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Biomedical subjects

H Hatakeyama

Publications and source records attributed to H Hatakeyama.

At least 55 records · Page 3Linked to original sources
PubMed1995

Production of aldosterone in isolated rat blood vessels.

Angiotensin I (Ang I), Ang II, angiotensinogen, and renin are formed locally in the vasculature. We undertook this study to determine whether the rat mesenteric artery produces aldosterone and to investigate the effects of adrenalectomy, an angiotensin-converting enzyme inhibitor, Ang II, or potassium on aldosterone production in vascular tissue. Isolated rat mesenteric arteries were perfused with Krebs-Ringer solution for 4 hours. The perfusate was collected and chromatographed in a reversed-phase high-performance liquid chromatographic (HPLC) system. The fraction corresponding to synthetic aldosterone was collected and analyzed by mass spectrometry. The aldosterone concentration in the perfusate from the adrenalectomized rats and rats treated with an angiotensin-converting enzyme inhibitor was measured using radioimmunoassay after HPLC separation. The mass spectra of synthetic aldosterone and aldosterone isolated from the perfusate of rat mesenteric arteries were identical. Aldosterone production in the mesenteric arteries of adrenalectomized rats was increased and of rats treated with an angiotensin-converting enzyme inhibitor was reduced compared with that of controls. Ang II (1.9 x 10(10) mol/L) and potassium (6.0 mmol/L) increased aldosterone production in mesenteric arteries. This study shows that the rat mesenteric artery produces aldosterone and that the intravascular renin-angiotensin-aldosterone system may contribute to vascular tone.

Adrenalectomy↗
PubMed1994

Vascular aldosterone. Biosynthesis and a link to angiotensin II-induced hypertrophy of vascular smooth muscle cells.

Mineralocorticoids have been suggested to act on blood vessels, leading to increased vasoreactivity and peripheral resistance. However, the site of their production has so far been believed to be only the adrenal cortex. Here, we show direct evidence that vascular cells per se are aldosteronogenic, possessing their own system that responds to the steroid. Using polymerase chain reaction after reverse transcription, the CYP11B2 mRNA encoding the key enzyme for the biosynthesis of aldosterone was detected in both endothelial cells and smooth muscle cells cultivated from human pulmonary artery. The aldosterone receptor (type 1 mineralocorticoid receptor) gene was also found to be expressed in smooth muscle cells and, to a lesser extent, in endothelial cells. CYP11B2 gene expression in smooth muscle cells was stimulated by angiotensin II, the effector peptide of the renin-angiotensin system. Furthermore, the angiotensin II-induced increase in [3H]leucine incorporation in smooth muscle cells was significantly enhanced by aldosterone but inhibited by ZK 91587, a type 1 mineralocorticoid receptor antagonist. This may indicate that vascular aldosterone participates in the angiotensin II-induced hypertrophy of vascular smooth muscle cells. The present study therefore provides the starting point for a novel understanding of the molecular basis of vascular remodeling and hypertension.

Aldosterone↗
PubMed1994

Decreased activity of 11 beta-hydroxysteroid dehydrogenase in mesenteric arteries of Dahl salt-sensitive rats.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) activity in mesenteric arteries of 4-week- and 8-week-old Dahl rats was determined to evaluate the relationship between glucocorticoids and norepinephrine in hypertension, 11 beta-HSD activity (expressed as the percentage conversion of 3H-corticosterone (B) to 3H-11-dehydrocorticosterone (A)) significantly decreased in 8-week-old Dahl salt-sensitive (DS) rats (11.4 +/- 1.4%) compared with Dahl salt-resistant (DR) rats (15.3 +/- 0.3%) (p < 0.05) when each group was fed a high-sodium chow (7%) for 4 weeks. There were no significant differences in 11 beta-HSD activity in the 4-week-old DS and DR rats. The enhanced response of mesenteric arteries to norepinephrine was observed only in 8-week-old DS rats. Our results suggest that a decreased 11 beta-HSD activity in the vascular walls contributes to the increased response of norepinephrine by local increment of glucocorticoids in DS hypertensive rats.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

The activities of 5 beta-reductase and 11 beta-hydroxysteroid dehydrogenase in essential hypertension.

The activities of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) and 5 beta-reductase were analyzed in 39 normotensive controls and 128 patients with essential hypertension. The activity of 11 beta-HSD was obtained by dividing the 24-hour urinary tetrahydrocortisone by the sum of tetrahydrocortisol (THF) and allotetrahydrocortisol (aTHF), whereas the activity of 5 beta-reductase was obtained by dividing the 24-hour urinary THF by aTHF. The activity of 5 beta-reductase was significantly lower in essential hypertensives compared with normotensive controls (P < 0.05). However, the activity of 11 beta-HSD did not differ between normotensive controls and essential hypertensives. A positive correlation between the activities of 11 beta-HSD and 5 beta-reductase was observed in essential hypertensives (r = 0.60, P < 0.01). Neither 11 beta-HSD nor 5 beta-reductase activity correlated with indices of renal mineralocorticoid receptor activation, which were assessed by determination of plasma potassium and urinary excretion of sodium as well as potassium. Taken together, these results suggest that disturbances of one of the inactivation pathways of cortisol may contribute to the pathogenesis of hypertension.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Effect of aging on urinary excretion of 18-hydroxycortisol.

