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Y Aso

Publications and source records attributed to Y Aso.

At least 91 records · Page 5Linked to original sources

Relative potency of antiandrogens with reference to intracellular testosterone in the rat prostate.

Mechanisms of relative potency in direct action of antiandrogens have not been fully elucidated. Using castrated rats, the effects of antiandrogens on the prostatic weight gain induced by exogenous testosterone (T), and on T uptake into prostatic cells were examined. Tested antiandrogens were cyproterone acetate, chlormadinone acetate, a new steroidal antiandrogen, 17acetoxy-6-chloro-2-oxa-4,6-pregnadiene-3,20-dione (TZP-4238), and one nonsteroidal type, flutamide (FL). Suppression of prostatic weight gain, T uptake and serum concentrations of compounds, correlated well each other among steroidal antiandrogens, while FL was five times more active in suppressing weight gain than TZP-4238, associated with a lower nuclear distribution of androgen. The results suggest that 1) suppression of T uptake is a major and common mechanism of steroidal antiandrogens and the relative potency is attributable to pharmacokinetic characteristics in vivo, and 2) FL suppress s nuclear T uptake more specifically than steroidal antiandrogens.

Androgen Antagonists↗

Clinical significance of measurements of urinary and serum thrombomodulins in patients with non-insulin-dependent diabetes mellitus.

UNLABELLED: The aim of our study was to elucidate whether serum thrombomodulin (S-TM) and urinary thrombomodulin (U-TM) levels would reflect the pathogenesis of diabetic complications. Studies were conducted in 188 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 132 age-matched healthy subjects. TM was measured by a newly developed enzyme immunoassay. Both S-TM and U-TM levels in NIDDM were much higher than those in healthy controls. S-TM values in NIDDM correlated significantly with age (P < 0.05), HbA1c (P < 0.05), serum 1.5 anhydroglucetol (AG) (P < 0.05) and urinary albumin concentration (UAC) (P < 0.01), respectively. On the other hand, fasting plasma glucose (FPG) (P < 0.001), HbA1c (P < 0 .01), serum fructosamine (P < 0.05) and serum 1.5 AG (P < 0.05) were closely correlated with U-TM values in NIDDM. Patients with clinical nephropathy showed obviously higher S-TM levels (P < 0.05) than patients with latent nephropathy. Furthermore, S-TM values in patients with diabetic proliferative retinopathy increased significantly compared with those in patients without diabetic retinopathy (P < 0.05). When all diabetic patients with normoalbuminuria were studied, no significant changes of S-TM were observed between the no diabetic retinopathy group and the proliferative diabetic retinopathy group. CONCLUSIONS: The present data suggest that an increase in U-TM reflects the grade of glucose metabolism, whereas an increase in S-TM appears to reveal the advance of diabetic microangiopathy, including nephropathy.

Adult↗

Determination of molecular mobility of lyophilized bovine serum albumin and gamma-globulin by solid-state 1H NMR and relation to aggregation-susceptibility.

PURPOSE: Feasibility of solid-state 1H NMR for determining the mobility of protein molecules in lyophilized cakes was considered. The mobility in cakes with various levels of water content was studied in relation to aggregation-susceptibility. METHODS: Spin-spin relaxation time T2) of protons in lyophilized bovine serum albumin (BSA) and gamma-globulin (BGG) was measured as a function of hydration level by solid state 1H NMR using a 'solidecho' pulse sequence. Moisture-induced aggregation of the lyophilized proteins was also determined by high performance size exclusion chromatography. RESULTS: Lyophilized BSA and BGG became susceptive to aggregation when water content exceeded about 0.2 g/g of protein. T2 of protein protons in the lyophilized cakes started to increase at lower water contents. The increase in aggregation susceptibility observed with increasing water content appears to follow the increase in T2 of protein protons. For lyophilized BGG, both aggregation and T2 of protein protons decreased at water contents above 0.5 g/g protein. CONCLUSIONS: Mobility of protein molecules in lyophilized cakes was successfully determined by solid-state 1H NMR. The aggregation susceptibility of proteins was strongly related to their molecular mobility as indicated by T2.

Chemistry, Pharmaceutical↗

Injection of glutaraldehyde cross-linked collagen for urinary incontinence: two-year efficacy by self-assessment.

