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Biomedical subjects

A Otsuka

Publications and source records attributed to A Otsuka.

At least 19 recordsLinked to original sources

Spectral change in heart rate variability in response to mental arithmetic before and after the beta-adrenoceptor blocker, carteolol.

Spectral analysis of heart rate fluctuation was evaluated before and after administration of carteolol, a non-selective beta-adrenoceptor-blocker, to investigate the neural regulatory mechanisms underlying the haemodynamic changes induced by mental stress. Mental stress increased blood pressure and heart rate, with an increased low frequency band, and low frequency/high frequency ratio of the power spectral analysis which are indices of sympathetic activity. Carteolol did not change basal and pre-mental stress measurements of blood pressure, heart rate and spectral density. However, carteolol altered the response to mental stress with a decrease in spectral density of the low frequency band and low frequency/high frequency ratio, and an increase in the high frequency component. These results confirm that mental stress elevates blood pressure by activating the sympathetic nervous system, and suggest that blockade of the beta-adrenoceptor attenuates the pressor response by preventing the autonomic responses to mental stress.

Blood Pressure

[An elderly case of hypertension with persistent orthostatic hypotension].

The authors report the successful control of labile hypertension associated with orthostatic hypotension in a 75-year-old male patient, by means of L-DOPS, a synthetic precursor of norepinephrine in combination with antihypertensive drugs. He had been known to be hypertensive for 15 years and developed a persistent floating sensation 2 years age. Despite good control of hypertension after admission, orthostatic hypotension was still observed. Passive tilt produced a blood pressure reduction of 60/20 mmHg. Spectral analysis of heart rate variability showed a disturbance in the activation of the sympathetic nervous system. Treatment with L-DOPS attenuated the blood pressure reduction in response to passive tilt (35/12 mmHg) and improved the sympathetic response. Because of an increase in blood pressure by L-DOPS, addition of either a calcium channel blocker or an angiotensin-converting enzyme inhibitor was necessary. These combinations of treatment successfully controlled blood pressure as well as orthostatic hypotension.

Aged

Comparative study of the effects of three angiotensin converting enzyme inhibitors on the cough reflex.

To compare the effects of three different angiotensin converting enzyme (ACE) inhibitors on the cough reflex, capsaicin and citric acid challenge tests were done in normal subjects and hypertensive patients before and after administration of delapril, captopril, or enalapril. Two groups of 7 normal subjects (single dose study: 15 mg delapril v 18.75 mg captopril or 2.5 mg enalapril) and a group of 6 mildly hypertensive patients (1 week study: cross-over administration of 30 mg/day delapril, 37.5 mg/day captopril, or 5 mg/day enalapril) were studied. Another group of 6 patients with essential hypertension was treated with three ACE inhibitors for 4 weeks in a randomized order, with a 2 week washout period between active therapies. Aerosols of 1 mumol/L and 3 mumol/L capsaicin and 0.68% citric acid in 0.9% NaCl were generated by an ultrasonic nebulizer, and the frequency of cough was counted during inhalation. Delapril treatment resulted in substantially fewer patients with a significant increase (greater than or equal to 4 coughs during treatment than during the control period) in the frequency of cough than did captopril treatment. In the 1 and 4 week studies, enalapril and captopril had substantially more occurrences of significantly increased capsaicin-induced cough than did delapril. These results indicate that delapril has the least cough stimulatory effect among these ACE inhibitors, which may be clinically beneficial.

Administration, Inhalation

Interferon-gamma inhibits thyroid-stimulating hormone-induced morphological changes and induces the expression of major histocompatibility complex class II antigen in thyroid follicles in suspension culture.

The effects of interferon-gamma (IFN gamma) on the morphology of thyroid follicles and the expression of major histocompatibility complex (MHC) class II antigens were examined. The thyroid follicles were suspended in RPMI-1640 containing 10% fetal calf serum with or without IFN gamma (200 U/ml). After culture for 5 days, follicles were incubated in the presence of TSH (10 mU/ml) for 1 h and fixed for electron microscopic and immunohistochemical examination. Regardless of the presence of IFN gamma, suspended follicles became inverted within 5 days. However, MHC class II antigens were expressed only in inverted follicles cultured with IFN gamma. In inverted follicles cultured without IFN gamma, TSH stimulation induced remarkable morphological changes, such as elongation of microvilli and an appearance of pseudopods. On the other hand, the follicles cultured with IFN gamma showed poor response to TSH. Thus, IFN gamma induced the expression of MHC class II antigens of cultured thyroid follicles and inhibited TSH-induced morphological changes in the cells.

Animals

Dissolution of solid dosage form. II. Equations for the dissolution of nondisintegrating tablet under the sink condition.

