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Biomedical subjects

T Aso

Publications and source records attributed to T Aso.

At least 127 records · Page 7Linked to original sources
PubMed1996

Intimal hyperplasia in human uterine arteries accompanied by impaired synergism between prostaglandin I2 and nitric oxide.

1. The present experiments were designed to investigate the mechanisms causing intimal hyperplasia in connection with the impaired synergism between prostaglandin I2 (PGI2) and nitric oxide (NO) in human uterine arteries (UAs). 2. In order to assess the magnitude of intimal hyperplasia, the intima:media ratio (%) was estimated with the aid of an image analyser. Human UAs were classified into two groups, I and II on the basis of the ratio and the degree of elastin deposition of histologically normal specimens. The intima:media ratio in group II was determined to be 38.9 +/- 7.7% (n = 6), which was significantly (P < 0.01) higher than that in group I (16.5 +/- 1.5%, n = 7). Less deposition of elastin was found in group I than in group II. 3. The relaxation activities of iloprost (IP) as a stable analogue of PGI2 and sodium nitroprusside (SNP) as a NO donor were not different between the two groups. When the minimum concentrations (Cmin) of IP and SNP in producing relaxation were applied together to the UA strips, these compounds interacted synergistically in group I. The observed relaxation (48.7 +/- 8.8%, n = 7) in this group was significantly (P < 0.01) greater than the predicted value of 18.8 +/- 3.1% (n = 7) (the mathematical sum of the relaxations caused by IP and SNP alone). By contrast, these agents interacted in an additive manner in group II. The observed relaxation (20.8 +/- 9.5%, n = 6) was not significantly different from the predicted value (18.6 +/- 2.4%, n = 6) in this group. 4. During the relaxation produced by the addition of IP and SNP alone or in combination, the changes in cyclic nucleotides (cyclic AMP and cyclic GMP) contents (pmol mg-1 protein) were assayed. When IP and SNP at Cmin were applied together to the UA strips, these compounds interacted synergistically in increasing cyclic nucleotides in group I. The observed net increase in the content was determined to be 1.46 +/- 0.30 (P < 0.05 vs. the predicted value of 0.67 +/- 0.12) in this group (n = 7). By contrast, the observed net increase (0.40 +/- 0.07, n = 6) did not exceed the predicted value (0.65 +/- 0.07, n = 6) in group II. 5. These results suggest that the formation of intimal hyperplasia in group II may be closely related to the impaired synergism between PGI2 and NO in the human UAs.

Adult↗
PubMed1996

Clinical utility of insulin-like growth factor-I (IGF-I) and IGF binding protein-3 levels in the diagnosis of GH deficiency (GHD) during childhood.

Diagnosis of GH deficiency (GHD) has been done traditionally by the combination of auxological data and the results of GH provocation tests. Recently, limitations of GH provocation tests have been advocated. Thus, three extreme subgroups (G-1; normal, G2; severe GHD, G-3; short children with normal GH secretion) were selected in order to show that insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) levels reflect GH secretion. In G-1 (n = 52), all had normal IGF parameters. In G-2 (n = 27), all had low IGF parameters. In G-3 (n = 28), all except for one patient had normal IGF parameters. Taken together with the assumption that GH secretion status is continuous from 0 to normal (or to acromegalic), the data on IGF parameters in the three subgroups indicate that they are functional tests for GH secretion. IGF-I and IGFBP-3, together with free IGF-I and acid-labile subunit, may replace GH provocation tests in the diagnosis of GH deficiency during childhood; these functional tests for GH secretion, which show minimal intradaily variation, are more physiological and cost-effective than GH provocation test.

Child↗
PubMed1996

[The influence of pregnancy and delivery on the climacteric symptoms].

This study was undertaken to investigate the influence of past pregnancy and delivery on the perimenopausal status in 144 women (48-52 years of age). Individual interviews to ascertain the personal profile, medical history, events at pregnancy, delivery and puerperium, and the kind and severity of climacteric symptoms were held. The subjects were divided into two groups by means of a simplified menopausal index (SMI): group A had climacteric symptoms (SMI > 50) and those in group B had mild symptoms (SMI < or = 50). The analysis of the principal components, and the correlation among the variables revealed that three factors--the impression and events at past pregnancies and deliveries, reproductive functions, and the psycho-character properties--had a significant influence on the status at the perimenopause, but the social-environmental factors appeared to have no significant influence on the severity of climacteric symptoms.

