SERCA2aの持続的過剰発現は、生理的条件下では膀胱機能に影響を及ぼすが、膀胱出口部閉塞亜急性期の病的条件下では膀胱機能に影響しない

A functional impairment of the bladder and heart in a decompensated state caused by a pressure overload is accompanied by a decrease in the sarcoplasmic reticulum Ca2+-ATPase (SERCA2). The beneficial effects of SERCA2 overexpression in preserving cardiac functions have been previously reported. The aim of the present study was to investigate the effects of overexpressed SERCA2 on bladder functions under physiological and pathological conditions using partial bladder outlet obstruction (BOO) in SERCA2a transgenic Wistar rats (TG). Bladder cystometry and western blot analysis were performed using the wild-type Wistar rats (WT), TG, and BOO models (WTBOO and TGBOO). Persistent overexpression of SERCA2 induces reduced bladder compliance without hypertrophy in TG. BOO induces reduced bladder compliance and hypertrophy in WT and TG in the sub-acute phase, but persistent overexpression of SERCA2a in TG does not aggravate the bladder compliance and hypertrophy. In conclusion, SERCA2a overexpression affects bladder functions under physiological conditions, but not in BOO-induced sub-acute pathological conditions.博士（医学）・甲第623号・平成26年5月28

飲水指導は夜間頻尿患者の頻尿症状を有効に改善する

OBJECTIVES: To evaluate how guidance on water-intake impacts the degree of nocturia. METHODS: A total of 67 male patients were enrolled in the present study. Patients were asked to adjust their water and food intakes so that their 24-h urine production/bodyweight would be equal or lower than 30 mL/kg. One month after the treatment, the therapeutic gain from and adverse effects of fluid restriction were examined by comparing the pretreatment and post-treatment value of various parameters. RESULTS: Overall, 65 eligible patients were evaluated. In 44 patients (67%), the frequency of nocturia was improved to one or more times. The change in frequency of nocturia showed a positive correlation with the change in nocturnal urine volume. The change in nocturnal urine volume showed a positive correlation with the changes in 24-h urine production/bodyweight, 24-h drinking volume and daytime drinking volume. The changes in 24-h urine production/bodyweight and daytime drinking volume were independent factors influencing therapeutic effect. None of the participants reported any adverse event. CONCLUSIONS: In patients with a 24-h urine production/bodyweight equal or higher than 30 mL/kg, guidance on water intake might be considered effective and safe as a lifestyle therapy. Water restriction should be carried out not only in the evening, but also during daytime.博士（医学）・乙第1348号・平成26年12月3日© 2014 The Japanese Urological Associatio

RETROPERITONEAL FIBROSARCOMA WITH DISTINCTIVE CHARACTERISTICS ON GROWTH P ATTERN AND FINDINGS IN DIAGNOSTIC IMAGING

A 47-year-old man with lumbago had been found to have a perirenal hematoma at the lower pole of the left kidney on CT. MR imaging also demonstrated a hematoma，8 X8X9αn in size. After 1-month observation，the mass had very rapidly increased in size，suggesting it to be a neoplasm. Consequent surgery resulted in noncurative tumor extirpation，because of invasion to the descending colon，left kidney and surrounding tissues. Histlogically，the tumor consisted of uniform spindle-shaped cells with interlacing solid and bundle forms，showing a herring-bone pattern. Immunohistochemical studies finally led to the diagnosis of fibrosarcoma with markedly high malignant potential. Additional therapy was not performed. Rapid local spread of the tumor was demonstrated when bowel obstruction developed 2 months later. The patient died of the disease 3 months after surgery. No distant metastasis was observed throughout the clinical course

