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Search Results: 1 - 10 of 132458 matches for " Marco T. Birke "
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Topical Application of PPADS Inhibits Complement Activation and Choroidal Neovascularization in a Model of Age-Related Macular Degeneration
Kerstin Birke, Erion Lipo, Marco T. Birke, Rajendra Kumar-Singh
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076766
Abstract: Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly. AMD patients have elevated levels of membrane attack complex (MAC) in their choroidal blood vessels and retinal pigment epithelium (RPE). MAC forms pores in cell membranes. Low levels of MAC result in an elevation of cytokine release such as vascular endothelial growth factor (VEGF) that promotes the formation of choroidal neovascularization (CNV). High levels of MAC result in cell lysis and RPE degeneration is a hallmark of advanced AMD. The current standard of care for CNV associated with wet AMD is intravitreal injection of anti-VEGF molecules every 4 to 12 weeks. Such injections have significant side effects. Recently, it has been found that membrane pore-forming proteins such as α-haemolysin can mediate their toxic effects through auto- and paracrine signaling and that complement-induced lysis is amplified through ATP release followed by P2X receptor activation. We hypothesized that attenuation of P2X receptor activation may lead to a reduction in MAC deposition and consequent formation of CNV. Hence, in this study we investigated topical application of the purinergic P2X antagonist Pyridoxalphosphate-6-azophenyl-2',4'-dis?ulphonicacid (PPADS) as a potential treatment for AMD. We found that 4.17 μM PPADS inhibited formation of HUVEC master junctions and master segments by 74.7%. In a human complement mediated cell lysis assay, 104 μM PPADS enabled almost complete protection of Hepa1c1c7 cells from 1% normal human serum mediated cell lysis. Daily topical application of 4.17 mM PPADS for 3 days attenuated the progression of laser induced CNV in mice by 41.8% and attenuated the deposition of MAC at the site of the laser injury by 19.7%. Our data have implications for the future treatment of AMD and potentially other ocular disorders involving CNV such as angioid streaks, choroidal rupture and high myopia.
Preventive Effects of Omega-3 and Omega-6 Fatty Acids on Peroxide Mediated Oxidative Stress Responses in Primary Human Trabecular Meshwork Cells
Theofilos Tourtas, Marco T. Birke, Friedrich E. Kruse, Ulrich-Christoph Welge-Lüssen, Kerstin Birke
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0031340
Abstract: Pathologic processes in glaucoma include increased apoptosis, accumulation of extracellular material in the trabecular meshwork and optic nerve, condensations of the cytoskeleton and precocious cellular senescence. Oxidative stress was shown to generate these alterations in primary ocular cells. Fatty acids omega-3 and -6 are alleged to constitute a prophylaxis against these deleterious effects. Here, we tested actual preventive effects omega-3 and -6 against peroxide induced stress responses in primary human trabecular meshwork cells. Changes of mitochondrial activity, proliferation, heat shock proteins, extracellular matrix components, and inflammatory markers were evaluated. Alterations of the cytoskeleton were evaluated by phalloidin labeling. Here we report a repressive effect of omega-6 on metabolic activity and proliferation, which was not detected for omega-3. Both agents were able to prevent the anti-proliferative effect of H2O2, but only omega-3 prevented metabolic repression. Expression of heat shock protein 27 was unaltered by both fatty acids, whereas heat shock protein 90 was significantly induced by both. Omega-6 increased fibronectin and connective tissue growth factor synthesis, as well as the amount of secreted fibronectin. Omega-3, instead, induced plasminogen activator inhibitor 1 synthesis. H2O2 further increased fibronectin production in omega-6 supplemented cells, which was not the case in omega-3 treated cells. H2O2 stimulation of plasminogen activator inhibitor 1 and connective tissue growth factor was repressed by both fatty acids. Both fatty acids appeared to abolish H2O2 mediated stimulation of nuclear factor κB and IL-6, but not IL-1α and IL-8. H2O2 induced formation of cross-linked actin networks and stress fibers, which was reduced by preemptive application of omega-3. Omega-6, in contrast, had no protective effect on that, and even seemed to promote condensation. Based on the observed side effects of omega-6, omega-3 appears to be the more beneficial fatty acid in respect of prophylactic intake for prevention of a glaucomatous disease.
