200 research outputs found
Author Correction: A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity (Nature Communications, (2022), 13, 1, (5104), 10.1038/s41467-022-3
In the author list of this article, the names of the authorswere incorrectly listed with initials and family name only. The incorrect author list read as “C. Kedor, H. Freitag, L. Meyer-Arndt, K. Wittke, L. G. Hanitsch, T. Zoller, F. Steinbeis, M. Haffke, G. Rudolf, B. Heidecker, T. Bobbert, J. Spranger, H. D. Volk, C. Skurk, F. Konietschke, F. Paul, U. Behrends, J. Bellmann-Strobl and C. Scheibenbogen”. The author list has now been amended to include the given and family names in the HTML and PDF versions of the article. The corrected author list reads as “Claudia Kedor, Helma Freitag, Lil Meyer-Arndt, Kirsten Wittke, Leif G. Hanitsch, Thomas Zoller, Fridolin Steinbeis, Milan Haffke, Gordon Rudolf, Bettina Heidecker, Thomas Bobbert, Joachim Spranger, Hans- Dieter Volk, Carsten Skurk, Frank Konietschke, Friedemann Paul, Uta Behrends, Judith Bellmann-Strobl and Carmen Scheibenbogen”
The role of gammadelta T cells in the immunity against Epstein-Barr virus
1-10 % der humanen peripheren Lymphozyten sind gammadelta(gd)-T-Zellen. Sie sind an der Abwehr von Infektionen beteiligt. In dieser Arbeit wurden mehrere hundert gd-T-Zell-Klone phänotypisch beschrieben und deren Zytotoxizität gegenüber EBV-infizierten B-Zellen untersucht, um eine mögliche Rolle bei der Bekämpfung von Epstein-Barr-Virus(EBV)-Infektionen zu erforschen. Es konnte gezeigt werden, dass zwischen gd-T-Zell-Klonen und B-Zellen zielgerichtete zytotoxische Interaktionen stattfanden, die meist vom EBV-Status der B-Zellen abhingen. Dies untermauert die Hypothese einer Rolle der gd-T-Zellen in der Immunität gegen EBV.Gammadelta(gd) T cells account for 1-10% of the human peripheral lymphocytes. They are involved in the defense of infections. In this study, we analyzed the phenotype and cytotoxic functions of several hundred gd T cell clones in order to determine a possible role in the protection against Epstein-Barr virus (EBV) infections. It could be demonstrated that cytotoxic interactions occur between gd T cell clones and B cells. These interactions were predominantly found to be dependent on the EBV status of the target cells. This strongly supports the hypothesis of a role of gd T cells in the immunity against EBV
CD4(+)-T-Zellantwort auf EBV-Strukturantigene: die Rolle der lytischen Antigene BNRF1 und gp350
The topic of this work is the MHC class II-restricted immune answer to the infection with Epstein-Barr virus (EBV), a ubiquitous human pathogenic virus. In a first step, the frequency of EBV-specific CD4+ T cells in the blood of healthy EBV-positive donors was detected and subsequently compared to the one of patients with infectious mononucleosis. In a second step, two structural antigens of EBV, gp350 and BNRF1, were used to generate specific CD4+ T cell lines. Their reactivity and specificity were analyzed and the HLA molecules relevant for antigen presentation were determined.Diese Arbeit beschäftigt sich mit der MHC Klasse II-restringierten Immunantwort auf die Infektion mit dem humanpathogenen Epstein-Barr-Virus (EBV). Zum einen wurde die Frequenz von EBV-spezifischen CD4(+)-T-Zellen im Blut gesunder EBV-positiver Spender untersucht und mit der von Patienten mit infektiöser Mononukleose verglichen. Zum anderen wurden für die Virusstrukturantigene gp350 und BNRF1 spezifische CD4(+)-T-Zelllinien hergestellt, deren Reaktivität und Spezifität, sowie die für die Antigenpräsentation relevanten HLA-Moleküle ermittelt
Analyse des Antibiotikaverbrauchs am Kinderklinikum der Technischen Universität München: Angriffspunkte für ein Antibiotic Stewardship Programm
This study analyzed the usage of antibiotics at an university children’s hospital over a period of four months. 339 patients with systemic antibiotic therapy or perioperative antibiotic prophylaxis were included. Antibiotic usage was measured in days of therapy per 1,000 patient days and antibiotic treatment was checked for guideline accordance. The results of this study paved the way for an antibiotic stewardship program with implementation of hospital-specific interventions.In dieser Studie wurde der Antibiotikaverbrauch an einer Universitätskinderklinik über vier Monate analysiert. Eingeschlossen wurden 339 Patienten mit systemischer antibiotischer Therapie oder perioperativer Antibiotikaprophlyaxe. Der Verbrauch wurde in Therapietagen pro 1.000 Patiententage berechnet und die Konformität mit aktuellen Behandlungsleitlinien überprüft. Die Ergebnisse lieferten die Basis für ein Antibiotic Stewardship-Programm mit krankenhausspezifischen Interventionen
