-
[show abstract]
[hide abstract]
ABSTRACT: To investigate morphological and physiological findings in the bladder of KIT mutant (WsRCWs/Ws) rats to clarify whether the disturbance of KIT pathways affects bladder activity. To discuss the potential role of KIT-positive interstitial cells of Cajal (ICC)-like cells in the urinary bladder.
Reverse transcriptase-polymerase chain reaction and western blotting was used to confirm the absence of c-kit mRNA and protein in the bladders of 12-week-old WsRCWs/Ws rats. Light and transmission electron microscopy was used to identify the differences in morphological and ultrastructural characteristics of the bladder between WsRCWs/Ws and wild-type (WsRC+/+) rats. The voiding pattern of WsRCWs/Ws rats and the effects of cyclophosphamide (CYP) and protamine sulphate on bladder function were examined using cystometry.
In WsRC+/+ rats, c-kit mRNA and KIT protein expression were observed in the urinary bladder, while they were not detectable in WsRCWs/Ws rats. Deformation of ICC-like cells with the collapse of the organelle was not observed in the bladders of WsRCWs/Ws rats. Each cystometry variable in WsRCWs/Ws rats was similar to that in WsRC+/+ rats. The reduction in the intercontraction intervals in WsRCWs/Ws rats with chemically (CYP and protamine sulphate) induced cystitis was significantly lower than in WsRC+/+ rats (P < 0.05).
Certain voiding disturbances might be associated with impaired KIT signalling in ICC-like cells, therefore, KIT could be a candidate target for medical therapy in the future.
BJU International 11/2010; 108(2 Pt 2):E97-103. · 2.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The reversal rate from clustering of cardiovascular disease (CVD) risk factors-components of the metabolic syndrome (MetS) is not known. Methods and Results. Among 35,534 subjects who received the annual health examinations at the NiigataHealth Foundation (Niigata, Japan), 4,911 subjects had clustering of 3 or more of the following CVD risk factors: (1) body mass index (BMI) ≥25 Kg/m(2), (2) blood pressure ≥130 mm Hg in systolic and/or ≥85 mm Hg in diastolic, (3) triglycerides ≥150 mg/dL, (4) high-density lipoprotein cholesterol ≤40 mg/dL in men, ≤50 mg/dL in women, and (5) fasting blood glucose ≥100 mg/dL. After 5 years 1,929 subjects had a reversal of clustering (39.4%). A reversal occurred more often in males. The subjects with a reversal of clustering had milder level of each risk factor and a smaller number of risk factors, while BMI was associated with the least chance of a reversal. Conclusion. We concluded that a reversal of clustering CVD risk factors is possible in 4/10 subjects over a 5-year period by habitual or medical interventions. Gender and each CVD risk factor affected the reversal rate adversely, and BMI was associated with the least chance of a reversal.
Journal of obesity 01/2010; 2010:623593.
-
[show abstract]
[hide abstract]
ABSTRACT: A delayed pericardial effusion developed in a recipient of a cardioverter defibrillator (ICD). After an uneventful implant procedure and postoperative recovery, the patient suffered loss of appetite and fatigue, and was re-admitted to the hospital 48 days later. Her vital signs were stable and cardiac silhouette on chest roentgenogram was normal. However, blood cell counts and chemistry revealed the presence of anemia and liver dysfunction, an echocardiogram showed a diffuse pericardial effusion, and computed tomography suggested that the ICD lead, screwed in the right ventricular outflow tract, had perforated the wall. In order to make a prompt diagnosis and initiate timely corrective treatment, the physician in charge of long-term follow-up should remember that a pericardial effusion can be delayed and accumulate in the absence of typical signs of cardiac tamponade after ICD lead implantation.
Internal Medicine 01/2010; 49(5):389-92. · 0.94 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To prospectively evaluate the ability of diffusion-weighted (DW) magnetic resonance (MR) imaging to be used to determine the T stage of bladder cancer and to measure the correlation between the apparent diffusion coefficient (ADC) and histologic grade.
This study was approved by the local institutional review board. All patients gave written informed consent. Forty patients with a total of 52 bladder tumors underwent MR imaging that included DW imaging. Histologic grade was determined for all tumors. Two radiologists interpreted four image sets (ie, T2-weighted images alone, T2-weighted plus DW images, T2-weighted plus dynamic contrast agent-enhanced images, all three image types together). Conventional criteria were used for interpreting T2-weighted and contrast-enhanced images. For DW images, new staging criterion developed on the basis of the hypothesis that tumors, submucosal tissue, and muscles show high, low, and intermediate signal intensity, respectively, was used. The McNemar test was used to examine differences in accuracy, sensitivity, and specificity. Differences in the performance were analyzed by comparing the areas under the receiver operating characteristic curves (A(z) values). To compare ADCs between three histologic grades, analysis of variance was used.
