Akihiro Kawauchi

Shiga University of Medical Science, Ōtu, Shiga, Japan

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Publications (201)476.32 Total impact

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    ABSTRACT: Abstract Objective: To evaluate the feasibility of regional cramp in laparoscopic partial nephrectomy, we performed partial nephrectomy using a kidney grasper that enabled the application of ischemia to a limited region of the kidney. Materials and Methods: The subjects were 5 renal cell carcinoma patients. The mean tumor diameter was 15 mm. There were 2 male and 3 female patients. A transperitoneal approach was used in all cases. Following the standard procedure of laparoscopic partial resection, the hilum of the kidney was confirmed and treated to prepare for rapidly applying clamping with forceps. Tumor resection and suture were then performed under partial warm ischemia using a kidney grasper. Results: Surgery could be completed in 4 patients using this method. In the remaining patient, control of bleeding was considered difficult during tumor resection after applying partial ischemia, and so the procedure was switched to renal artery clamping using bulldog forceps. In the 4 patients in whom a kidney grasper was used, the mean partial warm ischemia time was 23.6 minutes (range, 23-25 minutes), and the mean blood loss was 110 mL (range, 20-260 mL). Conclusions: This procedure may be a useful option in ischemia for partial nephrectomy.
    Journal of laparoendoscopic & advanced surgical techniques. Part A. 10/2014;
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    ABSTRACT: Objectives To investigate the long-term outcomes of hand-assisted laparoscopic radical nephrectomy compared with those of open nephrectomy.Methods Hand-assisted laparoscopic radical nephrectomy was carried out in 132 patients with T1 renal cell carcinoma (between November 1999 and November 2008). Their outcomes were compared with those of 61 patients treated with open nephrectomy. The durations of follow up were 6–121 months (median 65 months) and 7–146 months (median 84 months) in the hand-assisted laparoscopic radical nephrectomy and open nephrectomy groups, respectively.ResultsThe 7-year recurrence-free rates were 88.5 and 85.6% in the hand-assisted laparoscopic radical nephrectomy and open nephrectomy groups, respectively, showing no significant difference between the two groups. The 7-year cancer-specific survival rates were 92.3 and 91.4% in the hand-assisted laparoscopic radical nephrectomy and open nephrectomy groups, respectively, showing no significant difference between the two groups. Also, the 10-year recurrence-free rates were 85.4 and 78.1% in the hand-assisted laparoscopic radical nephrectomy and open nephrectomy groups, respectively. When changes in the recurrence-free rate were analyzed using the Kaplan–Meier method, no significant difference was observed between the two groups. The 10-year cancer-specific survival rates were 91.8 and 87.9% for hand-assisted laparoscopic radical nephrectomy and open nephrectomy, respectively, showing no significant difference between the groups.Conclusions Hand-assisted laparoscopic radical nephrectomy might be comparable with open nephrectomy with regard to long-term cancer control.
    International Journal of Urology 08/2014; · 1.73 Impact Factor
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    ABSTRACT: Androgen-independent prostate cancer is known as a hormone-refractory disease. Though the androgen receptor (AR) is considered to be a key regulator of androgen-independent prostate cancer progression, the mechanism through which AR gene expression is regulated is not well understood. Here, we showed that the AR gene was upregulated by paired box 2 (PAX2) in androgen-independent prostate cancer. When PAX2 upregulated AR gene expression, a decrease in DNA methylation of the AR gene locus was also observed. PAX2 was highly expressed and promoted cell growth in an androgen-independent prostate cancer cell line (22Rv1). The cell growth inhibition by PAX2 knockdown was rescued by AR overexpression in 22Rv1 cells. In a mouse xenograft model of androgen-independent prostate cancer, PAX2 knockdown inhibited tumor growth and AR gene expression and increased DNA methylation of the AR gene. Consistent with this, AR and PAX2 expression levels were positively correlated in prostate cancer patients. These findings suggested that PAX2 promoted cancer cell growth in androgen-independent prostate cancer by regulating AR gene expression through an epigenetic mechanism.This article is protected by copyright. All rights reserved.
    FEBS Journal 08/2014; · 4.25 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate our institution's experience in performing laparoscopic radical nephrectomy (LRN) and partial nephrectomy (PN) in patients with small renal masses.
