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Biomedical subjects

S Sakai

Publications and source records attributed to S Sakai.

At least 271 records · Page 15Linked to original sources

Inhibitory effect of alkaloids extracted from the stem bark of Hunteria zeylanica on 5-lipoxygenase activity in vitro.

The effects of alkaloid extract from the stem bark of Hunteria zeylanica Gard. (H. zeylanica) on the activities of cyclooxygenase and 5-lipoxygenase in A23187-stimulated rat mast cells were investigated. H. zeylanica alkaloid extract (0.3-300 micrograms/ml) inhibited leukotriene C4 (LTC4) production by 5-lipoxygenase in a concentration-dependent manner and it blocked the production by 50% at 300 micrograms/ml. On the other hand, the extract had no effect on prostaglandin D2 (PGD2) production by cyclooxygenase. Neither (-)-eburnamine nor pleiomutinine, major constituents of H. zeylanica alkaloid extract, inhibited the production of PGD2 and LTC4 in the A23187-stimulated mast cells. The inhibition of arachidonic acid metabolism via 5-lipoxygenase pathway may be due to minute amounts of other components as stated in the Discussion.

Alkaloids↗

[Chemical studies of indole alkaloids].

Up to now, more than two thousands indole alkaloids having structural variety have been found from the three families of Gentianales: Loganiaceae, Apocynaceae, and Rubiaceae plants. These compounds generally possess characteristic biological activities and many of them are utilized for the medicinal purpose and for the lead-compounds to develop new synthetic drugs. The author of this review has been investigated the alkaloidal constituents of the above mentioned plants native to Japan and overseas countries. Especially, a cooperative work with Thai researchers concerning the plants in Thailand was developed. On the basis of biogenetic consideration of the structures of monoterpenoid indole alkaloids, chemical bond cleavage between the C3-N4 linkage in the C/D ring of indole alkaloids was discovered. It was speculated that, either in biogenesis, the flexibility of the ring-opening compounds having ten membered ring enabled the construction of indole alkaloids having highly strained polycyclic structures. Along with this conception, the syntheses of structurally complex indole alkaloids utilizing a biomimetic procedure have been investigated. In this review, recent results on the chemical synthesis of many skeletally varied Gelsemium alkaloids (Loganiaceae plant) are mainly described.

Alkaloids↗

[Effect of anticancer drugs on invasive capacity of human small-cell lung cancer cells in vitro].

The effect of anticancer drugs on invasive capacity of Lu 135 human small-cell lung cancer cells was studied in vitro. the invasive capacity decreased in a dose-dependent manner when tumor cells were treated with the anticancer drugs cisplatin and etopside. The inhibition of tumor cell invasion was almost parallel with the inhibition of tumor cell growth. The anticancer drugs also suppressed tumor cell migration and the activity of the matrix-degrading protease, type IV collagenase, activity. But they did not suppress adhesion to basement membrane protein such as laminin, fibronectin, or type IV collagen. Because tumor cells express adhesion molecules on the cell surface, the effect of the anticancer drugs on the expression of one such molecule, integrin, was also studied. Lu 135 cells expressed alpha 4/beta 1 integrin on the cell surface, and the pattern of integrin expression did not change with exposure with the anticancer drugs. These data suggest that the anticancer drugs inhibit the invasive capacity by suppression of migration and type IV collagenase activity of tumor cells, and that they do not modulate adhesion to the extracellular matrix or cell surface adhesion molecules such as integrin. Furthermore, these findings indicate that anticancer drugs may be useful for anti-metastatic therapy in patients with small-cell lung cancer.

Antineoplastic Agents↗

Occult thymic carcinoma presenting as malignant cardiac tamponade.

A 66-year-old woman who presented with malignant cardiac tamponade of unknown origin was eventually found to have a tiny squamous cell carcinoma of the thymus. Thus, even a small thymic carcinoma can exhibit highly aggressive behavior. It should be included in the differential diagnosis of malignant cardiac tamponade of unknown origin.

Aged↗

Effect of intravenously applied canrenoate on ampullar endolymphatic potential.