The overall accuracy of T stage diagnosis was 67% for T2-weighted images alone, 88% for T2-weighted plus DW images, 79% for T2-weighted plus contrast-enhanced images, and 92% for all three image types together. The overall accuracy, specificity, and A(z) for diagnosing T2 or higher stages were significantly improved by adding DW images (P < .01). The mean ADC of G3 tumors was significantly lower than that of G1 and G2 tumors (P < .01).
DW images provided useful information for evaluating the T stage of bladder cancer, particularly in differentiating T1 or lower tumors from T2 or higher tumors. The ADC may in part predict the histologic grade of bladder cancer.
Radiology 05/2009; 251(1):112-21. · 5.73 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To evaluate the effects of dietary soy isoflavone on detrusor overactivity (DO) in ovariectomized (Ovx) rats and the association between these effects and expression of the gap junction protein, connexin-43, in the urinary bladder, and to discuss the usefulness of soy isoflavones for overactive bladder (OAB).
In all, 24 (8-week-old) virgin female Sprague-Dawley rats were divided equally into four groups: sham operation with control diet (with no dietary soy isoflavones; Sham-CD), bilateral Ovx with CD (Ovx-CD), sham operation with soy isoflavone diet (Sham-ID), bilateral Ovx with soy ID (Ovx-ID). Cystometry was performed after the 4-week CD or ID in each group while awake. Quantitative reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemical and Western blot analyses were also performed to examine the expression of connexin-43 in each group.
In Ovx-CD rats, there were some significant changes in cystometry variables, including shortening of the intercontraction interval and an increased number of non-voiding contractions compared with Sham-CD rats (P < 0.05). These changes were significantly improved by 4-week soy isoflavone administration (Ovx-ID; P < 0.05). Quantitative RT-PCR, immunohistochemical and Western blot analyses showed that the expression level of connexin-43 mRNA and protein was significantly greater in the urinary bladder of Ovx-CD rats compared with Sham-CD rats. Soy isoflavone administration significantly reduced this increased expression (Ovx-ID).
Soy isoflavone replacement improved DO with alteration of the connexin-43 expression pattern in the urinary bladder of Ovx rats. Routine consumption of diet soy isoflavones may be a useful treatment to prevent and improve OAB.
BJU International 05/2009; 103(10):1429-35. · 2.84 Impact Factor
-
Shinpei Kimura,
Masahiro Ito,
Masaomi Chinushi,
Komei Tanaka,
Yasutaka Tanabe,
Yukio Hosaka,
Satoru Komura, Shinsuke Okada,
Kenichi Iijima,
Hiroshi Furushima,
Koichi Fuse,
Masahito Sato,
Yoshifusa Aizawa
[show abstract]
[hide abstract]
ABSTRACT: Cardiac resynchronization therapy (CRT) has recently been introduced as a new option for patients with severe heart failure, but its effect on renal function remains unclear.
Twenty-three patients receiving CRT were studied. Responders were those who showed >0% increase in left ventricular ejection fraction after CRT by echocardiography. Clinical parameters, echocardiographic measurement, renal function, and prescriptions were examined before and 3 months after CRT, and the relationship between the response to CRT and renal function was examined. The responders had a better prognosis than the non-responders (p<0.05). There was a significant difference in the change in the estimated glomerular filtration rate between the responders and non-responders (p<0.05), even in patients with renal dysfunction before CRT (p<0.01). Prescriptions of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB) were 100% in the CRT responders and 60% in the non-responders (p<0.05). Up-titration of beta-blockers could be significantly achieved in the CRT responders compared with the non-responders (p<0.05).
Preservation of renal function was observed in the responders to CRT, even in patients with renal dysfunction. Prescription of ACEI/ARB and up-titration of beta-blockers increased in the CRT responders. These results may contribute to the beneficial effects of CRT.
Circulation Journal 11/2008; 72(11):1794-9. · 3.77 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is expressed in certain human cancers. Ligand-induced PPAR-gamma activation can result in growth inhibition and differentiation in these cancer cells; however, the precise mechanism for the anti-proliferative effect of PPAR-gamma ligands is not clear.
In this study, we examined the expression of PPAR-gamma in human prostate cancer and the effect of two PPAR-gamma ligands, 15 deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) and troglitazone, on prostate cancer cell growth.