    International journal of clinical oncology. 06/2014;
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    ABSTRACT: Purpose The Japanese Urological Association and Japanese Society of Endourology established a urological laparoscopic skills qualification system called the Endoscopic Surgical Skill Qualification (ESSQ) System in Urological Laparoscopy in 2004. The reliability of video assessments by referees was evaluated. Materials and Methods Videos of nephrectomies or adrenalectomies performed by the applicants were assessed by 2 referees selected among a pool of 42 referees. From 2004 to 2011, 1308 urologists applied and 60.2% were qualified after video assessments. The results of skills assessments on 1220 videos which had fixed points by 2 referees were analyzed statistically. Results The average number of videos which each referee assessed was 58.1, with a range of 16 to 87. The accordance rate of the results of the video assessment, pass or fail, by the two referees was 68.9%. The scores of the video assessment by each referee averaged 62.7+/-2.4(SD) (full score was set at 75 points and >=60 points was required to pass). There was statistically significant difference in the average video assessment score among the referees (p<0.001), and 5 referees showed significantly higher or lower average scores than the other referees. The percentage qualification of the final decision made by the referee committee on the videos originally assessed by each referee showed no significant differences among the 42 referees. The accordance rate of the results from the video assessment by each referee with the final decision by the committee showed a statistically significant positive correlation with the number of videos assessed by each referee (r=0.404, p=0.0080). Conclusions The ESSQ system showed moderate reliability for the video assessments by the referees. It was concluded that the video assessments by the referees were fair for all applicants, because the final qualification rates showed no significant differences among the referees.
    Journal of endourology / Endourological Society 05/2014; · 1.75 Impact Factor
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    ABSTRACT: To compare the outcomes of laparoendoscopic single-site pyeloplasty versus those of conventional laparoscopic pyeloplasty. A total of 26 laparoendoscopic single-site pyeloplasty cases carried out in University Hospital: Kyoto Prefectural University of Medicine, Kyoto, Japan, from 2008 to 2013 were compared with a control group of 26 age-matched laparoscopic pyeloplasty cases carried out during the same study period. The mean age of the patients was 20.4 years (range 1-56 years). Laparoendoscopic single-site pyeloplasty was carried out on the right in nine cases and on the left in 17 cases. The operative time was 246 ± 68 min. Regarding the 14 pediatric patients, the mean age was 7.1 years (range 1-14 years). The operative time was 243 ± 49 min. As for the 12 adult patients, the mean age was 35.8 years (range 16-56 years). The operative time was 248 ± 86 min. The mean operative time of the control group in age-matched laparoscopic pyeloplasty was 239 ± 51 min. Times were 229 ± 54 min for the pediatric patients and 253 ± 45 min for the adult patients. There was no significant difference in the operative time between the control group and the laparoendoscopic single-site group for both adults and children. Blood loss was minimal, and no intraoperative and postoperative complications were observed in the 26 laparoendoscopic single-site pyeloplasty cases. The present findings suggest that laparoendoscopic single-site pyeloplasty can be used in both pediatric and adult patients, offering a superior cosmetic outcome than conventional laparoscopic pyeloplasty, and a lower degree of postoperative pain. A large-scale prospective, randomized study is required to confirm these findings, and to define the future role of laparoendoscopic single-site pyeloplasty.
    International Journal of Urology 03/2014; · 1.73 Impact Factor
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    ABSTRACT: The objective of the present study was to evaluate the results of laparoendoscopic single-site (LESS) pyeloplasty and pyelolithotomy, which were performed concurrently in patients with pelviureteric junction obstruction (PUJO) and renal stones. Four patients with PUJO and renal stones underwent pyelolithotomy performed concurrently with LESS pyeloplasty. In 3 patients, a 2.5-cm incision was made in the umbilical region. In the fourth patient, the 2.5-cm vertical incision was made at a site 7 cm below the umbilical region because of a stone in the right lower calyx. After dissection of the pelviureteric junction, an incision of approximately 1 cm was made along the presumed transection line of the renal pelvis. The pyelolithotomy was performed using a 24F rigid nephroscope through a SILS port. Dismembered pyeloplasty was performed after extraction of the renal stones was completed. The mean operation time was 277 minutes (range, 225-373), and the mean lithotomy time was 31 minutes (range, 20-50). No intraoperative or postoperative complications were observed. For all 4 patients, discharge from the hospital was possible after a mean of 3.4 postoperative days (range, 3-4). All patients became stone free. Postoperative ultrasound revealed that hydronephrosis improved in all patients. In all patients, resolution of the symptoms was confirmed. LESS nephrolithotomy with pyeloplasty is a safe and effective procedure with a good cosmetic result for patients with PUJO and renal stones.
