Association between forest and greenspace walking and stress-coping skills among workers of Tsukuba Science City, Japan: A cross-sectional study.

Objectives: Recently, "sense of coherence" (SOC) as a concept of stress-coping, has been gaining considerable attention. Although many studies have investigated the factors related to strong SOC, we found little evidence about the associations between SOC and habits that are easy to perform in everyday life. The aim our study was to examine the prevalence of workers who engage in forest walking and greenspace walking and examine their association with SOC score. Study design: A cross-sectional study. Methods: An anonymous, self-report web questionnaire was conducted in November 2017. The study population included 19481 workers belonging to the Tsukuba Science City Network and data of 6466 participants (3965 men and 2501 women) were analyzed. Results: The percentage of participants who engage in forest and greenspace walking at least once a year were 55.9% and 75.9%, respectively. Associations between forest/greenspace walking and SOC score were calculated using Chi-squared tests. Multinomial logistic regression analyses with SOC score group (strong/middle/weak) as a dependent variable and forest/greenspace walking as explanatory variables were performed. Statistically significant positive associations were observed between strong SOC and those who engaged in forest/greenspace walking after adjusting for socioeconomic factors. The odds ratios for strong SOC were 3.65 (95% CI â€‹= â€‹1.70-7.85) for forest walking at least once a week and 2.12 for greenspace walking (95% CI â€‹= â€‹1.54-2.92) at least once a week. Conclusions: Our findings suggested that forest/greenspace walking may enhance workers' stress-coping skills.

Association between altered systemic inflammatory interleukin-1beta and natural killer cell activity and subsequently agitation in patients with Alzheimer disease.

OBJECTIVE: Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly and is frequently accompanied by emotional disorder, including agitation. Although evidence of neuroendocrine immune and inflammatory functions during emotional changes has been accumulated, the pathogenic mechanisms in the development of agitation accompanied by AD remain to be elucidated. METHODS: To clarify the involvement of neuroendocrine and immune and inflammatory systems in agitation in AD, we examined agitation levels, circadian rhythms of behavior, cortisol, interleukin-1beta (IL-1beta), and natural killer cell activity (NKCA) in controls without dementia and 16 AD patients who were recognized to be easily agitated in their nursing homes. These behavioral and blood indicators were assessed according to the progress of the stage of agitation in 16 AD patients (stable, pre-agitation, and agitation stages). RESULTS: Elevations in night behavior and blood cortisol, IL-1beta and an reduced blood NKCA level in the evening were observed not only in the agitation stage, but also when stable in AD patients as compared to the control. Increased IL-1beta and decreased NKCA occurred in both the morning and evening in pre-agitation and agitation stages in AD. CONCLUSIONS: The increased IL-1beta and decreased NKCA with the progress of agitation in AD suggest that inflammation produces agitation and aggravates AD.

[Survival after surgical resection for stage IV non-small cell lung cancer].

We analyzed 20 patients with stage IV non-small cell lung cancer operated from 1988 to 2003. Fourteen out of 20 were cases with pulmonary metastasis (pm2). The prognosis of patients with pm2 was better than that of those with distant organ metastasis. In pm2 patients, the survival rate of cases without lymph node metastases was higher than those with lymph node metastases. It is suggested that in cases of pm2 without lymph node metastases, surgical operation is possibly effective treatment of choice.

Blood endothelin-1 and cold-induced vasodilation in patients with primary Raynauld's phenomenon and workers with vibration-induced white finger.

