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N Sagawa

Publications and source records attributed to N Sagawa.

At least 37 records · Page 2Linked to original sources
PubMed1997

Identification of the human leptin 5'-flanking sequences involved in the trophoblast-specific transcription.

Leptin is an adipocyte-derived blood-borne satiety factor that is involved in the regulation of energy homeostasis. We have recently demonstrated nonadipose tissue production of leptin; leptin is synthesized in and secreted from placental trophoblasts (Nature Med. 3: 1029-1033, 1997). To understand the transcriptional regulation of the human leptin gene in placental trophoblasts, we examined the promoter activity of various lengths of the human leptin 5'-flanking sequences in BeWo cells, a human trophoblastic cell line. The 2080-bp human leptin gene promoter region (-2080 to +108) showed a high-level transcription activity in BeWo cells. When DNA sequences between -1885 and -1830 were deleted, the promoter activity was reduced dramatically in BeWo cells. No significant changes in the promoter activity were noted when tested in primary cultures of rat mature adipocytes. Electrophoretic mobility shift assays revealed the presence of nuclear protein(s) binding to the sequences in BeWo cells but not in isolated rat mature adipocytes. The present study provides new insight into the trophoblast-specific transcription of the human leptin gene.

Adipocytes↗
PubMed1997

The prostaglandin E2 and F2 alpha receptor genes are expressed in human myometrium and are down-regulated during pregnancy.

Prostaglandin (PG) E2 and PGF2 alpha are believed to play important roles in the myometrial contraction and the initiation of labor. Myometrial contraction by these prostanoids is mediated mainly through EP3 and FP, which are specific receptors to PGE2 and PGF2 alpha, respectively. During normal pregnancy, uterine myometrium are relaxed until term. To explore the involvement of EP3 and FP in the myometrial relaxation during pregnancy, we examined the EP3 and FP gene expressions in nonpregnant and pregnant myometrium obtained by hysterectomy for gynecological diseases. In all samples examined, expressions of EP3 and FP genes were detected. During pregnancy, the expression of EP3 gene in human myometrium was significantly reduced, to 60% of that in nonpregnant myometrium. The expression of FP gene in human myometrium also decreased during pregnancy to 55% of that in nonpregnant myometrium. In the myometrium from the nonpregnant women taking combined oral contraceptives, the gene expressions of EP3 and FP were not significantly changed as compared to those in nonpregnant controls. The down-regulation of EP3 and FP during pregnancy may play a role in the relaxation of myometrium and thus in the maintenance of normal pregnancy in humans.

Adult↗
PubMed1997

Nonadipose tissue production of leptin: leptin as a novel placenta-derived hormone in humans.

Leptin is a circulating hormone that is expressed abundantly and specifically in the adipose tissue. It is involved in the regulation of energy homeostasis, as well as the neuroendocrine and reproductive systems. Here, we demonstrate production of leptin by nonadipose tissue, namely, placental trophoblasts and amnion cells from uteri of pregnant women. We show that pregnant women secrete a considerable amount of leptin from the placenta into the maternal circulation as compared with nonpregnant obese women. Leptin production was also detected in a cultured human choriocarcinoma cell line, BeWo cells, and was augmented during the course of forskolin-induced differentiation of cytotrophoblasts into syncytiotrophoblasts. Plasma leptin levels were markedly elevated in patients with hydatidiform mole or choriocarcinoma and were reduced after surgical treatment or chemotherapy. Leptin is also produced by primary cultured human amnion cells and is secreted into the amniotic fluid. The present study provides evidence for leptin as a novel placenta-derived hormone in humans and suggests the physiologic and pathophysiologic significance of leptin in normal pregnancy and gestational trophoblastic neoplasms.

Adipose Tissue↗
PubMed1997

Cortisol and TGF-beta inhibit secretion of platelet-activating factor-acetylhydrolase in a monocyte-macrophage model system [corrected].

