One‐year test–retest reliability of a Japanese web‐based version of the WHO Composite International Diagnostic Interview (CIDI) for major depression in a working population

The purpose of this study was to investigate the one‐year test–retest reliability and the demographic correlates of a self‐administered web‐based depression section of the World Health Organization‐Composite International Diagnostic Interview (WHO‐CIDI) in a working population. Overall, 1060 out of all employees (N = 1279) from a manufacturing company in Japan responded to two web‐based surveys of depression of the WHO‐CIDI within a one‐year interval in 2009 and 2010. The concordance between lifetime diagnoses of major depressive disorder on two occasions was calculated as percent agreement (%), Gwet's AC₁, and Yule's Q indicators were compared by gender, age, education, and marital status. For the total sample, percent agreement was 94%, AC₁ was 0.93, and Yule's Q was 0.82. The concordance rate was low (0.15) among those who were diagnosed at either time or both times. The concordance differed significantly across education and marital status. While the agreement indicators were relatively high, consistent with previous reports based on face‐to‐face interviews conducted within a shorter interval, the low stability of positive cases may challenge the accuracy of lifetime diagnosis of major depressive disorder using a web version of the WHO‐CIDI. Education and marital status might affect the test–retest reliability. Copyright © 2014 John Wiley & Sons, Ltd.     

Association of glycemic profiles with whole blood polyamine among middle-aged Japanese men: colorimetric assay using oat and barley seedling polyamine oxidase

Objectives Polyamines have long been known to have an insulin-like action, but their antiglycating effect has only recently attracted the attention of researchers. The aim of our investigation was to determine the whole blood polyamine concentration in a healthy population in order to examine its relationship with glycemic profiles. Methods The study cohort comprised 622 men aged 40–59 who participated in a health checkup program conducted in 1997, when they underwent measurements of fasting plasma glucose (FPG), insulin (FPI), and fructosamine as glycemic indices. Colorimetric assay methods using oat and barley seedling polyamine oxidase were used to determine total polyamine (spermidine + spermine) and spermine concentrations in the whole blood, respectively. Polyamine concentrations adjusted for hemoglobin were quartiled for the analysis of covariance to assess the association with glycemic indices. Results A significant association was demonstrated between the FPG and total polyamine concentrations. In the trend test, FPG and fructosamine levels increased in accordance with the shift of quartiles of total polyamine concentrations from low to high. In contrast, the association between the spermine and glycemic indices was not statistically significant based on the test for difference of multivariate-adjusted means or trend for linearity. Conclusions This is the first epidemiological study to reveal that the concentrations of blood polyamines are related with either FPG or fructosamine level in a healthy population. There may be some feedback mechanism for the elevation of circulating polyamines to quench the glycation reaction under hyperglycemic conditions. In addition, total polyamines, rather than spermine alone, seem to be a sensitive biomarker representing the antiglycation effect of polyamines.     

The crucial role of granulocytes in the early host defense against Strongyloides ratti infection in mice

The involvement of granulocytes in the host early defense against the nematode, Strongyloides ratti, was studied. It was confirmed that granulocytes were effectively depleted for 4 days by anti-granulocyte monoclonal antibody (anti-Gr-1). To examine the involvement of granulocytes in the host defense against migrating larvae, 2000 S. ratti infective larvae (L³) were inoculated subcutaneously 1 day after antibody treatment. The number of S. ratti eggs secreted in feces (EPG) was higher in the granulocyte-depleted group than in the control group. The number of migrating larvae also increased in the granulocyte-depleted group in accordance with the increase in EPG. Therefore granulocytes are crucial for the host early defense against migrating larvae of S. ratti. Next, the involvement of granulocytes in the intestinal early defense was examined. Mice were treated with the antibody on day 3 post-infection. On that day, almost all inoculated larvae reached the intestine and molted to become adults. EPG on day 5 post-infection was increased by the antibody treatment, but no effect was observed on intestinal worm numbers. The fecundity (EPG/worm number) of S. ratti adult worms in the granulocyte-depleted group was higher than that in the control group. Thus granulocytes are also involved in the intestinal early defense through suppressing fecundity of the adult worms. On the other hand, the depletion of granulocytes had no effect on the late adaptive response against S. ratti adult worms (e.g. number of intestinal mucosal mast cells, time of worm expulsion). These results suggest that granulocytes are mainly involved in the host early defense against parasites. Received: 28 September 1999 / Accepted: 12 October 1999     

Psychological distress and associated factors among Japanese nursery school and kindergarten teachers: a cross-sectional study

The understaffing of nursery schools and kindergartens and the increasing workload of childcare workers are becoming significant issues in Japan. In this study, a cross-sectional survey was conducted to investigate the stress experienced by childcare workers and its antecedents. We distributed 2,640 questionnaires to childcare workers in Miyagi prefecture, obtaining a response rate of 51.9% (n=1,370). Finally, 1,210 valid questionnaires were used in the analysis. As a stress indicator, psychological distress was measured with the Kessler Screening Scale for Psychological Distress (K6). The mean K6 score was 7.0 (SD=5.4), and the prevalence of psychological distress (K6 score ≥5) was 60.0%. Considering work-related factors, the mean scores were as follows: supervisor support 11.8 (2.6), coworker support 12.1 (2.0), work engagement 3.2 (1.2), and effort-reward ratio 0.93 (0.53). A multivariate logistic regression analysis with adjustment for possible confounders revealed that increased psychological distress was associated with higher effort-reward ratio, lower support from supervisors and coworkers, lower work engagement, and insufficient sleep. These results suggest that elevated psychological distress is strongly associated with effort-reward imbalance, while high work engagement in childcare workers helped to reduce their distress.     

