A Naturally Occurring Lgr4 Splice Variant Encodes a Soluble Antagonist Useful for Demonstrating the Gonadal Roles of Lgr4 in Mammals
Pei-Jen Hsu, Fang-Ju Wu, Masataka Kudo, Chih-Lun Hsiao, Aaron J. W. Hsueh, Ching-Wei Luo
PLOS ONE, 9, 9, e106804, PUBLIC LIBRARY SCIENCE, 2014年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Leucine-rich repeat containing G protein-coupled receptor 4 (LGR4) promotes the Wnt signaling through interaction with R-spondins or norrin. Using PCR amplification from rat ovarian cDNAs, we identified a naturally occurring Lgr4 splice variant encoding only the ectodomain of Lgr4, which was named Lgr4-ED. Lgr4-ED can be detected as a secreted protein in the extracts from rodent and bovine postnatal gonads, suggesting conservation of Lgr4-ED in mammals. Recombinant Lgr4-ED purified from the conditioned media of transfected 293T cells was found to dose-dependently inhibit the LGR4-mediated Wnt signaling induced by RSPO2 or norrin, suggesting that it is capable of ligand absorption and could have a potential role as an antagonist. Intraperitoneal injection of purified recombinant Lgr4-ED into newborn mice was found to significantly decrease the testicular expression of estrogen receptor alpha and aquaporin 1, which is similar to the phenotype found in Lgr4-null mice. Administration of recombinant Lgr4-ED to superovulated female rats can also decrease the expression of estrogen receptor alpha, aquaporin 1, LH receptor and other key steroidogenic genes as well as bring about the suppression of progesterone production. Thus, these findings suggest that endogenously expressed Lgr4-ED may act as an antagonist molecule and help to fine-tune the R-spondin/norrin-mediated Lgr4-Wnt signaling during gonadal development.

Distribution of Lymph Node Metastasis Sites in Endometrial Cancer Undergoing Systematic Pelvic and Para-Aortic Lymphadenectomy: A Proposal of Optimal Lymphadenectomy for Future Clinical Trials
Tetsuji Odagiri, Hidemichi Watari, Tatsuya Kato, Takashi Mitamura, Masayoshi Hosaka, Satoko Sudo, Mahito Takeda, Noriko Kobayashi, Peixin Dong, Yukiharu Todo, Masataka Kudo, Noriaki Sakuragi
ANNALS OF SURGICAL ONCOLOGY, 21, 8, 2755, 2761, SPRINGER, 2014年08月, ［査読有り］
英語, 研究論文（学術雑誌）, The aim of this study was to demonstrate the precise mapping of lymph node metastasis (LNM) sites in endometrial cancer.A total of 266 patients who underwent primary radical surgery including systematic pelvic and para-aortic lymphadenectomy for endometrial cancer from 1993 to 2010 were enrolled in this study. We removed lymph nodes from the femoral ring to the para-aortic node up to the level of renal veins. We analyzed the distribution of positive-node sites according to their anatomical location.Overall, 42 of 266 patients (15.8 %) showed LNM. The median number of nodes harvested was 62.5 (range 40-119) in pelvic nodes (PLN), and 20 (range 3-47) in para-aortic nodes (PAN). Among 42 cases with positive-nodes, 16 cases (38.1 %) showed positive PLN alone, 7 cases (16.7 %) in PAN alone, and 19 cases (45.2 %) in both PLN and PAN. The most prevalent site of positive-nodes was PAN (9.8 %) followed by obturator nodes (9.4 %), internal iliac nodes (7.1 %), and common iliac nodes (5.6 %). Six of 19 cases (31.6 %) of positive PAN above the inferior mesenteric artery (IMA) showed negative PAN below IMA. Metastasis to the deep inguinal nodes was found to be extremely rare (0.38 %). Single-site LNM was the most frequently observed in obturator nodes, followed by PAN above IMA.Routine resection of deep inguinal nodes is not recommended, whereas para-aortic lymphadenectomy should be extended up to the level of renal veins for endometrial cancer.