The secretion of aldosterone declines with age. We reported that sodium depletion increased urinary excretion of 18-hydroxycortisol (18-OH-F). To elucidate the effect of aging on urinary excretion of 18-OH-F, we measured urinary 18-OH-F in 30 normotensive subjects aged 20-70 yr. There were significant negative correlations between age and urinary excretion of 18-OH-F or of aldosterone (r = -0.49, r = -0.58, P < 0.05, respectively) but not of urinary free cortisol. These results suggest that angiotensin may contribute to chronic regulation of 18-OH-F.

Adult↗
PubMed1994

Gene expression of 11 beta-hydroxysteroid dehydrogenase in the mesenteric arteries of genetically hypertensive rats.

11 beta-Hydroxysteroid dehydrogenase (11 beta-HSD) modulates the access of corticosteroids to their receptors and plays an important role in controlling blood pressure. We determined 11 beta-HSD activity and mRNA levels in the mesenteric arteries of genetically hypertensive rats, the Dahl salt-sensitive hypertensive rat, and compared them with Dahl salt-resistant and Sprague-Dawley rats. 11 beta-HSD activity was expressed as the percent conversion of [3H]corticosterone to [3H]11-dehydrocorticosterone. 11 beta-HSD activity was significantly decreased in the mesenteric arteries of 8-week-old Dahl salt-sensitive hypertensive rats (11.4 +/- 1.4%) compared with Dahl salt-resistant rats (17.4 +/- 1.4%) or Sprague-Dawley rats (18.0 +/- 1.5%) of the same age (P < .05). There were no significant differences in 11 beta-HSD activity between 4-week-old Dahl salt-sensitive hypertensive and Dahl salt-resistant rats of the same age (15.3 +/- 1.3% and 15.1 +/- 1.9%, respectively). The concentration of 11 beta-HSD mRNA in the mesenteric arteries of 8-week-old Dahl salt-sensitive hypertensive rats was significantly lower than in Dahl salt-resistant or Sprague-Dawley rats of the same age (P < .05). There were no significant differences in the concentration of 11 beta-HSD mRNA in the mesenteric arteries of 4-week-old Dahl salt-sensitive hypertensive rats, Dahl salt-resistant rats, and Sprague-Dawley rats. These results indicate that 11 beta-HSD in the vascular wall may play a role in the pathogenesis of hypertension in this rat model.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1994

Synthesis of corticosterone in the vascular wall.

Extra-adrenal steroid 21-hydroxylation and 11 beta-hydroxylation occur in a variety of human tissues. This study was undertaken to determine whether the rat mesenteric artery produces corticosterone and to demonstrate the CYP11B1 mRNA in the vascular tissue. Isolated rat mesenteric arteries were perfused with Krebs-Ringer solution for 4 h. The perfusate was collected and chromatographed in a reverse-phase HPLC system. The fraction corresponding to synthetic corticosterone was collected and analyzed by mass spectrometry. The concentration of corticosterone in the perfusate from the adrenalectomized rats was measured using radioimmunoassay after separation with the HPLC system. The mass spectra of synthetic corticosterone was identical with corticosterone isolated from the perfusate of the rat mesenteric arteries. The radioactive peak of corticosterone was detected in the perfusate after perfusing the mesenteric artery with Krebs-Ringer solution containing [14C]-pregnenolone. The expression of CYP11B1, 11B2, and 11A mRNA was detected in the mesenteric artery using a RT-PCR. The production of corticosterone in the vascular wall was increased in the adrenalectomized rats compared with that of the controls. This study shows that the rat mesenteric artery produces corticosterone, and the corticosterone synthase is existed in the vasculature.

Animals↗
PubMed1994

Angiotensin II up-regulates the expression of type A endothelin receptor in human vascular smooth muscle cells.

Using vascular smooth muscle cells, the effect of angiotensin II on endothelin receptor regulation was examined. Vascular smooth muscle cells cultivated from human pulmonary artery exhibited high affinity receptors for endothelin-1. When the cells were exposed to angiotensin II, the number of receptors was found to be increased without any change in their affinity. The ligand binding was effectively displaced by BQ123, a selective antagonist for type A endothelin receptor, but not by S6c, a selective ligand for type B receptor, in both control and angiotensin II-treated cells. The level of mRNA coding for the type A receptor was elevated in the latter. These results indicate that angiotensin II up-regulates type A endothelin receptors in human vascular smooth muscle cells through an increase in their corresponding mRNA, suggesting a link between the renin-angiotensin and the endothelin systems.

