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Biomedical subjects

S Usuki

Publications and source records attributed to S Usuki.

At least 73 records · Page 4Linked to original sources

Increased maternal plasma concentration of endothelin-1 during labor pain or on delivery and the existence of a large amount of endothelin-1 in amniotic fluid.

The concentration of endothelin-1 (ET-1) in plasma and amniotic fluid from normal pregnant women was determined by a sensitive sandwich-enzyme immunoassay system, established recently. The plasma ET-1 level increased gradually during normal pregnancy as the pregnancy advanced, the levels (0.40 +/- 0.02 pmol/l, n = 45) being significantly (p less than 0.05) higher after 29 weeks of gestation than those (0.32 +/- 0.01 pmol/l, n = 30) before 28 weeks of gestation. The plasma ET-1 level during labor pain was significantly higher (0.59 +/- 0.06 pmol/l, n = 10) than that (0.40 +/- 0.02 pmol/l, n = 45) in the 3rd trimester of pregnancy without labor pain (p less than 0.02). Moreover, a high level of ET-1 (17.38 +/- 0.25 pmol/l, n = 18) was detected in amniotic fluid on term delivery. The ET-1 level in amniotic fluid was significantly higher than the levels in maternal and umbilical cord plasma (p less than 0.001 and p less than 0.001, respectively). After delivery the maternal ET-1 level decreased gradually and 2 day postpartum ET-1 levels reached the normal non-pregnant level.

Adult↗

Hachimijiogan treatment is effective in the management of infertile women with hyperprolactinemia or bromocriptine-resistant hyperprolactinemia.

Twenty-seven infertile women with hyperprolactinemia were treated with Hachimijiogan (5.0 to 10.0 g/day), Chinese herbal medicine. In 15 out of 18 patients, who were treated with Hachimijiogan, the serum prolactin levels dropped to 19.4 +/- 10.5 ng/ml during Hachimijiogan treatment, and the levels in 8 patients remained essentially unchanged during 6 months after the cessation of Hachimijiogan treatment. Three patients with 100 to 300 ng/ml did not drop to the level below 30 ng/ml. Four of 6 patients with amenorrhea ovulated. Eleven patients conceived and delivered normally. The hormonal profiles during or after pregnancy were normal. These results indicate that Hachimijiogan is a new safe treatment for hyperprolactinemic women.

Adult↗

Relation between regional contractile dynamics and myocardial lesions in patients with hypertrophic cardiomyopathy.

To investigate the influence of wall hypertrophy and myocardial lesions on the regional contractile dynamics of the left ventricle (LV) in patients of hypertrophic cardiomyopathy (HCM), we obtained the thicknesses of the ventricular septum (VS) and posterior wall at end-diastole and systole (E.Td, E.Ts) from echocardiograms made before death for 11 patients of HCM and 6 patients of secondary concentric hypertrophic heart disease (SHH), and the percent regional systolic wall thickening normalized by that of 15 normal controls (%NRWT). We then compared the %NRWT with the pathological wall thickness (P.T.), myocyte diameter (MD), and percent areas of fibrosis (%F) and disarray (%D) in specimens of the corresponding portion from each autopsied heart. The %NRWT in the VS of HCM patients was significantly less than that in SHH patients. All of the MD, %F and %D in the LV wall of HCM patients were significantly greater than those in SHH patients. The %NRWT in the LV wall of HCM patients and SHH patients correlated inversely with the E.Td (r = -0.53, p less than 0.02 and r = -0.70, p less than 0.02, respectively), but not with the E.Ts or P.T. The %NRWT in the LV wall of HCM patients had an inverse correlation with the %F (r V -0.59, p less than 0.005). Furthermore, that in the VS had an inverse relationship with the %D (r = -0.63, p less than 0.05). Thus, it is suggested that not only LV hypertrophy, but also LV myocardial lesions affect the abnormality of the regional LV contractile dynamics in HCM patients. In addition, observation of the regional contractile dynamics by echocardiography may be useful for speculating on myocardial lesions associated with this disease.

Adult↗

[Secretary sialidase activity and GM3 ganglioside].

