Biomedical subjects

S Asada

Publications and source records attributed to S Asada.

At least 37 records · Page 2Linked to original sources

PubMed1998

Protein kinase C modulates the synthesis of nitric oxide by osteoblasts.

To determine the involvement of protein kinase C (PKC) in nitric oxide (NO) synthesis of osteoblast, a combination of proinflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma, bacterial lipopolysaccharide) were added on rat osteoblast-like cells. Results show that these cytokines clearly enhanced the synthesis of NO. The activation of PKC with phorbol ester also resulted in the stimulation of NO synthesis in these cells. These cytokines activated PKC and increased the levels of intracellular Ca2+. In addition, the cytokine-induced synthesis of NO was blocked by PKC inhibitors. Findings suggest the involvement of PKC in the synthesis of NO by rat osteoblasts.

Animals↗

PubMed1998

Cataract surgery in a patient with severe chronic iritis and corneal endothelial damage.

We report a patient with broad anterior synechias and corneal endothelial damage. The patient had chronic iritis and cataracts secondary to chronic iritis in both eyes. Because the right eye had broad anterior synechias and severe corneal endothelial damage, extracapsular cataract extraction and intraocular lens implantation were performed through the basal iris. Good postoperative visual acuity was obtained. The cornea showed little trauma from the surgery and remained clear 36 months postoperatively.

Cataract↗

PubMed1998

Effect of thioridazine or chlorpromazine on increased hepatic NAD+ level in rats fed clofibrate, a hypolipidaemic drug.

The effect of the phenothiazines, thioridazine and chlorpromazine, on the increased hepatic NAD+ level of rats fed clofibrate, a hypolipidaemic drug, has been investigated. Short-term (6 days) addition of phenothiazines to the diet negatively affected diet intake and body-weight gain, but increased liver weight and hepatic NAD+ levels, which was synergistic to clofibrate. The phenothiazines were shown to inhibit hepatic peroxisomal fatty acid oxidation in-vivo, as determined by the increased residual catalase activity. In hepatocytes prepared from clofibrate-fed rats, phenothiazines inhibited not only peroxisomal but also mitochondrial fatty acid oxidation to the same extent. In the hepatocytes, NAD+ was maintained at the high level until the phenothiazine concentration was increased to 0.2 mM. The result suggests that the increase of hepatic NAD+ in rats fed clofibrate is not related to peroxisomal fatty acid oxidation.

Animals↗

PubMed1998

Concurrent generation of nitric oxide and superoxide inhibits proteoglycan synthesis in bovine articular chondrocytes: involvement of peroxynitrite.

OBJECTIVE: Nitric oxide (NO), widely assumed to be a mediator of interleukin 1 (IL-1), inhibits proteoglycan synthesis in articular chondrocytes. IL-1 also produces superoxide anion. We hypothesized that the IL-1 inhibited proteoglycan synthesis is the result of peroxynitrite formed by the reaction of NO with superoxide. METHODS: Bovine articular chondrocytes were cultured in the presence of SIN-1, which leads to simultaneous generation of both NO and superoxide. Proteoglycan synthesis was measured based on the incorporation of [35S] sulfate, and the presence of peroxynitrite was confirmed using immunohistochemistry. RESULTS: SIN-1 inhibited proteoglycan synthesis and superoxide dismutase reversed SIN-1 inhibited proteoglycan synthesis, indicating the simultaneous generation of superoxide is essential to inhibit proteoglycan synthesis. IL-1 induced peroxynitrite in articular chondrocytes and addition of peroxynitrite inhibited proteoglycan synthesis. CONCLUSION: The concurrent generation of superoxide anion and NO is required for the action of IL-1 to inhibit proteoglycan synthesis. Peroxynitrite is a candidate for this underlying mechanism.

Animals↗

PubMed1997

Hyaluronic acid inhibits interleukin-1-induced superoxide anion in bovine chondrocytes.

OBJECTIVE: To examine the effect of hyaluronic acid (HA) on the induction of superoxide anion by IL-1 in chondrocytes. MATERIALS AND METHODS: Bovine articular chondrocytes were treated with different concentrations of IL-1. A chemiluminescent probe (L-012) was added to the medium and chemiluminescence detection was used to measure super oxide anion. RESULTS: IL-1 caused induction of superoxide anions in a dose-dependent manner. HA (10-100 micrograms/ml) countered superoxide induction caused by 20 ng/ml of IL-1. CONCLUSIONS: HA can afford protection against cartilage degradation, probably acting as a free-radical scavenger.