MicroRNA-101 targets EZH2, MCL-1 and FOS to suppress proliferation, invasion and stem cell-like phenotype of aggressive endometrial cancer cells
Yosuke Konno, Peixin Dong, Ying Xiong, Fumihiko Suzuki, Jiabin Lu, Muyan Cai, Hidemichi Watari, Takashi Mitamura, Masayoshi Hosaka, Sharon J. B. Hanley, Masataka Kudo, Noriaki Sakuragi
ONCOTARGET, 5, 15, 6049, 6062, IMPACT JOURNALS LLC, 2014年08月, ［査読有り］
英語, 研究論文（学術雑誌）, MicroRNA-101 has been implicated as a tumor suppressor miRNA in human tumors. However, its potential functional impact and the underlying mechanisms in endometrial cancer progression have not been determined. Here, we report that in aggressive endometrial cancer cells, re-expression of microRNA-101 leads to inhibition of cell proliferation and induction of apoptosis and senescence. Ectopic overexpression of microRNA-101 attenuates the epithelial-mesenchymal transition-associated cancer cell migration and invasion, abrogates the sphere-forming capacity and enhances chemosensitivity to paclitaxel. Algorithm and microarray-based strategies identifies potential microRNA-101 targets. Among these, we validated EZH2, MCL-1 and FOS as direct targets of miR-101 and silencing of these genes mimics the tumor suppressive effects observed on promoting microRNA-101 function. Importantly, further results suggest an inverse correlation between low miR-101 and high EZH2, MCL-1 and FOS expression in EC specimens. We conclude that, as a crucial tumor suppressor, microRNA-101 suppresses cell proliferation, invasiveness and self-renewal in aggressive endometrial cancer cells via modulating multiple critical oncogenes. The microRNA-101-EZH2/MCL-1/ FOS axis is a potential therapeutic target for endometrial cancer.

Impact of FDG PET in optimizing patient selection for cytoreductive surgery in recurrent ovarian cancer
Yasuhiko Ebina, Hidemichi Watari, Masanori Kaneuchi, Mahito Takeda, Masayoshi Hosaka, Masataka Kudo, Hideto Yamada, Noriaki Sakuragi
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 41, 3, 446, 451, SPRINGER, 2014年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose To investigate the impact of PET and PET/CT scanning on decision-making in management planning and to identify the optimal setting for selecting candidates for surgery in suspicious recurrent ovarian cancer.
Methods A retrospective chart review was performed in patients with possible recurrent ovarian cancer after primary optimal cytoreduction and taxane/carboplatin chemotherapy who had undergone FDG PET or FDG PET/CT scans from July 2002 to August 2008 to help make treatment decisions. The analysis included 44 patients who had undergone a total of 89 PET scans. The positive PET scans were classified as follows. (1) localized (one or two localized sites of FDG uptake), (2) multiple (three or more sites of FDG uptake), (3) diffuse (extensive low-grade activity outlining serosal and peritoneal surfaces).
Results Of the 89 PET scans, 52 (58.4 %) led to a change in management plan. The total number of patients in whom cytoreductive surgery was selected as the treatment of choice increased from 12 to 35. Miliary disseminated disease, which was not detected by PET scan, was found in 22.2 % of those receiving surgery. Miliary disseminated disease was detected in 6 of the 12 patients with recurrent disease whose treatment-free interval (TFI) was <12 months, whereas none of those with a TFI of >= 12 months had such disease (P = 0.0031).
Conclusion PET or PET/CT is useful for selecting candidates for cytoreductive surgery among patients with recurrent ovarian cancer. To avoid surgical attempts in those with miliary dissemination, patients with a TFI of >= 12 months are the best candidates for cytoreductive surgery.

Multivariate prognostic analysis of adenocarcinoma of the uterine cervix treated with radical hysterectomy and systematic lymphadenectomy
Tatsuya Kato, Hidemichi Watari, Mahito Takeda, Masayoshi Hosaka, Takashi Mitamura, Noriko Kobayashi, Satoko Sudo, Masanori Kaneuchi, Masataka Kudo, Noriaki Sakuragi
JOURNAL OF GYNECOLOGIC ONCOLOGY, 24, 3, 222, 228, KOREAN SOC GYNECOLOGY ONCOLOGY & COLPOSCOPY, 2013年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: The aim of this study was to investigate the prognostic factors and treatment outcome of patients with adenocarcinoma of the uterine cervix who underwent radical hysterectomy with systematic lymphadenectomy.
Methods: A total of 130 patients with stage IB to IIB cervical adenocarcinoma treated with hysterectomy and systematic lymphadenectomy from 1982 to 2005 were retrospectively analyzed. Clinicopathological data including age, stage, tumor size, the number of positive node sites, lymphovascular space invasion, parametrial invasion, deep stromal invasion (>2/3 thickness), corpus invasion, vaginal infiltration, and ovarian metastasis, adjuvant therapy, and survival were collected and Cox regression analysis was used to deteitnine independent prognostic factors.
Results: An estimated five-year survival rate of stage IB1 was 96.6%, 75.0% in stage IB2, 100% in stage IIA, and 52.8% in stage IIB. Prognosis of patients with one positive-node site is similar to that of those with negative-node. Prognosis of patients with multiple positive-node sites was significantly poorer than that of negative and one positive-node site. Multivariate analysis revealed that lymph node metastasis, lymphovascular space invasion, and parametrial invasion were independent prognostic factors for cervical adenocarcinoma. Survival of patients with cervical adenocarcinoma was stratified into three groups by the combination of three independent prognostic factors.
Conclusion: Lymph node metastasis, lymphovascular space invasion, and parametrial invasion were shown to be independent prognostic factors for cervical adenocarcinoma treated with hysterectomy and systematic lymphadenectomy.

