Biomedical subjects

I Shimizu

Publications and source records attributed to I Shimizu.

At least 127 records · Page 7Linked to original sources

PubMed1987

Neuroeffector function in mesenteric arteries isolated from beagles of different ages.

In helical strips of mesenteric arteries from 30-day (28-35 day), 3-month (80-110 day), 2-year (10-40 month) and 12-year (135-161 month)-old beagles, contractile responses to vasoconstrictors were compared. The responses to transmural stimulation and norepinephrine, relative to those caused by 30 mM K+, were greater in the infant beagle arteries than in those from the older beagles. Equipotent concentrations of the amine for producing the same magnitude of contraction as that evoked by 5 or 20 Hz stimulation in beagles of different ages did not differ. Treatment with 10(-9) M prazosin or 10(-8) M yohimbine attenuated the response to norepinephrine in 30-day and 12-year-old beagles to a similar extent. Contractions induced by transmural stimulation in the infant beagle arteries were potentiated slightly by 10(-9) M yohimbine and, in contrast, attenuated at 10(-8) M. On the other hand, the stimulation-evoked contraction in the senile beagle arteries was potentiated by these concentrations of yohimbine in a dose-dependent manner. Angiotensin II potentiated responses to electrical stimulation in 30-day and 12-year-old beagles to a similar extent. Contractions by angiotensin II and serotonin did not alter with age. It may be concluded that alpha adrenoceptor function reduces during an early postnatal period, but does not decline further through senescence. It appears that prejunctional, but not postjunctional, alpha-2 receptor function develops after birth, whereas pre- and postjunctional angiotensin receptors already mature in beagles until the age of 30 days.

Aging↗

PubMed1986

Beta-endorphin in the human gallbladder.

The presence of beta-endorphin-like immunoreactivity (beta-END-LI) in human gallbladder and its release were examined by means of radioimmunochemical measurements and immunohistochemical stainings. beta-END-LI was detected in the gallbladder (27.2 +/- 3.2 ng/g wet weight, mean +/- S.E.). The immunoreactivity in beta-END-LI extracted from the gallbladder was similar to that of synthetic beta-END, judging from the result of its inhibition curve parallel to that of the synthetic substance in the radioimmunoassay (RIA) system. On gel-filtration chromatography of a gallbladder extract, two components of beta-END-LI were found; one eluted on a position of beta-lipotropin (beta-LPH) and another on a position of synthetic beta-END. Specific beta-END-LI positive cells were detectable in metaplastic mucous glands. When human gallbladder mucosa was perfused with a solution of 10(-8) M or 10(-6) M cholecystokinin octapeptide (CCK-8), the release of beta-END-LI from mucosa into the perfusate increased 2-3 fold. These results indicate that beta-END-LI present in human gallbladder is released by the direct action of CCK-8 on the gallbladder mucosa and suggest that it may have a physiological or pathophysiological role.

Chromatography, Gel↗

PubMed1986

Concentrations of metallothionein and metals in malignant and non-malignant tissues in human liver.

Concentration of metallothionein in the malignant and non-malignant tissues of the human liver was determined by the Cd-hem method. The concentration of metallothionein was high in the non-malignant tissue (471 +/- 306 micrograms/g). Metallothionein in the non-malignant tissue was mainly Zn-thionein and metallothionein-bound Zn was a major chemical form of Zn in the non-malignant tissue. The concentration of metallothionein in the malignant tissue was 75.6 +/- 79.6 micrograms/g, and significantly lower than that in the nonmalignant tissue. A strong, positive relationship was observed between the Zn and metallothionein concentrations, and the regression equation was MT (microgram/g) = -94.7 + 11.9 Zn (micrograms/g).

Adult↗

PubMed1986

Danazol binds to progesterone receptors and inhibits the growth of human endometrial cancer cells in vitro.

Based on our recent findings that danazol, an isoxazol derivative of ethinyltestosterone, has a profound growth-inhibitory effect on an established human endometrial adenocarcinoma cell line, the effects of danazol on cancer cells from human endometrial adenocarcinomas obtained by hysterectomy were investigated in the present study. Of the 22 uterine adenocarcinomas, estrogen, progesterone, and androgen receptors were found in 12, 14, and 4 tumors, respectively. Competitive binding studies showed that danazol specifically binds to progesterone and androgen receptors but not to estrogen receptors. Of the five cancer cells from five patients succeeded in primary cell culture, a marked inhibition of cell growth was demonstrated by addition of danazol in two cancer cells having progesterone but not androgen receptors. However, danazol did not affect the growth of the remaining three cancer cells lacking progesterone receptors. These results strongly suggest that danazol has a significant growth-inhibitory effect on human endometrial adenocarcinoma cells, possibly through progesterone receptors in the cells.

