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Biomedical subjects

H Satake

Publications and source records attributed to H Satake.

At least 55 records · Page 3Linked to original sources

Intracranial blood flow measured with single photon emission computer tomography (SPECT) during transient -6 degrees head-down tilt.

Regional cerebral blood flow (CBF) during a transient head-down tilt of -6 degrees (-6 degrees HDT) was measured with single photon emission computer tomography (SPECT). CBF was measured and averaged for both sides of the brain areas; e.g., the bilateral anterior cerebral artery (bACA) area, the middle cerebral artery (bMCA) area, the posterior cerebral artery (bPCA) area, bilateral basal ganglia, and the cerebellum. Among these areas, a significant increase in CBF was observed in the basal ganglia and the cerebellum during -6 degrees HDT compared to pre-HDT. When CBF was measured separately in the left or right brain area, these significances disappeared, although a trend of increase or decrease was still observable. A trend of increase was observed in the left anterior cerebral artery (IACA) area, the right middle cerebral artery (rMCA) area, the right posterior cerebral artery (rPCA) area, the left and right basal ganglia, and the cerebellum. In rACA, IMCA and IPCA areas, a slight decrease in CBF was observed. At the same time, cardiac parameters were measured. Heart rate (HR), stroke volume (SV) and cardiac output (CO) did not change significantly, although SV slightly increased and HR slightly decreased during -6 degrees HDT.

Adult↗

[Experimental evaluation of combination chemotherapy with UFT and cisplatin for lung cancer].

Combined treatment of UFT with cisplatin (CDDP) achieved remarkable elongation of survival time of BDF1 mice, which were intravenously transplanted with Lewis lung carcinoma (LLC). Three cycles of weekly iv administration of CDDP and vindesine (VDS), and daily oral administration of UFT were scheduled. Combination UFT (18 mg/kg/day) with CDDP (6.0 mg/kg/day) yielded tumor-free survivors in all of the treated animals with slight body weight loss. Its efficacy was superior to that of the combination of CDDP with VDS. Supra-additive cytotoxic activity against LLC cells was observed by Isobologram method on the schedule of the exposure to 5-fluorouracil preceding the exposure to CDDP. Additive effect was observed by the reversed schedule of the treatment. Using human non-small-cell lung cancer (NSCLC) cell lines which derived from histologically different type, additive or greater additive sensitivity to both of the sequential treatment schedules with 5-FU and CDDP was observed. These results suggest that the combination chemotherapy of UFT with CDDP for lung cancer may show high antitumor efficacy with low toxicity in a clinical setting.

Animals↗

Neuronal responses to vestibular and callosal stimulation in the anterior suprasylvian gyrus of the cat.

Neuronal responses to electrical stimulation at the horizontal ampulla (HA), vestibular nerve (at the windows) and corpus callosum (CC) were investigated in neurons in the anterior suprasylvian gyrus of the cat. The field potentials to HA stimulation had short latency: 2.9 +/- 0.3 (mean +/- SD) ms from the stimulus to the onset and 5.6 +/- 1.9 ms to the peak. The focus of the evoked potentials was located in the anterior suprasylvian (ASS) gyrus or near the ASS sulcus. HA stimulation activated 6 neurons out of 674 examined, with the mean latency of 4.3 +/- 1.1 ms. Of these 6, four neurons also responded to window stimulation. Fifty-six neurons responded to window stimulation with the mean latency of 6.1 +/- 2.4 ms. The mean latency for CC stimulation was 1.9 +/- 0.9 ms (n = 76). Four neurons responded to CC stimulation antidromically (mean = 0.9 +/- 0.3 ms) and one of them also responded orthodromically. The convergence of CC inputs in relation to HA or window stimulation was examined. One (17%) of the 6 HA-activated cells responded to CC stimulation, compared with 8 (14%) of the 56 neurons activated by window stimulation. The other 612 neurons did not respond to either HA or window stimulation, and 80 (13%) of the 612 responded to CC stimulation. Therefore, it is concluded that neurons in the ASS gyrus received callosal input equally irrespective of the presence or absence of responses to ampulla or window stimulation. WGA-HRP was injected in the ASS gyrus to identify the passing callosal fibers in the CC. Fibers from the ASS area passed at the rostral third of the CC. The present results indicate that the ASS area received vestibular projection with short latency, but responses of this projection did not seem to be very strong, at least from the present unit study, to HA stimulation. Discussion was made on the poor neuronal responses to electrical HA stimulation in comparison with previous studies. Also consideration was made on neuronal activity to CC stimulation.

