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Biomedical subjects

C Aizawa

Publications and source records attributed to C Aizawa.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1989

Enhancement of immunoglobulin G responses in mice against hepatitis B virus surface antigen, influenza virus hemagglutinin vaccine, and tetanus toxoid by 6-O-acylated muramyl dipeptides.

The adjuvant activity of chemically synthesized 6-O-acylated muramyl dipeptides (MDP) was tested in aqueous form. The activity was assessed by determining immunoglobulin G (IgG) titers in sera of mice immunized with hepatitis B virus surface antigen, influenza virus hemagglutinin (HA) vaccine, or tetanus toxoid with an enzyme-linked immunosorbent assay. Administration of 6-O-acyl-MDP analogs with antigens induced marked enhancement of primary and secondary IgG antibody responses and maintained high antibody levels for at least 7 weeks. Among the analogs tested, an MDP methyl ester carrying a 6-O-3-hexadecanoyl-oxytetradecanoyl group (compound 309) exhibited the most intensive adjuvant activity. Its activity was stronger than that of 6-O-2-tetradecylhexadecanoyl (B3O)-MDP used as a positive control. However, accumulation of peritoneal cells and activation of peritoneal macrophages by compound 309 was weaker than that by 6-O-B30-MDP, suggesting that 309 as an immunoadjuvant is more suitable for vaccination in terms of its stronger enhancement of antibody formation and lower induction of inflammatory response than 6-O-B30-MDP.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1988

Molecular cloning and complete nucleotide sequence of the genome of Japanese encephalitis virus Beijing-1 strain.

The genomic RNA of the Japanese encephalitis virus (JEV) Beijing-1 strain was reversely transcribed and the synthesized cDNA was molecularly cloned. Six continuous cDNA clones that cover the entire virus genome were established and sequenced to determine the complete nucleotide sequence of the JEV RNA. The precise genomic size was estimated as 10,965 bases long. With flanking 95 bases at the 5' and 583 bases at the 3' non-coding regions, one long open reading frame (ORF) was revealed encoding a virus polyprotein with 3,429 amino acid residues. Because of sequence homologies observed between JEV and other flaviviruses, the genome organization of JEV appears to be identical with other flaviviruses. Genetic variation detected among flavivirus genomes is consistent with the established serological relatedness between JEV and other members of flaviviruses. The secondary structure of the JEV genome is deduced and discussed concerning its involvement in genome replication.

Base Sequence↗
PubMed1988

Protection against influenza virus infection by vaccine inoculated intranasally with cholera toxin B subunit.

Secretory IgA antibodies in mucosa are known to play an essential role in protection against various infectious agents. To enhance the induction of protective mucosal antibodies, influenza HA vaccine was inoculated intranasally into mice with the B subunit of cholera toxin (CTB), which is known to be an excellent mucosal self-adjuvanting molecule. This combination resulted in high levels of antiviral IgA antibodies in nasal secretions and enhanced serum haemagglutinin-inhibiting (HI) antibodies 4 weeks after inoculation, compared with the inoculation of vaccine alone which induced only a low level of HI serum antibodies and no local IgA antibodies. (Subcutaneous or intraperitoneal inoculation of the vaccine with CTB failed to induce detectable nasal antiviral IgA antibodies). Levels of nasal IgA and serum HI antibodies increased in a dose-dependent fashion with increasing nasal doses of both vaccine and CTB, and correlated with the degree of protection against viral challenge. A greater protective effect was seen with cholera toxin than with its B subunit. Moreover, a second administration of vaccine alone, 4 weeks after the inoculation of the vaccine with CTB, elevated the level of the antiviral IgA nasal antibodies to 10-100 times higher than that of the primary response. These results suggest that either CT or CTB could be used as a potent adjuvant to induce protective secretory antibodies by nasal vaccination against pathogens impinging on respiratory mucosa.

Adjuvants, Immunologic↗
PubMed1987

C1q solid-phase radioimmunoassay: evidence for detection of antibody directed against the collagen-like region of C1q in sera from patients with systemic lupus erythematosus.

