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Biomedical subjects

Kyoko Watanabe

Publications and source records attributed to Kyoko Watanabe.

12 recordsLinked to original sources
PubMed2017

Functional mapping and annotation of genetic associations with FUMA.

A main challenge in genome-wide association studies (GWAS) is to pinpoint possible causal variants. Results from GWAS typically do not directly translate into causal variants because the majority of hits are in non-coding or intergenic regions, and the presence of linkage disequilibrium leads to effects being statistically spread out across multiple variants. Post-GWAS annotation facilitates the selection of most likely causal variant(s). Multiple resources are available for post-GWAS annotation, yet these can be time consuming and do not provide integrated visual aids for data interpretation. We, therefore, develop FUMA: an integrative web-based platform using information from multiple biological resources to facilitate functional annotation of GWAS results, gene prioritization and interactive visualization. FUMA accommodates positional, expression quantitative trait loci (eQTL) and chromatin interaction mappings, and provides gene-based, pathway and tissue enrichment results. FUMA results directly aid in generating hypotheses that are testable in functional experiments aimed at proving causal relations.

Chromatin↗
PubMed2005

Effects of restricted feeding on daily fluctuations of hepatic functions including p450 monooxygenase activities in rats.

Hepatic P450 monooxygenase activities, assessed by measurement of 7-alkoxycoumarin O-dealkylase (ACD) activities, show obvious daily fluctuations in male rats with high values during the dark period and low values during the light period. We have already confirmed that the ACD activities are controlled by the suprachiasmatic nucleus (SCN), which is well known as the oscillator of circadian rhythm. Recently, it is reported that circadian oscillators exist not only in the SCN but also in peripheral organs. To date, it is unclear which circadian oscillators predominantly drive the daily fluctuations of hepatic ACD activities. To address this question, we examined the effects of restricted feeding, which uncouples the circadian oscillators in the liver from the central pacemaker in the SCN, on the daily fluctuations in hepatic ACD activities in male rats. Here we show that restricted feeding inverts the oscillation phase of the daily fluctuations in hepatic ACD activities. Regarding the hepatic P450 content, there were no fluctuations between the light and dark periods under ad libitum and restricted feeding conditions. Therefore, it is considered that the daily fluctuations in hepatic ACD activities are predominantly driven by the circadian factors in peripheral organs rather than by the oscillator in the SCN directly.

7-Alkoxycoumarin O-Dealkylase↗
PubMed2005

Utilization of a toxicogenomic biomarker for evaluation of chemical-induced glutathione deficiency in rat livers across the GeneChip data of different generations.

Previously, we reported 69 probe sets (GSH probe sets) of RG U34A GeneChip that were useful for the evaluation of chemical-induced glutathione depletion in rat livers. The aim of the present study was to investigate whether these probe sets could be applied to the analysis of RAE 230A GeneChip data. Since a straightforward data comparison of RG U34A and RAE 230A GeneChips could not overcome the generation-dependent discrepancy in signal profiles, we tried two methods to improve the data compatibility between the two GeneChips. First, we re-calculated the signal values by excluding the probes with poor-overlapping sequences between the two GeneChips, but the data compatibility did not improve from the view point of Spearman's and Pearson's correlation coefficients. On the other hand, the PCA result demonstrated that an adjustment of the baseline signal level between the RG U34A and RAE 230A GeneChip data on vehicle-treated rats dramatically improved the data compatibility, suggesting that the GSH probe sets identified from RG U34A GeneChip data can be utilized in RAE 230A GeneChip data as well. Such a baseline adjustment of signal data is an easy and practical way to utilize biomarkers across GeneChip data of different generations.

Animals↗
PubMed2005

Repeated injections of energy in the first 600 ms of the giant flare of SGR 1806-20.