Angiotensin II↗
PubMed1993

Epidemiologic analyses of spatial clustering of bovine ephemeral fever outbreaks. I. Application of the negative binomial distribution.

An epidemic that propagates through a population results in a contagious spatial pattern. The incidence per farm of bovine ephemeral fever (BEF) outbreaks in the 22 areas of Fukuoka Prefecture in 1988 was well explained by the negative binomial distribution, which is generally considered, as the clustering of the outbreaks. Furthermore, the clustering was analyzed with three categories of vaccination rate (No. 1-40%, and 40-80%). As a result, the no vaccination and high vaccination rate (41-80%) groups tended to shift to similarly the Poisson distribution. It may be speculated that an insufficient vaccination control of the BEF was influenced with the clustering.

Animals↗
PubMed1992

Serological studies of antigenic similarity between Japanese spotted fever rickettsiae and Weil-Felix test antigens.

Acute and convalescent-phase sera obtained from 10 patients infected with a Japanese strain of spotted fever group (SFG) rickettsia were tested by the indirect immunoperoxidase test, the Weil-Felix test, an enzyme-linked immunosorbent assay (ELISA), and immunoblotting. By the Weil-Felix test, the reactivity of these sera to the OX2 antigen was higher than those to the OX19 antigen, as is the case with sera from persons infected with other SFG rickettsiae. By ELISA, the titers of immunoglobulin M (IgM) antibodies against OX2 corresponded to the Weil-Felix test titers of these sera against OX2 but not to the titers obtained with IgG antibodies. The reactivity of the patient sera with the OX2 antigen in the Weil-Felix test was probably due to IgM antibodies against antigens which OX2 and SFG rickettsiae have in common. By immunoblotting tests, both IgG and IgM antibodies from the patient sera reacted with lipopolysaccharides from SFG rickettsiae and Proteus strain OX2. These results may show that these lipopolysaccharides contain similar epitopes.

Antibodies, Bacterial↗
PubMed1992

A novel class of platelet activating factor (PAF) antagonists. II. Modification of the 2-position of the glycerol backbone of PAF-sulfonamide isosteres.

In a continuing effort to obtain more potent platelet activating factor (PAF) antagonists, we tried to synthesize a series of PAF-sulfonamide isosteres in which the substituent at the 2-position was modified to an acetoxy equivalent other than the methoxy group. These modifications produced highly active PAF antagonists. Compound 3-[2-(5-methyl-2H-tetrazol-2-yl)-3-(octadecylcarbamoyloxy) propylaminosulfonyl]propylquinolinium iodide (52) showed the most potent activity in the in vitro inhibitory effect on PAF-induced platelet aggregation in rabbit platelet-rich plasma (IC50 = 125 nM) and also in the in vivo protective effect on PAF-induced lethality in mice, with prolonged duration of action. Optically active enantiomers of this compound were synthesized and the (S)-(-)-isomer (IC50 = 87 nM) was found to be three times more potent that the (R)-(+)-isomer (IC50 = 289 nM), clearly exemplifying the enantioselectivity in the PAF-antagonist action of this novel compound.

Animals↗
PubMed1992

Establishment of an IL-2-dependent bovine T cell line and an assay of lymphocyte response inhibition in leukemic bovine serum.

The mechanism of immunosuppression induced by leukemic bovine serum was investigated with respect to lymphokine reactions using an interleukin 2 (IL-2)-dependent bovine T cell line generated from bovine peripheral blood lymphocytes (PBLs). The suppression of concanavalin A (con A)-induced PBL blastogenesis was observed at a high rate in leukemic cattle sera. The growth of IL-2-dependent bovine T cells and IL-2 production from con A-induced bovine PBLs were also inhibited by these sera, and particularly, the latter was correlated significantly to the degree of lymphocyte blastogenesis by the mitogen. Therefore, the lesser sensitivity of lymphocytes to IL-2 and the reduced IL-2 production by activated lymphocytes seem to play a role in suppressing the lymphocyte reaction.

Animals↗
PubMed1992

The reactivity between rickettsiae and Weil-Felix test antigens against sera of rickettsial disease patients.

