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K Kawabe

Publications and source records attributed to K Kawabe.

At least 55 records · Page 3Linked to original sources
PubMed1999

The role of alpha 1L-adrenoceptor in rat urinary bladder: comparison between young adult and aged rats.

We examined the role of the alpha1L-adrenoceptors in the urinary bladder of young adult and aged rats in vitro. In the isolated body of the urinary bladder (corpus vesicae), phenylephrine-induced contractions were significantly facilitated in aged rats. Either prazosin, a non-selective alpha1-adrenoceptor antagonist, or JTH-601, an alpha1L-adrenoceptor antagonist, competitively inhibited the phenylephrine-induced contraction of isolated body of the urinary bladder. The antagonistic effect of JTH-601 was almost equipotent between young adult and aged rats (pA2 values were 9.61+/-0.12 and 9.79+/-0.07, respectively), although a statistically significant difference was noted for that of prazosin (pA2 values were 9.49+/-0.09 and 9.19+/-0.06, respectively). In macroscopic autoradiographic studies, specific binding of [3H]JTH-601 (5nM) was seen widely in the muscle layer of urinary bladder, but no differences were noted between young adult and aged rats. In the present study, there was no evidence to suggest a role of the alpha1L-adrenoceptors in the body of rat urinary bladder. On the other hand, alpha1A-adrenoceptors may play an important role in an age-related increase of alpha1-adrenoceptors response in this tissue. These results suggest that a facilitation of contractile response mediated by alpha1A-adrenoceptors may be a cause of unstable bladder in aged persons.

Adrenergic alpha-Agonists↗
PubMed1999

Age-related change of the role of alpha1L-adrenoceptor in canine urethral smooth muscle.

To examine age-related alteration of the role of alpha1L-adrenoceptor in the urethra, young non-parous and aged parous female dogs were used. In a functional study, we evaluated phenylephrine-induced contraction and antagonistic effects of JTH-601, a newly synthesized alpha1-adrenoceptor antagonist, and prazosin; in a localization survey using autoradiographic technique, we investigated specific [3H]JTH-601 and [3H]tamsulosin binding. Concentration-response curves were obtained for phenylephrine (pD2 = 5.0-5.3). JTH-601 and prazosin antagonized this contraction with pA2 values of 8.2-8.3 and 8.0-8.1, respectively. Specific binding of both [3H]JTH-601 and [3H]tamsulosin were observed in the bladder neck and proximal section of urethra. There were no significant differences of the pD2, pA2, and radio ligand binding between young non-parous and aged parous dogs.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1999

The effect of papaverine on morphologic differentiation, proliferation and invasive potential of human prostatic cancer LNCaP cells.

BACKGROUND: Intracellular cyclic adenosine monophosphate (AMP) level changes are thought to play an important role in inhibiting cell proliferation and inducing differentiation in several types of cells. It has been reported that cyclic AMP analogs induce terminal differentiation in human prostate cancer cells. Consequently, phosphodiesterase inhibitors may be useful in delineating the role of cyclic AMP in the differentiation of these cells. Therefore, the effect of phosphodiesterase inhibitors on morphologic differentiation, proliferation and invasive potential of human prostate cancer cells was investigated. METHODS: Three human prostate cancer cell lines PC-3, DU145 and LNCaP were treated with one of the phosphodiesterase inhibitors, papaverine, 3-isobutyl-1-methylxanthine (IBMX) or theophylline, for 6 days. Morphologic changes of these cells induced by phosphodiesterase inhibitors were observed by microscopy. Intracellular cyclic AMP levels in LNCaP cells were measured by radioimmunoassay using a cyclic AMP assay kit. The effect of papaverine on the proliferation and invasive potential of LNCaP cells were measured by cell counting and the Matrigel invasion chamber assay. RESULTS: Of the three agents, examined papaverine (10(-5) mol/L) is the most effective inducer of morphologic change and also raised intracellular cyclic AMP levels in LNCaP cells. However, unlike LNCaP cells, PC-3 and DU145 cells treated with phosphodiesterase inhibitors, including papaverine, showed little change in morphology. Additionally, proliferation and invasive potential of LNCaP cells were significantly inhibited by papaverine. CONCLUSION: The results suggest that papaverine induces terminal differentiation in LNCaP cells, which is correlated with an intracellular cyclic AMP-mediated pathway.

