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Biomedical subjects

K Takeya

Publications and source records attributed to K Takeya.

At least 127 records · Page 7Linked to original sources

Positive inotropic effect of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1 -piperazinyl]-2(1H)-quinolinone (OPC-8212) and mechanism of action in guinea pig ventricular myocardium.

Effects of 3,4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- qu inolinone ( OPC -8212) on the isolated guinea-pig ventricular myocardium was studied measuring the force of contraction and action potential under various experimental conditions. The positive inotropic effect (PIE) of OPC -8212 was observed at a concentration higher than 10(-5) mol/l. The following circumstantial evidence led to the conclusion that OPC -8212 caused an elevated cyclic AMP level in myocardial cells thereby producing the positive inotropic effect. The positive inotropic effect of OPC -8212 was unaffected by reserpinization, propranolol and cimetidine treatments. OPC -8212 strengthened the slow response of partially depolarized papillary muscle. This suggested an increased calcium influx across myocardial cell membrane. Carbachol inhibited the positive inotropic effect of OPC -8212 on ventricular myocardium. Concentration-effect curves for isoprenaline (isoproterenol) and histamine were shifted to the left but that for dihydro-ouabain was not affected at all by OPC -8212. Rested-state contraction of guinea-pig papillary muscle was strengthened by OPC -8212 the same as dibutyryl cyclic AMP and beta-agonists.

Animals↗

Cell growth-inhibitory effects of derivatives of antitumor cyclic hexapeptide RA-V obtained from Rubiae radix (V).

Alkylehter and ester derivatives of the antitumor cyclic hexapeptide RA-V obtained from the roots of Rubia cordifolia (Rubiaceae) were synthesized and bioassayed for activity against cultured tumor cells. RA-V and its n-hexylether showed significant effects against human nasopharynx carcinoma (KB), P388 lymphocytic leukemia and MM2 mammary carcinoma cells. The activity values (log 1/IC50) of ether derivatives of RA-V gave an upward parabolic or bilinear relationship when plotted against log P (P: partition coefficient determined with the 1-octanol/water system) as the carbon number of the side chain at the phenol moiety of RA-V was increased, the optimum log P values being in the range from 3.5 to 4.9. The ester derivatives showed a similar relationship, the optimum log P values being 6.3-6.7, which is higher than that of the ether derivatives. The lethal effect of RA-V on KB cells was clearly different from that of mitomycin C, and RA-V was concluded to be a "time-dependent drug" like vinblastine.

Animals↗

Development of immunity against Listeria monocytogenes in athymic nude versus neonatally thymectomized mice.

The thymus requirement for the development of immunological responsiveness was determined by estimation of immune responses raised to Listeria monocytogenes in athymic nude, neonatally thymectomized, and sham-operated mice at 6 weeks of age. Not only sham-operated mice, but also neonatally thymectomized mice could completely eliminate the bacteria from the spleen and liver, while athymic nude mice could not eliminate them and showed a persistent form of infection. A strong delayed footpad reaction and acquired cellular resistance could be raised in neonatally thymectomized mice just as well as in sham-operated mice, but not in athymic nude mice. The delayed footpad reaction could be induced in neonatally thymectomized mice without an accompanying ability to inhibit macrophage migration. These results suggest that T cells responsible for immunity against listerial infection require the presence of the thymus for only a very short period in their development.

Animals↗

Quantitative structure-inotropy relationship applied to substituted grayanotoxins.

Nine 14 beta-O-acylated grayanotoxins were synthesized by ozonolysis of 14,16-alkylidenegrayanotoxin III. The correlation between positive inotropic potency (PIE) in guinea pigs and physicochemical parameters (Vw, Mw, and Rm50) in 14 14-substituted grayanotoxins were quantitatively analyzed. It became clear that a parabolic relation existed between the bulkiness of the 14-substituents and PIE and that some electronic factor and the hydrophilic-hydrophobic balance would be related to the development of PIE.

Animals↗

Electron microscopic observations of cell division in Mycobacterium vaccae V1.

Cell division of Mycobacterium vaccae was initiated by deposition of new wall material in the cross wall. The surface layers of the old wall remained continuous until septum formation was complete. Subsequently, rupture of the outer cell wall layers occurred circumferentially, leaving rings on the cell wall. The two daughter cells remained connected with each other at the new pole and bent to form V-shaped structures at the connecting point.

Cell Division↗

Peritoneal exudation of macrophages by irritants and its effect on immune responses against sheep erythrocytes and Listeria monocytogenes.

Relation between the degradation of antigenic substances by peritoneal exudate macrophages induced by different irritants and subsequent induction of immune responses against SRBC or Listeria monocytogenes were studied. Delayed footpad reaction and antibody production to SRBC were both suppressed by pretreatment with thioglycollate or with killed Corynebacterium parvum. In contrast, delayed footpad reaction and acquired cellular resistance to Listeria were augmented by pretreatment with thioglycollate. When pretreated with C. parvum, however, such augmentations in immune responses to Listeria were not observed but these responses were suppressed. It was suggested that the amount of antigenic stimuli was determined by the mutual relationship between the level of macrophage activity as scavenger cells and the susceptibilities of the antigenic substances to degradation by macrophages, and that induction of immune responses were affected by this mutual relationship.

Animals↗

Augmented delayed footpad reaction in thymus cell-depleted mice induced by cholera toxoid.

