Biomedical subjects

Shin Yamazaki

Publications and source records attributed to Shin Yamazaki.

At least 19 recordsLinked to original sources

PubMed2006

Resetting of central and peripheral circadian oscillators in aged rats.

The mammalian circadian timing system is affected by aging. Analysis of the suprachiasmatic nucleus (SCN) and of other circadian oscillators reveals age-related changes which are most profound in extra-SCN tissues. Some extra-SCN oscillators appear to stop oscillating in vivo or display altered phase relationships. To determine whether the dynamic behavior of circadian oscillators is also affected by aging we studied the resetting behavior of the Period1 transcriptional rhythm of peripheral and central oscillators in response to a 6h advance or delay in the light schedule. We employed a transgenic rat with a luciferase reporter to allow for real-time measurements of transcriptional rhythmicity. While phase resetting in the SCN following an advance or a delay of the light cycle appears nearly normal in 2-year-old rats, resynchronization of the liver was seriously disrupted. In addition, the arcuate nucleus and pineal gland exhibited faster resetting in aged rats relative to 4-8-month-old controls. The consequences of these deficits are unknown, but may contribute to organ and brain diseases in the aged as well as the health problems that are common in older shift-workers.

Aging↗

PubMed2006

Health-related quality of life of predialysis patients with chronic renal failure.

BACKGROUND: Health-related quality of life (HQOL) of predialysis patients with chronic renal failure (CRF) has received less attention than that of dialysis patients. We investigated changes in SF-36 over 1 year and examined associations between clinical parameters and SF-36 in predialysis CRF patients. METHODS: Subjects were 471 predialysis CRF patients. SF-36 and clinical parameters were measured every 8 weeks for 48 weeks. Of the 471 subjects, 294 underwent one or more follow-ups. We analyzed the pooled dataset of the 294 CRF patients and 2002 subjects from Japanese general population using analysis of covariance. RESULTS: After adjustment for age and sex, the 1-year declines in SF-36 domains were significantly greater in the predialysis patients than in the general population. For a 10% decline in hematocrit from the baseline survey value, the decline in vitality of SF-36 was 4.5 points (p = 0.003), while for a 10% increase in serum creatinine from the baseline survey value, respective declines in physical functioning, role-physical and mental health were 1.2 (p = 0.004), 1.9 (p = 0.035), and 1.0 points (p = 0.008). CONCLUSION: Among these predialysis CRF patients, the decline in HQOL was faster than that in the general population, and was associated with an increase in serum creatinine and decline in hematocrit.

Cost of Illness↗

PubMed2006

Childhood leukemia and magnetic fields in Japan: a case-control study of childhood leukemia and residential power-frequency magnetic fields in Japan.

Residential power-frequency magnetic fields (MFs) were labeled as a possible human carcinogen by the International Agency for Research on Cancer panel. In response to great public concern, the World Health Organization urged that further epidemiologic studies be conducted in high-exposure areas such as Japan. We conducted a population-based case-control study, which covered areas inhabited by 54% of Japanese children. We analyzed 312 case children (0-15 years old) newly diagnosed with acute lymphoblastic leukemia (ALL) or acute myelocytic leukemia (AML) in 1999-2001 (2.3 years) and 603 controls matched for gender, age and residential area. Weekly mean MF level was determined for the child's bedroom. MF measurements in each set of a case and controls were carried out as closely in time as possible to control for seasonal variation. We evaluated the association using conditional logistic regression models. The odds ratios for children whose bedrooms had MF levels of 0.4 microT or higher compared with the reference category (MF levels below 0.1 microT) was 2.6 (95% CI=0.76-8.6) for AML+ALL and 4.7 (1.15-19.0) for ALL only. Controlling for some possible confounding factors did not alter the results appreciably. Even an analysis in which selection bias was maximized did not fully explain the association. Most of the leukemia cases in the highest exposure category had MF levels far above 0.4 microT. Our results provided additional evidence that high MF exposure was associated with a higher risk of childhood leukemia, particularly of ALL.

