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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Heparin, a highly sulfated glycosaminoglycan, is known to be obligatory for long-term endothelial cell cultures; it potentiates the mitogenic activities of endothelial cell growth factors and prolongs the replicative life span of the cells. Here we have shown that besides its growth factor-supportive role, heparin exerts a specific action on cerebral capillary endothelial cells (cECs), unrelated to serum or growth factors, by increasing activity of ornithine decarboxylase (ODC; EC 4.1.1.17) in these cells. For our experiments we have used two different types of cloned cECs: type I cECs, grown in the presence of endothelial cell growth factor and heparin, and type II cECs, usually cultivated without growth factors. Heparin action on ODC activity was shown to be dose dependent within the range of 1–100 μg/ml. Increasing concentrations of or depletion of endothelial cell growth factor from type I cultures had no effect on ODC activity. The increase in enzyme activity was highest after 30 min to 1 h of heparin treatment. As evidenced by northern analysis, the heparin-mediated enhancement of ODC activity was not accompanied by changes of ODC mRNA levels. Studies of DNA replication revealed that in the absence of heparin-binding growth factors, heparin did not affect the proliferative activity of cloned cECs.
    Type of Medium: Electronic Resource
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  • 2
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  124. Kongress der Deutschen Gesellschaft für Chirurgie; 20070501-20070504; München; DOC07dgch7343 /20071001/
    Publication Date: 2007-10-02
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 3
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    German Medical Science; Düsseldorf, Köln
    In:  GMS Mitteilungen aus der AWMF; VOL: 8; DOC28 /20111108/
    Publication Date: 2011-11-09
    Description: Eine Stellungnahme der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF) Erarbeitet von einer ad-hoc-Kommission der AWMF* und verabschiedet vom Präsidium der AWMF am 29. September 2011 * Mitglieder: Professor Dr. med. H. Bauer, Professor Dr. med. U. R. Fölsch, Professor Dr. med. W. Gaebel, Professor Dr. med. H. C. Korting, W. Müller M.A., Professor Dr. med. W. Niebling, Professor Dr. med. K. H. Rahn, Professor Dr. med. N. Roeder, Professor Dr. med. Dr. med. dent. W. Wagner, Dr. iur. A. Wienke Zusammenfassende Empfehlungen Die Verlagerung von Krankenversorgungsleistungen aus dem stationären in den ambulanten Sektor hat Konsequenzen für Forschung, Lehre und Weiterbildung in den Medizinischen Fakultäten und in den Universitätsklinika. Dadurch gewinnen Hochschulambulanzen zunehmend an Bedeutung. Nach § 117 Sozialgesetzbuch V ist der Zulassungsausschuss verpflichtet, auf Antrag Hochschulambulanzen zur ambulanten ärztlichen Behandlung von Versicherten in dem für Forschung und Lehre erforderlichen Umfang zu ermächtigen. Zu einer besseren Nutzung der Hochschulambulanzen hat die AWMF Empfehlungen erarbeitet. Hochschulambulanzen sind erforderlich, damit die Medizinischen Fakultäten ihre Aufgaben in Forschung, Lehre und Weiterbildung erfüllen können. Medizinische Fakultäten und Universitätsklinika müssen ihren Rechtsanspruch auf Ermächtigung zur ambulanten ärztlichen Behandlung durchsetzen. Die Patienten müssen unabhängig von einer Überweisung durch einen niedergelassenen Facharzt einen direkten Zugang zu den Hochschulambulanzen haben. Für den Zugang sollte es differenziert nach Fächern Fallzahlobergrenzen geben. Diese richten sich nach den Forschungsschwerpunkten der Fakultäten sowie nach den Aktivitäten der Fächer in Forschung, Lehre und Weiterbildung. Die Krankenversorgungskosten der Hochschulambulanzen müssen transparent und leistungsgerecht über Einzelleistungsvergütungen oder über Komplexpauschalen finanziert werden. Zusätzliche Kosten, die sich aus der Beteiligung an Forschung und Lehre ergeben, müssen aus dem Zuführungsbetrag der Medizinischen Fakultäten beglichen werden. Die Einrichtung von Ambulanzportalen wird für jedes Universitätsklinikum empfohlen. Von diesen Ambulanzportalen aus können die Patienten gezielt zu den jeweiligen Spezialambulanzen weitergeleitet werden. Die Ambulanzportale sollten eine eigene ärztliche Leitung haben. Hier bietet sich die Möglichkeit, Hochschullehrer für Allgemeinmedizin stärker in die Aktivitäten der Medizinischen Fakultäten einzubinden. An den Universitätsklinika sollte ein integriertes Informationssystem unter Einbeziehung der Hochschulambulanzen erarbeitet werden. Schnittstellen von den in den Hochschulambulanzen für die Krankenversorgung notwendigen Dokumentationssystemen zu den IT-Systemen der Forschung und des Studienmanagements müssen vorgesehen werden.
