Saitama, Japan
Saitama, Japan

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Matsumoto T.,Kitasato University | Matsumoto T.,Kitasato Institute | Noguchi M.,Kitasato University | Hayashi O.,Kagawa Nutrition University | And 3 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2010

The effect of oral administration of Hochuekkito (HET; Bu-Zhong-Yi-Qi-Tang in Chinese), a traditional Japanese herbal medicine, on mucosal IgA immune response was investigated. To induce the antigen-specific antibodies in mucosal site, ovalbumin (OVA)-entrapped biodegradable microparticles (OVA-microparticles) were used as an antigen. Mice were orally immunized with OVA-microparticles for 3 successive days with intragastric gavage. From 7 days after the onset of immunization, the mice were boosted twice a week with the same antigen for 2 weeks. HET or water alone was orally administered to the mice via the intragastric route from 7 days before to 27 days after the onset of immunization. Although no significant change in total secretory IgA antibody level was observed in intestinal and nasal washes, OVA-specific IgA titers in intestinal washes were significantly enhanced by oral administration of HET. When lymphocytes from spleen, peripheral blood and Payers patches were investigated for cytokines production, it was found that the IFN-γ secretion from the lymphocytes was increased by the administration of HET. Microarray analysis of Peyers patch cells revealed enhanced expression of L-selectin gene. The increase of L-selectin positive cells in B lymphocytes fraction was observed in Peyers patch cells and peripheral blood mononuclear cells by flow cytometry. These results suggest that the enhanced IFN-γ secretion and increased population of L-selectin positive B lymphocytes by orally administered HET may partly contribute to enhancement of IgA immune response against intestinal antigens, and orally administered HET may strengthen defensive systems against various pathogens and food antigens in intestine.


Ohkura T.,Kitasato University | Kikuchi Y.,Kitasato University | Kikuchi Y.,Iwaki Meisei University | Kono N.,Japan National Institute of Infectious Diseases | And 5 more authors.
Biochemical and Biophysical Research Communications | Year: 2012

The global spread of highly pathogenic avian influenza A H5N1 viruses raises concerns about more widespread infection in the human population. Pre-pandemic vaccine for H5N1 clade 1 influenza viruses has been produced from the A/Viet Nam/1194/2004 strain (VN1194), but recent prevalent avian H5N1 viruses have been categorized into the clade 2 strains, which are antigenically distinct from the pre-pandemic vaccine. To understand the antigenicity of H5N1 hemagglutinin (HA), we produced a neutralizing monoclonal antibody (mAb12-1G6) using the pre-pandemic vaccine. Analysis with chimeric and point mutant HAs revealed that mAb12-1G6 bound to the loop (amino acid positions 140-145) corresponding to an antigenic site A in the H3 HA. mAb12-1G6 failed to bind to the mutant VN1194 HA when only 3 residues were substituted with the corresponding residues of the clade 2.1.3.2 A/Indonesia/5/05 strain (amino acid substitutions at positions Q142L, K144S, and S145P), suggesting that these amino acids are critical for binding of mAb12-1G6. Escape mutants of VN1194 selected with mAb12-1G6 carried a S145P mutation. Interestingly, mAb12-1G6 cross-neutralized clade 1 and clade 2.2.1 but not clade 2.1.3.2 or clade 2.3.4 of the H5N1 virus. We discuss the cross-reactivity, based on the amino acid sequence of the epitope. © 2011 Elsevier Inc.


Arashima Y.,Nihon University | Yakubo S.,Nihon University | Ueda Y.,Nihon University | Nagaoka H.,Japan Institute for Environmental Sciences | And 3 more authors.
International Medical Journal | Year: 2013

Introduction: It has been claimed that 1-2% of children are infected with Coxiella. burnetii (C. burnetii) but reports of such children are few. In addition, hitherto there have been no reports of otalgia arising from C. burnetii infection. Case: The present case concerns a boy of 11 years with severe otalgia who approximately 6 months previously had begun complaining of a sense of constriction in the throat and bronchi and had come to be suspected of feigning illness. After serologic testing revealed C. burnetii infection, we treated him with Minocycline for six weeks, which led to improvement in his symptoms. It appears that this is the first reported case of otalgia due to C. burnetii infection. Conclusion: In otorhinology, when there are difficulties in pinning down the cause of symptoms and no signs of systemic inflammation, when severe otalgia is present despite the absence of obvious physical signs, it may be appropriate to consider C. burnetii as a possible cause. © 2013 Japan International Cultural Exchange Foundation and Japan Health Sciences University.


