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Biomedical subjects

N Mikuma

Publications and source records attributed to N Mikuma.

At least 19 recordsLinked to original sources

Magnetic resonance imaging of the male pelvic floor: the anatomical configuration and dynamic movement in healthy men.

The male pelvic organs and the rhabdosphincter were visualized using magnetic resonance imaging (MRI) in five young male volunteers (mean age, 25.6 years). The prostate was crescent-shaped in three subjects and doughnut-shaped in two subjects. The external urethral sphincter (EUS) was located anterior to and lateral to the urethra but was rare on the rectal side. The membranous urethral length measured 28-35 mm (average, 31.0 mm). The pubourethral portion of the levator ani embraced the urinary bladder, the prostate, and the membranous urethra, and the most distal portion of the levator was thickened. During anal contraction, the EUS became thinner on both coronal and sagittal images and the levator was approximated closer to the urethra. Consequently, the prostate and the bladder base were elevated and the membranous urethra was elongated by 0-12mm (average, 5.6 mm). On sagittal images, the prostate, the membranous urethra, and the rectum were pulled closer to the pubic bone by anal contraction and the retropubic area became narrower. This study clearly demonstrated that MRI was useful in examining the anatomical configuration of the male pelvic floor and its dynamic movement during anal contraction.

Adult

Ileal neobladder for bladder substitution after radical cystectomy.

BACKGROUND: Studer's ileal neobladder is technically simple, and favorable clinical results have been reported. However, there have been only a few follow-up studies on this type of ileal neobladder. We reviewed the clinical outcomes of patients who received Studer's ileal neobladder, with a minor modification, in our institution. METHODS: Twenty-five men underwent bladder reconstruction with Studer's ileal neobladder after radical cystectomy. The function of the ileal neobladder and voiding status were evaluated during follow-up. The follow-up period ranged from 3 to 42 months (mean, 24 months). RESULTS: The ileal neobladder achieved a large capacity at a low basal pressure, associated with a relatively low complication rate directly related to the neobladder. At 12 months after surgery, daytime and nighttime continence rates were 90% and 74%, respectively. In 5 patients who were incontinent, the maximal urethral closure pressure was statistically lower than in patients with continence. CONCLUSION: Studer's ileal neobladder is an easy operative procedure for bladder substitution, and has a relatively low complication rate directly related to the neobladder. Good compliance of the pouch and preservation of the external sphincter mechanism are the most important factors for achieving urinary continence, after construction of the ileal neobladder.

Adult

Morphological and pharmacological characterization of guinea-pig prostatic smooth muscle cells in vitro.

BACKGROUND: Prostatic smooth muscle is thought to play a major role in the pathogenesis of bladder outlet obstruction in patients with benign prostatic hypertrophy. However, the physiology of prostatic smooth muscle cells remains largely unknown, in part due to the lack of a suitable model system. We therefore sought to establish an in vitro culture of guinea pig prostatic smooth muscle cells. METHODS: Immature guinea pig prostate was treated by enzymatic digestion and the cells obtained were used to initiate the primary culture. After 3 to 4 passages, cultured smooth muscle cells were examined morphologically by immunocytochemistry and electron microscopy. The contractile properties of cultured smooth muscle cells were also examined. RESULTS: The cultured prostatic cells demonstrated hill and valley morphology, which is a hallmark of smooth muscle cells in vitro, and stained positively for desmin. In addition, electron microscopic examination of ultrastructural morphology revealed myofilaments. Confluent cultures of prostatic smooth muscle cells showed a clear, dose-dependent contractile response to phenylephrine. Furthermore, contraction of the prostatic smooth muscle cells by 10(-6) mol/L phenylephrine was completely inhibited by pretreatment with 10(-6) mol/L terazosin. CONCLUSIONS: An in vitro culture of prostatic smooth muscle cells was established. This culture is likely to provide a powerful tool for elucidating the physiology and pathophysiology of prostatic smooth muscle.

Adrenergic alpha-Agonists

Voiding dysfunction in ileal neobladder.

