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T Aso

Publications and source records attributed to T Aso.

At least 109 records · Page 6Linked to original sources
PubMed1997

Molecular cloning of DNAs encoding the regulatory subunits of elongin from Saccharomyces cerevisiae and Drosophila melanogaster.

The Elongin complex strongly stimulates the rate of elongation by RNA polymerase II by suppressing transient pausing by polymerase at many sites along the DNA. Elongin is composed of a transcriptionally active A subunit and two positive regulatory B and C subunits. The Elongin complex is a potential target for regulation by the von Hippel-Lindau (VHL) tumor suppressor protein, which is capable of binding stably to the Elongin BC complex and preventing it from activating Elongin A. Here, we report the molecular cloning of a Saccharomyces cerevisiae genomic DNA encoding Elongin C subunit and of Drosophila cDNAs encoding Elongin B and C subunits. The predicted amino acid sequence of each protein shows a high degree of similarity with the mammalian proteins. The recombinant yeast Elongin C protein interacts with both mammalian Elongin A and VHL tumor suppressor protein. Moreover, yeast Elongin C strongly induces the transcriptional elongation activity of mammalian Elongin A. The expression of yeast Elongin C mRNA is dramatically upregulated during sporulation; however, the gene is not essential for sporulation and viability in yeast cell.

Amino Acid Sequence↗
PubMed1997

Interaction of elongation factors TFIIS and elongin A with a human RNA polymerase II holoenzyme capable of promoter-specific initiation and responsive to transcriptional activators.

Affinity chromatography on columns containing the immobilized monomeric transcriptional elongation factor TFIIS or the essential large subunit, Elongin A, of the trimeric elongation factor, Elongin, was used to purify a human RNA polymerase II holoenzyme from HeLa whole cell extract. This holoenzyme contained nearstoichiometric amounts of all the general transcription factors, TFIIB, TFIID (TBP + TAFIIs), TFIIE, TFIIF, and TFIIH, required to accurately initiate transcription in vitro at the adenovirus major late promoter. It behaved as a large complex, slightly smaller than 70 S ribosomes, during gel filtration chromatography, and contained nearly half the TFIID that was present in the extract used for the affinity chromatography. It also contained the cyclin-dependent kinase CDK8, a human homologue of the Saccharomyces cerevisiae holoenzyme subunit SRB10, and many other polypeptides. Efficient interaction of holoenzyme with TFIIS or Elongin A required only the amino-terminal region of either protein. These regions are similar in amino acid sequence but dispensable for TFIIS or Elongin to regulate elongation in vitro by highly purified RNA polymerase II. The transcriptional activators GAL4-VP16 and GAL4-Sp1 activated transcription in vitro by purified holoenzyme in the absence of any additional factors.

Amino Acid Sequence↗
PubMed1997

The expression patterns of standard and variant CD44 molecules in normal uterine cervix and cervical cancer.

CD44 is a cell-surface glycoprotein postulated to play a role in tumor-cell metastasis. We have examined the expression of the standard CD44 (CD44s), and alternative spliced variants of CD44 containing variant exons v6, v9, and v1O (CD44v6, CD44v9, and CD44v10 respectively) in 9 samples of normal cervix, 6 samples of cervical intraepithelial neoplasia (CIN), and 11 samples with invasive cervical carcinomas. RT/PCR demonstrated the presence of CD44s in all samples of normal cervix and those with invasive carcinomas. CD44v6 was also found in all normal cervical samples and in 9 tissue samples of invasive carcinomas. The results also suggested that some tumor specimens had several higher molecular transcripts containing exon v6 compared to specimens of normal cervix. Immunohistochemistry detected the presence of CD44s and the absence of CD44v10 in both epithelial and stromal cells in all specimens. In contrast, CD44v6 and CD44v9 were stained positive in epithelial cells but were absent in stromal cells. The intensity of CD44v6 and CD44v9 staining was strongest in normal cervical epithelium followed by CIN, invasive squamous cell carcinoma, and adenocarcinoma. In the malignant samples, heterogeneity in staining intensity among different clusters of tumor cells was observed. Furthermore, poorly differentiated and undifferentiated carcinomas from patients having poor prognosis did not stain at all. This study suggests that variant CD44 molecules may serve an important function in the cell contact of cervical epithelial cells, and that cervical epithelium acquires heterogeneity in the expression of CD44 adhesion molecules during carcinogenesis, which may be related to tumor metastasis.

Cervix Uteri↗
PubMed1997

The mechanism of myometrial contractions induced by endothelin-1 in rat.