    Urology 10/2013; · 2.42 Impact Factor
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    ABSTRACT: To evaluate the outcome of low-dose-rate permanent brachytherapy combined with anti-androgen deprivation therapy for intermediate-risk prostate cancer excluding biopsy Gleason score 4 + 3. Patients included in the intermediate-risk group were those presenting clinical stage T1c to T2c (by magnetic resonance imaging staging), Gleason score 3 + 4 or lower and/or prostate-specific antigen less than 20 ng/mL, whereas those with clinical stage T1c to T2a, Gleason score 3 + 3 and prostate-specific antigen less than 10 ng/mL represented the low-risk group, and were used as controls. In the intermediate-risk group, therapy with a luteinizing hormone-releasing hormone analog was continued for at least 6 months before and after permanent brachytherapy. A total of 147 low-risk group patients and 139 intermediate-risk group patients were included in the study. The median follow up was 51 and 52 months for the intermediate-risk group and low-risk group, respectively. The 5-year overall, cause-specific and distant-metastasis-free survival rates in the low-risk group and intermediate-risk group were 97.6/99.2, 100/100 and 100/100%, respectively. The 5-year biochemical disease-free survival in these groups were 95.9 and 92.5%, respectively (P = 0.18). There was no sexual activity and desire for erection before treatment in 50%, and in 46% of the patients in the low-risk group and intermediate-risk group, respectively. Overall satisfaction score at 2 years after permanent brachytherapy significantly improved, compared with pretreatment (P = 0.0399). In intermediate-risk prostate cancer, excluding biopsy Gleason score 4 + 3, permanent brachytherapy combined with androgen deprivation therapy for 6 months or more represents an effective treatment option in Japanese patients, based on a favorable prognosis, adverse event profile and quality of life analysis.
    International Journal of Urology 08/2013; · 1.73 Impact Factor
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    ABSTRACT: To report an international, multi-institutional series of laparoendoscopic single-site pyeloplasty (LESS-P) with analysis of functional outcomes. LESS-P cases performed between October 2007 and June 2012 at 7 institutions worldwide per individual institutional protocols, entry criteria, and techniques were included. Patient characteristics, operative indications, perioperative outcomes, and postoperative follow-up were retrospectively collected and analyzed. The study included 140 adult patients (age 39.9 ± 15.7 years; body mass index 24.8 ± 4.2 kg/m(2); 15% with previous abdominal surgery) who underwent unilateral LESS-P, most of whom (94.3%) had dismembered reconstructions. Mean operative time was 202.1 ± 47 minutes with an estimated blood loss of 61.2 ± 44.6 mL. Robotic laparoendoscopic single-site surgery was applied in 31 patients (22.1%). A single 2-3 mm accessory port was used in 44 patients (31.4%) and a single 5-12 mm accessory port was added in 9 patients (6.4%), whereas 10 patients (7.1%) were converted to conventional multiport laparoscopy. No patients required conversion to open surgery, nor were any intraoperative complications reported. Length of hospitalization was 2.4 ± 1.6 days. The overall 90-day postoperative complication rate was 18.6%, mostly low-grade complications (Clavien I-II). With a mean follow-up of 14.0 ± 10.8 months, 93.4% had resolution of symptoms and 94.4% had radiographic evidence demonstrating resolution of ureteropelvic junction obstruction. Assessment of drainage with diuretic nuclear renal scan provided evidence of improvement in 86.5% of patients on their first postoperative renal scan. This study highlights the most comprehensive experience with LESS-P reported to date. Outcome measures parallel those of large published series of conventional laparoscopic pyeloplasty. Despite these encouraging findings, longer follow-up is needed to determine the efficacy and durability of this approach for the treatment of ureteropelvic junction obstruction.