The massive flare of 27 December 2004 from the soft gamma-ray repeater SGR 1806-20, a possible magnetar, saturated almost all gamma-ray detectors, meaning that the profile of the pulse was poorly characterized. An accurate profile is essential to determine physically what was happening at the source. Here we report the unsaturated gamma-ray profile for the first 600 ms of the flare, with a time resolution of 5.48 ms. The peak of the profile (of the order of 10(7) photons cm(-2) s(-1)) was reached approximately 50 ms after the onset of the flare, and was then followed by a gradual decrease with superposed oscillatory modulations possibly representing repeated energy injections with approximately 60-ms intervals. The implied total energy is comparable to the stored magnetic energy in a magnetar (approximately 10(47) erg) based on the dipole magnetic field intensity (approximately 10(15) G), suggesting either that the energy release mechanism was extremely efficient or that the interior magnetic field is much stronger than the external dipole field.

Journal Article↗
PubMed2004

Induction of proliferation by 15-deoxy-delta12,14-prostaglandin J2 and the precursors in monocytic leukemia U937.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is expressed in several human tumors including gastric, lung, colon, prostate and breast. However, the role of PPARgamma signals in leukemia is still unclear. The aim of this study is to evaluate the ability of 15-deoxy-Delta12,14-prostaglandin J2 (15dPGJ2), that is a ligand for PPARgamma, on proliferation of human leukemia cell line U937. 15dPGJ2 at 5 micromol/l stimulated the proliferation. In contrast, 15dPGJ2 at concentrations of >10 micromol/l inhibited the proliferation through the induction of apoptosis. PGD2, PGJ2 and Delta12-PGJ2 (DeltaPGJ2), those are precursors of 15dPGJ2, had similarly proliferative effects, whereas they showed antiproliferative effects at high concentrations. FACScan analysis revealed that PGD2 at 5 micromol/l, PGJ2 at 1 micromol/l, DeltaPGJ2 at 1 micromol/l and 15dPGJ2 at 5 micromol/l, all accelerated cell cycle progression. Immunoblotting analysis revealed that PGD2 at 5 micromol/l and 15dPGJ2 at 5 micromol/l inhibited the expression of phospho-p38, phospho-MKK3/MKK6 and phospho-ATF-2, and the expression of Cdk inhibitors including p18, p27. In contrast, PGJ2 at 1 micromol/l and DeltaPGJ2 at 1 micromol/l did not affect the expression of them. These results suggest that 15dPGJ2 and PGD2 may, through inactivation of the p38 MAPK pathway, inhibit the expression of Cdk inhibitors, leading to acceleration of proliferation.

Apoptosis↗
PubMed2004

Possible involvement of p38 in mechanisms underlying acceleration of proliferation by 15-deoxy-Delta(12,14)-prostaglandin J2 and the precursors in leukemia cell line THP-1.

15-deoxy-Delta(12,14)-prostaglandin J(2) (15dPGJ2), which is a ligand for peroxisome proliferator-activated receptor gamma (PPARgamma), induced apoptosis of several human tumors including gastric, lung, colon, prostate, and breast. However, the role of PPARgamma signals in other types of cancer cells (e.g., leukemia) except solid cancer cells is still unclear. The aim of this study is to evaluate the ability of 15dPGJ2 to modify the proliferation of the human leukemia cell line THP-1. 15dPGJ2 at 5 microM stimulated the proliferation in THP-1 at 24 to 72 h after incubation. In contrast, 15dPGJ2 at concentrations above 10 microM inhibited the proliferation through the induction of apoptosis. PGD2, PGJ2, and Delta12-PGJ2 (DeltaPGJ2), precursors of 15dPGJ2, had similar proliferative effects at lower concentrations, whereas they induced apoptosis at high concentrations. 15dPGJ2 and three precursors failed to induce the differentiation in THP-1 as assessed by using the differentiation marker CD11b. FACScan analysis revealed that PGD2 at 5 microM, PGJ2 at 1 microM, DeltaPGJ2 at 1 microM and 15dPGJ2 at 5 microM all accelerated cell cycle progression in THP-1. Immunoblotting analysis revealed that PGD2 at 5 microM and 15dPGJ2 at 5 microM inhibited the expression of phospho-p38, phospho-MKK3/MKK6, and phospho-ATF-2, and the expression of Cdk inhibitors including p18, p21, and p27 in THP-1. In contrast, PGJ2 at 1 microM and DeltaPGJ2 at 1 microM did not affect their expressions. These results suggest that 15dPGJ2 and PGD2 may, through inactivation of the p38 mitogen-activated protein kinase pathway, inhibit the expression of Cdk inhibitors, leading to acceleration of the THP-1 proliferation.

