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N Sagawa

Publications and source records attributed to N Sagawa.

At least 55 records · Page 3Linked to original sources
PubMed1994

Current topic: the role of amniotic endothelin in human pregnancy.

Endothelin (ET), a potent vasoconstrictor peptide, was originally isolated from culture medium of porcine aortic endothelial cells. Subsequently, ET was also reported to be produced by non-vascular tissues, and to be involved in various biological phenomena in these tissues. Recently, a high concentration of ET-1-like immunoreactivity (ET-1-LI) was detected in human amniotic fluid. Amnion tissue also contained a large amount of ET-1-LI, and cultured amnion cells secreted large amounts of ET-1-LI. The major component of ET-1-LI in these samples was ET-1. Moreover, the expression of prepro-ET-1 mRNA was detected in both amnion tissue and cultured amnion cells, indicating that ET-1 in the amniotic fluid originated from amnion cells. In addition, specific receptors for ET were detected in myometrium, decidua vera, chorion laeve and placenta, by both ligand binding analysis and Northern blot analysis. These findings suggest that ET-1 secreted from amnion cells plays a physiological role in human pregnancy. In this paper, the regulation of ET-1 production and expression of ET-receptors in avascular human amnion tissue are reviewed. The possible importance of amniotic ET in human pregnancy is also discussed.

Amniotic Fluid↗
PubMed1994

Characterization of CA125 glycoprotein using 3 monoclonal antibodies with different specificities.

CA125 and CA130 in various tissues were characterized using the monoclonal antibodies OC125, 130-22, and 145-9. CA125 and CA130 were eluted in the same fraction in 130-22 affinity chromatography. A sandwich immunoradiometric assay using these antibodies in combination was established. When the solid phase of the assay was changed from OC125 to 145-9, the amount of 125I-OC125 that reacted with CA125 in the amnion increased more than that in other samples. On SDS-PAGE, CA125 and CA130 epitopes in the amnion migrated to different positions. These results indicate that CA125 and CA130 are located on different subunits of the same glycoprotein, and that their synthesis is regulated differently in various tissues.

Amnion↗
PubMed1994

Transforming growth factor-beta stimulates, and glucocorticoids and epidermal growth factor inhibit brain natriuretic peptide secretion from cultured human amnion cells.

We previously reported the massive secretion of brain natriuretic peptide (BNP) from human amnion cells and suggested the possible role of BNP in the maintenance of human pregnancy. In this study, to elucidate the regulatory mechanism of BNP secretion from amnion cells, we measured the BNP level in the culture medium of amnion cells by RIA after incubation in the presence of various substances. Among the agents examined, cortisol (1 x 10(-7) to 1 x 10(-6) mol/L), dexamethasone (1 x 10(-8) to 1 x 10(-6) mol/L), and epidermal growth factor (EGF; 2 x 10(-11) to 2 x 10(-8) mol/L) inhibited BNP secretion from the cultured amnion cells in a dose-dependent manner. By contrast, transforming growth factor-beta (TGF beta; 4 x 10(-11) to 4 x 10(-9) mol/L) caused a 3- to 5-fold increase in BNP secretion. TGF beta-augmented BNP secretion was abolished by the addition of cortisol or EGF to the culture medium. Moreover, in this study, we revealed the presence of bioactive TGF beta in human amniotic fluid (approximately 4 x 10(-10) mol/L). The present finding of tight regulation of BNP secretion from amnion cells by cortisol, EGF and TGF beta, all at the concentrations physiologically present in human amniotic fluid, implies a physiological role of BNP secretion from amnion cells in the pregnant uterus.

Amnion↗
PubMed1994

Clinical application of pulsatility index of flow volume to detect the hemodynamic changes in IUGR fetus.

