Biomedical subjects

Yoshito Takahashi

Publications and source records attributed to Yoshito Takahashi.

At least 19 recordsLinked to original sources

PubMed2006

Effect of carbamazepine on the single oral dose pharmacokinetics of perospirone and its active metabolite.

Perospirone is a serotonin 5-HT(2A) and dopamine D(2) receptor antagonist which originated in Japan. It has been shown that perospirone is metabolized to ID-15036 mainly by CYP3A4 based on an in vitro study. To investigate the metabolism of perospirone in humans, the authors measured the concentration of perospirone and ID-15036 after a single oral dose of perospirone (8 mg) in 10 healthy male subjects, before and during coadministration of carbamazepine, known as a potent inducer of CYP3A4. Before carbamazepine coadministration, the peak plasma concentrations+/-SD of perospirone and ID-15036 were 4.0+/-4.3 and 11.7+/-7.1 ng/ml, respectively. During carbamazepine coadministration, the concentration of perospirone was decreased below the detection limit, and that of ID-15036 was 6.0+/-1.7 ng/ml. The concentrations of perospirone and ID-15036 were influenced significantly by the treatment with carbamazepine, and this was probably attributable to the induction of CYP3A4. This study provided an in vivo evidence of involvement of CYP3A4 in the metabolism of perospirone.

Administration, Oral↗

PubMed2006

Effects of itraconazole and tandospirone on the pharmacokinetics of perospirone.

Perospirone is an atypical antipsychotic agent originated and clinically used in Japan. Based on an in vitro study, it is reported that perospirone is mainly metabolized to ID-15036 by cytochrome P450 (CYP) 3A4. In this study, the authors investigated the effects of itraconazole, which is a specific inhibitor of CYP3A4, or tandospirone, which is mainly metabolized by CYP3A4 and is expected to competitively inhibit the activity of this enzyme, on single oral dose pharmacokinetics of perospirone. After pretreatment with 200 mg daily of itraconazole or 10 mg daily of tandospirone for 5 days, 9 healthy male subjects received 8 mg of perospirone. Plasma concentrations of perospirone and ID-15036 up to 10 hours after perospirone dosing were measured by high-performance liquid chromatography (HPLC). The metabolism of perospirone was significantly inhibited by treatment with itraconazole but not by tandospirone. The present study suggests that CYP3A4 is significantly involved in metabolism of perospirone in humans.

Adult↗

PubMed2006

Comparison of two alpha1-adrenoceptor antagonists, naftopidil and tamsulosin hydrochloride, in the treatment of lower urinary tract symptoms with benign prostatic hyperplasia: a randomized crossover study.

OBJECTIVES: To compare the efficacy of two alpha(1)-adrenoceptor antagonists, alpha(1A)-adrenoceptor-selective tamsulosin hydrochloride and alpha(1D)-adrenoceptor-selective naftopidil, in the treatment of lower urinary tract symptoms (LUTS) with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: Thirty-four patients (mean age 72.4 years, sd 4.3, range 66-79) with LUTS (International Prostate Symptom Score, IPSS >8) secondary to BPH were enrolled in a randomized crossover study. Seventeen patients were initially prescribed naftopidil 50 mg for 4 weeks, followed by tamsulosin 0.2 mg for 4 weeks (group A); another 17 were initially prescribed tamsulosin 0.2 mg, followed by naftopidil 50 mg (group B). Patients changed to the alternative treatment after a 1-week washout period. Efficacy criteria were improvement in LUTS (IPSS), quality of life (QoL), uroflowmetry, and pressure-flow study (PFS) values based on the treatment with each agent. RESULTS: At baseline there were no significant differences between the groups in IPSS, QoL, uroflowmetry values or PFS values, except for the volume at maximum desire to void. After treatment with each agent, the IPSS and QoL were significantly improved and the reduction in bladder outlet obstruction confirmed by PFS. Naftopidil was significantly more effective than tamsulosin in relieving nocturia. The increases from baseline (before treatment) to the endpoint (after treatment with each agent) in the volume at first desire and maximum desire to void were significantly higher with naftopidil than with tamsulosin. Involuntary contractions disappeared in two patients with relief of nocturia with naftopidil, but not with tamsulosin. The decrease in other symptoms of the IPSS, QoL, increase in uroflowmetry values and changes in other PFS values were similar for both agents. CONCLUSIONS: The two agents provided similar efficacy in the treatment of LUTS with BPH. However, naftopidil was better than tamsulosin for nocturia. The disappearance of involuntary contraction and the greater increase in first-desire volume with naftopidil may be associated with the relief of nocturia. The alpha(1D)-adrenoceptor antagonist is effective in alleviating both voiding and storage symptoms. The alpha(1D)-adrenoceptor antagonist may be more effective than the alpha(1A)-adrenoceptor antagonist in LUTS with BPH.