日本人男性における携帯式尿流量計(P-Flowdiary®)を用いた排尿量/尿流量に関する年齢階層別ノモグラムの作成

Background: To develop a nomogram of urinary volume and flow based on the data of Japanese men without lower urinary tract symptoms and multiple flows per participant whose characteristics were clear. Methods: Overall, 101 Japanese male volunteers without lower urinary tract symptoms aged between 20 and 59 years were enrolled. A portable uroflowmeter (P-Flowdiary®) was used to record urinary information (flow rate and volume) for 2 successive days. The model (quadratic, linear, or logarithmic regression) most fit for the relationship between maximum flow rate and voided volume was determined. The maximum flow rate at > 150 mL was compared among the 20-29-, 30-39-, 40-49-, and 50-59-year age groups. Nomograms appropriate for the age groups were created. Results: The mean age, International Prostate Symptom Score, and Overactive Bladder Symptom Score were 38.5 years, 0.42, and 0.24, respectively. The quadratic regression model was the most fit because its mean coefficient determination was 0.93 ± 0.06. The mean maximum flow rate was significantly lower in the 50-59-year age group (21.8 ± 5.05 mL/s, P < 0.01) than in the younger groups (24.14 ± 4.94, 24.05 ± 6.99, and 24.64 ± 5.72 mL/s). The 2 nomograms are Y = 28.99 {1 - exp(- 0.01 × X)} and Y = 25.67 {1 - exp(- 0.01 × X)} for the 20-49- and 50-59-year age groups, respectively. Conclusions: The nomogram can predict maximum flow rate based on voided volume in Japanese men aged 20-59 years without lower urinary tract symptoms.博士（医学）・甲第858号・令和4年12月22日© 2022. The Author(s). Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data

Life sciences

Aims: To examine the circadian expression changes in bladder clock genes in Dahl salt-sensitive rats following high salt intake. Main methods: Eighteen rats were divided into three groups: the high-salt diet group (HS group), the normal-salt diet group (NS group), and the salt-load interruption group (from a 4 % salt diet to a normal diet; salt-load interruption group [SI group]). Each rat was placed in an individual metabolic cage for 24 h twice weekly. Water intake, urine production, voiding frequency, and voided volume per micturition were recorded. Furthermore, 108 control rats were prepared. Bladders were harvested every 4 h at six time points. Furthermore, the mRNA expression of clock genes and mechanosensors was analyzed. Key findings: In the HS group, the bladder clock genes showed lower mRNA levels than in the NS group. The amplitude of circadian expression changes in bladder clock genes in the HS group was lower than that in the NS group. However, after changing from a 4 % salt diet to a normal diet, the waveforms of the clock gene expression in the SI group were closer to those of the NS group. The 24-h water intake and urinary volume of the SI group decreased to levels comparable to those of the NS group. Significance: Reduced salt intake partially restored the circadian rhythms of bladder clock genes.博士（医学）・甲第857号・令和4年12月22日Copyright © 2022 Elsevier Inc. All rights reserved

ラット膀胱での水吸収におけるアクアポリン-2の役割

AIM: We investigated the role of the bladder wall in permeating water, focusing on aquaporins. METHODS: Female Sprague-Dawley rats weighing 300 g were used to investigate the role of the bladder wall in saline permeation. Changes in intravesical fluid volume and sodium concentration were measured in the desmopressin acetate hydrate-loaded and control groups 3 h after administration. Bladders were resected to measure aquaporin-1, 2, and 3 gene expression using qRT-PCR. Additionally, the change of aquaporin-2 expression was measured using Western blotting and immunohistochemistry in intravesical aquaporin-2 siRNA-treated and control groups. RESULTS: Although the intravesical fluid volume and sodium concentration significantly decreased from 0 to 3 h (1.00 ± 0.00 vs 0.83 ± 0.08 mL, 157.80 ± 1.30 vs 146.8 ± 1.92 mEq/mL, P < 0.01, respectively in the control group), administration of desmopressin did not affect the extent of volume change. Aquaporin-2 expression was significantly higher in the 3-h distended bladders than in the empty bladder. Aquaporin-2 siRNA treatment suppressed aquaporin-2 expression and the change of intravesical fluid volume from 0 to 3 h (1.00 ± 0.00 and 0.99 ± 0.02 mL), which was related to the suppression of sodium concentration change in comparison with control siRNA treatment (149.6 ± 2.4 vs 143.6 ± 3.67 mEq/mL, P < 0.05). CONCLUSIONS: The rat urinary bladder absorbs water and salts under the full-filled condition. Aquaporin-2 plays an important role in the transport of water, accompanied by sodium concentration change. We demonstrated a part of the bladder absorption mechanism, which may lead to development of a new method for regulating bladder storage function.博士（医学）・甲第697号・平成31年3月15日© 2018 Wiley Periodicals, Inc.This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1002/nau.23715], which has been published in final form at [http://dx.doi.org/10.1002/nau.23715]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

