Socioeconomic status and self-rated health of Japanese people, based on age, cohort, and period

Background: Differences in health resulting from differences in socioeconomic status (SES) have been identified around the world. Age, period, and cohort (A-P-C) differences in health are vital factors which are associated with disparities in SES. However, few studies have examined these differences simultaneously. Moreover, although self-rated health (SRH) has been frequently used as an indicator of health, biases in reporting SRH that depend on the socioeconomic characteristics of respondents have been scarcely adjusted in the previous studies. To overcome these limitations, we investigated the associations between disparities in SES and adjusted SRH based on A-P-C, by using a repeated, cross-sectional survey of a nationally representative sample of Japanese people. In addition, we further investigated how exogenous (macroeconomic) conditions unique to a period or cohort would explain trends across successive periods and cohorts. Methods: Data were obtained from a sample of 653,132 Japanese people that responded to the Comprehensive Survey of Living Conditions (CSLC), which is a cross-sectional survey that had been conducted every three years from 1986 to 2013, on over 10 occasions. In the CSLC, SES has been assessed by household income. We simultaneously controlled for each A-P-C dimension by using the model for cross-classification of random effects, and adjusting SRH data for reporting biases caused by differences in income and A-P-C. Results: Differences in adjusted SRH associated with income differences decreased with age and reversed after 76 years of age. Period differences indicated that income differences peaked in 1992 and 2007. Moreover, differences in adjusted SRH associated with income differences decreased in periods with high unemployment across all periods. Furthermore, there were no cohort differences in adjusted SRH that were associated with income differences. Conclusion: In Japan, there are age and period variations associated with adjusted differences in SRH as assessed by income. Moreover, exogenous conditions in each period could help explain periodic trends across successive periods

Protein Kinase A Associates with HA95 and Affects Transcriptional Coactivation by Epstein-Barr Virus Nuclear Proteins

HA95, a nuclear protein homologous to AKAP95, has been identified in immune precipitates of the Epstein-Barr virus (EBV) coactivating nuclear protein EBNA-LP from EBV-transformed lymphoblastoid cells (LCLs). We now find that HA95 and EBNA-LP are highly associated in LCLs and in B-lymphoma cells where EBNA-LP is expressed by gene transfer. Binding was also evident in yeast two-hybrid assays. HA95 binds to the EBNA-LP repeat domain that is the principal coactivator of transcription. EBNA-LP localizes with HA95 and causes HA95 to partially relocalize with EBNA-LP in promyelocytic leukemia nuclear bodies. Protein kinase A catalytic subunit α (PKAcsα) is significantly associated with HA95 in the presence or absence of EBNA-LP. Although EBNA-LP is not a PKA substrate, HA95 or PKAcsα expression in B lymphoblasts specifically down-regulates the strong coactivating effects of EBNA-LP. The inhibitory effects of PKAcsα are reversed by coexpression of protein kinase inhibitor. PKAcsα also inhibits EBNA-LP coactivation with the EBNA-2 acidic domain fused to the Gal4 DNA binding domain. Furthermore, EBNA-LP- and EBNA-2-induced expression of the EBV oncogene, LMP1, is down-regulated by PKAcsα or HA95 expression in EBV-infected lymphoblasts. These experiments indicate that HA95 and EBNA-LP localize PKAcsα at nuclear sites where it can affect transcription from specific promoters. The role of HA95 as a scaffold for transcriptional regulation is discussed

EBウイルス癌遺伝子産物LMP1の上皮系細胞におけるシグナル伝達機能

金沢大学がん進展制御研究所Epstein-Barr(EB)ウイルスはバーキットリンパ腫や上咽頭癌を引き起こす癌ウイルスであり、試験管内発がんに重要な役割を持つウイルス蛋白の一つは膜蛋白LMP1である。本研究ではEBVによる上皮系細胞発がん機構を考察する事を目的とし、LMP1の上皮系細胞形質転換活性の検討を行い、以下の結果を得た。(1)LMP1を持続的に発現する細胞株を上皮系細胞株MDCK細胞より得たところ、上皮様から繊維芽細胞様の形態に形質転換し、さらに肝細胞増殖因子(HGF)なしでコラーゲンゲル内で管腔構造を取る浸潤性増殖能を獲得した。(2)遺伝子変化をdifferential display法などで調べるとPAI-1、uPA、Ets-1遺伝子の発現上昇が見られた。Ets-1のdominant negativeの導入で形質転換が抑えられ親細胞様形態に戻った。(3)変異株実験の結果、LMP1の機能に重要な2つの細胞質内ドメインのうちTRAFが直接結合する膜近傍ドメインが浸潤性増殖に必要であった。以上の結果から、LMP1はEts-1遺伝子発現上昇を誘導して上皮系細胞を浸潤性に形質転換する活性を持ち、B細胞の不死化に重要なLMP1ドメインが上皮系細胞の浸潤性増殖能獲得に不可欠である事が明らかとなった。(4)LMP1発現に伴う継時的遺伝子発現変化を見る目的で、loxP配列を持ったLMP1プラスミドをMDCK細胞に導入し、そのままでは発現しない細胞株を樹立した。その後、組み換え酵素Creを発現する組み換えアデノウイルスを感染させ100%の細胞で一斉にLMP1高発現を実現させたところ細胞死が誘導された。このように、Cre-loxP発現制御系を用いることで、LMP1の高発現によって上皮系細胞死が誘導されることが確認された。研究課題/領域番号:11139224, 研究期間(年度):1999出典：「EBウイルス癌遺伝子産物LMP1の上皮系細胞におけるシグナル伝達機能」研究成果報告書　課題番号11139224（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-11139224/)を加工して作

