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Biomedical subjects

S Egashira

Publications and source records attributed to S Egashira.

At least 19 recordsLinked to original sources
PubMed1999

Mode of action of a new indolocarbazole anticancer agent, J-107088, targeting topoisomerase I.

J-107088 [6-N-(1-hydroxymethyl-2-hydroxy)ethylamino-12,13-dihydro-2,10-dihydroxy- 13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]-pyrrolo[3,4-c]-carb azo le-5,7(6H)-dione] is a new derivative of NB-506, an indolocarbazole antitumor agent. J-107088 induced single-strand DNA cleavage only in the presence of topoisomerase I (top1) more effectively than NB-506 or camptothecin. The preferable sequences of the DNA cleaved by J-107088 were C/T / G as in the case of NB-506. This base-preference of J-107088 in top1-mediated cleavage was different from that of camptothecin, which was T / G/A. top1 poisons stabilize the complex between DNA and top1 (cleavable complex). This cleavable complex is released on addition of a high concentration of monovalent cation or removal of top1 poisons. The complex induced by J-107088 was quite stable; it was scarcely released on the addition of NaCl or dilution of J-107088, contrary to the case with camptothecin and NB-506. J-107088-inducing complexes were also stable in cultured cells, when the compound was added to the culture medium. These unique in vitro activities of J-107088 on top1 that differed from those of camptothecin and NB-506 may be relevant to its more potent in vivo antitumor efficacy in a human tumor xenographted nude mouse model.

Animals↗
PubMed1998

Relationship between the electrical resistivity of enamel and the relative humidity.

The present study was carried out to investigate the relationship between the relative humidity and the electrical resistivity of enamel in vitro. The electrical resistivity of enamel samples was measured in a thermo-hygrostat where the relative humidity varied between 60% and 90%, with the measurements carried out first in a descending direction and then in an ascending direction. When the electrical resistivity was measured from a low to high relative humidity in an ascending direction, a higher value of electrical resistivity was always obtained in comparison to that when measured in the reverse descending direction. The difference between the mean electrical resistivity in an ascending and a descending direction increased in proportion to the relative humidity. These findings suggest that the diffusion of electrolytes and water in enamel is sensitive to changes in the relative humidity.

Adult↗
PubMed1996

Influence of downscatter in simultaneously acquired thallium-201/technetium-99m-PYP SPECT.

UNLABELLED: Simultaneously acquired dual-isotope imaging is a unique and useful approach in SPECT. Photon spillover, however, is a potential limitation of this technique. METHODS: To investigate the degree of 99mTc downscatter into the 201Tl window in patients, simultaneously acquired dual-isotope 201Tl/99mTc-pyrophosphate imaging was performed in 17 patients with acute myocardial infarction (MI). Thallium-201 SPECT imaging was performed first, with a 201Tl photopeak window after the 201Tl injection (early 201Tl images), followed by 99mTc injection and SPECT acquisition using dual-isotope windows (dual 201Tl images). Twenty-four hours after the 99mTc injection, a third set of 201Tl images was obtained (24-hr 201Tl images). Thallium defect size (extent score) and defect severity (severity score) were calculated from these three sets of 201Tl images to quantify the MI. RESULTS: Technetium-99m accumulation of varying intensity was recognized in all patients. Extent scores and severity scores were identical in early 201Tl images and 24-hr 201Tl images. Both scores, however, in the dual 201Tl images were decreased by 36% and 53%, respectively. CONCLUSION: There in a considerable 99mTc downscatter into the 201Tl window, which prevents precise quantification of MI in simultaneously acquired dual-isotope 201Tl/99mTc-pyrophosphate imaging.

Female↗
PubMed1995

Iodine-123 metaiodobenzylguanidine images reflect intense myocardial adrenergic nervous activity in congestive heart failure independent of underlying cause.

