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Biomedical subjects

M Urabe

Publications and source records attributed to M Urabe.

At least 91 records · Page 5Linked to original sources
PubMed1994

Effects of N omega-nitro-L-arginine and capsaicin on neurogenic vasomotor responses in isolated mesenteric arteries of the monkey.

Monkey isolated mesenteric arterial rings denuded of endothelium constricted upon transmural nerve stimulation (TNS) in the absence of active muscle tone. The constriction was potentiated by N omega-nitro-L-arginine (3 x 10(-5) M), but not by the D-enantiomer (3 x 10(-5) M). The potentiation was reversed by L-arginine (3 x 10(-4) M). The neurogenic vasoconstriction of mesenteric arteries was also augmented by capsaicin, but to a lesser extent than that induced by N omega-nitro-L-arginine. Indomethacin (10(-5) M) did not affect TNS-induced vasoconstriction. These findings suggest that nerve-derived nitric oxide or a related substance may play a greater role than do capsaicin-sensitive vasodilator transmitters in neurogenic regulation of mesenteric arterial tone in the monkey. The transmitter mechanisms for vasodilation in mesenteric circulation vary among species.

Animals↗
PubMed1994

Disturbed lipid metabolism in patients with subclinical hypothyroidism: effect of L-thyroxine therapy.

To evaluate whether patients with subclinical hypothyroidism have a disturbance in lipid metabolism, and whether supplemental L-thyroxine (L-T4) therapy would improve their lipid parameters, we measured serum levels of thyroid hormones, TSH and lipid parameters in 34 patients with subclinical hypothyroidism before and 2 months after treatment with L-T4. Before treatment, patients with subclinical hypothyroidism had elevated serum low density lipoprotein cholesterol (LDL-C) concentrations compared with control subjects (P < 0.05). Overall, L-T4 therapy significantly decreased the serum level of TSH (P < 0.01), total cholesterol (TC; P < 0.02), high density lipoprotein cholesterol (P < 0.02), LDL-C (P < 0.05), and the ratio of apolipoprotein B to apolipoprotein A1 (P < 0.05). Lipid values in patients with basal serum TSH levels below 10 mU/l were not affected by L-T4 therapy, whereas serum levels of TC and LDL-C decreases significantly (P < 0.01) in patients with serum TSH levels above 10 mU/l. Thus, the L-T4 treatment appears to have a preventive effect on the disturbance of lipid metabolism in patients with subclinical hypothyroidism, especially in patients with serum TSH levels above 10 mU/l.

Adult↗
PubMed1993

MDBK cells which survived infection with a mutant of influenza virus A/WSN and subsequently received many passages contained viral M and NS genes in full length in the absence of virus production.

From a variant of MDBK cell line carrying the nucleotide sequences specific to a mutant of influenza virus A/WSN, we obtained cDNA clones representing viral M and NS genes in full length by polymerase chain reaction (PCR). The sequence analysis of five cDNA clones each for the respective genes revealed 4 to 10 base changes with M and 2 to 6 with NS compared with the corresponding genes of the original virus, although it was possible that at least some of them were ascribed to the artifacts during reverse transcription or Taq polymerase reaction.

Animals↗
PubMed1993

Persistence of viral genes in a variant of MDBK cell after productive replication of a mutant of influenza virus A/WSN.

The MDBK-R cell line is a variant of the MDBK cell line, which was derived by three consecutive high multiplicity superinfections of MDBK cells with AWBY-140 virus, a mutant of influenza virus A/WSN (H 1N 1). MDBK-R cells are permissive for productive replication of AWBY-140, but resist lysis by the virus and grew normally without producing infectious virus after replication of the mutant occurred there. By polymerase chain reaction (PCR), we demonstrated nucleotide sequences specific to all the 8 genes of AWBY-140 in MDBK-R cells which had been infected with the mutant at a high multiplicity and subsequently received 25 passages. This suggests that the genes of influenza virus mutant persisted in the dividing host cells for a long time after productive infection, when none of the cells was producing virus. We were also able to amplify the M gene related sequence of the mutant from both poly(A)+ and poly(A)- fractions of the RNA extracted from the cells at 27th passage level by PCR, which suggests that the persisting genes were replicated and transcribed, but we failed to demonstrate any viral protein in the cells by Western blotting.

