry – an update
Journal of biophotonics, 2009Co-Authors: Andreas O. H. Gerstner, Wiebke Laffers, Attila TárnokAbstract:Slide-based cytometric approaches open the possibility to obtain quantitative and objective data from specimens that so far have not been accessible to this kind of analysis. In this review, we will highlight the specific advantages of slide-based cytometry (SBC) and show the applications that have been established for clinical samples. Focuses are cytomic analyses of oncological and hematological samples where the slide-based concept turned out to open new dimensions in understanding underlying cellular networks. We review the recent literature and point out future applications. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
-
immunological changes following protein losing enteropathy after surgery total cavopulmonary connection tcpc by Cytomics
Proceedings of SPIE, 2008Co-Authors: Jozsef Bocsi, Anja Mittag, Dominik Lenz, Ursula Sauer, Lena Wild, John R. Hess, Dietmar Schranz, Jörg Hambsch, Peter Schneider, Attila TárnokAbstract:Complex immunophenotyping single-cell analysis are essential for systems biology and Cytomics. The application of Cytomics in immunology and cardiac research and diagnostics is very broad, ranging from the better understanding of the cardiovascular cell biology to the identification of heart function and immune consequences after surgery. TCPC or Fontan-type circulation is an accepted palliative surgery for patients with a functionally univentricular heart. Protein-losing enteropathy (PLE), the enteric loss of proteins, is a potential late complication after TCPC surgery. PLE etiology is poorly understood, but immunological factors seem to play a role. This study was aimed to gain insight into immune phenotype alterations following post-TCPC PLE. Patients were studied during routine follow-up up to 5yrs after surgery, blood samples of TCPC patients without (n=21, age 6.8±2.6 years at surgery; mean±SD) and with manifest PLE (n=12, age 12.8± 4.5 years at sampling) and age matched healthy children (control, n=22, age 8.6±2.5 years) were collected. Routine laboratory, immune phenotype and serological parameters were determined. Following PLE the immune phenotype dramatically changed with signs of acute inflammation (increased neutrophil and monocyte count, CRP, IL-8). In contrast, lymphocyte count (NK-cells, αβTCR+CD4+, αβTCR+CD8+ cells) decreased (p<0.001). The residual T-cells had elevated CD25 and CD69 expression. In PLE-patients unique cell populations with CD3+αβ/γδTCR- and αβTCR+CD4-8- phenotype were present in increased frequencies. Our studies show dramatically altered leukocyte phenotype after PLE in TCPC patients. These alterations resemble to changes in autoimmune diseases. We conclude that autoimmune processes may play a role in etiology and pathophysiology of PLE.© (2008) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
-
Cytomics in regenerative medicine
Imaging Manipulation and Analysis of Biomolecules Cells and Tissues VI, 2008Co-Authors: Attila Tárnok, Arkadiusz PierzchalskiAbstract:Cytomics is the high-content analysis of cell-systems [6, 78]. The area of Cytomics and Systems Biology received great attention during the last years as it harbours the promise to substantially impact on various fields of biomedicine, drug discovery, predictive medicine [6] and may have major potential for regenerative medicine. In regenerative medicine Cytomics includes process control of cell preparation and culturing using non-invasive detection techniques, quality control and standardization for GMP and GLP conformity and even prediction of cell fate based on sophisticated data analysis. Cytomics requires quantitative and stoichiometric single cell analysis. In some areas the leading cytometric techniques represent the cutting edge today. Many different applications/variations of multicolour staining were developed for flow- or slide-based cytometry (SBC) analysis of suspensions and sections to whole animal analysis [78]. SBC has become an important analytical technology in drug discovery, diagnosis and research and is an emerging technology for systems analysis [78]. It enables high-content high-throughput measurement of cell suspensions, cell cultures and tissues. In the last years various commercial SBC instruments were launched principally enabling to perform similar tasks. Standardisation as well as comparability of different instruments is a major challenge. Hyperspectral optical imaging may be implemented in SBC analysis for label free cell detection based on cellular autofluorescence [3]. All of these developments push the systemic approach of the analysis of biological specimens to enhance the outcome of regenerative medicine.
-
Immunological changes following protein losing enteropathy after surgery total cavopulmonary connection (TCPC) by Cytomics
Imaging Manipulation and Analysis of Biomolecules Cells and Tissues VI, 2008Co-Authors: Jozsef Bocsi, Anja Mittag, Dominik Lenz, Ursula Sauer, Lena Wild, John R. Hess, Dietmar Schranz, Jörg Hambsch, Peter Schneider, Attila TárnokAbstract:Complex immunophenotyping single-cell analysis are essential for systems biology and Cytomics. The application of Cytomics in immunology and cardiac research and diagnostics is very broad, ranging from the better understanding of the cardiovascular cell biology to the identification of heart function and immune consequences after surgery. TCPC or Fontan-type circulation is an accepted palliative surgery for patients with a functionally univentricular heart. Protein-losing enteropathy (PLE), the enteric loss of proteins, is a potential late complication after TCPC surgery. PLE etiology is poorly understood, but immunological factors seem to play a role. This study was aimed to gain insight into immune phenotype alterations following post-TCPC PLE. Patients were studied during routine follow-up up to 5yrs after surgery, blood samples of TCPC patients without (n=21, age 6.8±2.6 years at surgery; mean±SD) and with manifest PLE (n=12, age 12.8± 4.5 years at sampling) and age matched healthy children (control, n=22, age 8.6±2.5 years) were collected. Routine laboratory, immune phenotype and serological parameters were determined. Following PLE the immune phenotype dramatically changed with signs of acute inflammation (increased neutrophil and monocyte count, CRP, IL-8). In contrast, lymphocyte count (NK-cells, αβTCR+CD4+, αβTCR+CD8+ cells) decreased (p
