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Radioactive materials such as cesium were released into the atmosphere due to the accident at Tokyo Electric Power Company’ s Fukushima Daiichi Nuclear Power Plant following the Great East Japan Earthquake in March 2011. Fruit trees in the deciduous stage were contaminated on their surfaces, such as bark. Immediately after the accident, in collaboration with Fukushima Prefecture, we worked on elucidating the mechanism of radioactive cesium migration to fruits and developing decontamination technologies for radioactive cesium-contaminated orchards. Most of the radioactive cesium in the orchard soil remained in the surface layer of the soil. Since the roots of fruit trees are deeper than the radioactive cesium-retaining soil layer, radioactive cesium contamination of fruit trees was considered to be more influenced by transfer from the tree surfaces than from the soil. Therefore, removal of abovegroundparts, such as by bark washing and pruning, is likely effective for reducing radioactive cesium. It was also suggested that the removal of bark as soon as possible after contamination was the most important, since the migration of cesium from the bark to the inside of the tree progressed with time after the accident. In the production process of half-dried persimmons, locally namedampogaki, continuous risk management from cultivation to shipment has been implemented by ensuring that only raw fruits with a low concentration of radioactive cesium are harvested, by controlling the processing process, and inspecting the product for radioactive cesium., 2011 年3 月の東日本大震災に伴う東京電力福島第一原子力発電所事故により放射性物質が大気中に放出され，落葉期の果樹は，樹皮等の樹体表面が汚染された．福島県と連携し，果樹の樹体および果実への放射性セシウムの移行解明とその低減技術の開発に取り組んだ．土壌に沈着した放射性セシウムのほとんどが土壌表層に留まった一方で，吸収根域はそれよりも深いため，樹体内への放射性セシウムの移行は，土壌からの経根吸収よりも樹皮等の樹体表面から移行した割合が多いと考えられた．そのため，放射性セシウムの低減には，樹皮洗浄やせん定等の地上部の除去管理が有効であるが， 事故発生からの時間の経過に伴い， 樹皮から樹体内部への移行が進行するため，汚染後速やかに樹皮を除去することが最重要であることが示唆された．また，あんぽ柿の生産工程においては，放射性セシウム濃度の低い原料果実の確保，加工時の工程管理，および製品の放射性セシウム検査を行うことにより， 栽培から出荷まで一貫したリスク管理が実施されている．, 3章: 畑作物，草地，果樹における放射性セシウム移行抑制技術，および農産物の加工・調理による放射性セシウムの低減効果 /総説Chapter3: Technologies to reduce radiocesium in upland crops, grass, forage crops, fruit trees and domestic agricultural products /Review

In Japan, cultivars ‘Kober 5BB’ (Vitis berlandieri × Vitis riparia), ‘Riparia Gloire’ (V. riparia) ‘101-14’ (V. riparia × Vitis rupestris) are used as rootstocks for table or wine grapes. As newly emerging viruses were detected from some mother rootstocks, elimination of viruses from the three cultivars was performed using thermotherapy and meristem culture. Among sixteen to eighteen clones obtained, we selected six clones each in the first screening by reverse-transcription polymerase chain reaction (RT-PCR). Mixed RNA extracts from the six were analyzed by next-generation sequencing. No viruses were detected from all the clones, although some of them tested positive for viroids. Consequently, no viruses and viroids were detected from two to six clones of all the cultivars. The clones will be utilized as rootstocks for virus-free vines in Japan., 国内における生食用ブドウあるいは醸造用ブドウ栽培では, 「テレキ5BB」(Vitis berlandieri × Vitis riparia),「グロワール」(V. riparia), 「101-14」(V. riparia × Vitis rupestris) などが代表的な台木品種として使用される. 一部の台木母樹に, 新種ウイルスの感染事例が認められたことから, 熱処理と茎頂培養の併用による無毒化個体の作出を行った. 得られた16～18個体について, 逆転写ポリメラーゼ連鎖反応（RT-PCR）により一次選抜を行った. 選抜した6個体ずつを混合して, 現時点で最も信頼性の高い新たな手法である次世代シーケンス解析を用いたウイルス診断を行った. その結果, 「テレキ5BB」の一部の個体でウイロイドの陽性が認められた他は, 全ての供試個体においてウイルス感染は認められなかった. それぞれの2～6個体からはいずれのウイルス・ウイロイドも検出されず, 無毒化台木母樹としての利用が期待できる.