Incidence risk of cervical intraepithelial neoplasia 3 or more severe lesions is a function of human papillomavirus genotypes and severity of cytological and histological abnormalities in adult Japanese women
Masayoshi Hosaka, Hiromasa Fujita, Sharon J. B. Hanley, Takayuki Sasaki, Yozo Shirakawa, Mitsuharu Abiko, Masataka Kudo, Masanori Kaneuchi, Hidemichi Watari, Kohkichi Kikuchi, Noriaki Sakuragi
INTERNATIONAL JOURNAL OF CANCER, 132, 2, 327, 334, WILEY-BLACKWELL, 2013年01月, ［査読有り］
英語, 研究論文（学術雑誌）, We examined incidence probabilities of cervical intraepithelial neoplasia 3 (CIN3) or more severe lesions (CIN3+) in 1,467 adult Japanese women with abnormal cytology in relation to seven common human papillomavirus (HPV) infections (16/18/31/33/35/52/58) between April 2000 and March 2008. Sixty-seven patients with multiple HPV infection were excluded from the risk factor analysis. Incidence of CIN3+ in 1,400 patients including 68 with ASCUS, 969 with low grade squamous intraepithelial lesion (LSIL), 132 with HSIL without histology-proven CIN2 (HSIL/CIN2(-)) and 231 with HSIL with histology-proven CIN2 (HSIL/CIN2(+)) was investigated. In both high grade squamous intraepithelial lesion (HSIL)/CIN2(-) and HSIL/CIN2(+), HPV16/18/33 was associated with a significantly earlier and higher incidence of CIN3+ than HPV31/35/52/58 (p = 0.049 and p = 0.0060, respectively). This association was also observed in LSIL (p = 0.0002). The 1-year cumulative incidence rate (CIR) of CIN3+ in HSIL/CIN2(-) and HSIL/CIN2(+) according to HPV genotypes (16/18/33 vs. 31/35/52/58) were 27.1% vs. 7.5% and 46.6% vs. 19.2%, respectively. In contrast, progression of HSIL/CIN2(+) to CIN3+ was infrequent when HPV DNA was undetected: 0% of 1-year CIR and 8.1% of 5-year CIR. All cervical cancer occurred in HSIL cases of seven high-risk HPVs (11/198) but not in cases of other HPV or undetectable/negative-HPV (0/165) (p = 0.0013). In conclusion, incidence of CIN3+ depends on HPV genotypes, severity of cytological abnormalities and histology of CIN2. HSIL/CIN2(+) associated with HPV16/18/33 may justify early therapeutic intervention, while HSIL/CIN2(-) harboring these HPV genotypes needs close observation to detect incidence of CIN3+. A therapeutic intervention is not indicated for CIN2 without HPV DNA.

New revised FIGO 2008 staging system for endometrial cancer produces better discrimination in survival compared with the 1988 staging system
Tatsuya Kato, Hidemichi Watari, Daisuke Endo, Takashi Mitamura, Tetsuji Odagiri, Yousuke Konno, Masayoshi Hosaka, Noriko Kobayashi, Yukiharu Todo, Satoko Sudo, Mahito Takeda, Peixin Dong, Masanori Kaneuchi, Masataka Kudo, Noriaki Sakuragi
JOURNAL OF SURGICAL ONCOLOGY, 106, 8, 938, 941, WILEY, 2012年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Background and Objectives The aim of this study was to analyze the stage migration and survival of endometrial cancer by the revised FIGO 2008 staging system compared with the 1988 staging system. Methods A total of 355 patients with endometrial cancer, who underwent complete surgical staging, were enrolled. We compared the surgical stages and survival by FIGO 1988 staging system with those by FIGO 2008 staging system. Results 2008 FIGO staging system resulted in an increase of stage I patients and decrease of stage II and IIIa patients. The 5-year overall survival (OS) rates for patients with 2008 FIGO stage IA and IB disease were 98.2% and 91.9%, respectively (P?=?0.004). Five-year OS rate of new stage II (82.6%) was significantly worse than that of new stage IA (98.2%, P?=?0.003). Patients with positive washing cytology alone revealed a 5-year OS rate similar to that of patients with new stage IIIA disease (96.2% vs. 90.9%, respectively; P?=?0.53). The 5-year OS rate for patients with stage IIIC1 disease was improved compared with that for patients with stage IIIC2 disease (85.7% vs. 63.0%, respectively; P?=?0.08). Conclusion New revised FIGO 2008 staging system for endometrial cancer produced better discrimination in OS outcomes compared with the 1988 system. J. Surg. Oncol. 2012; 106: 938941. (c) 2012 Wiley Periodicals, Inc.

