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Golka K.,Leibniz Research Center for Working Environment and Human Factors
Frontiers in bioscience (Elite edition) | Year: 2012

There is a considerable discrepancy between the number of identified occupational-related bladder cancer cases and the estimated numbers particularly in emerging nations or less developed countries where suitable approaches are less or even not known. Thus, within a project of the World Health Organisation Collaborating Centres in Occupational Health, a questionnaire of the Dortmund group, applied in different studies, was translated into more than 30 languages (Afrikaans, Arabic, Bengali, Chinese, Czech, Dutch, English, Finnish, French, Georgian, German, Greek, Hindi, Hungarian, Indonesian, Italian, Japanese, Kannada, Kazakh, Kirghiz, Korean, Latvian, Malay, Persian (Farsi), Polish, Portuguese, Portuguese/Brazilian, Romanian, Russian, Serbo-Croatian, Slovak, Spanish, Spanish/Mexican, Tamil, Telugu, Thai, Turkish, Urdu, Vietnamese). The bipartite questionnaire asks for relevant medical information in the physician's part and for the occupational history since leaving school in the patient's part. Furthermore, this questionnaire is asking for intensity and frequency of certain occupational and non-occupational risk factors. The literature regarding occupations like painter, hairdresser or miner and exposures like carcinogenic aromatic amines, azo dyes, or combustion products is highlighted. The questionnaire is available on www.ifado.de/BladderCancerDoc.

Watzl C.,Leibniz Research Center for Working Environment and Human Factors
Advances in Immunology | Year: 2014

The functions of Natural Killer (NK) cells are regulated by a highly redundant set of germline-encoded surface receptors that can inhibit or activate NK cell activities. NK cells can be activated by cytokines or through the interaction with transformed or infected cells. This typically results in the production of cytokines, chemokines, and the induction of cellular cytotoxicity. However, the reactivity of NK cells is modulated on various levels and shaped by processes such as development, education, priming, exposure to antigens and cytokines, and the formation of memory-like phenotypes. Here, I will summarize our current understanding of these processes and describe how they influence NK cell reactivity on a molecular level. © 2014 Elsevier Inc.

Bezler M.,Max Planck Institute of Biochemistry | Hengstler J.G.,Leibniz Research Center for Working Environment and Human Factors | Ullrich A.,Max Planck Institute of Biochemistry
Molecular Oncology | Year: 2012

Resistance to chemotherapy is a serious problem for the successful treatment of ovarian cancer patients but signalling pathways that contribute to this chemoinsensitivity are largely unknown. We demonstrate that the chemotherapeutic drug doxorubicin induces activation of the HER3-PI3K-AKT signalling cascade in ovarian cancer cells. We further show that the induction of this anti-apoptotic signalling pathway is based on upregulated expression of HER3 ligands, their shedding by the metalloprotease ADAM17, and is dependent on the HER2 receptor. The doxorubicin-mediated activation of this important survival cascade can be blocked by the kinase inhibitors lapatinib or erlotinib as well as by the therapeutic monoclonal antibody trastuzumab. Inhibition of the doxorubicin-induced activation of HER3-PI3K-AKT signalling significantly increased apoptosis of ovarian cancer cells. Besides doxorubicin, treatment of cells with cisplatin resulted in activation of the HER3 receptor whereas other chemotherapeutics did not show this effect. The increase in HER3 phosphorylation was detected in well-established ovarian cancer cell lines which originate from patients previously treated with these chemotherapeutic drugs. Based on these results, we postulate that activation of the HER3-PI3K-AKT cascade represents a major mechanism of chemoresistance in ovarian cancer. © 2012 Federation of European Biochemical Societies.

Gajewski P.D.,Leibniz Research Center for Working Environment and Human Factors | Falkenstein M.,Leibniz Research Center for Working Environment and Human Factors
Frontiers in Human Neuroscience | Year: 2012

Cognitive control functions decline with increasing age. The present study examines if different types of group-based and trainer-guided training effectively enhance performance of older adults in a task switching task, and how this expected enhancement is reflected in changes of cognitive functions, as measured in electrophysiological brain activity (event-related potentials). One hundred forty-one healthy participants aged 65 years and older were randomly assigned to one of four groups: physical training (combined aerobic and strength training), cognitive training (paper-pencil and computer-aided), relaxation and well-ness (social control group), and a control group that did not receive any intervention. Training sessions took place twice a week for 90min for a period of 4months.The results showed a greater improvement of performance for attendants of the cognitive training group compared to the other groups. This improvement was evident in a reduction of mixing costs in accuracy and intraindividual variability of speed, indexing improved maintenance of multiple task sets in working memory, and an enhanced coherence of neuronal processing. These findings were supported by event-related brain potentials which showed higher amplitudes in a number of potentials associated with response selection (N2), allocation of cognitive resources (P3b), and error detection (Ne). Taken together, our findings suggest neurocogni-tive plasticity of aging brains which can be stimulated by broad and multilayered cognitive training and assessed in detail by electrophysiological methods. © 2012 Gajewski and Falken-stein.

Schneider D.,Leibniz Research Center for Working Environment and Human Factors
Psychophysiology | Year: 2012

According to recent models on visual attention, both the salience of signals (bottom-up) and the intention to search for particular stimuli (top-down) are determinants for attentional selection. We investigated these mechanisms by varying the top-down set of participants that had to detect either luminance or orientation changes of two symmetrically located bars. Irrelevant changes impaired target detection when they were presented spatially separated to the relevant change. Initial attentional selection was represented in posterior N1 asymmetries and was determined by both the relative salience of orientation changes and a subsequent intentional bias towards relevant stimuli. Only when salient orientation changes interfered with luminance target selection in the N1 time window did an N2pc occur. Thus, the selection of relevant information proceeds in a network whose activation is induced by a dynamic interplay of bottom-up and top-down processes. Copyright © 2012 Society for Psychophysiological Research.

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