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Biomedical subjects

Isao Araki

Publications and source records attributed to Isao Araki.

At least 19 recordsLinked to original sources
PubMed2006

Human muscarinic receptor binding characteristics of antimuscarinic agents to treat overactive bladder.

PURPOSE: We characterized the binding affinities of several antimuscarinic agents in human muscarinic receptors. MATERIALS AND METHODS: Competitive inhibitory effects of antimuscarinic agents on specific NMS [H] (PerkinElmer Life Sciences, Boston, Massachusetts) binding were examined in human tissue homogenates and in CHO-K1 cell membranes expressing human muscarinic receptor subtypes. RESULTS: Oxybutynin, propiverine, tolterodine, the respective metabolites DEOB, DPr-P-4(N-->O) and 5-HM, and darifenacin inhibited in concentration dependent fashion specific [(3)H]NMS binding in homogenates of the human bladder and parotid gland as well as in membranes of CHO-K1 cell lines expressing human muscarinic M(1) to M(5) receptor subtypes. Based on inhibition constant values the inhibitory effects of tolterodine, 5-HM and DPr-P-4(N-->O) were 1.4 to 1.7 times greater in the bladder than in the parotid gland, whereas the inhibitory effects of oxybutynin, DEOB, propiverine and darifenacin were 2 to 10 times greater in the parotid gland. Consequently tolterodine, 5-HM and DPr-P-4(N-->O) compared with oxybutynin, DEOB, propiverine and darifenacin were found to show 3 to 4 times greater affinity to muscarinic receptors in the human bladder than in the parotid gland. Tolterodine and 5-HM were 2-fold more potent for inhibiting specific [(3)H]NMS binding at cell membranes expressing the M(2) vs the M(3) subtype. Conversely oxybutynin, DEOB, propiverine, DPr-P-4(N-->O) and darifenacin showed 2 to 22 times higher affinity to the M(3) than to the M(2) subtype. CONCLUSIONS: Compared with oxybutynin, tolterodine, 5-HM and DPr-P-4(N-->O) may bind more selectively to muscarinic receptors in the human bladder than in the parotid gland.

Humans↗
PubMed2006

Real-time quantitative analysis for human telomerase reverse transcriptase mRNA and human telomerase RNA component mRNA expressions as markers for clinicopathologic parameters in urinary bladder cancer.

AIM: The expression of the telomerase subunits such as human telomerase reverse transcriptase (hTERT) and human telomerase RNA component (hTR) may be associated with tumor development and progression. We evaluated the relationship between mRNA quantification of both hTERT and hTR and clinicopathologic parameters in bladder cancer. METHODS: We examined the mRNA expression of hTERT and hTR in 29 specimens with bladder cancer (Grade: Grade I, 9 cases; Grade II, 13 cases and Grade III, 7 cases. Stage: pTa-pT1, 18 cases; pT2-T4, 11 cases). We immediately froze all of specimens obtained during TUR-Bt and isolated the total RNA from each specimen. We measured the quantity of hTERT, hTR and GAPDH mRNA by a real-time reverse transcription-polymerase chain reaction method based on TaqMan technology. RESULTS: The hTERT/GAPDH mRNA ratio and hTERT mRNA/total RNA in superficial bladder tumor was significantly lower than in invasive bladder tumor. The hTR/GAPDH mRNA ratio and hTR mRNA/total RNA in superficial tumor were significantly lower than in invasive bladder tumor. The hTERT mRNA expression significantly correlated with tumor grade, but the hTR mRNA expression did not correlate with tumor grade. There was no significant difference in the hTERT/GAPDH mRNA ratio and hTR mRNA/total RNA according to multiplicity of bladder tumor. CONCLUSIONS: Our results demonstrated that the expression of hTERT mRNA correlated with the progression of stage and grade in bladder cancer. The quantitative analysis of hTERT and hTR mRNA might be a marker for clinicopathologic parameters in bladder cancer.

Adult↗
PubMed2006

Decreased expression of G protein-coupled receptor kinases in the detrusor smooth muscle of human urinary bladder with outlet obstruction.

