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Biomedical subjects

N Minami

Publications and source records attributed to N Minami.

At least 181 records · Page 10Linked to original sources

Putative involvement of protein kinase C in proliferation of human myeloid progenitor cells.

The effects of two different potent inhibitors of protein kinase C, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7) and staurosporine on human myeloid (CFU-C) and late erythroid progenitor cells (CFU-E) were studied using an in vitro clonal assay. Our objective was to determine whether protein kinase C has a role in signal transduction related to proliferation of these committed progenitor cells. The presence of H-7 or staurosporine led to an inhibition of colony formation stimulated by crude colony-stimulating factor (CSF), interleukin-3 (IL-3), granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF), or macrophage CSF (M-CSF) in a dose-dependent manner. N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004), a weaker analog of H-7, did not inhibit proliferation of CFU-C. Neither H-7 nor staurosporine had any effect on CFU-E formation. H-7 and staurosporine dose-dependently inhibited the protein kinase C from K562 cells. The potential of these compounds to inhibit proliferation of CFU-C correlated well with the magnitude of their inhibition of protein kinase C from K562 cells. The inhibition of proliferation of CFU-C appears to relate to the potential of these compounds to inhibit protein kinase C. Thus, activation of protein kinase C is presumably involved in the proliferation of CFU-C, and the regulatory system of CFU-E appears to differ from that of CFU-C.

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

[A cyclic thrombocytopenia associated with Sjögren syndrome].

A 51-year-old women in menopause was admitted because of intermittent purpura. She was diagnosed as having cyclic thrombocytopenia. One platelet cycle lasted for about 22 days with platelet count fluctuating from 1.0 X 10(4)/microliters to 31.0 X 10(4)/microliters. The platelet-associated immunoglobulin was correlated with the platelet cycle. The rheumatic factor, antinuclear antibody, antimicrosome antibody, anti-thyroglobulin antibody and platelet binding immunoglobulin were all positive but did not fluctuate during the cycle. The platelet life-span was shortened. The mean platelet volume fluctuated during each cycle. The lipid emulsion test was prolonged. Symptoms of Sjögren syndrome and purpura appeared at the same time. It was strongly suggested that purpura was caused by cyclical destruction of platelets by reticuloendothelial system.

Autoantibodies↗

Exogenous glucocorticoid eliminates or reverses circadian blood pressure variations.

The effect of glucocorticoid on circadian variations of blood pressure was examined. In untreated patients with essential hypertension, a clear nocturnal fall in blood pressure and heart rate was observed and this was unaffected by combined treatment with antihypertensive drugs. The circadian blood pressure variation in patients with chronic glomerulonephritis (CGN) not receiving glucocorticoid treatment was essentially the same as that in patients with essential hypertension. In both groups there was a positive correlation between blood pressure and heart rate. On the other hand, in patients with CGN and systemic lupus erythematosus (SLE) who were treated with glucocorticoid, there was no nocturnal fall in blood pressure, and often a significant rise. In these patients the blood pressure was lowest in the afternoon and began to rise from then, and during the night, attaining a peak level in the morning. Despite this changed pattern of blood pressure variations, the heart rate in these patients was clearly reduced at night. In 10 patients with CGN and SLE, circadian rhythm of blood pressure and heart rate was examined before and during treatment with prednisolone (40.2 +/- 17.0 mg/day for 58.0 +/- 19.4 days, mean +/- s.d.). Prednisolone abolished the nocturnal fall of blood pressure, while the nocturnal fall of heart rate remained. There was no correlation between blood pressure and heart rate in patients with glucocorticoid treatment. These results suggest that the circadian blood pressure variation is influenced by the hypothalamo-pituitary-adrenal axis, probably through its action on the autonomic nervous system.

Adult↗

Influence of age on epidermal growth factor receptor level in the rat brain.

The influence of age on 125I-epidermal growth factor (EGF) binding to rat brain plasma membranes was investigated. The specific binding of EGF to membranes decreased gradually with age in both male and female rats. There was no significant difference in the specific binding between males and females. Scatchard analysis of the binding data showed that the decrease in EGF binding with age was due to a decrease in the number of EGF receptors.

Aging↗

Development of hamster two-cell embryos in the isolated mouse oviduct in organ culture system.

Hamster early two-cell embryos developed to the expanded blastocyst stage within the isolated mouse ampulla maintained in organ culture system. Mouse ampullae isolated at different times after treating the mice with human chorionic gonadotropin (hCG) (0-72 h) or pregnant mare's serum gonadotropin (PMSG) (30-32 h) were flushed with culture medium, and hamster early two-cell embryos were introduced into these ampullae. Mouse ampullae isolated at 14-32 h after hCG injection were more favorable for the development of the embryos than those isolated at 70-72 h. When mouse ampullae were isolated 30-32 h after hCG or PMSG treatment, 39% of the cultured eggs developed, some of them to the expanded blastocyst stage after additional culture for 65-70 h. These results indicate that unknown oviductal factors stimulate the development of hamster early two-cell embryos, and these factors are under the control of hCG or PMSG. In addition, these factors are common to the mouse and hamster.

