-
[show abstract]
[hide abstract]
ABSTRACT: Preoperative diagnosis of chronic ectopic pregnancy is often difficult because of the high incidence of negative results on pregnancy tests as a consequence of the very small amount of live villi, subtle symptoms, and the poor specificity of ultrasonographic patterns. A 45-year-old woman was referred to our department for evaluation of a mass 8 cm in diameter with solid parts in the right adnexal area. Transvaginal ultrasonography showed a mass consisting of a cystic part with an irregular thick capsule distinct from the right ovary. In the center of the cystic part, a fetus-like image, 20 mm in length was seen. Preoperative diagnosis was confirmed by the laparoscopy, which revealed a swollen right tube containing a fetus with highly necrotic changes. This case was unique because chronic ectopic pregnancy was detected at an early stage before absorption of the conceptus occurred, which coincidentally is an appropriate time for morphological diagnosis.
Journal of Obstetrics and Gynaecology Research 04/2010; 36(2):462-5. · 0.94 Impact Factor
-
Kenbun Sone,
Shunsuke Nakagawa,
Keiichi Nakagawa,
Shin Takizawa,
Yoko Matsumoto,
Kazunori Nagasaka,
Tetsushi Tsuruga,
Haruko Hiraike,
Osamu Hiraike-Wada,
Yuichiro Miyamoto,
Katsutoshi Oda,
Toshiharu Yasugi, Koji Kugu,
Tetsu Yano,
Yuji Taketani
[show abstract]
[hide abstract]
ABSTRACT: hScrib, human homologue of Drosophila neoplastic tumor suppressor, was identified as a target of human papillomavirus E6 oncoprotein for the ubiquitin-mediated degradation. Here, we report that hScrib is a novel death substrate targeted by caspase. Full-length hScrib was cleaved by caspase during death ligands-induced apoptosis, which generates a p170 C-terminal fragments in Hela cells. In vitro cleavage assay using recombinant caspases showed that hScrib is cleaved by the executioner caspases. DNA damage-induced apoptosis caused loss of expression of full-length hScrib, which was recovered by addition of capase-3 inhibitor in HaCat cells. TUNEL positive apoptotic cells, which were identified 4 h after UV irradiation in HaCat cells, showed loss of hScrib expression at the adherens junction. Mutational analysis identified the caspase-dependent cleavage site of hScrib at the position of Asp-504. Although MDCK cells transfected with GFP-fused wild-type hScrib showed loss of E-cadherin expression and shrinkage of cytoplasm by UV irradiation, cells transfected with hScrib with Ala substitution of Asp-504 showed resistance to caspase-dependent cleavage of hScrib and intact expression of E-cadherin. These results indicate that caspase-dependent cleavage of hScrib is a critical step for detachment of cell contact during the process of apoptosis.
Genes to Cells 06/2008; 13(7):771-85. · 2.68 Impact Factor
-
Lin Zhao,
Tetsu Yano,
Yutaka Osuga,
Shunsuke Nakagawa,
Hajime Oishi,
Osamu Wada-Hiraike,
Xiaohui Tang,
Naomi Yano, Koji Kugu,
Andrew V Schally,
Yuji Taketani
[show abstract]
[hide abstract]
ABSTRACT: The expression of growth hormone-releasing hormone (GHRH) and its receptors has been demonstrated in peripheral tissues as well as CNS. Recently, the functional splice variant SV1 of GHRH receptor was identified in various human cancers and cancer cell lines. Although antineoplastic activity of GHRH antagonists has been clearly demonstrated, the mechanism of action is incompletely understood. The objective of this study was the investigation of direct anti-proliferative effect of GHRH antagonist MZ-5-156 on HEC-1A human endometrial cancer cell line and the elucidation of underlying mechanisms. RT-PCR revealed the expression of mRNA for GHRH and SV1 of GHRH receptor in HEC-1A cells. MZ-5-156, at concentrations between 10(-7) and 10(-5) M, had a dose-dependent antiproliferative effect on HEC-1A cells, as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, (MTS) assay. Hoechst 33342 staining and flow cytometric analysis indicated that MZ-5-156, at 10(-6) M, induced apoptosis in HEC-1A cells after 48 h of treatment. Western blot analysis of apoptosis-related proteins demonstrated that treatment with MZ-5-156 (10(-6) M) for 48 h significantly increased the protein levels of Fas, phospho-p53 (Ser46), p53AIP1 (p53-regulated Apoptosis-Inducing Protein 1), and caspase-8, -9, and -3, and decreased the protein level of Bcl-2. These results demonstrate that MZ-5-156 can directly inhibit the proliferation of human endometrial cancer cells, which express mRNA for GHRH and SV1 of GHRH receptor, presumably through the induction of p53-dependent apoptosis coupled with the up-regulation of Fas, phospho-p53 (Ser46), p53AIP1, and caspase-8, -9, and -3, and the down-regulation of Bcl-2.
