Shingo Miyamoto

St.Mary's Hospital (Fukuoka - Japan), Hukuoka, Fukuoka, Japan

Are you Shingo Miyamoto?

Claim your profile

Publications (104)293.83 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: It can be difficult to differentiate diffuse malignant peritoneal mesothelioma (DMPM) from reactive mesothelial hyperplasia (RMH) or peritoneal dissemination of gynecologic malignancies, such as epithelial ovarian cancer (EOC), which cause a large amount of ascites. Detection of the homozygous deletion of p16/CDKN2A (p16) by fluorescence in situ hybridization (FISH) is an effective adjunct in the diagnosis of malignant pleural mesothelioma. The aim of this study was to investigate the ability of the p16 FISH assay to differentiate DMPM from RMH and EOC. p16 FISH was performed in 28 DMPMs (successful in 19), 30 RMHs, and 40 EOC cases. The cutoff values of p16 FISH were more than 10% for homozygous deletion and more than 40% for heterozygous deletion. According to the above criteria, nine (47.4%) of 19 successful DMPM cases were homozygous deletion positive, and three (15.8%) of 19 were heterozygous deletion positive, whereas all RMH cases were negative for the p16 deletion. In all four major histologic subtypes of EOC, neither p16 homozygous nor heterozygous deletions were detected. To differentiate DMPM from RMH or EOC, the sensitivity of the p16 homozygous deletion was 32% (9/28), and the specificity was 100%. Our study suggests that p16 FISH analysis is useful in differentiating DMPM from RMH and EOC when homozygous deletion is detected. Copyright© by the American Society for Clinical Pathology.
    American Journal of Clinical Pathology 06/2015; 143(6):830-8. DOI:10.1309/AJCPOATJ9L4GCGDA · 3.01 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Colorectal cancer (CRC) is one of the most frequently occurring cancers with high morbidity and mortality worldwide. Amphiregulin (AREG), a member of the epidermal growth factor family and a rational target for CRC therapy, is essential for the three-dimensional structure of tumor formation. To clone the genes associated with increased AREG expression, we performed a cDNA microarray analysis in two CRC cell lines undergoing two-dimensional (2DC) and three-dimensional culture (3DC). Upregulated (>2.0-fold) and downregulated (<0.5-fold) genes in 3DC compared with 2DC were selected. Pathway analysis using DAVID based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases revealed a number of genes involved in glycolysis. In CRC cells, glucose elevated the expression of GLUT1 and AREG as well as the activity of the hypoxia-inducible factor 1 (HIF-1) luciferase reporter promoter. The suppression of AREG expression reduced the uptake of glucose and production of lactate. Luciferase assay identified a critical regulatory region for AREG expression between −130 and −180 bp upstream of the start site, which contained a carbohydrate response element (ChoRE). Max-like protein X (MLX) bound to ChoRE and enhanced the expression of AREG. Together these data suggest that AREG plays a pivotal role in the development of CRC through activation of the Warburg effect.
    Cancer Medicine 01/2015; 4(4). DOI:10.1002/cam4.416
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ovarian clear cell carcinoma (OCCC) is a worst histological subtype than other ovarian malignant tumor. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a promising target for ovarian cancer therapy. The aims of this study were to validate the efficacy of HB-EGF–targeted therapy for OCCC and to identify the transcription factor that contributed to the induction of HB-EGF by SN38 treatment in OCCC cells. HB-EGF was highly expressed in OCCC cells, and an increase of HB-EGF was induced by SN38 which had only antitumor effect among conventional anticancer agents on OCCC. A specific inhibitor of HB-EGF, a cross-reacting material 197 (CRM197), led to a synergistic increase in the number of apoptotic OCCC cells with the treatment of SN38. The luciferase assay with 5′-deletion promoter constructs identified a GC-rich element between −125 and −178 (the distal transcription start site was denoted +1) as a cis-regulatory region, and the treatment of SN38 induced luciferase activity in this region. An in silico and chromatin immunoprecipitation analysis estimated that SP1 bound to the cis-regulatory region of HB-EGF in OCCC cells. Real-time PCR and cell viability assays showed that the transfection of a small interfering RNA targeting SP1 suppressed the expression of HB-EGF induced by SN38, resulting in the enhanced sensitivity of SN38. Taken together, these results indicate that induction of HB-EGF expression contributed to defense mechanism against treatment of SN38 through the transcriptional activity of SP1 in OCCC cells.
