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S Yamaguchi

Publications and source records attributed to S Yamaguchi.

At least 199 records · Page 11Linked to original sources
PubMed2000

The 5' upstream region of mPer1 gene contains two promoters and is responsible for circadian oscillation.

The mPer1 gene is assumed to be a key molecule in the regulation and functioning of the mammalian circadian clock, which is based on the oscillation generated by a transcription-(post)translation feedback loop of a set of clock genes [1]. Robust circadian oscillation and acute light-elicited induction of mPer1 mRNA expression have been observed in the suprachiasmatic nucleus (SCN), the mammalian circadian center [2] [3]. To investigate the mechanism underlying the complex regulation of mPer1 expression, we isolated and characterized the 5' upstream region of the mPer1 gene. Unexpectedly, we identified two promoters, each followed by alternative first exons of mPer1. Consistent with the presence of multiple E-boxes in the promoters, exon-specific in situ hybridization of the SCN established that both promoters function in circadian oscillation and in light-induction of mPer1 expression. Transgenic mice carrying the 5' upstream region of the mPer1 gene fused to the luciferase gene demonstrated that a DNA fragment carrying both promoter regions is sufficient to elicit striking circadian oscillation in the SCN and responsiveness to light. Moreover, luminescence in the SCN accurately mirrored the mPer1 transcriptional activity. These transgenic mice will be very useful for monitoring clock-specific mPer1 expression in intact organisms and to follow the circadian clock in real time.

Animals↗
PubMed2000

Dimerization and nuclear entry of mPER proteins in mammalian cells.

Nuclear entry of circadian oscillatory gene products is a key step for the generation of a 24-hr cycle of the biological clock. We have examined nuclear import of clock proteins of the mammalian period gene family and the effect of serum shock, which induces a synchronous clock in cultured cells. Previously, mCRY1 and mCRY2 have been found to complex with PER proteins leading to nuclear import. Here we report that nuclear translocation of mPER1 and mPER2 (1) involves physical interactions with mPER3, (2) is accelerated by serum treatment, and (3) still occurs in mCry1/mCry2 double-deficient cells lacking a functional biological clock. Moreover, nuclear localization of endogenous mPER1 was observed in cultured mCry1/mCry2 double-deficient cells as well as in the liver and the suprachiasmatic nuclei (SCN) of mCry1/mCry2 double-mutant mice. This indicates that nuclear translocation of at least mPER1 also can occur under physiological conditions (i.e., in the intact mouse) in the absence of any CRY protein. The mPER3 amino acid sequence predicts the presence of a cytoplasmic localization domain (CLD) and a nuclear localization signal (NLS). Deletion analysis suggests that the interplay of the CLD and NLS proposed to regulate nuclear entry of PER in Drosophila is conserved in mammals, but with the novel twist that mPER3 can act as the dimerizing partner.

Animals↗
PubMed2000

Toward new materials for organic electroluminescent devices: synthesis, structures, and properties of a series of 2,5-diaryl-3,4-diphenylsiloles

A series of 2,5-diaryl-3,4-diphenylsiloles, with various mono-substituted phenyl groups, extended pi-conjugated groups, and heteroaryl groups as aryl groups at the 2,5-positions, has been prepared by a one-pot synthesis from bis(phenylethynyl)silanes based on the intramolecular reductive cyclization followed by the palladium-catalyzed cross-coupling with aryl halides. Crystal structures and chemical reactivities toward the alkaline desilylation reactions have been studied on the 2,5-bis(p-mono-substituted phenyl)silole derivatives to elucidate the effects of the p-substituents. The UV-visible absorption and fluorescence spectra, and cyclic voltammetry of the 2,5-diarylsiloles have been systematically evaluated. Their photophysical properties as well as their electronic structures significantly depend on the nature of the 2,5-aryl groups.

Journal Article↗
PubMed2000

Cerebral asymmetry of the "top-down" allocation of attention to global and local features.

Neuropsychological and neuroimaging studies have indicated that global and local features of a visual scene are processed differentially by the two hemispheres. Although visual selective attention is suggested to play a role in the hemispheric asymmetry, the precise mechanism of attentional control for the global-local processing is not fully understood. We investigated the neural correlates of cerebral asymmetry in directing attention to the global pattern and local components of a hierarchical stimulus. Event-related brain potentials (ERPs) were recorded while the subjects shifted their attention to the global or local level of a hierarchically structured letter. The shift direction was controlled by a preceding cue stimulus. The ERPs to the cue stimuli demonstrated that the right temporal-parietal and left posterior temporal regions were differentially activated during attentional allocation to the global and local levels, respectively. These effects started 240 msec after the cue stimulus. The late ERP components to the target stimuli also manifested the hemispheric global-local asymmetry as seen during the attentional shift. These electrophysiological results provided an asymmetrical neural basis for the "top-down" allocation of attention to global and local features and revealed the contribution of the temporal-parietal cortex to this attentional mechanism.

