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Biomedical subjects

K Sakata

Publications and source records attributed to K Sakata.

At least 19 recordsLinked to original sources

An endothelin B receptor-selective antagonist: IRL 1038, [Cys11-Cys15]-endothelin-1(11-21)

In the inhibition of specific binding of [125I]endothelins (ETs) to membrane from various tissues of rats, guinea pigs, pigs and humans, [Cys11-Cys15]-ET-1(11-21), IRL 1038, has a much higher affinity for ETB receptors (Ki = 6-11 nM) than for ETA receptors (Ki = 0.4-0.7 microM). In contraction assays, with ET-3 as a stimulant, 3 microM IRL 1038 antagonized the ETB receptor-mediated contraction of guinea pig ileal and tracheal smooth muscle without any significant agonistic activity, but did not effect the ETA receptor-mediated contraction of rat aortic smooth muscle. IRL 1038 is therefore, considered to be the first antagonist selective to the ETB receptor.

Amino Acid Sequence

Effects of endothelin on cytosolic Ca2+ level and mechanical activity in rat uterine smooth muscle.

The effects of endothelin (ET) on cytosolic Ca2+ level ([Ca2+]i) and mechanical activity were examined in isolated rat uterine smooth muscle. ET-1, ET-2, ET-3 and sarafotoxin S6b (STX) induced rhythmic contractions superimposed on an increased muscle tone. The concentration needed to induce a half-maximum contraction (EC50) was 1.6-3.3 nM for ET-1, ET-2 and STX and higher than 200 nM for ET-3, suggesting that the ET(A) receptor is responsible for these contractions. The sensitivity to ET-1 of uterus at day 20 of gestation was higher than that of non-pregnant rat uterus. Contraction induced by ET-1 followed an increase in [Ca2+]i. The relation between [Ca2+]i and muscle tension, an an indicator of Ca2+ sensitivity of contractile elements, in the presence of ET-1 was identical to that in the presence of high K+ in non-pregnant and pregnant rat uteri. The ET-1-induced increases in [Ca2+]i and muscle tension were strongly inhibited by verapamil in non-pregnant rat uterus. In pregnant rat uterus, however, verapamil only partially inhibited the increases. The verapamil-insensitive portions of [Ca2+]i and contraction were inhibited by EGTA. In the absence of external Ca2+, ET changed neither [Ca2+]i nor muscle tension. These results suggest that ET-1 acts on ET(A) receptors, increase [Ca2+]i and induces contraction without changing Ca2+ sensitivity of contractile elements. The increase in [Ca2+]i seemed to be mediated by opening of L-type Ca2+ channels in non-pregnant rat uterus and also of non-L-type Ca2+ channels in pregnant rat uterus, but not by Ca2+ release from intracellular storage sites.

Animals

Neutrophil chemotactic factors produced by a cell line from thyroid carcinoma.

A neutrophil chemotactic factor (human interleukin 8, human granulocyte-macrophage colony-stimulating factor)-producing cell line, named KHM-5M, was established from a patient with an undifferentiated thyroid carcinoma, neutrophilia, and malignant pleurisy with many neutrophils and a few malignant cells. The cell line was transplanted into nude rats, and the infiltration of neutrophils was observed in and around the transplanted tumor tissue. Neutrophil chemotactic activity was predicted from the clinical features and pathological findings in this case. The extreme chemotactic activity of the neutrophils was demonstrated in conditioned medium from KHM-5M cells using the modified Boyden chamber technique. With sodium dodecyl sulfate-polyacrylamide gel electrophoresis, at least two neutrophil chemotactic activities in conditioned medium from the cell line were observed. The levels of these activities derived from KHM-5M cells were screened by measuring conditioned medium from the COS cells, which expressed a complementary DNA library from the KHM-5M cells. Chemotactic activities (human interleukin 8, human granulocyte-macrophage colony-stimulating factor) were identified by DNA cloning. These results show that the KHM-5M cells derived from an undifferentiated thyroid carcinoma produce multicytokines and suggest that those cytokines modified some pathological features in this case.

Aged

Physiologic capacity of well-developed collaterals in patients with isolated left anterior descending artery disease.