G. Valet - One of the best experts on this subject based on the ideXlab platform.
-
Cytomics and Predictive Medicine for Oncology
An Omics Perspective on Cancer Research, 2009Co-Authors: Andreas O. H. Gerstner, G. ValetAbstract:Cytomics combines the multimolecular cytometric analysis of cell and cell system (cytome, cytomes) heterogeneity on a single cell level with the exhaustive bioinformatic knowledge extraction from all analysis results (Cytomics = system cytometry + bioinformatics). It therefore yields a maximum of information about the apparent molecular cell phenotype.
-
Cytomics: From Cell States to Predictive Medicine
Computational Systems Biology, 2006Co-Authors: G. Valet, Robert F. Murphy, J.p. Robinson, A. Tarnok, A. KrieteAbstract:ABSTRACT Cytomics, the systematic study of biological organization and behavior at the cellular level, has developed out of computational imaging and flow cytometry and promises to provide essential data for systems biology. The ability to perform high-content and high-throughput imaging and analysis to reveal complex cellular phenotypes will not only further our understanding of how cells and tissues carry out their functions but also provide insight into the mechanisms by which these functions are disrupted. Advances in flow, chemical, and tissue cytometry extend the applicability of Cytomics to tissues, cytological smears, and blood and other body fluids. As such, Cytomics not only provides a new framework for spatiotemporal systems biology but enriches personalized or individualized medicine. This can take the form of individual disease course predictions for therapy selection purposes as well as identification of discriminatory bio-parameter patterns.
-
Cytomics, the human cytome project and systems biology: top-down resolution of the molecular biocomplexity of organisms by single cell analysis.
Cell proliferation, 2005Co-Authors: G. ValetAbstract:A large amount of structural and functional information is obtained by molecular cell phenotype analysis of tissues, organs and organisms at the single cell level by image or flow cytometry in combination with bioinformatic knowledge extraction (Cytomics) concerning nuclei acids, proteins and metabolites (cellular genomics, proteomics and metabolomics) as well as cell function parameters like intracellular pH, transmembrane potentials or ion gradients. In addition, differential molecular cell phenotypes between diseased and healthy cells provide molecular data patterns for (i) predictive medicine by Cytomics or for (ii) drug discovery purposes using reverse engineering of the data patterns by biomedical cell systems biology. Molecular pathways can be explored in this way including the detection of suitable target molecules, without detailed a priori knowledge of specific disease mechanisms. This is useful during the analysis of complex diseases such as infections, allergies, rheumatoid diseases, diabetes or malignancies. The top-down approach reaching from single cell heterogeneity in cell systems and tissues down to the molecular level seems suitable for a human cytome project to systematically explore the molecular biocomplexity of human organisms. The analysis of already existing data from scientific studies or routine diagnostic procedures will be of immediate value in clinical medicine, for example as personalized therapy by Cytomics.
-
Cytomics in predictive medicine
Advanced Biomedical and Clinical Diagnostic Systems II, 2004Co-Authors: Attila Tárnok, G. ValetAbstract:Predictive Medicine aims at the detection of changes in patient's disease state prior to the manifestation of deterioration or improvement of the current status. Patient-specific, disease-course predictions with >95% or >99% accuracy during therapy would be highly valuable for everyday medicine. If these predictors were available, disease aggravation or progression, frequently accompanied by irreversible tissue damage or therapeutic side effects, could then potentially be avoided by early preventive therapy. The molecular analysis of heterogeneous cellular systems (Cytomics) by cytometry in conjunction with pattern-oriented bioinformatic analysis of the multiparametric cytometric and other data provides a promising approach to individualized or personalized medical treatment or disease management. Predictive medicine is best implemented by cell oriented measurements e.g. by flow or image cytometry. Cell oriented gene or protein arrays as well as bead arrays for the capture of solute molecules form serum, plasma, urine or liquor are equally of high value. Clinical applications of predictive medicine by Cytomics will include multi organ failure in sepsis or non infectious posttraumatic shock in intensive care, or the pretherapeutic identification of high risk patients in cancer cytostatic. Early individualized therapy may provide better survival chances for individual patient at concomitant cost containment. Predictive medicine guided early reduction or stop of therapy may lower or abrogate potential therapeutic side effects. Further important aspects of predictive medicine concern the preoperative identification of patients with a tendency for postoperative complications or coronary artery disease patients with an increased tendency for restenosis. As a consequence, better patient care and new forms of inductive scientific hypothesis development based on the interpretation of predictive data patterns are at reach.
