Search PubMed⌕ Search

Biomedical subjects

C Aizawa

Publications and source records attributed to C Aizawa.

At least 55 records · Page 3Linked to original sources
PubMed1992

Stimulation of the transepithelial flux of influenza HA vaccine by cholera toxin B subunit.

Secretory antibodies in mucosal surfaces are known to play an essential role in protection against various infectious diseases. To enhance the production of such antibodies, influenza HA vaccine was inoculated intranasally into rabbits, together with cholera toxin B subunit (CTB) which is known to augment antibody response to an unrelated antigen. This combination resulted in high levels of serum IgG antibody responses against HA and CTB molecules, 3-4 weeks after inoculation, compared with the inoculation of HA vaccine alone. The adjuvant mechanism for CTB was studied by using Ussing chambers, in which nasal mucosa from rabbits were mounted. CTB was found to enhance the transepithelial flux of HA vaccine, from the mucosal side (lumen) into the serosal side (lamina propria), indicating that the permeability of the membrane was changed by CTB. Moreover, to achieve effective flux of HA vaccines, some interactions between the vaccine and CTB across the membrane were found, which may effect the effectiveness of the vaccine formulation. The results suggest that one of the mechanisms by which CTB enhances the production of mucosal antibody response is to enhance the transepithelial influx of vaccine into the nasal mucosa, where the cells involved in the antibody production are located. CTB may be used as a potent adjuvant to induce antibody response, by nasal vaccination, against pathogens impinging on mucosal surfaces.

Adjuvants, Immunologic↗
PubMed1992

Detection of feline immunodeficiency proviral DNA in peripheral blood lymphocytes by the polymerase chain reaction.

Feline immunodeficiency virus (FIV) proviral DNA was detected by the polymerase chain reaction method (PCR). PCR products were detected by gel electrophoresis and ethidium bromide staining. The P-10, P-15 and P-24 regions of the gag gene of FIV were chosen as the target sequences for amplification, and three primer pairs were prepared. The PCR products subjected to amplification with each primer pair were found to possess sites of digestion by a restriction enzyme, as hypothesized. They did not react with feline leukemia virus (FeLV)-infected or feline syncytium-forming virus (FeSFV)-infected cell-derived DNA, and specifically amplified FIV-infected cell-derived DNA. FIV proviral DNA was detected by the PCR method with either primer pair (one-step amplification: single PCR) in DNA derived from peripheral blood lymphocytes (PBL) from 7 of 12 FIV antibody-positive cats. When PCR products in each of the 12 cats were subjected to a second amplification using the same primer pair (two-step amplification: double PCR), FIV proviral DNA was detected in all of the cats. When PBL samples collected from three cats that were negative and three that were positive in the single PCR were cultured for a few weeks in the presence of interleukin 2, FIV proviral DNA was detected in all six cats by the single PCR method. The results suggest that either the use of cultured PBL as the sample or the performance of the double PCR method enables simple and specific detection of FIV proviral DNA in PBL.

Animals↗
PubMed1992

Effects of atrial natriuretic peptide on glycerol induced acute renal failure in the rat.

Acute and chronic experiments were performed in rats to examine whether atrial natriuretic peptide (ANP) has any beneficial effects on glycerol-induced acute renal failure (ARF). ANP infusion (Atriopeptin III, 1.0 microgram/kg+0.2 microgram/kg/min) improved the renal blood flow (RBF) and the glomerular filtration rate (GFR), and induced profound natriuresis in the early stage of ARF. By contrast, ANP decreased RBF in the control rats. In addition to these acute hemodynamic effects, long-term beneficial effects of ANP were also observed. A 75-min infusion of ANP significantly lessened the degree of azotemia as well as the extent of renal histologic damage assessed 24 hours after the glycerol injection. These results indicate that ANP can afford partial protection against both acute renal dysfunction and the chronic course of the glycerol-induced ARF, suggesting that ANP may be useful in the treatment of ARF.

Acute Kidney Injury↗
PubMed1992

A young female case of polyarteritis nodosa strongly suspected by typical angiographic findings which improved rapidly after prednisolone and cyclophosphamide therapy.

A 16-year-old girl was admitted with the complaints of headache, chest pain, low abdominal pain and left hemi-numbness. Her blood pressure was high and plasma renin activity and aldosterone levels were elevated. Renal angiography revealed vascular stenoses and microaneurysms although the renal artery and its main branches were not involved. Polyarteritis nodosa (PN) was strongly suspected and oral prednisolone and intravenous pulse therapy of cyclophosphamide were started. The second renal angiography which was performed 11 days after the therapy was started, showed marked improvement of vascular lesions. This is a case which suggests that the angiographic findings of PN can improve very rapidly with therapy.

