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Biomedical subjects

R Fujiwara

Publications and source records attributed to R Fujiwara.

At least 37 records · Page 2Linked to original sources

Relation of angiographically defined coronary artery disease and plasma concentrations of insulin, lipid, and apolipoprotein in normolipidemic subjects with varying degrees of glucose tolerance.

We investigated the association between hyperinsulinemia and changes in lipid, lipoprotein, and apolipoprotein that would increase the risk of coronary artery disease (CAD) independent of glucose tolerance. A coronary angiogram was recorded in 127 male subjects, including 41 with normal glucose tolerance, 41 with impaired glucose tolerance, and 45 with non-insulin-dependent diabetes mellitus (NIDDM). Subjects were divided into 2 groups according to results: the group with CAD (n = 94) and the group with normal coronary arteries (n = 33). All subjects were normolipidemic (total cholesterol < 230 mg/dl and triglycerides < 150 mg/dl). The CAD group had a significantly lower plasma level of high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I (apo A-I) and a higher level of apolipoprotein B (apo B) than the normal group with normal glucose tolerance. In considering subjects with impaired glucose tolerance or NIDDM, the CAD group had a significantly lower plasma level of HDL cholesterol and apo A-I and a significantly higher plasma level of total cholesterol, triglycerides, and apo B than the normal group. In each of the subjects with normal and impaired glucose tolerance, and NIDDM, the elevation of plasma insulin concentration during both the complete test period and the early phase of an oral glucose challenge was significantly higher in the CAD than in the normal group. In all subjects, graded reductions in HDL cholesterol and apo A-I and graded increases in plasma total cholesterol, triglycerides, and apo B were observed with increasing tertiles of the postglucose challenge measurements of insulinemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗

Potential antidepressant effects of lemon odor in rats.

Antidepressant effects brought about by olfactory stimulation with various odorants were investigated with the forced swimming test, a reliable means for screening antidepressant effects. Lemon odor significantly reduced total immobility time and potentiated the imipramine-induced reduction of total immobility time in the test. This synergistic effect of lemon odor and imipramine was not due to lemon odor decreasing the metabolism of imipramine. Lemon odor decreased locomotor activity in the open field, suggesting its effects to differ from those of psychostimulants but to be similar to those of antidepressants. The effects of citral, which is one of the main components of lemon odor, were as strong as those of lemon odor. The remaining odorants tested in this study failed to have any effects on total immobility time in the forced swimming test or on locomotor activity in the open field.

Animals↗

Effects of insulin, insulin-like growth factor-I, and phorbol esters on neutral cholesteryl esterase activity in cultured rat vascular smooth muscle cells.

We investigated the effects of insulin, insulin-like growth factor-I (IGF-I), and phorbol 12-myristate 13-acetate (PMA) on neutral cholesteryl esterase activity in cultured rat vascular smooth muscle cells. Insulin and IGF-I at concentrations between 10(-9) mol/L and 10(-6) mol/L significantly decreased neutral cholesteryl esterase activity in growth-arrested vascular smooth muscle cells in a dose-dependent manner but with no influences on the intracellular concentration of 3',5'-adenosine monophosphate (cyclic AMP). Treatment of cells with KT5720 (10(-7) mol/L to 10(-5) mol/L), a specific inhibitor of cyclic AMP-dependent protein kinase, significantly decreased neutral cholesteryl esterase activity in a dose-dependent manner. Incubation of cells for 6 to 12 hours with PMA (10(-9) mol/L to 10(-6) mol/L), an activator of protein kinase C, significantly increased neutral cholesteryl esterase activity in a dose-dependent manner. However, down-regulation of protein kinase C activity by long-term incubation (18 to 48 hours) with PMA resulted in a significant decrease in neutral cholesteryl esterase activity. Treatment of cells with UCN-01 (10(-7) mol/L to 10(-5) mol/L), a specific protein kinase C inhibitor, decreased the enzyme activity in a dose-dependent manner and completely blocked the activation of the enzyme by PMA. When insulin or IGF-I at a concentration of 10(-6) mol/L was present in the medium containing CL 277,082--an inhibitor of acyl coenzyme A:cholesterol acyltransferase--cellular cholesteryl ester content of the cells significantly increased. In contrast, after the treatment with PMA at a concentration of 10(-6) mol/L in the presence of CL 277,082, the net cholesteryl ester content of the cells significantly declined. These data suggest that both insulin and IGF-I may increase cholesteryl ester accumulation in arterial smooth muscle cells by decreasing arterial cholesteryl ester hydrolysis. The data also suggest that neutral cholesteryl esterase is activated not only by cyclic AMP-dependent protein kinase but also by protein kinase C. Thus growth factors may exert their antilipolytic or lipolytic actions specifically by modulating neutral cholesteryl esterase activity in vascular smooth muscle cells. Neutral cholesteryl esterase of vascular smooth muscle cells may be regulated by recholesteryl esterase of vascular smooth muscle cells may be regulated by reversible phosphorylation, with the phosphorylated form being the active form.

