[Studies on relative biological effectiveness and therapeutic gain factor of high energy protons modulated for radiotherapy].
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
S Satoh
Publications and source records attributed to S Satoh.
Studies on the induction of tolerance to alloantigens. II. The generation of serum factor(s) able to transfer alloantigen-specific tolerance for delayed-type hypersensitivity by portal venous inoculation with allogeneic cells.
The administration of C3H/He spleen cells into allogeneic BALB/c mice via portal venous (p.v.) route resulted in C3H/He alloantigen-specific tolerance for delayed-type hypersensitivity (DTH) responses. When serum from these tolerant BALB/c mice were transferred into naive syngeneic BALB/c mice, the recipient mice lost the capability of generating DTH responses as induced by s.c. immunization with C3H/He cells. Tolerance was transferred only by serum from BALB/c mice inoculated p.v. with C3H/He cells, but not by serum from C3H/He mice inoculated p.v. with C3H/He cells, or BALB/c mice inoculated i.v. with C3H/He cells. This tolerogenic activity in serum from p.v. inoculated BALB/c mice was C3H/He alloantigen specific, because the transfer of the serum did not interfere with the development of anti-C57BL/6 DTH responses in recipient BALB/c mice. Such a serum factor(s) was inducible as early as 1 wk after the inoculation of C3H/He cells into BALB/c mice and not associated with anti-C3H/He alloantibody activity. Moreover, anti-C3H/He or C57BL/6-specific tolerogenic factor(s) prepared in the respective BALB/c or C3H/He mice was successfully transferred into totally allogeneic recipient mice, indicating no requirement of H-2, as well as non-H-2 restriction for the function of serum tolerogenic factor(s). Thus this study demonstrates that p.v. inoculation of allogeneic cells generates serum factor(s) able to transfer in H-2 and non-H-2-unrestricted manners the in vivo tolerance of the alloreactivity specific for alloantigens used for p.v. inoculation.
Animals↗
The significance of beta-adrenoceptor down regulation in the desipramine action in the forced swimming test.
The present studies were undertaken to clarify whether central beta-adrenoceptor down regulation is responsible for the greater effect of chronic treatment with desipramine (DMI) compared with acute treatment in the forced swimming test in rats. Repetitive administration of DMI activated the rat behaviour pattern and consequently reduced the duration of immobility. The degree of activation depended on the length of treatment, i.e. no effect when given in a single dose, moderate effect when given subchronically (3 doses) and marked activation after chronic (31 doses) treatment. Chronic treatment with DMI also produced a decrease in 3H-dihydroalprenolol (3H-DHA) binding site in the cerebral cortex. Acute stimulation of brain beta-adrenoceptors by intracerebroventricular (i.c.v.) isoprenaline significantly, though partially, attenuated the behavioural effect of chronic DMI by beta 1-adrenoceptor-related mechanisms. Similarly, chronic i.c.v. co-administration of atenolol or practolol, beta 1-adrenoceptor antagonists, together with DMI attenuated both beta-adrenoceptor down regulation and the behavioural activation by chronic DMI. On the other hand, chronic i.c.v. administration of isoprenaline, supposedly leading to down regulation of beta-adrenoceptors, facilitated the activating behavioural effect of DMI, as a single dose became effective. Changes, however, in 3H-DHA binding parameters in the cerebral cortex were not observed after chronic isoprenaline. These results suggest that down regulation of beta-adrenoceptors in brain is responsible, at least in part, for the marked activatory effect of chronic DMI in the forced swimming test, possibly by reducing an inhibitory function of beta 1-adrenoceptor mediated mechanisms.
Adrenergic beta-Antagonists↗
Pharmacokinetics of TZU-0460, a new H2-receptor antagonist, in patients with impaired renal function.
