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Biomedical subjects

T Tsuchiya

Publications and source records attributed to T Tsuchiya.

At least 595 records · Page 33Linked to original sources

[Experimental study on the effectiveness of BRM in radiation therapy--OK-432 and cyclophosphamide].

We have previously demonstrated that specific antitumor cell-mediated immunity in host mice was induced or enhanced by local irradiation to tumor. In this study, the immunological status of host mice with transplanted tumor were modified by using OK-432 as immunostimulator and cyclophosphamide as suppressor of suppressor T-cells before and/or after local irradiation to tumor. The results indicate that the combined use of immunomodifier and radiation is more effective in the tumor radiotherapy. Three factors as follows: the interval of drug and radiation, the times of treatments and dose of immunostimulator and immunosuppressor, are very important in these combined therapy.

Animals↗

Quantitation of beta-tubulin mRNA in mouse brain by RNA-RNA hybridization kinetics with single-stranded riboprobes.

A quantitative procedure involving RNA-RNA hybridization kinetics was developed for measurement of specific mRNA accumulated in particular tissues and cells. Two types of riboprobes for quantitating mouse beta-tubulin mRNA were prepared; one was a truncated RNA covering only the coding portion of beta-tubulin cDNA and the other was a non-truncated RNA covering the vector portion as well as the coding portion. These antisense RNAs were hybridized with the mouse brain RNA, yielding heat-stable hybrids. The truncated and non-truncated antisense RNA probes showed similar hybridization kinetics. Hybridization of the sense RNA, consisting of the beta-tubulin coding portion, with the antisense RNA probe gave standards for determining the proportion of beta-tubulin mRNA in total brain RNA. By this method, the amounts of beta-tubulin mRNA included in the brains of mice of 10 and 50 days old were quantitated.

Animals↗

Antitumour activity of new semi-synthetic anthracyclines containing fluorotalopyranose.

The authors have synthesized 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) adriamycinone (FT-ADM) which exhibited strong antitumour activity and weak toxicity. These characteristics of FT-ADM are partly due to the presence of a 2'-fluoro atom which strengthens the glycoside bond. FT-ADM, however, is sparingly soluble in water because of lack of the 3'-amino group of adriamycin. To increase the solubility of FT-ADM, a hydrophilic group was added at the 14-OH group. Then, the 14-hemisuccinate, 14-hemiglutarate, 14-hemiadipiate, 14-hemipimelate and 14-hemisuberate derivatives of FT-ADM were synthesized. Among them, the 14-hemipimelate derivative (FAD-104) was selected for further development because of its potent antitumour activity and weak toxicity. When drugs were injected intraperitoneally every day from day 1 to 9, FAD-104 showed an apparently stronger antitumour effect against mouse L-1210 leukaemia than adriamycin with lower toxicities. FAD-104 was also more effective than adriamycin on L-1210 using other administration schedules. A characteristic feature is that FAD-104 is effective over a very broad range, which will be advantageous for safe clinical use. FAD-104 also showed marked antitumour effect against L-1210 when it was injected intravenously either once on day 1 or three times on days 1, 5 and 9. Thus, FAD-104 may be a more potent antitumour anthracycline than adriamycin.

Animals↗

Biological properties of ME2303 (FAD-104), a new anthracycline.

ME2303 (FAD-104) is a new anthracycline antibiotic whose structure is characterized by the presence of a 2'-fluoro atom and the lack of a 3'-amino group in the sugar moiety. Its cytocidal activity is superior to or equal to that of adriamycin (ADM). The LD50 value of ME2303 was about 140 mg/kg i.v. in mice and this value was about 7-fold higher than that of ADM. ME2303 was administered intravenously to Golden strain hamsters at doses of 25, 50, 75 and 150 mg/kg and the ECG was examined. From ECG changes, it seems that ME2303 did not show any effect on the heart in acute toxicity. Mutagenicity was recognized as with ADM in the back-mutation test.

Animals↗

Origin of unusual interaction between thick and thin filaments in shrunk skinned muscle fibers of frog.

Isometric tension, shortening velocity and instantaneous stiffness as a function of relative fiber width were measured in skinned muscle fibers from the frog. Fiber width was reduced by adding the long chain polymer PVP (polyvinylpyrrolidone) K30 or dextran T70 to the bathing solution. Both shortening velocity and isometric tension clearly decreased with the concentration of PVP. Instantaneous stiffness measured by a quick length step was detected in a relaxed, reduced-width fiber and it increased with degree of compression. In the presence of polymer, higher stiffness was observed always in activating solution than in relaxing one. The excess stiffness induced by activation above that in relaxing solution was nearly constant in the wide range of polymer concentration. The stiffness in a relaxed, reduced-width fiber was shown to decrease with the increase of sarcomere length. In rigor fibers also, stiffness increased as the fiber width was reduced. These facts suggest that two kinds of stiffnesses exist in a compressed fiber, one is active or rigor stiffness and another is the parallel "unusual" stiffness which may result from sliding filaments and that the latter has passive natures.