The sialidase activities with GM3 ganglioside and sialyllactitol were demonstrated in the conditioned medium of human fibroblasts. pH versus activity profiles of conditioned medium with GM3 as substrate suggested the presence of two sialidases with optimal activities at pH 4.5 and pH 6.5. The GM3 sialidase activity at pH 6.5 was suppressed in the medium of contact-inhibited cells. This sialidase may function in the metabolism of cell surface GM3 since there was a selective loss of labeled sialic acid from GM3 at different times of incubation after pulse-labeling with a radioactive sialic acid precursor ([3H]N-acetyl-mannosamine) and a radioactive ceramide precursor ([14C]serine). In addition, a sialidase inhibitor, 2-deoxy-2, 3-dehydro-N-acetyl-neuraminic acid (NeuAc-2-en) resulted in a reversible growth inhibitory effect and the suppression of the sialidase activity in the medium. We have speculated that GM3 hydrolysis on the cell surface by the sialidase may be coordinated with the cell cycle and may be at its maximum during early in the G1 phase.

Cell Cycle↗

Metabolic fate of the new Ca++-channel blocking agent (+)-(2S,3S)-3-acetoxy-8-chloro-(2-(dimethylamino)ethyl)-2,3-dihydro- 2-(4-methoxyphenyl)-2,5-benzothiazepin-4-(5H)-one maleate. Distribution, excretion and protein binding in rats and dogs.

Distribution, excretion and protein binding of (+)-(2S,3S)-3-acetoxy-8-chloro-(2-(dimethylamino)ethyl)-2,3-dihydro- 2-(4-methoxyphenyl)-2,5-benzothiazepin-4-(5H)-one maleate (TA-3090) in rats and dogs were investigated after oral (30 mg/kg (rats), 2 mg/kg(dogs] and intravenous (3 mg/kg (rats), 0.2 mg/kg (dogs) administration of 14C-TA-3090. Plasma level of radioactivity in rats reached plateau (6.04 micrograms equiv. of TA-3090 free base/ml) 1 h after oral administration. The plateau level continued at least up to 6 h. The plasma concentration of the unchanged drug (free base) reached the maximum (425 ng/ml) at 45 min after oral administration, and then decreased with a half-life of 1.16 h. Plasma level of radioactivity after intravenous administration to rats rose gradually up to 1 h and thereafter it was kept constant for 6 h. Plasma concentration of the unchanged drug decreased with half-lives of 0.43 h (alpha phase) and 1.33 h (beta phase) after intravenous administration. In dogs, the peak level of plasma radioactivity after oral administration was 227 ng/ml at 1 h. The Cmax, Tmax and t1/2 of unchanged drug were 31 ng/ml, 1.34 h and 4.13 h, respectively. The plasma levels of total radioactivity and unchanged drug after intravenous administration to dogs were 146 and 142 ng/ml at 1 min, respectively. The t1/2 of the plasma radioactivity were 0.02 h (alpha) and 4.02 h (beta). Those of unchanged drug were 0.03 h (alpha) and 1.66 h (beta).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Genesis of systolic anterior motion (SAM) of the mitral valve in patients with aortic regurgitation].

This study was performed to evaluate the incidence and genesis of systolic anterior motion (SAM) of the mitral valve apparatus in patients with aortic regurgitation (AR). The study population consisted of 44 patients with non-rheumatic AR, without significant aortic stenosis or mitral regurgitation. The presence and location of SAM in the short-axis view were determined by M-mode echocardiography guided by two-dimensional echocardiography. The extent and direction of the regurgitant jet were decided by pulsed or two-dimensional Doppler echocardiography. SAM was observed in 21 (48%) of the 44 patients, and it was more frequently observed in patients with an etiology of aortic valve prolapse or annuloaortic ectasia than in those of other etiology (10/14 vs 10/30; p less than 0.05). Twenty-eight patients whose regurgitant jet was directed posteriorly and impinged on the mitral valve apparatus had a significantly higher incidence of SAM than did the other 16 patients (18/28 vs 3/16; p less than 0.01). In eight of 10 patients in whom the direction of the regurgitant jet could be precisely observed by two-dimensional Doppler echocardiography. SAM was observed at the place where a regurgitant jet was directed along the anterior mitral valve in the short-axis view. M-mode measurements (LVDd, LVDs, %FS, LVDd-LVDs) of the patients with SAM had greater values than those of patients without SAM.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Growth control of human foreskin fibroblasts and inhibition of extracellular sialidase activity by 2-deoxy-2,3-dehydro-N-acetylneuraminic acid.

