OX40 ligand newly expressed on bronchiolar progenitors mediates influenza infection and further exacerbates pneumonia.

Influenza virus epidemics potentially cause pneumonia, which is responsible for much of the mortality due to the excessive immune responses. The role of costimulatory OX40-OX40 ligand (OX40L) interactions has been explored in the non-infectious pathology of influenza pneumonia. Here, we describe a critical contribution of OX40L to infectious pathology, with OX40L deficiency, but not OX40 deficiency, resulting in decreased susceptibility to influenza viral infection.

Good manufacturing practices production of a purification-free oral cholera vaccine expressed in transgenic rice plants.

The first Good Manufacturing Practices production of a purification-free rice-based oral cholera vaccine (MucoRice-CTB) from transgenic plants in a closed cultivation system yielded a product meeting regulatory requirements. Despite our knowledge of their advantages, plant-based vaccines remain unavailable for human use in both developing and industrialized countries. A leading, practical obstacle to their widespread use is producing plant-based vaccines that meet governmental regulatory requirements.

A Lipopolysaccharide from Pantoea Agglomerans Is a Promising Adjuvant for Sublingual Vaccines to Induce Systemic and Mucosal Immune Responses in Mice via TLR4 Pathway.

A lipopolysaccharide from Pantoea agglomerans (LPSpa) has been applied to various fields for human use as a Toll-like receptor 4 ligand and its safety has been confirmed. Here, we showed for the first time the application of LPSpa as an effective mucosal adjuvant for activating vaccine-induced antigen specific immune responses. Mice sublingually immunized with influenza vaccine (HA split vaccine) with LPSpa induced both HA-specific IgG (systemic) and IgA (mucosal) antibody responses, which led to a significant increase in survival rate against lethal influenza virus challenge compared with subcutaneous vaccination.

Identification of Bangladeshi domestic cats with GM1 gangliosidosis caused by the c.1448G>C mutation of the feline GLB1 gene: case study.

GM1 gangliosidosis is a fatal, progressive neurodegenerative lysosomal storage disease caused by mutations in the β-galactosidase (GLB1) gene. In feline GM1 gangliosidosis, a pathogenic mutation (c.1448G>C) in the feline GLB1 gene was identified in Siamese cats in the United States and Japan and in Korat cats in Western countries.

Comparison of the cross-reactive anti-influenza neutralizing activity of polymeric and monomeric IgA monoclonal antibodies.

Here we examined whether polymeric IgA (pIgA) and monomeric IgA (mIgA) antibodies differ in their ability to neutralize drift viruses within the same subtype. We used an IgA monoclonal antibody (mAb; H1-21) against influenza virus strain A/Hiroshima/52/2005 (A/Hiroshima; H3N2). The mAb was obtained after immunizing mice mucosally with a split-virion (SV) vaccine.

Mutation analysis of GM1 gangliosidosis in a Siamese cat from Japan in the 1960s.

GM1 gangliosidosis is a fatal, progressive neurodegenerative lysosomal storage disease caused by mutations of the β-galactosidase (GLB1) gene. In feline GM1 gangliosidosis, a pathogenic mutation (c.1448G>C) of the feline GLB1 gene was identified in Siamese and Korat cats previously diagnosed with the disease in the USA and Italy, respectively.

Intranasal immunization with a formalin-inactivated human influenza A virus whole-virion vaccine alone and intranasal immunization with a split-virion vaccine with mucosal adjuvants show similar levels of cross-protection.

The antigenicity of seasonal human influenza virus changes continuously; thus, a cross-protective influenza vaccine design needs to be established. Intranasal immunization with an influenza split-virion (SV) vaccine and a mucosal adjuvant induces cross-protection; however, no mucosal adjuvant has been assessed clinically. Formalin-inactivated intact human and avian viruses alone (without adjuvant) induce cross-protection against the highly pathogenic H5N1 avian influenza virus.

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.

Intranasal vaccination with pneumococcal surface protein A plus poly(I:C) protects against secondary pneumococcal pneumonia in mice.

Effective pneumococcal vaccines are required for preventing secondary bacterial pneumonia, a life-threatening condition, during epidemics of influenza. We examined whether nasal administration of a low dose of pneumococcal surface protein A (PspA) plus polyinosinic-polycytidylic acid (poly(I:C)) could protect against a fatal secondary pneumococcal pneumonia after influenza A virus infection in mice. PspA-specific IgG but not IgA level was higher in the airways and blood of mice nasally administered a low dose of PspA plus poly(I:C) than in mice nasally administered PspA alone or poly(I:C) alone.

Plasmacytoid dendritic cells delineate immunogenicity of influenza vaccine subtypes.