AIM: We examine the expression of mRNA of G protein-coupled receptor kinase (GRK) subtypes and muscarinic acetylcholine receptor (M) subtypes in the detrusor smooth muscle of the human urinary bladder. Furthermore, we confirm the presence and the localization of GRK proteins in the detrusor smooth muscle of the obstructed bladder in comparison with the control bladder. METHODS: Detrusor smooth muscle tissues of the human urinary bladder were obtained from 12 male patients; 6 patients did not have bladder outlet obstruction, and the other 6 patients had bladder outlet obstruction. Portions of the dome or anterior wall of the urinary bladder were used for the present study. Reverse transcription/polymerase chain reaction for GRK2, M2 and M3 was performed using total RNA extracted from human urinary bladder detrusor. Antibodies to GRK2, GRK3 and GRK4 were used to confirm the presence of the protein product in the human urinary bladder using immunohistochemical staining and the western blotting technique. RESULTS: All complementary DNA (cDNA) transcribed from three different mRNA (M2, M3 and GRK2) were successfully amplified and size-fractionated. The expression of GRK2 protein was strong in the human bladder detrusor, but was significantly weakened by western blotting in obstructed bladder in comparison with control bladder. CONCLUSIONS: Failure in desensitization mechanisms of muscarinic acetylcholine receptors might be related to storage symptom elicited by overactivity in obstructed bladder with benign prostatic hyperplasia.

Blotting, Western↗
PubMed2005

Prevalence and impact on generic quality of life of urinary incontinence in Japanese working women: assessment by ICI questionnaire and SF-36 Health Survey.

OBJECTIVES: To examine the prevalence of urinary incontinence (UI) and the relationship between UI and generic quality of life (QOL) in working women. METHODS: Of 7229 female hospital nurses in Japan, 3734 (51.7%) responded to a self-administered postal questionnaire that included the Rand Medical Outcomes Study 36-item Health Survey (SF-36) and the International Consultation on Incontinence questionnaire (ICIQ) for evaluating symptoms and health-related QOL. RESULTS: The overall prevalence of UI in Japanese working women aged 20 to 64 years (mean 35.2) was 16.7%. The main type of incontinence was stress UI (73%). Its prevalence increased with age and reached a plateau at age 45 to 49 years (34.7%). The ICIQ score also correlated significantly with age. Generic QOL, especially physical functioning, role-physical, social functioning, and role-emotional, was significantly impaired by UI. A comparison of subjects with and without UI revealed that the differences in the physical and mental component summary scores of the SF-36 were largest in the age groups of 25 to 29 and 55 to 59 years, respectively. The correlations of the ICIQ score with the physical and mental component scores were most significant in the age groups of 25 to 29 and 45 to 49 years, respectively. The impact of mixed UI on QOL showed a greater tendency than that of stress or urge UI. CONCLUSIONS: The prevalence of UI showed an age-related increase, with a peak at 45 to 49 years old. The impact of UI on physical health was great in individuals in their 20s, but its impact on mental health increased in the older age groups.

Adult↗
PubMed2005

Modified endoscopic live donor nephrectomy: retroperitoneoscopy followed by hand-assistance.

We have developed a novel modification of previous approaches to donor nephrectomy and herein review our original operative procedure. First, the posterior aspect of the kidney was dissected retroperitoneoscopically and dissection of the renal artery, ureter and gonadal vein was almost completed. Second, the anterior aspect of the kidney was dissected with transperitoneal hand-assistance, and dissection of the renal pedicle from the anterior surface was accomplished easily and safely. This operative procedure was successfully performed for two donors with no intraoperative or postoperative complications. Our modified endoscopic donor nephrectomy is feasible as a minimally invasive procedure because of its safety, and its ability to preserve renal function and establish an excellent operative field for both posterior and anterior aspects of the kidney.

Feasibility Studies↗
PubMed2005

Multifocal metastases of recurrent renal cell carcinoma successfully treated with a combination of low dose interleukin-2, alpha-interferon and radiotherapy.

