Now showing 1 - 10 of 35
  • 2006Journal Article
    [["dc.bibliographiccitation.firstpage","723"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Histochemistry and Cell Biology"],["dc.bibliographiccitation.lastpage","734"],["dc.bibliographiccitation.volume","126"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.author","Probst, Irmelin"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Krause, Petra"],["dc.date.accessioned","2018-11-07T08:53:50Z"],["dc.date.available","2018-11-07T08:53:50Z"],["dc.date.issued","2006"],["dc.description.abstract","Oval cells constitute a heterogeneous population of proliferating progenitors found in rat livers following carcinogenic treatment (2-acetylaminofluorene and 70% hepatectomy). The aim of this study was to investigate the cellular pattern of various differentiation and cell type markers in this model of liver regeneration. Immunophenotypic characterisation revealed at least two subtypes emerging from the portal field. First, a population of oval cells formed duct-like structures and expressed bile duct (CD49f) as well as hepatocytic markers (alpha-foetoprotein, CD26). Second, a population of non-ductular oval cells was detected between and distally from the ductules expressing the neural marker nestin and the haematopoietic marker Thy1. Following oval cell isolation, a subset of the nestin-positive cells was shown to co-express hepatocytic and epithelial markers (albumin, CD26, pancytokeratin) and could be clearly distinguished from anti-desmin reactive hepatic stellate cells. The gene expression profiles (RT-PCR) of isolated oval cells and oval cell liver tissue were found to be similar to foetal liver (ED14). The present results suggest that the two oval cell populations are organised in a zonal hierarchy with a marker gradient from the inner (displaying hepatocytic and biliary markers) to the outer zone (showing hepatocytic and extrahepatic progenitor markers) of the proliferating progeny clusters."],["dc.identifier.doi","10.1007/s00418-006-0204-3"],["dc.identifier.isi","242624400009"],["dc.identifier.pmid","16835754"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22524"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0948-6143"],["dc.title","Zonal hierarchy of differentiation markers and nestin expression during oval cell mediated rat liver regeneration"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
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  • 2011Journal Article
    [["dc.bibliographiccitation.firstpage","581"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Histochemistry and Cell Biology"],["dc.bibliographiccitation.lastpage","591"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Doratiotto, Silvia"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Serra, Maria Paola"],["dc.contributor.author","Marongiu, Fabio"],["dc.contributor.author","Sini, Marcella"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.author","Laconi, Ezio"],["dc.date.accessioned","2018-11-07T08:55:35Z"],["dc.date.available","2018-11-07T08:55:35Z"],["dc.date.issued","2011"],["dc.description.abstract","Overt neoplasia is often the end result of a long biological process beginning with the appearance of focal lesions of altered tissue morphology. While the putative clonal nature of focal lesions has often been emphasized, increasing attention is being devoted to the possible role of an altered growth pattern in the evolution of carcinogenesis. Here we compare the growth patterns of normal and nodular hepatocytes in a transplantation system that allows their selective clonal proliferation in vivo. Rats were pre-treated with retrorsine, which blocks the growth of resident hepatocytes, and were then transplanted with hepatocytes isolated from either normal liver or hepatocyte nodules. Both cell types were able to proliferate extensively in the recipient liver, as expected. However, their growth pattern was remarkably different. Clusters of normal hepatocytes integrated in the host liver, displaying a normal histology; however, transplanted nodular hepatocytes formed new hepatocyte nodules, with altered morphology and sharp demarcation from surrounding host liver. Both the expression and distribution of proteins involved in cell polarity, cell communication, and cell adhesion, including connexin 32, E-cadherin, and matrix metalloproteinase-2, were altered in clusters of nodular hepatocytes. Furthermore, we were able to show that down-regulation of connexin 32 and E-cadherin in nodular hepatocyte clusters was independent of growth rate. These results support the concept that a dominant pathway towards neoplastic disease in several organs involves defect(s) in tissue pattern formation."],["dc.description.sponsorship","AIRC (Italian Association for Cancer Research) [4927, 10604]"],["dc.identifier.doi","10.1007/s00418-011-0813-3"],["dc.identifier.isi","000291222300005"],["dc.identifier.pmid","21528371"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6622"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22939"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0948-6143"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","The growth pattern of transplanted normal and nodular hepatocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2014Book Chapter
