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Biomedical subjects

K Ando

Publications and source records attributed to K Ando.

At least 631 records · Page 35Linked to original sources

Changes in cardiac and hypothalamic noradrenergic activity with taurine in DOCA-salt rats.

We studied the role of the cardiac and hypothalamic noradrenergic systems in the hypotensive actions of dietary taurine supplementation in deoxycorticosterone acetate (DOCA)-salt rats. The supplementation with 1% taurine could reduce blood pressure when it was given after DOCA-salt hypertension had been established. The taurine supplementation could attenuate the increased depressor response to hexamethonium-induced ganglion blockade in the DOCA-salt rats. Moreover, noradrenergic activity was determined from the rate of decline of tissue norepinephrine (NE) concentration after the administration of alpha-methyl-p-tyrosine. At 23 degrees C, cardiac NE turnover was markedly accelerated in DOCA-salt rats compared with the vehicle-injected control rats, but the 1% taurine supplement restored it toward normal. In contrast, turnover time in the hypothalamus was delayed in the DOCA-salt rats compared with the control rats, whereas 1% taurine supplement normalized the hypothalamic NE turnover. Stimulation of sympathetic discharge by cold exposure (4 degrees C, 6 h) after the administration of alpha-methyl-p-tyrosine produced marked depletion of NE in most tissues. The NE deficit in both the hypothalamus and heart was significantly greater in the DOCA-salt rats than in the control rats, but the 1% taurine supplement could normalize this. Thus taurine loading could not only diminish the sympathetic overactivity under the normal condition but also attenuate the augmented hypothalamic and cardiac noradrenergic activity by cold stress in the DOCA-salt hypertensive rats. Evidence presented suggests, therefore, that the hypothalamic noradrenergic system might be involved in the hypotensive action of taurine in DOCA-salt rats.

Animals↗

Endotoxin-induced ATP depletion in thyrotoxic rats.

Effect of endotoxin from E. coli on the ATP content in heart muscle, the liver and the kidney of thyrotoxic rats was studied. When endotoxin (200-400 micrograms) was intravenously injected to rats taking drinking water containing 2-7.5 micrograms T3 per ml, body temperature rose and the heart rate increased. At the same time, a marked decrease in the ATP content in heart muscle and the kidney was observed together with an increase in Na+-K+-ATPase activity. Such changes were not observed or seen only to a small extent in euthyroid rats after endotoxin administration. Endotoxin-induced ATP depletion in T3-treated rats was prevented by administration of 5 mg hydrocortisone just prior to endotoxin injection. These findings indicate that endotoxin easily causes ATP depletion in some tissue or organs in thyrotoxicosis, even if the dose of endotoxin is not enough to produce such an effect in the euthyroid. These observations are of interest in relation to thyroid storm associated with bacterial infection.

Adenosine Triphosphatases↗

A novel method of screening for immunomodulating substances, establishment of an assay system and its application to culture broths of microorganisms.

A novel method of screening for immunomodulating substances is developed employing lymphocytes and three mitogens. Concanavalin A (Con A) and phytohemagglutinin (PHA) are applied as T cell specific stimulants and lipopolysaccharide (LPS) as a B cell specific stimulant respectively. The lymphocytes obtained from mouse spleen are cultured with an antibiotic or a sample extract in the presence or absence of mitogen for three days and pulsed with [3H]thymidine for five hours before harvest. Differential effects of a sample compound on [3H]thymidine incorporation by the activated and quiescent lymphocytes are scored. In this procedure most of the tested antibiotics or chemical compounds with different mode of actions show non-specific effects. Cyclosporin A, a potent immunosuppressive substance, suppresses both Con A and PHA responses more extensively than LPS response and quiescent cell growth, and two cytochrome bc1 complex inhibitors, funiculosin and antimycin A3, are less suppressive to PHA response than to the others. The present system was also applied to the methanol extracts of the culture broths prepared from the type strains of Actinomycetes and Penicillium.

Adjuvants, Immunologic↗

Selective suppression by prodigiosin of the mitogenic response of murine splenocytes.

In the course of screening for immunomodulating substances among microbial metabolites using a triple mitogen assay system, we detected an immunosuppressive activity which is similar to cyclosporin A. Two active components were isolated as red pigments from the fermentation broth of Streptomyces hiroshimensis and they were identified with prodigiosin 25-C and metacycloprodigiosin respectively. These compounds inhibited T lymphocyte proliferation which was induced by plant lectins, concanavalin A (Con A) and phytohemagglutinin (PHA), much more extensively than B lymphocyte proliferation which was induced by lipopolysaccharide (LPS). Prodigiosin 25-C completely inhibited induction of cytotoxic T cells in a mixed lymphocyte reaction (MLR) at 4 ng/ml.

Animals↗

Activation of natural cytotoxic activity and concomitant reduction of triglyceride content of murine spleen, treated with an antitumor antibiotic, ascofuranone.