Alkaloids↗

[Application of fragrances to treatments for depression].

High pressure stress was found to induce immunosuppression accompanied with the enhancement of motor activity in mice. Citrus fragrance restored stress-induced immunosuppression and induced calm behavior in mice. In the forced swimming test using rats, citrus fragrance reduced the total immobility time and potentiated the imipramine-induced reduction in total immobility time. The application of citrus fragrance to depressive patients made it possible to markedly reduce the doses of antidepressants needed for the treatment of patients.

Adult↗

Influence of pain stimulation on interleukin-2 production in mice.

We previously demonstrated that plaque-forming cell (PFC) production in the spleen of mice immunized with sheep red blood cells (SRBC) was enhanced by pain stimulation. This phenomenon was due to activation of antigen nonspecific L3T4-/Lyt-2- T lymphocytes (double-negative T cells) by the beta-adrenergic action of endogenous catecholamines released from the adrenal gland after pain stimulation. Further study also demonstrated that interleukin-2 (IL-2) production of spleen cells was enhanced in mice by pain stimulation. In this study spleen cells of BALB/c mice were cultured with Con A and SRBC, respectively, and the IL-2 level was measured by incorporation of 3H-thymidine into CTLL-2 cells during culture for 24 hours. Interleukin-2 production of spleen cells from mice given pain stimulation was significantly increased compared with spleen cells of normal mice. The IL-2 production of spleen cells of normal mice was also markedly enhanced by the mixed culture with spleen cells from pain-stimulated mice. Enhancement of IL-2 production in the spleen cells of mice given pain stimulation did not occur with anti-Thy-1.2 antibody and complement treatment, but production was maintained by treatment with anti-L3T4 antibody and complement. These data suggest that the enhanced production of IL-2 in mice given pain stimulation resulted from the activation of L3T4- T cells by endogenous catecholamines released from the adrenal gland after pain stimulation. It can be assumed that activated L3T4- T cells interact with antigen-specific L3T4+ T cells and lead to enhanced IL-2 production.

Animals↗

Diltiazem inhibits DNA synthesis and Ca2+ uptake induced by insulin, IGF-I, and PDGF in vascular smooth muscle cells.

Proliferation of vascular smooth muscle cells (VSMC) has been shown to play a key role in the atherosclerotic lesions. It has been demonstrated that serum-derived peptidic growth factors, such as insulin, platelet-derived growth factor (PDGF), or epidermal growth factor (EGF), provide mitogenic signals in VSMC and that the interplay of Ca2+ and other messengers is necessary for triggering proliferation. Since Ca2+ channel blockers act on the voltage-dependent Ca2+ channel to inhibit Ca2+ influx, it is conceivable that they affect the proliferative action of growth factors. In this study we have evaluated the effects of diltiazem, a 1,5-benzothiazepine-derived Ca2+ channel blocker, on [3H]thymidine incorporation into DNA stimulated by insulin, insulinlike growth factor I (IGF-I), or PDGF in cultured VSMC from rat aorta. We have also investigated the effects of insulin, IGF-I, and PDGF on Ca2+ uptake in VSMC. After exposure to insulin (10(-10) to 8 x 10(-6) M) or IGF-I (10(-10) to 10(-7) M) for 48 hours, VSMC incorporated [3H]thymidine to 200-280% of maximum (with insulin or IGF-I alone) compared to control. The effect of IGF-I was approximately 10-100 times more potent than that of insulin. PDGF (0.5-15 ng/ml) also induced an increase in [3H]thymidine incorporation into DNA of VSMC. Additivity is observed between PDGF with insulin or IGF-I, but not between insulin and IGF-I. Sixty minute treatment with insulin (5 x 10(-8) to 10(-6) M), IGF-I (10(-8) to 10(-6) M), or PDGF (1.0-15.0 ng/ml) increased the unidirectional 45Ca2+ uptake during a 5 minute period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Endogenous components of event-related potential appearing during NREM stage 1 and REM sleep in man.

