[Plasma levels of brain natriuretic peptide (BNP) in the women with severe pregnancy-induced hypertension].
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Biomedical subjects
Publications and source records attributed to N Sagawa.
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We describe a patient with high serum CA 125 levels before and after surgery (greater than 403 U/ml) who had no apparent pathologic foci of CA 125 production. Serum levels of CA 130, which exists on the same glycoprotein as CA 125, were within normal ranges (less than 35 U/ml) before and after surgery.
To examine the possible role of endothelin in the initiation of parturition, endothelin-1-like immunoreactivity (ET-1-LI) in the amniotic fluid (AF) was determined by a sensitive radioimmunoassay (RIA) system. The concentrations of ET-1-LI in AF were 24.7 +/- 6.1 pg/ml (mean +/- SD, n = 6) at the second trimester and were significantly increased to 40.4 +/- 15.1 pg/ml (n = 6) at term. These ET-1-LI concentrations are about three- to fourfold higher than those observed in the maternal plasma. The gel permeation chromatography (GPC) profile of ET-1-LI extracted from second-trimester AF indicated that the ET-1-LI consisted of only one component of 6kET, the molecular weight of which was 6,000, larger than big ET-1. In contrast, ET-1-LI in the AF at term consisted of two components, ET-1 and 6kET. These findings suggest that the level of biologically active ET-1 in the AF increases markedly from second trimester toward term. A significant amount of ET-1-LI was also detected in the supernatant of amnion cell culture. The level of ET-1-LI in the culture medium after 12 h of incubation was almost comparable with that in AF at term. Thus, it is suggested that amnion tissue may be the major source of ET-1-LI in the AF. Together with the fact that ET-1 increases cytoplasmic calcium ion in the target cell, the results of present study raise the possibility that endothelin plays an important role in the initiation of parturition by triggering the production of prostaglandins in fetal membranes.
To examine the role of endothelin (ET) in the maternal and fetal circulation, the levels of endothelin-1-like immunoreactivity (ET-1-LI) in the plasma of maternal vein (MV), umbilical vein (UV), and umbilical artery (UA) were determined by a sensitive radioimmunoassay (RIA). Levels of ET-1-LI in MV did not show any significant change (9.9 +/- 1.5 pg/ml, n = 26) throughout normal pregnancy and were similar to those of normal nonpregnant women (10.7 +/- 2.5 pg/ml, n = 5). Levels of ET-1-LI in UV and UA obtained at normal deliveries at term were about three times higher than those in MV. In the patients with mild and severe pre-eclampsia, the levels of plasma ET-1-LI were significantly higher than those of normal pregnancy (14.3 +/- 2.2 pg/ml, n = 5 and 27.2 +/- 8.6 pg/ml, n = 5, respectively). However, in pregnant women with chronic hypertension, the levels of ET-1-LI did not increase when the hypertension did not worsen during pregnancy (11.4 +/- 1.6 pg/ml, n = 7). Moreover, in two pregnant women with abnormally stimulated coagulation, such as acute or subacute DIC, the levels of ET-1-LI were extremely high and returned gradually to those of normal nonpregnant women after the coagulation was normalized by treatment. These results suggest the possibility that ET-1 plays an important role in the pathophysiology of preeclampsia.
