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Biomedical subjects

S Morimoto

Publications and source records attributed to S Morimoto.

At least 181 records · Page 10Linked to original sources

Potentiating effects of calcium chelators on basal and stimulated aldosterone production by bovine adrenal glomerulosa cells in vitro.

We previously reported the potentiation of basal aldosterone production by the addition of the calcium chelator ethyleneglycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) to an extracellular solution of bovine adrenal glomerulosa cells in vitro. To assess whether the addition of the calcium chelators ethylenediamine-N,N,N',N'-tetraacetic acid (EDTA) and EGTA can potentiate basal and stimulated aldosterone production, we compared the effect of EDTA with that of EGTA on basal and the agonist (potassium; 8 mM, angiotensin II; 10 nM, ACTH; 10 nM)-stimulated aldosterone production by the cells in vitro. These two chelators lowered the extracellular ionized calcium ([Ca2+]o) concentration in a similar manner. The levels of basal and the agonist-stimulated aldosterone production in the presence of EDTA (1 mM) and EGTA (1 mM) were significantly (P < 0.01 or less) increased when compared with those in the absence of EDTA and EGTA, respectively. These results show that the addition of EDTA and EGTA to an extracellular solution potentiates basal and the agonist-stimulated aldosterone production in vitro. Although an increase in basal aldosterone production in the presence of EDTA (1 mM) and EGTA (1 mM) was completely inhibited by the voltage-dependent calcium channel antagonist nifedipine (1 microM) or the calmodulin antagonist pimozide (1 microM), the potentiation of the agonist-stimulated aldosterone production does not seem to be induced by CA2+/calmodulin-dependent nor cAMP-dependent systems. These findings suggest that calcium chelators such as EDTA and EGTA may possess activating effect on basal and stimulated aldosterone production in bovine adrenal glomerulosa cells.

Aldosterone↗

Thoracic dumbbell-shaped neurinoma treated by unilateral hemilaminectomy with partial costotransversectomy--case report.

A 56-year-old male was admitted in January 1994, with back pain persisting for 2 months. Magnetic resonance imaging disclosed a homogeneously enhanced mass occupying the spinal canal at the T-8 level and extending into the retropleural space through the left intervertebral foramen between T-8 and T-9. The diagnosis was a thoracic dumbbell-shaped neurinoma. The tumor was successfully removed through a posterolateral approach using hemilaminectomy and partial costotransversectomy with preservation of ipsilateral joint facets. Histological examination indicated neurinoma. This approach allows excellent visualization of anterior paraspinal components of the tumor, preserves important anatomic structures, and requires minimal compression of the cord for removal of the lesion.

Humans↗

Subsets of activated T cells in patients with systemic lupus erythematosus: the relation to cell cycle.

The correlation among the various markers of activated T cells (soluble interleukin 2 receptor (sIL-2R), HLA-DR+ and HLA-DP+ T cells, proliferating cell nuclear antigen (PCNA) positive lymphocytes) were examined in patients with systemic lupus erythematosus (SLE), and related to the cell cycle. The concentration of sIL-2R and the proportion of HLA-DR+ T cells, HLA-DP+ T cells or PCNA+ lymphocytes were increased significantly as compared to that in normal subjects. And, the concentrations of sIL-2R correlated with the proportions of PCNA+ lymphocytes, but not with the proportions of HLA-DR+ T cells, HLA-DP+ T cells. The correlation between sIL-2R and PCNA+ lymphocytes was attributed to both indicators being increased during the G1B or S phase in normal T cells upon stimulation by phytohemagglutinin (PHA). Upon cell cycle analysis it was learned that activated T cells could be found in the G1A and the S phases.

Adult↗

[Urinary bacteria in elderly patients with urinary incontinence and low levels of daily activity].

