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K Kawabe

Publications and source records attributed to K Kawabe.

At least 109 records · Page 6Linked to original sources
PubMed1996

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↗
PubMed1996

Detection of alpha 1-adrenoceptor subtypes in human hypertrophied prostate by in situ hybridization.

Adrenergic stimulation induces contraction of hypertrophied prostatic tissue via the alpha 1 adrenoceptor, and the results of pharmacological studies suggested the existence of adrenoceptor subtypes. Recently three subtypes (alpha 1a, alpha 1b, and alpha 1d) were cloned. Using probes for these subtypes, we demonstrated their expression in the tissues of ten cases of benign prostatic hypertrophy, using in situ hybridization. To determine the ratio between these subtypes, an RNase protection assay was also performed in three cases. Expression of the alpha 1a and alpha 1d adrenoceptors was diffuse in the smooth muscles of the interstitium, but was absent in glandular epithelial cells. On the contrary, the alpha 1b adrenoceptor was hardly detectable. The RNase protection assay confirmed the absence of the alpha 1b adrenoceptor, the ratio of alpha 1a and alpha 1d being 4:1. These results supported the idea that the differences in prostatic contractile response to several adrenergic drugs are based on the affinities of these drugs for the different subtypes.

Aged↗
PubMed1996

Decreased contractile effect of endothelin-1 on hyperplastic prostate.

1. The contractile activity, binding activity and localization of endothelin (ET)-1 were evaluated in human nonhyperplastic (control) and hyperplastic prostates. 2. ET-1 caused contraction of both prostates in a dose-dependent manner. However, this contraction was markedly decreased in hyperplastic prostates. 3. Bmax and Kd values of hyperplastic prostates were greater than those of the control. 4. The muscle and proliferative epithelium of hyperplastic prostates showed strong staining for the anti-ET-1 antibody. However, the glandular epithelium of control prostates was weakly stained. 5. These findings indicate that responsiveness to ET-1 is decreased, though the ET-1 and ET-1 receptors increase in the hyperplastic prostate. Namely, the increase in ET-1 receptors is not effective in regulating the contractile response of the prostate, because its expression is rather dominant in proliferated gland. 6. These suggest that ET-1 may not have an important role in the release of the obstructive symptoms of benign prostatic hypertrophy.

Aged↗
PubMed1996

Determination of alpha 1-adrenoceptor antagonists in plasma by radioreceptor assay.

A simple, rapid and sensitive radioreceptor assay (RRA) for the quantification of alpha 1-adrenoceptor antagonists such as prazosin in plasma is described. The method involves the use of an RRA based on [3H]prazosin displacement in rat cerebral cortical membranes. The method is reliable, with intra-assay and inter-assay RSDs ranging from 5.9 to 9.2%. The limit of detection is 0.2 (prazosin hydrochloride), 0.05 (tamsulosin hydrochloride) and 0.3 (bunazosin hydrochloride) pmol per assay. Using this method the plasma levels of prazosin hydrochloride were determined in beagle dogs administered orally 2.39 mumol kg-1 of this drug. The plasma levels of prazosin in beagle dogs are in good agreement with those obtained using a high-performance liquid chromatography (HPLC). This RRA proved to be applicable to the monitoring of plasma prazosin levels in patients with essential hypertension and/or benign prostatic hypertrophy receiving therapy with this drug with the therapeutic dosage schedule. Thus, the concentrations of alpha 1-adrenoceptor antagonists in plasma can be adequately monitored by RRA as well as by HPLC.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1996

Histochemical detection of intranuclear DNA fragmentation and its relation to the expression of bcl-2 oncoprotein in human prostatic cancer.

OBJECTIVE: To assess the incidence of intranuclear DNA fragmentation and the expression of the bcl-2 oncoprotein in prostatic carcinoma, both of which are related to programmed cell death. PATIENTS, MATERIALS AND METHODS: Specimens of tumour obtained from 17 patients with newly diagnosed prostatic carcinoma and 16 with hormone-treated prostatic carcinoma undergoing total prostatectomy were evaluated. DNA fragmentation was detected using the terminal-labelling method (d-uridine triphosphate conjugated with digoxigenin) and the expression of bcl-2 was detected immunohistochemically. RESULTS: There was a high incidence of intranuclear DNA fragmentation in 14 of 17 untreated tumours and 15 of 16 hormone-treated tumours. There were no differences between the positive cases in hormone-treated tumours and untreated tumours. There was significantly greater expression of bcl-2 in tumours treated with non-steroidal anti-androgen drugs (eight of nine were positive) than in those untreated (seven of 17) or treated with other drugs (one of seven) (P < 0.05). There was a consistent and marked dissociation between DNA fragmentation and bcl-2 positivity; most of the cells positive for bcl-2 showed no DNA fragmentation. CONCLUSION: The results indicated that cells positive for bcl-2 might potentially be hormone resistant and that the administration of non-steroidal anti-androgen drugs might have a role in the induction of hormone-resistant cells.