An equation for dissolution from the whole surface of a nondisintegrating single component tablet under the sink condition was derived. Also, equations for several dissolution manners of the tablet under the sink condition were derived in the postulation of the dominant dissolution rate constant which determines the dissolution manner. The applicability or validity of these equations were examined by the dissolution measurements with nondisintegrating single component tablets. About one-tenth the amount of the amount needed to saturate the solution was used to prepare a tablet, and dissolution measurements were carried out with the tablet whose flat or side surface was masked with an adhesive tape in accordance with the conditions for derivation of equations. Among the derived equations, dissolution from the whole surface of a tablet was expressed by a form similar to the cube root law equation for particles. Hence, a single component tablet compressed by the use of a suitable amount was thought to behave like a single crystal. Also, equations derived for several dissolution manners were thought to be applicable for the dissolution of a nonspherical particle and crystal concerning the crystal's habit and its dissolution property, and the extended applicability was examined by converting the crystal into a simplified or idealized form, i.e., rectangle or plate.

Mathematics

Nicotinamide and 3-aminobenzamide reduce interferon-gamma-induced class II MHC (HLA-DR and -DP) molecule expression on cultured human endothelial cells and fibroblasts.

We investigated the effects of nicotinamide and 3-aminobenzamide, known as inhibitors of poly (ADP-ribose) synthetase, on the expression of interferon- gamma (IFN-gamma)-induced class I and II major histocompatibility complex (MHC) molecules on the surface of cultured human umbilical vein endothelial cells (HUVEC) and human dermal fibroblasts (HDF). Indirect immunofluorescent staining on HUVEC and HDF was performed using monoclonal antibodies against class I MHC (HLA-A,B,C) and class II MHC (HLA-DR, HLA-DP and HLA-DQ) molecules, and then the expression of these molecules was determined using a fluorescence flow cytometry. Human recombinant IFN-gamma (100 U/ml) increased the expression of HLA-A,B,C molecules, and induced the expression of HLA-DR molecules and, to a lesser extent, of HLA-DP on both HUVEC and HDF. HLA-DQ molecules were not induced by IFN-gamma on either cell type. Nicotinamide and 3-aminobenzamide in the concentration greater than or equal to 1 mM reduced the IFN- gamma -induced expression of HLA-DR and HLA-DP on both HUVEC and HDF, whereas neither agent in the concentration of up to 10 mM affected the IFN- gamma -induced increase in HLA-A,B,C molecule expression. These data suggest that nicotinamide and 3-aminobenzamide suppress antigen presenting function of class II MHC positive endothelial cells and fibroblasts at the site of tissue inflammation.

Animals

Lipopolysaccharide augments HLA-A,B,C molecule expression but inhibits interferon-gamma-induced HLA-DR molecule expression on cultured human endothelial cells.

The effect of bacterial lipopolysaccharide (LPS) on the expression of class I and II major histocompatibility complex (MHC) molecules on the surface of cultured human umbilical vein endothelial cells (HUVEC) was determined by indirect immunofluorescent staining followed by flow cytometric analysis. LPS at concentrations higher than 0.01 micrograms/ml augmented class I MHC (HLA-A,B,C) expression on HUVEC in a concentration-dependent manner. Optimal augmentation, approximately sixfold compared with control, was seen with 10 micrograms/ml of LPS. Time-course experiments indicated that the augmentation was maximal on Day 4. In contrast, LPS had no effect on the induction of class II MHC (HLA-DR) molecules and at concentrations higher than 0.01 micrograms/ml inhibited the interferon-gamma(IFN-gamma)-induced class II MHC expression. The inhibition was about 60% at the concentration of 100 micrograms/ml of LPS. Interleukin-1 (IL-1) had a similar effect as LPS on class I and II MHC expression. However, LPS appeared to affect MHC expression directly and not through production of IL-1 or cyclo-oxygenase pathway products, since anti-IL-1 antibodies or an inhibitor of cyclo-oxygenase pathway products, indomethacin, failed to reverse the effects of LPS. These data stress the role of LPS as a direct modulatory factor of class I and II MHC expression on endothelial cells during the development of immune and inflammatory response against Gram-negative bacteria.

Antibodies

Importance of the sympathetic nervous system in blood pressure elevation by subpressor intraventricular NaCl and angiotensin II in the rat.