A 59-year-old man presented with a 2-month history of left flank pain and a possibility of gross hematuria. Left renal cell carcinoma stage II was diagnosed and radical left nephrectomy was performed. Twenty-two months postoperatively, lung metastases were demonstrated and 6 x 10(6) units of alpha-interferon (IFN-alpha) were administered for 9 months, only to keep the sizes of the metastases unchanged. Thirty-four months after the operation, liver metastases and bone metastasis in the left sacroiliac joint were revealed. The combination cytokine therapy was performed with 1.4 x 10(6) U of interleukin-2 (IL-2) and 3 x 10(6) U of IFN-alpha for 16 weeks, and the left sacroiliac joint metastasis was treated with radiation therapy of 4 Gy per day for 7 days. Six months after the 16 weeks of immunotherapy, computed tomography and bone scintigraphy revealed that the metastases of the lung, liver and bone substantially disappeared and this complete response is still kept after 16 months.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Effects of pergolide on nocturia in Parkinson's disease: three female cases selected from over 400 patients.

We started the subject screening from over 400 patients with Parkinson's disease using strict selection criteria to identify the patients with nocturia who would allow accurate and efficient evaluation of the pergolide effects. The subjects were confined to female patients to exclude patients with potential prostate hypertrophy. The patients treated with bromocriptine at 7.5-15 mg/day adjunctive to l-dopa were selected to replace bromocriptine with pergolide of the equivalent dosage approved in Japan. The nocturia was defined as having more than two episodes of urination during sleep per night on average. The subjects received the urinary sediment test before and during the study for screening urinary tract infection and the study was discontinued when urinary tract infection was found. As a result, we identified total 11 patients with nocturia and three of those completed the 12-week study of switching dopamine agonist from bromocriptine to pergolide. We observed a decrease in nocturia frequency in all three patients, a decrease in irritative urinary symptoms in two and an improvement of sleep QOL in two. The effect of pergolide on nocturia was independent of improvement of parkinsonian symptoms, suggesting a distinct mechanism from that of anti-parkinsonian effects. Our study also suggests that switching from bromocriptine to pergolide improves nocturia, thereby improving sleep status of patients with Parkinson's disease.

Aged↗
PubMed2004

Overexpression of epithelial sodium channels in epithelium of human urinary bladder with outlet obstruction.

OBJECTIVES: To examine whether the epithelial sodium channel (ENaC) is expressed in the human urinary bladder and how its expression changes in association with outlet obstruction. Detrusor instability occurs in association with bladder outlet obstruction. The increase of afferent activity is one of the possible mechanisms for this detrusor instability. The ENaC expressed in mammals has been implicated in various mechanosensory functions. METHODS: Specimens of urinary bladder mucosa were obtained from 9 controls and 9 patients with bladder outlet obstruction verified by the International Prostate Symptom Score, prostate volume, and urodynamic tests. In 7 patients with outlet obstruction, involuntary detrusor contraction was demonstrated. The expression and localization of ENaC proteins was examined using immunofluorescent staining. The quantification of ENaC gene expression was assessed by real-time reverse transcriptase-polymerase chain reaction. RESULTS: The alpha-ENaC, beta-ENaC, and gamma-ENaC proteins were expressed in human urinary bladder epithelium with outlet obstruction, and the alpha-ENaC and gamma-ENaC proteins were virtually unstained in the control bladders. Alpha-ENaC, beta-ENaC, and gamma-ENaC mRNA were detected in 1, 6, and 4 of 9 control bladders, respectively. Each ENaC mRNA was clearly present in all obstructed bladders. The expression levels of each subunit in the obstructed bladders were significantly greater than those in controls. The quantified ENaC expression correlated significantly with the storage symptom score. CONCLUSIONS: The ENaC expressed in the bladder epithelium might be implicated in the mechanosensory transduction in the bladder afferent pathways, thereby inducing detrusor instability by outlet obstruction.

Aged↗
PubMed2003

Diagnosis and treatment of voiding symptoms.