-
Cytomics new technologies towards a human cytome project
Cytometry Part A, 2004Co-Authors: G. Valet, James F. Leary, Attila TárnokAbstract:Background Molecular cell systems research (Cytomics) aims at the understanding of the molecular architecture and functionality of cell systems (cytomes) by single-cell analysis in combination with exhaustive bioinformatic knowledge extraction. In this way, loss of information as a consequence of molecular averaging by cell or tissue homogenisation is avoided. Progress The Cytomics concept has been significantly advanced by a multitude of current developments. Amongst them are confocal and laser scanning microscopy, multiphoton fluorescence excitation, spectral imaging, fluorescence resonance energy transfer (FRET), fast imaging in flow, optical stretching in flow, and miniaturised flow and image cytometry within laboratories on a chip or laser microdissection, as well as the use of bead arrays. In addition, biomolecular analysis techniques like tyramide signal amplification, single-cell polymerase chain reaction (PCR), and the labelling of biomolecules by quantum dots, magnetic nanobeads, or aptamers open new horizons of sensitivity and molecular specificity at the single-cell level. Data sieving or data mining of the vast amounts of collected multiparameter data for exhaustive multilevel bioinformatic knowledge extraction avoids the inadvertent loss of information from unknown molecular relations being inaccessible to an a priori hypothesis. Challenge It seems important to address the challenge of a human cytome project using hypothesis-driven molecular information collection from disease associated cell systems, supplemented by systematic and exhaustive knowledge extraction. This will allow the description of the molecular setup of normal and abnormal cell systems within a relational knowledge system, permitting the standardised discrimination of abnormal cell states in disease. As one of the consequences, individualised predictions of further disease course in patients (predictive medicine by Cytomics) by characteristic discriminatory data patterns will permit individualised therapies, identification of new pharmaceutical targets, and establishment of a standardised framework of relevant molecular alterations in disease. This special issue of Cytometry, on new technologies in Cytomics, focuses on prominent examples of this presently fast-moving scientific field, and represents one of the preconditions for the formulation of a human cytome project. © 2004 Wiley-Liss, Inc.
Frank Emmrich - One of the best experts on this subject based on the ideXlab platform.
-
Cytomics and nanobioengineering.
Cytometry. Part B Clinical cytometry, 2008Co-Authors: Arkadiusz Pierzchalski, José-enrique O'connor, Andrea A. Robitzki, Anja Mittag, Frank Emmrich, Ulrich Sack, Jozsef Bocsi, Attila TárnokAbstract:The finding that an individual's genome differs as much as by many million variants from that of the human reference assembly diminished the great enthusiasm that every disease could be predicted based on nucleotide polymorphisms. Even individual cells of an organ may be specifically equipped to perform specific tasks and that the information of individual cells in a cell system is key information to understand function or dysfunction. Therefore, Cytomics received great attention during the last years as it allows to quantitatively and qualitatively analyzing great number of individual cells, cell constituents, and of their intracellular and functional interactions in a cellular system and also giving the concept of analysis of these data. Exhaustive data extraction from multiparametric assays and multiple tests are the prerequisite for prediction of drug toxicity. Cytomics, as novel approach for unsupervised data analysis give a chance to find the most predictive parameters, which describe best the toxicity of a chemical. Cytomics is intrinsically connected to drug development and drug discovery. Focused on small structures, nanobioengineering is the ideal partner of Cytomics, the systems biological discipline for cell population analysis. Realizing the idea “from the molecule to the patient” develops and offers chemical compounds, proteins, and other biomolecules, cells as well as tissues as instruments and products for a wide variety of biotechnological and biomedical applications. The integrative nanobioengineering combining different disciplines of nanotechnology will promote the development of innovative therapies and diagnostic methods. It can improve the precision of the measurements with focus on single cell analysis. By nanobioengineering and whole body imaging techniques, Cytomics covers the field from molecules through bacterial cells, eukaryotic tissues, and organs to small animal live analysis. Toxicological testing and medical drug development are currently strongly broadening. It harbors the promise to substantially impact on various fields of biomedicine, drug discovery, and predictive medicine. As the number of scientific data is rising exponentially, new data analysis tools and strategies like Cytomics and nanobioengineering take a lead and get closer to application. Bionanoengineering may strongly support the quantitative data supply, thus strengthening the rational for Cytomics approach. © 2008 Clinical Cytometry Society How to cite this article: Pierzchalski A, Robitzki A, Mittag A, Emmrich F, Sack U, O'Connor J-E, Bocsi J, Tarnok A. Cytomics and nanobioengineering. Cytometry Part B 2008; 72B: 416–426.
