Biomedical subjects

H Funato

Publications and source records attributed to H Funato.

30 records · Page 2Linked to original sources

PubMed1991

Cross-protection against influenza A virus infection by passively transferred respiratory tract IgA antibodies to different hemagglutinin molecules.

Mice that were intranasally immunized with different influenza A virus hemagglutinins (HA), derived from PR8 (H1N1), A/Yamagata (H1N1) or A/Fukuoka (H3N2) virus, together with cholera toxin B subunit as an adjuvant, were examined for protection against PR8 infection; PR8 HA and A/Yamagata HA immunization conferred complete protection, while A/Fukuoka HA immunization failed to confer protection. In parallel with protection, PR8 HA-, A/Yamagata HA-, and A/Fukuoka HA-immunized mice produced a high, a moderate and a low level of PR8 HA-reactive IgA in the respiratory tract, respectively. These IgA antibodies were not only higher in content in the nasal secretions, but also more cross-reactive than IgG. The purified IgA antibodies from respiratory tract washings of PR8 HA-immunized mice, which contained the HA-specific IgA corresponding to the amount detected in the nasal wash, were able to protect mice from PR8 challenge when transferred to the respiratory tract of naive mice. The transfer of IgA from A/Yamagata HA-immunized mice also afforded cross-protection against PR8 infection, whereas the IgA from A/Fukuoka HA-immunized mice failed to provide protection. The ability of transferred IgA to prevent viral infection was dependent on the amount of HA-reactive IgA remaining in the respiratory tract of the host at the time of infection. These experiments directly demonstrate that IgA antibodies to influenza A virus HA by themselves play a pivotal role in defence not only against homologous virus infection, but also against heterologous drift virus infection at the respiratory mucosa, the portal of entry for the viruses.

Animals↗

PubMed1991

Enhanced rectal absorption of insulin in rabbits from hollow-type suppositories containing insulin and glyceryl-1-monooctanoate.

The absorption of two kinds of insulin (from porcine or bovine pancreas) from the rectum of rabbits after the administration of hollow-type suppositories containing insulin and glyceryl-1-monooctanoate (GMO) as an absorption-enhancing agent was investigated. Two types of suppositories were employed: type I containing insulin in an aqueous solution (approx. 25 IU/mg/100 microliters citric buffer solution at pH 3.0) in the cavity of the suppository and GMO mixed with a base material (Witepsol H-15), and type II containing insulin in a crystalline form in the same amount as in type I. Without GMO, the insulin and glucose levels in plasma were unchanged, whereas a marked increase in the plasma levels of insulin and a decrease of glucose concentrations were found following coadministration of insulin and GMO by the type I suppository. Similar enhancement of rectal absorption of insulin was obtained from porcine and bovine sources. In the case of the crystalline insulin, despite the use of the same amount of GMO, porcine insulin was more efficiently absorbed than bovine insulin by the type II suppository. GMO enhances the absorption of insulin in an aqueous solution or a crystalline form, and the dissolution rate of insulin may be an important factor in the rectal absorption of insulin.

Administration, Rectal↗

PubMed1990

Comparison of intranasal inoculation of influenza HA vaccine combined with cholera toxin B subunit with oral or parenteral vaccination.

The antibody responses to influenza virus A/PR/8/34 HA vaccine and protection against virus challenge in mice given the vaccine together with the B subunit of cholera toxin (CTB) intranasally were compared with those in mice given the vaccine with CTB perorally, intraperitoneally or subcutaneously. Intranasal vaccination induced remarkably higher levels of antiviral IgA antibodies in both respiratory washings and serum than did other routes of vaccination. The titres of antiviral IgG antibodies in respiratory washings and serum, and haemagglutination-inhibiting (HI) antibodies in serum, were similar after intranasal and parenteral vaccination. Oral vaccination, however, induced low levels of antiviral IgG antibodies but no detectable HI antibodies. Moreover, intranasal immunization elicited significantly higher titres of antiviral IgA antibodies in intestinal secretions in comparison with oral immunization. In contrast, parenteral immunization failed to induce these IgA antibodies. In virus challenge studies, a greater protective effect was seen after intranasal and intraperitoneal vaccination than after other routes of vaccination. These results suggest that intranasal inoculation of combined HA vaccine and CTB is superior to oral or parenteral inoculation in protecting mice. Furthermore, the intestinal antiviral IgA responses suggest that intranasal administration of CTB-combined vaccines could be effective not only against respiratory pathogens but also against enteropathogens.

