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Biomedical subjects

Ikuo Sato

Publications and source records attributed to Ikuo Sato.

At least 19 recordsLinked to original sources

Interleukin-10-mediated inhibition of angiogenesis and tumor growth in mice bearing VEGF-producing ovarian cancer.

Interleukin-10 (IL-10) is an immunosuppressive cytokine produced by T lymphocytes and drawing attention as an inhibitor of tumor angiogenesis. In this study, we investigated antiangiogenic and tumor suppressive effects of IL-10 in ovarian cancer cells. mIL-10-expressing plasmid was transferred into two ovarian cancer cell lines, SHIN-3 [vascular endothelial growth factor (VEGF) producing] and KOC-2S (non-VEGF producing). After selection, mIL-10-expressing cells were obtained as SHIN-3/mIL-10 and KOC-2S/mIL-10. No significant differences were observed in in vitro growth properties between mIL-10-expressing cells and control (luciferase expressing) cells in either KOC-2S or SHIN-3. The angiogenic activities of mIL-10-expressing cells were measured by dorsal air sac assay, which detected the number of newly formed blood vessels within a chamber in vivo. In addition, tumor formation was evaluated by s.c. tumor transplantation, and survival was monitored after i.p. injection of ovarian cancer cells into BALB/c nude mice. Both in vivo angiogenic activity and tumor growth were significantly inhibited in SHIN-3/mIL-10 cells compared with the control. Moreover, peritoneal dissemination was inhibited, and the survival period was significantly prolonged (mean survival days > 90 versus 36). In contrast, in the case of KOC-2S cells, no significant differences were observed in any of the parameters tested. These results indicate that IL-10 has suppressive effects on angiogenesis, tumor growth, and peritoneal dissemination of VEGF-producing ovarian cancer cells. Although the mechanisms of the antiangiogenic effect of IL-10 are still unclear, the potential usefulness of IL-10-mediated gene therapy of ovarian cancer was suggested.

Animals↗

Usefulness and prognostic value of transvaginal hydrolaparoscopy in infertile women.

OBJECTIVE: To evaluate the usefulness and prognostic value of transvaginal hydrolaparoscopy (THL) in infertile women. DESIGN: Retrospective study. SETTING: Jichi Medical School Hospital, Tochigi, Japan. PATIENT(S): Thirty-six patients who were followed up for 6 months or longer after THL was performed. INTERVENTION(S): Transvaginal hydrolaparoscopy findings in comparison with hysterosalpingography (HSG). MAIN OUTCOME MEASURES: Transvaginal hydrolaparoscopy findings, HSG findings, treatment strategy, and prognosis. RESULT(S): Twenty of 36 patients (55.5%) became pregnant, including 7 by coitus, 7 by artificial insemination with the husband's semen, and 6 by assisted reproductive technology (ART). In 11 of these pregnant patients, information obtained during THL differed from findings on HSG. CONCLUSION(S): Transvaginal hydrolaparoscopy is useful in selecting a future treatment strategy.

Coitus↗

Effects of sera from infertile women with sperm immobilizing antibodies on fertilization and embryo development in vitro in mice.

PROBLEM: This study was performed to investigate if patients' sera with anti-human sperm antibodies show inhibitory effects on in vitro fertilization (IVF) and embryo development in mice. METHOD OF STUDY: Patients' sera were collected from eight infertile women having sperm immobilizing antibodies and 17 infertile women without the antibodies. Male ICR mice and female F1 mice (BALB/c X C57BL/6J) were used. In mouse IVF, pre-incubated sperm were cultured in the medium containing patient's serum with or without sperm immobilizing antibodies, or bovine serum albumin (BSA) as a control. The fertilization rates and the incidences of blastocyst formation were compared. RESULTS: A mouse sperm immobilization test was established. Five (62.5%) of eight serum samples with sperm immobilizing antibodies and nine (52.9%) of 17 serum samples without the antibodies showed sperm immobilizing activities in mice. There was no significant difference between the two groups. Five sera with sperm immobilizing activities in human and mice, and five sera without sperm immobilizing activities in human or mice were used for the further experiments. The fertilization rates in BSA, patient's serum with sperm immobilizing antibodies, and that without the antibodies were 82.5% (746/904), 43.6% (508/1165), and 64.5% (669/1037), respectively. There were significant differences between the groups. The incidences of blastocyst formation were 59.9% (447/746), 31.7% (161/508), and 47.7% (319/669), respectively. There were also significant differences between the groups. CONCLUSIONS: Some of the patient's serum with and without sperm immobilizing antibodies could immobilize sperm with complement. However, as compared with control, sera with sperm immobilizing activities against human and mouse sperm significantly blocked IVF and inhibited embryo development in mice. Further studies are required to investigate the mechanisms of the blocking effects of antisperm antibodies on fertilization and embryo development using the mouse model.