PURPOSE: We attempt to understand better the voiding mechanism and determine the causes of voiding dysfunction in ileal neobladder patients. MATERIALS AND METHODS: The voiding condition in 12 bladder cancer patients who had undergone neobladder construction after radical cystectomy was examined by pressure-flow study and voiding cystourethrography. The patients were classified into 2 groups based on the maximum flow rate in a pressure-flow study: fine voiders (6), with a maximum flow rate of 15 ml. per second or more, and poor voiders (4), with a maximum flow rate of less than 15 ml. per second. RESULTS: Maximum flow rate in the fine voiders was 26.2 +/- 8.7 ml. per second (mean plus or minus standard deviation) compared with 9.4 +/- 0.9 ml. per second in the poor voiders. The fine voiders strained 1.5 +/- 0.9 times to void 100 ml. of urine, whereas the poor voiders strained 7.0 +/- 6.3 times. The bladder capacity, vesical opening pressure and vesical pressure at the maximum flow rate were similar in both groups. Pelvic floor electrical activity was amplified when the neobladder was either full or close to its capacity, and it was relaxed in coordination with abdominal straining in all patients. Voiding cystourethrography revealed that, in fine voiders, the neobladder outlet was funnel-shaped when the bladder was full and opened wider when the patient strained to void. However, in poor voiders, the neobladder outlet did not funnel even on abdominal straining. CONCLUSIONS: Neobladder patients void by abdominal straining and relaxing the pelvic floor musculature. To obtain smooth voiding in such patients, it is crucial to locate the neobladder opening at the most caudal portion and preserve neobladder outlet elasticity.

Adult

[Recent progress in surgical management for urogenital cancers--improvement of patients' QOL following surgery].

We report our experience of urinary reconstruction with ileal neobladder, and nerves-paring radical cystoprostatectomy or radical prostatectomy in an attempt to improve quality of life (QOL) in patients following surgery. While the ileal neobladder is not always indicated for patients who require cystectomy for invasive bladder carcinoma, voiding through the urethra in this urinary reconstruction contributes to improvement of post-cystectomy QOL. Daytime continence is achieved in 90% of patients. However, nighttime incontinence was found in 30%, which indicates a need for further refinement of the operative procedures or more investigations into the mechanism of continence in this condition. Recovery of erectile function following nerve-sparing radical cystoprostatectomy or prostatectomy was found in 50% of the patients who received this procedure. Subjective and objective erectile capacity before operation partly determine post-operative erectile function. Several patients whose post-operative erectile function was recovered had not had sexual intercourse after surgery. Anxiety about the disease, still inadequate penile rigidity and a non-cooperative attitude of the sexual partner were involved in the results, suggesting that more careful care and counseling before and after operation are required.

Adult

Ectopic ureterocele with a horseshoe kidney in an adult.

A rare adult case of a left ectopic ureterocele associated with a duplex horseshoe kidney is reported. To the best of our knowledge, only one pediatric case of horseshoe kidney with an ectopic ureterocele has been reported. The present case was successfully treated by ureteropyelostomy, upper ureterectomy and unroofing of the ureterocele. The patient is currently followed with excretory urograms and renograms.

Choristoma

Bilateral deoxycorticosterone-secreting adrenocortical adenoma.

A case of a 58-year-old man with bilateral deoxycorticosterone (DOC)-secreting adrenocortical adenoma is reported. Before surgery, plasma levels of DOC and corticosterone were markedly elevated, but both adrenal hormone levels normalized after the surgical removal of the bilateral adrenal tumors. The histologic examination revealed bilateral adrenocortical adenoma, but curiously, the tissue concentrations of DOC and corticosterone were elevated only in the right adrenal gland.

Adrenal Cortex Neoplasms

Replacement with recombinant human inhibin immediately after orchidectomy in the hypophysiotropically clamped male rhesus monkey (Macaca mulatta) maintains follicle-stimulating hormone (FSH) secretion and FSH beta messenger ribonucleic acid levels at precastration values.

This study directly tested the inhibin hypothesis by examining the ability of replacement with recombinant human (rh-) inhibin, either alone or in combination with testosterone (T), to maintain FSH secretion and FSH beta messenger RNA (mRNA) at intact levels after orchidectomy in the hypophysiotropically clamped juvenile rhesus monkey. Thirteen male monkeys (11-21 months of age) received an intermittent i.v. infusion of GnRH (0.1 microgram/min for 3 min every 3 h). After 4-6 weeks of GnRH stimulation, 10 animals were orchidectomized, and 3 monkeys were sham castrated. Hormone replacement was initiated at castration and maintained for 4 days. Three monkeys received a combination of inhibin and T replacement, 4 monkeys received replacement with inhibin alone, and 3 monkeys received T replacement alone. A continuous i.v. infusion of rh-inhibin (832 ng/h.kg) was used to replace the testicular protein, whereas SILASTIC capsules were implanted sc for T replacement. The FSH response to castration and hormone replacement was determined by measuring circulating concentrations of this gonadotropin before a GnRH pulse and for 3 h thereafter on the day before surgery and on days 2 and 4 postcastration. Circulating immunoactive inhibin was measured by a RIA that recognizes the free alpha-subunit of inhibin as well as inhibin dimers. At the end of the study, anterior pituitaries were collected for analysis of steady state levels of FSH beta, LH beta, and alpha-subunit mRNAs. Steroid replacement alone, which produced circulating T concentrations in the upper physiological range, failed to prevent the postcastration increases in circulating FSH concentrations and pituitary FSH beta mRNA levels. In contrast, when circulating immunoactive inhibin in T-replaced monkeys was maintained at precastration levels (approximately 2 ng/ml) by infusion of rh-inhibin, FSH secretion and synthesis were held at control values. When T was omitted from combined replacement, the FSH-suppressing action of the recombinant hormone was not compromised. These results demonstrate that rh-inhibin is biologically active in the monkey, and the action of inhibin to suppress FSH synthesis and secretion does not require a concomitant action of T. Moreover, because the hypophysiotropic drive to the pituitary-testicular axis was clamped, the FSH-suppressing action of rh-inhibin must be at the pituitary.