Animals↗

Potentiation of the antitumor activity of 5-trifluoromethyl-2'-deoxyuridine by the use of depot forms of the parent compound.

5-Trifluoromethyl-2'-deoxyuridine (CF3dUrd), an antitumor agent, is known to be short-lived in human plasma. Since its rapid elimination from the bloodstream seems to have descouraged the clinical evaluation of this drug, we explored the potential use of masked derivatives of CF3dUrd as "depot" forms of the parent compound. First, we observed that the toxicity of CF3dUrd against HeLA cells in culture was 10(4) times greater for a 24-h treatment as compared with a 1-h treatment at identical concentrations of the drug, which suggests the importance of using a prolonged treatment period. In fact, the divided dosing of CF3dUrd to L1210-bearing mice was markedly more effective than its single administration. 5'-O-Hexanoyl-, N3-p-butylbenzoyl-, 5'-O-benzyloxy-methyl-, and 3'-O-benzyl-CF3dUrd were found to be effective in maintaining the CF3dUrd concentration in plasma. The oral doses of these agents required to achieve 50% growth inhibition (ED50) in mice bearing sarcoma 180 tumors were 19, 34, 10, and 13 mg kg-1 day-1, respectively, whereas that of CF3dUrd was 63 mg kg-1 day-1. The ED50 values for these compounds were inversely correlated with the residence time of CF3dUrd in plasma. The therapeutic indices of these compounds, calculated as the dose producing a 50% inhibition of body-weight gain (IB50) divided by the ED50 value (1.89, 1.21, 1.40, and 2.15, respectively), were significantly higher than that of CF3dUrd (0.78). Consequently, these depot forms of CF3dUrd, particularly 3'-O-benzyl-CF3dUrd, are expected to be more useful than the parent compound as antitumor agents.

Animals↗

Local anesthetic-sensitive electrodes: preparation of coated-wire electrodes and their basic properties in vitro.

Coated-wire electrodes with local anesthetic (LA) cation-selective membranes were prepared, and their properties in vitro were investigated. Copper wires (0.8-mm diameter) were coated with gel membranes of 110 mg of poly(vinyl chloride), 5 mg of ion pairs of tetraphenylborate anion with LA cation, 100 mg of dioctylphtalate, and 1.5 mL of tetrahydrofuran. This was the composition determined to be most suitable. Their electromotive force relative to an Ag/AgCl electrode was measured in LA solutions. The lidocaine, dibucaine, and mepivacaine electrodes all showed good Nernstian response at 25 degrees C in aqueous solutions in the concentration ranges of 1 x 10(-4) to 1 x 10(-2) mol/L, 4 x 10(-5) to 1 x 10(-2) mol/L, and 5 x 10(-5) to 1 x 10(-2) mol/L, respectively. The response time was within 10 s. The electrode potential decreased as the pH in the solution increased, with a corresponding decrease of the protonated form of LA. The hydrophobic nature of the LA was closely related to the electromotive force and to the selectivity of the electrode toward various LA cations. Dibucaine, the most hydrophobic, had the highest electrode potential. The more hydrophobic the LA of the electrode, the less it is interfered with by other LA molecules. The more hydrophobic the interferent cation, the more it acts on the electrode potential. The electrode system could also measure LA in human plasma at 37 degrees C, although the responsiveness was depressed in the low concentration range owing to binding of LA to the serum protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics, Local↗

Action of 5-trifluoromethyl-2'-deoxyuridine on DNA synthesis.

