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| 1 | Molecular phenotypes of human parvovirus B19 in patients with myocarditis显示文摘AIM:To investigate molecular phenotypes of myocardial B19V-infection to determine the role of B19V in myocarditis and dilated cardiomyopathy(DCM).METHODS:Endomyocardial biopsies(EMBs) from 498 B19V-positive patients with myocarditis and DCMwere analyzed using molecular methods and functional experiments.EMBs were obtained from the University Hospitals of Greifswald and Tuebingen and additionally from 36 German cardiology centers.Control tissues were obtained at autopsy from 34 victims of accidents,crime or suicide.Identification of mononuclear cell infiltrates in EMBs was performed using immunohistological staining.Anti-B19V-IgM and anti-B19V-IgG were analyzed by enzyme-linked immunosorbent assay(ELISA).B19V viral loads were determined using in-house quantitative real-time polymerase chain reaction(PCR).For B19V-genotyping a new B19V-genotype-specific restriction fragment length polymorphism(RFLP)-PCR was established.B19V-genotyping was verified by direct DNAsequencing and sequences were aligned using BLAST and BioEdit software.B19V P6-promoter and HHV6-U94-transactivator constructs were generated for cell culture experiments.Transfection experiments were conducted using human endothelial cells 1.Luciferase reporter assays were performed to determine B19Vreplication activity.Statistical analysis and graphical representation were calculated using SPSS and Prism5 software.RESULTS:The prevalence of B19V was significantly more likely to be associated with inflammatory cardiomyopathy(iCMP) compared to uninflamed DCM(59.6% vs 35.3%)(P < 0.0001).The detection of B19V-mRNA replication intermediates proved that replication of B19V was present.RFLP-PCR assays showed that B19V-genotype 1(57.4%) and B19V-genotype 2(36.7%) were the most prevalent viral genotypes.B19V-genotype 2 was observed more frequently in EMBs with iCMP(65.0%) compared to DCM(35%)(P = 0.049).Although there was no significant difference in gender-specific B19V-loads,women were more frequently infected with B19V-genotype 2(44.6%) than men(36.0%)(P = 0.0448).Coinfection with B19V and other cardiotropic viruses was found in 19.2% of tissuesamples and was associated with higher B19V viral load compared to B19V-monoinfected tissue(P = 0.0012).The most frequent coinfecting virus was human herpes virus 6(HHV6,16.5%).B19V-coinfection with HHV6 showed higher B19V-loads compared to B19V-monoinfected EMBs(P = 0.0033),suggesting that HHV6 had transactivated B19V.In vitro experiments confirmed a 2.4-fold increased B19V P6-promoter activity by the HHV6 U94-transactivator.CONCLUSION:The finding of significantly increased B19V loads in patients with histologically proven cardiac inflammation suggests a crucial role of B19V-genotypes and reactivation of B19V-infection by HHV6-coinfection in B19V-associated iCMP.Our findings suggest that B19V-infection of the human heart can be a causative event for the development of an endothelial cell-mediated inflammatory disease and that this is related to both viral load and genotype. | C-Thomas Bock Anja Düchting Friederike Utta Eva Brunner Bui Tien Sy Karin Klingel Florian Lang Meinrad Gawaz Stephan B Felix Reinhard Kandolf | 2014 | World Journal of Cardiology2014，6，4： | 3 |
| 2 | Mycobacterium bovis BCG-Induced Granuloma Formation Depends on Gamma Interferon and CD40 Ligand but Does Not Require CD28显示文摘 | Laura H Wes Markofski Anja Bock | 2001 | Infect Immun2001，69，4： | 1 |
| 3 | Presentation, Patterns of Myocardial Damage, and Clinical Course of Viral Myocarditis显示文摘 | Heiko Mahrholdt Anja Wagner Claudia C. Deluigi Eva Kispert Stefan Hager Gabriel Meinhardt Holger Vogelsberg Peter Fritz Juergen Dippon C Thomas Bock Karin Klingel Reinhard Kandolf Udo Sechtem | 2006 | Circulation2006，，15： | 1 |
| 4 | Diagnostic Performance of Cardiovascular Magnetic Resonance in Patients With Suspected Acute Myocarditis显示文摘 | Hassan Abdel-Aty Philipp Boyé Anja Zagrosek Ralf Wassmuth Andreas Kumar Daniel Messroghli Petra Bock Rainer Dietz Matthias G. Friedrich Jeanette Schulz-Menger | 2005 | Journal of the American College of Cardiology2005，，11： | 1 |
| 5 | Presentation, Patterns of Myocardial Damage, and Clinical Course of Viral Myocarditis显示文摘 | Heiko Mahrholdt Anja Wagner Claudia C. Deluigi Eva Kispert Stefan Hager Gabriel Meinhardt Holger Vogelsberg Peter Fritz Juergen Dippon C Thomas Bock Karin Klingel Reinhard Kandolf Udo Sechtem | 2006 | Circulation2006，，： | 1 |
| 6 | The Chlamydomonas Chloroplast HLP Protein Is Required for Nucleoid Organization and Genome Maintenance显示文摘叶绿体染色体(plastome ) 每房间发生在高拷贝数字。几个叶绿体染色体拷贝浓密地被挤进核蛋白粒子叫了 nucleoids。染色体包装怎么并且哪个发生蛋白质组织叶绿体 nucleoids 大部分是未知的。这里,我们分析了细菌的建筑上的 DNA 有约束力的蛋白质胡,的 Chlamydomonas reinhardtii 相当或相同的事物象 histone 一样蛋白质 HLP。我们证明 Chlamydomonas HLP 蛋白质与 nucleoids 被指向到叶绿体和伙伴。由 RNA 干扰(RNAi ) 的 HLP 基因表示击倒改变叶绿体 nucleoids 的结构并且看起来减少叶绿体 DNA 的压缩的水平。出人意料地,也,叶绿体染色体拷贝数字显著地在 RNAi 紧张被减少,建议除了它在 nucleoid 形成的建筑上的角色, HLP 蛋白质也涉及叶绿体染色体维护。 | Daniel Karcher Dietrich Koster Anne Schadach Anja Klevesath Ralph Bock | 2009 | Molecular Plant2009，2，6： | 0 |
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