Animals↗

Chemokine bioactivity of RANTES is elevated in the sera of infertile women with past Chlamydia trachomatis infection.

PROBLEM: It has been shown that Chlamydia trachomatis infection in infertile women is highly associated with tubal pathology. Chlamydia trachomatis antibody testing is a simple screening test for tubal factor subfertility, however, it is based on the detection of previous infection. Recently, association between some inflammatory diseases and chemokines has been investigated. This study was performed to clarify the relationship between chemokines in the sera of infertile women and past C. trachomatis infection. METHOD OF STUDY: Serum samples were collected from 10 infertile women having C. trachomatis antibodies [immunoglobulin (Ig)G and/or IgA] in their sera and 10 infertile women without the antibodies. All patients' tubo-ovarian structures were explored by transvaginal hydrolaparoscopy (THL). A CXC chemokine, interleukin-8, and six CC chemokines including macrophage inflammatory protein-1alpha (MIP-1alpha), MIP-1beta, monocyte chemotactic protein-1 (MCP-1), MCP-3, eotaxin, and regulated on activation, normal T cell expressed and secreted (RANTES) concentrations in their sera were analyzed using enzyme-linked immunosorbent assay. RESULTS: The serum concentration of RANTES was significantly higher in patients with C. trachomatis antibodies than those without the antibodies (P = 0.019). However, there were no significant differences of the concentrations of other chemokines between the sera of infertile women with and without C. trachomatis antibodies. The concentration of RANTES in the sera of infertile women did not correlate with C. trachomatis antibody titers or tubal pathology diagnosed by THL. CONCLUSIONS: These findings might indicate significant roles of some chemokines in the pathogenesis of C. trachomatis infection. Further studies are necessary to study the usefulness of evaluations of chemokines in tubal infertility investigations.

Adult↗

Woman with postpartum ventricular tachycardia and hypomagnesemia.

A 28-year-old Japanese woman who had received continuous intravenous infusion of magnesium sulfate from 24 weeks of pregnancy until delivery underwent cesarean section at 30 weeks and gave birth to twins. Serum magnesium sharply declined to a subnormal level of 1.5 mg/dL on postpartum day 4. The patient exhibited sinus bradycardia (48 b.p.m.) with intermittent supraventricular contraction on postpartum day 2, intermittent ventricular bigeminy on postpartum day 3, and frequent selfterminated polymorphic ventricular tachycardia on postpartum day 4. The electrocardiogram (ECG) disclosed that the patient had prolonged QTc of 0.45-0.67. Correction of serum magnesium improved ECG findings promptly, resulting in the disappearance of arrhythmias. Hypomagnesemia due to postpartum diuresis may have played a role causing ventricular tachyarrhythmia in this patient.

Adult↗

Effect of maternal age on blood loss during parturition: a retrospective multivariate analysis of 10,053 cases.

OBJECTIVE: An extensive study as to whether maternal age itself is a risk factor for blood loss during parturition. METHOD: A total of 10,053 consecutive women who delivered a singleton infant were studied. The excess blood loss was defined separately for women with vaginal and cesarean deliveries as > or = 90th centile value for each delivery mode. The effects of 13 potential risk factors on blood loss were analyzed using multivariate analysis. RESULTS: The 90th centile value of blood loss was 615 ml and 1,531 ml for women with vaginal and cesarean deliveries, respectively. A low lying placenta (odds ratio [OR], 4.4), previous cesarean (3.1), operative delivery (2.6), leiomyoma (1.9), primiparity (1.6), and maternal age > or = 35 years (1.5) were significant independent risk factors for excess blood loss in women with vaginal delivery. Placenta previa (6.3), leiomyoma (3.6), low lying placenta (3.3), and maternal age > or = 35 years (1.8) were significant independent risk factors for excess blood loss in women with cesarean sections. CONCLUSION: A maternal age of > or = 35 years was an independent risk factor for excess blood loss irrespective of the mode of delivery, even after adjusting for age-related complications such as leiomyoma, placenta previa, and low lying placenta.

Adult↗

Symphysis-fundus height and weight gain pattern in Japanese women with twin pregnancies.