Aged↗
PubMed1996

Geographical distribution of the human polyomavirus JC virus type A and B and isolation of a new type from Ghana.

The JC polyomavirus (JCV) is ubiquitous in humans infecting children asymptomatically, then persisting in renal tissue. Since JCV DNA can be readily isolated from urine, it should be a useful tool with which to study the evolution of DNA viruses in humans. We showed that JCV DNA from the urine of Japanese, Taiwanese, Dutch and German patients can be classified into A and B types, based upon restriction fragment length polymorphisms (RFLPs). This work was extended in the present study. We established multiple JCV DNA clones from the UK, Spain, Italy, Sweden, South Korea, People's Republic of China, Malaysia, Indonesia, Mongolia, India, Sri Lanka, Saudi Arabia, Ethiopia, Kenya, Zambia, South Africa and Ghana. Using type-specific RFLPs, most clones except the four clones from Ghana were classified as either type A or B. We constructed a molecular phylogenetic tree for the Ghanaian clones and several representative type A and B clones. According to the phylogenetic tree, the Ghanaian clones constituted a major new group, tentatively named type C. From the findings presented here and elsewhere, the following conclusions were drawn: (i) type A is prevalent only in Europe; (ii) type B is found mainly in Asia and Africa; and (iii) type C is localized to part of Africa. Our findings should help to clarify how JCV evolved in humans.

Base Sequence↗
PubMed1996

bl-2 [corrected] Expression on prostate cancer and its relationship to cell cycle and prognosis.

BACKGROUND: bcl-2 protein is an oncoprotein encoded by a protooncogene bcl-2 which is thought to be a key gene for the regulation of cell life and death. bcl-2 protein has been reported to be expressed in a subset of prostate cancers, and its biological role in this disease has not yet been elucidated. This present study focused on the cell cycle analysis of bcl-2 immunoreactivity in prostate tumor samples and correlated findings with the prognosis of the patients. METHODS: Archival tissues from 37 prostate cancers were submitted for immunohistochemistry and DNA analysis via flow cytometry. All tissues were obtained before the patients received any treatment. Immunohistochemistry was performed using streptavidin biotin procedures, and DNA flow cytometry was done by a combination of two methods. RESULTS: Fourteen of 37 prostate cancers (38%) exhibited bcl-2 immunoreactivity. bcl-2 positive prostate cancers significantly correlated with DNA aneuploidy and higher proliferation indices, but not with histological differentiation. Clinically, there was a poorer prognosis for patients with bcl-2 positive prostate cancer. CONCLUSIONS: Our data indicates that bcl-2 protein expression in prostate cancer is associated with cell proliferation and may serve as a predictive factor for the prognosis of prostate cancer.

Adenocarcinoma↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1996

Transition zone ratio and prostate-specific antigen density: the index of response of benign prostatic hypertrophy to an alpha blocker.

BACKGROUND: The aim of the present study was to determine whether the indices of transrectal ultrasonography (TRUS) are related to the clinical response to tamsulosin, a long-acting selective alpha 1-blocker. METHODS: Sixty patients with symptomatic benign prostatic hypertrophy (BPH) were treated with tamsulosin hydrochloride (0.2 mg/day) for 2 months. The findings on TRUS and uroflowmetry and the AUA symptom score before treatment were compared with those obtained at the end of the 2 month treatment period. For the indices of TRUS, transition zone (TZ) volume, transition zone ratio (TZ ratio = TZ volume/total prostate volume), total prostate volume, and prostate specific antigen density (PSAD) were calculated. RESULTS: There was a significant correlation between the pretreatment TZ ratio and the residual urine volume (r = 0.421, P = 0.0005). Patients with a lower TZ ratio and/or PSAD responded well to the treatment. The correlation between the PSAD value and the percent change in peak urinary flow rate was statistically significant (r = -0.432, P = 0.0009). CONCLUSION: TRUS provides simple parameters of PSAD that can be used to predict the response of patients to tamsulosin hydrochloride.

Adrenergic alpha-Antagonists↗
PubMed1996

PSA value adjusted for the transition zone volume in the diagnosis of prostate cancer.