Adenocarcinoma↗

PubMed1986

An elevated type of gastric ulcer scar in patients treated with cimetidine.

An elevated type of gastric ulcer scar (EUS) (A) was noted in 8 out of 227 ulcer patients treated with cimetidine. These were compared with 15 patients with EUS (B), not treated with cimetidine and the etiology of the lesion was discussed. The incidence of EUS (3.5%) and the average age of the patients were higher (61 years) in the A group than in the B group. The scar was seen all over the stomach in the A group. The period from detection of gastric ulcer to confirmation of EUS averaged 4 weeks, and there was no difference between the two groups. No difference was seen in the histological findings of elevated lesions either. In the A group, it appears that EUS was induced by rapid tissue regeneration due to the strong anti-ulcer effect of cimetidine in ulcer lesions, since it was noted in the regions where it had previously been considered unlikely to occur.

Adolescent↗

PubMed1986

Alterations with age of the response to vasodilator agents in isolated mesenteric arteries of the beagle.

Responses to vasodilator agents were compared in helical strips of mesenteric beagles of different ages (30 days, 3 months, 2 years and 12 years old), precontracted with prostaglandin F2 alpha (PGF2 alpha). Relaxations induced by isoprenaline and adenosine were related inversely to age, whereas those induced by PGI2 and K+ (5 mM) did not alter with age. Acetylcholine-induced relaxations were less in the arteries from the aged (12 year old) beagles than in those from the younger beagles. Histamine-induced relaxations related directly to age between 30 days and 2 years. Acetylcholine-induced relaxation was reversed to a contraction in infant (30 day old) beagle arteries by removal of the endothelium, and significantly attenuated in the older beagle arteries. In adult (2 year old) and aged beagle arteries, removal of the endothelium attenuated the histamine-induced relaxation. Treatment with indomethacin reversed the histamine-induced relaxation to a marked contraction in aged beagle arteries. It may be concluded that responses mediated by beta-adrenoceptors and P1-purinoceptors are less in aged mesenteric arteries than in those from the younger beagles, whereas responses mediated by PGI2 receptors and the electrogenic Na+ pump do not alter with age. The release of endothelium-derived relaxing factor(s) by acetylcholine appears to be inversely related to age. However, the release of PGI2 possibly caused by histamine may be less in infant beagle mesenteric arteries than in those from the older beagles.

Acetylcholine↗

PubMed1986

Analysis of ouabain-induced contractions in isolated coronary arteries.

Contractile responses to ouabain in helical strips of dog and monkey coronary arteries were investigated. Ouabain (5 X 10(-8) to 5 X 10(-6) M) caused a dose-related contraction in dog and monkey arteries; the response of monkey coronary arteries was significantly greater. In dog coronary arteries, contractile responses to high concentrations of ouabain were potentiated by treatment with propranolol. In the arteries contracted with ouabain, the addition of phentolamine caused a relaxation. Contractile responses of dog coronary arteries to ouabain were markedly suppressed by exposure to Ca2+-free media or by treatment with verapamil. Reduction of external concentration of K+ or lowering the temperature of bathing media did not selectively influence the ouabain-induced contraction. These results suggest that ouabain-induced contractions of dog coronary arteries are associated mainly with an increase in the Ca2+-influx, which does not result from an inhibition of the Na+, K+-activated ATPase nor from an activation of alpha adrenoceptors by noradrenaline released from adrenergic nerves. Ouabain in high concentrations seems to liberate noradrenaline from adrenergic nerves, which preferentially activates beta adrenoceptors in dog coronary artery.

Animals↗

PubMed1986

Responsiveness to vasoconstrictor and dilator agents of senescent beagle cerebral arteries.