Acute Disease↗

PubMed2006

Circadian organization of the mammalian retina.

The mammalian retina contains an endogenous circadian pacemaker that broadly regulates retinal physiology and function, yet the cellular origin and organization of the mammalian retinal circadian clock remains unclear. Circadian clock neurons generate daily rhythms via cell-autonomous autoregulatory clock gene networks, and, thus, to localize circadian clock neurons within the mammalian retina, we have studied the cell type-specific expression of six core circadian clock genes in individual, identified mouse retinal neurons, as well as characterized the clock gene expression rhythms in photoreceptor degenerate rd mouse retinas. Individual photoreceptors, horizontal, bipolar, dopaminergic (DA) amacrines, catecholaminergic (CA) amacrines, and ganglion neurons were identified either by morphology or by a tyrosine hydroxylase (TH) promoter-driven red fluorescent protein (RFP) fluorescent reporter. Cells were collected, and their transcriptomes were subjected to multiplex single-cell RT-PCR for the core clock genes Period (Per) 1 and 2, Cryptochrome (Cry) 1 and 2, Clock, and Bmal1. Individual horizontal, bipolar, DA, CA, and ganglion neurons, but not photoreceptors, were found to coordinately express all six core clock genes, with the lowest proportion of putative clock cells in photoreceptors (0%) and the highest proportion in DA neurons (30%). In addition, clock gene rhythms were found to persist for >25 days in isolated, cultured rd mouse retinas in which photoreceptors had degenerated. Our results indicate that multiple types of retinal neurons are potential circadian clock neurons that express key elements of the circadian autoregulatory gene network and that the inner nuclear and ganglion cell layers of the mammalian retina contain functionally autonomous circadian clocks.

Animals↗

PubMed2006

Effects of winter air pollution on pulmonary function of school children in Shenyang, China.

To assess the effects of air pollution associated with coal heating in winter on pulmonary function of school children, pulmonary function tests (FVC, FEV(1.0), PEF, FEF(75)) of 332 children in Shenyang, located in the northeast of China, were done four times between October 2001 and June 2002. The collected airborne particulate matter (PM) was analyzed for the concentrations of total suspended particles (TSP), PM of less than 7 microm in aerodynamic diameter (PM(7)), and PM of less than 2.1 microm (PM(2.1)). All four pulmonary function tests were completed in 244 school children. The airborne PM concentration was higher in April 2002 (end of heating) than in October 2001 (prior to heating). All four pulmonary function indices, adjusted for age and height, were significantly lower in April 2002 than in October 2001; the FEV(1.0) was lower in boys (0.233l, 95% CI: 0.167-0.299l) and girls (0.222l, 95% CI: 0.165-0.280l). The decrease continued to be significant in June 2002 compared to October 2001. The decreases in FEV and FEV(1.0) were also significantly associated with airborne PM concentration, which had a delayed effect on pulmonary function. An increase from the 25th to the 75th percentile of TSP, PM(7) and PM(2.1) was associated with a delayed decrease in FEV(1.0); 0.059l (95% CI: 0.020-0.106l), 0.095l (95% CI: 0.057-0.139l) and 0.110l (95% CI: 0.072-0.147l) in boys, and 0.066l (95% CI: 0.026-0.106l), 0.101l (95% CI: 0.063-0.139l) and 0.114l (95% CI: 0.080-0.152l) in girls, respectively. Our findings show that airborne PM might have a subacute effect on pulmonary function in children in Shenyang, and that PM(7) and PM(2.1) have more adverse effects on pulmonary function than TSP. The effects of airborne PM appear to be prolonged.

Air Pollution↗

PubMed2006

Constitutive expression of the Period1 gene impairs behavioral and molecular circadian rhythms.

