Updated on 2024/04/16

写真a

 
OBARA Kenji
 
Organization
Academic Assembly Institute of Medicine and Dentistry IGAKU KEIRETU Lecturer
Faculty of Medicine School of Medicine Lecturer
Graduate School of Medical and Dental Sciences Biological Functions and Medical Control Regenerative and Transplant Medicine Lecturer
Title
Lecturer
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Degree

  • Docter(Medicine) ( 1999.6   Niigata University )

Research Interests

  • 神経泌尿器科

  • 小児泌尿器科学

Research Areas

  • Life Science / Urology

Research History

  • Niigata University   Faculty of Medicine School of Medicine   Lecturer

    2009.1

  • Niigata University   Graduate School of Medical and Dental Sciences Biological Functions and Medical Control Regenerative and Transplant Medicine   Lecturer

    2009.1

  • Niigata University   University Medical and Dental Hospital   Assistant Professor

    2007.4 - 2008.12

  • Niigata University   University Medical and Dental Hospital   Research Assistant

    2003.10 - 2007.3

  • Niigata University   University Medical Hospital   Research Assistant

    1999.4 - 2003.9

  • Niigata University   Faculty of Medicine   Research Assistant

    1994.2 - 1998.1

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Education

  • Niigata University   Faculty of Medicine

    - 1988

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  • Niigata University   Faculty of Medicine   School of Medicine

    - 1988

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    Country: Japan

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Professional Memberships

Committee Memberships

  • 日本排尿機能学会   評議委員  

       

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    Committee type:Academic society

    日本排尿機能学会

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Papers

  • Asymptomatic bilateral delayed ureteral obstruction following dextranomer/hyaluronic acid copolymer (Deflux) injection for vesicoureteral reflux.: A case report. International journal

    Sayaka Hoshino, Kenji Obara, Tatsuhiko Hoshii, Yoshihiko Tomita

    Urology case reports   35   101539 - 101539   2021.3

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    We here present a case of a 4-year-old girl who exhibited an asymptomatic bilateral de novo hydroureteronephrosis seven months after undergoing endoscopic treatment for bilateral vesicoureteral reflux. The child underwent an open bilateral reimplantation. Intraoperatively, a 14 mm nodule on the right and a 16 mm on the left located periureteral orifice were observed. When a small incision was made on nodules, a yellowish-white mucinous fluid flowed out.

    DOI: 10.1016/j.eucr.2020.101539

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  • 母のアンドロゲン産生副腎腫瘍により女児外性器の男性化を生じた1例

    星野 さや香, 小原 健司, 星井 達彦, 黒木 大生, 渡邉 和博, 冨田 善彦

    日本小児泌尿器科学会雑誌   29 ( 2 )   234 - 234   2020.12

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  • Virilization of a female infant genitalia caused by a maternal androgen-producing adrenocortical tumor: A case report Reviewed International journal

    Sayaka Hoshino, Kenji Obara, Tatsuhiko Hoshii, Hiroo Kuroki, Kazuhiro Watanabe, Yoshihiko Tomita

    Urology Case Reports   32   101253 - 101253   2020.9

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Elsevier BV  

    A 4-month-old girl presented us with genital ambiguity. The patient had a persistent urogenital sinus, posterior labial fusion with clitoromegaly. MRI reveals ovary-like mass in left inguinal region and right abdominal cavity. Uterus and vagina was also identified. Her mother was diagnosed with a right androgen-producing adrenocortical tumor 14 months after the birth of a virilized infant.

    DOI: 10.1016/j.eucr.2020.101253

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  • Free Tube Graft Urethroplasty for Repair of Hypospadias Reviewed International journal

    Kenji Obara, Tatsuhiko  Hoshii, Sayaka Hoshino, Kazutoshi  Yamana, Tsutomu Anraku, Ryo Maruyama, Hiroo Kuroki, Fumio  Ishizaki, Hiroyuki  Yamazaki, Yoshihiko Tomita

    Urologia Internationalis   104 ( 5-6 )   386 - 390   2020.6

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    Authorship:Lead author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:S. Karger AG  

    INTRODUCTION: We aimed to assess the outcome of free tube graft urethroplasty for single-stage repair of hypospadias with chordee in children. MATERIALS AND METHODS: We retrospectively evaluated a series of 56 patients (16 months to 9 years old, median 24 months) who underwent free graft urethroplasty for repair of hypospadias with chordee between May 2005 and November 2017. The median follow-up was 7 years (range 1-11). RESULTS: After releasing the chordee, the hypospadiac orifice was retracted to become penile in 32 patients (57%), penoscrotal in 18 patients (32%), and scrotal in 6 patients (11%). Single-stage repair was achieved without complications in 42 patients (75%). Of the remaining 14 patients with postoperative complications requiring surgical intervention, 2 had meatal stenosis, 9 had urethrocutaneous fistula, 1 had urethral diverticulum without meatal stenosis, and 1 had meatal regression. One patient who complained the urine stream went upwards in an arc underwent cutback meatoplasty to correct the stream. In all patients, a neomeatus with a vertically oriented slit-like appearance was eventually achieved at the tip of the glans. CONCLUSION: A free graft is an appropriate choice for repairing hypospadias with chordee. Our procedure achieved favorable functional and cosmetic outcomes with a low postoperative morbidity rate.

