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Biomedical subjects

N Ogata

Publications and source records attributed to N Ogata.

At least 253 records · Page 14Linked to original sources

Pharmacological characterization of the magnocellular neuroendocrine cells of the guinea pig supraoptic nucleus in vitro.

The effects of various agents which have been implicated in the regulation of vasopressin release, on the supraoptic neuroendocrine cells were studied intracellularly. L-glutamate (10(-4)M) and gamma-aminobutyric acid (10(-6) M) had potent excitatory and inhibitory actions, respectively. Acetylcholine (10(-6) M) depolarized the membrane and increased the membrane input resistance. Norepinephrine (10(-5) M) produced either excitatory or inhibitory action on the spontaneous firing rate depending on the cell impaled. Morphine (10(-8)-10(-6) M) strongly depressed the spontaneous firing rate whereas it has no noticeable effect on the membrane potential and input resistance. Angiotensin II (10(-5) M) had no effect on any of the cells tested.

Acetylcholine↗

Protective mechanisms against infection by Listeria monocytogenes: accumulation and activation of macrophages.

The protective mechanisms against Listeria monocytogenes were analysed in mice. Listeria immune mice were rechallenged with viable listeria, and the degree of activation of macrophages, the degree of accumulation of macrophages to the infected sites, and these mechanisms were studied. Enhanced acquired resistance to the reinfection became detectable from the early stage of immunization. It was observed that activation of macrophages was mediated by pretreatment with antigen from the early stage of immunization. Enhanced accumulation of macrophages at the infected sites was observed only in the early stage. Enhanced accumulation and activation of macrophages in the early stage were generated by mediators from listeria antigen sensitized T lymphocytes which were different from classical tuberculin type. Enhanced activation of macrophages in the later stage was generated by MAF and/or MIF from sensitized T lymphocytes of classical tuberculin type. It was suggested that acquired cellular resistance to listeria in the early stage depends on both activation and accumulation of macrophages, and that in the later stage depends on activation of macrophages.

Animals↗

BCG-induced susceptibility of mice to challenge with Pseudomonas aeruginosa.

Mice infected with Mycobacterium bovis, BCG, were shown to be highly susceptible to subsequent challenge with Pseudomonas aeruginosa. The susceptibility was characterized by the enhanced mortality and shortened survival after challenge with P. aeruginosa. BCG-treated mice did not show any enhanced susceptibility to challenge with Gram-positive bacteria such as Staphylococcus aureus or Listeria monocytogenes. BCG-treated mice eliminated P. aeruginosa from their organs in a pattern similar to that in untreated mice. There was no significant difference in the bactericidal activities of polymorphonuclear cells and macrophages between BCG-treated and untreated mice. An equal amount of endotoxin was detected by the Limulus lysate assay in the blood of both BCG-treated and untreated mice after challenge with P. aeruginosa. The enhanced susceptibility induced by BCG pretreatment could be decreased when the mice were rendered LPS-tolerant by injections of small amounts of LPS. These results suggest that BCG-induced susceptibility to P. aeruginosa can be ascribed to an enhanced susceptibility to the lethal effect of LPS produced by challenge bacteria, and not to the impairment of the ability to eliminate infected bacteria.

Animals↗

The effects of vasopressin on electrical activity in the guinea-pig supraoptic nucleus in vitro.

Brain slices of the guinea-pig hypothalamus were used to determine the effects of vasopressin on intracellular potentials in neurones of the supraoptic nucleus. Vasopressin (0.05-1 i.u./ml.) depolarized the membrane without apparent change in the input resistance and decreased the spontaneous firing rate. This action of vasopressin was retained in the medium containing 0 mM-Ca2+, 12 mM-Mg2+ and 0.3 mM-EGTA. Amplitude of the vasopressin-induced depolarization was voltage-independent. Ion-substitution experiments showed that the changes in [K+]o, [Cl-]o and [Ca2+]o had little effect upon the amplitude of vasopressin-induced depolarization, whereas the depletion of [Na+]o slightly reduced the amplitude. The vasopressin-induced depolarization was blocked at a temperature of 15 degrees C and by ouabain in a dose of 10(-4) M. Dibutyryl cyclic AMP (2 mM) produced electrophysiological effects similar to those seen with vasopressin, and actions of both agents were potentiated by either papaverine (10(-4) M) or theophylline (10(-2) M). Contents of cyclic AMP in tissues incubated with vasopressin were significantly higher than in cases of incubation with normal Krebs solution. We conclude that vasopressin directly modulates the activity of supraoptic neurones, possibly through activation of adenylate cyclase.

Action Potentials↗

[The effects of gastrointestinal hormones on the growth and protein synthesis of gastric carcinomas].