AIM: Cold water-immersion induces vasoconstriction with an elevation of blood endothelin-1, which is a potent vasoconstrictor peptide, in patients with primary Raynaud's phenomenon (PRP). However, physiological involvement of endothelin-1 in cold-induced vasodilation (CIVD) remains to be elucidated. METHODS: We monitored changes of finger blood flow during cold water (10 degrees C) immersion and assayed blood endothelin-1 in 7 PRP patients and 7 workers with vibration-induced white finger (VWF) and in the respective control subjects. RESULTS: While significant reductions in finger blood flow at 2 min after the immersion were observed in PRP patients and VWF workers, its elevation at 4 min, which was considered to reflect CIVD, was recognized only in PRP patients. In healthy controls, blood endothelin-1 increased at 4 min and returned to the basal level immediately after the immersion. The increase in blood endothelin-1 at 4 min in PRP patients was greater than that in controls, and continued even after the immersion. Conversely, the increase neither at 4 min nor after immersion was seen in VWF workers. Local vascular changes produced by repetitive vibration may be responsible for the attenuated CIVD and unchanged blood endothelin-1 during cold water-immersion in VWF workers. CONCLUSION: Our results showing elevated blood endothelin-1 during and after immersion in PRP contrast with that in VWF suggesting that endothelin-1 is related to sympathetic hyperactivity which is more involved in PRP rather than VWF. It seems unlikely that endothelin-1 is functionally or directly associated with CIVD.

The association between intravenous haloperidol and prolonged QT interval.

Although intravenous haloperidol (HAL) is an effective medication that is often prescribed to treat agitation, several instances of torsade de pointes or prolonged QT interval have been reported. To investigate the association between intravenous HAL and QT prolongation and between intravenous HAL and ventricular tachyarrhythmia, a cross-sectional cohort study was performed that included measuring corrected QT intervals (QTc) on an emergency basis before intravenous HAL and continuously monitoring electrocardiographic (ECG) findings after intravenous HAL. During a 2-month period, 47 patients received intravenous injections to control psychotic disruptive behavior. According to clinical practice, patients were divided as follows. The FZ-alone group was treated with intravenous flunitrazepam (FZ), and the FZ-plus-HAL group received intravenous FZ followed by intravenous HAL. Although the difference in the mean QTc immediately after intravenous FZ between the two groups was not significant, the mean QTc after 8 hours in the FZ-plus-HAL group was longer than that in the FZ-alone group (p < 0.001). Four patients in the FZ-plus-HAL group had a QTc of more than 500 msec after 8 hours. The change in QTc during 8 hours significantly differed between the two groups (t = 2.64, p > 0.05). Furthermore, the change in QTc was moderately correlated with the dose of intravenous HAL, as evidenced by a coefficient of correlation of 0.48 (p < 0.001). However, ventricular tachyarrhythmia was not detected among 307 patients within a 1-year period, although the ECG was continuously monitored for at least 8 hours after intravenous HAL. The modest nature of QTc prolongation and the apparent absence of ventricular tachyarrhythmia under continuous ECG monitoring indicate that QTc prolongation associated with intravenous HAL is not necessarily dangerous. However, in an emergency situation, clinicians cannot exclude patients predisposed to torsade de pointes, such as those with inherited ion channel disorders. Therefore, clinicians should be aware of the association between intravenous HAL and QT prolongation.

Mental health of scientific researchers. I. Characteristics of job stress among scientific researchers working at a research park in Japan.

In order to clarify the characteristics of job stress in scientific researchers, a self-administered questionnaire survey for 16,330 workers was carried out at Tsukuba Research Park City, Japan. The data of 7,063 (43%) workers aged 20-59 years old were analyzed, and the characteristics of job stress in 3,290 scientific researchers were compared with those of 1,799 technicians and 1,849 clerks. The researchers perceived higher quantitative and qualitative workload, greater job control (job decision latitude), and greater reward from work, than did the other two job groups. In addition, young male researchers received a large amount of support from their coworkers, while middle-aged male researchers perceived difficulty in personal relationships with their coworkers. From the viewpoints of the demand-control-support model and the effort-reward imbalance model, the researchers, particularly men, were typically occupied in active jobs, and the large amount of effort required for their work seemed to be balanced by greater reward from work. Compared with male researchers, however, female researchers perceived lesser job demand, lesser job control, and lesser reward from work. The working environment of female researchers may be related to the so-called career stress of working women. The mental health status of these scientific researchers should be examined directly in a future study.

