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K Kawabe

Publications and source records attributed to K Kawabe.

At least 73 records · Page 4Linked to original sources
PubMed1998

Quantification and distribution of alpha1-adrenoceptor subtype mRNAs in human proximal urethra.

1. We performed RNase protection assays and in situ hybridization to investigate the ratio of the three alpha1-adrenoceptor subtype mRNAs, alpha1a, alpha1b and alpha1d, in human proximal urethra, and their localization in urethral cross-sections. As revealed by the RNase protection assays, alpha1a was the predominant subtype mRNA in both male and female urethral samples. Alpha1d mRNA was detected only in the female sample, and alpha1b mRNA was not detected in any of the samples tested. The ratio of the abundance of the subtype mRNAs, alpha1a:alpha1b:alpha1d, was 100:0:0 in the male urethra and 90:0:10 in the female urethra. 2. In situ hybridization studies showed no significant differences in the cross-sectional distribution of alpha1-adrenoceptor subtype mRNAs between male and female urethras. Intense alpha1a staining was observed in the smooth muscle of the urethra, but alpha1b and alpha1d staining was much less intense. 3. Of the three cloned alpha1 subtypes, alpha1a is the most likely to be responsible for the contraction of the human urethra. Owing to the side effects of nonselective alpha1 drugs, alpha1-selective drugs may be clinically superior to nonselective drugs for the treatment of urethral disorders.

Aged↗
PubMed1998

Evaluation of histological structure and its effect on the distribution of alpha1-adrenoceptors in human benign prostatic hyperplasia.

OBJECTIVE: To evaluate the histological structure of benign prostatic hyperplasia (BPH) and its relationship with the density of alpha1-adrenoceptors in smooth muscle. MATERIALS AND METHODS: Specimens from hyperplastic tissues obtained from 14 patients with BPH were evaluated for the density of alpha1-adrenoceptors in smooth muscle using autoradiography, Mallory-Azan staining and computer-assisted image analyses. The binding of [3H] tamsulosin (a selective alpha1-blocker) and the ratio of smooth muscle area was calculated, and the density of alpha1-adrenoceptors per area of smooth muscle determined by dividing the degree of binding by the ratio of smooth muscle to total area. RESULTS: There was a significant difference between the ratio of smooth muscle area in the hyperplastic acinar nodule and the surrounding stroma (P < 0.01). The density of alpha1-adrenoceptor per smooth muscle area was significantly higher in the hyperplastic acinar nodule than in the surrounding stroma (P < 0.05). There was no correlation between prostatic weight and the ratio of smooth muscle area or the density of alpha1-adrenoceptors in each region. CONCLUSION: The distribution of alpha1-adrenoceptors on smooth muscle differed with histological structure; both the histological conformation and the difference in the distribution of alpha1-adrenoceptors could affect urethral obstruction in BPH.

Autoradiography↗
PubMed1998

Immunohistochemical study of Fas, Fas ligand and interleukin-1 beta converting enzyme expression in human prostatic cancer.

OBJECTIVE: To determine the cellular expression of Fas, Fas ligand and interleukin-1 beta converting enzyme (ICE) in prostatic cancer. PATIENTS AND METHODS: Specimens of prostate were obtained from 21 patients (mean age 66 years, SD 5) undergoing radical prostatectomy for prostatic cancer. Nine of the 21 patients had received endocrine therapy before surgery. Specimens were also obtained from 10 patients with benign prostatic hypertrophy (BPH) and during autopsy from 10 patients who had died from hormone-unresponsive prostate cancer. Paraffin-embedded sections were cut from the specimens and stained immunohistochemically to detect Fas, Fas ligand and ICE. RESULTS: Fas was expressed in all 21 of the cancer specimens while Fas ligand was detected in none and ICE was expressed in 11. The difference between the expression of Fas and ICE was significant (P < 0.001). ICE was expressed in nine of 12 patients who were untreated before surgery and in two of nine treated with endocrine therapy (P < 0.05). Fas expression was detected in the specimens from all 10 patients with BPH and in all 10 autopsy specimens; the expression, tended to be more marked than that in specimens from total prostatectomy (P < 0.1). CONCLUSION: The expression of ICE was weaker than that of Fas in the total prostatectomy specimens, suggesting a possible interruption of the apoptotic signalling pathway. Prostates with BPH and hormone-unresponsive cancer therefore showed no appreciable change in Fas expression when compared with total prostatectomy samples.

Aged↗
PubMed1998

The alpha1L-adrenoceptor subtype in the lower urinary tract: a comparison of human urethra and prostate.

