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Biomedical subjects

K Onoda

Publications and source records attributed to K Onoda.

At least 73 records · Page 4Linked to original sources
PubMed1991

The enhancement of myocardial protection through an acalcemic storage solution containing nicardipine, a potent calcium channel blocker. A basic study using rat ventricular myocytes.

Adult rat ventricular myocytes were used as a model system for investigating the direct effects of nicardipine, a potent calcium-channel blocker, on preservation of the heart during periods of simple cold storage. Cells were stored at 4 degrees C for 24 hr with an acalcemic storage solution. The superfusate then was exchanged with hypoxic Tyrode solution (1.8 mmol/L CaCl2). After 2 hr of hypoxia at 20 degrees C, cells were reoxygenated and simultaneously warmed to 37 degrees C. The addition of nicardipine to both the storage solution and Tyrode solution resulted in the highest percentage of viable cells (70.5%). Using either the storage solution or Tyrode solution containing the compound, the percentages of viable myocytes were 51.9% and 52.2%, respectively. In the absence of the drug in either solution, the percentage was 38.0%. The effect of diltiazem, another potent calcium-channel blocker, was examined using the same experimental procedure. The addition of diltiazem to Tyrode solution elevated the viability of ventricular myocytes, but addition to the storage solution showed no cardioprotective effect. Moreover, the addition of 8-bromo cyclic GMP to the storage solution resulted in a cardioprotective effect. These results suggested that nicardipine exerts a direct effect on myocardial protection in hypothermic and acalcemic storage solution and that the pharmacological effect of nicardipine depends on a mechanism other than its calcium-channel blocking action.

Animals↗
PubMed1991

[Basal ganglia germinoma treated with interstitial brachytherapy; case report].

A case of primary intracranial germinoma in the left basal ganglia treated with interstitial brachytherapy was reported. A 15-year-old boy was referred to our hospital for evaluation of right hemiparesis. A CT scan showed a slightly hyperdense mass with multiple cystic low density in the left basal ganglia. The mass was heterogeneously enhanced after intravenous administration of contrast material. T1 weighted image showed a slightly hyperintense mass with cystic components and the mass was heterogeneously enhanced with Gd-DTPA. T2 weighted MR image showed a mixed intensity mass and peritumoral edema. Stereotactic needle biopsy and implantation of 3 catheters for interstitial brachytherapy were performed simultaneously using BRW CT guided stereotactic apparatus. After the histological diagnosis was confirmed to be two cell pattern germinoma, 9 iridium-192 seeds were inserted into the catheters and maintained for 10 days to give 35Gy of irradiation at the tumor periphery. Subsequent CT scans showed marked tumor regression and the clinical symptoms were improved. Germinoma originating in the basal ganglia is rare and hard to diagnose previous to biopsy. Histological confirmation is essential before initiation of treatment because germinoma is commonly thought to be radiosensitive tumor. The interstitial brachytherapy enables selective irradiation of the tumor and actually causes no complications such as bone marrow suppression or cerebral atrophy. The neuroradiological findings, especially of CT scan and MRI, were presented and the strategy for treatment of germinoma in basal ganglia was discussed.

Adolescent↗
PubMed1990

Different expression of protein kinase C isozymes in pancreatic islet cells.

To elucidate differential roles of protein kinase C isozymes in pancreatic islet cells, the precise localization of the isozymes in rabbit and rat islet endocrine cells was investigated using monoclonal antibodies specific for three types of the enzyme. We detected strong immunoreactivity for the type III protein kinase C in B cells. Immunoreactivity for the type II enzyme was seen in A cells, and no apparent immunoreactivity for type I was observed in the islet cells. The expression of the type III protein kinase C in B cells was confirmed using rat insulinoma cells. The predominant expression of the type III enzyme in these cells was shown by immunoblotting. Moreover, on the basis of an enzyme-linked sandwich immunoassay, the levels of protein kinase C isozymes were determined in these cells. The significant amounts of the type III enzyme was detected, but the contents of the type I and II enzyme were under detectable level. These results suggest that the type III protein kinase C is involved in the regulation of insulin release in pancreatic B cells.