Involvement of central, but not placental corticotropin releasing hormone (CRH) in heat stress induced immunosuppression during pregnancy.

To clarify whether corticotropin releasing hormone (CRH) and beta-endorphin (betaEP) system mediate maternal immunosuppression in pregnant rats exposed to heat through central or placental pathway, we examined the effects of intravenous (iv) (100 or 500 microg) or intracerebroventricular (icv) (5 microg) administration of CRH receptor antagonist alpha-helical CRH (9-41) on splenic natural killer cell activity (NKCA) as well as betaEP in blood, pituitary lobes, and placenta in pregnant rats at 15 to 16 days gestation. Two-way ANOVA revealed that heat reduced NKCA and elevated blood and pituitary betaEP but did not change placental betaEP. Iv administered 500 microg and icv administered alpha-helical CRH reversed the reduced NKCA and the elevated pituitary betaEP, while iv administration of 100 microg alpha-helical CRH did not. The increased blood betaEP was reversed by iv 100 and 500 microg alpha-helical CRH and icv administration. Both iv and icv administrations reduced placental betaEP independent of heat exposure. Thus, the response of placental betaEP to iv administration of alpha-helical CRH seemed to be stronger than that of pituitary betaEP. These results indicate that alpha-helical CRH which acts on pituitary betaEP antagonizes heat-induced immunosuppression during pregnancy, suggesting that immunosuppression produced by heat stress during pregnancy is mediated by the central CRH system. The placental CRH-betaEP system seems unlikely to be involved in the immunosuppression. Physiologic roles of placental CRH and opioid system should be clarified by future in vitro experiments using placenta specimen including placental immunocyte.

[A case of recurrent lung cancer successfully treated with vinorelbine and cisplatin].

A 56-year-old female underwent lobectomy with ND2a lymph node dissection for left lung cancer in April 1999. Histopathological examination demonstrated moderately differentiated adenocarcinoma (pT2N2M0, stage III A). She received one course of a combination of etoposide and cisplatin as adjuvant therapy, followed by oral intake of UFT. In November 1999, a left para-aortic lymph node recurrence was found. She received radiation therapy (total 60 Gy) to the mediastinum. In April 2000, new lung and left supraclavicular lymph node recurrences were found. She received three courses of vinorelbine 20 mg/m2 (days 1, 8) and cisplatin 80 mg/m2 (day 1) followed by radiation therapy (total 50.4 Gy) to the left supraclavicular lesion. After the chemotherapy, a complete response (CR) of all metastatic lesions was achieved. Adverse reactions were grade 1 alopecia, grade 2 nausea/vomiting, grade 3 neutropenia, hypochromia, and injection site reaction. The combination of vinorelbine and cisplatin is a useful regimen in non-small-cell lung cancer.

Cisplatin induces fas expression in esophageal cancer cell lines and enhanced cytotoxicity in combination with LAK cells.

OBJECTIVE: To establish a new therapeutic approach for the treatment of esophageal cancer, we investigated an alternative mechanism of immunotherapy for sensitizing target cells to effector cells. METHODS: Six human esophageal cancer cell lines were used. The expression of Fas antigen on tumor cells was determined by flow cytometry. The cytotoxic effect of cis-dichlorodiammineplatinum (CDDP) and anti-Fas antibody was evaluated using an MTT assay. The cytotoxic activity of LAK cells was measured by a (51)Cr release assay. RESULTS: Five out of six esophageal cancer cell lines expressed Fas antigen at various levels (26.2-61.5%), and Fas expression increased after CDDP treatment. The antitumor effect of anti-Fas antibody on the esophageal cancer cell line and the antitumor effect of LAK cells activated by IL-2 were enhanced by pretreatment with CDDP. After concanamycin A treatment to specifically evaluate Fas-dependent cytotoxicity, LAK cells expressing Fas ligand killed only Fas-positive cells, but not Fas-negative cells. An anti-Fas neutralizing antibody inhibited this cytotoxicity. DNA fragmentation was shown in a cell line that was treated with CDDP and anti-Fas antibody, and also in the targeted esophageal cancer cell line cocultured with LAK cells. CONCLUSION: Our results suggest a potential clinical application of CDDP as a Fas inducer to make esophageal tumors susceptible to Fas antigen and LAK cytotoxicity.