Animals↗

PubMed1997

Cyclic tensile stretch on bovine articular chondrocytes inhibits protein kinase C activity.

Osteoarthrosis, a common pathway of joint deterioration, is caused by mechanical stress loaded on articular cartilage. We previously demonstrated the involvement of protein kinase C (PKC) in the development of osteoarthritis in vitro. In this study, we examined the effect of mechanical stress on chondrocyte metabolism and the activity of PKC in vitro. Low frequency and magnitude of cyclic tensile stretch loaded on chondrocytes increased proteoglycan synthesis. However, high frequency and magnitude of stress decreased its synthesis. In this condition, activity of PKC was reduced. These results suggest an involvement of PKC in the stress-mediated inhibition of proteoglycan synthesis.

Animals↗

PubMed1997

Microtubule dynamics regulates the level of endothelin-B receptor in rat cultured astrocytes.

We investigated the effect of cytoskeleton modulators on endothelin-B (ET(B)) receptor expression in rat primary cultured astrocytes. Northern blot analysis and a binding study revealed that colchicine and nocodazole, microtubule-disrupting agents, decreased the levels of both ET(B) receptor mRNA and the number of ET-1 binding sites in quiescent astrocytes. Down-regulation of both ET(B) receptor mRNA and the number of binding sites for ET-1 was also observed in quiescent astrocytes treated with taxol, a microtubule-stabilizing agent. In contrast, neither beta-lumicolchicine, an inactive isomer of colchicine, nor cytochalasin D, a microfilament-disrupting agent, influenced ET(B) receptor expression. The level of ET(B) receptors in astrocytes was affected by the cell state, namely, proliferative, quiescent, or differentiated state. The order of ET(B) receptor expression according to the cell state was proliferative state < quiescent state << differentiated state induced by dibutyryl cyclic AMP. Also, in proliferative astrocytes and differentiated astrocytes, colchicine significantly down-regulated both ET(B) receptor mRNA and the number of binding sites for ET-1. However, thymidine assay revealed that colchicine did not change quiescent astrocytes and differentiated astrocytes to a proliferative state. Furthermore, the increase in glutamine synthetase activity in differentiated astrocytes was not affected by colchicine. These results suggest that microtubule dynamics possibly regulates ET(B) receptor expression in astrocytes without affecting the cell state.

Animals↗

PubMed1997

Stereoselective reductive metabolism of metyrapone and inhibitory activity of metyrapone metabolites, metyrapol enantiomers, on steroid 11 beta-hydroxylase in the rat.

Pharmacokinetics of metyrapone and metyrapol enantiomers was studied in the rat to determine the stereoselective reductive metabolism of metyrapone. The HPLC method using a chiral column was developed for the stereoselective analysis of metyrapol enantiomers in rat plasma. The AUC ratio of (-)- and (+)-metyrapol appeared in rat plasma after i.v. administration of metyrapone was about 3:1. The interconversion of (-)- or (+)-metyrapol to its antipode was negligible, and the reverse reaction from metyrapol to metyrapone was insignificant. There were similar kinetic parameters of (-)-metyrapol to those of (+)-metyrapol after i.v. administration of racemic metyrapol. These results indicate metyrapone displays product-stereoselective reductive metabolism in the rat. The inhibition of steroid 11 beta-hydroxylase by metyrapone, racemic metyrapol, (-)-metyrapol or (+)-metyrapol was analyzed in rat adrenal homogenates. Metyrapol was equally as potent as metyrapone in the inhibition of steroid 11 beta-hydroxylase and each enantiomer of metyrapol showed similar inhibitory activity on the rat adrenal steroid 11 beta-hydroxylase. These results indicate there is an insignificant difference in the inhibitory effects on steroid 11 beta-hydroxylase of metyrapol enantiomers, and that the inhibitory effects of metyrapol may be involved in the pharmacological activity of metyrapone in vivo.

Adrenal Glands↗

PubMed1995

Utility of Tc-99m GSA SPECT imaging in estimation of functional volume of liver segments in health and liver diseases.