Risk factors for lower-limb lymphedema after surgery for cervical cancer
Yoko Ohba, Yukiharu Todo, Noriko Kobayashi, Masanori Kaneuchi, Hidemichi Watari, Mahito Takeda, Satoko Sudo, Masataka Kudo, Hidenori Kato, Noriaki Sakuragi
INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 16, 3, 238, 243, SPRINGER TOKYO, 2011年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Lower-limb lymphedema (LLL) is a prevalent complication that is encountered after treatment for gynecological malignancies. The aim of this study was to evaluate the risk factors for postoperative LLL in patients with cervical cancer.
We conducted a retrospective chart review for patients who had undergone surgery, including systematic lymphadenectomy, for cervical cancer. Patients who died of cancer, were evaluated for short periods of time (< 2 years), had missing medical records, or were suffering from deep venous thrombosis were excluded. We utilized the International Society of Lymphology staging of lymphedema severity as the diagnostic criteria for LLL, and patients with stage II or III lymphedema, as objectively determined by physicians, were included in the group of patients with LLL. Multivariate analysis was performed to confirm independent risk factors.
A total of 155 patients with cervical cancer were evaluated. Thirty-one patients (20.0%) contracted LLL with a median follow-up of 6.1 years. Suprafemoral node dissection (odds ratio, 9.5; 95% confidence interval, 1.2-73.3; P = 0.031) and adjuvant radiotherapy (3.7; 1.2-10.9; P = 0.019) were identified as independent risk factors.
Given that the effectiveness of the above two therapeutic options for cervical cancer is currently controversial, the clinical benefits of these therapies should be reevaluated specifically to conserve the quality of life for patients with this disease.

Risk Factors for Persistent Low Bladder Compliance After Radical Hysterectomy
Yasunari Oda, Yukiharu Todo, Sharon Hanley, Masayoshi Hosaka, Mahito Takeda, Hidemichi Watari, Masanori Kaneuchi, Masataka Kudo, Noriaki Sakuragi
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 21, 1, 167, 172, LIPPINCOTT WILLIAMS & WILKINS, 2011年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Introduction: Bladder compliance deteriorates immediately after radical hysterectomy (RH), and low bladder compliance causes upper urinary tract dysfunctions such as progressive hydronephrosis. The aims of this study were to clarify risk factors for persistent low bladder compliance after RH and to propose a postsurgical management protocol for improved recovery of bladder function.
Methods: A total of 113 consecutive patients who underwent RH with the intention to preserve the pelvic autonomic nerve system were included in this prospective study. Urodynamic studies were performed according to a planned schedule: presurgery and 1, 3, 6, and 12 months after surgery. Autonomic nerves were preserved at least unilaterally in 95 (84.1%) of the 113 patients, but this was not possible in the remaining 18 patients (15.9%). Postoperative adjuvant radiation therapy (RT) was performed in 14 patients. The relationships between bladder compliance and various clinical factors were investigated using logistic regression analysis. Covariates included age, nerve-sparing procedure, adjuvant RT, and maximum abdominal pressure during the voiding phase. Bladder compliance at 12 months after surgery was used as the dependent variable.
Results: Radical hysterectomy with a non-nerve-sparing procedure (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.1-11.0), adjuvant RT (OR, 10.3; 95% CI, 2.5-43.5), and voiding with abdominal pressure at 3 months after surgery (OR, 2.9; 95% CI, 1.1-7.2) were risk factors for persistent low bladder compliance.
Conclusions: A nerve-sparing procedure and prohibition of voiding with abdominal strain during the acute and subacute phases after RH resulted in improved recovery of bladder compliance. Adjuvant RT should be avoided in patients who undergo nerve-sparing RH if an alternative postoperative strategy is possible.