Heat produces uteroplacental circulatory disturbance in pregnant rats through action of corticotropin releasing hormone (CRH).

There is some evidence showing an existence of corticotropin releasing hormone (CRH) and opioid peptides, including beta-endorphin (betaEP), in human placenta, whereas physiological roles of the placental peptides in response to stress remain to be elucidated. To clarify the involvement of CRH and opioid system in the uteroplacental circulation in the pregnant rats exposed to heat, we examined the effects of heat and intravenous administration of CRH receptor antagonist alpha-helical CRH (9-41) on the uteroplacental blood flow, as well as blood CRH, and blood and placental betaEP in pregnant rats. Heat did not change uterine blood flow in virgin rats, but reduced uteroplacental blood flow in pregnant rats. The reduced uteroplacental blood flow induced by heat in pregnant rats was reversed by the administration of alpha-helical CRH. Independent of the status of pregnancy, heat increased blood CRH, which was not reversed by alpha-helical CRH. Although heat did not change placental betaEP, alpha-helical CRH reduced blood and placenta betaEP in pregnant rats. These results suggest that the uteroplacental circulatory disturbance caused by heat is mediated by CRH, possibly through the involvement of CRH receptor in rat placenta. The placental opioid system seems unlikely to be involved in the mediation of uteroplacental circulation.

Uteroplacental circulatory disturbance mediated by prostaglandin f2alpha in rats exposed to microwaves. hiro-n@po.incl.ne.jp.

To clarify the effects of microwaves on pregnancy, uterine or uteroplacental blood flow and endocrine and biochemical mediators, including corticosterone, estradiol, prostaglandin E(2) (PGE(2)), and prostaglandin F(2)alpha (PGF(2)alpha), were measured in rats exposed to continuous-wave (CW) microwave at 2 mW/cm(2) incident power density at 2450 MHz for 90 min. Colonic temperature in virgin and pregnant rats was not significantly altered by microwave treatment. Microwaves decreased uteroplacental blood flow and increased progesterone and PGF(2)alpha in pregnant, but not in virgin rats. Intraperitoneal (i.p.) administration of angiotensin II, a uteroplacental vasodilator, before microwave exposure prevented the reduction in uteroplacental blood flow and the increased progesterone and PGF(2)alpha in pregnant rats. Increased corticosterone and decreased estradiol during microwave exposure were observed independent of pregnancy and pretreatment with angiotensin II. These results suggest that microwaves (CW, 2 mW/cm(2), 2450 MHz) produce uteroplacental circulatory disturbances and ovarian and placental dysfunction during pregnancy, probably through nonthermal actions. The uteroplacental disturbances appear to be due to actions of PGF(2)alpha and may pose some risk for pregnancy.

Involvement of granzyme B expression in the enhancement of natural killer activity by beta-endorphin.

Beta-Endorphin has been reported to enhance natural killer (NK) activity in vitro. However, few studies have examined the precise regulation of the cytolytic stage of NK cells. We therefore investigated the regulation by beta-endorphin of cytotoxicity-associated molecules such as granzyme B, perforin, and Fas ligand (FasL) in human CD16(+) NK cells. On semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) assay, the granzyme B mRNA level apparently increased in CD16(+) NK cells from high responding subjects having ratios >1.5 for the LU(30) ratio. An increase in intracellular granzyme B molecules was also detected in CD16(+) NK cells by flow cytometry. On the other hand, perforin and FasL appeared not to be involved in regulation by beta-endorphin. These findings suggest that up-regulation of granzyme B expression may be involved in the enhancement of NK activity by beta-endorphin.