The authors examined whether there was a difference in liver function among hepatic segments in liver cirrhosis cases, and in cases of hepatocellular carcinoma (HCC) associated with liver cirrhosis. If the average counts in the lateral segment of the left lobe were set at 1, the average counts in the right upper and lower segment of the liver were 0.75 approximately 1.02 (0.89 +/- 0.09, mean +/- SD) in normal cases, 0.38 approximately 2.24 (1.01 +/- 0.39) in liver cirrhosis cases, and 0.61 approximately 2.85 (1.15 +/- 0.58) in HCC cases. There is a significant difference between normal cases and liver cirrhosis cases or HCC cases (P < 0.001). Also, in HCC cases, if the average counts in the cancer-bearing segment of the liver were set at 1, the average counts in the noncancerous segment of the liver were 0.55 approximately 2.85 (1.23 +/- 0.58), and many average counts in the cancer-bearing segment were equal to, or lower than those in the noncancerous segment. It has been found that there were significant differences in function among hepatic segments in liver cirrhosis cases, and in HCC cases. Furthermore, the liver function in the cancer-bearing segment tended to be worse due to the existence of carcinoma compared with that in the noncancerous segment.

Adult↗

PubMed1995

Prediction of pulmonary function after resection of primary lung cancer. Utility of inhalation-perfusion SPECT imaging.

To help determine whether preoperative perfusion and inhalation SPECT imagings are useful in predicting postoperative lung function, Tc-99m MAA perfusion SPECT imaging, CT scans, and pulmonary function tests were prospectively performed in 33 patients with primary lung cancer before and after lobectomy or pneumonectomy. Tc-99m Technegas inhalation SPECT imaging was performed in 6 of 33 patients as well. The authors also studied changes in radioactivity on the operated and nonoperated sides before and after surgery, examined the lowest limit value for adaptability to the operation, and made a comparison of both perfusion and inhalation SPECT imaging. The predicted postoperative values obtained from the preoperative Tc-99m MAA SPECT images correlated more closely with the measured 6-month postoperative values than with the measured 3-month postoperative values. The highest correlation coefficient (r = 0.86) was observed between the predicted forced vital capacity (FVC) value and the measured 6-month postoperative FVC value. In many cases, there was not a great difference between the 6-month and 3-month radioactivity on the operated side obtained from Tc-99m MAA SPECT images. This appears to indicate that pulmonary blood flow on the operated side has completely recovered by 3 months after surgery. However, radioactivity in both the upper and lower lobes of the nonoperated side increased soon after surgery compared with that before the operation, and had not returned to preoperative levels 6 months after surgery. The radioactivity in the right middle lobe did not change before and after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

PubMed1995

Golgi membrane vesicles in HeLa mitotic cells are identified with monoclonal antibody made against Golgi cisternal membrane protein p138.

A monoclonal antibody (mAbG3A5) recognizing p138 antigen was used to identify the Golgi cisternal membrane and determine behavior of Golgi fragments during mitosis in HeLa cells. At the start of mitosis, Golgi stacks identified with the mAbG3A5 antibody were fragmented into fine membrane vesicles which were distributed throughout the cytoplasm leaving only the region of the chromosome cluster unoccupied. On Western immunoblotting analysis, p138 was found associated with the membrane fraction prepared from mitotic HeLa cells having a buoyant density the same as that of interphase Golgi membranes. In addition to the fine membrane vesicles, clusters labeled with mAbG3A5 antibody were frequently observed in mitotic cells. They numbered 11 on average per mitotic cell and consisted of fine membrane vesicles of which membrane region was labeled with the mAbG3A5 antibody. This fact indicates that the membrane vesicles in mitotic Golgi clusters were also part of the fragments of Golgi cisternae. The number of mitotic Golgi clusters per mitotic cell was constant from prophase to anaphase, increasing twofold at telophase, although the average size of mitotic Golgi cluster remained unchanged throughout mitosis. The increase in number of mitotic Golgi clusters at telophase was accompanied by decrease in immunofluorescence of fine membrane vesicles. Treatment with nocodazole caused the disappearance of the mitotic Golgi clusters from prophase cells; however upon removal of it, they were reformed. These results suggest that during mitosis the Golgi apparatus were fragmented to fine membrane vesicles leaving only a part as mitotic Golgi clusters and were reassembled through tentative clustering of the fine membrane vesicles at the end of mitosis.

Animals↗

PubMed1995

[Serial assessment of MIBG scintigraphy in a case of DCM with heart failure improved by beta-blocker therapy].