Information processing in the brain during sleep was studied by analyzing the evoked cortical response to auditory stimulations presented in the odd-ball paradigm. Eight subjects were examined in different sleep stages. The subjects could provide the correct behavioral response to the auditory stimulation by pressing a key button in the light part of stage 1 of NREM sleep, just succeeding to the waking state, but none of the subjects could give the correct behavioral response in the other sleep stages. In the deep part of stage 1 of NREM sleep and REM sleep, a cortical potential corresponding to P300, the endogenous component of the event-related potential (ERP) recorded in the waking state, was recorded in 6 of the 8 subjects in spite of the absence of the behavioral response. In stages 2, 3 and 4 of NREM sleep, emergence of this endogenous component of ERP could not be confirmed. The present findings provide electrophysiological evidence indicating that selective information processing corresponding to sensory discrimination of auditory stimuli is actively performed in stage 1 of NREM sleep and REM sleep.

Adult↗

Effects of nicorandil on cell proliferation and cholesteryl ester accumulation in arterial smooth muscle cells in culture.

Ca2+ regulates a variety of cellular mechanisms in vascular cells as well as in platelets. Nicorandil interacts with the intracellular Ca(2+)-activated processes in vascular smooth muscle cells, while Ca2+ channel blockers such as verapamil and diltiazem block voltage-dependent Ca2+ channels. The effects of nicorandil are due to the hyperpolarization of the membrane, interference with mobilization of Ca2+ from the intracellular storage sites, and blockade of receptor-operated Ca2+ channels. In the present study, the effects of nicorandil on cell proliferation and cholesteryl ester accumulation in rat arterial smooth muscle cells in culture were compared to Ca2+ channel blockers. Smooth muscle cells were prepared from rat thoracic aorta, and the rate of proliferation was determined by measuring the cell number and by [3H]-thymidine incorporation into cellular DNA. The effect of nicorandil on cholesteryl ester content in smooth muscle cells was determined by thin-layer chromatography of the cell extracts. Nicorandil at concentrations of 10(-6) to 10(-4) M, as well as Ca2+ channel blockers (verapamil and diltiazem) inhibited the proliferation and DNA synthesis of cultured smooth muscle cells. The acute inhibitory effects on cell proliferation were observed significantly 16 hours after the addition of the three agents in serum-stimulated cells. These effects were dose dependent, both in acute and in chronic treatment with the three agents. Addition of 10(-5) M nicorandil to medium supplemented with 10% serum resulted in a decrease of the net cholesteryl ester content by 18 +/- 1%, while cellular free cholesterol content was the same as control. Similar results were also obtained in the presence of verapamil and diltiazem.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Adrenal myelolipoma: comparison of diagnostic imaging and pathological findings.

Myelolipoma of the adrenal gland is a rare, benign, nonfunctioning lesion consisting of fat and bone marrow elements in varying proportions. This tumor is commonly asymptomatic and usually discovered during various diagnostic imaging examinations performed for unrelated diseases. If a primary malignant or metastatic adrenal tumor cannot be excluded, ultrasound- or computed tomography-guided needle biopsy of the tumor is necessary. We report a case of adrenal myelolipoma associated with advanced gastric carcinoma and compare the diagnostic imaging findings with the pathological findings of the adrenal myelolipoma.

Adenocarcinoma↗

Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture.

Cilostazol, a cyclic AMP phosphodiesterase inhibitor, has been used as an antiplatelet agent. In the present study, we investigated the in vitro effect of cilostazol on DNA synthesis in rat aortic arterial smooth muscle cells (SMCs) in culture stimulated with fetal calf serum (FCS), platelet-derived growth factor (PDGF), insulin, or insulin-like growth factor-I (IGF-I). Micromolar concentrations of cilostazol inhibited [3H]thymidine incorporation into DNA and cell growth as determined by cell number and protein concentration. Treatment with cilostazol increased the intracellular concentration of cyclic AMP, suggesting that the inhibition of SMC proliferation by cilostazol may be mediated through increased levels of cyclic AMP. The results suggested that cilostazol, by interfering with the proliferation of arterial SMCs, may have potential to prevent initiation and progression of atherosclerosis.

3',5'-Cyclic-AMP Phosphodiesterases↗

Effects of acupuncture on immune response in mice.