OBJECTIVE: To identify the alpha1-adrenoceptor subtypes present in the human urethra, by comparing the affinity of prazosin for alpha1-adrenoceptors in the rabbit, dog and human prostatic urethra, and in the dog and human prostate. MATERIALS AND METHODS: The study comprised samples of human prostate and prostatic urethra, obtained by open prostatectomy of patients with benign prostatic hyperplasia, and of the proximal urethra and prostate from male Beagle dogs and rabbits. Specimens were homogenized, filtered and pelleted by centrifugation. Nonspecific binding was determined in the presence of 1 mmol/L prazosin when assessing [3H]YM-617 (tamsulosin) binding, and 10 mmol/L phentolamine when assessing [3H]prazosin binding. Specific binding was defined as the difference between total binding and nonspecific binding. RESULTS: The dissociation constant for [3H]prazosin in the human prostate (0.088 nmol/L) was less than that in the rabbit urethra (0.299 nmol/L), dog urethra (0.604 nmol/L), dog prostate (0.482 nmol/L) and human urethra (0.254 nmol/L). The affinity of prazosin was also investigated by determining the potency of the inhibition of [3H]YM-617 binding. The affinity of prazosin for alpha1-adrenoceptors in the human urethra (Ki, 2.5 nmol/L) was lower than its affinity for alpha1-adrenoceptors in the human prostate (Ki, 0.25 nmol/L) and all of the cloned subtypes (Ki, 0.26-0.44 nmol/L). CONCLUSION: The alpha1L-adrenoceptor subtype is more prominent in the human, rabbit and dog urethra and dog prostate than in the human prostate.

Adrenergic alpha-Antagonists↗
PubMed1998

Identification of lipid inhibitor of mammalian phospholipase D.

Phospholipase D (PLD) is implicated in important cellular processes, such as hormone action, inflammation, secretion, mitogenesis, and neural activity. Recent studies using cell-free systems have shown that the enzyme activity is modulated by both positive and negative regulators. During an attempt to purify PLD from pig colon mucosa, we noted the presence of a PLD inhibitor in the tissue extract. The inhibitor was purified and identified as comprising lysophosphatidylserine, phosphatidylinositol, and lysophosphatidylinositol, of which lysophosphatidylserine was the most potent. These lipids affected all of the PLD isoforms examined, oleate-dependent PLD, ARF-dependent PLD (PLD1a, PLD1b), and phosphatidylinositol 4,5-bisphosphate-dependent PLD (PLD2), in the concentration range of the 1 or 10 microM order. In contrast to lysophosphatidylserine, the diacyl counterpart phosphatidylserine was without effect in the same concentration range. PLD inhibition by lysophosphatidylserine could not be reversed by an increase in the concentration of the substrate phosphatidylcholine or activator phosphatidylinositol 4,5-bisphosphate.

Animals↗
PubMed1998

Adrenocortical and gonadal expression of the mammalian Ftz-F1 gene encoding Ad4BP/SF-1 is independent of pituitary control.

Ad4BP/SF-1 is a transcription factor essential for the development of the adrenal gland and the gonads as well as for the maintenance of their functions through regulating tissue-specific gene transcription. In the whole body, hypothalamo-pituitary-gonadal and -adrenal axes are known to play prominent roles in mediating the function of the gonads and adrenal. In this study, the effects of the tropic peptide hormones secreted by the pituitary on the regulation of the rat Ftz-F1 (rFtz-F1) gene encoding Ad4BP/SF-1 were investigated. Immunochemical studies revealed that Ad4BP/SF-1 was expressed even in the adrenal cortex of hypophysectomized rats. Such persistent expression of Ad4BP/SF-1 was also observed in the testes and ovaries of the hypophysectomized animals. In contrast to Ad4BP/SF-1, the expressions of steroidogenic P450s were reduced significantly. The transcriptional activities of the endogenous and transfected rFtz-F1 genes were examined with Y-1 and I-10 cells derived from mouse adrenocortical and testicular Leydig cell tumors, respectively. Neither gene appeared to be activated significantly by cAMP, whereas both endogenous and exogenous CYP11A genes encoding P450(SCC) were activated. Taken together, these observations indicate that the expression of the rFtz-F1 gene is mainly regulated by a mechanism independent of the neuroendocrine axes.

Adrenal Cortex↗
PubMed1998

Predictability of conventional tests for the assessment of bladder outlet obstruction in benign prostatic hyperplasia.