Investigation of the CD4+ T cell response of healthy virus carriers against non-structural lytic-cycle proteins of EBV
Mehr als 90% der Weltbevölkerung sind seropositiv für das Epstein-Barr-Virus (EBV). Dieses ist mit bösartigen und gutartigen Erkrankungen assoziiert, einschließlich verschiedener Autoimmunerkrankungen. Einige der EBV-assoziierten Erkrankungen können durch adoptiven Transfer EBV-spezifischer T-Zellen geheilt werden. Die verfügbaren Ansätze sind allerdings nicht ausreichend schnell und breit genug verfügbar. Mit dem Ziel optimierter Behandlungsansätze wurde in dieser Arbeit die CD4+ T-Zell-Antwort gesunder Virusträger gegen nicht-Struktur-Proteine des lytischen Zyklus von EBV untersucht. Acht von neun generierten CD4+ T-Zelllinien zeigten eine Spezifität für das jeweilis eingesetzte, rekombinante EBV-Stimulatorprotein. Die Arbeit lieferte somit neue Evidenzen für ein sehr breit gefächertes, EBV-spezifisches CD4+ T-Zellgedächtnis in gesunden Virusträgern. Zudem wiesen die Ergebnisse auf eine mögliche Rolle zellulärer Autoantigene bei der MHC-Klasse-II-restringierten Immunerkennung des EBV.More than 90% of the world’s population is seropositive for the Epstein-Barr virus (EBV). EBV is associated with a number of benign and malignant diseases, as well as autoimmune disorders. Several of the EBV-associated diseases can be cured by the infusion of EBV-specific T cells. However, currently available adoptive T cell therapeutic options are still limited to few specialized centers worldwide. With the aim to improve EBV-specific immunotherapy, we investigated the CD4+ T cell response of healthy virus carriers against non-structural lytic-cycle proteins of EBV. Eight out of nine CD4+ T cell lines generated by repeated stimulation with recombinantly expressed and purified viral proteins showed specificity for the respective stimulator protein. These results provided evidence for an unexpected breadth of the EBV-specific CD4+ T cell memory response in healthy virus carriers. Furthermore our results implied a possible role of cellular autoantigens in the MHC class II-restricted immune response against EBV
Metallurgical processing of zinc-bearing residues
In this study metallurgical processing of two different kinds of zinc-bearing residues have been performed: Zinc A and Zinc B. These residues have been stored for over 15 years in Rotterdam Harbor. The chemical compositions of the residues have been determined and showed that zinc ferrite is a major phase present. Zinc ferrite is not soluble under normal alkaline and acidic conditions and is not recovered by the Waelz-process, which is commonly employed for such zinc-bearing residues. An innovative flowsheet for processing zinc ferrite-bearing residues has been developed during a pre-feasibility study, with goal to selectively recover zinc, including zinc from zinc ferrite. The innovative flowsheet consists of the following steps: (1) Water pre-washing: removing water soluble salts, in particular the chlorides in Zinc A (~9%). (2) 1st step alkaline leaching with caustic soda (NaOH): dissolving free ZnO into solution, for both water-washed Zinc A and original (unwashed) Zinc B. (3) Roasting of the first leach residue in the presence a suitable reagent: decomposing the zinc ferrite to free ZnO. (4) 2nd step alkaline leaching with NaOH: dissolving all free ZnO into solution. (5) Solution purification by cementation: removing impurities in particular lead and copper, by using zinc powder. (6) Electrowinning of zinc in NaOH solution: the purified zinc bearing solutions are subsequently precipitated to the final product of Zn metal. Optimal operating conditions for the processes are deduced from a literature review in which similar residues are processed. Additionally, optimal operating conditions for the conversion of zinc ferrite into zinc oxide has been investigated using synthetic zinc ferrite with addition of Mg(OH)2, Ca(OH)2, NaOH, or Na2CO3. Finally, Na2CO3 has been chosen as reagent and used in experiments with real zinc-bearing residues. Zinc A is water washed to remove the chlorides present. Then both the water washed residue of Zinc A, and Zinc B, are leached in an alkaline solution of 5M NaOH at 90?C for 1 hour. Both zinc and lead are selectively extracted, leaving iron oxides and zinc ferrite in the residue. The filtercake is fused with Na2CO3 at 950?C for 2 hours to convert