HTTP 200 OK
Allow: GET, HEAD, OPTIONS
Content-Type: application/json
Vary: Accept
{
"count": 515,
"next": "https://api-test.medunigraz.at/v1/research/search/project/?format=api&limit=20&offset=480",
"previous": "https://api-test.medunigraz.at/v1/research/search/project/?format=api&limit=20&offset=440",
"results": [
{
"text": "GENINCA - Genomic instability and genomic alterations in pre-cancerous lesions and/or cancer\n\nGENINCA\nDiagnostik Forschungsinstitut für Humangenetik\nForschungsförderung\nSpeicher, Michael\nSpeicher, Michael\n{'de': 'GENINCA will address two tumor entities, for which we have good access to pre-malignant lesions and in which genomic instability is a common feature: colorectal and liver cancer. \\r\\nGENINCA represents a collaborative study of 8 academic and 3 industrial partners from 5 European countries. GENINCA will focus on exploring pre-cancerous and cancer lesions of the two aforementioned tumor entities and their respective microenvironment. As the recent identification of human colon-cancer initiating cells by one of our academic consortium members paves the way for completely new strategies for studying mechanisms of tumorgenesis, a particular focus of this grant proposal will be the detailed characterization of these cancer initiating stem cells. At present, it is still a matter of debate which genomic changes are already present in precursor lesions and whether these lesions already show genetic instability. We will therefore address the occurrence of genomic instability and explore their underlying mechanisms especially in pre-cancerous and early cancer lesions. This will be greatly facilitated by in vivo endomicroscopy approaches, sophisticated animal models and large-scale genomic and proteomic analyses. Furthermore, we ill include an in-depth analysis of the corresponding microenvironment. As this represents a translational research effort, we expect to identify markers for novel therapeutic and/or preventative strategies, as well as facilitating tumor diagnosis, prognosis, and monitoring.', 'en': 'GENINCA will address two tumor entities, for which we have good access to pre-malignant lesions and in which genomic instability is a common feature: colorectal and liver cancer. \\r\\nGENINCA represents a collaborative study of 8 academic and 3 industrial partners from 5 European countries. GENINCA will focus on exploring pre-cancerous and cancer lesions of the two aforementioned tumor entities and their respective microenvironment. As the recent identification of human colon-cancer initiating cells by one of our academic consortium members paves the way for completely new strategies for studying mechanisms of tumorgenesis, a particular focus of this grant proposal will be the detailed characterization of these cancer initiating stem cells. At present, it is still a matter of debate which genomic changes are already present in precursor lesions and whether these lesions already show genetic instability. We will therefore address the occurrence of genomic instability and explore their underlying mechanisms especially in pre-cancerous and early cancer lesions. This will be greatly facilitated by in vivo endomicroscopy approaches, sophisticated animal models and large-scale genomic and proteomic analyses. Furthermore, we ill include an in-depth analysis of the corresponding microenvironment. As this represents a translational research effort, we expect to identify markers for novel therapeutic and/or preventative strategies, as well as facilitating tumor diagnosis, prognosis, and monitoring.'}\n\nEuropäische Kommission\n\n"
},
{
"text": "Mapping of the bound proton fraction in the elderly brain\n\nBOUND_PROTON_ELDERLY_BRAIN_FWF07\nKlinische Abteilung für allgemeine Neurologie\nForschungsförderung\nRopele, Stefan\nRopele, Stefan\n{'de': 'The aim of this proposal is to investigate whether the bound pool fraction as a new and quantitative MR measure allows more insight into age related brain tissue changes than other quantitative MR measures. The specific aims are:\\r\\n\\r\\n*Develop a MR pulse sequence that allows to map the bound proton fraction on high field systems (>=3T) within a clinically reasonable measurement time (<15min). The sequence should offer whole brain coverage and should overcome current limitations such as the susceptibility for motion and B1 effects.\\r\\n\\r\\n*Measure the BPF in brain tissue of a large cohort of the Ausitria Stroke Prevention Study (ASPS). This gives us the opportunity to study a representative and homogeneous group of normal elderly people without a history or signs of neuropsychiatric diseases. By using a younger control cohort, we want to investigate how the BPF changes as a function of age, sex and anatonic region including cortical structures. In addition, we want to find out how the BPF varies within WMH with different severity and how it relates to the BPF in normal appearing brain tissue and to the neurocognitive performance.\\r\\n\\r\\n*Compare the sensitivity and specificity of bound proton fraction mapping to more established measures of brain tissue changes including atrophy, diffusion weighted imaging, and magnetization transfer imaging.', 'en': 'The aim of this proposal is to investigate whether the bound pool fraction as a new and quantitative MR measure allows more insight into age related brain tissue changes than other quantitative MR measures. The specific aims are:\\r\\n\\r\\n*Develop a MR pulse sequence that allows to map the bound proton fraction on high field systems (>=3T) within a clinically reasonable measurement time (<15min). The sequence should offer whole brain coverage and should overcome current limitations such as the susceptibility for motion and B1 effects.\\r\\n\\r\\n*Measure the BPF in brain tissue of a large cohort of the Ausitria Stroke Prevention Study (ASPS). This gives us the opportunity to study a representative and homogeneous group of normal elderly people without a history or signs of neuropsychiatric diseases. By using a younger control cohort, we want to investigate how the BPF changes as a function of age, sex and anatonic region including cortical structures. In addition, we want to find out how the BPF varies within WMH with different severity and how it relates to the BPF in normal appearing brain tissue and to the neurocognitive performance.\\r\\n\\r\\n*Compare the sensitivity and specificity of bound proton fraction mapping to more established measures of brain tissue changes including atrophy, diffusion weighted imaging, and magnetization transfer imaging.'}\n\nFWF, Fonds zur Förderung der Wissenschaftlichen Forschung\n\n"
},
{
"text": "Influence of Antioxidative Agents like Resveratrol, Quercetin-dihydrate, and Seleno-L-Methionine on Human Synoviocytes of Osteoarthritis (OA), Rheumatoid Arthritis (RA) and Psoriasis Arthritis (PsA) Patients\n\nInfluence of Antioxidative Agents\nUniversitätsklinik für Orthopädie und Traumatologie\nForschungsförderung\nGlehr, Mathias\nGlehr, Mathias\n{'de': 'Osteoarthritis is the most prevalent disorder of the musculoskeletal system and has a very high socioeconomic impact. Current treatments for Osteoarthritis are only symptomatic, because they do not act on the causes of Arthritis and do not stop the progression of the disease. This study is designed to investigate the effect of Resveratrol, Quercetin, and Selenium on healthy human synovial cells compared to synovial cells from OA and RA patients. We propose that these chemo preventive agents cause a growth rate decrease in synovial tissue and furthermore an inhibition of proinflammatory factors as well as an increase in factors favouring apoptosis and cell death. \\r\\nEspecially Resveratrol is known as a potent specific inhibitor of inflammation, but its potency has not been tested on human synovial cells. If the potency in decreasing inflammatory Interleukins is similar to the results of animal experiments, it would be an enormous effort for treatment of Osteoarthritis and Rheumatoid Arthritis. This study should be undertaken to define a possible systemic or local application of Resveratrol compared to Quercetin and Selenium. A close interaction between clinicians and basic scientists is necessary because of the combination of analytical, functional and molecular methods.\\r\\n', 'en': 'Osteoarthritis is the most prevalent disorder of the musculoskeletal system and has a very high socioeconomic impact. Current treatments for Osteoarthritis are only symptomatic, because they do not act on the causes of Arthritis and do not stop the progression of the disease. This study is designed to investigate the effect of Resveratrol, Quercetin, and Selenium on healthy human synovial cells compared to synovial cells from OA and RA patients. We propose that these chemo preventive agents cause a growth rate decrease in synovial tissue and furthermore an inhibition of proinflammatory factors as well as an increase in factors favouring apoptosis and cell death. \\r\\nEspecially Resveratrol is known as a potent specific inhibitor of inflammation, but its potency has not been tested on human synovial cells. If the potency in decreasing inflammatory Interleukins is similar to the results of animal experiments, it would be an enormous effort for treatment of Osteoarthritis and Rheumatoid Arthritis. This study should be undertaken to define a possible systemic or local application of Resveratrol compared to Quercetin and Selenium. A close interaction between clinicians and basic scientists is necessary because of the combination of analytical, functional and molecular methods.\\r\\n'}\n\nÖsterreichische Nationalbank (Jubiläumsfonds)\n\n"