BACKGROUND: The degree of bladder outlet obstruction (BOO) in benign prostatic hyperplasia (BPH) is most accurately quantified by pressure flow studies (PFS), although these studies are more invasive and complicated than conventional tests. We examined how precisely conventional tests predicted the PFS-assessed degree of BOO. METHODS: The study population consisted of 232 BPH patients who had undergone routine conventional tests and PFS. Correlation of the conventional test results with the degree of BOO assessed by PFS was examined by Spearman's correlation coefficients. Regression and subgroup analyses were performed to predict the degree of BOO using the conventional test results as the explanatory variables. RESULTS: The degree of BOO correlated with prostate volume, the degree of endoscopic obstruction, and to a lesser extent, with the maximum flow rate (Qmax) and age. The predictability of conventional tests alone, or in combination, for BOO, was approximately 60% to 70%, which is not acceptable for investigational use. However, almost all patients with a prostate volume larger than 30 mL, or with severe obstruction on urethroscopic findings, had an obstructed bladder outlet. CONCLUSION: PFS is mandatory when the precise evaluation of the degree of BOO is required, and patients are highly likely to have an outlet obstruction when they have a prostate larger than 30 mL, or severely obstructed posterior urethra on endoscopy.

Aged↗
PubMed1998

Urologic morbidity and its influence on global satisfaction with treatment outcome after radical prostatectomy for prostate cancer.

BACKGROUND: This cross-sectional observational study examined urologic morbidity and its effects on Japanese patients' global satisfaction with their treatment outcome. METHODS: A questionnaire was mailed to 44 men who had undergone radical prostatectomy for prostate cancer at a mean age of 65.5 years and were free from recurrent symptoms at a mean follow-up of 3.3 years. Most (70%) had pathologic stage C or D1 disease and many (86%) had received adjuvant endocrine therapy. After reporting urinary symptoms, the patients estimated their overall urinary, sexual, physical, psychological, and social functioning, and global satisfaction level with their treatment outcome. Regression analysis was performed to detect significant factors in predicting overall urinary conditions or satisfaction. RESULTS: Daily urinary leakage and forceless urinary stream was noted in 30% and 23% of patients, respectively. Overall urinary conditions were evaluated as good or very good in 61 % of patients, and were most significantly associated with the patient's satisfaction with their force of urinary flow (P < 0.001). Global satisfaction with treatment outcome was estimated as good or very good in 80% of patients, and it was predicted by physical functions (P= 0.013) and psychological distress (P= 0.036), and to a lesser extent by urinary conditions (P= 0.195). CONCLUSION: A forceless urinary stream was the most significant determinant for overall urinary conditions in patients who had a radical prostatectomy. Global satisfaction with treatment outcome was only marginally affected by urinary conditions. Physical function and psychological distress were major factors affecting the satisfaction level in this population.

Aged↗
PubMed1998

Optimal conditions to induce rat adrenal medullary changes, such as pheochromocytoma, by nicotine.

BACKGROUND: Nicotine-induced adrenal medullary hypertrophy in rats has been suggested to be a model for pheochromocytoma. Study conditions for proving such an assertion, however, have not been optimized. METHODS: Studies on strain difference, dose dependency, and the time course of catecholamine metabolism in response to nicotine treatment were conducted. Under the putative optimal experimental conditions, metabolic and histologic changes in the adrenal medulla were investigated. RESULTS: Male Wistar rats treated with a maximum dose of 4 mg/kg per day of nicotine for 9 weeks, including a 2-week lead-in period, developed highly consistent changes in the adrenal medulla. Concerning metabolic indices, the norepinephrine content of the adrenal and the urinary excretion of epinephrine and metanephrine were significantly elevated. Hyperplastic and hyperactive states of the adrenal medulla were also indicated by a morphometric analysis on electron microscopic figures. These showed an enlarged cytoplasmic area, the development of a rough-surfaced endoplasmic reticulum, and an increased number and density of intracellular catecholamine granules. The metabolic changes were found to reverse 3 weeks after the cessation of nicotine administration. CONCLUSION: These results provide better-defined experimental conditions for an animal model of pheochromocytoma.

Adrenal Medulla↗
PubMed1998

Left postpneumonectomy syndrome successfully treated with endobronchial stent.

We describe a case of left pneumothorax-induced left postpneumonectomy syndrome in the absence of anatomical anomalies developing at 10 years after the operation. We placed an endobronchial stent into the right truncus intermidius and the procedure resulted in recovery of the syndrome. We consider endobronchial stent placement as an effective treatment for postpneumonectomy syndrome, especially when surgical management is not feasible.

