Gender differences in self-perceived changes among Japanese workers with depression.

BACKGROUND: The number of patients living with depression continues to increase in Japan. The economic effects of depression include loss of productivity due to both absenteeism and presenteeism. Gender differences have been reported in prevalence, onset pathways and subjective symptoms of depression. AIMS: To understand how workers with major depressive disorder (MDD) perceive problems in the workplace and examine gender differences in their self-perceived levels of functioning at work, noticed during the initial stages of depression. METHODS: This is a cross-sectional study of Japanese workers with MDD. Participants' self-perceived changes in the level of functioning at work were surveyed after the diagnosis during the first visit. The relationship between gender and changes in the level of functioning at work as initially perceived by the participants themselves was analysed using the chi-square test, supplemented by a residual analysis. RESULTS: We administered the survey to 147 workers with MDD. In terms of gender differences in initial self-perceived changes in the level of functioning at work, the proportion of men reporting reduced work efficiency was significantly higher than that of women, while the proportion of women reporting deterioration in relationships with colleagues and superiors was significantly higher than that of men. CONCLUSIONS: The findings suggest that greater attention to reduced work efficiency by men and to deterioration in work relationships by women with MDD should be essential components of self-care. Managers need to pay attention to the level of functioning and provide adequate social support for employees.

Dopamine D1 receptor subtype mediates acute stress-induced dendritic growth in excitatory neurons of the medial prefrontal cortex and contributes to suppression of stress susceptibility in mice.

Dopamine in prefrontal cortices is implicated in cognitive and emotional functions, and the dysfunction of prefrontal dopamine has been associated with cognitive and emotional deficits in mental illnesses. These findings have led to clinical trials of dopamine-targeting drugs and brain imaging of dopamine receptors in patients with mental illnesses. Rodent studies have suggested that dopaminergic pathway projecting to the medial prefrontal cortex (mPFC) suppresses stress susceptibility. Although various types of mPFC neurons express several dopamine receptor subtypes, previous studies neither isolated a role of dopamine receptor subtype nor identified the site of its action in mPFC. Using social defeat stress (SDS) in mice, here we identified a role of dopamine D1 receptor subtype in mPFC excitatory neurons in suppressing stress susceptibility. Repeated social defeat stress (R-SDS) reduces the expression of D1 receptor subtype in mPFC of mice susceptible to R-SDS. Knockdown of D1 receptor subtype in whole neuronal populations or excitatory neurons in mPFC facilitates the induction of social avoidance by SDS. Single social defeat stress (S-SDS) induces D1 receptor-mediated extracellular signal-regulated kinase phosphorylation and c-Fos expression in mPFC neurons. Whereas R-SDS reduces dendritic lengths of mPFC layer II/III pyramidal neurons, S-SDS increases arborization and spines of apical dendrites of these neurons in a D1 receptor-dependent manner. Collectively, our findings show that D1 receptor subtype and related signaling in mPFC excitatory neurons mediate acute stress-induced dendritic growth of these neurons and contribute to suppression of stress susceptibility. Therefore, we propose that D1 receptor-mediated dendritic growth in mPFC excitatory neurons suppresses stress susceptibility.

Depression and occupational stress in Japanese school principals and vice-principals.

BACKGROUND: Teaching is one of the most stressful occupations. Over the last decade, about 5000 Japanese public school teachers per year have taken sick leave due to a mental illness. School principals and vice principals also face occupational stress, although few studies have examined occupational stress in these groups. AIMS: To clarify the relationship between occupational stress, role problems and depressive symptoms among school principals and vice principals in Japan. METHODS: We conducted a cross-sectional study in 2013 with data from 262 principals and 268 vice principals in Japan. We used the Japanese version of Zung's Self-Rating Depression Scale (SDS) to evaluate depressive symptoms and the Generic Job Stress Questionnaire to evaluate occupational stress and social support. We categorized SDS scores above 49 as indicating depression. We examined the relationship between depressive symptoms and perceived occupational stress using stepwise forward multivariate logistic regression analyses. RESULTS: Thirty-six (14%) principals and 81 (30%) vice-principals were categorized into the depressive group. Quantitative workload (odds ratio, OR = 6.62 [2.63-16.70]) and role ambiguity (OR = 4.94[1.57-15.53]) were associated with higher depressive scores in principals. Social support from supervisors (OR = 4.14 [1.97-8.68]) and role ambiguity (OR = 9.71 [4.08-23.14]) were associated with higher depressive scores in vice-principals. CONCLUSIONS: Clarifying job roles for principals and vice-principals, reducing quantitative workload for principals and increasing supervisory support for vice-principals may be important for mitigating depression for school principals and vice-principals in Japan.

