@article{AlbertWeissenbergerVarrallyayRaslanetal.2012,
  author    = {Albert-Weißenberger, Christiane and V{\´a}rrallyay, Csan{\´a}d and Raslan, Furat and Kleinschnitz, Christoph and Sir{\´e}n, Anna-Leena},
  title     = {An experimental protocol for mimicking pathomechanisms of traumatic brain injury in mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75368},
  year      = {2012},
  abstract  = {Traumatic brain injury (TBI) is a result of an outside force causing immediate mechanical disruption of brain tissue and delayed pathogenic events. In order to examine injury processes associated with TBI, a number of rodent models to induce brain trauma have been described. However, none of these models covers the entire spectrum of events that might occur in TBI. Here we provide a thorough methodological description of a straightforward closed head weight drop mouse model to assess brain injuries close to the clinical conditions of human TBI.},
  subject      = {Medizin},
  language  = {en}
}
@phdthesis{Aumann2018,
  author    = {Aumann, Ralf},
  title     = {Vorkommen und Expression des opcA Gens in Meningokokkenst{\"a}mmen von Erkrankten und asymptomatischen Tr{\"a}gern},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157278},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Das Opc-Protein ist ein Außenmembranprotein von Meningokokken, das {\"u}ber extrazellul{\"a}re Matrixproteine mit Integrinen der Wirtszelle interagiert. Opc ist in Menschen immunogen und induziert bakterizide Antik{\"o}rper. Das Opc-Protein wurde daher als aussichtsreicher Impfstoff-Kandidat angesehen, da es außerdem relativ gut konserviert ist. Allerdings wird das Opc-Protein nicht von allen Meningokokkenst{\"a}mmen exprimiert. Einerseits fehlt das opc-Gen in einigen klonalen Komplexen (z.B. ST-8, ST-11, ST-53), andererseits ist die Opc-Expression nicht konstitutiv wegen einer phasenvariablen Transkription, die auf einem Poly-Cytidin-Bereich im Promotor des opc-Gens beruht. In dieser Arbeit wurde die Pr{\"a}senz des opc-Gens und die Opc-Expression in zwei großen Sammlungen deutscher Meningokokkenisolate von invasiven Erkrankungen (n=1141) und gesunden Tr{\"a}gern (n=792) untersucht. Das opc-Gen war bei 71\% der invasiven und 77\% der Tr{\"a}gerst{\"a}mme nachweisbar. Der gr{\"o}ßte Teil der opc-Gen negativen St{\"a}mme geh{\"o}rte zu den klonalen Komplexen ST-8, ST-11, ST-213, ST-231, ST-334 und ST-53. Der Anteil opc-positiver St{\"a}mme, die Opc in vitro exprimieren, war bei den invasiven St{\"a}mmen kleiner als bei den Tr{\"a}gerst{\"a}mmen (13\% vs. 29\%, p<0,001, Chi-square-Test). Der gr{\"o}ßere Anteil Opc-exprimierender Tr{\"a}gerst{\"a}mme ist u.a. am ehesten mit der {\"U}berrepr{\"a}sentation von wenig pathogenen klonalen Komplexen (ST-23, ST-35, ST-198) mit einer hohen Opc-Expressionsrate zu erkl{\"a}ren. 24 von den 176 invasiven St{\"a}mmen mit einer Anzahl von 11 - 14 Cs in der Promotor-Region, die die Opc-Expression beg{\"u}nstigt, zeigten weder im ELISA noch im Westernblot eine Opc-Expression. Bei 14 dieser 24 St{\"a}mme wurde als Ursache ein phasenvariabler, intragenischer Poly-Adenin-Bereich identifiziert, der zu einer Leserasterverschiebung f{\"u}hrte. Die Vermutung mehrerer Autoren, dass die Opc-Expression mit dem klinischen Bild der Meningitis verkn{\"u}pft ist, konnte mit der hier genutzten großen Stammsammlung nicht best{\"a}tigt werden. Invasive St{\"a}mme, die das Opc-Protein exprimierten, wurden genauso h{\"a}ufig von Patienten mit dem klinischen Bild der Meningitis isoliert wie St{\"a}mme, die das Opc-Protein nicht exprimierten (46\% vs. 47\%, Chi-square-Test: p<0,9). Allerdings gibt es eine starke Assoziation der Gegenwart des opc-Gens mit dem klinischen Merkmal Meningitis. Dieser Befund gibt Anlass zu der Hypothese, dass in vitro und in vivo Expression von Opc sich unterscheiden. Zusammenfassend l{\"a}sst sich festhalten, dass das Opc-Protein nur in 19,8\% aller Isolate (invasive und Tr{\"a}gerst{\"a}mme zusammengenommen) exprimiert wurde. Es zeigte sich eine Tendenz zu h{\"a}ufigerer Opc-Expression in apathogenen Tr{\"a}gerisolaten. Das Vorhandensein des opc-Gens, nicht aber die in vitro Expression konnten mit dem klinischen Merkmal Meningitis assoziiert werden. Zus{\"a}tzlich wurde ein weiterer Mechanismus der intragenischen Phasenvariation beschrieben.},
  subject      = {Neisseria meningitidis},
  language  = {de}
}
@article{BeckerSchmidtkeStoeberetal.1994,
  author    = {Becker, T. and Schmidtke, A. and St{\"o}ber, Gerald and Franzek, E. and Teichmann, E. and Hofmann, E.},
  title     = {Hyperintense Marklagerl{\"a}sionen bei psychiatrischen Patienten: r{\"a}umliche Verteilung und psychopathologische Symptome},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78288},
  year      = {1994},
