Effects of Streamer Discharge on PM2.5 Containing Endotoxins and Polyaromatic Hydrocarbons and Their Biological Responses In Vitro.

Experimental and epidemiological studies have demonstrated that fine particulate matter with a diameter of <2.5 µm (PM2.5) affects both the respiratory and immune systems. However, effective approaches to reduce PM2.5-induced hazardous effects have not been discovered yet. Streamer discharge is a category of plasma discharge in which high-speed electrons collide with oxygen and nitrogen molecules. Although streamer discharge can reportedly eliminate bacteria, molds, chemical substances, and allergens, its ability to decontaminate PM2.5 has not been previously demonstrated. The present study explored whether streamer discharge treatment could reduce PM2.5-induced inflammatory responses by employing an in vitro system. PM2.5 was collected under four conditions (Bangkok (Sep.−Dec.), Bangkok (Dec.−Mar.), Singapore, and Taipei). Airway epithelial cells and antigen-presenting cells exposed to non-treated PM2.5 in several conditions resulted in inflammatory responses. Streamer-discharged PM2.5 (Bangkok (Sep.−Dec.)) decreased the expression of interleukin (IL)-6 and IL-8 compared to non-treated PM2.5. Moreover, composition analysis demonstrated that streamer discharge reduced some compounds, such as endotoxins and polycyclic aromatic hydrocarbons, included in PM2.5 that can elicit inflammatory responses. Streamer discharge treatment can reduce endotoxins, polycyclic aromatic hydrocarbons, and the subsequent inflammatory responses induced by PM2.5 in vitro.

Human immune responses elicited by an intranasal inactivated H5 influenza vaccine.

Intranasally administered influenza vaccines could be more effective than injected vaccines, because intranasal vaccination can induce virus-specific immunoglobulin A (IgA) antibodies in the upper respiratory tract, which is the initial site of infection. In this study, immune responses elicited by an intranasal inactivated vaccine of influenza A(H5N1) virus were evaluated in healthy individuals naive for influenza A(H5N1) virus. Three doses of intranasal inactivated whole-virion H5 influenza vaccine induced strong neutralizing nasal IgA and serum IgG antibodies. In addition, a mucoadhesive excipient, carboxy vinyl polymer, had a notable impact on the induction of nasal IgA antibody responses but not on serum IgG antibody responses. The nasal hemagglutinin (HA)-specific IgA antibody responses clearly correlated with mucosal neutralizing antibody responses, indicating that measurement of nasal HA-specific IgA titers could be used as a surrogate for the mucosal antibody response. Furthermore, increased numbers of plasma cells and vaccine antigen-specific Th cells in the peripheral blood were observed after vaccination, suggesting that peripheral blood biomarkers may also be used to evaluate the intranasal vaccine-induced immune response. However, peripheral blood immune cell responses correlated with neutralizing antibody titers in serum samples but not in nasal wash samples. Thus, analysis of the peripheral blood immune response could be a surrogate for the systemic immune response to intranasal vaccination but not for the mucosal immune response. The current study suggests the clinical potential of intranasal inactivated vaccines against influenza A(H5N1) viruses and highlights the need to develop novel means to evaluate intranasal vaccine-induced mucosal immune responses.

Relationship of the quaternary structure of human secretory IgA to neutralization of influenza virus.

Secretory IgA (S-IgA) antibodies, the major contributors to humoral mucosal immunity to influenza virus infection, are polymeric Igs present in many external secretions. In the present study, the quaternary structures of human S-IgA induced in nasal mucosa after administration of intranasal inactivated influenza vaccines were characterized in relation to neutralization potency against influenza A viruses. Human nasal IgA antibodies have been shown to contain at least five quaternary structures. Direct and real-time visualization of S-IgA using high-speed atomic force microscopy (AFM) demonstrated that trimeric and tetrameric S-IgA had six and eight antigen-binding sites, respectively, and that these structures exhibited large-scale asynchronous conformational changes while capturing influenza HA antigens in solution. Furthermore, trimeric, tetrameric, and larger polymeric structures, which are minor fractions in human nasal IgA, displayed increased neutralizing potency against influenza A viruses compared with dimeric S-IgA, suggesting that the larger polymeric than dimeric forms of S-IgA play some important roles in protection against influenza A virus infection in the human upper respiratory tract.

Characterization of neutralizing antibodies in adults after intranasal vaccination with an inactivated influenza vaccine.