Base Sequence↗
PubMed1993

Transformation of estrone, estradiol, and estrone sulfate in uterine and vaginal isolated cells of fetal guinea pig. Effect of various antiestrogens in the conversion of estrone sulfate to estradiol.

The metabolism of physiological concentrations (5 x 10(-9) M) of [3H]estrone (E1), [3H]estradiol (E2), and [3H]estrone sulfate (E1S) was studied in isolated fetal uterine and vaginal cells of guinea pigs in culture. After 24 hours of incubation in both cells, a large percentage (40-60%) of E1 is converted to E2; however, after incubation of E2, most of the radioactive material (45-65%) corresponds to unchanged E2. Similarly, in the incubation medium the concentration of E2 is significantly higher related to E1 after incubation with E1 or E2. An intense sulfotransferase activity is found for both estrogens, whereas in the culture medium the respective sulfates represent 27-45% of the total radioactive material after incubation with the uterine cells and 15-24% for the vaginal cells. Using E1S, significant hydrolysis is observed in both cells and the analysis of the freed radioactive material indicated a high percentage in E2 (66% in the uterine cells and 71% in the vaginal cells). The conversion of E1S to E2 was strongly decreased by the antiestrogens: tamoxifen, 4-hydroxy-tamoxifen, and ICI 164,384. The inhibitory effect in relation to the incubation with E1S only was 43-66% in the uterine cells and 50-85% in the vaginal cells. The present data suggest that estrogen sulfates can play an important biological role in the target tissues of the fetus, and that the enzymatic mechanisms of the bioavailability of E2 for the biological responses of the hormone can be operated in the target tissue itself.

Animals↗
PubMed1993

Estrogen productivity of endometrium and endometrial cancer tissue; influence of aromatase on proliferation of endometrial cancer cells.

Aromatase, estrone (E1) sulfatase and E1 sulfotransferase activities were examined in endometrium and endometrial cancer tissue preparations. Aromatase and E1 sulfatase activities in endometrial cancer tissues were found to be significantly higher than in normal endometrial tissues. However, E1 sulfotransferase activity did not differ between benign and malignant tissue. We also examined the effect of testosterone (T) on aromatase activity and tritiated thymidine uptake (DNA synthesis) in various cultured cervical or corpus endometrial cancer cell lines (OMC-4, HHUA, Ishikawa, HEC-59). The results demonstrated that only the HEC-59 cell line had high aromatase activity and increased its DNA synthesis in response to T. This increase of DNA synthesis by T was not suppressed by simultaneous addition of cyproterone acetate, but was by tamoxifen. These data suggest that in situ estrogen production in endometrial cancer tissue is biologically important and that aromatase in cancer cells may contribute partially to cell proliferation if androgen substrate is provided.

Aromatase↗
PubMed1991

Search for immunobiological parameters predictive of clinical effects of OK-432 in patients with malignant ascites.

Although OK-432, a potent BRM, has been known to induce the remarkable improvement of clinical conditions in cancer patients through its strong effects on their immune capabilities, no specific immune parameters have been identified to best predict the clinical outcome after the OK-432 treatment. In an attempt to identify early parameters indicative of the clinical effects, we have administered 0.1 mg of OK-432 intraperitoneally to a total of 12 patients with malignant ascites and examined peritoneal fluid and peripheral blood obtained on 4 days before, 1, 3, and 7 days after the OK-432 injection using various immunobiological assays. Four weeks later, clinical improvements were evaluated by the disappearance of malignant cells from and/or substantial decrease in ascites. Four patients (responders) showed the improvements while 8 patients (nonresponders) showed no clinical evidence for improvement. In a few parameters among the many examined, significantly different patterns of changes were noted between responders and nonresponders. Thus, in nonresponder patients MO and T cell population returned to an initial low level after early increases (on days 1 and/or 3), while they remained increased day 1 through 7 in responders. In responder patients, the cytotoxicity of peritoneal mononuclear cells against K562 and Daudi cells were augmented on day 7, but not in nonresponder patients. The in vitro stimulation of the mononuclear cells with OK-432 enhanced the cytotoxic activity and induced the interferon (IFN) production in the responders but not in nonresponders. These parameters will be useful for the early prediction of the expected clinical effects of OK-432.