PPAR-gamma is frequently over-expressed in androgen independent prostate cancer cell lines and human prostate cancer tissues (22 of 47; 47%). Both 15d-PGJ2 and troglitazone inhibited proliferation and DNA synthesis of prostate cancer cell lines in a dose-dependent manner, and slightly increased the proportion of cells with S-phase DNA content. Prostate specific antigen (PSA) promoter reporter assays showed that troglitazone and 15d-PGJ2 down-regulated androgen stimulated reporter gene activity in prostate cancer cell lines LNCaP. Interestingly, LNCaP with troglitazone dramatically suppressed PSA protein expression without suppressing AR expression.
Taken together, these results suggest that PPAR-gamma ligands may be a useful therapeutic agent for the treatment of prostate cancer.
Cancer Detection and Prevention 10/2008; 32(3):259-66. · 2.52 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Slowly activating delayed-rectifier potassium currents in the heart are produced by a complex protein with alpha and beta subunits composed of the potassium voltage-gated channel KQT-like subfamily, member 1 (KCNQ1) and the potassium voltage-gated channel Isk-related family, member 1 (KCNE1), respectively. Mutations in KCNQ1 underlie the most common type of hereditary long QT syndrome (LQTS). Like other potassium channels, KCNQ1 has six transmembrane domains and a highly conserved potassium selectivity filter in the pore helix called "the signature sequence." We aimed to investigate the functional consequences of a newly identified mutation within the signature sequence.
Potassium channel genomic DNA from a family with clinical evidence of LQTS was amplified by polymerase chain reaction (PCR), and the resulting products were then sequenced. Three family members had a double-point mutation in KCNQ1 at nucleotides 938 (T-to-A) and 939 (C-to-A), resulting in an isoleucine-to-lysine change at amino acid position 313. These patients displayed prolonged QTc intervals (629, 508, and 500 ms(1/2,) respectively) and repetitive episodes of syncope, but no deafness. Three-dimensional structure modeling of KCNQ1 revealed that this mutation is located at the center of the channel pore. COS-7 cells displayed a lack of current when transfected with a plasmid expressing the mutant. In addition, the mutant displayed a dominant negative effect on current but appeared normal with respect to plasma membrane integration.
An I313K mutation within the selectivity filter of KCNQ1 results in a dominant-negative loss of channel function, leading to a long QT interval and subsequent syncope.
Journal of Cardiovascular Electrophysiology 06/2008; 19(5):541-9. · 3.06 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Alpha 1-adrenoceptors (alpha1-ARs) play a role in the regulation of prostatic smooth muscle tone, and are critical mediators of lower urinary tract symptoms (LUTS) and pathophysiology in benign prostatic hyperplasia (BPH). Three subtypes (alpha1a, alpha1b, alpha1d) have been identified by molecular cloning techniques. Although the reasons for the existence of three subtypes remain elusive, recent findings suggest a role of subtype and tissue-specific regulation. We examined the role of each alpha1-AR-subtype in the prostate to apply some new findings obtained from basic research for the clinical treatment. We have demonstrated that the mRNA expression levels of alpha1-AR-subtypes in the prostate differed among patients and that the genetic background differences of patients with BPH were responsible for the diverse responses to subtype-selective alpha1-blockers. In addition, both alpha1a- and alpha1d-AR-subtypes play a significant role in the spontaneous contraction of human prostate and, especially alpha1d-AR-subtypes may also control the cell growth of the prostate. Clarification of the mechanism of alpha1-AR subtypes in the prostate will provide more effective therapy for BPH patients.
Hinyokika kiyo. Acta urologica Japonica 06/2008; 54(6):457-62.
-
Journal of the American College of Cardiology 05/2008; 51(17):1720-1. · 14.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: We evaluated the efficacy of loxoprofen sodium for refractory nocturia. Twelve men (mean age, 75.1 +/- 5.7) with nocturia were enrolled in this study. All patients received 60 mg loxoprofen sodium prior to sleeping at night for 14 days. Nine of 12 patients (75%) felt more satisfaction than previous treatments. Patients were grouped into a loxoprofen sodium-effective (n = 7) and ineffective groups (n = 5) based on the results of the frequency-volume chart. In the effective group, interestingly, night-time urine volume showed significant reduction (P < 0.05). On the other hand, the average single voided volume at night and 24-h urine volume showed no significant change. There was a statistically significant difference in the night-time urine volume after treatment between groups (P < 0.01). Loxoprofen sodium is an effective treatment for some patients with refractory nocturia. The main effect mechanism of loxoprofen sodium may involve the reduction of night-time urine production.