We experienced a case of DCM (62-year-old man) improved by beta-blocker (Metoprolol) therapy and studied time course of MIBG scintigraphy. We measured cardiac functions by UCG and 99mTc cardiac pool imaging, and MIBG scintigraphy during 12 months of beta-blocker therapy. In planar images we measured washout rate (WR) in total myocardium and regional washout rate (rWR) in 6 segments of myocardium. Cardiac function improved after 3 months of therapy. The WR did not improve until 6 months, but improved after 9 months (Before: 35.1%, 3 months after: 34.6%, 6 months after: 33.6%, 9 months after: 27.6%, 12 months after: 25.4%). rWR in inferoapical segment first improved at 3 months (Before: 40.1%, 3 months after: 35.1%), whereas rWR in antero-apical segment improved after 6 months and that in anterior segment improved after 9 months. These results suggest that the improvement of cardiac sympathetic nerve function in DCM treated with beta-blocker was not identical in each myocardium region.

3-Iodobenzylguanidine↗

PubMed1995

Endothelin-1-induced downregulation of ETB receptor mRNA: participation of cAMP.

In this study we examined the participation of cAMP formation in endothelin-1 (ET-1)-induced downregulation of ETB receptor mRNA in ROS 17/2 rat osteosarcoma cells. Dibutyryl cAMP induced downregulation of ETB receptor mRNA in a time-dependent manner. ET-1 induced production of inositol phosphates and an increase of cAMP level in ROS 17/2 cells. A stimulatory effect on cAMP level was also observed when A23187 plus PMA was added to the cells. The increase in cAMP level induced either by ET-1 or by A23187 plus PMA was inhibited by indomethacin. The downregulation of ETB receptor mRNA induced by ET-1 was significantly inhibited by indomethacin. These results suggest that the ET-1-induced downregulation of ETB receptor mRNA in ROS 17/2 cells may be partly mediated through the increase in cAMP level secondary to the activation of the phosphoinositide hydrolysis/Ca2+ transduction cascade.

Animals↗

PubMed1994

Endothelin-1 activates mitogen-activated protein kinases through two independent signalling pathways in rat astrocytes.

Northern blot analysis and displacement study revealed that the endothelin (ET) receptor functionally expressed in rat primary cultured astrocytes is the ETB receptor. Mitogen-activated protein kinases (MAP kinases) in the cells were activated by 10 nM ET-1, a dose that maximally stimulated phosphoinositide hydrolysis. This activation was potently inhibited by pretreatment of the cells with phorbol 12-myristate 13-acetate (PMA) which leads to protein kinase C (PKC) down-regulation and was slightly inhibited by pretreatment with pertussis toxin (PTX). Pretreatment of the cells with PMA plus PTX completely inhibited the ET-1-augmented MAP kinase activity. Activation of MAP kinases was also induced by 0.1 nM ET-1, which hardly stimulated phosphoinositide hydrolysis. This activation was fully inhibited by pretreatment with PTX but insensitive to pretreatment with PMA. ET-1-stimulated production of inositol phosphates was not affected by pretreatment with PTX. These results suggest that activation of MAP kinases secondary to stimulation of the ETB receptor with ET-1 in rat primary cultured astrocytes was mediated through two independent signalling pathways. PKC-dependent pathway and PTX-sensitive G protein-mediated pathway.

Animals↗

PubMed1994

Increased levels of active pertussis toxin may aid a pertussis vaccine to pass the mouse body weight gain test.

The mouse weight gain test was evaluated for its value in toxicity testing for pertussis vaccines. When the reference whole cell pertussis vaccine was tested at dilutions of 1 in 1 and 1 in 16, the mice which received the 1 in 1 dilution achieved the greatest weight gain by the seventh day of injection, although they experienced a more significant weight loss during the first 24 hours than both the normal control mice or those that received the 1 in 16 dilution. A commercial diphtheria-tetanus-acellular pertussis vaccine with an increased level of pertussis toxin activity significantly accelerated the weight gain of mice. The effect was lost by heating the vaccine at 80 degrees C for 2 hours. A 1 micrograms dose of endotoxin induced a significant weight loss in mice during the first 24 hours of injection followed by weight gain at the same rate as that of the normal control. Pertussis toxin accelerated the weight gain of mice at a dose of 2 micrograms to a level exceeding that of the normal control mice throughout the observation period of 11 days. Pertussis toxin, when inoculated with endotoxin, showed a marked effect of helping mice to recover quickly from the endotoxin-induced initial weight loss to the level of those receiving only pertussis toxin. The effect of pertussis toxin on the acceleration of the weight gain of mice showed the possibility of inappropriate interpretation of the test results. It suggests, therefore, the necessity for separate quantitative tests for controlling the vaccine's toxicities.