  abstract  = {In einem Kollektiv von 130 MR-tomographisch untersuchten psychiatrischen Patienten (axiale T2-SE-Sequenz) wurden Zahl und r{\"a}umliche Verteilung von hyperintensen Marklagerl{\"a}sionen ("white matter lesions"; WM L) erfaßt und die Ventricle-to-brain-Ratio (VBR) bestimmt. Eine Konfigurationsfrequenzanalyse auf der Grundlage der r{\"a}umlichen WMLVerteilung erlaubte die Abgrenzung von vier Patientengruppen: 1. keine WML (n = 35), 2. WML rechts frontotemporal (n = 23), 3. WML bifrontal (n = 12), 4. WML ubiquit{\"a}r (n = 16). Die w{\"a}hrend 3 Jahren beobachteten psychopathologischen Symptome dieser Patienten wurden retrospektiv nach dem AMDP-Systemdokumentiert. In der Gruppe mit ubiquit{\"a}ren WML {\"u}berwogen organisch-psychopathologische Ttems, die VER war gr{\"o}ßer als in den anderen Gruppen (ANOVA;p < 0,001). Die r{\"a}umliche W M L- Verteilung erkl{\"a}rte 10,24 \% der Gesamtvarianz psychopathologischer M erkmalsverteilung in den Gruppen. Das Patientenalter (MANCOVA; p < 0,021), nicht aber die VER hattesignifikanten Einfluß auf das psychopathologische Symptomprofil. Nach Ausblendung der Patientengruppe mit ubiquit{\"a}ren WMLblieb der Einfluß der WML-Verteilung auf die psychopathologische Symptomatiksignifikantc (p <0,05). Bifrontale WML waren mit Denkst{\"o}rung, rechts frontotemporale WML mit affektiven Symptomen assoziiert. Die Befunde sprechen f{\"u}r einen Einfluß der r{\"a}umlichen Verteilung unspezifischer Marklagerl{\"a}sionen auf die psychopathologische Symptomatik.},
  subject      = {Medizin},
  language  = {de}
}
@article{BenkertDietzHartmannetal.2012,
  author    = {Benkert, Thomas F. and Dietz, Lena and Hartmann, Elena M. and Leich, Ellen and Rosenwald, Andreas and Serfling, Edgar and Buttmann, Mathias and Berberich-Siebelt, Friederike},
  title     = {Natalizumab Exerts Direct Signaling Capacity and Supports a Pro-Inflammatory Phenotype in Some Patients with Multiple Sclerosis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77905},
  year      = {2012},
  abstract  = {Natalizumab is a recombinant monoclonal antibody raised against integrin alpha-4 (CD49d). It is approved for the treatment of patients with multiple sclerosis (MS), a chronic inflammatory autoimmune disease of the CNS. While having shown high therapeutic efficacy, treatment by natalizumab has been linked to progressive multifocal leukoencephalopathy (PML) as a serious adverse effect. Furthermore, drug cessation sometimes induces rebound disease activity of unknown etiology. Here we investigated whether binding of this adhesion-blocking antibody to T lymphocytes could modulate their phenotype by direct induction of intracellular signaling events. Primary CD4+ T lymphocytes either from healthy donors and treated with natalizumab in vitro or from MS patients receiving their very first dose of natalizumab were analyzed. Natalizumab induced a mild upregulation of IL-2, IFN-c and IL-17 expression in activated primary human CD4+ T cells propagated ex vivo from healthy donors, consistent with a pro-inflammatory costimulatory effect on lymphokine expression. Along with this, natalizumab binding triggered rapid MAPK/ERK phosphorylation. Furthermore, it decreased CD49d surface expression on effector cells within a few hours. Sustained CD49d downregulation could be attributed to integrin internalization and degradation. Importantly, also CD4+ T cells from some MS patients receiving their very first dose of natalizumab produced more IL-2, IFN-c and IL-17 already 24 h after infusion. Together these data indicate that in addition to its adhesion-blocking mode of action natalizumab possesses mild direct signaling capacities, which can support a pro-inflammatory phenotype of peripheral blood T lymphocytes. This might explain why a rebound of disease activity or IRIS is observed in some MS patients after natalizumab cessation.},
  subject      = {Medizin},
  language  = {en}
}
@phdthesis{Betz2005,
  author    = {Betz, Christian},
  title     = {Scalable authoring of diagnostic case based training systems},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-17885},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {Diagnostic Case Based Training Systems (D-CBT) provide learners with a means to learn and exercise knowledge in a realistic context. In medical education, D-CBT Systems present virtual patients to the learners who are asked to examine, diagnose and state therapies for these patients. Due a number of conflicting and changing requirements, e.g. time for learning, authoring effort, several systems were developed so far. These systems range from simple, easy-to-use presentation systems to highly complex knowledge based systems supporting explorative learning. This thesis presents an approach and tools to create D-CBT systems from existing sources (documents, e.g. dismissal records) using existing tools (word processors): Authors annotate and extend the documents to model the knowledge. A scalable knowledge representation is able to capture the content on multiple levels, from simple to highly structured knowledge. Thus, authoring of D-CBT systems requires less prerequisites and pre-knowledge and is faster than approaches using specialized authoring environments. Also, authors can iteratively add and structure more knowledge to adapt training cases to their learners needs. The theses also discusses the application of the same approach to other domains, especially to knowledge acquisition for the Semantic Web.},
