[Radioreceptor assay of ACTH].
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Biomedical subjects
Publications and source records attributed to M Homma.
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Fusaric acid and its derivative, FD-008, are selective and potent dopamine-beta-hydroxyalse inhibitors in vitro and in vivo. Effects of the drugs on blood pressure and norepinephrine levels in the heart of spontaneously hypertensive rats (SHR) and normotensive control rats (NCR) in a state of increased sympathetic nerve activity induced by immobilization stress were investigated. The blood pressure of NCR rose immediately after the onset of stress. In SHR, the blood pressure did not rise after stress in spite of a marked increase in heart rate. Fusaric acid or FD-008 (100 MG/KG P.O.) given 4 hours before stress markedly inhibited the increase in blood pressure by stress in NCR and decreased blood pressure in SHR. The increase in heart rate in SHR during stress was completely inhibited by FD-008 but the increase in NCR was not inhibited. Endogenous norepinephrine levels in the heart were decreased by immobilization stress in NCR and SHR, and further significant decreases in norepinephrine levels were caused by FD-008 in SHR and NCR of fusaric acid in SHR. The effect of FD-008 was greater than that of fusaric acid. The effects of picolinic acid derivatives on blood pressure and norepinephrine levels in the heart were more remarkable in a stressed state than in a resting state. The present data support the hypothesis that the hypotensive action of picolinic acid derivatives may be attributable to the decrease in sympathetic nerve norepinephrine release caused by dopamine-beta-hydroxylase inhibition.
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The interaction of measles virus with RG-6 cells derived from rat glioma was investigated. When a culture of RG-6 cells was infected with measles virus, the synthesis of viral antigens was detected in very few cells, at most 5%. The apparent resistance to measles virus infection was also repeatedly found in all of the subclonal cells derived form RG-6 cells. Although all of the virus-synthesizing cells had the ability to form plaques on Vero cells, they produced only a reduced amount of infectious virus, i.e., 0.1 plaque-forming units per cell. These results imply the existence of some mechanism that regulates growth of measles virus in cultures of RG-6 cells. The transmission of genetic material of measles virus from infected RG-6 cells to Vero cells was not inhibited in the presence of antiviral serum. This fact may provide a basis for interpretation of the persistence of virus, in the presence of antibody, in patients with subacute sclerosing panencephalitis.
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Effect of a new dopamine beta-hydroxylase inhibitor, 5-(4'-chlorobutyl)-picolinic acid (FD-008) on endogenous amine levels in various tissue of normotensive and spontaneously hypertensive rats were determined in comparison with its mother compound, fusaric acid, and disulfiram. FD-008 decreased norepinephrine (NE) levels in the brain and heart with a slight increase of dopamine (DA) level in the brain. NE lowering activity of FD-008 was stronger than that of fusaric acid. Disulfiram was less active and the activity was one-tenth of FD-008. FD-008 lowered NE level even when DA was increased by pretreatment with L-DOPA or iproniazid but did not cause a further significant reduction of NE when catecholamines were practically depleted by pretreatment with reserpine.
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Polypeptides of egg-borne Sendai virus (egg Sendai), which is biologically active on the basis of criteria of the infectivity for L cells and of hemolytic and cell fusion activities, were compared by polyacrylamide gel electrophoresis with those of L cell-borne (L Sendai) and HeLa cell-borne Sendai (HeLa Sendai) viruses, which are judged biologically inactive by the above criteria. Densitometer profiles on the stained gels of egg Sendai resolved six polypeptides (virion protein [VP] 1 to VP6), in which VP2 and VP4 were identified as glycoproteins by PAS stain. Comparative electropherograms of both L Sendai and HeLa Sendai revealed that there were significantly larger amounts in the VP2 region of these viruses but VP4 was present only in greatly reduced amounts as compared to egg Sendai. It was also found that VP2 of L Sendai and HeLa Sendai consisted of two components, VP2a and VP2b, but the one of egg Sendai consisted of only VP2a. A mild trypsin treatment which converts both L Sendai and HeLa Sendai to a biologically active form selectively removed VP2b from these viruses and increased concomitantly the amounts of materials in the VP4 region. The same treatment of egg Sendai affected neither its biological activities nor its electropherogram. Consequently, gross polypeptide profiles on the stained gels of L Sendai and HeLa Sendai after trypsin treatment became favorably comparable to that of egg Sendai. Electrophoresis of labeled L Sendai and HeLa Sendai with a (3)H-amino acids mixture and (14)C-glucosamine resolved at least three glycoproteins, GP1, GP2, and GP3, each corresponding to VP2a, VP2b, and VP4, respectively. The trypsin treatment of these viruses removed almost all the radioactivity of GP2 and simultaneously increased the radioactive counts of GP3 and raised small amounts of rapidly moving heterogeneous glycoprotein, GP4. A possible relationship between the biological modification and the above characteristic polypeptide patterns of Sendai virus was discussed.