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Biomedical subjects

M Urabe

Publications and source records attributed to M Urabe.

At least 109 records · Page 6Linked to original sources
PubMed1989

[The study of direct effect of methimazole on thymidine incorporation in FRTL-5 cells].

During the course of treatment of Graves' disease with the anti-thyroid drug, methimazole (MMI), a decrease in a patient's goiter size is sometimes observed. Using rat thyroid cell strain, FRTL-5, the direct effect of MMI on thyroid cell growth was investigated. FRTL-5 cells (2 X 10(5)) were cultured for 48 hours with TSH, (Bu)2 cAMP or forskolin in the presence of [3H]-thymidine. All three stimulators increased cell growth, expressed as [3H]-thymidine incorporation into DNA in a dose-dependent fashion. When FRTL-5 cells were cultured for 48 hours in the presence of MMI at 10(-6)-10(-3) M with these stimulators (TSH 250 microU/ml, (Bu)2 cAMP 10(-3) M, forskolin 10(-5) M), [3H]-thymidine incorporation was suppressed in dose-dependent fashions (MMI 10(-5) M-10(-3) M). From the present study, it is suggested that methimazole directly modulates thyroid cell growth induced by thyroid growth stimulators which are involved in adenylate cyclase-cyclic AMP system and that the site of its action exists beyond cAMP production.

Animals↗
PubMed1989

In vivo effects by estrone sulfate on the central nervous system-senile dementia (Alzheimer's type).

Seven women with senile dementia-Alzheimer's type (SDAT) were treated with conjugated estrogen [main content: estrone sulfate (E1-S)], at a dose of 1.25 mg/day over a 6-week period. A New Screening Test for Dementia developed by Japanese National Institute of Mental Health (NS) and the scores of Hasegawa Scale for dementia (HS) were performed every 3 weeks. Six women showed improvements in NS (P less than 0.05) and 5 women showed improvements in HS. Untreated women with SDAT did not show any improvement. Serum E1-S was measured by a direct radioimmunoassay. Serum E1-S was 911 +/- 156 pg/ml in 7 women with SDAT and lower than that of 7 normal women (1020 +/- 216 pg/ml). Following the treatment, serum E1-S increased to a level of 21.1 +/- 8.1 ng/ml. Estrone and estradiol-17 beta also increased. The results suggest a possibility for the future clinical use of estrogen for senile dementia, after careful clinical research trials including the side effects.

Aged↗
PubMed1989

Estrone sulfate and sulfatase activity in human breast cancer and endometrial cancer.

Estrone sulfate (E1-S) in the serum and tissues of patients with breast cancer or endometrial cancer was measured by a direct radioimmunoassay without hydrolysis. The concentration of E1-S in breast cancer tissue was 1.64 +/- 0.28 ng/g wet wt (+/- SE), lower than in surrounding normal breast tissue (4.46 +/- 1.23). Estradiol-17 beta(E2)/E1-S was higher in endometrial cancer tissue than normal endometrial tissue. Estrone sulfatase activity in breast cancer tissue was 0.81 +/- 0.23 nmol/h/mg protein, higher than in surrounding normal breast tissue (0.35 +/- 0.11). These results suggest that E1-S, which is abundant in the peripheral circulation, is hydrolyzed by sulfatase in breast cancer tissue or endometrial cancer tissue and liberates free estrogens, which may stimulate the growth of these malignant tumors.

Adipose Tissue↗
PubMed1989

Estrone sulfatase activity in normal and neoplastic endometrial tissues of human uterus.

Estrone sulfatase activity was measured in normal and neoplastic endometrial tissues of human uterus. The tissue homogenates were incubated in air with [3H] estrone sulfate (E1-S, 20 microM) at 37 degrees C for 30 min. After the enzyme reaction was terminated with ethyl ether, the ethyl ether extract was purified by thin-layer chromatography. The apparent Km of sulfatase was 3.0 microM, and the maximum velocity was 14.7 nmol/h/mg protein. Estrone sulfatase activity in endometrial tissues was detected throughout the menstrual cycle with no significant change. Moreover, estrone sulfatase activity in endometrial cells was not stimulated by the addition of progestogen. The enzyme activity in cancer tissue was significantly higher than in normal tissue. Thus we concluded that this enzyme may play a role in regulating the estrogen action by sifting the intracellular equilibrium between free estrogens and estrogen sulfates. We also concluded that in the endometrial cancer tissue, sulfatase appears to act on local production of estrone.