To assess the physiologic significance of well-developed collaterals, 34 patients, with isolated left anterior descending artery disease (LAD) and without overt prior myocardial infarction, underwent cardiac catheterization and exercise thallium-201 emission computed tomography. The patients were divided into 3 groups; 11 patients with 90% stenosis of the proximal LAD and without collaterals (group 1), 11 with 99% stenosis of the proximal LAD, and without collaterals (group 2) and 12 with a total occlusion of the proximal LAD which was completely filled by well-developed collaterals (group 3). On left ventriculography, shortening fractions of the anterior wall were significantly reduced in group 2 as compared to group 1 and 3 (group 1 vs group 2: p less than 0.01, group 2 vs group 3: p less than 0.05), which reflected the lower ejection fraction of group 2 (p less than 0.01 and p less than 0.05, respectively). The perfusion defects of the anterior wall on both the initial and the delayed images were severer in groups 2 and 3 than in group 1 (group 1 vs group 2 and group 1 vs group 3 on the initial image: p less than 0.01, for both, group 1 vs group 2 and group 1 vs group 3 on the delayed image: p less than 0.05, for both). However, recovery of the perfusion defects from the initial image to the delayed image was better in group 3 than in groups 1 and 2 (group 1 vs group 2 and group 1 vs group 3: p less than 0.05, for both). Therefore, coronary blood flow through well-developed collaterals was considered to be comparable to the flow through a diseased vessel with 90% stenosis at rest. During maximal exercise, blood flow through well-developed collaterals was considered to be comparable to the flow through a diseased vessel with 99% stenosis, although the blood flow through well-developed collaterals was considered to be better than that through 99% stenosis during the recovery period. These findings suggest that patients with well-developed collaterals must be treated like those with severe stenosis.

Aged

Circulating myosin light chain I levels after coronary reperfusion: a comparison with myocardial necrosis evaluated from single photon emission computed tomography with pyrophosphate.

This study was performed to assess the influence of coronary reperfusion on the serial serum myosin light chain (LC)I levels and to evaluate the relationship between the peak LCI level and the infarct size calculated from single photon emission computed tomography (SPECT) with technetium-99m pyrophosphate (Tc-99m PYP) in 11 patients who underwent coronary reperfusion. Blood was drawn before reperfusion, immediately after reperfusion, and once a day for 14 days, to estimate the time course of serum LCI release. The infarct size estimated by Tc-99m PYP ranged from 7.3 to 62.4 ml. The LCI levels obtained before reperfusion were less than 2.5 ng/ml but those obtained immediately after reperfusion were much higher. The value ranged from 2.7 to 9.7 ng/ml and that expressed as a percentage of peak LCI (% peak LCI) ranged from 19 to 83%. Collateral circulation, reperfusion arrhythmia and the degree of residual stenosis had no influence upon the % peak LCI. The correlation between peak LCI levels and SPECT-determined infarct size was good, with a correlation of 0.76 (p less than 0.01, regression line by least squares method y = 3.31 + 1.53x). Early serum LCI might be influenced by coronary reperfusion but the peak LCI value reflected acute myocardial necrosis in patients who underwent coronary reperfusion.

Adult

Circadian fluctuations of tissue plasminogen activator antigen and plasminogen activator inhibitor-1 antigens in vasospastic angina.

To elucidate the circadian variation of fibrinolytic components in vasospastic angina, plasma levels of tissue plasminogen activator antigen (t-PA), free plasminogen activator inhibitor antigen (free PAI-1), t-PA/PAI-1 complex, and total PAI-1 were measured in venous plasma samples. Samples were taken every 6 hours (6:00 AM, noon, 6:00 PM, and midnight) for 24 hours in 14 patients with vasospastic angina, in 9 patients with exertional angina, and in 19 normal subjects. Twenty-four-hour Holter monitoring (Holter monitor, Del Mar Avionics, Irvine, Calif.) was also carried out in all subjects. All of the fibrinolytic components showed circadian variation, with a peak level at 6:00 AM in every study group except for the t-PA/PAI-1 complex in the group of patients with exertional angina. The values for all or the fibrinolytic components at each sampling time were higher in patients with coronary artery disease than in normal subjects. In particular, the mean value of free PAI-1 at 6:00 AM in patients with vasospastic angina was significantly higher than that in normal subjects and that in patients with exertional angina. This value of free PAI-1 in patients with vasospastic angina was closely associated with the duration of ischemic attacks. These results suggested that the circadian fluctuation of fibrinolytic components may be an important factor that leads to coronary thrombosis at the time of coronary spasm, especially in the early morning.