One hundred microgram of cholera toxoid was injected intravenously into DDD and AKR mice and its effects on lymphoid tissues and immune responses against sheep erythrocytes (SRBC) were examined at various times after the injection. (1) A remarkable reduction of thymus cells was revealed from day 1 to 7 and from day 1 to 4 in DDD and AKR mice, respectively. (2) Cholera toxoid exhibited only slight effects on the numbers of spleen cells and peripheral blood leukocytes in both strains. (3) Delayed footpad reactions to SRBC were augmented by a pretreatment with cholera toxoid 4 or 7 days before immunization in both strains. The delayed reactions were not suppressed in the presence of a prominent antibody production and were accompanied by positive macrophage migration inhibition. (4) Antibody production against SRBC, especially of IgG class, was facilitated, when cholera toxoid was given 7 days before the immunization through the footpad in DDD mice. On the other hand, antibody production was suppressed irrespective of immunizing routes and mouse strains, when cholera toxoid was given 1 day before immunization.

Animals↗

Entrance of cholera enterotoxin subunits into cells.

Quantitative analysis of the staining of cholera enterotoxin on the surface of cells with specific antibodies against each subunit of cholera toxin, using a Fluorescence-Activated Cell Sorter, showed that not only subunit A but also subunit B penetrates the cell membrane. The detection of each subunit inside the cell was facilitated by the use of saponin, an agent which increases membrane permeability.

Animals↗

Direct correlation between delayed footpad reaction and resistance to local bacterial infection.

The resistance to bacteria was studied at the site of delayed footpad reaction in mice immunized with Listeria monocytogenes. When a challenge injection of listeria was given into the footpad of immune mice, no enhancement of bacterial elimination was observed before the generation of delayed footpad reactivity. After the generation of delayed reactivity, an enhanced elimination of listeria or Salmonella typhimurium was observed only at the site of strongly positive delayed footpad reaction elicited with listerial antigen. Such an enhancement in bacterial elimination was also found at the site of delayed footpad reaction induced by immunization with heterologous erythrocytes. Both delayed footpad reaction and local resistance could be transferred locally by immune spleen cells in a dose-dependent fashion, but were completely abrogated when recipient mice were treated with carrageenan or whole-body X irradiation. Macrophage accumulation was an important factor in the expression of resistance at the reaction site. These results suggest that the delayed footpad reaction contributes to host defense by enhancing the local resistance to bacteria.

Animals↗

Enhanced resistance to Listeria monocytogenes due to non-specifically activated macrophages in aged mice.

Age-related modification of protection to L. monocytogenes by macrophages was examined. Cumulative mortality rates of old (15-month-old) or very old (24 to 26-month-old) mice were lower than that of young (3-month-old) mice after an intravenous inoculation of L. monocytogenes. The numbers of bacteria in the livers and spleens of old or very old mice were smaller than that of young mice at an early stage of infection (1 day or 3 days). Adversely, the numbers of bacteria in old or very old mice were larger than in young mice at a late stage (7 days). Enhanced resistance to L. monocytogenes was shown not only in the case of systemic infection after an intravenous bacterial challenge, but also in the case of local infection in the thigh muscle or subcutaneous air cavity. The number of macrophages accumulating to the infected sites in old mice was not larger over a five day period than that in young mice in the case of local infection in a subcutaneous air cavity. Peritoneal macrophages derived from old mice suppressed more effectively the bacterial growth within macrophages in vitro than did those derived from young mice. These results suggest that the macrophage function of aged mice is not impaired and non-specifically activated macrophages contribute to the protection to L. monocytogenes in aged mice.

Aging↗

Two steps in the generation of acquired cellular resistance against Listeria monocytogenes: accumulation and activation of macrophages.

Mice were immunized with 1 X 10(3) viable Listeria monocytogenes, and the mechanism of the acquired resistance against challenge infection with 5 X 10(4) L. monocytogenes was studied by the use of the peritoneal cavity of mice as the site of challenge. An enhanced elimination of bacteria from the peritoneal cavity became detectable on day 5 after immunization, and lasted thereafter. Before day 10 postimmunization, a marked accumulation of macrophages was observed after the challenge but the in vitro listericidal activity of macrophages was not so enhanced. After day 15 postimmunization, peritoneal macrophages did not increase in number after the challenge but the in vitro listericidal activity of macrophages was the stronger. Accumulation of non-activated macrophages seemed to contribute mainly to the expression of acquired resistance against challenge in the early stage of immunization. So-called activated macrophages appeared to be generated only in the later stage of immunization. Thus it was suggested that there may be at least two steps in the expression of acquired listerial resistance.

Animals↗

The synergistic contribution of macrophages and antibody to protection against Salmonella typhimurium during the early phase of infection.

The contribution of phagocytes and antibody to protection against Salmonella typhimurium during the early phase of infection in mice was analysed. Following intravenous injection, most of the bacteria were trapped in the liver and spleen within 10 to 60 min and killed within 6 h; surviving organisms began to multiply in these tissues after 24 h and reached a maximum at 5 to 7 d. The transient killing phase was abrogated by treatment with carrageenan, a macrophage blocker, but not by whole-body X-irradiation. These observations suggest that carrageenan-sensitive, but radio-resistant macrophages play an important role in the early phase of the infection. Actively immunized mice showed accelerated trapping and killing; the protection observed at the early stage of infection in immunized mice could be passively transferred to normal mice, whereas carrageenan-treated mice did not kill the bacterial even after receiving immune serum. It seems that the synergistic action of macrophages and antibody provided the main initial primary defence in immune animals.

Animals↗

FK phage for differentiating the classical and El T or groups of Vibrio cholerae.

A new vibrio-infecting phage (FK phage) isolated from sewage lysed all strains of Vibrio cholerae biovar cholerae, whereas all strains of V. cholerae biovar El Tor were resistant to it. FK phage was entirely different from Mukerjee group IV phage in morphology and antigenicity. In addition to group IV phage, the use of FK phage will be useful in the examination and typing of V. cholerae.

Antigens, Viral↗