Osteopontin Is Induced by TGF-β2 and Regulates Metabolic Cell Activity in Cultured Human Optic Nerve Head Astrocytes
Carolin Neumann, Fabian Garreis, Friedrich Paulsen, Christian M. Hammer, Marco T. Birke, Michael Scholz
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0092762
Abstract: The aqueous humor (AH) component transforming growth factor (TGF)-β2 is strongly correlated to primary open-angle glaucoma (POAG), and was shown to up-regulate glaucoma-associated extracellular matrix (ECM) components, members of the ECM degradation system and heat shock proteins (HSP) in primary ocular cells. Here we present osteopontin (OPN) as a new TGF-β2 responsive factor in cultured human optic nerve head (ONH) astrocytes. Activation was initially demonstrated by Oligo GEArray microarray and confirmed by semiquantitative (sq) RT-PCR, realtime RT-PCR and western blot. Expressions of most prevalent OPN receptors CD44 and integrin receptor subunits αV, α4, α 5, α6, α9, β1, β3 and β5 by ONH astrocytes were shown by sqRT-PCR and immunofluorescence labeling. TGF-β2 treatment did not affect their expression levels. OPN did not regulate gene expression of described TGF-β2 targets shown by sqRT-PCR. In MTS-assays, OPN had a time- and dose-dependent stimulating effect on the metabolic activity of ONH astrocytes, whereas TGF-β2 significantly reduced metabolism. OPN signaling via CD44 mediated a repressive outcome on metabolic activity, whereas signaling via integrin receptors resulted in a pro-metabolic effect. In summary, our findings characterize OPN as a TGF-β2 responsive factor that is not involved in TGF-β2 mediated ECM and HSP modulation, but affects the metabolic activity of astrocytes. A potential involvement in a protective response to TGF-β2 triggered damage is indicated, but requires further investigation.
Signal Archiving and Retrieval: Essential Long Term Performance Tuning Tool
R. Bakker,T. Birke,R. Mueller
Physics , 2001,
Abstract: The first two years of user service of the third generation light source BESSY II emphasized the importance of a reliable, comprehensive and dense logging of a few thousand setpoints, readbacks, status and alarm values. Today data from sources with various characteristics residing in different protected networks are centrally collected and retrievable via an uncomplex CGI program to any desktop system on the site. Data post-processing tools cover Windows applications, IDL, SDDS and custom programs matching users skills and preferences. In this paper illustrative sample data explorations are described that underline the importance of the logging system for operations as well as for the understanding of singular events or long term drifts. Serious shortcomings of the present installation and focus of further development are described.
Introducing I/O Channels into the Device Database Opens New Potentialities for Configuration Management
T. Birke,B. Franksen,R. Lange,P. Laux,R. Mueller
Physics , 2001,
Abstract: The reference RDBMS for BESSY II has been set up with a device oriented data model. This has proven adequate for e.g. template based RTDB generation, modelling etc. But since assigned I/O channels have been stored outside the database (a) numerous specific conditions had to be maintained within the scripts generating configuration files and (b) several generic applications could not be set up automatically by scripts. In a larger re-design effort the I/O channels are introduced into the RDBMS. That modification allows to generate a larger set of RTDBs, map specific conditions into database relations and maintain application configurations by relatively simple extraction scripts.
A decision aid to rule out pneumonia and reduce unnecessary prescriptions of antibiotics in primary care patients with cough and fever
Johann Steurer, Ulrike Held, Anne Spaar, Birke Bausch, Marco Zoller, Roger Hunziker, Lucas M Bachmann
BMC Medicine , 2011, DOI: 10.1186/1741-7015-9-56
Abstract: This was a prospective cohort study in which we enrolled patients older than 18 years with a new or worsened cough and fever without serious co-morbidities. Physicians recorded results of a standardized medical history and physical examination. C-reactive protein was measured and chest radiographs were obtained. We used Classification and Regression Trees to derive the decision tool.A total of 621 consenting eligible patients were studied, 598 were attending a primary care facility, were 48 years on average and 50% were male. Radiographic signs for pneumonia were present in 127 (20.5%) of patients. Antibiotics were prescribed to 234 (48.3%) of patients without pneumonia. In patients with C-reactive protein values below 10 μg/ml or patients presenting with C-reactive protein between 11 and 50 μg/ml, but without dyspnoea and daily fever, pneumonia can be ruled out. By applying this rule in clinical practice antibiotic prescription could be reduced by 9.1% (95% confidence interval (CI): 6.4 to 11.8).Following validation and confirmation in new patient samples, this tool could help rule out pneumonia and be used to reduce unnecessary antibiotic prescriptions in patients presenting with cough and fever in primary care. The algorithm might be especially useful in those instances where taking a medical history and physical examination alone are inconclusive for ruling out pneumoniaRespiratory tract infections are the most frequent reasons for unnecessary antibiotic prescriptions and inappropriate treatment with antibiotics is one of the avoidable causes for the world-wide increasing problem of antibiotic resistance [1-3]. Guidelines [4-6] and patient information leaflets [7] emphasize this serious problem by recommending antibiotics only for patients with bacterial pneumonia and not for patients with acute bronchitis or mild exacerbations of chronic bronchitis [8,9]. The reasons for the still high rate of inappropriate prescriptions in patients with cough and fever are man
Hepatitis B and C Viruses and Hepatocellular Carcinoma
Birke Bartosch
Viruses , 2010, DOI: 10.3390/v2081504
Abstract: Chronic liver disease is responsible for over 1.4 million deaths annually ?[1] and is characterized by permanent inflammatory processes that predispose to liver cancer and in particular hepatocellular carcinoma (HCC). In healthy liver, inflammatory processes stimulate growth and repair and restore normal liver architecture. However, if liver inflammation becomes chronic, the balance of damage versus regeneration in the liver is disrupted and can lead to the formation of excessive scar tissue, termed fibrosis. In the long-term, an exacerbation of fibrosis will lead to cirrhosis, which is characterized by abnormal liver architecture and function and is associated with a significant reduction in overall health and wellbeing. At cirrhotic stages, liver damage is often irreversible or difficult to treat. Cirrhosis leads frequently to death from liver failure or to HCC (Figure 1). Indeed, HCC is the first cause of death in cirrhotic patients?[2], and is a tumor with poor prognosis, ranking third in terms of death by cancer. Furthermore, it is the fifth most prevalent cancer worldwide, with 800,000 new cases per year in the world?[2,3]. [...]