Adrenergic alpha-Antagonists↗

PubMed2006

[Analysis of factors affecting reccurence and prognosis of superficial bladder cancer--study of 800 patients--].

PURPOSE: The purpose of the present paper was to evaluate clinical factors responsible for recurrence and prognosis of superficial bladder cancer. SUBJECTS AND METHOD: We reviewed date from 800 patients who were initially treated between 1991 and 2000. Recurrent and prognostic factors were examined with univariate and multivariate analysis. Kaplan-Meier Method and log rank test were used for comparing the significance of recurrence free curve and survival curve. Cox's proportional hazard model was used for univariate and multivariate analysis. A 5% level of significance was used for all statistical testing. RESULTS: Of 800 cases 282 patients (35.2%) had recurrence and 27 patients (3.4%) were died in during follow up. Progression was defined as the development of muscle invasion or metastasis, progression were noted on 10 metastasis cases and 16 muscle invasion cases. Univariate analysis revealed that tumor numbers, shape, size, stage and grade were significant recurrent and prognostic factors. Multivariate analysis revealed that tumor numbers (P<0.0001), shape (P = 0.066) and size (P = 0.0178) were significant recurrent factors, and tumor shape (P = 0.0422), size (P = 0.0140) and stage (P = 0.0330) were significant prognostic factors. Of 272 recurrent cases, univariate analysis revealed that tumor shape, stage and grade were significant prognostic factors, and multivariate analysis revealed that tumor shape (P = 0.0164) and stage (P = 0.0017) were significant prognostic factors. CONCLUSION: We conclude that tumor numbers, shape and size are predictive value in recurrence and tumor shape, size and stage are predictive value in prognosis, and when recurrent case, tumor shape and stage are predictive value.

Adult↗

PubMed2006

[A case of ruptured renal artery aneurysm treated effectively by endovascular embolization].

Previously, renal arterial aneurysms were thought to be extremely uncommon. However, these lesions are now being detected more frequently as incidental findings on computed tomography (CT) and magnetic resonance imaging (MRI). The incidence of ruptured renal artery aneurysms is very low. A 58-year-old man presented to a physician complaining of left flank pain and was diagnosed as having a left kidney stone. Abdominal CT scan demonstrated a mass in the left renal pelvis. The mass measured 40mm in diameter and showed calcification. The patient was referred to our hospital 5 days after the first attack. Left renal mass was diagnosed as renal aneurysm based on clinical signs and perirenal findings on CT. Emergent endvascular embolization was performed. The postoperative course was uneventful. Hypertension improved after embolization.

Aneurysm, Ruptured↗

PubMed2005

Association of Lys173Arg polymorphism with CYP11B2 expression in normal adrenal glands and aldosterone-producing adenomas.