We attempted to assess feto-placental circulation in fetuses with intrauterine growth retardation (IUGR) by calculating the pulsatility index of flow volume (PIQ) based on the quantitative measurement of blood flow. Doppler sound was processed by an analog to digital converter and a frequency analyzer. Multiplication of frequency and signal strength of the Doppler sound at a certain time theoretically represents a value proportional to flow volume. Using this value, we calculated PIQ of the descending aorta, umbilical artery, and middle cerebral artery in normal fetuses, IUGR fetuses, and distressed fetuses during 24-41 weeks gestation. The PIQ of the fetal descending aorta in the IUGR fetus was significantly higher than that of the normal fetus. When cutoff value was set to mean +1 SD, abnormal PIQ was observed in 88% of IUGR fetuses. In contrast, the abnormal pulsatility index of maximal flow velocity (PIV) of the descending aorta was observed in only 62% of IUGR fetuses. In the distressed fetuses, both PIQ and PIV of the umbilical artery increased, and these indices of the middle cerebral artery markedly decreased. It is suggested that the increased PIQ of the descending aorta is an early indicator of changes in the fetal circulation in IUGR fetuses.

Aorta↗
PubMed1994

Platelet-activating factor-acetylhydrolase activity in maternal and umbilical venous plasma obtained from normotensive and hypertensive pregnancies.

OBJECTIVE: To elucidate whether plasma platelet-activating factor-acetylhydrolase activities in women with pregnancy-induced hypertension and in their fetuses are different from those in normotensive mothers and fetuses. METHODS: We measured platelet-activating factor-acetylhydrolase activity in the plasma of 11 normotensive nonpregnant women, 39 normotensive pregnant women, 30 pregnant women with pregnancy-induced hypertension, 31 fetuses delivered from normotensive pregnant women, and 12 fetuses delivered from women with pregnancy-induced hypertension. RESULTS: Plasma platelet-activating factor-acetylhydrolase activity in normotensive pregnant women at 28-31 weeks' gestation was significantly lower than that in normotensive nonpregnant women (P < .001). In contrast, in women with pregnancy-induced hypertension at 28-31 weeks' gestation, the activity of this enzyme was significantly higher than that in gestational age-matched, normotensive pregnant women (P < .01). Platelet-activating factor-acetylhydrolase activity in the umbilical venous plasma of fetuses delivered from women with pregnancy-induced hypertension at 37-40 weeks' gestation was significantly higher than that in the gestational age-matched term fetuses of normotensive mothers (P < .001). CONCLUSION: These findings indicate that the hydrolysis of platelet-activating factor is decreased during a normal pregnancy and that such modulation does not occur in pregnant women with pregnancy-induced hypertension or in their fetuses.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1994

[A study on the regulation of intrauterine milieu by bioactive substances of fetal origin in the human amniotic fluid--the analyses of interactions among amnion, chorion laeve, and decidua vera tissues].

To elucidate the regulatory mechanism of human intrauterine milieu, the effects of various substances on the production of endothelin (ET) and brain natriuretic peptide (BNP) by amnion cells were investigated. In addition, we examined the regulation of phospholipase D (PLD) activity, which has been shown to be involved in the signal transduction in various tissues such as ovary, adrenal gland, etc. The ET production by cultured amnion cells was stimulated by epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), or interleukin-1 (IL-1). Ligand binding analyses indicated that both ET-A receptor and ET-B receptor are present in chorion laeve, decidua vera, and myometrium, but not in the amnion tissue at term. However, amnion tissue in the second trimester showed a significant amount of binding capacity for ET-1 but not for ET-3, indicating the presence of ET-A receptor in this tissue in the second trimester. These observations were confirmed by Northern blot analyses. In cultured amnion cells, ET-B receptor was detected by Northern blot analysis. The expression of this ET-B receptor in cultured amnion cells was down-regulated by the addition of EGF, but not by ET-1, IL-1 or A23187. Moreover, ET-1 inhibited the secretion of prostaglandin E2 (PGE2) by cultured amnion cells. These results suggest that ET-1 secreted from amnion cells may block prostaglandin synthesis in amnion cells during the second trimester, but this block may be released at term by the action of EGF. The BNP production by cultured amnion cells was dose-dependently stimulated by TGF-beta, but was inhibited by cortisol or EGF. TGF-beta (approximately 400 pM) was detected in the human amniotic fluid by a bioassay. The TGF-beta augmented BNP production was blocked by the simultaneous treatment with cortisol or EGF. The receptor for BNP (particulate guanylate cyclase A-type: GC-A) was identified in chorion, decidua, and myometrium by both cGMP generation assay and Northern blot analysis. However, GC-A was not detected in amnion tissues in the second trimester and at term. In an in vitro experiment with rat pregnant uterus, both BNP and cGMP dose-dependently inhibited the prostaglandin F2 alpha induced uterine contraction. Thus, BNP secreted from amnion cells may not act on amnion tissue, but on the decidua and myometrium, and generate cGMP, the second messenger of BNP, and finally block uterine contraction during the second trimester.(ABSTRACT TRUNCATED AT 400 WORDS)

