Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: radiotherapy ; SUSCEPTIBILITY ; DAMAGE ; MUTATIONS ; MAMMALIAN-CELLS ; OXIDATIVE STRESS ; METAANALYSIS ; SINGLE-NUCLEOTIDE POLYMORPHISMS ; GENOME-WIDE ASSOCIATION ; MITOCHONDRIAL-DNA
    Abstract: Base excision repair (BER) removes DNA damage induced by endogenous reactive oxygen species or ionizing radiation, important breast cancer risk factors. Genetic variation associated with impaired BER might thus increase breast cancer risk. Therefore, we assessed risk associations of 123 common single nucleotide polymorphisms (SNPs) in 19 BER genes in 1,639 postmenopausal breast cancer cases and 1,967 controls from the German population-based case-control study MARIE. SNPs were tagging SNPs representing genetic variation across the gene together with potentially functional SNPs. Risk associations were assessed using conditional logistic regression, adjusted for potential breast cancer risk factors. Significant associations between polymorphisms and breast cancer risk were found for one SNP in PARP2 and three SNPs in the mitochondrial DNA polymerase gamma, POLG. A SNP in the promoter region of POLG (rs2856268, A〉G) showed a protective effect for homozygous GG carriers (odds ratio 0.81, 95% confidence intervals 0.65-1.00). Joint analysis of an enlarged sample set and haplotype analysis supported the results for POLG. Quantification of POLG mRNA expression in lymphocytes of 148 breast cancer patients revealed higher mRNA levels for rs2856268 GG carriers (p value = 0.038). A luciferase promoter assay showed significant differences between constructs harboring the respective alleles. Taken together, our results suggest that genetic variation in the POLG promoter region affects DNA polymerase gamma levels in mitochondria. This could contribute to the reported increase in mitochondrial mutation frequency resulting in dysfunction and altered breast cancer risk. Risk effects and the functional impact of the POLG promoter variant require further confirmation.
    Type of Publication: Journal article published
    PubMed ID: 22684821
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Abstract: Base excision repair (BER) removes DNA damage induced by endogenous reactive oxygen species or ionizing radiation, important breast cancer risk factors. Genetic variation associated with impaired BER might thus increase breast cancer risk. Therefore, we assessed risk associations of 123 common single nucleotide polymorphisms (SNPs) in 19 BER genes in 1,639 postmenopausal breast cancer cases and 1,967 controls from the German population-based case-control study MARIE. SNPs were tagging SNPs representing genetic variation across the gene together with potentially functional SNPs. Risk associations were assessed using conditional logistic regression, adjusted for potential breast cancer risk factors. Significant associations between polymorphisms and breast cancer risk were found for one SNP in PARP2 and three SNPs in the mitochondrial DNA polymerase gamma, POLG. A SNP in the promoter region of POLG (rs2856268, A〉G) showed a protective effect for homozygous GG carriers (odds ratio 0.81, 95% confidence intervals 0.65-1.00). Joint analysis of an enlarged sample set and haplotype analysis supported the results for POLG. Quantification of POLG mRNA expression in lymphocytes of 148 breast cancer patients revealed higher mRNA levels for rs2856268 GG carriers (p value = 0.038). A luciferase promoter assay showed significant differences between constructs harboring the respective alleles. Taken together, our results suggest that genetic variation in the POLG promoter region affects DNA polymerase gamma levels in mitochondria. This could contribute to the reported increase in mitochondrial mutation frequency resulting in dysfunction and altered breast cancer risk. Risk effects and the functional impact of the POLG promoter variant require further confirmation.
    Type of Publication: Journal article published
    PubMed ID: 22684821
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: IN-VIVO ; LUNG-CANCER ; PROGRESSION ; intraepithelial neoplasia ; C-MYC ; KRAS ; SELECTIVE-INHIBITION ; ENGINEERED MOUSE MODELS ; BROMODOMAIN INHIBITION ; DRUG-COMBINATION
    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal human cancers and shows resistance to any therapeutic strategy used. Here we tested small-molecule inhibitors targeting chromatin regulators as possible therapeutic agents in PDAC. We show that JQ1, an inhibitor of the bromodomain and extraterminal (BET) family of proteins, suppresses PDAC development in mice by inhibiting both MYC activity and inflammatory signals. The histone deacetylase (HDAC) inhibitor SAHA synergizes with JQ1 to augment cell death and more potently suppress advanced PDAC. Finally, using a CRISPR-Cas9-based method for gene editing directly in the mouse adult pancreas, we show that de-repression of p57 (also known as KIP2 or CDKN1C) upon combined BET and HDAC inhibition is required for the induction of combination therapy-induced cell death in PDAC. SAHA is approved for human use, and molecules similar to JQ1 are being tested in clinical trials. Thus, these studies identify a promising epigenetic-based therapeutic strategy that may be rapidly implemented in fatal human tumors.
