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Biomedical subjects

N Ogata

Publications and source records attributed to N Ogata.

At least 235 records · Page 13Linked to original sources
PubMed1987

Contrasting properties of K+ conductances induced by baclofen and gamma-aminobutyric acid in slices of the guinea pig hippocampus.

Properties of membrane K+ conductances induced by baclofen and gamma-aminobutyric acid (GABA) in the hippocampus were investigated by using guinea-pig brain slices. Baclofen hyperpolarized the membrane and decreased the input resistance of pyramidal cells through the activation of a membrane K+ conductance. GABA caused a biphasic response in pyramidal cells, consisting of hyperpolarizing and depolarizing components. Combined application of picrotoxin and bicuculline eliminated the major part of the depolarizing component of the biphasic response and produced a relatively pure hyperpolarizing response which was also mediated by an increase in K+ conductance. The K+ conductance change induced by baclofen showed prominent inward rectification. However, the K+ conductance induced by GABA did not show an obvious rectifying property. The K+ conductance activated by baclofen was strongly antagonized by a low concentration (5 x 10(-6) M) of 4-aminopyridine (4-AP). In contrast, the K+ conductance activated by GABA was insensitive to 4-AP even at a high concentration of 10(-3) M. The slow inhibitory postsynaptic potential (slow i.p.s.p.) evoked by stimulation of the mossy fibres was totally suppressed by a low concentration of baclofen (5 x 10(-6) M). Whereas GABA (10(-3) M) decreased the amplitude of the slow i.p.s.p., the reduction of the amplitude was proportional to the decrease in the amplitude of the electrotonic potentials produced by constant inward current injections. These results suggest that the hyperpolarizations induced by GABA and baclofen may be generated by K+ conductances of different kinetic and pharmacologic properties.

Animals↗
PubMed1987

Potent effects of the monoclonal antibody-mitomycin C conjugate on human colon cancers.

The effects of the monoclonal antibody-mitomycin C conjugate against human colon cancers were studied, in vitro and in vivo. Mitomycin C (MMC) was conjugated with the human colon cancer-specific monoclonal antibody, using a cyanogen bromide method. The effect of the conjugate and free MMC, in vitro, was measured by incubation with human colon cancer SW1116 cells. The MMC concentration of the conjugate and of free MMC needed for 50 per cent killing of target cells was 0.11 microgram/ml and 7.00 micrograms/ml, respectively. The effect of the conjugate and of free MMC, in vivo, was assayed by the growth inhibition of human colon cancer xenografted in nude mice, after intraperitoneal injections of 30 micrograms MMC/kg. Antitumor effects of the conjugate against the cancer in nude mice were significantly more potent than that of free MMC.

Animals↗
PubMed1986

The effects of catecholamines on electrical activity of neurons in the guinea pig supraoptic nucleus in vitro.

The role of the central noradrenergic system in the supraoptic neuroendocrine regulation was investigated using slices of the guinea pig hypothalamus. Noradrenaline produced a complex membrane effect comprising two distinct depolarizations: one, associated with a moderate increase in input resistance and resulting in an augmentation of the spontaneous firing rate; the other, unaccompanied by a detectable change in input resistance and resulting in depression of the firing rate. The former depolarization was reproducible by applying specific alpha-agonist, phenylephrine, whereas the latter was induced by a beta-adrenergic agonist, isoproterenol. The actions of phenylephrine and isoproterenol were blocked by phentolamine and propranolol, respectively. Amplitude of the phenylephrine-induced depolarization was voltage-dependent with the estimated reversal potential of about - 115 mV and changed as a function of [K+]o. On the contrary, amplitude of the isoproterenol-induced depolarization was voltage-independent and was insensitive to changes in external concentrations of K+, Na+, Cl- and Ca2+. We conclude that catecholamines directly modulate the activity of supraoptic neurons through two functionally distinct adrenoceptive sites on neurosecretory cells. The activation of alpha-receptors may increase cellular excitability through suppression of membrane K+ conductance while the activation of beta-receptors would depress neuronal firings, possibly through some mechanism which is not directly linked to ionic channels.