Complete hydatidiform mole with coexisting dichorionic diamniotic twins following testicular sperm extraction and intracytoplasmic sperm injection
Takahiro Yamada, Takao Matsuda, Masataka Kudo, Takashi Yamada, Masashi Moriwaki, Shinya Nishi, Yasuhiko Ebina, Hideto Yamada, Hidenori Kato, Tomoo Ito, Norio Wake, Noriaki Sakuragi, Hisanori Minakami
JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH, 34, 1, 121, 124, BLACKWELL PUBLISHING, 2008年02月, ［査読有り］
英語, 研究論文（学術雑誌）, We present the first report of complete hydatidiform mole (HM) with coexisting dichorionic diamniotic twins. This pregnancy was achieved after testicular sperm extraction and intracytoplasmic sperm injection (ICSI) for azoospermia in the woman's husband. Standard in vitro fertilization may cause multisperm fertilization and increase triploid partial HM and complete HM, which arise from dispermic fertilization. In contrast, ICSI can avoid multisperm fertilization. In our case, paternal isodisomy in the molar tissue was confirmed by microsatellite analysis suggesting that it resulted from duplication of a haploid paternal genome following monospermic fertilization of an inactivated oocyte or from monospermic fertilization of an inactivated oocyte with a diploid sperm. Although the patient was eager to continue the pregnancy, the size of the HM component increased rapidly and termination of the pregnancy was required for pre-eclampsia-like symptoms at 15 weeks of gestation. After the operation, chemotherapy was initiated for persistent trophoblastic disease.

Bioactivity of human chorionic gonadotropin produced in frozen-thawed embryo transfer cycles with exogenous hormone replacement.
Naher N, Sudo S, Kudo M, Nishi S, Moriwaki M, Minakami H, Sakuragi N
[Hokkaido igaku zasshi] The Hokkaido journal of medical science, 81, 3, 187, 195, 3, 2006年05月, ［査読有り］
英語

Spontaneous uterine rupture of a twin pregnancy after a laparoscopic adenomyomectomy: A case report
S Wada, M Kudo, H Minakami
JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY, 13, 2, 166, 168, ELSEVIER SCIENCE INC, 2006年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Adenomyomectomy is a treatment option to preserve fertility and reduce symptoms associated with adenomyosis. Although this procedure is reasonably expected to increase the risk of uterine rupture during pregnancy, reports on this issue are scarce. We recently encountered a 33-year-old nulliparous woman with a twin pregnancy who experienced a spontaneous uterine rupture at 30 weeks' gestation. This patient was the first to conceive after undergoing laparoscopic adenomyomectomy at our institution. Her pregnancy was established with in vitro fertilization-embryo transfer 12 months after laparoscopic adenomyomectomy. The uterine rupture was heralded by a sudden onset of severe abdominal pain while she was receiving intravenous ritodrine. This case reinforces that pregnancy after adenomyomectomy should be closely monitored with respect to uterine rupture. (c) 2006 AAGL. All rights reserved.

A study of oligosaccharide variants of alpha-fetoproteins produced by normal fetuses and fetuses with trisomy 21
R Yamamoto, T Ohkouchi, K Tabata, Y Ebina, H Watari, M Kudo, K Shimizu, S Satomura, H Minakami, N Sakuragi
ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA, 84, 12, 1145, 1149, BLACKWELL PUBLISHING, 2005年12月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. The mechanisms of the increase in the percentage of alpha-fetoproteins (AFPs) that strongly binds to Lens culinaris agglutinin (AFP-L3) in pregnancies with a trisomy 21 fetus have not been analyzed. To investigate the oligosaccharide variants of AFP produced by normal fetuses and fetuses with trisomy 21, the lectin reactivity of AFP was analyzed.
Methods. Fetal liver tissue, amniotic fluid, and maternal serum were obtained from five normal pregnancies and five pregnancies with a trisomy 21 fetus. The percentages of AFP reactive to lectins were determined by lectin-affinity electrophoresis coupled with antibody-affinity blotting.
Results. The percentages of AFP-L3 in the fetal liver and the maternal serum were 23.9 and 27.0%, respectively, in normal pregnancies, and 28.7 and 38.5%, respectively, in pregnancies with a trisomy 21 fetus. There was no statistically significant difference between the percentage in the fetal liver and the percentage in the maternal serum in normal pregnancies; however, a significant difference (P < 0.01) was found in pregnancies with a trisomy 21 fetus. In regard to the percentage of AFP-L3 in the fetal liver, there was no significant difference; however, a significant difference (P < 0.05) was found in the maternal serum between normal pregnancies and pregnancies with a trisomy 21 fetus.
Conclusions. The transference of the AFP-L3 fraction might be relatively high in the placentas of women carrying a trisomy 21 fetus, and this could be the one of the reasons for the increase in the percentage of AFP-L3 in the maternal serum in pregnancies with a trisomy 21 fetus.

