Post-marketing surveillance of zinc acetate dihydrate for hypozincemia in Japan.

Zinc is an essential microelement, and its deficit causes various diseases and symptoms. In adults, especially in elderly individuals, zinc shortage can cause symptoms such as taste disorder, dermatitis, and susceptibility to infection. In children, zinc deficiency can lead to growth retardation. In 2017, the indication for zinc acetate dihydrate (NOBELZIN®) was expanded from Wilson's disease to include hypozincemia, leading to wider use of zinc acetate dihydrate. At five years after this broadening of use, we conducted a post-marketing study (PMS) to investigate the utilization, safety, and effectiveness of zinc acetate dihydrate. Over 52 weeks, the overall incidence of adverse drug reactions (ADRs) was 9.4% (87/928). The most common ADR was copper deficiency (2.4%), followed by nausea (1.4%). Among 928 patients, 19 (2%) developed serious ADRs. Of the patients with copper deficiency, 92% were >65 years of age, and all had comorbidities at baseline. Physicians evaluated the effectiveness of zinc acetate dihydrate using three categories: "effective", "not effective", and "indeterminate". The overall efficacy rate was 83.0%. The average serum zinc levels were elevated from 50-60 µg/dL to >90 µg/dL within 12 weeks, and were maintained up to 52 weeks after administration. Among the symptomatic sub-categories, the efficacy rate was highest in pressure ulcer (96.2%; 25/26), followed by in stomatitis (87.5%; 42/48), and taste disorder (87.4%; 181/207). Among pediatric patients with developmental symptoms, an efficacy rate of 66% was achieved. In conclusion, zinc acetate dihydrate has been safely used, and has produced beneficial effects on various diseases and symptoms.

Bioassay technique using seed shrimps for comparative studies regarding the aquatic acute lethality of biodegradable lubricants.

To evaluate the environmental load resulting from the spillage of biodegradable lubricants in aquatic systems, a comparative acute lethality test wherein an oil-water interfacial area could be examined was considered. In this study, oleic acid was employed as a model biodegradable lubricant. Measurements of the pH value and dissolved oxygen (DO) level of water during the exposure tests indicate that water degradation depends on the oil-water interfacial area, exposure duration, and water temperature. Furthermore, 72 h acute lethality tests were performed using two types of freshwater ostracods (seed shrimps) as test organisms: the large species Stenocypris hislopi and the small species Cypretta seurati. The longevity of the small species, which was physically more active, was strongly affected by water pollution. During the exposure test, the DO in water was significantly consumed by the degradation of the lubricant floating on it. Water exposed to a lubricant containing copper (Cu) demonstrated strong toxicity even after the recovery of the pH value and DO level by aging. The decrease in the DO level of water and increase in the concentration of metal compounds are dominant factors responsible for the mortality of aquatic organisms.

Downregulation of an AIM-1 kinase couples with megakaryocytic polyploidization of human hematopoietic cells.

During the late phase of megakaryopoiesis, megakaryocytes undergo polyploidization, which is characterized by DNA duplication without concomitant cell division. However, it remains unknown by which mechanisms this process occurs. AIM-1 and STK15 belong to the Aurora/increase-in-ploidy (Ipl)1 serine/threonine kinase family and play key roles in mitosis. In a human interleukin-3-dependent cell line, F-36P, the expressions of AIM-1 and STK15 mRNA were specifically observed at G2/M phase of the cell cycle during proliferation. In contrast, the expressions of AIM-1 and STK15 were continuously repressed during megakaryocytic polyploidization of human erythro/megakaryocytic cell lines (F-36P, K562, and CMK) treated with thrombopoietin, activated ras (H-ras(G12V)), or phorbol ester. Furthermore, their expressions were suppressed during thrombopoietin-induced polyploidization of normal human megakaryocytes. Activation of AIM-1 by the induced expression of AIM-1(wild-type) canceled TPA-induced polyploidization of K562 cells significantly, whereas that of STK15 did not. Moreover, suppression of AIM-1 by the induced expression of AIM-1 (K/R, dominant-negative type) led to polyploidization in 25% of K562 cells, whereas STK15(K/R) showed no effect. Also, the induced expression of AIM-1(K/R) in CMK cells provoked polyploidization up to 32N. These results suggested that downregulation of AIM-1 at M phase may be involved in abortive mitosis and polyploid formation of megakaryocytes.