Three mammalian Period (Per) genes, termed Per1, Per2, and Per3, have been identified as structural homologues of the Drosophila circadian clock gene, period (per). The three Per genes are rhythmically expressed in the suprachiasmatic nucleus (SCN), the central circadian pacemaker in mammals. The phases of peak mRNA levels for the three Per genes in the SCN are slightly different. Light sequentially induces the transcripts of Per1 and Per2 but not of Per3 in mice. These data and others suggest that each Per gene has a different but partially redundant function in mammals. To elucidate the function of Per1 in the circadian system in vivo, we generated two transgenic rat lines in which the mouse Per1 (mPer1) transcript was constitutively expressed under the control of either the human elongation factor-1alpha (EF-1alpha) or the rat neuron-specific enolase (NSE) promoter. The transgenic rats exhibited an approximately 0.6-1.0-h longer circadian period than their wild-type siblings in both activity and body temperature rhythms. Entrainment in response to light cycles was dramatically impaired in the transgenic rats. Molecular analysis revealed that the amplitudes of oscillation in the rat Per1 (rPer1) and rat Per2 (rPer2) mRNAs were significantly attenuated in the SCN and eyes of the transgenic rats. These results indicate that either the level of Per1, which is raised by overexpression, or its rhythmic expression, which is damped or abolished in over expressing animals, is critical for normal entrainment of behavior and molecular oscillation of other clock genes.

Animals↗

PubMed2006

Association between high voltage overhead transmission lines and mental health: a cross-sectional study.

We examined the association between residential proximity to 60 Hz high voltage (22-500 kV) overhead transmission lines (HVOTLs) and mental health (MH). The subjects were 223 mothers with a mean age of 37 years. The distance from the subject's residence to the closest HVOTL was measured on a map. MH status was assessed by the SF-36 Health Survey, which was scored on a 0-100 point scale, and an individual with a score of 52 points or less was defined as having poor MH. Logistic regression models were used to examine the association between the distance from the subjects' residence to the closest HVOTL and MH status. The prevalence of poor MH was 15%. Among the 223 subjects, 10 lived within 100 m of a HVOTL. The adjusted odds ratios (OR) for poor MH among those who lived 101-300 m or within 100 m from HVOTL were 1.29 (95% confidence interval (CI): 0.35-10.13) and 1.87 (95% CI: 0.35-10.13), respectively, against the reference category (300+ m). MH status was not significantly associated with the distance between the subject's residence and the closest HVOTL.

Adult↗

PubMed2006

Gender differences in effects of physical activity on quality of life and resource utilization.

BACKGROUND: Physical activity is associated with health-related quality of life (HRQOL) in the general population, but the effects may be different between sexes. In addition, the effects on resource utilization are not well elucidated. METHODS: A population-based cross-sectional survey was conducted in a rural town, and follow-up data were obtained after 1 year. Physical activity was measured in two ways: amount and maximum intensity. The association between physical activity and the MOS Short Form-36 (SF-36) at baseline, and hospitalization, sick days, and medications in the following year were assessed by multiple regression models. RESULTS: Among 4018 adult residents eligible, 3529 (62.4%) had completed the follow-up questionnaire. A greater amount of exercise was positively correlated with all domains of the SF-36: 2.4-9.5 increase in 100-scale at baseline, but association between maximum intensity and SF-36 was observed in only women. It was also associated with a 20-50% higher utilization of over-the-counter drugs in the following year in both sexes, but the effects of maximum intensity on sick days had different directions for men (relative risk, 2.0-2.4) and women (relative risk, 0.3-0.5). CONCLUSION: The amount of physical activity had positive effects on HRQOL for both men and women, but women had more preferable effects of maximum intensity on HRQOL and resource utilization than men.

Adult↗

PubMed2006

Associations between exposure to ambient photochemical oxidants and the vitality or mental health domain of the health related quality of life.

