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Biomedical subjects

S Tanaka

Publications and source records attributed to S Tanaka.

At least 415 records · Page 23Linked to original sources

Secretory activity of gonadotropin and the responsiveness of gonadotrophs to gonadotropin-releasing hormone during the annual reproductive cycle of male bats, Rhinolophus ferrumequinum: analysis by cell immunoblot assay.

The purpose of this study was to examine secretory activity of gonadotropin (Gn) and the responsiveness of Gn secretion to Gn-releasing hormone (GnRH) in male horseshoe bats, Rhinolophus ferrumequinum, during the annual reproductive cycle. Anterior pituitary cells were monodispersed and subjected to cell immunoblot assay for Gn. Cell blots specific for follicle stimulating hormone (FSH) or luteinizing hormone (LH) were quantified using a microscopic image analyzer. The percentages of LH- or FSH-secreting cells detected as immunoreactive cell blots were markedly increased in the spermatogenic period (summer) and decreased in the hibernation period (winter). The mean Gn secretion from individual cells and total Gn secretion per unit area of the transfer membrane also showed similar changes. The responsiveness of Gn secretion to GnRH was greater in the spermatogenic period than in other seasons. On the other hand, although the secretory activity of Gn was markedly decreased during hibernation, a stimulatory effect of GnRH on Gn secretion was observed. These findings suggest that seasonal changes in the release of Gn required for gametogenesis and gonadal steroidogenesis varied depending on the reproductive activity and seasonal changes in Gn sensitivity to stimulatory effects of GnRH due to alterations in GnRH receptor numbers and/or in postreceptor events of gonadotrophs.

Animals↗

The role of

The effect of [His(7)]-corazonin on the body color in Locusta migratoria was examined by varying the injected dose and the time of injection in both an albino and a normal (pigmented) strain. Albino nymphs injected with a high dose (100pmol) of [His(7)]-corazonin at the beginning of the third instar turned completely black in the following instar, whereas those injected with the same dose in the middle of the instar developed black patterns with an orange background color, the body coloration characteristic of normal gregarious (crowded) individuals. Injection at the end of the third instar induced a reddish color with few black spots. Irrespective of the time of injection of the peptide, most of these individuals became completely black after ecdysis to the fifth instar. A similar result was obtained with a lower dose (1pmol), although the color expressed was lighter. In the normal strain, injection of 1nmol or 100pmol into crowded third instar nymphs also caused most of them to become completely black in the fourth and fifth instars, but a lower dose apparently had no influence. These results suggest that the temporal changes in hemolymph titer of [His(7)]-corazonin are important in the expression of body color in L. migratoria.

Journal Article↗

Evaluation of expressed emotion (EE) status in mood disorders in japan: inter-rater reliability and characteristics of EE.

The reliability of expressed emotion (EE) ratings by the Camberwell Family Interview (CFI) and characteristics of EE were evaluated in families of patients with mood disorders in Japan. The subjects were 27 patients with mood disorders and 31 members of their families. The CFI was carried out with the family members. EE was rated by two raters independently, and the inter-rater reliability was evaluated according to Spearman's correlation coefficient by ranks and the kappa-value. The distribution of subscales of EE in these subjects was compared with that in families of patients with schizophrenia in Japan and families of patients with mood disorders abroad. Concerning critical comments (CC), hostility (H), and emotional over-involvement (EOI), which are important for EE rating, Spearman's correlation coefficient and the kappa-values were 0.4-0.8, and the reliability of EE ratings in mood disorders was not high. The proportion of positive agreement was particularly low in H and EOI. CCs were fewer in families of Japanese patients with mood disorders than in those with schizophrenia or families of American or European patients with mood disorders. Re-evaluation of the inter-rater reliability of EE ratings in mood disorders is needed. Expressed emotion was more suppressed in families of patients with mood disorders than in those of patients with schizophrenia. Expressed emotion was also more reserved in the Japanese subjects than in their Western counterparts.

Adult↗

Dmc1 of Schizosaccharomyces pombe plays a role in meiotic recombination.