BACKGROUND: Glutaraldehyde cross-linked (GAX) collagen has recently become available as injection material for treatment of urinary incontinence and should be evaluated for its long-term efficacy. METHODS: The subjects included 78 females with genuine stress incontinence (GSI) and 19 male or female patients with intrinsic sphincter deficiency (ISD: urinary incontinence due to urethral sphincter damage). GAX collagen was injected transperineally or transurethrally through an injection needle under direct endoscopic observation. The efficacy was evaluated by the patients' overall assessment at two years post-treatment. RESULTS: Under local or regional anesthesia, GAX collagen was injected 1.9 times on average (total injection volume: 23.5 mL) in GSI patients and 2.2 times (40.1 mL) in ISD patients. Improvement at two years post-treatment by patients' assessment was observed in 71.7% of GSI patients and 53.3% in ISD patients. Side effects were urinary retention and difficulty in voiding after 48 of the total of 188 injections (25.5%), a large amount of residual urine in four (2.1%) and miscellaneous in 19 (10.1%), for a short period after injection and were not serious. CONCLUSION: Our study indicates that GAX collagen injection is an effective, safe and easy non-medical treatment for urinary incontinent patients.

Aged↗

Estimate criteria for diagnosis and severity in benign prostatic hyperplasia.

BACKGROUND: Standard severity criteria for benign prostatic hyperplasia (BPH) are needed to facilitate clinical and epidemiologic investigations in the common terminology. PATIENTS AND METHODS: A total of 692 BPH patients from 8 institutions were judged by specialized physicians for their overall disease severity and severity in 4 domains: symptom, function, anatomy, and quality of life (QOL). The items measuring severity in these 4 domains were the International Prostate Symptom Score (I-PSS) questionnaire, uroflowmetry, transrectal ultrasonography (TRUS), and questionnaires on bother and I-PSS QOL index, respectively. By Spearman's rank correlation and multiple regression analysis using physicians' judgement as the criterion variable (gold standard) the items and their cut-off levels were selected so that high predictivity, practicality and clinical significance were maintained, while the number of items in use was minimized. RESULTS: The item(s) and their ranges of values for each severity grade were summarized as follows; the evaluation domain (the selected item(s): range of mild, moderate, severe): symptom (I-PSS: 0-7, 8-19, 20-35), function (maximum flow rate and residual urine volume: > or = 15 mL/s and < 50 mL, > or = 5 mL/s and < 100 mL, < 5 mL/s or > or = 100 mL), anatomy (prostate volume on TRUS: < 20 mL, < 50 mL, > or = 50 mL), QOL (QOL index: 0 and 1, 2 to 4, 5 and 6). The overall severity was efficiently predicted when defined according to the combinations of severity grades of the 4 domains. These criteria predicted physicians' judgement with accuracy of about 80% for overall severity and severity of individual domains. CONCLUSION: The proposed criteria are valid, practical, and would be useful for the common scale of the BPH severity in clinical and epidemiologic studies.

Humans↗

Estimate criteria for efficacy of treatment in benign prostatic hyperplasia.

BACKGROUND: Various treatment modalities for benign prostatic hyperplasia (BPH) have emerged and are now in use or await evaluation of clinical usefulness. It is difficult, however, to compare their efficacies on a single scale, because standardized criteria for therapeutic efficacy of BPH treatments have not been established. PATIENTS AND METHODS: A total of 692 BPH patients from 8 institutions in Japan received various treatments, and were judged by specialized physicians for overall efficacy, and for efficacy in 4 domains: symptom, function, anatomy, and quality of life (QOL). Efficacy of treatment was graded as excellent, good, fair or poor, and assessed using items based on conventional clinical measurements. These items included 1) the difference (post-pretreatment value), 2) relative ratio (post/pre) and, 3) the individual values of pre- or posttreatment measurements. The cut off levels for each grade were heuristically selected by Spearman's rank correlation and multiple regression analysis so that the results accurately predicted physicians' judgement, while the feasibility was maintained. RESULTS: The results for each efficacy grade (range of excellent, range of good, range of fair, range of poor) were summarized as follows: Symptom: (post/pre treatment ratio of I-PSS) < or = 0.25, < or = 0.5, < or = 0.75, > 0.75. Function: (post-pre of Qmax) > or = 10 mL/s, > or = 5 mL/s, > or = 0.25 mL/s, < 0.25 mL/s. Anatomy: (post/pre ratio of prostate volume) < or = 0.5, < or = 0.75, < or = 0.9, > 0.9. QOL: (pre-post of QOL index) > or = 4, 3, 2 and 1, < or = 0. The overall efficacy grade was defined as the median of efficacy grades of 3 domains: symptom, function and QOL. The agreement rates between the criteria and physicians' judgement on the dichotomous efficacy (either excellent plus good, or fair plus poor) were approximately 80% in individual domains and overall estimate, and consistent among various treatments. CONCLUSION: The proposed criteria are fairly accurate, simple, and practical, and thus may be useful as a standard method for assessing the clinical efficacy of BPH treatments.