Sargassum horneri (Akamoku) is a brown algae and is distributed over the shallow sea of Japan, except east of Hokkaido. In the present study, we analyzed the arsenic contained in the algae, evaluated therapeutic effects of Akamoku powder against influenza A virus infection using mouse model, and virucidal activities of the extract of the algae. The inner states of Arsenic was evaluated by XAFS using a synchrotron radiation. The oral administration of Akamoku poder in influenza virus-infected mice suppressed viral proliferation in the lung, and had stimulatory effects on neutralizing antibody production. The ethanol extract of Akamoku showed potent virucidal activities against herpes simplex virus type 2, influenza A virus and feline calicivirus. In summary, Akamoku is a potential candidate for the treatment of viral infections.

Samples from Valeriana fauriei Briq. plants were collected from six prefectures to survey viral pathogens. By next-generation sequencing and RT-PCR analysis, asparagus virus 2 (AV-2), broad bean wilt virus 2 (BBWV-2), cucumber mosaic virus (CMV), gaillardia latent virus (GaILV), ligustrum necrotic ringspot virus (LNRSV), and tomato spotted wilt orthotospovirus (TSWV) were detected. Many collected samples were coinfected with 2–4 viruses. V. officinalis was also back-inoculated with one or a mixture of isolated viruses to confirm pathogenicity of isolated viruses. This report is the first of GaILV and LNRSV in Japan and the first of AV-2 on V. fauriei.

An epidemiologically successful subtypes of persistently circulating viruses such as influenza H3N2 subtype are those that can evade host s herd immunity by continuously changing their antigenicity. During the antigenic drift,the substitutions occurred on the genome are subject to selection. On the proteins that determine the antigenicity of the virus, the selection pressure is distributed, making the virus adapt to the change of host s herd immunity. On the other hand, the herd immunity reflects the change of antigenicity of the virus. To properly analyze the fate of a viral subtype that performs such antigenic drift, we introduced a new measure, meta-R0, that describes whether a subtype can persist in the face of the herd immunity mounted against each antigenic strain. The meta-R0 is defined as the expected number of the new antigenicity strains produced during the epidemic outbreak of the primary strain that will cause the next epidemic outbreak. This approach enables us to understand two contrasting epidemiological characteristics of the influenza H3N2 subtype: the persistent circulation in the human population and the slim phylogenic tree for their antigenic evolution. We revealed that by simply restricting the co-infection of viruses to the host, a viral subtype can securely persist by alternating its antigenic properties with keeping a slender phylogenetic tree shape. The coexistence of these two characteristics is protected due to the negative feedback between the within-year viral diversity and the meta-R0. Here we review epidemiological characteristics of the antigenic evolution of influenza H3N2 subtype.

The accumulations of viral RNA and siRNA in dark green and yellow tissues of mosaic leaves of Nicotiana benthamiana inoculated with a Japanese isolate (HM) or a European isolate (PSI4) of the plum pox virus strain M were compared. The accumulation of viral RNA was suppressed in the dark green tissue, but the accumulation of siRNA was higher, similarly in both strains. When the proportion of dark green areas in the five systemic leaf positions from the 9th to the 13th leaf of N. benthamiana was compared between the strains, the result was significantly higher in HM at all leaf positions, reaching 100% in the 13th leaf. Comparison of the amino acid sequence of the RNA silencing suppressor domain in the two strains showed differences in two residues upstream of N' terminus of the FRNK motif in that.

