Biomedical subjects
Publications and source records attributed to K Takeda.
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N-Nitroso-N-(hydroxymethyl)alkylamines, which are key intermediates in the metabolic activation of nitrosamines having a methyl group, were synthesized and their chemical and mutagenic properties were examined. Six N-nitroso-N-(hydroxymethyl)alkylamines (alkyl = methyl, ethyl, n-propyl, n-butyl, sec-butyl, tert-butyl) were prepared by the deoxygenation of N-nitroso-N-(hydroperoxymethyl)alkylamines. Their stability in aqueous solution was highly dependent on pH, being stable in acidic media, but unstable in neutral or alkaline media. The structure also exerted a profound effect on the stability. Thus a branched alkyl group accelerated the decomposition, although compounds with a normal alkyl group showed a similar response to the change of pH. The alkylating activity of the compounds toward deoxyguanosine and thymidine was demonstrated, and was dependent on the reaction solvent used. The overall alkylating activity was found to be highest with the compound ultimately yielding a methylating agent, while a more selective alkylation towards the oxygen, compared to the nitrogen, was observed with the ethylating, propylating and butylating species. Reactions with cysteine and histidine were also observed. A potent mutagenic effect of the N-nitroso-N-(hydroxymethyl)alkylamines was demonstrated in Salmonella typhimurium TA1535 and Escherichia coli WP2 and WP2 hcr-, in the absence of the S9 mix. A good correlation of the activities of the N-nitroso-N-dialkylamines and the N-nitroso-N-(hydroxymethyl)alkylamines with the same alkyl group was demonstrated.
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A radioimmunoassay procedure for plasma 11-deoxycortisol (S) was developed using an antiserum prepared by immunizing rabbits with S-21-hemisuccinate bovine serum albumin and S-3-oxime-bovine serum albumin. Thereafter plasma S, cortisol (F) and adrenocorticotropic hormone (ACTH) responses to metyrapone were investigated in 13 normal adult males and 39 patients with prostatic cancer. The results were as follows: 1) The antiserum against S-3-oxime-bovine serum albumin had less cross reactivity (less than 10%) with other steroids than that against S-21-hemisuccinate bovine serum albumin and obtained a good standard curve. The intra-assay variance and interassay variance of this method using the former antiserum (N = 10) were 12.4% asd 14.9% respectively, and the blank value was 3.7 +/- 1.6 pg. 2) Basal levels of S. F and ACTH in plasma from 13 normal adult males, ranged 21 approximately 80 years, old, were 98.4 +/- 15.7 ng/dl (mean value +/- S.E.), 12.7 +/- 0.78 micrograms/dl and 30.6 +/- 3.02 pg/ml respectively. Those level increased to 7060 +/- 598 ng/dl, 24.3 +/- 1.69 micrograms/dl and 24.3 +/- 1.6 pg/ml at 9 a.m. following oral administration of metyrapone (30 mg/kg b.w.) at midnight. 3) Both basal levels and responses of plasma S and F to metyrapone increased remarkably, while those of ACTH were within the normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and AC normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and AC normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and ACTH responses to metyrapone were unchanged compared to normal adult males 2 approximately 4 weeks after discontinuation of the therapy, and this data suggested that estrogens had no inhibitory effect on the pituitary-adrenal axis. However, in cases treated with progestational agents over a long-term period, plasma S and ACTH responses to metyrapone decreased slightly but returned to the normal range 2 approximately 4 weeks after discontinuation of the therapy. This suggested that the inhibitory effect of these agents on the pituitary-adrenal axis was mild and reversible.
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Blood pressure and sympathetic nerve activity were recorded before and after intracisternal injections of hypertonic NaCl solution in urethane anesthetized normotensive and deoxycorticosterone acetate (DOCA) hypertensive rats. Dose dependent pressor effects were recorded by intracisternal injections using normotensive Wistar rats. And the early phase of responses which were significantly depressed by blocking alpha-adrenergic receptors with phentolamine, accompanied by increased frequency of sympathetic nerve firing. Pressor responses and acceleration of the rate of sympathetic nerve firing produced by intracisternal injections of hypertonic NaCl were appreciably larger in DOCA hypertensives whose basal sympathetic nerve activity was elevated significantly than in normotensive rats. Pressor responses to intravenous injection of norepinephrine were also augmented, but responses to intracisternal injection were augmented more than those to norepinephrine injection. These findings suggest that sodium sensitive site which connects to pressor systems supposedly located around lower brain stem could be hypersensitive and eventually contribute to peripheral sympathetic hyperactivity in DOCA hypertension.
Using histopathological and immunofluorescent techniques, we investigated the development of the glandular system of the larynx from 12 human fetuses. Glandular buds were first observed at the fourth month of gestation and glandular distribution became evident from the fifth month in the larynx. Ciliated or nonciliated epithelium covered the cavity of the larynx, with the exception of the true vocal cord. Immunofluorescent examination revealed the presence of IgG in the fetal larynx, but there was little fluorescence for IgA, IgM and IgE. Secretory component (SC) synthesis, on the other hand, was found in each serous-type glandular epithelium or acinus from the fourth month on. Our observations suggest that the local immune system by SC, which binds to IgA as SIgA in human laryngeal mucosa, is inherently acquired in the fetal larynx.
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NADH dehydrogenase [EC 1.6.99.3] in membranes of Bacillus caldotenax was solubilized with sodium N-lauroylsarcosinate and purified 50-fold from membranes to 75-80% homogeneity, as judged by SDS-polyacrylamide gel electrophoresis. The enzyme was considered to be located on the electron transport chain and to be an FAD-containing protein. The molecular weight of the subunit was estimated to be 44,000. The enzyme (or the enzyme bound to the B. caldotenax membrane lipids) follows a ping-pong mechanism. The enzyme can oxidize NADH, but not NADPH, with 2,6-dichlorophenol indophenol, ferricyanide, menadione, and cytochrome c as electron acceptors. Membrane lipids or Triton X-100 stimulated the enzyme activity, except that with menadione. Lipids decreased the apparent affinity of electron acceptors and NADH to the enzyme, and increased the maximum velocity, except when menadione was used as the electron acceptor. Lipids partially protected the enzyme from thermal inactivation. The enzyme exhibited a continuous Arrhenius plot, while the lipids- or membrane-bound enzyme exhibited a discontinuous plot.
Effects of an antihypertensive drug, guanfacine, on blood pressure and heart rate were studied in comparison with findings in a related drug, clonidine. Conscious rats (normotensive rat, SHR, DOCA-hypertensive rat and renal hypertensive rat), anesthetized rats and pithed rats were used. Effects of guanfacine resembled those of clonidine but were about 10 times less potent. Both drugs produced an initial transient increase in blood pressure and a prolonged decrease then followed. In the SHR, a decrease in blood pressure occurred. The vasopressor effect of guanfacine was inhibited by phentolamine (1 mg/kg i.v.) and potentiated after previous treatment of the rats with reserpine (5 mg/kg i.p. 24 hr prior to drug administration, indicating that the effect was produced through activation of peripheral alpha-adrenoceptors. The vasodepressor effect of guanfacine was clearly dose-dependent, and was more marked when the initial level of the blood pressure was high, while that of clonidine was dose-dependent, only within a limited dosage range. Vasodepressor effects of guanfacine were associated with a decrease in the efferent discharges of the renal sympathetic nerve. Guanfacine, when given intracisternally produced a greater fall of blood pressure and a greater inhibition of the renal nerve activity than when given intravenously. It is concluded that the antihypertensive effects of guanfacine are due to stimulation of alpha-adrenoceptors within the central nervous system.
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