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  • 1
    Keywords: GENE ; immunohistochemistry ; FUSION ; INSIGHTS ; pleura ; NAB2
    Abstract: Solitary fibrous tumors (SFTs) are rare mesenchymal neoplasms, displaying variable morphological and clinicopathological features. Supportive immunohistochemical markers such as CD34, CD99, BCL2 and LSD1 are commonly applied in the differential diagnosis of SFTs, although none is sufficiently sensitive or specific enough. The aim of the present study was to examine the most differential markers for the reliable distinction of SFTs from histological mimics. We investigated the expression of STAT6, NAB2, ALDH1, GRIA2 and IGF2 in 454 comprehensive soft tissue tumors, comprising formalin-fixed paraffin-embedded (FFPE) tissue samples from 80 SFTs and 374 other mesenchymal tumors. The Duolink in situ proximity ligation assay (PLA) was adopted for the detection of NAB2-STAT6 fusion proteins. STAT6 was expressed in all 80 SFT cases with a moderate-strong nuclear staining intensity. In contrast, only 4/374 (1%) non-SFT mesenchymal tumors showed a nuclear STAT6 staining pattern. Strong expression of NAB2 and IGF2 was detected in SFT and non-SFT cases. Positive GRIA2 immunoreactivity was found in 64% (SFT) and 8% (non-SFT), respectively. Expression of ALDH1 was moderate-strong in 76% (SFT), whereas only 2 non-SFT lesions showed positive ALDH1 immunoreactivity. Moreover, the presence of NAB2STAT6 fusion proteins was indicated in 71/78 (91%) SFT cases by PLA. Nuclear STAT6 and cytoplasmic ALDH1 expression are the most sensitive and specific markers in the differential diagnosis of SFTs. Furthermore, application of Duolink in situ proximity ligation assay can be helpful to detect the NAB2-STAT6 fusion protein in the majority of SFTs.
    Type of Publication: Journal article published
    PubMed ID: 25901508
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  • 2
    Abstract: Purpose: Myxoid liposarcoma is an aggressive disease with particular propensity to develop hematogenic metastases. Over 90% of myxoid liposarcoma are characterized by a reciprocal t(12;16)(q13;p11) translocation. The resulting chimeric FUS-DDIT3 fusion protein plays a crucial role in myxoid liposarcoma pathogenesis; however, its specific impact on oncogenic signaling pathways remains to be substantiated. We here investigate the functional role of FUS-DDIT3 in IGF-IR/PI3K/Akt signaling driving myxoid liposarcoma pathogenesis.Experimental Design: Immunohistochemical evaluation of key effectors of the IGF-IR/PI3K/Akt signaling axis was performed in a comprehensive cohort of myxoid liposarcoma specimens. FUS-DDIT3 dependency and biological function of the IGF-IR/PI3K/Akt signaling cascade were analyzed using a HT1080 fibrosarcoma-based myxoid liposarcoma tumor model and multiple tumor-derived myxoid liposarcoma cell lines. An established myxoid liposarcoma avian chorioallantoic membrane model was used for in vivo confirmation of the preclinical in vitro results.Results: A comprehensive subset of myxoid liposarcoma specimens showed elevated expression and phosphorylation levels of various IGF-IR/PI3K/Akt signaling effectors. In HT1080 fibrosarcoma cells, overexpression of FUS-DDIT3 induced aberrant IGF-IR/PI3K/Akt pathway activity, which was dependent on transcriptional induction of the IGF2 gene. Conversely, RNAi-mediated FUS-DDIT3 knockdown in myxoid liposarcoma cells led to an inactivation of IGF-IR/PI3K/Akt signaling associated with diminished IGF2 mRNA expression. Treatment of myxoid liposarcoma cell lines with several IGF-IR inhibitors resulted in significant growth inhibition in vitro and in vivoConclusions: Our preclinical study substantiates the fundamental role of the IGF-IR/PI3K/Akt signaling pathway in myxoid liposarcoma pathogenesis and provides a mechanism-based rationale for molecular- targeted approaches in myxoid liposarcoma cancer therapy. Clin Cancer Res; 23(20); 6227-38. (c)2017 AACR.