    Keywords: ddc: 610
    Language: German
    Type: article
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  • 4
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2014); 20141028-20141031; Berlin; DOCPO12-1366 /20141013/
    Publication Date: 2014-10-14
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 5
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    German Medical Science GMS Publishing House; Düsseldorf
    In:  Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA); 20100923-20100925; Bochum; DOC10gma94 /20100805/
    Publication Date: 2010-08-06
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 6
    Keywords: brain ; CELLS ; EXPRESSION ; SURVIVAL ; tumor ; TUMOR-CELLS ; BLOOD ; CELL ; Germany ; THERAPY ; DISEASE ; LONG-TERM ; TUMORS ; TIME ; PATIENT ; INFECTION ; prognosis ; SKIN ; T cell ; T cells ; T-CELL ; T-CELLS ; cell culture ; culture ; MEMORY ; virus ; NERVOUS-SYSTEM ; NO ; immunohistochemistry ; ASSAY ; NUMBER ; VACCINE ; SAFETY ; CD8(+) ; immune response ; IMMUNE-RESPONSE ; IMMUNITY ; T-LYMPHOCYTES ; vaccination ; T lymphocyte ; side effects ; NEWCASTLE-DISEASE VIRUS ; ESTABLISHMENT ; TUMOR CELLS ; LONG-TERM SURVIVORS ; GLIOMAS ; T lymphocytes ; IMMUNIZATION ; ONCOLOGY ; AUTOLOGOUS TUMOR ; overall survival ; NEWCASTLE-DISEASE-VIRUS ; SURVIVORS
    Abstract: Purpose Prognosis of patients with glioblastoma is poor. Therefore, in glioblastoma patients, we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe. Also, we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity. Patients and Methods In a nonrandomized study, 23 patients were vaccinated and compared with nonvaccinated controls (n = 87). Vaccine was prepared from patient's tumor cell cultures by infection of the cells with Newcastle Disease Virus, followed by gamma-irradiation, and applied up to eight times. Antitumor immune reactivity was determined in skin, blood, and relapsed tumor by delayed-type hypersensitivity skin reaction, ELISPOT assay, and immunohistochemistry, respectively. Results Establishment of tumor cell cultures was successful in approximately 90% of patients. After vaccination, we observed no severe side effects. The median progression-free survival of vaccinated patients was 40 weeks (v 26 weeks in controls; log-rank test, P =.024), and the median overall survival of vaccinated patients was 100 weeks (v 49 weeks in controls; log-rank test, P 〈.001). Forty-five percent of the controls survived 1 year, 11% survived 2 years, and there were no long-term survivors (greater than or equal to3 years). Ninety-one percent of vaccinated 39% survived 2 years, and 4% were long-term survivors. In the patients survived I year, vaccinated group, immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity, numbers of tumor-reactive memory T cells, and numbers of CD8(+) tumor-infiltrating T-lymphocytes in secondary tumors. Conclusion Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with gliobiastomas. This could be substantiated by the observed antitumor immune response. (C) 2004 by American Society of Clinical Oncology
    Type of Publication: Journal article published
    PubMed ID: 15452186
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  • 7
    Keywords: CELLS ; INHIBITOR ; CELL ; Germany ; human ; INHIBITION ; SYSTEM ; ENZYMES ; GENE ; GENOME ; GENOME SEQUENCE ; PROTEIN ; CONTRAST ; SEQUENCE ; SEQUENCES ; chromosome ; VARIANTS ; SUBUNIT ; ACTIVE-SITE ; DESIGN ; DIFFERENCE ; Drosophila ; DROSOPHILA-MELANOGASTER ; ERYTHROCYTES ; ESCHERICHIA-COLI ; genome analysis ; GLUTATHIONE ; GLUTATHIONE-REDUCTASE ; INSECTICIDE RESISTANCE ; MELANOGASTER ; PHAGOCYTOSIS ; resistance ; SELENOCYSTEINE ; SINGLE-COPY ; VECTOR ; Plasmodium falciparum ; Anopheles gambiae ; Drosophila melanogaster ; Diptera ; insect redox metabolism
    Abstract: The mosquito, Anopheles gambiae, is an important vector of Plasmodium falciparum malaria. Full genome analysis revealed that, as in Drosophila melanogaster, the enzyme glutathione reductase is absent in A. gambiae and functionally substituted by the thioredoxin system. The key enzyme of this system is thioredoxin reductase-1, a homodimeric FAD-containing protein of 55.3 kDa per subunit, which catalyses the reaction NADPH + H+ + thioredoxin disulfide. NADP+ + thioredoxin dithiol. The A. gambiae trxr gene is located on chromosome X as a single copy; it represents three splice variants coding for two cytosolic and one mitochondrial variant. The predominant isoform, A. gambiae thioredoxin reductase-1, was recombinantly expressed in Escherichia coli and functionally compared with the wild-type enzyme isolated in a final yield of 1.4 U.ml(-1) of packed insect cells. In redox titrations, the substrate A. gambiae thioredoxin-1 (K-m = 8.5 muM, k(cat) = 15.4 s(-1) at pH 7.4 and 25degreesC) was unable to oxidize NADPH-reduced A. gambiae thioredoxin reductase-1 to the fully oxidized state. This indicates that, in contrast to other disulfide reductases, A. gambiae thioredoxin reductase-1 oscillates during catalysis between the four-electron reduced state and a two-electron reduced state. The thioredoxin reductases of the malaria system were compared. A. gambiae thioredoxin reductase-1 shares 52% and 45% sequence identity with its orthologues from humans and P. falciparum, respectively. A major difference among the three enzymes is the structure of the C-terminal redox centre, reflected in the varying resistance of catalytic intermediates to autoxidation. The relevant sequences of this centre are Thr-Cys-Cys-SerOH in A. gambiae thioredoxin reductase, Gly-Cys-selenocysteine-GlyOH in human thioredoxin reductase, and Cys-X-X-X-X-Cys-GlyOH in the P. falciparum enzyme. These differences offer an interesting approach to the design of species-specific inhibitors. Notably, A. gambiae thioredoxin reductase-1 is not a selenoenzyme but instead contains a highly unusual redoxactive Cys-Cys sequence