    Urology 06/2013; · 2.42 Impact Factor
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    ABSTRACT: BACKGROUND: Metastasis is a consequence of many biological events, during which cancer stem cells are shifted into a malignant state. Among these events, invasion of prostate cancer cells into host tissues is possible to be assessed by means of an in vitro invasion model, and is thought to be coupled to altered expression of membrane proteins. Dysregulated functions of the factors regulating organogenesis during embryogenesis are known to facilitate metastasis of many types of cancers. PAX2 (paired box 2) is a member of the PAX transcription factor family, which regulates prostatic ductal growth and branching in organogenesis of mammalian prostates. However, the role of PAX2 in prostate cancer development remains to be determined. METHODS: PAX2 expression in human prostate cancers and normal prostate epithelium were examined by quantitative RT-PCR and immunohistochemistry. Matrigel invasion assay and a gene array analysis were performed using prostate cancer cell lines transfected with either control or PAX2 siRNA. RESULTS: In human prostate cancers, PAX2 was hyper-expressed in metastatic cancers, but was expressed at lower levels in non-metastatic cancers. Consistent with this, PAX2 knockdown repressed cell growth and invasion in a Matrigel invasion assay. Gene ontology analysis revealed that many cell membrane proteins were downregulated after PAX2 knockdown. CONCLUSIONS: Our data suggested that PAX2 hyper-expression promotes the development of the metastatic state in prostate cancer cells, presumably through upregulating the expression of cell membrane proteins. Prostate 9999: 1-10, 2013. © 2013 Wiley Periodicals, Inc.
    The Prostate 06/2013; · 3.84 Impact Factor
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    ABSTRACT: Purpose: The aim of this study was to assess the screenees' knowledge on prostate cancer and attitude to PSA screening using the Fact Sheet from one district, Kyoto, Japan. Methods: A PSA screening program is offered to people aged more than 54 years since 1995. The Fact Sheet consists of several chapters, as follows: (1) possibility of diagnosing prostate cancer in terms of the PSA threshold, and future morbid risk, (2) benefit and harm of biopsy, (3) necessary examinations after the diagnosis of prostate cancer and risk for overdiagnosis and overtreatment, and (4) comorbidity of main treatments such as surgery and radiation therapy. Each screenee was asked how well the Fact Sheet was understood. Results: Of the 330 men, 288 read the Fact Sheet for the first time. Of those, 59 and 75% did not know that biopsy indication was determined based on the PSA value and the concept of overdiagnosis, respectively. Furthermore, 68% did not know that active surveillance is established as one option for prostate cancer treatment. However, the screenee's knowledge in the 42 men who read the Fact Sheet previously improved substantially. Conclusions: The degree of comprehension of examinees is currently insufficient, and repeated enlightenment is required.
    Urologia Internationalis 04/2013; · 1.07 Impact Factor
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    ABSTRACT: OBJECTIVE: To evaluate the hemostatic effect of newly developed medical adhesive in animal partial nephrectomy models. MATERIALS AND METHODS: A total of 30 experimental rabbits were used in the first study. After clamping the renal vessels, partial nephrectomy was performed up to the opening of the calices. Bioglue was applied to the resection stumps using the new glue (group 1, n = 10) or fibrin glue (group 2, n = 10) for 2 minutes, and the blood loss was measured after unclamping the vessels. Simple unclamping without glue (group 3, n = 10) was also evaluated. For the second study, we used 9 dogs with blood pressure monitoring. After preparation similar to that for the first study, the new glue was applied in 3 dogs (group 4), fibrin glue in 3 dogs (group 5) and no glue in 3 dogs (group 6). Histologic evaluation was performed at 7 days and 1 month after surgery. RESULTS: The mean blood loss was significantly less in group 1 (1.45 g) than in groups 2 (6.59 g) and 3 (19.77 g; P <.001 for both). It was also significantly less in group 4 (12.5 g) than in group 5 (182.5 g; P <.001). Group 4 maintained their initial blood pressure throughout the study, but a significant decrease was observed in group 5. No hematoma was observed at day 7. CONCLUSION: The new glue showed acceptable hemostasis when applied to the resection stumps after partial nephrectomy in both the rabbit and the dog models. These findings indicate that it could be useful for hemostasis after partial nephrectomy.