Administration, Intranasal↗

PubMed1990

Functional role of respiratory tract haemagglutinin-specific IgA antibodies in protection against influenza.

Intranasal inoculation of haemagglutinin (HA) purified from influenza virus A/PR/8/34 (PR8, H1N1) together with cholera toxin B subunit, into Balb/c mice resulted in complete protection against PR8 infection in parallel with the induction of high levels of HA-specific IgA and IgG antibodies on the respiratory tract. The respiratory tract IgA and IgG were purified from nasal and lung washings of the immunized mice using affinity columns, and their HA-specific activities were measured by enzyme-linked immunosolvent, plaque neutralization and haemagglutination inhibition assays. The purified IgA and IgG had the following properties: (1) They were able to neutralize virus in vitro. (2) The purified IgA included major antibodies directed against PR8 virus and minor antibodies cross-reactive with A/Yamagata/120/86 (H1N1) or A/Fukuoka/C29/85 (H3N2) virus, while the purified IgG included major antibodies to the homotypic virus, minor antibodies to the H1N1 virus and only a trace amount of antibodies to the H3N2 virus. (3) When separated on a Sephacryl column, most of the IgA anti-HA activities occurred in the polymeric fractions of purified IgA, whereas the IgG anti-HA activities occurred in the monomeric fractions. (4) When passively administered to normal mouse respiratory tract before infection, the purified IgA protected against PR8 infection. These results suggest that HA-specific, polymeric IgA antibodies on the respiratory tract by themselves provide not only protection against the homotypic virus but also higher levels of heterotypic immunity than IgG.

Animals↗

PubMed1989

Protection against influenza virus infection by a two-dose regimen of nasal vaccination using vaccines combined with cholera toxin B subunit.

The effectiveness of the two-dose regimen, composed of a primary intranasal inoculation of influenza A-type virus HA vaccine together with B subunit of cholera toxin (CTB) and the subsequent intranasal inoculation of vaccine alone 4 weeks later, was examined. In mice given a relatively high dose of virus A/PR/8/34 (PR-8, H1N1) HA vaccine (1.5 micrograms) both as a primary antigen with CTB (1 microgram) and as the second antigen, the secondary responses of both antiviral IgA antibodies in nasal wash and haemagglutination-inhibiting (HI) antibody in serum were much higher than those of primary responses and persisted for greater than 12 weeks after the second inoculation. Even in mice that received reduced amounts of a primary vaccine (0.03 microgram) [prepared from virus PR-8, A/Yamagata/120/86 (H1N1) or A/Fukuoka/C29/85 (H3N2)] together with reduced amounts of CTB (0.05 microgram), the subsequent inoculation of PR-8 vaccine produced both nasal IgA and serum HI antibodies and provided complete protection against homologous A-type virus (PR-8) infection. Moreover, the combination of the reduced amounts of heterologous A-type virus vaccine (A/Yamagata or A/Fukuoka) with CTB for primary inoculation and the secondary heterologous A-type virus vaccine [A/Yamagata, A/Kumamoto/37/79 (H1N1), or A/Fukuoka] resulted in high levels of cross-reactive IgA antibodies and partial cross-protection against PR-8 infection. On the other hand, a second inoculation of B/Ibaraki/2/85 vaccine failed to produce cross-reactive antibodies and to protect against PR-8 infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗

PubMed1989

Effectiveness of cholera toxin B subunit as an adjuvant for nasal influenza vaccination despite pre-existing immunity to CTB.

In a previous paper, it was shown that cholera toxin B subunit (CTB) augments the production of protective antibodies to influenza virus when CTB is inoculated intranasally into Balb/c mice together with influenza HA vaccine. The present study was designed to determine whether the effectiveness of CTB as a potent adjuvant for nasal vaccination could be limited by pre-existing immunity to CTB. Mice were sensitized by intranasal inoculation of either 1 or 0.05 microgram of CTB 2, 4 and/or 6 weeks before nasal vaccination. They were then vaccinated by either a single inoculation of vaccine together with 1 microgram of CTB or a two-dose regimen, composed of a primary inoculation of vaccine together with 0.05 microgram of CTB and a subsequent inoculation of vaccine alone. Levels of nasal IgA antibodies to CTB increased with the increase of the dose of CTB and the frequency of CTB-inoculation. Pre-existing immunity to CTB, however, did not significantly reduce the levels of both nasal IgA and serum haemagglutination-inhibiting (HI) antibodies to influenza virus and did not change the ability of the vaccinated mice to resist viral challenge. These results suggest that a relatively low dose of CTB could be inoculated repeatedly into animals as an adjuvant for nasal vaccination.