},
{
"text": "Albumin an acute-on-chronic liver failure: more than just volume? A randomized, controlled study\n\nLIVER_FAILURE\nKlinische Abteilung für Gastroenterologie und Hepatologie\nForschungsförderung\nStadlbauer-Köllner, Vanessa\nStadlbauer-Köllner, Vanessa\n{'de': 'Acute-on-chronic liver failure (ACLF) often results in multiple organ dysfunction and mortality rates are in the order of 50-90%.\\r\\nAlbumin is the major plasma protein and is produced in the liver. Albumin undertakes a variety of functions including: fatty acid transport; metal chelation; drug-binding; and anti-oxidant activity. In liver disease its concentration is diminished but the mechanism of this reduction is uncertain. Currently, albumin infusion in patients with cirrhosis is used primarily as a volume expander. However, recent studies showing reduction in severity of hepatic encephalopathy and improved survival of cirrhotic patients with spontaneous bacterial peritonitis and hepatorenal syndrome treated with albumin infusion is compelling.\\r\\nOne of the substances that bind to albumin is endotoxin. Endotoxin is a lipopolysaccharid derived from the wall of gram-negative bacteria that causes immediate and strong immune response.\\r\\n\\r\\nWe hypothesize that infusion of albumin can improve endotoxin binding capacity and thereby prevent inappropriate neutrophil activation and neutrophil dysfunction in patients with spontaneous bacterial peritonitits. Therefore we aim to investigate neutrophil function (oxidative burst and phagocytosis) and endotoxin binding capacity as well as albumin function in patients with spontaneous bacterial peritonitis before, during and after high-dose albumin infusions as compared to standard therapy. We will also record the occurence of organ failure as a clinical endpoint.', 'en': 'Acute-on-chronic liver failure (ACLF) often results in multiple organ dysfunction and mortality rates are in the order of 50-90%.\\r\\nAlbumin is the major plasma protein and is produced in the liver. Albumin undertakes a variety of functions including: fatty acid transport; metal chelation; drug-binding; and anti-oxidant activity. In liver disease its concentration is diminished but the mechanism of this reduction is uncertain. Currently, albumin infusion in patients with cirrhosis is used primarily as a volume expander. However, recent studies showing reduction in severity of hepatic encephalopathy and improved survival of cirrhotic patients with spontaneous bacterial peritonitis and hepatorenal syndrome treated with albumin infusion is compelling.\\r\\nOne of the substances that bind to albumin is endotoxin. Endotoxin is a lipopolysaccharid derived from the wall of gram-negative bacteria that causes immediate and strong immune response.\\r\\n\\r\\nWe hypothesize that infusion of albumin can improve endotoxin binding capacity and thereby prevent inappropriate neutrophil activation and neutrophil dysfunction in patients with spontaneous bacterial peritonitits. Therefore we aim to investigate neutrophil function (oxidative burst and phagocytosis) and endotoxin binding capacity as well as albumin function in patients with spontaneous bacterial peritonitis before, during and after high-dose albumin infusions as compared to standard therapy. We will also record the occurence of organ failure as a clinical endpoint.'}\n\nÖsterreichische Nationalbank (Jubiläumsfonds)\n\n"
},
{
"text": "Therapie-assoziierte aktue myeloische Leukämie bei Trägern von C-RAF Keimbahnmutationen: Identifikation der Leukämie-manifestierenden Mutation(en)\n\nMYELOISCH_LEUKAEMIE_C-RAF_MUTATION\nKlinische Abteilung für Hämatologie\nForschungsförderung\nSill, Heinz\nSill, Heinz\n{'de': 'Therapie-assoziierte akute myeloische Leukämie (t-AML) und Therapie-assoziiertes myelodysplastisches Syndrom (t-MDS) werden durch Chemo- und/oder Radiotherapie eines Primärtumors verursacht und sind durch eine besonders schlechte Prognose mit einer 5-Jahres Überlebensrate von weniger als zehn Prozent gekennzeichnet. Diese Spätkomplikationen weisen eine in den letzten Jahren stark steigende Inzidenz auf, was vor allem auf die Tatsache zurückzuführen ist, dass immer mehr Krebspatienten durch verbesserte Chemo- und/oder Radiotherapie ihren Primärtumor überleben. Um den betroffenen Patienten in Zukunft effiziente Therapiemöglichkeiten anbieten zu können, ist es von eminenter Bedeutung, die pathogenetischen Grundlagen dieser Malignome aufzuklären. \\r\\nDas Ziel dieser Arbeit ist es, die Lücke in unserem Verständnis zwischen Prädisposition zur t-AML Entstehung, verursacht durch die von uns beschriebenen C-RAF Keimbahnmutationen, und der Manifestation der t-AML nach dem Auftreten einer oder mehrerer zusätzlicher Mutationen zu schließen. Zu diesem Zwecke werden wir versuchen, die so genannten "second hits" dieser Patienten zu identifizieren, also jene eine oder mehrere erworbenen genetischen Alterationen, die auf dem Boden der prädisponierenden C-RAF Keimbahnmutationen zum finalen Zusammenbruch des oben erwähnten Kompensationssystems und somit zur Entstehung der t-AML führen. Eine Kenntnis dieser " second hits" würde nicht nur einen wichtigen Schritt in der Entschlüsselung der Karzinogenese durch onkogene Keimbahnmutationen bedeuten, sondern könnte darüber hinaus auch neue therapeutische Angriffspunkte für dieses durch konventionelle Therapieansätze inkurable Patientenkollektiv leifern.', 'en': 'Therapie-assoziierte akute myeloische Leukämie (t-AML) und Therapie-assoziiertes myelodysplastisches Syndrom (t-MDS) werden durch Chemo- und/oder Radiotherapie eines Primärtumors verursacht und sind durch eine besonders schlechte Prognose mit einer 5-Jahres Überlebensrate von weniger als zehn Prozent gekennzeichnet. Diese Spätkomplikationen weisen eine in den letzten Jahren stark steigende Inzidenz auf, was vor allem auf die Tatsache zurückzuführen ist, dass immer mehr Krebspatienten durch verbesserte Chemo- und/oder Radiotherapie ihren Primärtumor überleben. Um den betroffenen Patienten in Zukunft effiziente Therapiemöglichkeiten anbieten zu können, ist es von eminenter Bedeutung, die pathogenetischen Grundlagen dieser Malignome aufzuklären. \\r\\nDas Ziel dieser Arbeit ist es, die Lücke in unserem Verständnis zwischen Prädisposition zur t-AML Entstehung, verursacht durch die von uns beschriebenen C-RAF Keimbahnmutationen, und der Manifestation der t-AML nach dem Auftreten einer oder mehrerer zusätzlicher Mutationen zu schließen. Zu diesem Zwecke werden wir versuchen, die so genannten "second hits" dieser Patienten zu identifizieren, also jene eine oder mehrere erworbenen genetischen Alterationen, die auf dem Boden der prädisponierenden C-RAF Keimbahnmutationen zum finalen Zusammenbruch des oben erwähnten Kompensationssystems und somit zur Entstehung der t-AML führen. Eine Kenntnis dieser " second hits" würde nicht nur einen wichtigen Schritt in der Entschlüsselung der Karzinogenese durch onkogene Keimbahnmutationen bedeuten, sondern könnte darüber hinaus auch neue therapeutische Angriffspunkte für dieses durch konventionelle Therapieansätze inkurable Patientenkollektiv leifern.'}\n\nLand Steiermark\n\n"
},
{
"text": "Genetische Ursachen der Meningokokkenerkrankung bei Kindern\n\nMeningokokken\nKlinische Abteilung für allgemeine Pädiatrie\nForschungsförderung\nZenz, Werner\nBinder, Alexander\n{'de': 'Meningokokkenerkrankungen betreffen fast immer vorher vollkommen gesunde Kinder und können innerhalb weniger Stunden zum Tod führen. Die Erkrankung ist selten, in Österreich werden jährlich zwischen 80 und 100 Fälle beobachtet. Betroffen sind fast ausschließlich Kinder. \\r\\nWir konnten in dem vom Land Steiermark unterstützten Vorprojekt (A3-16K8/2006-9) bereits einen hochsignifikanten Einfluss des Protein C/Protein C Rezeptor-Systems auf den Verlauf dieser Erkrankung zeigen, eine bestimmte Kombination von Mutationen führte zu einem 14fach erhöhten Risiko für einen tödlichen Ausgang der Erkrankung. \\r\\nWir wollen nun in diesem Forschungsprojekt den direkten Einfluss dieser genetischen Unter-schiede im Gerinnungssystem auf die Dichte des exprimierten Protein C Rezeptors und die Plasmaspiegel von Protein C und Protein C Rezeptor bestimmen. Diese Untersuchung kann in der Folge eine Erklärung für das Auftreten und die verschiedenen Verläufe von Meningokokke-nerkrankungen bieten. Durch unsere guten internationalen Kontakte bietet sich uns die Mög-lichkeit, eine britische Patientenkohorte als Bestätigungskollektiv für unsere Resultate zu ver-wenden sowie die von der Gruppe von Prof. Levin in London gesammelten Daten zur Auswer-tung des Einflusses der von uns gefundenen genetischen Varianten auf physiologische Parame-ter wie Protein C Blutspiegel zu verwenden.\\r\\nDie Entdeckung des zugrundeliegenden Pathomechanismuses der von uns gefundenen Korrela-tion einer spezifischen Kombinationen von Genotypen der zwei untersuchten Proteine (PC und EPCR) mit dem Verlauf der Meningokokkenerkrankung wäre ein starkes Argument für die Durchführung einer Protein C Studie an diesen anhand ihres genetischen Profils selektierten Patienten.