Prenatal trisomy 21 screening using the Lens culinaris agglutinin-reactive alpha-fetoprotein ratio.
Yamamoto R, Minobe S, Ebina Y, Watari H, Kudo M, Henmi F, Satomura S, Fujimoto S, Minakami H, Sakuragi N
Congenital anomalies, 44, 2, 87, 92, 2, 2004年06月, ［査読有り］
英語

Activation of the luteinizing hormone receptor in the extracellular domain
K Nakabayashi, M Kudo, AJW Hsueh, T Maruo
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 202, 1-2, 139, 144, ELSEVIER SCI IRELAND LTD, 2003年04月, ［査読有り］
英語, 研究論文（学術雑誌）, Glycoprotein hormone receptors have ligand-binding ectodomains consisting of leucine-rich repeats, followed by a conserved cysteine-rich hinge region to the seven transmembrane (TM) region. Based on constitutively active mutations at Ser-281 in the hinge region of the thyroid-stimulating hormone receptor, we mutated the conserved serine in the luteinizing hormone (LH) receptor (S2771) and observed increased basal cAMP production and ligand affinity by mutant receptor. Conversion of Ser-277 to all natural amino acids led to varying degrees of receptor activation. Hydropathy index analysis indicated that substitution of neutral serine with selective nonpolar hydrophobic residues (Len > Val > Met > Ile) confers constitutive receptor activation. Furthermore, mutation of the angular proline near Ser-273 to flexible Gly also led to receptor activation. The findings suggest the ectodomain of LH receptor constrains the TM region. Point mutations in the hinge region or ligand binding could cause conformational changes in the TM region that result in Gs activation. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.

Genetic and functional analyses of polymorphisms in the human FSH receptor gene
S Sudo, M Kudo, S Wada, O Saito, AJW Hsueh, S Fujimoto
MOLECULAR HUMAN REPRODUCTION, 8, 10, 893, 899, OXFORD UNIV PRESS, 2002年10月, ［査読有り］
英語, 研究論文（学術雑誌）, To determine the influence of FSH receptor variants Thr307-Asn680 (TN) and Ala307-Ser680 (AS) on ovarian function, we investigated the frequency of these gene polymorphisms by using restriction fragment length polymorphism analysis and observed their effects on clinical manifestations. In a population of 522 Japanese women, the overall frequency of TN/TN (NN), TN/AS (NS), and AS/AS (SS) was 41.0, 46.9 and 12.1% respectively. In polycystic ovary patients, the NS population was significantly larger when compared with the spontaneously ovulating group (66.7 versus 43.5%, P < 0.05). In the SS group, a significantly higher (46%) basal level of serum FSH was observed as compared with that in the NS group (P < 0.05). A higher dose of the exogenous gonadotrophin was required to achieve ovulation induction in the SS group as compared with the NS group (P < 0.05). At the time of hCG administration, estradiol levels per oocyte retrieved for IVF in the SS group were significantly lower as compared with the levels in the NS and NN groups (P < 0.05). There were no significant differences in FSH-stimulated cAMP production and PI turnover as well as ligand-binding affinity between the two receptor isoforms when overexpressed in transfected 293T cells. These results suggest that although FSH receptor polymorphisms have no discernible effect on FSH receptor function in vitro, there are associations between the genotype and some aspects of patient status.

Activation of orphan receptors by the hormone relaxin.
Hsu SY, Nakabayashi K, Nishi S, Kumagai J, Kudo M, Sherwood OD, Hsueh AJ
Science (New York, N.Y.), 295, 671, 674, 5555, 2002年01月, ［査読有り］

新生児マス・スクリーニング検査で発見され経過中に卵巣嚢腫茎捻転を起こしたP450オキシドレダクターゼ欠損症の1例
石津 桂, 中村 明枝, 城 和歌子, 工藤 正尊, 田島 敏広, 日本マス・スクリーニング学会誌 = Journal of Japanese Society for Mass-screening, 21, 3, 243, 246, 2011年12月01日
日本語

子宮体癌における腹腔鏡下後腹膜リンパ節郭清術の徹底度に関する考察 : 部位別摘出リンパ節個数の観点から
木川 聖美, 野村 英司, 光部 兼六郎, 石本 真紀, 中谷 真紀子, 蒲牟田 恭子, 小田切 哲二, 金野 陽輔, 明石 大輔, 工藤 正尊, 櫻木 範明, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 26, 2, 486, 492, 2010年12月01日
<B>Objective:</B> This study was conducted to assess the validity of laparoscopic lymphadenectomy for gynecologic malignancies at our hospital.<BR><B>Methods:</B> Twenty-five patients undergoing laparoscopic (LS) paraaortic and pelvic lymphadenectomy for endometrial carcinoma were compared with 21 control subjects similarly treated via laparotomy (LT). Only surgeries involving systematic lymphadenectomy were included. Extracted lymph nodes were classified using The General Rules for Clinical and Pathological Management of Uterine Cervical Cancer<SUP>1)</SUP>. For the two groups, the count o..., 日本産科婦人科内視鏡学会, 日本語