Evaluation Studies as Topic↗

Recommended dose of flutamide with LH-RH agonist therapy in patients with advanced prostate cancer.

BACKGROUND: In a recent study by the Casodex Combination Study Group, USA, patients in a flutamide (750 mg/day) plus LH-RH agonist group showed a high treatment failure rate, mainly due to flutamide-induced diarrhea and hepatotoxicity. Our current study was conducted to determine the optimal dose of flutamide for use in this type of combination therapy. METHODS: In a randomized, multicenter study, 30 patients (hormone untreated; stage C or D) were divided into 2 groups: flutamide 250 mg (125 mg x 2; 14 patients) and flutamide 375 mg (125 mg x 3; 16 patients, and each dose combined with either goserelin acetate (3.6 mg every 4 weeks) or leuprolide acetate (3.75 mg every 4 weeks). Goserelin and leuprolide were administered to patients in a 1:1 ratio. Flutamide monotherapy at a daily dose of 375 mg was determined to be the optimal dose in Japan in our previous phase II study. The endpoints of this pilot study were the objective response and adverse events during the 12-week treatment. RESULTS: The objective response rate was 83.3% in the flutamide 250 mg group and 85.7% in the flutamide 175 mg group according to the Japanese response criteria for prostate cancer. Elevated PSA levels fell to within the normal range in 83.3% of the patients in the former group and in 93.3% of the patients in the latter group. One patient administered 250 mg of flutamide experienced diarrhea, while the serum GOT and/or GPT were elevated in 3 patients administered 250 mg of flutamide and 4 patients administered 375 mg of flutamide. CONCLUSIONS: Based on the findings of this pilot study of maximal androgen-depletion therapy for advanced prostate cancer, 375 mg/day of flutamide is recommended in combination with an LH-RH agonist. Assessment of the effects of our recommended regimen on longer term survival, quality of life and antiandrogen withdrawal syndrome of patients treated requires additional patients and time for follow-up.

Aged↗

Parathyroid carcinoma with metastatic calcification identified by technetium-99m methylene diphosphonate scintigraphy.

We describe herein a case of parathyroid carcinoma accompanied with metastatic calcification identified by technetium-99m methylene diphosphonate (Tc-99m MDP) scintigraphy in the lungs, kidneys and stomach. Parathyroid carcinoma remains a rare disorder despite the increased prevalence of primary hyperparathyroidism. Metastatic calcification is noted infrequently even in primary hyperparathyroidism and it may cause respiratory failure. Tc-99m MDP scintigraphy three months after surgery showed a complete disappearance of Tc-99m uptake in the stomach and an obvious reduction in the kidneys but no significant change in the lungs, indicating metastatic calcification can be reversibly reabsorbed. This case indicates that the adequate excision of parathyroid carcinoma as well as the early detection of metastatic calcification by Tc-99m MDP are obligatory.

Calcinosis↗

[Urothelial carcinoma of the navicular fossa].

We report a case of transitional cell carcinoma arising in the fossa navicularis. The patient was a 74-year-old man. He had no history of sexually transmitted disease or urethral stricture. Clinically, the tumor was suspected to be a condyloma acuminatum; however, the pathological diagnosis yielded an unexpected result: transitional cell carcinoma. Radiological examinations and cystoscopy showed no other tumor besides the primary cancer in the fossa navicularis. Partial resection of the urethra was performed and the patient has been without evidence of disease for 3 years.

Aged↗

[Phase I study of bicalutamide (Casodex), a nonsteroidal antiandrogen in patients with prostatic cancer].