Endometrium↗
PubMed1989

Estrogen biosynthesis in human uterine adenomyosis.

Estrogen biosynthesis (aromatase activity) was investigated in human adenomyosis tissue and compared with that of the normal myometrium, endometrium, and endometrial cancer tissues. Homogenates were incubated with [1,2,6,7-3H]androstenedione and NADPH at 37 degrees C for 1 h. After stopping the enzymatic reaction with ethyl acetate, [4-14C]estrone and [4-14C]estradiol-17 beta were added to the incubated sample. Estrone and estradiol were purified and identified by Bio-Rad AG1-X2 column chromatography, thin-layer chromatography and co-crystallization. Estrogen formed in the incubated sample was calculated from the 3H/14C ratio of the final crystal. The value for estrone formed from androstenedione was 52-132 fmol.h-1.g-1 wet weight. Aromatase activity in the adenomyosis tissues was higher than that in normal endometrial or myometrial tissues, but lower than that found in myometrial or endometrial tumour tissue. Furthermore, we investigated the effect of danazol, progesterone, and medroxyprogesterone acetate on adenomyosis cells in primary cultures. Aromatase activity in adenomyosis was blocked by danazol, but stimulated by progesterone and MPA. These results indicate that aromatase activity in adenomyosis may contribute to the growth of the ectopic endometrial tissue which occurs in this disease.

Adult↗
PubMed1989

[Tissue culture and estrogen, to clarify the roles of estrone sulfate].

Estrone sulfate (E1-S) has been shown to be quantitatively the most important estrogen in peripheral blood. But, the physiological and/or pathological role of E1-S is not yet clarified. At present, we tried to clarify it using tissue cultures. In tissue cultures of human endometrium, secretory endometrium showed higher activity of estrone sulfatase (E1----E1-S) than proliferative endometrium. Progesterone added in the medium induced an increase of estrone sulfotransferase in the proliferative endometrium. The results suggest a reducing effect of estrogen by progesterone in secretory endometrium in physiological conditions. Estrogen dependent malignant tumors (breast cancer, endometrial cancer) have high estrone sulfatase. It converts E1-S to E1 (----E2) which are abundant in these tumors. Ishikawa cell line increased estrone sulfotransferase activity with progesterone, somewhat like the physiological conditions. From out study in vivo, there is a possibility of some ameliorative effects of E1-S on the central nervous system of patients with senile dementia (Alzheimer's type). Effects of E1-S on central nerves were investigated using tissue cultures.

Alzheimer Disease↗
PubMed1988

Thyroid functions before and after maintenance hemodialysis in patients with chronic renal failure.

To study the factors involved in the low thyroid hormone levels in patients with chronic renal failure (CRF), we investigated thyroid functions just before and after hemodialyses (HD) in 32 such patients who were on maintenance HD. In addition, we measured serum thyroid hormone binding inhibitor activities (THBI) in another set of 37 patients. None of the patients had been suspected of having thyroid diseases. HD duration and aging did not have a significant effect on the results of the thyroid function tests. Before each HD, the serum concentrations of T3, T4, FT3, FT4, rT3, PBI, FT3I, FT4I, FT3/T3, FT4/T4, T4/TBG, T4/TSH and FT4/TSH were lower, and those of TSH, TBG, and thyroglobulin (Tg) were higher in the patients than in normal controls. The thyroid hormone concentrations were negatively correlated with the BUN and creatinine levels. The Tg levels were positively correlated with the BUN levels. After each HD, almost all the thyroid function tests including T4/TBG ratio showed improvements, which indicated that hemodilution and a decrease in the T4-binding affinity of TBG with thyroid hormones were the major factors in the low thyroid hormone levels in CRF patients. However, even after HD, T3, FT3, rT3, T4/TSH and FT4/TSH were still lower and TSH and Tg were still higher in the patients. These data suggested that the CRF patients were in a subclinical hypothyroid state. THBI was high in patients with CRF and did not change following HD. NEFA did not seem to contribute to the high THBI before HD, because they were in the normal range. However, as NEFA became very high after HD and possessed THBI, we calculated the corrected THBI (C-THBI) by subtracting the effect of NEFA from total THBI. C-THBI was high before HD and decreased after HD. Therefore, it was suggested that this C-THBI contributed to the abnormalities in the affinity of TBG with thyroid hormones. From these studies, it is concluded that (1) the patients with CRF may be in a subclinical hypothyroid state, although hemodilution was seen to have a strong effect on the thyroid hormone concentrations, and (2) C-THBI may have an effect on the affinity of TBG with thyroid hormones and play an additional role in low thyroid hormone levels in these patients. The mechanisms of hypothyroidism and the nature of C-THBI remain to be clarified.