Endothelin (ET), a novel vasoconstrictor peptide containing three isopeptides [ET-1, ET-2, and ET-3 (ETs)], has various biological effects including vasoconstriction, mitogenesis, and steroidogenesis. We examined the ET-1-like immunoreactivity level in porcine follicular fluid and culture medium of porcine granulosa cells by RIA. The ET level in the follicular fluid was 9.4-14.2 pg/ml. These levels were within 0.42 to 0.62-fold of the porcine plasma level (22.7 +/- 3.1 pg/ml) (mean +/- SE). ET was detected in the culture medium of granulosa cells with and without LH treatment at the concentration of 56 +/- 9.3 and 4.9 +/- 1.2 pg/10(6) cells.h, respectively. We also examined whether ETs affect the luteinization of granulosa cells. ETs inhibited the LH-stimulated progesterone and cAMP accumulation in cultured porcine granulosa cells in a dose-dependent manner with an EC50 of 5 x 10(-11) M. ET-1, ET-2, and ET-3 (5 x 10(-8)M inhibited progesterone accumulation by 62.3 +/- 1.8, 59.8 +/- 4.0, and 63.3 +/- 5.7% in 6-day cultures, respectively, and significant inhibition was observed within 24 h of culture. ET-1, ET-2, and ET-3 (5 x 10(-8) M) inhibited the LH-stimulated cAMP accumulation in granulosa cells by 54.8 +/- 2.3, 55.4 +/- 7.1, and 55.5 +/- 6.2%, respectively, whereas they did not affect basal cAMP levels. As well as progesterone accumulation, ETs partially inhibited LH-stimulated morphological transformation of granulosa cells. In this study, we demonstrated that ET exists in follicular fluid and in the culture medium of granulosa cells, and that ET inhibited LH-induced progesterone accumulation, morphological transformation, and cAMP accumulation in cultured porcine granulosa cells. These findings suggest that ET acts as a modulator of steroid metabolism in preovulatory follicles.
To investigate whether the platelets in the ovaries are activated by the action of platelet-activating factor (PAF) during gonadotropin-induced ovulation, we examined the changes in the platelet count in immature rats after administration of PMSG followed 48 h later by human CG (hCG). The platelet count in the inferior vena cava was significantly decreased 48 h after PMSG administration and was further decreased after hCG administration. When both ovaries of rats were extirpated, the administration of PMSG and hCG did not decrease the platelet count. Subcutaneous administration of a PAF antagonist, Y24180 (0.5-5 mg/kg.6 h), after PMSG injection decreased the number of ova shed in a dose-dependent manner. The decrease in the platelet count induced by the administration of PMSG and hCG was reversed to the level of the untreated control group by Y24180 (2.5 mg/kg.6 h). This inhibitory activity of Y24180 on ovulation and thrombocytopenia was completely reversed by the ip injection of synthetic PAF. Subcutaneous administration of indomethacin (IDM) also reduced the number of ova shed in a dose-dependent manner. However, thrombocytopenia was not reversed by IDM. Moreover, the inhibition of ovulation by IDM was not reversed by synthetic PAF. The present study suggests that: 1) platelets are activated by PAF during gonadotropin-induced ovulation in immature rats; 2) PAF is also involved in the rupture of follicles; 3) the presence of the ovary is indispensable for the generation of PAF in gonadotropin-stimulated immature rats; and 4) the mechanism of PAF action on ovulation may be different from that of prostaglandins.
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A murine monoclonal antibody, 130-22, produced against a human lung adenocarcinoma cell line (PC-9) has been suggested as recognizing an antigenic determinant (CA130) which is different from an epitope recognized by OC125 on CA125 glycoprotein molecules. The immunohistochemical reactivity with the 130-22 antibody (anti-CA130) was examined in human fetal tissues, and normal and neoplastic tissues of female genital tracts, and compared to those using OC125. Among the fetal tissues, the amnion and the cells of coelomic epithelium and mullerian-derived epithelia reacted with anti-CA130. In normal adult tissues, cervical and endometrial gland cells, tubal epithelial cells, and ovarian surface cells reacted with anti-CA130. In addition, predecidual cells in the late secretory endometrium and decidual cells during gestation were positive. Among the neoplastic tissues, tubal and endometrial adenocarcinomas and epithelial ovarian tumors were positive for anti-CA130. There were no differences in the respective specimens between the immunohistochemical localization of anti-CA130 and of OC125. Therefore, anti-CA130 is considered to be useful in the immunohistochemical detection of CA125 glycoprotein molecules as well as OC125.