BACKGROUND: Ambient air pollution may affect the health related quality of life (HRQOL) of people, as assessed by the vitality (VT) and mental health (MH) domains of the SF-36 health survey (SF-36). METHODS: In a nationwide survey, 4500 people aged 20 years and older were selected from the entire population of Japan by stratified random sampling in October 2002. A total of 2896 subjects filled out the self administered questionnaire that included the SF-36 and demographic characteristics. Data were linked from the questionnaires with the data on air pollutants in the cities where the subjects resided. The paper examined the relations between the mean concentration of each air pollutant and the VT or MH score on the SF-36 using analysis of covariance. RESULTS: On crude analysis, the respondents who were exposed to a higher mean two month concentration of photochemical oxidants (Ox) showed a significant linear trend toward lower VT score (p = 0.028). This association remained even after adjustment for subjective demographic characteristics and meteorological variables (p = 0.033). There was a common tendency that subjects who were exposed to higher concentrations of Ox had a lower mean VT or MH score; however, there was a significant association only between Ox concentration and VT score. CONCLUSION: The score on the VT domain of the SF-36 was associated with the mean concentration of Ox during the previous two month period. Assessing the health effects of air pollution by measuring the HRQOL, such as by using the SF-36, may provide a new method of formulating air pollution policies.

Adult↗

PubMed2005

Usefulness of five-item and three-item Mental Health Inventories to screen for depressive symptoms in the general population of Japan.

BACKGROUND: The five-question Mental Health Inventory (MHI-5) is a brief questionnaire that can be used to screen for depressive symptoms. Removing the 2 anxiety-related items from the MHI-5 yields the MHI-3. We assessed the performance of the Japanese versions of the MHI-5 and MHI-3 in detecting depressive symptoms in the general population of Japan. METHODS: From the population of Japan, 4500 people 16 years old or older were selected by stratified-random sampling. The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36, which includes the MHI-5) and the Zung Self-rating Depression Scale (ZSDS) were included in a self-administered questionnaire. ZSDS scores of 48 and above were taken to indicate the presence of moderate or severe depressive symptoms, and scores of 56 and above were taken to indicate the presence of severe depressive symptoms. We computed the correlation coefficient between the ZSDS score and the scores on the MHI-5 and MHI-3. We also computed the sensitivity, specificity, and area under the receiver operating characteristic (ROC) curve. RESULTS: Of the 3107 subjects (69% of the 4500 initially selected), 14.0% had moderate or severe depressive symptoms, and 2.0% had severe depressive symptoms as measured with the ZSDS. The correlations of ZSDS scores with MHI-5 scores and with MHI-3 scores were similar: -0.63 and -0.61, respectively. These correlation coefficients were almost the same whether or not the data were stratified by age and sex. For detecting severe depressive symptoms with the MHI-5, the area under the ROC curve was 0.942 (95%CI: 0.919 - 0.965); for the MHI-3, it was 0.933 (95%CI: 0.904 - 0.962). CONCLUSION: The MHI-5 and MHI-3 scores were correlated with the ZSDS score, and can be used to identify people with depressive symptoms in the general population of Japan.

Adult↗

PubMed2005

Differential response of Period 1 expression within the suprachiasmatic nucleus.

The suprachiasmatic nuclei (SCNs) of the hypothalamus contain a circadian clock that exerts profound control over rhythmic physiology and behavior. The clock consists of multiple autonomous cellular pacemakers distributed throughout the rat SCN. In response to a shift in the light schedule, the SCN rapidly changes phase to achieve the appropriate phase relationship with the shifted light schedule. Through use of a transgenic rat in which rhythmicity in transcription of the Period 1 gene was measured with a luciferase reporter (Per1-luc), we have been successful in tracking the time course of molecular rhythm phase readjustments in different regions of the SCN that occur in response to a shift in the light schedule. We find that different regions of the SCN phase adjust at different rates, leading to transient internal desynchrony in Per1-luc expression among SCN regions. This desynchrony among regions is most pronounced and prolonged when the light schedule is advanced compared with light schedule delays. A similar asymmetry in the speed of phase resetting is observed with locomotor behavior, suggesting that phase shifting kinetics within the SCN may underlay the differences observed in behavioral resetting to advances or delays in the light schedule.