1-Methyl-3-isobutylxanthine↗
PubMed1999

Effect of Bcl-2 overexpression in human prostate cancer cells in vitro and in vivo.

BACKGROUND: Cancer cells often develop mechanisms to resist apoptosis and the extent of such anti-apoptotic ability has been shown to parallel tumor progression in various malignancies. Among various molecules implicated in regulating apoptosis pathway, bcl-2 and its family members are best characterized. METHODS: To investigate the effect of bcl-2-mediated anti-apoptotic ability on tumor growth and progression in prostate cancer, a cell line overexpressing bcl-2 (LNCaP/bcl-2) was established by genetically engineering a prostate cancer cell line LNCaP. Tumor growth of LNCaP/bcl-2 was compared with the parental cell line in vitro and in vivo. RESULTS: LNCaP/bcl-2 cells show resistance to apoptosis caused by nutrient deprivation and did not arrest when cultured in serum-free or androgen-free medium, while parental LNCaP cells or LNCaP cells transfected with the vector only (LNCaP/control) underwent extensive apoptosis on nutrient deprivation and sustained growth suppression in serum-free or androgen-free medium. When injected subcutaneously into nude mice, tumors deriving from LNCaP/bcl-2 cells grew faster compared with LNCaP/control for about 3 weeks (P = 0.02), but this effect was not evident after 5 weeks. Upon castration, the control tumors regressed but LNCaP/bcl-2-derived tumors showed resistance, as was previously reported. CONCLUSIONS: These data confirm the notion that anti-apoptotic function of bcl-2 is oncogenic and confers resistance to androgen deprivation and also indicate that it may also play a critical role in earlier stages of tumorigenesis.

Androgens↗
PubMed1999

Urinary nuclear matrix protein 22 as a new marker for the screening of urothelial cancer in patients with microscopic hematuria.

PURPOSE: The aim of the present study was to determine the clinical usefulness of nuclear matrix protein 22 (NMP22) as a new urinary marker for the screening of urothelial cancer in patients with microscopic hematuria, especially in comparison with that of voided urine cytology. METHODS: Patients with microscopic hematuria detected at a health examination, who were advised by a consulted urologist to have a cystoscopical examination, were asked to enter this study. Urine samples were collected before cystoscopy and divided into two portions for NMP22 test and voided urine cytology. RESULTS: Of the 309 patients with microscopic hematuria, 22 cases (7.1%) of urothelial cancer and one case of prostate cancer were detected. For the other cases, 128 (41.4%) were of benign diseases and 158 (51.1%) were designated as having no evidence of disease (NED). The median NMP22 values for urothelial cancer, other diseases and NED were 35.5, 6.7 and 6.0 U/mL, respectively, with 95% confidence intervals of 19.9-228.2, 5.1-9.3 and 5.4-7.2, respectively. The sensitivity of the NMP22 test for urothelial cancer was 90.9% (20/22), whereas the sensitivity of voided urine cytology was only 54.5% (12/22). CONCLUSIONS: The present study indicates that urinary NMP22 is a useful tool for the screening of urothelial cancer in patients with microscopic hematuria.

Adult↗
PubMed1999

Distribution of alpha1-adrenoceptor subtype mRNAs in human renal cortex.

OBJECTIVE: To determine the quantity and distribution of alpha1-adrenoceptor subtype mRNAs in human renal cortex. MATERIALS AND METHODS: Specimens of renal cortex tissue were obtained at the time of radical nephrectomy or total nephroureterectomy from 46 patients (mean age 59.0 years, sd 14.7) with renal cell carcinoma, renal pelvic or ureteric tumour. Using the reverse-transcriptase polymerase chain reaction (RT-PCR), the RNase protection assay and in situ hybridization, the presentation, quantity and distribution of alpha1-adrenoceptor subtype mRNAs were determined. RESULTS: Expression of the three alpha1-adrenoceptor subtype mRNAs (alpha1a, alpha1b and alpha1d) was confirmed in the arteries of the renal cortex (arciform, interlobular, arteriole), but among the three subtypes, the alpha1b was less apparent by in situ hybridization. Intense alpha1-mRNA staining was apparent especially in the smooth muscle of arterial walls. In both proximal and distal renal tubules, each of the alpha1-mRNAs was less marked in cytoplasm than in the arteries. In the glomeruli weak staining was detected in the endothelium but there was no obvious staining in the veins. RT-PCR showed all three subtypes of alpha1-adrenoceptor. The RNase protection assay showed that the predominant alpha1-adrenoceptor subtype mRNA in human renal cortex was alpha1a. However, the abundance of alpha1a-mRNA in human kidney was much less than in the prostate. CONCLUSION: Three alpha1-adrenoceptor subtype mRNAs were recognized in human renal cortex and detected particularly in the smooth muscle of the arteries. There was more alpha1a-adrenoceptor subtype in human renal cortex than the other subtypes. It is not known how each subtype operates against adrenergic stimulation; further studies are needed to examine receptor density or receptor function.