    Type of Publication: Journal article published
    PubMed ID: 26390243
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: CANCER ; EXPRESSION ; SURVIVAL ; IN-VIVO ; THERAPY ; GENE-EXPRESSION ; PROTEIN ; ACTIVATION ; FAMILY ; TRANSCRIPTION FACTORS ; PROMOTER ; REPRESSION ; METHYLATION ; histone modification ; BINDING DOMAIN ; GRANULOSA-CELL TUMORS
    Abstract: Human lung cancer is a disease with high incidence and accounts for most cancer-related deaths in both men and women. Metastasis is a common event in non-small cell lung carcinoma (NSCLC), diminishing the survival chance of the patients with this type of tumor. It has been shown that MYC is involved in the development of metastasis from NSCLC, but the mechanism underlying this switch remained to be identified. Here, we focus on GATA4 as a MYC target in the development of metastasis with origin in lung adenocarcinoma, the most common type of NSCLC. Epigenetic alterations at the GATA4 promoter level were observed after MYC expression in lung adenocarcinoma in vivo and in vitro. Such alterations include site-specific demethylation that accompanies the displacement of the MYC-associated zinc finger protein (MAZ) from the GATA4 promoter, which leads to GATA4 expression. Histone modification analysis of the GATA4 promoter revealed a switch from repressive histone marks to active histone marks after MYC binding, which corresponds to active GATA4 expression. Our results thus identify a novel epigenetic mechanism by which MYC activates GATA4 leading to metastasis in lung adenocarcinoma, suggesting novel potential targets for the development of antimetastatic therapy.
    Type of Publication: Journal article published
    PubMed ID: 23239811
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1432-1238
    Keywords: Airway occlusion pressure ; Mechanical ventilation ; Weaning ; Respirator technology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The airway occlusion pressure, P0.1, is an index for the neuro-muscular activation of the respiratory system. It has been shown to be a very useful indicator for the ability of patients receiving ventilatory support to be weaned from mechanical ventilation. Since the standard measurement technically complex, it is not widely available for clinical purposes. For that reason a P0.1 measurement technique was developed as an integrated function in a standard respirator (Evita, Dräger, Lübeck, Germany). This technique is easy to use and does not need any further equipment. We validated this new technique by comparing it to standard P0.1 measurements in a mechanical lung model as well as in ventilated patients. In the lung model we found a correlation between the Evita measurement and standard measurements ofr=0.99. In 6 ventilated patients the correlation wasr=0.78. Since the Evita P0.1 and the standard measurement had to be performed during two different breaths, this little poorer correlation in patients may be due to a significant breath-by-breath variability in P0.1. Comparing the Evita P0.1 and the standard measurement within one breath resulted in a clearly better correlation (r=0.89). We conclude that this new measurement technique provides and easy and accurate P0.1 measurement using standard respiratory equipment when tested in a lung model. In patient measurements the method is less precise, which is probably due to the variable waveforms of the inspiratory driving pressure seen in patients, for example when intrinsic PEEP is present. However, the new method makes the P0.1 measurement as a “bed-side” method clinically available, although the values should be interpreted cautiously.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1433-0458
    Keywords: Schlüsselwörter Kinetose ; Space Adaption Syndrome ; Otolithen ; Sakkulus ; Utrikulus ; Key words Motion sickness ; Space adaption syndrome ; Otoliths ; Saccule ; Utricle
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Several different theories exist about the orign of kinetosis and the space adaption syndrome, with individual sensitivities differing significantly. One explanation involves the hypothesis of a different otolith mass between the right and left statolith organ and especially a difference in the utricles. A difference in mass results in a different sensitivity to acceleration. For this reason we measured interindividual variances in saccular and utricular otolith mass. Since the anatomy of the vestibular organ in vertebrates is based as similar principles, we selected fish (salmon and trout) as our study model to facilitation preparations. The maximum difference in mass in the saccule was 17% and was generally smaller in the utricle, although in individual cases was much higher. We assume that a misbalanced sensitivity of the statolith organs occurs but is totally compensated for by the vestibular system as long as physiological motion patterns take place. Decompensation leads to kinetosis under non-physiological motion patterns. When the vestibular system is better balanced and has an equally distributed otolith mass to both sides, the possibility for developing kinetosis or space adaption syndrome is much less likely.