Recent studies have suggested that platelet activating factor (PAF) plays an important role in various reproductive functions, including ovulation, implantation and parturition, and that the local concentration of PAF is modulated by PAF-acetylhydrolase (PAF-AH), a potent PAF inactivator. In this study, we investigated the possible effects of various bioactive substances, which are present at high concentrations in the human pregnant uterus, on PAF-AH secretion from decidual macrophages using a monocyte-macrophage model system, human myelocytic leukaemia cells (HL-60). By treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), HL-60 cells were transformed to macrophage-like cells, which secreted PAF-AH into the culture medium time- and dose-dependently. After treatment with 10(-8) M TPA, the effects of various substances on the secretion of PAF-AH were examined. Among the substances examined, cortisol and TGF-beta suppressed PAF-AH secretion from TPA-stimulated HL-60 cells in a significant and dose-dependent way. Endothelin, epidermal growth factor, and brain natriuretic peptide had no significant effect on PAF-AH secretion from TPA-stimulated HL-60 cells. These results suggest that local PAF concentrations in the pregnant uterus might be regulated, at least partly, by cortisol and TGF-beta; thus these substances may play a role in the initiation of parturition via regulation of local PAF concentrations.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Diffuse cystic change of a term placenta with a normal newborn.

We recently encountered a case of term placenta with a diffuse cystic lesion of the villi. A 19-year-old primipara at 36 weeks of gestation underwent cesarean section due to breech presentation with premature rupture of the membranes; she delivered a mature male baby of 2,502 g with an Apgar score of 9/9. The placenta was 940 g in weight and 29 x 20 x 3 cm in size, and macroscopically had multiple cystic lesions (3-8 mm in diameter) that resembled hydatidiform moles. However, histopathological examination revealed that the severe hydropic change was localized in the stem villi but not remarkable in the terminal chorionic villi. Moreover, abnormal proliferation of the trophoblast was not observed. However, the hypertrophic change was observed in the vascular wall of stem villi, in which hyperplasia of smooth muscle-like cells was present. The urinary hCG levels at 1 month and 2 months after delivery were less than 50 IU/l. These findings indicate that the multiple cystic lesions of the placenta in this case are essentially different from those of a trophoblastic disease, and that the diffuse cystic lesion of the villi might have been secondary to changes in the local circulation.

Actins↗
PubMed1997

Spontaneous resolution of a postcesarean arteriovenous fistula of the uterine cervix: the usefulness of transvaginal color Doppler scanning.

We encountered in a woman at the 28th day after cesarean delivery the transient appearance of a uterine cervical mass with a prominent blood flow, that was revealed to be an acquired arteriovenous fistula. The size and blood flow of the mass were monitored using transvaginal color Doppler scanning and magnetic resonance imaging (MRI). Based on these findings, the arteriovenous fistula was managed conservatively without any adverse complications.

Adult↗
PubMed1997

Impaired guanosine 3',5'-cyclic phosphate production in severe pregnancy-induced hypertension with high plasma levels of atrial and brain natriuretic peptides.

To investigate the activation of particulate guanylate cyclase in pregnant women with pregnancy-induced hypertension (PIH), plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and guanosine 3',5'-cyclic phosphate (cGMP) were measured by radioimmunoassays specific to each substance. Ten normal nonpregnant women, and 30 normal pregnant women, 17 pregnant women with mild PIH and 11 pregnant women with severe PIH in the third trimester were included in this retrospective observational study. The diagnosis and classification of hypertension were carried out according to the technical bulletin (No. 91) of the American College of Obstetricians and Gynecologists. In the pregnant women with mild PIH, plasma cGMP levels as well as ANP and BNP levels were significantly (P < 0.05) higher than those in gestational age-matched normal pregnant or nonpregnant women. But in the pregnant women with severe PIH, plasma cGMP levels were significantly lower than those in pregnant women with mild PIH (P < 0.05), although plasma ANP and BNP levels were higher than those in pregnant women with mild PIH.

Adult↗
PubMed1996

Rapid growth of an ovarian clear cell carcinoma expressing LH/hCG receptor arising from endometriosis during early pregnancy.

The complete clinical course of a case of ovarian clear cell carcinoma expressing luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor arising from endometriosis in a pregnant woman is presented. A 31-year-old woman visited a private clinic in May 1993 for screening tests for infertility. Transvaginal ultrasonography revealed no abnormal findings in the uterus or ovaries. Her menstrual cycle was regular; however, a slight luteal insufficiency was noted. She had been treated with clomiphene, and soon became pregnant. She was diagnosed to be at 5 weeks gestation in June, and at the same time, an ovarian tumor with the diameter of 5 cm was identified. Since the tumor had grown rapidly and was 9 cm in diameter 1 week later, she was referred to our hospital. When she was admitted to our hospital at 9 weeks gestation, the tumor diameter was 14 cm and we found the solid portion within the ovarian tumor. The levels of the tumor markers CA125 and CA19-9 were 106 and 51 U/ml, respectively. The crown-rump length of the fetus (24 mm) was compatible with the gestational age, and fetal heartbeat was confirmed. Under the diagnosis of ovarian carcinoma, right salpingo-oophorectomy was performed at 10 weeks of gestation. Postoperative histological examination revealed a clear cell carcinoma and endometriosis of the right ovary. Immunohistochemically, the clear cell carcinoma stained positively for LH/hCG receptors and estrogen receptors, but not progesterone receptor. No malignant cells were detected by ascitic cytology. Exploratory specimens obtained at the time of operation from the left ovary and pelvic lymph nodes exhibited no malignant cells. Based on these findings, the pregnancy was allowed to proceed, and she delivered a 3010-g male baby at 39 weeks of gestation. She had no signs of recurrence for 2 years after the operation.

