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  • 1
  • 2
    Keywords: EXPRESSION ; proliferation ; INHIBITION ; MICE ; BONE-MARROW ; KERATINOCYTE GROWTH-FACTOR ; MOBILIZATION ; FRACTIONATED-IRRADIATION ; TONGUE EPITHELIUM
    Abstract: Early oral mucositis occurs in response to accidental upper partial body exposure as well as to radiotherapy in the head-and-neck region. This study was initiated to define the potential of mobilization of endogenous bone marrow (BM) stem cells by rHuG-CSF or of bone marrow transplantation (BMT) to reduce the effect of single-dose irradiation on mouse oral epithelium. A 3 x 3 mm2 area of the lower tongue surface of mice was irradiated with graded single doses (day 0). Mucosal ulceration was used as the endpoint for dose-response analyses. Stem cells were mobilized by rHuG-CSF (8 times/4 days), timed to achieve a maximum of circulating stem cells on days 0, +1, +4, +8 or +10. Alternatively, syngeneic BM was transplanted on these days. The ED50 (dose at which ulceration is expected in 50 % of the animals) for irradiation alone was 11.9 +/- 3.4 Gy. Mobilization of stem cells with a maximum of circulating stem cells on days +4, +8 or +10 significantly increased the ED50 to 25.5 +/- 10.1, 23.5 +/- 10.1 and 26.5 +/- 13.0 Gy. In contrast, a maximum of circulating stem cells on day 0 or day +1 had no effect. BMT did not result in a significant change in isoeffective doses in any of the protocols. In conclusion, the response of oral mucosal epithelium to a single-radiation exposure can be significantly reduced by post-exposure mobilization, but not by transplantation, of BM stem cells.
    Type of Publication: Journal article published
    PubMed ID: 24929346
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  • 3
    Keywords: GROWTH ; IRRADIATION ; radiotherapy ; carcinoma ; THERAPY ; DEPENDENCE ; ACCELERATED ELECTRONS ; FADU
    Abstract: The long-term goal to integrate laser-based particle accelerators into radiotherapy clinics not only requires technological development of high-intensity lasers and new techniques for beam detection and dose delivery, but also characterization of the biological consequences of this new particle beam quality, i.e. ultra-short, ultra-intense pulses. In the present work, we describe successful in vivo experiments with laser-driven electron pulses by utilization of a small tumour model on the mouse ear for the human squamous cell carcinoma model FaDu. The already established in vitro irradiation technology at the laser system JETI was further enhanced for 3D tumour irradiation in vivo in terms of beam transport, beam monitoring, dose delivery and dosimetry in order to precisely apply a prescribed dose to each tumour in full-scale radiobiological experiments. Tumour growth delay was determined after irradiation with doses of 3 and 6 Gy by laser-accelerated electrons. Reference irradiation was performed with continuous electron beams at a clinical linear accelerator in order to both validate the dedicated dosimetry employed for laser-accelerated JETI electrons and above all review the biological results. No significant difference in radiation-induced tumour growth delay was revealed for the two investigated electron beams. These data provide evidence that the ultra-high dose rate generated by laser acceleration does not impact the biological effectiveness of the particles.
    Type of Publication: Journal article published
    PubMed ID: 25600561
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  • 4
    Abstract: It is well known that exposures like those from (226)Ra, (224)Ra and Thorotrast((R)) injections increase the risk of neoplasia in bone marrow and liver. The thorium-based radioactive contrast agent Thorotrast((R)) was introduced in 1929 and applied worldwide until the 1950s, especially in angiography and arteriography. Due to the extremely long half-life of several hundred years and the life-long retention of the thorium dioxide particles in the human body, patients suffer lifetime internal exposure. The health effects from the incorporated thorium were investigated in a few cohort studies with a German study being the largest among them. This retrospective cohort study was set up in 1968 with a follow-up until 2004. The study comprises 2326 Thorotrast patients and 1890 patients of a matched control group. For those being alive at the start of the study in 1968 follow-up was done by clinical examinations on a biannual basis. For the others, causes of death were collected in various ways. Additionally, clinical, radiological and biophysical studies of patients were conducted and large efforts were made to best estimate the radiation doses associated with incorporation of the Thorotrast. The aim of this paper is to describe the cohort, important results and some open questions. The data from the German Thorotrast Study are available to other interested researchers. Information can be found at http://storedb.org .