\\r\\n', 'en': 'Meningokokkenerkrankungen betreffen fast immer vorher vollkommen gesunde Kinder und können innerhalb weniger Stunden zum Tod führen. Die Erkrankung ist selten, in Österreich werden jährlich zwischen 80 und 100 Fälle beobachtet. Betroffen sind fast ausschließlich Kinder. \\r\\nWir konnten in dem vom Land Steiermark unterstützten Vorprojekt (A3-16K8/2006-9) bereits einen hochsignifikanten Einfluss des Protein C/Protein C Rezeptor-Systems auf den Verlauf dieser Erkrankung zeigen, eine bestimmte Kombination von Mutationen führte zu einem 14fach erhöhten Risiko für einen tödlichen Ausgang der Erkrankung. \\r\\nWir wollen nun in diesem Forschungsprojekt den direkten Einfluss dieser genetischen Unter-schiede im Gerinnungssystem auf die Dichte des exprimierten Protein C Rezeptors und die Plasmaspiegel von Protein C und Protein C Rezeptor bestimmen. Diese Untersuchung kann in der Folge eine Erklärung für das Auftreten und die verschiedenen Verläufe von Meningokokke-nerkrankungen bieten. Durch unsere guten internationalen Kontakte bietet sich uns die Mög-lichkeit, eine britische Patientenkohorte als Bestätigungskollektiv für unsere Resultate zu ver-wenden sowie die von der Gruppe von Prof. Levin in London gesammelten Daten zur Auswer-tung des Einflusses der von uns gefundenen genetischen Varianten auf physiologische Parame-ter wie Protein C Blutspiegel zu verwenden.\\r\\nDie Entdeckung des zugrundeliegenden Pathomechanismuses der von uns gefundenen Korrela-tion einer spezifischen Kombinationen von Genotypen der zwei untersuchten Proteine (PC und EPCR) mit dem Verlauf der Meningokokkenerkrankung wäre ein starkes Argument für die Durchführung einer Protein C Studie an diesen anhand ihres genetischen Profils selektierten Patienten.'}\n\nLand Steiermark\n\n"
},
{
"text": "The role of C/EBPa on the development of monocyte subsets\n\nC/EBPa\nKlinische Abteilung für Hämatologie\nForschungsförderung\nWoelfler, Albert\nWoelfler, Albert\n{'de': 'The integrity of the hematopoietic system depends on a large number of blood cell lineages being continuously replenished from a rare population of pluripotent heatopoietic stem cells(HSC), representing a paradigm for how multilineage diversity can be achieved from a common stem cell through lineage commitment and subsequent differentiation.\\r\\nMonocytes are mononuclear cells and represent about 10% of leukocytes in human blood and 4% of leukocytes in mouse blood. The best known function of monocytes is their role as accessory cells, which link inflammation and the innate defense system against microorganisms to adaptive immune response.\\r\\nMany factors are involved in monocyte differentiation like PU.1, IRF8, KLF-4, MafB, c-maf and C/EBPalpha. C/EBPalpha (CCAAT/enhancer binding protein alpha) is a basic region-leucine zipper transcription factor and indispensable for formation of mature neutrophils and eosinophils. It is expressed at low levels in HSC, and is up-regulated to its highest levels in GMP(granulocyte/monocyte progenitors), whereas it is not expressed in precursors of lymphoid cells and is downregulated as CMP differentiate to MEP(megakaryocyte/erythrocyte progenitors). Mice-studies indicate that C/EBPalpha is essential for transition of CMP to GMP.\\r\\n\\r\\nWe hypothesize that C/EBPalpha positive and C/EBPalpha negative monocytes represent distinct subgroups of monocytes, which also differ in their function. In addition, we speculate that they are derived from different progenitors. To experimentally approach this hypothesis we want to use the C/EBPalphaCRE EYFP reporter mouse model.', 'en': 'The integrity of the hematopoietic system depends on a large number of blood cell lineages being continuously replenished from a rare population of pluripotent heatopoietic stem cells(HSC), representing a paradigm for how multilineage diversity can be achieved from a common stem cell through lineage commitment and subsequent differentiation.\\r\\nMonocytes are mononuclear cells and represent about 10% of leukocytes in human blood and 4% of leukocytes in mouse blood. The best known function of monocytes is their role as accessory cells, which link inflammation and the innate defense system against microorganisms to adaptive immune response.\\r\\nMany factors are involved in monocyte differentiation like PU.1, IRF8, KLF-4, MafB, c-maf and C/EBPalpha. C/EBPalpha (CCAAT/enhancer binding protein alpha) is a basic region-leucine zipper transcription factor and indispensable for formation of mature neutrophils and eosinophils. It is expressed at low levels in HSC, and is up-regulated to its highest levels in GMP(granulocyte/monocyte progenitors), whereas it is not expressed in precursors of lymphoid cells and is downregulated as CMP differentiate to MEP(megakaryocyte/erythrocyte progenitors). Mice-studies indicate that C/EBPalpha is essential for transition of CMP to GMP.\\r\\n\\r\\nWe hypothesize that C/EBPalpha positive and C/EBPalpha negative monocytes represent distinct subgroups of monocytes, which also differ in their function. In addition, we speculate that they are derived from different progenitors. To experimentally approach this hypothesis we want to use the C/EBPalphaCRE EYFP reporter mouse model.'}\n\nLeukämiehilfe Steiermark\n\n"
},
{
"text": "SFB: Biomembranes: Molecular Aspects of Ion Channels \n\nSFB: Biomembranes: Molecular Aspects of Ion Channels\n\nSFB007/708 Biomembranes\nLehrstuhl für Biophysik\nForschungsförderung\nSchreibmayer, Wolfgang\nSchreibmayer, Wolfgang\n{'de': 'Molecular aspects of ion channels \\r\\nIon channels as cellular targets and origin of atherogenic processes are studied by a multidisciplinar approach utilizing the logistic framework of the SFB "Biomembranes".\\r\\nParticular emphases is given to the modulation of ion channel functins by protein-lipid interactions and by redox modification of channel proteins.\\r\\n\\r\\nThe project which takes place at both the Departmentsof Medical Physics and Biophysics and of Pharmacology and Toxicology of the University in Graz is aimed at clarifying the following general questions:\\r\\n\\r\\nAre ion channels involved in atherogenesis? \\r\\nWhich channels are those? \\r\\nHow are cahnnels modulated by lipid peroxides? \\r\\nHow are channels modulated by the cellular redox state? \\r\\nWhat are the structural motifs on proteins, responsible for interaction with lipids and for redox sensitivity? \\r\\nOur activities focus on the following topics:\\r\\n\\r\\nIdentification of endothelial ion channels which are modulated by reactive oxygen species and disturbances of the cellular redox state. \\r\\nScreening of mRNA from endothelial cells for potential redox sensitive channels, i.e. Kir channels and nonselective cation channels. \\r\\nCharacterization of the modulation by reactive oxygen species of G-protein activated inward rectifying K+ channels (GIRK channels) of artial muscle expressed in Xenopus laevis oocytes. \\r\\nCharacterization of the modulation by reactive oxygen species of smooth muscle Ca2+ channels expressed in HEK 293 cells. \\r\\nKey words: Ion channels, K+ channels, Ca2+ channels, atherosclerosis, redox sensitivity, cardiovascular system, endothelial cells\\r\\n', 'en': 'Molecular aspects of ion channels \\r\\nIon channels as cellular targets and origin of atherogenic processes are studied by a multidisciplinar approach utilizing the logistic framework of the SFB "Biomembranes".\\r\\nParticular emphases is given to the modulation of ion channel functins by protein-lipid interactions and by redox modification of channel proteins.\\r\\n\\r\\nThe project which takes place at both the Departmentsof Medical Physics and Biophysics and of Pharmacology and Toxicology of the University in Graz is aimed at clarifying the following general questions:\\r\\n\\r\\nAre ion channels involved in atherogenesis? \\r\\nWhich channels are those? \\r\\nHow are cahnnels modulated by lipid peroxides? \\r\\nHow are channels modulated by the cellular redox state? \\r\\nWhat are the structural motifs on proteins, responsible for interaction with lipids and for redox sensitivity? \\r\\nOur activities focus on the following topics:\\r\\n\\r\\nIdentification of endothelial ion channels which are modulated by reactive oxygen species and disturbances of the cellular redox state. \\r\\nScreening of mRNA from endothelial cells for potential redox sensitive channels, i.e. Kir channels and nonselective cation channels. \\r\\nCharacterization of the modulation by reactive oxygen species of G-protein activated inward rectifying K+ channels (GIRK channels) of artial muscle expressed in Xenopus laevis oocytes. \\r\\nCharacterization of the modulation by reactive oxygen species of smooth muscle Ca2+ channels expressed in HEK 293 cells. \\r\\nKey words: Ion channels, K+ channels, Ca2+ channels, atherosclerosis, redox sensitivity, cardiovascular system, endothelial cells\\r\\n'}\n\nFWF, Fonds zur Förderung der Wissenschaftlichen Forschung\n\n"
},
{