  subject      = {Computerunterst{\"u}tztes Lernen},
  language  = {en}
}
@article{BeyrichLoefflerKobsaretal.2011,
  author    = {Beyrich, Claudia and L{\"o}ffler, J{\"u}rgen and Kobsar, Anna and Speer, Christian P. and Kneitz, Susanne and Eigenthaler, Martin},
  title     = {Infection of Human Coronary Artery Endothelial Cells by Group B Streptococcus Contributes to Dysregulation of Apoptosis, Hemostasis, and Innate Immune Responses [Research Article]},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68834},
  year      = {2011},
  abstract  = {Early onset sepsis due to group B streptococcus leads to neonatal morbidity, increased mortality, and long-term neurological deficencies. Interaction between septicemic GBS and confluent monolayers of human coronary artery endothelial cells (HCAECs) was analyzed by genome wide expression profiling. In total, 124 genes were differentially expressed (89 upregulated, 35 downregulated) based on a more than 3-fold difference to control HCAEC. Regulated genes are involved in apoptosis, hemostasis, oxidative stress response, infection, and inflammation. Regulation of selected genes and proteins identified in the gene array analysis was confirmed by Real-time RT-PCR assay (granulocy te chemotactic protein 2), ELISA (urokinase, cyclooxygenase 2, granulocyte chemotactic protein 1), and western blotting (Heme oxygenase1, BCL2 interacting protein) at various time points between 4 and 24 hours. These results indicate that GBS infection might influence signalling pathways leading to impaired function of the innate immune system and hemorrhagic and inflammatory complications during GBS sepsis.},
  subject      = {Medizin},
  language  = {en}
}
@article{BuschTschernitzThurneretal.2013,
  author    = {Busch, Albert and Tschernitz, Sebastian and Thurner, Anette and Kellersmann, Richard and Lorenz, Udo},
  title     = {Fatal Paraneoplastic Embolisms in Both Circulations in a Patient with Poorly Differentiated Neuroendocrine Tumour},
  series = {Case Reports in Vascular Medicine},
  journal   = {Case Reports in Vascular Medicine},
  doi       = {10.1155/2013/739427},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-97335},
  year      = {2013},
  abstract  = {Arterial embolism with lower limb ischemia is a rare manifestation of paraneoplastic hypercoagulability in cancer patients. We report a unique case of fatal thromboembolism involving both circulations associated with a poorly differentiated neuroendocrine tumor of the lung with rapid progress despite high doses of unfractioned heparin and review the current literature on anticoagulative regimen in tumour patients.},
  language  = {en}
}
@incollection{CantoreggiGuptaLutz1993,
  author    = {Cantoreggi, S. and Gupta, R. C. and Lutz, Werner K.},
  title     = {An improved 32P-postlabelling assay for detection and quantitation of styrene 7,8-oxide-DNA adducts},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86305},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1993},
  abstract  = {Using DNA modified with [7-3H]styrene 7,8-oxide (SO) in vitro we have standardized the 32P-postlabelling assay for detecting SO-DNA adducts. Nuclease P 1-enriched adducts were 32P-labelled and purified by high-salt ( 4.0 M ammonium formate, pH 6.1} C1s reverse-phase TLC. After elution from the layer with 2-butoxyethanol:H20 (4:6), adducts were separated by two-dimensional PEI cellulose TLC in non-urea solvents (2.0 M ammonium formate, pH 3.5, and 2.7 M sodium phosphate, pH 5.6). One major, three minor and several trace adducts were detected. The efficiency of the kinase reaction depended on the ATP concentration. Use of standard labelling conditions (['Y· 32P]ATP, <3000 Ci/mmol; <2 Mikromol) resulted in poor ( 4-7\%) adduct recovery. An ATP concentration of 40 Mikromol, however, increased the labeJling efficiency by a factor of 5-8 (35-55\% based on 3H-SO labelied DNA). The results indicate that the new separation technique is suitable for the relatively polar SO-DNA adducts and that high labelling efficiency can be achieved.},
  subject      = {Medizin},
  language  = {en}
}
@article{ChenPalmLeschetal.2011,
  author    = {Chen, Y. and Palm, F. and Lesch, K. P. and Gerlach, M. and Moessner, R. and Sommer, C.},