OBJECTIVES: This study was undertaken to assess myocardial adrenergic activity using iodine-123 metaiodobenzylguanidine (MIBG) imaging in patients with heart failure. BACKGROUND: In patients with congestive heart failure, adrenergic nerve activity is accelerated. However, whether myocardial adrenergic nerve activity reflects the severity of heart failure and its relation to the underlying cause have not yet been elucidated. METHODS: Planar MIBG images were obtained from 96 patients with heart failure and compared with images from 9 age-matched healthy subjects. Groups 1 and 2 included 65 patients with heart failure related to impaired myocardial function and whose left ventricular ejection fraction was < 40% (group 1 = 40 patients with dilated cardiomyopathy; group 2 = 25 patients with ischemic cardiomyopathy). Group 3 included 31 patients with heart failure related to a mechanical abnormality and whose left ventricular ejection fraction was > 40% (mitral regurgitation in 16, aortic regurgitation in 9, aortic and mitral regurgitation in 4, ruptured aneurysm of Valsalva in 2). Myocardial uptake of MIBG was calculated as the heart/mediastinal activity ratio. Storage and release of MIBG were calculated as percent myocardial MIBG washout from 15 min to 4 h after isotope injection. RESULTS: The heart/mediastinal activity ratio in the immediate images (15 min) showed a significant decrease only in patients with severe heart failure (groups 1 and 2). The myocardial washout was accelerated in all three heart failure groups. The level of myocardial washout was related to severity of heart failure and correlated well with New York Heart Association functional classification. CONCLUSIONS: In severe heart failure associated with cardiomyopathy, norepinephrine uptake is reduced. In addition, myocardial adrenergic nerve activity is accelerated in proportion to severity of heart failure, independent of the underlying cause.

3-Iodobenzylguanidine↗
PubMed1995

Pathogenicity of bacteria using a simulated root canal system.

The purpose of this study was to investigate the reliability of an implantation test using Teflon-simulated root canals for evaluating the pathogenicity of root canal bacteria. Models including suspensions of lyophilized strains (Actinomyces israelii, Streptococcus faecalis, and Porphyromonas asaccharolyticus) were implanted in rat subcutaneous tissue for 1 wk, and histological changes were observed. Severe inflammation occurred around the models. Among them, P. asaccharolyticus induced the severest inflammatory response. Further study using P. asaccharolyticus was conducted to compare the implantation test's ability to evaluate pathogenicity with that of an injection test at 1, 2, or 4 wk. Tissue injected with a bacterial suspension showed no clear response through the experimental periods, whereas tissue around implantation sites showed a severe response at 1 wk. However, the inflammatory response subsided at later stages. Consequently, further improvement is needed to investigate pathogenicity for long periods.

Actinomyces↗
PubMed1995

Augmentation of coronary responsiveness to serotonin at the site of X-ray-induced intimal thickening in miniature pigs.

OBJECTIVE: X-irradiation is known to enhance atherosclerotic change. We tested whether coronary vasoconstrictor responses are augmented at the sites of X-ray-induced intimal thickening in Göttingen miniature pigs. METHODS: In 17 pigs, a major branch of the left coronary artery was denuded with a balloon catheter. In 10 pigs, the denuded portion of the left coronary artery was selectively irradiated with 15 Gy of X-rays twice at 3 and 4 months after denudation (group 1). The remaining 7 pigs were not irradiated (group 2). The effects of intracoronary administration of serotonin, histamine and phenylephrine on the coronary diameter were studied 3 (3M) and 5 months (5M) after denudation. After the angiographical study at 5M, the vessels were isolated and isometric tension was measured in an organ chamber. RESULTS: The percent reduction in coronary diameter evoked with 10 micrograms.kg-1 of serotonin increased from 39(s.e.m. 4)% before X-irradiation (3M) to 75(6)% after X-irradiation (5M) in group 1 (P < 0.01), while it did not differ in group 2 [39(6)% at 3M vs. 33(8)% at 5M[ [39(6)% at 3M vs. 33(8)% at 5M]. In group 1, serotonin-induced coronary constriction was frequently accompanied by ischemic ECG changes. Histamine (10 micrograms.kg-1)-induced vasoconstriction was also augmented but to a smaller degree [47(6)% at 3M vs. 62(4)% at 5M; P < 0.05] in group 1, while it remained unchanged in group 2[52(5)% at 3M vs. 44(7)% at 5M]. Phenylephrine did not cause detectable contraction in either group at 3M or 5M. Methysergide and ketanserin attenuated serotonin-induced hypercontraction in a dose-dependent fashion. In the in vitro studies, endothelium-dependent relaxation to serotonin was impaired at the denuded site with (group 1) and without (group 2) X-irradiation to a similar extent. Isometric tension of medial smooth muscle developed by serotonin was significantly greater at the denuded site with X-irradiation (group 1) than the control site and the denuded site without X-irradiation (group 2) (P < 0.05). Intimal thickening was significantly greater at the denuded sites with X-irradiation [group 1, 238(45) microns] than at the denuded sites without X-irradiation [group 2, 58(5) microns] (P < 0.05). CONCLUSIONS: These results indicate that X-irradiation augments the coronary vasoconstrictor responses to autacoids, predominantly to serotonin, and that this augmentation is accompanied by enhanced intimal thickening. Serotonin-induced hypercontraction after X-irradiation resulted mainly from the hyperreactivity of medial smooth muscle.

