Hypermethylation of the tumor-suppressor cell adhesion molecule 1 in human papillomavirus-transformed cervical carcinoma cells.

Epigenetic modification at CpG islands located on the promoter regions of tumor-suppressor genes has been associated with tumor development in many human cancers. Our study showed that the cell adhesion molecule 1 (CADM1) is downregulated in human papillomavirus (HPV)-infected cervical cancer cell lines via its hypermethylation and demethylation using 5-aza-2'-deoxycyticine (5-aza-dC) restored the expression of CADM1 protein. Overexpression of CADM1 inhibited cell proliferation. p53 was involved in the regulation of CADM1. Our results demonstrate that epigenetic alteration of CADM1 was more frequent in HPV-positive cervical cancers and that restoration of CADM1 expression may be a potential strategy for cervical cancer therapy.

Usefulness of impulse oscillometry and fractional exhaled nitric oxide in children with Eosinophilic bronchitis.

BACKGROUND: Eosinophilic bronchitis (EB) is a common cause of chronic cough. Although EB shares many immunopathologic features with asthma, it does not show airway hyperresponsiveness or reversible airway obstruction by spirometry. OBJECTIVE: Compared to healthy children without pulmonary disease, we hypothesized that EB patients would demonstrate abnormal pulmonary function and inflammation with impulse oscillometry (IOS) and fractional exhaled nitric oxide (FeNO), which are more sensitive tests of these parameters than spirometry. METHODS: A total of 232 children with asthma, 109 with EB, and 115 control subjects were enrolled. We compared pulmonary function parameters and FeNO levels among the three groups. Additionally, we designated a screening cutoff value of FeNO combined with IOS parameters to distinguish EB from the control group, and identify which children with EB have more asthmatic characteristics. RESULTS: By IOS, the bronchodilator response of the EB and asthma groups increased significantly compared to controls for both reactance at 5 Hz (Δ X5) and reactance area (Δ AX) (P < 0.0001). Cutoff values to distinguish EB from controls were a Δ X5 of -20% (sensitivity, 77.5%; specificity, 49.6%), and Δ AX of -30% (sensitivity, 75.0%; specificity, 46.0%), when the FeNO is 20 ppb. CONCLUSIONS: Reversible airway obstruction in IOS and elevated FeNO levels can be detected in children with EB. This would support that EB in children shows airway characteristics similar to those of asthma, and that a continuum exists between asthma and EB.

Sublingual administration of bacteria-expressed influenza virus hemagglutinin 1 (HA1) induces protection against infection with 2009 pandemic H1N1 influenza virus.

Influenza viruses are respiratory pathogens that continue to pose a significantly high risk of morbidity and mortality of humans worldwide. Vaccination is one of the most effective strategies for minimizing damages by influenza outbreaks. In addition, rapid development and production of efficient vaccine with convenient administration is required in case of influenza pandemic. In this study, we generated recombinant influenza virus hemagglutinin protein 1 (sHA1) of 2009 pandemic influenza virus as a vaccine candidate using a well-established bacterial expression system and administered it into mice via sublingual (s.l.) route. We found that s.l. immunization with the recombinant sHA1 plus cholera toxin (CT) induced mucosal antibodies as well as systemic antibodies including neutralizing Abs and provided complete protection against infection with pandemic influenza virus A/CA/04/09 (H1N1) in mice. Indeed, the protection efficacy was comparable with that induced by intramuscular (i.m.) immunization route utilized as general administration route of influenza vaccine. These results suggest that s.l. vaccination with the recombinant non-glycosylated HA1 protein offers an alternative strategy to control influenza outbreaks including pandemics.