Association between work role stressors and sleep quality.

Background: Work-related stressors are associated with low sleep quality. However, few studies have reported an association between role stressors and sleep quality. Aims: To elucidate the association between role stressors (including role conflict and ambiguity) and sleep quality. Methods: Cross-sectional study of daytime workers whose sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Work-related stressors, including role stressors, were assessed using the Generic Job Stress Questionnaire (GJSQ). The association between sleep quality and work-related stressors was investigated by logistic regression analysis. Results: A total of 243 participants completed questionnaires were received (response rate 71%); 86 participants reported poor sleep quality, based on a global PSQI score ≥6. Multivariable logistic regression analysis revealed that higher role ambiguity was associated with global PSQI scores ≥6, and that role conflict was significantly associated with sleep problems, including sleep disturbance and daytime dysfunction. Conclusions: These results suggest that high role stress is associated with low sleep quality, and that this association should be considered an important determinant of the health of workers.

Prevention of retained fetal membranes and improvement in subsequent fertility with oxytocin administration in cows with assisted calving.

In dairy cows, the efficacy of oxytocin treatment for preventing retained fetal membranes (RFM) is controversial. The physiological condition of cows associated with the calving process may affect the action of oxytocin. This study aimed to elucidate the difference in the efficacy of exogenous oxytocin treatment immediately after calving among cows that received various obstetric interventions. The calving ease was recorded using a score of 1-5, and assisted birth was defined as a score of 2 or more. Cows that required calving assistance (assisted, n = 28) due to delayed calving progression had a prolonged time from calving to expulsion of the fetal membrane (P < 0.01), and impaired reproductive performance compared to cows that did not receive calving assistance (unassisted, n = 78). The effect of oxytocin treatment was determined using cows that did not expel their fetal membrane within 3 h after calving. Cows were randomly divided into the control (unassisted, n = 41; assisted, n = 22) or oxytocin group (unassisted, n = 33; assisted, n = 10). Oxytocin (50 IU) was administered intramuscularly to the cows in the oxytocin group between 3 and 6 h after calving, while no treatment was administered in the control group. In cows with assisted birth, oxytocin administration accelerated placental expulsion (P < 0.05) and improved several reproductive parameters, such as the number of services until conception (P < 0.05) and the calving to conception intervals (P < 0.05) compared to the control group. On the other hand, oxytocin administration slightly accelerated placental expulsion (P < 0.05), but failed to improve fertility in cows with unassisted birth. The results indicate that the action of oxytocin varies depending on the calving situation of the cows. Oxytocin administration during the early postpartum period could prevent RFM and improve the decline in reproductive performance associated with calving assistance.

High level expression of the homeobox gene HB24 in a human T-cell line confers the ability to form tumors in nude mice.