Adult↗
PubMed1999

Surgical treatment of renal cell carcinoma associated with Budd-Chiari syndrome: report of four cases and review of the literature.

AIMS: Renal cell carcinoma is sometimes associated with inferior vena caval tumour thrombus, but occlusion of hepatic veins by the tumour thrombus causing liver dysfunction, the so-called Budd Chiari syndrome, is relatively uncommon. There are only a few reports in the literature which discuss this condition. METHODS: Four cases admitted to our hospital over a 7-year period and eight cases reported in detail in the English and the Japanese literature were included in this study. They are classified into two groups: mild/silent, without liver failure, and severe, with liver failure. RESULTS: Five patients were classified as mild/silent and seven as severe. Clinical manifestations were mild in the former cases and acute in the latter. Surgery was performed in four of the former cases but only in one case of the latter cases. CONCLUSIONS: In mild cases, surgical treatment seems to avoid imminent hepatic failure effectively and should be performed as soon as possible. In such cases Budd Chiari syndrome in itself does not affect the prognosis. In severe cases, however, surgical treatment is very difficult and risky due to the existing hepatic failure.

Adult↗
PubMed1999

Goserelin acetate with or without antiandrogen or estrogen in the treatment of patients with advanced prostate cancer: a multicenter, randomized, controlled trial in Japan. Zoladex Study Group.

OBJECTIVE: The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade. METHODS: Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate). RESULTS: There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone. CONCLUSIONS: Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.

Aged↗
PubMed1999

A multicenter placebo-controlled, double-blind trial of urapidil, an alpha-blocker, on neurogenic bladder dysfunction.

OBJECTIVES: To assess the efficacy of urapidil, an alpha-blocker, on neurogenic bladder dysfunction in a placebo-controlled, double-blind trial. METHODS: 149 patients were randomly assigned to receive a placebo or 60 mg/day of urapidil for 4 weeks. The evaluation of efficacy included changes in urinary symptom scores and the results of a pressure/flow study. RESULTS: There were significant intergroup differences with regard to straining and the sum of urinary symptom scores, with the urapidil group showing marked improvements (p = 0.016 and p = 0.011, respectively). In the urapidil group, the average and maximum flow rates were unchanged, but the residual urine volume decreased significantly (p < 0.001) as compared with the baseline value. The pressure at maximum flow and the minimum urethral resistance decreased significantly (p = 0.040 and p = 0.040, respectively) in the urapidil group, and there was a significant (p = 0.005) intergroup difference with regard to pressure at maximum flow. There was also a significant (p < 0.001) inter-group difference with regard to the overall therapeutic effect. Side effects were noted in 2 patients treated with urapidil and 6 in the placebo group. CONCLUSION: Urapidil is effective for the treatment of voiding dysfunction in patients with neurogenic bladder.

Adrenergic alpha-Antagonists↗
PubMed1999

Dax-1 as one of the target genes of Ad4BP/SF-1.