Amniotic Fluid↗
PubMed1993

Identification and partial characterization of phospholipase D in the human amniotic membrane.

The enzymatic activity of phospholipase D and its characteristics have been examined in human amnion tissue. The phospholipase D activity was not Ca(2+)- or Mg(2+)-dependent and was activated by unsaturated fatty acids. The optimal pH of phospholipase D was 5.5. The phospholipase D activity in amnion tissue was highest in the microsomal fraction, and preferentially utilized phosphatidylcholine as a substrate. The phospholipase D activity of the microsomal fraction of amnion tissue obtained at term before labor onset (34.0 +/- 16.3 nmol/hour/mg protein, mean +/- SD, n = 11) was significantly (p < 0.05) higher than the activity in this tissue obtained from women in the mid-trimester (15.0 +/- 7.5 nmol/hour/mg protein, n = 9).

Amnion↗
PubMed1993

Maternal serum CA125 levels in early intrauterine and tubal pregnancies.

Using an immunoradiometric assay, serum CA125 levels were measured in 13 women with a normal pregnancy, 9 with a spontaneous abortion, 3 with a hydatidiform mole, and 15 with a tubal pregnancy. Serum CA125 levels were high in patients with a normal pregnancy (154 +/- 169 U/ml; mean +/- S.D.), a spontaneous abortion (244 +/- 258 U/ml), or a hydatidiform mole (54 +/- 16 U/ml). In contrast, CA125 levels in patients with a tubal pregnancy (33 +/- 25 U/ml) were low, and almost all of those without uterine bleeding (25 +/- 9 U/ml) were within the normal range for non-pregnant women (< 35 U/ml). The difference between serum CA125 levels with intrauterine pregnancy and with tubal pregnancy may be ascribed to the difference of the amount of decidual tissues at the site of trophoblastic invasion.

Abortion, Spontaneous↗
PubMed1993

Lupus anticoagulant (LAC) and its relation to pregnancy outcome: a report of five cases.

We examined the relation between the spontaneous remission and prednisolone-induced suppression of lupus anticoagulant (LAC) or anticardiolipin antibody (ACA) and pregnancy outcome in 5 LAC-positive women. Two women showed a spontaneous remission of LAC and ACA during the observation period. One of these 2 women became pregnant and delivered healthy twin infants at 36 weeks of pregnancy without any therapy. The other woman became LAC positive again after 1 year of remission, and experienced 2 more fetal losses. Two of the remaining LAC-positive women received prednisolone and aspirin. Only 1 woman, whose ACA was suppressed by medication, delivered a healthy newborn. The pregnancy of the other woman, whose LAC and ACA remained positive in spite of medication, terminated in an IUFD. These results suggest that the administration of prednisolone and aspirin is the first choice of therapy for LAC-positive women, and that encouraging such women to become pregnant while LAC is negative might be an alternative therapy.

Adult↗
PubMed1993

The sources and biochemical characteristics of cobalamin-binders in human amniotic fluid.