    [["dc.bibliographiccitation.firstpage","29"],["dc.bibliographiccitation.lastpage","39"],["dc.bibliographiccitation.seriesnr","1213"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Rave-Frank, Margret"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.editor","Christ, Bruno"],["dc.contributor.editor","Oerlecke, Jana"],["dc.contributor.editor","Stock, Peggy"],["dc.date.accessioned","2021-06-02T10:44:23Z"],["dc.date.available","2021-06-02T10:44:23Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1007/978-1-4939-1453-1_3"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87018"],["dc.notes.intern","DOI-Import GROB-425"],["dc.publisher","Springer New York"],["dc.publisher.place","New York, NY"],["dc.relation.crisseries","Methods in Molecular Biology"],["dc.relation.eisbn","978-1-4939-1453-1"],["dc.relation.isbn","978-1-4939-1452-4"],["dc.relation.ispartof","Methods in Molecular Biology"],["dc.relation.ispartof","Animal Models for Stem Cell Therapy"],["dc.relation.ispartofseries","Methods in Molecular Biology; 1213"],["dc.title","Preconditioning of the Liver for Efficient Repopulation by Primary Hepatocyte Transplants"],["dc.type","book_chapter"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]
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  • 2014Journal Article
    [["dc.bibliographiccitation.firstpage","805"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cell Transplantation"],["dc.bibliographiccitation.lastpage","817"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Unthan-Fechner, Kirsten"],["dc.contributor.author","Probst, Irmelin"],["dc.contributor.author","Koenig, Sarah"],["dc.date.accessioned","2018-11-07T09:46:06Z"],["dc.date.available","2018-11-07T09:46:06Z"],["dc.date.issued","2014"],["dc.description.abstract","Clinical studies have proved the therapeutic potential of hepatocyte transplantation as a promising alternative to whole organ liver transplantation in the treatment of hereditary or end-stage liver disease. However, donor shortage seriously restricts cell availability, and the lack of appropriate cell culture protocols for the storage and maintenance of donor cells constitutes a significant obstacle. The aim of this study was to stimulate mature hepatocytes in culture to multiply in vitro and track their fate on transplantation. Rat hepatocytes isolated nonenzymatically were cultured serum free for up to 10 days. They were stimulated into proliferation in the presence of growth factors and conditioned media from nonparenchymal and hepatocyte culture supernatants, as well as 10 mM lithium chloride (LiCl). Cell proliferation was assessed by determining DNA content. Additionally, the extent of cell differentiation was estimated using immunofluorescence staining of hepatic, biliary, progenitor, and mesenchymal markers and gene expression analyses. Transplantation studies were performed on the Fischer CD26-mutant rat following pretreatment with retrorsine and partial hepatectomy. Proliferating hepatocytes increasingly adopted precursor characteristics, expressing progenitor (OV6, CD133), hepatic lineage (CK18), biliary (CD49f, CK7, CK19), and mesenchymal (vimentin) markers. The supplement of LiCl further enhanced the proliferative capacity by 30%. Transplantation studies revealed extensive repopulation by large donor hepatocyte clusters. Furthermore, bile duct-like structures deriving from donor cells proved to be immunoreactive to ductular markers and formed in close proximity to endogenous bile ducts. Mature hepatocytes reveal their potential to \"switch\" between phenotypes, adopting progenitor characteristics during proliferation in vitro. Following transplantation, these \"retrodifferentiated\" cells further expanded in vivo, thereby generating bipotentially differentiated progenies (hepatocytes and bile duct-like structures). This apparent plasticity of mature hepatocytes may open new approaches for cell-based strategies to treat liver disease."],["dc.identifier.doi","10.3727/096368913X664856"],["dc.identifier.isi","000337989700002"],["dc.identifier.pmid","23485196"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10644"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34784"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cognizant Communication Corp"],["dc.relation.issn","1555-3892"],["dc.relation.issn","0963-6897"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Cultured Hepatocytes Adopt Progenitor Characteristics and Display Bipotent Capacity to Repopulate the Liver"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]
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  • 2019Journal Article