OBJECTIVE: To determine the normogram for symphysis-fundus height and weight gain pattern in Japanese women with twin pregnancies and to examine whether fundus height and weight gain pattern are altered in women who give birth to twin infants complicated by fetal growth restriction (FGR). STUDY DESIGN: A retrospective review of the medical records of 186 twin gestations that had been followed at our institution together with 229 singleton pregnancies as a control. We examined maternal symphysis-fundus height, body weight gain and increase in body mass index (BMI) according to gestational age and compared them between women with and without FGR. RESULTS: As compared to women with singleton pregnancies, those with twins exhibited larger fundus height, larger weight gain and larger increase in BMI, all of which were observed from as early as 16-18 weeks of gestation until delivery. Mothers of twins with at least one FGR infant showed smaller fundus height, smaller weight gain and smaller increase in BMI as compared to those without. CONCLUSION: We constructed the normogram for symphysis-fundus height and weight gain pattern in Japanese twin gestations and determined the characteristic change in these parameters in FGR in women with twins. These results may be of use in identifying mothers of twins with FGR.

Adult↗

Reproductive performance after ultrasound-guided transvaginal ethanol sclerotherapy for ovarian endometriotic cysts.

OBJECTIVE: Ultrasound-guided transvaginal ethanol sclerotherapy (TV-EST) has been widely practised in Japan for ovarian endometriotic cysts. We investigated the possible adverse effects of TV-EST for ovarian endometriotic cysts on reproductive performance. PATIENTS AND METHODS: We reviewed retrospectively medical records and compared clinical outcomes of 45 subfertile women who underwent TV-EST for ovarian endometriotic cysts (Study group) with those of 65 subfertile women without ovarian endometriotic cysts (Comparison group). Patients were followed up monthly for 24 months. Serum levels of LH, FSH, CA125 and CA19-9 were determined before and after TV-EST. RESULTS: No complications associated with TV-EST were observed. There were no differences in the numbers of pregnancies (47% (21/45) versus 39% (25/65)), term deliveries (76% (16/21) versus 76% (19/25)), abortions (19% (4/21) versus 24% (6/25)), retrieved oocytes, or quality of embryos between the Study and Comparison groups, respectively. The serum levels of LH and FSH did not increase after TV-EST. The serum levels of CA125 and CA19-9 did not significantly decrease after TV-EST. Ovarian cysts recurred in six (13.3%) of the 45 women 5.2+/-3.9 months after TV-EST. CONCLUSION: Although only a small number of women were studied, our observational study suggested that TV-EST appeared not to adversely affect reproductive performance in subfertile women with ovarian endometriotic cysts.

Adult↗

Involvement of microsatellite instability in lymph node metastasis of endometrial carcinoma.

We evaluated microsatellite instability (MSI) in primary lesions and lymph node metastatic lesions in 66 patients with endometrial carcinoma (FIGO stage IIIC) accompanied by lymph node metastasis. DNA was extracted from paraffin-embedded tissue of both the primary and lymph node metastatic lesions of endometrial carcinoma, and MSI was evaluated using microsatellite markers at five loci. Microsatellite instability was positive in the primary lesion in 27 patients (41%). All patients with MSI-positive primary lesions also showed MSI-positive in lymph node metastatic lesions. Of the other 39 patients with MSI-negative primary lesions, 4 showed MSI-positive in lymph node metastatic lesions. As the result of individual identification by polymerase chain reaction (PCR) using short tandem repeat loci in these 4 patients, PCR profiles of primary and metastatic lesions matched with those of normal controls in all 4 patients. Therefore, it was confirmed that both primary and metastatic lesions developed from the same individual. These results suggest that MSI is also involved in lymph node metastasis in the development and/or progression of endometrial carcinoma in some patients.

Adult↗

Two-dimensional electrophoretic analysis of sperm antigens recognized by sperm immobilizing antibodies detected in infertile women.

In this study, high resolution two-dimensional (2-D) gel electrophoresis was used to identify human sperm antigens recognized by the sera from infertile women having sperm immobilizing (SI) antibodies. Two-D gel electrophoresis was employed to separate Percoll purified human sperm proteins using isoelectric focusing (IEF), followed by polyacrylamide gel electrophoresis (PAGE). Sperm proteins were transferred to the nitrocellulose membranes and immunoblotted with seven sera from infertile women with high titers of SI antibodies and 6 sera from those without SI antibodies. The blots were compared to the 2-D composite image of human sperm proteins [Sperm Protein Encyclopedia] and sperm surface index and the sperm surface proteins recognized by infertile sera were identified. Fifty-two human sperm surface proteins reacted with sera containing SI antibodies, while 35 of these were reactive with the SI-negative control sera. The average numbers of protein spots reacted with test and control sera were 24.6 and 15.0 respectively. A subset of sperm surface proteins which were unique to the SI antibodies were identified by the following criteria; the sperm protein spots which were highly reactive with the infertile sera containing SI antibodies but not reactive with any of the SI-negative infertile sera. The coordinates of 4 prominent immunoreactive sperm proteins were considered as possibly relevant to antibody mediated female infertility.