"text": "Zellbasierte nichtinvasive Pränataldiagnostik\n\nCell-based non-invasive prenatal diagnosis\n\nZELLBAS NICHTINV PRAENATALDIAG\nLehrstuhl für Zellbiologie, Histologie und Embryologie\nForschungsförderung\nSedlmayr, Peter\nSedlmayr, Peter\n{'de': 'Genetische Pränataldiagostik erfordert die Gewinnung von Zellen des Kindes. Dies erfolgt durch invasive Methoden wie Amniozentese oder Chorionzottenbiopsie. Das Risiko, daß es durch diese Eingriffe zu einem Abort kommt, ist nicht vernachlässigbar und liegt bei 0,5 \\x96 1%. Aus diesem Grund ist genetische Pränataldiagnostik auf Schwangerschaften mit einem erhöhten Risiko einer genetischen Krankheit des Fetus beschränkt, wie z. B. einem Alter der Schwangeren von über 35 Jahren. Tatsächlich wird aber die Mehrzahl von Kindern mit genetischen Krankheiten nach Schwangerschaften geboren, die nicht primär als mit erhöhtem Risiko behaftet eingestuft werden können und bei denen das Risiko einer invasive Diagnostik in keinem vertretbaren Verhältnis zum Risiko durch den Eingriff steht.\\r\\nAusgehend von einer von uns entwickelten Methode zur geschlechtsunabhängigen Analyse der fötalen Identität von Zellen wollen wir in dem vorgeschlagenen Projekt ein Verfahren etablieren, das auf der Basis der Analyse von Einzelzellen eine nicht-invasive pränatale Diagnostik numerischer Chromosomenaberrationen und monogenetisch bedingter Krankheiten ermöglicht. Wir vergleichen die Effizienz etablierter Protokolle zur Anreicherung fetaler Zellen aus dem peripheren Blut schwangerer Frauen. Weiters etablieren wir die Amplifikation des gesamten Genoms von Einzelzellen, kombinieren die Analyse der fetalen Identität mittels array comparative genomic hybridization zur Analyse von Trisomien und analysieren als Beispiel der prinzipiellen Machbarkeit Mutationen des CFTR Gens.\\r\\nAuf Basis dieser Arbeiten wollen wir unter Nutzung von Ressourcen der Medizinischen Universität Graz im Sinn einer kommerziellen Anwendung ein überregionales Zentrum zur zellbasierten nichtinvasiven Pränataldiagnostik etablieren.\\r\\n', 'en': 'Genetic prenatal diagnosis is dependent on procurement of fetal cells. This is done my invasive methods such as amniocentesis and chorionic villous sampling. These methods are associated to a risk of 0.5 \\x96 1% of subsequent abortus. For this reason genetic prenatal diagnosis is restricted to pregnancies with are associated with an increased risk of renetik disease of the fetus, such as age of the pregnant women higher than 35 years. In fact the majority of children with genetic diseases is born at the end of pregnancies which have not abeen associated with an increased risk, where the risk of invasive procedures cannot be justified.\\r\\nBased on a method which we developed previously for sex-independent analysis of the fetal identity of cells in a fetal microchimeric setting, we plan to establish a technique allowing for non-invasive prenatal diagnosis of both numeric chromosomal aberrations and monogenetic hereditary diseases, using analysis of single cells. We will compare the efficiency of established protocols for enrichment of fetal cells from the peripheral blood of pregnant women. Furthermore, we will establish whole genome amplification of single cells and combine the analysis of fetal identity with analysis of trisomy by means of array comparative genomic hybridization. As a proof of principle for feasibility of analysis of monogenic hereditary diseases using the preamplified genome of single cells we will analyze mutations of the CFTR gene.\\r\\nThe results of this work will be commercially exploited as we plan to establish an supra-regional center for cell-based non-invasive prenatal diagnosis by using the facilities of the Medical University of Graz.\\r\\n'}\n\nFWF, Fonds zur Förderung der Wissenschaftlichen Forschung\n\n"
},
{
"text": "Doktoratskolleg "Metabolische und kardiovaskuläre Erkrankungen" \n\nDoktoratskolleg "Metabolic disorders and cellular dysfunction" \n\nDK_METABOL_DISORDERS\nAbteilung Zentrum für Medizinische Forschung\nForschungsförderung\nBirner-Grünberger, Ruth\nBirner-Grünberger, Ruth\n{'de': 'Proteomic investigation of lipotoxicity in tumor-associated cachexia\\r\\nObjective: To elucidate possible causes and effects of tumor-induced lipotoxicity on the proteome level.\\r\\nCachexia is commonly recognized as progressive weight loss with depletion of host reserves of adipose tissue and skeletal muscle and associated with cancers of gastrointestinal tract and lung. Survival of cancer patients is directly related to weight loss. The reduction of food intake alone is unable to explain the metabolic changes seen in cachexia. Moreover, loss of muscle and adipose tissue precedes the fall in food intake. The causes and mechanisms responsible for tumor-associated cachexia remain to be unravelled. Preliminary data generated in Gerald Hoefler´s laboratory demonstrate an involvement of adipose triglyceride lipase (ATGL) in the development of cachexia. While implantation of Lewis lung carcinoma cells into wild-type mice resulted in a vast reduction of gastrognemious muscle and white adipose tissue and a minor reduction in heart weight, none of these effects were seen in ATGL-ko mice.\\r\\nTissues from cachexia mouse models will be obtained from G. Hoefler. Proteomes from gastrognemious muscle, adipose tissues, liver, heart and spleen of wild-type and ATGL-ko mice with and without transplanted tumor will be profiled with respect to protein abundance by differential gelelectrophoresis (DIGE) and/or isotope labeling, liquid chromatography and mass spectrometry (LC-MS). Phosphoproteomics of selected cellular fractions will be performed using immobilized metal affinity chromatography (IMAC, TiO2) for phosphopeptide enrichment, isotopic labeling for quantification, LC-MS with phospho-group neutral loss scanning and database search for phospho-group modifications. Differences in lipase and esterase activities will be assessed by activity-based proteomics employing suitable probes (developed by the applicant) and by standard proteomic techniques.\\r\\n\\r\\nRegulatory and compensatory mechanisms of lipolytic pathways\\r\\nBackground: While the lipolytic proteome of mouse adipose tissue has been identified (3), many of the underlying regulatory processes remain unknown. Therefore, regulatory and compensatory mechanisms of lipolytic pathways as well as changes in the overall proteome will be determined upon shut down of individual pathways (e.g. in hormone sensitive lipase (HSL)- and ATGL-deficient mice). The phenotypes of the respective mouse models differ greatly with regard to body weight, lipid accumulation, fertility and organ specific defects. Thus, large effects are expected to be observed on the protein level in adipose and other tissues as well as in macrophages and foam cells.\\r\\nObjective: To elucidate the underlying regulatory, compensatory and pathogenic mechanisms of lipid accumulation on the proteome level.\\r\\nProteins interacting with recently identified lipases, as well as lipid droplet-associated proteins, which might regulate substrate accessibility, will be isolated from tissue fractions or cell lines, identified by LC-MS and analyzed for the presence of isomers and post-translational modifications, especially phosphorylation. Related tissue/cell fractions or immunoprecipitations will be profiled with respect to protein abundance by DIGE and/or isotopic labelling and LC-MS. Selected proteins will be confirmed by Western blotting. Phosphoproteomics and activity-based proteomics will be applied as described in Project 1.\\r\\n', 'en': None}\n\nFWF, Fonds zur Förderung der Wissenschaftlichen Forschung\n\n"
},
{
"text": "EMBIC: The Control of Embryo Implantation\n\nEMBIC:The Control of Embryo Implantation\n\nEMBIC\nLehrstuhl für Zellbiologie, Histologie und Embryologie\nForschungsförderung\nSedlmayr, Peter\nSedlmayr, Peter\n{'de': 'We aim to build an European virtual laboratory on major mechanism of implantation by thoroughly exploring what knock out mice have recently established as cellular - cytokine networks/ key pathways promoting the development of 2 de novo organs: the decidua basalis and the mature placenta. At present, fragmentation of experimental capacity and disparate approaches result in lack of a comprehensive skills base, and lack of access to very specialised approaches and technological platforms such as animal experimentation in very strict conditions, genomics and proteomics facilities or multicentric clinical evaluation. These require to be used in a coordinated fashion to maximise their effect in this area.\\r\\nWe will thus: 1.) Assemble critical talents and approaches, to develop an integrative, evaluative, capacity to set up EMBIC; 2.) Integrate EMBIC laboratories using crucial models and coordination of the joint programme of activities; 3.) Constitute a European cohort of infertile women with creation of RT generated DNA, sera and micro-biopsy tissue samples banks; 4.) Establish guidelines for management of infertile women combined with diagnosis procedures and ultimately recombinant technologies therapies for selected pathologies; 5.) Open the network of validated platforms for education and cooperative experimentation.\\r\\nEMBIC will contribute and benefit from the creation of integrated platforms based on animal models, genomic and proteomic facilities, protein intra-net database set-up, integrated clinical set-up. EMBIC will spread excellence by facilitaing the exchange of scientists within the laboratories, promote recruitment/training of out network post-docs, organise workshops and satellite meetings in pan European or regional Immunology/Fertility meetings and an annual summer school.', 'en': 'We aim to build an European virtual laboratory on major mechanism of implantation by thoroughly exploring what knock out mice have recently established as cellular - cytokine networks/ key pathways promoting the development of 2 de novo organs: the decidua basalis and the mature placenta. At present, fragmentation of experimental capacity and disparate approaches result in lack of a comprehensive skills base, and lack of access to very specialised approaches and technological platforms such as animal experimentation in very strict conditions, genomics and proteomics facilities or multicentric clinical evaluation. These require to be used in a coordinated fashion to maximise their effect in this area.\\r\\nWe will thus: 1.) Assemble critical talents and approaches, to develop an integrative, evaluative, capacity to set up EMBIC; 2.) Integrate EMBIC laboratories using crucial models and coordination of the joint programme of activities; 3.) Constitute a European cohort of infertile women with creation of RT generated DNA, sera and micro-biopsy tissue samples banks; 4.) Establish guidelines for management of infertile women combined with diagnosis procedures and ultimately recombinant technologies therapies for selected pathologies; 5.) Open the network of validated platforms for education and cooperative experimentation.\\r\\nEMBIC will contribute and benefit from the creation of integrated platforms based on animal models, genomic and proteomic facilities, protein intra-net database set-up, integrated clinical set-up. EMBIC will spread excellence by facilitaing the exchange of scientists within the laboratories, promote recruitment/training of out network post-docs, organise workshops and satellite meetings in pan European or regional Immunology/Fertility meetings and an annual summer school.'}\n\nEuropäische Kommission\n\n"
