Biomedical subjects

Keishi Miwa

Publications and source records attributed to Keishi Miwa.

7 recordsLinked to original sources

PubMed2006

Antibodies against superantigenic exotoxins produced by Staphylococcus aureus in sera from mothers and their infants' cord blood.

A novel neonatal disease and puerperal toxic shock syndrome (TSS) induced by a superantigen, TSS toxin-1 (TSST-1), has spread throughout Japan. It is important to investigate serum titers against exotoxins in new mothers and in their infants' cord blood. We investigated antitoxin antibodies against TSST-1, staphylococcal enterotoxin (SE) A (SEA), SEB, and SEC, including immunoglobulin G (IgG) subclass specificity by enzyme-linked immunosorbent assay, in sera from 221 mothers and 97 cord blood samples. The rate of mothers with negative anti-TSST-1 antibody titer was high (more than 40%). Although antitoxin antibody titers in the sera of cord blood were well correlated with those in the sera of the mothers for every toxin, the tendencies of antibody transmission differed between toxins. Anti-TSST-1 antibody consisted mainly of IgG1 and IgG4 subclasses. Anti-TSST-1 IgG1- and IgG4-specific antibody titers in cord blood were well correlated with those in the sera of the mothers. The low frequency of pregnant women with positive anti-TSST-1 antibody titers could be one reason for the spread of TSS in Japan. Neonates whose mothers have positive IgG titers against TSST-1 should be protected because the antibody is composed of the subclasses transferred well through the placenta.

Adult↗

PubMed2006

The role of immune response to Staphylococcus aureus superantigens and disease severity in relation to the sensitivity to tacrolimus in atopic dermatitis.

BACKGROUND: Staphylococcus aureus-producing superantigens (SAgs), such as staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin-1 (TSST-1), are frequently observed in atopic dermatitis (AD). However, little has been done to establish the association of immune responses to SAgs and the therapeutic response to immunosuppressive drugs in AD. Therefore, we investigated the prevalence and role of SAgs in the pathophysiology and immunosuppressive drug sensitivity in AD patients. METHODS: We classified 29 patients into two groups on the basis of their clinical AD scores: a low-score group (n = 14) corresponding to mild to moderate patients and a high-score group (n = 15) corresponding to severe patients. We estimated the plasma anti-SEB or TSST-1 IgE of these patients and healthy subjects by ELISA. We also estimated individual drug sensitivity by determining drug concentrations that would give 50% inhibition (IC(50)) of peripheral-blood mononuclear cell (PBMC) proliferation in vitro. RESULTS: The levels of plasma anti-SEB or TSST-1 IgE in the severe patients were significantly higher than those in the mild to moderate patients (p < 0.05 and p < 0.01, respectively). When stimulated with concanavalin A in vitro, PBMCs in the severe patients exhibited low sensitivity to the suppressive efficacy of tacrolimus (FK506) as compared to the mild to moderate patients (p < 0.01). Furthermore, there was a significant correlation between the IC(50)s of FK506 and plasma anti-TSST-1 IgE levels (p < 0.01). CONCLUSIONS: We showed that PBMCs in severe AD patients exhibited lower sensitivity to FK506, and had higher plasma levels of anti-TSST-1 IgE as compared to the mild AD patients. SAgs appear to be one of the causes of decreased PBMC sensitivity to FK506, and therefore an alternative treatment would be useful based on the individual drug sensitivity data and anti-TSST-1 IgE levels.

Adult↗

PubMed2006

Physiological response to superantigen-adsorbing hemoperfusion in toxin-concentration-controlled septic swine.

BACKGROUND/AIMS: Superantigens are suspected of being potent initiators of gram-positive sepsis, and new therapies for superantigen elimination are required. The effects of hemoadsorption with a superantigen-adsorbing device (SAAD) were evaluated in septic swine. METHODS: Toxic shock syndrome toxin-1 (TSST-1) was infused, and blood concentration was maintained at the clinical level for 6 h. Endotoxin was then infused to induce lethal shock. All animals were hemoperfused with SAAD or a control column for 8 h and changes in pathological parameters and mortality were examined. RESULTS: Animals perfused with SAAD had a highly significant (p < 0.01) survival advantage compared with control groups at 24 h after initiation of the TSST-1 infusion. SAAD also suppressed the increase in the arteriovenous shunt ratio and decrease of partial arterial oxygen pressure at 6 h after TSST-1 infusion initiation. CONCLUSION: We suggest that there is a potential application of SAAD in treating superantigen-induced respiratory dysfunction and sepsis.

Adsorption↗

PubMed2005

Superantigen-induced multiple organ dysfunction in a toxin-concentration-controlled and sequential parameter-monitored swine sepsis model.