Animals↗

Muscle stiffness changes during enhancement and deficit of isometric force in response to slow length changes.

The mechanism of the enhancement and the deficit of isometric force in response to slow length changes in tetanized frog muscle fibers was studied by recording the stiffness changes with sinusoidal vibrations (0.5-1.9 kHz, peak-to-peak amplitude 0.1% of L0). When a tetanized fiber was slowly stretched, the fiber stiffness first rose abruptly and then decreased linearly while the stretch went on; after the completion of stretch, the stiffness decreased towards a steady value which was equal to that during the ordinary isometric tetanus at the same fiber length, though the force decayed towards a steady level higher than that of the ordinary isometric tetanus at the same fiber length. This indicates that the enhancement of isometric force after stretch is associated with decreased stiffness. If, on the other hand, a tetanized fiber was slowly released, the force and the stiffness changed in parallel with each other. Recordings of the segmental length changes along the fiber with a high-speed video system (200 frames/s) indicated that all the segments lengthened in response to slow stretch, while the segmental length changes in response to slow release was markedly nonuniform. These results are discussed in connection with the cross-bridge performance and the filament-lattice structures.

Animals↗

Properties of a Na+-coupled serine-threonine transport system in Escherichia coli.

Based on the following experimental results we conclude that the serine-threonine transport system in Escherichia coli is a Na+-coupled cotransport system. (1) Addition of serine to cell suspensions induced H+ efflux in the presence of Na+. (2) Addition of serine to cell suspensions induced Na+ uptake by cells. (3) Imposition of an artificial electrochemical potential of Na+ in starved cells induced serine uptake. Some of these phenomena were observed when threonine was added instead of serine or inhibited when cells were preincubated with threonine. The Na+/serine (threonine) cotransport system was considerably repressed when cells were grown on a mixture of amino acids. Serine transport in cells grown in the absence of amino acids mixture was stimulated by Na+. The half maximum concentration of Na+ was 21 microM. Sodium ion increased the Vmax of serine transport without affecting the Km.

Amino Acid Transport Systems↗

Synthesis of antitumor-active 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl)-daunomycinone and -adriamycinone.

The title compounds (17 and 23) were prepared by coupling 3,4-di-O-acetyl-2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl bromide (15) with daunomycinone. The key step in the preparation of 15 was the epoxide-ring opening of methyl 2,3-anhydro-4-O-benzyl-6-deoxy-alpha-L-gulopyranoside with KHF2 in ethylene glycol, whereupon 2-fluoro-alpha-L-idopyranoside was obtained. Compounds 17 and 23 showed strong antitumor activity.

Animals↗

Na+/adenosine co-transport in Vibrio parahaemolyticus.

Adenosine transport in Vibrio parahaemolyticus was studied. Na+ greatly stimulated adenosine uptake. Addition of adenosine to a cell suspension under anaerobic conditions elicited Na+ uptake, and the Na+ uptake was inhibited by monensin, an Na+ ionophore. Imposition of an electrochemical potential of Na+ or a membrane potential in energy-depleted cells elicited adenosine uptake. Therefore, adenosine transport in this organism was concluded to proceed by an Na+/adenosine co-transport mechanism. The Na+/adenosine co-transport system was induced when cells were grown in the presence of adenosine, and repressed by glucose. Although Na+ uptake elicited by adenosine was reduced by glucose, it was enhanced by methyl alpha-glucoside, which reduced the intracellular ATP level. Thus, the effects of glucose and the glucoside on the Na+/adenosine co-transport system did not seem to be due to inducer exclusion, but to be related to the intracellular ATP level.

Adenosine↗

Isolation and properties of a mutant of Escherichia coli possessing defective Na+/H+ antiporter.

A mutant of Escherichia coli with defective Na+/H+ antiporter was isolated. The rationale for its isolation was that cells possessing defective Na+/H+ antiporter, which is essential for establishment of a Na+ gradient, could not grow with a carbon source that was taken up with Na+. The mutant had no appreciable Na+/H+ antiporter activity, but its K+/H+ antiporter and Ca2+/H+ antiporter activities were normal. Judging from the reversion frequency, the defect seems to be due to a single mutation. The mutant could not grow at alkaline pH. Therefore, the Na+/H+ antiporter, but not the K+/H+ antiporter or the Ca2+/H+ antiporter, seems to be responsible for pH regulation in alkaline medium. This mutant will be useful for cloning the Na+/H+ antiporter gene and for detection of Na+-substrate cotransport systems.