Adult↗
PubMed2000

Autonomic failure in ALS with a novel SOD1 gene mutation.

The authors report a patient with ALS and a novel SOD1 gene mutation who was in the totally locked-in state and developed autonomic failure followed by sudden cardiac arrest. A neuropathologic study showed widespread multisystem degeneration, including involvement of the autonomic nuclei in the medulla and spinal cord. SOD1 gene analysis detected a missense mutation of V118L in exon 4. These findings show notable phenotypic heterogeneity for SOD1-associated ALS.

Adult↗
PubMed2000

Dual-viral vector approach induced strong and long-lasting protective immunity against very virulent infectious bursal disease virus.

To induce strong protective immunity against very virulent infectious bursal disease virus (vvIBDV) in chickens, two viral vector systems, Marek's disease and Fowlpox viruses expressing the vvIBDV host-protective antigen VP2 (rMDV, rFPV), were used. Most of chickens vaccinated with the rFPV or rMDV alone, or vaccinated simultaneously with both at their hatch (rMDV-rFPV(1d)), were protected against developing clinical signs and mortality; however, only zero to 14% of the chickens were protected against gross lesions. In contrast, gross lesions were protected in 67% of chickens vaccinated primarily with the rMDV followed by boosting with the rFPV 2 weeks later (rMDV-rFPV(14d)). Protection against the severe histopathological lesions of rFPV, rMDV, rMDV-rFPV(1d), and rMDV-rFPV(14d) vaccine groups were 33, 42, 53, and 73%, respectively. Geometric mean antibody titers to VP2 of chickens vaccinated with the rFPV, rMDV, rMDV-rFPV(1d), and rMDV-rFPV(14d) before the challenge were 110, 202, 254, and 611, respectively. Persistent infection of the rMDV in chickens after the booster vaccination with rFPV was suggested by detection of the rMDV genes from peripheral blood lymphocyte DNA at 28 weeks of age. These results indicate that the dual-viral vector approach is useful for quickly and safely inducing strong and long-lasting protective immunity against vvIBDV in chickens.

Animals↗
PubMed2000

Construction of a new multi-turn time-of-flight mass spectrometer.

A new type of multi-turn time-of-flight mass spectrometer was constructed, consisting of four cylindrical electric sectors and 28 electric quadrupole lenses, the size of the vacuum chamber being 60 x 70 x 20 cm. It was demonstrated that the mass resolution can be increased according to the number of cycles of the ions through the ion optical system.

Mass Spectrometry↗
PubMed2000

Cancer prevention by natural carotenoids.

Various natural carotenoids were proven to have anticarcinogenic activity. Epidemiological investigations have shown that cancer risk is inversely related to the consumption of green and yellow vegetables and fruits. Since beta-carotene is present in abundance in these vegetables and fruits, it has been investigated extensively as possible cancer preventive agent. However, various carotenoids which co-exist with beta-carotene in vegetables and fruits also have anti-carcinogenic activity. And some of them, such as alpha-carotene, showed higher potency than beta-carotene to suppress experimental carcinogenesis. Thus, we have carried out more extensive studies on cancer preventive activities of natural carotenoids in foods; i.e., lutein, lycopene, zeaxanthin and beta-cryptoxanthin. Analysis of the action mechanism of these natural carotenoids is now in progress, and some interesting results have already obtained; for example, beta-cryptoxanthin was suggested to stimulate the expression of RB gene, an anti-oncogene, and p73 gene, which is known as one of the p53-related genes. Based on these results, multi-carotenoids (mixture of natural carotenoids) seems to be of interest to evaluate its usefulness for practice in human cancer prevention.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Y-24180, an antagonist of platelet-activating factor, suppresses interleukin 5 production in cultured murine th(2)cells and human peripheral blood mononuclear cells.

Interleukin (IL)-5 has been shown to play an essential role in the pathogenesis of airway inflammation. We investigated the effect of 4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6, 9-dimethyl-6 H -thieno[3,2- f ][1,2,4]triazolo[4,3- a][1,4]diazepine (Y-24180), an antagonist of platelet-activating factor (PAF), on the production of IL-5 in cultured D10.G4.1 cells, a murine Th(2)clone, and human peripheral blood mononuclear cells (PBMC). As a result, Y-24180 was found to suppress both the mRNA expression of IL-5 and the subsequent secretion of this cytokine in antigen-stimulated D10.G4.1 cells. Y-24180 also suppressed the production of IL-4, another Th(2)type cytokine, at the level of mRNA expression, however, it hardly affected the mRNA expression for IL-6 or IL-10, thus indicating it to have a selective action against IL-5 and IL-4. The suppressive effect of Y-24180 on the secretion of IL-5 by human PBMC was more potent than that of WEB2086, which is another PAF-antagonist. These results suggest that Y-24180 suppresses IL-5 production through a common pathway which also affects the production of IL-4, even though the mechanism remains to be elucidated as to whether the PAF-antagonistic actions are involved or not.

