@phdthesis{Filser2012, author = {Filser, J{\"o}rg}, title = {Mislokalisation von Nup214/CAN auf beiden Seiten des Kernporenkomplexes in akuten myeloischen Leuk{\"a}mien - Eine erstmalige Darstellung des DEK-CAN Fusionsproteins auf der nukleoplasmatischen Seite des Zellkerns}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75977}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2012}, abstract = {Das elementare Kennzeichen der eukaryontischen Zelle ist der Zellkern, in welchem die Erbinformation in Form der DNA vorliegt. Dieser ist von einer {\"a}ußeren Kernh{\"u}lle umgeben, welche kontinuierlich in das endoplasmatische Retikulum {\"u}bergeht. An der inneren Kernh{\"u}lle setzt die Kernlamina an. Unterbrochen wird die Kernh{\"u}lle durch die Kernporen. Diese bestehen aus Untereinheiten, welche als Nukleoporine bezeichnet werden. Eine wesentliche Aufgabe der Kernporen ist der Transport von Makromolek{\"u}len, welche durch spezifische Transportsignalsequenzen gekennzeichnet sind. Es mehren sich die Hinweise, dass die Nukleoporine nicht allein f{\"u}r den Kerntransport verantwortlich sind, sondern auch regulatorische Eigenschaften bei Mitose, der Expression von Proteinen und der Stabilisierung des Genoms {\"u}bernehmen. Nach der Entdeckung der Philadelphia Translokation bei der chronisch myeloischen Leuk{\"a}mie wurden eine Reihe weiterer chromosomaler Translokationen im Rahmen von h{\"a}matologischen Neoplasien beschrieben. Hierbei sind auch Nukleoporine involviert. Es entstehen Fusionsproteine, welche ein neues Verteilungsmuster der Proteine erzeugen und m{\"o}glicherweise auch neue Funktionen innehaben. Nup214/CAN ist ein Onkogen, welches in akuten myeloischen Leuk{\"a}mien mit einer chromosomalen Translokation einhergeht t(6;9). Diese Translokation t(6;9) ist mit einer schlechteren Prognose f{\"u}r den Patienten verbunden. Der genaue onkogene Mechanismus ist noch nicht ausreichend verstanden. Ziel dieser Doktorarbeit war die Frage, welches Verteilungsmuster Nup214 als Fusionsprotein mit einer ver{\"a}nderten NLS in Leuk{\"a}miezellen der chromosomalen Translokation t(6;9) aufweist, zu beantworten. Zu diesem Zweck wurden die Fusionsproteinfragmente DEK, CAN Mitte und CAN 80/81 in E. coli exprimiert, aufgereinigt und der Herstellung eines spezifischen Antik{\"o}rpers zugef{\"u}hrt. Hierzu wurden die mit den Proteinfragmenten transfizierten E. coli amplifiziert. Nach Lyse der Zellen wurden die Proteinfragmente elektrophoretisch getrennt und den ermittelten Molekulargewichten zugeordnet. Mit Hilfe einer Affinit{\"a}tschromatographie und einem Proteintransfer auf Nitrozellulosemembran wurde mit polyvalentem Serum eine Affinit{\"a}tsreinigung des Antik{\"o}rpers durchgef{\"u}hrt. Dadurch konnten spezifische Antik{\"o}rper generiert werden, welche in der Immunfloureszenz die physiologischen Verteilungsmuster zeigten. In einem nachfolgenden Schritt konnte in Kooperation mit dem Biologischen Institut Basel mittels Immuno-Gold-Lokalisation von Nup214/CAN in Leuk{\"a}miezellen mit einer chromosomalen Translokation t(6;9) erstmalig die Lokalisation des Proteins auf zytoplasmatischer und nukleoplasmatischer Seite einer Kernpore gezeigt werden. Dies legt die Vermutung nahe, dass es durch diese Mislokalisation zu einer St{\"o}rung des nukle{\"a}ren Transports kommen kann, der wiederum zu einem Wachstumsvorteil oder einer Inhibition der Apoptose der Leuk{\"a}miezellen f{\"u}hrt.}, subject = {Kernpore}, language = {de} } @article{FilserDickMeyeretal.2015, author = {Filser, J{\"o}rg and Dick, Anke and Meyer, Thomas and Germer, Christoph-Thomas and von Rahden, Burkard H. A.}, title = {Peroral endoscopic myotomy for the treatment of achalasia in a 10-year-old male patient.}, series = {European Journal of Pediatric Surgery Reports}, volume = {3}, journal = {European Journal of Pediatric Surgery Reports}, number = {1}, doi = {10.1055/s-0034-1372461}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149502}, pages = {18-22}, year = {2015}, abstract = {Peroral endoscopic myotomy (POEM) is a new endoscopic treatment for achalasia with very good short-term results in adults. Data about POEM in pediatric patients are missing. We present the case of a 10-year-old male patient with type I (classic) achalasia, successfully treated with POEM. The procedure was accomplished in a similar fashion to the technique used in adults. Short-term results were fine, with a complete control of dysphagia and absence of reflux. We suggest that POEM is a suitable option in pediatric patients—similar to adults—but long-term results must be awaited.