Neurotransmitter signalling via NMDA receptors leads to decreased T helper type 1‐like and enhanced T helper type 2‐like immune balance in humans

Given the pivotal roles that CD4⁺ T cell imbalance plays in human immune disorders, much interest centres on better understanding influences that regulate human helper T‐cell subset dominance in vivo. Here, using primary CD4⁺ T cells and short‐term T helper type 1 (Th1) and Th2‐like lines, we investigated roles and mechanisms by which neurotransmitter receptors may influence human type 1 versus type 2 immunity. We hypothesized that N‐methyl‐d ‐aspartate receptors (NMDA‐R), which play key roles in memory and learning, can also regulate human CD4⁺ T cell function through induction of excitotoxicity. Fresh primary CD4⁺ T cells from healthy donors express functional NMDA‐R that are strongly up‐regulated upon T cell receptor (TCR) mediated activation. Synthetic and physiological NMDA‐R agonists elicited Ca²⁺ flux and led to marked inhibition of type 1 but not type 2 or interleukin‐10 cytokine responses. Among CD4⁺ lines, NMDA and quinolinic acid preferentially reduced cytokine production, Ca²⁺ flux, proliferation and survival of Th1‐like cells through increased induction of cell death whereas Th2‐like cells were largely spared. Collectively, the findings demonstrate that (i) NMDA‐R is rapidly up‐regulated upon CD4⁺ T cell activation in humans and (ii) Th1 versus Th2 cell functions such as proliferation, cytokine production and cell survival are differentially affected by NMDA‐R agonists. Differential cytokine production and proliferative capacity of Th1 versus Th2 cells is attributable in part to increased physiological cell death among fully committed Th1 versus Th2 cells, leading to increased Th2‐like dominance. Hence, excitotoxicity, beyond its roles in neuronal plasticity, may contribute to ongoing modulation of human T cell responses.     

Styrene-maleic acid-copolymer conjugated zinc protoporphyrin as a candidate drug for tumor-targeted therapy and imaging

Previous studies indicated the potential of zinc protoporphyrin (ZnPP) as an antitumor agent targeting to the tumor survival factor heme oxygenase-1, and/or for photodynamic therapy (PDT). In this study, to achieve tumor-targeted delivery, styrene-maleic acid-copolymer conjugated ZnPP (SMA-ZnPP) was synthesized via amide bond, which showed good water solubility, having ZnPP loading of 15%. More importantly, it forms micelles in aqueous solution with a mean particle size of 111.6?nm, whereas it has an apparent Mw of 65?kDa. This micelle formation was not detracted by serum albumin, suggesting it is stable in circulation. Further SMA-ZnPP conjugate will behave as an albumin complex in blood with much larger size (235?kDa) by virtue of the albumin binding property of SMA. Consequently, SMA-ZnPP conjugate exhibited prolonged circulating retention and preferential tumor accumulation by taking advantage of enhanced permeability and retention (EPR) effect. Clear tumor imaging was thus achieved by detecting the fluorescence of ZnPP. In addition, the cytotoxicity and PDT effect of SMA-ZnPP conjugate was confirmed in human cervical cancer HeLa cells. Light irradiation remarkably increased the cytotoxicity (IC₅₀, from 33 to 5?μM). These findings may provide new options and knowledge for developing ZnPP based anticancer theranostic drugs.     

Pustular‐type drug‐induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms due to carbamazepine with systemic muscle involvement

Drug‐induced hypersensitivity syndrome (DIHS)/drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe reaction usually associated with maculopapular eruptions and systemic involvement. Here we report the first case, to our knowledge, of DIHS/DRESS due to carbamazepine with acute generalized pustular bacterid‐like (AGPB‐like) eruptions and skeletal muscle involvement. Reviewing our case and the published work, we discuss pustular‐type DIHS/DRESS which, in most cases, involves acute generalized exanthematous pustulosis (AGEP)‐like skin eruptions in response to carbamazepine. Pustular eruptions may appear in relatively few cases of DIHS/DRESS, in particular, when the causative drug is carbamazepine and, even in cases of intractable pustular bacterid‐like eruptions, a reaction to a drug should be suspected. Skeletal muscle involvement may be associated with DIHS/DRESS as one of its systemic manifestations.     

Opposite regulation of epithelial-to-mesenchymal transition and cell invasiveness by periostin between prostate and bladder cancer cells

We previously showed that periostin expression is downregulated in human bladder cancer tissues and that ectopic expression of periostin suppresses the invasiveness of bladder cancer cells. However, in most other human cancers studied, the expression of periostin promotes cell invasiveness. In the present study, we investigated the regulation of the epithelial-to-mesenchymal transition (EMT) and cell invasiveness by periostin in bladder and prostate cancer cell lines, and found opposite regulation of EMT and cell invasiveness by periostin. Periostin upregulated E-cadherin expression in bladder cancer cells but downregulated it in prostate cancer cells. Periostin suppressed cell invasiveness in bladder cancer cells but promoted it in prostate cancer cells. Snail, a negative regulator of E-cadherin, was upregulated by periostin in prostate cancer cells, while Twist, another negative regulator of E-cadherin, was downregulated in bladder cancer cells. The C-terminal region of periostin was sufficient for these functions in bladder cancer cells but not in prostate cancer cells. Knockdown of endogenous Snail by siRNA suppressed cell invasiveness in prostate cancer cells expressing periostin. Periostin also suppressed Akt phosphorylation in bladder cancer cells but enhanced it in prostate cancer cells. Treatment with Akt inhibitor increased E-cadherin expression and suppressed both Twist expression and cell invasiveness of bladder cancer cells. These results indicate that Akt signaling plays a role in the cell-type-dependent regulation of E-cadherin expression and cell invasiveness by periostin via Snail and Twist.