The levels and properties of neutralizing antibodies in nasal wash and serum collected from five healthy adults were examined after intranasal administration of an A/Uruguay/716/2007 (H3N2) split vaccine (45 µg hemagglutinin (HA) per dose; five doses, with an interval of 3 weeks between each dose). Prior to the assays, nasal wash samples were concentrated so that the total amount of antibodies was equivalent to about 1/10 of that found in the natural nasal mucus. Vaccination induced virus-specific neutralizing antibody responses, which increased with the number of vaccine doses given. Neutralizing antibodies were produced more efficiently in the nasal passages than in the serum: A ≥4-fold increase in nasal neutralization titres was observed after the second vaccination in four out of five subjects, whereas a rise in serum neutralization titres was observed only after the fifth vaccination. Nasal and serum neutralizing antibodies were mainly found in the polymeric IgA and monomeric IgG fractions, respectively, after gel filtration. Taken together, these results suggest that intranasal administration of an inactivated split vaccine induces high levels of nasal neutralizing antibodies (primarily polymeric IgA) and low levels of serum neutralizing antibodies (primarily monomeric IgG).

GATA-2 anomaly and clinical phenotype of a sporadic case of lymphedema, dendritic cell, monocyte, B- and NK-cell (DCML) deficiency, and myelodysplasia.

A Japanese patient presented with lymphedema, severe Varicella zoster, and Salmonella infection, recurrent respiratory infections, panniculitis, monocytopenia, B- and NK-cell lymphopenia, and myelodysplasia. The phenotype was a mixture of the monocytopenia and mycobacterial infection (MonoMAC) and Emberger syndromes. Sequencing of the GATA-2 cDNA revealed the heterozygous missense mutation 1187 G > A. This mutation resulted in the amino acid mutation Arg396Gln in the zinc fingers-2 domain, which is predicted to cause significant structural change and prevent a critical interaction with DNA. Functional analysis of the patient's GATA-2 mutation is required to understand the relationship between these distinctive syndromes.

Zymosan enhances the mucosal adjuvant activity of poly(I:C) in a nasal influenza vaccine.

The synthetic double-stranded RNA polyriboinocinic polyribocytidylic acid [poly(I:C)] is a potent mucosal adjuvant in mice immunized intranasally with an inactivated influenza vaccine. In an attempt, to increase the effectiveness of a nasal poly(I:C)-combined vaccine, the effect of zymosan, a cell wall extract from Saccharomyces cervisiae was investigated, on the adjuvant activity of poly(I:C) in BALB/c mice. The addition of zymosan (10 microg) as an adjuvant in mice which were immunized intranasally with a poly(I:C) (1-5 microg)-combined vaccine (1 microg) enhanced the ability of the mice to mount an effective immune response to a lethal dose of influenza virus, and resulted in a synergistic increase in secretory IgA and serum IgG antibody levels. To define the mechanism by which zymosan enhanced the adjuvant activity of poly(I:C), bone marrow-derived dendritic cells (BM-DCs) were cultured in the presence of poly(I:C) and/or zymosan. There was a synergistic increase in cytokine production (TNF-alpha, IL-6, IL-10, and IFN-beta) in BM-DCs, together with an increase in the expression of co-stimulatory molecules (CD86 and CD40) in response to co-treatment with poly(I:C) and zymosan. This synergistic effect on cytokine production was mimicked by co-treatment with poly(I:C) and a Toll-like receptor 2 (TLR2) ligand, which represented one of the components of zymosan. The results of the current study suggest that one of the mechanisms by which zymosan enhances the adjuvant activity of poly(I:C) is through increased cytokine production by DCs involving the synergistic activation of poly(I:C)-induced TLR3- and zymosan-induced TLR2-mediated signaling pathways. J. Med. Virol. 82:476-484, 2010. (c) 2010 Wiley-Liss, Inc.

Induction of cross-protective immunity against influenza A virus H5N1 by an intranasal vaccine with extracts of mushroom mycelia.

