16 research outputs found

    Global gene expression analyses of bystander and alpha particle irradiated normal human lung fibroblasts: Synchronous and differential responses

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    <p>Abstract</p> <p>Background</p> <p>The existence of a radiation bystander effect, in which non-irradiated cells respond to signals from irradiated cells, is now well established. It raises concerns for the interpretation of risks arising from exposure to low doses of ionizing radiation. However, the regulatory mechanisms involved in the bystander response have not been well elucidated. To provide insight into the signaling pathways responding in bystanders, we have measured global gene expression four hours after bystander and direct alpha particle exposure of primary human lung fibroblasts.</p> <p>Results</p> <p>Although common p53-regulated radiation response genes like <it>CDKN1A </it>were expressed at elevated levels in the directly exposed cultures, they showed little or no change in the bystanders. In contrast, genes regulated by NFκB, such as <it>PTGS2 </it>(cyclooxygenase-2), <it>IL8 </it>and <it>BCL2A1</it>, responded nearly identically in bystander and irradiated cells. This trend was substantiated by gene ontology and pathway analyses of the microarray data, which suggest that bystander cells mount a full NFκB response, but a muted or partial p53 response. In time-course analyses, quantitative real-time PCR measurements of <it>CDKN1A </it>showed the expected 4-hour peak of expression in irradiated but not bystander cells. In contrast, <it>PTGS2, IL8 </it>and <it>BCL2A1 </it>responded with two waves of expression in both bystander and directly irradiated cells, one peaking at half an hour and the other between four and six hours after irradiation.</p> <p>Conclusion</p> <p>Two major transcriptional hubs that regulate the direct response to ionizing radiation are also implicated in regulation of the bystander response, but to dramatically different degrees. While activation of the p53 response pathway is minimal in bystander cells, the NFκB response is virtually identical in irradiated and bystander cells. This alteration in the balance of signaling is likely to lead to different outcomes in irradiated cells and their bystanders, perhaps leading to greater survival of bystanders and increased risk from any long-term damage they have sustained.</p

    In-vitro physiochemical responses of Viola odorata plant to combined salt and drought stress

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    Nowadays sweet violet (Viola odorata) is an ornamental-medical plant that considered as endangered and threatened species. On the other hand, biotic and abiotic stresses impose a major threat to agriculture. Here, we investigated the effects of salinity and drought stresses, based on polyethylene glycol (PEG; 1, 1.5, 2, 2.5, 3 and 4%) and NaCl (0, 50, 100 and 150 mM), on growth characteristics, physiological parameters and antioxidant defense system of sweet violet under in-vitro conditions. The influences of NaCl and PEG gradients in the culture media on plant height, green leaf percentage, root dry weight (DW), and electrolyte leakage (EL) was described by a linear or quadratic model. All measured parameters (except EL) decreased when NaCl or PEG concentration increased. In contrast, EL increased other traits. Moreover, with increasing in salinity and drought severity, shoot DW decreased, while antioxidant enzymes activity such as catalase (CAT), peroxidase (POX) and superoxide dismutase (SOD) and proline content increased. However, total soluble carbohydrates (TSC), at all drought levels, increased with increasing NaCl concentration up to 50 or 100 mM, and then decreased. Most variations in the shoot DW, CAT activity, proline and TSC contents due to salt stress occurred at low concentration of PEG. Overall, our findings highlight that the effect of combined drought and salt stress was more severe. However, the sensitivity of the plant to drought or salinity stress was higher in the absence of other stress

    Is Emergency Department Closure Resulting in Increased Distance to the Nearest Emergency Department Associated With Increased Inpatient Mortality?

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    STUDY OBJECTIVE: We sought to determine if patients living in areas affected by emergency department (ED) closure, with subsequent increased distance to the nearest ED, had a higher risk of inpatient death from time-sensitive conditions. METHODS: Using the California Office of Statewide Health and Planning Development (OSHPD) database, we performed a non-concurrent cohort study of hospital admissions in California between 1999-2009 for patients admitted for acute myocardial infarction (AMI), stroke, sepsis and asthma/chronic obstructive pulmonary disease (COPD). We used generalized linear mixed effects models comparing adjusted inpatient mortality for patients experiencing increased distance to the nearest ED versus no change in distance. RESULTS: Of 785,385 patient admissions, 67,577 (8.6%) experienced an increase in distance to ED care due to an ED closure. The median change for patients experiencing an increase in distance to the nearest ED was only 0.8 miles with a range of 0.1 to 33.4 miles. Patients with an increase did not have a significantly higher mortality (adjusted odds ratio 1.04, 95% CI 0.99, 1.09). In subgroups, we also noted no statistically significant differences in adjusted mortality among patients with AMI, stroke, asthma/COPD, and sepsis. We did not observe any significant variations in mortality for time-sensitive conditions in sensitivity analyses that incorporated a lag effect of time after change in distance, allowance for a larger affected population, or removal of ST-elevation myocardial infarction (STEMI) from the AMI subgroup. CONCLUSIONS: In this large population-based sample, less than 10% of the patients experienced an increase in distance to the nearest ED, and of that group, the majority had less than a one-mile increase. These small increased distances to the nearest ED were not associated with higher inpatient mortality among time-sensitive conditions
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