Analysis of Variance

[Effects of anti-cancer agents on cultured rat Sertoli cells].

We performed primary immature Sertoli cell culture to investigate whether or not anti-cancer agents would have a direct effect on rat Sertoli cells. Sertoli cells, isolated from testes of 18-day-old rats, were cultured in pellets with medium for 5 days. The concentration of transferrin in cultured medium were measured as the function of Sertoli cells. The anti-cancer agents cis-diamminedichloroplatinum (CDDP), adriamycin and vinblastine were selected for this study, and added to the culture medium. CDDP decreased the level of transferrin concentration in cultured medium, namely 0.5 microgram/ml of CDDP resulted in 54.9% of the transferrin concentration in the medium compared with that without any anti-cancer agents (p < 0.05), and 1.0 micrograms/ml of CDDP produced transferrin concentrations of 57.5% and 46.2% (p < 0.05), respectively. Adriamycin (0.4 microgram/ml) and vinblastine (0.5 microgram/ml) produced transferrin concentrations of 35.2% and 31.3% in cultured medium (p < 0.05), respectively. These findings revealed that anti-cancer agents have direct damaging effects on rat Sertoli cells.

Animals

Remote and chronic access to the third cerebral ventricle of the unrestrained prepubertal rhesus monkey.

One channel of a commercially available standard-size three-channel fluid swivel was modified to permit continuous access to the brain of unrestrained prepubertal rhesus monkeys via a continuous length of small-bore Teflon tube originating from a swivel device on top of the animal's cage and terminating in the third cerebral ventricle. This system was employed to achieve continuous access to the third cerebroventricle in four monkeys for periods of up to 12 mo. The value of the system for studies of the neurochemical control of hypothalamic-releasing factor secretion was established by monitoring adenohypophysial responses to neurotransmitter receptor agonists infused into the third ventricle. Specifically, repetitive infusions of morphine (30 micrograms/infusion) elicited a robust train of prolactin discharges, and third ventricular administration of N-methyl-DL-aspartic acid (NMA; 20 micrograms) resulted in striking discharges of LH.

Aging

Cholecystokinin stimulates gonadotropin-releasing hormone release in the monkey (Macaca mulatta).

There is evidence to suggest that the arginine vasopressin release observed in association with emesis after i.v. injection of cholecystokinin (CCK) and N-methyl-D-aspartate (NMDA) is mediated by stimulation of emetic centers in the brainstem. That the GnRH-releasing action of NMDA is also sometimes accompanied by emesis led to the suggestion that stimulation of this parvocellular system by the glutamate agonist may also be mediated in part via activation of brainstem pathways. If this is the case, then other nauseogenic agents, such as CCK, should similarly elicit GnRH release. The foregoing prediction was tested in the castrated juvenile male monkey, an experimental model characterized by the absence of spontaneous GnRH release. GnRH discharges were monitored indirectly by measuring changes in circulating LH concentrations after the responsivity of the gonadotroph had been heightened by a chronic intermittent i.v. infusion of the decapeptide. An i.v. bolus of CCK at 10 and 30 micrograms/kg BW led to a distinct discharge of GnRH accompanied by emesis or other behaviors suggestive of nausea. Lower doses of CCK (1 and 3 micrograms/kg BW) failed to significantly perturb GnRH release or cause emesis, although NMDA (5 mg/kg BW; racemic form) injected i.v. 3 h after the CCK challenge led to a robust rise in GnRH. In a parallel study, three repetitive i.v. CCK injections at 2h intervals maintained intermittent GnRH release. Pretreatment with a long-acting GnRH receptor antagonist ([AcD2Nal1,4ClPhe2,DTrp3,DArg6,DAla10]GnRH -HOAc) abolished the LH response to CCK, confirming that the action of this peptide was mediated by GnRH release. Although a direct hypothalamic site of action for these agents remains the most likely possibility, since both NMDA and CCK receptors are present in the infundibular region, the present data are consistent with the notion that CCK and, by inference, NMDA may activate GnRH release in part via the stimulation of brainstem emetic centers. Plasma GH, PRL, and cortisol concentrations were also monitored during the course of some of these experiments, and the release of these hormones was observed after the administration of either the 10 or 30 micrograms/kg BW dose of CCK.