Adenoma, Islet Cell↗
PubMed1990

[Evaluation of aortocoronary bypass operation using a He-Ne laser flowmeter--comparison between internal mammary artery grafts and saphenous vein grafts].

It was very difficult to measure myocardial blood flow in clinical cases. Recently, a He-Ne laser doppler flowmeter was developed, and we made it possible to measure the pre-and post-operative myocardial blood flow in cases of coronary artery bypass grafting (CABG). We applied a laser flowmeter to 30 cases of bypass grafting to the left anterior descending coronary artery (18 cases with IMAG and 12 cases with SVG). The preoperative myocardial blood flow at the right ventricular anterior wall was 77 +/- 15 ml/min/100 gr, and the postoperative flow at the same point was 81 +/- 12 ml/min/100 gr. There was no significant change between the pre-operative value and the postoperative one. Myocardial blood flow at the left ventricular anterior wall in SVG group significantly increased from the preoperative value of 58 +/- 11 ml/min/100 gr to the postoperative value of 86 +/- 9 ml/min/100 gr (p less than 0.001). In IMAG group, myocardial blood flow at the left ventricular anterior wall similarly increased from 73 +/- 14 ml/min/100 gr to 83 +/- 15 ml/min/100 gr (p less than 0.01). The postoperative value of IMAG group was almost equal to the value of SVG group. The increased rate of myocardial blood flow at the left ventricular anterior wall was 52 +/- 32% in SVG group and 18 +/- 12% in IMAG group. These rates were obviously distinguished from the increased rate at the right ventricular anterior wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

[Surgical treatment and long-term results of aneurysms of Valsalva sinus in 24 cases].

Twenty-four patients with aneurysm of Valsalva sinus were surgically repaired over a 23 year period (1965-1988). These patients were ranged 2 to 54 years of age and eleven of them were male. Rupture of aneurysm of Valsalva sinus was combined with aneurysm in 20 cases, ventricular septal defect in 12 cases and aortic regurgitation in 6 cases. At present, our routine operative procedure for ruptured aneurysm is direct closure of the defect with patch closure of aneurysm after resection of the aneurysm, but when the diameter of aneurysm is smaller than 7 mm, direct closure of the defect of the aneurysm was used. Only one patient after patch closure of ruptured sinus of Valsalva (Konno type I) required reoperation for penetration into left ventricle. This case might be avoided if patch was sutured to annulus of aortic valve. There were two operative death and one late death. The former died of cerebral infarction and low output syndrome, the latter died of sepsis. The mean follow-up period (+/- standard deviation) was 8.2 +/- 6.0 years. All patients that were followed were thirteen and found to be in New York Heart Association class I.

Adolescent↗
PubMed1989

Selective low level of protein kinase C isozyme in a tumor promoter-dependent mouse leukemia cell line.

It was found that the activity of protein kinase C in the tumor promoter-dependent cell line (A65T) was significantly lower than that in the independent cell line (A65IND) which was mutated from the dependent cell line. On the other hand, there was no significant difference between these cell lines with regard to cAMP-dependent protein kinase activity. It was found that the maximal binding capacity of [20-3H]phorbol-12,13-dibutyrate of the tumor promoter-dependent cells is lower than that of the independent cells with similar affinities of the two cell lines. Moreover, we found that the level of immunoreactive antigen with monoclonal antibody for type III of protein kinase C in A65T cells was significantly lower than that in the A65IND cells. Thus, this selective lower level of type III of protein kinase C in A65T cells, as compared with A65IND cells means that this difference may be linked to its tumor promoter-dependent cell proliferation.

Animals↗
PubMed1989

Monoclonal antibody assessment of tissue- and species-specific myosin light chain kinase isozymes.