Plum pox virus (PPV) is regarded as an agriculturally important virus outside of Japan, and molecular biological analysis using infectious cDNA clones is widely performed for its pathogenicity analysis. Therefore, the purpose of this study is to construct infectious cDNA clones of PPV isolated in Japan and to establish research methods using infectious cDNA clones in Japanese apricot and Nicotiana plants. The cDNA clones of Japanese isolates using the 35S promoter were constructed, and the infectivity was confirmed in Nicotiana benthamiana. Then using the infectious cDNA clones, the research methods such as inoculating protoplasts of Japanese apricot and the leaves with particle delivery system (PDS) were established. Inoculation into protoplasts showed PPV infection and proliferation at the single-cell level, and inoculation with PDS showed cell-to-cell movement of PPV in the leaf. The chimeric clones between PPV Japanese isolates were constructed, and the inoculation test into N. benthamiana suggested that the 3´-latter half region of the PPV genome was involved in systemic infection.

To classify lower extremity alignment exhibited in a wall squat (WS) as a wall squat normal (WSN) or an wall squat abnormal (WSA) and to examine the association between alignment and weight bearing. ［Subjects and methods］ Subjects were 54 volunteers with a mean age of 21 years. The subjects performed a WS, and their posture was classified as WSN or WSA. The association between the squatting posture routinely adopted and weight-bearing forces exerted in different WS postures was analyzed using a paired t-test. ［Results］ A significant shift in weight-bearing force was not noted in a WSN, force shifted significantly in a WSA. ［Conclusion］ These results revealed that weight-bearing force during a WS shifts in a WSA but remains constant in a WSN.

PLoS neglected tropical diseases. 2020 Jun 22;14(6):e0008051., 令和2年度

Two types of granules were observed in the neutrophils of red seabream Pagrus major infected with body surface cloudiness (BSC). Both granule types had similar morphologies but different cytochemical characteristics to those of ordinary chromophobic granules (oβG-1, oβG-2) from non-infected fish. In this paper, we called the two granule-types from the fish infected with BSC to extraordinary chromophobic granules (type 1, eoβG-1^{BSC}； type 2, eoβG-2^{BSC}). The eoβG-1^{BSC} showed chromophobic, simple morphology (without stratified structure), peroxidase positive, SBB negative and lack of lysozomal enzymes. The eoβG-2^{BSC} was stratified granule with two-layer structure (inner eosinophilic layer (L0) and outer chromophobic layer (L1)). Lysozomal enzymes (acid phosphatase, β-glucuronidase (β-Glu) and esterases) and peroxidase (PO) were localized in L0 and L1, respectively. Both types of extraordinary granules were Sudan black B negative. Spot formation, a curious phenomenon appeared in PO- stained oβG-2 (positive L1 and negative L0), was not observed in eoβG-2^{BSC}. Almost all L0 of eoβG-2^{BSC} were β-Glu positive. Contrastively, this enzyme activity was detected in a few L0 of oβG-2.

Following the lead of Dr. Toru Nakao and Emeritus Professor Shunzo Chiba, we have conducted epidemiological and virological research on viral infections frequently observed in children. The present report is an overview of the research we have conducted. Amongst our research, we have demonstrated that the genetic evolution of the respiratory syncytial virus (RSV) undergoes both geographical and temporal clustering. Additionally, we have shown that the cytomegalovirus (CMV), a DNA virus, is widely disseminated under very stable genetic conditions. We have also clarified the situation concerning the genetic evolution of rotaviruses collected in Sapporo. In addition, we have attempted to identify the virulence-associated genome mutations of murine and human rotaviruses. Furthermore, we have indicated how the considerable genetic mutations of human parvovirus B19 could be associated with outbreaks of exanthema infectiosum every few years. Finally, we have examined viral reactivation in patients who underwent allogeneic hematopoietic stem cell transplantation and identified human herpesvirus 6 as a prominent pathogen causing important clinical events in these patients.