The sources and biochemical characteristics of cobalamin-binders in amniotic fluid were investigated. Using gel-permeation chromatography, cobalamin-binder, extracted from amniotic fluid at term, was recovered in a single peak with the molecular size of haptocorrin. Neonatal saliva also contained only haptocorrin. However, neonatal gastric juice contained two types of cobalamin-binders: haptocorrin and intrinsic factor. Amniotic fluid in midtrimester contained three types of cobalamin-binders: haptocorrin, intrinsic factor, and transcobalamin II. The cultured amnion cells secreted mainly apo-transcobalamin II. Concentrations of both apo-haptocorrin and salivary amylase in amniotic fluid increased as gestation advanced. These results suggest that cobalamin-binder in amniotic fluid in midtrimester originates from the fetal salivary gland, fetal gastric mucosa, and amnion cells, and that the contribution by the fetal salivary gland increases at term, when almost all cobalamin-binders in amniotic fluid are haptocorrin.

Amniotic Fluid↗
PubMed1993

Brain natriuretic peptide levels in the umbilical venous plasma are elevated in fetal distress.

We measured, by a specific radioimmunoassay, brain-natriuretic-peptide-like immunoreactive (BNP-LI) levels in the umbilical venous and arterial plasma of normal and distressed newborns. The indicated BNP-LI level in umbilical arterial plasma of normal newborns (3.5 +/- 0.9 fmol/ml, mean +/- SEM, n = 10) was significantly higher than that in umbilical venous plasma of the same newborns (2.2 +/- 0.5 fmol/ml). In the distressed newborns at term, the indicated BNP-LI level in umbilical venous plasma was 62.2 +/- 25.7 fmol/ml (n = 4), which was 19-fold higher than that of elective cesarean section cases (3.2 +/- 0.3 fmol/ml, n = 6; p < 0.05). The findings demonstrated that BNP was present in the human fetal circulation and that the plasma BNP level was elevated under fetal distress conditions.

Atrial Natriuretic Factor↗
PubMed1993

Brain natriuretic peptide is present in the human amniotic fluid and is secreted from amnion cells.

The presence and biochemical characteristics of human brain natriuretic peptide (hBNP) in the amniotic fluid at various gestational ages were investigated. The hBNP-like immunoreactivity (hBNP-LI) levels in amniotic fluid, determined by RIA, were 118.7 +/- 57.6 pmol/L (mean +/- SEM; n = 5) and 107.7 +/- 8.7 pmol/L (n = 9) in the first and second trimesters of pregnancy, respectively; it was significantly decreased to 28.4 +/- 5.1 pmol/L (n = 9) in the third trimester. However, human atrial natriuretic peptide-like immunoreactivity (hANP-LI) was not detected (< 0.3 pmol/L) in any of these samples. Northern blot analysis demonstrated hBNP mRNA in human amnion tissue. Moreover, cultured amnion cells secreted a significant amount of hBNP-LI (100-200 fmol/10(6) cells/day), but not hANP-LI, into the culture medium. The synthesis of hBNP in cultured amnion cells was further confirmed using the polymerase chain reaction. High performance gel permeation chromatography of hBNP-LI extracted from human amniotic fluid and the culture medium of amnion cells revealed that the predominant molecular form of hBNP-LI in both samples was the hBNP precursor, with an approximate mol wt of 12 kilodaltons. These findings indicate that hBNP is present in the human amniotic fluid, and that amnion cells synthesize hBNP and secrete it into the amniotic cavity.

Amniotic Fluid↗
PubMed1993

Nuchal-fold thickening in Down syndrome fetuses: transient appearance and spontaneous resolution in the second trimester.