    Cancer Medicine 10/2014; 3(5). DOI:10.1002/cam4.301
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although DNA methylation is considered to play an important role during myogenic differentiation, chronological alterations in DNA methylation and gene expression patterns in this process have been poorly understood. Using the Infinium HumanMethylation450 BeadChip array, we obtained a chronological profile of the genome-wide DNA methylation status in a human myoblast differentiation model, where myoblasts were cultured in low-serum medium to stimulate myogenic differentiation. As the differentiation of the myoblasts proceeded, their global DNA methylation level increased and their methylation patterns became more distinct from those of mesenchymal stem cells and skeletal muscle tissues. Gene ontology analysis revealed that genes whose promoter region was hypermethylated upon myoblast differentiation were highly significantly enriched with muscle-related terms such as "muscle contraction" and "muscle system process." Sequence motif analysis identified 8-bp motifs somewhat similar to the binding motifs of ID4 and ZNF238 to be most significantly enriched in hypermethylated promoter regions. ID4 and ZNF238 have been shown to be critical transcriptional regulators of muscle-related genes during myogenic differentiation. An integrated analysis of DNA methylation and gene expression profiles revealed that de novo DNA methylation of non-CpG island (CGI) promoters was more often associated with transcriptional down-regulation than that of CGI promoters. These results strongly suggest the existence of an epigenetic mechanism in which DNA methylation modulates the functions of key transcriptional factors to coordinately regulate muscle-related genes during myogenic differentiation.
    Human Molecular Genetics 09/2014; DOI:10.1093/hmg/ddu457 · 6.68 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective This retrospective study aimed to determine the predictive factors for the efficacy of pelvic arterial embolization for postpartum hemorrhage. Materials and methods Twenty-one patients who underwent pelvic arterial embolization for postpartum hemorrhage of >1000 mL between September 2006 and September 2011 were enrolled in this study. The patients were divided into two subgroups according to the blood loss and time from the end of pelvic arterial embolization to complete hemostasis: good-response (16 patients) and poor-response groups (5 patients). The following predictive factors were compared between the groups: (1) patient characteristics; (2) blood loss; (3) time between delivery (or onset of bleeding) and pelvic arterial embolization; (4) obstetrical disseminated intravascular coagulation score comprising clinical background, clinical signs, and laboratory data; (5) individual disseminated intravascular coagulation score; (6) shock index; and (7) laboratory data including platelet count, prothrombin time-international normalized ratio, fibrinogen, fibrin degradation products, and antithrombin-III at the time of pelvic arterial embolization. Results In the poor-response group, the obstetrical and individual disseminated intravascular coagulation scores and prothrombin time-international normalized ratio were higher than those in the good-response group (p < 0.05). Platelet count, fibrinogen, and fibrin degradation products were lower than those in the good-response group (p < 0.05). All obstetrical disseminated intravascular coagulation scores in the poor-response group were >9 points. Conclusion The efficacy of pelvic arterial embolization is related to the presence or absence of coagulation disorders. When the obstetrical disseminated intravascular coagulation score is high (>9 points), the efficacy may be poor.
    Taiwanese Journal of Obstetrics and Gynecology 09/2014; 53(3):366–371. DOI:10.1016/j.tjog.2013.04.043 · 1.26 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We report the first case of the successful detection of postpartum unruptured vaginal pseudoaneurysm using power- and pulsed-Doppler ultrasonography after delivery.