Role of DNA methylation for expression of novel stem cell marker CDCP1 in hematopoietic cells.

CDCP1, a novel stem cell marker, is expressed in hematopoietic cell line K562 but not in Jurkat. When CDCP1 promoter was transfected exogenously, Jurkat showed comparable promoter activity with K562, suggesting that the factor to enhance transcription was present but interfered to function in Jurkat. The reporter assay and si-RNA-mediated knockdown experiment revealed that zfp67, a zinc-finger protein, enhanced CDCP1 transcription. Amount of zfp67 in Jurkat was comparable with K562, but chromatin immunoprecipitation showed that zfp67 bound to CDCP1 promoter in K562 but not in Jurkat. There are CpG sequences around the promoter of CDCP1, which were heavily methylated in Jurkat but not in K562. Addition of demethylating reagent to Jurkat induced CDCP1 expression, and increased the zfp67 binding to CDCP1 promoter. Among normal hematopoietic cells such as CD34+CD38- cells, lymphocytes and granulocytes, inverse correlation between proportion of methylated CpG sequences and CDCP1 expression level was found. Demethylation of CpG sequences in lymphocytes, in which CpG sequences were heavily methylated, induced CDCP1 expression and its expression level further increased through zfp67 overexpression. The methylation of DNA appeared to regulate the cell-type-specific expression of CDCP1 through the control of interaction between chromatin DNA and transcription factors.

Effects of marital status and position on personality traits in engineers of a computer manufacturing plant.

To investigate the effects of marital status and position on DSM-III-R personality traits, we administered the self-rating questionnaires of the Structured Clinical Interview for DSM-III-R Personality Disorders to 757 male computer engineers, aged 20 to 49 years, at a computer manufacturing plant. The scores for six of eleven personality traits were significantly higher in single computer engineers than in married ones. Also, among the engineers aged 40 to 49, the scores for six personality traits of section-heads were significantly higher than those among persons in the other positions. These findings suggest that "maladaptive" personality traits, defined by the DSM-III-R, differ with marital status and position in a company.

Difference between genomic actions of estrogen versus raloxifene in human ovarian cancer cell lines.

Although there is growing evidence that estrogens promote tumor progression in epithelial ovarian cancer, the molecular mechanisms accounting for this are still unclear. Selective estrogen receptor modulators (SERMs) mimic estrogen action in certain tissues while opposing it in others. The molecular mechanisms of the effects of SERMs such as raloxifene on the tumor progression of epithelial ovarian cancer are also still unclear. Here, we show that various genomic actions of estrogen differ from those of raloxifene in human ovarian cancer cell lines expressing estrogen receptor alpha (ERalpha). 17beta-Estradiol (E2) induced the gene expression of c-Myc and IGF-1 and increased the binding of ERalpha to the AP1 site of the promoters of c-Myc and IGF-1. ERalpha silencing abolished the E2-stimulated c-Myc expression. E2 induced the recruitment of co-activators such as SRC-1, SRC-3 and CBP to the promoters of c-Myc and IGF-1, and SRC-1 silencing abolished both the E2-stimulated c-Myc expression and cell-cycle progression. In contrast, although raloxifene increased the binding of ERalpha to the AP1 site of the promoters of c-Myc and IGF-1, raloxifene had no effect on the gene expression of c-Myc or IGF-1. Raloxifene induced the recruitment of co-repressors such as HDAC2, N-CoR and SMRT to the promoter of IGF-1. Thus, the difference between the genomic actions exerted by estrogen and raloxifene in human ovarian cancer cell lines expressing ERalpha appear to be dependent on the recruitment of co-regulators.