International Journal of Oncology 04/2008; 32(3):593-601. · 2.40 Impact Factor
-
Takeo Minaguchi,
Shunsuke Nakagawa,
Yutaka Takazawa,
Tomomi Nei,
Koji Horie,
Toshihiro Fujiwara,
Yutaka Osuga,
Toshiharu Yasugi, Koji Kugu,
Tetsu Yano,
Hiroyuki Yoshikawa,
Yuji Taketani
[show abstract]
[hide abstract]
ABSTRACT: Young patients with complex atypical hyperplasia (CAH) or stage Ia, G1 adenocarcinoma (IaG1) of the endometrium, who desire to preserve fertility, can select the conservative therapy by oral progestin, medroxyprogesterone acetate (MPA). However, conservative treatments involve potential risks of progression and recurrence. In an attempt to find out molecular markers for sensitivity to MPA, we performed immunohistochemical analysis of PTEN, phospho-Akt, p53, ER and PgR in MPA-treated 31 cases with CAH or IaG1. Eleven of 12 cases (92%) with CAH and 15 of 19 cases (79%) with IaG1 demonstrated an initial complete response, while five patients underwent hysterectomy due to no response. Four of 11 responders (36%) with CAH and five of 15 responders (33%) with IaG1 later developed relapse. Five of nine patients (56%) with CAH and three of 11 patients (27%) with IaG1 became pregnant after infertility treatment. Immunohistochemical analysis revealed that phospho-Akt expression was significantly decreased by MPA administration (p=0.002). Furthermore, combination of two factors, weak phosho-Akt or PTEN-null expression, was found to be significantly associated with receiving hysterectomy (p=0.04), while each factor showed a trend without statistical significance (p=0.07 and 0.2, respectively). Strong expression of both ER and PgR significantly correlated with successful pregnancy after infertility treatment following complete response to MPA (p=0.02). Our observations in vivo suggest that anti-tumor action of MPA may be mediated by dephosphorylation of Akt, and that immunohistochemical evaluation of phospho-Akt and PTEN may be able to predict the outcome of MPA therapy.
Cancer Letters 05/2007; 248(1):112-22. · 4.24 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Aim: Hysterosalpingography (HSG) is one of the most commonly used methods in order to evaluate the condition of fallopian tubes in infertility clinics. In the present paper, we retrospectively compared the findings of HSG and laparoscopy to elucidate the relationship between tubal dysfunction and background factors, such as Chlamydia trachomatis infection, endometriosis and previous surgery.Methods: We retrospectively reviewed clinical records of 314 patients who were examined by both HSG and laparoscopy between 1996 and 2001 in the Department of Obstetrics and Gynecology, University of Tokyo.Results: When HSG findings were evaluated in reference to those of laparoscopy, sensitivity and specificity for tubal patency were 0.63 and 0.79, respectively, whereas those for peri-tubal adhesion were 0.65 and 0.61, respectively. We compared the percentage of existence of background factors between the patients who were diagnosed as normal by both HSG and laparoscopy (Group L[+]) and those whose fallopian tubes were observed as patent by HSG, but were not patent by chromopertubation under laparoscopy (Group L[–]). The percentage of patients with positive chlamydial antibodies in Group L(–) (42.9%, 15/35) was significantly higher than that of patients with positive chlamydial antibodies in Group L(+) (22.8%, 44/193, P < 0.05).Conclusions: These finding suggested that even if HSG showed normally patent tubes in a patient with positive Chlamydia trachomatis antibodies, the possibility of tubal occulusion still remains high and further examination by laparoscopy is recommended. (Reprod Med Biol 2007; 6: 39–43)
Reproductive Medicine and Biology 02/2007; 6(1):39 - 43.