Adenocarcinoma, Clear Cell↗
PubMed1996

Spontaneous conception and intrauterine pregnancy in a symptomatic missed abortion of ectopic pregnancy conceived in the previous cycle.

We encountered a rare case of combined intrauterine and extrauterine pregnancy that occurred following separate spontaneous ovulations. A 33 year old woman visited our hospital with the chief complaint of abdominal pain on April 16, 1993. Her last menstruation was from March 23 for 6 days. However, the urinary human chorionic gonadotrophin (HCG) on April 19 was 1024 IU/l. Pelvic examination and ultrasonography indicated an extrauterine pregnancy, which was confirmed by laparotomy and histological identification of trophoblast cells. The urinary HCG concentration markedly decreased after the operation. However, the HCG level increased again on the fifth post-operative day, and a gestational sac (11 mm) was identified in the uterine cavity on the 11th post-operative day, indicating that this intrauterine pregnancy was established following spontaneous ovulation which occurred before the removal of the extrauterine pregnancy. This case indicates that a combined pregnancy can occur not only after simultaneous multiple ovulations but also after the separate spontaneous ovulations.

Adult↗
PubMed1996

Type 2 angiotensin II receptor is expressed in human myometrium and uterine leiomyoma and is down-regulated during pregnancy.

Angiotensin II (Ang II) acts on at least two receptor subtypes, type 1 (AT1) and type 2 (AT2). The AT2 receptor is abundant in the fetus and decreases rapidly after birth. The uterus expresses the AT2 receptor abundantly even in adults, suggesting its role in reproduction. To explore the roles and regulation of the AT2 receptor in human uterus and to examine whether its expression is related to the proliferative characteristics of leiomyoma, we studied Ang II receptor gene expressions in nonpregnant and pregnant myometrium and in uterine leiomyomas obtained from patients who underwent gynecological surgery. Receptor binding studies revealed that all samples exhibited high-affinity binding for [Sar1, Ile5]Ang II, most (> 90%) of which was of the AT2 subtype. In nonpregnant myometrium (n = 5), receptor density [maximum binding capacity (Bmax)] and dissociation constant (Kd) for AT2-selective CGP42112A were 287 +/- 46 fmol/mg protein and 0.48 +/- 0.09 nM, respectively. In the myometrium of early (n = 6) and late pregnancy (n = 3), Bmax for the AT2 receptor was significantly decreased (62 +/- 17 and 25 +/- 6 fmol/mg protein, respectively). Furthermore, administration of combined oral contraceptive pills induced a comparable reduction in AT2 Bmax (54 +/- 12 fmol/mg protein, n = 4). AT2 Bmax or Kd values in uterine leiomyomas from nonpregnant women showed no significant differences from those in nonpregnant myometrium. Changes of AT2 Bmax in uterine leiomyomas during pregnancy or with oral contraceptive were similar to those in the myometrium. Northern blots revealed AT1 and AT2 receptor messenger RNA (mRNA) expressions in all samples examined; the former was much lower than the latter. Although the AT1 receptor mRNA expression did not change significantly, the AT2 receptor mRNA level was significantly decreased during pregnancy or with oral contraceptives. These results indicate that AT1 and AT2 receptors are expressed in human myometrium and uterine leiomyoma, in which the AT2 receptor is predominant. AT2 receptor gene expression is down-regulated during pregnancy, possibly mediated by sex steroids.

Adult↗
PubMed1996

Endothelin-1-like immunoreactivity and endothelin receptors in the human placenta from normotensive and hypertensive pregnancies.