  title     = {5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, is responsible for complete Freund's adjuvant-induced thermal hyperalgesia in mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68858},
  year      = {2011},
  abstract  = {Background: The role of serotonin (5-hydroxytrptamine, 5-HT) in the modulation of pain has been widely studied. Previous work led to the hypothesis that 5-hydroxyindolacetic acid (5-HIAA), a main metabolite of serotonin, might by itself influence pain thresholds. Results: In the present study, we investigated the role of 5-HIAA in inflammatory pain induced by intraplantar injection of complete Freund's adjuvant (CFA) into the hind paw of mice. Wild-type mice were compared to mice deficient of the 5-HT transporter (5-HTT-/- mice) using behavioral tests for hyperalgesia and high-performance liquid chromatography (HPLC) to determine tissue levels of 5-HIAA. Wild-type mice reproducibly developed thermal hyperalgesia and paw edema for 5 days after CFA injection. 5-HTT-/- mice treated with CFA had reduced thermal hyperalgesia on day 1 after CFA injection and normal responses to heat hereafter. The 5-HIAA levels in spinal cord and sciatic nerve as measured with HPLC were lower in 5-HTT-/- mice than in wild-type mice after CFA injection. Pretreatment of wild-type mice with intraperitoneal injection of para-chlorophenylalanine (p-CPA), a serotonin synthesis inhibitor, resulted in depletion of the 5-HIAA content in spinal cord and sciatic nerve and decrease in thermal hyperalgesia in CFA injected mice. The application of exogenous 5-HIAA resulted in potentiation of thermal hyperalgesia induced by CFA in 5-HTT-/- mice and in wild-type mice pretreated with p- CPA, but not in wild-type mice without p-CPA pretreatment. Further, methysergide, a broad-spectrum serotonin receptor antagonist, had no effect on 5-HIAA-induced potentiation of thermal hyperalgesia in CFA-treated wildtype mice. Conclusion: Taken together, the present results suggest that 5-HIAA plays an important role in modulating peripheral thermal hyperalgesia in CFA induced inflammation, probably via a non-serotonin receptor mechanism.},
  subject      = {Medizin},
  language  = {en}
}
@article{ChenBoettgerReifetal.2010,
  author    = {Chen, Yong and Boettger, Michael K. and Reif, Andreas and Schmitt, Angelika and Ueceyler, Nurcan and Sommer, Claudia},
  title     = {Nitric oxide synthase modulates CFA-induced thermal hyperalgesia through cytokine regulation in mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68349},
  year      = {2010},
  abstract  = {Background: Although it has been largely demonstrated that nitric oxide synthase (NOS), a key enzyme for nitric oxide (NO) production, modulates inflammatory pain, the molecular mechanisms underlying these effects remain to be clarified. Here we asked whether cytokines, which have well-described roles in inflammatory pain, are downstream targets of NO in inflammatory pain and which of the isoforms of NOS are involved in this process. Results: Intraperitoneal (i.p.) pretreatment with 7-nitroindazole sodium salt (7-NINA, a selective neuronal NOS inhibitor), aminoguanidine hydrochloride (AG, a selective inducible NOS inhibitor), L-N(G)-nitroarginine methyl ester (L-NAME, a non-selective NOS inhibitor), but not L-N(5)-(1-iminoethyl)-ornithine (L-NIO, a selective endothelial NOS inhibitor), significantly attenuated thermal hyperalgesia induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA). Real-time reverse transcription-polymerase chain reaction (RT-PCR) revealed a significant increase of nNOS, iNOS, and eNOS gene expression, as well as tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1b), and interleukin-10 (IL-10) gene expression in plantar skin, following CFA. Pretreatment with the NOS inhibitors prevented the CFA-induced increase of the pro-inflammatory cytokines TNF and IL-1b. The increase of the antiinflammatory cytokine IL-10 was augmented in mice pretreated with 7-NINA or L-NAME, but reduced in mice receiving AG or L-NIO. NNOS-, iNOS- or eNOS-knockout (KO) mice had lower gene expression of TNF, IL-1b, and IL-10 following CFA, overall corroborating the inhibitor data. Conclusion: These findings lead us to propose that inhibition of NOS modulates inflammatory thermal hyperalgesia by regulating cytokine expression.},
  subject      = {Medizin},
  language  = {en}
}
@phdthesis{Ehrmann2007,
  author    = {Ehrmann, Christian},