BACKGROUND: The aim of the present study was to improve the accuracy of the prostate-specific antigen (PSA) density for detecting prostate cancer by using the transition zone (TZ) volume instead of the total prostate volume. METHODS: From April 1994 to October 1995, we examined 164 consecutive patients (52-88 years old), with an elevated PSA and/or abnormal digital rectal examination. All patients underwent a transrectal ultrasound-guided biopsy. The PSA density for total prostate volume (PSAD) and for TZ volume (PSAT) were calculated from the transrectal ultrasound measurements. RESULTS: Forty-four of the 162 patients (27.2%) had histological confirmation of prostate cancer on biopsy. The area under the receiver-operator characteristic curve was 0.667 for PSA, 0.663 for PSAD, and 0.826 for PSAT. These areas were not significantly different for PSA and PSAD. However, PSAT was significantly superior to PSAD in differentiating benign hyperplasia from prostate cancer (P < 0.01). CONCLUSION: The TZ volume-adjusted PSA density (PSAT) is useful for selecting patients for prostate biopsy from those with suspected prostate cancer.

Aged↗
PubMed1996

Transrectal ultrasonography to predict the clinical outcome of transurethral microwave thermotherapy in patients with benign prostatic hyperplasia.

BACKGROUND: This study evaluated the long-term efficacy of transurethral microwave thermotherapy (TUMT) in the treatment of benign prostatic hyperplasia (BPH), and determined whether the indices obtained with transrectal ultrasonography (TRUS) can predict the clinical response to TUMT. METHOD: Between November 1991 and June 1992, 43 patients with symptomatic BPH were treated with TUMT using the Prostcare device. The therapy consisted of a 1-hour treatment under topical anesthesia. The findings of uroflowmetry and AUA symptom score before treatment were compared with those obtained at each visit after the therapy. As the indices, the transition zone (TZ) volume, transition zone ratio (TZ ratio = TZ volume/total prostate volume), total prostate volume, and presumed circle area ratio (PCAR) were calculated. RESULTS: There was a significant correlation between pretreatment TZ ratio and residual urine volume (r = 0.472, P = 0.0022). The efficacy rates calculated by response criteria on the 3 point scale at 2 months, 12 months, and 30 months were 44.2%, 30.2%, and 25%, respectively. The significant prognostic factors that predicted the clinical effect 1 year after treatment were the TZ ratio and intraprostatic temperature. After controlling for the treatment temperature, the multivariate logistic regression model demonstrated that the TZ ratio was the significant predictor (P = 0.049) of 1 year efficacy of treatment. CONCLUSION: The present study showed that the efficacy rate of TUMT at 30 months was 25%, and that TRUS provides a simple parameter, the TZ ratio, which predicts the efficacy of TUMT.

Aged↗
PubMed1996

Microlith formation in vitro by Madin Darby canine kidney (MDCK) cells.

BACKGROUND: The mechanism of renal stone genesis as well as the location of stone crystal formation in the kidney remains unclear. Possible sites of stone generation are either in the tubular lumen or tubular cell. METHODS: We cultured Madin Darby canine kidney (MDCK), LLC-PK1 and Magen Krebs Niigata-28 (MKN-28) cells in DMEM + 10% FBS medium in a well without passage for 30 days. RESULTS: MDCK cells produced microliths at the basolateral side but not on the lumen side of these cells. The other two cell lines did not form microliths. CONCLUSION: Our data show that microlith formation is a characteristic of MDCK cells and that biological mineralization of MDCK cells may serve as a human urolithiasis model in vitro. The findings support a significant role of the renal distal convoluted tubule and collecting ducts in the in vitro generation of urinary stones.

Alkaline Phosphatase↗
PubMed1996

Alpha 1a-adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy.