Adult↗
PubMed1991

Effect of endothelium removal on the vasoconstrictor response to neuronally released 5-hydroxytryptamine and noradrenaline in the rat isolated mesenteric and femoral arteries.

1. The role of the vascular endothelium in the vasoconstrictor response to transmural nerve stimulation (TNS) was studied in isolated ring segments of rat mesenteric and femoral arteries. 2. In both types of artery, TNS (1 to 16 Hz) produced frequency-dependent vasoconstriction, which was abolished by 100 nM tetrodotoxin, 10 microM guanethidine or 10 nM prazosin, indicating that the response was mediated by endogenous noradrenaline (NA) released from noradrenergic nerves. NA-mediated vasoconstriction in response to TNS was significantly potentiated by removal of the endothelium. 3. In the presence of 10 nM prazosin, the reduced vasoconstriction in response to TNS was restored by incubation with 10 microM 5-hydroxytryptamine (5-HT) for 20 min. Restoration of the response to TNS was markedly attenuated by treatment with 10 nM ketanserin, 100 nM tetrodotoxin, or 10 microM guanethidine, indicating that the restored response was mediated by 5-HT released from noradrenergic nerves. Vasoconstriction mediated by 5-HT in response to TNS was not modified by removal of the endothelium. 4. In both types of artery with intact endothelium, treatment with 3 microM methylene blue potentiated the NA-mediated contractile response to TNS, but did not potentiate the 5-HT-mediated response to TNS. 5. In both types of artery, the contractile responses to exogenous NA and 5-HT were potentiated by removal of the endothelium. 6. These results suggest that endothelial cells regulate neurogenic vasoconstriction by releasing endothelium-derived relaxing factor. Furthermore, it appears likely that the response to neuronally released 5-HT is not affected by the endothelium.

Animals↗
PubMed1991

Effect of lithium on function and growth of thyroid cells in vitro.

Lithium has been reported to alter thyroid function and cause goiter in some patients. To explain the mechanism of lithium action in the thyroid gland, we studied the effect of lithium on thyroid function and cell growth in FRTL-5 rat thyroid cells and on de novo thyroid hormone formation in primary cultures of porcine thyroid follicles. TSH-induced iodide uptake was suppressed at 2 mM lithium in both FRTL-5 cells and porcine follicles. In porcine thyroid follicles, iodide uptake stimulated by 8-bromo-cAMP, iodine organification, and de novo thyroid hormone formation were also reduced by lithium; however, 2 mM lithium did not inhibit TSH-induced cAMP production. In FRTL-5 cells, lithium also inhibited forskolin-stimulated iodide uptake. These results suggested that lithium exerts its effect at a step involving cAMP signal transduction rather than inhibiting cAMP production. In both FRTL-5 thyroid cells and porcine follicles, lithium enhanced cell growth in basal states (lacking TSH) and with TSH treatment. In porcine thyroid cells, the protein kinase C activator, tetradecanoyl phorbol-13-acetate, increased cell growth, and lithium had an additive effect with tetradecanoyl phorbol-13-acetate on cell growth. To examine the possibility that the action of lithium was mediated by the protein kinase C pathway, porcine cells were incubated with lithium and H7, a selective protein kinase C inhibitor. Lithium-induced cell growth was suppressed to the basal level by H7. These results suggest that lithium exerts its growth-promoting effect through the protein kinase C system.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1991

[Electroencephalographic and cardiovascular effects of milnaciplan hydrochloride (TN-912), a novel antidepressant].

