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Biomedical subjects

N Sagawa

Publications and source records attributed to N Sagawa.

At least 19 recordsLinked to original sources
PubMed2000

Reconstruction after total pharyngolaryngoesophagectomy. Comparison of elongated stomach roll with microvascular anastomosis with gastric pull up reconstruction or something like that.

BACKGROUND: We have performed total pharyngolaryngoesophagectomy in case of double cancer, head-neck and thoracic esophageal cancer, or cervical esophageal cancer that extended down to the level of aortic arch. The procedure is very challenging. METHODS: From April 1984 to May 1998, 14 patients underwent the procedures for double cancer of head-neck and thoracic esophagus (n=10), hypopharyngeal or cervical esophageal cancer (n=3), and synchronous esophageal cancer (n=1). The grafts used were whole stomach (n=6), elongated stomach roll (n=5), and stomach roll with free jejunum (n=3). The routes of reconstruction were posterior mediastinum (n=10), antesternal (n=3), and retrosternal (n=1). RESULTS: Elongated stomach roll with microvascular anastomoses was long enough for reconstruction and the blood supply of the graft was sufficient. There was no fatal complication in this procedure. Oral feeding was achieved in 13 (93%) patients. CONCLUSIONS: The elongated stomach roll with microvascular anastomosis is efficient and the placement of the conduit in the posterior mediastinum is recommended to allow a better alimentary comfort in total pharyngolaryngoesophagectomy.

Adult↗
PubMed2000

Changes in the serum levels of human chorionic gonadotropin and the pulsatility index of uterine arteries during conservative management of retained adherent placenta.

OBJECTIVE: Our purpose was to assess the natural course of retained adherent placenta at term. METHODS: Five cases of retained adherent placenta, clinically diagnosed as placenta accreta, were managed conservatively without methotrexate. To assess the biochemical and circulatory changes in the placentas, the serum levels of human chorionic gonadotropin (hCG) and the pulsatility index (PI) of the uterine arteries were examined. RESULTS: Serum hCG levels decreased spontaneously; the half-life of serum hCG was calculated to be 5.2 +/- 0.26 days (mean +/- SEM). The PI of the uterine arteries remained at the level of pregnant women at term, but became elevated within a few days after the removal of the placentas. All the placentas were successfully removed transvaginally within 6 weeks postpartum. CONCLUSIONS: The changes in serum hCG observed in this study indicated the spontaneous degeneration of the placenta. Such changes might be similar to those reported to occur during treatment with methotrexate. In contrast, the PI of the uterine arteries did not reflect degeneration of the placenta.

Adult↗
PubMed2000

Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin.

Excess or loss of body fat can be associated with infertility, suggesting that adequate fat mass is essential for proper reproductive function. Leptin is an adipocyte-derived hormone that is involved in the regulation of food intake and energy expenditure, and its synthesis and secretion are markedly increased in obesity. Short-term administration of leptin accelerates the onset of puberty in normal mice and corrects the sterility of leptin-deficient ob/ob mice. These findings suggest a role for leptin as an endocrine signal between fat depots and the reproductive axis, but the effect of hyperleptinemia on the initiation and maintenance of reproductive function has not been elucidated. To address this issue, we examined the reproductive phenotypes of female transgenic skinny mice with elevated plasma leptin concentrations comparable to those in obese subjects. With no apparent adipose tissue, female transgenic skinny mice exhibit accelerated puberty and intact fertility at younger ages followed by successful delivery of healthy pups. However, at older ages, they develop hypothalamic hypogonadism characterized by prolonged menstrual cycles, atrophic ovary, reduced hypothalamic gonadotropin releasing hormone contents, and poor pituitary luteinizing hormone secretion. This study has demonstrated for the first time to our knowledge that accelerated puberty and late-onset hypothalamic hypogonadism are associated with chronic hyperleptinemia, thereby leading to a better understanding of the pathophysiological and therapeutic implication of leptin.