Antigens, Surface↗

Glucose-6-phosphate dehydrogenase in rat hepatic stellate cells: an ultrastructural enzyme-cytochemical study.

Glucose-6-phosphate dehydrogenase (G6PD) is the key enzyme of the pentose phosphate pathway in carbohydrate metabolism. This enzyme plays an important role in various cell functions, including cell proliferation, lipid/retinol metabolism, etc. Although marked cell proliferation and retinol metabolism take place in hepatic stellate cells (HSCs), it has not been determined whether cytochemically detectable G6PD is present in HSCs. The distribution pattern of G6PD within these cells, if it is present, is also unknown. The purpose of this study was to investigate the subcellular localization of G6PD in rat HSCs using a newly developed enzyme-cytochemistry (copper-ferrocyanide) method. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of HSCs. The cytochemical controls ensured specific detection of the enzyme activity. HSCs possessed enzyme-cytochemically detectable G6PD activity. This enzyme may play a role in normal liver biology and liver disease pathophysiology, by supplying HSCs with NADPH and ribose-5-phosphate as a substance/substrate/co-factor for cell proliferation, oxidoreductase enzymes, and retinol metabolism, respectively.

Journal Article↗

Antithrombin III activity and platelet count are more likely to decrease in twin pregnancies than in singleton pregnancies.

BACKGROUND: It is not known whether antithrombin III activity and platelet count are more likely to decrease in women with twin pregnancies than singleton pregnancies. METHODS: We enrolled 56 consecutive women with twin pregnancies and 692 consecutive women with singleton pregnancies. Antithrombin III activity and platelet count were determined at 26-31 weeks and again at 32-40 weeks of gestation. Thrombin-antithrombin complex, and plasmin-alpha2 plasmin inhibitor complex were measured simultaneously in some women. RESULTS: In twin pregnancies, both antithrombin III activity (111 +/- 8.2%) and platelet count (244 +/- 60 x 109/l) at 28.6 +/- 1.0 weeks decreased over time to 91 +/- 12% and 205 +/- 59 x 109/l, respectively, at 35.2 +/- 1.2 weeks; these decreases were significantly greater than in singleton pregnancies. However, a small number of women with singleton pregnancies had a significant decrease in antithrombin III activity in the absence of preeclampsia. The serum thrombin-antithrombin complex was significantly higher in twin pregnancies than in singleton pregnancies (9.7 +/- 4.2 ng/ml vs. 6.7 +/- 4.4 ng/ml, respectively, p < 0.01), and this increase correlated significantly with the decrease in antithrombin III activity in twin pregnancies (r = -0.459, p < 0.001). CONCLUSIONS: Antithrombin III activity and platelet count show a greater decrease in twin than in singleton pregnancies, perhaps due to a greater increase in thrombin generation.

Adult↗

Relationship between blood pressure level in early pregnancy and subsequent changes in blood pressure during pregnancy.

BACKGROUND: It is not known whether women with high blood pressure in the first trimester are likely to exhibit a large increase in blood pressure during pregnancy. METHODS: We conducted a retrospective, longitudinal study of 1599 pregnant women, among whom 29 women (1.8%) received antihypertensive medication during pregnancy. The blood pressure levels measured during the first (7.9 +/- 2.4 weeks), second (20.7 +/- 1.2 weeks) and third trimesters (38.4 +/- 1.7 weeks) were analyzed. The obstetric outcomes were examined in five subgroups divided according to the quintile of the first-trimester mean arterial pressure level. RESULTS: The net change in blood pressure levels (third-trimester value minus first-trimester value) was significantly inversely correlated with the first-trimester blood pressure levels irrespective of the use or lack of use of antihypertensive drugs. Women with the highest quintile first-trimester mean arterial pressure had the largest body weight, exhibited a fall in blood pressure and had the smallest increase in body weight during pregnancy, and were significantly more likely to have a growth-restricted infant. CONCLUSIONS: Women with high initial blood pressure tended to exhibit a fall in blood pressure, whereas women with low initial blood pressure tended to exhibit a large increase in blood pressure during pregnancy. Women with high initial blood pressure and a small increase in body weight during pregnancy tended to have growth-restricted infants.

Adolescent↗

Dynamic changes of the immunoglobulins in patients with severe ovarian hyperstimulation syndrome: efficacy of a novel treatment using peritoneo-venous shunt.