zinc ferrite into zinc oxide. The calcined product is leached in fresh alkaline solution of 5M NaOH to recover zinc. The final residue is then water washed to remove residual sodium. The filtrates from the first and second leaching step are purified, with use of zinc dust, or directly used for electrowinning experiments. The removal efficiency of chloride, sodium and potassium during water washing of Zinc A were 62%, 41% and 71% respectively. Overall dissolution yields for Zinc A and Zinc B of zinc and lead were 82%, 80% and 64%, 78% respectively. Cementation of impurities (Pb, Cu, Cr) with zinc dust followed by an electrowinning step achieving a grade zinc deposit of 94%. Finally, it can be concluded that the combined hydro -and pyrometallurgical flowsheet is technically feasible. Furthermore, results can be improved further by optimization of major operating steps.Mineral EngineeringResource EngineeringCivil Engineering and Geoscience
Incidence, diagnostics, therapy and outcome of children with necrotizing enterocolitis - a retrospective comparative study of the years 1992 to 2010
In der retrospektiven Studie wurden die Daten von 220 neugeborenen NEC-Patienten der Kinderchirurgie des Klinikums München-Schwabing und der Kinderklinik der TU München erhoben. Die Untersuchungsergebnisse hinsichtlich Inzidenz, Diagnostik, Therapie und Outcome wurden mit den Ergebnissen einer älteren Studie (Zeitraum 1984 bis 1991) sowie den Ergebnissen externer neonatologischer Zentren verglichen.Based on data of n=220 newborn children with NEC from the departments of paediatric surgery of the Klinikum München-Schwabing and the paediatric clinic of the TU München findings on incidence, diagnostics, therapy and outcome have been compared with a former study (covering the years 1984 to 1991) and with findings of external neonatologic centers
Herstellung von Ewing-Sarkom-Antigen CHM1- und EZH2-spezifischen, HLA-A*0201-restringierten, T-Zell-Rezeptor-transgenen T-Zellen
Despite multimodal therapeutic approaches, advanced Ewing’s sarcomas are associated with poor prognosis. During the past years, adoptive T-cell therapy emerged as a potential therapeutic strategy for different cancer entities. Here, we generated the first Ewing’s sarcoma-specific, HLA-A*0201-restricted T-cell receptor transgenic T cells expressing a CD62L+/CD45R0+ central memory phenotype up to 80%. These cells may serve to render future donor-lymphocyte infusions more specific and less toxic.Trotz multimodaler Therapieansätze gehen fortgeschrittene Ewing-Sarkome weiterhin mit einer schlechten Prognose einher. In den letzten Jahren zeigte sich der adoptive T-Zell-Transfer als potentieller neuer Therapieansatz bei verschiedensten malignen Erkrankungen. In dieser Arbeit haben wir erstmals Ewing-Sarkom-spezifische, HLA-A*0201-restringierte T-Zell-Rezeptor-transgene T-Zellen hergestellt, die mit einem Anteil von bis zu 80 % einen CD62L+/CD45R0+ Central-memory-Phänotypen exprimieren. Diese Zellen sollen zu einer Effektivitätssteigerung sowie Toxizitätsminderung von zukünftigen Donor-Lymphozyten-Infusionen beitragen
Identification of Tumour Antigens in Osteosarcoma by Serological Analysis of a Tumour cDNA Expression Library
Die Arbeit hatte zum Ziel, neue immunogene Zielstrukturen in Osteosarkomgewebe zu identifizieren. Durch Screening einer Osteosarkom-cDNA-Expressionsbibliothek aus Tumorgewebe eines 8-jährigen Mädchens mit gepooltem Serum von fünf Patienten mit Osteosarkom wurden insgesamt 20 Antigene identifiziert. Die Antigene wurden durch cDNA-Sequenz- und mRNA-Expressionsanalysen sowie serologische Untersuchungen mit Proben von gesunden Probanden und anderen pädiatrischen Tumorpatienten näher charakterisiert. Auf diese Weise wurden Antigene mit potentieller pathophysiologischer, diagnostischer und/oder therapeutischer Bedeutung im Kontext des Osteosarkoms identifiziert.To identify immunogenic targets in osteosarcoma tissue a cDNA expression library was constructed from the diagnostic tumour biopsy of an eight year old girl with osteosarcoma. By serological screening with pooled, diluted sera of five osteosarcoma patients 20 antigens were identified. The antigens were further characterised by cDNA sequence and mRNA expression analyses, and antibody responses against these antigens were determined in sera of healthy controls and patients with paediatric tumours. By this approach, antigens with potential impact in the pathophysiology, diagnosis and/or therapy of osteosarcoma were identified
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