The effect of acupuncture points stimulation on the induction of plaque-forming cells (PFC) in spleen cells of BALB/c mice was investigated in vivo and in vitro tests. In in vivo experiment, mice were immunized with 2 x 10(8) sheep red blood cells (SRBC) and the PFC was markedly increased by daily (once a day for 4 days) acupuncture stimulation. The enhancement of PFC by acupuncture was completely blocked by preadministration of procain, hexamethonium, naloxone, propranolol, but not by phentolamine. The enhancement of PFC by acupuncture was also observed in spleen cells of non-immunoized mice when spleen cells of the acupunctured mice were cultured with SRB in vitro. The enhancement of PFC in spleen was observed after stimulation with acupuncture, and a similar effect was also found in bone marrow cells of normal mice, but not in thymic cells. The spleen cells of mice given acupuncture showed no enhancement of PFC after treatment with anti-Thy 1.2 antibody and complement. Furthermore, these helper T cells were found to be not restricted by the H-2 gene complex. These data demonstrate that the helper T cells induced by acupuncture lack the H-2 restriction, and thus suggest that they may be drived from the bone marrow, but not from the thymus. It is therefore concluded that the helper T cells derived from the bone marrow were activated via the sympathetic nervous system stimulated by acupuncture.

Acupuncture Therapy↗

Immunological and behavioral effects of fragrance in mice.

The aim of this study was to determine the effects of olfactory stimulation on immunological and behavioral states in mice. Anti-SRBC (IgM) plaque forming cell (PFC) count and spontaneous running activity (SRA) were measured to demonstrate the effects of exposure to a given fragrance. The decreased PFC count and thymic involution induced by high pressure stress in mice were recovered after exposing the stressed mice to the fragrance continuously for 4 days after the stress was given. The PFC and SRA also appeared to be maintained at normal levels by oflactory stimulation with the fragrance for 24 hrs after the given stress. The immunological suppression induced by high pressure stress was considered to be caused by the induction and activation of suppressor cells. However, exposure to the fragrance after the stress did not enhance suppressor activity. The restoration of the stress-induced immune suppression by olfactory stimulation was blocked by procain administration onto the olfactory cells.

Animals↗

Metabolic risk factors in the normolipidemic male patients with angiographically defined coronary artery disease.

The relationship of plasma lipid and apolipoprotein (apo) concentrations and plasma insulin response to oral glucose load to angiographically determined coronary artery disease (CAD) was investigated in 65 normolipidemic (plasma cholesterol less than 230 mg/dl and plasma triglyceride less than 150 mg/dl) males. According to the results of coronary angiography, the patients were divided into 2 groups: patients with normal coronary artery, NCA group (n = 21); and patients with coronary artery disease, CAD group (n = 44). No significant differences in concentrations of plasma cholesterol and triglyceride were observed between the CAD and NCA groups. In the CAD group cumulative lifetime tobacco consumption was higher and high density lipoprotein (HDL) cholesterol concentration was lower than those in the NCA group. The variables that correlated with the severity of CAD, defined by the number of lesions and percent stenosis, were levels of plasma apo A-I and apo B. Prevalence of subjects with reduced oral glucose tolerance did not differ between 2 groups. However, hyperinsulinemic response to oral glucose load was present in the CAD group. HDL-cholesterol concentration, the sum of plasma insulin levels and the magnitude of the early insulin response during oral glucose challenge were accurate predictors of the presence of but not the severity of CAD. Multivariate analysis of the data confirmed the independent effect of plasma levels of apo A-I and apo B on the severity of CAD. The present data indicated that plasma levels of apo A-I and apo B were powerful discriminators in the normolipidemic CAD patients and that a high insulin response might be an indicator of enhanced susceptibility to the distinct coronary atherosclerosis.

Adult↗

Effectiveness of long-acting nifedipine in pheochromocytoma.

In the present study, we report a case of pheochromocytoma whose high blood pressure was well controlled by single-agent therapy with long-acting nifedipine, in spite of the failure of the combination of labetalol and prazosin in lowering blood pressure satisfactorily. A 48 year old female was first noted to have hypertension (160/100 mmHg) at 45 years of age. Hypertension was not controlled by conventional antihypertensive drugs. She was admitted to Fukui Prefectural Hospital in September, 1985. Her blood pressure on admission was 210/110 mmHg. Extraction of the left adrenal gland containing a pheochromocytoma (30 x 37 x 10 mm) was performed in November, 1985. Her hypertension and abnormally high plasma noradrenaline (NA) concentration (1,760 pg/ml, normal value 40-350 pg/ml) were sustained even after operation. Combination therapy with labetalol (400 mg/day) and prazosin (6 mg/day) was unsatisfactory, and the addition of long-acting nifedipine (40 mg/day) produced a marked decrease in blood pressure. Furthermore, single therapy with long-acting nifedipine was effective. No reduction of urinary NA excretion was observed in our patient during long-acting nifedipine therapy, suggesting that the decrease in blood pressure was not caused by suppression of NA release from pheochromocytoma tissue.

Adrenal Gland Neoplasms↗