Animals↗

PubMed2005

A noncanonical E-box enhancer drives mouse Period2 circadian oscillations in vivo.

The mouse Period2 (mPer2) locus is an essential negative-feedback element of the mammalian circadian-clock mechanism. Recent work has shown that mPer2 circadian gene expression persists in both central and peripheral tissues. Here, we analyze the mouse mPer2 promoter and identify a circadian enhancer (E2) with a noncanonical 5'-CACGTT-3' E-box located 20 bp upstream of the mPer2 transcription start site. The E2 enhancer accounts for most circadian transcriptional drive of the mPer2 locus by CLOCK:BMAL1, is a major site of DNaseI hypersensitivity in this region, and is constitutively bound by a transcriptional complex containing the CLOCK protein. Importantly, the E2 enhancer is sufficient to drive self-sustained circadian rhythms of luciferase activity in central and peripheral tissues from mPer2-E2::Luciferase transgenic mice with tissue-specific phase and period characteristics. Last, genetic analysis with mutations in Clock and Bmal1 shows that the E2 enhancer is a target of CLOCK and BMAL1 in vivo.

ARNTL Transcription Factors↗

PubMed2005

Constant light desynchronizes mammalian clock neurons.

Circadian organization can be disrupted by constant light, resulting in behavioral arrhythmicity or 'splitting' of rhythms of activity and rest. By imaging molecular rhythms of individual clock neurons in explanted mouse clock nuclei, we now find that constant light desynchronizes clock neurons but does not compromise their ability to generate circadian rhythms. Cellular synchrony within clock nuclei is disrupted during arrhythmicity, whereas neurons in the left and right clock nuclei cycle in antiphase during 'splitting.'

Animals↗

PubMed2005

Health-related quality of life of mothers of children with leukemia in Japan.

OBJECTIVE: The study compared the health-related quality of life (HRQOL) of Japanese mothers of children with leukemia to that of mothers of children without leukemia. METHOD: We used the Medical Outcomes Study 36-item Short-Form (SF-36) to measure the HRQOL of 97 mothers of children (average age 6.2, range 0-14) with leukemia diagnosed between 1999 and 2000, and compared their scores to those of 240 mothers of children without leukemia matched to the children with leukemia. MAIN RESULTS: Of the eight unadjusted domain scores of the SF-36, five were significantly low among mothers of children with leukemia compared to mothers of children without leukemia: 'role-physical functioning' (RP), 'general health perception' (GH), 'vitality' (VT), 'social functioning' (SF) and 'mental health' (MH). Their SF-36 domain scores, when adjusted for demographic and clinical factors were also significantly low in RP, GH, VT, SF, RE and MH. The MH and SF scores in mothers of children with leukemia requiring hospital care were, respectively, approximately 20 points (1 standard deviation (SD), p < 0.0001) and 30 points (1.5 SD, p < 0.0001) lower than that of mothers of children without leukemia. CONCLUSION: Mothers of children with leukemia requiring hospital care have poor HRQOL, particularly with regard to mental health and social functioning, and are at a greater risk for depression. These results suggest that the current system for treating leukemic diseases of children in Japan should also include close monitoring of mothers' mental health, and provision of appropriate treatment and psycho-social support.

Adolescent↗

PubMed2005

Real-time luminescence reporting of circadian gene expression in mammals.

Luminescence reporters have been used successfully in studies of circadian rhythms. Real-time measurements of circadian variations in gene expression were made in living cells, cultured tissues, and whole organisms. Because this technique is relatively easy and continuous noninvasive measurement from tissue cultures allows for a drastic reduction in the number of experimental animals, we believe this method will become a common technique for studying circadian rhythms. Using a multichannel recording apparatus, it may also become a powerful tool for the discovery of new drugs. In the past, measurements were done using hand-made apparatuses or by modifying commercially available equipment. We, along with other investigators, have developed user-friendly equipment for performing circadian rhythms experiments, and these systems are now available commercially. This article describes the use of luminescence reporters in circadian research and provides detailed methods used in these experiments. One of our goals in this article is to reduce experimental variability in different laboratories by proposing standard protocols.

