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Biomedical subjects

K Kawabe

Publications and source records attributed to K Kawabe.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of intracavernous administration of adrenomedullin on erectile function in rats.

We have reported that adrenomedullin (AM)-induced vasodilation is at least in part nitric oxide (NO)-cGMP-dependent in the rat. Although it is well known that NO is much involved in the erectile function, it is controversial as to whether AM influences the erectile function. Thus, we examined the effects of AM on intracavernous pressure (ICP) during penile erection. The left carotid artery of rats was cannulated to monitor of mean arterial pressure (MAP). Bipolar electrodes were positioned on the cavernous nerve. The right cavernous body was cannulated with a needle connected to a pressure transducer to monitor ICP. Electrical stimulation (ES) increased ICP in a voltage-dependent manner. Elevation of ICP continued during ES. The intracavernous injection of 0.5 nmol AM significantly potentiated ES-induced increases in both maximal developed ICP/MAP and area under the curve (ICP trace; AUC). Since AM slightly lowered MAP, ICP was normalized by MAP. i.v. administration of N(omega)-nitro-L-arginine, a NO synthase inhibitor, markedly decreased AM/ES-induced ICP elevation. However, in the presence of E-4021, a cGMP-specific phosphodiesterase inhibitor, AM further increased both ICP/MAP and AUC. These results suggest that a NO-cGMP pathway is involved in the regulation of AM-induced rat cavernous vasorelaxation.

Adrenomedullin↗
PubMed2001

Age-related changes in cholinergic and purinergic neurotransmission in human isolated bladder smooth muscles.

We evaluated the correlation among age, cholinergic and purinergic neurotransmissions in the electrical field stimulation-induced contractions in human isolated urinary bladder smooth muscles, using the muscle bath technique. Human bladder specimens were divided into three groups (G1, under 50years; G2, 51-70years; G3, over 70years old), and each muscle strip was suspended in a thermostatically controlled organ bath filled with oxygenated Krebs-Henseleit solution, connected to an isometric force displacement transducer, and an isometric tension development was recorded. The contractile responses induced by KCl, carbachol, adenosine triphosphate (ATP) and electrical field stimulation, and the effects of atropine and alpha, beta methylene ATP on electrical field stimulation-induced contractions were observed. The contractile response to KCl and concentration-response curves for carbachol and ATP, and frequency-response curves for electrical field stimulation were not significantly different among the three groups. The atropine sensitive and resistant parts of contraction induced by electrical field stimulation were decreased and increased with age, respectively. There are significant positive and negative correlations between age and the purinergic, and age and the cholinergic neurotransmissions in human isolated bladder smooth muscles, respectively. The age-related changes in neurotransmissions may contribute to the changes in bladder function in the elderly.

Adenosine Triphosphate↗
PubMed2001

A new portable measuring cup for voided volume.

When recording daily urine volumes for the frequency-volume chart, a patient must measure voided urine volume throughout the whole day. Unless the patient stays at home, the conventional 500-mL paper or plastic cup must be carried with at all times, which can be very embarrassing and troublesome for the patient, so a collapsible, portable measuring cup has been developed. To determine the measuring accuracy of the new cup, the visual estimate was compared with the actual volume. The cup was found to be a highly accurate and useful container for measuring voided urine volume.

Drinking↗
PubMed2001

Transvaginal ultrasound of urethral sphincter at the mid urethra in continent and incontinent women.

PURPOSE: Few studies are available on imaging the urethral sphincter. We performed transvaginal ultrasonography to examine the muscle in continent and incontinent women. MATERIALS AND METHODS: Transvaginal ultrasonography was performed using a 7.5 MHz. transrectal probe in 19 continent and 69 incontinent supine women. Incontinent cases were classified as urge (14) and stress (55), and included urethral hypermobility (22) and intrinsic sphincter deficiency (33). Cadaver specimens were also examined to confirm the anatomy of ultrasound images. RESULTS: Transvaginal ultrasonography showed the urethra as a round structure consisting of a relatively high echogenic central zone and a relatively low echogenic peripheral zone. Matching ultrasound images with the anatomy of cadaver specimens indicated that the peripheral zone represents rhabdosphincter most reliably at the lateral aspects. Thus, its thickness was measured at the 9 o'clock position of the mid urethra. Mean thickness plus or minus standard error of mean was significantly decreased in stress incontinence compared with continence and urge incontinence (2.14 +/- 0.04, 2.78 +/- 0.08 and 2.87 +/- 0.11 mm., respectively, p <0. 001), while in intrinsic sphincter deficiency it was thinner than in hypermobility (2.00 +/- 0.05 versus 2.35 +/- 0.06 mm., p <0.01). There was no difference in central zone thickness according to continence status. CONCLUSIONS: Urethral structures may be visualized by transvaginal ultrasonography. The rhabdosphincter image was thinner in stress incontinence, especially in intrinsic sphincter deficiency. Transvaginal ultrasonography may be a useful clinical test for examining the morphology of the urethral sphincter muscle in women.