  title     = {Outsourcing von medizinischen Daten - strafrechtlich betrachtet -},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-28917},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Nach der vorliegenden Untersuchung zum Outsourcing medizinischer Daten aus strafrechtlicher Sicht kann folgendes Gesamtergebnis festgehalten werden. Beim Outsourcing medizinischer Daten sind regelm{\"a}ßig personenbezogene Informationen betroffen. Personenbezogene Information umfasst als Oberbegriff „Geheimnisse" i.S.v. \S 203 StGB sowie personenbezogene Daten im Sinne des Datenschutzrechts. Bei der Bestimmung des Personenbezuges ist es trotz der grunds{\"a}tzlichen Parallelgeltung von Datenschutzrecht und \S 203 StGB zul{\"a}ssig, auf Grunds{\"a}tze aus dem Datenschutzrecht zur{\"u}ckzugreifen. F{\"u}r den Outsourcer medizinischer Daten droht eine Strafbarkeit nach \S 203 StGB, wenn private IT-Dienstleistungsunternehmen vom schweigepflichtigen Outsourcer zur Erledigung von Aufgaben herangezogen werden und in Kontakt mit den Geheimnissen geraten. Daneben kann sich eine Strafbarkeit im Wege der Teilnahme an einer nach \S 203 StGB strafbaren Geheimnisverletzung ergeben. Bei Sachverhalten mit Auslandsbezug kann es dabei zu einer Anwendung deutschen Strafrechts kommen, wenn die Teilnahmehandlung im Inland sich auf ein im Ausland erfolgendes Outsourcing bezieht oder die Teilnahmehandlung im Ausland sich auf ein im Inland erfolgendes Outsourcing bezieht. Bei \S 85a SGB X und \S 44 BDSG k{\"o}nnen sich ausl{\"a}ndische Outsourcingpartner auch als Mitt{\"a}ter strafbar machen, da es sich bei diesen Delikten nicht um Sonderdelikte handelt. Allerdings l{\"a}sst sich durch eine entsprechende Gestaltung des Outsourcingvorhabens im Einzelfall, unabh{\"a}ngig davon, ob ein Schweigepflichtiger nach \S 203 Abs. 1 oder Abs. 2 StGB betroffen ist, eine Strafbarkeit vermeiden. Ansatz ist dabei die Tatbestandsebene des \S 203 StGB, n{\"a}mlich das Merkmal „Geheimnis" sowie das Merkmal „Offenbaren". So kann einerseits durch eine wirksame Verschl{\"u}sselung ein „Geheimnis" i.S.v. \S 203 StGB entfallen. Andererseits besteht die M{\"o}glichkeit, Mitarbeiter des privaten externen Dienstleistungsunternehmens als Gehilfen in den Kreis der zum Wissen Berufenen zu integrieren. Hierzu muss der Dritte an die Funktion des Schweigepflichtigen so angebunden werden, dass aus objektiv-normativer Sicht von einer tatbestandlichen Verantwortungseinheit gesprochen werden kann. Auf der Ebene der Rechtswidrigkeit l{\"a}sst sich der Gefahr einer Strafbarkeit nach \S 203 StGB durch eine Einwilligung begegnen. Außerhalb des Rechtfertigungsgrundes der Einwilligung bestehen f{\"u}r das Outsourcing von medizinischen Daten regelm{\"a}ßig keine strafrechtlichen Erlaubniss{\"a}tze. Allenfalls in unvorhergesehenen Ausnahmesituationen ist eine Rechtfertigung nach \S 34 StGB denkbar. F{\"u}r den Regelfall des Outsourcings ist \S 34 StGB nicht als Rechtfertigungsgrund tauglich. Neben einer Strafbarkeit nach \S 203 StGB kommt beim Outsourcing medizinischer Daten eine Strafbarkeit nach \S 44 BDSG bzw. nach entsprechenden Vorschriften der Landesdatenschutzgesetze sowie eine Strafbarkeit nach \S 85a SGB X in Betracht. Die Gefahr einer Strafbarkeit kann ausgeschlossen werden, wenn das Outsourcing datenschutzrechtlich bzw. sozialrechtlich zul{\"a}ssig ist. Neben der M{\"o}glichkeit einer Einwilligung, die nur ausdr{\"u}cklich erfolgen kann, ist die Zul{\"a}ssigkeit eines Outsourcings medizinischer Daten {\"u}ber eine Ausgestaltung als Auftragsdatenverarbeitung erreichbar. Vorschriften zur Auftragsdatenverarbeitung existieren sowohl im Datenschutzrecht als auch im Sozialrecht. Diese Vorschriften erm{\"o}glichen, sofern nicht spezielle Vorschriften des sektorspezifischen Datenschutzrechts wie beispielsweise Art. 27 Bayerisches Krankenhausgesetz entgegenstehen, in bestimmten Grenzen ein Outsourcing medizinischer Daten unter Beteiligung privater IT-Dienstleistungsunternehmen. Die Normen der Auftragsdatenverarbeitung erm{\"o}glichen nicht eine selbst{\"a}ndige und eigenverantwortliche Aufgabenerf{\"u}llung durch den Outsourcingnehmer im Sinne einer Funktions{\"u}bertragung. Vielmehr muss der Outsourcer nach einer Gesamtbetrachtung das Gesamtgeschehen erkennbar beherrschen und steuern. Die Aufgabe darf nicht durch den Auftraggeber insgesamt aus den H{\"a}nden gegeben werden. Andere Vorschriften, die eine Funktions{\"u}bertragung beim Outsourcing medizinischer Daten erm{\"o}glichen w{\"u}rden, bestehen nicht. Die straflose M{\"o}glichkeit des Outsourcings medizinischer Daten h{\"a}ngt von der Gestaltung im Einzelfall ab. Dies kann unter dem Aspekt der Rechtssicherheit und Rechtsklarheit beklagt werden. W{\"u}nschenswert ist eine bundeseinheitliche Regelung, die das Outsourcing strafrechtlich regelt. Unter den verschiedenen gesetzgeberischen M{\"o}glichkeiten ist eine Neuregelung des \S 203 StGB zu favorisieren.},
  subject      = {Schweigepflicht},
  language  = {de}
}
@article{FassnachtSbieraDexneitetal.2011,
  author    = {Fassnacht, Martin and Sbiera, Silviu and Dexneit, Thomas and Reichardt, Sybille D. and Michel, Kai D. and van den Brandt, Jens and Schmull, Sebastian and Kraus, Luitgard and Beyer, Melanie and Mlynski, Robert and Wortmann, Sebastian and Allolio, Bruno and Reichardt, Holger M.},