-
Koji Kugu
Nippon rinsho. Japanese journal of clinical medicine 05/2006; 64 Suppl 4:135-40.
-
[show abstract]
[hide abstract]
ABSTRACT: We describe a 37-year-old woman with giant cystic adenomyosis who underwent a hysterectomy, providing magnetic resonance imaging and gross and microscopic images.
Fertility and sterility 04/2006; 85(3):748-9. · 3.97 Impact Factor
-
Chieko Morimoto,
Yutaka Osuga,
Tetsu Yano,
Yuri Takemura,
Miyuki Harada,
Tetsuya Hirata,
Yasushi Hirota,
Osamu Yoshino,
Kaori Koga, Koji Kugu,
Yuji Taketani
[show abstract]
[hide abstract]
ABSTRACT: GnRH II is the second form of GnRH and is widely distributed in peripheral tissues of the female reproductive tract as well as in the central nervous system. In the present study, we studied the possible implication of GnRH II in endometriosis.
Effects of GnRH II on 5-bromo-2'-deoxyuridine (BrdU) uptake by cultured endometriotic stromal cells were examined. Effects of GnRH II on interleukin (IL)-1beta-induced expression of cyclooxygenase (COX)-2 and IL-8 were also studied. mRNA levels of GnRH I, GnRH II, type I GnRH receptor and type II GnRH receptor were determined by real-time quantitative RT-PCR in endometrial tissues of women with or without endometriosis and in endometriotic tissues.
GnRH II dose-dependently suppressed BrdU uptake by endometrial stromal cells. Treatment with IL-1beta markedly increased mRNA levels of COX-2 and IL-8 in endometrial stromal cells and IL-8 protein secretion by these cells, while these increments were significantly suppressed by supplementation with GnRH II. The mRNA levels of GnRH II were lower in endometrial and endometriotic tissues of women with endometriosis than in endometrial tissues of women without endometriosis, both in the proliferative phase and the secretory phase. In addition, as for GnRH I, type I GnRH receptor and type II GnRH receptor, the mRNA levels were lower in endometrial tissues of women with endometriosis than in those without endometriosis in the secretory phase.
In the light of the demonstrated antiproliferative and anti-inflammatory effects of GnRH II on endometrial stromal cells, the lower expression of GnRH II in eutopic and ectopic endometrium of women with endometriosis suggests that endogenous GnRH II-mediated cytostatic regulation may be impaired in the development of endometriosis.
Human Reproduction 12/2005; 20(11):3212-8. · 4.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To report a case of sciatic endometriosis diagnosed by computerized tomography (CT)-guided biopsy in combination with CD10 immunohistochemical staining.
Case report.
University hospital.
A 33-year-old Japanese woman complaining of right-sided sciatica.
Transgluteal computerized tomography (CT)-guided needle biopsy of a mass in the course of the right sciatic nerve was conducted for a histologic diagnosis.
Histologic study with hematoxylin and eosin staining and CD10 immunohistochemical staining was performed.
Computerized tomography-guided biopsy was performed without any complication. CD10 staining distinguished endometrial stromal cells.
Computerized tomography-guided biopsy followed by CD10 immunohistochemical staining is a minimally invasive procedure for accurate diagnosis of sciatic endometriosis.