The action of 5-trifluoromethyl-2'-deoxyuridine (CF3dUrd) on DNA synthesis was investigated in vitro assay systems with purified DNA polymerases. CF3dUrd was incorporated into the DNA of mammalian cells in culture. We studied the incorporation of CF3dUrd 5'-triphosphate (CF3dUTP) into DNA and effect of CF3dUrd residue on DNA synthesis. Therefore, we synthesized oligonucleotides that allow site specific introduction of a CF3dUrd residue into a synthetic DNA oligonucleotide. After CF3dUTP incorporation, the primer was extended for human DNA polymerase alpha (pol. alpha). When CF3dUrd residue was located at an internucleotide site in the template, however, pol. alpha was exhibited a strong arrest band one nucleotide after the CF3dUrd residue site, and Escherichia coli polymerase I (Klenow fragment) also exhibited a weaker arrest band one nucleotide before the CF3dUrd residue. These results suggested that a mechanism of antitumor activity of CF3dUrd is inhibition of DNA replication.

Base Sequence↗

Antitumor activity of FTC-092, a masked 5-trifluoromethyl-2'-deoxyuridine derivative.

1-(3-O-Benzyl-2-deoxy-beta-D-ribofuranosyl)-5-trifluoromethyl-2,4(1H,3)- pyrimidinedione (FTC-092), a fluorinated pyrimidine derivative, appeared to be effective against various transplantable tumors in mice following oral administration, and its activity was superior to that of several other antitumor fluorinated pyrimidines. The ED50 value for FTC-092 the dose effective in achieving 50% inhibition of tumor growth against the solid form of sarcoma 180 was 13.3 mg/kg daily, whereas those for 5-trifluoromethyl-2'-deoxyuridine (CF3dUrd), the parent compound of FTC-092, for 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur, FT), the prodrug of 5-fluorouracil (FUra), and for FUra were 64.1, 122, and 28 mg/kg daily, respectively. The therapeutic indices (LD10/ED50) of FTC-092, CF3dUrd, FT, and FUra were 4.39, 1.7, 1.35, and 1.65, respectively. FTC-092 itself is not an active agent. After it has been absorbed from the gastrointestinal tract, FTC-092 undergoes a gradual biotransformation, mainly via the action of liver microsomes, releasing CF3dUrd over a long period. The levels of CF3dUrd in the stomach and small intestine of mice after the oral administration of FTC-092 were undetectable, whereas those following the administration of CF3dUrd at the same dose were high for a period of several hours. In contrast, the CF3dUrd level generated in plasma after the administration of FTC-092 remained at a high level for a longer period than did that observed on the administration of CF3dUrd. The low levels of CF3dUrd measured in stomach and small-intestine tissues and the maintenance of CF3dUrd in blood over long periods after the administration of FTC-092 are features that favor the possible clinical application of FTC-092.

Administration, Oral↗

ECG analysis of golden hamsters exposed to long-term -Gz conditions: ordinary and pathological findings.

Changes of ECG due to long and intense -Gz acceleration was investigated in anesthetized Syrian golden hamsters. The R-R interval decreased (heart rate increased) slightly at the very initial phase of steady -Gz load. However, the R-R interval increased during the rest of the whole steady -Gz period. The P-R interval increased with a smaller -Gz load (-4 and -6 Gz), but it decreased with a larger -Gz (-8 and -10 Gz). The size of the QRS complex was measured as R amplitude. It decreased in all -Gz conditions. Effects were a little different for smaller and larger -Gz, as was observed in the case of P-R changes. Pathological ECGs were frequently observed. They were: (1) Arrhythmia of heart rate with or without atrio-ventricular blocks. (2) Abnormal P wave; e.g., splitting, flattening, or abolition of P wave. (3) Alteration of the QRS complex in amplitude or contour. (4) Changes in ST-T components. In spite of all these changes, however, it should be noted that several Syrian golden hamsters could tolerate up to -10 Gz for as long as 1,000 s.

Acceleration↗

The vestibulo-autonomic function viewed from cardiac responses in centrifuged monkeys.

Vestibulo-autonomic function was examined as the change of cardiac parameters (HR and SV) to +Gz and -Gx accelerations for 1,000 s in intact and bilaterally labyrinthectomized monkeys. Under anesthetized conditions, HR and SV slightly changed to +2Gz acceleration in both monkeys. In +3Gz acceleration, changes were remarkable and significant. HR increased in intact monkeys by as much as 30% while it decreased in labyrinthectomized monkeys, although a moderate initial increase was observed. SV decreased in intact as well as labyrinthectomized monkeys, but the reduction was significant and larger for the latter. This implies that vestibular input could modulate autonomic function. For larger +Gz, both intact and labyrinthectomized monkeys could tolerate no more due to severe cardiac dysfunction (rapid HR and SV decrease) which appeared soon after +4Gz application. In case of -Gx application, HR increased, although slightly, in proportion to the amplitude of applied -Gx in both monkeys, with less changes in labyrinthectomized ones. SV hardly changed in smaller -Gx, while it increased in larger -Gx. Difference between intact and labyrinthectomized monkeys was observed in -6Gx and -8Gx conditions.

