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Biomedical subjects

E Kondo

Publications and source records attributed to E Kondo.

At least 145 records · Page 8Linked to original sources

An experimental model of chemotherapy on dormant tuberculous infection, with particular reference to rifampicin.

Mice were infected intravenously with a streptomycin (SM)-dependent strain of tubercle bacilli which had been starved of the antibiotic. The inoculum persisted in the spleen for a fairly long period, especially keeping almost the initial level of viable counts in the first few weeks. Isoniazid (INH) administration exerted little effect on such fate of the infection at a bactericidal dose to the same strain multiplying under the supply of SM. Rifampicin (RFP) was, however, highly effective in either case. Similar results were obtained in the corresponding in vitro experiments. The data suggest that this animal model is a convenient system for screening drugs effective on the dormant tuberculous infection.

Animals↗

Antitumor activity of synthetic alkylphospholipids with or without PAF activity.

1-O-Octadecyl-2-O-methyl-sn-glycero-3-phosphocholine (ET-18-OMe) has been reported to possess definite antitumor activity in vivo. Twenty-two alkyl lysophospholipid analogs were chemically synthesized, and their antitumor activity against mouse experimental tumors (Sarcoma 180, MM46, P388) was examined. Among them, 1-O-octadecyl-2-O-acetoacetyl-rac-glycero-3-phosphocholine was found to show antitumor activity similar to ET-18-OMe with less acute toxicity. Intravenous injection of the ET-18-OMe with sn-3 configuration retarded the subcutaneous growth of Sarcoma 180 cells effectively, while the growth inhibition by the sn-1 isomer was much less effective. This stereospecificity was similar to that observed in their activities as platelet-activating factor (PAF) agonists. The acetoacetyl compound, another PAF agonist, showed similar stereospecific antitumor action in vivo. These findings suggest that some alkyl lysophospholipids may activate host cells to a cytostatic stage against tumor cells in vivo through binding to a PAF receptor. Our preliminary results indicated that the responsible cells under these conditions might be primarily immature macrophages present in the bone marrow. No appreciable or even adverse stereospecificity was observed in the different sets of experiments where the activity of ET-18-OMe against MM46 tumor cells in vivo or the direct cytotoxicity against human promyelocytic leukemia HL-60 cells in vitro was examined. Under some conditions, the antitumor activity of ET-18-OMe in vivo may be revealed through direct cytotoxicity and/or modulation of the host defense system by "nonspecific" mechanisms. Some alkylphospholipids without PAF activity may also show antitumor activity through similar "nonspecific" mechanisms.

Animals↗

PB-5266 A, B and C, new monobactams. I. Taxonomy, fermentation and isolation.

New monobactams, PB-5266 A, B and C were isolated from the culture filtrate of Cytophaga johnsonae PB-5266 by various types of column chromatography and preparative reverse phase HPLC. PB-5266 A, B and C exhibited weak antibacterial activity against a sensitive mutant of Escherichia coli to beta-lactam antibiotics.

Anti-Bacterial Agents↗

Dopamine-induced amylase secretion from rat parotid salivary gland in vitro: an effect mediated via noradrenergic and cholinergic nerves.

The effect of dopamine on amylase secretion by rat parotid tissue was examined in vitro. Dopamine induced marked amylase secretion from the tissue in a dose-dependent manner. Its EC50 value was about 4 microM and the maximal response was obtained at a concentration of 100 microM. The dopamine-induced secretion was inhibited by the dopamine-antagonists haloperidol, (+)-butaclamol and spiroperidol. Atropine reduced the dopamine-induced secretion significantly, and physostigmine enhanced the secretion. Parasympathectomy of the gland resulted in a significant decrease in the dopamine-induced secretion, but did not reduce the secretion induced by dopamine with atropine. Dopamine-induced ACh release from parasympathetic nerve terminals in the tissue was studied in tissue preparations that had been loaded with [3H]-choline. Dopamine elicited Ca2+-sensitive tritium release, and dopamine antagonists or parasympathectomy prevented this release. Sympathectomy or reserpine treatment of rats resulted in significant decrease in the dopamine-induced secretion, but increase in noradrenaline (NA)- or isoprenaline-induced secretion. Dopamine-induced NA release was studied by preloading the parotid tissue with [3H]-NA. Dopamine induced Ca2+-sensitive tritium release, and dopamine antagonists or sympathectomy prevented the release. Several lines of circumstantial evidence strongly suggested that dopamine has a specific site for action in the parotid tissue that is independent of NA receptors. In sympathectomized or reserpine-treated glands, atropine completely inhibited the dopamine-induced amylase secretion, suggesting that dopamine did not have a direct effect on postsynapses. These findings indicate that dopamine induces amylase secretion in two indirect ways mediated through ACh and NA released from parasympathetic and sympathetic nerve terminals, respectively.

Amylases↗

Nucleotide sequence of the hag gene encoding flagellin of Escherichia coli.

We determined the DNA sequence of the hag gene of Escherichia coli K-12 and deduced the primary structure of the flagellin consisting of 497 amino acid residues. Comparison of the amino acid sequence with those of other bacterial flagellins revealed a high homology in the NH2- and COOH-terminal regions.

Amino Acid Sequence↗

Melittin-stimulated antimycobacterial activity of the membrane fraction isolated from phagocytes of guinea pigs.

Virulent tubercle bacilli were incubated in Kirchner semi-solid agar medium with the membrane fraction prepared from guinea-pig peritoneal exudate cells. A marked inhibition of mycobacterial growth was observed in the presence of added melittin which is known as an activator of membrane phospholipase A. The bactericidal activity in a buffer environment was also demonstrated by the fraction alone and that stimulated by melittin.