Behavioral lifestyle and mental health status of Japanese factory workers.

BACKGROUND: Lifestyle factors, sometimes associated with physical health and mortality, have also been known to be associated with mental health status. This study seeks to correlate behavioral lifestyles with major components of mental health among Japanese factory workers. METHOD: We administered the 28-item version of the General Health Questionnaire (GHQ-28) and a questionnaire concerning eight personal health practices to 2,132 male and 668 female factory workers at a camera-manufacturing company in Japan. RESULTS: There were strong negative relationships of a higher total number of favorable lifestyles as indicated by the Health Practice Index (HPI) to psychological distress and its components: somatic symptoms, anxiety-insomnia, and social dysfunction. After controlling for the effects of confounding factors that included age, marital status, and somatic condition, multiple logistic regression analysis indicated that five of the eight health factors among male workers--mental stress, nutritional balance, eating breakfast regularly, physical exercise, and working hours--were significantly related to the grade of psychological distress or its three components. Among female workers, five health practices, i.e., mental stress, physical exercise, sleeping hours, working hours, and cigarette smoking, were significantly associated with the grade of psychological distress or its three components. CONCLUSION: Good health practices might be individually and as a whole associated with better mental health status in factory workers.

Quantitative assessment of stressors and stress reaction: a review.

To survey methods for assessing stress and to examine the relationship of stress to health and the factors of lifestyle, we reviewed the literature on stressors and stress reactions. Firstly, we reviewed the representative methods for assessing stressors. Secondly, self-report questionnaires based on a theoretical model of occupational stressors were surveyed and factors in work stress were listed. Then, we reviewed stress reactions including physiological, psychological and behavioral reactions. Finally, we examined the relationship of perceived stress measured by a single question to mental health status determined by the General Health Questionnaire (GHQ-28), lifestyles and personality based on the Egogram in Transactional Analysis. It is suggested that we need to assess subjective aspects as well as using objective indices such as data from physical examinations, to evaluate the level of stress and to promote mental health.

Assessment of personality traits and psychiatric symptoms in workers in a computer manufacturing plant in Japan.

To investigate personality traits and psychiatric symptoms, we administered the Structured Clinical Interview for DSM-III-R Personality Questionnaire (SCID-II Screen), the Zung Self-Rating Depression Scale (SDS), and the 30-item version of the General Health Questionnaire (GHQ-30) to 781 male computer engineers and 214 male clerical workers in a computer manufacturing factory. Subjects, aged from 20 to 49 years, were divided into university and high school graduates. Among the university graduates, scores for schizotypal and avoidant personality traits were significantly higher in computer engineers than in clerical workers (the effect of age was controlled by analysis of covariance). No significant correlation between personality traits and years employed was found in the university-graduate computer engineers. In high school graduates, scores for borderline and dependent personality traits were significantly lower in computer engineers than in clerical workers (the effect of age was controlled by analysis of covariance). Because of the lack of significant association of personality traits and symptoms with duration of employment in the university-educated computer engineers, the greater prevalence of schizotypal and avoidant personality traits might be related to their process of self-selection of job rather than to computer manufacturing work. In summary, these data suggest that computer engineering work does not cause abnormal personality traits or psychiatric symptoms.

Work stress in Japanese computer engineers: effects of computer work or bioeducational factors.