Animals↗
PubMed2000

Cell dynamics and expression of tumor necrosis factor (TNF)-alpha, interleukin-6, and TNF receptors in angioimmunoblastic lymphadenopathy-type T cell lymphoma.

Angioimmunoblastic lymphadenopathy (AILD)-type T cell lymphoma is histologically characterized by a mixed infiltrate of atypical T cells and B cells including B immunoblasts and plasma cells as well as eosinophils accompanied by proliferation of high endothelial venules. These morphological peculiarities are widely believed to reflect an abnormal pattern of cytokine expression. To clarify the cell dynamics and cytokine expression pattern in the lymph nodes of AILD-type T cell lymphoma, the frequency of proliferating/apoptotic cells and localization of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 producing cells were determined. Double staining was performed for (1) cell markers and Ki-67 antigen, (2) cell markers and the terminal deoxytransferase-mediated dUTP nick end labeling (TUNEL) method, or (3) cell markers and cytokines. The proliferating cell ratio in atypical T cells of AILD-type T cell lymphoma determined by Ki-67 labeling was 20.2+/-5.0%, while other peripheral T cell lymphomas (PTL) exhibited a ratio of 32.9+/-2.5%. TUNEL-positive apoptotic cells were 0.8+/-0.1% of total cells in AILD-type T cell lymphoma. They were dominantly atypical cells with positive T cell markers. In contrast, lymphoma cells in other types of PTL or paracortical cells in reactive follicular hyperplasia had only 0.3+/-0.1 or 0.4+/-0.1% TUNEL-positive cells, respectively. Thus, lymphoma cells in AILD-type T cell lymphoma demonstrated suppressed proliferating activity and enhanced apoptosis when compared to other types of PTL. TNF-alpha-producing cells were observed in all of the lymph nodes from AILD-type T cell lymphoma cases (15/15) and positive staining was obtained in the majority of atypical T cells and scattered macrophages. In contrast, IL-6 was localized to clusters of atypical T cells in some of the cases (9/15). Further, the expression of TNF-alpha, IL-6, and TNF receptors I and II (TNFRI and TNFRII) was examined by RT-PCR. The TNF-alpha message (2/2) and IL-6 message (2/2) was present in the lymph nodes of AILD-type T cell lymphoma by examination using RT-PCR, while both messages were negative in control cases (0/7). As far as an expression of mRNA for TNF receptors in AILD-type T cell lymphoma cases, mRNA for TNFRI was definitely expressed in both of the cases (2/2) while TNFRII mRNA was weakly expressed in one case (1/2). Overexpression of TNF-alpha as well as TNFRI may play a role in controlling T cell proliferation through an autocrine (T cell-T cell interaction) and paracrine (macrophage-T cell interaction) fashion. IL-6, which was also expressed by part of lymphoma cells of AILD-type T cell lymphoma, facilitates the proliferation of B cells, plasma cells, and T cells or endothelial cells in the lymph nodes of AILD-type T cell lymphoma.

Adult↗
PubMed2000

Apoptosis in rat cardiac myocytes induced by Fas ligand: priming for Fas-mediated apoptosis with doxorubicin.

Fas/Fas ligand (FasL) is well known for its role in delivering apoptotic signals; however, it is unclear whether FasL can mediate apoptosis in cardiomyocytes. We hypothesized that apoptosis via Fas/FasL system may be augmented in damaged cardiomyocytes. To determine whether FasL mediates cardiomyocyte apoptosis, recombinant FasL (rFasL) was added to the culture of neonatal rat ventricular myocytes pretreated with and without doxorubicin. Without doxorubicin, high dose of rFasL caused an increase in TUNEL-positive cardiomyocytes and a mild decrease in MTT activities. When cardiomyocytes were pretreated with doxorubicin (0.5 microM), rFasL dramatically augmented TUNEL-positive cardiomyocytes in a concentration-dependent manner, which was accompanied with nuclear fragmentations. The rFasL also caused a concentration-dependent reduction in MTT activities in cardiomyocytes. The rFasL-induced caspase-8 activity was greatly facilitated by pretreatment of doxorubicin. TUNEL-positive nuclei with rFasL was inhibited by Fas-Fc, neutralizing agent of rFasL, and Z-IETD-FMK, caspase-8 inhibitor. Fas mRNA transcript by RT-PCR was up-regulated in cardiomyocytes with doxorubicin. We conclude that FasL can induce cardiomyocyte apoptosis particularly when cardiomyocyte becomes susceptible for Fas-mediated apoptosis.