We examined the CA130 concentration in the amniotic fluid, maternal sera, amnion, chorion, decidua and placenta. CA130 in the maternal sera showed an initial increase during early pregnancy, remained low from the 15th weeks of pregnancy until delivery, and then increased after term delivery (249u/ml, mean, n = 27) or mid-trimester abortions (844u/ml, n = 22). The CA130, concentration in the amniotic fluid was high in the mid-trimester and remarkably low at term. Among the tissues examined, amnion and decidua contained a relatively high concentration of CA130. Immunohistochemical examination also demonstrated abundant CA130 in the cytosol of amnion and decidua tissues. The pattern of changes in CA130 in amniotic fluid was similar to that in the amnion and decidua tissue. The results suggest that the amnion cells are the source of CA130 in the amniotic fluid and that the high concentration of CA130 in maternal serum after delivery originates in decidua tissue affected by the separation of the placenta.
To investigate the sources and biologic significance of CA 125 and CA 19-9 in amniotic fluid, immunohistochemical and biochemical localization of these tumor-associated glycoproteins in the decidua and fetal membranes was studied. Immunohistochemically, CA 125 and CA 19-9 were localized in the cytoplasm of decidua cells and amnion epithelial cells but not in the chorion and placental tissue. Biochemically, the 12,000 X g supernatant fractions of decidua and amnion tissues contained relatively large amounts of CA 125 and CA 19-9, 73% to 96% of which was present in the cytosolic fractions of these tissues. The CA 125 levels in the amniotic fluid decreased, whereas those of CA 19-9 increased with gestation, which correlated well with the respective levels in amnion tissues. These findings suggest that amnion cells produce and secrete these glycoproteins into the amniotic cavity. However, it is possible that the decidua also secretes CA 125 into the amniotic cavity through the chorion and amnion such as in the case of prolactin.
To clarify the mechanism of CA 125 elevation in maternal sera, serum levels of CA 125 and CA 19-9 were measured in 122 apparently healthy pregnant women (fifth to fortieth week of gestation) and 50 postpartum women (26 term deliveries and 24 second-trimester induced abortions). Serum levels of CA 125 showed an initial increase by the tenth week and then decreased to less than 35 U/ml, remaining below this level until delivery. However, within 1 hour after term delivery or second-trimester induced abortion, the CA 125 levels showed a second increase and decreased rapidly thereafter. In contrast, serum levels of CA 19-9 did not change significantly during these periods. Combined with our previous finding that the decidua contains abundant CA 125 but little CA 19-9, these results indicate that the elevated CA 125 levels in maternal sera originate from the decidual cells affected by chorionic invasion or the placental separation.
To verify whether analysis of the levels of CA125, carcinoembryonic antigen (CEA), and CA19-9 in the cervical mucus is effective for a detection of cervical adenocarcinomas or not, simultaneous measurement of these three tumor markers in the cervical mucus samples from women without gynecologic disorders, with leiomyoma, with cervical squamous cell carcinomas, and with cervical adenocarcinomas was performed. Extremely high levels of CA125 with low levels of both CEA and CA19-9 were demonstrated in the cervical mucus samples from women without gynecologic disorders and with leiomyoma. The cervical mucus samples from cervical adenocarcinomas showed low CA125 levels with extremely high CEA and/or CA19-9 levels. Therefore, analysis of the levels of these three tumor markers in the cervical mucus possibly helps in the diagnosis of cervical adenocarcinomas if CEA and/or CA19-9 show extremely high levels. When a ratio of (CEA + CA19-9)/CA125 was calculated, all women without gynecologic disorders and with leiomyoma showed a ratio less than 0.5, whereas ten of 11 cases of cervical adenocarcinomas had a ratio greater than or equal to 0.5. Only one case of microinvasive adenocarcinoma showed a ratio less than 0.5. Accordingly, the ratio greater than or equal to 0.5 strongly suggested an existence of cervical adenocarcinoma, although it included some cases of squamous cell carcinomas (four of 17 cases).