Hallo, wer spricht?“ Kommentar zu Margit Mayers Urbane soziale Bewegungen in der neoliberalisierenden Stadt“
Peter Birke
s u b u r b a n : zeitschrift für kritische stadtforschung , 2013,
Abstract: [Dieser Artikel ist Teil einer Debatte] Die von Margit Mayer vorgestellten Vorschl ge zur theoretischen Verortung der aktuellen stadtpolitischen Bewegungen sind aus meiner Sicht sehr wichtig. Kein Zweifel kann daran bestehen, dass eine flie ende, historisierende Sichtweise notwendig ist, die die fragmentierenden Wirkungen der Neoliberalisierung“ betont. Dies ist ein berechtigter Hinweis auf die Kurzschlüsse, die gerade auch in der marxistisch inspirierten politischen Linken verbreitet waren und sind, in denen Neoliberalismus“ als eine Figur, als eine Art gro es Monster gezeichnet worden ist, das sich immer“ und überall“, also überhistorisch und lückenlos durchzusetzen scheint. Von sehr gro er und sogar zunehmender Bedeutung erscheint mir auf dieser Grundlage auch der Versuch, eine Einteilung vorzunehmen, die die konomie der aktuellen Krise diesem historischen Prozess zuordnet und (was im Rahmen des vorliegenden Textes natürlich nur angedeutet werden kann) die Bezugnahme zwischen globalen, nationalstaatlichen und lokal-urbanen Austerit tspolitiken thematisiert. Ebenso wichtig wie schlüssig sind auch die Hinweise auf gegenw rtige Polarisierungstendenzen, die in diesem Kontext zu bemerken sind, so auch die Polarisierung von wachsenden“ und schrumpfenden“ Territorien und – was ja gerade die Pointe dieses Textes ist – der verschiedenen Pole der Sozialbewegungen selbst.
Detection of Postoperative Intestinal Ischemia in Small Bowel Transplants
Hanne Birke-Sorensen
Journal of Transplantation , 2012, DOI: 10.1155/2012/970630
Abstract: Small bowel transplantation is acknowledged as auto- and allotransplantation. In both instances, there is up to a 4%–10% risk of postoperative ischemia, and as the small bowel is extremely susceptible to ischemia, the timely diagnosis of ischemia is important. The location of the transplant, whether it is buried in the abdominal cavity or in the neck region, increases the challenge, as monitoring becomes more difficult and the consequences of neglect more dangerous. All methods for the early detection of postoperative ischemia in small bowel transplants are described together with the requirements of the ideal monitoring method. A small bowel transplant can be inspected directly or indirectly; the blood flow can be monitored by Doppler or by photoplethysmography, and the consequences of the blood flow can be monitored. The ideal monitoring method should be reliable, fast, minimally invasive, safe, objective, easy, cheap, and comfortable. No monitoring methods today fulfill the criteria of the ideal monitoring method, and evidence-based guidelines regarding postoperative monitoring cannot be made. The choice of whether to implement monitoring of ischemia—and if so, which method to choose—has to be made by the individual surgeon or center.
Recent Advances in Hepatitis C Virus Cell Entry
Birke Bartosch,Jean Dubuisson
Viruses , 2010, DOI: 10.3390/v2030692
Abstract: More than 170 million patients worldwide are chronically infected with hepatitis C virus (HCV). Prevalence rates range from 0.5% in Northern European countries to 28% in some areas of Egypt. HCV is hepatotropic, and in many countries chronic hepatitis C is a leading cause of liver disease including fibrosis, cirrhosis and hepatocellular carcinoma. HCV persists in 50–85% of infected patients, and once chronic infection is established, spontaneous clearance is rare. HCV is a member of the Flaviviridae family, in which it forms its own genus. Many lines of evidence suggest that the HCV life cycle displays many differences to that of other Flaviviridae family members. Some of these differences may be due to the close interaction of HCV with its host’s lipid and particular triglyceride metabolism in the liver, which may explain why the virus can be found in association with lipoproteins in serum of infected patients. This review focuses on the molecular events underlying the HCV cell entry process and the respective roles of cellular co-factors that have been implied in these events. These include, among others, the lipoprotein receptors low density lipoprotein receptor and scavenger receptor BI, the tight junction factors occludin and claudin-1 as well as the tetraspanin CD81. We discuss the roles of these cellular factors in HCV cell entry and how association of HCV with lipoproteins may modulate the cell entry process.
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