Climacteric↗
PubMed1995

Inhibition of transcription elongation by the VHL tumor suppressor protein.

Germline mutations in the von Hippel-Lindau tumor suppressor gene (VHL) predispose individuals to a variety of tumors, including renal carcinoma, hemangioblastoma of the central nervous system, and pheochromocytoma. Here, a cellular transcription factor, Elongin (SIII), is identified as a functional target of the VHL protein. Elongin (SIII) is a heterotrimer consisting of a transcriptionally active subunit (A) and two regulatory subunits (B and C) that activate transcription elongation by RNA polymerase II. The VHL protein was shown to bind tightly and specifically to the Elongin B and C subunits and to inhibit Elongin (SIII) transcriptional activity in vitro. These findings reveal a potentially important transcriptional regulatory network in which the VHL protein may play a key role.

Amino Acid Sequence↗
PubMed1995

Elongin (SIII): a multisubunit regulator of elongation by RNA polymerase II.

The Elongin (SIII) complex activates elongation by mammalian RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin is a heterotrimer composed of A, B, and C subunits of 110, 18, and 15 kilodaltons, respectively. Here, the mammalian Elongin A gene was isolated and expressed, and the Elongin (SIII) complex reconstituted with recombinant subunits. Elongin A is shown to function as the transcriptionally active component of Elongin (SIII) and Elongin B and C as regulatory subunits. Whereas Elongin C assembles with Elongin A to form an AC complex with increased specific activity, Elongin B, a member of the ubiquitin-homology gene family, appears to serve a chaperone-like function, facilitating assembly and enhancing stability of the Elongin (SIII) complex.

Amino Acid Sequence↗
PubMed1995

Positive regulation of general transcription factor SIII by a tailed ubiquitin homolog.

General transcription factor SIII, a heterotrimer composed of 110-kDa (p110), 18-kDa (p18), and 15-kDa (p15) subunits, increases the catalytic rate of transcribing RNA polymerase II by suppressing transient pausing by polymerase at multiple sites on DNA templates. Here we report molecular cloning and biochemical characterization of the SIII p18 subunit, which is found to be a member of the ubiquitin homology (UbH) gene family and functions as a positive regulatory subunit of SIII. p18 is a 118-amino acid protein composed of an 84-residue N-terminal UbH domain fused to a 34-residue C-terminal tail. Mechanistic studies indicate that p18 activates SIII transcriptional activity above a basal level inherent in the SIII p110 and p15 subunits. Taken together, these findings establish a role for p18 in regulating the activity of the RNA polymerase II elongation complex, and they bring to light a function for a UbH domain protein in transcriptional regulation.

Amino Acid Sequence↗
PubMed1995

Lactational anovulation in non-human primates: restriction of nursing inhibits Prl secretion without precipitating the return of ovulatory menstrual cyclicity in cynomolgus monkeys.

To test the hypotheses that nighttime suckling and elevated nocturnal prolactin concentrations are essential for the continuation of lactational anovulation, the effects of restricting nursing to twelve h per day (either day or night) on maternal prolactin (Prl) levels and resumption of ovulatory menstrual cycles were studied in five groups of cynomolgus monkeys: Group 1: baby weaned: Group 2: baby fully nursed: Group 3: baby nursed night only; Group 4: baby nursed day only; and Group 5: baby housed with mother but not allowed to nurse. Restrictions were initiated at approximately 150 days postpartum and were achieved by placing a non-nursing jacket over the nursing jacket, which was worn 24 h/day. Fifteen out of seventeen monkeys remained anovulatory while housed with their infants, irrespective of the type of nursing restriction. First postpartum ovulations occurred approximately two months post-weaning. Plasma prolactin concentrations during both day and nighttime were significantly (p < 0.05) greater in the fully nursing group(s) than in all other groups. Fully nursing mothers had significantly (p < 0.01) greater prolactin concentrations at night than during the day. Among the restricted groups, the night only suckling group had significantly greater prolactin concentrations at night than the other restricted groups. There were no differences between daytime values, and within each restricted group there were no significant differences between day and night prolactin levels. We conclude that 1) nighttime suckling is not an absolute prerequisite for sustained lactational anovulation, and 2) suckling-induced hyperprolactinemia is not the principle mediator of lactational anovulation.

Animals↗
PubMed1995

Clinical information on serum IGFBP-3 levels and IGFBP-3 proteolytic activity in childhood.