},
{
"text": "EuroSTEC: Soft tissue engineering for congenital birth defects in children: from "biomatrix - cell interaction - model system" to clinical trials\n\nIMPPACT\nKlinische Abteilung für Transplantationschirurgie\nForschungsförderung\nStiegler, Philipp\nStiegler, Philipp\n{'de': "IMPPACT will develop an intervention planning and monitoring application for Radiofrequency Ablation (RFA) of malignant liver tumours. RFA is a minimally invasive form to treat cancer without open surgery, by placing a needle inside the malignancy and destroying it through intensive heating. Though the advantages of this approach ale obvious, the intervention is currently hard to plan, almost impossible to monitor or assess, and therefore is not the first choice for treatment. IMPPACT will develop a physiological model of the liver and simulate the intervention's result, accounting for patient specific physiological factors. Gaps in the understanding of particular aspects of the RFA treatment will be closed by multi-scale studies on cells and animals. New findings will be evaluated microscopically and transformed into macroscopic equations. The long-established bio-heat equation will be extended to incorporate multiple scales. Validation will be performed at multiple levels. Images from ongoing patient treatment will be used to cross check validity for human physiology. Final validation will be performed at macroscopic level through visual comparison of simulation and treatment results gathered in animal studies and during patient treatment. This extensive validation together with a user-centered software design approach will guarantee suitability of the solution for clinical practice. The consortium consists of two Hospitals, three Universities, one Research Institute and one industrial SME. The final project deliverables will be the patient specific intervention planning system and an augmented reality training simulator for the RFA intervention.", 'en': "IMPPACT will develop an intervention planning and monitoring application for Radiofrequency Ablation (RFA) of malignant liver tumours. RFA is a minimally invasive form to treat cancer without open surgery, by placing a needle inside the malignancy and destroying it through intensive heating. Though the advantages of this approach ale obvious, the intervention is currently hard to plan, almost impossible to monitor or assess, and therefore is not the first choice for treatment. IMPPACT will develop a physiological model of the liver and simulate the intervention's result, accounting for patient specific physiological factors. Gaps in the understanding of particular aspects of the RFA treatment will be closed by multi-scale studies on cells and animals. New findings will be evaluated microscopically and transformed into macroscopic equations. The long-established bio-heat equation will be extended to incorporate multiple scales. Validation will be performed at multiple levels. Images from ongoing patient treatment will be used to cross check validity for human physiology. Final validation will be performed at macroscopic level through visual comparison of simulation and treatment results gathered in animal studies and during patient treatment. This extensive validation together with a user-centered software design approach will guarantee suitability of the solution for clinical practice. The consortium consists of two Hospitals, three Universities, one Research Institute and one industrial SME. The final project deliverables will be the patient specific intervention planning system and an augmented reality training simulator for the RFA intervention."}\n\nEuropäische Kommission\n\n"
},
{
"text": "MICRO-WEDGE\n\nMICRO-WEDGE\nLehrstuhl für Biophysik\nForschungsförderung\nPlank, Gernot\nPlank, Gernot\n{'de': 'Several multicenter clinical trials have provided consistent evidence that implantable defibrillation therapy prolongs patient life. This convincing demonstration of the efficacy of defibrillation has led to a nearly exponential growth, over the last decade, in the number of patients receiving implantable devices. The current wide application of defibrillation raises new concerns regarding the safety and optimization of the therapy. Improved understanding of defibrillation mechanisms is therefore\\r\\nimperative to the development of better and safer strategies for prevention of sudden cardiac death. Despite the importance of this therapy, understanding of mechanisms by which electric shocks halt life-threatening arrhythmias remains incomplete. While recent experimental advances have provided new characterizations of tissue\\r\\nresponses to shocks, mechanistic inquiry into the success and failure of defibrillation is hampered by the inability of current experimental techniques to resolve, with sufficient accuracy, electrical behavior confined to the depth of the ventricles.\\r\\nThe overall objective of this research is, by employing realistic 3D computer simulations, to bring a new level of understanding of the post-shock events in the heart that lead to the failure of the shock. Current models do not incorporate anatomical microheterogeneities, which could play an important role. Specifically, this project proposes to examine, in bidomain models of cardiac micro-structure, mechanisms underlying the ``isoelectric window", the quiescent period often preceding the first postshock activation following failed shocks. We hypothesize that the isoelectric window arises from small-scale shock-induced polarization, such as polarization of trabeculae and papillary muscle. Understanding the isoelectric window mechanisms could pave the way to new strategies for extending it indefinitely, and thus converting a failed shock into a successful one.', 'en': 'Several multicenter clinical trials have provided consistent evidence that implantable defibrillation therapy prolongs patient life. This convincing demonstration of the efficacy of defibrillation has led to a nearly exponential growth, over the last decade, in the number of patients receiving implantable devices. The current wide application of defibrillation raises new concerns regarding the safety and optimization of the therapy. Improved understanding of defibrillation mechanisms is therefore\\r\\nimperative to the development of better and safer strategies for prevention of sudden cardiac death.\\r\\nDespite the importance of this therapy, understanding of mechanisms by which electric shocks halt life-threatening arrhythmias remains incomplete. While recent experimental advances have provided new characterizations of tissue\\r\\nresponses to shocks, mechanistic inquiry into the success and failure of defibrillation is hampered by the inability of current experimental techniques to resolve, with sufficient accuracy, electrical behavior confined to the depth of the ventricles.\\r\\nThe overall objective of this research is, by employing realistic 3D computer simulations, to bring a new level of understanding of the post-shock events in the heart that lead to the failure of the shock. Current models do not incorporate anatomical microheterogeneities, which could play an important role. Specifically, this project proposes to examine, in bidomain models of cardiac micro-structure, mechanisms underlying the ``isoelectric window", the quiescent period often preceding the first postshock activation following failed shocks. We hypothesize that the isoelectric window arises from small-scale shock-induced polarization, such as polarization of trabeculae and papillary muscle. Understanding the isoelectric window mechanisms could pave the way to new strategies for extending it indefinitely, and thus converting a failed shock into a successful one.'}\n\nEuropäische Kommission\n\n"
},
{