We have studied pharmacokinetics of a new H2-receptor antagonist, TZU-0460, in patients with varying degrees of renal impairment. The apparent volume of distribution at steady-state was 1.70 l/kg, and the plasma protein binding of TZU-0460 or its active metabolite, desacetyl TZU-0460 was less than 10% in normal subjects. These variables were not altered with renal impairment. Sixty percent of TZU-0460 given orally was excreted via the kidney, mainly by tubular secretion. The half-time of elimination was 3.94 h in normal subjects, and was prolonged to 12.13 h in severe renal failure (creatinine clearance below 30 ml/min/1.48 m2). Dosage adjustment of TZU-0460 is necessary in renal failure.
Adult↗
Alterations in myocardial perfusion during exercise after isosorbide dinitrate infusion in patients with coronary disease: assessment by thallium-201 scintigraphy.
We studied the effect of intravenous isosorbide dinitrate (ISDN) on myocardial perfusion of patients with coronary artery disease, by using exercise thallium-201 (TI-201) myocardial scintigraphy. A control study was conducted initially to assess regional myocardial perfusion rate. Left ventricular myocardium was divided into six parts: anterior, lateral, apical, inferior, posterior, and septal segments. The segmental myocardial perfusion was characterized according to TI-201 initial uptake index (IUI) of relative distribution and redistribution index (RDI) of TI-201 washout. The normal limit of IUI and RDI was established from the data of 17 persons with normal coronary arteries, and then the IUI less than or equal to 84% and the RDI greater than or equal to 1.12 was defined as abnormal. Based on IUI and RDI, each segment was characterized into three types: A type = IUI less than or equal to 84%, RDI greater than or equal to 1.12; B type = IUI less than or equal to 84%, RDI less than 1.12; and C type = IUI greater than 84%, RDI less than 1.12. ISDN was given as a dose of 0.1 mg/kg/hr, and then treadmill testing was repeated for the same duration of exercise time using the same protocol as in the control period. The segments of A type showed a significant improvement in IUI and RDI after receiving ISDN infusion, while the B and C type segments showed no change. It was also shown that the improvement of IUI and RDI of the A type segments was not as marked in multivessel disease as in cases of single-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Beneficial effect of new thiol protease inhibitors, epoxide derivatives, on dystrophic mice.
We studied the effect of E-64, a new thiol protease inhibitor derived from Aspergillus japonicus TPR-64, and of its synthesized analogue, E-64-d, on dystrophic mice (C57BL/6J-dy). The locomotor activity of normal mice increased markedly, reaching a plateau at 8 weeks of age. In dystrophic mice, it increased until they were 7 weeks old, thereafter, it decreased gradually. This decrease reflected the degradation of the hind legs. Serum activities of creatine phosphokinase were significantly greater in dystrophic than in normal mice. When 3-week-old dystrophic mice were injected with E-64 (1 mg/kg, i.p.) or E-64-d (40 to 60 mg/kg, p.o.), the decrease in their locomotor activity was retarded and their serum enzyme activities decreased significantly. In addition, the survival time of treated dystrophic mice was prolonged. The locomotor activity of normal mice and their serum enzyme levels were not affected by the administration of E-64-d. We posit that the new thiol protease inhibitors we tested retard the progression of dystrophy in mice.
Animals↗
Beneficial effect of chymostatin on dystrophic mice.
We studied the effect of chymostatin on dystrophic mice (C57BL/6J-dy). The locomotor activity of normal mice increased markedly, attaining a plateau at 8 weeks of age, whereas in dystrophic mice, it increased until the age of 7 weeks, and thereafter decreased gradually. Serum levels of creatine phosphokinase were significantly higher in dystrophic mice compared with normal mice, and dystrophic mice had a reduced muscle protein content. When 3-week-old dystrophic mice received chymostatin (1 mg/kg, i.p.), the decrease in locomotor activity was retarded, serum enzyme levels decreased significantly, and muscle protein content increased significantly. In addition, the survival time of treated dystrophic mice was prolonged. The locomotor activity, serum enzyme levels, and muscle protein content of normal mice were not affected by chymostatin. Therefore, we posit that chymostatin retarded the progression of dystrophy in mice.
Animals↗
Elevations of cathepsin B and cathepsin L activities in forelimb and hind limb muscles of genetically dystrophic mice.