    SpringerPlus 08/2014; 3:482. DOI:10.1186/2193-1801-3-482
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heparin-binding epidermal growth factor-like growth factor (HB-EGF), a member of the epidermal growth factor family, is a target for ovarian cancer therapy. The present study investigated the administration schedule of BK-UM, an anticancer agent targeting HB-EGF.
    Anticancer research 08/2014; 34(8):4615-20. · 1.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The patient was a 76-year-old female with a chief complaint of sudden abdominal pain. She was subsequently transferred to another hospital due to acute abdomen. She was suspected to have superior mesenteric artery embolism based on the findings of enhanced abdominal computed tomography (CT). Reexamination of the CT scans showed ascites and enlargement of the uterus with wall thickening. The patient was transferred to our center due to suspected perforative pyometra. Under a diagnosis of perforative pyometra, abdominal total hysterectomy was performed, which revealed an intrauterine device (IUD) in the uterine according to the pathological findings. The IUD was believed to have caused the patient’s perforative pyometra. Her general condition improved, and she was moved to the Gynecology Department on day 9 after the surgery. Differentiating perforative pyometra from lower intestinal perforation is sometimes difficult. Focusing on the observed low-density area which was associated with the gas image in the uterine cavity based on the findings of a CT scan, it is therefore important to make an accurate and definitive diagnosis preoperatively in the case of this disease. Furthermore, it should be carefully taken into consideration that an IUD can cause a perforated pyometra.
    Nihon Kyukyu Igakukai Zasshi 01/2014; 25(9):729-733. DOI:10.3893/jjaam.25.729
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recently developed transcription activator-like effector nuclease (TALEN) technology has enabled the creation of knockout mice, even for genes on the Y chromosome. In this study, we generated a knockout mouse for Sry, a sex-determining gene on the Y chromosome, using microinjection of TALEN RNA into pronuclear stage oocytes. As expected, the knockout mouse had female external and internal genitalia, a female level of blood testosterone and a female sexually dimorphic nucleus in the brain. The knockout mouse exhibited an estrous cycle and performed copulatory behavior as females, although it was infertile or had reduced fertility. A histological analysis showed that the ovary of the knockout mouse displayed a reduced number of oocytes and luteinized unruptured follicles, implying that a reduced number of ovulated oocytes is a possible reason for infertility and/or reduced fertility in the KO mouse.
    Scientific Reports 11/2013; 3:3136. DOI:10.1038/srep03136 · 5.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The majority of human tumors display a high rate of glycolysis under aerobic conditions. This phenomenon was recognized approximately seven decades ago and is known as the Warburg effect. Several key enzymes required to maintain this high level of glucose metabolism are found in tumor cells. The effects of the glycolytic enzymes are known to be directly or indirectly regulated by various signaling pathways, oncogenes, suppressor genes and transcription factors. Recent molecular biology studies have shown that multiple genetic alterations are related to tumor development. Therefore, these factors may be rational targets for cancer therapy. In this short review, we describe several important molecules that affect aerobic glycolysis and discuss their possible use as therapeutic targets for cancer.
    Anticancer research 07/2013; 33(7):2855-60. · 1.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report anesthetic management of a 38-year-old woman with pulmonary thromboembolism for total hysterectomy. She had been taking oral contraceptives for adenomyosis of the uterus. She had thrombi in the arteries from pulmonary trunk to bilateral main pulmonary arteries. Thrombolytic and anticoagulant therapies did not decrease the thrombi. Removal of the swollen uterus suspected to be the origin of the thrombi, rather than thromboembolectomy, was scheduled. Cannulation for percutaneous cardiopulmonary support was set up just in case of hemodynamic derangement, before the surgery. Cardiac contraction was evaluated with transesophageal echocardiography during the surgery. There was no untoward perioperative event. Pulmonary thromboembolectomy was not done because the postoperative CT revealed shrinkage of the pulmonary thrombi after anticoagulation treatment.