    Type of Publication: Journal article published
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  • 8
    Abstract: Background: While IMRT is widely used in treating complex oncological cases in adults, it is not commonly used in pediatric radiation oncology for a variety of reasons. This report evaluates our 9 year experience using stereotactic-guided, inverse planned intensity-modulated radiotherapy (IMRT) in children and adolescents in the context of the current literature. Methods: Between 1999 and 2008 thirty-one children and adolescents with a mean age of 14.2 years (1.5-20.5) were treated with IMRT in our department. This heterogeneous group of patients consisted of 20 different tumor entities, with Ewing's sarcoma being the largest (5 patients), followed by juvenile nasopharyngeal fibroma, esthesioneuroblastoma and rhabdomyosarcoma (3 patients each). In addition a review of the available literature reporting on technology, quality, toxicity, outcome and concerns of IMRT was performed. Results: With IMRT individualized dose distributions and excellent sparing of organs at risk were obtained in the most challenging cases. This was achieved at the cost of an increased volume of normal tissue receiving low radiation doses. Local control was achieved in 21 patients. 5 patients died due to progressive distant metastases. No severe acute or chronic toxicity was observed. Conclusion: IMRT in the treatment of children and adolescents is feasible and was applied safely within the last 9 years at our institution. Several reports in literature show the excellent possibilities of IMRT in selective sparing of organs at risk and achieving local control. In selected cases the quality of IMRT plans increases the therapeutic ratio and outweighs the risk of potentially increased rates of secondary malignancies by the augmented low dose exposure
    Type of Publication: Journal article published
    PubMed ID: 19775449
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  • 9
    Keywords: CELLS ; INVASION ; IN-VIVO ; THERAPY ; VOLUME ; DISEASE ; ADHESION MOLECULES ; TISSUE ; INFECTION ; REDUCTION ; T cell ; T-CELLS ; NERVOUS-SYSTEM ; LYMPHOCYTES ; MULTIPLE-SCLEROSIS ; inflammation ; FOCAL CEREBRAL-ISCHEMIA ; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS ; REGULATORY T-CELLS ; TRANSENDOTHELIAL MIGRATION ; VCAM-1 ; INFLAMMATORY RESPONSE ; ALPHA-4 INTEGRIN ; brain ischaemia ; NEUTROPHIL DEPLETION ; VLA-4
    Abstract: T lymphocytes are increasingly recognized as key modulators of detrimental inflammatory cascades in acute ischaemic stroke, but the potential of T cell-targeted therapy in brain ischaemia is largely unexplored. Here, we characterize the effect of inhibiting leukocyte very late antigen-4 and endothelial vascular cell adhesion molecule-1-mediated brain invasion-currently the most effective strategy in primary neuroinflammatory brain disease in murine ischaemic stroke models. Very late antigen-4 blockade by monoclonal antibodies improved outcome in models of moderate stroke lesions by inhibiting cerebral leukocyte invasion and neurotoxic cytokine production without increasing the susceptibility to bacterial infections. Gene silencing of the endothelial very late antigen-4 counterpart vascular cell adhesion molecule-1 by in vivo small interfering RNA injection resulted in an equally potent reduction of infarct volume and post-ischaemic neuroinflammation. Furthermore, very late antigen-4-inhibition effectively reduced the post-ischaemic vascular cell adhesion molecule-1 upregulation, suggesting an additional cross-signalling between invading leukocytes and the cerebral endothelium. Dissecting the specific impact of leukocyte subpopulations showed that invading T cells, via their humoral secretion (interferon-gamma) and immediate cytotoxic mechanisms (perforin), were the principal pathways for delayed post-ischaemic tissue injury. Thus, targeting T lymphocyte-migration represents a promising therapeutic approach for ischaemic stroke
    Type of Publication: Journal article published
    PubMed ID: 21354973
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  • 10
    Keywords: intensity modulated radiotherapy ; NUCLEAR ; - ; radiotherapy ; Germany ; NUCLEAR-MEDICINE ; imaging ; Jun ; EXPERIENCE ; treatment ; ONCOLOGY ; ADULT ; ADULTS ; YOUNG ; radiology ; SINGLE ; CHILDREN ; INTENSITY-MODULATED RADIOTHERAPY ; nuclear medicine
    Type of Publication: Meeting abstract published
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