  title     = {Influence of Short-Term Glucocorticoid Therapy on Regulatory T Cells In Vivo},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-74749},
  year      = {2011},
  abstract  = {Background: Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(Treg) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs). Objective: We readdressed the influence of GC therapy on Treg cells in immunocompetent human subjects and na{\i}¨ve mice. Methods: Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and Treg cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood Treg cells were analyzed prior and after a 14 day GC therapy based on different markers. Results: Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of Treg cells in blood (100 mg dexamethasone/kg body weight: 2.861.86104 cells/ml vs. 336116104 in control mice) and spleen (dexamethasone: 2.861.96105/spleen vs. 956226105/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3+ Treg cells amongst the CD4+ T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of Treg cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating Treg cells in a relevant manner, although there was some variation depending on the definition of the Treg cells (FOXP3+: 4.061.5\% vs 3.461.5\%*; AITR+: 0.660.4 vs 0.560.3\%, CD127low: 4.061.3 vs 5.063.0\%* and CTLA4+: 13.8611.5 vs 15.6612.5\%; * p,0.05). Conclusion: Short-term GC therapy does not induce the hitherto supposed increase in circulating Treg cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating Treg cell numbers.},
  subject      = {Medizin},
  language  = {en}
}
@article{FehrholzBersaniKrameretal.2012,
  author    = {Fehrholz, Markus and Bersani, Iliana and Kramer, Boris W. and Speer, Christian P. and Kunzmann, Steffen},
  title     = {Synergistic Effect of Caffeine and Glucocorticoids on Expression of Surfactant Protein B (SP-B) mRNA},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-77927},
  year      = {2012},
  abstract  = {Administration of glucocorticoids and caffeine is a common therapeutic intervention in the neonatal period, but possible interactions between these substances are still unclear. The present study investigated the effect of caffeine and different glucocorticoids on expression of surfactant protein (SP)-B, crucial for the physiological function of pulmonary surfactant. We measured expression levels of SP-B, various SP-B transcription factors including erythroblastic leukemia viral oncogene homolog 4 (ErbB4) and thyroid transcription factor-1 (TTF-1), as well as the glucocorticoid receptor (GR) after administering different doses of glucocorticoids, caffeine, cAMP, or the phosphodiesterase-4 inhibitor rolipram in the human airway epithelial cell line NCI-H441. Administration of dexamethasone (1 mM) or caffeine (5 mM) stimulated SP-B mRNA expression with a maximal of 38.8611.1-fold and 5.261.4-fold increase, respectively. Synergistic induction was achieved after coadministration of dexamethasone (1 mM) in combination with caffeine (10 mM) (206659.7-fold increase, p,0.0001) or cAMP (1 mM) (2136111-fold increase, p = 0.0108). SP-B mRNA was synergistically induced also by administration of caffeine with hydrocortisone (87.9639.0), prednisolone (154666.8), and betamethasone (12366.4). Rolipram also induced SP-B mRNA (64.9621.0-fold increase). We detected a higher expression of ErbB4 and GR mRNA (7.0- and 1.7-fold increase, respectively), whereas TTF-1, Jun B, c-Jun, SP1, SP3, and HNF-3a mRNA expression was predominantly unchanged. In accordance with mRNA data, mature SP-B was induced significantly by dexamethasone with caffeine (13.869.0-fold increase, p = 0.0134). We found a synergistic upregulation of SP-B mRNA expression induced by co-administration of various glucocorticoids and caffeine, achieved by accumulation of intracellular cAMP. This effect was mediated by a caffeinedependent phosphodiesterase inhibition and by upregulation of both ErbB4 and the GR. These results suggested that caffeine is able to induce the expression of SP-transcription factors and affects the signaling pathways of glucocorticoids, amplifying their effects. Co-administration of caffeine and corticosteroids may therefore be of benefit in surfactant homeostasis.},
  subject      = {Medizin},
  language  = {en}
}
@article{FeuersteinSiren1987,
  author    = {Feuerstein, G. and Sir{\´e}n, Anna-Leena},
  title     = {Cardiovascular effects of enkephalins},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-49048},
  year      = {1987},
  abstract  = {Enkephalins and their receptors are found in neurons and nerve terminals known to be involved in central cardiovascular control as well as the peripheral sympathetic and parasympathetic systems. Enkephalins and opioid receptors were also iden tified in the heart, kidneys, and blood vessels. The enkephalins interact with several specific receptors, of which p, 0, and K have been best characterized. Enkephalins administered to humans or animals produce cardiovascular effects which depend on the spedes, route of administration, anesthesia, and the selectivity for receptor subtype. While little information exists on the role of enkephalins in normal cardiovascular control, current data suggest that enkephalins might have a role in cardiovascular stress responses such os in shock and trauma.},