"text": "Psycho-Neuro-Immunologie. Einfluss einer psychosozialen Intervention auf T und NK Zellfunktion von Patientinnen mit Mammakarzinom\n\nPsycho-Neuro-Immunologie Mammakarzinom\nKlinische Abteilung für Onkologie\nForschungsförderung\nBauernhofer, Thomas\nBauernhofer, Thomas\n{'de': 'The autonomic, neuroendocrine, and the immune systems are orchestrated in part to preserve conditions compatible with life. The critical question in immunosurveillance against cancer is whether differences between individuals with regard to immunologic host-defense mechanisms can predict the incidende or progression of cancer. Acute as well as chronic stressors have been associated with reduction of various in vitro measures of immune function. Even acute commonplace stressful events like a final examination scenario for medical students or "the public speaking situation" are associated with transient changes in immunologic parameters (e.g. natural killer(NK) cell number and cytotoxity, T helper/inducer cell number, production of interferon (IFN) gamma by lymphocytes stimulated with Concavalin-A, etc.) along with elevated stress hormone levels and cardiovascular activation compared to controls. The aims of the study are: * Further evaluation of differences in immune parameters of patients with breast cancer compared to their significant others and non related healthy volunteers focusing on differences in the relative number of T and NK cell subpopulations, onset of apoptosis and functional parameters like the kinetics of perforin release of stimulated T and NK cells. *Assessment of hormonal parameters in the three study populations and their correlation to immune parameters as well as psychosocial parameters. * Investigation of the influence of psychosocial intervention on the immune system with special regard to T cell- and NK cell subpopulations, rate of apoptosis and perforin release of these immune cells in patients with operated breast cancer compared to significant others and healthy volunteers.', 'en': 'The autonomic, neuroendocrine, and the immune systems are orchestrated in part to preserve conditions compatible with life. The critical question in immunosurveillance against cancer is whether differences between individuals with regard to immunologic host-defense mechanisms can predict the incidende or progression of cancer. Acute as well as chronic stressors have been associated with reduction of various in vitro measures of immune function. Even acute commonplace stressful events like a final examination scenario for medical students or "the public speaking situation" are associated with transient changes in immunologic parameters (e.g. natural killer(NK) cell number and cytotoxity, T helper/inducer cell number, production of interferon (IFN) gamma by lymphocytes stimulated with Concavalin-A, etc.) along with elevated stress hormone levels and cardiovascular activation compared to controls. The aims of the study are: * Further evaluation of differences in immune parameters of patients with breast cancer compared to their significant others and non related healthy volunteers focusing on differences in the relative number of T and NK cell subpopulations, onset of apoptosis and functional parameters like the kinetics of perforin release of stimulated T and NK cells. * Assessment of hormonal parameters in the three study populations and their correlation to immune parameters as well as psychosocial parameters. * Investigation of the influence of psychosocial intervention on the immune system with special regard to T cell- and NK cell subpopulations, rate of apoptosis and perforin release of these immune cells in patients with operated breast cancer compared to significant others and healthy volunteers'}\n\nÖsterreichische Nationalbank (Jubiläumsfonds)\n\n"
},
{
"text": "MPO-modifiziertes High-Density Lipoprotein und Rezeptoren\n\nMPO-modified high-density lipoprotein and receptors\n\nMPO-mod. HD LDL\nLehrstuhl für Molekularbiologie und Biochemie\nForschungsförderung\nMalle, Ernst\nMalle, Ernst\n{'de': 'The vascular endothelium is a wide spread organ responsible for the regulation of hemodynamics, angiogenic vascular remodeling, metabolic, synthetic, antiinflammatory, and antithrombogenic processes. Diminished nitric oxide (NO) availability has been linked to vascular disease and a heightened state of inflammation is characterized, in part, by an increase in vascular myeloperoxidase and proteins in vivo modified by its principal oxidant, hypochlourous acid/hypochlorous acid/hypochlorite (HOCI/OCI). Modification of high-density lipoprotein (HDL) by HOCI generates a proatherogenic and proinflammatory lipoprotein particle. HOCI-HDL, present in human lesions material and on endothelial cells, attenuates the expression and activity of vasuloprotective endothelial NO synthase (eNOS). Therefore, one part of this application is to clarify the mechanisms that governs interaction of HODI-HDL and its lipid (plasmalogen)-derived oxidant 2-chlorohexadecanal with eNOS, to focus whether caveolae-located proteins are involved, to profile alterations in endothelial gene expression patterns, and to investigate endothelium-dependent vascular relaxation in aortic rings and perfused vessels. As endothelial dysfunction may be induced by receptor-ligand interaction, the other part of this application will focus on interaction of HOCI-HDL with candidate receptors mediating (patho)physiologically relevant cellualar responses, i.e. activation of transcription factors, kinases and production of cytokines, leadng to the perpetuation of the inflammatory response and endothelial dysfunction. To answer these questions cell lines overexpressing candidate receptors will be used before adapting the cellular signaling cascade patterns to a specific endothelial cell line. We propose that myeloperoxidase-modified HDL- a unique and clinically significant marker for atherosclerosis - mediates endothelial dysfunction by specific receptor-evoked intracellular signaling pathways. ', 'en': 'The vascular endothelium is a wide spread organ responsible for the regulation of hemodynamics, angiogenic vascular remodeling, metabolic, synthetic, antiinflammatory, and antithrombogenic processes. Diminished nitric oxide (NO) availability has been linked to vascular disease and a heightened state of inflammation is characterized, in part, by an increase in vascular myeloperoxidase and proteins in vivo modified by its principal oxidant, hypochlourous acid/hypochlorous acid/hypochlorite (HOCI/OCI). Modification of high-density lipoprotein (HDL) by HOCI generates a proatherogenic and proinflammatory lipoprotein particle. HOCI-HDL, present in human lesions material and on endothelial cells, attenuates the expression and activity of vasuloprotective endothelial NO synthase (eNOS). Therefore, one part of this application is to clarify the mechanisms that governs interaction of HODI-HDL and its lipid (plasmalogen)-derived oxidant 2-chlorohexadecanal with eNOS, to focus whether caveolae-located proteins are involved, to profile alterations in endothelial gene expression patterns, and to investigate endothelium-dependent vascular relaxation in aortic rings and perfused vessels. As endothelial dysfunction may be induced by receptor-ligand interaction, the other part of this application will focus on interaction of HOCI-HDL with candidate receptors mediating (patho)physiologically relevant cellualar responses, i.e. activation of transcription factors, kinases and production of cytokines, leadng to the perpetuation of the inflammatory response and endothelial dysfunction. To answer these questions cell lines overexpressing candidate receptors will be used before adapting the cellular signaling cascade patterns to a specific endothelial cell line. We propose that myeloperoxidase-modified HDL- a unique and clinically significant marker for atherosclerosis - mediates endothelial dysfunction by specific receptor-evoked intracellular signaling pathways. '}\n\nFWF, Fonds zur Förderung der Wissenschaftlichen Forschung\n\n"
},
{
"text": "Immunreaktion auf resorbierbare Implantate im Femur der wachsenden Ratte\n\nIMMUNREAKTION_IMPLANT_FEMUR_RATTE\nUniversitätsklinik für Kinder- und Jugendchirurgie\nForschungsförderung\nWeinberg, Annelie-Martina\nWeinberg, Annelie-Martina\n{'de': 'Der Wegfall einer zweiten Operation zur Implantatentfernung ist der größte Vorteil der resorbierbaren Implantate. Dies erlaubt dem Patienten eine frühe Rückkehr in die Schule bzw. an den Arbeitsplatz. Zusätzlich sind bioresorbierbare Implantate kompatibler zum Frakturheilungsprozess als steife Metallimplantate, die die Belastung direkt auf den Knochen übertragen. Bisher wurden bioresorbierbare Implantate vor allem in der Gesichtschirurgie, Orthopädie und Unfallchirurgie verwendet. Gute Resultate wurden dabei besonders bei der Versorgung von Sprunggelenks-, Knie- und Ellenbogenläsionen erzielt.\\r\\nIn der Kinderchirurgie wurden solche Implantate zur Stabilisierung von Ellenbogenbrüchen und bei der Gesichtschirurgie verwendet Insgesamt sind Publikationen über die Verwendung bioresorbierbarer Implantate in der Kindertraumatologie-orthopädie jedoch selten.\\t\\r\\n\\r\\nIn diesem Projekt werden ein kommerziell erhältliches Implantat aus PLLA/PGA mit einem neu designeten Implantat aus Magnesiumsulfat und einem der Technischen Universität Graz (TUG)® verglichen.\\r\\n\\r\\nZiel des Projektes ist es die Verwendung von bioresorbierbaren Implantaten in der (Kinder)traumatologie \\x96 und orthopädie zu steigern. In der Hoffnung auf Reduktion der in der Literatur beschriebenen Komplikationen bei der Verwendung etablierter Implantate sind zwei neuartige bioresorbierbare Materialien entwickelt worden. Zum Vergleich der Implantate werden die akute und chronische Entzündungsreaktion sowie Mikro-CT und Biomechnik herangezogen.