The electroencephalographic (EEG) and cardiovascular effects of milnaciplan hydrochloride (TN-912) were compared with those of imipramine (IMP) and maprotiline (MPT) in rats, guinea pigs and dogs. In conscious rats with chronic electrode implants, TN-912 (10-100 mg/kg, p.o.) had little effect on either the EEG activity or the EEG arousal response to auditory stimulation (2000 Hz). Both IMP (10-100 mg/kg, p.o.) and MPT (10-100 mg/kg, p.o.) tended to increase the drowsy EEG pattern period in the cortical and hippocampal EEG and inhibited the EEG arousal response to auditory stimulation. In conscious rats with a chronic arterial catheter, TN-912 (100 mg/kg, p.o.) slightly elevated the mean blood pressure (MBP) and decreased the heart rate (HR), while both IMP (10-100 mg/kg, p.o.) and MPT (10-100 mg/kg, p.o.) dose-dependently increased MBP and HR. In anesthetized dogs, i.v. injection of TN-912 (1-10 mg/kg), IMP (0.3-10 mg/kg) and MPT (1-20 mg/kg) produced a dose-dependent fall in MBP. IMP and MPT but not TN-912 dose-dependently increased HR. TN-912 did not show typical effects on femoral blood flow. TN-912 (30 mg/kg) had little effect on lead II electrocardiogram (ECG), while IMP and MPT markedly increased height of the T-wave on ECG. In the in vitro study with the isolated guinea pig atrium, TN-912 caused a slight positive inotropic and negative chronotropic effect, while both IMP and MPT showed marked negative inotropic and chronotropic actions. These results suggest that TN-912 has less EEG effect and cardiac toxicity, indicating that TN-912 may be safe in clinical use.

Animals↗
PubMed1991

Disturbance of thyroidal iodine metabolism in BB/W rat.

To investigate the thyroid function in Bio-Breeding Worcester (BB/W) rats, we have examined the iodine metabolism, serum TSH and thyroid hormone levels in 8- and 16-week-old BB/W and normal Wistar (W) rats. At 8 weeks of age, serum TSH levels were significantly higher in BB/W rats than in W rats, although there was no difference in the serum levels of free T3 and free T4. Furthermore, the thyroidal radioactive iodine incorporation at 48 h was significantly lower in BB/W rats, suggesting that they might have some defects in iodine organification. At 16 weeks of age, serum TSH levels were also significantly higher in BB/W rats than in W rats. Furthermore, serum TSH levels in 16-week-old BB/W rats were significantly higher than in 8-week-old BB/W rats. The thyroid weight was significantly greater in BB/W rats, probably due to the increased serum TSH. The thyroidal radioactive iodine uptake at 48 h and the iodine content in the thyroid homogenates were significantly lower in BB/W rats. These results suggest that BB/W rats have some defect in iodine metabolism resulting in impaired thyroid hormone synthesis.

Animals↗
PubMed1990

Estrone sulfatase activity in human uterine leiomyoma.

Human uterine leiomyoma is a benign tumor and its development is closely related to estrogen. In this study, estrone sulfatase (E1SF) activity and concentrations of estrone (E1) and estrone sulfate (E1S) were measured in endometrial, leiomyoma, and myometrial tissues of the same human uterus (n = 11) with a leiomyoma. E1SF activity in endometrial tissue overlying a leiomyoma was 2.62 +/- 0.29 nmole/hr/mg protein (mean +/- SD), this activity being significantly higher (P less than 0.01) compared with that in normal endometrial tissue (2.0 +/- 0.24 nmole/hr/mg protein). E1SF activity in normal endometrial tissue was significantly higher (P less than 0.001) compared with that in leiomyoma tissue (0.49 +/- 0.82 nmole/hr/mg protein) or myometrial tissue (0.76 +/- 0.10 nmole/hr/mg protein). We also found a significant difference (P less than 0.05) in E1SF activity between leiomyoma tissue and myometrial tissue. On the other hand, the E1 concentration in endometrial tissue overlying a leiomyoma (10.9 +/- 8.9 pg/mg protein) proved to be higher than that in endometrial tissue overlying normal myometrium (1.23 +/- 1.97 pg/mg protein). E1S concentrations in these tissues, however, were 631 +/- 339 and 902 +/- 482 pg/mg protein, respectively, these values showing a trend opposite that of the E1 concentration data. Thus, these results suggest that high E1SF activity and high E1 concentration in the endometrium overlying a leiomyoma may be related to estrogen supply to a uterine leiomyoma node.

Endometrium↗
PubMed1990

Selective aromatase inhibition by pyridoglutethimide, an analogue of aminoglutethimide.