-
Cytomics and nanobioengineering
Cytometry Part B: Clinical Cytometry, 2008Co-Authors: Arkadiusz Pierzchalski, José-enrique O'connor, Andrea A. Robitzki, Anja Mittag, Frank Emmrich, Ulrich Sack, Jozsef Bocsi, Attila TárnokAbstract:The finding that an individual's genome differs as much as by many million variants from that of the human reference assembly diminished the great enthusiasm that every disease could be predicted based on nucleotide polymorphisms. Even individual cells of an organ may be specifically equipped to perform specific tasks and that the information of individual cells in a cell system is key information to understand function or dysfunction. Therefore, Cytomics received great attention during the last years as it allows to quantitatively and qualitatively analyzing great number of individual cells, cell constituents, and of their intracellular and functional interactions in a cellular system and also giving the concept of analysis of these data. Exhaustive data extraction from multiparametric assays and multiple tests are the prerequisite for prediction of drug toxicity. Cytomics, as novel approach for unsupervised data analysis give a chance to find the most predictive parameters, which describe best the toxicity of a chemical. Cytomics is intrinsically connected to drug development and drug discovery. Focused on small structures, nanobioengineering is the ideal partner of Cytomics, the systems biological discipline for cell population analysis. Realizing the idea from the molecule to the patient develops and offers chemical compounds, proteins, and other biomolecules, cells as well as tissues as instruments and products for a wide variety of biotechnological and biomedical applications. The integrative nanobioengineering combining different disciplines of nanotechnology will promote the development of innovative therapies and diagnostic methods. It can improve the precision of the measurements with focus on single cell analysis. By nanobioengineering and whole body imaging techniques, Cytomics covers the field from molecules through bacterial cells, eukaryotic tissues, and organs to small animal live analysis. Toxicological testing and medical drug development are currently strongly broadening. It harbors the promise to substantially impact on various fields of biomedicine, drug discovery, and predictive medicine. As the number of scientific data is rising exponentially, new data analysis tools and strategies like Cytomics and nanobioengineering take a lead and get closer to application. Bionanoengineering may strongly support the quantitative data supply, thus strengthening the rational for Cytomics approach
-
Systems biology and clinical Cytomics : The 10th leipziger workshop and the 3rd international workshop on slide-based cytometry
Cytometry. Part A : the journal of the International Society for Analytical Cytology, 2006Co-Authors: Attila Tárnok, G. Valet, Frank EmmrichAbstract:Despite very significant technical and software improvements in flow cytometry (FCM) since the 1980's, the demand for a cytometric technology combining both quantitative cell analysis and morphological documentation in Cytomics became evident. Improvements in microtechnology and computing permit nowadays similar quantitative and stoichiometric single cell-based high-throughput analyses by microscopic instruments, like Slide-Based Cytometry (SBC). SBC and related techniques offer unique tools to perform complex immunophenotyping, thereby enabling diagnostic procedures during early disease stages. Multicolor or polychromatic analysis of cells by SBC is of special importance not only as a Cytomics technology platform but also because of low quantities of required reagents and biological material. The exact knowledge of the location of each cell on the slide permits repetitive restaining and reanalysis of specimens. Various separate measurements of the same specimen can be ultimately fused to one database increasing the information obtained per cell. Relocation and optical evaluation of cells as typical SBC feature, can be of integral importance for cytometric analysis, since artifacts can be excluded and morphology of measured cells can be documented. Progress in cell analytic: In the SBC, new horizons can be opened by the new techniques of structural and functional analysis with the high resolution from intracellular and membrane (confocal microscopy, nanoscopy, total internal fluorescence microscopy (TIRFM), and tissue level (tissomics), to organ and organism level (in vivo cytometry, optical whole body imaging). Predictive medicine aims at the detection of changes in patient's state prior to the manifestation of the disease or the complication. Such instances concern immune consequences of surgeries or noninfectious posttraumatic shock in intensive care patients or the pretherapeutic identification of high risk patients in cancer cytostatic therapy. Preventive anti-infectious or anti-shock therapy as well as curative chemotherapy in combination with stem cell transplantation may provide better survival chances for patient at concomitant cost containment. Predictive medicine-guided optimization of therapy could lead to individualized medicine that gives significant therapeutic effect and may lower or abrogate potential therapeutic side effects. The 10th Leipziger Workshop combined with the 3rd International Workshop on SBC aimed to offer new methods in Image- and Slide-Based Cytometry for solutions in clinical research. It moved towards practical applications in the clinics and the clinical laboratory. This development will be continued in 2006 at the upcoming Leipziger Workshop and the International Workshop on Slide-Based Cytometry.
-
Immune consequences of pediatric and adult cardiovascular surgery: report of the 7th Leipzig workshop.