We report here a Schizosaccharomyces pombe gene (dmc1(+)) that resembles budding yeast DMC1 in the region immediately upstream of the rad24(+) gene. We showed by northern and Southern blot analysis that dmc1(+) and rad24(+) are co-transcribed as a bicistronic mRNA of 2.8 kb with meiotic specificity, whereas rad24(+) itself is constitutively transcribed as a 1.0-kb mRNA species during meiosis. Induction of the bicistronic transcript is under the control of a meiosis-specific transcription factor, Ste11. Disruption of both dmc1(+) and rad24(+) had no effect on mitosis or spore formation, and dmc1Delta cells displayed no change in sensitivity to UV or gamma irradiation relative to the wild type. Tetrad analysis indicated that Dmc1 is involved in meiotic recombination. Analysis of gene conversion frequencies using single and double mutants of dmc1 and rhp51 indicated that both Dmc1 and Rhp51 function in meiotic gene conversion. These observations, together with a high level of sequence identity, indicate that the dmc1(+) gene of S. POMBE: is a structural homolog of budding yeast DMC1, sharing both similar and distinct functions in meiosis.

Cell Cycle Proteins↗

Regional difference of neuronal vulnerability in the murine hippocampus after transient forebrain ischemia.

We have investigated the regional difference of neuronal vulnerability within the hippocampus in the C57BL/6 strain mice after forebrain ischemia. Both common carotid arteries of fifty mice were occluded for 12 min and the mouse brain was examined with cresyl violet staining. The CA4 sector was found to be the most vulnerable within the hippocampus. The CA2 and the medial CA1 sector was the 2nd and 3rd most vulnerable regions. However, The lateral part of the CA1 sector, CA3 sector and the dentate gyrus were resistant to ischemic insult.

Animals↗

Comparison of G-protein activation in the brain by mu-, delta-, and kappa-opioid receptor agonists in mu-opioid receptor knockout mice.

Mice lacking the mu-opioid receptor gene have been developed by a gene knockout procedure. In this study, the activity of opioid receptor coupled G-proteins was examined to investigate whether there is a change in the extent of coupling for mu, delta-, and kappa-opioid receptors in mu-opioid receptor knockout mice. Selective agonists of mu- (DAMGO), delta- (DPDPE), and kappa- (U-69,593) opioid receptors stimulated [(35)S]GTPgammaS binding in the caudate putamen and cortex of wild-type mice. In contrast, only U-69,593 stimulated [(35)S]GTPgammaS binding in these regions of mu-opioid receptor knockout mice. These results confirmed the absence of G-protein activation by a mu-opioid receptor agonist in mu-opioid receptor knockout mice, and demonstrated that coupling of the kappa-opioid receptor to G-proteins is preserved in these mice. However, G-protein activation by the delta-opioid receptor agonist, DPDPE, was reduced in the mu-opioid receptor knockout mice, at least in the brain regions studied using autoradiography.

Alleles↗

Et(3)B-Induced Hydrogermylation of Alkenes and Silyl Enol Ethers.

Tri-2-furanylgermane in the presence of a catalytic amount of Et(3)B adds to internal alkenes as well as terminal alkenes effectively to give the corresponding adducts in good to excellent yields. The addition of tri-2-furanylgermane to silyl enol ethers followed by elimination of germyl and siloxy moieties provides a new route for the conversion of ketones into alkenes.

Journal Article↗

Transcriptional activation of JC virus by human T-lymphotropic virus type I Tax protein in human neuronal cell lines.

Polyomavirus JC (JCV) causes the human demyelinating disease, progressive multifocal leukoencephalopathy (PML). The recent demonstration of cases of PML in association with human T-lymphotropic virus type I (HTLV-I) infection prompted us to examine whether the HTLV-I-encoded regulatory protein Tax activates JCV transcription. By employing a dual luciferase assay, we initially found that the expression of Tax activated the transcriptional potential of both early and late promoters of JCV in human neuronal but not in non-neuronal cells. We subsequently analyzed the mechanism of Tax-induced activation of the JCV promoter in neuronal cells with the following results: 1) the JCV promoter that lacks the NF-kappaB-binding motif could not be activated by Tax; 2) the overexpression of IkappaBalpha abolished Tax-induced transcriptional activation of the JCV promoter; 3) a Tax mutant (M22) lacking the potential for activation via the NF-kappaB pathway did not activate the JCV promoter. Furthermore, Tax enhances the gene expression of JCV T antigen and VP1. We examined mechanisms of the cell-specific activation of the JCV promoter by Tax. Electrophoretic mobility shift assay demonstrated the presence of Tax-bound protein(s) that were specifically present in non-neuronal cells. This study is the first demonstration of the activation of JCV promoter by HTLV-I Tax in an NF-kappaB-dependent manner.

Base Sequence↗

Cooperative interactions between PBX, PREP, and HOX proteins modulate the activity of the alpha 2(V) collagen (COL5A2) promoter.