Adolescent↗
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

Preparation of Japanese encephalitis virus nonstructural protein NS1 obtained from culture fluid of JEV-infected Vero cells.

The Japanese encephalitis virus (JEV) nonstructural protein NS1 was released efficiently into culture fluid of JEV-infected Vero cells. The JEV NS1 protein in the infected culture fluid was found almost as a high-molecular-weight form, probably a dimer form of NS1, and was converted to a monomer by boiling. Large amounts of NS1 protein were accumulated in the infected culture fluid. The NS1 protein, separated from JE virions by centrifugation through sucrose layer, could be obtained in large quantities.

Animals↗
PubMed1991

Tubuloglomerular feedback response in rats with antithymocyte serum-induced glomerular lesions.

Glomerular function and tubuloglomerular feedback (TGF) responses were studied in rats treated with antithymocyte rabbit serum (ATS). Microscopic findings revealed extensive mesangial cell loss and injury, enlarged capillary lumen, and decreased tortuosity of glomerular capillaries. Whole kidney GFR and SNGFR were lower in ATS-treated rats than in control rats (1.04 +/- 0.04 vs 0.94 +/- 0.03 ml/min/g kidney weight, 32 +/- 2 vs 27 +/- 1 nl/min, respectively) due to a decrease in Kf (0.017 +/- 0.001 vs 0.021 +/- 0.001 nl/s/mmHg). The magnitude of the TGF responses of SNGFR was less in ATS rats than in control rats (17% +/- 4% vs 34% +/- 5%), but that of SFP was not significantly different (18% +/- 2% vs 23% +/- 1%). These results indicate that the mesangial cells are necessary for full expression of the TGF mechanism and suggest the involvement of changes in Kf in the TGF mechanism.

Animals↗
PubMed1991

H-2-unrestricted adjuvant effect of cholera toxin B subunit on murine antibody responses to influenza virus haemagglutinin.

Cholera toxin B subunit (CTB) has been shown to augment the antibody responses to influenza virus haemagglutinin (HA) in BALB/c mice immunized with HA vaccine together with CTB. In this study, mouse strain differences in the adjuvant effect of CTB on anti-HA antibody responses were investigated along with those in the antibody responses to CTB or HA, using various inbred and H-2 congenic strains. The antibody responsiveness to CTB depended on the H-2 haplotype of the strain: strains with the H-2b haplotype were high responders, those with H-2a, H-2k and H-2s were low responders, and those with H-2d were intermediate. The responsiveness to HA was also related to the H-2 haplotype: H-2a and H-2k strains were high responders, H-2b and H-2s strains were low responders, and H-2d strains were intermediate. However, the degree of the adjuvant effect of CTB on anti-HA antibody responses was almost constant, regardless of the H-2 haplotype or other genetic backgrounds of the strain. The lack of genetic restriction of the adjuvant effect would be favourable for application of CTB-combined HA vaccine to humans, who are genetically diverse. Moreover, these results suggest that the immunogenicity and adjuvanticity of CTB differ essentially in their mechanisms.

Adjuvants, Immunologic↗
PubMed1990

Cross-protection against influenza B type virus infection by intranasal inoculation of the HA vaccines combined with cholera toxin B subunit.

The relationship between the antibody responses to various influenza B type virus HA vaccines and protection against live B virus infection was investigated in Balb/c mice which had been inoculated intranasally with a combination of the HA vaccines and B subunit of cholera toxin (CTB) 4 weeks previously. The inoculation of HA vaccine, prepared from B/Ibaraki/2/85 (B/Ibaraki), B/Nagasaki/1/87 (B/Nagasaki) or B/Aichi/5/88 (B/Aichi) viruses, combined with CTB induced high levels of both nasal IgA and serum HI antibodies to any of B/Ibaraki, B/Nagasaki and B/Aichi viral antigens. Simultaneous inoculation of each CTB-combined HA vaccine provided complete protection against B/Ibaraki virus infection which is demonstrated by both rapid clearance of pulmonary virus and complete survival. On the other hand, the inoculation of HA vaccine prepared from B/Yamagata/16/88 (B/Yamagata) virus together with CTB induced only a low level of nasal IgA antibodies, cross-reactive to B/Ibaraki, B/Nagasaki and B/Aichi viral antigens and protected only partially against B/Ibaraki virus challenge. The involvement of the B type virus-specific immunity in this protection was suggested by the absence of protection against B/Ibaraki virus infection in mice previously inoculated with both A/PR/8/34 (H1N1) virus HA vaccine and CTB. These results suggest that antibodies to various influenza B viruses are cross-reactive to each B type virus antigens and that cross-protection against B virus infection could be conferred depending on the degree of B type virus cross-reactive immunity including secretory IgA antibodies.