The effect of canrenoate, an aldosterone antagonist, on the ampullar endolymphatic potential (AEP) was examined to assess a possible role for aldosterone in the ampulla. Intravenous administration of canrenoate increased the AEP amplitude in a dose-dependent manner, with a significant reduction of the AEP negative component induced by anoxia. Pretreatment with aldosterone attenuated the AEP change produced by canrenoate. The results suggest that aldosterone may be involved in the modulation of ampullar function.

Aldosterone↗

[A case of post-traumatic arteriovenous fistula of the subclavian artery].

A 67-year-old woman was admitted to our hospital for a complete medical evaluation of a pulmonary nodule on a chest X-ray film, which was found during an annual check-up. A loud bruit was audible over the left chest and the supraclavicular region. Computerized tomography (CT) scan and magnetic resonance imaging revealed an arteriovenous fistula from a branch of the left subclavian artery into the paravertebral veins. Angiography disclosed that the arteriovenous fistula was fed by the left costocervical artery. Transarterial embolization of the arteriovenous fistula was done with 5 mechanical detachable coils and 2 micro coils. Postembolization angiography showed a marked decrease in blood flow and near-elimination of the arteriovenous fistula. The shrinkage of the arteriovenous fistula was also observed on CT scan. This patient had been in a traffic accident, and had been clinically well before the accident. Post-traumatic arteriovenous fistula was strongly suspected, because a pulmonary nodule on chest X-ray film and a bruit were found after a traffic accident.

Accidents, Traffic↗

[Correlation between tissue blood flow and tissue concentration of 5-FU and its metabolite in hepatic metastasis model for rats].

Correlation between 5-FU (20mg/kg) administrated via the peripheral vein and tissue concentration of its metabolite was studied in hepatic metastasis model prepared for rats. The measurement of tissue samples collected 30 min. after the 5-FU administration suggested a possible negative correlation between the F-dUMP concentration and the blood flow in the normal hepatic tissue of the control group and the tumor tissue in the metastasis group. In administering 5-FU, a time-dependent anticancer drug, to the tumor rich in the tissue blood flow, washing-off effect of the drug by blood outflow cannot be neglected. Some device of prolonging the exposure time of anti-cancer agent to the tumor tissue will be necessary.

Animals↗

[ECG-gated dual isotope myocardial SPECT with 99mTc-MIBI and 123I-BMIPP in patients with ischemic heart disease].

Simultaneous dual-isotope SPECT with 99mTc-methoxy isobutyl isonitrile (MIBI) and 123I-beta-methyl iodophenyl-pentadecanoic acid (BMIPP) was performed in 25 patients with ischemic heart disease. ECG-gated myocardial SPECT was acquired following the injection of MIBI (555 MBq) and BMIPP (148 MBq). Both MIBI and BMIPP scans provided high-quality myocardial images. Then, myocardial count increase rate (%WT = ES-ED/ED x 100) was calculated as an index of left ventricular contraction using MIBI gated SPECT data. The %WT was well correlated with severity scores of both MIBI image (r = -0.70) and BMIPP image (r = -0.72). Thus, ECG-gated dual-isotope SPECT with MIBI and BMIPP was considered to be useful method for assessment of left ventricular contraction as well as myocardial perfusion and fatty acid metabolism.

Aged↗

[A case of invasive thymoma with myasthenia gravis and pure red cell aplasia].

The patient was a 42-year-old man whose main complaints were ptosis, diplopia and muscle weakness. Chest X-ray film revealed a right hilar mass and chest CT showed a solid mass at right anterior superior mediastinum. Laboratory studies revealed myasthenia gravis (MG) on EMG and pure red cell aplasia (PRCA) on hematology. An extended thymectomy, including the thymoma, was performed. Thrombocytopenia appeared postoperatively, but it improved when a platelet transfusion was given. Steroid was administered for postoperative adjuvant therapy, and the MG and PRCA were alleviated. This rare case of simultaneous MG and PRCA as complications of a thymoma is reported.

Adult↗

[Low-dose dobutamine stress test for the evaluation of cardiac function using ECG-gated SPECT scintigraphy with 99mTc-MIBI].