A variety of different vaccine types are available for H1N1 influenza A virus infections; however, their immunological mechanisms of action remain unclear. Here, we show that plasmacytoid dendritic cells (pDCs) and type I interferon (IFN)-mediated signaling delineate the immunogenicity of live attenuated virus, inactivated whole-virus (WV), and split-virus vaccines. Although Toll-like receptor 7 acted as the adjuvant receptor for the immunogenicity of both live virus and WV vaccines, the requirement for type I IFN production by pDCs for the immunogenicity of the vaccines was restricted to WV.

Effects of acetazolamide on transient K+ currents and action potentials in nodose ganglion neurons of adult rats.

The aim of the present study was to determine whether acetazolamide (AZ) contributes to the inhibition of the fast inactivating transient K(+) current (I(A) ) in adult rat nodose ganglion (NG) neurons. We have previously shown that pretreatment with either AZ or 4-AP attenuated or blocked the CO(2) -induced inhibition of slowly adapting pulmonary stretch receptors in in vivo experiments. The patch-clamp experiments were performed by using the isolated NG neurons.

Poly(gamma-glutamic acid) nano-particles combined with mucosal influenza virus hemagglutinin vaccine protects against influenza virus infection in mice.

Adding poly(gamma-glutamic acid) nano-particles (gamma-PGA-NPs), a safe, natural material, to subcutaneous immunization with influenza virus hemagglutinin (HA) vaccine increases the protective immune responses against influenza virus in mice. Here, we examined whether intranasal administration of the HA vaccine with gamma-PGA-NPs would induce protection from influenza virus challenge in mice. Intranasal immunization with the mixture of gamma-PGA-NPs and HA vaccine from an influenza virus strain A/PR/8/34 (H1N1) or A/New Caledonia/20/99 (H1N1) enhanced protection of mice from A/PR/8/34 infection.

Measurement of varicella-zoster virus (VZV)-specific cell-mediated immunity: comparison between VZV skin test and interferon-gamma enzyme-linked immunospot assay.

Cell-mediated immunity (CMI) is critical for the prevention and control of varicella-zoster virus (VZV)-related disease. To assess CMI to VZV, a varicella skin test and interferon-gamma enzyme-linked immunospot (ELISPOT) assay were both performed in healthy volunteers, and the results were compared. A total of 151 subjects were examined: 16 aged 20-29 years, 26 aged 30-39 years, 18 aged 40-49 years, 73 aged 50-59 years, and 18 aged 60-69 years.

Differential role of TLR- and RLR-signaling in the immune responses to influenza A virus infection and vaccination.

The innate immune system recognizes influenza A virus via TLR 7 or retinoic acid-inducible gene I in a cell-type specific manner in vitro, however, physiological function(s) of the MyD88- or interferon-beta promoter stimulator 1 (IPS-1)-dependent signaling pathways in antiviral responses in vivo remain unclear. In this study, we show that although either MyD88- or IPS-1-signaling pathway was sufficient to control initial antiviral responses to intranasal influenza A virus infection, mice lacking both pathways failed to show antiviral responses, resulting in increased viral load in the lung. By contrast, induction of B cells or CD4 T cells specific to the dominant hemagglutinin or nuclear protein Ags respectively, was strictly dependent on MyD88 signaling, but not IPS-1 signaling, whereas induction of nuclear protein Ag-specific CD8 T cells was not impaired in the absence of either MyD88 or IPS-1.

Temporomandibular joint inflammation decreases the voltage-gated K+ channel subtype 1.4-immunoreactivity of trigeminal ganglion neurons in rats.

Voltage-gated K+ (Kv) channels are one of the important physiological regulators of the membrane potentials in excitable cells, including sensory ganglion neurons. The aim of the present study was to investigate whether temporomandibular joint (TMJ) inflammation alters expression of Kv channel subtype 1.4 (Kv1.

Effect of 8-bromo-cAMP on the tetrodotoxin-resistant sodium (Nav 1.8) current in small-diameter nodose ganglion neurons.

We examined whether 8-bromo-cAMP (8-Br-cAMP)-induced modification of tetrodotoxin-resistant (TTX-R) sodium current in neonatal rat nodose ganglion neurons is mediated by the activation of protein kinase A (PKA) and/or protein kinase C (PKC). In 8-Br-cAMP applications ranging from 0.001 to 1.

Enhanced excitability of nociceptive trigeminal ganglion neurons by satellite glial cytokine following peripheral inflammation.

Peripheral nerve injury activates satellite cells to produce interleukin 1beta (IL-1beta) which mediates inflammation and hyperalgesia. This study investigated the hypothesis that activation of satellite glial cells modulates the excitability of trigeminal ganglion (TRG) neurons via IL-1beta following inflammation. Inflammation was induced by injection of complete Freund's adjuvant (CFA) into the whisker pad area.