Animals↗
PubMed1994

The effect of cycloplegia on measurement of the ocular components.

PURPOSE: The purpose of this study was to examine the effect of cycloplegic agent on the measurement of refractive error and the ocular components. METHODS: We compared two commonly used topical cycloplegic agents, 1% tropicamide and 1% cyclopentolate, for their effect on the measurement of refractive error (by Canon R-1 autorefraction), accommodative response (by Canon R-1 autorefraction and by the conventional, subjective "pushup" method), crystalline lens power (by video phakometry and by calculation), and axial ocular dimensions (by A-scan ultrasonography) in 20 emmetropic to moderately hyperopic children. RESULTS: Comparison of refractive error at each drug's reported time of maximum cycloplegia (30 minutes for tropicamide and 60 minutes for cyclopentolate) showed that distance autorefraction in the vertical meridian differed by +0.20 +/- 0.30 diopters (D) (P = 0.008). The average difference was +0.07 +/- 0.10 mm for anterior chamber depth (P = 0.004), -0.03 +/- 0.05 mm for crystalline lens thickness (P = 0.025), -0.65 +/- 0.69 D for phakometrically measured crystalline lens power (P < 0.001), +0.03 +/- 1.55 D for calculated crystalline lens power (P = 0.94), and -0.09 +/- 0.19 mm for vitreous chamber depth (P = 0.062, all paired t tests; positive signs denote greater values with cyclopentolate). Residual accommodation was 0.47 and 0.67 D greater with tropicamide when measured by autorefraction and the pushup method (P = 0.013 and 0.08 respectively, paired t test). All significant differences were consistently in the direction of poorer cycloplegia with tropicamide. CONCLUSIONS: Although tropicamide, as expected, showed poorer cycloplegia compared to cyclopentolate, the degree of difference appeared to be small, with minimal effect on the measurement of distance refractive error and the ocular optical components.

Accommodation, Ocular↗
PubMed1993

Role of coronary artery spasm in progression of organic coronary stenosis and acute myocardial infarction in a swine model. Importance of mode of onset and duration of coronary artery spasm.

BACKGROUND: Coronary spasm may play an important role in progression of organic coronary stenosis and myocardial infarction, but the mechanisms responsible for these complications are not known. This study aimed to examine whether the mode of onset and the duration of coronary spasm influenced progression of organic coronary stenosis and acute myocardial infarction in a swine model of coronary spasm. METHODS AND RESULTS: Göttingen miniature pigs were subjected to cholesterol feeding, balloon-induced coronary arterial denudation, and x-ray irradiation. Five months later, coronary spasm was induced by intracoronary injection of serotonin. In 10 pigs, coronary spasm was provoked abruptly and maintained for 25 minutes by five repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes (group A, abrupt onset and short duration). In group B, coronary spasm was provoked gradually by intracoronary injections of serotonin at graded doses of 0.1, 0.3, and 0.6 microgram/kg every 5 minutes and was then maintained for 25 minutes in four pigs (group B1, gradual onset and short duration) and for 120 minutes in six pigs (group B2, gradual onset and long duration) by repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes. Intramural hemorrhage was noted histologically at the spastic site more frequently in group A with abrupt onset (nine of 10 pigs) than in group B with gradual onset (two of 10 pigs) (p < 0.01). Progression of organic coronary stenosis due to intramural hemorrhage was noted in seven pigs (six pigs in group A and one pig in group B), including three cases of total coronary occlusion. Evidence for the evolution of acute myocardial infarction (serial ECG findings, left ventriculograms, and histological findings) was noted in one pig (7%) of group A or B1 with short duration and in five of six pigs (83%) in group B2 with long duration (p < 0.01 versus group A and B1). CONCLUSIONS: These results indicate that: 1) intramural hemorrhage was frequently induced by coronary spasm of abrupt but not of gradual onset, 2) intramural hemorrhage resulted in acute progression of coronary stenosis and sometimes resulted in persistent total coronary occlusion leading to acute myocardial infarction, and 3) prolonged coronary spasm resulted in acute myocardial infarction without progression of organic coronary stenosis.