International Journal of Urology 05/2008; 15(5):462-4. · 1.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Androgen plays an important role in the growth of prostate cancer, but the molecular mechanism that underlies the development of resistance to anti-androgen therapy remains unknown. In this paper, we review the role of cell cycle regulators and steroid receptor co-activators for prostate cancer growth and survival. Cyclin E has been shown to increase the transactivation activity of the human androgen receptor and the proliferation of prostate cancer cells. On the other hand, p27 using an adenovirus vector was shown to reduce the size of tumors of human prostate cancer xenografts. Steroid receptor coactivator-3 (SRC-3) is often over-expressed in prostate cancers. Our results indicate that overexpression of SRC-3 can modulate the AKT (protein kinase B) signaling pathway and stimulate cell growth in prostate cancer. In contrast, down-regulation of SRC-3 expression by small interfering RNA suppresses cell growth.
Hinyokika kiyo. Acta urologica Japonica 02/2008; 54(1):57-61.
-
[show abstract]
[hide abstract]
ABSTRACT: We performed a radical retropubic prostatectomy on a 59-year-old male patient who was diagnosed with prostatic carcinoma. Pathological findings revealed a ductal adenocarcinoma in the left lobe of the prostate, and a conventional well-differentiated adenocarcinoma in the right lobe. Immunohistochemistry revealed that CA19-9 was positive in the ductal adenocarcinoma, and prostate-specific antigen was positive in the conventional well-differentiated adenocarcinoma. Since there was an increase in the level of serum CA19-9, which had decreased postoperatively, along with the appearance of local recurrence and bone metastasis, we treated the patient with cisplatin and gemcitabine. As a result, the level of serum CA19-9 was normalized and a reduction of the metastatic focus was observed.
International Journal of Urology 01/2008; 14(12):1103-6. · 1.75 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: In both Brugada syndrome (BS) and arrhythmogenic right ventricular cardiomyopathy (ARVC), electrical abnormalities in the right ventricular outflow tract (RVOT) are important for arrhythmogenesis.
The aim of this study was to compare conduction delay in the right ventricular in BS with that in ARVC using the signal-averaged electrocardiogram.
Twenty patients with BS (18 men and 2 women; 55 +/- 12 years old; 9 symptomatic and 11 asymptomatic) and eight patients with ARVC (six men and two women; 53 +/- 16 years old) were included. We assessed the presence of late potentials (LPs) and the filtered QRS duration (fQRSd) in V(2) and V(5) using a high-pass filter of 40 Hz (fQRSd:40) and 100 Hz (fQRSd:100).
In ARVC, there was no significant difference in fQRSd:40 between V2 and V5 (158 +/- 19 vs. 145 +/- 17 ms, respectively): however, in BS, fQRSd:40 in V2 was significantly longer than fQRSd:40 in V5 (147 +/- 15 vs. 125 +/- 10 ms, P < 0.001). In ARVC, there was no significant difference between fQRSd:40 and fQRSd:100 in V(2) and V(5) (158 +/- 19 vs. 142 +/- 23 ms and 145 +/- 17 vs. 132 +/- 9 ms, respectively). In contrast, in BS, fQRSd:100 was significantly shorter than fQRSd:40 in V2 (110 +/- 8 ms vs. 147 +/- 15, P < 0.001). The relative decrease in fQRSd:100 compared with fQRSd:40 in V2 was significantly greater in BS than in ARVC.
The dominant prolongation of the fQRSd in the right precordial lead in BS was different from the characteristics of ARVC, which may be caused by the conduction delay due to fibro-fatty replacement in RV.
