Einfluss der Genkopiezahlvariation der beta-Defensine drei und vier auf die Inzidenz der Sepsis

In der vorliegenden Arbeit wurde untersucht, ob eine unterschiedliche Anzahl an Genkopien der humanen beta-Defensine drei und vier einen Einfluss auf die Inzidenz der Sepsis haben. Es zeigte sich kein signifikanter Unterschied der Genkopiezahlen zwischen septischen und gesunden Individuen, so dass für die Entstehung einer Sepsis die Anzahl an Genkopien der Defensine keinen Einfluss zu besitzen scheint. Ferner ergab die Genkopiequantifizierung eine intraindividuelle Variabilität der beta-Defensine drei und vier

Cardiac Glycosides Induce Cell Death in Human Cells by Inhibiting General Protein Synthesis

BACKGROUND: Cardiac glycosides are Na(+)/K(+)-pump inhibitors widely used to treat heart failure. They are also highly cytotoxic, and studies have suggested specific anti-tumor activity leading to current clinical trials in cancer patients. However, a definitive demonstration of this putative anti-cancer activity and the underlying molecular mechanism has remained elusive. METHODOLOGY/PRINCIPAL FINDINGS: Using an unbiased transcriptomics approach, we found that cardiac glycosides inhibit general protein synthesis. Protein synthesis inhibition and cytotoxicity were not specific for cancer cells as they were observed in both primary and cancer cell lines. These effects were dependent on the Na(+)/K(+)-pump as they were rescued by expression of a cardiac glycoside-resistant Na(+)/K(+)-pump. Unlike human cells, rodent cells are largely resistant to cardiac glycosides in vitro and mice were found to tolerate extremely high levels. CONCLUSIONS/SIGNIFICANCE: The physiological difference between human and mouse explains the previously observed sensitivity of human cancer cells in mouse xenograft experiments. Thus, published mouse xenograft models used to support anti-tumor activity for these drugs require reevaluation. Our finding that cardiac glycosides inhibit protein synthesis provides a mechanism for the cytotoxicity of CGs and raises concerns about ongoing clinical trials to test CGs as anti-cancer agents in humans

Comparison of multiplex ligation-dependent probe amplification and real-time PCR accuracy for gene copy number quantification using the beta-defensin locus

The reliable quantification of gene copy number variations is a precondition for future investigations regarding their functional relevance. To date, there is no generally accepted gold standard method for copy number quantification, and methods in current use have given inconsistent results in selected cohorts. In this study, we compare two methods for copy number quantification. beta-defensin gene copy numbers were determined in parallel in 80 genomic DNA samples by real-time PCR and multiplex ligation-dependent probe amplification (MLPA). The pyrosequencing-based paralog ratio test (PPRT) was used as a standard of comparison in 79 out of 80 samples. Realtime PCR and MPLA results confirmed concordant DEFB4, DEFB103A, and DEFB104A copy numbers within samples. These two methods showed identical results in 32 out of 80 samples; 29 of these 32 samples comprised four or fewer copies. The coefficient of variation of MLPA is lower compared with PCR. In addition, the consistency between MLPA and PPRT is higher than either PCR/MLPA or PCR/PPRT consistency. In summary, these results suggest that MLPA is superior to real-time PCR in beta-defensin copy number quantification

Interference of Mycoplasma Infection in a Gene Expression Study: It Was the Environment and Not the Gene▿

We show that short-term exposure to doxycycline, as used in tetracycline-inducible gene expression models, protects cells from stress-induced death in cultures infected with Mycoplasma arginini. Coinciding with the expected maximum level of gene activity, antimicrobial effects of tetracyclines might be mistaken for antiapoptotic properties of the expressed gene product

Characterization and referral patterns of ST-elevation myocardial infarction patients admitted to chest pain units rather than directly to catherization laboratories. Data from the German Chest Pain Unit Registry

Background: Direct transfer to the catheterization laboratory for primary percutaneous coronary intervention (PCI) is standard of care for patients with ST-segment elevation myocardial infarction (STEMI). Nevertheless, a significant number of STEMI-patients are initially treated in chest pain units (CPUs) of admitting hospitals. Thus, it is important to characterize these patients and to define why an important deviation from recommended clinical pathways occurs and in particular to quantify the impact of deviation on critical time intervals. Methods and results: 1679 STEMI patients admitted to a CPU in the period from 2010 to 2015 were enrolled in the German CPU registry (8.5% of 19,666). 55.9% of the patients were delivered by an emergency medical system (EMS), 16.1% transferred from other hospitals and 15.2% referred by a general practitioner (GP). 12.7% were self-referrals. 55% did not get a pre-hospital ECG. Compared to the EMS, referral by GPs markedly delayed critical time intervals while a pre-hospital ECG demonstrating ST-segment elevation reduced door-to-balloon time. When compared to STEMI patients (n = 21,674) enrolled in the ALKK-registry, CPU-STEMI patients had a lower risk profile, their treatment in the CPU was guideline-conform and in-hospital mortality was low (1.5%). Conclusions: CPU-STEMI patients represent a numerically significant group because a pre-hospital ECG was not documented. Treatment in the CPU is guideline-conform and the intra-hospital mortality is low. The lack of a pre-hospital ECG and admission via the GP substantially delay critical time intervals suggesting that in patients with symptoms suggestive an ACS, the EMS should be contacted and not the GP. (C) 2016 Elsevier Ireland Ltd. All rights reserved