    Urology 02/2013; · 2.42 Impact Factor
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    ABSTRACT: We report our experience of extraperitoneal nerve-sparing laparoscopic retroperitoneal lymph node dissection after chemotherapy. Six patients were diagnosed with non-seminomatous germ cell tumor after orchiectomy and clinical stage IIB disease. Nerve-sparing laparoscopic retroperitoneal lymph node dissection was carried out for residual retroperitoneal tumors after cisplatin-based chemotherapy. The median tumor diameter was 2.95 cm before chemotherapy and 1.95 cm after chemotherapy. A modified left (n = 1), right (n = 1) and bilateral (n = 4) template for the dissection area was used. Surgery was successfully completed in all patients and no conversion to open surgery was necessary. Median operative time was 394 min (range 212-526 min). Median blood loss was 75 mL (range 10-238 mL). The overall complication rate was 33.3% (2/6). Two patients had prolonged lymphatic leakage (grade I), which was managed conservatively. Antegrade ejaculation was preserved in all six patients. The histopathological findings showed that two patients had mature teratoma and four patients had necrotic tissue. After a median follow up of 30 months (range 24-36), no recurrence of disease was observed. We can conclude that extraperitoneal nerve-sparing laparoscopic retroperitoneal lymph node dissection for residual tumors after chemotherapy is a feasible operation. The oncological outcomes need to be confirmed in a certain number of patients with longer follow up.
    International Journal of Urology 01/2013; · 1.73 Impact Factor
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    ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is endogenously expressed in immune cells and contributes to immunosurveillance for cancer. TRAIL induces apoptosis preferentially in various cancer cells, including renal cell carcinoma (RCC) cells. In this study, the serum TRAIL level was examined using an enzyme-linked immunosorbent assay in 52 healthy controls and in 84 RCC patients prior to surgery and its significance as a biomarker was evaluated. The median serum TRAIL level was lower in RCC patients compared to the healthy controls (55.9 vs. 103.1 pg/ml; P=0.019). RCC with lymph node metastasis (N1-2), distant metastasis (M1), stage III-IV, or microscopic venous invasion was associated with decreased serum TRAIL levels (P=0.032, 0.067, 0.020 and 0.011). When comparing serum TRAIL levels in the same RCC patients prior and subsequent to surgery (n=11), the levels were significantly higher after surgery (P=0.031). The cause-specific survival rate was significantly higher in RCC patients with high serum TRAIL levels compared to those with low serum TRAIL levels (P=0.0451). TRAIL was estimated to contribute 64 and 13% of the lymphocyte-mediated cytotoxicity against human RCC ACHN and Caki-1 cells, respectively. These data suggest that the serum TRAIL level may be useful as a prognostic biomarker in RCC patients.
    Molecular and Clinical Oncology 01/2013; 1(1):69-74.
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    ABSTRACT: When the whole human genome sequence was determined by the Human Genome Project, the number of identified genes was fewer than expected. However, recent studies suggest that undiscovered transcripts still exist in the human genome. Furthermore, a new technology, the DNA microarray, which can simultaneously characterize huge amounts of genome sequence data, has become a useful tool for analyzing genetic changes in various diseases. A version of this tool, the tiling DNA microarray, was designed to search all the transcripts of the entire human genome, and provides huge amounts of data, including both exon and intron sequences, by a simple process. Although some previous studies using tiling DNA microarray analysis have indicated that numerous novel transcripts can be found in the human genome, none of them has reported any novel full-length human genes. Here, to find novel genes, we analyzed all the transcripts expressed in normal human prostate cells using this microarray. Because the optimal analytical parameters for using tiling DNA microarray data for this purpose had not been established, we established parameters for extracting the most likely regions for novel transcripts. The three parameters we optimized were the threshold for positive signal intensity, the Max gap, and the Min run, which we set to detect all transcriptional regions that were above the average length of known exons and had a signal intensity in the top 5%. We succeeded in obtaining the full-length sequence of one novel gene, located on chromosome 12q24.13. We named the novel gene "POTAGE". Its 5,841-bp mRNA consists of 26 exons. We detected part of exon 2 in the tiling data analysis. The full-length sequence was then obtained by RT-PCR and RACE. Although the function of POTAGE is unclear, its sequence showed high homology with genes in other species, suggesting it might have an important or essential function. This study demonstrates that the tiling DNA microarray can be useful for identifying novel human genes.