Lower urinary tract symptoms (LUTS) are associated with lower urinary tract dysfunction. Symptoms are the subjective indicator of a disease or change in condition as perceived by the patient, caregiver, or partner and may lead the individual to seek help from health care professionals. LUTS are usually qualitative and, therefore, cannot usually be used to make a definitive diagnosis. LUTS also can indicate pathologies other than lower urinary tract dysfunction, such as urinary infection. LUTS are divided into 7 groups: storage, voiding (obstructive), postmicturition symptoms and 4 others. Voiding symptoms, which are caused by lower urinary tract obstruction, include slow stream, splitting or spraying, intermittency, hesitancy, straining, and terminal dribble. Postmicturition symptoms, which are experienced immediately after micturition, consist of the feeling of incomplete emptying and postmicturition dribble. Postmicturition dribble describes the involuntary loss of urine immediately after the individual has finished passing urine; in men, usually after leaving the toilet and in women, after rising from the toilet. Hence, postmicturition dribble is elicited by different situations or is considered as having different implications. For example, although postmicturition dribble usually implies incomplete emptying (voiding symptoms) in elderly men with benign prostatic hyperplasia, postmicturition dribble is often considered as urinary incontinence (a storage symptom) in many patients, even with bladder outlet obstruction. In such cases, detailed history taking and further evaluation, such as urinary flowmetry, postvoid residual volume, and comprehensive urodynamic evaluation, should be performed as appropriate. If no urodynamic abnormalities of either the detrusor or the outlet can be detected despite significant LUTS, factors unrelated to the lower urinary tract may be responsible for the voiding symptoms.

Female↗
PubMed2003

The methylentetrahydrofolate reductase C677T point mutation is a risk factor for vascular access thrombosis in hemodialysis patients.

BACKGROUND: Many reports indicate that a high homocysteine (Hcy) level is a potential risk factor for such thrombotic diseases as arteriosclerosis, myocardial infarction, and cerebral infarction in healthy individuals or hemodialysis (HD) patients. The methylentetrahydrofolate reductase (MTHFR) C677T polymorphism has been reported to be closely related to plasma Hcy level. METHODS: Using a cross-sectional design in this study, the relationship between arteriovenous fistula (AVF) obstruction and the MTHFR C677T point mutation was examined in 337 HD patients. RESULTS: Results of multivariate analysis showed no significant influence of age, HD therapy duration, sex, or the presence of diabetes mellitus, cerebral infarction, or myocardial infarction. Only the presence of the MTHFR C677T polymorphism yielded a significant difference. Percentages of patients who experienced AVF obstruction were as follows: CC (12.6%), CT (20.3%), and TT (31.8%). The number of those who experienced obstruction was significantly larger with the TT than CC (P < 0.01). Moreover, total obstruction episode ratios were as follows: CC, 1 in 107.21 episodes/patient-month; CT, 1 in 74.08 episodes/patient-month; and TT, 1 in 50.33 episodes/patient-month. Episode percentages tended to be greater when the degree of mutation was greater, and a significant difference was observed between the CC and TT alleles (P < 0.01). CONCLUSION: Although AVF obstruction is affected by numerous factors, there was a strong relationship between MTHFR C677T mutation and AVF obstruction. These findings suggest that the MTHFR C677T point mutation could serve as an important indicator in identifying susceptibility to AVF obstruction.

Arteriovenous Shunt, Surgical↗
PubMed2003

Retroperitoneoscopic nephron-sparing surgery of renal tumor using a microwave tissue coagulator without renal ischemia: comparison with open procedure.

PURPOSE: It is ideal to use not a transperitoneal but a retroperitoneal approach for both open and endoscopic partial nephrectomy. We compared the results of retroperitoneoscopic nephron-sparing surgery for small renal tumors using a microwave tissue coagulator without renal pedicle clamping with those of a retroperitoneal open procedure. PATIENTS AND METHODS: Between 1996 and 2002, eight patients with small renal tumors underwent retroperitoneoscopic partial nephrectomy without renal ischemia, and nine patients with small renal tumors underwent open partial nephrectomy via a retroperitoneal approach. Both groups were operated on using a microwave tissue coagulator. RESULTS: Retroperitoneoscopic partial nephrectomy without renal ischemia was performed without any major or minor complications in any patient. The mean operation time for retroperitoneoscopic surgery was significantly longer than that for open partial nephrectomy (221.9 minutes v 145.9 minutes; P = 0.0004). However, the mean estimated blood loss for retroperitoneoscopic surgery was less than that for open partial nephrectomy (137.5 mL v 334.8 mL; P = 0.012). In addition, the retroperitoneoscopic group seemed to recover more rapidly than the open surgery group. CONCLUSIONS: Retroperitoneoscopic nephron-sparing surgery of small renal tumors using a microwave tissue coagulator without renal ischemia is feasible as minimally invasive procedure. It results in saving renal function, minimal blood loss, and rapid recovery.