In earlier studies we showed that the C1q-binding IgG in the sera from patients with systemic lupus erythematosus (SLE) tested by C1q solid-phase radioimmunoassay is cofractionated with monomeric IgG on gel filtration and mostly binds to C1q via the F(ab')2 region. In this study, we found that C1q, even when stripped of its immune complex-binding globular regions by pepsin digestion, retained a substantial part of its ability to bind IgG from SLE sera, suggesting that the collagen-like region of C1q is involved in binding to the SLE IgG. Heat-inactivation of C1q also failed to abolish its ability to bind IgG from SLE sera. In contrast, the binding of C1q to heat-aggregated IgG was completely abrogated by these treatments. In addition, the reaction of heat-aggregated IgG with the solid-phase C1q was markedly dependent on ionic strength whereas the binding of IgG from SLE sera with the solid-phase C1q persisted at high concentrations of salt. These findings suggest that the Clq-binding IgG in SLE sera is, at least in part, antibody directed against the collagen-like region of C1q.

Autoantibodies↗
PubMed1986

Intra- and inter-nephron heterogeneity of gluconeogenesis in the rat: effects of chronic metabolic acidosis and potassium depletion.

The intra- and inter-nephron heterogeneity of renal gluconeogenesis within rat proximal tubules and the effects of chronic metabolic acidosis and chronic potassium(K)-depletion were studied using isolated proximal tubules of rats by directly measuring glucose synthesized. The gluconeogenic activity from pyruvate and glutamine in control rats was almost limited to within the early proximal tubule (S1: 45.4 +/- 5.7 pmol/mm/60 min from pyruvate; 58.0 +/- 6.0 from glutamine). Very low, but detectable gluconeogenesis was observed in the middle portion of the proximal tubule (S2: 9.9 +/- 2.2 from pyruvate; 4.8 +/- 1.1 from glutamine). The rate of glucose production in the terminal proximal tubule (S3) was negligible. Furthermore, gluconeogenesis from glutamine of superficial (SF) nephrons was significantly higher than that of juxtamedullary (JM) ones, whereas no difference was seen in gluconeogenesis from pyruvate. In acidotic and K-depleted rats, significant increase could be seen in S1 and S2, but the increase in S3 was not significant. By the serial determination in acidosis, the glucose production from both substrates was found to be the highest at the second 1 mm segment from the glomerulus, and it decreased downward along the proximal tubule. In acidosis, glucose production from both substrates in SF nephrons and that from glutamine in JM ones were elevated significantly compared with the control, but that from pyruvate in JM nephrons did not change. These results suggest that S1 of the SF nephron plays the most important role in gluconeogenesis in the control, whereas S1 of the JM nephron and S2 contribute to gluconeogenesis in acidotic and/or possibly K-depleted rats.

Acidosis↗
PubMed1984

C1q solid-phase radioimmunoassay: binding properties of solid-phase C1q and evidence that C1q-binding IgG complexes in systemic lupus erythematosus are not bound to endogenous C1q.

The binding properties of C1q solid-phase radioimmunoassay (C1q SPRIA) were examined, using heat-aggregated IgG (HAG) as the model of immune complexes (IC). The free, liquid-phase C1q, which was added to the C1q-coated tubes prior to the addition of HAG, had little inhibitory effect on binding of HAG to the solid-phase C1q, suggesting that the solid-phase C1q has a higher affinity for HAG than the liquid-phase C1q. On the other hand, more than 60% inhibition was seen when HAG was preincubated with the liquid-phase C1q. These binding properties of HAG to the solid-phase C1q in the presence of the liquid-phase C1q were not essentially altered by the heat inactivation or the addition of EDTA, suggesting that these pretreatments are not essential in C1q SPRIA. Next, in similar kinds of experiments, the binding properties of C1q-binding IgG complexes in SLE sera were investigated. In contrast to HAG, the binding capacity of IgG complexes in SLE sera to the solid-phase C1q was not inhibited by the preincubation with excess liquid-phase C1q. These findings suggest that C1q-binding IgG complexes in SLE sera detected by C1q SPRIA may not be bound to endogenous C1q in the circulation.

Antigen-Antibody Complex↗
PubMed1984

Characterization of C1q-binding IgG complexes in systemic lupus erythematosus.