Adjuvants, Immunologic↗

PubMed1987

[Study of mechanism and effect of sodium 5-hydroxydecanoate on experimental ischemic ventricular arrhythmia].

We investigated the effects of sodium 5-hydroxydecanoate (5-HD) on experimentally induced ischemic arrhythmia and its mechanisms of action by biochemical and electrophysiological techniques. 5-HD, at the single dose of 200 mg/kg (p.o.) or at the one week multiple doses of 3 to 100 mg/kg (p.o.), suppressed the incidence of ventricular fibrillation induced by coronary ligation in rats. 5-HD at the dose of 3 or 10 mg/kg (i.v.) elevated the ischemically decreased ventricular fibrillation threshold in the coronary ligated dogs. In isolated rat heart, 5-HD suppressed the K+ release from ischemic myocardium at the doses of 10(-5) to 10(-3) M. 5-HD at the dose of 10(-4) M decreased the open state probability of ATP regulated K+ channel in isolated myocardial cell of guinea pig. Contents of high-energy-phosphate compounds were markedly decreased in ischemic myocardium of rats, and they were not affected by 5-HD. These results demonstrate the efficacy of 5-HD against experimental ischemic ventricular arrhythmia. Its antiarrhythmic action may be attributed, at least in part, to the suppression of K+ release from ischemic myocardium by possibly inhibiting the ATP regulated K+ channel.

Animals↗

PubMed1986

[Pharmacological studies of intracoronary administered urokinase].

The pharmacokinetics of intracoronary administered urokinase was investigated in anesthetized open-chest dogs, together with its effect on the cardiovascular system, and the influence of urokinase in isolated guinea-pig heart was also examined. After intracoronary administration of 20,000 IU/kg of 125I-urokinase, radioactivity in plasma was eliminated biexpomentially with half-lives of 6.8 min and 4.4 hr. At 4 hr after the administration of 125I-urokinase, 32% of the total radioactivity remained in the TCA-insoluble fraction of plasma, and only 0.13% of the administered radioactivity was excreted as a TCA-insoluble fraction in the urine, suggesting that the administered urokinase may be metabolized for the most part into low molecular weight compounds. In hemodynamic measurements, we observed some decrease in cardiac function which was thought to be attributable to bleeding from the incision of open-chest surgery, probably caused by the fibrinolytic activity of urokinase, and urokinase, up to the dose of 2,000,000 IU/kg (approximately 100 times of therapeutic dose), did not appear to show any direct action on the cardiovascular system. This result was supported by the fact that urokinase (10,000-1,000,000 IU/heart) did not have any effects on contractile force, heart rate and coronary flow in isolated guinea-pig heart. From these results, we confirmed that the pharmacokinetics of intracoronary administered urokinase was essentially the same as that of intravenously administered urokinase and that intracoronary administered urokinase showed virtually no direct effect on the cardiovascular system.

Animals↗

PubMed1986

[Pharmacological studies of MO-8282, a new antidepressant].

We investigated the pharmacological characteristics of MO-8282 as a novel antidepressant. MO-8282 inhibited the specific binding of 3H-clonidine to cerebro-cortical membrane fractions from rats about five times more potently than mianserin, and it competed with clonidine in the twitch response of the isolated guinea-pig ileum under field stimulation. The results indicated that MO-8282 possessed alpha 2-adrenergic receptor blocking activity. MO-8282 in a dose of 30 mg/kg (p.o.) showed no inhibition against the uptake of noradrenaline, dopamine and serotonin in the rat brain, whereas mianserin inhibited the uptake of serotonin specifically. MO-8282, similar to mianserin, had no effect on spontaneous release of 3H-noradrenaline and slightly stimulated the release of 3H-serotonin from the rat cerebrocortical synaptosome. The turnover rate of noradrenaline in rat brain was accelerated by administration of MO-8282 (30 mg/kg) for 15 days; however, that of dopamine and serotonin was not affected. The above findings indicate that MO-8282, unlike tricyclic antidepressants, mainly exerts alpha 2-adrenoceptor blocking action on the central noradrenergic system, similar to mianserin. In addition, the fact that MO-8282 unlike mianserin showed no inhibition against uptake of serotonin in brain suggests that the alpha 2-adrenoceptor blocking of MO-8282 is more specific and potent than that of mianserin.