The present study was performed to examine the effect of chemical sympathectomy with guanethidine on the BP change and humoral factors in rats which received continuous and concomitant infusion of i.c.v. hypertonic NaCl with i.v. Ang II, both at subpressor doses for 7 days. Male rats were divided into 3 groups which received the following infusions using an osmotic minipump at a rate of 1 microliter/min: Group 1 (n = 11), 0.15 M NaCl i.c.v. and Ang II (5.4 pmol/kg/min) i.v.; Group 2 (n = 9), 0.8 M NaCl i.c.v. and Ang II i.v.; Group 3 (n = 5), 0.8 M NaCl i.c.v. and Ang II i.v. with daily i.p. injection of guanethidine (40 mg/kg). Significant increase in BP was observed only in Group 2 (from 103 +/- 3 mmHg to 132 +/- 5 mmHg on day 7, p less than 0.001). Addition of i.p. guanethidine to i.c.v. infusion of 0.8 M NaCl and the subpressor dose of Ang II completely prevented increase in the BP, suggesting that the presence of the intact sympathetic nervous system is necessary for the development of BP elevation in response to i.c.v. hypertonic NaCl plus i.v. Ang II. Thus, the sodium status in the central nervous system is important in the regulation of BP and is closely related to the activity of the sympathetic nervous system.

Angiotensin II

No beneficial effect of splenectomy in hereditary high red cell membrane phosphatidylcholine hemolytic anemia: clinical and membrane studies of 20 patients.

The clinical features and red cell membrane characteristics of 20 patients with hereditary high red cell membrane phosphatidylcholine hemolytic anemia (HPCHA) were studied in relation to the effect of splenectomy. After splenectomy, anemia worsened and the extent of increased hemolysis in these patients was unchanged, indicating a contraindication for splenectomy. Concomitant with these results in clinical hematology, marked stomatocytic changes, increased red cell phosphatidylcholine content, and enhanced sodium transport, which were observed before splenectomy, were not improved by splenectomy.

Adolescent

Preventive effect of a new immunosuppressant FK-506 on insulitis and diabetes in non-obese diabetic mice.

We investigated the effect of an immunosuppressant FK-506 on histological change of islets, the onset of diabetes, and the change of spleen cell subsets in female non-obese diabetic mice. Mice administered intraperitoneally with FK-506 from 5 to 20 weeks of age showed marked suppression of mononuclear cell infiltration (insulitis) at 10 weeks of age. Among the subsets of the spleen cells, a significant decrease in the population of Thyl.2-positive T cells (pan-T), L3T4-positive T cells (mainly helper/inducer), and Lyt2-positive T cells (mainly suppressor/cytotoxic) was observed in FK-506-treated mice. Furthermore, glucose tolerance of the mice at 15 weeks of age was clearly improved. Cumulative incidence observed up to 40 weeks of age was 86% in control mice and 23% in FK-506-treated mice (p less than 0.01). These data indicate that FK-506 has a preventive effect on insulitis and diabetes by the suppression of cell-mediated autoimmunity in non-obese diabetic mice.

Animals

Differential blood pressure responses to oral and central salt administration in two substrains of Dahl rats.

Studies were made on whether oral or intraventricular (icv) NaCl had different effects on the blood pressure (BP) of Dahl rats. Five groups of each strain of Dahl rats, salt-sensitive (S) and salt-resistant (R) rats, were given, respectively, a diet containing 0.3% and icv infusion of 0.15 mol/L NaCl (group 1, control group) or 0.8 mol/L NaCl (group 2), a diet containing 8% NaCl and icv infusion of 0.15 mol/L (group 3) or 0.8 mol/L NaCl (group 4) for 12 days, or an 8% NaCl diet and icv infusion of 5% glucose (group 5). The icv infusions were made into the third cerebral ventricle with an osmotic minipump. In the control group of S rats (group 1) the BP was 120 +/- 4 mm Hg, whereas the BP in groups 3, 4 and 5 were 154 +/- 4, 161 +/- 5 and 153 +/- 3 mm Hg, respectively, and that in group 2 was 142 +/- 3 mm Hg on day 12. In the R rat, group 2 and group 4 showed a significant increase in BP over that of the control group. Multivariate analysis (quantification I) of these data confirmed that the BP of S rats was more sensitive to oral salt loading and that of the R rat was more strongly influenced by central salt administration. These results indicate that the two substrains of Dahl rats show different BP responses to oral and central administrations of NaCl.

Animals

Haemodynamic effect of endothelin, a novel potent vasoconstrictor in dogs.