Of the sera which were positive to Rickettsia tsutsugamushi by indirect immunoperoxidase test, approximately 80% sera were positive to a Proteus OXK antigen by Weil-Felix test at 10 or more days after the onset of fever, while only 10% sera were positive within 9 days from the onset of fever. In ELISA using the OXK antigen, almost all of the paired sera of tsutsugamushi disease (TD) patients increased on the IgM antibody titres with the rise of their titres by Weil-Felix test, whereas the IgG antibody titres of these sera were unrelated with the titres of Weil-Felix test. We suspect that the reactivity of TD patients sera to the OXK antigen in Weil-Felix test was derived from the reactivity of the IgM antibody against the OXK antigen common with R. tsutsugamushi. The patient sera infected with a Japanese isolate of spotted fever group rickettsia (SFGR) cross-reacted with the Thai Tick Typhus (TTT) strain of SFGR by indirect immunoperoxidase test. In Weil-Felix test, the reactivity of these sera to OX2 antigen were higher than that to OX19 antigen, like the sera infected with other SFGR, except of R. rickettsii. These sera also reacted with TTT and OX2 antigens by ELISA. The titres of IgM antibody against OX2 antigen in the sera in ELISA were in parallel with the titres of the sera against OX2 antigen in Weil-Felix test, but not the titres of IgG antibody. We suggest that the reactivity of the patient sera infected with SFGR to OX2 antigen of Weil-Felix test is dependent on the IgM antibody.

Antigens, Bacterial↗
PubMed1991

Electron microscopic studies on the in vitro proliferation of spotted fever group rickettsia isolated in Japan.

Rickettsia was isolated from a patient with Japanese spotted fever, and its proliferation in cultured green monkey kidney cells was observed by electron microscopy. In the course of this study, we observed fusion of infected cells to uninfected cells which may be a way of spreading the rickettsiae from a cell to another. On the other hand, whirlpool-like, multilayer membranous structures, similar to the mesosomes of gram-negative bacteria, were sometimes seen in the rickettsial cells. The other profiles common to the other rickettsiae in spotted fever group were observed, such as the electron-lucent halo zone around the rickettsiae, and external fibrous materials on their surface, but intranuclear multiplication was rarely observed.

Cell Division↗
PubMed1990

[A case of malignant neuroepithelioma in the retroperitoneum].

Reported is a case of a malignant neuroepithelioma in the retroperitoneum. The patient was a 37-year-old male suffering from lumbago and edema of the lower extremities. After ultrasonography and a CT scan, a diagnosis of a retroperitoneal tumor was made and a surgical resection of the tumor was performed in October, 1985. The subsequent pathological diagnosis was malignant neuroepithelioma which showed epithelioid cell clusters that stained positively to NSE. Eleven months later, metastatic tumors were seen present in the lungs and the liver though they regressed markedly after adjuvant chemotherapy with ADM, CPM, and VCR. Forty-one months after his first operation, the patient continues to work. In this case, adjuvant chemotherapy has proved effective.

Adult↗
PubMed1989

[In vitro susceptibility of a strain of Rickettsia recently isolated from a case of Japanese spotted fever to chemotherapeutic agents].

The in vitro susceptibilities to five chemotherapeutic agents against a rickettsial strain which was isolated from a case of Japanese spotted fever were determined by cell culture system. Minocycline was the most effective (MIC, 0.15 micrograms/ml) followed by Tetracycline and Demethylchlor tetracycline (0.31 micrograms/ml 0.16 micrograms/ml). Chloramphenicol was less effective (5 micrograms/ml) and Aminobenzyl-penicillin was not effective with the MIC of 10 micrograms/ml or less. Thus, the earlier administration of Minocycline is recommended to clinically suspicious cases of Japanese spotted fever as well as Tsutsugamushi disease.

Anti-Bacterial Agents↗
PubMed1989

Effect of a novel thromboxane A2 receptor antagonist, S-145, on collagen-induced ECG changes and thrombocytopenia in rodents.

The effects of S-145, a newly synthesized thromboxane, A2 (TXA2) receptor antagonist, were studied on collagen-induced changes of electrocardiograms (ECG) in rats and thrombocytopenia in rats and mice. Intravenous injection of collagen induced abnormal ECG changes such as elevation or depression of the ST segment, arrhythmia and in severe cases, cardiac arrest. These changes peaked at 3-5 min and lasted for 10 min. S-145 showed remarkable improvement of the ECG changes by both intravenous and oral administration, and the action lasted over 4 hr with 10 mg/kg, p.o. Reference compounds ONO-3708, dazoxiben and aspirin also improved the ECG changes significantly, but ticlopidine was ineffective. S-145 prevented the collagen-induced thrombocytopenia in rats but did not affect the increase in plasma TXB2 levels. S-145 also prevented collagen-induced thrombocytopenia in mice after either intravenous or oral administration in a dose-dependent manner. The efficacy of S-145 was 4-13 times greater than those of the reference compounds, and the duration of action was over 4 hr with 10 mg/kg, p.o. These results indicate that S-145 is a potent, orally, active and long-lasting TXA2 receptor antagonist, which will be promising as a drug for thromboembolism and ischemic heart disease caused by platelet activation.

Administration, Oral↗