In this review paper, three pieces of clinical information in childhood are presented: (1) IGFBP-3 may replace GH provocation tests in the diagnosis of GH deficiency (GHD); (2) IGFBP-3 levels are regulated by IGF-I levels in a short period, and (3) ratio of free IGF-I to total IGF-I is high in serum of early infancy, similarly to serum of pregnancy, only partially owing to the presence of IGFBP-3 proteolytic activity. Each paper will be published soon.

Adolescent↗
PubMed1995

Endothelin synthesis and receptors in human endometrium throughout the normal menstrual cycle.

This study was undertaken to investigate the presence of messenger RNA (mRNA) for prepro-endothelin-I (ET-1) and the known receptor subtypes (ETA and ETB) in human endometrium at different stages of the menstrual cycle obtained at hysterectomy. Northern blot analysis revealed expression of ET-1 mRNA in human endometrium during the normal menstrual cycle. The concentration of ET-1 mRNA in endometrial tissue was greater during the menstrual and proliferative phases than during the ovulatory and secretory phases. Immunoreactive ET-1 was secreted into the medium of isolated endometrial stromal cells. Oestradiol and progesterone significantly attenuated ET-1 release in endometrial stromal cells cultured for 6 days. ETA and ETB mRNA were also present in endometrial tissue of the normal cycle. The concentration of ETA receptor mRNA was greater in the proliferative phase than in the secretory phase, whereas expression of ETB mRNA increased in menstrual phase. ET-1 significantly increased extracellular accumulation of cyclic AMP (cAMP), intracellular generation of inositol phosphates and significantly enhanced DNA synthesis in cultured endometrial stromal cells from the proliferative phase. Our results showed that human endometrial cells synthesized and released ET-1, and contained ETA and ETB receptors which were functionally coupled to phosphoinositide breakdown and to adenylate cyclase with the increase of cAMP by ET-1 stimulation. Our findings suggest that ET-1 may have a potential autocrine and/or paracrine function in human endometrial stromal cells.

Cells, Cultured↗
PubMed1995

Effects of matrix proteins and heparin-binding components in fetal bovine serum upon the proliferation of ectoplacental cone cells in mouse blastocysts cultured in vitro.

Trophoblastic invasion of the endometrium is among the events that are crucial for successful implantation and hemochorial placentation. To understand the mechanism underlying the trophoblastic invasion, we investigated effects of fibronectin substratum and heparin-binding components in fetal bovine serum (FBS) upon trophoblast and ectoplacental cone (EPC) cells derived from mouse blastocysts produced by IVF and cultured in vitro. The results demonstrated that 1) in these blastocysts, contact of EPC cells with fibronectin-coated glass substratum in the presence of FBS triggered an outburst of cell proliferation with the eventual differentiation of the EPC cells into secondary giant trophoblast cells and 2) frequencies of blastocysts that exhibited EPC cell proliferation significantly increased if FO medium (modified Eagle's minimum essential medium) was supplemented with FBS depleted of heparin-binding substances (H-FBS). One possible interpretation of the effect of H-FBS is that free fibronectins or related substances in the serum might interfere with EPC cell proliferation, for which the presence of substratum-bound fibronectin is essential. Alternatively, the serum might contain heparin-binding competitive inhibitors of yet unidentified growth factor(s) necessary for EPC cell proliferation.

Animals↗
PubMed1995

The RNA polymerase II elongation complex.

The initiation stage of transcription by RNA polymerase II has long been regarded as the primary site for regulation of eukaryotic gene expression. Nevertheless, a growing body of evidence reveals that the RNA polymerase II elongation complex is also a major target for regulation. Biochemical studies are implicating an increasing number of transcription factors in the regulation of elongation, and these transcription factors are being found to function by a diverse collection of mechanisms. Moreover, unexpected features of the structure and catalytic mechanism of RNA polymerase II are forcing a reconsideration of long-held views on the mechanics of some of the most basic aspects of polymerase function. In this review, we will describe recent insights into the structures and functions of RNA polymerase II and the transcription factors that control its activity during the elongation stage of eukaryotic messenger RNA synthesis.

Animals↗
PubMed1995

Role of endothelium in the human uterine arteries during normal menstrual cycle.