\\r\\nEs wird vermutet, dass die Verträglichkeit der neuartigen Implantate zu geringeren Entzündungsreaktionen führen als die bisher hauptsächlich verwendeten PLLA/PGA Polymere. Auf Grund der geringeren Entzündungsreaktion wird auch eine geringere Osteolyse im Bereich des Knochen-Implantat-Interface, und damit eine bessere Performance bei den biomechanischen Tests und dem Mikro-CT erwartet.\\r\\nEs wird erhofft, mit dem präsentierten Projektdesign ein besseres Verständnis über die Entzündungsreaktion bei der Verwendung bioresorbierbarer Implantate zu erlangen.\\r\\n\\r\\n', 'en': 'Der Wegfall einer zweiten Operation zur Implantatentfernung ist der größte Vorteil der resorbierbaren Implantate. Dies erlaubt dem Patienten eine frühe Rückkehr in die Schule bzw. an den Arbeitsplatz. Zusätzlich sind bioresorbierbare Implantate kompatibler zum Frakturheilungsprozess als steife Metallimplantate, die die Belastung direkt auf den Knochen übertragen. Bisher wurden bioresorbierbare Implantate vor allem in der Gesichtschirurgie, Orthopädie und Unfallchirurgie verwendet. Gute Resultate wurden dabei besonders bei der Versorgung von Sprunggelenks-, Knie- und Ellenbogenläsionen erzielt.\\r\\nIn der Kinderchirurgie wurden solche Implantate zur Stabilisierung von Ellenbogenbrüchen und bei der Gesichtschirurgie verwendet Insgesamt sind Publikationen über die Verwendung bioresorbierbarer Implantate in der Kindertraumatologie-orthopädie jedoch selten.\\t\\r\\n\\r\\nIn diesem Projekt werden ein kommerziell erhältliches Implantat aus PLLA/PGA mit einem neu designeten Implantat aus Magnesiumsulfat und einem der Technischen Universität Graz (TUG)® verglichen.\\r\\n\\r\\nZiel des Projektes ist es die Verwendung von bioresorbierbaren Implantaten in der (Kinder)traumatologie \\x96 und orthopädie zu steigern. In der Hoffnung auf Reduktion der in der Literatur beschriebenen Komplikationen bei der Verwendung etablierter Implantate sind zwei neuartige bioresorbierbare Materialien entwickelt worden. Zum Vergleich der Implantate werden die akute und chronische Entzündungsreaktion sowie Mikro-CT und Biomechnik herangezogen.\\r\\nEs wird vermutet, dass die Verträglichkeit der neuartigen Implantate zu geringeren Entzündungsreaktionen führen als die bisher hauptsächlich verwendeten PLLA/PGA Polymere. Auf Grund der geringeren Entzündungsreaktion wird auch eine geringere Osteolyse im Bereich des Knochen-Implantat-Interface, und damit eine bessere Performance bei den biomechanischen Tests und dem Mikro-CT erwartet.\\r\\nEs wird erhofft, mit dem präsentierten Projektdesign ein besseres Verständnis über die Entzündungsreaktion bei der Verwendung bioresorbierbarer Implantate zu erlangen.'}\n\nLorenz Böhler Gesellschaft - Verein zur Förderung der Forschung auf dem Gebiet der Unfallheilkunde\n\n"
},
{
"text": "Einfluss von genetischen Variationen des VEGF-Gens auf Entstehung, Therapieansprechen und Metastasierung bei Darmkrebs\n\nInfluence of genetic variants in the VEGF-gene on development, response to therapy and risk of de-veloping metastases in colorectal cancer\n\nVEGF-Gens bei Darmkrebs\nKlinische Abteilung für Onkologie\nForschungsförderung\nHofmann, Guenter\nHofmann, Guenter\n{'de': 'Tumorwachstum im Allgemeinen erfordert die Bildung von neuen Gefäßen(Angiogenese). Eine Schlüsselrolle in der Regulation der Angiogenese spielt der Vascular endothelian growth factor (VEGF), ein dimeres Glykoprotein, das in verschiedenen Tumorgeweben überexprimiert wird. VEGF-Plasmaspiegel korrelieren mit dem Vorhandensein und dem Stadium von Darmkrebs.\\r\\nIm VEGF-Gen sind verschiedene genetische Polymorphismen ("single nucleotide polymorphisms", SNPs) bekannt, einige von diesen zeigen einen Einfluss auf die Expression des VEGF Gens und/oder einen Zusammenhang mit einem klinischen Phänotyp. Die Arbeitsgruppe für molekulare Onkologie (Univ.-Doz.Dr. Peter Krippl) an der MUG analysierte kürzlich die Rolle einer dieser genetischen Variante, nämlich 936C>T, als potentiellen Risikofaktor für Brustkrebs.\\r\\nDie Rolle dieser genetischen Variation für das Darmkrebs-Risiko ist bisher unbekannt. Weiters ist nicht geklärt, ob andere genetische Variationen im VEGF Gen ebenfalls einen Einfluss auf Entstehung und/oder Wachstum von Darmtumoren haben.\\r\\nIn der gelanten Fall-Kontroll-Studie möchten wir der Frage nachgehen, od es eine Assoziation zwischen VEGF-Genotypen und Haplotypen mit VEGF Plasmaspiegeln gibt. Darüberhinaus werden wir untersuchen, ob das Darmkrebsrisiko durch VEGF-Genotypen oder Haplotypen beeinflusst wird.\\r\\nDie Identifikation der Bedeutung von VEGF-Genotypen und Haplotypen für das Darmkrebsrisiko kann zu einem besseren Verständnis der Krankheitsentstehung führen. Zusätzlich könnte das Wissen über genetische Risikofaktoren dazu beitragen, Personen mit hereditären Prädispositionen für Darmkrebs zu identifizieren und diese, frühzeitig prophylaktischen Maßnahmen zuzuführen.', 'en': 'Tumor growth generally requires the development and formation of new blood vessels (angiogenesis). The vascular endothelial growth factor (VEGF), a dimeric glycoproteine which is overexpressed in different tumour tissues, plays a key role in the regulation of angiogenesis. Recently it was demonstrated, that VEGF-levels in plasma correlate with the presence and the stage of colorectal cancer.\\r\\nSeveral genetic polymorphisms ("single nucleotide polymorphisms ", SNP`s) in the VEGF-gene are known and some of them seem to have an influence on the expression of the VEGF gene and/or a connection with the clinical phenotype of VEGF. A short time ago, the working group for molecular oncology (head: Peter Krippl; M.D.) of the MUG analyzed the role of one this genetic variants, i.e. 936C>T SNP, and was able to show that this SNP is a potential risk factor for breast cancer.\\r\\nThe role of this SNP for colorectal cancer risk is unknown. Furthermore, it is not clear whether other genetic variations in the VEGF gene have an influence on development and/or growth as well as metastazing risk of colorectal cancer. In our case-control study, we would like to answer the question whether there exists an association between VEGF-genotypes and VEGF-haplotypes with colorectal cancer risk. We want to analyze whether VEGF plasma levels are affected by VEGF genotypes or haplotypes, as well. \\r\\nThe answers to these questions could lead to a better understanding of the development of colorectal cancer. Additionally, the knowledge about genetic risk factors could identify persons with hereditary predispositions for this tumour and make it possible to prevent tumour development in a more effective way.\\r\\n'}\n\nÖsterreichische Krebshilfe Steiermark\n\n"
},
{
"text": "Effects of hepoxilin A3 and its analogues on the function of human eosiophil and basophil granulocytes\n\nEffects of hepoxilin A3 on granulocytes\nLehrstuhl für Pharmakologie\nForschungsförderung\nPeskar, Bernhard\nHeinemann, Akos\n{'de': 'Hepoxilins are formed from arachidonic acid via 12-lipoxygenase pathway. Three isoforms of 12-lipoxygenase have been described and are widely expressed in immune cells an tissue, such as skin and lung. With respect to its diverse biological actions hepoxilin A3 is considered as the most relevant of this class of eicosanoids. In vivo and in vitro studies suggest that hepoxilin A3 has both pro-inflammatory and anti-inflammatory actions, and might play a role in the resolution phase of inflammatory conditions. Although hepoxilins are likely to be abundant at sites of allergic reactions, such as lung and skin, no data is available to-date on the effect of hepoxilins on eosinophil and basophil function, which are important effector cells involved in early- and late-phase allergic responses. In preliminary experiments we observed that hepoxilin A3 is a potent and highly effective inhibitor of eosinophil chemotaxis in vitro. Therefore, the proposed studies aim at further clarifying the actions of hepoxilin A3 on eosinophil and basophil function, including chemotaxis to a wide range of chemoattratants, degranulation, respiratory burst, cell survival and mobilisation of eosinophils from the bone marrow. In addition to their cytotoxic products eosinophils are also an important source of inflammatory mediators, such as leukotrienes and cytokienes.\\r\\nWe expect this study to provide better insights into the role of 12-lipogenases in general, and hepoxilins in particular, in regulating eosinophil and basophil function in order to predict the biological and pharmacological relevance hepoxilins in allergic disease. The study might hence yield novel regimes for the treatment of allergic diseases.', 'en': 'Hepoxilins are formed from arachidonic acid via 12-lipoxygenase pathway. Three isoforms of 12-lipoxygenase have been described and are widely expressed in immune cells an tissue, such as skin and lung. With respect to its diverse biological actions hepoxilin A3 is considered as the most relevant of this class of eicosanoids. In vivo and in vitro studies suggest that hepoxilin A3 has both pro-inflammatory and anti-inflammatory actions, and might play a role in the resolution phase of inflammatory conditions. Although hepoxilins are likely to be abundant at sites of allergic reactions, such as lung and skin, no data is available to-date on the effect of hepoxilins on eosinophil and basophil function, which are important effector cells involved in early- and late-phase allergic responses. In preliminary experiments we observed that hepoxilin A3 is a potent and highly effective inhibitor of eosinophil chemotaxis in vitro. Therefore, the proposed studies aim at further clarifying the actions of hepoxilin A3 on eosinophil and basophil function, including chemotaxis to a wide range of chemoattratants, degranulation, respiratory burst, cell survival and mobilisation of eosinophils from the bone marrow. In addition to their cytotoxic products eosinophils are also an important source of inflammatory mediators, such as leukotrienes and cytokienes.\\r\\nWe expect this study to provide better insights into the role of 12-lipogenases in general, and hepoxilins in particular, in regulating eosinophil and basophil function in order to predict the biological and pharmacological relevance hepoxilins in allergic disease. The study might hence yield novel regimes for the treatment of allergic diseases.'}\n\nÖsterreichische Nationalbank (Jubiläumsfonds)\n\n"