腹腔鏡下子宮内膜症手術時に虫垂切除術を追加施行した19例の検討
金野 陽輔, 工藤 正尊, 明石 大輔, 木川 聖美, 西 信也, 加藤 達矢, 首藤 聡子, 越田 高行, 涌井 之雄, 大河内 俊洋, 水上 尚典, 櫻木 範明, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 26, 2, 560, 564, 2010年12月01日
<B>Objective:</B> Considered to be a cause of unexplained chronic pelvic pain, appendiceal endometriosis is relatively rare, accounting for only 3% of all pathologic lesions of this disorder. In this study, we analyzed the clinicopathologic findings of resected appendices with an abnormal appearance discovered during laparoscopic surgery for endometriosis.<BR><B>Patients and Methods:</B> We performed laparoscopic surgery on 309 patients with endometriosis between January 2006 and December 2008 in Hokkaido University Hospital and its affiliated hospitals. Nineteen patients underwent laparos..., 日本産科婦人科内視鏡学会, 日本語

当科における子宮体癌に対する腹腔鏡下手術
光部 兼六郎, 勘野 真紀, 中谷 真紀子, 工藤 正尊, 野村 英司, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 26, 1, 281, 287, 2010年07月01日
<B>Objectives:</B> The aims of this study were to report the feasibility of laparoscopic surgery for early-stage endometrial cancer and to assess the effects of laparoscopic surgery on the survival of patients.<BR><B>Methods:</B> Twenty-three patients with clinical stage I and IIa endometrial cancer were treated by laparoscopy (laparoscopy group [LS]). The surgical procedures included hysterectomy, salpingo-oophorectomy, and para-aortic-pelvic lymphadenectomy. Peri-operative morbidities and outcomes were compared with 20 control patients who were treated with traditional open surgery (lapar..., 日本産科婦人科内視鏡学会, 日本語

浸潤子宮頸癌に対する鏡視下広汎子宮全摘出術および準広汎子宮全摘出術の feasibilty について
保坂 昌芳, 工藤 正尊, 明石 大輔, 三田村 卓, 加藤 達矢, 森脇 征史, 首藤 聡子, 武田 真人, 蝦名 康彦, 渡利 英道, 金内 優典, 櫻木 範明, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 25, 2, 432, 437, 2009年12月01日
<B>Objectives:</B> The purpose of this study was to determine the feasibility and radicality of endoscopic radical hysterectomy (ERH) and endoscopic modified radical hysterectomy (EmRH) combined with pelvic lymphadenectomy (ELND) in invasive cervical cancer patients.<BR><B>Methods:</B> Five patients with invasive cervical cancer underwent ERH or EmRH between May 2003 and March 2007 at Hokkaido University Hospital. Two patients with stage I a adenocarcinoma underwent an EmRH, and two patients with stage I b1 and one patient with stage II a underwent an ERH. All patients gave their informed ..., 日本産科婦人科内視鏡学会, 日本語

腹腔鏡下婦人科悪性腫瘍手術と肺血栓塞栓症リスク
光部 兼六郎, 勘野 真紀, 小田切 哲二, 加藤 秀則, 金内 優典, 工藤 正尊, 野村 英司, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 24, 2, 349, 355, 2008年12月01日
Objectives: The true incidence of pulmonary embolism (PE) in patients undergoing laparoscopic surgery for gynecologic malignancies is unknown. The aims of this study were to determine the incidence of PE in laparoscopically-treated cancer patients, to compare the results with those treated with open surgery, and to investigate the efficacy of low-dose unfractionated heparin (LDUH) to prevent the occurrence of PE.<BR>Methods: Thirty-three patients with gynecologic malignancies were laparoscopically-treated (laparoscopy group [LS] ) . The procedures included paraaortic-pelvic lymphadenectomy ..., 日本産科婦人科内視鏡学会, 日本語

粘膜下筋腫に対する全腹腔鏡下筋腫核出術の経験
森脇 征史, 工藤 正尊, 首藤 聡子, 西 信也, 加藤 達矢, 和田 真一郎, 光部 兼六郎, 保坂 昌芳, 藤堂 幸治, 蝦名 康彦, 渡利 英道, 大河内 俊洋, 水上 尚典, 櫻木 範明, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 24, 1, 204, 208, 2008年07月01日
Background: Submucosal myoma has been treated with hysteroscopic transcervical resection (TCR) . However, in cases of unstalked submucosal myoma over 3cm in diameter, TCR could lead to not only extended operation time but also extensive thermal damage on endometrium by electrocoagulation. In this study, we validated the feasibility and utility of total Laparoscopic approach for submucosal myoma treatment.<BR>Materials and Methods: Total laparoscopic myomectomy (TLM) was performed on 12 women with submucosal myoma. Our TLM procedure was as follows: a balloon catheter was detained in the uter..., 日本産科婦人科内視鏡学会, 日本語