The combined activities of cathepsin B and cathepsin L were studied in the forelimb and hind limb muscles of dystrophic mice. The activities of these proteases in the forelimb and hind limb muscles of young and adult dystrophic mice were significantly higher than those in normal mice. However, clinical involvement of dystrophy appeared in the hind limbs but not in the forelimbs. We therefore suggest that the increase in protease activity begins at a very early age and that the clinical involvement is not linked with the increase in cathepsin B and L.
Animals↗
Auxin-controlled glycoprotein release into the medium of embryogenic carrot cells.
Glycoproteins released from carrot cells into culture media were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by staining with Coomassie brilliant blue or with the periodic-acid Schiff procedure. The appearance or disappearance of two glycoproteins of M(r) 65,000 (GP65) and M(r) 57,000 (GP57) was closely related to the formation of somatic embroys. GP65 was released specifically from embryogenic cells cultured in a medium without 2,4-dichlorophenoxyacetic acid, in which they can form somatic embryos. GP57 was released from the same embryogenic cells, if they were cultured in a medium with 2,4-dichlorophenoxyacetic acid, in which they cannot form somatic embryos. Nonembryogenic cells which cannot form somatic embryos, released only GP57.
Journal Article↗
The inhibitory effect of selenium on mice inoculated with B16 melanoma cells.
Explore the source record for details and available documents.
Animals↗
Measurement of instantaneous viscoelastic properties by impedance-frequency curve of the ventricle.
We developed a method for estimating the instantaneous viscoelastic properties of the left ventricle (LV). This impedance-curve method is based on the instantaneous impedance-frequency curve of the left ventricle generated by a rapidly oscillating mechanical impulse applied to the epicardial surface of the heart. The theoretical basis of the method and experimentally obtained instantaneous impedance-frequency curves were examined to evaluate the validity of our basic assumptions. Using these impedance-curve data, we calculated the instantaneous viscoelastic properties of the LV during the cardiac cycle. The impedance curve shows a configuration that is almost the same as the theoretical curve based on the assumption that an RCL (R, resistor; C, capacitor; L, inductor) parallel circuit is the electrical analog for the LV. The impedance curve varied moment by moment during the development of instantaneous LV pressure. The elastic and viscous coefficients, calculated from the impedance curve, increased with increase of LV pressure. We concluded that the impedance-curve method can delineate the instantaneous viscoelastic properties of the ventricle (especially of the ventricular myocardium).
Animals↗
Chromosome elimination in the Japanese hagfish, Eptatretus burgeri (Agnatha, Cyclostomata).
The modal number of chromosomes in Eptatretus burgeri was 36 in 297 (81.8%) of 363 somatic cells, 52 in 13 (30.2%) of 43 spermatogonia, and 25 (46.8%) or 26 (40.3%) in 162 of 186 first spermatocytes. The relative amount of DNA in a somatic cell to that in a spermatogonium averaged 79.2%. C-band-positive chromatin was observed along almost the entire length of the associated dumbbell-shaped bivalents and part of two other bivalents in the metaphases of first spermatocytes, but was rarely observed in somatic cells. These results indicate that, in E. burgeri, chromosome elimination takes place during the early stages of cleavage, except for the ancestral germ-line cells.
Animals↗
Immunohistochemical demonstration of papillomavirus antigen in cervical dysplasia and vulvar condyloma.
Biopsies from 30 cases of vulvar condyloma, 460 cases of cervical dysplasia, 30 cases of carcinoma in situ and 75 cases of invasive carcinoma of the cervix were screened for the presence of human papillomavirus (HPV) antigen by means of the peroxidase-antiperoxidase method. Positive reaction for HPV was detected in 14 cases of condyloma and 80 cases of dysplasia as a brown intranuclear precipitate in the superficial layer of the epithelium. None of the cases of carcinoma in situ and invasive cancer were positive for HPV. The mean age of the women with HPV-positive dysplasia was significantly lower than that of the women with HPV-negative dysplasia. Condylomatous dysplasia showed a significantly higher positive rate than did noncondylomatous dysplasia. Cases of condylomatous dysplasia with severe stromal inflammation were negative for HPV more frequently than those with mild stromal inflammation.