    Notes: Zusammenfassung Über die Entstehung der Kinetose und des „space adaption syndrome” (SAS) gibt es zahlreiche Vorstellungen, wobei die individuelle Empfindlichkeit sehr unterschiedlich ist. Die Annahme einer zwischen rechtem und linkem Otolithenorgan, speziell dem Utrikulus, ungleich verteilten Otolithenmasse vermag dieses möglicherweise zu erklären. Eine ungleiche Masse bewirkt eine ungleiche Sensibilität der Organe auf Beschleunigungsreize. Deshalb wurden Messungen der individuellen Streubreite der Otolithenmassen in Sakkulus und Utrikulus vorgenommen. Bei ubiquitär verbreitetem Bauprinzip des Vestibularorgans wurde aus präparatorischen Gründen der Fisch (Lachs, Forelle) gewählt. Die Gewichtsdifferenzen waren im Sakkulus maximal 17%, im Utrikulus meist geringer, allerdings vereinzelt auch erheblich größer. Es muß angenommen werden, daß die seitendifferente Sensibilität der Otolithenorgane im Rahmen normaler Bewegungsreize vom vestibulären System akzeptiert und vollständig kompensiert werden kann. Nur unter unphysiologischen Bewegungsmustern kommt es zur Dekompensation und Kinetoseentwicklung. Bei seitengleich verteilter Otolithenmasse ist aufgrund einer nicht erforderlichen „Vorkompensation” ein wesentlich stabileres vestibuläres System anzunehmen. Die Möglichkeit eine Kinetose oder ein SAS zu entwickeln ist wahrscheinlich deutlich geringer.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1432-055X
    Keywords: Schlüsselwörter Assistierte Spontanatmung ; Entwöhnung von der Beatmung ; Atemarbeit ; Key words Assisted spontaneous breathing ; Weaning from mechanical ventilation ; Work of breathing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Abstract Study objective: To investigate whether automatic tube compensation (ATC) or conventional pressure support (PS) is suit- able to compensate for the work of breathing imposed by the breathing circuit without altering the breathing pattern. Methods: Breathing pattern and work of breathing were measured in healthy volunteers. After a 20 min period of quiet breathing through a mouth piece (control) the volunteers were breathing through a 8.0 mm ID endotracheal tube (ETT) with four different settings: CPAP at 0 mbar, ATC, PS 5 mbar, PS 10 mbar. Each mode was applied for a 20 min period. At the end of each period data from 10 consecutive breaths were analyzed and aver-aged. Tidal volume (VT), breathing frequency (f), and minute ventilation (Ve) were determined from the stored gas flow tracings. Work of breathing was assessed as the pressure time product (PTP) calculated from the transdiaphragmatic pressure (Pdi) using a combined esophageal and gastric balloon catheter. Results: During the control period the breathing pattern was as follows: VT=882±277 ml, f=13,7±5/min, Ve=11,5±4,2 L/min. Maximal Pdi was 9,2±5,4 mbar and PTP was 11,3±7,1 mbar×s. Breathing CPAP through the ETT resulted in a slight increase in Pdi (10,8±5,4 mbar) and PTP (14,8±10,4 mbar×s) with an unchanged breathing pattern. How-ever, for the same amount of unloading from respiratory workload ATC did not alter the breathing pattern, whereas PS 5 mbar and PS 10 mbar resulted in a clear increase in VT (1014±202 ml, 1336±305 ml, respectively). Conclusion: From the presented data in healthy volunteers it might be concluded that ATC and PS 5 mbar and 10 mbar are suitable modes for unloading the respiratory system from work imposed by the breathing circuit. ATC does not alter the breathing pattern in contrast to PS which results in an increased tidal volume. Therefore, the exact compensa-tion of the work imposed by the ETT during ATC seems to be advantageous over ATC to assess the actual breathing pattern.