The human homeobox gene HB24 is constitutively expressed in bone marrow progenitor cells and is inducible in lymphocytes. Transfection of HB24 into the T-cell line Jurkat under the control of the beta-actin promoter resulted in enhanced cell growth and induction of several growth-related genes. In this study we have examined whether the presence of high levels of HB24 alters the tumorigenicity of Jurkat cells in nude mice. Subcutaneous injection of 1-2 x 10(6) Jurkat cells or Jurkat cells transfected with a control expression vector into nude mice failed to produce tumors. However, injection of a similar number of HB24-transfected Jurkat cells resulted in local tumor formation within 4 weeks and grossly apparent metastatic lesions within 8 weeks. Histopathological analysis of tissues from the local and metastatic lesions demonstrated predominantly lymphoid cells, consistent with the morphological appearance of the injected cell line. Freshly isolated tumor cells from the nude mice incorporated similar levels of [3H]thymidine as the HB24-transfected Jurkat cells and 2-fold more than the parent Jurkat cells. Northern blot analysis of RNA prepared from the tumors revealed expression of human interleukin 2, interleukin 2 receptor alpha-chain, HB24, and CD4. Flow cytometric analysis of the tumor cells revealed human CD4 expression but not murine CD4, confirming the human origin of the tumor cells. Media conditioned by the tumor cells contained large amounts of interleukin 2. Since natural killer cell activity is the primary immunological response against tumors in nude mice, the effects of HB24 on the responsiveness to natural killer cell-mediated cell lysis was examined. No differences in natural killer cell killing of the parent Jurkat cells and the HB24-transfected cells were observed. These data, in conjunction with recent data implicating other homeobox-containing genes in the pathogenesis of human leukemias, suggest that overexpression of HB24 in hematopoietic progenitors or T-cells may contribute to oncogenic transformation.

High expression of two diverged homeobox genes, HB24 and HB9, in acute leukemias: molecular markers of hematopoietic cell immaturity.

Homeobox genes encode for sequence-specific DNA-binding proteins which have been implicated in the control of gene expression during development and in certain adult tissues. Two recently characterized human homeobox-containing genes, HB9 and HB24, are known to be expressed in hematopoietic progenitors and to be involved in the regulation of growth and differentiation of progenitor cells to mature hematopoietic cell types. In this study, elevated levels of HB24 and HB9 mRNA expression were detected in bone marrow and peripheral blood mononuclear cells (PBMC) isolated from patients with acute myelogenous or acute lymphocytic leukemia. While the levels of both mRNAs were elevated in all the patients with acute leukemias, the levels of HB9 mRNA were more variable than those of HB24. Immunohistochemical analysis utilizing an HB24 polyclonal antiserum demonstrated elevated levels of HB24 protein in cytopreparations of acute leukemic cells. Nuclear run-on experiments showed that the increases of HB9 and HB24 mRNA transcripts in patients' cells were, at least in part, secondary to increased transcription. The expression of HB9 and HB24 correlated with the clinical status of the patient. No significant level of expression of either HB9 or HB24 was detected in PBMC isolated from patients in remission. In contrast to the findings with cells isolated from patients with acute leukemias, no significant increase in either HB9 or HB24 transcript levels were found in cells from patients with chronic lymphocytic or chronic myelogenous leukemia when compared to normal controls. These findings demonstrate that high levels of HB9 and HB24 expression are common features of acute leukemia and suggest the possibility that the dysregulated expression of these two genes may contribute to leukemogenesis. However, since these two genes are markers of immature hematopoietic cells they may not have an etiologic role in leukemogenesis.

Application of an in vivo brain microdialysis technique to studies of drug transport across the blood-brain barrier.

There is a wide range of methods available for studying the transport of drugs across the blood-brain barrier (BBB) which is equipped with several systems to transport drugs as well as endogenous nutrients and waste products. The in vivo brain microdialysis technique, which allows direct sampling of the brain interstitial fluid (ISF), is a powerful means of characterizing influx and efflux transport across the BBB. In this paper, we review our results from the successful application of this technique to BBB drug transport studies. The drugs investigated include novel and CNS-active peptides, some agents that are actively removed from the brain ISF across the BBB, and a brain-directed prodrug.

Enhanced transcription of c-myc proto-oncogene in spleen lymphocytes from lupus-prone mice during the growing process.

The expression of c-myc proto-oncogene in spleen lymphocytes has been studied in lupus-prone mice (MRL/Mp-lpr/lpr), an animal model for the human autoimmune disease systemic lupus erythematosus, during the growing process, in comparison to control mice (MRL/Mp-+/+). By Northern blot assay and nuclear run on transcription assay, we demonstrated the enhancement of c-myc proto-oncogene expression in spleen lymphocytes from lupus-prone mice in comparison to control mice and the level of expression of c-myc proto-oncogene increased during the growing process and deterioration of lupus symptoms, such as production of autoantibodies and lymphoproliferation, in this study.