A phase I study (open trial) of bicalutamide (Casodex), a non-steroidal antiandrogen, was conducted on 16 patients with prostatic cancer (stage C to D). The patients were given 10, 30, 50, 80 or 100 mg of bicalutamide orally daily for 12 weeks. Adverse reactions were observed in 8 out of 16 patients, but almost all were mild. Breast pain, gynecomastia and hot flushes were observed in 6 patients. Adverse reactions regarding liver function tests were observed in 3 patients. These were increased glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), alkaliphosphatase (AL-P) or gamma guanosine 5'-triphosphate (gamma-GTP). However, during or after the treatment period the elevated values were reversed to the pretreatment level. In terms of efficacy, anti-tumor effect was observed in 1 or 2 patients at each dose. Serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone and estradiol increased during treatment. Plasma concentrations of the R (-) enantiomer, which has antiandrogenic activity, reached the steady state 6-8 weeks after the initiation of treatment; its apparent plasma elimination half-life observed following repeated administration was 8.4 +/- 1.1 days. In conclusion, bicalutamide (10-100 mg od) is considered to be tolerated well enough to be administered to patients with prostatic cancer and has shown evidence of anti-tumor effect.

Administration, Oral↗

[Clinical early phase II study of bicalutamide (Casodex) in patients with prostatic cancer].

To investigate the efficacy and safety of bicalutamide (Casodex) with its clinically recommended dose, the randomized early phase II study was performed in 124 patients with prostatic cancer (stage C, D). The patients were given 50, 80 or 100 mg of bicalutamide orally once a day in fixed doses for 12 weeks; 122 patients were eligible for evaluation. The overall response rate was 50.0% (20/40), 61.0% (25/41) and 53.7% (22/41) in the 50 mg, 80 mg and 100 mg groups, respectively. The response rate in prostate lesion, bone and lymph node metastases was slightly higher in the 80 mg group than in the 50 mg and 100 mg groups. The proportion of patients showing a response with regard to serum PSA (CR and PR) was 84.2, 92.7 and 97.6% in the 50, 80 and 100 mg groups, respectively. The incidence of adverse reactions was 65.0, 61.0 and 61.0% in the 50, 80 and 100 mg groups, respectively, and there was no significant difference in overall safety rating in the three groups. Frequent adverse reactions were gynecomastia and breast pain. Only one patient in the 80 mg group was withdrawn due to shortness of breath. Serum concentrations of LH, testosterone and estradiol increased significantly after treatment. Bicalutamide was concluded to be effective and well tolerated in patients with prostatic cancer, and its recommended dose was 80 mg once daily.

Administration, Oral↗

[Shelf-life estimation of pharmaceutical products by matrixing].

The shelf-life estimates of pharmaceutical products obtained by matrixing are compared with those obtained by ordinary analysis, using stability data generated by the Monte Carlo method. The effect of the variation in stability due to different packaging and formulations on the shelf-life estimates is described. Analysis of variance is proposed for the evaluation of shelf-life estimates obtained by matrixing. The relationship between the power of the test and the significance level is discussed as well as the effect of assay error on the power of test.

Analysis of Variance↗

Bacillus Calmette-Guérin treatment of existing papillary bladder cancer and carcinoma in situ of the bladder. Four-year results. The Bladder Cancer BCG Study Group.

BACKGROUND: Intravesical instillation therapy of Bacillus Calmette-Guérin (BCG) has become a standard treatment for carcinoma in situ (CIS) of the urinary bladder. However, there have been few reports concerning the direct effect of BCG on existing tumors classified as Ta or T1. In the first stage of this clinical study, 157 patients were treated with BCG intravesical instillation (Tokyo 172 strain [BCG Co. Ltd., Tokyo, Japan]; 80 mg weekly for eight times) by our Study Group. The efficacy on existing tumors was a complete response (CR) rate of 84.4% and 66.4% and a partial response (PR) of 6.3% and 20.8% for 32 cases of CIS and 125 cases of Ta or T1 tumors, respectively. METHODS: In the second stage of this study, the authors investigated the outcome of the 138 patients who had achieved CR or PR in the first stage. One hundred twenty (87.0%) of the patients were followed fully. Of those patients, 52 were randomized to receive prophylactic (maintenance) therapy consisting of BCG of 40 mg monthly for 12 times (Group A), whereas 55 were randomized to an untreated control group (Group B). Thirteen other patients refused to be randomized and were followed without prophylactic instillation. RESULTS: The median follow-up period was 48 months for Group A and 42 months for Group B. In Groups A and B, the beneficial effect of the BCG therapeutic instillation persisted for a long time, and the 3-year nonrecurrence rate was 77.6% in Group A and 74.2% in Group B. Disease progression was observed rarely. CONCLUSION: For patients in whom transurethral resection of tumors of the bladder (TUR-Bt) alone is unlikely to eliminate the tumor, intravesical BCG is potentially the treatment of choice.