1. Two restriction fragment length polymorphisms of the human alpha 1a-adrenoceptor gene digested with PstI restriction enzyme exist; the nucleotide change causes the substitution of C residue for T at nucleotide 1441, thereby Arg492 to Cys492 transition, which might confer an additional putative palmitoylation site in the carboxy-terminal segment of the alpha 1a-adrenoceptor. In the present study, we compared their pharmacological properties and examined whether this alpha 1a-adrenoceptor polymorphism is associated with benign prostatic hypertrophy (BPH). 2. The frequency of alpha 1a-adrenoceptor polymorphism was not differently distributed between patients with benign prostatic hypertrophy (BPH) and normal subjects in Japan; thus, the relative frequencies of the C and T alleles were 0.90 : 0.10 in normal male subjects (n = 45) and 0.87 : 0.13 in BPH patients (n = 222), respectively. However, the frequency distribution of this polymorphism was significantly different between the Japanese and U.S. populations; thus, C and T alleles were 0.34 and 0.66 in U.S. populations. 3. Utilizing Chinese hamster ovary (CHO) cells stably expressing the two polymorphic alpha 1a-adrenoceptors (Arg492 and Cys492), we compared their binding affinity and signal transduction. Radioligand binding studies with 2-[beta-(4-hydroxy-3[125I]-iodophenyl) ethylamino-methyl]tetralone ([125I]-HEAT) showed no marked difference in the antagonist or agonist binding affinities between the two receptors. Also, both receptors were found to be coupled to the calcium signaling, and the concentration-cytosolic Ca2+ concentrations ([Ca2+]i) response relationships for noradrenaline were similar for the two polymorphic receptors. Furthermore, the receptor-mediated [Ca2+]i response was markedly desensitized after a 2 h exposure of phenylephrine (10 microM), and the extent of the desensitization was not significantly different between the two receptors. 4. In summary, the results showed that the two alpha 1a-adrenoceptors generated by genetic polymorphism have similar pharmacological characteristics, and the receptor-mediated [Ca2+]i response can be desensitized in a similar manner. The study did not provide any evidence to support the hypothesis that alpha 1a-adrenoceptor gene polymorphism is associated with BPH.

Aged↗
PubMed1996

Quantification and distribution of alpha 1-adrenoceptor subtype mRNAs in human prostate: comparison of benign hypertrophied tissue and non-hypertrophied tissue.

1. There are at least three alpha 1-adrenoceptor subtypes, alpha 1a, alpha 1b and alpha 1d, in human tissues. Using an RNase protection assay, we have now determined the amount of each subtype mRNA in human prostatic tissue, for both benign prostatic hypertrophy (BPH) and non-BPH. In all tissue samples examined, the predominant subtype mRNA was alpha 1a. The total abundance of alpha 1-adrenoceptor mRNA in BPH samples was over six times that in non-BPH samples. This increase was mostly accounted for by alpha 1a, which was almost nine times as abundant in BPH samples as in non-BPH samples. The abundance of alpha 1b was almost the same between BPH and non-BPH samples, and the abundance of alpha 1d in BPH samples was about three times that in non-BPH samples. The ratio of the numbers of the subtype mRNAs, alpha 1a: alpha 1b: alpha 1d, was 85:1:14 in BPH samples and 63:6:31 in non-BPH samples. 2. In situ hybridization studies showed no significant differences in the tissue localization of alpha 1-adrenoceptor subtype mRNAs between BPH and non-BPH samples. alpha 1a and alpha 1d were clearly detected in the interstitium of the prostate, where alpha 1a was stained more intensely than alpha 1d, and the positive sites were primarily smooth muscle cells. In contrast, alpha 1b staining was very faint. 3. This increase in mRNA abundance may be directly related to the contraction of prostatic tissue that leads to obstruction of the urinary tract in BPH patients. Specifically, our data suggest that increased expression of the alpha 1a subtype may be primarily responsible for the contraction of the prostate.

Aged↗
PubMed1996

Nuclear deoxyribonucleic acid ploidy of testicular tumors: peculiar features and clinical significance.

To verify the usefulness of testicular DNA ploidy measurement, we tried some approaches to tumorous and nontumorous testes. Separation of paraffin-embedded specimens into single dissociated nuclei was performed by Hedley's technique and nuclei were stained with propidium iodide. Control nontumorous testes were clearly separated into the three-peak type with a high G2M percentage and the two-peak type with a low G2M percentage. Among testicular tumors, 25% (8 of 32) had a normal DNA diploid pattern, 15.6% (5 of 32) had an increased DNA tetraploid pattern including DNA polyploidy, and 59.4% (19 of 32) were DNA aneuploid. In detail, 26.3% (5 of 19) of seminomas and 23.1% (3 of 13) of nonseminomas were DNA diploid. Interestingly, seminomas showed a variety of DNA histogram profiles. Among DNA aneuploid tumors, the DNA index of a seminoma was significantly higher than that of a nonseminoma. Among patients who received curative orchiectomy, postoperative metastases did not occur in any of the 8 DNA diploid or 5 tetraploid tumors, but did occur in 4 (21.1%) of 19 DNA aneuploid tumors during an at least 6-year follow-up. Clinicopathological findings were not as predictable as DNA ploidy. Flow cytometry appeared to be useful to characterize testicular tumors.

Adolescent↗