CONTEXT: CYP11B2, the gene encoding aldosterone synthase, has several frequent polymorphisms. In particular, the Lys173Arg (K173R) polymorphism is in complete genetic linkage disequilibrium with the -344T/C polymorphism in the promoter of CYP11B2 that involves a binding site for the steroidogenic factor-1 transcription factor. These polymorphisms have been associated with cardiovascular parameters, including hypertension, but not directly with gene expression. OBJECTIVE: The objective of this study was to correlate CYP11B2 genotype with gene expression in adrenal tissue. DESIGN: We measured mRNA levels of CYP11B2 [presented as a ratio against glyceraldehyde-3-phosphate dehydrogenase (B2/G)] and CYP11B1 in relation to the K173R polymorphism. SUBJECTS: We studied 28 subjects with aldosterone-producing adenomas (APA) and 18 subjects with normal adrenals. MAIN OUTCOME MEASURE: The main outcome measure was CYP11B2 expression levels. RESULTS: Preoperative treatment with spironolactone or beta-blocker in five APA patients was associated with higher B2/G. The B2/G and B2/B1 ratios were much higher even in the remaining 23 APA patients than in subjects with normal adrenals. The B2/G and B2/B1 ratios in normal adrenals and APA were higher in the KK genotype than in the RR genotype. In patients with APA, urinary aldosterone excretion was higher in those with the KK genotype than in those with the KR genotype. Measurement of cDNA band intensities from normal and APA samples of the KR genotype revealed that the R173 allele was transcribed at levels 46.6 +/- 12.2% (mean +/- sd; n = 7) and 49.1 +/- 20.8% (n = 6), respectively, those of the K173 allele. CONCLUSIONS: A CYP11B2 haplotype including -344T and K173 is associated with higher gene expression than the -344C/R173 haplotype, supporting reported associations of -344T with higher aldosterone production and blood pressure.

Adenoma↗

PubMed2005

Time course of dopamine D2 receptor occupancy by clozapine with medium and high plasma concentrations.

Most antipsychotics were thought to induce antipsychotic action at an excess of 70% striatal dopamine D2 receptor occupancy, while the clinical dose of clozapine was reported to show less than 60% occupancy. High-dose clozapine could occupy as high as 80% of striatal dopamine D2 receptor in monkey PET studies. Although the time course of dopamine D2 receptor occupancy is an important property of antipsychotics, that by clozapine has not been investigated in a clinical setting. We measured the time course of extrastriatal dopamine D2 receptor occupancy with different doses of clozapine and evaluated whether the measured occupancies fitted the binding theory. Three consecutive PET scans with [11C]FLB 457 were performed for two patients with schizophrenia, chronically taking 600 mg/day and 200 mg/day of clozapine, respectively. Series of occupancies were also measured in combination with fluvoxamine or paroxetine in one patient. Dopamine D2 receptor occupancies were also simulated using individual clozapine plasma data and previously determined in vivo ED50 value. The occupancy of one patient with high plasma concentration (1207 ng/ml at peak time) was around 75% at peak and around 60% after 26 h. Another patient with medium plasma concentration (649 ng/ml at peak time) showed less than 50% occupancy at peak, decreasing to 15% after 25 h. The measured occupancy values fitted well with the simulated occupancy values. At high plasma concentration, clozapine can induce high extrastriatal dopamine D2 receptor occupancy in the human brain, and this finding fitted well with the theoretical estimation.

Adult↗

PubMed2005

Efficacy of carbamazepine against neuroleptic-induced akathisia in treatment with perospirone: case series.

Neuroleptic-induced akathisia is a distressing side effect of antipsychotics, and it is unmanageable in some cases. The authors report three cases of schizophrenia whose neuroleptic-induced akathisia did not respond to representative anti-akathisia drugs such as beta-adrenergic antagonists, anticholinergic agents, benzodiazepines and antihistaminergics, and they showed a marked improvement of it without worsening of psychotic symptoms during a combination treatment with carbamazepine and perospirone, a serotonin-dopamine antagonist developed in Japan. As the mechanism of current observation, we assumed that carbamazepine affected the pharmacokinetics of perospirone, and change in the proportion of perospirone and its major active metabolite (ID-15036). Further investigations including the monitoring pharmacokinetics of perospirone and ID-15036 under concomitant use of carbamazepine should be carried out to explain the mechanism of the current experience.