    DOI: 10.1159/000504146

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  • Retrospective Analysis to Determine the Optimal Timing to Discontinue Continuous Antibiotic Prophylaxis in Patients with Primary Vesicoureteral Reflux Reviewed International journal

    Tsutomu Anraku, Kenji Obara, Masayuki Tasaki, Yoshihiko Tomita

    Urologia Internationalis   102 ( 4 )   462 - 467   2019.6

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:S. Karger AG  

    BACKGROUND: The management of febrile urinary tract infection (fUTI) in patients with vesicoureteral reflux (VUR) is crucial to prevent renal scarring. Continuous antibiotic prophylaxis (CAP) is the most widely used initial treatment for VUR. However, the optimal duration of CAP is still unclear. We aimed to clarify an appropriate patient population and the optimal timing to discontinue CAP. METHODS: We reviewed the records of 247 patients with primary VUR between January 2000 and December 2015. Seventy-two patients who discontinued CAP despite persistent VUR were enrolled. Kaplan-Meier method and Cox proportional hazard model was used in statistical analysis. RESULTS: Following the discontinuation of CAP, fUTI developed in 25 patients after a median of 9 months (range 0-81). VUR resolved spontaneously in 9 out of 47 patients without recurrence during follow-up. Multivariate analysis showed bilateral VUR and duration of CAP of less than 1 year after the last fUTI were significant risk factors for recurrence. CONCLUSION: Among the risk factors examined, patients administered CAP for less than 1 year after the last fUTI and those with bilateral VUR had significantly more frequent recurrence. Our study suggests that the administration of CAP for more than 1 year after the last fUTI is beneficial in avoiding recurrent fUTI.

    DOI: 10.1159/000497312

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  • 後部尿道弁の3症例

    星野 さや香, 小原 健司, 星井 達彦, 山名 一寿, 冨田 善彦

    日本小児泌尿器科学会雑誌   28 ( 2 )   200 - 200   2019.6

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  • Ulcerative interstitial cystitis in an adolescent successfully treated with complete transurethral ulcer resection: A case report Reviewed International journal

    Eri Yuki, Kenji Obara, Hiroo Kuroki, Hiroyuki Yamazaki, Kazutoshi Yamana, Akira Tadokoro, Kaede Hiruma, Yoshihiko Tomita

    IJU Case Reports   2 ( 1 )   51 - 53   2019.1

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)   Publisher:Wiley  

    Introduction: Interstitial cystitis is difficult to treat and may affect adolescents. Case presentation: A 15-year-old girl presented with severe pain upon terminal micturition that persisted for approximately 2 hours. The pain had been present for more than 1 month. Cystoscopy revealed severe erosion throughout the trigone. Transurethral fulguration did not improve her symptoms. However, complete electric resection of the ulcer markedly reduced the symptom. After complete resection, pain on urination disappeared and she has had no pain without medication for 15 months. Conclusion: Complete resection not fulguration of the ulcer is effective for interstitial cystitis in adolescent female patients.

    DOI: 10.1002/iju5.12038

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    Other Link: https://onlinelibrary.wiley.com/doi/full-xml/10.1002/iju5.12038

  • 重複腎盂尿管に伴う異所性尿管瘤に対して経尿道的尿管瘤切開術を施行した症例

    小原 健司, 星井 達彦, 山名 一寿, 石崎 文雄, 黒木 大生, 晝間 楓, 結城 恵里, 星野 さや香, 冨田 善彦, 水澤 隆樹

    日本泌尿器科学会総会   106回   OP - 456   2018.4

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  • Congenital Scaphoid Megalourethra: A Case Report Reviewed

    Kenji Obara, Hiroyuki Yamazaki, Kazutoshi Yamana, Hiroo Kuroki, Yoshihiko Tomita

    Urology Case Reports   14   3 - 4   2017.9

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    A congenital megalourethra is an enlargement of the pendulous urethra without evidence of distal obstruction. A 1-month-old boy presented to us with complaint of weak stream, ballooning of the penis before and during voiding and post voiding dribbling, since birth. Physical examination and cystourethroscope confirmed the diagnosis of congenital scaphoid megalourethra. He underwent reduction urethroplasty. During postoperative follow up, he had normal looking penis with good urinary stream.

    DOI: 10.1016/j.eucr.2017.05.002

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  • Angiomyomatous Leiomyoma of a Female Urethral Meatus Recurrence After Seven Years of the Resection: A Case Report Reviewed International journal

    Tatsuhiko Hoshii, Go Hasegawa, Yohei Ikeda, Shigeko Takaki, Kenji Obara, Tsutomu Nishiyama

    Urology Case Reports   9   24 - 26   2016.11

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    A 20 years old woman had an external urethral orifice mass and received an excision operation. Seven years later, she complained a tumor with pain that was similar to the previous tumor. She underwent the tumor removal. Pathological diagnosis was a urethral angiomyomatous leiomyoma in the new concept of estrogen receptor-positive smooth muscle tumors.