    Type of Publication: Journal article published
    PubMed ID: 28637688
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  • 3
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    German Medical Science; Düsseldorf, Köln
    In:  Deutscher Kongress für Orthopädie und Unfallchirurgie; 70. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 92. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie und 47. Tagung des Berufsverbandes der Fachärzte für Orthopädie; 20061002-20061006; Berlin; DOCP.2.10-567 /20060928/
    Publication Date: 2007-03-09
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 4
    Publication Date: 2017-04-10
    Description: In the past years infections caused by multidrug-resistant Gram-negative bacteria have dramatically increased in all parts of the world. This consensus paper is based on presentations, subsequent discussions and an appraisal of current literature by a panel of international experts invited by the Rudolf Schülke Stiftung, Hamburg. It deals with the epidemiology and the inherent properties of Gram-negative bacteria, elucidating the patterns of the spread of antibiotic resistance, highlighting reservoirs as well as transmission pathways and risk factors for infection, mortality, treatment and prevention options as well as the consequences of their prevalence in livestock. Following a global, One Health approach and based on the evaluation of the existing knowledge about these pathogens, this paper gives recommendations for prevention and infection control measures as well as proposals for various target groups to tackle the threats posed by Gram-negative bacteria and prevent the spread and emergence of new antibiotic resistances.
    Description: In den letzten Jahren haben die durch multiresistente Gram-negative Bakterien (MRGN) verursachten Infektionen in allen Teilen der Welt dramatisch zugenommen. Der vorliegende Konsensus basiert auf Vorträgen mit sich anschließenden Diskussionen und späterer Auswertung der einschlägigen Literatur durch ein internationales Expertengremium, das von der Rudolf Schülke Stiftung, Hamburg, zu dem Meeting nach Hamburg eingeladen worden war. Im Fokus standen die Epidemiologie und die besonderen Eigenschaften Gram-negativer Bakterien, die Ausbreitung der Antibiotikaresistenz, die Reservoire, Übertragungswege und Risikofaktoren für Infektionen, die Mortalität, die Therapie und die Möglichkeiten der Prävention einschließlich der Konsequenzen des Vorkommens in der industriellen Tierhaltung. Dem One Health Ansatz folgend und basierend auf der Bewertung des Wissensstandes zu diesen Erregern werden Empfehlungen zur Prävention und Bekämpfung sowie Vorschläge für verschiedene Zielgruppen unterbreitet, um der Bedrohung durch MRGN zu begegnen, ihre Ausbreitung zu verhindern und die Entstehung neuer Antibiotikaresistenzen zu unterbinden.
    Keywords: multidrug-resistant Gram-negative bacteria ; epidemiology ; surveillance ; reservoirs ; resistance patterns ; therapy ; infection control measures ; biocides ; disinfection ; agriculture ; multiresistente Gram-negative Bakterien ; Epidemiologie ; Surveillance ; Reservoire ; Resistenzmuster ; Therapie ; Prävention ; Infektionsbekämpfung ; Biozide ; Desinfektion ; Landwirtschaft ; ddc: 610
    Language: English
    Type: article
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  • 5
    Publication Date: 2015-02-05
    Description: In developing hygiene strategies, in recent years, the major focus has been on the hands as the key route of infection transmission. However, there is a multitude of lesser-known and underestimated reservoirs for microorganisms which are the triggering sources and vehicles for outbreaks or sporadic cases of infection. Among those are water reservoirs such as sink drains, fixtures, decorative water fountains and waste-water treatment plants, frequently touched textile surfaces such as private curtains in hospitals and laundry, but also transvaginal ultrasound probes, parenteral drug products, and disinfectant wipe dispensers. The review of outbreak reports also reveals Gram-negative and multiple-drug resistant microorganisms to have become an increasingly frequent and severe threat in medical settings. In some instances, the causative organisms are particularly difficult to identify because they are concealed in biofilms or in a state referred to as viable but nonculturable, which eludes conventional culture media-based detection methods. There is an enormous preventative potential in these insights, which has not been fully tapped. New and emerging pathogens, novel pathogen detection methods, and hidden reservoirs of infection should hence be given special consideration when designing the layout of buildings and medical devices, but also when defining the core competencies for medical staff, establishing programmes for patient empowerment and education of the general public, and when implementing protocols for the prevention and control of infections in medical, community and domestic settings.