Adult↗

PubMed2005

Olanzapine increases plasma ghrelin level in patients with schizophrenia.

OBJECTIVE: Increased appetite and weight gain are frequently reported in treatment with olanzapine. However, the mechanism behind this appetite gain remains unclear. Ghrelin is a newly discovered appetite-stimulating peptide that has a role in the regulation of feeding behavior. Ghrelin is synthesized principally in the stomach, and the concentration of circulating ghrelin is negatively correlated with leptin and body fat mass. To elucidate the mechanism of appetite and weight gain during olanzapine treatment, we investigated the circulating ghrelin levels. METHODS: Seven patients with schizophrenia were examined before and after 6-month administration of olanzapine. The concentrations of circulating ghrelin, leptin, glucose and lipid metabolic parameters were measured. RESULTS: Body fat percentage (P=0.0121) and serum leptin (P=0.0284) were significantly increased after 6-month administration of olanzapine. Both plasma total ghrelin (P=0.0188) and active ghrelin levels (P=0.0057) were significantly increased. Six of the seven patients reported increased appetite during olanzapine treatment. Other glucose and lipid parameters were not altered significantly. CONCLUSIONS: Although, the leptin level and body fat percentage were significantly increased, the concentration of circulating ghrelin was also significantly increased. Olanzapine may directly act on the secretion of ghrelin and induce appetite, resulting in weight gain.

Adult↗

PubMed2005

Polymerase chain reaction-based subtyping of ureaplasma parvum and ureaplasma urealyticum in first-pass urine samples from men with or without urethritis.

BACKGROUND: Our previous study suggested a significant association between Ureaplasma urealyticum and nongonococcal urethritis (NGU). However, association of the serovars of U. urealyticum with NGU remains unclear. A polymerase chain reaction (PCR)-based assay can distinguish 4 serovars of Ureaplasma parvum from each other and categorize 10 serovars of U. urealyticum into 3 subtypes: subtype 1 (serovars 2, 5, 8, and 9), subtype 2 (serovars 4, 10, 12, and 13), and subtype 3 (serovars 7 and 11). GOAL: The goal of this study was to determine which subtypes of U. urealyticum are associated with NGU as determined by PCR-based assay. STUDY: The prevalence of U. urealyticum subtypes in 106 ureaplasma-positive men with urethritis was compared with that in 30 ureaplasma-positive men without urethritis. RESULTS: : In men with nonchlamydial NGU and men with Mycoplasma genitalium-negative nonchlamydial NGU, only U. urealyticum subtype 1 (serovars 2, 5, 8, and 9) was detected significantly more often than in men without urethritis. CONCLUSION: This study suggests that subtype 1 of U. urealyticum (serovars 2, 5, 8, and 9) is associated with NGU independently of Chlamydia trachomatis or M. genitalium.

DNA, Bacterial↗

PubMed2005

Decreased gene expression responsible for post-ultraviolet DNA repair synthesis in aging: a possible mechanism of age-related reduction in DNA repair capacity.

A reduction in the post-ultraviolet (UV) DNA repair capacity is associated with aging. To clarify the mechanism of this change, we examined the DNA repair capacity of skin fibroblasts from healthy donors of different ages by the two methods: host cell reactivation (HCR) assay and ELISA of cyclobutane pyrimidine dimers and pyrimidine-pyrimidone (6-4) photoproducts. In HCR assay, cells from elderly donors exhibited significant declines in the ability to restore transfected reporter DNA damaged by UV light. In contrast, the ability to remove DNA damage declined little with age in ELISA. These results imply that the age-sensitive step took place after the damage excision in nucleotide excision repair (NER). The mRNA expression of DNA repair synthesis-related genes (DNA polymerase delta, replication factor C, and proliferating cell nuclear antigen) were markedly decreased in the cells from multiple elderly subjects compared with those from young subjects. Further, the protein level of DNA polymerase delta1, a catalytic subunit of the pivotal factor in repair synthesis, correlated with the mRNA level. These findings suggest that the reduced post-UV DNA repair capacity in aging results from an impairment in the latter step of NER by the decreased expression of factors in repair synthesis.