1. The present experiments were designed to investigate the role of endothelium in the human uterine arteries during the normal menstrual cycle. 2. Acetylcholine (ACh) produced a concentration-dependent relaxation response during the higher level of plasma 17 beta-oestradiol (E2) (follicular and luteal phases, E2 = 131.9 +/- 15.9 pg ml-1, n = 13; group I). However, the agent did not produce a definite relaxation, but produced a slight contraction during the ovulatory and menstruation phases (E2 = 19.8 +/- 2.9 pg mg-1, n = 5; group II). During the follicular and luteal phases (E2 = 181.1 +/- 9.0 pg ml-1, n = 6), ACh produced a slight contraction, but not relaxation in 6 cases (group III). Relaxation in response to A23187 in group II was not different from that in group I, while it was significantly (P < 0.05 and P < 0.005) reduced in group III. Sodium nitroprusside (SNP)-induced relaxation was similar in the three groups. 3. Correlation between the maximum response to ACh and the plasma E2 was highly significant (gamma = 0.8142, P < 0.001) in 18 cases of groups I and II, but not in all 24 cases including group III (gamma = 0.1183, NS). 4. Relaxations in response to ACh in group I or A23187 in all groups were abolished after removal of the endothelium. In group I, ACh- and A23187-induced relaxations were greatly inhibited by methylene blue or NG-nitro-L-arginine (L-NOARG) and partially inhibited by indomethacin. None of these treatments except for methylene blue modified the SNP-induced relaxation, which was significantly inhibited by methylene blue.5. The A23187-induced relaxation was hardly affected by methylene blue or L-NOARG in group III,but was partially inhibited by these agents in group II. The effect of indomethacin in inhibiting the A23187 induced-relaxation was most potent (58.9%) in group III and least (16.9%) in group I.6. There were no histological changes in 14 cases out of 18 (groups I and II), but very slight intimal thickening was observed in 4 cases in group I. On the other hand, severe intimal thickening was observed in all 6 cases in group III.7. These results indicate that, in human uterine artery strips, ACh and A23187 cause endothelium dependent relaxations, which are mediated mainly through EDRF/NO in group I, mainly prostacyclin(PGI2) in group III, or both in group II. It is suggested that lack of the production/release of EDRF/NO and/or of interaction between EDRF/NO and PGI2 might play a role in the formation of intimal thickening in human uterine arteries.

Acetylcholine↗
PubMed1995

Direct effect of danazol on the DNA synthesis and ultrastructure of human cultured endometrial stromal cells.

The direct effect of danazol on the DNA synthesis and ultrastructure of human cultured endometrial stromal cells was studied. The analysis of the [3H]thymidine incorporation in the endometrial stromal cells cultured for 10 days indicated that the DNA synthesis was inhibited in a dose-dependent manner by danazol and testosterone, but not by medroxyprogesterone. The effect of 10(-7) M of danazol was blocked by cyproterone acetate, but RU-486 did not show any influence. The observation of the ultrastructure of the cultured cells revealed that 10(-7) M of danazol increased cytoplasmic lysosomes; however, 10(-5) M of danazol destroyed cell organelles and cytoskeleton resulted from the cell death. These results indicated that the biological effects of danazol were mainly mediated by androgen receptors, and 10(-5) M of danazol exhibited the toxic effect on the endometrial stromal cells.

Cells, Cultured↗
PubMed1995

The role of endothelin-1 in regulating human granulosa cell proliferation and steroidogenesis in vitro.