    Gene 12/2012; · 2.20 Impact Factor
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    ABSTRACT: PURPOSE: In analysis of a bladder diary with the patient's self-reported urinary perception grades, we developed a quantitative measure of bladder hypersensitivity, which we refer to as the urge perception index (UPI). The aim of this study was to evaluate the impact of the UPI on defining the severity of overactive bladder (OAB). MATERIALS AND METHODS: We retrospectively evaluated 69 female patients to visit our outpatient clinic with complaining storage symptoms. The patients were asked to complete OAB symptom score, and a 3-day bladder diary with a self-reported grading of urinary perception (range 1 to 5) per void, and diagnosed as OAB (n=43) or non-OAB (n=26). UPI was defined as a quotient of voided volume/urinary perception grade at every single void. RESULTS: A total of 1578 voids reporting were analysed. According to the grade of urinary perception, values of UPI in OAB demonstrated significantly lower values than those in non-OAB (p<0.001 in all perception grades of 1-4). The averages of UPIs in 3-day bladder diary was lower in OAB (55±28) than non-OAB (133±73) (p<0.0001). The most severe (the lowest) single UPI value during the 3-day was significantly lower in OAB (20±12) than non-OAB (62±40) (p<0.0001). There were negative linear correlations of UPI value with total OAB symptom scores (r=-0.598, p<0.0001) and with a symptom score of urgency (r=-0.557, p<0.0001). CONCLUSIONS: UPI, the integrated parameter of patient-reported bladder perception and voided volume, could be promising for quantifying the severity of OAB or bladder hypersensitivity through the analysis of a bladder diary.
    The Journal of urology 11/2012; · 3.75 Impact Factor
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    ABSTRACT: Purpose There have been few reports addressing how nocturnal enuresis affects the health related quality of life of patients and their mothers. Thus, we evaluated the health related quality of life of enuretic children and their mothers. Materials and Methods The health related quality of life of 139 patients with nocturnal enuresis and that of their mothers were evaluated before and after treatment. The children's health related quality of life was evaluated with the Kid-KINDL® protocol. The mothers' health related quality of life was evaluated using the SF-36®, the SDS (Self-Rating Depression Scale) for rating depression and the STAI (State-Trait Anxiety Inventory) for assessing anxiety. Results In the health related quality of life of enuretic children, the family domain score was significantly lower than that of controls (p = 0.02). In the health related quality of life of the mothers as shown by SF-36, the vitality domain score was significantly lower compared to controls (p = 0.01). The evaluation of the STAI score demonstrated a higher state anxiety score (p = 0.003), which represents current suffering from anxiety, and a similar trait anxiety score (p = 0.22), which represents a similar level of underlying tendency to anxiety. There was no significant difference between the mothers of enuretic children and the controls in the SDS evaluation. After treatment for enuresis the health related quality of life score was improved not only for the enuretic children as assessed by the Kid-KINDL protocol, but also for the mothers of enuretic children as assessed by the SF-36 and STAI. Conclusions Similar to other pediatric chronic diseases, nocturnal enuresis is a condition that negatively affects the health related quality of life of children and their mothers. Impaired health related quality of life can be improved after the successful treatment of nocturnal enuresis.
    The Journal of urology 11/2012; 188(5):1910–1914. · 3.75 Impact Factor
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    ABSTRACT: The aim of this study was to develop a novel technique for a minimally invasive ultrasound measurement of postvoid residual urine (PVR) in conscious mice using a miniature ultrasound probe and a transrectal approach. The PVR was determined by the ellipsoid formula in the maximum sectional image of the bladder visualized with a 20-MHz ultrasound probe (2 mm in diameter) inserted into the rectum. The accuracy, including the intra- and interobserver reproducibilities, of the ultrasonic PVR measurements (in 10 5- to 50-week-old mice) was evaluated, which revealed excellent internal consistency. In M(3) muscarinic acetylcholine receptor knockout male mice, a chronological evaluation of the PVR identified abnormal urinary retention present at infancy and exacerbated with aging, suggesting significant voiding dysfunction. Our technique for the measurement of PVR in conscious mice was accurate and useful for identifying the voiding dysfunction in mice.