    Notes: Zusammenfassung Fragestellung: Ist die automatische Tubuskompensation (ATC) oder die konventionelle inspiratorische Druckunterstützung (pressure support, PS) geeignet, die zusätzliche, durch den endotrachealen Tubus und das Beatmungsgerät entstehende, Atemarbeit zu kompensieren? Methodik: In dieser Untersuchung an freiwilligen gesunden Probanden wurden die Atemarbeit und das Atemmuster gemessen. Nach einer Kontrollperiode mit Atmung über ein Mundstück atmeten die Probanden durch einen 8,0 mm Endotrachealtubus mit fünf verschiedenen Einstellungen: Kontinuierlich positiver Atemwegsdruck (CPAP) von 0 mbar, ATC während Inspiration, PS 5 mbar, PS 10 mbar. Jeder Modus wurde 20 min angewendet, bevor die Messung der Daten als Mittelwert von 10 konsekutiven Atemzügen vorgenommen wurde. Das Atemzugvolumen (VT), die Atemfrequenz (f) und das resultierende Atemminutenvolumen (Ve) wurden aus den gespeicherten Gasflußkurven bestimmt. Die Atemarbeit wurde als transdiaphragmaler Druck (Pdi) mit Hilfe eines Doppelballonkatheters im Magen und Ösophagus gemessen. Hiervon wurde das Druck-Zeit-Produkt (PTP) als Integral über die Inspirationszeit abgeleitet. Ergebnisse: Während der Kontrollphase betrugen VT=882±277 ml, f=13,7±5,0/min, so daß ein Ve von 11,5±4,2 l/min resultierte. Der maximale Pdi betrug im Mittel 9,2±5,4 mbar, das PTP 11,3±7,1 mbar×s. Bei Atmung durch einen endotrachealen Tubus ergaben sich ein leichter Anstieg des Pdi (10,8±5,4 mbar) und des PTP (14,8±10,4 mbar×s) bei relativ unverändertem Atemmuster. Während ATC zu einer Entlastung der Atemarbeit führte, ohne das Atemmuster zu beeinträchtigen, resultierten PS 5 mbar und PS 10 mbar in einer deutlichen Zunahme des VT auf 1014±202 ml bzw. 1336±305 ml bei einer vergleichbaren Abnahme der Atemarbeit. Schlußfolgerungen: Bei Probanden können sowohl ATC als auch PS zur Kompensation zusätzlicher Atemarbeit eingesetzt werden. Während das Atemmuster bei Anwendung von ATC dem der Spontanatmung ohne Tubus gleicht, führt PS zu einer deutlichen Erhöhung des Atemzugvolumens. Durch die gezielte Wegnahme lediglich der zusätzlichen Atemarbeit scheint ATC das bessere Verfahren zur Abschätzung des spontanen Atemmusters zu sein.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 1432-0630
    Keywords: PACS: 61.72.Tt; 78.30.Am; 78.90.+t
    Source: Springer Online Journal Archives 1860-2000
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Abstract. The lattice damage of silicon produced by ion implantation at extremely high current density of 0.8 A/cm2 (2.5×1018 cm-2 s-1) was investigated. In a focused ion beam system, implantation was carried out with 70 keV Co ions, fluences of 1.2×1016 cm-2 and 6.7×1015 cm-2 into Si (111) at room temperature and elevated temperatures between 355 °C and 400 °C. Radiation damage measurements were performed by Rutherford backscattering/channeling spectroscopy and micro-Raman analysis. The radiation damage was studied as a function of pixel dwell-time and implantation temperature. The critical temperature for amorphization increases with current density. Although the fluence of the focused ion implantation was constant, crystalline layers were obtained for short and amorphous layers for long pixel dwell-times. The critical dwell-time of crystalline/amorphous transition increases with implantation temperature. From the results a typical time for defect annealing of 10-5 s at 400 °C and an activation energy of (2.5±0.6) eV were deduced.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1573-1561
    Keywords: Onion fly ; Delia antiqua ; Diptera ; Anthomyiidae ; Erwinia carotovora varcarotovora ; Klebsiella pneumoniae ; food attractant ; ovipositional stimulant ; dipropyl disulfide ; 2-phenylethanol ; pentanoic acid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract Decomposing onions at certain microbial successional stages produce potent volatile attractants and ovipositional stimulants of the onion fly,Delia antiqua (Diptera: Anthomyiidae). A reproducible source of these compounds was obtained by culturingErwinia carotovora var.carotovora (EC) on sterile onion tissue. In laboratory choice tests, EC-inoculated onion was more attractive thanKlebsiella pneumoniae (KP) cultured on onion, EC cultured on potato (a nonhost of onion fly), or the chemical synthetic baits dipropyl disulfide and an aqueous solution of 2-phenylethanol and pentanoic acid. Onion flies were mildly attracted to potato after inoculation with EC, but females did not accept EC-inoculated potato for oviposition. This work emphasizes that sources of semiochemicals may need to be defined microbiologically as well as physically and chemically.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Liebigs Annalen 89 (1854), S. 112-114 
    ISSN: 0075-4617
    Keywords: Chemistry ; Organic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...