Monoclonal antibodies raised against chicken gizzard smooth muscle myosin light chain kinase were used for immunological and structural studies of this enzyme. Epitope mapping of trypsin-digested chicken gizzard enzyme showed that MM-1, 2, 3, 4, 5, 6, and 7 bind to 65 kDa (trypsin-digested) and 60 kDa (chymotrypsin-digested) fragments which contain the catalytic domain of the kinase. Kinetic analysis demonstrated that MM-7 inhibited kinase activity competitively with respect to ATP and noncompetitively with respect to myosin light chain, thereby indicating that MM-7 binds at or near the ATP binding site of the enzyme. Immunoblot analysis revealed that all these antibodies (MM-1 to 12) reacted with the enzyme (130 kDa) from intestinal and vascular smooth muscles, whereas 5 (MM-1, 3, 4, 6, and 9) or 3 (MM-1, 3, and 4) of 12 antibodies did not cross-react with chicken cardiac muscle or with blood platelet myosin light chain kinase (130 kDa), respectively. None of these antibodies showed cross-reactivity against skeletal muscle myosin light chain kinase. As for mammalian species, MM-11 and 12 reacted with myosin light chain kinase of vascular smooth muscle (140 kDa) and MM-11 cross-reacted with the enzyme (140 kDa) from cardiac muscle of rat and rabbit. These data suggest the existence of at least 4 subspecies of myosin light chain kinase in chicken tissues and the heterogeneity of tissue- and species-specific isozyme forms.

Animals↗
PubMed1989

Anti-gizzard MLCK monoclonal antibody MM13 inhibits superprecipitation and phosphorylation of bovine aortic smooth muscle actomyosin.

We prepared monoclonal antibodies directed against chicken gizzard myosin light chain kinase (MLCK) and used them to study the contractile system of aortic smooth muscle. One monoclonal antibody, MM13, dose dependently inhibited actomyosin superprecipitation of bovine aortic smooth muscle, in accord with the suppression of 20 kDa myosin light chain phosphorylation by endogenous kinase. Immunoblotting analysis demonstrated that MM13 cross-reacted with the 150,000 Mr peptide of bovine aortic actomyosin preparation. The bovine aortic MLCK was purified approximately 2,400-fold to apparent homogeneity by three steps of column chromatography. The purified enzyme has a molecular weight of 150,000 and a slower mobility than chicken gizzard MLCK (130,000 Mr), as determined by SDS-polyacrylamide gel electrophoresis. MM13 also cross-reacted with purified bovine aortic MLCK and inhibited the kinase activity, in vitro. We interpret these findings to mean that binding of the anti-gizzard MLCK monoclonal antibody directly to aortic smooth muscle MLCK (150,000 Mr) decreases the phosphorylation of the 20 kDa myosin light chain, thus suppressing the aortic smooth muscle myosin-actin interaction.

Actomyosin↗
PubMed1989

[Dihydroergotoxine mesylate in the treatment of functioning pituitary adenoma].

Although it is well known that bromocriptine (BC) is effective in the treatment of functioning pituitary adenoma, this agent sometimes causes severe gastrointestinal side effects. In this study, dihydroergotoxine mesylate (EX), which is composed of ergot alkaloids and is similar to BC, was administered to 11 patients with functioning pituitary adenomas who could not tolerate the adverse effects of BC. Three patients (27%) showed clinical improvement with EX treatment alone (1 to 6 mg/day). In another patient, computed tomography demonstrated tumor shrinkage. The remaining seven patients experienced adverse effects while taking EX. These results indicate that EX is a useful alternative to BC in the treatment of functioning pituitary adenoma, particularly in patients who cannot tolerate the side effects of BC. Moreover, pretreatment with EX appears to reduce the incidence of side effects of BC.

Adenoma↗
PubMed1988

Monoclonal antibody recognition of two subtype forms of protein kinase C in human platelets.

Using a hydroxylapatite column chromatographic technique, we obtained the evidence for two subtype forms of protein kinase C in human platelets. These subtypes had a similar chromatographic property to Type II, Type III protein kinase C from the rabbit brain. In addition, in monoclonal antibodies (MC-1a, 2a, 3a) (1) which reacted with specifically Type I, II, III rabbit brain protein kinase C, respectively, only MC-2a and MC-3a reacted with human platelet protein kinase C. All these brain and platelet subtypes have a similar Km value for ATP, the range being from 8.0 to 20.0 microM and a similar IC50 value with regard to the effect of the protein kinase C inhibitor, H-7. Thus, the possibility that specific functions of platelet may be derived from a deficiency of Type I protein kinase C warrants attention.

Animals↗
PubMed1988

Cell type-specific expression of protein kinase C isozymes in the rabbit cerebellum.