Aged↗

PubMed2005

Retrospective study of 101 cases with incidental prostate cancer stages T1a and T1b.

PURPOSE: The purpose of this retrospective study was to clarify the character of incidental prostate cancer, stages T1a and T1b. METHODS: We analysed 101 cases of incidental prostate cancer. Incidental prostate cancer was diagnosed on the basis of normal digital rectal examination findings, a serum prostate-specific antigen (PSA) level of less than 4.0 ng/mL, and no abnormal computed tomography or ultrasonography findings. All patients were treated at Gifu University Hospital or an affiliated hospital during the period January 1992 through December 2001. RESULTS: There were 64 stage T1a cancers and 37 stage T1b cancers. The mean age of patients was 71.3 years (range 51-87 years). The mean serum PSA level was 1.63 ng/mL (range 0.2-4.0 ng/mL). Thirty-five stage T1a patients (56.5%) and thirty-two stage T1b patients (86.5%) underwent some type of treatment. Total prostatectomy was performed in eight stage T1a cases and fifteen stage T1b cases. Pathological diagnoses were as follows: pTx (n = 1), pT0 (n = 5) and pT2 (n = 2) for stage T1a cancers, and pT0 (n = 6), pT2 (n = 8) and pT3 (n = 1) for stage T1b cancers. Only one stage T1b cancer recurred. CONCLUSION: The outcome of patients with incidental prostate cancer was satisfactory; disease recurred in only one case of stage T1b cancer and there were no cases of PSA failure, although the pathological diagnosis in nine of the fifteen stage T1b cases (60.0%) treated with total prostatectomy was pT2 or pT3. Careful monitoring was indicated for stage T1a cancer, and some treatment was necessary for stage T1b cancer.

Aged↗

PubMed2005

[A clinical isolate of Leclercia adecarboxylata from a patient of pyelonephritis].

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Enterobacteriaceae↗

PubMed2005

Emergence and spread of Neisseria gonorrhoeae clinical isolates harboring mosaic-like structure of penicillin-binding protein 2 in Central Japan.

Of 150 clinical isolates of Neisseria gonorrhoeae recovered in 2001, we examined 55 clinical isolates of N. gonorrhoeae for which cefixime MICs were > or=0.125 microg/ml and randomly selected 15 isolates for which cefixime MICs were < or =0.06 microg/ml for analysis of alterations in the penicillin-binding protein 2 (PBP 2) gene. We found insertion of an extra codon (Asp-345a) in the transpeptidase domain of PBP 2, and this insertion occurred alone or in conjunction with other amino acid substitutions. We also found a mosaic PBP 2 that was composed of fragments of the PBP 2 proteins from Neisseria cinera and Neisseria perflava. This mosaic PBP 2 was significantly associated with decreased susceptibilities to penicillin and cephalosporins, especially oral cephalosporins. For most of the isolates with a mosaic PBP 2, the cefixime MICs were > or =0.5 microg/ml and the cefdinir MICs were > or =1 microg/ml. Analysis of chromosomal DNA restriction patterns by pulsed-field gel electrophoresis revealed that most isolates with the mosaic PBP 2 were genetically similar. The recombination events that generated the mosaic PBP 2 would likely have contributed to the decreased sensitivities to cephalosporins. Isolates with the mosaic PBP 2 appear to threaten the efficacy of the currently recommended regimen with cefixime. The emergence of such strains may be the result of the in vivo generation of clones in which interspecies recombination occurred between the penA genes of N. gonorrhoeae and commensal Neisseria species.

Amino Acid Sequence↗

PubMed2005

[Recurrence of bladder cancer in fossa navicularis 17 months after cystourethrectomy: a case report].