The identification of a safe and effective adjuvant that is able to enhance mucosal immune responses is necessary for the development of an efficient inactivated intranasal influenza vaccine. The present study demonstrated the effectiveness of extracts of mycelia derived from edible mushrooms as adjuvants for intranasal influenza vaccine. The adjuvant effect of extracts of mycelia was examined by intranasal co-administration of the extracts and inactivated A/PR8 (H1N1) influenza virus hemagglutinin (HA) vaccine in BALB/c mice. The inactivated vaccine in combination with mycelial extracts induced a high anti-A/PR8 HA-specific IgA and IgG response in nasal washings and serum, respectively. Virus-specific cytotoxic T-lymphocyte responses were also induced by administration of the vaccine with extract of mycelia, resulting in protection against lethal lung infection with influenza virus A/PR8. In addition, intranasal administration of NIBRG14 vaccine derived from the influenza A/Vietnam/1194/2004 (H5N1) virus strain administered in conjunction with mycelial extracts from Phellinus linteus conferred cross-protection against heterologous influenza A/Indonesia/6/2005 virus challenge in the nasal infection model. In addition, mycelial extracts induced proinflammatory cytokines and CD40 expression in bone marrow-derived dendritic cells. These results suggest that mycelial extract-adjuvanted vaccines can confer cross-protection against variant H5N1 influenza viruses. The use of extracts of mycelia derived from edible mushrooms is proposed as a new safe and effective mucosal adjuvant for use for nasal vaccination against influenza virus infection.

Intranasal administration of adjuvant-combined vaccine protects monkeys from challenge with the highly pathogenic influenza A H5N1 virus.

The effectiveness in cynomolgus macaques of intranasal administration of an influenza A H5N1 pre-pandemic vaccine combined with synthetic double-stranded RNA (polyI/polyC12U) as an adjuvant was examined. The monkeys were immunized with the adjuvant-combined vaccine on weeks 0, 3, and 5, and challenged with the homologous virus 2 weeks after the third immunization. After the second immunization, the immunization induced vaccine-specific salivary IgA and serum IgG antibodies, as detected by ELISA. The serum IgG antibodies present 2 weeks after the third immunization not only had high neutralizing activity against the homologous virus, they also neutralized significantly heterologous influenza A H5N1 viruses. The vaccinated animals were protected completely from the challenge infection with the homologous virus. These results suggest that intranasal immunization with the Double stranded RNA-combined influenza A H5N1 vaccine induce mucosal IgA and serum IgG antibodies which could protect humans from homologous influenza A H5N1 viruses which have a pandemic potential.

Influenza PR8 HA-specific Fab fragments produced by phage display methods.

Anti-influenza hemagglutinin (HA) Fabs were isolated from a phage display library using purified HA of influenza virus A/Puerto Rico/8/34 (PR8; H1N1) as an antigen. Four Fab clones displaying a 25-50-fold higher binding signal to PR8 HA than the control were selected for further analysis and comparison with anti-PR8 monoclonal antibody (mAb). All four Fabs and mAb recognized the PR8 HA under non-reducing conditions but rarely bound to reduced PR8 HA. Inhibition of influenza virus infection on MDCK cells was observed with Fab1 and mAb in a dose-dependent manner while Fab3 and 4 exhibited only a partial inhibitory effect. Moreover, Fab1 clone and mAb exhibited cross-reactivity with the A/Peking/262/95 (A/Peking; H1N1) strain. The inhibitory effects of mAb on both influenza strains were more potent than Fab1, which is likely attributed to its higher affinity for the antigen. SPR analyses, in fact, revealed that Fab1 and mAb have K(D) of 1.5 x 10(-8) and 3.2 x 10(-9)M, respectively. These results strongly suggest that phage library-derived Fabs can be readily prepared and that such HA-specific Fabs with inhibitory action on influenza infection may be used to treat influenza patients.

IgA polymerization contributes to efficient virus neutralization on human upper respiratory mucosa after intranasal inactivated influenza vaccine administration.

Unlike the current injectable influenza vaccines, intranasally administered influenza vaccines induce influenza virus-specific IgA antibodies in the local respiratory mucosa as well as IgG antibodies in the systemic circulation. Our previous study showed that after five volunteers underwent intranasal administration with inactivated H3N2 or H5N1 vaccines, their IgA antibodies on the upper respiratory tract were present as monomers, dimers, and multimers (trimers and tetramers). Moreover, the multimers associated with the highest virus neutralizing activity. However, it has remained elusive whether a more practical intranasal vaccination strategy could induce the high-performance IgA multimers in the nasal mucosa. In the present study, volunteers were administered with two doses of the intranasal trivalent whole-virus inactivated influenza vaccine and showed that in nasal wash samples the amount of multimeric IgA correlated positively with virus neutralizing titers, indicating that the multimeric IgA antibodies play an important role in the antiviral activity at the nasal mucosa. Surface plasmon resonance analysis of the binding dynamics of nasal wash derived IgA monomers, dimers, and multimers against recombinant trimeric influenza virus HA showed that sample fractions containing IgA multimers dissociated from HA less well than sample fractions without IgA multimers. Thus, IgA multimers may "stick" to the antigen more tightly than the other structures. In summary, intranasal administration of two doses of multivalent inactivated influenza vaccines induced multimeric IgA. Multimerization of mucosal IgA antibodies conferred higher neutralizing activity against viruses in the nasal mucosa, possibly by increasing their cohesion to virus antigens.