Action Potentials↗
PubMed1986

Potent depressant action of baclofen on hippocampal epileptiform activity in vitro: possible use in the treatment of epilepsy.

Effects of baclofen on the cortical electrical paroxysm were examined using slices of the guinea pig hippocampus. A very low concentration of baclofen (10(-8) M) readily suppressed spontaneous epileptiform discharges of CA3 pyramidal cells, whereas synaptic transmission between mossy fibers and CA3 pyramidal cells were not affected even by 10(-4) M of this drug. Such a strikingly selective depressant action of baclofen on the epileptiform activity raises a possibility that this drug may be effective in the treatment of epilepsy.

Animals↗
PubMed1986

Effect of microstructure of poly(propylene-oxide)-segmented polyamides on platelet adhesion.

The relationship between microstructure and platelet adhesivity of six types of poly(propylene oxide) (PPO)-segmented polyamides based on the polyamide segments nylon 210, 310, 410, 510, 610, and 710 were investigated. These multiblock PPO-segmented copolymers were prepared by interfacial polycondensation. Physical characterization of these copolymers was by means of thermal analysis, transmission electron microscope, wide-angle X-ray diffraction (WAXD), and small-angle X-ray scattering (SAXS). The WAXD and SAXS measurements showed that the copolymers had microstructures containing crystalline and amorphous phases and that these microstructures, represented by means of crystallite thickness and long period, varied with incorporation of PPO segments. Blood compatibility of these copolymers was evaluated by estimating the amount of adhering platelets on the copolymer surfaces. The amount of adhering platelets was minimum for the surfaces of the copolymers having a crystallite thickness of 6.0-6.5 nm and a long period of 12-13 nm. This result suggests that the particular size and distribution of the crystalline and amorphous phases in the copolymer could be determining factors for suppressing platelet adhesion on the copolymer surface, and that the control of these factors could lead to ideal antithrombogenic polymers.

Animals↗
PubMed1986

Regulatory effects of gastrin and secretin on carcinomas of the stomach and colon.

Gastrin (10 micrograms/ml) enhanced 14C-leucine uptake in cultured tissue of stomach and colon carcinomas and content of 14C-labelled protein in the medium was increased. One of 2 stomach and one of 3 colon carcinomas transplanted into nude mice were enhanced in growth by pentagastrin injected in a dose of 250 micrograms/kg every day. On the other hand, secretin (100 U/kg) inhibited the trophic action of pentagastrin.

Adenocarcinoma↗
PubMed1986

[Anti-cancer treatment with prostaglandin synthetase inhibitor in animal models].

Carcinomas produce elevated quantities of prostaglandins (PGs), particularly the E series, which can play an important role in the suppression of the cellular immune reaction in tumor-bearing individuals. These findings have raised the possibility that PG synthetase inhibitor can restore the immune activity against tumors. The anti-tumor activity of indomethacin, a potent PG synthetase inhibitor, was investigated in mice implanted with colon carcinoma 38, colon carcinoma 26 and Lewis lung carcinoma in a series of model studies for cancer treatment in man. Treatment with indomethacin substantially reduced the levels of PGs, particularly PGE2 in tumor tissue, inhibited the tumor growth, particularly the early stage of cell proliferation, prolonged the survival time, eliminated tumors in the abdominal cavity, and inhibited metastatic tumor recurrence after surgery. Also, the treatment reduced the growth of human gastric and colon carcinomas transplanted into nude mice. Thus, indomethacin might also be effective against human carcinomas. It is postulated that PG synthetase inhibitor may prove to be a good therapeutic tool effective against human cancer when used in combination with chemotherapeutic and other immunotherapeutic drugs as well as with low-dose radiation therapy.