高齢者における睡眠の質と夜間頻尿関連 : 在宅脳波データを用いた地域密着研究

PURPOSE: We objectively investigated the relationship between sleep quality/efficiency and factors associated with micturition using at-home electroencephalogram assessment. MATERIALS AND METHODS: Participants were recruited from among those enrolled in the Fujiwara-kyo Study, a community based longitudinal evaluation that began in Nara Prefecture, Japan, in 2007. Included participants were men at least 65 years old who woke up in the middle of the night/early morning at least 3 times per week with the urge to void. We evaluated lower urinary tract symptoms using the I-PSS and subjective sleep quality using the Pittsburgh Sleep Quality Index. Uroflowmetry and 3-day frequency volume charting measurements were also obtained. Electroencephalogram recordings were obtained during sleep to evaluate objective sleep quality. RESULTS: Final analysis included data from 47 participants. I-PSS-quality of life score and slow wave sleep time were independent predictors of good subjective sleep quality as determined by Pittsburgh Sleep Quality Index scores. Nocturnal urinary volume was an independent predictor of greater sleep efficiency. Maximum flow rate was an independent predictor of longer slow wave sleep time. CONCLUSIONS: In elderly men with nocturia, sleep quality is associated with lower urinary tract function. Higher subjective sleep quality is associated with longer slow wave sleep time and less severe lower urinary tract symptoms. Higher objective sleep quality is further associated with a higher urinary flow rate and lower nocturnal urinary volume.博士（医学）・甲第669号・平成29年3月15日Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved

臥床早期の下肢水分移行はHUSを減少させる

OBJECTIVE: To investigate whether or not the leg fluid displacement observed when moving from the standing to recumbent position at bedtime reduces the hours of undisturbed sleep (HUS). METHODS: Men aged 50 years or older who were hospitalized for urological diseases were investigated. Body water evaluation was performed three times with a bioelectric impedance method: (i) 17:00, (ii) 30 min after (short-term), and (iii) waking up (long-term). A frequency volume chart was used to evaluate the status of nocturnal urine production, and the factors affecting HUS were investigated. RESULTS: A total of 50 patients (mean age: 68 years) were enrolled. Short-term changes in extracellular fluid (ECF in the legs showed a significant positive correlation with urine production per unit of time at the first nocturnal voiding (UFN/HUS) (r = 0.45, P = 0.01). In the comparison between patients who had <3 HUS vs. those who had ≥3 HUS, the <3 HUS group showed significantly greater short-term changes in leg fluid volume, night-time water intake (17:00-06:00), and UFN/HUS. Multivariate analysis to assess the risk factors for <3 HUS indicated UFN/HUS as a risk factor in the overall model, and short-term changes in leg ECF and night-time water intake as risk factors in the model that only considered factors before sleep. CONCLUSIONS: Nocturnal leg fluid displacement may increase urine production leading up to first voiding after going to bed, and consequently, induce early awakening after falling asleep.博士（医学）・甲第703号・平成31年3月15日© 2017 John Wiley & Sons Australia, LtdThis is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/10.1111/luts.12176], which has been published in final form at [http://dx.doi.org/10.1111/luts.12176]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Novel missense mutation in the FH gene in familial renal cell cancer patients lacking cutaneous leiomyomas

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare tumor predisposition syndrome characterized by cutaneous and uterine leiomyomas and papillary type 2 renal cell cancer. Germline mutation of the fumarate hydratase (FH) gene is known to be associated with HLRCC. CASE PRESENTATION: We describe a 64-year-old father and his 39-year-old son with HLRCC who developed papillary type 2 RCCs lacking cutaneous leiomyomas at any site. A common missense mutation in the FH gene, (c.1021G > A, p.D341N) in exon 7, was detected in the 2 cases. Functional prediction with the bioinformatics programs, SIFT and Polyphen-2, reported “damaging (SIFT score 0.00)” and “probably damaging (PSIC score 1.621)” values, respectively. In 162 healthy individuals, there were no cases of a G transition to any base. Finally, (c.1021G > A) in exon 7, was identified as a point mutation. CONCLUSION: We report a family with HLRCC in which a novel missense mutation was detected. A familial papillary type 2 renal cancer should be considered HLRCC unless typical cutaneous leiomyomas do not occur

筋層浸潤性膀胱癌における壁浸潤長は予後予測因子であり、血清cell-free DNAと関連する

Background: We investigated the potential of the depth of invasion (DOI) as a prognostic factor in patients with muscle-invasive bladder cancer (MIBC) who underwent radical cystectomy (RC). Moreover, we examined the association between the preoperative levels of circulating cell-free DNA and DOI.博士（医学）・甲第876号・令和5年3月15