Normal human fibroblasts have two extreme modes of existence in culture, quiescent and proliferative. The growth and division of these cells are usually well regulated by the action of various endogenously generated stimulators and inhibitors. We have speculated that an extracellular sialidase may be involved in the regulation of growth and that inhibition of this activity might decrease or abolish cell growth. To test this hypothesis, we have incubated preconfluent cultures of fibroblasts in the presence and absence of a potent sialidase inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid. Treatment of cells with this inhibitor resulted in the inhibition of an extracellular sialidase activity for up to 24 h and had a marked growth inhibitory effect in a concentration-dependent manner. The effect of the inhibitor on cell proliferation was specific and reversible. During a chase period of 48 h after pulse labeling cells with [3H]N-acetylmannosamine and [14C]serine, there was a 15% decrease of [3H]sialic acid in the membrane-bound GM3 with 80 microM inhibitor in the medium, as compared with a 32% decrease in the controls. Our results suggest that an extracellular sialidase may participate in cell-surface modifications that accompany (or control) the changes observed when cells traverse the cell cycle, from the quiescent to the proliferative phase.

Cell Division↗

Sialidase activities of cultured human fibroblasts and the metabolism of GM3 ganglioside.

Free sialic acid has been found in the cell-conditioned medium of human foreskin fibroblasts. It is proposed that the accumulation of extracellular sialic acid may result from the hydrolysis of GM3 ganglioside on the cell surface of these fibroblasts. Sialidase activities with GM3 ganglioside and sialyllactitol as substrates were demonstrated in cell-conditioned medium, and the levels of their activities correlated positively with cell density. The GM3 sialidase activity at pH 4.5 was 4.1 and 38 pmol/h/ml of medium at sparse and confluent densities, respectively; the corresponding activities with sialyllactitol as the substrate were 12 and 75 pmol/h/ml of medium (pH 4.5). The pH versus activity profiles with GM3 as the substrate suggested the presence of a second sialidase with an optimal activity at pH 6.5 in the conditioned medium of preconfluent cells. This activity was virtually absent in the medium of contact-inhibited cells and could not be assayed with sialyllactitol as the substrate. The turnover of cell surface GM3 was assessed by pulse labeling human foreskin fibroblasts with a radioactive precursor of sialic acid ([1-14C]N-acetylmannosamine) and a radioactive precursor of ceramide ([3,3-3H2]serine). During a chase period of 24 h turnover of the doubly labeled cellular GM3 was observed; there was a loss of about 35% of the 14C-labeled sialic acid without any measureable loss of 3H-labeled ceramide from GM3. We have speculated that the enzyme-catalyzed removal of sialic acid from the GM3 ganglioside on the extracellular aspect of the plasma membrane may be a necessary event involved in the modulation of cell growth.

Carbon Radioisotopes↗

Deoxyribonucleic acid polymerase alpha activity in the endometrium of the human uterus during the menstrual cycle.

Deoxyribonucleic acid polymerase alpha (a replicative enzyme of cellular deoxyribonucleic acid) activity in the endometrium of the human uterus changed in parallel (p less than 0.001) with the concentration of estrogen in serum during the proliferative phase of the menstrual cycle. This suggests that estrogen stimulates cell proliferation via regulation of the enzyme activity.

Adult↗

Effects of Tokishakuyakusan and its components on rat corpus luteum function in vitro.

27-day-old female rats received 20 IU PMS and 56 hours later, 40 IU hCG. Seven days after hCG treatment, the resected ovaries were perifused with NIH-LH, Tokishakuyakusan (TJ-23) or its components. LH and TJ-23 increased progesterone in media and LH was more effective than TJ-23. Hoelen, Peony root, Alisma rhizome and Japanese angelica root also augmented progesterone. 17 alpha-hydroxyprogesterone and 20 alpha-hydroxyprogesterone were not stimulated by TJ-23. These results suggest that TJ-23 stimulates corpora lutea to secrete progesterone without direct luteotropic or luteolytic effect and that the effect may be attributable to Hoelen, Peony root, Alisma rhizome or Japanese angelica root.