Arashima Y.,Nihon University | Yakubo S.,Nihon University | Nagaoka H.,Japan Institute for Environmental Sciences | Komiya T.,Kitasato Institute | And 3 more authors.
International Medical Journal | Year: 2012

We report a 46-year-old male infected with Coxiella burnetii, complaining of slight fever, general fatigue, and trouble sleeping. Minocycline therapy for 3 months relieved his symptoms, including a depressive state, resulting in thoughts of death. This case is the first report on post-Q fever fatigue syndrome associated with depression. © 2012 Japan International Cultural Exchange Foundation & Japan Health Sciences University.


Hirose T.,Kitasato Institute | Maita N.,Kitasato University | Gouda H.,Tokushima University | Koseki J.,Tokushima University | And 10 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2013

The Huisgen cycloaddition of azides and alkynes, accelerated by target biomolecules, termed in situ click chemistry," has been successfully exploited to discoèer highly potent enzyme inhibitors. We haèe preèiously reported a specific Serratia marcescens chitinase B (SmChiB)-templated syn-triazole inhibitor generated in situ from an azide-bearing inhibitor and an alkyne fragment. Seèeral in situ click chemistry studies haèe been reported. Although some mechanistic eèidence has been obtained, such as X-ray analysis of [protein]-[click ligand"] complexes, indicating that proteins act as both mold and template between unique pairs of azide and alkyne fragments, to date, obserèations haèe been based solely on postclick" structural information. Here, we describe crystal structures of SmChiB complexed with an azide ligand and an O-allyl oxime fragment as a mimic of a click partner, reèealing a mechanism for accelerating syn-triazole formation, which allows generation of its own distinct inhibitor. We haèe also performed density functional theory calculations based on the X-ray structure to explore the acceleration of the Huisgen cycloaddition by SmChiB. The density functional theory calculations reasonably support that SmChiB plays a role by the cage effect during the pretranslation and posttranslation states of selectièe syn-triazole click formation.


Yakubo S.,Nihon University | Ueda Y.,Nihon University | Tanekura N.,Nihon University | Arashima Y.,Nihon University | And 4 more authors.
International Medical Journal | Year: 2013

Introduction: The present paper reports on a case in which Shakuyaku-kanzo-To (SKT), a Kampo formula, proved effective in treating a patient with Coxiella burnetii (C. burnetii) infection complaining of muscle spasms. Clinical report: A 71-year-old woman came to our clinic complaining of a sensation of spasms in her left hand, low-grade fever in the afternoons, and general malaise. Six years previously, she had been bitten by a stray cat in the second finger of her left hand, and the low-grade fever and general malaise had been fairly constant since that time. Two months prior to her visit, she had started to experience sensations of spasm in her left arm that lasted for between one and two minutes. We administered Tsumura SKT extract granules (7.5 g/day), a Kampo formula known to ameliorate muscle contractions, and the sensation of spasm disappeared. Based on C. burnetii antibody titers, we judged that C. burnetii infection was the cause of her symptom. Conclusion: Use of SKT in cases of this kind featuring numbness or spasm caused by C. burnetii warrants further research. © 2013 Japan International Cultural Exchange Foundation & Japan Health Sciences University.


Yakubo S.,Nihon University | Ueda Y.,Nihon University | Tanekura N.,Nihon University | Arashima Y.,Nihon University | And 3 more authors.
International Medical Journal | Year: 2012

Introduction: Marmion et al. recently reported a new condition, post-Q fever fatigue syndrome (QFS), in which nonspecific symptoms such as a slight fever, general malaise, headache, arthralgia, and myalgia continue indefinitely after a Q fever infection with Coxiella burnetii (C. burnetii). Case: We report the case of a 53-year-old male infected with C. burnetii, who complained of nausea, stomach pain, an abnormal sensation in the mouth, sore throat, general fatigue, and trouble sleeping, symptoms which suggested QFS. An evaluation with the self-rating depression scale led to the conclusion that the patient was in a depressive state, which can sometimes lead to suicide. In this case, the patient did indeed attempt suicide in spite of treatment with an antidepressant as well as an antibiotic against the C. burnetti infection. Conclusion: This report is the first case of a patient led to attempt suicide due to depression arising from QFS. © 2012 Japan International Cultural Exchange Foundation and Japan Health Sciences University.