Animals

[Dopaminergic control of gonadotropin secretion in male senescence].

To verify the role of the dopaminergic mechanism in the control of gonadotropin secretion and aging of this mechanism in men, we studied serum gonadotropin response to LH-RH (100 micrograms i.v.) in basal condition and during dopamine infusion (DA 4 micrograms/kg/min). Seven young males (24-29yr.) and twenty aged males (50-80yr.) without endocrinological diseases were included in the present study. Aged male subjects were divided into hyperresponders, in whom maximal LH response to LH-RH without DA infusion exceeded 153.5mIU/ml (mean + 2SD of young male subjects), and non-hyperresponders, in whom maximal LH responses to LH-RH without DA infusion were less than 153.5mIU/ml. In hyperresponders, serum LH response at 30 minutes after LH-RH administration was significantly (p less than 0.05) suppressed by DA infusion. In non-hyperresponders and young male subjects, however, serum LH response to LH-RH was not affected by DA infusion. Basal levels of serum LH and FSH in hyperresponders tended to be higher than that of non-hyperresponders. Total serum testosterone, free testosterone and estradiol levels of hyper and non-hyperresponders failed to reveal any significant differences. These observations suggest that 1) DA directly suppresses gonadotroph responsiveness to LH-RH, 2) in aging men, inhibitory tone imposed on gonadotrophs by DA is decreased, and 3) this decline of DA system can cause hypergonadotropism in aging men, independent of serum sex steroids levels.

Adult

[Salivary testosterone levels in normal boys at puberty].

Salivary testosterone (Salivary-T) was measured in 133 normal boys at puberty (8-14 years old) and 21 adult males (24-36 years old) by using radioimmunoassay. Also, a simultaneous measurement was performed on salivary-T and serum total testosterone (Total-T) and free testosterone (Free-T) in order to study the correlation between saliva and serum. The results were summarized as follows: (1) Good correlations were observed in the values between Salivary-T and Total-T or Free-T. The correlation coefficient value was 0.54 between Salivary-T and Total-T, 0.84 between Salivary-T and Free-T when measured by DPC kit. Correlation coefficient value was 0.59 between Salivary-T by Wien kit and Total-T by DPC kit, also 0.77 between Salivary-T by Wien kit and Free-T by DPC kit. (2) Salivary-T, in the mean level, increased by age. The most rapid increase of Salivary-T was observed at 13 years of age. (3) Diurnal change of Salivary-T was observed at 13 years of age through adult age. Salivary-T level was highest in the morning and declined toward evening. (4) These results suggest that Salivary-T measurement was highly reliable and applicable for use in the monitoring of androgen status.

Adolescent

The assessment of bioavailable androgen levels from the serum free testosterone level.

Recently, it has been concluded that measurement of the serum free testosterone level is crucial for evaluating male gonadal function. However, the extent of the decline of serum free testosterone levels with aging and the actual levels in male infertility have not yet been clearly defined. In this study, the clinical significance of serum free testosterone levels was evaluated in a total of 248 subjects, including 120 healthy adult males (54 males aged 20-39, 26 males aged 40-59 and 41 males aged more than 60), 94 infertile males, 28 male hemodialysis patients, and 6 patients with Klinefelter's syndrome. Since the serum free testosterone levels correlate significantly with serum LH and FSH levels among 120 normal adult males, it appears that free testosterone has a biological action on the organ. In the subjects aged over 60, serum free testosterone levels were significantly decreased compared with the decrease of serum total testosterone. Thus, biologically active androgen levels decreased with aging. Serum free testosterone levels tended to decrease significantly from 40 years onwards. In infertile males, serum total testosterone levels were equal to those in normal adult males, but their serum free testosterone levels were significantly lower. This decrease of serum free testosterone may be one of the causes of their hypospermatogenesis. In male hemodialysis patients, serum total and free testosterone levels were not lower than in normal adult males. It is considered that the decline of percentage of serum free testosterone levels in aged males and infertile males was caused by increased serum sex hormone binding globulin (SHBG) levels. Several workers have shown that the production of SHBG is regulated by sex steroid hormones. In this study, however, serum SHBG levels were not correlated with the E2/T ratio. We concluded that measurement of the serum free testosterone level is of value in the endocrinological evaluation of male gonadal function.