OBJECTIVE: In order to examine the biological activity of low-dose and continuously infused superantigen, and to establish a superantigen-induced multiple organ dysfunction animal model, several pathophysiological parameters were sequentially monitored in a toxin-concentration-controlled pig model. METHODS: Anesthetized, mechanically ventilated and Swan-Ganz thermodilution catheter-inserted pigs were treated with toxic shock syndrome toxin-1 (TSST-1) by infusion at 2 microg/kg/h for 5 h. Monitoring was performed for both the infusion period and a subsequent 1-h post-infusion period. RESULTS: The serum concentration of TSST-1 was controlled so as to elevate it to a level over 1000 pg/mL within 1 h of initiation of infusion, and then gradually increased further and reached a plateau of about 2500 pg/mL at 4h after initiation. The animals showed a significant increase in cardiac output, the intrapulmonary arteriovenous shunt ratio, and infiltration of white blood cells into the lung. Although the observed increase in pulmonary vascular resistance was not statistically significant, it did correlate with the reduction in white blood cell counts. CONCLUSION: The superantigen TSST-1 plays an important role in the pathogenesis of Gram-positive bacterial sepsis by inducing multiple organ dysfunction. Thus, this model provides the first tool to allow the simultaneous examination of the serum toxin levels and other organ parameters in a time-course manner.

Animals↗

PubMed2005

Mixed bacterial infection model of sepsis in rabbits and its application to evaluate superantigen-adsorbing device.

BACKGROUND: Superantigens are suspected to be the potent and lethal pathogens of gram-positive sepsis, and a new therapy that targeted to superantigens are required. METHODS: A mixed infection model was developed in rabbits by the cecal ligation and puncture associated with the intraperitoneal injection of Staphylococcus aureus, which produces toxic shock syndrome toxin 1 (TSST-1). Animals were also hemoperfused with a superantigen-adsorbing device (SAAD), or a control column. RESULTS: The model animals revealed multiple organ failure and died 6-12 h after the injection of S. aureus. The plasma levels of TSST-1, but not of lipopolysaccharide (LPS), significantly (p < 0.01) and inversely correlated with mean arterial pressure (r = -0.63). Plasma TSST-1 level was significantly reduced and shock-onset time was significantly retarded in the SAAD treated group, although the survival time was not significantly affected. CONCLUSIONS: The animal model developed could serve as a model for sepsis. It is suggested that there is the potential application of SAAD in treating superantigen-related sepsis.

Adsorption↗

PubMed2003

Preparation of a superantigen-adsorbing device and its superantigen removal efficacies in vitro and in vivo.

OBJECTIVE: A new superantigen-adsorbing device (SAAD) was developed, and its characteristics and efficacy in septic animals were evaluated. METHODS: The SAAD was prepared by stepwise chemical modification of a polystyrene-based composite fiber reinforced with polypropylene. Adsorption affinities for several factors and the biological effect of superantigen (SAg) removal were measured in vitro. Also, superantigen-infused rabbits were treated with SAAD, and the efficacy was evaluated in vivo. RESULTS: When the SAAD was evaluated for its ability to adsorb SAg in human plasma (1 ng/mL each), the adsorption rates were 74%, 76% and 85% for staphylococcal enterotoxins A, B and C, respectively, and 80% and 72% for toxic shock syndrome toxin-1 (TSST-1) and streptococcal pyrogenic exotoxin A, respectively. In addition, the SAAD showed some affinity towards other molecules, such as streptococcal pyrogenic exotoxin B, beta2-microglobulin, and vancomycin. Residual activities in whole blood samples containing TSST-1 (1 ng/mL) after incubation with the SAAD were 125 pg/mL for tumor necrosis factor alpha (TNF-alpha) production, and 359 pg/mL for interleukin-8 (IL-8) production (the initial activities: 194 pg/mL for TNF-alpha production, and 1029 pg/mL for IL-8 production). When TSST-1/lipopolysaccharide (LPS)-infused rabbits were subjected to extracorporeal blood purification with a SAAD column, 50% of the animals survived for a 14-day period after the infusion. In contrast, all control animals died within 3 days after the infusion. CONCLUSION: These results indicate that the SAg-adsorbing device may be useful in treating SAg-related diseases.

Adsorption↗

PubMed2002

Continuous exposure of mice to superantigenic toxins induces a high-level protracted expansion and an immunological memory in the toxin-reactive CD4+ T cells.

We analyzed the responses of several T cell fractions reactive with superantigenic toxins (SAGTs), staphylococcal enterotoxin A (SEA), or Yersinia pseudotuberculosis-derived mitogen (YPM) in mice implanted with mini-osmotic pumps filled with SEA or YPM. In mice implanted with the SEA pump, SEA-reactive Vbeta3(+)CD4(+) T cells exhibited a high-level protracted expansion for 30 days, and SEA-reactive Vbeta11(+)CD4(+) T cells exhibited a low-level protracted expansion. SEA-reactive CD8(+) counterparts exhibited only a transient expansion. A similar difference in T cell expansion was also observed in YPM-reactive T cell fractions in mice implanted with the YPM pump. Vbeta3(+)CD4(+) and Vbeta11(+)CD4(+) T cells from mice implanted with the SEA pump exhibited cell divisions upon in vitro restimulation with SEA and expressed surface phenotypes as memory T cells. CD4(+) T cells from mice implanted with the SEA pump exhibited high IL-4 production upon in vitro restimulation with SEA, which was due to the enhanced capacity of the SEA-reactive CD4(+) T cells to produce IL-4. The findings in the present study indicate that, in mice implanted with a specific SAGT, the level of expansion of the SAGT-reactive CD4(+) T cell fractions varies widely depending on the TCR Vbeta elements expressed and that the reactive CD4(+) T cells acquire a capacity to raise a memory response. CD8(+) T cells are low responders to SAGTs.

Animals↗