Administration, Intravesical↗

Water mobility in poly(ethylene glycol)-, poly(vinylpyrrolidone)-, and gelatin-water systems, as indicated by dielectric relaxation time, spin-lattice relaxation time, and water activity.

The mobility of water molecules present in poly(ethylene glycol) (PEG)-, poly(vinylpyrrolidone) (PVP)-, and gelatin-water systems was determined by dielectric relaxation and 17O NMR spectroscopy. Water activity was also measured. Dielectric relaxation spectra indicate that all the polymer systems studied contained water exhibiting a dispersion at a frequency > 10(9) Hz; in other words, water with high mobility close to that of bulk water. The dielectric relaxation time of the highly mobile water increased as polymer concentration increased. The PVP- and gelatin-water systems also contained water exhibiting a dispersion at a frequency < 10(9) Hz, which can be considered to be "bound water" with a restricted mobility because of its association with polymer molecules. Dielectric relaxation spectroscopy was used to determine water mobility separately for the populations of highly mobile water and bound water, whereas NMR relaxation spectroscopy was used to determine the average mobility of both populations. The spin-lattice relaxation time of water in these polymer-water systems showed a deviation from the isotropic two-state model. Dielectric relaxation data indicate that this deviation can be ascribed to variations in the relaxation time of highly mobile water caused by a change in polymer concentration. The dielectric relaxation time of highly mobile water in the gelatin system did not change with a change in polymer concentration to the extent that it did in the PEG and PVP systems. This result is consistent with a slight change in water activity of the gelatin system with increasing polymer concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Chemical Phenomena↗

Homogeneity of the pyruvate dehydrogenase multienzyme complex from Bacillus stearothermophilus.

The pyruvate dehydrogenase multienzyme complex was purified from Bacillus stearothermophilus by means of six gel-filtration column chromatographies; once on Cellulofine GCL-2000, twice on Sepharose CL-2B, and three times on Sephacryl S-500HR. The molecular size distribution of the complex was examined in detail by gel-filtration chromatography, analytical and sucrose-density ultracentrifugations, and dynamic light scattering. The complex was found to be homogeneous; a dimeric complex was undetectable even with a high concentration of protein (below 6.8 mg/ml).

Centrifugation, Density Gradient↗

Treatment of benign prostatic hyperplasia with high intensity focused ultrasound: an initial clinical trial in Japan with magnetic resonance imaging of the treated area.

BACKGROUND: High intensity focused ultrasound (HIFU) is a method of delivering acoustic energy to a focal point and is expected to induce tissue thermal ablation. Transrectal HIFU was applied to symptomatic benign prostatic hyperplasia (BPH) for relief of intravesical obstruction without injury to surrounding tissue. The clinical effectiveness and safety of transrectal HIFU were investigated. METHODS: Thirty-seven Japanese men with symptomatic BPH were treated with HIFU. The treatment was minimally invasive; operating time was less than 40 minutes, and a posttreatment indwelling catheter was left in place for 3-4 days. RESULTS: The maximum urinary flow rate (ml. per second) increased from 7.6 +/- 0.6 to 9.3 +/- 0.6 at three months in 37 patients (P < 0.05). During the same period the International Prostatic Symptom Score and Quality of Life score (points) decreased from 23.6 +/- 1.4 to 10.5 +/- 0.3, 5.2 +/- 0.3 to 2.6 +/- 0.1 (P < 0.001), respectively. Overall response estimated by these three individual parameters were as follows; excellent 18.9%, good 48.6%, fair 10.8% and poor 21.6% at three months. Magnetic resonance imaging using an endorectal coil showed coagulative necrosis defined in the therapy zone at one month after treatment. Side effects were transient urinary retention in six patients (16.2%), gross hematuria in four patients (10.8%) and hematospermia in four patients (10.8%). There was almost no intraoperative blood loss. CONCLUSIONS: Transrectal HIFU treatment of symptomatic BPH is safe, reduces symptoms significantly, and leads to a slight increase in uroflow.

Aged↗