The inhibitory effects of pyridoglutethimide (3-ethyl-3-(4-pyridyl)piperidine-2,6-dione), an analogue of aminoglutethimide, on aromatase and other cytochrome P-450-dependent steroid-metabolizing enzymes were studied in vitro. Pyridoglutethimide and aminoglutethimide showed competitive inhibition of human placental aromatase activity with apparent Ki values of 1.7 and 0.7 mumol/l, respectively. Both pyridoglutethimide and aminoglutethimide inhibited the aromatase activity of uterine leiomyoma and cultured choriocarcinoma Enami cells as well as immunopurified human placental aromatase cytochrome P-450 by more than 90%, with IC50 values of 10-19 and 5-7 mumol/l, respectively. These results might suggest that the inhibitors interacted directly with the aromatase cytochrome P-450 of these tissues. Aminoglutethimide inhibited bovine adrenal cholesterol side-chain cleavage activity with an IC50 value of 40 mumol/l and inhibited 21-hydroxylase activity slightly, but did not inhibit 17 alpha-, 11 beta- and 18-hydroxylase at concentrations up to 100 mumol/l. On the other hand, pyridoglutethimide had no inhibitory effect on any of these enzymes at concentrations up to 50 mumol/l, although it inhibited 11 beta- and 18-hydroxylase slightly at 100 mumol/l. These results indicated that pyridoglutethimide was an aromatase inhibitor of a comparable potency to aminoglutethimide, but that it did not inhibit other steroid hydroxylases.

Aminoglutethimide↗
PubMed1990

[Study on the local estrogen biosynthesis in human uterine leiomyoma].

The growth of uterine leiomyoma is regulated not only by the estrogen levels in blood, but also by estrogen production in the tumor itself. In this study, we investigated both the estrone formation (estrone sulfatase activity) and the transformation from estrone to estrone sulfate (estrone sulfotransferase activity) in human leiomyoma tissue. We compared them with those in the myometrium and endometrial tissues overlying and opposite a uterine leiomyoma node. We also measured the tissue concentrations of estrone, estradiol and estrone sulfate. Estrone sulfatase activity in the uterine leiomyoma was 0.49 +/- 0.08 nmol/h/mg protein (Mean +/- SE), and was lower than that in the myometrial tissue (0.76 +/- 0.09). Moreover, the enzyme activity was higher in the endometrium overlying the leiomyoma node (2.62 +/- 0.29) than in the endometrium opposite to it (2.10 +/- 0.24). On the other hand, estrone sulfotransferase activity in the myoma (20.2 +/- 2.4 pmol/h/mg protein) was higher than in myometrial tissue (16.7 +/- 2.3). The concentrations of estrone and estradiol in leiomyoma tissue were lower than in the tissues surrounding the leiomyoma. The tissue concentration of estrone sulfate was higher in leiomyoma tissues. These results suggest that estrone sulfate is hydrolyzed mainly by estrone sulfatase in the endometrium and myometrium surrounding leiomyoma nodes and the estrone formed may affect the growth of leiomyoma.

Adult↗
PubMed1989

Presynaptic alpha 2-adrenoceptor modulation of 5-hydroxytryptamine and noradrenaline release from vascular adrenergic nerves.

Modulation of the stimulation-evoked release of 5-hydroxytryptamine (5-HT) and noradrenaline (NA) by presynaptic alpha 2-adrenoceptors was characterized in the perfused mesenteric vascular bed of the rat. The vasoconstrictor response to periarterial nerve stimulation (PNS; 8 Hz), previously abolished in the presence of 30 nM prazosin, was restored after 15 min treatment with 10 microM 5-HT, without a significant effect on the pressor response to 1 nmol of infused NA, which was previously abolished with prazosin. The restored pressor response to PNS was abolished by 100 nM tetrodotoxin and 100 nM ketanserin. Clonidine (1-10 microM) in the presence of prazosin induced a dose-dependent potentiation of the restored pressor response to PNS after 5-HT treatment while BHT 920 (10 nM-1 microM) and 100 nM clonidine inhibited the restored response. In the presence of 100 nM phentolamine, the restored pressor response to PNS was not altered by clonidine, but was inhibited by BHT 920. The PNS (8 Hz)-evoked tritium release in a preparation labeled with [3H]5-HT was facilitated by clonidine (100 nM-10 microM) while BHT 920 (10 nM-1 microM) and cocaine (1-10 microM) reduced the release. Yohimbine (1 microM) antagonized the effects of clonidine and cocaine but not of BHT 920 on the PNS-evoked tritium release. In the preparation labeled with [3H]NA, clonidine did not alter the PNS-evoked tritium release while BHT 920 inhibited it and cocaine facilitated it. Yohimbine did not antagonize the effect of BHT 920.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