    Masui. The Japanese journal of anesthesiology 06/2013; 62(6):696-8.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is one of several pro-angiogenic factors, and represents a possible therapeutic target for patients with triple-negative breast cancer (TNBC). However, the role of HB-EGF in promoting tumor aggressiveness in TNBC remains unclear. In order to investigate specific genes and pathways involved in TNBC tumorigenesis, we profiled gene expression changes in two TNBC cell lines under two-dimensional culture (2DC) and three-dimensional culture (3DC) and in a tumor xenograft model. We identified simultaneous upregulation of HB-EGF, vascular endothelial growth factor A (VEGFA) and angiopoietin-like 4 (ANGPTL4) in 3DC and tumor xenografts, compared with 2DC. We show that HB-EGF regulates the expression of VEGFA or ANGPTL4 via transcriptional regulation of hypoxia inducible factor-1 alpha and nuclear factor kappa B. Furthermore, suppression of VEGFA or ANGPTL4 expression enhanced HB-EGF expression, highlighting a unique regulatory loop underlying this angiogenesis network. Targeted knockdown of HB-EGF significantly suppressed tumor formation in a TNBC xenograft model, compared with individual knockdown of either VEGFA or ANGPTL4, by reducing the expression of both VEGFA and ANGPTL4. In patients with TNBC, VEGFA or ANGPTL4 expression was also significantly correlated with HB-EGF expression. Low concentrations of exogenously added HB-EGF strongly activated the proliferation of endothelial cells, tube formation and vascular permeability in blood vessels, in a similar fashion to high doses of VEGFA and ANGPTL4. Taken together, these results suggest that HB-EGF plays a pivotal role in the acquisition of tumor aggressiveness in TNBC by orchestrating a molecular hierarchy regulating tumor angiogenesis.
    Molecular Cancer Research 02/2013; 11(5). DOI:10.1158/1541-7786.MCR-12-0428 · 4.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acute pulmonary thromboembolism (PTE) is a common illness that causes death and disability. Deep vein thrombosis (DVT) is often found in patients with a large myomatous uterus, and can occasionally result in acute PTE. Here, we describe the achievement of a favorable outcome in a case of acute PTE. The patient presented with acute PTE caused by a large uterine leiomyoma, without DVT of the lower extremities. Percutaneous cardiopulmonary support (PCPS) was used as an adjunct to thrombolytic therapy to treat the right ventricular thrombus with acute PTE. According to emergency practice, PCPS was initiated, and the patient was successfully treated with thrombolytic and anticoagulant therapy associated with total abdominal hysterectomy. This case suggests that PCPS can lead to favorable clinical outcomes in patients with large uterine leiomyomata and severe PTE.
    Taiwanese journal of obstetrics & gynecology 12/2012; 51(4):639-42. DOI:10.1016/j.tjog.2012.09.023 · 1.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose To evaluate the accuracy of prenatal diagnosis of congenital heart defect at the referral level in our institution. Methods One hundred and thirty-two cases were referred for prenatal diagnosis of congenital heart defect (CHD). Cases having CHDs were divided into isolated and complex CHDs, and the prenatal and postnatal diagnoses were compared. Results Thirty-nine cases were diagnosed with CHDs. The remaining 93 cases were diagnosed as normal. Postnatal diagnosis confirmed that 39 cases had CHDs; there were 19 cases of isolated CHD and 20 cases of complex CHD. Among the 19 cases of isolated CHD, all four cases with a false negative diagnosis had ventricular septal defects of an outlet or muscular type with a small defect. Cases with a false positive diagnosis had coarctation of the aorta (3 cases) or total anomalous pulmonary venous connection (1 case). Among the 20 cases of complex CHD, the prenatal diagnoses in two cases were not the same as the postnatal diagnosis and the prognosis was worse than expected. In one case with a single ventricle, pulmonary stenosis, and pulmonary venous atresia, the prenatal diagnosis was hypoplastic left heart syndrome with a suboptimal study at 38 weeks’ gestation. In the other case, the diagnosis of corrected transposition of the great arteries had been missed because of misinterpretation of the anatomically right and left ventricles in utero. Conclusions There were three possible causes of misdiagnosis or overdiagnosis of CHD: disease orientation, timing of diagnosis, and skill of the examiners. This information may be helpful for the improvement of diagnosis.