Adult↗
Preferential inhibitory effect of nifedipine on angiotensin II-induced renal vasoconstriction.
The inhibitory effects of nifedipine on renal vasoconstrictor response to angiotensin II, norepinephrine, or renal nerve stimulation were tested in anesthetized dogs. Intrarenal infusions of nifedipine (0.3, 1, and 3 micrograms/min) dose-dependently suppressed the renal vasoconstriction induced by intrarenal injections of angiotension II (0.03, 0.05, and 0.1 microgram) or norepinephrine (0.3-1 micrograms) but not that by renal nerve stimulation (4-7 Hz). However, the inhibitory effect of nifedipine on angiotensin II-induced vasoconstriction was greater than its effect on norepinephrine-induced or renal nerve stimulation-induced vasoconstriction (i.e., 50% reduction in renal blood flow). Furthermore, a greater renal vasodilation induced by intrarenal bolus injections of nifedipine (1,3, and 10 micrograms) but not by acetylcholine (0.1 and 0.3 microgram) was observed during the reduction in the perfusion pressure of the contralateral kidney to approximately 50 mm Hg, which resulted in an increase in plasma renin activity and plasma angiotensin II concentration but no change in plasma norepinephrine concentration. There was a significant positive correlation between plasma renin activity and plasma angiotensin II concentration before nifedipine injections and the subsequent increase in renal blood flow produced by each dose of nifedipine. These results indicate that nifedipine has a relatively preferential inhibitory effect on the renal vasoconstriction produced by both exogenous and endogenous angiotensin II in canine renal vasculature.
Angiotensin II↗
Effects of preload alteration on the degree of ischemia and function of ischemic myocardium under constant mean aortic pressure, coronary perfusion pressure and heart rate in isolated perfused canine heart.
We examined the effects of preload alteration on global and regional (i.e., non-ischemic and ischemic areas) function in the presence of regional myocardial ischemia and on the degree of ischemia using 18 isolated, metabolically supported canine left ventricles. For this purpose, cardiac output (CO), systolic segment length change (SL), myocardial CO2 tension (PmCO2) and ST level of epicardial ECG were measured at 3 levels of left ventricular end-diastolic pressure (LVEDP), i.e., approximately 7 (low LVEDP), 11 (middle LVEDP), and 16 mmHg (high LVEDP) without and with left circumflex artery (LCx) stenosis under a constant mean aortic pressure (90 mmHg), mean coronary perfusion pressure (90 mmHg) and heart rate. In the Pre-ischemic stage, CO and SL increased significantly when LVEDP was elevated in a stepwise fashion by changing the height of the reservoir connected to the left atrium. There were no significant changes in PmCO2 or ST level. On the other hand, with LCx stenosis, CO did not show a subsequent increase at higher LVEDPs (i.e., from 796 +/- 103 ml/min at middle LVEDP to 931 +/- 153 ml/min at high LVEDP). Furthermore, there was no significant SL response in the LCx area following alterations of LVEDP, although there was considerable lengthening of end-diastolic length. Both increased PmCO2 and ST level of the LCx area, following LCx stenosis, further increased significantly with elevation of LVEDP. These results suggest the possibility that considerable elevation of LVEDP worsens the degree of ischemia and does not significantly augment ischemic regional myocardial function or global function, while mild elevation of preload improves or tends to improve simultaneously regional ischemic and global functions without aggravating the ischemic injury significantly. Therefore, we conclude that the preload level is quite important in managing ischemia induced myocardial dysfunction.
Animals↗
The changes in ECG ST segment and mechanical function of regional ischemic myocardium during afterload reduction in isolated dog hearts with coronary stenosis.
