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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 | Immunological aspects of liver cell transplantation显示文摘Within the field of regenerative medicine, the liver is of major interest for adoption of regenerative strategies due to its well-known and unique regenerative capacity. Whereas therapeutic strategies such as liver resection and orthotopic liver transplantation(OLT) can be considered standards of care for the treatment of a variety of liver diseases, the concept of liver cell transplantation(LCTx) still awaits clinical breakthrough. Success of LCTx is hampered by insufficient engraftment/long-term acceptance of cellular allografts mainly due to rejection of transplanted cells. This is in contrast to the results achieved for OLT where longterm graft survival is observed on a regular basis and, hence, the liver has been deemed an immuneprivileged organ. Immune responses induced by isolated hepatocytes apparently differ considerably from those observed following transplantation of solid organs and, thus, LCTx requires refined immunological strategies to improve its clinical outcome. In addition, clinical usage of LCTx but also related basic research efforts are hindered by the limited availability of high quality liver cells, strongly emphasizing the need for alternative cell sources. This review focuses on the various immunological aspects of LCTx summarizing data available not only for hepatocyte transplantation but also for transplantation of non-parenchymal liver cells and liver stem cells. | Felix Oldhafer Michael Bock Christine S Falk Florian WR Vondran | 2016 | World Journal of Transplantation2016，6，1： | 3 |
| 3 | Central corneal epithelium self-healing after ring-shaped glycerin-cryopreserved lamellar keratoplasty in Terrien marginal degeneration显示文摘Dear Sir, I am Dr Yan-Long Bi, from the Department of Ophthalmology, Tongji University Affiliated to Tongji University School of Medicine, Shanghai, China. I write to present a case report of total limbal stem cells deficiency after treatment with ring-shaped lamellar keratoplasty secondary to Terrien marginal degeneration. During 3 | Yan-Long Bi Felix Bock Qi Zhou Claus Cursiefen | 2013 | International Journal of Ophthalmology(English edition)2013，6，2： | 3 |
| 4 | Bevacizumab (Avastin) eye drops inhibit corneal neovascularization显示文摘 | Felix Bock Yanyan K?nig Friedrich Kruse Martin Baier Claus Cursiefen | 2008 | Graefe’s Archive for Clinical and Experimental Ophthalmology2008，，2： | 2 |
| 5 | K_(2P)18.1 translates T cell receptor signals into thymic regulatory T cell development显示文摘It remains largely unclear how thymocytes translate relative differences in T cell receptor(TCR)signal strength into distinct developmental programs that drive the cell fate decisions towards conventional(Tconv)or regulatory T cells(Treg).Following TCR activation,intracellular calcium(Ca^(2+))is the most important second messenger,for which the potassium channel K_(2P)18.1 is a relevant regulator.Here,we identify K_(2P)18.1 as a central translator of the TCR signal into the thymus-derived Treg(tTreg)selection process.TCR signal was coupled to NF-κB-mediated K_(2P)18.1 upregulation in tTreg progenitors.K_(2P)18.1 provided the driving force for sustained Ca^(2+) influx that facilitated NF-κB-and NFAT-dependent expression of FoxP3,the master transcription factor for Treg development and function.Loss of K_(2P)18.1 ion-current function induced a mild lymphoproliferative phenotype in mice,with reduced Treg numbers that led to aggravated experimental autoimmune encephalomyelitis,while a gain-of-function mutation in K_(2P)18.1 resulted in increased Treg numbers in mice.Our findings in human thymus,recent thymic emigrants and multiple sclerosis patients with a dominant-negative missense K_(2P)18.1 variant that is associated with poor clinical outcomes indicate that K_(2P)18.1 also plays a role in human Treg development.Pharmacological modulation of K_(2P)18.1 specifically modulated Treg numbers in vitro and in vivo.Finally,we identified nitroxoline as a K_(2P)18.1 activator that led to rapid and reversible Treg increase in patients with urinary tract infections.Conclusively,our findings reveal how K_(2P)18.1 translates TCR signals into thymic T cell fate decisions and Treg development,and provide a basis for the therapeutic utilization of Treg in several human disorders. | Tobias Ruck Stefanie Bock Steffen Pfeuffer Christina B.Schroeter Derya Cengiz Paul Marciniak Maren Lindner Alexander Herrmann Marie Liebmann Stjepana Kovac Lukas Gola Leoni Rolfes Marc Pawlitzki Nils Opel Tim Hahn Udo Dannlowski Thomas Pap Felix Luessi Julian A.Schreiber Bernhard Wunsch Tanja Kuhlmann Guiscard Seebohm Bjorn Tackenberg Patricia Seja Frank Doring Erhard Wischmeyer Achmet Imam Chasan Johannes Roth Luisa Klotz Gerd Meyer zu Hörste Heinz Wiendl Tobias Marschall Stefan Floess Jochen Huehn Thomas Budde Tobias Bopp Stefan Bittner Sven G.Meuth | 2022 | Cell Research2022，32，1： | 1 |
| 6 | Recurrent interface abscess secondary to Acanthamoeba keratitis treated by deep anterior lamellar keratoplasty显示文摘Dear Sir,I am Dr. Yan-Long Bi, from the Department of Ophthalmology of the Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China. I write to present a case report of recurrent amoebic corneal | Yan-Long Bi Felix Bock Qi Zhou Claus Cursiefen | 2012 | International Journal of Ophthalmology(English edition)2012，5，6： | 0 |
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