    DOI: 10.1016/j.eucr.2016.08.006

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  • 小児原発性膀胱尿管逆流症(VUR)に対する内視鏡的hyaluronic acid/dextranomer注入療法の成績

    小原 健司, 秋山 さや香, 鳥羽 智貴, 星井 達彦, 瀧澤 逸大, 安樂 力, 山名 一寿, 乾 幸平, 冨田 善彦

    泌尿器外科   29 ( 臨増 )   890 - 890   2016.5

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  • Case of Large Cecoureterocele with Contralateral Renal Rupture in Neonate Reviewed

    Kenji Obara, Tsutomu Anraku, Masahiro Ikeda, Shuichi Komatsu, Takaki Mizusawa, Ryo Maruyama, Yoshihiko Tomita

    UROLOGIA INTERNATIONALIS   97 ( 2 )   238 - 240   2016

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    A cecoureterocele is a rare form of ectopic ureterocele that the orifice of the affected ureter is within the bladder, but the cavity of the ureterocele extends beyond the bladder neck into the urethra. We present a case of a newborn boy with a large cecoureterocele with contralateral renal rupture. He required an emergency transurethral incision of the ureterocele for the treatment of acute renal failure and respiratory disorder. (C) 2016 S. Karger AG, Basel

    DOI: 10.1159/000445525

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  • 尿管瘤に対して内視鏡的瘤切開を施行した症例

    小原 健司, 池田 正博, 白野 侑子, 晝間 楓, 星井 達彦, 瀧澤 逸大, 冨田 善彦, 水澤 隆樹

    日本小児泌尿器科学会雑誌   24 ( 2 )   214 - 214   2015.6

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  • 尿管異所開口による持続性尿失禁を来たした低形成腎に対する後腹膜鏡下腎摘除術の検討

    風間 明, 西山 勉, 小原 健司, 星井 達彦, 丸山 亮, 田所 央

    Japanese Journal of Endourology   27 ( 3 )   228 - 228   2014.11

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  • 二分脊椎症による神経因性下部尿路機能障害患者における清潔間欠導尿の尿失禁に対する効果

    小原 健司, 秋山 さや香, 星井 達彦, 丸山 亮, 田所 央

    日本排尿機能学会誌   25 ( 1 )   182 - 182   2014.9

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  • 尿道下裂手術 そのゴールは?自然な外観を目指して Reviewed

    小原 健司

    泌尿器外科   27 ( 臨増 )   673 - 676   2014

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    Free graft法を用いて尿道下裂修復術を行った症例の外観をHOPEスコアを用いて検討した。Free graft法を用いて尿道下裂修復術を行った19例を対象とした。外尿道口の位置、外尿道口の形態、亀頭の形態、包皮の形態、陰茎捻転の程度、陰茎前屈の程度を術者以外の3例の日本泌尿器科学会専門医が複数の写真セットより判定した。判定結果より外尿道口の形態は縦のスリットであるがスリットか長すぎる傾向があった。また、亀頭形態では外尿道口のスリットの近位に正常な亀頭のブリッジがなくスリットが冠状溝にかかっている症例かみられた。包皮形態では包皮の非対称やたるみが指摘された症例があった。

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  • 当科における異所開口尿管症例の検討

    小原 健司, 星井 達彦, 小松 集一, 新井 啓, 安藤 崇, 結城 恵理, 西山 勉, 高橋 公太

    日本泌尿器科学会雑誌   104 ( 2 )   293 - 293   2013.3

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  • Free tube graft法による尿道下裂修復術の成績

    小原 健司, 筒井 寿基, 水澤 隆樹, 星井 達彦, 小松 集一, 丸山 亮, 新井 啓, 原 昇, 笠原 隆, 石崎 文雄, 高橋 公太

    日本泌尿器科学会雑誌   103 ( 2 )   520 - 520   2012.3

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  • A case of true ureteral diverticulum on functional solitary kidney Reviewed

    Tsutomu Anraku, Takaki Mizusawa, Kenji Obara, Hiromi Sato, Yoichi Ajioka, Kota Takahashi

    Japanese Journal of Urology   103 ( 3 )   569 - 572   2012

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    Language:Japanese   Publishing type:Research paper (scientific journal)   Publisher:Japanese Urological Association  

    A 13-year-old girl presented with an occult blood in urine. CT revealed right rudimentary kidney and left hydronephrosis. Renogram demonstrated right poor renal function pattern and left obstructive pattern. She underwent left pyeloplasty. Histologic examination revealed the true ureteral diverticulum. True ureteral diverticulum is a rare congenital anomaly and synonymous with blind-ending bifid ureter. This is a sixth case in the Japanese literature. © 2012 Japanese Urological Association.

    DOI: 10.5980/jpnjurol.103.569

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  • Clinical feature of men who benefit from dose escalation of naftopidil for lower urinary tract symptoms: A prospective study Reviewed

    Noboru Hara, Takaki Mizusawa, Kenji Obara, Etsuko Isahaya, Yuki Nakagawa, Kota Takahashi

    Advances in Urology   2011

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    Objectives. To examine the feature of men who benefit from dose escalation of naftopidil for lower urinary tract symptoms (LUTSs). Methods. Based on the IPSS, men reporting LUTS were prospectively studied using 50mg/day of naftopidil for the first 4 weeks
    satisfied patients continued its 50mg/day (n=11), and those reporting unsatisfactory improvement received its 75mg/day (n=35) for the next 4 weeks. Results. The 75mg group showed improvement in the total IPSS and QOL score in a dose-dependent manner (at 4 weeks: P&lt
    .001, at 4 weeks versus 8 weeks: P&lt
    .05). In the 50mg group, both scores reduced at 4 weeks, thereafter unchanged. The baseline slow stream score alone was higher in the 75mg group (P=.013). The rate of change in the QOL score during the initial 4 weeks (ΔQOL) and Δnocturia was smaller in the 75mg group (P&lt
    .05). Conclusions. Men with high slow stream score and unsatisfactory improvement in nocturia may benefit from dose escalation of naftopidil. Copyright © 2011 Takaki Mizusawa et al.