The effects of gastrointestinal hormones on gastric carcinomas were examined in vitro and in vivo. In five of seventeen cases of human gastric carcinomas, the uptake of 14C-leucine into the tumor tissue in organ culture was enhanced by 10 micrograms/ml of gastrin. Also, in four of thirteen cases of human gastric carcinomas, the production of 14C-labelled proteins in medium was increased by gastrin. All the cases in which protein synthesis was enhanced by gastrin were histologically poorly differentiated adenocarcinomas. The effects of gastrin and secretin on the growth of gastric carcinoma, which was serially transplanted in athymic mice, were examined. The doubling time of the tumor was 7.1 days. The doubling time was shortened to 4.1 days by daily administration of 250 micrograms/kg of gastrin. This topic effect of gastrin on gastric carcinoma was inhibited by 100 U/kg of secretin. These results showed that the growth and protein synthesis of gastrointestinal tumor may be regulated by gastrointestinal hormones.

Adenocarcinoma↗

Substance P decreases membrane conductance in neurons of the guinea pig hypothalamus in vitro.

Substance P (SP) depolarized the membrane and increased the spontaneous firing rate of neurons in slices of the guinea pig hypothalamus. These excitatory actions of SP were accompanied by a decrease in membrane conductance, and this reduction was observed even during a perfusion of the medium which was Ca2+ free and in which the concentration of Mg/+ had been increased to 12 mM. Therefore, the contribution of possible presynaptic or indirect effects of SP to the decreased membrane conductance can be ruled out. These observations suggest that SP exerts an excitatory action on neurons in the guinea pig hypothalamus by decreasing the membrane ionic permeability of these neurons.

Animals↗

Ionic mechanism for the osmotically-induced depolarization in neurones of the guinea-pig supraoptic nucleus in vitro.

1. Effects of hypertonic solutions prepared by adding NaCl or sucrose to Krebs solution on intracellular potentials were observed in neurones of the supraoptic nucleus using brain slices of the guinea-pig hypothalamus. 2. Hypertonic solutions (306-488 m-osmole/kg) depolarized the membrane, increased the input resistance and augmented the spontaneous firing rate in supraoptic neurones, whereas cells in the hippocampus and anterior or ventromedial hypothalamus were not affected by the hypertonic solutions. 3. The excitatory action of hypertonic solutions on supraoptic neurones was retained in the medium containing 0 mM-Ca2+ and 12 mM-Mg2+. 4. Amplitude of the depolarization induced by superfusion of hypertonic solutions was voltage-dependent. The reversal potential for the depolarization was about -90 mV. 5. The reversal potential for the depolarization induced by hypertonic solution shifted as a function of [K+]0. 6. These results suggest that the supraoptic neurones are themselves osmosensitive and that the local osmotic-related information is transduced to neural signals in these cells by alteration in the membrane ionic permeability, probably due to suppression of K+ conductance.

Animals↗

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↗

Further support for the postsynaptic action of substance P and its blockade with baclofen in neurons of the guinea-pig hypothalamus in vitro.

Effects of substance P on neurons of the guinea-pig hypothalamus in vitro and antagonism between substance P and baclofen were investigated. Substance P increased the firing rate of neurons in the medium containing 0 mM Ca2+ and 12 mM Mg2+. The excitatory action of substance P was antagonized by a low dose of baclofen whereas that of acetylcholine was not antagonized even by much higher doses of baclofen.

Acetylcholine↗

Poly(ADP-ribose) synthetase, a main acceptor of poly(ADP-ribose) in isolated nuclei.

Poly(ADP-ribose) synthetase was identified as the main acceptor of this polymer produced in isolated nuclei of rat liver. When the nuclei were incubated with [32P]NAD at a limited concentration (2.4 microM) and for a brief period (10 s), a protein with Mr = 110,000 was predominantly poly(ADP-ribosyl)ated, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The modification of this protein increased upon longer incubations or at higher NAD concentrations, and induced a marked increase in the apparent molecular weight. A comparison with poly(ADP-ribose) synthetase (Mr = 110,000) of rat liver under various conditions suggested that the increase in the molecular weight of the acceptor resembled that of the synthetase undergoing multiple auto-poly(ADP-ribosyl)ation. This interpretation was further supported by the following observations: 1) [32P]poly(ADP-ribose) attached to the acceptor co-eluted with the synthetase activity from a hydroxyapatite column; 2) the [32P]poly(ADP-ribose).acceptor complex isolated on the column was converted to a very large complex by further incubation with NAD; and 3) a group of large poly(ADP-ribose).acceptor complexes were reduced to a single molecular species with Mr = 110,000 by extensive digestion with poly(ADP-ribose) glycohydrolase. These findings altogether suggested that poly(ADP-ribose) synthesized in isolated nuclei was principally bound to the synthetase itself.

Animals↗