The results of bacteria isolated from the urine of inactive elderly patients with urinary incontinence in 1982, 87, 93 and 95 were compared and the chronological changes of urinary bacteria were analyzed. The following results were obtained: (1) The most common bacteria isolated from the patients in 1995 were D-group Enterococcus, followed by Providencia rettgeri, E. coli, Pseudomonas aeruginosa and Proteus mirabilis. It is thought that the main cause of the more frequent isolation of Enterococcus is an abuse of cephems and fecal contamination. (2) The most common bacteriaisolated from the patients who were managed with an indwelling urethral catheter were Proteus and Providencia species, and their incidence tended to decrease from 1982 to 1995. (3) Infection with Pseudomonas species tended to increase, as did that Staphylococcus species, especially Methicillin-resistant Staphylococcus aureus and then decreased. Based on these findings, it is important to assess and treat dysuria before inserting an indwelling urethral catheter, and to select an antibacterial agent that is effective in elderly patients with urinary incontinence and limited activity.

Activities of Daily Living↗

[Cerebral infarction and asymptomatic arteriosclerosis obliterans in the elderly].

We examined the associations between cerebral infarction (CI), asymptomatic arteriosclerosis obliterans (ASO), and known risk factors for these diseases. The subjects were 67 elderly patients (11 men and 56 women, mean +/- SD age of 79.6 +/- 8.5 years). in 44 patients CI was diagnosed by CT scan; 23 were classified as having cortical infarction and 21 as having lacunar infarction. In 41 patients asymptomatic ASO was diagnosed by an ankle-pressure index (API) of less than 0.9. To identify risk factors for these diseases, we examined the association among these diseases and hypertension (blood pressure > or = 140/90 mmHg), hypercholesterolemia (total cholesterol concentration > or = 220 mg/dl), hypertriglyceridemia (triglyceride concentration > or = 150 mg/dl), low HDL-cholesterolemia (HDL-C concentration < 40 mg/dl), high LDL-cholesterolemia (LDL-C concentration > or = 150 mg/dl), and glucose intolerance (fasting blood sugar concentration > or = 110 mg/dl). The incidence of asymptomatic ASO in the subjects with CI was significantly higher than that in the subjects without CI (chi 2 test; p < 0.05, odds ratio 6.4), including cortical infarction (p < 0.05, odds ratio 8.9) and lacunar infarction (p < 0.05, odds ratio 3.8). Patients with lacunar infarction were more likely to have hypertension than were controls (p < 0.05). Cortical infarction was not associated with these risk factors. Both low HDL-C and high LDL-G were more common in patients with asymptomatic ASO than patients without asymptomatic ASO (p < 0.05). These results indicate that CI and asymptomatic ASO are strongly associated in the elderly, especially in subjects with cortical infarction, and that aging itself contributes to cortical infarction.

Aged↗

[Hemorrhagic colon ulcer as a side effect of non-steroidal anti-inflammatory drugs in five aged patients].

A report is presented of five aged patients with hemorrhagic colon ulcer, which was strongly suspected to be a side effect of non steroidal anti-inflammatory drugs (NSAID). All patients were suffering from orthopedic diseases and NSAIDs were administered for pain: Zaltoprofen for one patient and slow-releasing diclofenac for the other four. Four patients had being treated underlying diabetes mellitus and three of them were being treated with sulfonylurea. Appetite loss was the earliest symptom, 1-2 weeks after administration of NSAID began. Diarrhea occurred 1-2 weeks after appetite loss, and finally hemorrhagic stool developed 1-2 weeks after that. Acute gastric mucosal lesion, hemorrhagic colon ulcer and colitis were diagnosed in all patients by emergency gastro-duodenocolonoscopy. NSAID and oral diet were ceased, and intravenous hyperalimentation was instituted when the patients revealed severe anemia due to bleeding. All patients could take an oral diet after a few weeks. In conclusion hemorrhagic colon ulcer must be prevented in patients treated with NSAID especially those who are aged and have a history of diabetes mellitus.

Aged↗

Effects of sarafotoxin S6c on antidiuresis and norepinephrine overflow induced by stimulation of renal nerves in anesthetized dogs.