Cytometry. Part B Clinical cytometry, 2003Co-Authors: Attila Tárnok, Frank EmmrichAbstract:Cardiovascular surgery in children and adults is among the most common types of interventions in the western hemisphere for innate and acquired defects. In the recent decades, the risk of cardiovascular surgery has been reduced substantially. Nevertheless, open heart surgery is risky for the patient and can lead to postoperative complications such as postpericardiotomy syndrome, capillary leak syndrome, or multiple organ failure. To gain further understanding into the response to cardiovascular surgery, it is necessary to join forces from several disciplines of medicine and natural sciences. Interdisciplinarity is the basic concept of the Leipzig Workshop. The consensus of the workshop was that cardiovascular surgery with cardiopulmonary bypass induces a systemic antiinflammatory response due to (a) elimination of activated cells, (b) compensatory reaction to a local proinflammatory responses, (c) interleukin-10 release, (d) anesthetics and medication, and (e) leukocyte extravasation. The subsequent proinflammatory reaction is the response to surgical trauma modulating the antiinflammatory reaction. Novel therapeutic approaches include the introduction of autologous endothelial progenitor cells from the peripheral blood into the sites of injury. The analysis of immune response and outcome prediction require novel analytical tools that allow fast, accurate, and quantitative determination of the desired parameters in a multiplexed manner (i.e., Cytomics), such as flow cytometric microbead array assays and slide-based cytometry. The major goal is predictive medicine by Cytomics, i.e., the individualized risk assessment by analyzing the cytome in combination with sophisticated data pattern recognition. These developments may lead to individualized therapy for the benefit of the patient and cost reduction.
Anja Mittag - One of the best experts on this subject based on the ideXlab platform.
-
immunological changes following protein losing enteropathy after surgery total cavopulmonary connection tcpc by Cytomics
Proceedings of SPIE, 2008Co-Authors: Jozsef Bocsi, Anja Mittag, Dominik Lenz, Ursula Sauer, Lena Wild, John R. Hess, Dietmar Schranz, Jörg Hambsch, Peter Schneider, Attila TárnokAbstract:Complex immunophenotyping single-cell analysis are essential for systems biology and Cytomics. The application of Cytomics in immunology and cardiac research and diagnostics is very broad, ranging from the better understanding of the cardiovascular cell biology to the identification of heart function and immune consequences after surgery. TCPC or Fontan-type circulation is an accepted palliative surgery for patients with a functionally univentricular heart. Protein-losing enteropathy (PLE), the enteric loss of proteins, is a potential late complication after TCPC surgery. PLE etiology is poorly understood, but immunological factors seem to play a role. This study was aimed to gain insight into immune phenotype alterations following post-TCPC PLE. Patients were studied during routine follow-up up to 5yrs after surgery, blood samples of TCPC patients without (n=21, age 6.8±2.6 years at surgery; mean±SD) and with manifest PLE (n=12, age 12.8± 4.5 years at sampling) and age matched healthy children (control, n=22, age 8.6±2.5 years) were collected. Routine laboratory, immune phenotype and serological parameters were determined. Following PLE the immune phenotype dramatically changed with signs of acute inflammation (increased neutrophil and monocyte count, CRP, IL-8). In contrast, lymphocyte count (NK-cells, αβTCR+CD4+, αβTCR+CD8+ cells) decreased (p<0.001). The residual T-cells had elevated CD25 and CD69 expression. In PLE-patients unique cell populations with CD3+αβ/γδTCR- and αβTCR+CD4-8- phenotype were present in increased frequencies. Our studies show dramatically altered leukocyte phenotype after PLE in TCPC patients. These alterations resemble to changes in autoimmune diseases. We conclude that autoimmune processes may play a role in etiology and pathophysiology of PLE.© (2008) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
-
Immunological changes following protein losing enteropathy after surgery total cavopulmonary connection (TCPC) by Cytomics
Imaging Manipulation and Analysis of Biomolecules Cells and Tissues VI, 2008Co-Authors: Jozsef Bocsi, Anja Mittag, Dominik Lenz, Ursula Sauer, Lena Wild, John R. Hess, Dietmar Schranz, Jörg Hambsch, Peter Schneider, Attila TárnokAbstract:Complex immunophenotyping single-cell analysis are essential for systems biology and Cytomics. The application of Cytomics in immunology and cardiac research and diagnostics is very broad, ranging from the better understanding of the cardiovascular cell biology to the identification of heart function and immune consequences after surgery. TCPC or Fontan-type circulation is an accepted palliative surgery for patients with a functionally univentricular heart. Protein-losing enteropathy (PLE), the enteric loss of proteins, is a potential late complication after TCPC surgery. PLE etiology is poorly understood, but immunological factors seem to play a role. This study was aimed to gain insight into immune phenotype alterations following post-TCPC PLE. Patients were studied during routine follow-up up to 5yrs after surgery, blood samples of TCPC patients without (n=21, age 6.8±2.6 years at surgery; mean±SD) and with manifest PLE (n=12, age 12.8± 4.5 years at sampling) and age matched healthy children (control, n=22, age 8.6±2.5 years) were collected. Routine laboratory, immune phenotype and serological parameters were determined. Following PLE the immune phenotype dramatically changed with signs of acute inflammation (increased neutrophil and monocyte count, CRP, IL-8). In contrast, lymphocyte count (NK-cells, αβTCR+CD4+, αβTCR+CD8+ cells) decreased (p
-
Cytomics and nanobioengineering.