Recently, normal cervical glandular cells have been reported to synthesize and secrete CA125 as a common constituent of normal cervical mucus. However, the levels of CA125 in the cervical mucus samples during the menstrual cycle and with cervical inflammatory diseases have not been determined. Therefore, we measured CA125 in cervical mucus samples in various phases of the menstrual cycle and in patients with cervical polyp or vaginitis. In addition to CA125, CEA and CA19-9 were also examined in the same samples. CA125 levels in the mucus samples of women (45 cases) without any gynecologic disorders (control) were 102,200 +/- 8,600 (M +/- S.E.) U/ml. Significantly higher levels were noted in the samples obtained in the follicular phase than in the luteal phase. CA125 levels in the mucus with atrophic vaginitis (12 cases) were significantly lower than those of controls. CEA and CA19-9 levels in the control samples were 3,400 +/- 550 ng/ml and 3,470 +/- 500 U/ml, respectively, and both of these showed no significant difference between the follicular and luteal phases. However, both CEA and CA19-9 levels in the cervical mucus with cervical polyps (15 cases) or vaginitis were much higher than in the controls. Accordingly, the present study revealed that CA125 in the cervical mucus fluctuates during the menstrual cycle, probably under the influence of ovarian sex steroids. In addition, CEA and CA19-9 in the cervical mucus samples obtained from women without any gynecologic disorders showed low levels, but those with inflammatory diseases were high, and this suggested that inflammatory diseases in the cervix and/or vagina may affect the constituent of the tumor-associated carbohydrate antigens in the cervical mucus.
The effects of nicotine administration on the synthesis and secretion of surfactant in the rabbit fetal lung were studied by measuring phosphatidylcholine (PC) and phosphatidylglycerol (PG) in the fetal lung tissue and amniotic fluid. The concentrations of both PC and PG in the lung tissue were decreased by administering nicotine to the mother. On the other hand, the concentrations of PC and PG in the amnniotic fluid were not altered by nicotine administration. Moreover, the PG/PC ratio in the amniotic fluid of the nicotine group was similar to that of the control group. The plasma catecholamine levels were elevated in the growth retarded fetuses from nicotine-treated mothers. These findings indicated that the administration of nicotine to the mother suppressed the synthesis of surfactant in the fetal lung but enhanced the secretion of surfactant to the alveolar cavity, probably via the stimulation of beta-receptor by catecholamine, and that the biochemical maturity of the surfactant was not altered by the administration of nicotine to the mother. The results of the present study might provide basic information to help to understand the clinical experiences reported by others i.e. that in the newborn from a smoking mother, respiratory distress occurred less frequently than in those from non-smokers.
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Amniotomy was performed in 12 multiparas at term but not in labor. In 6 of these patients (group I), the fetal head and cervix condition were favorable for amniotomy, and in the other 6 (group II), they were not favorable. In all group I patients, a sudden and progressive descent of the fetal head, and onset and progress of labor were noted within 5 hours. Plasma 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) levels increased significantly (P less than 0.05) in 4 of these cases with time. In group II patients, descent of the head was less than that in group I patients (P less than 0.05), and neither strong labor nor rise of PGFM levels was noted within 5 hours. These data support our view that amniotomy at an appropriate time results in the onset and progress of labor, and the rise of plasma PGFM in virtue of the sudden and exponential increase of the head to cervix force, but amniotomy at an inappropriate time does not, because this force is unchanged.
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To examine the mechanical forces involved in cervical distention, actual tensions of the fetal membranes up to the bursting level were measured experimentally with the use of five circular membrane holders that simulate various cervical dilatations (radii 1 to 5 cm). The results show that the force of cervical dilatation with the head alone increases remarkably as the cervix dilates, and this force is always larger than that when the membranes are intact. Thus the membranes appear to interfere with effective cervical dilatation and progress of labor after fixation of the fetal head to the cervix.