The effects of endothelin-1 (ET-1) on luteinized human granulosa cells (L-HGCs) have not been examined. It is well known that there are differences of actions of several autocrine/paracrine regulators between L-HGCs and GCs of other species, and therefore the present study was designed to examine the effects of ET-1 1) on intracellular Ca2+ concentrations ([Ca2+]i) using the Ca(2+)-responsive fluorescent indicator Fura-2, 2) on cell proliferation by the nonradioactive method using bromodeoxyuridine, and 3) on basal and gonadotropin-stimulated steroidogenesis, and to examine the expression of ET receptor messenger RNA (mRNA) using freshly isolated and cultured L-HGCs obtained from patients undergoing in vitro fertilization. ET-1 increased [Ca2+]i in L-HGCs in a dose-dependent manner between 1 and 1000 nmol/L. High concentrations (100-1000 nmol/L) of ET-1 produced a more rapid and transient increase in [Ca2+]i than that observed with low concentrations (1-10 nmol/L) of ET-1. The increase in [Ca2+]i elicited by ET-3 (1000 nmol/L) and IRL-1620 (1000 nmol/L), a selective ETB receptor agonist, was 16% and 3% (vs. ET-1, 100%), respectively. BQ-123 (1000 nmol/L), an ETA receptor antagonist, inhibited the increase in [Ca2+]i elicited by ET-1 (by 50% at 1000 nmol/L ET-1 and by > 90% at < 500 nmol/L ET-1). mRNAs for the two known receptor subtypes (ETA and ETB) were also present in L-HGCs; however, the expression of ETA receptor mRNA was much greater than that of ETB receptors. ET-1 stimulated cell proliferation in L-HGCs in a dose-dependent manner (1000 nmol/L, 210.5 +/- 13.1%; 100 nmol/L, 198 +/- 11%; 10 nmol/L, 146 +/- 18%; and 1 nmol/L, 103 +/- 9%; vs. control, 100%). These stimulatory effects were completely blocked by BQ-123 (1000 nmol/L). ET-3 and IRL-1620 had no effects on cell proliferation in L-HGCs. Significant stimulatory effects on cell proliferation by the calcium ionophore, ionomycin (10-1000 nmol/L), were observed. ET-1, ET-3, and IRL-1620 attenuated basal progesterone secretion in L-HGCs. These results suggest that ETA receptor predominantly exist in L-HGCs and that ET-1 may stimulate cell proliferation of L-HGCs by increasing [Ca2+]i via ETA receptors.

Calcium↗
PubMed1995

Proteolytic activity of IGFBP-3 in various clinical conditions during childhood studied by means of western immunoblotting.

Insulin-like growth factors (IGFs) have 6 types of binding proteins (IGFBPs), and IGFBP-3 is the major IGFBP in human sera. A proteolytic enzyme for IGFBP-3 has recently been reported to be present in human and animal pregnant sera. Although the physiological significance of a pregnancy-associated IGFBP-3 protease remains to be established, the proteolysis could result in lowering the affinity for IGFs, thereby enhancing their delivery to target tissues by increasing free IGFs in the circulation. The methods for detection of IGFBP-3 protease which have been widely used so far are a method reported by Lamson et al. which used affinity crosslinking or western ligand blotting. These methods need radioactive materials (iodinated IGFs and IGFBP-3) and it takes at least a few days to get the results. We have now developed a simple assay for the proteolysis of IGFBP-3. The method is western immunoblotting without radioactive materials. The results can be obtained in a day. With this method, we proved the absence of significant proteolytic activity in sera from rapidly growing children (early stage of puberty or precocious puberty), and sera from a severe type of growth hormone deficiency. Significant proteolytic activity, as in pregnant women, was detected in 6 out of 11 patients with acute disorders such as measles, Kawasaki disease, bacterial meningitis and mycoplasma pneumonia, some of whom were probably in a catabolic condition. These data suggests that the proteolysis of IGFBP-3 might also be important in modulating IGF action in some acute diseases during childhood. The increased bioavailability of IGFs by IGFBP-3 proteolysis may play a role in overcoming catabolic conditions.

Adolescent↗
PubMed1994

Role of core promoter structure in assembly of the RNA polymerase II preinitiation complex. A common pathway for formation of preinitiation intermediates at many TATA and TATA-less promoters.

Efforts to understand the impact of core promoter architecture on the mechanism of transcription initiation by RNA polymerase II have been hampered by lack of well defined, reconstituted transcription systems responsive both to efficiently transcribed consensus and near consensus TATA box-containing promoters and to considerably weaker TATA-less promoters. In this report, we investigate the influence of core promoter structure on the mechanism of assembly of the RNA polymerase II preinitiation complex using a highly purified, holoTFIID-dependent transcription system that permits sensitive measurement of transcription initiation from a wide variety of TATA and TATA-less promoters in the absence of transactivators. A direct comparison of the requirements for formation of stable preinitiation intermediates at these promoters led to the discovery that, whereas holoTFIID binds avidly to the consensus TATA- and strong initiator-containing adenovirus major late (AdML) promoter to form the first stable intermediate on the pathway leading to formation of the complete preinitiation complex, it binds poorly not only to TATA-less promoters but also to promoters with consensus or near consensus TATA elements. With the exception of the AdML promoter, formation of stable preinitiation intermediates at each of the promoters tested was found to be strongly dependent on RNA polymerase II, holoTFIID, and TFIIB and was stimulated by TFIIF. Based on these observations, we suggest that RNA polymerase II assembles with many TATA and TATA-less promoters by a common pathway.

Base Sequence↗