    DOI: 10.1155/2011/804583

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  • Efficacy of Clean Intermittent Catheterization for Urinary Incontinence in Children with Neurogenic Bladder Dysfunction Secondary to Myelodysplasia Reviewed

    Kenji Obara, Takaki Mizusawa, Etsuko Isahaya, Kazuya Suzuki, Noboru Hara, Kota Takahashi

    LUTS-LOWER URINARY TRACT SYMPTOMS   2 ( 2 )   100 - 105   2010.9

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    Objectives: To evaluate the efficacy of clean intermittent catheterization for urinary incontinence in myelodysplastic children.
    Methods: The cohort comprised of 38 children (19 boys and 19 girls, aged between 10 months to 16 years) with neurogenic bladder secondary to myelodysplasia. Group A included 16 children who had dilated upper urinary tract or vesicoureteral reflux when clean intermittent catheterization was introduced. The remaining 22 children with normal upper urinary tract were enrolled to group B. In the present study, we defined socially acceptable continence as having completely dry or slight stress incontinence that patients can manage with several small pads.
    Results: Of the 16 group A patients, 9 obtained socially acceptable continence by conservative management. Of the 22 group B patients, 11 reported socially acceptable continence by conservative management. Vesical compliance was significantly higher in cases who reported socially acceptable continence than in those with incontinence persistent regarding all participants (10 +/- 7.2 vs 6.8 +/- 6.2 mL/cmH(2)O, P = 0.0347) and group A (9.1 +/- 6.7 vs 3.7 +/- 1.4 mL/cmH(2)O, P = 0.0350). Leak point pressure was significantly higher in patients who obtained socially acceptable continence than in those having persistent incontinence regarding all participants (50 +/- 17.2 vs 25 +/- 6.6 mL/cmH(2)O, P = 0.0003), group A (51 +/- 21.4 vs 26 +/- 7.2 mL/cmH(2)O, P = 0.0348) and also, group B (49 +/- 12.8 vs 23.7 +/- 6.3 mL/cmH(2)O, P = 0.0043).
    Conclusion: In our series, socially acceptable continence was obtained in only 20 patients (52%) by conservative management. The present study suggests that the limitation of conservative treatment seems to be apparent when they have urethral closure deficiency and/or intractable poor vesical compliance.

    DOI: 10.1111/j.1757-5672.2010.00070.x

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  • 小児の過活動膀胱患者に対するコハク酸ソリフェナシンの使用経験 Reviewed

    小原 健司

    小児科臨床   63 ( 9 )   20272032   2010

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  • Primitive neuroectodermal tumor of the adrenal gland Reviewed

    Shuichi Komatsu, Ryusuke Watanabe, Masaaki Naito, Takaki Mizusawa, Kenji Obara, Tsutomu Nishiyama, Kota Takahashi

    International Journal of Urology   13 ( 5 )   606 - 607   2006.5

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    We report a rare case of primitive neuroectodermal tumor arising from adrenal gland in adulthood, diagnosed preoperatively as having non-functional adrenocortical adenoma. Laparoscopic adrenalectomy was performed. Immunohistological examination revealed the definite diagnosis as primitive neuroectodermal tumor of the adrenal gland. Although primitive neuroectodermal tumor is a highly malignant neoplasm, there is no evidence of local recurrence and distant metastasis 16 months after surgery.

    DOI: 10.1111/j.1442-2042.2006.01361.x

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  • Role of connective tissue growth factor in fibronectin synthesis in cultured human prostate stromal cells. International journal

    Kazuya Suzuki, Kenji Obara, Kazuhiro Kobayashi, Kazutoshi Yamana, Vladimir Bilim, Toshiyuki Itoi, Kota Takahashi

    Urology   67 ( 3 )   647 - 53   2006.3

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    OBJECTIVES: To clarify the correlation of connective tissue growth factor (CTGF) expression and fibronectin (FN) synthesis after transforming growth factor-beta-1 (TGF-beta1) stimulation in human prostate stromal cells. METHODS: Primary cultures of human prostate stromal cells were established from nine normal prostates by the explant method. The gene and protein expressions of CTGF and FN after TGF-beta1 treatment were examined. We also investigated the effect of CTGF blockade on TGF-beta1-induced FN synthesis by CTGF antisense oligodeoxynucleotide treatment. RESULTS: CTGF expression was detected in all nine prostate stromal cells by reverse transcriptase-polymerase chain reaction and immunoblotting. In prostatic tissues, CTGF expression was observed more strongly in epithelial cells than in the stromal area by immunohistochemistry. The upregulation of both CTGF and FN protein by TGF-beta1 treatment was demonstrated in a dose-dependent manner. CTGF antisense oligodeoxynucleotide inhibited TGF-beta1-stimulated FN synthesis. CONCLUSIONS: CTGF plays a crucial role in extracellular matrix production as a TGF-beta1 downstream mediator in human prostate stromal cells, suggesting that CTGF blockade is likely to be a therapeutic target against benign prostatic hyperplasia.

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  • Obstruction of the ileal ureter by mesenteric vessels occurring 5 years after total ureteral substitution for bilateral ureteral stenosis due to systemic lupus erythematosus Reviewed

    Kazuhiro Kobayashi, Kenji Obara, Ryusuke Watanabe, Noboru Hara, Akiyoshi Katagiri, Kota Takahashi

    International Journal of Urology   13 ( 1 )   80 - 83   2006.1

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    We previously reported a case of bilateral ureteral stenosis accompanied by systemic lupus erythematosus, which was successfully managed by total ureteral reconstruction using a segment of the ileum. Herein, we describe an unusual complication in the same patient, which we experienced 5 years after the ileal-ureteral substitution. Left-sided back pain repeated together with transient obstruction of the ileal ureter interposed between the right and left renal pelvis. Consequently, exploratory laparotomy revealed that left colic vessels oppressed and caused obstruction, and the obstructed ileal ureter was released by reconstitution of these vessels instead of re-anastomosis of the ileal ureter. Left hydronephrosis and related back pain disappeared postoperatively. The number of patients with an indication of ileal-ureteral substitution is increasing for various disorders, and thus, the present report gives additional suggestions for the follow up of patients with ileal ureter.