Acceleration↗

Synerazol, a new antifungal antibiotic.

Synerazol, a new antifungal antibiotic, was isolated from cultured broth of Aspergillus fumigatus SANK 10588. The structure was determined based on NMR and mass spectral evidences. Synerazol was found to be a related substance to pseurotin A. Synerazol was active against Candida albicans and other fungi, and showed marked synergistic activity with azole-type antifungal agents.

Antifungal Agents↗

Inhibition of in vitro DNA chain elongation of 5-trifluoromethyl-2'-deoxyuridine residue in the template.

5-Trifluoromethyl-2'-deoxyuridine (CF3dUrd) is incorporated into the DNA of mammalian cells in culture. We have synthesized oligonucleotides that allows site specific introduction of CF3dUrd residue into synthetic DNA oligonucleotide. We described here the utilization of these oligonucleotides as template for in vitro DNA synthesis. When CF3dUrd residue located at an internucleotide site in the template, the chain elongation was partially arrested one nucleotide after or before the CF3dUrd residue of template using Escherichia coli polymerase I (Klenow fragment) or human polymerase alpha (pol alpha). These results suggested that a mechanism of antitumor activity of CF3dUrd is inhibition of DNA replication.

Base Sequence↗

Development of skill of children in the performance of the family computer game "Super Mario Brothers".

The development of skill of children in the performance of a family computer game (Super Mario Brothers) was investigated among three groups of different age: kindergarten children (6 years old) and primary school children (9 and 12 years old). The skill to perform the game with either hand was evaluated by the mean scores gained by the children. In the normal (right and dominant) situation, the mean score improved significantly with advancement of age. Similar was true in the reversed (left hand dominant) situation, but more distinctly. The mean scores were significantly higher in the normal than in the reversed situations. The experienced children were superior to the inexperienced children in playing the game. The correlation between the reaction time and the game score was also investigated with the same subjects for the 9- and 12-year-old school children. Almost no correlation could be elucidated.

Age Factors↗

The influences of dexamethasone and indomethacin on 67Ga uptake by normal tissues.

Dexamethasone (DEX) increased 67Ga uptake by the liver and spleen at 4, 8, and even 24 h after the injection of 67Ga. These results showed that DEX influenced 67Ga accumulation as well as the initial entry of 67Ga in the liver and spleen. On the other hand, indomethacin (IM) decreased 67Ga uptake by the liver and spleen at 4 h after the injection of 67Ga but did not influence the uptake at 8 or 24 h after the injection of 67Ga. Moreover, DEX or IM little influenced 67Ga uptake by the kidney and muscle. These results suggest that the influence of DEX or IM on 67Ga uptake or accumulation is specific for the liver and spleen.

Animals↗

Mode of [14C] 2-deoxy-D-glucose uptake into retrosplenial cortex and other memory-related structures of the monkey during a delayed response.

Physiological studies on the monkey retrosplenial (RS) cortex have been few, and its functional role remains to be investigated. In the present study, activity of the RS cortex was investigated using radioactive 2-DG while the monkey was performing a visual tracking task with a delay (a delayed-response task) for 45 minutes. A remarkable increase in 2-DG uptake was observed equally in the left as well as in the right RS cortex. The anterior nucleus of the thalamus also showed increased 2-DG uptake. In addition, other memory-related structures (prefrontal cortex, dorsomedial nucleus of the thalamus, amygdala and hippocampus) showed a similar increase in 2-DG uptake compared to control monkeys, though their respective absolute values were different from one another. Since the RS cortex receives afferents from the anterior nucleus of the thalamus, which is one of the main nuclei of the Papez circuit, it is assumed that the RS cortex is important in memory function. Therefore, the remarkable increase in 2-DG uptake in the present study could reflect some aspects of memory or learning processes required to perform the delayed response.

Animals↗