Experiments were performed to characterize endothelin-1-induced contractions and the role of endothelin (ET) receptor subtypes in rat myometrium. The binding sites of [(125)I]-ET-1 were saturable with high affinity. Scatchard plot analysis revealed that ET-1 binding sites in the myometrium constituted a single population. The dissociation equilibrium constant (Kd) and the maximum binding sites (Bmax) were determined to be 48.9+/-3.0 pM and 1364.0+/-210.3 fmol/mg protein respectively. Specific [(125)I]-ET-1 binding was inhibited completely by unlabelled ET-1 and Ro 46-2005 (mixed-type ET receptor antagonist), but not fully (90.7+/-1.4%) by BQ 123 (a selective ETA receptor antagonist), and not at all by RES 701-1 (a selective ETB receptor antagonist). ET-1 induced myometrial contractions were composed of two types, an increase in resting tone and rhythmic contractions. These contractions were inhibited by BQ 123 and Ro 46-2005, but not by RES 701-1. ET-1-induced contractions were greatly reduced in Ca2+-free Krebs' solution. Nifedipine abolished the rhythmic contractions without affecting the increase in resting tone. These results suggest that ETA receptors are predominantly localized in rat myometrium and that excitation of ETA receptors evokes two types of contractions by increasing the cytoplasmic Ca2+ concentration.

Animals↗
PubMed1997

Nitric oxide inhibits steroidogenesis in cultured porcine granulosa cells.

Recent evidence suggested that nitric oxide (NO) acts as an important factor in a variety of physiological and pathological roles, including reproductive functions. The purpose of the present study was to investigate whether NO might significantly induce any change in steroidogenesis in cultured porcine granulosa cells (PGC). An NO donor, NOC18, significantly suppressed the oestradiol release from basal (unstimulated) and gonadotrophin-stimulated PGC in a 2 h culture. NOC18 also significantly inhibited the aromatase activity of basal and gonadotrophin-stimulated PGC as measured by a modified tritiated water method. However, the cGMP analogue, 8-bromo-cGMP, had no significant effect on the accumulation of oestradiol and progesterone in basal and gonadotrophin-stimulated PGC during 24 h culture. An NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (LNMMA), significantly stimulated the basal oestradiol release and dose-dependently enhanced the oestradiol and progesterone release from follicle stimulating hormone (FSH)-stimulated PGC in a 24 h culture. However, NG-monomethyl-D-arginine, which does not inhibit NOS, did not enhance the release of oestradiol and progesterone under the same experimental conditions. LNMMA also significantly suppressed the nitrite concentrations in the media as measured by chemiluminescence. These results demonstrate for the first time that NO inhibits oestradiol secretion independent of cGMP by inhibiting P450 aromatase activity in moderately mature PGC.

Animals↗
PubMed1997

Subclinical REM sleep behavior disorder in a patient with corticobasal degeneration.

Various neurodegenerative diseases have been reported to be associated with rapid eye movement (REM) sleep behavior disorder (RBD). This is the first report of a patient with corticobasal degeneration (CBD) associated with subclinical RBD. A 72-year-old woman was admitted complaining of fine tremor of the right hand and weakness of the right lower extremity. She was diagnosed as having CBD on the basis of clinical features and neuroimaging studies. Her family noticed snoring and increase in sleep talk, but they did not regard them as pathological. All-night polysomnography (PSG) revealed REM sleep without atonia (RWA) during which 14 episodes of talking and singing were observed. They ranged from the utterance of one word to that of comprehensible words of a song for about 3 minutes accompanied by various nonpurposeful movements of the mouth, hands, and limbs. These episodes were not associated with any sleep-disturbed breathing. Future PSG studies on CBD patients together with postmortem analysis of brain stem structures that are crucial for generating REM sleep-related atonia are warranted for further understanding of the pathophysiological mechanism of RBD.

Aged↗
PubMed1997

High ratios of free to total insulin-like growth factor-I in early infancy.

Insulin-like growth factor-I (IGF-I) is a major effector of somatic growth and metabolism. In normal, nonpregnant plasma, most of the IGF-I is complexed to specific IGF-binding proteins (IGFBPs), particularly IGFBP-3; only a minor fraction of plasma IGF-I exists in a free form. Recently, we have reported that free IGF-I levels, as measured using a new immunoradiometric assay, are relatively high in maternal plasma during pregnancy because of increased IGFBP-3 proteolytic activity. These high free IGF-I levels are physiologically important for the growth of maternal tissues such as uterus and placenta, which are related to the fetal growth. Growth during early infancy may be a continuation of fetal growth. In the present study, we have analyzed free and total plasma IGF-I and IGFBP-3 proteolytic activity in early infancy. Although the levels of free and total IGF-I were not significantly different in early infancy as compared with prepubertal periods, the ratio of free to total IGF-I (mean = 2.04%) was relatively increased and was similar to the ratio in pregnancy plasma (1.86%). However, unlike in maternal plasma, the high ratios were not totally caused by increased IGFBP-3 proteolytic activity. Our results suggest that there may be an increased conversion of plasma IGF-I to a free form in early infancy. The resultant increase in IGF-I bioavailability could contribute to the rapid somatic growth in early infancy.

Adult↗
PubMed1997

Relationship between the release of prolactin and endothelin-1 in human decidualized endometrial cells.