Animals↗

Difference in the nocturnal behaviour of blood pressure between monitorings with the arm-cuff method and with the finger-volume oscillometric method.

The nocturnal behaviour of blood pressure obtained by a new portable device for monitoring ambulatory blood pressure (ABPM 630) was compared with that obtained by a finger-volume oscillometric device (BP-100); the former uses a conventional arm-cuff inflated by CO2 gas to eliminate the noise of the motorized pump, and is based on a cuff-oscillometric as well as the Korotkoff sound technique (microphone method). With the microphone method in ABPM 630, the mean differences from the conventional auscultatory method were -0.28 +/- 6.15 mmHg (mean +/- s.d.) for systolic and 0.96 +/- 6.28 mmHg for diastolic blood pressure, and there was a highly significant correlation between blood pressure values measured by the ABPM 630 and by the auscultatory method. In 40 patients with mild to moderate hypertension 24-h blood pressure was monitored simultaneously with the ABPM 630 and BP-100. The daytime average of systolic blood pressure measured with the ABPM 630 was similar to that measured with the BP-100, whereas the night-time average assessed by the former was significantly higher than that assessed by the latter. Arm-cuff inflation by ABPM 630 caused some degree of sleep disturbance in 35 of 40 subjects, whereas finger-cuff inflation scarcely disturbed the sleep. The performance of the ABPM 630 was excellent.

Arm↗

Reversed circadian rhythm of blood pressure in adult spontaneously hypertensive rats.

The diurnal rhythms of blood pressure and heart rate were examined in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) when they were 5-6 weeks old (young), 17-20 weeks old (adult) and 30-32 weeks old (old). Blood pressure was recorded continuously for 24 h in conscious, unrestrained rats. Hourly averages of blood pressure and heart rate were calculated by an on-line computer. The circadian variation of blood pressure and heart rate remained unchanged regardless of age in WKY, but the difference in blood pressure between the daytime average and the night-time average decreased as they grew older. A well-defined circadian variation of blood pressure and heart rate was observed in young rats of both strains, i.e. a nocturnal rise in blood pressure and heart rate. An inverted circadian variation of blood pressure, a nocturnal fall in blood pressure, was observed in adult and old SHR, whereas the ordinary circadian variation of the heart rate remained unchanged. A significant positive correlation was observed between the hourly averages of blood pressure and heart rate in WKY in all the age groups (r = 0.9, P less than 0.001 in each age group) and a weak positive correlation was observed in young SHR (r = 0.6, P less than 0.05, 5-6 weeks old). This positive correlation disappeared in adult and old SHR and, instead, a negative correlation was observed (r = -0.5, P less than 0.02 for 17-20-week-old rats: r = -0.8, P less than 0.001 for 30-32-week-old rats).(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Altered circadian blood pressure rhythm in patients with Cushing's syndrome.

The circadian blood pressure rhythm was compared in patients with Cushing's syndrome, essential hypertension, and primary aldosteronism. In patients with essential hypertension or primary aldosteronism, a clear nocturnal fall in systolic and diastolic blood pressure and heart rate was observed. This fall was seen in untreated subjects as well as in patients receiving combined treatment with a calcium antagonist, diuretic, converting enzyme inhibitor, alpha-blocker and beta-blocker, or sympatholytic drug. In these groups, there was a positive correlation between heart rate and systolic or diastolic blood pressure. On the other hand, in patients with Cushing's syndrome, there was no nocturnal fall in blood pressure but in some patients a rise was observed. In all patients there was a nocturnal fall in heart rate. Thus, there was no significant correlation between heart rate and blood pressure in these patients. Exogenous glucocorticoid eliminated the normal nocturnal fall of blood pressure in patients with chronic glomerulonephritis or systemic lupus erythematosus. These results suggest that the changed circadian blood pressure pattern in patients with Cushing's syndrome is not due to antihypertensive treatment or to the mineralocorticoid excess accompanying this disease, but it is attributable to excess glucocorticoid or the associated disturbance in the adrenocorticotropic hormone-glucocorticoid system (or both). This conclusion also implies that the normal circadian rhythm of blood pressure may be regulated at least in part by the adrenocorticotropic hormone-glucocorticoid system.

Adolescent↗

Sex difference in epidermal growth factor receptor levels in rat liver plasma membrane.