Cytometry. Part B Clinical cytometry, 2008Co-Authors: Arkadiusz Pierzchalski, José-enrique O'connor, Andrea A. Robitzki, Anja Mittag, Frank Emmrich, Ulrich Sack, Jozsef Bocsi, Attila TárnokAbstract:The finding that an individual's genome differs as much as by many million variants from that of the human reference assembly diminished the great enthusiasm that every disease could be predicted based on nucleotide polymorphisms. Even individual cells of an organ may be specifically equipped to perform specific tasks and that the information of individual cells in a cell system is key information to understand function or dysfunction. Therefore, Cytomics received great attention during the last years as it allows to quantitatively and qualitatively analyzing great number of individual cells, cell constituents, and of their intracellular and functional interactions in a cellular system and also giving the concept of analysis of these data. Exhaustive data extraction from multiparametric assays and multiple tests are the prerequisite for prediction of drug toxicity. Cytomics, as novel approach for unsupervised data analysis give a chance to find the most predictive parameters, which describe best the toxicity of a chemical. Cytomics is intrinsically connected to drug development and drug discovery. Focused on small structures, nanobioengineering is the ideal partner of Cytomics, the systems biological discipline for cell population analysis. Realizing the idea “from the molecule to the patient” develops and offers chemical compounds, proteins, and other biomolecules, cells as well as tissues as instruments and products for a wide variety of biotechnological and biomedical applications. The integrative nanobioengineering combining different disciplines of nanotechnology will promote the development of innovative therapies and diagnostic methods. It can improve the precision of the measurements with focus on single cell analysis. By nanobioengineering and whole body imaging techniques, Cytomics covers the field from molecules through bacterial cells, eukaryotic tissues, and organs to small animal live analysis. Toxicological testing and medical drug development are currently strongly broadening. It harbors the promise to substantially impact on various fields of biomedicine, drug discovery, and predictive medicine. As the number of scientific data is rising exponentially, new data analysis tools and strategies like Cytomics and nanobioengineering take a lead and get closer to application. Bionanoengineering may strongly support the quantitative data supply, thus strengthening the rational for Cytomics approach. © 2008 Clinical Cytometry Society How to cite this article: Pierzchalski A, Robitzki A, Mittag A, Emmrich F, Sack U, O'Connor J-E, Bocsi J, Tarnok A. Cytomics and nanobioengineering. Cytometry Part B 2008; 72B: 416–426.
-
Cytomics and nanobioengineering
Cytometry Part B: Clinical Cytometry, 2008Co-Authors: Arkadiusz Pierzchalski, José-enrique O'connor, Andrea A. Robitzki, Anja Mittag, Frank Emmrich, Ulrich Sack, Jozsef Bocsi, Attila TárnokAbstract:The finding that an individual's genome differs as much as by many million variants from that of the human reference assembly diminished the great enthusiasm that every disease could be predicted based on nucleotide polymorphisms. Even individual cells of an organ may be specifically equipped to perform specific tasks and that the information of individual cells in a cell system is key information to understand function or dysfunction. Therefore, Cytomics received great attention during the last years as it allows to quantitatively and qualitatively analyzing great number of individual cells, cell constituents, and of their intracellular and functional interactions in a cellular system and also giving the concept of analysis of these data. Exhaustive data extraction from multiparametric assays and multiple tests are the prerequisite for prediction of drug toxicity. Cytomics, as novel approach for unsupervised data analysis give a chance to find the most predictive parameters, which describe best the toxicity of a chemical. Cytomics is intrinsically connected to drug development and drug discovery. Focused on small structures, nanobioengineering is the ideal partner of Cytomics, the systems biological discipline for cell population analysis. Realizing the idea from the molecule to the patient develops and offers chemical compounds, proteins, and other biomolecules, cells as well as tissues as instruments and products for a wide variety of biotechnological and biomedical applications. The integrative nanobioengineering combining different disciplines of nanotechnology will promote the development of innovative therapies and diagnostic methods. It can improve the precision of the measurements with focus on single cell analysis. By nanobioengineering and whole body imaging techniques, Cytomics covers the field from molecules through bacterial cells, eukaryotic tissues, and organs to small animal live analysis. Toxicological testing and medical drug development are currently strongly broadening. It harbors the promise to substantially impact on various fields of biomedicine, drug discovery, and predictive medicine. As the number of scientific data is rising exponentially, new data analysis tools and strategies like Cytomics and nanobioengineering take a lead and get closer to application. Bionanoengineering may strongly support the quantitative data supply, thus strengthening the rational for Cytomics approach
-
Quantitative tissue cytometry (Tissomics): multimodal slide-based cytometry, confocal imaging, and volume rendering is the key
Imaging Manipulation and Analysis of Biomolecules Cells and Tissues V, 2007Co-Authors: Attila Tárnok, Anja Mittag, Jens-peer Kuska, Ulf-dietrich Braumann, Birgit Mosch, Thomas ArendtAbstract:Multiplexed high-content cytometric analysis of cells is a prerequisite for Cytomics and Systems Biology. Slide Based Cytometry (SBC) analysis yields quantitative cell related data on various cell constituents. It allows to measure and identify in high-throughput hundred-thousands of objects and obtain cytometric data on light absorption, scatter and fluorescence signals. Selected cells of interest can be rescanned and morphologically evaluated. To be cytometric SBC measurement needs high focal depth in order to acquire the fluorescence of the whole cell. For tissue analysis section thickness of >30μm is needed to reduce cell sectioning leading in multiple labelled specimens to an overestimation of multiple stained cells due to stereology, mimicking co-expression or elevated expression that is in fact due to coincidences in the z-axis direction. By confocal sectioning and 3D-reconstruction these overlays could be eliminated but confocal 3D imaging is slow and the resulting data are not cytometric. To overcome this obstacle, we combined SBC analysis with confocal imaging using a Laser Scanning Cytometer (iCys, Compucyte Corp., MA). Single to triple labelled 30-120μm thick human brain sections were scanned cytometrically (up to three laser 405nm, 488nm, 633nm) and double and triple labeled cells were identified. In the second step these objects were relocated, scanned confocally and 3D-reconstructed (Mathematica®, MathGL3d). This combination of high-throughput SBC and high-resolution confocal imaging enables for unequivocal identification of multiple labelled objects and is a prerequisite for Cytomic tissue analysis, Tissomics. (Support: HBFG 036/379-1)
Jozsef Bocsi - One of the best experts on this subject based on the ideXlab platform.
