NK/T-cell lymphoma (NKTL) is strongly associated with latent Epstein-Barr virus (EBV) infection. Recently, latent membrane protein 1 (LMP1), an EBV oncoprotein, was reported to activate the phosphatidylinositol-3 kinase (PI3K)/Akt pathway for cell survival. Because geldanamycin (GA) and its derivative, 17-allylamino-17-demethoxygeldanamycin (17-AAG), exhibit anti-tumour activity by degrading HSP90 client proteins, including Akt, we investigated the effect of GA and 17-AAG on the survival of NKTL cell lines. EBV-positive NKTL cell lines, Hank-1 and NK-YS, and an EBV-negative NK leukaemia cell line, NK-L, were treated with PI3K and Akt inhibitors, GA, and 17-AAG, and were subjected to apoptosis and cell viability assays, and immunoblot analysis. EBV-positive B-lymphoblastoid cell lines IM9 and LMP1-transfected IM9 (IM9-LMP1) were also included. Hank-1 and NK-YS cell viability was compromised and apoptosis was induced by LY294002 (PI3K inhibitor) or Akt inhibitor II. GA or 17-AAG administration resulted in the apoptosis of NKTL cells, accompanied by Akt and pAkt down-regulation, caspase 3 activation, and mitochondrial membrane potential disruption. The intrinsic level of pAkt was higher in EBV-positive NKTL cells than in EBV-negative NK-L, and GA or 17-AAG decreased the viability of NKTL cells more efficiently than NK-L. Moreover, IM9-LMP1 was more sensitive to Akt inhibitor II or HSP90 inhibitors than IM9. Importantly, GA showed little effect on the viability of normal peripheral NK cells as non-neoplastic counterparts for comparison. In conclusion, this study suggests that the PI3K/Akt pathway is frequently activated in EBV-positive NKTL and that therapeutic modalities based on targeting the PI3K/Akt pathway with HSP90 inhibitors could be useful for achieving NKTL control.
Spontaneous non-aneurysmal aortic rupture is a rare and life threatening clinical entity. A 23-year-old female patient who visited a nearby hospital due to intractable seizure was transferred to our hospital with the impression of hypotension and decreased level of haemoglobin. She had a history of seizure attacks once a month. However, in the 2 weeks before presentation, the frequency of seizure attacks had increased to 2 to 3 times a day. An abdominal-pelvic computed tomogram scan showed extravasation of contrast from the abdominal aorta at L3 level. An emergency laparotomy revealed a 0.3 cm diameter tear in the posterior wall of the aorta, superior to the iliac bifurcation. We discuss the mechanism of spontaneous aortic rupture and the possibility of aortic rupture related to seizure attacks. (Hong Kong j.emerg.med. 2014;21:103-106)
BackgroundSince 2005, the Songpa District has implemented the Safety Doctor Program (SDP), which involves having a dedicated doctor for a nursery facility to quickly respond to safety-related incidents at nursery facilities. By analysing cooperative relations among local community members in a network that was established by the SDP, this study ascertains the characteristics of the safe community program network and defines the direction of development.MethodsA social network analysis survey was conducted on 233 people from the Songpa Public Health Centre (SPHC), Songpa Medical Association, and Songpa Nursery Facility Association that are participating in the SDP. This was followed by a network relations analysis using social network analysis indicators – centrality, centralization, density, and exchange relations.ResultsFirst, from among the SDP members, the SPHC indicates the highest centrality (degree centrality: 0.650) and the highest centralization (in-degree centralization: 64.469%), and thus leads the flow of information and resources.Second, network density is overall low. Network density that excluded the SPHC (0.9%) is lower than the network density that included the centre (1.2%). If the SPHC does not participate in the SDP, several subgroups would emerge among the members, preventing the smooth flow of resources and information and resulting in weak exchange relations.Third, exchange relations of the network that includes the SPHC consist of education, medical services, and public interests. A cooperation evaluation indicated a high level.ConclusionsThe SDP member network is focused on the SPHC, but the Program has great significance in that it promoted discussions among local community member groups. The social network analysis results can be used to motivate local community members to engage in participation and cooperation, thus further developing the infant and child injury prevention program.
BackgroundSongpa District was initially designated as an international safe community in 2008 and re-designated in 2013. Its Injury Surveillance System (ISS) comprises the Web-based ISS, injury yearbook, and infant and child ISS for the high-risk group. An attempt was made to strengthen the ISS by using the U-Health-based Smart Doctor Program, which is being implemented by the Songpa Public Health Centre to more easily and extensively collect citizen injury data.Description of the problemMethods previously used to collect the local community’s injury data include home visits, requests to public and relevant organisations for materials, visits to locations with an injury risk environment, local resident surveys, injury reports of nursery facilities and materials from national statistical institutions. Materials of national statistical institutions were mostly on the entire nation, pointing to the need for more personnel and resource input to obtain local community-level data. There was thus a need to strengthen the ISS using the ubiquitous healthcare.ResultsThe U-Health-based Smart Doctor System is an information technology-based health management system that is customizable for individuals. Songpa District residents use kiosks to easily check their health information (physical data, blood pressure, BMI, etc.). Collected data is interfaced to the website and mobile phone application to enable real-time receipt of help from doctors and nutrition and exercise experts. This system is used by a great number of citizens, and is used to collect injury data along with health data to strengthen the local community’s ISS.ConclusionsThe U-Health-based Smart Doctor System is provided free based on Songpa District’s independently developed program. It is regarded as an effective system for collecting resident health and injury data in the nation’s large cities that have a good ubiquitous mobile environment. Also, system advancements can be made to obtain diverse information using big data.
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