骨盤痛に対する腹腔鏡下手術 : 術前に子宮内膜症と診断されなかった症例について
小田切 哲二, 勘野 真紀, 光部 兼六郎, 加藤 秀則, 金内 優典, 藤野 敬史, 鈴木 昭, 工藤 正尊, 野村 英司, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 24, 1, 218, 223, 2008年07月01日
OBJECTIVE: The aim of this study was to assess the efficacy of laparoscopic resection of pelvic peritoneum in addition to conventional laparoscopic uterosacral nerve ablation (LUNA) procedure on the relief of treatment refractory pelvic pain in patients without preoperative diagnosis of endometriosis.<BR>METHODS: We performed laparoscopic peritonectomy combined with LUNA in 13 patients who had not been diagnosed as endometriosis. Intraoperative findings were re-assessed by videos recorded during surgery. Peritoneal specimens were pathologically reviewed. Postoperative details on dysmenorrho..., 日本産科婦人科内視鏡学会, 日本語

TESE-ICSI後に発生した二絨毛膜性双胎と共存した全胞状奇胎
山田 崇弘, 松田 貴雄, 工藤 正尊, 山田 俊, 森脇 征史, 西 信也, 蝦名 康彦, 山田 秀人, 加藤 秀則, 伊藤 智雄, 和氣 徳夫, 櫻木 範明, 水上 尚典, 日本産科婦人科學會雜誌, 60, 3, 999, 999, 2008年03月01日
日本語

当科における卵巣癌と腹腔鏡手術
野村 英司, 光部 兼六郎, 石本 真紀, 木川 聖美, 藤野 敬史, 西 信也, 森脇 征史, 加藤 達矢, 工藤 正尊, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 22, 2, 431, 436, 2006年12月01日
日本産科婦人科内視鏡学会, 日本語

当科における腹腔鏡下悪性腫瘍手術の経験 : 20症例の術中・術後経過について
光部 兼六郎, 石本 真紀, 木川 聖美, 森脇 征史, 工藤 正尊, 野村 英司, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 22, 1, 191, 196, 2006年07月01日
日本産科婦人科内視鏡学会, 日本語

当科における骨盤痛に対する腹腔鏡下手術 : LUNAに加えての骨盤腹膜切除の試み
野村 英司, 光部 兼六郎, 石本 真紀, 木川 聖美, 森脇 征史, 工藤 正尊, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 22, 1, 228, 232, 2006年07月01日
日本産科婦人科内視鏡学会, 日本語

腹腔鏡下リンパ節郭清におけるフィブリン糊使用によるリンパ浮腫並びにリンパ嚢胞予防の試み
石本 真紀, 光部 兼六郎, 木川 聖美, 森脇 征史, 工藤 正尊, 野村 英司, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 21, 2, 418, 423, 2005年12月01日
日本産科婦人科内視鏡学会, 日本語

当科における腹腔鏡下悪性腫瘍手術の経験腹腔内アプローチによる腎静脈下PAN郭清について
野村 英司, 光部 兼六郎, 石本 真紀, 木川 聖美, 森脇 征史, 工藤 正尊, 日本産科婦人科内視鏡學會雜誌 = The journal of the Japan Endoscopy Society of Obstetrics and Gynecology, 21, 2, 430, 435, 2005年12月01日
日本産科婦人科内視鏡学会, 日本語

ヒト黄体化ホルモン受容体の恒常的活性化における第Vから第VI膜貫通領域の役割に関する研究
工藤 正尊, 北海道醫學雜誌 = Acta medica Hokkaidonensia, 74, 1, 53, 65, 1999年01月01日
日本語

酢酸ナファレリンShort Protocolを利用した体外受精・胚移植(IVF-ET)の過排卵刺激法
工藤 隆之, 和田 真一郎, 工藤 正尊, 牧野田 知, 藤本 征一郎, 吉田 博, 日本不妊学会雑誌 = Japanese journal of fertility and sterility, 42, 2, 7, 15, 1997年04月01日
日本不妊学会, 日本語

腹腔鏡下MTX局所投与による子宮外妊娠の保存的治療
日下 真純, 田中 俊誠, 工藤 正尊, 桜田 芳弘, 藤野 敬史, 牧野田 知, 藤本 征一郎, 日本産科婦人科學會雜誌, 43, 12, 1721, 1724, 1991年12月01日
社団法人日本産科婦人科学会, 日本語

超音波断層法ならびに腹腔鏡検査で診断され, Methotrexate (MTX)で非観血的治療がなされた卵巣妊娠の一例
工藤 正尊, 田中 俊誠, 藤本 征一郎, 日本産科婦人科學會雜誌, 40, 6, 811, 813, 1988年06月01日
社団法人日本産科婦人科学会, 日本語