Adolescent↗
PubMed1987

[The inhibitory effect of miconazole on aromatase activity for androstenedione in human placental and ovarian preparations].

The inhibitory effects of miconazole, an antimycotic agent, on aromatase activity for androstenedione in human placenta (105,000 X g pellet fraction) and ovary (800 X g supernatant fraction) were investigated. Various concentrations (0.1-100 microM) of miconazole, aminoglutethimide or delta 1-testololactone were added to the human placental preparation (1 mg protein) and then the mixture was incubated with [1 beta-3 H]-androstenedione (300 pmol) and NADPH (0.5 mg), at 37 degrees C for 30 minutes in air. The reaction was stopped by 10%-trichloroacetic acid (0.8 ml) and the mixture was extracted with chloroform (3 ml). The residual aqueous phase was subjected to Amberlite XAD-II resin-charcoal column chromatography. The amount of 3H2O obtained was regarded as aromatase activity for androstenedione. The effects of miconazole on aromatase activity in human ovarian preparation was also investigated. Aromatase activity in human placenta was suppressed concentration-dependently by miconazole. The inhibition of aromatase activity by miconazole was significantly higher than that by aminoglutethimide and delta 1-testololactone. The I50 values for the inhibition of aromatase activity by miconazole, aminoglutethimide and delta 1-testololactone were 0.60 microM, 15 microM and 34 microM, respectively. The apparent Km value for androstenedione was 320 nM and the apparent Ki value was 120 nM in this assay. The inhibition of aromatase by miconazole in human ovary was also significantly higher than that by aminoglutethimide (I50 value for miconazole = 0.98 microM; I50 value for delta 1-testololactone = 15 microM). These results indicate that miconazole suppresses aromatase activity for androstenedione reversibly in human placenta and ovaries in vitro.

Aminoglutethimide↗
PubMed1987

Pre- and postsynaptic effects of angiotensins in the femoral artery of spontaneously hypertensive and Wistar-Kyoto rats.

The effects of angiotensin I (AI) and angiotensin II (AII) on ring segments of femoral arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were studied. AI and AII elicited significantly greater direct contractile response in arteries from SHR than those from WKY. These peptides also potentiated the contractile response to transmural adrenergic nerve stimulation (TNS) in both preparations, but to a greater extent in those of WKY than SHR, without potentiating the contractile response to exogenous norepinephrine (NE). The potentiation of the TNS response and direct contraction caused by AI were markedly attenuated by captopril, an AI-converting enzyme inhibitor. Destruction of endothelium failed to alter the contractile response to AI in both WKY and SHR but augmented that to AII in WKY. Isoproterenol and salbutamol produced significant potentiation of TNS response only in arteries of SHR. Yohimbine and prostaglandin F2 alpha potentiated TNS response to a similar extent in arteries of WKY and SHR. These results suggest that AII locally generated from AI can act postsynaptically to cause contraction and presynaptically to promote adrenergic neurotransmission in the isolated rat femoral artery. The AI to AII conversion appears to take place mainly at sites other than endothelial cells. The postsynaptic effect of AII is greater in SHR than WKY, but its presynaptic effect is diminished in SHR unlike some other agents which facilitate adrenergic neurotransmission, and unlike that in mesenteric arteries of SHR.