    [["dc.bibliographiccitation.firstpage","711"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Surgical Education"],["dc.bibliographiccitation.lastpage","719"],["dc.bibliographiccitation.volume","76"],["dc.contributor.author","Backhaus, Joy"],["dc.contributor.author","Huth, Katrin"],["dc.contributor.author","Entwistle, Andrew"],["dc.contributor.author","Homayounfar, Kia"],["dc.contributor.author","Koenig, Sarah"],["dc.date.accessioned","2020-12-10T14:25:27Z"],["dc.date.available","2020-12-10T14:25:27Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.jsurg.2018.12.001"],["dc.identifier.issn","1931-7204"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72557"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Digital Affinity in Medical Students Influences Learning Outcome: A Cluster Analytical Design Comparing Vodcast With Traditional Lecture"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]
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  • 2014Journal Article
    [["dc.bibliographiccitation.firstpage","876"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","International Journal of Radiation Biology"],["dc.bibliographiccitation.lastpage","883"],["dc.bibliographiccitation.volume","90"],["dc.contributor.author","Serra, Maria Paola"],["dc.contributor.author","Marongiu, Fabio"],["dc.contributor.author","Sini, Marcella"],["dc.contributor.author","Marongiu, Michela"],["dc.contributor.author","Contini, Antonella"],["dc.contributor.author","Wolff, Hendrik"],["dc.contributor.author","Rave-Frank, Margret"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Laconi, Ezio"],["dc.contributor.author","Koenig, Sarah"],["dc.date.accessioned","2018-11-07T09:34:32Z"],["dc.date.available","2018-11-07T09:34:32Z"],["dc.date.issued","2014"],["dc.description.abstract","Purpose: Exposure to radiation primes the liver for extensive replacement of the resident parenchymal cells by transplanted hepatocytes. The mechanisms underlying this repopulation remain to be clarified. In these studies, we examined the possible occurrence of cell senescence in vivo following radiationassociated preconditioning of the host liver. Materials and methods: Fischer 344 rats underwent externalbeam, computed-tomography-based partial liver irradiation. A single dose of 25 Gy was delivered to the right liver lobes (40% of liver mass). An additional group of animals received a 1/3 partial hepatectomy (removal of the left anterior lobe) four days after irradiation. Non-irradiated groups served as controls. All rats were sacrificed four weeks after the initial treatment. Results: The irradiated livers displayed several markers of cell senescence, including expression of senescence-associatedp-galactosidase (SA-I3-gal), increase in cell size, and up-regulation of cyclin-dependent kinase inhibitors (CDK-I) p16 and p21. Furthermore, quantitative reverse-transcriptase polyrnerase chain reaction (qRT-PCR) analysis revealed activation of the senescence-associated secretory phenotype (SAW), including the cytokines interleukin 6 (IL6) and le (ILla). The senescencerelated changes were more prominent in rats undergoing partial hepatectomy (PH) following irradiation (IR). Conclusions: We conclude that priming with radiation for liver repopulation results in the induction of cell senescence and the up-regulation of a senescence-associated secretory phenotype. The latter can contribute to the extensive growth of transplanted cells in this system."],["dc.identifier.doi","10.3109/09553002.2014.922714"],["dc.identifier.isi","000343001200006"],["dc.identifier.pmid","24827852"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32189"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Informa Healthcare"],["dc.relation.issn","1362-3095"],["dc.relation.issn","0955-3002"],["dc.title","Hepatocyte senescence induced by radiation and partial hepatectomy in rat liver"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
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  • 2016Journal Article
    [["dc.bibliographiccitation.firstpage","139"],["dc.bibliographiccitation.issue","3-4"],["dc.bibliographiccitation.journal","European Surgical Research"],["dc.bibliographiccitation.lastpage","154"],["dc.bibliographiccitation.volume","57"],["dc.contributor.author","Schwarz, Laura"],["dc.contributor.author","Sippel, Sonia"],["dc.contributor.author","Entwistle, Andrew"],["dc.contributor.author","Hell, Anna-Kathrin"],["dc.contributor.author","Koenig, Sarah"],["dc.date.accessioned","2018-11-07T10:19:53Z"],["dc.date.available","2018-11-07T10:19:53Z"],["dc.date.issued","2016"],["dc.description.abstract","Purpose: Given the high attrition rate in the field of academic surgery, we aimed to characterise the professional and personal situations of female and male academic surgeons as well as to gather data on their respective perceptions of career advancement and work satisfaction. Methods: We conducted a cross-sectional survey in Germany, inviting all identifiable academically highly qualified female surgeons and their male counterparts in a 1: 2 ratio to participate. An anonymous 