    Type of Publication: Journal article published
    PubMed ID: 27154786
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  • 5
    Keywords: CANCER ; radiotherapy ; Germany ; THERAPY ; imaging ; RESOLUTION ; radiation ; BIOLOGY ; PROTON ; DAMAGE ; BEHAVIOR ; DOSE DISTRIBUTIONS ; SCIENCE ; dosimetry ; BEAMS ; PHOTON ; DOSE-RATE
    Abstract: Modern radiotherapy facilities for cancer treatment such as the Heavy Ion Therapy Center (HIT) in Heidelberg, Germany, allow for sub-millimeter precision in dose deposition. For measurement of such dose distributions and characterization of the particle beams, detectors with high spatial resolution are necessary. Here, a detector based on the commercially available COTS photodiode (BPW-34) is presented. When applied in hadronic beams of protons and carbon ions, the detector reproduces dose distribution well, but its response decreases rapidly by radiation damage. However, for MeV photon beams, the detector exhibits a similar behavior as found in diode detectors usually applied in radiotherapy
    Type of Publication: Journal article published
    PubMed ID: 20549226
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  • 6
    Keywords: EPIDEMIOLOGY ; EXPOSURE ; RISK ; HEALTH ; CHILDREN ; DOWN-SYNDROME ; CHERNOBYL ACCIDENT ; CONGENITAL-MALFORMATIONS ; LEVEL IONIZING-RADIATION ; LOTHIAN REGION
    Abstract: Living in the vicinity of nuclear power plants (NPP) is discussed here in terms of adverse health effects. A prospective population-based cohort study was conducted to evaluate whether the prevalence of birth defects in the vicinity of NPPs is elevated and scrutinize a possible distance correlation. A birth cohort born to mothers living within 10 km of two selected NPPs (study region) was compared to a region without NPP (comparison region), and an active surveillance of all live births, stillbirths, and induced abortions in the defined regions was performed. Between 01/2007 and 02/2008, all newborns were examined by specially trained study paediatricians according to the protocols of the Birth Registry Mainz Model. The cohort consisted of 5,273 infants (90% completeness). The outcome measure was an infant with birth defect(s). The prevalence of infants with birth defects was 4.5% in the study region and 4.7% in the comparison region, which corresponds to a relative risk (RR) of 0.94 (lower 95% confidence level (CL): 0.76). Thus, the prevalence of birth defects in the regions surrounding NPPs was not increased compared to those of the comparison region. Adjustment for potential confounders did not substantially change the result (RR 0.90, lower 95% CL 0.73). The adjusted and unadjusted distance approach (1/distance in km) did not show any correlation to vicinity to a NPP (p = 0.38). Specifically, within the study region, the prevalence of birth defects showed no upward trend with decreasing distance. Birth defect prevalence and most descriptive parameters in the comparison region were identical to those in the Birth Registry Mainz Model
    Type of Publication: Journal article published
    PubMed ID: 21213111
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  • 7
    ISSN: 1432-2099
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Zusammenfassung An getrocknetem Federkeratin wurde nach Röntgenbestrahlung mittels ESR noch nach Bestrahlungsende die langsame Neubildung eines Radikals im Gebiet niedriger g-Faktoren beobachtet. Die Geschwindigkeitb der Reaktion nimmt mit der Meßtemperatur zu. Es ergab sich ein nahezu linearer Zusammenhang zwischen Inb und 1/T; als Aktivierungsenergie wurde ein Wert vonΔE=0,6 eV gefunden. Weiter ist die momentane Reaktionsgeschwindigkeit in erster Näherung proportional zur Differenz zwischen dem momentanen und dem Sättigungswert der Konzentration des gebildeten Radikals. Die Reaktion ist als indirekter Wirkungsmechanismus in Festkörpern zu verstehen.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2099
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Description / Table of Contents: Summary Experiments were carried out with a 15-MeV-betatron. By means of a special electronic device it was possible to quench radiation pulses in the injector of the accelerator. In this way the frequency of radiation pulses was varied between 2 and 50 pps. The ultrafractionated radiation was compared with the continuous gamma-radiation of a 1000-curie-60Co-source. The influence of ultrafractionation on the relative biological efficiency of fast electrons was tested in embryos of drosophila melanogaster of different stages of development. In these experiments either the average dosage rate or the dose of the particular radiation pulses was kept constant. Dose-effect curves show a significant influence of the pulse frequency on the percentage of killed “eggs”, which may be due to the existence of an effect of recovery.