  subject      = {Medizin},
  language  = {en}
}
@article{FeuersteinSiren1986,
  author    = {Feuerstein, G. and Sir{\´e}n, Anna-Leena},
  title     = {Effect of naloxone and morphine on survival of conscious rats after hemorrhage},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-48669},
  year      = {1986},
  abstract  = {The endogenous opioid system has been reported to depress the cardiovascular system during shock states, since naloxone, a potent opiate antagonist, enhances recovery of hemodynamic variables in various shock states. However, the effect of naloxone on long-term survival of experimental animals exposed to hypovolemic hypotension is not clear. The present studies tested the capacity of various doses of naloxone to protect conscious rats from mortality following various bleeding paradigms. In addition, the effect of morphine on survival of rats exposed to hemorrhage was also examined. In the six different experimental protocols tested, naloxone treatments failed to improve short- or long-term survival; in fact, naloxone treatment reduced short-term survival in two of the experimental protocols. Morphine injection, however, enhanced the mortality of rats exposed to hemorrhage in a dose-dependent manner. It is concluded that while opiates administered exogenously decrease survival after acute bleeding, naloxone has no protective action in such states and, like morphine, it may decrease survival in some situations.},
  subject      = {Medizin},
  language  = {en}
}
@article{FeuersteinSirenGoldsteinetal.1989,
  author    = {Feuerstein, G. and Sir{\´e}n, Anna-Leena and Goldstein, DS and Johnson, AK and Zerbe, RL},
  title     = {The effect of morphine on the hemodynamic and neuroendocrine responses to hemorrhagic shock in conscious rats},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-49033},
  year      = {1989},
  abstract  = {We have previously reported that analgesic doses of morphine accelerate mortality of rats exposed to hemorrhage (Feuerstein and Siren: Circ Shock 19:293-300, 1986). To study the potential mechanisms involved in this phenomenon, rats were chronically implanted with catheters in the femoral vessels and morphine (1.5 or 5 mg/kg) was administered 30 min or 24 hr after bleeding (8.5 mll300 g over 5 min) while arterial blood pressure and heart rate were continuously monitored. Furthermore, the effect of morphine (5 mg/kg) on cardiac output (CO) response to hemorrhage was studied in rats chronically equipped with a mini thermistor for CO monitoring by a thermodilution technique. In addition, plasma catecholamines (HPLC), plasma renin activity (PRA, RIA), vasopressin (RIA), pH, and blood gases were also determined. Morphine administration 30 min after hemorrhage produced a pressor response and tachycardia which were in marked contrast to its depressor effect in intact rats. Morphine elevated PRA and epinephrine but not vasopressin, while blood pH and gases showed no consistent change as compared to salinetreated hemorrhaged rats. Morphine given after the bleeding resulted in enhanced cardiac depression in response to a second bleed of 2 m1l300 g. Our data suggest that activation of pressor mechanisms by morphine during hypovolemic hypotension might enhance vasoconstriction in essential organs, depress cardiac function, and further reduce effective tissue perfusion.},
  subject      = {Medizin},
  language  = {en}
}
@article{FeuersteinSiren1987,
  author    = {Feuerstein, Giora and Sir{\´e}n, Anna-Leena},
  title     = {The Opioid System in cardiac and vascular regulation of normal and hypertensive states},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-47418},
  year      = {1987},
  abstract  = {The endogenous opioid system includes three major families of peptides: dynorphins (derived from pre-proenkephalin B), endorphins (derived from pre-proopiomelanocortin), and enkephalins (derived from pre-proenkephalin A). Multiple species of opioid peptides are derived from these major precursors and many of them possess potent cardiovascular properties. Opioid peptides and opioid receptors, of which multiple forms have been defined, are present in the central nervous system and peripheral neural elements. In the central nervous system, opioid peptides and receptors are found in forebrain and hindbrain nuclei involved in baroregulation, sympathoadrenal activation, and several other vital autonomic functions. In the periphery, opioid peptides are found in autonomic ganglia, adrenal gland, heart, and other organs; multiple opioid receptors are also found in vascular tissue, heart, and kidneys. Although little is known to date on the regulatory mechanisms of the opioid system in normal cardiovascular states, it became clear that cardiovascular stress situations substantially modify the activity of the endogenous opioid system. The purpose of this review is to clarify the sites of interaction of the opioid system with all major components of the cardiovascular system and indicate the potential role of this system in the ontogenesis of cardiac malfunction, vascular diseases, and hypertension.},