The molecular size of C1q-binding immunoglobulin (Ig) G complexes in systemic lupus erythematosus (SLE) sera was studied by gel filtration using C1q solid-phase radioimmunoassay (C1q SPRIA). All 15 SLE sera tested contained predominantly small-sized IgG complexes, cofractionating with monomeric IgG. In contrast to heat-aggregated IgG, these small-sized IgG complexes retained C1q-binding activity even after pepsin digestion, exposure to low pH, or reduction and alkylation, suggesting that the F(ab')2 region is involved in C1q-binding activity of these complexes. To see whether anti-C1q antibodies or small antigen-IgG complexes, which bind to C1q via their antigens, are responsible for C1q-binding activity via the F(ab')2 region, the pepsin-digested Ig fractions of SLE sera were fractionated at high salt. C1q-binding activity in the fractions corresponding to the F(ab')2 region increased 2.5- to 3.9-fold at high salt. These results suggest that the C1q-binding, small-sized IgG complexes may be comprised mostly of anti-C1q antibodies and that some of the antibodies, which are dissociated with their antigens at high salt, might be cross-reactive with C1q.

Adult↗
PubMed1980

Large-scale purification of Japanese encephalitis virus from infected mouse brain for preparation of vaccine.

Large volumes of Japanese encephalitis (JE) virus propagated in mouse brain can be easily purified by polyethylene glycol 6,000. By using the polyethylene glycol precipitation method, mouse hemoglobin was almost all separated from the viral suspension, and consequently the total amount of nonviral protein in the viral suspension decreased. The recovery of infectivity was about 100%. The removal of residual polyethylene glycol in the viral suspension was possible without difficulty by means of ethanol precipitation. This method is recommended as an initial step in large-scale purification of Japanese encephalitis virus propagated in mouse brain because it is simple, rapid, and inexpensive.

Animals↗
PubMed1977

Failure to abolish reactive hyperemia by indomethacin in denervated kidneys of rabbits.

The effect of indomethacin (10 mg/kg) on the distribution of cortical blood flow during postocclusive reactive hyperemia was evaluated in denervated kidneys of anesthetized rabbits by the radioactive microsphere technique. Renal denervation caused a slight but not significant increase in renal blood flow with no remarkable alteration in the distribution of cortical blood flow. After release of 1-min occlusion of the renal artery, hyperemic responses developed with a fractional flow redistribution toward the inner cortex. The absolute perfusion rate increased in the inner cortex but did not significantly change in the outer cortex. Indomethacin produced a decrease in renal blood flow despite elevated blood pressure. Even in the indomethacin-treated animals, postocclusive reactive hyperemia appeared concomitantly with the fractional flow redistribution to the inner cortex. The percentage repayment by reactive hyperemia of ischemia during the artery clamping was not significantly different before and after indomethacin administration. The findings indicate that indomethacin did not significantly affect the postocclusive vascular response in denervated kidneys of rabbits, thereby giving evidence against the role of prostaglandins as mediators of reactive hyperemia.

Animals↗
PubMed1977

Absence of renal circulatory autoregulation during perfusion with paraffin oil.

Autoregulation of vascular flow as a function of arterial pressure was studied in isolated dog and rat kidneys, perfused serially with an oxygenated aqueous colloidal medium and with oxygenated paraffin oil. Square wave elevations in arterial pressure eleicited autoregulatory adjustments in flow within the first few seconds of elevated pressure during colloidal perfusion but not during oil perfusion of the same kidneys. Before oil perfusion, the steady state autoregulatory efficiency ratios (% flow change/% pressure change) over pressures ranging from 95 to 180 mm Hg averaged 0.37 +/- 0.13 and 0.51 +/- 0.16 (mean +/- SD) in dog and rat kidneys, respectively. During oil perfusion, the autoregulatory efficiency ratios exceeded 1.0 in every instance. Following oil perfusion, vasoactive autoregulation of colloidal perfusate flow returned, at very low organ flows. Our results do not confirm the previous findings of LEICHTWEISS, SCHRODER, and WEISS [Pflügers Arch. ges. Physiol. 293: 303 1967] concerning the presence of autoregulation during oxygenated renal oil perfusion. Our findings suggest that renal circulatory autoregulation is either primarily myogenic or else primarily dependent upon a rapidly acting tubulovascular feedback mechanism.

Animals↗