    DOI: 10.1111/j.1442-2042.2006.01232.x

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  • Transforming growth factor-β1 regulates cell growth and causes downregulation of SMemb/non-muscle myosin heavy chain B mRNA in human prostate stromal cells Reviewed

    Kenji Obara, Vladimir Bilim, Kazuya Suzuki, Kazuhiro Kobayashi, Noboru Hara, Takashi Kasahara, Tsutomu Nishiyama, Kota Takahashi

    Scandinavian Journal of Urology and Nephrology   39 ( 5 )   366 - 371   2005

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    Objectives. SMemb/non-muscle myosin heavy chain B (SMemb/NMMHC-B) is most abundantly expressed in proliferating smooth muscle cells and correlates with phenotypic changes from a contractive to a proliferative type. The stromal cells of the prostate play a crucial role in the regulation of prostatic growth and function. The aim of this study was to investigate the effects of the multifunctional cytokine transforming growth factor-β1 (TGF-β1) on SMemb/NMMHC-B mRNA expression and stromal cell growth. The expression of the SM2 isoform of smooth muscle myosin heavy chain (SMMHC) mRNA was also examined. Material and methods. Primary cultures of prostate stromal cells were established by means of an explant method from eight normal prostates. The effects of TGF-β1 on stromal cell growth were determined by means of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide conversion assay. SMemb/NMMHC-B and SM2 mRNA expression were analyzed quantitatively by means of real-time polymerase chain reaction. Results. In the absence of TGF-β1, cells expressed α-smooth muscle actin and vimentin. After TGF-β1 treatment, the expression of α-smooth muscle actin increased and cells also expressed desmin. TGF-β1 at concentrations of 1.0, 5.0 and 10 ng/ml suppressed cell growth by 72%, 62% and 56%, respectively, downregulated SMemb/NMMHC-B mRNA expression by 71%, 52% and 38%, respectively and upregulated SM2 mRNA expression 2.1-, 3.0- and 5.3-fold, respectively. Conclusions. These results demonstrate that TGF-β1 modulates the smooth muscle cell phenotype from a proliferative to a contractile type and that the inhibitory effects of TGF-β1 on stromal cell growth correlate with downregulation of the SMemb/NMMHC-B gene. © 2005 Taylor &amp
    Francis.

    DOI: 10.1080/00365590500192918

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  • 腹腔鏡下骨盤内手術時の術中陰茎海綿体神経モニタリング

    小林 和博, 西山 勉, 車田 茂徳, 渡辺 竜助, 郷 秀人, 黒川 公平, 星井 達彦, 小原 健司, 若月 俊二, 谷川 俊貴, 高橋 公太

    日本泌尿器科学会雑誌   95 ( 2 )   402 - 402   2004.3

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  • Inducible Nitric Oxide Synthase in Renal Cell Carcinoma: Expression in Tumor Thrombi and Induction under Hypoxic Conditions Reviewed

    Noboru Hara, Vladimir Bilim, Takashi Kasahara, Kenji Obara, Kazuhide Saito, Kota Takahashi, Yoshihiko Tomita

    Anticancer Research   23 ( 6 C )   4641 - 4649   2003.11

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    Background: Nitric oxide (NO) has been suggested to have polar roles in carcinogenesis with both antitumor and tumor promoting activity, and the status of NO synthase (NOS) in renal cell carcinoma (RCC) has not yet been completely elucidated. Materials and Methods: We investigated the expression and induction of inducible NOS (iNOS) in RCC specimens and cell lines, respectively. Results: Although the expression of iNOS was not observed in primary lesions or in metastatic sites, it was found in 6 cases of 11 tumor thrombi. The cause-specific survival rate of patients with iNOS-positive tumor thrombi was lower than that of patients with iNOS-negative tumor thrombi, showing borderline significance. iNOS-mRNA and protein were expressed in A498 and A704 RCC cells under hypoxic conditions. Conclusion: iNOS is suggested to be a significant molecule for RCC to acquire not only hypoxic adaptation but also the ability to invade into veins and form tumor thrombi.

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  • von Hippel-Lindau病に合併した両側褐色細胞腫,異時性両側腎細胞癌の1例

    鈴木 一也, 小瀬川 悦子, 星井 達彦, 宮島 憲生, 高橋 英祐, 渡辺 竜助, 小原 健司, 冨田 善彦, 高橋 公太, 吉田 実, 矢尾 正祐

    日本泌尿器科学会雑誌   93 ( 6 )   710 - 714   2002.9

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    Language:Japanese   Publisher:(一社)日本泌尿器科学会  

    症例は38歳男で,2年9ヶ月前,両側副腎褐色細胞腫に対して副腎切除術を行った.2年4ヶ月前に左腎腫瘍を認め,左腎部分切除術を施行した.病理所見は腎細胞癌で,遺伝子解析ではcodon167番のmissense変異が同定された.8ヶ月前,右腎腫瘍を認めたが,拡張型心筋症に伴う心機能低下のため手術は困難と考え,現在経過観察中である

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    Other Link: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2002&ichushi_jid=J01175&link_issn=&doc_id=20021002090008&doc_link_id=110003060635&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F110003060635&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • [Bilateral pheochromocytomas and asynchronous bilateral renal cell carcinomas associated with von Hippel-Lindau disease: a case report].