Cadaver↗
PubMed2001

A prodrug of NMDA/glycine site antagonist, L-703,717, with improved BBB permeability: 4-acetoxy derivative and its positron-emitter labeled analog.

4-Acetoxy derivative (1) of L-703,717, a high-affinity (IC50=4.5 nM) antagonist for the glycine site of NMDA receptors, was synthesized and its brain uptake was examined using a carbon-11 labeled analog ([11C]1). Initial radioactivity in the brain after intravenous injection of [11C]1 was a 2-fold that of [11C]L-703,717 in mice. Rapid bioconversion of [11C]1 into [11C]L-703,717 was demonstrated by metabolite analyses of rat brain after [11C]1 injection. Ex vivo autoradiography of [11C]1 in rat brain showed the same cerebellar localization of radioactivity as [11C]L-703,717. These results indicate that 1 is a promising pharmacological tool as a prodrug of L-703,717 with improved BBB permeability.

Animals↗
PubMed2001

In vivo and in vitro effects of magnesium deficiency on hepatic haptoglobin mRNA levels.

We previously showed that haptoglobin (Hp) was increased in the plasma of dietary magnesium (Mg)-deficient rats. The present study was performed to examine the effects of dietary Mg-deficiency and Mg2+ deficit in culture medium on Hp mRNA levels in liver and isolated hepatocytes, respectively. The Hp mRNA level in the liver increased significantly from day 10 to day 30 in rats on a Mg-deficient diet (Mg; 0.001 per cent). In the cultured hepatocytes, lowering the Mg2+ level in the culture medium from 0.92 mM to 0.46 mM did not affect the Hp mRNA level of hepatocytes. When IL-1beta or IL-6 was added to the culture medium, the Hp mRNA level increased much more in the hepatocytes cultured in low Mg2+ medium (Mg2+; 0.46 mM) than in those cultured in the control Mg2+ medium (Mg2+; 0.92 mM). These results suggest that the increase in plasma Hp level during dietary Mg deficiency depends on the increase in Hp mRNA level in the liver, and that this increase in mRNA is not only directly correlated with a low Mg level in plasma, but also indirectly correlated with cytokines.

Animals↗
PubMed2000

Electromyographic study of the striated urethral sphincter in type 3 stress incontinence: evidence of myogenic-dominant damages.

OBJECTIVES: To determine the electromyographic features of the striated urethral sphincter in patients with type 3 stress incontinence (SI) due to intrinsic sphincteric deficiency (ISD). METHODS: We performed electromyography (EMG) of the striated urethral sphincter muscle and urodynamic studies in a total of 51 women, 41 female patients with type 3 SI and 10 women with normal urinary control (NUC). The results were analyzed in both groups, and the correlation of EMG findings with the patient characteristics and urodynamic parameters was evaluated. RESULTS: Motor unit potentials (MUP) of SI patients showed significantly shorter duration (P = 0.0014), lower amplitude (P = 0.0008), and larger number of phases (P = 0.0022) compared with those in the NUC group. Thirty (73%) of the SI patients showed an obvious low amplitude (less than 350 microV)/short duration (less than 4.5 milliseconds)/polyphasic pattern and early recruitment of interference activity with low amplitude at voluntary contraction of the striated sphincter, both indicating existence of myogenic damages. These patients showing myogenic damages had significantly lower Valsalva leak point pressure (P = 0.002) and more leakage in the pad-weigh test (P = 0.010) compared with the SI patients without myogenic damage findings. CONCLUSIONS: These results suggested that myogenic-dominant damages of the striated urethral sphincter may contribute to the etiology of ISD in most patients with type 3 SI.

Aged↗
PubMed2000

Nocturia in the adult: classification on the basis of largest voided volume and nocturnal urine production.