    Description: Bei der Konzeption von Hygienestrategien standen in den letzten Jahren die Hände als Hauptübertragungsweg für Infektionen im Mittelpunkt. Es gibt jedoch noch eine Vielzahl weiterer, weniger bekannter und unterschätzter Infektionsquellen für Mikroorganismen, die als Verursacher und Infektionsweg für Ausbrüche oder sporadische Infektionsgeschehen in Frage kommen. Zu diesen zählen wasserführende Systeme wie Waschbeckenablauf, Armaturen, Zierbrunnen und Kläranlagen, textile Kontaktflächen wie Patientenvorhänge in Krankenhäusern und Wäsche, aber auch transvaginale Ultraschallsonden, parenteral verabreichte Medikamente und vorgetränkte Tuchspendersysteme für Flächendesinfektionsmittel. Eine Analyse vorhandener Berichte über Ausbrüche zeigt zudem, dass Gram-negative und multiresistente Erreger eine zunehmend häufige und ernste Gesundheitsgefahr im medizinischen Umfeld darstellen. In einigen Fällen ist es besonders schwierig, den Infektionserreger zu finden, weil er sich in Biofilmen verbirgt oder im sogenannten VBNC-Status befindet - viable but nonculturable (VBNC) bedeutet lebensfähig, aber nicht kultivierbar. In diesem Status entzieht sich der Mikroorganismus den konventionellen, auf Kultivierbarkeit basierten Nachweismethoden. In diesen Erkenntnissen liegt ein großes Präventionspotential, das noch nicht ausreichend genutzt wird. Neue und wiederauftretende Krankheitserreger, neuartige Nachweismethoden und verborgene Infektionsquellen sollten daher zukünftig größere Beachtung finden, auch wenn es darum geht, neue Medizinprodukte zu entwerfen oder Gebäude zu planen. Diese Erkenntnisse müssen mit einfließen in die Kernkompetenzen medizinischen Personals, in die Patientenaufklärung und die Aufklärung der Allgemeinbevölkerung sowie in die Strategien für die Prävention und Kontrolle von Infektionen in medizinischen und öffentlichen Bereichen sowie im privaten Umfeld.