    Notes: Zusammenfassung Mit Hilfe eines speziell für diese Untersuchungen entwickelten elektronischen Gerätes ist es möglich, die Strahlungsimpulse eines 15-MeV-Betatrons wahlweise zu unterdrücken und dadurch die Impulsfrequenz dieses Beschleunigers zwischen 2 und 50 Hz zu variieren. Als Vergleich diente die kontinuierliche Gamma-Strahlung einer 1000-Curie-60Co-Quelle (Gammatron). Der Einfluß der Ultrafraktionierung auf die relative biologische Wirksamkeit schneller Elektronen wurde an „Eiern“ von Drosophila melanogaster verschiedener Entwicklungsstadien getestet. Hierbei wurde entweder die mittlere Dosisleistung oder die Dosis der einzelnen Strahlungsimpulse konstant gehalten. Die Dosis-Effektkurven zeigen einen deutlichen Einfluß der Impulsfrequenz auf die Abtötungsrate, der auf das Vorhandensein eines Erholungseffektes hindeutet.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-2099
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Zusammenfassung Der Zufallscharakter zellulärer Strahleneffekte muß nicht stets auf einer Variabilität der Strahlenempfindlichkeit oder auf einer inhomogenen Verteilung der absorbierten Energie auf die Einheiten einer bestrahlten Population oder ihre „Treffbereiche“ beruhen, sondern kann auch bei einer kontinuierlich mit der Dosis zunehmenden „dispersen Vorschädigung“aller Einheiten zustandekommen, wenn diese die inhärente Labilität des lebenden Systems erhöht. Das zufallsartige „kritische Ereignis“, das über das Eintreten der Testreaktion entscheidet, muß daher nicht unbedingt schon durch die Energieabsorption gegeben sein, sondern kann in einem späteren Glied der Ursachenkette liegen. Charakteristisch für den Verlauf von Überlebenskurven ist ihre Neigung in halblogarithmischer Darstellung; wir bezeichnen diese Größe als „Reaktivität“. Kurvenformen, die bisher durch den Mehrtreffer- oder Mehrbereichsansatz gedeutet wurden, ergeben sich auch, wenn man allein die Tatsache berücksichtigt, daß die Reaktivität mit der Dosis ansteigen kann. Strebt die Reaktivität mit steigender Dosis einem Endwert zu, so kann dies darauf beruhen, daß eine dem vitalen Objekt inhärente Kompensationsfähigkeit sich mit der Dosis erschöpft. In einigen Fällen wird die biochemische Natur einer solchen Kompensationsfähigkeit bereits deutlich.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-2099
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Physics
    Notes: Zusammenfassung 1 Durch Bestrahlung 5stündiger Vorpuppen von Drosophila melanogaster wird die Flügelstellung der adulten Fliege im Sinne einer Spreizung verändert. Die Entstehung dieser Strahlenmodifikation, die gleichzeitig eine Phänokopie darstellt, ist von genetischen Faktoren abhängig, da sich zwei verschiedene Inzuchtstämme der Wildform in ihrer Strahlensensibilität voneinander unterscheiden. 2. Ultraharte, energiereiche Betatronstrahlen (30-MeV-Elektronen und 31-MeV-Photonen) sind in ihrer biologischen Wirksamkeit den gleichen Meßwerten von 180-keV-Strahlen deutlich unterlegen. Interessanterweise liegt die RBW für 31-MeV-Photonen mit 0,8 höher als die RBW für 30-MeV-Elektronen mit dem Werte von 0,7. Die 31-MeV-Photonen mit einer durchschnittlichen linearen Ionisationsdichte von 6,3 Ionenpaaren/μ sind damit biologisch effektiver als die schnellen 30-MeV-Elektronen, bei denen entlang der primären Bahnspur mit lediglich 3 Ionenpaaren/μ zu rechnen ist. 3. Bestrahlung in reinem N2 verhindert drastisch die Entstehung der Anomalie (Reduktion einer 98% igen Schädigung nach 5000 r 30-MeV-Elektronen auf 5%). Es konnte kein Unterschied im Ausmaß des Schutzeffektes für 30-MeV-Elektronen und 180-keV-Photonen festgestellt werden. 4. Es wird die Entstehung der Entwicklungsstörung diskutiert. Die gleichzeitige Abhängigkeit des Effektes vom Sauerstoffgehalt des Milieus und von der linearen Energieübertragung spricht für die große Beteiligung chemisch aktiver Bestrahlungsprodukte des Wassers an der Strahlenschädigung. Als weitere Hypothese zur Deutung des Sauerstoffeffektes wird eine Blockierung von Vorgängen im makromolekularen Bereich (Entstehung von RNS, usw.) durch Sauerstoffentzug postuliert.
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