    Ultrasound in medicine & biology 05/2012; 38(8):1357-62. · 2.46 Impact Factor
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    ABSTRACT: Although molecular targeted therapy has improved the clinical outcome of metastatic renal cell carcinoma, a complete response is rare and there are various side effects. Identifying novel target molecules is necessary to improve the clinical outcome of metastatic renal cell carcinoma. HMGA1 is over expressed in many types of cancer and it is associated with metastatic potential. It is expressed at low levels or not expressed in normal tissue. We examined HMGA1 expression and function in human renal cell carcinoma. HMGA1 expression in surgical specimen from patients with renal cell carcinoma was examined by immunoblot. HMGA1 expression in 6 human renal cell carcinoma cell lines was examined by immunoblot and immunofluorescence. The molecular effects of siRNA mediated knockdown of HMGA1 were examined in ACHN and Caki-1 cells. Immunoblot using surgical specimen showed that HMGA1 was not expressed in normal kidney tissue but it was expressed in tumor tissue in 1 of 30 nonmetastatic (3%) and 6 of 18 metastatic (33%) cases (p=0.008). Immunoblot and immunofluorescence revealed significant nuclear expression of HMGA1 in ACHN and Caki-1 cells derived from metastatic sites. HMGA1 knockdown remarkably suppressed colony formation and induced significant apoptosis in ACHN and Caki-1 cells. HMGA1 knockdown significantly inhibited invasion and migration in vitro, and induced anoikis associated with P-Akt down-regulation in ACHN cells. HMGA1 is a potential target for novel therapeutic modalities for metastatic renal cell carcinoma.
    The Journal of urology 04/2012; 187(6):2215-22. · 3.75 Impact Factor
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    ABSTRACT: We previously reported that cationic multilamellar liposome containing the human interferon-β (huIFN-β) gene (IAB-1) demonstrated significant cytotoxic effect in the NC65 human renal cell carcinoma (RCC) cell line. In this study, we investigated the molecular mechanisms of IAB-1-induced apoptosis and cytotoxicity in RCC cells. Remarkable in vitro cytotoxic and apoptosis-inducing effects of IAB-1 against NC65 cells were observed by a colorimetric method and TUNEL staining, respectively. In contrast, treatment of NC65 cells with exogenously added huIFN-β protein induced low-level cytotoxicity without apoptosis. Neutralizing antibodies against huIFN-β significantly suppressed the cytotoxic effect of huIFN-β protein, but they were unable to block the effect of IAB-1. Cytotoxicity assays using transwell plates revealed that NC65 cells treated with IAB-1 did not secrete cytotoxic soluble factors other than IFN-β. Substantial enhancement of interferon-stimulated response element (ISRE) activity of NC65 cells by IAB-1 was demonstrated by promoter reporter assays. In addition, immunofluorescence using confocal microscopy revealed the intracellular expression of IFN-β and its receptor induced by IAB-1. The induction of c-Myc by IAB-1 was suggested by a cDNA macroarray and was confirmed by western blot analysis. These findings indicate that IAB-1 induces significant cytotoxicity and apoptosis in NC65 cells, possibly through enhanced ISRE activity, that is associated with increased intracellular localization of huIFN-β and IFN-receptor. Our data support the potential clinical application of IAB-1 gene therapy for RCC resistant to IFN.
    International Journal of Oncology 02/2012; 40(5):1441-6. · 2.66 Impact Factor

Publication Stats

1k Citations
476.32 Total Impact Points


  • 2014
    • Shiga University of Medical Science
      Ōtu, Shiga, Japan
  • 1988–2014
    • Kyoto Prefectural University of Medicine
      • Department of Urology
      Kioto, Kyōto, Japan
  • 2002–2010
    • Fukushima Medical University
      • Department of Neurophysiology
      Hukusima, Fukushima, Japan
  • 1999–2010
    • Meiji University of Oriental Medicine
  • 2007
    • Kyoto Prefectural University
      Kioto, Kyōto, Japan