Mediators of Life-Course and Late-Life Financial Strain on Late-Life Health in Japan : Based on a Cross-Sectional Survey

Purpose: Few studies have examined together the psychosocial mediators of how life-course and late-life socioeconomic status (SES) influence late-life health. This study explored psychosocial mediators of influences of not only life-course but also late-life financial strain on late-life health in Japan, using a cross-sectional survey. It was hypothesized that: 1) both life-course and late-life financial strain will influence late-life health through common mediators, and 2) such mediating influences will be large on health indicators strongly related to psychosocial resources, such as depressive tendencies and self-rated health. Methods: The participants (N = 739) were aged 65 years and older and lived in metropolitan Tokyo, Japan. Life-course financial strain was measured retrospectively by the number of financially strenuous experiences over the participants’ life-courses. Possible mediators included stressors (life-course and late-life major traumatic life events) and psychosocial resources (self-esteem, sense of control, health literacy, social networks, and social support). Health indicators included multimorbidity, disabled activities of daily living (ADL), depressive tendency, and poorer self-rated health. Results: Having a sense of control mediated the significant influences of both life-course and late-life financial strain on disabled ADL. Furthermore, self-esteem significantly mediated the influences of both life-course and late-life financial strain on depressive tendencies and poorer self-rated health. All such mediating influences were significant at p < 0.05. Psychosocial resources did not mediate significant influences of life-course and financial strain on multimorbidity. Conclusion: The results support our hypotheses and make three main contributions on the mechanism through which SES influences late-life health: 1) psychosocial resources mediate the effect of life-course SES on late-life health; 2) the influence differs depending on health type; and 3) these results can generalize to older adults in not only Japan but also Western countries

Residues 231 to 280 of the Epstein-Barr Virus Nuclear Protein 2 Are Not Essential for Primary B-Lymphocyte Growth Transformation

ABSTRACT Epstein-Barr virus (EBV) nuclear protein 2 (EBNA-2) is a transcriptional transactivator of cellular and viral gene expression and is essential for the transformation of resting human B lymphocytes into long-term lymphoblastoid cell lines (LCLs). Previous molecular genetic analyses identified three domains that are critical for transformation and showed that the rest of EBNA-2 is not critical. We now find that codons 231 to 280 that were part of one of the critical domains (J. I. Cohen, F. Wang, and E. Kieff, J. Virol. 65:2545–2554, 1991) can be deleted with only a small effect on the ability of EBNA-2 to transactivate gene expression. In transient transfection assays, EBNA-2 deleted for codons 231 to 280 accumulated to higher levels and was similar to wild-type EBNA-2 in activation of the Bam C promoter and in association with RBPJk, a cellular transcription factor that is important for EBNA-2 interaction with promoter regulatory elements. However, EBNA-2 d 231–280 activated the viral latent membrane protein 1 (LMP1) promoter with only 60% of wild-type efficiency. Recombinant EBVs specifically deleted for EBNA-2 codons 231 to 280 were efficient in initiating the transformation of resting primary human B lymphocytes into LCLs. However, these LCLs grew less well than wild-type EBV-transformed LCLs, and 4- to 10-fold more cells were required for outgrowth following limit dilution. EBNA-2 d 231–280 accumulated to unusually high levels in the recombinant transformed LCLs, and this was associated with somewhat higher EBNA-1 and lower LMP1 expression, consistent with the near-wild-type activation of the Bam C EBNA promoter and the abnormally low activation of the LMP1 promoter in transient transfection assays. Thus, EBNA-2 d 231–280 modestly perturbed the regulation of viral gene expression and resulted in less LMP1, while having surprisingly subtle effects on LCL outgrowth. Deletion of EBNA-2 codons 292 to 310, which are closer to the site that specifies interaction with RBPJk, was more disruptive of RBPJk association and of the ability to transform B lymphocytes. </jats:p