Aged↗
PubMed2003

Relationship of bladder dysfunction to lesion site in multiple sclerosis.

PURPOSE: We investigated the relationship of voiding dysfunction type and the lesion site in patients with multiple sclerosis. MATERIALS AND METHODS: Voiding dysfunction was evaluated in 32 patients with multiple sclerosis using the International Prostate Symptom Score and urodynamic tests. Lesion sites were determined by combined neurological examination and magnetic resonance imaging findings. RESULTS: Compared with reports from Western countries the ratio of emptying-to-filling symptoms was high in Japan. Of urinary symptoms only filling correlated with disability status and disease duration. Urinary symptoms were not related to lesion sites. Urodynamic evaluation revealed detrusor hyperreflexia in 14 of 32 patients, hyporeflexia or areflexia in 12, detrusor hyperreflexia with impaired contractile function in 4, a low compliance bladder in 1 and normal function in 1. Of 14 patients with hyperreflexia 13 had overactive sphincter concurrently. Incompetent sphincter was identified in 2 patients who had detrusor hyperreflexia with impaired contractility and in 1 with a low compliance bladder. A significant correlation was noted for a pontine lesion and detrusor hyporeflexia, and for a cervical cord lesion and detrusor-sphincter dyssynergia. CONCLUSIONS: Detrusor hyporeflexia and detrusor-sphincter dyssynergia are indicative of a pontine and cervical spinal cord lesion, respectively. Thus, the lesion site in the central nervous system may be a major determinant of the type of bladder and urethral sphincter dysfunction. The high prevalence of emptying symptoms in Japanese patients may reflect the prevalence of detrusor hyporeflexia and detrusor-sphincter dyssynergia.

Adolescent↗
PubMed2003

Lower urinary tract symptoms in men and women without underlying disease causing micturition disorder: a cross-sectional study assessing the natural history of bladder function.

PURPOSE: We examined the influence of aging on bladder function in men and women. MATERIALS AND METHODS: Using the International Prostate Symptom Score questionnaire with an additional question on urinary incontinence lower urinary tract symptoms were evaluated in all outpatients who first visited our urological department from June 2001 to December 2002. In 550 of the 1,201 patients who completed the questionnaire any pathological conditions that might cause micturition disorder could not be detected with urological examinations. Symptom scores of these patients without underlying disease causing micturition disorder were the basis of this study. RESULTS: In men and women total and storage symptom scores but not the voiding symptom score increased significantly with age. In each age group total, storage and voiding symp-tom scores were not significantly different between men and women. Women 50 to 69 years old had significant higher incontinence scores than men of the same age, whereas a significant increase in the incontinence score with age was found only in men. The quality of life score increased with age in men but not in women. However, the 2 sexes did not significantly differ in quality of life score. CONCLUSIONS: Lower urinary tract symptoms, especially storage symptoms, showed age related alterations in the 2 sexes without any underlying disease causing micturition disorder. The prevalence of urinary symptoms was not different between men and women. Therefore, bladder function in each sex might be subject to a gender independent aging process.

Age Factors↗
PubMed2003

[Molecular biological researches of the lower urinary tract function].