Age-related changes of proliferative response, kinetics of expression of protooncogenes after the mitogenic stimulation and methylation level of the protooncogene in purified human lymphocyte subsets.

Proliferative responses of highly purified T and B cells from aged persons to the combined stimulation with ionomycin and PMA were more significantly reduced than that from young ones although the degree of the age-related reduction was more significant in T cells than in B cells. In B cells, the levels and kinetics of c-myc gene expression after the stimulation were comparable between aged and young groups. In T cells, the maximum level of c-myc gene expression after the stimulation was comparable between the two age groups but the rate of reduction of c-myc mRNA was significantly retarded in the aged. The results of nuclear run on transcription assay showed the reduction of the rate of c-myc mRNA degradation seemed to be the cause. The levels and kinetics of c-myb gene expression in either T or B cells were comparable between the two age groups. We further examined the level of methylation of Xho I site of c-myc gene. The level of the methylation was significantly lower in the aged T cells and more significant in aged CD 8 positive T cells although that in aged B cells was comparable to that in young ones. The relation between a reduced proliferation, a retarded rate of c-myc mRNA degradation and reduction of methylation level of c-myc gene was discussed.

Age-related changes of expression of IL-2 receptor subunits and kinetics of IL-2 internalization in T cells after mitogenic stimulation.

The age-associated changes of the expression of IL-2 binding molecules p55/Tac(alpha chain) and p70/75(beta chain) were examined after phytohemagglutinin (PHA) stimulation. The expressions of both p55/Tac molecules and p70/75 molecules were significantly reduced in the aged compared with those in the young persons. The amounts of p55/Tac and p70/75 molecules on T cells from the aged were 55% and 59% of those on young ones, respectively. The ratio of the amount of p70/75 to that of p55/Tac in aged T cells was 0.28 and that in young ones was 0.26. The ratio was somewhat higher in the aged but not significantly. We also examined the kinetics of IL-2 internalization mediated by its receptor. The calculated t1/2 of receptor-mediated IL-2 internalization was 17 min in the aged and 16 min in the young, respectively. There was no kinetic difference between the 2 groups. The percentage of the internalized IL-2 to the sum total was 58.2% in the aged and 73.4% in the young (P less than 0.02). the amount of internalized IL-2 in T cells from the aged was 48.6% of that from the young (P less than 0.01).

The effect of taurine on age-related immune decline in mice: the effect of taurine on T cell and B cell proliferative response under costimulation with ionomycin and phorbol myristate acetate.

Proliferative responses to the costimulation with phorbol-12-myristate-13-acetate (PMA) and suboptimal doses of ionomycin in the purified T and B cells from old mice were lower than those from young mice. The degree of the age-related decline was more significant in T cells than in B cells. Taurine, a sulfur containing amino acid, augmented the proliferative responses of T cells from both young and old mice. The augmentation of the proliferative response by taurine was more marked in old T cells than in young ones. The concentration of intracellular free calcium ion ([Ca2+]i) was significantly lower in the old T cells under the stimulation with PMA and ionomycin than that in the young ones. In the presence of taurine, the concentration of [Ca2+]i in the old T cell significantly increased under the stimulation. The results indicate that taurine improved the proliferative response of old T cells by the restoration of the increment of the concentration of [Ca2+]i under the stimulation.

Longer longitudinal atrial dimension in patients with idiopathic paroxysmal atrial fibrillation: A possible cause of atrial fibrillation.

BACKGROUND: The ostium of the superior pulmonary veins or superior vena cava has been reported to be an important source of the ectopic beats that initiate paroxysmal atrial fibrillation (PAF). The structural details of the atria in patients with idiopathic PAF, however, remain unknown. METHODS: We studied 113 patients (92 men and 21 women) with idiopathic PAF and 128 normal control subjects (100 men and 28 women). None of the subjects in either group were found to have any evidence of structural cardiac disease. The echocardiographic measurements were performed in the apical 4-chamber view during end-systole of sinus rhythm. RESULTS: The longitudinal dimension of the left and right atria was longer in patients with PAF who were not administered any drugs (non-drug-taking patients) than in the control subjects (P <.001 and P <.01, respectively). However, there were no significant differences in the transverse dimension of either atrium between such patients and control subjects. The longitudinal and transverse dimensions and volume determinations of atria were greater in the patients with idiopathic PAF who were administered class 1 antiarrhythmic drugs than in non-drug-taking patients (P <.05 to.001). In non-drug-taking patients, prolongation of the atrial longitudinal dimension did not depend on either age, the total frequency of PAF, or the interval from the first episode of PAF. The longitudinal dimension of the left and right atria was longer even in the patients with a short history of PAF (<1 month) as compared with control subjects (P <.001 and.05, respectively). CONCLUSIONS: These observations suggest that there is prolongation of the longitudinal dimension in patients with idiopathic PAF independent of PAF frequency and age (and that PAF is probably a consequence of the prolongation).

