CD44 is an adhesion molecule expressed in cancer stem-like cells. Here, we show that a CD44 variant (CD44v) interacts with xCT, a glutamate-cystine transporter, and controls the intracellular level of reduced glutathione (GSH). Human gastrointestinal cancer cells with a high level of CD44 expression showed an enhanced capacity for GSH synthesis and defense against reactive oxygen species (ROS). Ablation of CD44 induced loss of xCT from the cell surface and suppressed tumor growth in a transgenic mouse model of gastric cancer. It also induced activation of p38(MAPK), a downstream target of ROS, and expression of the gene for the cell cycle inhibitor p21(CIP1/WAF1). These findings establish a function for CD44v in regulation of ROS defense and tumor growth.

This virus typically causes illness in young children but was found to be associated with illness in adults.

To clarify the epidemiology of enterovirus 68 (EV68), which is one of the most rarely identified enteroviruses, virus isolation and molecular screening using RT-PCR was performed on 6307 respiratory specimens collected at pediatric clinics in Yamagata, Japan between 2005 and 2010. In the years 2005-2009, 10, 1, 2, 0, and 2 (40) EV68-positive cases, respectively, were identified by RT-PCR. In 2010, 40 cases were identified altogether: 2 by isolation only, 26 by RT-PCR only, and 12 by both isolation and RT-PCR. Phylogenetic analysis indicated that plural genetically distinct clusters co-circulated. These results suggest that that difficulty in EV68 isolation leads to an underestimation of the prevalence of EV68 infections.

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SUMMARY:The available literature on human coronaviruses (HCoVs) in Japan is limited to epidemiological studies conducted over a maximum of 1 year. We conducted a 4-year study of HCoVs by analyzing 4,342 respiratory specimens obtained in Yamagata, Japan, between January 2010 and December 2013. A pan-coronavirus reverse transcription-PCR screening assay was performed, and all HCoVpositive specimens were subsequently confirmed by sequencing of the PCR products. We detected in 332 (7.6z) HCoV strains during the study period, comprising 133 (3.1z) HCoV-NL63, 83 (1.9z) HCoV-HKU1, 78 (1.8z) HCoV-OC43, and 38 (0.9z) HCoV-229E strains. HCoV detection per year ranged from 3.5z to 9.7z. HCoVs were detected mainly in winter,

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SUMMARY: Most acute respiratory infections (ARIs) are thought to be associated with respiratory viruses that cause similar symptoms. Therefore, assessment of clinical and epidemiologic features of these viruses is important for diagnosing a viral infection. We collected 13,325 nasopharyngeal specimens from patients with ARIs and isolated the virus using a microplate method involving 7 cell lines between 2004 and 2011 in Yamagata, Japan. We isolated a total of 5,483 viruses. Respiratory syncytial virus (RSV), influenza A virus (FluA), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (hPIV3) showed clear yearly seasonal patterns; generally, RSV infections peaked at the end of the year, FluA infections peaked between January and March, hMPV infections peaked between March and April, and hPIV3 showed seasonal outbreaks between May and July. Further, RSV, hMPV, and hPIV3 were commonly isolated in 12.0-13.1z of specimens from children aged less than 4 years, whereas FluA was isolated in 7.3-8.2z of specimens from school-aged children. A generalized view of seasonality and age distribution, particularly on the basis of longitudinal epidemiological data, will be helpful for medical decision-making, including decisions related to the use of rapid test kits, selection of antiviral treatments, restriction of antibiotic therapy, and implementation of infection control strategies.

To clarify the epidemiology of viral acute respiratory infections (ARIs), 305 human parainfluenza virus types 1 (HPIV1), 154 HPIV2 and 574 HPIV3 strains were isolated from 16,962 nasopharyngeal swabs obtained between 2002 and 2011 at pediatric clinics in Yamagata, Japan. The total isolation frequency for HPIV1-3 was 6.1%. Unlike HPIV1 infections, HPIV3 showed clear seasonality with yearly outbreaks in the spring-summer season. HPIV2 tended to appear biannually in autumn-winter. Although no reliable techniques for the laboratory diagnosis of these infections have been established, the present results suggest that HPIV1-3 are an important causative agent of ARIs in children.