Ascofuranone (AF) elevated natural cytotoxic activity of spleen when it was administered intraperitoneally to male mice. The elevation was observed both in low and high responder mice. AF-activated splenocytes lysed NK-resistant tumor cells, FM3A, P388 and sarcoma 180 cells as well as NK-sensitive YAC-1 cells. However, AF suppressed other lymphatic functions such as mitogenic responses and interleukin 2 production. Because AF did not activate splenic NK activity in vitro, the activation is assumed to be caused by a host-mediated process. One of the possibilities is modulation of the lipid metabolism of splenocytes. Thus, we examined splenic lipid contents and revealed that AF decreased splenic triglycerides without affecting other lipids. In contrast, the antibiotic significantly increased triglyceride in muscle.

Animals↗

[Intra-arterial administration of epirubicin in the treatment of non-resectable hepatocellular carcinoma. Epirubicin Study Group for Hepatocellular Carcinoma].

A group study was conducted to investigate the effect of intra-hepatic arterial administration of epirubicin in the treatment of non-resectable hepatocellular carcinoma(HCC). Sixty-four patients were entered into the study. There were 51 males and 13 females, with an age range from 32 to 79 years, the average being 59.1 years. Fifty-four patients had associated cirrhosis of the liver. Epirubicin at a dose of 60-90 mg/m2 was infused as a bolus into the hepatic artery 1 to 4 times (average 1.8) at an interval of 3 weeks to 3 months. Tumor size was properly evaluated in 53 patients. There were 1 CR, 7 PR, 7 MR, 27 NC, and 11 PD. Thus, the response rate (CR + PR) was 15.1%. Seventeen patients are still alive 305 to 720 days (mean 505 days) after the initial treatment. The most common side effects of this drug were bone marrow suppression, gastrointestinal complaints, and alopecia. Cardiac toxicity was negligible at the doses used in this study. A retrospective comparison of the present results with those for patients treated by intra-arterial administration of doxorubicin demonstrated that epirubicin is more effective than doxorubicin in terms of survival rate. The current study indicates that epirubicin may be a promising alternative in the treatment of HCC. The appropriate dosage of the drug and the interval for infusion are to be elucidated. Also, the combination of epirubicin with other cytostatic drugs is open for study.

Adult↗

In vitro effects of an antitumor antibiotic, ascofuranone, on the murine immune system.

Effects of an antitumor antibiotic, ascofuranone (AF) on the murine immune system were studied. Unlike lectins, AF did not induce any proliferative response of splenocytes. Furthermore, AF significantly inhibited proliferative response of splenocytes in response to lectins, such as concanavalin A, lipopolysaccharide, or phytohemagglutinin above 5 micrograms/ml. In concanavalin A-induced T-lymphocyte response, AF selectively inhibited the formation of interleukin 2 (IL-2) receptors, which was observed above 0.4 micrograms/ml. On the other hand, the inhibitory effect on the proliferative response to IL-2 of T-lymphocytes, which had already obtained IL-2 receptors, was observed above 10 micrograms/ml. IL-2 production of splenocytes in response to concanavalin A was also suppressed by AF above 2 micrograms/ml and only 3% of IL-2 was produced in the presence of AF, 10 micrograms/ml. However, AF-activated macrophages and their glycolysis was significantly stimulated. Activation of macrophages by AF was also confirmed by stimulation of interleukin 1 production and tumoricidal activity. However, natural killer activity of splenocytes was suppressed at the concentration where significant activation of tumoricidal activity of macrophages was observed. Therefore, AF had a dual effect on the immune system. Macrophages were activated to produce interleukin 1 and to kill tumor cells. On the other hand, functions of lymphocytes were suppressed.

Animals↗

[Effect of DN-1417 on ataxia in Rolling mouse Nagoya and Staggerer mouse in comparison with the effect of TRH].

The behavioral effects of thyrotropin-releasing hormone (TRH) and a TRH analogue, DN-1417 (butyrolactone-carbonyl-L-histidyl-L-prolinamide citrate) on the ataxia of Rolling mouse Nagoya and Staggerer mouse were examined using open-field methods. The ataxic gaits improved after injection of TRH (25 mg/kg, ip) and DN-1417 (5.25 mg/kg ip), compared with injection of saline. As a whole, the improving effect of DN-1417 persisted about 2 or more times as long in duration as that of TRH.

Animals↗

[Combined effect of the topical administration of OK-432 with radiation on the C3H mouse fibrosarcoma (NFSa)--TCD50 and the mechanism of action].

Optimal timing of topical administration of OK-432 and TCD50 were studied using weakly immunogenic and radioresistant C3H mouse fibrosarcoma (NFSa). The mechanism of action of this combined therapy was examined histologically and electron microscopically. Topical administration of OK-432 was performed from 2 days before irradiation to 7 days after irradiation and tumor volumes on the 20th day after irradiation were compared with a control group given radiation alone. Significant difference was observed only in the group which was given OK-432 just after irradiation. The TCD50 of the combined therapy of radiation with topical administration of OK-432, 4 KE which was given just after irradiation was 64.5 Gy and that of radiation alone was 83.5 Gy. Combined therapy shifted the TCD50 curve about 20Gy to the left. Histological examination of the tumor on the 6th day after combined therapy showed marked degeneration and necrosis of tumor cells with marked infiltration of lymphocytes. These lymphocytes were electron microscopically seen surrounding not only damaged cells, but also apparently active tumor cells. We postulate the latter cells had a tendency to be degenerative. This phenomenon suggests that lymphocytes recognize as foreign these tumor cells which are apparently active but some what damaged by radiation.

Administration, Topical↗