Animals↗
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↗
PubMed1990

Enhancement of DTH response by cholera toxin B subunit inoculated intranasally together with influenza HA vaccine.

The effects of B subunit of cholera toxin (CTB) on delayed-type hypersensitivity (DTH) response to influenza vaccine derived from influenza virus A/PR/8/34 (PR-8, HlNl) virus were investigated in B10 mice that were immunized intranasally with both influenza vaccine and CTB. The result showed that intranasal inoculation of this combination augmented DTH response to influenza vaccine, which reached its peak 6 days after inoculation, and also induced accelerated DTH response upon a second inoculation of influenza vaccine alone 4 weeks later, that the cross-reactive DTH response to PR-8 vaccine was elicited by the injection of the different influenza A-type virus vaccine into the footpad of the vaccinated mice, but was not by influenza B-type virus vaccine, that the DTH-mediating T cells were detected selectively in the lungs of mice that received the nasal inoculation of the vaccine and CTB together, but that subcutaneous inoculation of this combination failed to induce DTH-mediating T cells in the lungs. These results, together with the previous papers (Tamura et al, Vaccine 7: 257-262; 314-320, 1989), suggest that CTB could augment both humoral and DTH responses against influenza vaccine in the respiratory mucosal tract.

Adjuvants, Immunologic↗
PubMed1989

Immunostimulatory activity of 1-O-acylated muramyl dipeptides, with or without a 6-O-phosphoryl group, in aqueous form.

Immunostimulatory effects of 1-O-acylated derivatives of N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP) methyl ester, with or without the 6-O-phosphoryl group, on augmentation of IgG antibody response against influenza hemagglutinin (HA) vaccine, in vivo macrophage activation and enhancement of non-specific host resistance against Pseudomonas aeruginosa infection were investigated. The activities were tested intraperitoneally (i.p.) in mice administered test samples solubilized or suspended in saline. The introduction of longer chain acyl groups into MDP methyl esters significantly induced enhancement of the IgG antibody response. Among them, the adjuvant activity of 1-O-linked 2-tetradecylhexadecanoyl (B30)-MDP methyl ester was comparable to that of 6-O-B30-MDP used as a positive control. Phosphorylation at the C6 position of the acylated MDP analogs did not induce a significant increment in the activity. With respect to phagocytic, cellular acid phosphatase and cytostasis-inducing activities, i.p. administration of acylated MDP analogs caused significant increment and activation of peritoneal macrophages. The cytostasis-inducing activity of 1-O-octadecanoyl- or 1-O-B30-MDP methyl ester with or without a phosphoryl group was more intensive than that of 6-O-B30-MDP. Acylated MDP analogs enhanced non-specific resistance against P. aeruginosa infection when the analogs were administered i.p. on the day before the infection. The enhancement was closely related to the accumulation of polymorphonuclear cells in the peritoneal cavity. The manifestation of these immunostimulatory activities by 1-O-acylated MDP analogs depended closely on the increasing carbon chain length of fatty acid substituents when administered in aqueous form.

Acetylmuramyl-Alanyl-Isoglutamine↗
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

Enhancement of protective antibody responses by cholera toxin B subunit inoculated intranasally with influenza vaccine.

Effects of the B subunit of cholera toxin (CTB) on the primary antibody responses to influenza virus A/PR/8/34 (PR-8) (H1N1) HA vaccine and on protection against viral challenge were investigated in Balb/c mice which were immunized intranasally with both the vaccine and CTB. The dose of CTB (greater than or equal to 1 microgram) inoculated with the vaccine (greater than or equal to 0.15 microgram) induced high responses of both antiviral IgA antibodies in the nasal wash and haemagglutinin-inhibiting (HI) antibody in the serum, enough to provide complete protection against viral challenge four weeks after immunization. High levels of antibody were maintained for more than 16 weeks after inoculation, affording complete protection during this interval. The inoculation of HA vaccine prepared from influenza viruses A/Yamagata/120/86 (H1N1) or A/Fukuoka/C29/85 (H3N2) together with CTB provided partial protection against PR-8 infection, with production of antiviral IgA antibodies which were cross-reactive to PR-8 antigens whereas immunization with CTB and HA vaccine prepared from a different type of influenza virus (B/Ibaraki/2/85) failed to protect against PR-8 infection. These results indicate that CTB can produce an augmented and persistent antibody response to PR-8 HA vaccine, which is cross-protective to other A-type virus infections. The mechanisms by which CTB enhances the protective antibody responses to the nasally inoculated vaccine were investigated. The ability of CTB to augment antibody responses was lost, either when CTB was inoculated via the intravenous or subcutaneous route, or when CTB was introduced into nasal site one day before or after the vaccine inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Intranasal↗