PURPOSE: We propose a criterion to clarify the underlying etiologies of nocturia. MATERIALS AND METHODS: Frequency-volume charts were recorded for 24 hours by 35 men and 32 women who were subjectively free of lower urinary tract symptoms and had no evidence of voiding disorders. At least 5 subjects were included in each of 5 age groups of 20 to 49, 50 to 59, 60 to 69, 70 to 79, 80 to 89 years for both genders. The charts were used to make a tentative criterion, which was validated in 39 elderly individuals with nocturnal frequency. RESULTS: Correlation and regression analyses indicated that the quotients of nocturnal urine output divided by body weight (U(N)/BW) and largest voided volume divided by body weight (V(L)/BW) were useful classification factors. Cutoffs, which were set close to worst quartiles, were 10 ml./kg. for U(N)/BW and 4 ml./kg. for V(L)/BW, respectively. Correction by body weight made the same criterion applicable irrespective of weight. Symptomatic elderly patients were classified into 3 mutually exclusive groups of nocturnal polyuria (U(N)/BW greater than 10 ml./kg.), low bladder capacity (V(L)/BW less than 4 ml./kg.) and combined nocturia. Of 20 subjects who voided 2 times a night 11 (55%) were classified as having nocturnal polyuria and 15 of 19 who voided 3 or 4 times (79%) were classified as having low bladder capacity or combined nocturia. CONCLUSIONS: The criterion provides a reasonable distinction of etiologies of nocturia, and may be usefulness in examination and treatment.

Adult↗
PubMed2000

Distribution of alpha1-adrenoceptor subtype mRNA and identification of subtype responsible for renovascular contraction in human renal artery.

This study was intended to quantify the amounts of the alpha1-adrenoceptor subtype mRNAs in human renal artery and to demonstrate the distribution of receptor subtypes responsible for the contraction of the renal artery. RNase protection assay showed that the mean amount of alpha1a mRNA was much greater than that of alpha1b or alpha1d mRNAs in both the main and branch renal arteries. However, the abundance of alpha1a mRNA in human renal artery was much less than in our previous data in the prostate. In situ hybridization showed that all alpha1 subtype mRNAs were localized in the smooth muscle cells of the tunica media of the artery, and the distribution pattern of these three mRNAs in the main artery was the same as in the branch artery. However, the intensity of signals for alpha1d and alpha1b antisense RNAs probes was lower than that for the alpha1a antisense RNA probe. In the functional study, concentration-response curves to noradrenaline pretreated with KMD-3213, an alpha1A/L-adrenoceptor selective antagonist, seemed to be biphasic in nature. Chloroethyclonidine (CEC) failed to inactivate the noradrenaline-induced contraction, and prazosin showed relatively low affinity with a pA2 value of 8.8. These data suggest that the alpha1A/L-adrenoceptor mediates primarily those responses to noradrenaline in this artery. The other alpha1-adrenoceptor subtypes could also mediate the secondary contractile response to noradrenaline in this artery.

Adrenergic alpha-Antagonists↗
PubMed2000

A strategy for increasing the brain uptake of a radioligand in animals: use of a drug that inhibits plasma protein binding.

A positron-emitter labeled radioligand for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor, [(11)C]L-703,717, was examined for its ability to penetrate the brain in animals by simultaneous use with drugs having high-affinity separate binding sites on human serum albumin. [(11)C]L-703,717 has poor blood-brain barrier (BBB) permeability because it binds tightly to plasma proteins. Co-injection of warfarin (50-200 mg/kg), a drug that binds to albumin and resembles L-703,717 in structure, dose-dependently enhanced the penetration by [(11)C]L-703,717 in mice, resulting in a five-fold increase in the brain radioactivity at 1 min after the injection. Drugs structurally unrelated to L-703,717, salicylate, phenol red, and L-tryptophan, were less effective or ineffective in increasing the uptake of [(11)C]L-703,717. These results suggest that the simultaneous use of a drug that inhibits the binding of a radioligand to plasma proteins is a useful way to overcome the poor BBB permeability of the radioligand triggered by its tight binding to plasma proteins. In brain distribution studies in rodents, it was found that, after the increase in brain uptake with warfarin, much of the glycine site antagonist accumulates in the cerebellum but its pharmacological specificity did not match the glycine site of NMDA receptors.

Animals↗
PubMed2000

Effects of castration on contraction and alpha(1)-adrenoceptor expression in rat prostate.