We report a case of bladder cancer recurrence in fossa navicularis of urethra 17 months after cystourethrectomy for bladder cancer. A 75-year-old man had undergone cystourethrectomy preserving between fossa navicularis and external meatus, and ileal conduit urinary diversion for advanced bladder cancer on June 24, 2002. Histopathological findings showed urothelial carcinoma, G2>G3, pT1N0. The patient had been followed regularly for 17 months without evidence of recurrence until he suffered the onset of hemorrhagic urethral discharge. Endoscopic examination of the residual urethra showed multiple, papillary sessile tumors which almost filled the fossa navicularis. He was admitted to our hospital on December 15, 2003. The urethral wash cytology revealed urothelial carcinoma. Since computed tomography, magnetic resonance imaging, and bone scintigraphy showed no evidence of lymph node and distant metastasis, partial penectomy was performed. Histopathological findings showed urothelial carcinoma pTa, G2>G3, which was identical to primary tumor. Tumor had not invaded the corpus cavernosum. Careful follow-up of the patients with preservation of fossa navicularis is important.

Aged↗

PubMed2005

Renal transcatheter arterial embolization for autosomal dominant polycystic kidney disease: report of two cases.

We report the results of renal transcatheter arterial embolization (renal-TAE) in two patients with autosomal dominant polycystic kidney disease (ADPKD) treated with hemodialysis (HD). A 73-year-old man and a 65-year-old woman on HD visited our department complaining of abdominal fullness, abdominal pain and appetite loss. Abdominal computerized tomography (CT) revealed polycystic kidneys. Both patients underwent renal-TAE. Approximately 1 month later, the symptoms had improved and CT showed decreased cyst volume. These results suggest that renal-TAE is a useful therapy for patients with ADPKD.

Aged↗

PubMed2004

N-methylethanolamine attenuates cardiac fibrosis and improves diastolic function: inhibition of phospholipase D as a possible mechanism.

AIM: Ventricular fibrosis is promoted by many effectors that chronically activate phospholipase D (PLD), and induces cardiac dysfunction and heart failure in cardiovascular diseases. Since ethanolamine is a product of PLD, we hypothesised that an administration of an analogue of ethanolamine, N-methylethanolamine (MEA), decreases PLD activity through a negative feedback mechanism, suppresses collagen accumulation, and thus prevents organ dysfunction. METHODS AND RESULTS: In human fibroblasts 1-butanol inhibited collagen synthesis and enhanced collagenase production, but iso-butanol did not. These indicate crucial roles of PLD in collagen synthesis and degradation. In fibroblasts, MEA dose-dependently decreased PLD activity, inhibited collagen synthesis and enhanced collagenase production. In a hypertensive heart failure model using Dahl-Iwai salt-sensitive rats, PLD activity increased with progressive ventricular fibrosis, leading to myocardial stiffening and overt heart failure. Long-term administration of MEA did not significantly decrease blood pressure, however, but decreased PLD activity and collagen content with inhibited gene expression of collagens, leading to the prevention of myocardial stiffening and haemodynamic deterioration. MEA also attenuated ventricular hypertrophy, another detrimental structural alteration. CONCLUSION: MEA may exert therapeutic effects on cardiac disorders due to ventricular fibrosis through suppression of PLD activity and modulation of the fibrosis pathway even without relief from mechanical stress.

Animals↗

PubMed2004

Remarkable increase in central Japan in 2001-2002 of Neisseria gonorrhoeae isolates with decreased susceptibility to penicillin, tetracycline, oral cephalosporins, and fluoroquinolones.

Four hundred sixty-two clinical isolates of Neisseria gonorrhoeae recovered from 1999 through 2002 in central Japan were examined for MICs of antimicrobial agents. The majority was sensitive to ceftriaxone and spectinomycin, but a remarkable increase in isolates with decreased susceptibility to penicillin, tetracycline, oral cephalosporins, and fluoroquinolones was observed from 2001 through 2002.

Cephalosporin Resistance↗