Komatsu E.,Kitasato Institute | Yamaguchi F.,Kitasato Institute | Abe A.,Kitasato University | Weiss A.A.,University of Cincinnati | Watanabe M.,Kitasato University
Clinical and Vaccine Immunology | Year: 2010

The Bordetella pertussis pertussis toxin and pertactin (Prn) are protective antigens and are contained in acellular pertussis vaccines. Polymorphisms in the A subunit of pertussis toxin (PtxA) and pertactin have been proposed to mediate vaccine resistance and contribute to pertussis reemergence. To test this hypothesis, previous studies compared clinical isolates expressing different alleles for the proteins. However, other virulence factors or virulence factor expression levels also may vary, confounding the analysis. To overcome these limitations, we constructed isogenic mutants of B. pertussis Tohama expressing the alleles ptxA1 or ptxA2 and prn1 or prn2 and compared the efficacies of an acellular pertussis vaccine against the mutants in a mouse model. While the vaccine was effective against all of the B. pertussis strains regardless of the allele expression pattern, the strain expressing ptxA1 and prn2 displayed a survival advantage over the other strains. These results suggest that an allele shift to the ptxA1 prn2 genotype may play a role in the emergence of pertussis in vaccinated populations. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Komatsu E.,Kitasato Institute | Yamaguchi F.,Kitasato Institute | Eguchi M.,Kitasato University | Watanabe M.,Kitasato University
Vaccine | Year: 2010

Bordetella parapertussis causes typical whooping cough, as does Bordetella pertussis. However, current commercial vaccines are ineffective against B. parapertussis. In an effort to develop vaccines that are effective in protecting against both B. pertussis and B. parapertussis, we examined the protective effects of vaccines prepared from whole-cells and from recombinant proteins derived from B. parapertussis in a mouse intranasal challenge model. We confirmed current pertussis vaccines did not induce protective immunity against B. parapertussis in the mouse model. A whole-cell vaccine prepared from B. parapertussis induced protective immunity against B. parapertussis but not against B. pertussis, suggesting a combination of a current pertussis vaccine with a whole-cell parapertussis vaccine might prevent whooping cough caused by both species of Bordetella. We also found that filamentous hemagglutinin was a protective antigen of B. parapertussis. Our observations should lead to the development of new pertussis vaccines that can control the two prevalent forms of whooping cough. © 2010 Elsevier Ltd. All rights reserved.


Ito N.,Kitasato Institute | Nagai T.,Kitasato Institute | Nagai T.,Kitasato University | Oikawa T.,Kitasato Institute | And 3 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2011

Perillae Herba (a leaf of Perilla frutescens) has been prescribed as one of the component herbs in certain Kampo (Japanese herbal) medicines that are used clinically for the improvement of depressive mood. l-Perillaldehyde (PAH) is a major component in the essential oil containing in Perillae Herba, but its antidepressant-like effect has not been reported. To clarify the antidepressant-like effect of PAH, the inhaled effect of PAH on stress-induced depression-like model mice prepared by subjection to a combination of forced swimming and chronic mild stresses was investigated. The degree of the depression-like state was measured by the animal's duration of immobility using a forced swimming test. Inhalation of PAH (0.0965 and 0.965 mg/mouse/day, 9 days) significantly shortened the duration of immobility of the depression-like model mice and did not affect locomotor activity. However, another odor substance, cinnamaldehyde containing in Cinnamomi Cortex, exhibited no reduction in the immobility. The reduction in the immobility induced by the inhalation of PAH was prevented on anosmia-induced mice prepared by intranasal irrigation with zinc sulfate. These results suggest that the inhalation of PAH shows antidepressant-like activity through the olfactory nervous function. Copyright © 2011 N. Ito et al.

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