Intranasal immunization with H5N1 vaccine plus Poly I:Poly C12U, a Toll-like receptor agonist, protects mice against homologous and heterologous virus challenge.

The avian H5N1 influenza virus has the potential to cause a new pandemic. Since it is difficult to predict which strain of influenza will cause a pandemic, it is advantageous to produce vaccines that confer cross-protective immunity. Mucosal vaccine administration was reported to induce cross-protective immunity by inducing secretion of IgA at the mucosal surface. Adjuvants can also enhance the development of fully protective mucosal immunity. Here we show that a new mucosal adjuvant, poly I:poly C12U (Ampligen), a Toll-like receptor 3 agonist proven to be safe in a Phase III human trial, is an effective adjuvant for H5N1 influenza vaccination. Intranasal administration of a candidate influenza vaccine with Ampligen resulted in secretion of IgA, and protected mice that were subsequently challenged with homologous A/Vietnam/1194/2004 and heterologous A/HK/483/97 and A/Indonesia/6/2005 virus.

Fluoroscopic bone fragment tracking for surgical navigation in femur fracture reduction by incorporating optical tracking of hip joint rotation center.

A new method for fluoroscopic tracking of a proximal bone fragment in femoral fracture reduction is presented. The proposed method combines 2-D and 3-D image registration from single-view fluoroscopy with tracking of the head center position of the proximal femoral fragment to improve the accuracy of fluoroscopic registration without the need for repeated manual adjustment of the C-arm as required in stereo-view registrations. Kinematic knowledge of the hip joint, which has a positional correspondence with the femoral head center and the pelvis acetabular center, allows the position of the femoral fragment to be determined from pelvis tracking. The stability of the proposed method with respect to fluoroscopic image noise and the desired continuity of the fracture reduction operation is demonstrated, and the accuracy of tracking is shown to be superior to that achievable by single-view image registration, particularly in depth translation.

Intranasal Administration of Whole Inactivated Influenza Virus Vaccine as a Promising Influenza Vaccine Candidate.

The effect of the current influenza vaccine, an inactivated virus vaccine administered by subcutaneous/intramuscular injection, is limited to reducing the morbidity and mortality associated with seasonal influenza outbreaks. Intranasal vaccination, by contrast, mimics natural infection and induces not only systemic IgG antibodies but also local secretory IgA (S-IgA) antibodies found on the surface of the mucosal epithelium in the upper respiratory tract. S-IgA antibodies are highly effective at preventing virus infection. Although the live attenuated influenza vaccine (LAIV) administered intranasally can induce local antibodies, this vaccine is restricted to healthy populations aged 2-49 years because of safety concerns associated with using live viruses in a vaccine. Instead of LAIV, an intranasal vaccine made with inactivated virus could be applied to high-risk populations, including infants and elderly adults. Normally, a mucosal adjuvant would be required to enhance the effect of intranasal vaccination with an inactivated influenza vaccine. However, we found that intranasal administration of a concentrated, whole inactivated influenza virus vaccine without any mucosal adjuvant was enough to induce local neutralizing S-IgA antibodies in the nasal epithelium of healthy individuals with some immunological memory for seasonal influenza viruses. This intranasal vaccine is a novel candidate that could improve on the current injectable vaccine or the LAIV for the prevention of seasonal influenza epidemics.

Intranasal administration of adjuvant-combined recombinant influenza virus HA vaccine protects mice from the lethal H5N1 virus infection.