Adipose Tissue↗
PubMed1999

A case of clitoral metastasis without skin involvement from rectal cancer.

An 84-year-old woman visited a private dermatologist and gynecologist due to pain in the external genitals. However, no abnormality was found. She was referred to a surgeon in our hospital to clarify the etiology of the pain. Rectal cancer and liver metastatic tumor were detected, and the rectal cancer was resected. However, the pain increased after the operation and she was referred to our department. No macroscopic abnormalities of the external genitals were found. However, a vaginal examination could not be performed due to severe pain. By local examination under anesthesia, enlargement of the clitoris was detected. A simple clitoridectomy was performed. Histological examination revealed that the clitoral tumor was metastatic cancer originating from rectal cancer.

Adenocarcinoma↗
PubMed1999

Activity of platelet-activating-factor-acetylhydrolase and the nitric oxide metabolite level in the plasma of pregnant women who develop transient hypertension during later pregnancy.

It is reported that plasma platelet-activating-factor-acetylhydrolase (PAF-AH) is elevated in patients with essential hypertension. In this study, plasma PAF-AH activity was measured during pregnancy and after delivery to examine the relationship between plasma PAF-AH activity and the development of transient hypertension (TH) during pregnancy. Moreover, in order to examine the involvement of endothelial injury in TH, the plasma level of nitric oxide metabolite (NOx; NO2+NO3) was measured. The plasma PAF-AH activity in 51 pregnant women was consecutively measured in the 1st, 2nd and 3rd trimesters of gestation, and after delivery. Forty-one cases were normal pregnancies and 10 cases were complicated by TH later during pregnancy. The PAF-AH activity in the normal pregnancy group decreased in the 2nd trimester of gestation compared with the 1st trimester, but was elevated in the TH group. The incidence of elevation of PAF-AH in the TH group was significantly (7/10; 70.0%; P<0.01, Chi-squared test) higher than in the normal pregnancy group (9/41; 22.0%). The plasma NOx levels in the 2nd trimester were higher than those in the 1st trimester in both the normotensive and TH group (P<0.05 for both comparisons). The 51 patients were classified into two groups according to the change in the PAF-AH in the 2nd trimester: group A consisted of 35 patients whose PAF-AH activity did not increase, and group B consisted of 16 patients whose PAF-AH activity increased. The incidence of development of TH during later pregnancy in group B was significantly (7/16; 43.8%; P<0.01, Chi-squared test) higher than in group A (3/35; 8.6%). Hypertension developed after 36 weeks' gestation in all patients in the TH group. The results of the present study suggest that changes in PAF metabolism may relate to regulation of blood pressure in pregnant women whose pregnancy is complicated with TH, whereas NO metabolism does not differ between women with TH and those having a normal pregnancy.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1998

A positive umbilical venous-arterial difference of leptin level and its rapid decline after birth.

OBJECTIVE: We investigated the site of leptin production in the fetoplacental circulation. STUDY DESIGN: We simultaneously determined plasma leptin levels in cord vessels and maternal peripheral veins of 38 healthy pregnant women. We also compared plasma leptin levels in 20 neonates at birth and on the fifth day after birth. RESULTS: Leptin levels in cord vessels were significantly (p < 0.001) lower than those in maternal veins (mean 29.5 ng/ml). Leptin levels in umbilical arteries (mean 9.8 ng/ml) were significantly (p < 0.01) lower than those in umbilical veins (mean 12.9 ng/ml). Leptin levels in neonatal veins on the fifth day (mean 3.0 ng/ml) were markedly (p < 0.001) lower than those in umbilical arteries of the same neonates (mean 10.9 ng/ml). CONCLUSION: The higher leptin levels in umbilical veins than in umbilical arteries and the marked decrease during the neonatal period suggest that the placenta is one of the major sources of leptin in the fetal circulation.

Adult↗
PubMed1998

Nitric oxide metabolite concentrations in maternal plasma decrease during parturition: possible transient down-regulation of nitric oxide synthesis.