},
{
"text": "Prostaglandin D2 als Mediator der Allergie\n\nPROSTAGLANDIN_ALLERGIE\nLehrstuhl für Pharmakologie\nForschungsförderung\nHeinemann, Akos\nHeinemann, Akos\n{'de': 'Prostaglandin (PG) D2 is released by mast cells during the allergic response. Others and our group have recently produced considerable evidence that PGD2 might be involved in the initiation and perpetuation of allergic inflammation by orchestrating the recruitment of eosinophil granulocytes to the tissue, where they might cause tissue damage and induce the symptoms of allergic inflammation. The biological effects of PGD2 are mediated by three distinct receptors, the DP receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), or at higher concentrations by the thromboxane receptor, TP. Small molecule antagonists of these receptors have recently become available and are currently being developed for the treatment of inflammatory diseases, such as bronchial asthma and eczema. However, the relative contributions of DP, CRTH2 and TP to PGD2-induced biological responses have still remained unclear, but the knowledge thereof is mandatory in order to predict which of these receptors are the most promising targets for the treatment of allergic disease and highlight their potential limitations. Eosinophil function will be investigated with respect to the release of eosinophils from the bone marrow, their recruitment into the tissue, the cells\\x92 life span, and the release of pro-inflammatory mediators from eosinophils, such as reactive oxygen species, leukotrienes or exocytosed toxic granule contents. Moreover, we will test the potential clinical usefulness of CRTH2 and DP antagonists in vivo, using a murine model of ovalbumin-induced allergic pulmonary inflammation and airway hyperresponsiveness. Since the different biological responses to PGD2 can be mediated by CRTH2 or DP, respectively, a combined therapy with CRTH2 plus DP antagonists also needs to be given consideration. The study might hence lead to novel therapeutic regimens for the treatment of allergic inflammation and asthma.\\r\\n\\r\\n', 'en': 'Prostaglandin (PG) D2 is released by mast cells during the allergic response. Others and our group have recently produced considerable evidence that PGD2 might be involved in the initiation and perpetuation of allergic inflammation by orchestrating the recruitment of eosinophil granulocytes to the tissue, where they might cause tissue damage and induce the symptoms of allergic inflammation. The biological effects of PGD2 are mediated by three distinct receptors, the DP receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), or at higher concentrations by the thromboxane receptor, TP. Small molecule antagonists of these receptors have recently become available and are currently being developed for the treatment of inflammatory diseases, such as bronchial asthma and eczema. However, the relative contributions of DP, CRTH2 and TP to PGD2-induced biological responses have still remained unclear, but the knowledge thereof is mandatory in order to predict which of these receptors are the most promising targets for the treatment of allergic disease and highlight their potential limitations. Eosinophil function will be investigated with respect to the release of eosinophils from the bone marrow, their recruitment into the tissue, the cells\\x92 life span, and the release of pro-inflammatory mediators from eosinophils, such as reactive oxygen species, leukotrienes or exocytosed toxic granule contents. Moreover, we will test the potential clinical usefulness of CRTH2 and DP antagonists in vivo, using a murine model of ovalbumin-induced allergic pulmonary inflammation and airway hyperresponsiveness. Since the different biological responses to PGD2 can be mediated by CRTH2 or DP, respectively, a combined therapy with CRTH2 plus DP antagonists also needs to be given consideration. The study might hence lead to novel therapeutic regimens for the treatment of allergic inflammation and asthma.'}\n\nFWF, Fonds zur Förderung der Wissenschaftlichen Forschung\n\n"
},
{
"text": "Whole Genome Screening des Menschen bei der Menigokokkensepsis\n\nMeningokokkensepsis\nKlinische Abteilung für allgemeine Pädiatrie\nForschungsförderung\nZenz, Werner\nBinder, Alexander\n{'de': 'Meningokokkenerkrankungen betreffen fast immer vorher vollkommen gesunde Kinder und können innerhalb weniger Stunden zum Tod führen. Die Erkrankung ist selten, in Österreich werden jährlich zwischen 80 und 100 Fälle beobachtet. Betroffen sind fast ausschließlich Kinder. Die septische Verlaufsform ist durch die rasche Entwicklung eines schweren Schocks mit verminderter Durchblutung der Haut, Bewusstlosigkeit, Multiorganversagen und schwerer Stö-rung der Blutgerinnung charakterisiert, die Sterblichkeit liegt trotz intensivmedizinischer Bemü-hungen noch immer bei etwa 25%.\\r\\nEs sind nun Genomanalysen verfügbar, mit denen das gesamte menschliche Genom (3 Mrd. Basenpaare) untersucht werden kann. Mit diesen neuen Methoden können alle genetischen Än-derungen, die für das Auftreten und den Verlauf einer Erkrankung verantwortlich sind, unter-sucht werden. In den letzten 2 Jahren sind bereits mehrere solche whole genome association studies (GWAs) veröffentlicht worden, jedoch wurden noch keine Ergebnisse zur Genetik der Sepsis gezeigt.\\r\\nMit Hilfe unseres Netzwerkes wäre es uns möglich, mit zwei weiteren Forschungsgruppen eine Kooperation zur Klärung der genetischen Ursachen der Meningokokkensepsis zu etablieren. Das so gebildete Kollektiv würde das weltweit größte Netzwerk zur Untersuchung von Meningo-kokkenerkrankungen darstellen. Es würde über 3000 europäischen Patienten sowie 700 Kon-trollproben umfassen und sich aus einer britischen, niederländischen, sowie unserer mitteleuro-päischen Kohorte zusammensetzen.\\r\\nIn Summe würden sich bei dem von uns primär eingesetzten Probenkollektiv von 200-400 Pati-enten 220 \\x96 440 Millionen Einzeluntersuchungen zur Darstellung des gesamten Genoms jeder einzelnen Patienten- bzw. Kontrollprobe ergeben.\\r\\nDas Ziel dieser weltweiten Kooperation ist es, die genetischen Variablen, welche zu einer Me-ningokokkensepsis führen, aufzudecken. Es soll so eine erste komplette Übersicht über die Ge-netik der Sepsiserkrankung erreicht werden. Die Aufklärung der involvierten Gene kann als An-gelpunkt für die weiterführende Forschung gesehen werden und bildet eine erste Grundlage für die Entwicklung selektiver (Kombinations-) Therapien.', 'en': 'Meningokokkenerkrankungen betreffen fast immer vorher vollkommen gesunde Kinder und können innerhalb weniger Stunden zum Tod führen. Die Erkrankung ist selten, in Österreich werden jährlich zwischen 80 und 100 Fälle beobachtet. Betroffen sind fast ausschließlich Kinder. Die septische Verlaufsform ist durch die rasche Entwicklung eines schweren Schocks mit verminderter Durchblutung der Haut, Bewusstlosigkeit, Multiorganversagen und schwerer Stö-rung der Blutgerinnung charakterisiert, die Sterblichkeit liegt trotz intensivmedizinischer Bemü-hungen noch immer bei etwa 25%.\\r\\nEs sind nun Genomanalysen verfügbar, mit denen das gesamte menschliche Genom (3 Mrd. Basenpaare) untersucht werden kann. Mit diesen neuen Methoden können alle genetischen Än-derungen, die für das Auftreten und den Verlauf einer Erkrankung verantwortlich sind, unter-sucht werden. In den letzten 2 Jahren sind bereits mehrere solche whole genome association studies (GWAs) veröffentlicht worden, jedoch wurden noch keine Ergebnisse zur Genetik der Sepsis gezeigt.\\r\\nMit Hilfe unseres Netzwerkes wäre es uns möglich, mit zwei weiteren Forschungsgruppen eine Kooperation zur Klärung der genetischen Ursachen der Meningokokkensepsis zu etablieren. Das so gebildete Kollektiv würde das weltweit größte Netzwerk zur Untersuchung von Meningo-kokkenerkrankungen darstellen. Es würde über 3000 europäischen Patienten sowie 700 Kon-trollproben umfassen und sich aus einer britischen, niederländischen, sowie unserer mitteleuro-päischen Kohorte zusammensetzen.\\r\\nIn Summe würden sich bei dem von uns primär eingesetzten Probenkollektiv von 200-400 Pati-enten 220 \\x96 440 Millionen Einzeluntersuchungen zur Darstellung des gesamten Genoms jeder einzelnen Patienten- bzw. Kontrollprobe ergeben.\\r\\nDas Ziel dieser weltweiten Kooperation ist es, die genetischen Variablen, welche zu einer Me-ningokokkensepsis führen, aufzudecken. Es soll so eine erste komplette Übersicht über die Ge-netik der Sepsiserkrankung erreicht werden. Die Aufklärung der involvierten Gene kann als An-gelpunkt für die weiterführende Forschung gesehen werden und bildet eine erste Grundlage für die Entwicklung selektiver (Kombinations-) Therapien.'}\n\nLand Steiermark\n\n"
}
]
}