Carrier Proteins↗

[Combined radiotherapy and local external hyperthermia in advanced cancer--animal experiment and clinical study].

The response of a mouse's foot to heat was studied. Transplanted syngeneic tumor, C3H mouse mammary carcinoma, was treated with irradiation and hyperthermia in a waterbath. The tumor did not disappear in any of the mice treated with radiotherapy with a dose of 20 Gy alone, but disappearance of the tumor was observed in 11 of 15 and 6 of 8 of the mice treated with combined therapy of irradiation and hyperthermia. There was a significant difference between these two groups. Synergistic effect was confirmed (P less than 0.001, P less than 0.005). Hyperthermia using Thermotron RF-8 was performed on 19 patients (5 bladder cancers, 3 uterine cancers, 3 rectal cancers, 4 soft tissue tumors, 2 oral cancers, 1 biliary tract cancer, 1 renal cancer) between April, 1986 and December, 1986. They were irradiated with a daily dose of 1.5-2.0 Gy, 5 times a week and hyperthermia was performed within 30 minutes after each irradiation once or twice a week. Intratumoral temperature was kept at 43 degrees C-45 degrees C. Temperature over 41 degrees C was maintained in most patients. Clinical response was assessed by tumor regression rates. Partial response a (PRa), defined as 80% or more regression in tumor volume, was obtained in 1 bladder cancer patient and PRb, defined as 50% to less than 80% regression, was obtained in another 5 patients. Side effects were observed in all patients including mild skin burn, nausea and diarrhea. Rectovaginal fistula developed in 1 patient. Combined radiotherapy and hyperthermia seems to be useful in advanced cancer patients.

Adult↗

A novel mechanism for utilization of extracellular AMP in Vibrio parahaemolyticus.

Vibrio parahaemolyticus could grow with AMP, ADP or ATP as the sole source of carbon. In the presence of Cl-, a membrane-bound Cl(-)-dependent 5'-nucleotidase seemed to hydrolyze the nucleotides extracellularly, and then the cells took up the resulting adenosine. In the absence of Cl-, although no significant dephosphorylation of the nucleotides occurred, the cells could still grow with AMP, but not with ADP or ATP. Moreover, in the presence of Cl-, Zn2+ inhibited the 5'-nucleotidase, and inhibited growth of the cells with ADP or ATP, but not with AMP, as the carbon source. V. parahaemolyticus was unable to grow with adenine or ribose 5-phosphate. These results suggested that the cells might have an AMP transport system. In fact, Na+ uptake was observed on addition of AMP to a cell suspension in the absence of Cl-, indicating Na+-AMP cotransport.

5'-Nucleotidase↗

Correlations in one-dimensional fully developed chaos.

Correlations in the baker map and the tent map as examples of one-dimensional, fully developed chaos are considered. It is shown, utilizing symbolic dynamical systems derived from these maps, that the vanishing second-order correlation function is not sufficient to guarantee uncorrelatedness. Importance of the higher-order, especially third-order, correlation functions is emphasized for chaotic systems. In search of the quantities that grasp correlational behaviors as a whole in chaotic systems, it is proposed to use the fixed-separation correlation integral, which is a modified quantity of the usual correlation integral devised to calculate the fractal dimension of strange attractors, for these maps. It is shown that the new quantity contains all the even-number orders of autocorrelation function that are commonly considered.

Mathematics↗

Effects of benzimidazoles on mouse and rat limb bud cells in culture.

Benzimidazoles exhibited an inhibitory action on the chondrogenesis in a mouse limb bud cell culture system; further, nitro and chloro groups at the 5 position in 2-(2-pyridyl)benzimidazole were found to be potent substituents. However, 2-(2-pyridyl)benzoxazole and 5-methoxy-2-(2-pyridyl)benzothiazole exhibited no inhibitory action under our experimental conditions. Thus, imidazole NH proton seemed to be important in the inhibitory action in the mouse cell system. The concentrations of thiabendazole (TBZ), 5-hydroxy-TBZ (5-HY-TBZ) and N-methyl-TBZ necessary to reduce the amounts of cartilage proteoglycan by 50% (TP50) were estimated to be about 0.35, 0.25 and 0.70 mM, respectively, in the rat limb bud cell culture system. The TP50 of TBZ and 5-HY-TBZ in the rat cell system were 3- to 4-fold higher than those in the mouse cell system.

Adenosine Triphosphate↗