PROBLEM: To evaluate the efficacy of continuous auto-transfusion system of ascites (CATSA) for the treatment of patients with severe ovarian hyperstimulation syndrome (OHSS) at the risk of febrile morbidity, the dynamic changes of immunoglobulins in the sera and the peritoneal fluid from patients with severe OHSS treated by CATSA were estimated. METHOD OF STUDY: Ten patients with severe OHSS after superovulation for in vitro fertilization-embryo transfer (IVF-ET) were treated by CATSA. Immunoglobulin concentrations were examined in the serum and in the peritoneal fluid before and after CATSA. As controls, serum samples from 15 infertile women, who did not develop OHSS after the same superovulation protocol, were obtained on the day of mid-luteal period (Control-1). Serum samples from 15 patients with OHSS, who were treated by albumin infusion without paracentesis, were also obtained before and after the treatment (Control-2). RESULTS: Before the treatments, serum immunoglobulin G (IgG) concentrations in patients with severe OHSS treated with CATSA and those in patients of Control-2 were significantly lower than those in patients of Control-1 (P < 0.01). Following CATSA, the concentration of IgG increased in the sera, while it decreased in the peritoneal fluid. CONCLUSIONS: Serum IgG in patients with severe OHSS exuded into their peritoneal cavity, indicating that they might be at the status of immunodeficiency and at the risk of febrile morbidity. However, non-infectious febrile morbidity attributed to endogenous pyrogenic mechanism might be considerable. It is also suggested that CATSA might be effective in improving hypoimmunoglobulinemia of the patients with severe OHSS by the peritoneo-venous shunt.

Adult↗

Changes in the number of polymorphonuclear leukocytes and concentrations of IL-8 and granulocyte elastase in the vaginas of normal pregnant women.

PROBLEM: It is unknown whether the number of vaginal polymorphonuclear leukocytes (vPMNs) of healthy pregnant women changes during pregnancy. METHOD OF STUDY: We studied 23 women after 14.7 +/- 3.6 weeks, 37 women after 25.2 +/- 3.1 weeks, and 26 women after 32.9 +/- 2.0 weeks of gestation. Numbers of total vPMNs, viable vPMNs, dead vPMNs, percentage viability of vPMNs, and concentrations of IL-8 and elastase activity were determined in vaginal washings. RESULTS: The vPMNs, including viable and dead vPMNs, significantly increased with advancing gestation from 9.9 +/- 8.6 x 10(5) to 13.1 +/- 13.4 x 10(5), and to 27.1 +/- 26.6 x 10(5) (r=0.315, P < 0.01). Vaginal IL-8 significantly increased with advancing gestation. However, increases in vaginal elastase activity did not occur. CONCLUSIONS: These results suggested that an increase in vPMNs is an early event, and that the increase in vaginal elastase activity is a late event in relation to the ripening of the uterine cervix.

Adult↗

Sperm immobilizing antibodies in the sera of infertile women cause low fertilization rates and poor embryo quality in vitro.

PROBLEM: The effects of sperm immobilizing antibodies in the sera of infertile women on fertilization and embryo quality in vitro were investigated. METHOD OF STUDY: Before the introduction of sperm immobilization test (SIT) as a routine test for female infertility, 85 oocytes were collected in nine in vitro fertilization (IVF) cycles from four infertile women who were afterward found having had sperm immobilizing antibodies in their sera and the oocytes were inseminated with swim-up sperm in a medium containing the patient's serum. Fifty oocytes were collected in five IVF cycles from five infertile women possessing the antibodies in their sera and the oocytes were inseminated with swim-up sperm in a medium supplemented with human serum albumin (HSA). RESULTS: In the former group, 41 of 85 oocytes were fertilized, giving a fertilization rate of 48.2%. In the latter group, 43 of 50 oocytes were fertilized, giving a fertilization rate of 86.0%. There was a significant difference of the fertilization rate between the groups (P < 0.0001). Embryo quality was assessed by the Veeck's classification. The grade 1 and grade 2 embryos were considered good quality. Using this classification, 16 (39.0%) of 41 embryos incubated in the medium containing the patient's serum were good quality, while 34 (79.1%) of 43 embryos incubated in the medium supplemented with HSA were good quality. There was also a significant difference between the groups (P = 0.0003). CONCLUSIONS: These findings might indicate that sperm immobilizing antibodies in the sera of infertile women cause low fertilization rates and poor embryo quality in vitro. It is suggested that SIT in the sera of infertile women should be performed at least before proceeding IVF. The manipulation of gametes and embryos from patients having sperm immobilizing antibodies should be carefully carried out especially to avoid contaminating patient's serum and follicular fluid in the culture medium in order to have a better IVF result.

Culture Media↗