Animals↗

Tokishakuyakusan stimulates cyclic adenosine 3',5'-monophosphate accumulation and progestin production by corpora lutea.

The effect of Tokishakuyakusan (TS) on rat corpora lutea was examined in vivo and in vitro. In an in vivo study, TS stimulated cyclic adenosine 3',5'-monophosphate (cyclic AMP) accumulation and steroidogenesis by corpora lutea, induced by PMS and hCG. In an incubation study, TS increased cyclic AMP accumulation and progesterone secretion. These results suggest that TS stimulates the corpora lutea to produce progestins via the mediation of cyclic AMP.

Animals↗

Hachimijiogan and Tokishakuyakusan enhance deoxyribonucleic acid alpha-nucleotidyltransferase activity in relationship to DNA synthesis by ovarian follicles via a cyclic AMP system.

The ovaries resected from twenty-nine day old female rats primed with 10 IU of PMS for 48 hours were incubated for 120 minutes with 2-20 micrograms/ml of Hachimijiogan (HZ) and Tokishakuyakusan (TS). The animals in another group were injected intravenously with 20 micrograms of HZ and TS 48 hours after PMS injection, and 20 minutes later decapitated. Deoxyribonucleic acid (DNA) alpha-nucleotidyltransferase activity and cyclic AMP accumulation in ovarian tissue were significantly increased by HZ and TS. These results suggest that HZ and TS enhance DNA alpha-nucleotidyltransferase activity via cyclic AMP by ovarian follicles.

Animals↗

Hachimijiogan produces testosterone in adult rat testes.

The effect of Hachimijiogan (HZ) and Keishibukuryogan (KB) on the steroid production in rats was examined in vivo and in vitro. In an in vivo study, HZ stimulated the testes from ten-week old male rats to produce testosterone, whereas KB decreased the tissue testosterone concentrations. The delta 4-androstenedione and estradiol-17 beta (E2) showed no significant changes. In an incubation study, HZ also stimulated the testosterone production. The data suggested that HZ produces testosterone in rat testes. The role of KB is questionable.

Androstenedione↗

Blended effects of herbal components of tokishakuyakusan on rat corpus luteum function in vivo.

The effect of herbal components of Tokishakuyakusan on progestin levels in serum and ovarian tissue from rats treated with PMS and hCG was examined in vivo. Hoelen + peony root + Japanese angelica root increased progesterone/20 alpha-OHP ratio in serum, and hoelen or peony root also increased the ratio in ovarian tissue, while atractylodes lanceae rhizome or hoelen + atractylodes lanceae rhizome decreased the ratio in serum and ovarian tissue. These data suggested that hoelen or peony root has a luteotropic effect but that atractylodes lanceae rhizome develops luteolysis. Furthermore, the data indicated a blended effect of herbal components of Tokishakuyakusan on the corpus luteum.

Animals↗

Metabolism of diltiazem. I. Structures of new acidic and basic metabolites in rat, dog and man.

The metabolites of diltiazem in the urine of rats, dogs and man and rat bile were investigated. New metabolites including six acidic metabolites (A1-A6) and four basic metabolites (M9, MB, MC, MD) were isolated by high performance liquid chromatography and their structures were characterized by gas chromatography-mass spectrometry. Acidic metabolites A1, A2, A3, A4 and basic metabolite MD identified by comparing their properties with the synthetic compounds; (+)-(2S, 3S)-2-(4-methoxyphenyl)-3-acetoxy-4-oxo-2,3,4,5-tetrahydro-1,5- benzothiazepin-5-acetic acid (A1), 3-deacetyl-A1 (A2), O-demethyl-A1 (A3), O-demethyl-3-deacetyl-A1 (A4) and N-didemethyl-diltiazem (MD). All acidic metabolites have a CH2COOH group which may be formed by oxidative deamination of the CH2CH2N(CH3)2 group of diltiazem.

Animals↗