Orexin-induced food intake involves neuropeptide Y pathway.

Orexins (orexin-A and -B) are recently identified neuropeptides, which are thought to be implicated in the regulation of feeding behavior. We used a NPY-Y1 receptor specific antagonist, BIBO3304, to examine whether NPY is involved in orexin-induced feeding behavior. Intracerebroventricular administration of orexin-A (10 nmol) induced food intake in rats (food intake for 3 h; vehicle 0.3+/-0.2 g vs. orexin-A 10 nmol, 4.0+/-0.5 g, n=4). Orexin-induced feeding behavior was partially inhibited by prior administration of BIBO3304 (3 h food intake: orexin-A 10 nmol, 4.0+/-0.5 g vs. BIBO3304 (60 microgram) + orexin-A 10 nmol, 2.2+/-0.2 g, n=4). A low dose of BIBO3304 (30 microgram) did not show a significant inhibitory effect. BIBO3457, an inactive enantiomer, used as a negative control, did not show any inhibitory effect on orexin-A-induced feeding behavior. Fos expression was observed in NPY-containing neurons in the arcuate nucleus 1 h after orexin-A (10 nmol) was administered intracerebroventricularly (control 0.3+/-0.08%, orexin-A 10.2+/-0.8%, n=5 rats/group). These observations suggest that NPY is involved in orexin-induced feeding behavior. However, BIBO3304 did not completely abolish the effect of orexin-A. These results suggest that orexin-A elicits feeding behavior partially via the NPY pathway. The NPY system could be the one of downstream pathways by which orexin-A induces feeding behavior. Another pathway may also be involved in orexin-A-induced feeding behavior, because BIBO3304 did not completely abolish orexin-A-induced feeding behavior.

Orexins/hypocretins regulate drinking behaviour.

Orexin/hypocretins are recently identified neuropeptides which regulate feeding behaviour. We found orexins increased water intake when administrated intracerebroventricularly to rats. The effect of orexin-A was more potent as compared with orexin-B, suggesting the possible involvement of OX(1) receptor. The efficacy of orexin-A was almost comparable with that of angiotensin II, and the effect lasted more than 3 h. Prepro-orexin mRNA level was up-regulated when rats were deprived of water. Orexin-immunoreactive varicose axons were observed in the subfornical organ and area postrema, regions implicated in drinking behaviour. These observations suggest a physiological role for orexin as mediators that regulate drinking behaviour.

The predictive value of benzodiazepine tolerance in persistently aggressive schizophrenia.

The aim of this study was to determine whether benzodiazepine tolerance might provide a predictive marker for persistent aggression in schizophrenia. Seventy-seven male schizophrenic patients newly admitted to our psychiatric intensive care unit due to violent behavior during a 4-month period were examined. As a result, a high dose of benzodiazepine required for sedation or a short duration until regaining consciousness after the initial sedation, was related to severer aggression on waking up after sedation. Despite the small number of subjects examined, a conservative claim can be made that the level of the effect of benzodiazepine required for sedation seems to predict persistent severe aggression in schizophrenia.

U5 monoclonal antibody identifies a novel lymphocyte surface antigen preferentially expressed in human circulating natural killer cells with high cytotoxic activity.

U5 monoclonal antibody (mAb), developed against Japanese monkey lymphocytes, identified a glycoprotein of 32 000 MW that is expressed in a subset of human circulating natural killer (NK) cells. The distribution of U5 molecules was restricted among CD16+ cells, and U5 antigen was preferentially expressed in the CD38+ subset. U5+ CD16+ CD56+ cells were highly active on NK assay against K562 target cells. Variations in cytolytic activities and mRNA expression of perforin, granzyme B and Fas ligand (FasL) were observed in U5- CD16+ CD56+ cells depending on the donor. We found that in some donors, a phenotypically mature (CD16+ CD56+) but functionally immature subset was present in the peripheral circulation. The U5- CD16+ CD56+ cells of some donors exhibited negligible cytolytic activity with no detectable expression of the above mRNAs, whereas those of the other donors had a significant but lower cytolytic activity with a reduced expression of granzyme B mRNA as compared with those of U5+ CD16+ CD56+ cells. Concanavalin A (Con A) stimulation induced an expression of U5 antigen in U5- CD16+ CD56+ cells accompanied by an up-regulation of granzyme B mRNA expression. These findings suggest that U5 antigen may be a novel molecule involved in the maturation or differentiation of human circulating NK cells.