N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists suppress the superior sagittal sinus-evoked activity of C1 spinal neurons responding to tooth pulp electrical stimulation in rats.

The aim of the present study was to determine whether there is a convergence of inputs from tooth pulp (TP) and the superior sagittal sinus (SSS) on rat C1 spinal neurons, and to examine the effects of iontophoretically applied N-methyl-D: -aspartate (NMDA) and non-NMDA receptor antagonists on the SSS-evoked activity of C1 neurons. Extracellular single unit-recordings were made from 20 C1 units responding to TP electrical stimulation with a constant temporal relationship to a digastric electromyogram signal, using a multibarrel electrode in pentobarbital-anesthetized rats. Ninety percent of C1 neurons (18/20) responding to TP stimulation also responded to the SSS stimulation.

Tooth-pulp-evoked rostral spinal trigeminal neuronal excitation is attenuated by the activation of 5-HT3 receptors via GABAergic interneurons in the rat.

The effect of iontophoretic application of the 5-HT3 receptor agonist, phenylbiguanide (PBG), on the excitation of the trigeminal spinal nucleus oralis (TSNO) neurons to tooth-pulp (TP) stimulation was examined. The PBG application inhibited the TP-evoked TSNO neuronal excitation, and this inhibition was completely blocked by co-application of a GABAA receptor antagonist, bicuculline. The results suggest that the activation of 5-HT3 receptors elicits GABA release in the TSNO.

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.

The inhibitory effect of ouabain on the response of slowly adapting pulmonary stretch receptors to hyperinflation in the rabbit.

The combined effects of ouabain (Na(+)-K(+) ATPase inhibitor) and hyperinflation (inflation volume=three tidal volumes) on slowly adapting pulmonary stretch receptors (SARs) were studied before and after administration of nifedipine (an L-type Ca(2+) channel blocker) and KB-R7943 (a reverse-mode Na(+)-Ca(2+) exchanger blocker) in anesthetized, artificially ventilated rabbits after bilateral vagotomy. Before ouabain administration, hyperinflation stimulated SAR activity. After 20 min of ouabain administration (30 microg/kg) the SARs increased discharge rates in normal inflation.

Activation of NK1 receptor of trigeminal root ganglion via substance P paracrine mechanism contributes to the mechanical allodynia in the temporomandibular joint inflammation in rats.

The aim of this study was to investigate whether under in vivo conditions, temporomandibular joint (TMJ) inflammation alters the excitability of Abeta-trigeminal root ganglion (TRG) neuronal activity innervating the facial skin by using extracellular electrophysiological recording with multibarrel-electrodes. Complete Freund's adjuvant (CFA) was injected into the rat TMJ. Threshold for escape from mechanical stimulation applied to the whisker pad area in inflamed rats (2 days) was significantly lower than that in control rats.

Estimation of the neuraminidase content of influenza viruses and split-product vaccines by immunochromatography.

The neuraminidase (NA) of the influenza virus, as well as the hemagglutinin, is the most important protective components in the vaccine. However, the NA content of the vaccine remains to be standardized because of the labile nature of this glycoprotein during various chemical treatments and storage. In the present study, the NA content of the split-product (SP) vaccine (virus treated with ether then formalin) was estimated together with that of the virus by an immunochoromatography technique using monoclonal antibodies (mAbs) to viral NA for A/Panama/2007/99 (A/Pa) (H3N2), B/Shangdong/7/97 (B/S) or A/New Caledonia/20/99 (A/NC) (H1N1) viral strains.

Immunohistochemical co-expression of carbonic anhydrase II with Kv1.4 and TRPV1 in rat small-diameter trigeminal ganglion neurons.

The co-expression of carbonic anhydrase II (CAII) with the voltage-gated potassium channel subtype 1.4 (Kv1.4) or the vanilloid receptor (TRPV1) was examined in adult rat trigeminal ganglion (TG) neurons by using the immunofluorescence method.

Prostaglandin E2-induced modification of tetrodotoxin-resistant Na+ currents involves activation of both EP2 and EP4 receptors in neonatal rat nodose ganglion neurones.

1 The aim of the present study was to investigate which EP receptor subtypes (EP1-EP4) act predominantly on the modification of the tetrodotoxin-resistant Na+ current (I(NaR)) in acutely isolated neonatal rat nodose ganglion (NG) neurones. 2 Of the four EP receptor agonists ranging from 0.01 to 10 muM, the EP2 receptor agonist (ONO-AE1-259, 0.