Apoptosis↗
PubMed2004

Yeast Delta 12 fatty acid desaturase: gene cloning, expression, and function.

In an effort to elucidate the molecular mechanisms of fatty acid desaturation in yeast, a complete gene encoding Delta 12 fatty acid desaturase of Saccharomyces kluyveri was cloned. The open reading frame of this gene (named Sk-FAD2) consists of 1,251 bp, encoding 416 amino acids. The deduced Sk-FAD2 protein had 37-55% identity with those from other filamentous fungi. Unlike the genes of these other fungi, S. cerevisiae expressing Sk-FAD2 was found to be capable of synthesizing the dienoic fatty acid hexadecadienoic acid as well as linoleic acid. Moreover, the Sk-FAD2-disrupted strain of S. kluyveri was unable to produce polyunsaturated fatty acids. These results suggested that Sk-FAD2 protein is a unique Delta 12 fatty acid desaturase in S. kluyveri. Analysis of transcriptional expression revealed that Sk-FAD2 was not repressed by exogenous unsaturated fatty acids but responded to low-temperature stress.

Amino Acid Sequence↗
PubMed2003

[Prevention of dermatophytoses].

Preventive measures against tinea pedis were discussed based on our mycological studies using foot-press method and house dust cultures. 1) Untreated patients with tinea pedis frequently disseminate pathogenic fungi into the environment, but dissemination could be easily controlled by simple application of antifungal agents. 2) A high proportion of dermatophytes disseminated in house dust perished naturally within a month under dry conditions, while under moist conditions they survived several months or more. Therefore, humid areas such as the floor and carpet of a bathroom should be cleaned or washed regularly. 3) Adhesion of dermatophytes onto healthy feet usually happens in public spaces where people enter without shoes. Wearing socks cannot prevent dermatophyte adhesion. Cleaning the feet by wiping with a towel or washing with soap seemed to be an effective prophylactic measure after stepping into such spaces.

Dermatomycoses↗
PubMed2002

Precedents of perceived social support: personality, early life experiences and gender.

The perception of social support may be a trait-like construct stemming from the current personality and early environment as well as a summation of the actual support perceived. A total of 220 community individuals were examined for the effects of Eysenck Personality Questionnaire (EPQ) items and early life experience at home and outside on the number of sources of perceived social support and satisfaction with that support. High extraversion and low neuroticism scores of the EPQ were correlated with the availability of support only in women, while high maternal care and low maternal overprotection in childhood were correlated with the satisfaction with support only in men. Availability of support was also correlated with some types of early life events. The quantity and quality of perception of social support differ in their links to personality and early environment, and may be, to some extent, explainable in terms of them.

Adolescent↗
PubMed2002

Human olfactory contrast changes during the menstrual cycle.

Several lines of studies have reported that olfactory perception is influenced by physical and hormonal conditions. In the present study, we investigated changes of olfactory perception during the menstrual cycle of the human. Cyclopentadecanolide vapor was used and its perception intensity was measured by 6-point category scale methods. We especially focused on a novel concept termed "olfactory contrast" that has been just very recently derived from the patch clamp experiment that uses the solitary olfactory receptor cell. The results obtained from 18 trials (15 subjects) showed that olfactory contrast was significantly enhanced at the ovulatory and/or menstrual phases. It is suggested that olfactory contrast, which we defined as a new parameter, provides a useful tool in many kinds of studies exploring the olfactory perceived ability.

Adult↗