103-item online questionnaire was designed and the data collected between July and September 2014. Results: The questionnaire was sent to 93 female and 200 male surgeons, of whom 63 women (67.7%) and 70 men (35.0%) replied. The average age was 47.5 and 47.1 years, respectively. Respondents identified 'high degree of expertise', 'ambition', and 'clarity of one's professional aims' as important factors affecting professional career development. Both groups felt 'workload', 'working hours/shifts', and 'gender' to be a hindrance, the latter of significantly greater importance to female surgeons. The mean work satisfaction scores were high in both female (69.5%) and male (75.7%) surgeons. The predictors ;support from superiors' (standardised beta coefficient = 0.41) and 'manual aptitude' (beta = 0.41) contributed incrementally to the variance in 'high degree of work satisfaction' (90-100%) observed for female surgeons. However, childcare provided by 'kindergarten/crche/after-school care' had the greatest negative predictive value (beta = -1.33). Conclusions: Although there are many parallels, female faculty members experience the culture of academic surgery to some extent differently from their male counterparts, especially when impacted by parenthood and childcare. Faculty development programmes need to develop strategies to improve perceived equality in career opportunities by respecting individuals' requirements as well as offering gender-appropriate career guidance. (C) 2016 S. Karger AG, Basel"],["dc.identifier.doi","10.1159/000446874"],["dc.identifier.isi","000386887600001"],["dc.identifier.pmid","27376374"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41760"],["dc.language.iso","en"],["dc.notes.intern","DeepGreen Import"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","S. Karger AG"],["dc.relation.eissn","1421-9921"],["dc.relation.issn","1421-9921"],["dc.relation.issn","0014-312X"],["dc.rights","https://www.karger.com/Services/SiteLicenses"],["dc.title","Biographic Characteristics and Factors Perceived as Affecting Female and Male Careers in Academic Surgery: The Tenured Gender Battle to Make It to the Top"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
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  • 2019-12Journal Article
    [["dc.bibliographiccitation.firstpage","532-535"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Zentralblatt für Chirurgie"],["dc.bibliographiccitation.lastpage","535"],["dc.bibliographiccitation.volume","144"],["dc.contributor.author","Adili, Farzin"],["dc.contributor.author","Dahmen, Uta"],["dc.contributor.author","Heinemann, Markus K"],["dc.contributor.author","Kadmon, Martina"],["dc.contributor.author","Kauffels-Sprenger, Anne"],["dc.contributor.author","König, Sarah"],["dc.contributor.author","Meder, Adrian"],["dc.contributor.author","Obertacke, Udo"],["dc.contributor.author","Schwanitz von Keitz, Paul"],["dc.contributor.author","Stefanescu, Christina"],["dc.contributor.author","Sterz, Jasmina"],["dc.contributor.author","Rüsseler, Miriam"],["dc.date.accessioned","2020-04-02T14:59:09Z"],["dc.date.available","2020-04-02T14:59:09Z"],["dc.date.issued","2019-12"],["dc.description.abstract","The \"Masterplan Medizinstudium 2020\" from the German Federal Government should not be underestimated as only one among many announcement. Thus, the Surgical Working Group on Medical Education (CAL) of the German Association of Surgeons (DGCH) comments on the intended measures of the \"Masterplan Medizinstudium 2020\" and discusses the challenges, consequences and duties arising from the \"Masterplan Medizinstudium 2020\" for the representatives of the surgical societies and those engaged in surgical undergraduate training."],["dc.identifier.doi","10.1055/a-0869-8081"],["dc.identifier.pmid","31067573"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/63568"],["dc.language.iso","other"],["dc.relation.eissn","1438-9592"],["dc.relation.issn","0044-409X"],["dc.relation.issn","1438-9592"],["dc.title","Position Paper of the Surgical Working Group for Teaching of the German Society of Surgery Regarding the \"Master Plan 2020\""],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]
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  • 2008Journal Article