    Journal of Medical Ultrasonics 10/2012; 39(4):235-240. DOI:10.1007/s10396-012-0362-y · 0.74 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Emmprin is a transmembrane glycoprotein known as a matrix metalloproteinase inducer and is highly up-regulated in malignant cancer cells. The monocarboxylate transporters (MCTs) are responsible for H(+)-linked transport of monocarboxylates across the cell membrane. It was recently demonstrated that proper plasma membrane localization and activity of MCTs require the presence of emmprin as a chaperone and that MCT-1 also acts as chaperone for emmprin. The objectives of this study were to clarify emmprin and MCT-1 expression patterns in ovarian epithelial tumors and to elucidate the clinicopathological significance of co-localization of the two molecules. Immunohistochemical analysis of 205 epithelial tumors indicated that emmprin is always localized in cell membranes but its distribution differs according to tumor type: in lateral membranes in 89 % of adenomas, in lateral and basal membranes in 76 % of borderline tumors, and in membranes surrounding the entire cell in 98 % of carcinomas. Most carcinomas in situ also showed a lateral and basal expression pattern. In only 21 % of the carcinomas, the cells expressing membranous MCT-1 showed co-localized emmprin expression. Poor co-localization of the two molecules was more frequently found in serous carcinomas. However, the overall survival was not significantly different for the good and poor co-localization carcinoma groups. These findings indicate that the emmprin expression pattern might discriminate between invasive carcinomas and borderline tumors including carcinoma in situ. Moreover, there may be an as yet unidentified regulatory mechanism(s), for localization of MCT-1 and emmprin in cell membranes in vivo.
    Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 08/2012; 461(4):457-66. DOI:10.1007/s00428-012-1302-3 · 2.56 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We previously established a three-dimensional (3-D) colonic crypt model using HKe3 cells which are human colorectal cancer (CRC) HCT116 cells with a disruption in oncogenic KRAS, and revealed the crucial roles of oncogenic KRAS both in inhibition of apoptosis and in disruption of cell polarity; however, the molecular mechanism of KRAS-induced these 3-D specific biological changes remains to be elucidated. Among the genes that were upregulated by oncogenic KRAS in this model, we focused on the phosphodiesterase 4B (PDE4B) of which expression levels were found to be higher in clinical tumor samples from CRC patients in comparison to those from healthy control in the public datasets of gene expression analysis. PDE4B2 was specifically overexpressed among other PDE4 isoforms, and re-expression of oncogenic KRAS in HKe3 cells resulted in PDE4B overexpression. Furthermore, the inhibition of PDE4 catalytic activity using rolipram reverted the disorganization of HCT116 cells into the normal physiologic state of the epithelial cell polarity by inducing the apical assembly of ZO-1 (a tight junction marker) and E-cadherin (an adherens junction marker) and by increasing the activity of caspase-3 (an apoptosis marker) in luminal cavities. Notably, rolipram reduced the AKT phosphorylation, which is known to be associated with the disruption of luminal cavity formation and CRC development. Similar results were also obtained using PDE4B2-shRNAs. In addition, increased expression of PDE4B mRNA was found to be correlated with relapsed CRC in a public datasets of gene expression analysis. These results collectively suggested that PDE4B is upregulated by oncogenic KRAS, and also that the inhibition of PDE4 catalytic activity can induce both epithelial cell polarity and luminal apoptosis in CRC, thus highlighting the utility of our 3-D culture (3 DC) model for the KRAS-induced development of CRC in 3-D microenvironment. Indeed, using this model, we found that PDE4B is a promising candidate for a therapeutic target as well as prognostic molecular marker in CRC. Further elucidation of the signaling network of PDE4B2 in 3 DC would provide a better understanding of CRC in vivo.