Adrenergic Fibers↗
PubMed1987

Serum and urinary estrone sulfate during the menstrual cycle, measured by a direct radioimmunoassay, and fate of exogenously injected estrone sulfate.

Serum and early-morning urinary levels of estrone sulfate during the menstrual cycle were measured by a direct radioimmunoassay without hydrolysis. These levels were high and showed prominent peaks [serum, 2.67 +/- 0.37 ng/ml (mean +/- SE); urine, 5.82 +/- 2.3 micrograms/l] around the day of the preovulatory estradiol-17 beta peak, and increased again during the luteal phase. Following intravenous injection of estrone sulfate, serum estrone sulfate, estrone and estradiol-17 beta were measured. The conversion of estrone sulfate to estrone and/or estradiol-17 beta was very small during their transit in the general circulation.

Adolescent↗
PubMed1987

Enhanced 5-hydroxytryptamine release from vascular adrenergic nerves in spontaneously hypertensive rats.

The release of 5-hydroxytryptamine from the vascular adrenergic nerve by periarterial nerve stimulation in spontaneously hypertensive rats (SHR) was compared with that in normotensive Wistar-Kyoto rats (WKY). The isolated mesenteric vascular bed was perfused at a constant flow rate of 5 ml/min. Vasoconstrictor responses to periarterial nerve stimulation (4, 8, 12, and 16 Hz for 30 seconds) and 5-hydroxytryptamine (1 microM), but not norepinephrine (1 nmol), were significantly greater in SHR than in WKY. After treatment with 5-hydroxytryptamine (1 microM) for 15 minutes, vasoconstrictor responses to periarterial nerve stimulation previously reduced by prazosin (50 nM) were restored and a frequency-dependent pressor response reappeared. However, 5-HT treatment did not significantly affect the pressor response to exogenously administered norepinephrine (1 nmol), which was previously inhibited by prazosin. The degree of the restoration in SHR was significantly greater than that in WKY at all frequencies used. The restoration of the pressor response to periarterial nerve stimulation after 5-hydroxytryptamine treatment did not occur in the presence of the selective 5-hydroxytryptamine2 receptor antagonists ketanserin (10 nM) or LY53857 (10 nM). In the perfused mesenteric vascular bed of both WKY and SHR prelabeled with [3H]5-hydroxytryptamine, periarterial nerve stimulation (4-16 Hz) evoked a frequency-dependent increase in tritium efflux that was abolished by Ca2+-free Krebs-Ringer solution or tetrodotoxin (100 nM) and treatment with 6-hydroxydopamine. The tritium efflux evoked by periarterial nerve stimulation was significantly greater in SHR than in WKY at all frequencies used. These results suggest that the release of 5-hydroxytryptamine from adrenergic nerve endings by periarterial nerve stimulation is enhanced in the mesenteric vascular bed of the SHR.

Animals↗
PubMed1987

[Electroencephalographic study of Sch 161 (quazepam), a new benzodiazepine hypnotic, in rats and rabbits].