Acetylcholine

A method for observing cross-sectional views of biomembranes.

Cross-sectional views of intact biomembranes and synthetic lipid bilayer membranes were observed by electron cryomicroscopy using spontaneous orientation of disk-shaped membranes; purple membrane, thylakoid membrane, synthetic phospholipid membrane and a microcrystalline sheet made of Er-binding polypeptide were observed. The membranes were observed fully hydrated, embedded in vitreous ice, and their self-orientation was most probably caused by repulsion between their hydrophobic edges and their hydrophilic environment which forced their edges to be exposed to the air-water interface. The cross-sectional profiles of the native biomembranes were asymmetric and characteristic, whilst those of the synthetic membranes were symmetric and predictable by a simple model. Simple Fourier analysis showed that the cross-sectional images retained structural information up to a medium resolution.

Amino Acid Sequence

Cell culture of Taxus as a source of the antineoplastic drug taxol and related taxanes.

Callus cultures of Taxus cuspidata and Taxus canadensis were induced using different tissue explants including green and red arils, seed contents, young stems and needles. Callus derived from stem segments displayed the best growth in defined media. The culture medium was supplemented with reducing agents and phenolic-binding compounds to inhibit callus darkening and subsequent growth reduction. T. cuspidata explant growth was affected by different concentrations and ratios of 2,4-D and kinetin. Callus tissues of T. cuspidata were extracted for taxol after 2 months in culture and analysed by HPLC. The presence of taxol (0.020 +/- 0.005% of the extracted dry weight) was indicated based on retention time, U.V. spectra, peak purity as assessed by photo-diode array spectroscopy and compared with an authentic taxol standard, as well as by 1H-NMR analysis. Suspension cultures of T. cuspidata were established from the callus cultures, subsequently immobilized onto glass fiber mats, and maintained as immobilized cultures for 6 months. The immobilized cell cultures also produced taxol at levels up to 0.012 +/- 0.007% of the extracted dry weight.

2,4-Dichlorophenoxyacetic Acid

Linear quadratic model of radiocurability on multicellular spheroids of human lung adenocarcinoma LCT1 and mouse fibrosarcoma FSA.

The LCT1 cells derived from a human lung adenocarcinoma and the FSA cells from a mouse fibrosarcoma were found to form spheroids. The cure-dose relationship of spheroids and the survival curves of their component cells were analysed by using a linear-quadratic model for cell survival and a Poisson distribution for cure. The analysis resulted in three conclusions: (1) the double minus logarithm of cure probability was linearly related to radiation dose, (2) the critical cell number was constant at any given cure probability, and (3) cellular radiosensitivity was also constant. The experiments seem to meet these conditions for each of two kinds of spheroids. Control doses (50%) were 20 Gy for LCT1 spheroids and 21 Gy for FSA spheroids, both 400 microns in diameter. The analysis showed that the lower cellular radiosensitivity and the higher number of clonogenic cells made LCT1 spheroids more radioresistant than FSA spheroids and that the higher critical number of 130 cells made the LCT1 spheroids more sensitive than the FSA spheroids with 18 such cells. The overall radiocurability of spheroids was a result of these three opposing effects, indicating that the critical cell number can be one important factor in determining the radiocurability of multicellular systems.

Adenocarcinoma

Distribution of the collagen binding heat-shock protein in chicken tissues.

We examined the tissue distribution of heat-shock protein MW 47,000 D, hsp47, which binds to native and denatured collagen including Types I, III, and IV, in various chicken tissues by Western blotting and immunohistochemical methods. hsp47 was located on fibrocytes or fibroblasts in the connective tissue in various organs, chondrocytes in the cartilage, smooth muscle cells in the gastrointestinal tract and blood vessels, vitamin A storage cells in sinusoidal area of liver, endothelial cells in blood vessels, and epithelial cells of renal glomeruli, tubules, and basal layer of epidermis. These cells also co-expressed a certain type of collagen molecule. Furthermore, in developing embryos, fibroblasts and chondrocytes expressed hsp47 before the deposition of collagen Type I or Type II in the surrounding tissue. These results indicate that the binding of hsp47 to collagen molecules has important biological significance.