Adrenergic alpha-Antagonists↗

PubMed1984

Effects of 2-[(5-chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434) on hemorrhagic, cardiogenic, and endotoxin shock in rats and rabbits.

The effects of 2-[(5-chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434) were investigated in experimental models of lethal shock produced by hemorrhage, injection of endotoxin, or coronary ligation. M6434 improved the survival rate of rabbits in hemorrhagic shock. M6434, at the dose of 3 or 10 micrograms/kg/min, completely reversed the decreases in the blood pressure and the urine output of shocked rabbits, but did not affect the decreased regional blood flow through the kidneys in the animals. Survival rates of cardiogenic-shock rats improved, and the content of ATP and creatine phosphate in myocardium of these animals were restored by the treatment with 1 or 3 micrograms/kg/min of M6434. Intravenous infusion of M6434, at a dose of 3 or 10 micrograms/kg/min for 3 hr, increased the survival rate of the endotoxin-shocked rabbits. These results indicate that M6434 may be evaluated as a possible therapeutic agent for shock.

Adenosine Triphosphate↗

PubMed1980

[Pharmacological properties of trapidil: comparison with other coronary vasodilators (author's transl)].

Effects of trapidil and other coronary vasodilators on retrograde blood flow in acute coronary-ligated dogs, isolated large and small coronary arteries of pig, platelet aggregation, biosynthesis of prostacyclin in isolated aortic rings and hyperlipemia in quails were investigated. Trapidil showed an increase in retrograde blood flow while dipyridamole, nifedipine, diltiazem and dilazep did not. Trapidil and nitroglycerin relaxed large coronary arteries, while dipyridamole, diltiazem, dilazep and adenosine relaxed small arteries. Trapidil, dipyridamole, diltiazem and aspirin protected against the secondary phase of ADP-induced platelet aggregation in guinea-pig platelet rich plasma more effectively than did nifedipine and dilazep. Trapidil and aspirin protected only against rabbit platelet aggregation as induced by arachidonic acid. Moreover, only trapidil protected against platelet aggregation as induced by prostaglandin G2-thromboxane A2 mixture. Trapidil and dipyridamole enhanced the platelet aggregation protection of prostacyclin. Trapidil also facilitated biosynthesis of prostacyclin more markedly than did the other drugs. Trapidil increased serum content of HDL cholesterol and significantly lowered serum content of triglyceride and the ratio of LDL cholesterol to HDL cholesterol in hyperlipemic quails. Dipyridamole, diltiazem, nifedipine and dilazep, however, showed little effect.

Animals↗

PubMed1979

Effects of 1-(2-chloro-4-hydroxyphenyl)-t-butylaminoethanol (HOKU-81), a new bronchodilator, on isolated trachea and atria of guinea pig.

Effects of 1-(2-chloro-4-hydroxyphenyl)-2-t-butylaminoethanol hydrochloride (HOKU-81), one of the metabolites of tulobuterol, on isolated trachea and atria of guinea pigs were compared with those of various bronchodilators. All test drugs abolished the resting tone of tracheal muscle completely. The potencies of test drugs which induced relaxation were in the order of: trimetoquinol greater than HOKU-81 greater than or equal to isoproterenol greater than salbutamol greater than terbutaline greater than or equal to tulobuterol greater than metaproterenol greater than clorprenaline. In acetylcholine-, histamine- or potassium-stimulated preparations, the intrinsic activities of 2-chlorophenyl derivatives were less than those of 3,4- or 3,5-dihydroxyphenyl derivatives and that of HOKU-81, 2-chloro-4-hydroxyphenyl derivative, lay between two groups. HOKU-81 showed weak positive chronotropic and inotropic actions and the potency ratio of HOKU-81 to isoproterenol was about 3/100 and less than 3/1000, respectively. Both chronotropic and inotropic actions of 2-chlorophenyl derivatives, including HOKU-81, were weak and the inotropic actions of drugs with N-t-butylamino radical were weaker than chronotropic actions. Effects of test drugs on trachea and atria were antagonized by propranolol 1 x 10(-6) or 1 x 10(-7) M. HOKU-81 appears to be a potent and selective beta 2-stimulant with a slight inotropic action.

Acetylcholine↗