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Biomedical subjects

T Kikuchi

Publications and source records attributed to T Kikuchi.

At least 685 records · Page 38Linked to original sources

Generation of hydroxyl radical by anticancer quinone drugs, carbazilquinone, mitomycin C, aclacinomycin A and adriamycin, in the presence of NADPH-cytochrome P-450 reductase.

The generation of hydroxyl free radicals in the system consisting of purified NADPH-cytochrome P-450 reductase and anticancer quinone drugs, such as carbazilquinone, mitomycin C, aclacinomycin A and adriamycin, has been confirmed by two methods. In the spin trapping study, using N-tert-butyl-alpha-phenylnitrone as the spin trapping agent, four drugs generated hydroxyl radical-trapped signals, and the formation of the spin adduct was dependent on time and the enzyme concentration. Among the four drugs, the generation time of signal was in the order of carbazilquinone, aclacinomycin A, adriamycin and mitomycin C, but the magnitude of signal intensity was different. In both aclacinomycin A and adriamycin, the signal disappeared in a few minutes. Catalase completely inhibited the formation of the spin adduct, while superoxide dismutase did not significantly inhibit, but effected in some manner. The generation of hydroxyl radical was also confirmed by the ethylene production from methional. Among the four drugs, the order of the magnitude of ethylene production was different from that of signal intensity by ESR study. Catalase potently inhibited the ethylene production, while superoxide dismutase effected in some manner. From these results, the interactions of anticancer quinone drugs with NADPH-cytochrome P-450 reductase and oxygen, and the possible relations of the enzymes to the radical related actions of these drugs are discussed.

Aclarubicin↗

Recovery from inhibition of transcription in gamma-irradiated Euglena cells.

1. Transcriptional activity was inhibited with low doses of gamma-irradiation which did not cause the death of cells, but induced the delay of cell division in the unicellular alga Euglena. 2. The incorporation of [14C]uracil into cells was inhibited to about 50% of non-irradiated cells immediately after 3 krad irradiation. 3. The suppressed transcriptional activity was gradually recovered after irradiation. At about 12 h post-irradiation, the rate of incorporation of [14C]uracil recovered to that of non-irradiation cells. 4. The synthesis of ribosomal RNA was inhibited immediately after 3 krad irradiation, but it was recovered within 12 h after irradiation. The synthesis of cytosol ribosomal RNA precursor was more strongly inhibited than that of other cytosol ribosomal RNAs. 5. The synthesis of cytoplasmic organelle ribosomal RNA was also inhibited and recovered after 3 krad irradiation.

Euglena gracilis↗

Permeability of heparinized hydrophilic polymer (H-RSD): application to semipermeable membrane for microencapsulation of activated charcoal.

A series of heparinized hydrophilic polymers (H-RSD) composed of a hydrophobic element, a nonionic hydrophilic element, a cationic element and ionically bound heparin was synthesized. The permeability of the H-RSD polymers with various chemical compositions and water contents was investigated. From the studies on the permeability, it has been found that in order to maintain good permeability after heparinization, the nonionic hydrophilic element is necessary. In addition, the microencapsulation of activated charcoal granules using a H-RSD polymer with a similar permeability to that of Cuprophan was examined. In vitro adsorption studies and in vivo direct hemoperfusion studies on the activated charcoal microencapsulated with the H-RSD polymer, show that the H-RSD coating prevents clot formation without loss of the absorption power of the activated charcoal.

Absorption↗

The influence of heparinized polymers on the retention of platelets aggregability during storage.

The change in aggregability of the platelets stored in the storage tube fabricated from a newly developed heparinized hydrophilic polymer (H-RSD) has been studied in comparison with plasticized poly(vinyl chloride) (PVC) which is widely used for blood bags. Rabbit blood was directly withdrawn into the storage tube containing an anticoagulant from the carotid. Then the tube was mechanically sealed with screw cocks and centrifugated to prepare platelet-rich plasma (PRP) in the tube and again mechanically clamped to separate the PRP from the residual precipitate. The PRP was stored in situ in the storage tube at room temperature under agitation. During storage, the change in the aggregability of the PRP induced by adenosine diphosphate (ADP) was studied and the morphological change in the platelets adhered onto the inner surface of the storage tube was observed by scanning electron microscopy. In the H-RSD tube, the aggregability was maintained during two-day storage, while in the PVC tube, the aggregability was completely lost after one-day storage. The scanning electron microscopic studies demonstrated that the reduction in the aggregability of the stored platelets is closely correlated with the morphological deformation of the platelets adhered onto the surface of the storage tube.