Although 201TlCl myocardial scintigraphy has so far been widely used for the evaluation of the viability of the myocardial infarcted area, functional evaluation using low dose dobutamine (DOB) loaded echography also became recently available. We performed 99mTc-mIBI gated SPECT on eight cases of myocardial infarction at rest and low dose (4-6 micrograms/kg/min) DOB-loading and related data were collected. Next, we calculated myocardial count increase rate (% WT = ES-ED/ED x 100) with left ventricular contraction from end-diastolic (ED) and end-systolic (ES) pictures in short-axial image, and made a comparative examination of regional contractilities at rest and DOB-loading. DOB-loaded echography performed on the same cases at the same dose revealed 15 segments as infarcted area (WM (+)) presenting improvement in wall movement at loading and 5 segments as infarcted area (WM (-)) presenting no such improvement, and %WT at rest and loading were 29.1 +/- 6.2 and 33.2 +/- 2.4 for (WM (-)) and 26.8 +/- 9.8 and 40.0 +/- 12.3 for (WM (+)), indicating a significant increase (p < 0.05) at loading. Contractility analysis using MIBI gated SPECT in combined use of DOB-loading was considered as a useful method of examination in view of its reflectability in the evaluation of the wall movement in DOB-loaded echography and of its high quantitativity.

Aged↗

Influence of pulmonary blood pressure and flow on endothelin-1 production in humans.

To investigate the regulation of endothelin-1 (ET-1) production, cardiac catheterization was performed in young patients with congenital heart disease (27 +/- 5 months old, mean +/- SEM), and plasma levels of ET-1 in the inferior vena cava were measured by a sandwich-enzyme immunoassay. Plasma ET-1 levels of age-matched healthy controls were 1.55 +/- 0.07 pg/ml (n = 6). In patients with atrial septal defect [without pulmonary hypertension (PH)] who had volume but not pressure overload to the pulmonary circulation (PC), plasma ET-1 levels were significantly lower than in controls. In patients with PH due to ventricular septal defect (VSD) who had both volume and pressure overload to PC, the levels were significantly higher than in controls. In patients with PH and severe pulmonary congestion due to pulmonary venous stenosis (PVS), plasma ET-1 levels were significantly higher than in those with VSD, suggesting that ET-1 production is also augmented by pulmonary congestion. The present findings suggest that ET-1 production is increased by pressure overload to PC but decreased by volume overload to PC.

Endothelins↗

Increased endothelin-1 binding sites in the cardiac membranes in rats with chronic heart failure.

The effects of experimental chronic heart failure (CHF) on the density and affinity for endothelin-1 (ET-1) binding was studied in the rat heart. Because it has been reported that ET-1 binding sites on cultured cardiocytes are downregulated by pretreatment with ET-1, we also studied the plasma concentrations of ET-1 in rats with CHF. Three weeks after ligation of the left coronary artery, rats developed chronic heart failure (CHF rats). The plasma concentrations of ET-1, as measured by a sandwich-enzyme immunoassay, were significantly higher in CHF rats than in sham-operated rats [4.80 +/- 0.33 vs. 0.91 +/- 0.11 (mean +/- SEM) pg/ml; p < 0.01]. [125I]ET-1 binding experiments on rat cardiac membranes revealed that the binding site density (Bmax) was significantly higher in the CHF rats than in the sham-operated rats (243.0 +/- 20.0 vs. 154.8 +/- 17.4 fmol/mg protein; p < 0.05), whereas the values for the dissociation constant (Kd) were not different between the two groups (28.7 +/- 7.0 vs. 29.8 +/- 1.9 pM). Therefore, in the CHF rats, although plasma concentrations of ET-1 were elevated, the density of myocardial ET receptors was increased. Because ET-1 has potent inotropic and hypertrophic effects on cardiac myocytes, it is suggested that the effects of endogenous ET-1 in the heart are different between the CHF rats and the sham-operated rats.

Animals↗

Altered production of endothelin-1 in the hypertrophied rat heart.