The electroencephalographic (EEG) effects of 7-chloro-5-(o-fluorophenyl)-1,3-dihydro-1-(2,2,2-trifluoroethyl)-2H-1, 4-benzodiazepine-2-thione (Sch 161, quazepam) were investigated in unanesthetized rats and rabbits with chronic electrode implants, and the effects were compared with those of flurazepam and diazepam. In freely moving rats, quazepam at doses of 10 to 30 mg/kg, p.o., induced an increase in drowsy EEG pattern periods: high amplitude slow waves and spindle bursts in the cortical EEG and desynchronization of the hippocampal theta waves. Quazepam at doses of 10 to 30 mg/kg significantly decreased the onset of the drowsy EEG pattern after p.o. administration of rats in a dose-dependent manner, while flurazepam and diazepam reduced it only at higher doses of 20 to 30 mg/kg, p.o. In rabbits, quazepam at doses of 0.5 to 5 mg/kg, i.v., evoked a drowsy EEG pattern similar to that of flurazepam (1 to 5 mg/kg) or diazepam (1 to 2 mg/kg). Quazepam at higher doses caused sedation and a slight muscle relaxation in both rats and rabbits, which were weaker than those of flurazepam or diazepam. In both rats and rabbits, quazepam and flurazepam depressed the EEG arousal response to auditory stimulation but not to electrical stimulation of the midbrain reticular formation or the posterior hypothalamus, while the arousal response to either auditory or brain stimulation was markedly suppressed by diazepam. The recruiting response was not altered by quazepam, flurazepam and diazepam. Quazepam has no effect on the photic driving response to flash light in the occipital cortex of the rabbit, while the response was suppressed moderately by flurazepam and markedly suppressed by diazepam. Quazepam (2 mg/kg) suppressed either the hippocampal or amygdaloid afterdischarges. These results suggest that the EEG effect of quazepam is different to those of flurazepam and diazepam in qualitative aspects and that quazepam is likely to be an effective sleep-promoting drug with slight adverse reactions.

Animals↗
PubMed1987

Effects of methamphetamine on the twitch response in the rat isolated vas deferens.

The effect of methamphetamine, an indirectly acting sympathomimetic amine, on presynaptic adrenergic regulation in isolated rat vas deferens was studied by comparing it with those of tyramine, cocaine and clonidine. These drugs markedly attenuated the twitch response to electrical field stimulation in a concentration-dependent manner. The relative order of potency for the drugs was: clonidine (10(-10)-3 x 10(-8) M) greater than methamphetamine (10(-8)-3 x 10(-6) M) greater than tyramine (10(-7)-10(-4) M) greater than cocaine (10(-6)-3 x 10(-5) M). Only tyramine (3 x 10(-6)-10(-4) M) elicited a concentration-dependent contractile response, which was abolished by prazosin (10(-6) M) and the reserpinization. The twitch inhibitory effect of these drugs was antagonized by yohimbine (10(-8)-10(-6) M). Both the methamphetamine- and tyramine-induced twitch inhibition were partially (about 50%) attenuated by chronic reserpinization (3 mg/kg, s.c., twice) in combination with alpha-methyl-p-tyrosine (200 mg/kg, s.c., twice), while the clonidine-induced inhibition was not affected by this application at all, and the cocaine-induced twitch inhibition was abolished by the reserpinization. Both the clonidine- and tyramine-induced twitch inhibition were not affected by pretreatment with cocaine (10(-5) M) in combination with estradiol (4 x 10(-5) M), whereas the effect of methamphetamine was slightly attenuated. These results suggest that methamphetamine as well as tyramine and cocaine indirectly activates presynaptic alpha-2 adrenoceptors via norepinephrine released from adrenergic nerves to inhibit the twitch response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗
PubMed1987

Suicide inactivation of androstenedione aromatase in human placenta by fluoroethindrone (10 beta-fluoro-17 alpha-ethynyl-19-nortestosterone).

The inhibitory effects of androstenedione aromatase activity in human placenta using fluoroethindrone (10 beta-fluoro-17 alpha-ethynyl-19-nortestosterone), which is a derivative of norethindrone (17 alpha-ethynyl-19-nortestosterone, ENT) and, unlike ENT, is considered to be refractory to aromatization, was investigated in this study. When fluoroethindrone was added to the placental microsomes in the presence of NADPH, androstenedione aromatase activity in the placental microsomes was decreased time dependently and dose-dependently by fluoroethindrone compared with the samples without NADPH. This finding suggests that fluoroethindrone acts as a suicide substrate for androstenedione aromatase in human placenta.

Aromatase Inhibitors↗
PubMed1986

Aromatization of norethindrone to ethynylestradiol in human adult liver.

Homogenates of human adult liver are capable of aromatizing norethindrone (17 alpha-ethynyl-19-nortestosterone) to ethynylestradiol (17 alpha-ethynylestradiol). The evidence of ethynylestradiol formation was obtained using a Bio-Rad AG1-X2 column, thin layer chromatographies and co-crystallization. Neither acid nor base was used in any step in product identification.

Adult↗