In vivo evidence for ATP-dependent and P-glycoprotein-mediated transport of cyclosporin A at the blood-brain barrier.

To evaluate the significance of P-glycoprotein (P-gp)-mediated active efflux on the blood-brain barrier (BBB) permeability of cyclosporin A (CsA) in vivo, we investigated the effects of ATP depletion in the brain and of a multidrug-resistant (MDR) reversing agent on the transport of CsA across the BBB. Using transient brain ischemia obtained by 4-vessel occlusion of vertebral and common carotid arteries in rats to deplete ATP content in the brain, the estimated permeability surface area product (PS) value of [3H]CsA was increased 2.7-fold compared with that in normal rats, whereas the PS value of [14C]sucrose was not altered. Additionally, when quinidine hydrochloride (QND) was infused into the brain through a microdialysis probe implanted in the rat hippocampus, the extravascular extraction of CsA was increased to approximately 2.5-fold of the control, whereas no difference in the extravascular extraction between control and normal rats having no implanted dialysis probe was observed. Furthermore, the efflux rate from brain to blood of CsA was decreased remarkably to 5% of control at steady-state by co-administration of CsA with QND directly into the brain through the dialysis probe. The ATP-dependent and QND-sensitive efflux of CsA from the brain strongly indicates that P-gp in the brain capillary endothelial cells functions as an efflux pump under the physiological state, and that P-gp-mediated efflux of CsA is a major mechanism of the restricted transfer from blood into the brain.

Enhanced expression of heat shock protein gene in kidney lymphoid cells of lupus-prone mice during growing process.

In the present study, the spontaneous elevation of the transcription of heat shock protein (hsp 70) gene in kidney lymphoid cells of lupus-prone mice (MRL-lpr/lpr) is shown by Northern blot and nuclear run on transcription assay. By quantification analysis of hsp 70 gene transcription, more than ten times of the enhanced transcription of hsp 70 gene in kidney lymphoid cells of lupus-prone mice was first found, in comparison to normal control mice (MRL(-)+/+). The elevation of transcriptional level of hsp 70 gene was also found to increase during growing process and seemed to have positive correlation with deterioration of lupus-related renal disorders in lupus-prone mice. Our observation suggests that heat shock proteins may be involved in possible significance in the pathophysiology of nephrotic lesions of lupus-prone mice due to lupus-related change of kidney lymphoid cells.

Occurrence of tetrodotoxin and anhydrotetrodotoxin in Vibrio sp. isolated from the intestines of a xanthid crab, Atergatis floridus.

Vibrio sp. isolated from a xanthid crab, Atergatis floridus, was cultured, and tetrodotoxin (TTX) and anhydroTTX were indicated to be present in several fractions of the cell extract and the culture medium by reverse phase HPLC. The presence of the C9-base in alkaline hydrolyzates of these fractions was confirmed by GC-MS and UV spectrometry. These results showed the production of TTX and anhydroTTX in the Vibrio sp., thus indicating one of the origins of TTX in nature.

Enhancement of c-sis proto-oncogene transcription in bronchoalveolar mononuclear cells from patients with pulmonary sarcoidosis.

The expression of c-sis proto-oncogene in bronchoalveolar mononuclear cells was studied in seven patients with pulmonary sarcoidosis. By means of nuclear run on transcription assay, the transcriptional level of c-sis proto-oncogene in bronchoalveolar mononuclear cells was investigated. Expression of c-sis proto-oncogene in bronchoalveolar mononuclear cells was enhanced. Enhancement of c-sis transcription may be involved in the process of activation of bronchoalveolar mononuclear cells in patients with pulmonary sarcoidosis.