Aged↗
PubMed1998

Total hip arthroplasty for failed rotational acetabular osteotomy: a report of three cases.

Three female patients with osteoarthrotic hips received total hip replacement arthroplasties after failed rotational acetabular osteotomies (RAO) were reported. In the first case, there was necrosis of the thin acetabular fragment and a collapse of the large grafted iliac bone because of technical problems. The second case had residual development dislocation of the hip preoperatively which resulted in pseudoarthrosis and instability of the pubic bone postoperatively. This patient was considered to be a bad candidate for rotational acetabular osteotomy. The last case was 65 years old, too old to treat by osteotomy. Deterioration of the articular cartilage was expected. All of them were successfully treated with total hip arthroplasties. The ages of the patients, the stage of osteoarthrosis, the thickness of the osteotomized acetabular fragment, and the size of the grafted bone seemed to be factors influencing the outcome of the RAO.

Acetabulum↗
PubMed1997

KMD-3213, a novel alpha1A-adrenoceptor antagonist, potently inhibits the functional alpha1-adrenoceptor in human prostate.

KMD-3213, (-)-(R)-1-(3-hydroxypropyl)-5-[2-[[2-[2-(2,2,2-trifluoroethoxy)phe noxy]ethyl]amino]propyl]indoline-7-carboxamide, is a novel and selective alpha1A-adrenoceptor antagonist. The potency of this drug to antagonize functional alpha1-adrenoceptor-mediated contraction in human prostatic smooth muscle was evaluated and compared with that of other alpha1-adrenoceptor antagonists. KMD-3213 inhibited noradrenaline-induced contractions with an apparent pK(B) value of 9.45 +/- 0.039, indicating a potency similar to that of tamsulosin. The affinity of prazosin for prostatic alpha1-adrenoceptors is given as potency for the alpha1L-adrenoceptor with an estimated pA2 value of 8.84 +/- 0.044. The data obtained in this study suggest that KMD-3213, an alpha1A-adrenoceptor-selective antagonist, has strong affinity for the alpha1L-adrenoceptor in the human prostate.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1997

Murine interleukin 4 transgenic heart allograft survival prolonged with down-regulation of the Th1 cytokine mRNA in grafts.

BACKGROUND: Data supporting the differential activation of T helper (Th) 2 cells in transplantation acceptance/tolerance in rodents have been presented by several investigators. However, the differential activation of Th2 cells may be simply the result of allograft acceptance/tolerance induction instead of a contribution to the maintenance of grafts. METHODS: Therefore, we established interleukin (IL)-4 transgenic mice under the control of a cardiac alpha-myosin heavy chain promotor and transplanted IL-4-expressing heart allografts into unmodified recipients to determine the actual contribution of the Th2 bias to allograft acceptance. RESULTS: Among 16 newborn C57BL/6J (B6) mice, three were positive for the IL-4 transgene. Serum IL-4 levels of transgenic versus control B6xC3H F1 mice were not statistically different. Reverse-transcriptase polymerase chain reaction showed that the transgenic B6xC3H F1 mice expressed IL-4 mRNA in the heart and in the lung, whereas control mice did not express IL-4 in any organ. IL-4 mRNA expression in the transgenic but not in the control heart was also confirmed by RNAse protection assay and fluorescence in situ hybridization. The survival of IL-4 transgenic B6xC3H heart grafts heterotopically placed in C3H recipients was prolonged compared with that of nontransgenic grafts (19.0+/-9.1 vs. 6.8+/-2.2 days, P=0.003). Interferon-gamma mRNA expression in IL-4 transgenic heart grafts on the fifth posttransplant day as assessed by Northern blotting was suppressed compared with that in control grafts. Reverse-transcriptase polymerase chain reaction analysis showed that IL-2 mRNA was suppressed in the IL-4 transgenic grafts compared with that in control grafts, while IL-4 mRNA was observed only in IL-4 transgenic grafts. IL-10 mRNA was detected at similar levels in both transgenic and control grafts. CONCLUSIONS: A Th2 bias may contribute to allograft acceptance in part by inducing the down-regulation of Th1-cytokine mRNAs, but it may not be sufficient to induce indefinite graft survival.

Animals↗
PubMed1997

Inhibition of rat prostate carcinogenesis by a 5alpha-reductase inhibitor, FK143.