The DAX-1 (also known as AHC) gene encodes an unusual member of the nuclear hormone receptor superfamily. DAX-1 plays a critical role during gonadal and adrenal differentiation since mutations of the human DAX-1 gene cause X-linked adrenal hypoplasia congenita associated with hypogonadotropic hypogonadism. In recent studies, DAX-1 was reported to function as a transcriptional suppressor of Ad4BP/SF-1, a critical transcription factor in gonadal and adrenal differentiation. With respect to implication of Ad4BP/SF-1 in the transcriptional regulation of the DAX-1 gene, inconsistent findings have been previously reported. We investigated the upstream region of the mouse Dax-1 (also known as Ahch) gene and identified a novel Ad4/SF-1 site by transient transfection and electrophoretic mobility shift assays. In addition, immunohistochemical analyses with a specific antibody to Dax-1 indicated the presence of immunoreactive cells in steroidogenic tissues, pituitary gland, and hypothalamus. Although the distributions of Dax-1 and Ad4BP/SF-1 were very similar, they were not completely identical. The expression of Dax-1 was significantly impaired in knock-out mice of the Ftz-f1 gene, which encodes Ad4BP/ SF-1. Taken together, our findings indicate that Ad4BP/SF-1 controls the transcription of the Dax-1 gene.

Adrenal Cortex Neoplasms↗
PubMed1999

Increased renal retention of 99mTc-methylene diphosphonate after nephron-sparing surgery.

UNLABELLED: Nephron-sparing surgery has become established as an effective treatment for localized renal cell carcinoma when preservation of renal function is necessary. The surgery usually requires temporary renal artery occlusion and may induce ischemic renal damage. In this study, we retrospectively evaluated renal activity on bone scintigraphy after nephron-sparing surgery. METHODS: Eleven patients who underwent nephron-sparing surgery for renal cell carcinoma and had a normal contralateral kidney were studied. A total of 12 bone scintigraphy images with 99mTc-labeled methylene diphosphonate were obtained within 1 y after surgery in these patients to assess skeletal metastasis. Activity in the spared renal parenchyma was compared visually with that in the contralateral normal kidney. RESULTS: The tumor was successfully resected in every patient, and no clinically significant complications occurred. Activity in the spared renal parenchyma was elevated in six of seven examinations performed within 21 d after surgery. In three examinations, the increase in renal activity was heterogeneous, being relatively prominent near the surgical margin. Increased renal activity was not observed on five examinations performed 3 mo or more after surgery. CONCLUSION: Renal retention of bone-seeking agents is elevated in the early period after nephron-sparing surgery, probably as a result of ischemic insult during the surgical procedure. Bone scintigraphy may aid in evaluating the presence and degree of ischemic damage of the spared renal parenchyma.

Adult↗
PubMed1998

Intrahippocampal D-cycloserine improves MK-801-induced memory deficits: radial-arm maze performance in rats.

In order to investigate whether strychnine-insensitive glycine sites coupled with hippocampal NMDA (N-methyl-d-aspartate) receptors are involved in spatial memory in rats, we examined the effects of intrahippocampal treatment of d-cycloserine (DCS), a glycine-site agonist, on spatial-memory deficits which were produced by an NMDA antagonist MK-801 (dizocilpine) on the radial-arm maze task. After the acquisition of this task, the radial-maze performance was tested under the combined treatments of intraperitoneal MK-801 or saline (SAL) and intrahippocampal DCS or SAL. The results showed that MK-801 impaired the performance, and that DCS improved the MK-801-induced performance impairment. These results suggest that glycine sites are involved in spatial memory through their modulatory action on hippocampal NMDA receptors.

Analysis of Variance↗
PubMed1998

Effects of intrahippocampal AP5 treatment on radial-arm maze performance in rats.

The purpose of the present study was to investigate the possible involvement of hippocampal NMDA (N-methyl-d-aspartate) receptors in spatial memory in rats by means of intrahippocampal injection of an NMDA antagonist, AP5 (D,L-2-amino-5-phosphonopentanoic acid). In Expt. 1, spontaneous motor activity (locomotor activity and rearing) was measured in an open-field after bilateral AP5 injection into the hippocampus, and it was shown that AP5 did not affect general activities within the dosage used in the present study. In Expt. 2, radial-maze performance was observed after the intrahippocampal injection of AP5. Rats were required to consume all the pellets which were put on each of the eight arms of the maze without revisiting the arms. AP5 produced dose-dependent impairment on the choice performance in the radial-arm maze, but did not have any effect on their running time. These results suggest that hippocampal NMDA receptors are involved in spatial memory.

2-Amino-5-phosphonovalerate↗
PubMed1998

In vivo receptor binding of novel alpha1-adrenoceptor antagonists for treatment of benign prostatic hyperplasia.