    Kazuya Suzuki, Etsuko Kosegawa, Tatsuhiko Hoshii, Norio Miyajima, Eisuke Takahashi, Ryusuke Watanabe, Kenji Obara, Yoshihiko Tomita, Kohta Takahashi, Minoru Yoshida, Masahiro Yao

    Nihon Hinyokika Gakkai zasshi. The japanese journal of urology   93 ( 6 )   710 - 4   2002.9

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    A 38-year-old man who had been followed with diagnosis of dilated cardiomyopathy and retinal angioma was referred to our hospital because of incidentally detected bilateral adrenal masses. Although he was normotensive, levels of catecholamine in urine were elevated and I131-MIBG scintigraphy showed accumulation in bilateral adrenal glands. Screening of central nervous system by MRI revealed cerebellar hemangioblastoma. Right adrenalectomy and left partial adrenalectomy were performed, both of which tumors pathologically diagnosed as pheochromocytoma, followed by resection of the cerebellar hemangioblastoma. Five months later, abdominal CT revealed a left renal tumor and underwent left partial nephrectomy, being diagnosed as renal cell carcinoma. A right renal tumor was detected on follow up CT at 1 year after the partial nephrectomy. Since cardiac function was deteriorated, we have followed with careful observation. This is the second documented case of bilateral renal cell carcinomas and bilateral pheochromocytomas with VHL in Japan.

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  • Reverse transcription-polymerase chain reaction detection of prostate-specific antigen, prostate-specific membrane antigen, and prostate stem cell antigen in one milliliter of peripheral blood: Value for the staging of prostate cancer Reviewed

    Noboru Hara, Takashi Kasahara, Takashi Kawasaki, Vladimir Bilim, Kenji Obara, Kota Takahashi, Yoshihiko Tomita

    Clinical Cancer Research   8 ( 6 )   1794 - 1799   2002

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    Purpose: There have been several studies on the presence of circulating tumor cells in the peripheral blood of patients with malignant tumors including prostate cancer (PCa) using reverse transcription-PCR (RT-PCR). One of the aims of these studies was to obtain high sensitivity that would enable early-stage diagnosis. However, they varied in their detection rates, and the methods were rather complicated. We have improved the RT-PCR assay combining three prostate-associated molecules, prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), and prostate stem cell antigen (PSCA) to reveal patients with poor prognosis. Experimental Design: Peripheral blood samples were obtained from 129 patients including 58 cases of PCa and 71 cases of nonmalignant disorders. Total RNA was extracted from 1 ml of whole blood using a commercially available kit. Results: The sensitivity of PSA-, PSMA-, and PSCA-nested RT-PCR was verified with positive signals of a single LNCaP cell in 1 ml of female blood sample. PSA-, PSMA-, and PSCA-mRNA were detected in 7 (12.1%), 12 (20.7%), and 8 (13.8%) PCa, and in 1, 2, and 0 samples in nonmalignant disorders, respectively. Among 58 PCa patients, each PCR indicated the prognostic value in the hierarchy of PSCA&gt
    PSA&gt
    PSMA RT-PCR, and extraprostatic cases with positive PSCA PCR indicated lower disease-progression-free survival than those with negative PSCA PCR. Conclusions: The present findings suggest that PSCA PCR would be most promising for the molecular staging of PCa. The present RT-PCR is a highly cost-effective and rapid procedure, enabling the molecular staging of PCa with RT PCR as a diagnostic routine.

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MISC

  • The role of naftopidil in the management of benign prostatic hyperplasia

    Noboru Hara, Takaki Mizusawa, Kenji Obara, Kota Takahashi

    Therapeutic Advances in Urology   5 ( 2 )   111 - 119   2013

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    Language:English   Publishing type:Book review, literature introduction, etc.  

    Naftopidil, which to a certain extent shows an affinity to α1D-adrenoceptor subtype in addition to a high affinity to α1A-adrenoceptor, has been used for the treatment of benign prostatic obstruction and benign prostatic hyperplasia (BPH) associated lower urinary tract symptoms (LUTS). The aim of the present review is to systematically refer to the published studies on this unique agent for BPH. Based on a randomized prazosin-controlled study and another double-blind placebo-controlled study, which verified the dose-dependent effects of naftopidil, the Japanese Ministry of Health, Labor and Welfare approved naftopidil for treating men with BPH in 1996. Several tamsulosin-controlled studies have suggested treatment effects of naftopidil similar to those of tamsulosin and potentially higher efficacy for alleviating storage symptoms by naftopidil. Although well-designed, randomized studies are warranted to confirm the long-term outcomes and effector/target of naftopidil, the α1A-antagonist naftopidil, which also blocks α1D-adrenoceptor, improves voiding symptoms, and may also be useful for the management of men with storage symptoms represented by nocturia, retrieving their quality of life impaired by BPH-associated LUTS. © 2012, SAGE Publications. All rights reserved.

    DOI: 10.1177/1756287212461681

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  • Smad7 mediates growth suppression induced by transforming growth factor-beta in human prostate stromal cells.