Fertility and sterility 12/2005; 84(5):1508. · 3.97 Impact Factor
-
Qiumei Chen,
Tetsu Yano,
Hirotaka Matsumi,
Yutaka Osuga,
Naomi Yano,
Jiping Xu,
Osamu Wada,
Kaori Koga,
Toshihiro Fujiwara, Koji Kugu,
Yuji Taketani
[show abstract]
[hide abstract]
ABSTRACT: Recent studies have shown the involvement of Fas/Fas ligand (FasL) system and nitric oxide (NO) in ovarian follicle atresia. Here we asked whether Fas/Fas ligand system interacts with NO using rat granulosa cell culture. Soluble recombinant Fas ligand (rFasL), at 100 ng/ml, significantly decreased cell viability, as measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay, in the presence of 200 U/ml interferon-gamma, whereas the concurrent addition of a caspase inhibitor, Z-VAD-FMK, at 20 microm, significantly inhibited rFasL-induced cytotoxicity. Hoechst 33342 staining and flow cytometric analysis confirmed the induction of apoptosis in granulosa cells by 100 ng/ml rFasL in the presence of interferon-gamma, which was blocked by the concomitant addition of an NO donor, S-nitroso-N-acetylpenicillamine. Western blot analysis demonstrated that rFasL significantly up-regulated caspase-3, -8, and -9 activities in granulosa cells, which were attenuated by concurrent treatment with S-nitroso-N-acetylpenicillamine. Real-time quantitative RT-PCR revealed a significant decrease in inducible NO synthase mRNA levels in rFasL-induced apoptotic granulosa cells. In conclusion, we demonstrated the involvement of Fas/FasL system in inducing apoptosis through activation of a caspase-mediated cascade in rat granulosa cells, which is coupled with a decrease in inducible NO synthase expression. We further showed that NO inhibited Fas/FasL system-induced apoptosis by suppressing activation of the caspases, pointing to a cross-talk between Fas/FasL system-induced apoptosis pathway and NO-mediated antiapoptotic pathway in ovarian follicle atresia.
Endocrinology 03/2005; 146(2):808-15. · 4.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Recent developments in genetic analysis allow determination of the origin of choriocarcinoma (ie, gestational or nongestational), which helps determine the strategy for clinical treatment of the disease.
We present a case of ovarian choriocarcinoma forming a huge ovarian mass 40 days after the patient's last menstrual period. Deoxyribonucleic acid microsatellite analysis of the tumor revealed that it contained a single maternal and two paternal alleles at several independent loci, consistent with the tumor resulting from ovarian pregnancy of a partial hydatidiform mole.
This is the first description of an ovarian pregnancy of a partial hydatidiform mole-derived ovarian choriocarcinoma.
Obstetrics and Gynecology 12/2003; 102(5 Pt 1):991-4. · 4.73 Impact Factor
-
Osamu Yoshino,
Yutaka Osuga,
Kaori Koga,
Yasushi Hirota,
Tetsu Yano,
Osamu Tsutsumi,
Akihisa Fujimoto, Koji Kugu,
Mikio Momoeda,
Toshihiro Fujiwara,
Yuji Taketani
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the effect of hypoxia on interleukin (IL)-8 expression in human ovarian follicles.
Follicular fluid (FF) from each follicle was separately collected from women undergoing in vitro fertilization and embryo transfer. Concentrations of oxygen, progesterone, estradiol, IL-1alpha/beta, IL-8, and tumor necrosis factor (TNF)-alpha in FF were measured. Isolated granulosa-lutein cells (GLC) from obtained FF were cultured under normoxic or hypoxic conditions, and concentrations of IL-8 in culture media were measured.
Simple regression analysis demonstrated a significant negative correlation between the concentrations of IL-8 and oxygen in FF (r = 0.50, P < 0.0001). However, none of the concentrations of progesterone, estradiol, IL-1beta, and TNF-alpha in FF showed a significant correlation with IL-8 concentrations. Hypoxia stimulated the secretion of IL-8 by cultured GLC over twofolds compared with a normoxic control (P < 0.05).
These findings suggest that IL-8, like other angiogenic factors, is upregulated under hypoxic condition, which argues that hypoxia in the ovarian follicles comes into play in ovarian functions by inducing a range of proangiogenic and chemoattractive substances.
American journal of reproductive immunology (New York, N.Y.: 1989) 11/2003; 50(4):286-90. · 3.05 Impact Factor
-
Osamu Yoshino,
Yutaka Osuga,
Kaori Koga,
Yasushi Hirota,
Osamu Tsutsumi,
Tetsu Yano,
Yutaka Morita,
Mikio Momoeda,
Toshihiro Fujiwara, Koji Kugu,
Yuji Taketani
[show abstract]
[hide abstract]
ABSTRACT: To assess whether interferon-gamma-induced protein-10 (IP-10), a chemokine that has antiangiogenic activities, may be involved in the pathogenesis of endometriosis.