Monoclonal antibodies raised against rabbit brain protein kinase C were classified into at least three types, MC-1a, MC-2a, and MC-3a, which selectively interact with hydroxyapatite column chromatographically resolved isozymes type I, II, and III of protein kinase C, respectively, determined on the basis of immunoblotting experiments. Immunoprecipitating analysis revealed that MC-1a, -2a, and -3a interacted with protein kinase C expressed in the brain and MC-2a and -3a, but MC-1a immunoprecipitated the protein kinase from rabbit spleen. Immunocytochemical localization of the protein kinase isozymes in the rabbit cerebellum and spleen was studied using these monoclonal antibodies. Staining with MC-1a was restricted to Purkinje cells of the rabbit cerebellum, and there was no reaction product in the Purkinje cells with either MC-2a or MC-3a. Cells in the granular layer of the cerebellum were labeled with MC-2a, and oligodendroglia in the white matter of the cerebellum was stained with MC-3a. The rabbit spleen contained no product reacting with MC-1a, but MC-2a and MC-3a reacted with lymphocytes in the mantle zone and the periarterial lymphatic sheath of the white pulp, respectively. These results suggest that expression of the protein kinase C isozyme in the rabbit cerebellum may depend on the cell type.

Animals↗
PubMed1988

Immunocytochemical evidence for translocation of protein kinase C in human megakaryoblastic leukemic cells: synergistic effects of Ca2+ and activators of protein kinase C on the plasma membrane association.

Immunological analysis using monoclonal antibodies against subspecies of protein kinase C revealed the predominant expression of the isozyme, type II, in human megakaryoblastic leukemic cells. We investigated the effects of phorbol diester 12-O-tetradecanoyl phorbol-13-acetate (TPA), the Ca2+ ionophore ionomycin and synthetic diacylglycerol 1-oleoyl-2-acetylglycerol (OAG) on the immunocytochemical localization of protein kinase C in these cells. Indirect immunofluorescence techniques revealed the enzyme to be located in a diffuse cytosolic pattern, in the intact cells. When the cells were exposed to 100 nM TPA, the immunofluorescent staining was translocated from the cytoplasm to the plasma membrane. The translocation was protracted and staining on the membrane decreased in parallel with the Ca2+, phospholipid-dependent protein kinase activity. Treatment of the cells with 500 nM ionomycin caused an apparent translocation comparable with that seen with TPA, however, this translocation was transient and most of the cytosolic staining was within 60 min. We also found that 30 micrograms/ml OAG did not have significant effects on distribution of the staining, but rather acted synergistically on the translocation with the suboptimal concentration of 100 nM ionomycin. A similar synergism was also observed with 10 nM TPA and 100 nM ionomycin. These results obtained in situ provide evidence that intracellular Ca2+ and diacylglycerol regulate membrane binding of the enzyme in vivo.

Anti-Bacterial Agents↗
PubMed1988

Effects of cilostazol, a selective cAMP phosphodiesterase inhibitor on the contraction of vascular smooth muscle.

The effects of cilostazol (OPC-13013, 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quin olinone) on cyclic nucleotide metabolism and Ca2+-induced contraction of intact and skinned rabbit arterial smooth muscles were investigated. The concentrations of cilostazol producing 50% inhibition of cyclic adenosine monophosphate phosphodiesterase and Ca2+-dependent cyclic nucleotide phosphodiesterase were 0.4 microM and above 100 microM, respectively. This compound has no significant effect on adenylate cyclase in concentrations of up to 100 microM. Addition of cilostazol increased significantly the cAMP content without significant effect on cyclic guanosine monophosphate level of rabbit thoracic aorta in the presence of forskolin. Moreover, the ED50 value of cilostazol in relaxation of rabbit mesenteric arterial strips was decreased selectively by addition of 0.01 microM forskolin, which alone at this concentration has no effect on vascular contraction. Cilostazol of up to 30 microM did not suppress the Ca2+-induced contraction of the chemically skinned rabbit mesenteric artery. Therefore, cilostazol may produce the relaxation of intact vascular smooth muscle by its inhibition of cyclic adenosine monophosphate hydrolysis.

3',5'-Cyclic-AMP Phosphodiesterases↗