-
immunological changes following protein losing enteropathy after surgery total cavopulmonary connection tcpc by Cytomics
Proceedings of SPIE, 2008Co-Authors: Jozsef Bocsi, Anja Mittag, Dominik Lenz, Ursula Sauer, Lena Wild, John R. Hess, Dietmar Schranz, Jörg Hambsch, Peter Schneider, Attila TárnokAbstract:Complex immunophenotyping single-cell analysis are essential for systems biology and Cytomics. The application of Cytomics in immunology and cardiac research and diagnostics is very broad, ranging from the better understanding of the cardiovascular cell biology to the identification of heart function and immune consequences after surgery. TCPC or Fontan-type circulation is an accepted palliative surgery for patients with a functionally univentricular heart. Protein-losing enteropathy (PLE), the enteric loss of proteins, is a potential late complication after TCPC surgery. PLE etiology is poorly understood, but immunological factors seem to play a role. This study was aimed to gain insight into immune phenotype alterations following post-TCPC PLE. Patients were studied during routine follow-up up to 5yrs after surgery, blood samples of TCPC patients without (n=21, age 6.8±2.6 years at surgery; mean±SD) and with manifest PLE (n=12, age 12.8± 4.5 years at sampling) and age matched healthy children (control, n=22, age 8.6±2.5 years) were collected. Routine laboratory, immune phenotype and serological parameters were determined. Following PLE the immune phenotype dramatically changed with signs of acute inflammation (increased neutrophil and monocyte count, CRP, IL-8). In contrast, lymphocyte count (NK-cells, αβTCR+CD4+, αβTCR+CD8+ cells) decreased (p<0.001). The residual T-cells had elevated CD25 and CD69 expression. In PLE-patients unique cell populations with CD3+αβ/γδTCR- and αβTCR+CD4-8- phenotype were present in increased frequencies. Our studies show dramatically altered leukocyte phenotype after PLE in TCPC patients. These alterations resemble to changes in autoimmune diseases. We conclude that autoimmune processes may play a role in etiology and pathophysiology of PLE.© (2008) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
-
Immunological changes following protein losing enteropathy after surgery total cavopulmonary connection (TCPC) by Cytomics
Imaging Manipulation and Analysis of Biomolecules Cells and Tissues VI, 2008Co-Authors: Jozsef Bocsi, Anja Mittag, Dominik Lenz, Ursula Sauer, Lena Wild, John R. Hess, Dietmar Schranz, Jörg Hambsch, Peter Schneider, Attila TárnokAbstract:Complex immunophenotyping single-cell analysis are essential for systems biology and Cytomics. The application of Cytomics in immunology and cardiac research and diagnostics is very broad, ranging from the better understanding of the cardiovascular cell biology to the identification of heart function and immune consequences after surgery. TCPC or Fontan-type circulation is an accepted palliative surgery for patients with a functionally univentricular heart. Protein-losing enteropathy (PLE), the enteric loss of proteins, is a potential late complication after TCPC surgery. PLE etiology is poorly understood, but immunological factors seem to play a role. This study was aimed to gain insight into immune phenotype alterations following post-TCPC PLE. Patients were studied during routine follow-up up to 5yrs after surgery, blood samples of TCPC patients without (n=21, age 6.8±2.6 years at surgery; mean±SD) and with manifest PLE (n=12, age 12.8± 4.5 years at sampling) and age matched healthy children (control, n=22, age 8.6±2.5 years) were collected. Routine laboratory, immune phenotype and serological parameters were determined. Following PLE the immune phenotype dramatically changed with signs of acute inflammation (increased neutrophil and monocyte count, CRP, IL-8). In contrast, lymphocyte count (NK-cells, αβTCR+CD4+, αβTCR+CD8+ cells) decreased (p
-
Cytomics and nanobioengineering.