By measuring ECG ST segment deviation and regional mechanical dysfunction, we assessed the effects of an alteration in afterload pressure on regional myocardial ischemia due to a partial coronary occlusion of the left circumflex coronary artery (CFX). Eight isolated, perfused and paced dog hearts were loaded with an artificial arterial system which simulated the aortic input impedance of the dog arterial tree. Afterload pressure was altered by stepwise changes in peripheral resistance (Rp), while left ventricular end-diastolic pressure (LVEDP) and heart rate were kept constant. Coronary perfusion pressure (CPP) was kept equal to mean aortic pressure (AoP). ECG and myocardial systolic segment shortening (SS) were measured in both areas perfused by the CFX and the left anterior descending coronary artery (LAD). In the presence of CFX stenosis, mean AoP decreased from 96 +/- 7 to 46 +/- 7 mmHg following a decrease in Rp and cardiac output increased progressively from 465 +/- 30 to 1055 +/- 100 ml/min. In this situation, CFX coronary blood flow decreased from 75 +/- 2 to 28 +/- 6 ml/100 g/min. Epicardial ECG in the ischemic region showed two types of ST segment deviation after CFX stenosis: ST segment elevation and ST segment depression. Moreover, following afterload reduction, these individual ECG ST segment changes showed further deviations. The levels of mean AoP, below which further ST segment deviations significantly occurred, were as follows: 71 +/- 6 mmHg in ST segment elevation cases and 52 +/- 7 mmHg in ST segment depression cases. Myocardial systolic segment shortening in the ischemic region also significantly decreased following CFX stenosis (91 +/- 8% of pre-ischemic control, p less than 0.05). Then, during afterload reduction, SS in the CFX area appeared to be bimodal and it definitely decreased when mean AoP was 46 +/- 7 mmHg. To enhance the sensitivity of detection of further mechanical dysfunction throughout afterload reduction following regional myocardial ischemia, we calculated percentage values of the SS in the CFX area to the SS in the LAD area at each Rp. By this normalization, mechanical dysfunction was found when mean AoP was below 67 +/- 5 mmHg. These results suggest that reduction in afterload pressure below a certain level aggravated the regional ischemia, despite an increase in cardiac output, and to detect this change in the ischemic region during afterload reduction, ECG ST segment deviation seems to be a useful indicator.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Head-twitches induced by p-hydroxyamphetamine in mice.
Head-twitches have been regarded as an experimental model of hallucination, and we have recently observed that p-hydroxyamphetamine (p-OHA) markedly induced head-twitches in mice. The present work was undertaken to study possible participation of a serotonergic system in the mechanism of head-twitches induced by p-OHA. Head-twitches induced by p-OHA continued for 20-80 min, and the peak time of this effect was approximately 30-40 min after the administration. The i.c.v. administration of p-OHA (20, 40, 80 and 160 micrograms/mouse) produced characteristic head-twitches in a dose-dependent manner. Simultaneous injection of serotonin (10 micrograms/mouse, i.c.v.) and p-OHA caused a 2-2.5-fold increase in the number of head-twitches compared with non-serotonin controls. Pretreatment with p-chlorophenylalanine (200 mg/kg, i.p. and 500 micrograms/mouse, i.c.v.), in contrast, reduced head-twitches as did the pretreatment with cyproheptadine or dimethothiazine. These results suggest that p-OHA-induced head-twitches may involve the central serotonergic system which may exert an excitatory effect on head-twitches.
Amphetamines↗
Effects of major coronary artery stenosis on the pressure-flow relationship of an adjacent intact coronary artery branch in isolated supported canine left ventricle.
We investigated whether the relationship between the mean left anterior descending and septal coronary blood flow and the mean perfusion pressure varies with left circumflex coronary stenosis. We used excised, perfused canine heart preparations (n = 10), in which variables to influence the myocardial oxygen demand and supply relation can be fairly well controlled. The results showed that coronary blood flow in the adjacent, non-stenosed coronary artery increased significantly following LCX stenosis; this increased flow was found at the same values of heart rate, left ventricular end-diastolic pressure and perfusion pressure, as those in the preischemic state. Moreover, this increased flow was also observed when the values of peak left ventricular pressure and pressure-length loop area were similar between the pre-ischemic and ischemic states. Thus, contributions of neurohumoral factors or alterations in mechanical factors determining the myocardial oxygen demand and supply relation are negligible. This increased flow may be important in maintaining overall cardiac function in cases of acute coronary stenosis or coronary occlusion.
Animals↗