1. The effects of endothelin (40 and 400 pmol/kg, intravenous (i.v.), a novel vasoconstrictor, on haemodynamics were evaluated in normal dogs and dogs treated with hexamethonium. 2. The lower dose of endothelin caused no significant changes in mean blood pressure (MBP), heart rate (HR), cardiac output (CO), or total peripheral resistance (TPR) in normal dogs. In dogs treated with hexamethonium MBP decreased transiently associated with decrease in TPR. 3. In both dogs, the higher dose of endothelin caused MBP increase with CO increase in an early phase, and with TPR increase in a later phase. In normal dogs, the CO decreased 60 min after endothelin, but in dogs treated with hexamethonium the decrease in CO was not significant. 4. Electrocardiograms showed ST changes and arrhythmias. 5. Thus, endothelin has dual effects on both the vasculature and the heart, its effect depending on its dose and the time after its administration: initial vasodilation followed by prolonged vasoconstriction, and cardiostimulation followed by cardiosuppression. The cardiosuppression appears to be mediated in part by a neural mechanism.

Animals

Absence of nocturnal fall in blood pressure in elderly persons with Alzheimer-type dementia.

Circadian changes of the blood pressure and heart rate in elderly normotensive bedridden patients with severe dementia of the Alzheimer type (group D) were compared with those in elderly normotensive bedridden patients without dementia (group R), normotensive subjects with normal daily activity (group N), and hypertensive patients with normal daily activity (group H). In groups R, N, and H, the blood pressure increased in the afternoon and decreased at midnight; in group D, however, although it increased in the afternoon, it did not decrease at night. The circadian changes of the heart rate were similar in all four groups, showing maxima in the afternoon and minima at midnight. Thus, a specific alteration was found in the circadian rhythm of the blood pressure in patients with Alzheimer-type dementia.

Activities of Daily Living

Interferon-gamma reduces actin filaments and inhibits thyroid-stimulating hormone-induced formation of microvilli and pseudopods in mouse monolayer thyrocytes.

To study the role of interferon-gamma (IFN gamma), which is released from activated lymphocytes in the development of lymphocytic thyroiditis, we investigated the effects of IFN gamma on the morphology of mouse thyrocytes, using scanning electron microscopy. Thyrocytes were cultured in monolayers for 5-7 days and incubated with TSH (10 mU/ml) for 1 h before fixation. IFN gamma (200 U/ml) was added to the culture medium for 1 h to 5 days before TSH stimulation. Coculture of thyrocytes with IFN gamma for more than 24 h inhibited TSH-induced morphological changes in the thyrocytes; IFN gamma inhibited the increase in the number of and elongation of microvilli and the appearance of pseudopods. IFN gamma also reduced the number of actin filaments in thyrocytes, as confirmed by immunofluorescence photometry. These results suggest that IFN gamma inhibits the morphological response of thyrocytes to TSH stimulation by the reduction of actin filaments.

Actins

[Circadian changes of blood pressure in the elderly with Alzheimer's type dementia].

We evaluated the circadian changes of blood pressure in the elderly with Alzheimer's type dementia with ambulatory blood pressure monitoring (ABPM-630, Nihon Colin, Aichi, Japan). Blood pressure and heart rate were high in the daytime and low in the nighttime in the elderly without dementia. Blood pressure did not decrease in the nighttime in the elderly with dementia, although heart rate decreased. Thus, the circadian rhythm of blood pressure was selectively impaired in the elderly with Alzheimer's type dementia.

Aged

Increased plasma level of endothelin with vasoconstriction after dextran infusion.

Our previous study demonstrated that volume expansion with dextran produced blood pressure elevation due to vasoconstriction 3 hours after the cessation of infusion. To examine whether endogenous endothelin contributes to this vasoconstriction, we measured plasma level of endothelin before, immediately after, and 3 hours after the administration of dextran. Plasma level of endothelin decreased immediately after the administration (from 1.5 +/- 0.3 pg/ml to 1.1 +/- 0.2 pg/ml, P less than 0.05), and increased 3 hours after the administration (2.1 +/- 0.3 pg/ml, P less than 0.05). However, the changes in the plasma level of endothelin did not significantly correlated with those in blood pressure or total peripheral resistance. Thus, vasoconstriction after dextran infusion was accompanied by an increase in the plasma level of endothelin, but further evaluation is needed for the direct role of this peptide in the vasoconstrictive blood pressure elevation.

Animals

Effect of aspirin on the pressor activity of endothelin.

To examine the inhibition of prostaglandins to the pressor activity of endothelin, hemodynamic changes of dogs pretreated with aspirin in response to endothelin were compared with those of control. In control dogs, endothelin rose blood pressure due to vasoconstriction, with a transient vasodilation in some dogs in the initial phase. In dogs treated with aspirin, the initial vasodilation and the subsequent vasoconstriction were also noted, but the zenith of the total peripheral resistance was observed earlier, compared with control dogs. Thus, prostaglandins do not appear to have a role in the initial vasodilatory action of endothelin, but may modify the long lasting vasoconstriction in the late phase.

Animals