Although endothelin-1 (ET-1) has been shown to have potent hypertrophic effects in cultured cardiac myocytes, there is no evidence that the production of ET-1 is altered in the hypertrophied heart in vivo. We investigated mRNA and peptide levels of ET-1 in the rat heart hypertrophied due to pressure or volume overload. One week after surgery of abdominal aortic banding (AB) or aortic valve regurgitation (AR; the aortic valve was destroyed by a polyethylene catheter), the rats were sacrificed. Control sham-operated rats were also studied (AB-sham and AR-sham). The left ventricular (LV) weight to body weight ratio was significantly higher in AB rats than in AB-sham rats. It was also significantly higher in AR rats than in AR-sham rats. Therefore, AB rats and AR rats developed LV hypertrophy due to pressure and volume overload, respectively. The expression of ET-1 mRNA in the LV was markedly higher in AB rats than in AB-sham rats. The peptide level of ET-1 was also significantly higher in the LV of AB rats than in that of AB-sham rats. However, the expression of ET-1 mRNA in the LV of AR rats was similar to that of AR-sham rats. The present findings suggest that the production of ET-1 in the heart differs between pressure and volume overload-induced hypertrophy in rats.

Animals↗

Plasma endothelin-1 levels after exercise in patients with congenital heart disease.

We have previously reported that plasma endothelin-1 (ET-1) levels were significantly increased after exercise in healthy athletes. In the present study, venous plasma ET-1 levels were measured to investigate whether the role of ET-1 during exercise differs between healthy athletes and patients with congenital heart disease. Seven patients (mean age 13 years) performed symptom-limited treadmill exercise (Bruce protocol). All patients were in class I of the NYHA functional classification. The mean end-exercise O2 utilization was 32 ml/min/kg (166% of ventilatory threshold). Blood sampling was carried out in the seated position. The plasma ET-1 level was 1.21 pg/ml before exercise and did not alter immediately after or 30 min after exercise. The plasma level of norepinephrine was markedly elevated immediately after exercise and returned to the basal level 30 min after exercise. The present study demonstrated that exercise failed to alter plasma ET-1 levels in patients with congenital heart disease.

Adolescent↗

Molecular cloning and analysis of the cDNA for an auxin-regulated calmodulin gene.

An auxin-regulated calmodulin cDNA (arCaM) were isolated by differential screening from a mung bean (Vigna radiata) cDNA library. The expression of the arCaM transcript in the etiolated mung bean hypocotyl was examined by RNA gel blot analysis. The arCaM transcript was induced depending on indole-3-acetic acid (IAA) concentrations. An increase in level of the arCaM transcript upon treatment of hypocotyl segments with 10 microM IAA was detected after 1 h and a maximum level was detected at 2 h. Induction of the arCaM transcript occurred upon treatment with 10 microM 2,4-dichlorophenoxyacetic acid (2,4-D) or naphthalene-1-acetic acid (NAA) as well as with IAA, while treatment with 10 microM p-chlorophenoxyisobutyric acid (PCIB) as an anti-auxin, prevented the induction. Ethylene did not have any effect. Other stress conditions, such as exposure to salt stress, heavy metal ions and heat shock, also had no effect on the induction. The levels of the arCaM transcript in leaves of light-grown mung bean plants treated with IAA showed steady but small increases with time.

Amino Acid Sequence↗

Mechanism of prolactin action on the dissociation of prolactin from rabbit mammary gland receptor.

In order to elucidate the action of prolactin (PRL) on the dissociation of PRL from the receptor, Triton-solubilized and concanavalin A-purified rabbit mammary gland PRL receptor was immobilized onto a nitrocellulose membrane, and the dissociation of PRL was determined in the presence of PRL. PRL accelerated the dissociation of PRL in a concentration dependent manner for the first 3 h of incubation. The effects of PRL on dissociation were independent of the occupancy of PRL at the zero-time dissociation. In particular, PRL-dependency was influenced by the PRL-binding capacity of the membrane. The dissociation reaction was PRL-independent in the low-binding capacity membrane, indicating that PRL itself had no accelerating actions. With greater binding capacity, the dissociation reaction was seen to become PRL-dependent. It was concluded that PRL accelerated the dissociation of PRL through the formation of PRL-receptor complex when the receptor was located closely to the neighboring receptors.

Animals↗