Natural killer cell activity reduced by microwave exposure during pregnancy is mediated by opioid systems.

We have previously demonstrated immunosuppression including reduced splenic natural killer cell activity (NKCA) in pregnant rats exposed to microwaves produced mainly by their thermal action. To examine the involvement of opioid systems in reduced NKCA in pregnant rats exposed to microwaves at a relatively low level (2 mW/cm2 incident power density at 2450 MHz for 90 min), we assayed beta-endorphin (betaEP) in blood, pituitary lobes, and placenta as well as splenic NKCA in virgin and/or pregnant rats. Although microwaves elevated colonic temperatures by 0.8 degreesC for virgin and 0.9 degreesC for pregnant rats, and betaEP in blood and anterior pituitary lobes (AP) significantly, it did not change blood corticosterone as an index of hypothalamic-pituitary adrenal axis. There were significant interactions between pregnancy and microwave exposure on splenic NKCA, betaEP in both blood and AP, and blood progesterone. Intra-peritoneal administration of opioid receptor antagonist naloxone prior to microwave exposure increased NKCA, blood, and placental betaEP in pregnant rats. Alterations in splenic NKCA, betaEP and progesterone in pregnant rats exposed to microwaves may be due to both thermal and nonthermal actions. These results suggest that NKCA reduced by microwaves during pregnancy is mediated by the pituitary opioid system.

Central administration of interleukin-1 beta reduces natural killer cell activity in non-pregnant rats, but not in pregnant rats.

To examine responses of natural killer cell activity (NKCA) to interleukin-1 beta (IL-1 beta) during pregnancy, we determined splenic NKCA as well as blood and brain indicators in virgin and pregnant rats (14 or 21 days gestation) with intracerebroventricular (i.c.v.) administration of IL-1 beta. NKCA was reduced and blood beta-endorphin (beta EP) was increased with the progress of pregnancy. I.c.v. administration of IL-1 beta reduced NKCA and corticotropin-releasing hormone (CRH) in the median eminence (ME), and increased beta EP in virgin rats, but did not change any parameters in pregnant rats with 21 days gestation. These data suggest that the immunosuppressive effect of central administration of IL-1 beta is blocked by pregnancy. CRH in the ME and opioid system seem to be involved in the inhibitory effect of pregnancy on IL-1 beta-induced immunosuppression.

Opioid peptides mediate heat stress-induced immunosuppression during pregnancy.

To clarify the involvement of the opioid system in enhanced immunosuppression induced by heat stress during pregnancy, we examined the effects of heat exposure and intraperitoneal administration of opioid receptor antagonist naloxone on beta-endorphin (beta-EP) in blood, pituitary lobes, and placenta as well as splenic natural killer cell activity (NKCA) and placental steroids in pregnant rats at 15-16 days gestation. Two-way analysis of variance revealed significant increases in blood beta-EP induced by heat and naloxone and a significant interaction between heat and naloxone on blood beta-EP and progesterone (P). Whereas heat reduced NKCA, intraperitoneal administration of naloxone reversed it. Significant increases in blood and placental beta-EP induced by both heat and naloxone administration and a significant interaction on blood and placental beta-EP was observed. These results suggest that immunosuppression produced by heat stress during pregnancy is mediated by the opioid system. A positive correlation between beta-EP in blood and placenta during heat and naloxone administration suggests that increased placental beta-EP during heat results in hypersecretion of beta-EP into blood. P increased by heat during pregnancy may be involved in the immunosuppression.