Background : Neuraminidase (NA) is an essential surface protein for influenza virus replication. NA inhibitors are commonly used for the treatment of influenza patients in Japan, thus emergence of resistant viruses is of great concern. We sequenced the NA segment of isolated virus from influenza patients in the 2015-16 influenza season and investigated the relation between the deduced NA amino acid sequence and the 50% inhibitory concentration (IC_50) of four NA inhibitors. Materials and Methods : A total of 59 viruses (20 A/H1N1pdm09, 19 A/H3N2, and 20 B) that showed high or low IC_50 to NA inhibitors were sequenced using a “next generation sequencer”, and the deduced amino acid sequences were analyzed. Results : Two A/H1N1pdm09 viruses that showed very high IC_50 for oseltamivir (150 nM and 130 nM) contained the H275Y mutation that has been reported in several previous seasons. Except for this H275Y mutation, no significant relation was found between the NA amino acids and the IC_50 of the four NA inhibitors in A/H1N1pdm09 viruses. There was no significant relation between the NA amino acids and the IC_50 of the four NA inhibitors for A/H3N2. NA amino acids sequences of B were divided into two groups. There was no significant relation between the NA amino acids and the IC_50 of the four NA inhibitors for B. Conclusion : The previously reported H275Y mutation that causes oseltamivir resistance was found in two A/H1N1pdm09 viruses that showed a very high IC_50 for oseltamivir. No additional NA amino acid sequences related to the IC_50 of four NA inhibitors was found in other virus in the 2015-16 influenza season.

The epithelium plays a crucial role as an interface of adaptive responses and innate responses to prevent invasion of inhaled environmental pathogens. This paper summarizes the recent progress in our understanding of the regulation of defense mechanisms in the upper airway epithelium under normal and viral-infected conditions. Among respiratory viruses, respiratory syncytial virus (RSV) is the major infectious agent that causes serious respiratory tract inflammation in infants. RSV upregulates a receptor for Streptococcus pneumoniae. In our study, we found that clarithromycin and fosfomycin significantly suppressed RSV-induced adhesion of S. pneumonia in the airway epithelium. Moreover, these macrolide antibiotics are known to exert immunomodulatory activity by reducing pro-inflammatory cytokine and interferon production. Meanwhile, we found that biological products such as curcumin and humulone have protective effects against RSV and prevent the disruption of the epithelial barrier by viral infections in human nasal mucosa. Therefore, they are useful for both the prevention and treatment of respiratory viral infections.

本研究は青枯病防除の生物防除資材であるバクテリオファージ（ファージ）の形態を透過型電子顕微鏡により観察を行った。これらのファージは、その形態的特徴からMyoviridae とPodoviridae に属するファージと類似していた。一方で、繊維状の構造をしているInoviridae と類似するファージは観察されなかった。We observed morphology of bacteriophages（ phages） for use in the biological control of the bacterial wilt disease using transmission electron microscope. These morphological characteristics of the phages were similar to those of P2 or T7 belonging to the families Myoviridae and Podoviridae. The filamentous phages belonging to the family Inoviridae were not observed in this study.

Background : Neuraminidase (NA) is a surface protein essential for influenza virus replication. NA inhibitors are commonly used for the treatment of influenza patients in Japan. Several mutations that reduce the effect of NA inhibitors have been reported. We sequenced the whole NA segment of isolated virus from influenza patients and investigated the relation between the NA amino acid sequence and the 50％ inhibitory concentration (IC_50) of four NA inhibitors. Materials and Methods : Forty A/H3N2 and 19 B influenza virus isolated from patients in the 2014/15 influenza season were analyzed. The IC_50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. Viral RNA was amplified by RT-PCR and the genome was sequenced using a next generation sequencer. The deduced amino acid sequences were analyzed. Results : There was no AA change in the NA catalytic site of the A/H3N2 and B viruses isolated in the 2014-15 influenza season. There was no significant relation between the NA amino acids and the IC_50 of the four NA inhibitors for A/H3N2 or B viruses. Conclusion : The catalytic site of NA was highly conserved for these A/H3N2 and B viruses. No emergence of NA amino acid mutations related to the sensitivity of the four currently used NA inhibitors was observed.