A total of 120 patients undergoing laparoscopy for pain and/or infertility were recruited, and peritoneal fluid (PF) and bone marrow derived cells in PF were collected. Concentrations of IP-10 in PF were measured with a specific enzyme-linked immunosorbent assay. Expression of IP-10 and IP-10 receptor, CXCR3, in bone marrow derived cells in PF, peritoneum and endometriotic cells was analyzed by reverse transcription-polymerase chain reaction.
All of the PF samples examined contained detectable concentrations of IP-10. In women with advanced stages of endometriosis, IP-10 concentrations in PF were significantly lower than those of women in early stages (P = 0.02). The IP-10 concentrations in women with advanced endometriosis also appeared to be lower than those without endometriosis although the difference was statistically marginal (P = 0.06). The expression of both IP-10 and CXCR3 was clearly detected in the bone marrow derived cells in PF, peritoneum and endometriotic stromal cells.
Decreased concentrations of IP-10 in PF from women with advanced stages of endometriosis may imply that the peritoneal environment of these women is permissive to the development of the disease by enhancing angiogenesis and/or modulating inflammatory/immunological responses.
American journal of reproductive immunology (New York, N.Y.: 1989) 08/2003; 50(1):60-5. · 3.05 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the usefulness of transvaginal and transrectal ultrasonography for diagnosis and management of deeply infiltrating rectosigmoid endometriosis.
A series of six patients (aged 32-39 years) with rectosigmoid endometriosis underwent transvaginal and transrectal ultrasonography. In three patients undergoing surgical resection of the intestine, the ultrasonographic findings were compared with macroscopic and microscopic findings. In one patient, sequential observations of the lesion using ultrasonography were conducted before and after medical treatment and following childbirth.
In all cases, the lesion was detected as a hypoechoic irregular-shaped area surrounded by a hyperechoic rim located posterior to the uterus, with size ranging from 18 x 17 to 29 x 28 mm in diameter. The comparison of the ultrasonographical findings with histology revealed that the hypoechoic irregular-shaped area corresponded to a layer of hypertrophic muscularis propria of the lesion, while the hyperechoic rim represented the layer including the mucosa, submucosa and serosa. In one patient, the lesion decreased in size and lost its central hypoechoic area after childbirth in association with pain relief.
Transvaginal and transrectal ultrasonography provides characteristic appearances for rectosigmoid endometriosis that correlate well with its histological findings. The procedures would be useful in the management of rectosigmoid endometriosis.
Human Reproduction 07/2003; 18(6):1328-33. · 4.47 Impact Factor
-
Akihisa Fujimoto,
Yutaka Osuga,
Toshihiro Fujiwara,
Tetsu Yano,
Osamu Tsutsumi,
Mikio Momoeda, Koji Kugu,
Kaori Koga,
Yutaka Morita,
Osamu Wada,
Yuji Taketani
[show abstract]
[hide abstract]
ABSTRACT: To investigate how late-midluteal estradiol levels relate to the pregnancy outcome in IVF cycles, and to assess whether human chorionic gonadotropin (hCG) for luteal support benefits the pregnancy outcome of patients with low late-midluteal estradiol levels.
The pregnancy rate of 436 women undergoing first IVF cycles with long protocol and luteal support with progesterone alone were analyzed. Unsuccessful women with low late-midluteal estradiol levels (< 100 pg/mL) proceeded with the exploratory second IVF cycles where they were randomly given with either progesterone alone (P protocol) or hCG +progesterone (P+hCG protocol) for luteal support.
Pregnancy rate in women with low late-midluteal estradiol levels was significantly lower compared to that with medium (100-500 pg/mL) and high (> 500 pg/mL) levels (13.3, 26.8, and 36.3%, respectively). P+hCG protocol increased late-midluteal estradiol levels and produced a significantly higher pregnancy rate (31.7%) than P protocol (13.7%).
hCG in combination with progesterone for luteal support was suggested to benefit women undergoing IVF with low late-midluteal estradiol levels.