New types of alpha1-adrenoceptor antagonists (tamsulosin, KMD-3213 and JTH-601) are currently receiving a great deal of attention, especially in terms of developing effective therapeutic agents to treat bladder outlet obstruction with less side effects, such as postural hypotension, in patients with benign prostatic hyperplasia (BPH). In vivo alpha1-adrenoceptor binding properties of these antagonists in prostate and other tissues of rats were examined. Intravenous injections of tamsulosin, KMD-3213 and JTH-601 inhibited dose-dependently in vivo specific [3H]tamsulosin binding in various tissues. Ratios of ID50(aorta) to ID50(prostate) of KMD-3213 and JTH-601 were greater than those of tamsulosin and prazosin. Further, the ratios of ID50(spleen) to ID50(submaxillary gland) of these drugs were greater than that of prazosin. Following intravenous injections of [3H]KMD-3213 in rats, the amount of specific binding in prostate was significantly greater than that of [3H]prazosin, but that in aorta or spleen was much smaller. Interestingly, [3H]JTH-601 showed little in vivo specific binding in aorta. These data suggest that KMD-3213 and JTH-601 exhibit higher affinity to alpha1-adrenoceptors in prostate and submaxillary gland than in vascular tissues in vivo.

Adrenergic alpha-Antagonists↗
PubMed1998

Immunohistochemical study of p21WAF1 and p53 proteins in prostatic cancer and their prognostic significance.

Mutations of p53 tumor suppressor gene occur in a subset of aggressive prostatic carcinomas and are detectable by immunohistochemistry. However, it is uncertain whether p53 overexpression really reflects p53 gene mutation or loss of p53 function. p21WAF1, an inhibitor of cyclin-dependent kinases, is activated by wild-type p53 protein, not by mutant type. Therefore, it is possible that combined analysis of p21WAF1 and p53 proteins aids in determining the functional status of p53 immunostaining. Routinely processed prostatic tissues from 60 patients with prostatic adenocarcinomas were examined by immunohistochemistry for p21WAF1 and p53 expression. As for tissue distribution, p21WAF1 protein was expressed mostly in the luminal layers, in contrast, p53 protein was restricted to the basal layers of benign prostatic glands. In prostatic adenocarcinomas, p21WAF1 protein was more likely to be expressed in well-differentiated areas; in contrast, p53 protein was more likely in poorly differentiated areas in the tumors. The percentage of positive nuclear areas for p21WAF1 and p53 proteins in prostatic adenocarcinomas, assessed by CAS200 computerized image analyzer, were 8.6+/-10% and 16+/-14% (mean+/-SE), respectively. The survival study showed that the p53+/ p21- phenotype showed poorer prognosis than p53+/p21+. Multivariate analysis showed that p21WAF1 expression, clinical stage, and Gleason score were independent prognosticators. In conclusion, p21WAF1 immunohistochemistry is a useful method for interpretation of p53 immunohistochemical results. Combined analysis by p21WAF1 and p53 immunostaining would predict the patient survival more accurately than p53 immunostaining alone.

Adenocarcinoma↗
PubMed1998

Co-expression of hepatocyte growth factor and its receptor in human prostate cancer.

Hepatocyte growth factor acts differently depending on the organs or tumours involved. It may be produced simultaneously with its receptor, c-Met, in several types of malignant tumour cells and may exercise an autocrine regulation. To analyse the effect of hepatocyte growth factor in human prostate cancer, we conducted immunohistochemistry, in situ hybridization and the reverse transcriptase polymerase chain reaction. The first two techniques revealed the growth factor in prostate cancer cells, and the polymerase chain reaction confirmed this expression. c-Met is expressed in prostate cancer cells, but not in interstitial cells. Hepatocyte growth factor is expressed in interstitial cells, especially in hormone-treated cancer tissue, indicating that the growth factor pathway changes with the hormonal status. Low-grade tumours expressed c-Met at the plasma membrane. Higher grade tumours tended to express it in the cytoplasm, suggesting that the role of c-Met as the hepatocyte growth factor receptor was blocked in higher grade tumours. The relationship between the growth factor and its receptor is thus influenced by hormonal status and differentiation in prostate cancer and is not explained simply in terms of autocrine or paracrine action.

Aged↗