Cytometry. Part B Clinical cytometry, 2008Co-Authors: Arkadiusz Pierzchalski, José-enrique O'connor, Andrea A. Robitzki, Anja Mittag, Frank Emmrich, Ulrich Sack, Jozsef Bocsi, Attila TárnokAbstract:The finding that an individual's genome differs as much as by many million variants from that of the human reference assembly diminished the great enthusiasm that every disease could be predicted based on nucleotide polymorphisms. Even individual cells of an organ may be specifically equipped to perform specific tasks and that the information of individual cells in a cell system is key information to understand function or dysfunction. Therefore, Cytomics received great attention during the last years as it allows to quantitatively and qualitatively analyzing great number of individual cells, cell constituents, and of their intracellular and functional interactions in a cellular system and also giving the concept of analysis of these data. Exhaustive data extraction from multiparametric assays and multiple tests are the prerequisite for prediction of drug toxicity. Cytomics, as novel approach for unsupervised data analysis give a chance to find the most predictive parameters, which describe best the toxicity of a chemical. Cytomics is intrinsically connected to drug development and drug discovery. Focused on small structures, nanobioengineering is the ideal partner of Cytomics, the systems biological discipline for cell population analysis. Realizing the idea “from the molecule to the patient” develops and offers chemical compounds, proteins, and other biomolecules, cells as well as tissues as instruments and products for a wide variety of biotechnological and biomedical applications. The integrative nanobioengineering combining different disciplines of nanotechnology will promote the development of innovative therapies and diagnostic methods. It can improve the precision of the measurements with focus on single cell analysis. By nanobioengineering and whole body imaging techniques, Cytomics covers the field from molecules through bacterial cells, eukaryotic tissues, and organs to small animal live analysis. Toxicological testing and medical drug development are currently strongly broadening. It harbors the promise to substantially impact on various fields of biomedicine, drug discovery, and predictive medicine. As the number of scientific data is rising exponentially, new data analysis tools and strategies like Cytomics and nanobioengineering take a lead and get closer to application. Bionanoengineering may strongly support the quantitative data supply, thus strengthening the rational for Cytomics approach. © 2008 Clinical Cytometry Society How to cite this article: Pierzchalski A, Robitzki A, Mittag A, Emmrich F, Sack U, O'Connor J-E, Bocsi J, Tarnok A. Cytomics and nanobioengineering. Cytometry Part B 2008; 72B: 416–426.
-
Cytomics and nanobioengineering
Cytometry Part B: Clinical Cytometry, 2008Co-Authors: Arkadiusz Pierzchalski, José-enrique O'connor, Andrea A. Robitzki, Anja Mittag, Frank Emmrich, Ulrich Sack, Jozsef Bocsi, Attila TárnokAbstract:The finding that an individual's genome differs as much as by many million variants from that of the human reference assembly diminished the great enthusiasm that every disease could be predicted based on nucleotide polymorphisms. Even individual cells of an organ may be specifically equipped to perform specific tasks and that the information of individual cells in a cell system is key information to understand function or dysfunction. Therefore, Cytomics received great attention during the last years as it allows to quantitatively and qualitatively analyzing great number of individual cells, cell constituents, and of their intracellular and functional interactions in a cellular system and also giving the concept of analysis of these data. Exhaustive data extraction from multiparametric assays and multiple tests are the prerequisite for prediction of drug toxicity. Cytomics, as novel approach for unsupervised data analysis give a chance to find the most predictive parameters, which describe best the toxicity of a chemical. Cytomics is intrinsically connected to drug development and drug discovery. Focused on small structures, nanobioengineering is the ideal partner of Cytomics, the systems biological discipline for cell population analysis. Realizing the idea from the molecule to the patient develops and offers chemical compounds, proteins, and other biomolecules, cells as well as tissues as instruments and products for a wide variety of biotechnological and biomedical applications. The integrative nanobioengineering combining different disciplines of nanotechnology will promote the development of innovative therapies and diagnostic methods. It can improve the precision of the measurements with focus on single cell analysis. By nanobioengineering and whole body imaging techniques, Cytomics covers the field from molecules through bacterial cells, eukaryotic tissues, and organs to small animal live analysis. Toxicological testing and medical drug development are currently strongly broadening. It harbors the promise to substantially impact on various fields of biomedicine, drug discovery, and predictive medicine. As the number of scientific data is rising exponentially, new data analysis tools and strategies like Cytomics and nanobioengineering take a lead and get closer to application. Bionanoengineering may strongly support the quantitative data supply, thus strengthening the rational for Cytomics approach
-
Novel aspects of systems biology and clinical Cytomics.
Cytometry. Part A : the journal of the International Society for Analytical Cytology, 2006Co-Authors: Jozsef Bocsi, Andreas O. H. Gerstner, Anja Mittag, Ulrich Sack, Markus J. Barten, Attila TárnokAbstract:The area of Cytomics and Systems Biology became of great impact during the last years. In some fields of the leading cytometric techniques it represents the cutting edge today. Many different applications/variations of multicolor staining were developed for flow- or slide-based cytometric analysis of suspensions and sections to whole animal analysis. Multispectral optical imaging can be used for studying immunological and tumorigenic processes. New methods resulted in the establishment of lipidomics as the systemic research of lipids and their behavior. All of these development push the systemic approach of the analysis of biological specimens to enhance the outcome in the clinic and in drug discovery programs.