To elucidate the cause of the wide variation of sensitivity of the nuchal-fold thickness (NFT) for a noninvasive prenatal screening test for fetal Down syndrome, we consecutively measured the NFT throughout pregnancy in eight fetuses with Down syndrome and 100 normal fetuses (negative controls) using video-recorded ultrasonography. When 6 mm was set as the cutoff value, 6/8 Down syndrome fetuses showed a NFT above this value at least once during pregnancy. However, the thickening was transient in 5 of them and resolved spontaneously during the second trimester. Persistent thickening of nuchal-fold was only observed in one fetus. From the results of the present study, we recommend that the NFT be measured repetitively during the first and second trimesters as a noninvasive prenatal screening test for Down syndrome.

Down Syndrome↗
PubMed1993

Plasma brain natriuretic peptide level in pregnant women with pregnancy-induced hypertension.

OBJECTIVE: To investigate the involvement of brain natriuretic peptide in the circulation of pregnant women with pregnancy-induced hypertension. METHODS: We determined the plasma levels of brain and atrial natriuretic peptides in a cross-sectional study of 36 normal pregnant women and 17 women with pregnancy-induced hypertension. RESULTS: During normal pregnancy, the plasma brain natriuretic peptide level was similar to that in nonpregnant women, but the plasma atrial natriuretic peptide level in the second trimester was significantly higher than that in nonpregnant women (P < .05). In women with severe pregnancy-induced hypertension, the plasma brain natriuretic peptide level was eight times higher than that in normal pregnant women in the third trimester; the plasma atrial natriuretic peptide level in the same patients was three times higher than that in normal pregnancy. The plasma brain natriuretic peptide level showed a positive correlation with the mean blood pressure (r = 0.62, P < .001). CONCLUSION: The present findings suggest that brain natriuretic peptide is increased in the plasma of women with pregnancy-induced hypertension and that brain natriuretic peptide, in concert with atrial natriuretic peptide, participates in maintaining homeostasis of the maternal circulation.

Adult↗
PubMed1992

Fetal viability does not affect the onset of stretch-induced labor and the increase in amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite levels.

The role of the fetus in the onset and progress of stretch-induced labor and in the change in amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite levels was evaluated in six normal pregnant women (group 1) and six women whose fetuses had been dead for more than one week (group 2). The uterus was distended by a balloon inflated with physiologic saline. Regular uterine contractions occurred, and increased in all patients. Within 21 hours, all patients delivered a normal baby in group 1 and a macerated fetus in group 2. There was no significant difference in induction-delivery interval between the two groups. Both groups showed a significant and similar range of increases in the levels of amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite during treatment (P less than 0.001). Thus, the fetus has no functional role in the onset and progress of stretch-induced labor or in the rise of amniotic fluid prostaglandin F2 alpha and plasma prostaglandin F2 alpha metabolite levels.

Adult↗
PubMed1992

[Clinical significance of serum CA130 level in women with spontaneous abortion, hydatidiform mole and early normal and tubal pregnancy].

We examined the serum CA130 level in women in early pregnancy with normal (n = 13), and abnormal (n = 28) course. The abnormal course consisted of intrauterine spontaneous abortion (n = 10), hydatidiform mole (n = 3) and tubal pregnancy (n = 15). The serum CA130 level was higher than for normal nonpregnant women (35u/ml) in 69% (9/13) of women with normal pregnancy, 90% (9/10) of those with intrauterine spontaneous abortion and 100% (3/3) of those with hydatidiform mole; the mean value and standard deviation for these three groups were 131 +/- 150u/ml (n = 13), 197 +/- 253u/ml (n = 10), and 47 +/- 15u/ml (n = 3), respectively. In contrast, the serum CA130 level of the 15 women with tubal pregnancy was 28 +/- 21u/ml. Among these patients, all of the 13 women without genital bleeding had a CA130 level within the normal range for nonpregnant women (mean +/- SD; 20 +/- 6u/ml). Since CA130 is abundant in the decidual tissue but is scant in tubal tissue, a high CA130 level in maternal sera during early pregnancy may indicate the presence of the destruction of decidual tissue, while a low or normal CA130 level throughout early pregnancy is regarded as characteristic of tubal pregnancy.

Abortion, Spontaneous↗