    K Obara, Bilim, V, K Kobayashi, Y Tomita, N Hara, T Kasahara, K Arai, K Takahashi

    JOURNAL OF UROLOGY   167 ( 4 )   218 - 219   2002.4

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    Language:English   Publishing type:Research paper, summary (international conference)   Publisher:LIPPINCOTT WILLIAMS & WILKINS  

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  • G-protein coupled receptor kinase 2 and 3 expression in human detrusor cultured smooth muscle cells

    K Obara, K Arai, Y Tomita, A Hatano, K Takahashi

    UROLOGICAL RESEARCH   29 ( 5 )   325 - 329   2001.10

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    Language:English   Publisher:SPRINGER-VERLAG  

    The aim of this study was to investigate the expression of G-protein coupled receptor kinases (GRKs) mRNA by RT-PCR and GRKs protein by immunohistochemistry in human detrusor cultured smooth muscle. Primary cultures of human detrusor smooth muscle cells were established using the explant method from three normal bladders. The expression of each GRK, beta -adrenergic receptor and muscarinic acethylcholine receptor (mAchR) mRNA was examined by reverse transcription polymerase chain reaction (RT-PCR). Immunohistochemical staining was also performed using primary antibodies for GRKs. The GRK2 and GRK3 transcripts were detected by RT-PCR. The m2, m3 and m5 mAchR and beta1, beta2 and beta3 adrenergic receptor subtypes mRNA were also detected. Using immunohistochemistry, both GRK2 and GRK3 were found to be expressed in detrusor smooth muscle cells. These results demonstrated the existence of GRK2 and GRK3 and the co-expression of m2, m3 and m5 mAchR and beta1, beta2 and beta3 adrenergic receptor subtypes in detrusor smooth muscle cells. The possibility exists that these kinases play a role in the desensitization mechanism of mAchR and beta adrenergic receptors.

    DOI: 10.1007/s002400100207

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  • Expression of m2 muscarinic acetylcholine receptor mRNA in primary culture of human prostate stromal cells

    K Obara, K Arai, N Miyajima, A Hatano, Y Tomita, K Takahashi

    UROLOGICAL RESEARCH   28 ( 3 )   196 - 200   2000.6

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    The aim of this study was to investigate the expression of the muscarinic acetylcholine receptor (mAchR) subtypes mRNA in primary culture of human prostate stromal cells using the reverse transcription polymerase chain reaction (RT-PCR), RNA blotting and in situ hybridization (ISH). Using an explant method, we obtained a primary culture of prostate stromal cells from three patients with benign prostatic hypertrophy. Total RNA was extracted using the acid guanidinium method for cDNA synthesis. First-strand cDNA was then used for PCR with primers designed to amplify the fragments of each mAchR subtypes (m1-m5) cDNA sequence. The m2, m3 and m4 subtype expected bands were detected: in particular m2 transcripts was strongly detected in the stromal cell culture. Each of the PCR products were subcloned into the pGEM-T plasmid vector, sequenced and random primer labeled using P-32. Digoxigenin-labeled cRNA probes were synthesized by in vitro transcription. RNA blotting using a m2 muscarinic receptor cDNA probe revealed a 4.5 kb single transcript. However, m3 and m4 probes did not hybridize. Using in situ hybridization (ISH), m2 receptor mRNA signals were detected in several smooth muscle cells. The staining was predominantly localized to the perinuclear cytoplasm. The m3 and m4 probes did not hybridize. These results suggested that mi receptor subtype plays a role in smooth muscle activity of the human prostate.

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  • Expression of the ETA and ETB endothelin receptor subtype mRNA in human detrusor cultured smooth muscle cells

    K Obara, PD Walden, A Hatano, Y Tomita, K Takahashi, H Lepor

    UROLOGIA INTERNATIONALIS   65 ( 2 )   68 - 72   2000

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    Language:English   Publisher:KARGER  

    The aim of this study was to determine the expression of the endothelin receptor subtype mRNAs in human detrusor cultured smooth muscle cells using reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization (ISH), First strand cDNA was made from human detrusor cultured smooth muscle cells total RNA and used for PCR with primers designed to amplify fragments of the ETA and ETB endothelin receptor subtype cDNA sequences. Subcloned fragments of the ETA and ETB endothelin receptor cDNAs were used to synthesize digoxigenin-labeled cRNA probes by in vitro transcription, COS-7 cells transfected with the ETA and ETB receptor cDNAs were used as positive control and to confirm the absence of cross-hybridization due to sequence homology, Both ETA and ETB receptor mRNAs were detected by RT-PCR analysis. By ISH, both ETA and ETB receptor subtype mRNAs were detected. However, ETA signal was much more intense than ETB signal. These results indicate that mRNAs for both ETA and ETB receptors are expressed in detrusor smooth muscle cells of human urinary bladder. The ETA receptor is the predominant detrusor ET receptor. Copyright (C) 2000 S. Karger AG, Basel.

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  • ヒト前立腺間質細胞におけるm2ムスカリン性アセチルコリンセプターの発現について

    Urol. Res.   28 ( 3 )   196 - 200   2000

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  • ヒト膀胱平滑筋におけるETA,ETBエンドセリンレセプターの発現について

    Urol. Int.   ( 65 )   68 - 72   2000

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  • Localization of P-2Y1 purinoceptor transcripts in the rat penis and urinary bladder