Adult

Transitional cell carcinoma of the bladder or renal pelvis in children.

Transitional cell carcinoma (TCC) of the bladder or renal pelvis is rare in children. We report 2 children with TCC of the bladder and 1 with TCC of the renal pelvis. One of the two children with bladder carcinoma experienced frequent intravesical recurrences, which is in contrast to the usual clinical course of bladder carcinoma in children. In the 3rd child, renal pelvic carcinoma was found incidentally in a renal pelvis specimen removed during pyeloplasty.

Adolescent

[Therapeutic efficacy of testolactone (aromatase inhibitor) to oligozoospermia with high estradiol/testosterone ratio].

To our knowledge, the action of estradiol which is produced from testosterone by aromatase on human spermatogenesis has not been fully clarified. In oligozoospermia, with high values of E2/T ratio, it is considered that the role of estradiol is suppressive to spermatogenesis. In this study, alteration of spermatogenesis was evaluated when serum estradiol levels were decreased by suppression of aromatase activity. Nine male infertile patients were treated with testolactone (Teslac: 1.0 g/day, for 3 months), one of the aromatase inhibitors. Four of them had an increase in sperm count (more than 10 x 10(6)/ml relative to base line). In endocrinological findings, serum estradiol levels and E2/free T ratio were significantly decreased after treatment. Serum free testosterone levels were significantly increased in all cases, presumably from decreased sex hormone binding globulin (SHBG) levels. These findings suggested the effectiveness of the administrated aromatase inhibitor. In particular four patients whose sperm counts were improved after testolactone treatment had high values of basal serum estradiol levels and E2/free T ratio before treatment, and these values were normalized after treatment. In conclusion we suggest that an aromatase inhibitor may be effective to male infertile patients with high serum estradiol levels.

Adult

[Nocturnal luteinizing hormone secretion patterns at the onset of puberty measured using a highly sensitive immunofluorometric assay].

Nocturnal LH pulse was analyzed in 4 prepubertal, 3 early pubertal and 2 midpubertal boys by measuring serum LH concentrations. Blood samples were taken every 30 minutes while awake, and every 20 minutes after subjects had gone to sleep. Serum LH was measured by using immunofluorometric assay (IFMA) with a lower detection limit of 0.02mIU/ml. Pulsatile LH secretion during sleep was detected in all subjects examined. LH pulse amplitude had the tendency to increase with the advance of pubertal stage. After the onset of puberty, LH pulse amplitude was significantly larger than before. The LH pulse was also detected while awake in 4 (1 prepubertal, 2 early pubertal and 1 mid-pubertal) boys. LH pulse frequency was almost the same in each pubertal stage. Serum testosterone levels gradually increased with the progress of pubertal stage. These results suggest that 1) LH is secreted in a pulsatile manner in the prepubertal subjects as well as in the pubertal subjects, 2) the increase of LH pulse amplitude plays an important role for the onset of puberty, and 3) LH pulse amplitude could be a biological marker that indicates the degree of maturation of the hypothalamo-pituitary unit in prepubertal children.

Adolescent

[Determination of the normal range of serum LH and FSH levels in normal adult males--comparison with IRMA and RIA].

To determine the normal range of serum LH and FSH levels, blood samples from 53 normal adult males were measured by a double antibody radioimmunoassay system and a new immunoradiometric assay (IRMA) system. It was necessary to evaluate the individual pulsatile secretion and the differences in measured values among laboratories to determine the normal range. Therefore, in 53 normal adult males lacking any evidence of hormonal abnormalities, blood was sampled at 9:00 a.m. daily for 3 days, and these samples were measured in 3 laboratories. The result of the hormone concentration of blood sample was not appropriate as the normal range because of the high amplitude of LH and FSH pulses. Coefficient values (CV) between the mean value of the first two samples and the mean value of all three samples were small. Therefore, the mean value of the first two samples was clinically accurate for use as the normal range. Significant differences in measured values were observed among the 3 laboratories. The normal range, which included individual pulsatile secretion, and the differences in measured values among the laboratories was as followings: LH (RIA): 7.6-13.7 mIU/ml, LH (IRMA): 2.1-4.7 mIU/ml, FSH (RIA): 4.7-9.5 mIU/ml, FSH (IRMA): 3.0-7.4 mIU/ml. The serum LH and FSH levels of 68 untreated male infertility patients tended to rate high with respect to our normal range. It was considered that the normal range determined in this study was useful for clinical management.

Adult