Animals↗
PubMed1991

Effects of endothelin-1 on epicardial coronary tone, coronary blood flow, ECG-ST change and regional wall motion in anesthetized dogs.

The effects of intracoronary-administrated endothelin-1 on coronary hemodynamics and regional myocardial function were studied in anesthetized open-chest dogs. Epicardial coronary diameter (CoD) and coronary blood flow (CBF) were measured by a sonomicrometer of 10 MHz piezoelectric crystals and an electro-magnetic flow probe on the left circumflex coronary artery (LCX). Regional wall motion was sonomicrometrically measured at regions supplied by the LCX and left anterior descending artery (LAD) and electrocardiograms were recorded. Endothelin-1, administered as a bolus injections into the LCX via an intracoronary cannula, in a dose-dependent manner reduced COD and CBF. The extent of the reduction of COD and CBF at a dose-dependent manner reduced COD and CBF. The extent of the reduction of COD and CBF at a dose of 300 pmol was 12.3 +/- 1.5% (P less than 0.01) and 86 +/- 5% (P less than 0.01), respectively, of the control. The extent of CBF reduction and deterioration of systolic wall motion were linearly related with the dosage of endothelin-1. ST-elevation (lead II) and fatal ECG abnormalities, including complete atrioventricular block or ventricular fibrillation, were observed with doses above 60 and 100 pmol, respectively. Coronary angiography revealed that filling defects of dye were propagated from the third or distal branches to those of more proximal arteries when the doses of endothelin-1 were cumulatively infused into the LCX. Accordingly, lethal myocardial ischemia induced by endothelin-1 is produced by critical obstruction of rather small coronary vessels.

Animals↗
PubMed1990

Smooth muscles from spastic coronary artery segments show hypercontractility to histamine.

An animal model of coronary spasm was produced in Göttingen miniature pigs by a selective endothelial denudation of the coronary artery. Five months after the denudation, intracoronary bolus administration of 10 micrograms/kg histamine reduced the luminal diameter angiographically by 57 +/- 16 and 17 +/- 10% (P less than 0.01) in the previously denuded and contralateral control coronary arteries. Muscle fibers of 0.08-0.1 mm wide were prepared from circumferential bundles of the medial smooth muscle in the spastic and nonspastic coronary arteries. Upward shifts of either dose-tonic contraction relationships in Ca2(+)-containing solution or dose-monophasic contraction relationships in Ca2(+)-free solution were noted in muscle fibers taken from the spastic site compared with those from the nonspastic site with no difference between the mean effective dose values. After skinning the muscle fibers with saponin, there was no significant difference in the Ca2+ concentration-tension relationships between the two fibers. These findings suggest that an increased number of histaminergic receptors and/or augmentation of signal transduction, but not Ca2+ sensitivity of the contractile proteins in the medial smooth muscle cells, cause histamine-induced coronary hypercontraction.

Animals↗
PubMed1989

Sustained dilatation of large coronary artery by alpha-human atrial natriuretic peptide in conscious dogs: a comparison with nitroglycerin.