The specific binding of [125I]epidermal growth factor [( 125I]EGF) to hepatic microsomal membranes was about 2-fold higher in adult male than in adult female rats. Scatchard analysis of the binding data showed that the sex difference in EGF binding was due to the difference in EGF receptor concentration rather than to a change in receptor affinity. From the developmental study, an apparent sex difference in EGF binding was observed from the pubertal period (4 weeks of age). Castration of adult male rats slightly, but significantly, decreased the EGF receptor level; and moreover, treatment of adult females with testosterone increased it only slightly. On the other hand, castration of neonatal male rats decreased the EGF receptor content almost to the female level. The decreased level of the receptor was completely restored by the combination of neonatal and pubertal treatments with testosterone. Neonatal or pubertal treatment alone of castrated animals had no significant effect on the decreased level of EGF receptors. These effects of testosterone were similarly observed when normal female rats were treated with the steroid. Moreover, hypophysectomy of the rats resulted in the marked decrease in EGF receptors only in the male animals. Treatment of hypophysectomized rats with either testosterone or T3 had no apparent effect on the EGF receptors. The membrane protein, cross-linked with [125I]EGF, had a mol wt of 170,000, and this protein (EGF receptor) was phosphorylated basally or by the addition of EGF. The rate of affinity labeling, or phosphorylation of EGF receptors, was in good agreement with the results of the EGF binding study. These results strongly suggest that the EGF receptor level in rat liver plasma membranes is in part regulated by the hypothalamopituitary unit and that neonatal androgens are essential for this regulation, probably through their effects on the hypothalamus.

Animals↗

The hypotensive mechanism of percutaneous transluminal dilatation (PTD) in renovascular hypertension due to bilateral renal artery stenosis.

The hypotensive mechanism of percutaneous transluminal dilatation (PTD) in renovascular hypertension due to bilateral renal artery was investigated in two patients. Blood pressure was monitored continuously before, during and after PTD by use of a new automated blood pressure monitoring device based on finger volume-oscillometry. Plasma renin activity was measured repeatedly before, during and after PTD. A hypotensive effect appeared immediately after PTD and blood pressure remained low in the following observation period without any hypotensive medication. In these cases, the hypotension was accompanied by a transient decrease in heart rate immediately after PTD. The hypotensive response to PTD was not parallel to the basal plasma renin activity, suggesting that the renin-angiotensin system is not necessarily involved in the maintenance of the hypertension before PTD. The autonomic nervous system seemed to play a certain role. Since the hypotension was accompanied by a transient decrease in heart rate immediately after PTD, the hypotension may be induced either by a decrease in sympathetic tone or by an increase in vagal tone at least just after PTD. It is hypothesized that these changes in autonomic nervous activity are mediated centrally through the renal afferent mechanism in response to rapid changes in renal hemodynamics induced by PTD.

Adult↗

The differential cardiovascular response to centrally administered carbachol seen in Brattleboro and normal Long-Evans rats.

The cardiovascular effects of centrally administered carbachol were examined in conscious Long-Evans (LE) and Brattleboro (DI) rats. Carbachol induced a long-lasting increase in blood pressure and a decrease in heart rate in LE rats, whereas in DI rats no bradycardia was observed and the pressor response was significantly less than that in Long-Evans rats. Intravenous vasopressin antagonist, d(CH2)5 Tyr(Me)AVP, significantly attenuated the pressor response and eliminated the bradycardic response to carbachol in LE rats. However, the pressor response to carbachol in DI rats was still significantly less than that in LE rats treated with vasopressin antagonist. Intravenous phentolamine partially inhibited the pressor response to carbachol in LE rats and completely eliminated it in DI rats. These results suggest that hypertensive response to i.c.v. carbachol in normal rats is mediated both by an increase in central sympathetic outflow and in circulating vasopressin. The bradycardia seems to be mediated mainly by an increase in circulating vasopressin.

Animals↗

Involvement of the hypothalamo-pituitary-adrenal axis in the control of circadian blood pressure rhythm.

The circadian blood pressure rhythm was compared between patients with Cushing's syndrome and those with essential hypertension or primary aldosteronism. In patients with essential hypertension or primary aldosteronism, clear nocturnal falls in systolic and diastolic blood pressure and the heart rate were observed. In contrast, in patients with Cushing's syndrome there was no nocturnal fall in blood pressure, and even a rise in some cases. In all cases with Cushing's syndrome, there was a nocturnal fall in the heart rate. Exogenous glucocorticoid abolished a nocturnal fall of blood pressure in patients with chronic glomerulonephritis or systemic lupus erythematosus, but did not affect nocturnal falls in the heart rate. These results indicate that the normal circadian rhythm of blood pressure may be regulated, at least in part, by the hypothalamopituitary-adrenal system.

Blood Pressure↗