Cell type-specific expression of the human alpha2(V) collagen (COL5A2) gene depends on a cis-acting element that consists of two contiguous protein binding sites (FPA and FPB) located between nucleotides -149 and -95, relative to the transcription start site. The present study focused on the characterization of the FPB-bound complex. DNA binding assays and cell transfection experiments revealed that the bipartite core sequence of FPB (5'-ATCAATCA-3') binds the PBX1/2, PREP1, and HOXB1 proteins, and this in turn leads to promoter transactivation. In the presence of all three nuclear factors, cooperative interactions between recombinant PBX1 and PREP1 or PBX1 and HOXB1 result in binding of the heterodimers to FPB in vitro. Similarly, overexpression of different combinations of PBX1, PREP1, and HOXB1 transactivates FPB-driven transcription. In contrast to the composition of the FPB complex purified from COL5A2-positive cells, the FPB complex from COL5A2-negative cells contains PBX2 and PREP1 but lacks PBX1. However, PBX1 exogenously introduced into COL5A2-negative cells cannot stimulate FPB-driven transcription unless co-expressed with PREP1. Within the intrinsic limitations of the experimental model, our results indicate that combinatorial interactions among PBX and PREP or HOX proteins are involved in regulating tissue-specific production of collagen V.

Base Sequence↗

Identification of

The neuropeptides inducing dark color in albino nymphs of the migratory locust Locusta migratoria were isolated from the larval brain of the silkworm, Bombyx mori and from the adult corpora cardiaca (CC) of the cricket Gryllus bimaculatus, respectively, and their amino acid sequences identified. The two peptides isolated from the two different species are identical to [Arg(7)] corazonin, a neuropeptide known to be present in a cockroach and others. This peptide induces a dark color in albino nymphs of L. migratoria at fmol levels, and a high dose of >/=100 pmol caused albino locusts to turn completely black, but it influenced neither body color nor metamorphosis in B. mori and G. bimaculatus. Therefore, the physiological functions of [Arg(7)] corazonin in the silkworm and the cricket remain unknown. The present study demonstrated the usefulness of the albino strain of L. mirgatoria as a specific bioassay system for this peptide.

Journal Article↗

Establishment of an Aging Farm of F344/N Rats and C57BL/6 Mice at the National Institute for Longevity Sciences (NILS).

In 1996 the National Institute for Longevity Sciences (NILS) started an aging/aged farm (Aging Farm), an animal farm for producing aging/aged laboratory rodents on inbred strains, F344/N rats and C57BL/6 mice at its Experimental Animal Facility Wing, based on plans prepared by the Laboratory Animal Research Facilities (LARF). The NILS Aging Farm, being well established, began internal supply of aging/aged laboratory rodents in 1999 to promote both aging and longevity science. This report describes development of the NILS Aging Farm under NILS Aging Farm Guide and the effectiveness of the Guide.

Journal Article↗

Human dolichol-phosphate-mannose synthase consists of three subunits, DPM1, DPM2 and DPM3.

Dolichol-phosphate-mannose (DPM) synthase generates mannosyl donors for glycosylphosphatidylinositols, N-glycan and protein O- and C-mannosylation. In Saccharomyces cerevisiae, this enzyme is encoded by DPM1. We reported previously that mammalian DPM synthase contains catalytic DPM1 and regulatory DPM2 subunits, and that DPM1 requires DPM2 for its stable expression in the endoplasmic reticulum. Here we report that human DPM synthase consists of three subunits. The third subunit, DPM3, comprises 92 amino acids associated with DPM1 via its C-terminal domain and with DPM2 via its N-terminal portion. The stability of DPM3 was dependent upon DPM2. However, overexpression of DPM3 in Lec15 cells, a null mutant of DPM2, restored the biosynthesis of DPM with an increase in DPM1, indicating that DPM3 directly stabilized DPM1. Therefore, DPM2 stabilizes DPM3 and DPM3 stabilizes DPM1. DPM synthase activity was 10 times higher in the presence of DPM2, indicating that DPM2 also plays a role in the enzymatic reaction. Schizosaccharomyces pombe has proteins that resemble three human subunits; S.pombe DPM3 restored biosynthesis of DPM in Lec15 cells, indicating its orthologous relationship to human DPM3.

Amino Acid Sequence↗

p53 polymorphism in human papillomavirus-associated esophageal cancer.