With advancing age from 2 to 12 years, contractions of isolated beagle cerebral arteries mediated by histamine H1 and serotonin receptors increased, whereas those induced by noradrenaline and angiotensin II did not differ. Relaxations by vasodilator substances, such as prostaglandin (PG) I2, isoproterenol, adenosine and K+ (5 mM), and by stimulation of vasodilator nerves in the adult and senescent beagle arteries did not significantly differ.

Adenosine↗

PubMed1986

Clomiphene citrate induces pituitary GnRH receptors in ovariectomized rats: its possible role in induction of ovulation.

Since our previous studies have shown that clomiphene citrate (clomiphene) acts directly on the pituitary gland and exerts a facilitatory role on oestradiol-17 beta (E2)-induced LH surge in chronically ovariectomized rats, the effect of clomiphene on pituitary GnRH receptors was investigated. A single ip injection of either 5 micrograms E2 or 200 micrograms clomiphene did not induce LH release in adult rats ovariectomized 1-2 weeks before the injection. However, a significant increase in serum LH was noted 24 h after a single injection of E2 in the ovariectomized rats, if clomiphene was pre-injected 48 h before the E2 injection. The content of pituitary GnRH receptors in the ovariectomized rats (62 +/- 9 fmol/pituitary) remained almost unchanged until 24 h after a single injection of clomiphene but significantly increased 48 h after the injection (105 +/- 13 fmol/pituitary) without any alterations in the affinity for GnRH. To determine steroid specificity for the increase in pituitary GnRH receptors, other classes of steroids were injected in the ovariectomized rats. A single dose of E2 increased GnRH receptors, but either progesterone or 5 alpha-dihydrotestosterone failed to show any effect on the level of GnRH receptors. These results suggest that clomiphene may augment oestrogen-induced pre-ovulatory LH surge in anovulatory women, at least in part by increasing the number of pituitary GnRH receptors.

Animals↗

PubMed1986

Dexamethasone inhibits the effects of oestrogen on the pituitary gland in rats.

The administration of glucocorticoids has been shown to be effective for the induction of ovulation in patients with anovulation. In the present study, we investigated the effects of a glucocorticoid on oestrogen-induced changes in the pituitary gland. A single ip injection of 10 micrograms oestradiol-17 beta (E2) in ovariectomized and adrenalectomized rats resulted in a significant increase in pituitary weight and progesterone receptor (PgR) concentration. In these animals, serum LH level was initially suppressed and restored to control level 24 h after E2 injection. However, 1 mg of dexamethasone (Dex) injected before E2, but not after E2 administration, completely inhibited both the increases in pituitary weight and PgR concentration. The restoration of serum LH level 24 h after E2 was also prevented. These antioestrogenic effects of Dex were blocked by ip administration of the synthetic antiglucocorticoid, RU486. Dex treatment alone did not have any effect on E2-induced changes in the dynamics of pituitary oestrogen receptor. Finally, E2-pellet implanted sc in ovariectomized and adrenalectomized rats for 7 days caused marked increases in pituitary weight and PgR concentration. A single ip injection of 250 micrograms clomiphene citrate (clomiphene) significantly reduced both the pituitary weight and PgR concentration in these animals, but 1 mg of Dex failed to have a similar effect. These results suggest that glucocorticoids antagonize E2 effects on the pituitary by a mechanism different from antioestrogens such as clomiphene. These antioestrogenic effects of glucocorticoid may be involved in induction of ovulation in anovulatory women.

Adrenalectomy↗

PubMed1985

[In vivo and in vitro effects of bradykinin on the release of beta-endorphin-like immunoreactivity].

The effect of bradykinin (BK) on the release of beta-endorphin-like immunoreactivity (beta-END-LI) in rats was studied in in vivo and in vitro. Intraperitoneal injection of BK at 5 micrograms/100 g body weight resulted in a significant increase in the plasma beta-END-LI level after 15 min. BK at concentrations of 10(-12)-10(-7) M also caused dose-dependent stimulation of beta-END-LI release from the dispersed cells of the anterior pituitary of rats. On gel chromatography, the beta-END-LI released by incubation of the cells with 10(-7) M BK separated into two components; one eluted in the same positions as human beta-lipotropin and the other as human beta-endorphin. BK did not stimulate beta-END-LI release in Ca++-free medium. Addition of 10(-3) M verapamil, 10(-6) M dexamethasone or 10(-7) M somatostatin to the incubation medium inhibited BK-induced beta-END-LI release from the cells. Ouabain (10(-5) M) also stimulated beta-END-LI release, but its effect was not additive with that of BK. These results indicate that BK stimulates beta-END-LI release and that calcium ion is involved in the mechanism of this effect.