Animals

Percutaneous transluminal coronary angioplasty in a patient with Kawasaki disease. A case report of an unsuccessful angioplasty.

A 13-year-old boy with severe coronary stenosis due to Kawasaki disease underwent percutaneous transluminal coronary angioplasty (PTCA). The guide wire and the balloon catheter easily passed through the stenosis in the left anterior descending artery. However, effective dilatation could not be achieved even when the balloon size was increased to 2.5 mm in diameter. We discontinued further inflation of the balloon because serious resistance was encountered on withdrawal of the balloon catheter. In patients with Kawasaki disease, the value of PTCA as a treatment for coronary stenosis is questionable.

Adolescent

Localization of exercise-induced myocardial ischemia with ST depression.

This study was undertaken to determine whether the site of ST depression on 12-lead exercise electrocardiography can identify the ischemic site assessed by myocardial Tl-201 emission computed tomography in 409 patients with transient defects. ST depression in some leads was more frequent in those with inferior or lateral ischemia than in those with anterior ischemia. In 214 patients with ST depression and no ST elevation, however, the frequency of ST depression in each lead was similar between those with and without anterior ischemia. In 63 patients with ST depression, single vessel disease and no infarction, the frequency of ST depression in each lead was similar among those with anterior, inferior and lateral ischemia. Moreover, in patients with abnormal Q waves, the site of ST depression was not related to the location of ischemia. In conclusion, the site of exercise-induced ST depression could not be used to determine an ischemic region.

Arteriosclerosis

[The prevalence of diabetes mellitus and impaired glucose tolerance studied by 75 gram oral glucose tolerance test in a rural island population].

A mass health examination was performed to assess the glucose tolerance of inhabitants of the island of Ojika, in the Goto islands, Nagasaki prefecture Japan. There were 554 males and 820 females older than 34 years who participated in the mass health examination, a response rates of 42 percent and 52 percent for males and females respectively. Serum glucose levels after overnight fasting and at 2 hours after a 75 gram oral glucose tolerance were used with WHO criteria to classify individuals. Among these subjects, the prevalence of diabetes mellitus increased with age, with a prevalence of diabetes mellitus of around 10 percent in the older subjects. The prevalence for males was higher than that for females. Prevalences of impaired glucose tolerance were roughly in the 15-25 percent range and did not show clear differences among different age groups and sexes. From a questionnaire survey of all island inhabitants, it was considered that the degree of bias of the results was small, if any. The true prevalence for all the inhabitants may be a little larger than the observed prevalence of these subjects.

Adult

[Intra-arterial infusion chemotherapy for hepatocellular carcinoma using an implantable drug delivery system].

Intra-arterial chemotherapy and chemoembolization using implantable drug delivery system were performed in sixty-one cases of unresectable hepatocellular carcinoma (HCC). The following results were obtained. (1) The follow-up period was 253 days, and the administrations numbered 13.9 times on average. (2) Response rate was 31.1%. (3) AFP decreased in 80% cases, and PIVKA-II in 83.3% cases. (4) Tumor thrombus in the portal vein disappeared in 4 of 40 cases(10%). (5) Free-CDDP continued for 60 minutes after injection of cisplatin-phosphatidyl-choline-Lipiodol (CPL), and the response rate was 47%. (6) The survival rates were 56% in one year, 25% in two years, and 20% for three years. These results were significantly higher than those of one shot therapy. It is suggested that good therapeutic effects can be obtained by the implantable drug delivery system, and CPL was a useful anticancer agent for the therapy.

Biomarkers

[Effects of isosorbide dinitrate on coronary and systemic circulation in children: comparison with dipyridamole].