Human papillomavirus type 16/18 (HPV-16/18) is implicated in the pathogenesis of squamous cell carcinoma (SCC) of the cervix and esophagus. The arginine allele at codon 72 of p53 was found to be more susceptible to degradation by HPV E6 protein than is the proline allele in vivo, thus resulting in a high frequency of cervical SCC in individuals homozygous for arginine at the codon. There are controversial results from several clinical studies of cervical SCC. In the present study, encoding regions of p53 codon 72 and HPV-16/18 E6 were directly sequenced, using pairs of primary esophageal SCC tissue and corresponding normal mucosa, which were from 75 patients (Japanese, n = 38; Chinese, n = 37). The arginine allele alone was detected in 70.6% (12 of 17) of HPV-positive cases but only in 43.1% (25 of 58) of HPV-negative cases (P < 0.05). In contrast, such a significant correlation between p53 polymorphism and HPV infection was not evident in corresponding normal mucosae. Because our findings between tumor specimens and the normal mucosae differed, we suggest that the frequent loss of proline allele in HPV-associated carcinogenesis of the esophagus major plays some role. The particular type of p53 polymorphism may indicate a potential candidate for HPV-associated SCC.

Alleles↗

Involvement of mu-opioid receptors in potentiation of apomorphine-induced climbing behavior by morphine: studies using mu-opioid receptor gene knockout mice.

The present study examined the hypothesis that mu-opioid receptors contribute to a behavioral stimulation produced by stimulation of dopamine receptors by comparing responses in mu-opioid receptor knockout and wild type mice. Apomorphine-induced climbing behavior was augmented by 65%, in wild type mice, but not in mu-knockout, following subcutaneous administration of morphine (15 mg/kg). Moreover, pretreatment with either naloxone (an opioid receptor antagonist) or haloperidol (a mixed D(1)/D(2) receptor antagonist) eliminated the enhancement by morphine of climbing behavior in wild type mice. These results indicate that expression of mu-opioid receptors plays an important role in the enhancement of climbing behavior induced by the dopamine receptor agonist, apomorphine. Furthermore, this augmentation is mediated by interaction between dopamine and mu-opioid receptors.

Analgesics, Opioid↗

Peroxisome proliferator-activated receptor-gamma agonists increase vascular endothelial growth factor expression in human vascular smooth muscle cells.

Vascular endothelial growth factor (VEGF), expressed in a variety of mesenchymal cells including vascular smooth muscle cells (VSMC), is a potent mitogen for endothelial cells, and is used clinically applied for ischemic disease of peripheral vessels. To determine whether peroxisome proliferator-activated receptor gamma (PPARgamma) regulates VEGF production in VSMC, we examined VEGF secretion from VSMC treated with PPAR agonists. Troglitazone increased VEGF secretion in a time- and dose-dependent manner (261 +/- 35% with 25 mM of troglitazone for 24 h), and also increased levels of VEGF mRNA. VEGF secretion was also increased by other PPARgamma agonists, pioglitazone, LY171883, and 15d-PGJ2 (224 +/- 17.1%, 247 +/- 36.8% and 171 +/- 7.8%, respectively), but not the PPARgamma agonists bezafibrate and Wy14643 (85.2 +/- 1.5%, 94.6 +/- 3.2, respectively). Our findings suggest that thiazolidinediones might be useful for the therapeutic angiogenesis for ischemic artery disease.

Acetophenones↗

The Ras-mitogen-activated protein kinase pathway is critical for the activation of matrix metalloproteinase secretion and the invasiveness in v-crk-transformed 3Y1.

To search for the intracellular signaling pathway critical for the secretion of matrix metalloproteinases (MMP), we studied the effects of dominant negative Ras (S17N Ras) and dominant negative MEK1 (MEK1AA) expression in v-crk-transformed 3Y1. Expression of either S17N Ras or MEK1AA dramatically suppressed the augmented secretion of MMP-2 and MMP-9 in v-crk-transfected 3Y1. Similarly, a Ras farnesyltransferase inhibitor, manumycin A, and a MEK1 inhibitor, U0126, suppressed MMP secretion in a dose-dependent manner, whereas a PI3 kinase inhibitor, wortmannin, could not. In addition, the suppression of MMP secretion by S17N Ras showed good correlation with the inhibition of in vitro invasiveness of the cells. In contrast, expression of dominant negative C3G did not suppress MMP secretion, although it substantially blocked the c-Jun N-terminal kinase activation. Taken together, the Ras-MEK1 pathway, but not the C3G-JNK pathway, seems to play a key role in the activation of MMP secretion and, hence, the invasiveness of v-crk-transformed cells.

Androstadienes↗