Animals↗

PubMed1985

Dexamethasone suppresses estrogen action at the pituitary level without modulating estrogen receptor dynamics.

The administration of glucocorticoid combined with antiestrogen such as clomiphene has been shown to be effective for the induction of ovulation in patients with anovulation. The present study was undertaken to examine the effects of glucocorticoid on estrogen-induced changes in the pituitary gland. A single intraperitoneal (i.p.) administration of 10 micrograms estradiol-17 beta (E2) in ovariectomized and adrenalectomized rats resulted in a significant stimulation of pituitaries with regard to wet tissue weight and progesterone receptor content. An i.p. administration of 1 mg dexamethasone in these animals had no effects on both the values. However, the E2-induced increases in pituitary weight and progesterone receptor content were significantly inhibited by pretreatment with 1 mg of dexamethasone. The pretreatment with dexamethasone, on the other hand, had no significant effect on the dynamics of pituitary estrogen receptor induced by the injection of E2, i.e. the degree of nuclear translocation, occupancy and cytoplasmic receptor replenishment. The inhibitory effect of dexamethasone, therefore, does not seem to be mediated through estrogen receptor system in the pituitary. These results suggest that dexamethasone acts directly on the pituitary gland to suppress the action of E2, and which may be involved in the process of induction of ovulation by glucocorticoid-clomiphene treatment.

Adrenalectomy↗

PubMed1985

Postmortem functional changes in coronary and cerebral arteries from humans and monkeys.

Contractile responses to 30 mmol . litre-1 K+ of helical strips of coronary arteries from human cadavers did not change within 5 h after death; however, they were suppressed 8 h after death. In coronary arteries from monkey cadavers, the K+-induced contractions did not significantly differ within the first 5 h, but were suppressed 12 h after death. On the other hand, K+-induced contractions were retained without deterioration in cerebral artery strips from human cadavers 20 to 24 h after death and those from monkey cadavers 8 to 16 h. Acetylcholine caused contractions of human coronary arteries, but caused only a relaxation of monkey coronaries which was abolished by rubbing off the endothelium. These responses were attenuated by no more than K+-induced contractions up to 12 h after death. Maximum contractions induced by noradrenaline, histamine and serotonin remained the same in human coronary arteries for 3 to 5 h after death. Similar magnitudes of contraction were elicited by noradrenaline in human cerebral arteries up to 20 h after death. It appears that the reactivity of human coronary arteries to K+ and other vasoconstrictor agents used is normally retained for at least 6 h after death and that of human cerebral arteries up to 24 h.

Adolescent↗

PubMed1985

In vivo and in vitro effects of bradykinin on the release of beta-endorphin-like immunoreactivity.

The effect of bradykinin (BK) on the release of beta-endorphin-like immunoreactivity (beta-EpLI) in rats was studied in vivo and in vitro. Intraperitoneal injection of BK at 5 micrograms/100 g body weight resulted in significant increase in the plasma beta-EpLI level after 15 min. BK at concentrations of 10(-12)-10(-7) M also caused dose-dependent stimulation of beta-EpLI release from dispersed cells of rat anterior pituitary. On gel chromatography, the beta-EpLI released by incubation of the cells with 10(-7) M BK separated into two components, eluted in the same positions as human beta-lipotropin and human beta-endorphin, respectively. BK did not stimulate beta-EpLI release in Ca++-free medium. Addition of 10(-3) M verapamil or 10(-6) M dexamethasone to the incubation medium inhibited BK-induced beta-EpLI release from the cells. Quabain (10(-5) M) also stimulated beta-EpLI release, but its effect was not additive with that of BK. These results indicate that BK stimulates beta-EpLI release and that calcium ion is involved in the mechanism of this effect.

Animals↗

PubMed1985

A possible role of clomiphene citrate in the control of pre-ovulatory LH surge during induction of ovulation.