BACKGROUND: Androgen levels in the prostate may influence carcinogenesis in this organ. Inhibitors of the enzyme 5alpha-reductase block conversion of testosterone to the more active androgen dihydrotestosterone. The use of a 5alpha-reductase inhibitor, finasteride, in the chemoprevention of prostate cancer is being evaluated in a clinical trial. PURPOSE: This study was conducted to determine if a 5alpha-reductase inhibitor, FK143, inhibits the development of prostate cancer in rats. METHODS: Male ACI/Seg rats, which spontaneously develop prostate cancer, were randomly assigned at 80 weeks of age to receive one of three diets (n = 35/group) containing 0 (i.e., control group), 20, or 200 ppm FK143. At 140 weeks of age, the animals were killed, and the prostates were removed and examined for histopathologic features in addition to being assayed for androgen concentrations. Two-sided statistical tests were used to calculate all P values. RESULTS: The incidence of prostate carcinoma in the control group was 62.9% (22 of 35 rats); in the group fed the 20 ppm FK143-containing diet, it was 45.7% (16 of 35); and in the group fed the 200 ppm FK143-containing diet, it was 67.6% (23 of 34) (overall, P = .153). The corresponding incidences of macroscopic lesions were 17.1% (six of 35 rats), 0% (none of 35), and 23.5% (eight of 34), respectively (overall, P = .004). The incidence of macroscopic lesions in the prostates of rats in the 20-ppm diet group was significantly lower than that in the control group (P = .029) or that in the 200-ppm diet group (P = .003). Intraprostatic dihydrotestosterone content was significantly lower in rats in the groups fed diets containing 20 or 200 ppm FK143 (mean values: 4.51 and 4.33 pg/mg wet weight of prostate tissue, respectively) than in the control group (6.10 pg/mg) (overall, P<.001); by contrast, testosterone was higher in the 200-ppm diet group (2.09 pg/mg) than in the control group (1.08 pg/mg) or the 20-ppm diet group (1.21 pg/mg) (overall, P<.001). CONCLUSIONS: FK143, when fed to rats at 20 or 200 ppm, significantly reduced the level of dihydrotestosterone in their prostate tissue. However, the incidence of macroscopic cancer in the prostate was suppressed in rats consuming the 20 ppm FK143-containing diet but not in those consuming the 200-ppm diet. The lack of dose dependence for the chemopreventive activity of FK143 may be explained by the reciprocal increase of tissue testosterone in the 200-ppm diet group. IMPLICATIONS: The 5alpha-reductase inhibitor FK143 may, at specific doses, reduce the incidence of spontaneously developing prostate cancer; however, whether these findings in rats will apply to humans remains to be determined.

5-alpha Reductase Inhibitors↗
PubMed1997

Swine influenza virus strains recognize sialylsugar chains containing the molecular species of sialic acid predominantly present in the swine tracheal epithelium.

We determined the ratio of N-glycolylneuraminic acid (Neu5Gc) to N-acetylneuraminic acid (Neu5Ac) in swine respiratory epithelia by fluorometric high-performance liquid chromatography, and examined the binding specificity of swine influenza virus strains for gangliosides containing different molecular species of sialic acid (Neu5Ac and Neu5Gc), and for bovine erythrocyte sialoglycoprotein 2 (GP-2) containing Neu5Gc as its predominate sialic acid (96% of total sialic acids). The presence of Neu5Gc, which had not been detected in human tracheal epithelia, and Neu5Ac in swine tracheal epithelia was observed in a 1:1 ratio. The swine influenza virus H1 and H3 isolates tested, except for A/swine/Iowa/15/30 (H1N1), displayed a marked binding ability for sialylsugar chains containing Neu5Gc compared with that of the human influenza virus strains. These results suggest that swine influenza viruses recognize sialylsugar chains containing the molecular species of sialic acid present predominantly in the swine tracheal epithelium.

Animals↗
PubMed1997

Morphological analysis of renal cell culture models of calcium phosphate stone formation.

Cell culture models of calcium phosphate renal stone formation were established using the MDCK cell line. Renal microliths were detected within pseudocysts in three-dimensional soft agar cultures, and were also observed in the basal region of cells lining the cell sheet, and immediately beneath domes or blisters in monolayers and collagen gel cultures. Light and scanning electron microscopy indicated that these microliths had a similar lamellated and spherical appearance to those in humans. These microliths were first detected microscopically after 21 days of culture, and were found to be composed of calcium phosphate by X-ray and micro-infrared spectroscopic analyses. These culture models may provide a powerful new tool to study the pathogenesis of renal stone diseases and/or calcium phosphate stone formation in humans and animals.

Animals↗