Europace 11/2007; 9(10):951-6. · 1.98 Impact Factor
-
Wataru Mitsuma,
Makoto Kodama,
Haruo Hanawa,
Masahiro Ito,
Mahmoud M Ramadan,
Satoru Hirono,
Hiroaki Obata, Shinsuke Okada,
Fumihiro Sanada,
Takao Yanagawa,
Takeshi Kashimura,
Koichi Fuse,
Naohito Tanabe,
Yoshifusa Aizawa
[show abstract]
[hide abstract]
ABSTRACT: The role of endostatin in coronary heart disease (CHD) is not well known. This study aimed to investigate the dynamics of endostatin, an antiangiogenic growth factor, within the coronary circulation and to elucidate its relation to coronary collateral formation in patients with CHD. We recruited 72 subjects with suspected or previously diagnosed CHD. Blood samples from the left ventricular (LV) cavity and coronary sinus (CS) were obtained during coronary angiography, and the serum concentration of endostatin was measured by enzyme-linked immunosorbent assay kits. Patients were then divided into 2 groups: the normal group (n = 15) defined as patients with atypical chest pain and no evidence of organic cardiac diseases and the CHD group (n = 57) defined as patients with >or=75% coronary stenosis at coronary angiography and chest pain on exertion. Endostatin in CS sera was significantly elevated in patients with CHD compared with normal subjects (median 79.7 [interquartile range 46.2 to 130.3] vs median 49.6 [interquartile range 29.1 to 84.5] ng/ml, p = 0.02). Spillover of endostatin (CS - LV value) from the coronary circulation in patients with CHD with severe stenosis was higher than in those with moderate stenosis (28.2 [4.8 to 48.6] vs 7.3 [-37.0 to 25.6] ng/ml, p = 0.01). In addition, endostatin production within the coronary circulation was higher in patients with poorly developed collaterals than in those with well-developed collaterals. In conclusion, endostatin is suggested to be produced from the coronary circulation in patients with CHD and may play an important role in the regulation of the growth of coronary collateral vessels.
The American Journal of Cardiology 03/2007; 99(4):494-8. · 3.37 Impact Factor
-
Hiroshi Watanabe,
Masaomi Chinushi,
Daisuke Izumi,
Akinori Sato, Shinsuke Okada,
Kazuki Okamura,
Satoru Komura,
Yukio Hosaka,
Hiroshi Furushima,
Takashi Washizuka,
Yoshifusa Aizawa
[show abstract]
[hide abstract]
ABSTRACT: Intracardiac electrograms are important for discrimination of tachyarrhythmia by implantable cardioverter defibrillators (ICD). A low R-wave can cause not only undersensing of ventricular tachyarrhythmia but also inappropriate discharges due to oversensing of unexpected signals because of its characteristic sensing algorithm. Therefore, this study aimed to investigate adverse events associated with R-wave amplitude. We included 115 consecutive patients followed-up over one year after implantation of a transvenous ICD system. The status of the ICD was checked every 3 months and intracardiac ventricular electrograms were analyzed. The decrease in R-wave amplitude was high in arrhythmogenic hypertrophy cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy (ARVC), and sarcoidosis. Low R-waves (< 5.0 mV) were observed in 13 patients at a follow-up of 15 +/- 16 months after implantation, and the mean R-wave was 3.0 +/- 0.8 mV. The frequency of low R-waves was high in ARVC (38%), sarcoidosis (33%), and dilated cardiomyopathy (17%). All of the dilated cardiomyopathy patients with low R-waves had severe left ventricular dysfunction. Inappropriate ICD therapy resulting from T-wave oversensing occurred in 7 patients and the R-wave was < 5.0 mV in 6 of the patients. The frequency of inappropriate therapy was high in patients with sarcoidosis. In 3 patients, inappropriate therapy caused ventricular tachyarrhythmia. In conclusion, decreases in R-wave amplitude occurred in some progressive cardiac disorders and caused inappropriate ICD discharges having arrhythmogenicity. Physicians should attempt to obtain a high R-wave amplitude during ICD implantation and careful follow-up is required, especially in patients with ARVC or sarcoidosis.
International Heart Journal 06/2006; 47(3):363-70. · 1.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although catecholaminergic polymorphic ventricular tachycardia (CPVT) is associated with fatal ventricular arrhythmias and sudden death, the ECG findings are not fully understood. In this paper, we report on alterations in the U-wave. Seven patients from 6 families with CPVT in which bidirectional tachycardia and polymorphic VT were induced by exercise or isoproterenol infusion visited our hospitals. VT was not inducible by programmed electrical stimulation. A novel gene mutation of the ryanodine receptor 2 (RyR2) was confirmed in 2 families. In one of these patients, U-wave alternans was observed following ventricular pacing at 160 beats/min. In the other patient, U-wave alternans was observed during the recovery phase after the exercise stress test, which was terminated because of polymorphic VT. In both cases, leads V3-V5 were the leads showing alternans most clearly. In the third patient, a negative U-wave became positive following a pause from sinus arrest and a change in T-wave was also noted. Since such findings were not found in the other subjects who underwent electrophysiologic study, isoproterenol infusion or exercise stress testing, the phenomenon seems to be relevant to the underlying pathogenesis of CPVT. The genesis and significance of U-wave alteration need to be determined.
International Heart Journal 06/2006; 47(3):381-9. · 1.16 Impact Factor