    Molecular Cancer 07/2012; 11:46. DOI:10.1186/1476-4598-11-46 · 5.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heparin binding epidermal growth factor-like growth factor (HB-EGF) is involved in development and homeostasis as well as in pathological processing of chronic diseases, especially cancer. Enhancement of HB-EGF expression is directly or indirectly regulated by transcriptional factors, including activator protein-1 (AP-1), specificity protein (SP)1, SP3, nuclear factor kappa B (NF-κB), hypoxia inducible factor 1, alpha subunit (HIF-1α, myogenic differentiation 1 (MyoD), Wilms tumor 1 (WT-1) and snail homolog 1 (Snail), and also by microRNAs. These transcription or post-transcription factors may communicate to form an autocrine HB-EGF amplification loop. Emerging evidence has indicated that HB-EGF is a rational target for the therapy of cancer and atherosclerosis. In this review, we discuss the relationship between the HB-EGF autocrine loop and HB-EGF transcriptional factors, and we highlight HB-EGF as a therapeutic target in diverse diseases.
    Anticancer research 06/2012; 32(6):2347-52. · 1.87 Impact Factor
  • Article: Preface.
    Anticancer research 06/2012; 32(6):2225. · 1.87 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We previously found that oncogenic KRAS induces increased expression of microRNAs (miRNAs), such as miR-200c and miR-221/222, in human colorectal cancer (CRC) HCT116 cells in a three-dimensional (3D)-specific manner, however, the regulation of miRNA expression through oncogenic KRAS in other types of CRC remains unclear. The differential expression of 94 cancer-related miRNAs was examined in DLD-1 and DKO-4 cells (DLD-1 cells with a disrupted oncogenic KRAS) in 3D cultures. Increased miR-15b, miR-16, miR-23a, miR-24, miR-103 and miR-222 expression was observed in 3D and in 2D cultures. Of note, increased miR-181a, miR-200c and miR-210 expression was only observed in 3D cultures. Furthermore, miR-181a and miR-210 were significantly overexpressed in DLD-1 cells in 3D culture compared with those in HCT116 cells, and were significantly overexpressed in human CRC specimens. Oncogenic KRAS regulates 3D-specific miRNAs that are possibly associated with CRC development in vivo.
    Anticancer research 06/2012; 32(6):2271-5. · 1.87 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The management of malignant ascites is critical for the treatment of patients with advanced gynecological cancer. The purpose of this study was to assess the clinical significance of cell-free and concentrated ascites re-infusion therapy (CART). Adverse events, alterations in Eastern Cooperative Oncology Group performance status, serum albumin, body weight and abdominal circumference, and overall survival were examined in 22 patients with advanced gynecological cancer which were treated with CART. Most of the adverse events were grade 1 or 2 fever. CART treatment had little effect on ECOG performance status and on levels of serum albumin. There was a significant decrease in body weight and in abdominal circumference post-treatment with CART, relative to pre-treatment (p<0.01). The overall survival rate was significantly prolonged in 14 patients after CART plus chemotherapy, as compared with eight patients after CART alone (p<0.01). CART may contribute to the improvement of quality of life and of survival in patients with advanced gynecological cancer.
    Anticancer research 06/2012; 32(6):2353-7. · 1.87 Impact Factor

Publication Stats

1k Citations
293.83 Total Impact Points

Institutions

  • 2008–2015
    • St.Mary's Hospital (Fukuoka - Japan)
      Hukuoka, Fukuoka, Japan
  • 2006–2015
    • Fukuoka University
      • • Department of Obstetrics and Gynecology
      • • Department of Biochemistry
      Hukuoka, Fukuoka, Japan
  • 1989–2009
    • Kyushu University
      • • Department of Obstetrics and Gynecology
      • • Medical Institute of Bioregulation - MIB Hospital
      Fukuoka-shi, Fukuoka-ken, Japan
  • 2001
    • National Cancer Center, Japan
      Edo, Tōkyō, Japan
  • 2000
    • National Hospital Organization Kyushu Cancer Center
      Hukuoka, Fukuoka, Japan
  • 1995
    • Kagoshima University
      • Department of Obstetrics and Gynecology
      Kagosima, Kagoshima, Japan