Neuroblastoma is the third-most-common solid tumor of childhood. To date, no reliable blood marker for neuroblastoma has been established. The growth factor midkine is highly expressed in human carcinomas and its knockdown leads to tumor growth suppression in animal models. The present study evaluated the plasma midkine level in human neuroblastoma patients. Plasma samples were obtained from patients found through mass screening, as well as from sporadic neuroblastoma patients. The total number of cases examined was 756. Among them, prognostic information was available for 175 sporadic cases and 287 mass-screening cases. Midkine levels were significantly higher in neuroblastoma patients, including both mass-screening cases and sporadic cases, than in non-tumor controls (P < 0.0001). The midkine level was significantly correlated with the statuses of MYCN amplification, TRKA expression, ploidy, stage and age (P < 0.0001, < 0.0001, = 0.004, < 0.0001 and < 0.0001, respectively), which are known prognostic factors for neuroblastoma. There was a striking correlation between high plasma midkine level and poor prognosis (P < 0.0001). Within sporadic cases, the midkine level was also strikingly higher than in non-tumor controls (P < 0.0001), and correlated with the statuses of MYCN amplification and stage (P = 0.0005 and = 0.003, respectively). There was a significant correlation between high plasma midkine level and poor prognosis (P = 0.04). Taken N euroblastoma (NBL) is the third-most-common malignant tumor of childhood, accounting for 15% of cancer-related death. (1) In spite of an enormous amount of research devoted to curing this disease, its prognosis remains poor. NBL has several established prognostic factors, i.e. MYCN amplification, TRKA expression level, ploidy, stage and age. (1,2) Cases with tumors with an amplified MYCN gene, low TRKA expression or diploidy show poor prognosis. Cases at stage 3 or 4, or at ages older than 18 months also show poor prognosis. Since molecular fingerprints within tumor tissues, such as MYCN amplification, TRKA expression level and ploidy, require a tumor biopsy or its removal, a blood marker for NBL has long been awaited. (1,2) A blood marker would not only be useful for the initial diagnosis but would also be beneficial for the sequential monitoring of the tumor status.The growth factor midkine (MK) was originally found in embryonal carcinoma cells, and has been implicated in cancer development. (3)(4)(5) MK is highly and frequently expressed in human carcinomas, including Wilms' tumor, tumors of the digestive tract, brain tumors, urinary bladder tumors and breast tumors, whereas its expression is scarcely detected in normal adult tissues. (6-10) Strong MK expression is also detected in precancerous stages of human colorectal cancer and human prostate cancer. (11,12) Knockdown of MK expression leads to suppression of xenografted tumors of mouse colorectal cancer cells and human prostate cancer cells. (13,14) We previously reported that the plasma MK level was correlated wit...

Okinawa is located in a subtropical area and is well-known for low mortality due to ischemic heart disease (IHD) and cerebrovascular disease (CVD). However, the factors that contribute to these low mortality rates remain unclear. We examined the seasonal variation in the mortality due to IHD and CVD among Okinawa and Osaka residents, aged 45 to 84 years, between 1992 and 1996. In addition, we studied if there was a relationship between the monthly mortality rate from IHD or CVD and the monthly mean daily air temperature in Naha City and Osaka City. Data on the monthly mean daily air temperature was obtained from the meteorological stations in Naha City and Osaka City. Our results showed that there were inverse correlations between the monthly mean daily temperature in a city and each of the monthly mortality from IHD in Okinawa (r=-0.794, p<0.01), the monthly mortality from CVD in Okinawa (r=-0.837, p<0.001), and the monthly mortality from CVD in Osaka (r=-0.954, p<0.001). In Osaka, the monthly mortality rate from IHD was at or near its minimum value when the mean daily temperature was approximately 25 (in September), and it increased in a linear fashion as the mean monthly temperature fell (r=-0.975, p<0.001). The difference between the monthly mortality from IHD or CVD among the Okinawa and the Osaka residents increased in the winter season in comparison with that in the other seasons, with the exception for IHD in July and in August. These findings indicate that the lower mortality from IHD and CVD in Okinawa is affected, at least in part, by Okinawa's warm winter.

Aim: The aim of this study was to develop a new scale, the Competence Scale for Senior Clinical Nurses (CS-SCN), to assess and evaluate senior clinical nurses in hospitals, and to confirm the validity and reliability of the scale. Method: A cross-sectional questionnaire survey was undertaken at a hospital in Japan, using an anonymous self-administered questionnaire administered to clinical nurses (n = 374). A useable sample of 218 was achieved, which was used in the analysis. Statistical analysis examined exploratory/confirmatory factor analysis, internal consistency, and construct validity. Results: A five factor solution with 22 items was extracted for nursing competence in senior clinical nurses, which was the interpretable questionnaire. In the confirmatory factor analysis, the indices of fitness supported these results. Cronbach's alpha coefficient was 0.93 for the total score and varied between 0.63 and 0.90 in the five factors. Five factors emerged from an oblique factor analysis, with a cumulative variance of 66.7%: "role accomplishment"; "self-management"; "research"; "practice and coordination"; and "work implementation". The five factors had only a moderate correlation (0.30-0.77, P < 0.001) with each other, which indicated construct validity. Conclusion:The CS-SCN, a concise scale to measure and evaluate the competence of senior clinical nurses, was developed. Results suggest initial support for the new instrument as a measure of competence of senior clinical nurses, but it must be further refined, tested, and evaluated. Both the validity and reliability of the scale were verified. Future studies using the CS-SCN might lead to improvement in the competence of senior clinical nurses.

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The aims of this study were twofold: (1) to determine the prevalence and clinical features of hepatitis delta virus (HDV) infection among subjects positive for hepatitis B surface antigen (HBsAg) living in the Miyako Islands, Okinawa Prefecture, Japan, and (2) to clarify the relationship between HDV-RNA level and severity of HDV-related liver disease. One hundred and ninety-nine HBsAg-positive subjects (123 asymptomatic carriers [ASCs], 3 patients with acute hepatitis [AH], 50 patients with chronic hepatitis [CH], 15 patients with liver cirrhosis [LC], and 8 patients with hepatocellular carcinoma [HCC], were tested for antibody to HDV (anti-HDV) by radioimmunoassay. Anti-HDV-positive individuals were examined to determine semi-quantified HDV-RNA level by polymerase chain reaction (PCR). The overall prevalence of anti-HDV among the 199 subjects was 21.1%. The positivity rate tended to increase with age or the severity of the underlying liver disease: anti-HDV-positive rates were 10.6% (13/123) in ASCs, 32.0% (16/50) in patients with CH, 40.0% (6/15) in patients with LC, and 87.5% (7/8) in patients with HCC. None of the patients with AH were positive for anti-HDV. There was no correlation between semi-quantified serum HDV-RNA levels and the severity of chronic liver disease in patients positive for anti-HDV. The present study showed the local spread of HDV infection in the Miyako Islands, Okinawa, Japan. Although the anti-HDV positivity rate tended to increase with the severity of the underlying liver disease, the severity of HDV-related liver disease did not correlate with the semi-quantified serum HDV-RNA level.