A possible role of clomiphene citrate (clomiphene) in the control of ovulation in anovulatory women was investigated. Since a single ip administration of 5 micrograms oestradiol-17 beta (E2) to long-term ovariectomized rats did not induce LH surge, the following studies were designed to determine whether pretreatment with clomiphene followed by administration of E2 could induce LH surge in the ovariectomized rats. Changes in cytoplasmic and nuclear oestrogen receptors (ER) were also examined in the pituitaries of these animals. An ip injection of 200 micrograms clomiphene suppressed serum LH levels significantly for 72 h. The clomiphene injection rapidly caused an elevation of nuclear ER with a concomitant depletion of cytoplasmic ER level in the pituitary and the ER levels remained almost unchanged for 72 h. An administration of E2 12 or 24 h after the clomiphene injection had no significant effects on either the serum LH levels or the cytoplasmic and nuclear ER levels, compared with those induced by clomiphene alone. However, LH surge and the depletion of nuclear ER in the pituitary occurred 24 h later when E2 was injected 48 h after the clomiphene administration. The E2-induced LH release seems to be induced by a replacement of clomiphene by E2 on the nuclear receptor complex. These results suggest that clomiphene may exert actions directly on the pituitary gland to augment oestrogen-induced LH release.

Animals↗

PubMed1985

Prolactin inhibits oestradiol-induced luteinizing hormone release at the pituitary level.

The direct action of prolactin (Prl) on pituitary LH secretion was studied by examining its effect on oestradiol (E2)-induced luteinizing hormone (LH) release from the rat pituitary in a perifusion system and determining the oestrogen receptor (ER) content of the pituitary in hyperprolactinaemic female rats. When the pituitary from rats in pro-oestrus was perifused with medium alone, 10(-7) M E2 significantly (P less than 0.05) increased the LH concentration in the effluent by 60-130% of the basal level, but in medium containing 1 microgram/ml Prl it did not cause LH release. In hyperprolactinaemic rats produced by implanting 2 anterior pituitary glands under the kidney capsule, the ER content of the cytosol of the pituitary (53.2 +/- 2.9 fmol/pituitary) was significantly increased (P less than 0.05), but that of the nuclei (6.8 +/- 0.2 fmol/pituitary) was significantly decreased (P less than 0.05) compared with the contents in rats in pro-oestrus. These data suggest that Prl has a direct suppressive effect on LH secretion from the pituitary in the rat, and that decreased translocation of ER into the nucleus might relate to impaired LH release by E2 from the pituitary of hyperprolactinaemic rats.

Animals↗

PubMed1985

Decrease of LRH receptors in the pituitary gland in streptozotocin-induced diabetic rats.

In studies into the mechanism of anovulation in the diabetic condition, the LRH receptor content of the pituitary gland of rats with diabetes mellitus was determined. Normal female rats weighing 180-200 g were injected iv with either streptozotocin (6 mg/100 g body weight) or vehicle in dioestrus of the oestrous cycle. The rats were sacrificed by decapitation 9 days after treatment, and serum LH concentrations and the LRH content of the medial basal hypothalamus (MBH) were measured by radioimmunoassay (RIA), and the LRH receptor content of the pituitary gland was determined. The serum concentration of LH and the LRH content of the MBH in diabetic rats were 34.4 +/- 4.8 ng/ml (mean +/- SEM) and 2.05 +/- 0.04 ng/MBH, respectively, which were similar to the respective values of normal rats in dioestrus. However, the LRH receptor content of diabetic rats (13.2 +/- 3.9 fmol/pituitary) was significantly (P less than 0.05) lower than that of normal rats in dioestrus (68.0 +/- 7.1 fmol/pituitary) and pro-oestrus (59.4 +/- 13.6 fmol/pituitary). These results suggest that anovulation in diabetic rats is at least partly attributable to a low content of LRH receptors in the pituitary gland.

Animals↗

PubMed1985

Increased platelet aggregation in psoriasis.

Platelet aggregation was measured in fasting platelet-rich plasma in 25 psoriatics, 6 of whom were diabetic, 50 normal controls, and 24 diabetics. The aggregating agents employed to induce platelet aggregation included ADP, epinephrine and collagen. Platelet aggregation was significantly increased in psoriatics compared with normal controls. An additive effect was observed when diabetes was associated with psoriasis, with platelet aggregation being further increased by ADP. Platelet aggregability was re-evaluated in 7 psoriatics after they presented with clearing of the rash. The increased platelet aggregation with ADP and epinephrine was significantly reduced when the skin lesions had cleared.

Adenosine Diphosphate↗