Prior to distributing scions of new citrus cultivars developed by the Institute of Fruit Tree Science at Japan's National Agriculture and Food Research Organization (NARO), viruses and viroids are eliminated, and the scions are inoculated with a mild Citrus tristeza virus (CTV) strain. NARO has not previously published the method for elimination and certification, and therefore, there have been some inquiries from other organizations. Therefore, we aimed to demonstrate the method for virus and viroid elimination and certification of clean citrus seedlings. We perform shoot tip grafting (Takahara et al. 1986) with some modification to recover virus- and viroid-free plants. Derived seedlings are grafted by approach for growth promotion, according to Takahara et al. (1981). We then test these seedlings for a multitude of viruses and viroids present in Japan, based on RT-PCR. The seedlings must pass the test twice ; in approximately one year, and in one and a half years after approach grafting, they are certified as virus- and viroid-free plants. M16a is used as a mild CTV strain, and the infection is confirmed according to the method of Kano et al. (2006). Virusand viroid-free and M16a-infected trees are kept in isolation structures, and scissors are disinfected at the time of pruning and correcting scions to reduce reinfection. Subsequently, we perform DNA marker typing, create a map of trees, and attach nameplates to avoid mixing up varieties. It would be impossible to certify seedlings as free for every type of virus and viroid. Nevertheless, each research station should choose the best method for the most complete elimination and certification as is possible and should distribute virus- and viroid-free seedlings to prevent multiple infections in orchards.

During my first 20 years at Sapporo Medical University, I was engaged primarily with tumor virology research in the Department of Molecular Biology, Cancer Research Institute. In the subsequent 18 years, my focus has been on research of melanocytes and melanoma in the Department of Dermatology. I have been involved in many research fields including transforming genes of human adenoviruses and human papillomaviruses (HPVs), tumor suppressor genes, adenovirus vectors, melanin biosynthesis, molecular biology of melanoma, topical treatment of skin cancer, skin-whitening agent and reactive oxygen species (ROS) and diagnosis of xeroderma pigmentosum. In this present report, I describe several research projects with which I struggled until publications. These include expression of adenovirus transforming genes, structure and function of HPV16 E6E7 genes, construction of recombinant adenoviruses, depigmentation induced by cosmetics and diagnosis of complementation groups of xeroderma pigmentosum through the use of adenovirus vectors. It is my sincere hope that this manuscript will be able to provide some semblance of assistance and encouragement to young doctors and medical students

本研究で、我々は宿主遺伝子を改変しない心筋誘導センダイウイルスベクターを新たに開発し心筋誘導を行ったところ心筋作製効率は約10%と従来法の100倍に改善し、さらに拍動する心筋細胞を約10日間で作成することができた。次にマウス心筋梗塞モデルで3つの心筋誘導遺伝子をセンダイウイルスベクターでマウス心臓内に導入したところ心筋誘導効率が約1.5%に上昇した。さらに心筋誘導センダイウイルスベクターによる治療群では、無治療群と比較して、1か月後の心臓のポンプ機能が改善した。上記に示した本研究の成果を国際科学雑誌に発表した（Miyamoto et al., Cell Stem Cell 2017）。 In this study, we show that Sendai virus (SeV) vectors expressing cardiac reprogramming factors efficiently and rapidly reprogram both mouse and human fibroblasts into integration-free iCMs via robust transgene expression. SeV-GMT generated 100-fold more beating iCMs than retroviral-GMT and shortened the duration to induce beating cells from 30 to 10 days in mouse fibroblasts. In vivo lineage tracing revealed that the gene transfer of SeV-GMT was more efficient than retroviral-GMT in reprogramming resident cardiac fibroblasts into iCMs in mouse infarct hearts. Moreover, SeV-GMT improved cardiac function and reduced fibrosis after myocardial infarction. Thus, efficient, non-integrating SeV vectors may serve as a powerful system for cardiac regeneration. Finally, we reported these result on one of authoritative scientific journals（Miyamoto et al., Cell Stem Cell 2017)., 研究種目 : 若手研究(B) 研究期間 : 2016～2018 課題番号 : 16K19428 研究分野 : 心筋再生

