Staphylococcal enterotoxin sensitization in a community-based population : a potential role in adult-onset asthma

Background: Recent studies suggest that Staphylococcus aureus enterotoxin sensitization is a risk factor for asthma. However, there is a paucity of epidemiologic evidence on adult-onset asthma in community-based populations. Objective: We sought to evaluate the epidemiology and the clinical significance of staphylococcal enterotoxin sensitization in community-based adult populations. Methods: The present analyses were performed using the baseline data set of Korean adult population surveys, consisting of 1080 adults (mean age=60.2years) recruited from an urban and a rural community. Questionnaires, methacholine challenge tests, and allergen skin tests were performed for defining clinical phenotypes. Sera were analysed for total IgE and enterotoxin-specific IgE using ImmunoCAP. Results: Staphylococcal enterotoxin sensitization (0.35kU/L) had a prevalence of 27.0%. Risk factors were identified as male sex, current smoking, advanced age (61years), and inhalant allergen sensitization. Current asthma was mostly adult onset (18years old) and showed independent associations with high enterotoxin-specific IgE levels in multivariate logistic regression tests. In multivariate linear regressions, staphylococcal enterotoxin-specific IgE level was identified as the major determinant factor for total IgE level. Conclusions and Clinical Relevance: Staphylococcal enterotoxin sensitization was independently associated with adult-onset asthma in adult community populations. Strong correlations between the enterotoxin-specific IgE and total IgE levels support the clinical significance. The present findings warrant further studies for the precise roles of staphylococcal enterotoxin sensitization in the asthma pathogenesis

Optimizing DC Vaccination by Combination With Oncolytic Adenovirus Coexpressing IL-12 and GM-CSF

Dendritic cell (DC)-based vaccination is a promising strategy for cancer immunotherapy. However, clinical trials have indicated that immunosuppressive microenvironments induced by tumors profoundly suppress antitumor immunity and inhibit vaccine efficacy, resulting in insufficient reduction of tumor burdens. To overcome these obstacles and enhance the efficiency of DC vaccination, we generated interleukin (IL)-12- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-coexpressing oncolytic adenovirus (Ad-ΔB7/IL12/GMCSF) as suitable therapeutic adjuvant to eliminate immune suppression and promote DC function. By treating tumors with Ad-ΔB7/IL12/GMCSF prior to DC vaccination, DCs elicited greater antitumor effects than in response to either treatment alone. DC migration to draining lymph nodes (DLNs) dramatically increased in mice treated with the combination therapy. This result was associated with upregulation of CC-chemokine ligand 21 (CCL21+) lymphatics in tumors treated with Ad-ΔB7/IL12/GMCSF. Moreover, the proportion of CD4+CD25+ T-cells and vascular endothelial growth factor (VEGF) expression was decreased in mice treated with the combination therapy. Furthermore, combination therapy using immature DCs also showed effective antitumor effects when combined with Ad-ΔB7/IL12/GMCSF. The combination therapy had a remarkable therapeutic efficacy on large tumors. Taken together, oncolytic adenovirus coexpressing IL-12 and GM-CSF in combination with DC vaccination has synergistic antitumor effects and can act as a potent adjuvant for promoting and optimizing DC vaccination

A childhood case of spinal tuberculosis misdiagnosed as muscular dystrophy

Tuberculosis is primarily a pulmonary disease, but extra-pulmonary manifestations are not uncommon, especially in children and adolescents. Ten percent of extra pulmonary tuberculosis localizes to the bones and joints, and 56% of such cases affect the spine. We treated a childhood case of spinal tuberculosis misdiagnosed as muscular dystrophy in a patient without specific constitutional symptoms. We report this case because the patient had an unusual presentation of spinal tuberculosis

β-Lapachone Significantly Increases the Effect of Ionizing Radiation to Cause Mitochondrial Apoptosis via JNK Activation in Cancer Cells

β-lapachone (β-lap), has been known to cause NQO1-dependnet death in cancer cells and sensitize cancer cells to ionizing radiation (IR). We investigated the mechanisms underlying the radiosensitization caused by β-lap. cells induced ROS generation, triggered ER stress and stimulated activation of ERK and JNK. Inhibition of ROS generation by NAC effectively attenuated the activation of ERK and JNK, induction of ER stress, and subsequent apoptosis. Importantly, inhibition of ERK abolished ROS generation and ER stress, whereas inhibition of JNK did not, indicating that positive feedback regulation between ERK activation and ROS generation triggers ER stress in response to combined treatment. Furthermore, prevention of ER stress completely blocked combination treatment-induced JNK activation and subsequent apoptotic cell death. In addition, combined treatment efficiently induced the mitochondrial translocation of cleaved Bax, disrupted mitochondrial membrane potential, and the nuclear translocation of AIF, all of which were efficiently blocked by a JNK inhibitor. Caspases 3, 8 and 9 were activated by combined treatment but inhibition of these caspases did not abolish apoptosis indicating caspase activation played a minor role in the induction of apoptosis. cells are treated with combination of IR and β-lap, positive feedback regulation between ERK and ROS leads to ER stress causing JNK activation and mitochondrial translocation of cleaved Bax. The resultant decrease in mitochondrial membrane leads to translocation of AIF and apoptosis

Impact of time to treatment of oseltamivir on influenza hospitalization cost among Korean children

BackgroundAlthough oseltamivir is a common influenza treatment, there is a lack of data on the economic benefits of timely oseltamivir treatment.MethodsFrom February 2004 through June 2007, 116 hospitalized children ≤15 years of age with laboratory‐confirmed influenza who received oseltamivir were identified via retrospective medical chart review. Demographic, clinical, and cost data were abstracted and multivariate linear regression was used to assess the association between oseltamivir time to treatment and treatment‐related costs among hospitalized children with laboratory‐confirmed influenza.ResultsOverall, 28% (n = 33) of patients were treated with oseltamivir ≥day 3 of admission. Rapid influenza diagnostic test was used in a significantly lower proportion of patients treated with oseltamivir ≥day 3 of admission compared with those who received oseltamivir earlier. On multivariate linear regression, initiation of oseltamivir ≥day 3 of admission was associated with a 60.84% increase (95%CI: 32.59–95.11) in treatment‐related hospital costs, compared with initiation on admission.ConclusionDelayed initiation of oseltamivir was found to be associated with increased treatment‐related hospital costs among children hospitalized with laboratory‐confirmed influenza.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111958/1/ped12526.pd