Attenuated recombinant H5N1 influenza virus was constructed to develop a safe H5N1 influenza vaccine. The immunogenicity and protective effect of the vaccine prepared from haemagglutinin-modified recombinant H5N1 influenza virus was evaluated in mice intranasally co-administered with cholera toxin B subunit containing a trace amount of holotoxin (CTB*), synthetic double-stranded RNA, poly (I:C) or chitin microparticles (CMP) as adjuvants. Intranasal administration of recombinant H5 HA split vaccine with CTB* or poly(I:C) and/or CMP elicited an immunological response with both anti-H5 HA IgA in the nasal wash and anti-H5 HA IgG antibody in the serum, and showed a protective against lethal H5N1 A/Hong Kong/483/97 (HK483) infection. We also demonstrated that intranasal co-administration of antigen with both poly (I:C) and CMP enhanced the expression of Toll-like receptor (TLR) 3, TLR7 in the spleen. These results indicate that poly (I:C) and CMP are highly effective as mucosal adjuvants for use with the nasal H5N1 vaccine.

[Intranasal inactivated influenza vaccine].

Natural influenza virus infection is well known to be superior to parenteral inactivated vaccines, which induce serum IgG antibodies(Abs) alone, in inducing the broad-spectrum cross-protection against variant virus infection. Secretory IgA Abs, which provide cross-protection strongly against infection with variant viruses within the same subtype mainly in the upper respiratory tract, serum IgG Abs, which provide cross-protection weakly against infection with variant viruses mainly in the lower respiratory tract, and cytotoxic T lymphocytes, which provide cross-protection against infection with different subtype viruses and whose role is not always big in humans, are involved in the defence mechanisms induced by natural infection. The development of intranasal inactivated vaccine, capable of inducing both IgA and IgG Abs, is important to improve the efficacy of current inactivated vaccine.

Graphene/nitrogen-functionalized graphene quantum dot hybrid broadband photodetectors with a buffer layer of boron nitride nanosheets.

A high performance hybrid broadband photodetector with graphene/nitrogen-functionalized graphene quantum dots (NGQDs@GFET) is developed using boron nitride nanosheets (BN-NSs) as a buffer layer to facilitate the separation and transport of photoexcited carriers from the NGQD absorber. The NGQDs@GFET photodetector with the buffer layer of BN-NSs exhibits enhanced photoresponsivity and detectivity in the deep ultraviolet region of ca. 2.3 × 106 A W-1 and ca. 5.5 × 1013 Jones without the application of a backgate voltage. The high level of photoresponsivity persists into the near-infrared region (ca. 3.4 × 102 A W-1 and 8.0 × 109 Jones). In addition, application in flexible photodetectors is demonstrated by the construction of a structure on a polyethylene terephthalate (PET) substrate. We further show the feasibility of using our flexible photodetectors towards the practical application of infrared photoreflectors. Together with the potential application of flexible photodetectors and infrared photoreflectors, the proposed hybrid photodetectors have potential for use in future graphene-based optoelectronic devices.

Intranasal Inactivated Influenza Vaccines: a Reasonable Approach to Improve the Efficacy of Influenza Vaccine?

Influenza is a contagious, acute respiratory disease caused by the influenza virus. The mucosal lining in the host respiratory tract is not only the site of virus infection, but also the site of defense; it is at this site that the host immune response targets the virus and protects against reinfection. One of the most effective methods to prevent influenza is to induce specific antibody (Ab) responses in the respiratory tract by vaccination. Two types of influenza vaccines, intranasal live attenuated influenza virus (LAIV) vaccines and parenteral (injectable) inactivated vaccines, are currently used worldwide. These vaccines are approved by the European Medicines Agency (EMA) and the US Food and Drug Administration. Live attenuated vaccines induce both secretory IgA (S-IgA) and serum IgG antibodies (Abs), whereas parenteral vaccines induce only serum IgG Abs. However, intranasal administration of inactivated vaccines together with an appropriate adjuvant induces both S-IgA and IgG Abs. Several preclinical studies on adjuvant-combined, nasal-inactivated vaccines revealed that nasal S-IgA Abs, a major immune component in the upper respiratory tract, reacted with homologous virus hemagglutinin (HA) and were highly cross-reactive with viral HA variants, resulting in protection and cross-protection against infection by both homologous and variant viruses, respectively. Serum-derived IgG Abs, which are present mainly in the lower respiratory tract, are less cross-reactive and cross-protective. In addition, our own clinical trials have shown that nasal-inactivated whole virus vaccines, including a built-in adjuvant (single-stranded RNA), induced serum hemagglutination inhibition (HI) Ab titers that fulfilled the EMA criteria for vaccine efficacy. The nasal-inactivated whole virus vaccines also induced high levels of nasal HI and neutralizing Ab titers, although we have not yet evaluated the nasal HI titers due to the lack of official criteria to establish efficacy based on this parameter. Data suggest that adjuvant-combined nasal-inactivated vaccines have advantages over the current injectable vaccine because the former induce both S-IgA and serum IgG Abs. In addition, nasal-inactivated vaccines seem to be superior to the LAIV vaccines, because non-infectious preparations could be used in high-risk groups. Thus, the development of intranasal inactivated vaccines is recommended, because such vaccines are expected to improve the efficacy of influenza vaccines.