The study was undertaken to investigate the interaction between the release of endothelin-1 (ET-1) and prolactin (PRL) from human decidualized endometrial cells, and the effects of transforming growth factor (TGF)-beta 1 on the release of ET-1 and PRL from human decidual cells in the early stage of pregnancy. Stromal cells derived from human endometrial tissues were cultured on a type-1 collagen membrane in serum-free medium with or without 100 nmol/l oestradiol and 1 mumol/l medroxyprogesterone acetate (MPA) for 12 days. In addition, decidual cells of early pregnancy were cultured with or without TGF-beta 1 for 48 h. PRL and ET-1 levels in the media were measured by a specific enzyme immunoassay and RIA respectively. In decidualized endometrial cells induced by ovarian steroid hormones in vitro, PRL release increased and ET-1 release decreased in a time-dependent manner. Ovarian steroid hormones significantly attenuated ET-1 release. In the decidual cells of early pregnancy, TGF-beta 1 significantly attenuated the PRL release, whereas this growth factor dose-dependently increased ET-1 release. There was a significant negative correlation between the release of PRL and that of ET-1. These results demonstrate that the regulation of PRL release is quite different from that of ET-1 release in the human decidualized endometrial cells, and suggest that TGF-beta 1 has significant effects on PRL and ET-1 release in the human decidua of early pregnancy.

Adult↗
PubMed1997

[The regulation mechanism of the female menstrual cycle].

The hormonal patterns during menstrual cycle, which consist of cyclic alterations in gonadotropins, estradiol, and progesterone, are controlled by hypothalamic-pituitary-ovarian feedback mechanism. GnRH produced in hypothalamus acts on the pituitary cells to secrete FSH and LH, which stimulate the follicular development. The developed follicles secrete estradiol, progesterone, inhibin, activin, and follistatin. Estradiol and progesterone, at different concentrations and/or ratios, either positively or negatively control the feedback of hypothalamic-pituitary axis in regulating the secretion of GnRH, FSH and LH. Inhibin and follistatin selectively suppress, whereas activin enhances the secretion of FSH in the pituitary. Recently, various additional factors produced by the ovary have been identified to contribute to the follicular development by paracrine and/or autocrine regulation as well as to feedback on hypothalamic-pituitary unit.

Amino Acid Sequence↗
PubMed1996

The inducible elongin A elongation activation domain: structure, function and interaction with the elongin BC complex.

The elongin (SIII) complex strongly stimulates the rate of elongation by RNA polymerase II by suppressing transient pausing by polymerase at many sites along the DNA. Elongin (SIII) is composed of a transcriptionally active A subunit and two small regulatory B and C subunits, which bind stably to each other to form a binary complex that interacts with elongin A and strongly induces its transcriptional activity. The elongin (SIII) complex is a potential target for negative regulation by the von Hippel-Lindau (VHL) tumor suppressor protein, which is capable of binding stably to the elongin BC complex and preventing it from activating elongin A. Here, we identify an elongin A domain sufficient for activation of elongation and demonstrate that it is a novel type of inducible activator that targets the RNA polymerase II elongation complex and is evolutionarily conserved in species as distantly related as Caenorhabditis elegans and man. In addition, we demonstrate that both the elongin A elongation activation domain and the VHL tumor suppressor protein interact with the elongin BC complex through a conserved elongin BC binding site motif that is essential for induction of elongin A activity by elongin BC and for tumor suppression by the VHL protein.

Amino Acid Sequence↗
PubMed1996

A human cDNA encoding the 110-kDa A subunit of RNA polymerase II transcription factor elongin.

A full-length cDNA encoding a human homolog of the approx. 110-kDa subunit (elongin A; El A) of the RNA polymerase II transcription factor, elongin, was isolated and sequenced. Comparison of the open reading frames of the human el A cDNA and the previously characterized rat El A cDNA [Aso et al., Science 269 (1995) 1439-1443] indicates that they are 84% conserved in nucleotide sequence and encode 84% identical proteins.

Amino Acid Sequence↗
PubMed1996

Effect of estriol on bone loss in postmenopausal Japanese women: a multicenter prospective open study.

OBJECTIVES: To assess the effects of oral estriol on the bone mineral density (BMD) and bone metabolism in postmenopausal women. METHODS: Seventy-five natural postmenopausal women with a BMD of more than 10% below the peak bone density were treated for 50 weeks with 2 mg/day estriol (E3) cyclically and 0.8 g/day of calcium lactate continuously. BMDs at L2-L4 were measured by dual energy X-ray absorptiometry (DXA). RESULTS: The BMD increased 1.79% (p < 0.01 vs. pretreatment) after 50 weeks, accompanied with decrease of biochemical markers of bone turnover. With regard to climacteric symptoms, Kupperman's menopausal index improved (p < 0.01 vs. pretreatment) after 5 weeks of treatment. As to the incidence of adverse events genital bleeding was observed in only 8.0% of the subjects. Endometrial histology and cytology showed neither abnormalities nor hyperplasia during and after the treatment. CONCLUSIONS: Estriol prevented postmenopausal bone loss and improved climacteric symptoms effectively with low incidence of genital bleeding.

Bone Density↗