To elucidate the possible involvement of nitric oxide (NO) in parturition, we measured the maternal plasma concentrations of the NO metabolites, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and guanosine 3',5'-cyclic phosphate (cGMP) in pregnant women at various gestational ages including those at vaginal and elective Caesarean deliveries. The plasma cGMP and NO metabolite concentrations at vaginal delivery were significantly lower than those of the pregnant women in the third trimester of pregnancy. These concentrations remained low until 4 h after delivery but returned 24 h after delivery to values similar to those of the non-pregnant women. Such suppressions of plasma cGMP and NO metabolite concentrations were not observed in the women who underwent elective Caesarean section before the onset of labour. Moreover, no significant changes were observed in the plasma ANP and BNP concentrations at the time of vaginal and Caesarean deliveries, except that a slight but significant elevation of the plasma ANP concentration was observed 1 h after Caesarean delivery. In conclusion, the plasma concentrations of cGMP and NO metabolites significantly decreased at vaginal delivery but not at Caesarean delivery. These changes were independent of the plasma ANP and BNP concentrations, suggesting the possible down-regulation of maternal NO synthesis during parturition.

Adult↗
PubMed1998

Augmentation of leptin synthesis and secretion through activation of protein kinases A and C in cultured human trophoblastic cells.

Leptin is a fat cell-derived hormone that regulates food intake and energy expenditure. We previously demonstrated that leptin is produced by nonadipose cells, i.e. by placental trophoblasts. We also reported that a human trophoblastic cell line, BeWo cells, expresses leptin gene and secretes leptin into culture media. To elucidate the regulatory mechanisms of leptin production by human trophoblasts, we investigated synthesis and secretion of leptin in BeWo cells and in explant cultures of human placental tissue. Leptin production and gene expression in BeWo cells were increased by treatment with forskolin. The forskolin-induced increase in leptin production was completely suppressed by H89, an inhibitor of protein kinase A. Leptin production and gene expression in BeWo cells were increased by treatment with phorbol myristate acetate (PMA). The PMA-induced increase in leptin production was completely suppressed by H7 and staurosporine, both of which are inhibitors of protein kinase C. Leptin secretion from first trimester chorionic tissue was approximately 50-fold greater than that from term placental tissue. Leptin production and gene expression in explant cultures of placental tissue at both stages of pregnancy were augmented markedly by treatment with forskolin or PMA. The present study demonstrated augmentation of leptin production by protein kinase A and protein kinase C in cultured human trophoblasts, thereby leading to a better understanding of the regulatory mechanisms of leptin production in human trophoblasts in vivo.

Cell Line↗
PubMed1998

Augmented placental production of leptin in preeclampsia: possible involvement of placental hypoxia.

Preeclampsia (PE) is a hypertensive disorder, which develops in late pregnancy and is usually associated with placental hypoxia and dysfunction. We have recently demonstrated that leptin is a novel placenta-derived hormone in humans and suggested its significance in human pregnancy (see Ref. 19). To explore the changes in the leptin production in placenta in PE, we measured the plasma leptin level and placental leptin messenger RNA expression in pregnant women with PE. Plasma leptin levels in preeclamptic women were elevated significantly, compared with gestational age- and body mass index-matched normal pregnant women (P < 0.0001). Plasma leptin levels in the severe PE group were significantly higher than those in the mild PE group (P < 0.0001). Plasma leptin levels in preeclamptic women were reduced, soon after the placental delivery, to those expected for their body mass indices. Northern blot analysis revealed that leptin messenger RNA levels are increased in the placentas from preeclamptic women, compared with normal pregnant women. Leptin secretion was increased significantly in a human trophoblastic cell line (BeWo cells) cultured under hypoxic conditions (5% O2), compared with those cultured under standard conditions (20% O2; P < 0.01). The present study demonstrated that placental production of leptin is augmented in severe PE, probably because of placental hypoxia, thereby suggesting the possible significance of leptin as a marker of placental hypoxia in severe PE.

Adult↗
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↗