Mechanisms of broad cross-protection provided by influenza virus infection and their application to vaccines.

Mice recovered from influenza A virus infection have been shown to be cross-protected against challenge infection with either drift viruses within a subtype (subtype-specific immunity) or different subtype viruses (heterosubtypic immunity). The mechanisms of broad-spectrum of cross-protection could be explained as follows. (i) Pre-existing S-IgA and IgG antibodies (Abs) induced by infection are involved in the elimination of challenge viruses by forming virus-Ig complexes shortly after re-infection. Due to their polymeric nature, the S-IgA Abs, existing more abundant on the mucosa than are IgG Abs, are strongly cross-reactive with challenge viruses, whereas the IgG Abs are weakly cross-reactive with challenge viruses, due to their monomeric nature. The specificity of Abs is directed mainly at hemagglutinin and neuraminidase. (ii) CD8+ memory T cells induced by infection are involved in the elimination of challenge viruses by the accelerated killing of host cells infected with different subtype viruses from day 3 onwards after re-infection. The specificity of memory T cells is directed against viral internal proteins. (iii) The accelerated IgA and IgG Ab responses, produced by B memory cells after a challenge, are also involved in cross-protection from day 4 onwards after re-infection. (iv) In the epithelial cells of infected mice, dimeric IgA that is trafficked through the epithelial cells can contribute to the prevention of viral assembly by binding to newly synthesized viral proteins. Natural infection is well known to be superior to parenteral inactivated vaccines in inducing the broad-spectrum cross-protection. To improve the efficacy of current inactivated vaccines, many trials have been conducted to mimic natural infection, including intranasal or epidermal administration of inactivated vaccine with or without an adjuvant; such studies are still ongoing. In the near future, some of these trials may provide new, safer and more effective broad-spectrum vaccines than those currently available.

Enhanced resistancy of thioredoxin-transgenic mice against influenza virus-induced pneumonia.

Thioredoxin (TRX) is a small redox-active protein with anti-oxidant effect and redox-regulating functions. Using TRX transgenic (Tg) mice in which human TRX is overexpressed systemically under the control of beta-actin promoter, the effects of influenza virus infection were examined in TRX Tg mice and wild type C57BL/6 mice. (1) Median lethal dose (LD50) against influenza virus infection in wild-type C57BL/6 mice was 10(-5.3) dilution, while that of TRX Tg mice was 10(-4.2) dilution. Thus, TRX Tg mice were more resistant against the virus infection than wild-type mice. (2) The body weights of wild-type mice 7 days after infection with a sublethal dose of the virus (10(-6) dilution) decreased significantly, whereas those of TRX Tg mice increased slightly. (3) Histopathology of the lung at 3 weeks after sublethal infection of influenza virus showed that severe alveolar or bronchiolar destruction was observed in wild-type mice, while mild viral pneumonia was seen in the TRX Tg mice. (4) Local (IgA) and systemic (IgG) antibody productions against influenza virus hemagglutinin in mice surviving 3 weeks after infection were similar between wild-type and TRX Tg mice. These results indicate that overexpression of TRX in Tg mice suppresses the inflammatory overshoot of viral pneumonia caused by influenza virus infection, resulting in the reduction of mortality without affecting the host's systemic immune responses to the infection. TRX may play some important roles in regulating the inflammatory process in the primary host defense against infection.

Induction of heat shock protein 40 and GrpE mRNAs following transient focal cerebral ischemia in the rat.

Cerebral ischemia is associated with the induction of several heat shock proteins (HSPs), but the effects on HSP40 and GrpE are less clear. The present study investigated the induction of Hsp40 and GrpE mRNAs following 30 min of middle cerebral artery occlusion in the rat model. Reverse transcription-polymerase chain reaction (PCR) and in situ hybridization analyses showed significant induction of both mRNAs in the ischemic cortex. These results demonstrate the synergic induction of HSP70 molecular chaperone machinery in cerebral ischemia.