The levels of endothelin-1-like immunoreactivity (ET-1-LI) and characteristics of endothelin receptors in the chorionic villous tissue of human placenta were determined. The ET-1-LI level in chorionic villous tissue obtained from normal term placenta was 2,450 +/- 940 pg/g wet weight (mean +/- SD, n = 4). Further analysis using gel permeation chromatography and reverse-phase high performance liquid chromatography showed that the main ET-1-LI constituent of ET-1-LI in this tissue was ET-1. Scatchard analysis of [125I]ET-1 binding to the membrane fraction of chorionic villous tissue obtained from term placenta showed high affinity receptor sites with an apparent dissociation constant (Kd) of 23.6 +/- 11.1 pM and a Bmax value of 388 +/- 238 fmol/mg protein (n = 5). The same binding study with [125I]ET 3 showed a Kd of 13.9 +/- 3.8 pM and a Bmax value of 176 +/- 78 fmol/mg protein (n = 5). These results suggest that both ET-A and ET-B receptors (ET-AR and ET-BR) are expressed in chorionic villous tissue. This finding was further confirmed by Northern blot analysis showing the expression of both ET-AR and ET-BR mRNAs in this tissue. ET-1-LI in the umbilical venous plasma of the newborns from women with pregnancy-induced hypertension (PIH) (38.3 +/- 10.4 pg/mL, n = 5) was significantly (P < 0.05) higher than that in the normal newborns from normotensive pregnant women (26.3 +/- 5.2 pg/mL, n = 12). However, in placental chorionic villous tissue obtained from PIH women, both ET-1-LI level and ET binding profile were not different from those in chorionic villous tissue from normotensive pregnant women. These results suggest that the abundant ET-ET receptor system is present in the placental chorionic villous tissue and that this system is not the major factor of the pathogenesis of placental dysfunction occurring in PIH because these systems are similar in normotensive and hypertensive pregnancies.

Chorionic Villi↗
PubMed1995

Umbilical venous guanosine 3',5'-cyclic phosphate (cGMP) concentration increases in asphyxiated newborns.

Guanosine 3',5'-cyclic phosphate (cGMP) is known to be the second messenger of natriuretic peptides and nitric oxide (NO). To investigate the involvement of natriuretic peptides in the regulation of the feto-placental circulation, specific radioimmunoassays were used to measure the concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cGMP in the umbilical venous plasma of normal and asphyxiated newborns. The plasma concentrations of ANP, BNP and cGMP in asphyxiated newborns were 48.3 +/- 12.9 pm, 24.5 +/- 9.4 pm and 4.4 +/- 1.6 nM (mean +/- s.e.m., n = 10), respectively. These values were significantly higher than those in the normal newborns (17.4 +/- 1.9 pm, 4.7 +/- 1.0 pm, and 0.78 +/- 0.14 nM, respectively). Moreover, the expression of both ANP-A and ANP-B receptor, biologically active receptors for natriuretic peptides, was detected in term human placenta by Northern bolt analysis. The expression of natriuretic peptide receptors was further confirmed by binding assay using [125I]-labelled ANP and solubilized crude membrane preparations of placental tissue. These findings suggest that cGMP is produced in the placenta, at least partly, by the action of ANP and BNP secreted from fetal heart, in pathophysiological conditions such as fetal hypoxia.

Asphyxia Neonatorum↗
PubMed1995

Relationship between lupus anticoagulant (LAC) and pregnancy-induced hypertension.

Lupus anticoagulant (LAC), a serum antiphospholipid autoantibody, is believed to be one of the causes of infertility or fetal loss. The purpose of the present study was to evaluate the role of LAC in the pathogenesis of hypertension during pregnancy. In this study, 20 pregnant women with hypertension were classified into two groups: 14 patients who did not have hypertension before the pregnancy but developed it during the pregnancy (pregnancy-induced hypertension; Group A) and 6 patients who had hypertensive or renal disease before the pregnancy, and developed further hypertension during the pregnancy (pregnancy-aggravated hypertension; Group B). A LAC coagulation assay was performed, and the presence of LAC in each group was compared. All 14 patients in group A were LAC-negative. In contrast, 3 of the 6 patients in group B were LAC-positive, and had clinical autoimmune diseases. The incidence of pregnancy-induced hypertension was also examined in 15 pregnancies from 9 LAC-positive women who had a history of repeated fetal loss but no systemic autoimmune disease (Group C). None of these 15 pregnancies had hypertensive complications, even when they reached term. In the placentas of LAC-positive women, no characteristic changes other than fibrinoid degeneration and microscopic infarction were observed upon histological examination. These results suggest that LAC does not relate with the onset of hypertension during pregnancy.