We previously reported that endothelin (ET) may function as an inhibitory modulator of renal noradrenergic neurotransmission (Suzuki et al., J. Cardiovasc. Pharmacol. 19: 905-910, 1992). In our study, we examined the effect of sarafotoxin S6c (S6c), a selective ET(B) receptor agonist, on changes in renal function and norepinephrine overflow induced by renal nerve stimulation (RNS) in anesthetized dogs. RNS at a low frequency (0.5-2.0 Hz) caused significant decreases in urine flow, urinary excretion of sodium and fractional excretion of sodium and increased norepinephrine secretion rate, without affecting systemic and renal hemodynamics. RNS at a high frequency (2.5-5.0 Hz), which diminishes renal hemodynamics, produced more potent decreases in urine formation and increase in norepinephrine secretion rate than seen with low frequency RNS. When S6c (1 ng/kg/min) was infused intrarenally, there was a slight and transient increase in renal blood flow, and then this response was followed by a gradual reduction. S6c administration produced increase in the basal level of urine flow with no apparent effects on urinary excretion of sodium and fractional excretion of sodium. During S6c infusion, low frequency RNS-induced antidiuretic action and increase in norepinephrine secretion rate were markedly attenuated. Qualitatively, similar results were observed in the case of high frequency RNS. In addition, high frequency RNS-induced decreases in glomerular filtration rate and filtration fraction were significantly suppressed by S6c infusion. Taken together with our previous findings, it seems likely that ET plays an important role as an inhibitory modulator of renal noradrenergic neurotransmission, through ET(B) receptor mechanisms.

Anesthesia, General↗

[Angle of defect on 123I-MIBG myocardial SPECT].

The quantitative assessment of infero-posterior defect on 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy was studied in 150 patients with non-ischemic heart diseases at rest. The bull's eye map, obtained from the SPECT images at 4 hours after MIBG injection, was evaluated by generating the blacked out map which exhibits regions with reduced % uptake under mean-2 SD of 13 normal controls. The blacked out regions involved infero-posterior segments and were closely resembled to the sector form. The central angle of this sector, which was named as angle of defect (AOD), significantly correlated with both the heart-to-mediastinum activity ratio (H/M) and the myocardial clearance of MIBG. Because H/M and clearance are widely used as quantitative indices in MIBG myocardial scintigraphy, these results indicate that AOD can also be used as a quantitative index of abnormal cardiac sympathetic nervous function, which is likely to appear in infero-posterior regions in non-ischemic cardiac diseases.

3-Iodobenzylguanidine↗

[Clinical phase III study of cimetropium bromide (DA3177) on the pain with upper urinary calculus: a double-blind study in comparison with scopolamine butylbromide. DA3177 Study Group].

A double-blind study was conducted to evaluate the efficacy, safety and usefulness of cimetropium bromide (DA3177) in the patients with pain caused by upper urinary calculus at a daily dose of 75 mg t.i.d. (Group D, 97 patients) in comparison with scopolamine butylbromide at a daily dose of 60 mg t.i.d. (Group B, 101 patients). According to patient's impression, the rate of "moderately improved" or better was significantly higher in Group D (68.7%) than in Group B (53.5%; Wilcoxon 2 sample test: p = 0.0044). For pain, the rate of "moderately improved" or better was 69.1% in Group D and 60.4% in Group B. In global improvement, the rate of "moderately improved" or better was significantly higher in Group D (70.1%) than in Group B (61.4%; Wilcoxon 2 sample test: p = 0.0469). The rate of "no problem in safety" showed no significant difference between Group D (91.5%) and Group B (93.3%). Adverse reactions occurred in 8.5% in Group D and 6.7% in Group B. The major adverse reactions were "dry mouth", "abdominal distension", "constipation" and "nausea". The rate of "useful" or better was 68.7% in Group D, and 60.4% in Group B. In conclusion, DA3177 was confirmed to be a useful drug for patient with pain caused by upper urinary calculus.

Adult↗

[Diuretics for therapy of patients with hypertension].