    Keywords: Infection reservoir ; pathogen detection method ; outbreak ; hygiene ; viable but nonculturable status ; prevention strategy ; Infektionsquelle ; Infektionserreger ; Ausbruch ; Hygiene ; viable but nonculturable Status (VBNC) ; Nachweismethode ; Präventionsstrategie ; ddc: 610
    Language: English
    Type: article
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  • 6
    ISSN: 1432-1041
    Keywords: Zidovudine ; acquired immunodeficiency syndrome (AIDS) ; pharmacokinetics ; bioavailability ; food intake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The systemic availability of oral zidovudine has been studied in 13 patients with the acquired immunodeficiency syndrome (AIDS) dosed either fasting or with breakfast. The mean peak plasma concentration and AUC of zidovudine were significantly 2.8- and 1.4-times higher in fasting patients than in those treated during meal. In both conditions the mean half-life was about 1.5 h and the period of plasma zidovudine concentrations 〉1 μmol · l−1 was 2 h (NS). It is concluded that if zidovudine is taken on an empty stomach, high peak plasma concentrations and decreased variation in pharmacological parameters may be expected. Whether or not this will influence toxicity and efficacy remains to be shown.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Inflammatory exudates obtained in rats after subcutaneous implantation of carrageenin-soaked sponges were found to contain relatively large amounts of 15-hydroxy-5,8,11,13-eicosatetraenoic acid (15-HETE) and smaller amounts of cysteinyl-leukotrienes (LT) in addition to LTB4, thromboxane (TX) B2 and prostaglandin (PG) E2. Concentrations of 15-HETE and cysteinyl-LT were high 5 hours after sponge implantation and decreased significantly within 24 hours. This time-course, which is smilar to that of TXB2, but differs from that of PGE2, suggests migrating leukocytes as a major source of 15-HETE and cysteinyl-LT. Aspirin, sodium salicylate, dipyrone (100 mg/kg each) and indomethacin (2 and 20 mg/kg) decrease the concentrations of cyclooxygenase products of arachidonate metabolism, but did not significantly affect levels of 15-HETE. Cysteinyl-LT were increased by 20 mg/kg indomethacin, but remained unaffected by 2 mg/kg indomethacin and by the other non-steroidal anti-inflammatory drugs (NSAID) tested. 15-HETE and cysteinyl-LT could play a mediator role in inflammation. In addition, they could modulate the release and effects of other inflammatory mediators.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0630
    Keywords: 33.20E ; 42.55K ; 92.90
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract This paper describes a new method for the determination of the deuterium content in water samples. The absorption of the radiation of a cw deuterium fluoride laser by HDO in water vapor is measured by means of a nonresonant spectrophone (optoacoustic detector). This method enables one to evaluate the isotope ratio of hydrogen in a rather simple and straightforward way. Advantage is taken of the fact that HDO absorbs some of the DF laser lines whereas H2O shows no absorption. Due to the small concentration in natural water deuterium is practically entirely present as HDO. Therefore a selective determination of the deuterium content is possible. In the course of the investigation the absorption coefficients of HDO for the different laser lines were determined. It was thereby established that there exists a strong coincidence of an HDO absorption line with the 2P2 DF laser line. The detection sensitivity of the method was then examined for some selected laser lines. The concentration of HDO in natural water samples could be determined with an accuracy of better than 10%. The experiments, however, show that with appropriate improvements it should be possible to achieve an accuracy of better than 1%. This makes the method very interesting as an analytical tool in hydrology.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1435-1285
    Keywords: Key words sleep apnea – myocardial infarction – circadian rhythm ; Schlüsselwörter Schlafapnoe – Myokardinfarkt – zirkadiane Rhythmik
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Das Auftreten des Myokardinfarktes zeigt ein zirkadianes Muster mit einem Maximum in den frühen Morgenstunden. Bei Patienten mit schlafbezogenen Atmungsstörungen (SBAS) ist zu mutmaßen, daß diese aufgrund der akuten apnoeassoziierten Veränderungen von Hämodynamik, Blutgasen und Rheologie vermehrt Myokardinfarkte im Schlaf aufweisen. In dieser Untersuchung wird die zirkadiane Verteilung von Myokardinfarkten bei Patienten mit und ohne SBAS analysiert. Bei 59 von 89 männlichen Patienten, die konsekutiv innerhalb eines Zeitraums von 20 Monaten mit akutem Myokardinfarkt auf die Intensivstation aufgenommen wurden, konnte zwischen dem 6. und 10. Tag nach Infarkt (Meßzeitpunkt I), bei 43 der 59 Patienten zwischen dem 22. und 28. Tag nach Infarkt (Meßzeitpunkt II) eine nächtliche Langzeitregistrierung von transkutaner Sauerstoffsättigung, Herzfrequenz, Atemgeräuschen und Körperlage mittels 4-Kanal-Diagnostiksystem (MESAM IV) durchgeführt werden. Eine Schlafapnoe mit einem RDI≥10/h war zum MZP I bei 44,1 % der Patienten nachweisbar, zum MZP II bei 39,5 %. Bei 22 % der Patienten mit sicher festzulegendem Infarktzeitpunkt trat der Infarkt im Schlaf auf. Die Patienten mit Myokardinfarkt im Schlaf hatten im Vergleich zu Patienten mit Myokardinfarkt im Wachzustand einen deutlich höheren RDI (MZP I: 22,7 vs. 9,4/h; p=0,08; MZP II: 20,3 vs. 7,3/h; p〈0,05). 53,6 % aller Infarkte waren im Zeitraum von 5.00 bis 11.00 Uhr nachweisbar. Untersuchungen an größeren Patientenkollektiven sind notwendig, um die vorliegenden Ergebnisse sowie die Relevanz des kardiovaskulären Risikofaktors Schlafapnoe zu bestätigen.