    [["dc.bibliographiccitation.firstpage","285"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","International Journal of Radiation Biology"],["dc.bibliographiccitation.lastpage","298"],["dc.bibliographiccitation.volume","84"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Schmidt, Thordis-Karen"],["dc.contributor.author","Rave-Fraenk, Margret"],["dc.contributor.author","Rothe, Hilka"],["dc.contributor.author","Hermann, Robert Michael"],["dc.contributor.author","Becker, Heinz"],["dc.contributor.author","Hess, Clemens Friedrich"],["dc.contributor.author","Christiansen, Hans"],["dc.date.accessioned","2018-11-07T11:20:07Z"],["dc.date.available","2018-11-07T11:20:07Z"],["dc.date.issued","2008"],["dc.description.abstract","Purpose: Hepatocyte transplantation following liver irradiation (IR) and partial hepatectomy (PH) leads to extensive liver repopulation. We investigated the changes in the liver induced by IR explaining the loss of reproductive integrity in endogenous hepatocytes. Materials and methods: Right lobules of rat liver underwent external beam IR (25 Gy). A second group was subjected to additional 33% PH of the untreated left liver lobule. Liver specimens and controls were analyzed for DNA damage, apoptosis, proliferation and cell cycle related genes (1 hour to up to 12 weeks). Results: Double strand breaks (phosphorylated histone H2AX) induced by IR rapidly declined within hours and were no longer detectable after 4 days. No significant apoptosis was noted and steady mRNA levels (B-cell lymphoma 2-associated X protein (BAX), caspase 3 and 9) were in line with the lack of DNA fragmentation. However, gene expression of p53 and p21 in irradiated liver tissue increased. Transcripts of cyclin D1, proliferating cell nuclear antigen (PCNA), and cyclin B augmented progressively, whereas cyclin E was only affected moderately. Following PH, irradiated livers displayed persistently high protein levels of p21 and cyclin D1. However, cell divisions were infrequent, as reflected by low PCNA levels up to four weeks. Conclusion: IR leads to a major arrest in the G1/S phase and to a lesser extent in the G2/M transition of the cell cycle, resulting in reduced regenerative response following PH. The persistent block of at least four weeks may promote preferential proliferation of transplanted hepatocytes in this milieu."],["dc.identifier.doi","10.1080/09553000801953359"],["dc.identifier.isi","000254631200004"],["dc.identifier.pmid","18386194"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/55458"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Taylor & Francis Ltd"],["dc.relation.issn","1362-3095"],["dc.relation.issn","0955-3002"],["dc.title","Irradiation as preparative regimen for hepatocyte transplantation causes prolonged cell cycle block"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
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  • 2010Journal Article
    [["dc.bibliographiccitation.firstpage","220"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Nitric Oxide"],["dc.bibliographiccitation.lastpage","226"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Waetzig, Esther"],["dc.contributor.author","Acil, Hasan"],["dc.contributor.author","Koenig, Sarah"],["dc.contributor.author","Unthan-Fechner, Kirsten"],["dc.contributor.author","Tsikas, Dimitrios"],["dc.contributor.author","Probst, Irmelin"],["dc.date.accessioned","2018-11-07T08:37:45Z"],["dc.date.available","2018-11-07T08:37:45Z"],["dc.date.issued","2010"],["dc.description.abstract","During liver regeneration in vivo carbon monoxide (CO) and nitric oxide (NO) are supposed to play a significant role. We raise the question whether CO and NO are involved in the growth process of cultured hepatocytes. Rat hepatocytes were stimulated into proliferation, growth being estimated by DNA content, mRNA by quantitative RT-PCR, and inducible NO synthase (iNOS) activity by GC-MS. Dexamethasone proved obligatory for fast proliferation. It suppressed the spontaneous rise of iNOS-mRNA in cultures devoid of glucocorticoids, but did not counteract the rise in mRNA in actively dividing cultures. Expression of iNOS-mRNA and cell growth were further enhanced by LiCl (10 mM). NOS activity was completely suppressed by the iNOS-specific inhibitors N-(3-(aminomethyl)benzyl) acetamidine (1400 W,100 mu M) and L-N(6)-(1-iminoethyl)lysine (L-NIL, 500 mu M), however, without a decrease in hepatocyte growth. Proliferation was attenuated only by very high concentrations (>0.5 mM) of N-nitro-L-arginine methyl ester NAME) and asymmetric dimethylarginine (ADMA). Various NO donors (at 100 mu M) did not stimulate cell growth. The furoxan CAS 1609 stimulated growth, decreased iNOS-mRNA expression and transiently increased haem oxygenase-1 (HO-1)-mRNA without releasing considerable amounts of NO. 1H-[1,2,4]Oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ) attenuated the action of CAS 1609. Proliferation was stimulated by Co-protoporphyrin and tricarbonyldichlororuthenium(II) dimer (CORM-2). We conclude that CAS 1609 triggers hepatocyte mitosis most likely via direct, NO-independent induction of HO-1 expression, pointing to CO as a growth-promoting signal in the proliferation cascade in cultured hepatocytes. (C) 2010 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.niox.2010.06.007"],["dc.identifier.isi","000281659600010"],["dc.identifier.pmid","20619352"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18610"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","1089-8603"],["dc.title","Role of carbon monoxide and nitric oxide in adult rat hepatocytes proliferating in vitro: Effects of CAS 1609"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]
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