  subject      = {Medizin},
  language  = {en}
}
@article{FreyHoubenBroecker2010,
  author    = {Frey, Li­dia M. and Houben, Roland and Br{\"o}cker, Eva-B.},
  title     = {Pigmentation, Melanocyte Colonization, and p53 Status in Basal Cell Carcinoma},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68283},
  year      = {2010},
  abstract  = {Basal cell carcinoma (BCC) is the most common neoplasm in the Caucasian population. Only a fraction of BCC exhibits pigmentation. Lack of melanocyte colonization has been suggested to be due to p53-inactivating mutations in the BCC cells interfering with the p53-proopiomelanocortin pathway and the production of alpha melanocyte-stimulating hormone in the tumor. To evaluate this, we determined tumor pigmentation as well as expression of melan-A and of p53 in 49 BCC tissues bymeans of immunohistochemistry. As expected, we observed a positive relation between tumor pigmentation and melan-A positive intratumoral melanocytes.Melanocyte colonization and, to a lesser extent, p53 overexpression showed intraindividual heterogeneity in larger tumors. p53 overexpression, which is indicative of p53 mutations, was not correlated to melanocyte colonization of BCC. Sequencing of exon 5-8 of the p53 gene in selected BCC cases revealed that colonization by melanocytes and BCC pigmentation is neither ablated by p53 mutations nor generally present in BCCs with wild-type p53.},
  subject      = {Medizin},
  language  = {en}
}
@article{FreyJansenDohtetal.2013,
  author    = {Frey, S{\"o}nke Percy and Jansen, Hendrik and Doht, Stefanie and Filgueira, Luis and Zellweger, Rene},
  title     = {Immunohistochemical and Molecular Characterization of the Human Periosteum},
  series = {The Scientific World Journal},
  journal   = {The Scientific World Journal},
  doi       = {10.1155/2013/341078},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96623},
  year      = {2013},
  abstract  = {Purpose. The aim of the present study was to characterize the cell of the human periosteum using immunohistological and molecular methods. Methods. Phenotypic properties and the distribution of the cells within the different layers were investigated with immunohistochemical staining techniques and RT-PCR, focussing on markers for stromal stem cells, osteoblasts, osteoclasts and immune cells. Results. Immunohistochemical results revealed that all stained cells were located in the cambium layer and that most cells were positive for vimentin. The majority of cells consisted of stromal stem cells and osteoblastic precursor cells. The density increased towards the deeper layers of the cambium. In addition, cells positive for markers of the osteoblast, chondrocyte, and osteoclast lineages were found. Interestingly, there were MHC class II-expressing immune cells suggesting the presence of dendritic cells. Using lineage-specific primer pairs RT-PCR confirmed the immunofluorescence microscopy results, supporting that human periosteum serves as a reservoir of stromal stem cells, as well as cells of the osteoblastic, and the chondroblastic lineage, osteoclasts, and dendritic cells. Conclusion. Our work elucidates the role of periosteum as a source of cells with a high regenerative capacity. Undifferentiated stromal stem cells as well as osteoblastic precursor cells are dominating in the cambium layer. A new outlook is given towards an immune response coming from the periosteum as MHC II positive immune cells were detected.},
  language  = {en}
}
@article{GattenloehnerJoerissenHuhnetal.2010,
  author    = {Gattenloehner, Stefan and Joerissen, H. and Huhn, M. and Vincent, A. and Beeson, D. and Tzartos, S. and Mamalaki, A. and Etschmann, B. and Muller-Hermelink, H. K. and Koscielniak, E. and Barth, S. and Marx, A.},
  title     = {A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model [Research Article]},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68200},
  year      = {2010},
  abstract  = {Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) γ-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA).While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20\% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms.},
  subject      = {Medizin},
  language  = {en}
}