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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 | Long-Term Follow-Up of Biopsy-Proven Viral Myocarditis显示文摘 | Stefan Grün Julia Schumm Simon Greulich Anja Wagner Steffen Schneider Oliver Bruder Eva-Maria Kispert Stephan Hill Peter Ong Karin Klingel Reinhardt Kandolf Udo Sechtem Heiko Mahrholdt | 2012 | Journal of the American College of Cardiology2012，，18： | 2 |
| 3 | Meniscal disorders:normal, discoid, and cysts 显示文摘 | Kocher MS Klingele K Rassman SO | 2003 | Orthop Clin North Am2003，34，3： | 2 |
| 4 | Pupilsparingoculomotor palsies with internal carotidposteriorcommunicating artery aneurysms显示文摘 | Kissel JT Burde RM Klingele TG | 1983 | AnnNeurol1983，13，： | 1 |
| 5 | Expression of cell volume-regulated kinase h-SGK in pancreatic tissue显示文摘 | KLINGEL K WARNTGES S BOCK J | 2000 | Am J Physiol Gastrointest Liver Physiol2000，279，5： | 1 |
| 6 | Hemodynamlc effects of pneumoper-itoneum in lithotomy position显示文摘 | Rist M Rauh R Klingel R | 2001 | Zentralblatt für Chirurgie2001，，01： | 1 |
| 7 | Directed evolution of ionizing radiation resistance in Escherichia coli 显示文摘 | Harris D R Pollock S V Wood E A Goiffon R J Klingele A J Cabot E L Schackwitz W Martin J Eggington J Durfee T J Middle C M Norton J E Popelars M C Li H Klugman S A Hamilton L L Bane L B Pennacchio L A Albert T J Perna N T Cox M M Battista J R | 2009 | Journal of Bacteriology2009，191，16： | 1 |
| 8 | Iloprost preserves renal ox- ygenation and restores kidney function in endotoxernia-related acute renal failure in the rat显示文摘 | Johannes T Ince C Klingel K | 2009 | Crit Care Med2009，37，4： | 1 |
| 9 | Meniscus Tears in Children显示文摘 | Greg Bellisari Walter Samora Kevin Klingele | 2011 | Sports Medicine and Arthroscopy Review2011，，1： | 1 |
| 10 | Comparison of the Melbourne Assessment of Unilateral Upper Limb Function and the Quality of Upper Extremity Skills Test in hemiplegic CP显示文摘 | Klingels K De Cock P Desloovere K | 2008 | Dev Med Child Neurol2008，50，12： | 1 |
| 11 | Total - to-ionized calcium ratio predicts mortality in continuous renal replacement therapy with anticoagulation in critically ill patients显示文摘 | Link A Klingele M Speer T | 2012 | Crit Care2012，16，3： | 1 |
| 12 | High prevalence of viral genomes and inflammation in peripartum cardiomyopathy显示文摘 | Bultmann BD Klingel K Nabauer M | 2005 | Am J Obstet Gyncol2005，193，2： | 1 |
| 13 | Regulated on acti- vation,normal T-cell-expressed and-secreted mRNA ex- pression in normal endometrium and endometriotic im- plants:Assessment of autocrine/paracrine regulation by in situ hybridization显示文摘 | Hornung D Klingel K Dohrn K | 2001 | Am J Pathol2001，158，6： | 1 |
| 14 | Low dose dexamethasone-supplemented fluid resuscitation reverses endotoxin-induced acute renal failure and prevents cortical microvascular hypoxia 显示文摘 | Johannes T Mik EG Klingel K eta| | 2009 | Shock2009，31，5： | 1 |
| 15 | High prevalence of viral genomes and inflammation in peripartum cardiomyopathy显示文摘 | Klingel K Nabauer M | 2005 | Am J Obstet Gynecol2005，193，2： | 1 |
| 16 | Catecholamine refractory'cardiogenic shock?bridging-to-recovery'by implantation of a percutaneous cardiac assist device显示文摘 | Wilde J Klingel K Kandolf R | 2013 | DMW:Deutsche Medizinische Wochenschrift2013，138，12： | 1 |
| 17 | 脂蛋白机采对脂蛋白a相关心血管病的影响:前瞻性5年随访研究显示文摘自2008年,进展性高脂蛋白a血症合并心血管病(lipoprotein a-hyperlipoproteinemia,Lp(a)-HLP)已是德国常规机采脂蛋白(lipoprotein apheresis,LA)的适应证。该研究旨在评估LA的长期预防效果,并分析载脂蛋白a基因型和表型的临床相关性。方法:该前瞻性多中心临床研究纳入170例Lp(a)-HLP合并进展性心血管病的患者(平均基线低密度脂蛋白胆固醇2.56、治疗后1.72mmol/L),确诊时年龄中位数为48.9岁。 | 刘莉 叶鹏 Roeseler E Julius U Heigl F Spitthoever R Heutling D Breitenberger P Leebmann J Lehmacher W Kamstrup PR Nordestgaard BG Maerz W Noureen A Schmidt K Kronenberg F Heibges A Klingel R Pro(a)LiFe-Study Group | 2016 | 中华高血压杂志2016，24，8： | 1 |
| 18 | Meniscal disorders显示文摘 | Mininder S. Kocher Kevin Klingele Sean O. Rassman | 2003 | Orthopedic Clinics of North America2003，，3： | 1 |
| 19 | Deranged transcriptional regulation of cell-volume-sensitive kinase hSGK in diabetic nephropathy显示文摘 | Lang F Klingel K Wagner CA | 2000 | Proc Natl Acad Sci USA2000，97，14： | 1 |
| 20 | Advantages of using the vertical gradient of gravity for 3-D interpretation 显示文摘 | Marson I Klingele E E | 1993 | Geophysics1993，58，11： | 1 |
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