Animals↗

Volatile sulfur compounds responsible for an offensive odor of the flat-head, Calliurichthys doryssus.

1. The volatiles of a flat-head, Calliurichthys doryssus, which gives out a characteristic offensive odor in living time, were analyzed by gas chromatography. 2. A large quantity of volatile sulfur compounds was detected in the flat-head; of which methyl mercaptan and/or dimethyl disulfide were judged to be responsible for the offensive odor. 3. The contents of methyl mercaptan and dimethyl disulfide were much higher in skin than in muscle and viscera.

Animals↗

Serum enhances the cycling and survival of HeLa cells treated with 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole.

We have defined the growth kinetics of HeLa cell populations by determining the frequencies of mitoses and deaths and the lengths of intermitotic intervals. This was done by time-lapse cinemicrography. Untreated control cells proliferated at closely similar rates in medium enriched with 5% or 15% fetal calf serum, with an average of 4% dividing and less than 0.1% dying per hr. The mean intermitotic interval was 16 hr during exponential growth of the control populations. In contrast, in cultures treated with 40 or 60 microM 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a selective inhibitor of heterogeneous nuclear RNA synthesis, the frequency of mitoses was markedly and directly dependent on serum concentration, whereas the frequency of deaths was inversely dependent. DRB prolonged the intermitotic interval in cells cycling in the presence of the drug, but the effect was less in 15% than in 5% serum. After prolonged treatment of HeLa cells with DRB, the inhibition of heterogeneous nuclear RNA synthesis by DRB appeared to be reduced, which was not due to inactivation of DRB in the culture medium.

Cell Cycle↗

Acute functional changes of platelets in left ventricular assist in a dog model.

Left ventricular assist bypass was performed in nine dogs using pneumatically actuated blood pumps fabricated of segmented polyurethane and heparinized hydrophilic polyurethane (H-USD) newly developed so as to render excellent antithrombogenicity. The survival of the dogs ranged from 1 to 82 days. In all cases, significant reductions in platelet count and in platelet aggregability were observed. Simultaneously, severe hemorrhage from the anastomosed descending aorta occurred four to six hours after the pump implantation. This hemorrhage, leading to death, was not related to systemic heparinization, but was closely related to the mechanical impairment of platelets by the pumping operation. Five days after the pump implantation, complete recovery of the platelet aggregability was observed and no further hemorrhage occurred in the dog that survived for 82 days.

Animals↗

[Pharmacological properties of buprenorphine, a new analgesic agent. Part II. (author's transl)].

Pharmacological properties of buprenorphine were compared with those of morphine and pentazocine. Buprenorphine scarcely showed any effects on spontaneous EEGs and sleep-wakefulness cycles. Buprenorphine tended to depress the recruiting and augmenting responses and the spindle burst, and it also inhibited the hypothalamic arousal response. Buprenorphine had weaker emetic action than morphine and protected against apomorphine-induced emesis in the same manner as morphine. Buprenorphine scarcely affected respirations, blood pressure, heart rate, blood flow, ECG, cardiac contractile force, cornary flow, and intracranial pressure. However, morphine and pentazocine caused depressed respiration, decreased blood pressure, increased blood flow and cardiac contractile force, and elevated intracranial pressure. Buprenorphine, morphine, and pentazocine did not affect bile secretion, but produced contraction of the sphincter of Oddi. Buprenorphine had very little effect on renal function, but morphine and pentazocine reduced this function to depress urine flow. Buprenorphine and morphine inhibited carrageenin-induced edema. Buprenorphine had no effect on blood histamine level, but morphine increased the concentration of histamine. These results indicate that buprenorphine has little effect on the central nervous system, respiratory and cardiovascular system, and renal function.

Analgesics, Opioid↗

[A clinical investigation of the combination therapy of 1-(2-tetrahydrofuryl)-5-fluorouracil (FH) fine granules and 5-FU dry syrup].

The anticancer effect and side effect of 1-(2-Tetrahydrofuryl)-5-fluorouracil (FH Fine granules "MI-TSUI") plus 5-FU Dry Syrup combination therapy was evaluated in 24 patients with cancer of the digestive organs. In this study, it was suggested that the daily oral administration of 400mg of FH Fine granules combined with 100mg of 5-FU Dry Syrup is most adequate and effective among them.

Adult↗