}, language = {en} } @article{BauerOpitzFilseretal.2019, author = {Bauer, Maria and Opitz, Anne and Filser, J{\"o}rg and Jansen, Hendrik and Meffert, Rainer H. and Germer, Christoph T. and Roewer, Norbert and Muellenbach, Ralf M. and Kredel, Markus}, title = {Perioperative redistribution of regional ventilation and pulmonary function: a prospective observational study in two cohorts of patients at risk for postoperative pulmonary complications}, series = {BMC Anesthesiology}, volume = {19}, journal = {BMC Anesthesiology}, doi = {10.1186/s12871-019-0805-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200730}, pages = {132}, year = {2019}, abstract = {Background Postoperative pulmonary complications (PPCs) increase morbidity and mortality of surgical patients, duration of hospital stay and costs. Postoperative atelectasis of dorsal lung regions as a common PPC has been described before, but its clinical relevance is insufficiently examined. Pulmonary electrical impedance tomography (EIT) enables the bedside visualization of regional ventilation in real-time within a transversal section of the lung. Dorsal atelectasis or effusions might cause a ventral redistribution of ventilation. We hypothesized the existence of ventral redistribution in spontaneously breathing patients during their recovery from abdominal and peripheral surgery and that vital capacity is reduced if regional ventilation shifts to ventral lung regions. Methods This prospective observational study included 69 adult patients undergoing elective surgery with an expected intermediate or high risk for PPCs. Patients undergoing abdominal and peripheral surgery were recruited to obtain groups of equal size. Patients received general anesthesia with and without additional regional anesthesia. On the preoperative, the first and the third postoperative day, EIT was performed at rest and during spirometry (forced breathing). The center of ventilation in dorso-ventral direction (COVy) was calculated. Results Both groups received intraoperative low tidal volume ventilation. Postoperative ventral redistribution of ventilation (forced breathing COVy; preoperative: 16.5 (16.0-17.3); first day: 17.8 (16.9-18.2), p < 0.004; third day: 17.4 (16.2-18.2), p = 0.020) and decreased forced vital capacity in percentage of predicted values (FVC\%predicted) (median: 93, 58, 64\%, respectively) persisted after abdominal surgery. In addition, dorsal to ventral shift was associated with a decrease of the FVC\%predicted on the third postoperative day (r = - 0.66; p < 0.001). A redistribution of pulmonary ventilation was not observed after peripheral surgery. FVC\%predicted was only decreased on the first postoperative day (median FVC\%predicted on the preoperative, first and third day: 85, 81 and 88\%, respectively). In ten patients occurred pulmonary complications after abdominal surgery also in two patients after peripheral surgery. Conclusions After abdominal surgery ventral redistribution of ventilation persisted up to the third postoperative day and was associated with decreased vital capacity. The peripheral surgery group showed only minor changes in vital capacity, suggesting a role of the location of surgery for postoperative redistribution of pulmonary ventilation.}, language = {en} } @article{JurowichLichthardtKastneretal.2019, author = {Jurowich, Christian and Lichthardt, Sven and Kastner, Caroline and Haubitz, Imme and Prock, Andre and Filser, J{\"o}rg and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Laparoscopic versus open right hemicolectomy in colon carcinoma: A propensity score analysis of the DGAV StuDoQ|ColonCancer registry}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0218829}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202184}, pages = {e0218829}, year = {2019}, abstract = {Objective To assess whether laparoscopy has any advantages over open resection for right-sided colon cancer. Summary background data Right hemicolectomy can be performed using either a conventional open or a minimally invasive laparoscopic technique. It is not clear whether these different access routes differ with regard to short-term postoperative outcomes. Methods Patients documented in the German Society for General and Visceral Surgery StuDoQ|ColonCancer registry who underwent right hemicolectomy were analyzed regarding early postoperative complications according to Clavien-Dindo (primary endpoint), operation (OP) time, length of postoperative hospital stay (LOS), MTL30 and number of lymph nodes retrieved (secondary endpoints). Results A total of 4.997 patients were identified as undergoing oncological right hemicolectomy without additional interventions. Of these, 4.062 (81.3\%) underwent open, 935 (18.7\%) laparoscopic surgery. Propensity score analysis showed a significantly shorter LOS (OR: 0.55 CI 95\%0.47-.64) and a significantly longer OP time (OR2.32 CI 1.98-2.71) for the laparoscopic route. Risk factors for postoperative complications, anastomotic insufficiency, ileus, reoperation and positive MTL30 were higher ASA status, higher age and increasing BMI. The surgical access route (open / lap) had no influence on these factors, but the laparoscopic group did have markedly fewer lymph nodes retrieved. Conclusion The present registry-based analysis could detect no relevant advantages for the minimally invasive laparoscopic access route. Further oncological analyses are needed to clarify the extent to which the smaller lymph node harvest in the laparoscopic group is accompanied by a poorer oncological outcome.}, language = {en} }