Efficacy of Influenza Vaccine in Elderly Persons in Welfare Nursing Homes: Reduction in Risks of Mortality and Morbidity During an Influenza A (H3N2) Epidemic.

BACKGROUND: The effect of influenza vaccination on the occurrence and severity of influenza virus infection in a population residing in nursing homes was studied through a program by the Osaka Prefectural Government, which is the first and official support for influenza vaccination of the elderly population during an influenza A (H3N2) epidemic in JAPAN: METHODS: A cohort study located in the Osaka Prefecture, Japan, followed the outcomes of elderly nursing home residents who received influenza vaccinations (n = 10,739) in comparison with control subjects who did not receive influenza vaccinations (n = 11,723) and monitored clinically the onset of serious morbidity and mortality of influenza illness. Subjects were 22,462 persons older than 65 years who resided in 301 welfare nursing homes in the Osaka Prefecture, Japan during an influenza A (H3N2) epidemic in 1998 to 1999. RESULTS: Of 22,462 individuals living in 301 nursing homes, 10,739 received either one dose (2027 subjects) or two doses (8712 subjects) of inactivated, subunit trivalent influenza vaccine. Through the period from November 1998 to March 1999, there were 950 cases of influenza infection diagnosed clinically with cases by virus isolation and/or serology. There were statistically significantly fewer clinical cases of influenza, hospital admissions due to severe infection, and deaths due to influenza in the vaccinated cohort (256 cases, 32 hospital admissions, and one death) compared with the unvaccinated controls (694 cases, 150 hospital admissions, and five deaths). Vaccination was equally effective in those who received one dose of vaccine as in those who received two doses. No serious adverse reactions to vaccination were recorded. Thus, influenza vaccination is safe and effective in this population and should be an integral part of the routine care of persons aged 65 years and older residing in nursing homes. CONCLUSIONS: This study provides an analysis of the clinical efficacy of influenza vaccination in a large cohort of nursing home residents in JAPAN: Annual influenza vaccine administration requires the attention of all nursing home attendants, physicians, and public health organizations.

Inhibition of brain cyclooxygenase-2 activity and the antipyretic action of nimesulide.

The antipyretic action and the mechanism of action of 4-nitro-2-phenoxymethanesulfonanilide (nimesulide), a new nonsteroidal antiinflammatory drug, were investigated in yeast-induced febrile rats. Yeast-injected rats developed marked fever and exhibited an approximately 7-fold increase in brain levels of prostaglandin E2 and an approximately 2-fold increase in the expression of cyclooxygenase-2 mRNA despite an almost unchanged expression of cyclooxygenase-1 mRNA. Nimesulide produced a dose dependent antipyretic action, which was stronger than that of indomethacin and ibuprofen, and decreased dose dependently the increased brain prostaglandin E2 levels, whereas it did not influence the expression of cyclooxygenase-2 mRNA. It inhibited markedly the enhanced brain cyclooxygenase activity, primarily cyclooxygenase-2, in vivo and dose dependently increased brain cyclooxygenase activity in vitro. These results suggest that the marked antipyretic action of nimesulide is primarily mediated through the selective inhibition of the activity of brain cyclooxygenase-2 induced under febrile conditions.

Potential roles for two human homeodomain containing proteins in the proliferation and differentiation of human hematopoietic progenitors.

Two human homeobox genes, HB9 and HLX, are expressed in hematopoietic progenitors and activated lymphocytes. They are implicated in the proliferation of hematopoietic progenitors in response to growth factors and the differentiation of hematopoietic progenitors to mature cell lineages. RNAs from bone marrow cells of patients with acute myeloid or lymphocytic leukemia have high levels of these two genes while similar RNAs from patients with chronic lymphocytic or myeloid leukemias have nearly normal levels. While the significance of these two genes in leukemogenesis is unknown, they are likely to regulate gene transcription during hematopoiesis and their dysregulation may have dire consequences for hematopoietic cells.