The effects of alpha-human atrial natriuretic peptide (alpha-hANP) on the coronary circulation were compared with those of nitroglycerin in 16 conscious dogs chronically instrumented with a pair of miniature sonomicrometers and an electromagnetic flow probe placed on the left circumflex coronary artery. alpha-hANP (1 and 10 micrograms) and nitroglycerin (0.1, 1 and 10 micrograms) were administered intracoronarily via a cannula implanted in the proximal left circumflex coronary artery. Both alpha-hANP and nitroglycerin dose dependently increased the coronary diameter and coronary blood flow. Although alpha-hANP (10 micrograms) and nitroglycerin (1 microgram) dilated the large coronary artery to almost the same extent (92 +/- 10 vs. 98 +/- 8 microns), the time course of the dilating action differed; the peak dilatation occurred at 5.6 +/- 0.8 and 0.9 +/- 0.07 min (P less than 0.01), and full recovery occurred at 31.5 +/- 3.8 and 5.5 +/- 1.3 min (P less than 0.01) after alpha-hANP and nitroglycerin, respectively. Topical application of alpha-hANP (50 micrograms) to the epicardial coronary artery of three anesthetized open-chest dogs did not affect the coronary diameter and coronary blood flow, while nitroglycerin (50 micrograms) increased both variables. Thus, intracoronary alpha-hANP dilates the large coronary artery more gradually and more sustainedly than nitroglycerin does.

Animals↗
PubMed1989

Effects of ionic and nonionic contrast media on coronary diameter and blood flow in chronically instrumented dogs.

The effects of intracoronary administration of ionic and nonionic contrast media on coronary circulation were studied in 14 chronically instrumented dogs. A pair of 10 MHz piezoelectric crystals and an electromagnetic flow probe were placed on the left circumflex coronary artery, under sterile conditions, to measure the epicardial coronary diameter and coronary blood flow, respectively. A polyethylene tube for drug infusion was inserted into the circumflex coronary artery proximal to the sonomicrometers. In the conscious dogs (n = 8), iopamidol, 2 ml and 5 ml increased the coronary diameter by 64 +/- 19 microns and 66 +/- 19 microns and coronary blood flow by 35 +/- 10% and 61 +/- 18%, respectively (p less than 0.01 vs control level). Meglumine diatrizoate, 2 ml and 5 ml, increased coronary diameter by 102 +/- 20 microns and 114 +/- 18 microns and coronary blood flow by 87 +/- 32% and 107 +/- 26%, respectively (p less than 0.01 vs control level). In the anesthetized dogs (n = 6), a bolus intracoronary injection of 5 ml iopamidol and meglumine diatrizoate within few seconds increased the coronary diameter by 103 +/- 23 microns and 164 +/- 39 microns (p less than 0.05) and increased the coronary blood flow by 126 +/- 33% and 180 +/- 40% (p less than 0.05), respectively. Balloon denudation of the endothelium was performed in six anesthetized dogs. The increases in coronary diameter and coronary blood flow after a bolus injection of contrast medium remained the same after the denudation. Thus application of iopamidol seems to be more suitable than meglumine diatrizoate for quantitative coronary angiography because of the milder and more transient effects on coronary circulation.

Acetylcholine↗
PubMed1988

Clinical characteristics and long-term prognosis of patients with variant angina. A comparative study between western and Japanese populations.

To determine the factors influencing the prognosis of variant angina, the clinical characteristics and long-term prognosis of 158 consecutive Japanese patients were examined and compared with those in previous major western studies (Pisa, Montreal, and Duke studies). The Japanese patients were characterized by relatively low prevalences of coronary risk factors, significant coronary stenoses and previous myocardial infarction. Survival and survival without myocardial infarction for the entire group or for the subpopulation with significant coronary artery disease were significantly better in the Japanese population than in the western populations; however, in the subpopulation without significant coronary artery disease, the prognosis was excellent in all four studies. If the prevalence of coronary artery disease was corrected for the Japanese population, there would be no difference in the prognosis between the Japanese and the western populations. It is concluded: (1) the overall prognosis of variant angina may be better in Japanese patients, and (2) coronary artery disease appears to be the strongest prognostic factor for assessing the differences in the prognosis between the Japanese and the western populations.

Adult↗
PubMed1988

The NFLD antigen in Japan.

The low-frequency red cell antigen NFLD was identified in 2 Japanese donors. A family study showed that the antigen is not part of the P1 blood group system. Anti-NFLD was found in serum of several donors (frequency of 0.044%).

Blood Group Antigens↗