Adult↗
PubMed1995

Endothelin receptors in the human amnion, chorion laeve, decidua vera and placenta.

The levels of endothelin-1 (ET-1) and the characteristics of endothelin (ET) receptors were investigated in the amnion, chorion laeve, decidua vera and placenta by using a specific radioimmunoassay for ET-1 and a saturation binding assay for ET. ET receptor gene expression in these tissues was also examined by Northern blot analysis. The levels of ET-1-like immunoreactivity (ET-1-LI) in the human amnion, chorion laeve, decidua vera and placenta obtained at elective Caesarean section before labour onset at term (mean +/- s.e.m.) were 1260 +/- 380 (n = 6), 3740 +/- 980 (n = 4), 4550 +/- 780 (n = 4) and 2450 +/- 470 (n = 4) pg g-1 wet weight, respectively. The levels of ET-1-LI in the tissues obtained after spontaneous vaginal deliveries at term did not differ from these. Gel-permeation chromatography and reverse-phase high-performance liquid chromatography revealed that the ET-1-LI in these tissues was mainly composed of ET-1. Scatchard analysis of the saturation binding assay for [125I]-labelled ET-1 and [125I]-labelled ET-3 indicated that high concentrations of both ET-A and ET-B subtypes of receptor were present in membrane fractions from the chorion laeve, decidua vera and placenta. However, in membrane fractions from the amnion, no ET receptors could be detected. These results were confirmed by Northern blot analysis using human ET-A and ET-B receptor cDNA probes. Taken together, these results suggest that the amnion is not the site of action of amniotic ET, and that ET may be involved in the regulation of functions of the chorion laeve or decidua vera.

Amnion↗
PubMed1995

Activation of phospholipase D in cultured human amnion cells.

The regulation of phospholipase D (PLD) activity in the human amniotic membrane was examined using primary cultures of amnion cells. Cultured amnion cells were labelled with [3H]oleic acid, and PLD activity was determined as the amount of [3H]phosphatidylethanol (PEt) produced during incubation in the presence of 0.1% ethanol. PLD activity in cultured amnion cells was activated by addition of arginine vasopressin and oxytocin. PLD activity was also stimulated by treatment was arachidonic acid, the product of phospholipase A2 (PLA2), and phospholipase C (PLC). These results indicate that PLD in amnion cells is activated by substances present in amniotic fluid, and that cross-talk between phospholipases A2, C and D may occur in amnion cells.

Amnion↗
PubMed1995

Biochemical and topological analysis of adult T-cell leukaemia-derived factor, homologous to thioredoxin, in the pregnant human uterus.

Adult T-cell leukaemia-derived factor (ADF), homologous to thioredoxin, displays various biological activities, such as radical scavenging action and the reduction of protein disulphide bonds. We examined the biochemical and immunohistochemical localization of ADF in the pregnant human uterus, using two heteroantibodies to ADF, antibody C and W. Immunohistochemically, decidua and trophoblast cells were intensely stained by antibody C. The concentration of ADF-like substance in the decidua was 95.9 ng/mg protein, determined by enzyme-linked immunosorbent assay. The molecular weight of ADF-like substance in these tissues was determined by gel electrophoresis to be 13 kDa, the same as that of recombinant ADF. These findings indicate that abundant ADF is present in decidua and trophoblast cells; the localization of such a potent dithiol reducing substance may be beneficial in protecting the fertilized egg and placental trophoblasts from the cytotoxic effects of oxygen radicals.

Adult↗
PubMed1994

Expression of biologically active receptors for natriuretic peptides in the human uterus during pregnancy.

Human amnion cells secrete a large amount of brain natriuretic peptide (BNP). In the present study, to elucidate the possible roles of amniotic BNP during the course of human pregnancy, the tissue distributions of biologically active receptors of natriuretic peptides, atrial natriuretic peptide (ANP)-A receptor and ANP-B receptor in the human uterus during pregnancy were investigated by Northern blot analysis and an in vitro guanosine 3',5'-cyclic phosphate (cGMP) generation assay, the second messenger of natriuretic peptides, using crude membrane preparations. Both ANP-A and ANP-B receptor mRNAs were detected in the tissues of decidua vera, chorion laeve, myometrium and placenta. The in vitro cGMP generation assay revealed that the expression of ANP-A receptor was more prominent than that of ANP-B receptor in these tissues. On the other hand, in amniotic tissue only ANP-B receptor mRNA was weakly expressed but ANP-A receptor mRNA was not detected.

Atrial Natriuretic Factor↗