1. The prostate function is regulated by androgens and alpha-adrenergic activity. Clinically, antiandrogens and/or alpha(1)-adrenergic antagonists are commonly used to treat symptomatic prostatic hypertrophy. To elucidate the effects of androgen deprivation on prostate contractility via alpha(1)-adrenoceptor, the characteristics and expression of alpha(1)-adrenoceptors were examined in castrated rats. 2. Isolated prostate strips from intact and castrated rats were subjected to a phenylephrine stimulated contraction. Prazosin (10 nM), [(3)H]-prazosin and phenoxybenzamine (3 - 300 nM) were used for inhibition assay, receptor characterization and partial alkylation of alpha-adrenoceptor, respectively. The mRNA content of three subtypes of alpha-adrenoceptors was determined by reverse transcription combined with polymerase chain reaction (RT - PCR). 3. Contractile response to phenylephrine increased in castrated rats, which could be explained by a relative increase of the stromal component. A lowered contraction potency was also noted in castrated rats. Receptor binding assay indicated minimal changes in the affinity or density of alpha(1)-adrenoceptor. Escalating alkylation of the alpha(1)-adrenoceptor population resulted in a rightward shift in the contraction-response curves before depressing maximal contractile force, and the suppression was detected at lower doses in castrated rats. RT - PCR study confirmed the expression of three types of alpha(1)-adrenoceptor, alpha(1a), alpha(1b) and alpha(1d)-adrenoceptors, in intact rat prostate, and revealed that alpha(1a)-adrenoceptor, but not alpha(1b) or alpha(1d)-adrenoceptors, was down-regulated in castrates. 4. The results show that androgen deprivation suppressed alpha(1)-adrenergic contractility of rat prostate strips, and the suppression was associated with down-regulation of receptor reserve for the alpha(1a)-adreneroceptor population expressed in intact rat prostate.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2000

Reproducibility of cystometry in overactive detrusor.

OBJECTIVE: To examine the reproducibility of cystometry in the overactive detrusor. METHODS: The study sample involved 30 patients of the placebo arm in double-blind clinical trials for an overactive detrusor. They had demonstrated detrusor overactivity and underwent the second cystometry after 2-4 weeks. Nonparametric tests for paired data were used to examine the reproducibility of four variables: volume at first desire to void, volume at first involuntary contraction, cystometric capacity, and the maximum pressure of involuntary contraction. Percent change and within-subject standard deviation were calculated to assess intraindividual variability. RESULTS: The second test results showed a significant and systematic change for the better. Volume variables increased by 10-13% (p<0.01), involuntary contraction was not elicited in 3 cases (10%), and the maximum contraction pressure decreased by 18% in the remaining cases. Intraindividual variability was not small. Seventeen patients (57%) demonstrated > or = 25% change in one or more variables, and the 95% confidence interval of cystometric capacity, for example, was calculated as (x -57, x +57), where x is a test result. No specific patients' demographics were found related to variability. CONCLUSION: Repeat cystometry in the overactive detrusor is not highly reproducible and may be subject to a systematic effect for the 'better'. Whether this is due to the placebo effect or the learning effect could not be determined.

Double-Blind Method↗
PubMed2000

Distribution of alpha1L-adrenoceptors in canine prostate: characterization by quantitative autoradiography.

Our aim was to determine the distribution of alpha1L-adrenoceptors in canine prostate by an autoradiographic technique using [3H]JTH-601 (an alpha1L-adrenoceptor antagonist) and [3H]JTH-601-G1 (an active metabolite of JTH-601). Prostates were removed from three male beagle dogs. Several slices of the specimens were incubated with 5 nM of [3H]JTH-601, [3H]JTH-601-G1 and [3H]tamsulosin (an alpha1A-adrenoceptor antagonist). For macroscopic autoradiography, visualization was performed using an imaging plate and image-analyser. To examine microscopic localization of binding sites, preparations were exposed, developed and fixed. Specific binding of [3H]JTH-601 and [3H]JTH-601-G1 was observed diffusely throughout the entire interstitium on macroscopic autoradiography. Specific binding of [3H]tamsulosin was also recognized although the binding was weaker than that of [3H]JTH-601. On microscopic autoradiograms, the grains of each ligand were mainly distributed on smooth muscle. These results indicate morphologically that specific binding sites of JTH-601 and JTH-601-G1 exist in canine prostate, suggesting the distribution of alpha1L-adrenoceptors in this tissue, in addition to alpha1A-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1999

Butyrolactone I induces cyclin B1 and causes G2/M arrest and skipping of mitosis in human prostate cell lines.