Animals↗

Triton WR-1339 as a biological-response modifier in mycobacterial infection.

A non-ionic detergent, Triton WR-1339, prolonged markedly the survival time of mice infected fatally with virulent mycobacteria, though it exerted only a limited effect on the fate of tissue viable counts. The combined administration of Triton WR-1339 with lentinan (a glucan purified from the Japanese mushroom Lentinus edodes) was more effective than the single administration of each. This detergent was not lytic to red blood cells or lysosomes, but its substantial effect on the biomembrane was suggested by cold-shock experiment of hemolysis. It was considered that Triton WR-1339 is a biological-response modifier, possibly altering the interaction between the mycobacterial surface and the membrane structure of phagocytes.

Animals↗

Ultrastructural studies on the effect of Triton WR-1339 on macrophage-mycobacteria interaction.

Mycobacterium bovis (BCG organisms) suspended in saline or a 5% solution of a non-ionic detergent, Triton WR-1339, was injected intraperitoneally into mice. Electron-microscopic observation was carried out on peritoneal exudate cells harvested therefrom. Electron-lucent vacuoles limited by the membrane structure were found in macrophages of the mice injected with BCG suspended in the detergent, but not in polymorphonuclear leukocytes or lymphocytes. Mycobacterial cells were present within such vacuoles. Without the detergent, the ingested mycobacterial cells were in close contact with the phagosomal membrane. Within the electron-lucent vacuoles, however, such close contact was not present. These observations, together with other collateral findings, led us to a view that Triton WR-1339 may inhibit the interaction between mycobacteria and the phagosomal membrane by intervening between them thus making the progress of infection delayed.

Animals↗

Bactericidal activity of the membrane fraction isolated from phagocytes of mice and its stimulation by melittin.

The membrane fraction prepared from mouse peritoneal exudate cells was incubated with mycobacteria, staphylococci, or E. coli in acetate buffer of pH 5.6 to follow the fate of viable bacilli. The membrane fraction exhibited bactericidal effect on mycobacteria and staphylococci, but not on E. coli. The activity to kill mycobacteria, as well as the endogenous phospholipase A2 activity, of the membrane fraction was markedly enhanced by melittin, a basic peptide from bee venom, and inhibited by indomethacin and EDTA. The role of the enzyme activity in the bactericidal activity was discussed.

Animals↗

Prevention of supersensitivity-like phenomena in rat vas deferens by colchicine.

Rat vas deferens has been shown to become supersensitive to alpha-adrenergic agonists on brief treatment with epinephrine (Epi-treatment). Epi-treatment increased the contractile response and the number of alpha-adrenoceptors in the tissue. The application of colchicine (2.5 mM) during Epi-treatment prevented the supersensitivity-like phenomena and increase in number of alpha-adrenoceptors. Vinblastine (10 microM) also counteracted the effect of Epi-treatment but cytochalasin B (100 microM) and strychnine (2.5 mM) did not. It is suggested that the supersensitivity-like phenomena induced in rat vas deferens by Epi-treatment were due to a change in microtubular components of the membrane.

Animals↗

Electron microscopy of monoclonal antibody-linked chains of thyroglobulin molecules.

Negative staining electron microscopy visualized immune complexes of hog thyroglobulin produced by 3 monoclonal antibodies, each towards a different conformation-dependent antigenic structure of the thyroglobulin. Equimolar mixtures of the thyroglobulin and any one of the 3 antibodies formed peculiar unbranched chains of 'ovoid' thyroglobulin molecules linked by the antibody molecules in an 'end to end' fashion. A mixture of the thyroglobulin and the 2 different antibodies produced branched chains. A set of 3 conformation-dependent antigenic structures was thus located near each end of the elongated thyroglobulin molecule. The results also indicated a topological similarity between the 2 subunits of thyroglobulin.

Animals↗

Aldosterone antagonists. 1. Synthesis and biological activities of 11 beta,18-epoxypregnane derivatives.

Several steroid derivatives having the 11 beta,18-epoxypregnane skeleton, 7, 8, 19, 20, 21, and 31, were synthesized to evaluate their antialdosterone activity. Among them, 3-(9 alpha-fluoro-17 beta-hydroxy-3-oxoandrost-4-en-17 alpha-yl)propionic acid gamma-lactone (31) possessed fairly strong binding affinity for the cytoplasmic mineralocorticoid receptor of rat kidney and exhibited good aldosterone antagonist activity in an in vivo assay. However, its agonistic nature cannot be ignored. The properties of 31 as an aldosterone antagonist were enhanced by its very low to negligible binding affinity for the androgen, progestin, estrogen, and glucocorticoid receptors.

Animals↗

Forskolin induces supersensitivity of the amylase secretory response of rat parotid tissue.

The stimulatory effect of forskolin on amylase secretion was studied by pretreating rat parotid tissue with forskolin for 10 min, incubating it in medium without forskolin for 10 min, and then treating it with forskolin again. Pretreatment with 10 microM forskolin for 10 min resulted in increased amylase secretion and enhanced accumulation of cyclic AMP in the tissue during the second incubation with forskolin. In the presence of colchicine or vinblastine, the enhancement in cyclic AMP accumulation during the second incubation with forskolin was prevented, but the increased amylase secretion remained unchanged. The increased amylase secretion was counteracted only in the presence of concanavalin A. On the other hand, increased amylase secretion induced by isoproterenol (IPR) pretreatment was counteracted by colchicine, vinblastine, concanavalin A or strychnine. These data suggest that the total amount of cyclic AMP in the tissue does not have any essential role in the supersensitivity of the amylase secretory response, and that the supersensitivity induced by forskolin differs from that induced by IPR.

Amylases↗