Animals↗
PubMed2000

Propofol prevents lipid peroxidation following transient forebrain ischemia in gerbils.

PURPOSE: To ascertain whether propofol prevents lipid peroxidation on delayed neuronal death induced by transient forebrain ischemia in the hippocampal CA1 subfield in gerbils. METHODS: Forty gerbils were randomly assigned to five groups: Group I, control, sham operation treated with physiological saline solution (PSS); Group II, ischemia/reperfusion treated with PSS; Group III, ischemia/reperfusion treated with 50 mg x kg(-1) propofol; Group IV, ischemia/reperfusion treated with 100 mg x kg(-1) propofol; Group V, ischemia/reperfusion treated with 150 mg x kg(-1) propofol. Transient forebrain ischemia was induced by occluding the bilateral common carotid arteries for four minutes under N2O/O2/halothane anesthesia after propofol or PSS. Five days later, the cerebrum was removed and each forebrain was cut into two including the hippocampus. Lipid peroxidation was determined using the production of malondialdehyde (MDA), and histopathological changes in the hippocampal CA1 subfield were examined. RESULTS: In group II, the pyramidal cells were atrophic and pycnotic; vacuolation and structural disruption of the radial striated zone was observed. In the other four groups, these changes were not observed. Degenerative ratios of pyramidal cells were: Group I: 4.9 +/- 2.3, Group II: 94.1 +/- 4.5 (P < 0.01), Group III: 12.5 +/- 5.7, Group IV: 11.0 +/- 4.6, Group V: 9.6 +/- 4.9%. Production of MDA was: Group I: 83 +/- 22, Group II: 198 +/- 25 (P < 0.01), Group III: 153 +/- 39, Group IV: 113 +/- 34, Group V: 106 +/- 27 nmol x g(-1) wet tissue. CONCLUSION: Propofol attenuated delayed neuronal death by preventing lipid peroxidation induced by transient forebrain ischemia in the hippocampal CA1 subfield in gerbils.

Animals↗
PubMed2000

Small-cell carcinoma of the gallbladder: report of a case.

We report herein the case of an 81-year-old woman in whom a mass in the gallbladder was revealed by an ultrasound examination conducted as part of a follow-up study for a silent gallstone. The mass showed evidence of invasion into the adjacent liver parenchyma. Under the tentative diagnosis of malignant neoplastic disease originating in the gallbladder, a cholecystectomy with partial hepatectomy was performed. Histological examination of the tumor confirmed a diagnosis of small-cell carcinoma of the gallbladder, which is considered to be a rare type of neoplasm.

Aged↗
PubMed2000

Effect of Y-24180, a receptor antagonist to platelet-activating factor (PAF), on allergic cutaneous reactions in actively sensitized mice.

OBJECTIVE AND DESIGN: We examined the effect of Y-24180, a potent antagonist to platelet-activating factor (PAF), on allergic cutaneous reactions in actively sensitized mice. MATERIALS: Male BALB/c and BALB/c-nu/nu mice were used. TREATMENT: Y-24180, ketotifen fumarate (ketotifen), and suplatast tosilate (suplatast) were orally administered twice a day for 3 days beginning 2 days before an ovalbumin (OA) challenge. Hydrocortisone 17-butyrate (hydrocortisone) was applied topically to ear surface once a day for 3 days, beginning 2 days before the OA challenge. METHODS: Mice actively sensitized with OA were challenged by intradermally injecting OA into both ears. Ear thickness was measured with a dial thickness gauge. RESULTS: Increase in ear thickness, with peak responses at 1 h (immediate phase reaction, IPR) and 24 h (late phase reaction, LPR) after the challenge, were induced in actively sensitized BALB/c mice. The reactions were not induced in T cell-deficient BALB/c-nu/nu mice. Y-24180 suppressed both the IPR and LPR of BALB/c mice. Although suplatast suppressed the LPR, the IPR was not affected. Ketotifen suppressed the IPR, but not the LPR. Hydrocortisone suppressed both the IPR and LPR of BALB/c mice. Furthermore, Y-24180 in combination with hydrocortisone significantly enhanced the effect of hydrocortisone on both the reactions. CONCLUSIONS: Y-24180 was demonstrated not only to suppress the IPR and LPR, but also to show strong suppressive effects in combination with topical hydrocortisone. Therefore, Y-24180 is expected to contribute to the treatment of inflammatory skin diseases including atopic dermatitis.

Administration, Oral↗