Several naturally occurring cyclin-dependent kinase (CDK) inhibitors have been isolated from different lower organisms. In this report, we examined the effect of one of the CDK inhibitors, butyrolactone I (BL), on the expression of cyclins D2, A and B1 in three human prostatic cancer cell lines (DU145, PC-3, LNCaP) using two colored flow cytometric analysis. The percentage of DU145 cells in the 4C phase of the cell cycle were increased significantly at both 70 microM and 100 microM BL. Furthermore, an additional 8C peak was observed which had double the DNA content of the 4C phase at these concentrations of BL. The appearance of the 8C peak increased gradually and was more evident in DU145 and PC-3 than LNCaP. Cells in the 8C peak had either two nuclei or abnormal nuclei as observed by Papanicolaou stain. BL also increased the amount of cyclin B1 positive cells in the 4C phase. This increase was apparent on day 1 and returned to normal by day 3. Since BL selectively inhibits cyclin-dependent kinase, cyclin B1 might accumulate without being degraded. Other cyclins were not significantly changed by BL. The data demonstrate that BL inhibited Cdc2 of unsynchronized cultured prostate cancer cells, and interrupted the cell cycle progression toward cell division. The BL inhibition of Cdc2 led to the accumulation of cells in the 4C phase without mitosis resulting in an accumulation of cyclin B1. The appearance of cells in the 8C phase may be due to the progression of cells in the 4C phase through the cell cycle skipping mitosis. Cyclin B1 decreased in correlation with the progression through a new cell cycle. These results suggest that BL does not cause a complete arrest of the cell cycle in G2/M but that BL occasionally allows for the skipping of mitosis and subsequent progression through the cell cycle to occur.

4-Butyrolactone↗
PubMed1999

Correlation between proliferation, apoptosis, and angiogenesis in prostate carcinoma and their relation to androgen ablation.

BACKGROUND: Proliferation, apoptosis, and angiogenesis are essential for carcinogenesis. Little is known regarding the relation between proliferation, apoptosis, and angiogenesis in untreated prostate carcinoma as well as alterations associated with androgen ablation. METHODS: Eighty patients who underwent radical prostatectomy for clinically localized prostate carcinoma were recruited for the study. The study population included 2 groups: 35 patients receiving 3-month neoadjuvant hormonal treatment using a combination of luteinizing hormone-releasing hormone analogue and the antiandrogen flutamide (NHT group) and 45 patients without prior treatment (non-NHT group). The authors measured the Ki-67 labeling index (Ki-67 LI) by MIB-1 immunohistochemistry, the apoptotic index (AI) by the terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling technique, and intratumoral microvessel density (IMVD) by CD31 immunohistochemistry on serial sections of formalin fixed, paraffin embedded tissues. Correlations among these parameters were examined in both groups. RESULTS: A significant decrease in the Ki-67 LI coupled with a significant increase in AI was found in the NHT group compared with the non-NHT group, whereas IMVDs in both groups were not significantly different. AI was related to IMVD inversely in the non-NHT group (correlation coefficient [r] = -0.327; P = 0.03); in contrast, AI was related to IMVD positively in the non-NHT group (r = 0.579; P < 0.001). The Ki-67 LI was related to AI significantly in the non-NHT group but not in the NHT group. There was no correlation between Ki-67 LI and IMVD in either group. CONCLUSIONS: Correlations between proliferation, apoptosis, and angiogenesis in prostate carcinoma are altered significantly in association with androgen ablation. The results indicate that spontaneous apoptosis is suppressed by neovascularization, whereas hormone-induced apoptosis is enhanced in hypervascular tumors.

Adenocarcinoma↗
PubMed1999

Semiquantitative evaluation of alpha1A-adrenoceptor subtype mRNA in human hypertrophied and non-hypertrophied prostates: regional comparison.

The main purpose of this study was to compare semiquantitatively the amount of alpha1a-adrenoceptor subtype mRNA in urethral, central and peripheral areas in benign hypertrophied prostates and non-hypertrophied prostate by the competitive reverse transcriptase polymerase chain reaction (RT-PCR) method. Prostates from twenty cases of men with benign prostatic hypertrophy (BPH) and 5 cases of bladder tumor without BPH were obtained for this study. The mRNA was extracted from the urethral, central and peripheral areas of each prostate, and quantitative RT-PCR was performed using the ratio of PCR product of alpha1a-adrenoceptor mRNA/beta2-microglobulin mRNA. The ratio for the central area of the hypertrophied prostate was significantly greater than that for the same area of the non-hypertrophied prostate (p < 0.05). In contrast, the urethral area showed no significant difference between the two prostate conditions. The central area of the hypertrophied prostate showed the tendency to have an increased alpha1a-adrenoceptor mRNA level compared with the urethral area, though no statistical difference was recognized because of the high standard error. Regional differences in the alpha1a-adrenoceptor mRNA in the non-hypertrophied prostate were rarely observed. The present finding demonstrates that the increased alpha1a-adrenoceptor mRNA content found in the hypertrophied prostate (1) was due to that in the central area.

Aged↗