Animals↗
PubMed1986

Specific binding of human pancreatic secretory trypsin inhibitor to various cultured cells.

Pancreatic secretory trypsin inhibitor from human pancreatic juice bound specifically to cultured cells derived from a variety of human and nonhuman tissues. The binding pattern of pancreatic secretory trypsin inhibitor to various cells was quite different from that of epidermal growth factor, and these two polypeptides did not compete in binding to cultured cells with one another, indicating that the binding site for pancreatic secretory trypsin inhibitor was distinct from the receptor for epidermal growth factor.

Animals↗
PubMed1986

Pulmonary defence mechanism in mice. A comparative role of alveolar macrophages and polymorphonuclear cells against infection with Candida albicans.

The protective roles of alveolar macrophages and polymorphonuclear cells were analyzed against intratracheal challenge with Candida albicans in mice. When mice were treated with carrageenan, a known cytotoxic agent for macrophages, there was no change in susceptibilities to the challenge in terms of the survival and the progressive elimination of fungi from the lung and kidney, in spite of a decreased in vitro phagocytosis of Candida albicans by their alveolar macrophages. On the other hand, irradiated mice (whole body irradiation with 800 rads) showed an enhanced mortality and a progressive growth of Candida albicans in their lungs and kidneys, although no change was observed in the in vitro phagocytic activity of alveolar macrophages until day 6 after irradiation. In normal and carrageenan treated mice, there was a progressive increase in the recruitment of polymorphonuclear cells into the lung after the challenge as shown by bronchoalveolar lavage and histological examination. In irradiated mice, on the other hand, there was a decreased recruitment of polymorphonuclear cells at 24 hr after the challenge, and a complete impairment at a late stage. When phagocytes were obtained from normal mice and examined for in vitro phagocytic activity to Candida albicans, polymorphonuclear cells showed higher activity than that of alveolar macrophages. These results suggest that polymorphonuclear cells play a very important role in the protection against intratracheal infection with Candida albicans.

Animals↗
PubMed1985

Reversibility of granulocyte adhesion using polyamine-grafted nylon-6 as a new column substrate for granulocyte separation.

Reversibility of leucocytes adhered onto the surface of polyamine-grafted nylon-6 was investigated to estimate its feasibility as a new column substrate for granulocyte separation from whole blood. Polyamine-grafted nylon-6 was synthesized by a radical polymerization of 2-diethylaminoethyl methacrylate monomer onto nylon-6. The surfaces of these graft copolymers were found to show a microphase-separated structure composed of island-like phases of cationic polyamine and continuous phases of nonionic nylon-6. Interaction between leucocytes and these copolymer surfaces was studied by passing rabbit heparinized blood through a column packed with glass beads precoated with these copolymers. Columns of these copolymers showed a selective adhesion of granulocytes among leucocyte populations. Also, the adhering granulocytes were able to be recovered from the column by a gentle elution procedure. From these results, it was concluded that polyamine-grafted nylon-6 having a microphase-separated structure is suitable for use as a column substrate in granulocyte separation from whole blood.

Animals↗
PubMed1985

A simple perfusion system for brain slice electrophysiology.

A simple perfusion system for brain slice experiments was designed to improve stability of intracellular recordings and to enable rapid application of drugs. This system can easily be installed in most conventional apparatuses for electrophysiological experiments, with minimal and inexpensive modifications.

Animals↗
PubMed1985

Possible involvement of K+-conductance in the action of gamma-aminobutyric acid in the guinea-pig hippocampus.