Diuretic agents have antihypertensive effects mainly be decreasing extracellular volume and cardiac output. These diuretics are described with regard to mechanism of action, site of action, adverse effects, and drug interactions. Thiazide diuretics inhibit the Na(+)-Cl- symporter in the distal convoluted tubule, by competing for the Cl- binding site, and increase Na+ and Cl- excretion. Loop diuretics are inhibitors of Na(+)-K(+)-2Cl- symporter in the thick ascending limb of the loop of Henle. However, loop diuretics are not the diuretic of first choice and should be reserved for patients in whom other diuretics or antihypertensive drugs do not result in a satisfactory response. The potassium sparing diuretics are used primarily to reduce the kaliuresis and potenciate the hypotensive effect of a thiazide.

Benzothiadiazines↗

Activated T cells induce up-regulation of Fas antigen in cultured endothelial cells.

Recent evidence has shown that apoptotic cells are present in human atherosclerotic lesions. However, the molecular mechanism of the induction of apoptosis in atherosclerotic lesions is not clear. Since T cells are present in almost all stages of atherosclerosis, we examined whether T cells can modulate the expression of Fas, a death signal, in endothelial cells (ECs), using a coculture system. Human umbilical vein ECs were cultured alone or cocultured with human peripheral T cells activated with phorbol myristate acetate and ionomycin. Flow cytometric (FACscan) analysis showed that Fas antigen was up-regulated in ECs when ECs were cocultured for 24 h with activated T cells. However, Fas antigen was not up-regulated in ECs cocultured with non-activated T cells. The up-regulation of Fas antigen induced by coculturing ECs with activated T cells was partially, but significantly, neutralized by antibody against interferon-gamma (IFN-gamma). Actually, incubation with IFN-gamma induced a dose-dependent increase in the level of Fas antigen in ECs cultured alone. These findings indicate that activated T cells induce up-regulation of Fas antigen in ECs. Thus, the Fas system induced by activated T cells could participate in the mechanism of EC injury in atherosclerotic lesions.

Apoptosis↗

Purification and characterization of cannabidiolic-acid synthase from Cannabis sativa L.. Biochemical analysis of a novel enzyme that catalyzes the oxidocyclization of cannabigerolic acid to cannabidiolic acid.

We identified a unique enzyme that catalyzes the oxidocyclization of cannabigerolic acid to cannabidiolic acid (CBDA) in Cannabis sativa L. (CBDA strain). The enzyme, named CBDA synthase, was purified to apparent homogeneity by a four-step procedure: ammonium sulfate precipitation followed by chromatography on DEAE-cellulose, phenyl-Sepharose CL-4B, and hydroxylapatite. The active enzyme consists of a single polypeptide with a molecular mass of 74 kDa and a pI of 6.1. The NH2-terminal amino acid sequence of CBDA synthase is similar to that of Delta1-tetrahydrocannabinolic-acid synthase. CBDA synthase does not require coenzymes, molecular oxygen, hydrogen peroxide, and metal ion cofactors for the oxidocyclization reaction. These results indicate that CBDA synthase is neither an oxygenase nor a peroxidase and that the enzymatic cyclization does not proceed via oxygenated intermediates. CBDA synthase catalyzes the formation of CBDA from cannabinerolic acid as well as cannabigerolic acid, although the kcat for the former (0.03 s-1) is lower than that for the latter (0.19 s-1). Therefore, we conclude that CBDA is predominantly biosynthesized from cannabigerolic acid rather than cannabinerolic acid.

Amino Acid Sequence↗

Roles of dopamine D1 receptors in delta 9-tetrahydrocannabinol-induced expression of Fos protein in the rat brain.