Adrenergic alpha1 and beta receptors are present in the target organs of sympathetic nerve and they participate in the signal transduction mechanism of the lower urinary tract. Adrenergic alpha1 receptors are present in urethral and prostatic smooth muscles, and contract these muscles. Among these receptor subtypes, the alpha1-A receptor has the most important role, and mRNA expression of the corresponding alpha1-a subtype is predominant. In the human urinary bladder detrusor smooth muscle, the expression of adrenergic beta3 receptor subtype mRNA is predominant, and relaxation of detrusor smooth muscle is mediated mainly via beta3 receptor. Afferent nerve with lower threshold can easily transmit bladder sensation and takes an important role in the pathophysiology of urge urinary incontinence. Successful molecular cloning of vanilloid receptors, which are present in these afferent nerves, revealed that vanilloid receptors are ion-channels, sensitive for heat and pH, and termed VR1 and VRL1. Among purinergic receptors, ion channel type P2X3 receptor is found in afferent nerve fibers and plays some roles in the signal transduction of bladder sensation. In the near future, agonist for the adrenergic beta3 receptor and selective antagonists for VR1, VRL1, or P2X3 will possibly become drugs for pollakisuria and urge urinary incontinence.

Humans↗
PubMed2003

[Pharmacokinetics of paclitaxel and carboplatin in a hemodialysis patient with metastatic urothelial carcinoma--a case report].

A 69-year-old-man undergoing hemodialysis for 8 years developed metastatic urothelial carcinoma and received combination chemotherapy with paclitaxel and carboplatin. Paclitaxel 175 mg/m2 was given as a 3-hour intravenous infusion, and carboplatin was dosed to the area under the plasma concentration-time curve (AUC) of 5 mg.min/ml calculated according to the Calvert formula as a 30-minute intravenous infusion immediately after paclitaxel. Hemodialysis was started 1 hour after carboplatin, then their pharmacokinetics was determined in the patient. The AUC of paclitaxel and carboplatin were 15.2 and 64.56 micrograms.h/ml, respectively. The metastatic tumor size was reduced by more than 20% after 3 courses of this chemotherapy. Grade 3 neutropenia and grade 1 thrombopenia were observed. This is the first report that the combination of paclitaxel and carboplatin is feasible in a patient with metastatic urothelial carcinoma undergoing hemodialysis, with low toxicity and safety.

Aged↗
PubMed2003

[Clinical effects of naftopidil on nocturia associated with benign prostatic hyperplasia].

We studied the efficacy of naftopidil (50 mg/day) on nocturia associated with benign prostatic hyperplasia in 35 patients (62-80 years old). The patients had BPH > 20 ml, nocturia, more than 3 times, international prostate symptom score (IPSS) > 7, quality of life score (QOL) < 1, and maximum flow rate (Qmax) < 15 ml/sec. They received naftopidil for more than 6 weeks. IPSS, QOL, Qmax, micturition volume, and side effects were analyzed. Naftopidil was effective for nocturia associated with benign prostatic hyperplasia, especially when taken at night.

Adrenergic alpha-Antagonists↗
PubMed2002

Inhibition of c-Jun N-terminal kinase ameliorates apoptosis induced by hydrogen peroxide in the kidney tubule epithelial cells (NRK-52E).

BACKGROUND: Hydrogen peroxide (H2O2)-induced apoptosis has been shown to be involved in ischemic and toxic tubular damage. Recent studies have revealed that oxidative stress can activate c-Jun N-terminal kinase (JNK), and the oxidative stress-JNK pathway is an important apoptotic pathway of cells exposed to various stresses. The present study was designed to investigate JNK activation and the effects of the JNK pathway inhibition during H2O2-induced apoptosis in kidney epithelial tubule cells (NRK-52E). MATERIALS AND METHODS: NRK-52E cells were treated with 0-500 microM H2O2 and/or 100 microM quercetin (an inhibitor of the JNK pathway). Apoptosis was assessed by flow cytometry analysis and DNA ladder. JNK activity was assessed by the GST-c-Jun (1-169) binding/protein kinase assay. RESULTS: H2O2 induced apoptosis in NRK-52E cells in a concentration-dependent manner, which was demonstrated by the reduced DNA PI staining, externalization of phosphatidylserine and DNA ladder. Apoptosis induced by H2O2 was accompanied by JNK activation and up-regulated JNK activity. Quercetin treatment suppressed the JNK activity and ameliorated apoptosis induced by H2O2. CONCLUSIONS: H2O2 induced apoptosis in NRK-52E cells, which was associated with activation and up-regulation of JNK. Quercetin treatment could decrease JNK activity and ameliorate H2O2-induced apoptosis.

Animals↗