The effects of isosorbide dinitrate (ISDN) on the coronary and systemic circulation were evaluated in comparison with the effects of dipyridamole (DP) in 8 children with histories of Kawasaki disease and angiographically normal coronary arteries. ISDN (100 micrograms/kg) was administered as an intracoronary injection. DP was administered intravenously at the rate of 0.56 mg/kg for 4 min. In the coronary circulation, DP induced a significant reduction of the afterload, resulting in an increase in cardiac output. However, the pulmonary artery pressure, pulmonary capillary wedge pressure and left ventricular end-diastolic pressure, which are related to the preload, were significantly reduced one min after the ISDN injection. The systolic blood pressure was reduced, while the heart rate was increased. The cardiac output, pressure-rate product or systemic vascular resistance showed no significant change. The systolic work index, however, was significantly reduced. In the coronary circulation, DP significantly increased the coronary sinus blood flow due to dilatation of the resistant vessels. However, ISDN significantly dilated the conductant vessels by 4.0 to 12.9% in diameter. There was, however, no change in the coronary blood flow, coronary perfusion pressure nor coronary vascular resistance. The grade of dilatation of the coronary vessels caused by ISDN was lower in children than in adults.

Adolescent

[A case of infective endocarditis with multiple embolic complications].

A 13-year-old girl was admitted to a hospital because of fever and sore throat. Staphylococcus aureus was obtained on blood culture, and she was treated with antibiotics under the diagnosis of sepsis and DIC. Echocardiography showed huge vegetation attached to the posterior leaflet of mitral valve and severe mitral regurgitation. CT scan revealed multiple heterogeneous high density areas in her brain. She was transferred to our hospital for further examination and treatment. Large verrucae on the mitral valve, severe regurgitation and repeated embolism urged us to the emergency mitral valve replacement. Debridement of abscess on the posterior wall of the left atrium and ventricle necessitated patch plasty of those structures and mitral ring as well. Operative and postoperative examination showed mycotic aneurysm of right coronary artery, multiple brain hemorrhage, arterial obstructions of extremities and splenic infarction. Sooner she recovered except for slight macular degeneration caused by retinal embolism.

Adolescent

[Left ventricular approach for muscular ventricular septal defects in infant].

Two infants less than 4 months of age underwent repair of apical muscular VSD with left ventriculotomy. First case was 3 months old boy who had already undergone enlargement of the hypoplastic aortic arch with subclavian flap aortoplasty and pulmonary artery banding because of the associated aortic coarctation. Second case was 4 months old Down syndrome girl who associated with ASD and PDA. Both infants were diagnosed the apical muscular VSD with echocardiography and left ventriculography. We performed short longitudinal left ventriculotomy which was parallel to the left anterior descending coronary artery between the diagonal branch and left circumflex artery. VSD was closed with Gore-Tex patch using 6-0 prolene buttress stitches. Post operative echocardiography showed good LV contractile function (Ejection Fraction = 71%, 80%), and no residual interventricular shunt. Left ventriculotomy for the apical VSD closure allowed good exposure and did not reduce the LV function even in infants. Therefore, we concluded that left ventriculotomy was an useful procedure for the apical muscular VSD in infants.

Cardiac Surgical Procedures

[Clinical study of bronchial inhalation challenge in summer-type hypersensitivity pneumonitis induced by Trichosporon cutaneum].

To evaluate the methods and criteria of judgement for the bronchial antigen inhalation challenge test, the test was performed with culture filtrate antigen of serotype I and II of Trichosporon cutaneum in 18 patients with summer-type hypersensitivity pneumonitis from 15 families. The quantity of 15 mg of culture filtrate antigen was adequate, and had no side effects. In the tests, 17 of 18 patients showed a positive reaction to both or either, serotype of antigen. In 36 performances of inhalation, there were 21 positive reactions and 15 negative reactions. According to the criteria of judgment for inhalation challenge test, the positive response rates of observation items were 75% for symptoms and signs, and 51% for laboratory data. Items with a high positive rate were cough, crepitant rales, and decrease of PaO2. On the other hand, low positive rates were observed for decrease of DLco, VC and positive CRP. Items with both high sensitivity and high specificity were cough, crepitant rales and decrease of PaO2. The low positive rate of decreased DLco was due to insufficient improvement before inhalation challenge. It was concluded that our methods and criteria of judgment for bronchial inhalation challenge test are useful.

Adolescent