We examined whether administration of delta 9-tetrahydrocannabinol (THC) induces the expression of Fos protein or not in the rat brain. A single administration of 3.2 and 10 mg/kg THC produced a dose-dependent and significant increase in Fos-immunoreactive cells in the striatum, particularly in its dorsomedial portions. The peak increase was reached 2 h after THC treatment and was absent at 8 h. Fos induction was also observed in the nucleus accumbens after administration of 10 mg/kg THC. However, in the globus pallidus, hippocampus and substantia nigra pars reticula, abundant in cannabinoid receptors, there were few or no Fos-immunoreactive cells induced by 10 mg/kg THC. SCH-23390, a selective dopamine D1 receptor antagonist, at 0.32 mg/kg produced a significant block of the effects of THC on Fos expression in the striatum and the nucleus accumbens. Administration of 100 mg/kg (-)-sulpiride, a selective dopamine D2 receptor antagonist, failed to block the effect of THC on Fos expression in both the striatum and the nucleus accumbens. These findings indicate that THC induces the expression of Fos protein and that this expression is mediated at least by dopamine D1 receptors.

Animals↗

Calcitonin prevents CCl4-induced hydroperoxide generation and cytotoxicity possibly through C1b receptor in rat hepatocytes.

The effects of calcitonin (CT) on oxyradical generation and cellular damage induced by carbon tetrachloride (CCl4) were investigated in rat hepatocytes. Addition of CCl4 to the cells concentration dependently increased intracellular production of hydroperoxides and release of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The hepatocytes expressed mRNA for a CT receptor, C1b. Coaddition of CT to the cells concentration dependently suppressed the CCl4-induced increase in hydroperoxide production and also decreased the release of AST and ALT. The suppressive effect of CT on hydroperoxide production was reversed by further addition of H7 or by pretreatment with phorbol 12-myristate 13-acetate for 24 h. These results suggest that CT prevents CCl4-induced oxyradical production and cellular damage through activation of protein kinase C in hepatocytes.

Animals↗

Investigation of the relationship between regression of hypertensive cardiac hypertrophy and improvement of cardiac sympathetic nervous dysfunction using iodine-123 metaiodobenzylguanidine myocardial imaging.

Although many theories exist on the subject, the mechanisms responsible for a reduction of hypertensive cardiac hypertrophy in response to antihypertensive therapy are still unclear. In order to investigate the relationship between regression of hypertensive cardiac hypertrophy and cardiac nervous function, we studied ten patients with untreated essential hypertension (six men and four women, 62+/-12 years old). Both echocardiography and iodine-123 metaiodobenzylguanidine (MIBG) myocardial imaging were performed before and after antihypertensive therapy. Left ventricular mass (LVM) was significantly reduced in conjunction with the reduction of blood pressure following treatment. MIBG myocardial images showed that the heart-to-mediastinum activity ratio (H/M) was significantly increased while the washout ratio was significantly decreased. Patients were divided into two groups according to the ratio of the LVM values before and after therapy (LVM ratio). Patients with an LVM ratio of less than 0.75 were classified as group A and those with values higher than 0.75 as group B. Neither the change in blood pressure nor the length of treatment was significantly different between these two groups. On the other hand, both the increase in H/M and the decrease in the washout ratio were significantly greater in group A than in group B. These results indicate that an improvement in cardiac sympathetic nervous function may be related to the regression of hypertensive cardiac hypertrophy. Increasing the subject base in these studies and a more precise analysis of the relevance of the data obtained from MIBG myocardial images are recommended to clarify how changes in cardiac sympathetic nervous function relate to the regression of hypertensive cardiac hypertrophy.

3-Iodobenzylguanidine↗

Soluble Fas molecule in the serum of patients with systemic lupus erythematosus.

The serum level of soluble Fas (sFas) molecules in 35 patients with SLE was determined by enzyme-linked immunosorbent assay (ELISA) and its relation to other lymphocyte activation markers and clinical parameters was examined. The level of sFas increased significantly compared to that in normal subjects, consistent with previous reports. There was a significant correlation between the level of sFas and that of sCD4, suggesting some relation between sFas and activation of CD4+ T cell. Patients with lymphopenia tended to have low levels of sFas, making it possible to hypothesize that sFas protects against apoptosis. Although the change in the level of sFas protects steroid therapy was variable, some relation to the differential activation of T cell subsets was suggested.

CD4 Antigens↗