Animals↗

PubMed2005

Living close to automobile traffic and quality of life in Japan: a population-based survey.

The objective of this study was to evaluate the association between living close to traffic and health related quality of life (HRQOL) that is important to the health outcome. We administered a questionnaire including the Medical Outcome Study Short Form-36-item Health Survey to all 6197 residents living in Naie, aged 20 years and older, and received 5107 (82.4%) responses. The respondents were classified into three groups: those whose bedrooms were located to an arterial road (AR), located to other roads (OR), and not located to any road (NR). We used analysis of covariance to estimate the mean differences among the three groups for each SF-36 domain. HRQOL scores of the AR and the OR group were lower than those of the NR group in all domains. The adjusted mean scores of the AR group on "mental health" and "vitality" domains were significantly lower than those of the NR group. This study suggests that the HRQOL is an effective tool for evaluating the many impacts of road transportation on aspects of health.

Adult↗

PubMed2005

Association between ambient air pollution and health-related quality of life in Japan: ecological study.

To assess the association between air pollution and health-related quality of life (HRQOL), we performed an ecological study by a two-stage stratified random sampling of the Japanese general population. A total of 3395 subjects, aged 16 and older, filled out questionnaires, including the Medical Outcomes Study Short Form-36 Health Survey (SF-36). Air pollutants examined in this study were nitrogen oxides (NOx) and suspended particulate matter (SPM). We used analysis of covariance to estimate the mean differences for each SF-36 domain among four groups categorized according to concentrations of air pollutants to which they were exposed. We observed a significant linear trend of a lower 'vitality' domain score in the SF-36 in groups exposed to higher concentrations of NOx (p = 0.013). The results of the present study are important for, and needed by, public health policy makers, because assessing the health effects of air pollution by measuring the HRQOL would provide a new method for formulating air pollution policies.

Adolescent↗

PubMed2005

Pineal circadian clocks gate arylalkylamine N-acetyltransferase gene expression in the mouse pineal gland.

In mammals it has been thought that the circadian clock localizes only in the suprachiasmatic nucleus of the hypothalamus. Recent studies have revealed that certain brain regions and peripheral tissues may also have intrinsic circadian clocks. However, the roles played by 'peripheral circadian clocks' have not been fully elucidated. In this study, we investigated their function using mouse pineal glands, and found that expression of the arylalkylamine N-acetyltransferase (Aa-Nat, EC 2.3.1.87, the rate-limiting enzyme of melatonin synthesis) gene after adrenergic receptor stimulation depended on the time of day even in vitro (gating). Phase-dependent Aa-Nat responses were observed in both melatonin-proficient and melatonin-deficient mouse pineal glands. Phosphodiesterases are unlikely to suppress Aa-Nat induction because a phosphodiesterase inhibitor itself had no effect on the mRNA levels. Puromycin was ineffective in inducing Aa-Nat mRNA levels in either the presence or absence of isoproterenol, suggesting that newly synthesized proteins may not be necessary to gate the Aa-Nat responses. We also discovered circadian dependence of the expression of Period1-luminescence in Period1-luciferase transgenic mouse pineal glands: circadian clocks may be functional in culture. Aa-Nat mRNA levels showed no significant circadian rhythms in the absence of isoproterenol, thus suggesting that Aa-Nat mRNA levels are induced by adrenergic mechanisms, not by a pineal circadian clock. Our results suggest that the pineal circadian clock may determine timing when Aa-Nat gene expression can respond to inputs from the master circadian clock in the suprachiasmatic nucleus, e.g. adrenergic stimulation.

1-Methyl-3-isobutylxanthine↗