The mechanism underlying the action of gamma-aminobutyric acid (GABA) in the hippocampus was investigated using guinea-pig brain slices. GABA either superfused or applied directly by microiontophoresis produced a biphasic response in pyramidal cells, comprising hyperpolarizing and depolarizing components. When different concentrations of GABA were applied to the same neurone, the lower concentrations generally produced a hyperpolarization-predominant response, while higher concentrations resulted in a depolarization-predominant response. The depolarizing component of the response to GABA was augmented in a medium containing a low concentration of Cl-, relatively unaffected by a change in external K+ concentration, and blocked by picrotoxin (2 X 10(-5) M). The depolarizing response to GABA persisted in a Ca2+-free medium in which the concentration of Na+ was reduced to 13 mM. Combined application of low doses of picrotoxin and bicuculline eliminated the major part of the depolarizing component of the biphasic response to GABA and produced a relatively pure hyperpolarizing response. The reversal potential of this pharmacologically 'isolated' hyperpolarizing response to GABA was estimated, from the current-voltage relationships, to be about -90 mV and was the same as that of the hyperpolarization induced by baclofen. When the membrane was successively hyperpolarized by inward direct current (d.c.) injections, the reversal point of the 'pharmacologically isolated' hyperpolarizing response to GABA coincided with that of the post-burst hyperpolarization. Low concentrations of Cl- in the bathing medium had no noticeable effect on the hyperpolarizing component of the response to GABA, whereas it markedly increased the amplitude of the depolarizing component. These results suggest that the action of GABA in the hippocampus may involve an activation of K+ conductance.

Animals↗
PubMed1985

Baclofen activates voltage-dependent and 4-aminopyridine sensitive K+ conductance in guinea-pig hippocampal pyramidal cells maintained in vitro.

The ionic mechanism underlying the effect of (-)-baclofen in the hippocampus was investigated using guinea-pig brain slices. (-)-Baclofen either perfused or applied directly by microiontophoresis hyperpolarized the membrane and decreased the membrane input resistance of pyramidal cells in a dose-dependent manner. The value of the reversal potential for the baclofen-induced hyperpolarization, as estimated from the current-voltage relationships, was about -95mV. The reversal potential of the baclofen-induced hyperpolarization measured directly coincided with that for the post-burst hyperpolarization which is known to result from an activation of Ca2+-activated K+ conductance. The amplitude of the baclofen-induced hyperpolarization was increased in low K+ (1.24 mM) medium whereas the hyperpolarization was decreased or abolished in high K+ (12.4 and 25 mM). Low Cl- (10.2 mM) medium had no noticeable effect on the baclofen-induced hyperpolarization. The effect of baclofen was antagonized by a low dose of 4-aminopyridine (5 X 10(-6) M) whereas it was unaffected by picrotoxin (2 X 10(-5) M). These results strongly suggest that the effect of baclofen is mediated by an increase in K+ conductance.

4-Aminopyridine↗
PubMed1985

Characterization of pre- and postsynaptic actions of (-)-baclofen in the guinea-pig hippocampus in vitro.

The effects of (-)-baclofen on evoked potentials in the hippocampus were examined through intracellular recordings from guinea-pig brain slices. The evoked responses were recorded in two fibre connections within the hippocampus: the Schaffer collateral/commissural-CA1 pyramidal cell, and the mossy fibre-CA3 pyramidal cell. The Schaffer collateral/commissural-CA1 response was suppressed by (-)-baclofen in concentrations over 2 X 10(-5)M, whereas (+)-baclofen, an inactive isomer, in a concentration of 10(-4)M had no effect on the response. A compound action potential of Schaffer collateral/commissural axons was unaffected by (-)-baclofen even at 10(-4)M, a concentration that almost completely depressed the evoked response in the CA1 pyramidal cell. The mossy fibre-CA3 response was not inhibited by (-)-baclofen (10(-4)M). The depressant action of (-)-baclofen on the Schaffer collateral/commissural-CA1 response was unaffected by bicuculline (10(-4)M), whereas the direct membrane effects of (-)-baclofen were antagonized by bicuculline (10(-5)M). It is suggested that (-)-baclofen may modulate neuronal transmission through presynaptic recognition sites possibly by decreasing transmitter release from nerve terminals and also may directly regulate the endogenous neuronal excitability through an activation of the postsynaptic recognition sites.

Action Potentials↗