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The impact of shift work induced chronic circadian disruption on IL-6 and TNF-α immune responses
(2010)
Aim: Sleep disturbances induce proinflammatory immune responses, which might increase cardiovascular disease risk. So far the effects of acute sleep deprivation and chronic sleep illnesses on the immune system have been investigated. The particular impact of shift work induced chronic circadian disruption on specific immune responses has not been addressed so far.
Methods: Pittsburgh-Sleep-Quality-Index (PSQI) questionnaire and blood sampling was performed by 225 shift workers and 137 daytime workers. As possible markers the proinflammatory cytokines IL-6 and TNF-alpha and lymphocyte cell count were investigated. A medical examination was performed and biometrical data including age, gender, height, weight, waist and hip circumference and smoking habits were collected by a structured interview.
Results: Shift workers had a significantly higher mean PSQI score than day workers (6.73 vs. 4.66; p < 0.001). Day workers and shift workers had similar serum levels of IL-6 (2.30 vs. 2.67 resp.; p = 0.276), TNF-alpha (5.58 vs. 5.68, resp.; p = 0.841) or lymphocytes count (33.68 vs. 32.99, resp.; p = 0.404). Furthermore there were no differences in cytokine levels (IL-6 p = 0.761; TNF-alpha p = 0.759) or lymphocyte count (p = 0.593) comparing the sleep quality within the cohorts. When this calculation of sleep quality was stratified by shift and day workers irrespective of their sleep quality day workers and shift workers had similar serum levels of IL-6, TNF-alpha or lymphocytes count. Multiple linear regression analysis showed a significant correlation of lymphocytes count and smoking habits.
Conclusion: Shift work induces chronic sleep debt. Our data reveals that chronic sleep debt might not always lead to an activation of the immune system, as we did not observe differences in lymphocyte count or level of IL-6 or TNF-alpha serum concentration between shift workers and day workers. Therefore chronic sleep restriction might be eased by a long-term compensating immune regulation which (in healthy) protects against an overstimulation of proinflammatory immune mechanisms and moderates metabolic changes, as they are known from short-term sleep deprivation or sleep related breathing disorders.
Background: Cancer gene therapy will benefit from vectors that are able to replicate in tumor tissue and cause a bystander effect. Replication-competent murine leukemia virus (MLV) has been described to have potential as cancer therapeutics, however, MLV infection does not cause a cytopathic effect in the infected cell and viral replication can only be studied by immunostaining or measurement of reverse transcriptase activity. Results: We inserted the coding sequences for green fluorescent protein (GFP) into the proline-rich region (PRR) of the ecotropic envelope protein (Env) and were able to fluorescently label MLV. This allowed us to directly monitor viral replication and attachment to target cells by flow cytometry. We used this method to study viral replication of recombinant MLVs and split viral genomes, which were generated by replacement of the MLV env gene with the red fluorescent protein (RFP) and separately cloning GFP-Env into a retroviral vector. Co-transfection of both plasmids into target cells resulted in the generation of semi-replicative vectors, and the two color labeling allowed to determine the distribution of the individual genomes in the target cells and was indicative for the occurrence of recombination events. Conclusions: Fluorescently labeled MLVs are excellent tools for the study of factors that influence viral replication and can be used to optimize MLV-based replication-competent viruses or vectors for gene therapy.
Das Phänomen der Inkorporation, spezieller Nominalinkorporation (NI), wurde ursprünglich in der Forschung vor allem in nordamerikanischen Indianersprachen untersucht und zu ihrer typologischen Beschreibung herangezogen. Daraus ergab sich eine Definition von NI als einem morphologischen Verfahren, bei dem ein prädikativer Ausdruck (V) einen referenzfähigen Ausdruck (N) inkorporiert, um einen komplexen prädikativen Ausdruck (V) abzuleiten. Nach heutigen Erkenntnissen jedoch gilt NI als relativ universell vertretenes Verfahren, das in den Sprachen der Welt mehr oder weniger prominent zu finden ist. Strittig ist dabei, ob das Inkorporat nur seinen syntaktischen Status – dies wäre als weit gefaßte Definition zu bezeichnen – oder auch seinen Wortstatus – dagegen eng gefaßte Definition (=Komposition) – verliert. Mit dieser Frage verbunden scheint die Diskussion um den Status von NI innerhalb eines Sprachmodells: Handelt es sich um ein syntaktisches Verfahren und ist als solches produktiv mit einer relativen Eigenständigkeit der Elemente (Sadock 1986/Baker 1988) oder um Lexikalisierung (Mithun 1984), also um einen Wortbildungsmechanismus mit einer zumindest tendenziellen Verfestigung der beteiligten Elemente? Allen diesen Modellen gemeinsam bleibt jedoch die Tatsache, daß sie im Bereich der Morphologie ansetzen. Wir wollen in dieser Arbeit den umgekehrten Weg beschreiten und anhand des von Mithun (1984) aufgestellten Katalogs von Charakteristika nach Phänomenen "nicht-morphologischer" NI suchen und sie am Material der jeweiligen Sprache erörtern.