    Notes: Summary Myocardial infarction shows a circadian pattern with a maximum in the early morning hours. In patients with sleep-related breathing disorders (SRBD), it is assumed that apnea-associated changes of hemodynamics, blood gases, and rheology lead to a higher frequency of myocardial infarction during sleep. This investigation analyzes the circadian pattern of myocardial infarction in patients with and without SRBD. Within a time period of 20 months, 89 male patients with acute myocardial infarction were consecutively admitted to the intensive care unit. A nocturnal long-term registration of oxygen saturation, heart rate, breathing sounds, and body position by means of a 4-channel recording system (MESAM IV) was carried out in 59 of the 89 patients 6 to 10 days (evaluation I) and in 43 of 59 patients 22 to 28 days after infarction (evaluation II). Sleep apnea with a respiratory-disturbance-index (RDI≥10/h was found in 44.1/39.5% of the patients (evaluation I/II). In 22 % of the patients, time of infarction was during a sleeping period. Patients with myocardial infarction during sleep had a clearly higher RDI in comparison to patients with a myocardial infarction during wakefulness (evaluation I: 22.7 versus 9.4/h; p=0.08;evaluationII: 20.3 versus 7.3;p〈0.05). 53.6 % of all myocardial infarctions occurred during the time period 5:00–11:00 a.m. Investigations in a larger number of patients are necessary to confirm these results as well as the relevance of sleep apnea as a cardiovascular risk factor.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1433-8580
    Keywords: Peptide-1(7–36) ; Physiologic incretin ; RINm5F cells ; GLP-1-receptor complex
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Glucagon-like peptide-1(7–36)amide [GLP-1(7–36)amide] is supposed to be an important physiologic incretin. Recently, high affinity receptors for GLP-1(7–36)amide have been demonstrated on rat insulinomaderived RINm5F cells. The present study examined the internalization and degradation of the GLP-1-receptor complex. Internalization of the peptide was time- and temperature-dependent. At 37°C binding and internalization was rapid. At 60 min 35% of125I-labeled GLP-1(7–36)amide was internalized. Incubation in the presence of increasing concentrations of nonlabeled GLP-1(7–36)amide resulted in a decrease of internalization of125I-labeled peptide indicating that this process is saturable. Incubation in the presence of 0.2 mM chloroquine, an inhibitor of intracellular hormone degradation, resulted in intracellular accumulation of125I-GLP-1(7–36)amide. HPLC-supported analysis of cell content after internalization of125I-GLP-1(7–36)amide during a 60-min incubation period at 37°C revealed an elution profile showing two maxima of radioactivity: one represented intact labeled GLP-1(7–36)amide, the other an intracellular degradation product of the peptide. Chloroquine caused a 5-fold increase of the peak representing intact125I-GLP-1(7–36)amide thus demonstrating inhibition of degradation of labelled peptide. Furthermore, a 4-fold increase of the other peak occurred possibly mirroring a delay of release of degradation products by chloroquine. It was excluded that chloroquine is able to interfere with GLP-1(7–36)amidebinding to its receptor.
    Type of Medium: Electronic Resource
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