    K Obara, H Lepor, PD Walden

    JOURNAL OF UROLOGY   160 ( 2 )   587 - 591   1998.8

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    Purpose: The aim of this study was to determine the expression and localization of the P2Y(1) purinoceptor mRNA in rat penis and urinary bladder using reverse transcription polymerase chain reaction (RT-PCR), northern blotting and in situ hybridization (ISH).
    Materials and Methods: RT-PCR: First strand cDNA was prepared from rat penis and urinary bladder dome total RNA and used for PCR with primers designed to amplify fragments of the P2Y(1) purinoceptor cDNA sequence. Northern blotting: PCR products were subcloned into the pGEM-5Zf(+) plasmid vector, sequenced and random primer labeled using P-32. Labeled probe was hybridized, ISH: Digoxigenin labeled cRNA probes were synthesized by in vitro transcription,
    Results: P2Y1 purinoceptor mRNA was detected by RT-PCR analysis in both rat penis and urinary bladder. RNA blotting using a P2Y(1) purinoceptor cDNA probe revealed a single transcript of 4.2kb in both tissues. This band was the same size as that expressed by the heart, which contains high levels of P2Y(1) purinoceptor (Burnstock, G,: Physiological and pathological roles of purines: an update. Drug. Dev. Res., 28: 195, 1993). By ISH, P2Y(1) purinoceptor mRNA was localized in detrusor smooth muscle cells and blood vessels in urinary bladder. In penis, positive signals were detected in endothelial cells which line the lacunar space and blood vessels. No hybridization was seen in corpus cavernosum smooth muscle cells and urethra.
    Conclusion: These results indicate that mRNAs for P2Y(1) purinoceptor are expressed in detrusor smooth muscle cells and blood vessels of rat urinary bladder. However, in penis, this receptor is expressed in endothelial cells which lines the lacunar space and blood vessels, but not expressed in corpus cavernosum smooth muscle cells and urethra.

    DOI: 10.1016/S0022-5347(01)62963-X

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  • ラット陰茎,膀胱におけるP<sub>2</sub>Y<sub>1</sub>プリンレセプターの局在

    J. Urol.   160   587 - 591   1998

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Research Projects

  • 低酸素環境に暴露されたヒト膀胱平滑筋細胞に生ずる小胞体ストレス応答機構

    Grant number:19659408

    2007

    System name:科学研究費助成事業

    Research category:萌芽研究

    Awarding organization:日本学術振興会

    小原 健司

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    Grant amount:\3200000 ( Direct Cost: \3200000 )

    この研究は、ヒト膀胱平滑筋細胞を用いて低酸素刺激による小胞体ストレス関連遺伝子の発現を検索することにより、虚血や低酸素による小胞体ストレスへの応答機構とこれによって引き起こされるアポトーシスが疾患の進行にどのように関与しているかを解明することを目的としている。
    われわれは、ヒト膀胱平滑筋細胞より調製したprimary cell cultureを用いて酸素吸着、二酸化炭素発生パックによる慢性的な酸素欠乏モデル、ならびにミネラルオイルを用いて急性虚血モデルを作成した。細胞数あるいは増殖活性に関する影響は、^3H-チミジン法、MTT assayにて解析し、XBP1のスプライシングはRT-PCR、 sequencing法を用いて検討した。
    酸素欠乏モデルを用いた実験では、低酸素状態に対する小胞体ストレス応答機構として小胞体シャペロン遺伝子の発現に重要な役割を持つXBP1遺伝子のスプライシングが検出された。具体的には、ヒト膀胱平滑筋細胞において低酸素刺激はunspliced XBP-1 mRNAより26塩基のスプライシングを生じさせた。
    これと平行して糖鎖の付加阻害を生じさせるツニカマイシン処理や内腔カルシウムの枯渇を生じさせるタプシガルギン処理を行い小胞体ストレスを引き起こし反応を見たがやはり酸素欠乏刺激と同じように、小胞体シャペロン遺伝子の発現に関与するXBP1分子のスプライシング反応を検出した。

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  • Significance of newly identified apoptosis-related p19^<ARF> gene alteration in Urological tumors.

    Grant number:12470329

    2000 - 2001

    System name:Grants-in-Aid for Scientific Research

    Research category:Grant-in-Aid for Scientific Research (B)

    Awarding organization:Japan Society for the Promotion of Science

    TOMITA Yoshihiko, OBARA Kenji, TANIKAWA Toshik

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    Grant amount:\2700000 ( Direct Cost: \2700000 )

    p19^<ARF> (p14^<ARF> in human) binds and inhibits MDM2 function leading to sound function of p53 as a guardian of genome. In this project we have investigated gene status and function of p14^<ARF> in Urological tumors, and obtained results as follows :
    1. Among transitional cell cancer cell lines, RT4 did not have mRNA suggesting homozygous deletion (HD).
    2. Out of 4 renal cell carcinoma (RCC) cell lines, ACHN and KRC/Y expressed p14^<ARF> mRNA.
    3. Using quantitative DNA-PCR evaluating HD, 3 RCC cell lines were suggested to have HD.
    4. Immunihistochemical staining for p14^<ABF> using 3 different antibodies, no positive staining was detected in RCC samples.
    5. Eight of thirty-four DNA extracted for tumor specimens revealed HD pattern and also poorer prognosis.
    6. Introduction of p14^<AEF> gene in deficient cell lines resulted in lethal, and one stable transfectant showing p14^<ARF> mRNA positivity did not have any protein, indicating presence of epigenetic mechanism inactivating p14^<AHF> function. Thus, RCC showing infrequent p53 gene alteration may carry malfunction of p14^<ARF> because of HD or inactivation by epigenetical mechanism(s).

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  • Molecular analysis of smooth muscle cell phynotype in genitourinary tract

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    Grant type:Competitive

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  • autonomons receptor in genitourinary tract

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  • 尿路性器平滑筋細胞の形質変換とその分子機構の解析

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    Grant type:Competitive

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  • 尿路性器における自律神経系レセプターの研究

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