To examine whether computer work and bioeducational factors (age and school career) have significant effects on work stress in computer engineers in Japan, we administered a stress questionnaire to 764 male computer engineers and 211 male office workers in a computer-manufacturing factory in Tokyo. Four scales of perceived psychological stress at work examined were work overload, poor human relationships at work, unsuitable job, and competition-dismissal anxiety. The results of the three-way analysis of variance, in which age (20-29, 30-39, and 40-49 years), school career (high school and university graduates), and computer work (computer engineers and office workers) were three variation factors, indicated that: (1) there were no significant differences in all scores of work stress between computer engineers and office workers (P > 0.05); (2) scores for unsuitable job and poor human relationships at work were significantly higher in high school graduates than in university graduates (P < 0.05); and (3) there were significant age differences in scores for three scales of work stress (unsuitable job, competition-dismissal anxiety, and work overload: P < 0.001, P < 0.01, and P < 0.05, respectively). These findings suggest that computer work has no significant effect on perceived work stress in computer engineers; on the other hand, age and school career do have effects.

Biologic significance of GATA-1 activities in Ras-mediated megakaryocytic differentiation of hematopoietic cell lines.

Lineage-specific transcription factors play crucial roles in the development of hematopoietic cells. In a previous study, it was demonstrated that Ras activation was involved in thrombopoietin-induced megakaryocytic differentiation. In this study, constitutive Ras activation by H-ras(G12V) evoked megakaryocytic maturation of erythroleukemia cell lines F-36P and K562, but not of myeloid cell line 32D cl3 that lacks GATA-1. However, the introduction of GATA-1 led to reprogramming of 32D cl3 toward erythrocytic/megakaryocytic lineage and enabled it to undergo megakaryocytic differentiation in response to H-ras(G12V). In contrast, the overexpression of PU.1 and c-Myb changed the phenotype of K562 from erythroid to myeloid/monocytic lineage and rendered K562 to differentiate into granulocytes and macrophages in response to H-ras(G12V), respectively. In GATA-1-transfected 32D cl3, the endogenous expression of PU.1 and c-Myb was easily detectable, but their activities were reduced severely. Endogenous GATA-1 activities were markedly suppressed in PU.1-transfected and c-myb-transfected K562. As for the mechanisms of these reciprocal inhibitions, GATA-1 and PU.1 were found to associate through their DNA-binding domains and to inhibit the respective DNA-binding activities of each other. In addition, c-Myb bound to GATA-1 and inhibited its DNA-binding activities. Mutant GATA-1 and PU.1 that retained their own transcriptional activities but could not inhibit the reciprocal partner were less effective in changing the lineage phenotype of 32D cl3 and K562. These results suggested that GATA-1 activities may be crucial for Ras-mediated megakaryocytic differentiation and that its activities may be regulated by the direct interaction with other lineage-specific transcription factors such as PU.1 and c-Myb.

Chromosome alterations in peripheral lymphocytes as indices of lifestyle and genotoxicity.

Short-term cultures of human lymphocytes were used to investigate the in vitro metabolism of benzene and its genotoxicity, and to monitor genetic health effects of lifestyles. Metabolic (S9) activation of benzene and its metabolites, catechol, hydroquinone, and phenol, caused an increase in sister-chromatid exchanges (SCEs) with different optimal concentrations of S9 mix for converting each compound into further reactive forms. The data indicate that catechol and hydroquinone can be optimally metabolized to produce reactive species, presumably benzo(semi)quinones, under conditions of lower metabolic activity than those necessary for phenol and benzene. We have further investigated the correlations between chromosome alterations (SCEs, structural aberrations and micronuclei) in peripheral lymphocytes and individual lifestyles. Healthy lifestyles, or "good health practices" examined were 1) not smoking, 2) not drinking too much alcohol, 3) doing physical exercise regularly, 4) sleeping more than 6 h per night, 5) keeping nutritional balance in meals, 6) not snacking, 7) having breakfast everyday, and 8) not having too much perceived stress. The persons were categorized into 3 groups having good, moderate and poor lifestyles by the number of good health practices they do. Mean frequencies of chromosome alterations in lymphocytes from men with poor lifestyles have been shown to be significantly higher than those in cells from men having good lifestyles.(ABSTRACT TRUNCATED AT 250 WORDS)