Animals↗

PubMed1994

Effects of 16, 16-dimethyl prostaglandin E2 on lysosomal membrane stability in rat stomach.

The lysosomal membrane encloses numerous hydrolytic enzymes and prevents the cytoplasm from being damaged by these enzymes. It is possible that the fragility of this membrane may be implicated in the pathogenesis of gastric mucosal damage. We investigated the effects of 16,16-dimethyl prostaglandin E2 (dmPGE2), which is known to protect the gastric mucosa from various noxious agents, on lysosomal membrane stability in the rat stomach. Sodium taurocholate (TC) was used as the damaging agent. To assess lysosomal membrane stability in the gastric mucosa, we assayed acid phosphatase released from lysosomes isolated from a gastric mucosal homogenate. To assess lysosomal membrane stability in gastric surface epithelial cells, we used laser scanning confocal microscopy to observe the fading of red fluorescence in living cells vitally stained with acridine orange. Exogenous dmPGE2 enhanced lysosomal membrane stability in the gastric mucosa, whereas TC decreased it. In gastric surface epithelial cells, exogenous dmPGE2 protected the cells against TC-induced damage and prevented TC-induced decreased lysosomal membrane stability. It was concluded that a decrease in lysosomal membrane stability seemed to be closely involved in the pathogenesis of gastric mucosal damage. Moreover, it appears that stabilization of the lysosomal membrane by exogenous dmPGE2 may contribute to its protective effect in the gastric mucosa, both at the level of gastric surface epithelial cells and in regard to the entire gastric mucosa.

Acid Phosphatase↗

PubMed1994

Effect of successful angioplasty following thrombolysis on infarct size and left ventricular function.

The role of the angioplasty following thrombolysis in acute myocardial infarction has been discussed in several studies, however the effect of successful angioplasty on infarct size and left ventricular function has not been properly evaluated. Successful reperfusion was achieved in 79 out of 104 patients with primary anterior acute myocardial infarction. These patients were classified as follows, according to the type of intervention during the acute phase: 50 patients in which thrombolysis was successful (the thrombolysis group); 12 patients who underwent successful immediate angioplasty following successful thrombolysis (the immediate angioplasty group); and 17 patients in which rescue angioplasty was successful (the rescue angioplasty group). The 25 patients whose infarct-related vessels were not reperfused after intervention were classified as the non-reperfused group. Infarct size, evaluated as defect volume by T1-201 SPECT, 1 month after the onset, was 840 +/- 154 units (mean +/- S.D.) in the immediate angioplasty group and was similar to that in the thrombolysis group (948 +/- 88 units), but significantly smaller than in the non-reperfused group (1759 +/- 108 units). There were no significant differences in left ventricular function in the immediate angioplasty group and the thrombolysis group. Successful rescue angioplasty did not have any beneficial effect on left ventricular functions or infarct size, when compared with the failed thrombolytic group (1105 +/- 169 units vs. 1617 +/- 169 units). End-diastolic volume (52 +/- 3 ml/m2) in the successful rescue angioplasty group, however, was significantly smaller than in the failed thrombolysis group (67 +/- 3 ml/m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

[Superselective bronchial arterial infusion therapy with cisplatin and epirubicin hydrochloride, mitomycin C-iohexol-Lipiodol emulsion (EMILE) for hilar lung adenocarcinoma: preliminary clinical experience].

A case of hilar lung adenocarcinoma was treated by superselective bronchial arterial infusion therapy with cisplatin and epirubicin hydrochloride, mitomycin C-iohexol-Lipiodol emulsion (EMILE) using Tracker -18 infusion catheter. The tumor size was reduced on follow-up CT scans. However, EMILE was also distributed to nontumorous lung tissues around the tumor, and a shrinkage of the right upper lobe and elevations of the right hilus and diaphragm followed. No major complaints and clinical complications during and after the treatment occurred. This therapy was safe and effective for local tumor reduction in a case of hilar lung adenocarcinoma.

Adenocarcinoma↗