Journal of Assisted Reproduction and Genetics 12/2002; 19(12):550-4. · 1.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The sentinel node biopsy has been established as a standard procedure in many types of cancer. To date, only one case was reported for successful detection of the sentinel node using a radiopharmaceutical-directed mapping technique in malignant melanoma of the vagina.
An 81-year-old woman developed malignant melanoma arising from the lower third of the vagina. She underwent local resection of the tumor and exploration of the sentinel node using blue dye. The sentinel node was detected successfully in the groin, and was negative for metastasis. Intra-cavity irradiation was given as an adjuvant therapy.
In view of relative ease and minimal trauma, sentinel node mapping could be a routine procedure in malignant melanoma arising from the vagina or vulva.
Gynecologic Oncology 10/2002; 86(3):387-9. · 3.89 Impact Factor
-
Xiaohui Tang,
Tetsu Yano,
Yutaka Osuga,
Hirotaka Matsumi,
Naomi Yano,
Jiping Xu,
Osamu Wada,
Kaori Koga, Koji Kugu,
Osamu Tsutsumi,
Andrew V Schally,
Yuji Taketani
[show abstract]
[hide abstract]
ABSTRACT: We investigated the direct effects of LH-releasing hormone (LH-RH) antagonist, Cetrorelix, on the growth of HTOA human epithelial ovarian cancer cell line. RT-PCR revealed the expression of mRNA for LH-RH and its receptor in HTOA cells. Cetrorelix, at concentrations between 10(-9) and 10(-5) M, exerted a dose-dependent antiproliferative action on HTOA cells, as measured by 5-bromo-2'-deoxyuridine incorporation into DNA. Flow cytometric analysis indicated that Cetrorelix, at 10(-5) M, arrested cell cycle in HTOA cells, at G1 phase, after 24 h of treatment. Western blot analysis of cell cycle-regulatory proteins demonstrated that treatment with Cetrorelix (10(-5) M) for 24 h did not change the steady-state levels of cyclin D1, cyclin E, and cyclin-dependent kinase (Cdk)4 but decreased the levels of cyclin A and Cdk2. The protein levels of p21 (a Cdk inhibitor) and p53 (a suppressor of tumor cell growth and a positive regulator for p21 expression) were increased by Cetrorelix, but the levels of p27 (a Cdk inhibitor) did not change significantly. Flow cytometric analysis and terminal deoxynucleotidyltransferase-mediated deoxyuridine 5-triphosphate nick end labeling staining demonstrated that Cetrorelix (10(-5) M) induced apoptosis in HTOA cells. In conclusion, Cetrorelix directly inhibits the proliferation of human epithelial ovarian cancer cells through mechanisms mediated by LH-RH receptor and involving multiple events in cell cycle progression, including G1 phase cell cycle arrest coupled with down-regulation of cyclin A-Cdk2 complex levels, presumably attributable to an up-regulation of p53 and p21 protein levels and apoptosis.
Journal of Clinical Endocrinology & Metabolism 09/2002; 87(8):3721-7. · 6.50 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Endometriosis is assumed to be one of the causative factors of infertility, although the mechanism remains to be elucidated. Mechanical factors distorting the pelvic anatomy and/or changes in the biochemical and cellular environment in the peritoneal cavity are possible contributing factors impairing fertility. Laparoscopy is a widely used diagnostic and therapeutic means of treating endometriosis-associated infertility. However, pregnancy outcome after laparoscopy varies depending on preexisting tubal adhesions and endometriosis. Without tubal adhesions, the pregnancy rate is essentially the same irrespective of the presence or stages of endoemetriosis. Minimal/mild endometriosis benefited the most from laparoscopic manipulation when tubal adhesions were present. On the other hand, IVF-ET outcome of patients who previously underwent laparoscopy was not influenced by preexisiting tubal adhesions and endometriosis.
Gynecologic and Obstetric Investigation 02/2002; 53 Suppl 1:33-9. · 1.28 Impact Factor