生体内のリプログラミングでは、共同研究でのMiyamotoらは、3つの心筋誘導遺伝子を同時に発現するセンダイウイルスベクターを開発した。この心筋誘導センダイウイルスベクターを用いて、培養皿上で、効率よく短期間でマウスおよびヒト線維芽細胞から心筋細胞をゲノムの損傷なく、直接的に作製することに成功した。さらに心筋誘導センダイウイルスベクターをマウス心筋梗塞モデルの心臓に導入すると、1週間で心筋再生が始まり、1か月後には心機能が改善することを確認した。 By the in vivo reprogramming,Miyamoto et al, who was our collaborators, developed the Sendai virus vector which developed three cardiac-specific genes at the same time. Using these cariacrecprogramming Sendai virus vectors, We succeeded in making cardiac-like cells (induced cardiomyocytes: iCMs) without the genomic damage from a mouse and a human fibroblast directly efficiently in a short term on a culture dish. Furthermore, iCM reproduction began in one week when I introduced cardiomyocytes instruction Sendai virus vector into the heart of the mouse myocardial infarction model and confirmed that cardiac function was improved one month later., 研究種目 : 基盤研究 (C) (一般) 研究期間 : 2015～2018 課題番号 : 15K09147 研究分野 : 再生医療

Background : Neuraminidase (NA) is an essential surface protein for influenza virus replication. NA inhibitors are commonly used for the treatment of influenza patients in Japan. Several mutations that reduce the effect of NA inhibitors have been reported. We sequenced the whole NA segment of isolated virus from influenza patients and investigated the relation between the NA amino acid sequence and the 50% inhibitory concentration (IC_) of four NA inhibitors. Materials and Methods : A total of 20 viruses that showed high or low IC_ of NA inhibitors were selected from A/H1N1pdm09, A/H3N2, and B isolates from the viruses isolated from patients in the 2013-14 influenza season. Viral RNA was extracted and RT-PCR was done. The amplified genome was sequenced using a “next generation sequencer”, and the deduced amino acid sequences were analyzed. Results : Two A/H1N1pdm09 viruses that showed very high IC_ for oseltamivir (150nM and130nM) contained the H275Y mutation. Otherwise, no significant relation was found between the NA amino acids and the IC_ of the four NA inhibitors. There was no significant relation between the NA amino acids and the IC_ of the four NA inhibitors for A/H3N2 viruses. The B viruses that showed a high IC_ for oseltamivir and laninamivir shared some amino acids. The B viruses that showed a high IC_ of zanamivir and peramivir also shared some amino acids. They were different from the shared amino acids found for oseltamivir and laninamivir. Conclusion : The previously reportedH275 Y mutation that causes oseltamivir resistance was found in the two A/H1N1pdm09 viruses that showed a very high IC_ for oseltamivir. No additional NA amino acid sequences related to the IC_ of the four NA inhibitors was found. The meaning of the shared amino acids among B viruses that showed a high IC_ would be an interesting target for further investigation.

日本脳炎ウイルス（JEV）感染リスク評価の一環で， 2009年と 2010年に紀伊半島大台ヶ原で捕獲されたニホンジカ Cervus nippon（以下，シカ）の JEV抗体保有状況を調査した。JEV，Oki431S株に対し 87頭中 9頭（10.3％）が，Beijing-1株に対し 1頭（ 1.1％）が抗体を保有し，年齢階層が高くなるに従い，抗体保有率の上昇傾向がみられた。これらより，シカに JEVに対する感受性がある事，大台ヶ原で JEV感染環が成立し， JEVの活動は低いが常在している地域である事が強く示唆された。 Sero-epidemiological study of Japanese encephalitis virus was conducted on sika deer (Cervus nippon) captured in Odaigahara, a forested area, on Kii peninsula, Japan, in 2009 and 2010. Nine (10.3%) out of 87 deer had neutralizing antibodies against Japanese encephalitis virus (JEV) Oki431S strain, belonging to genotype 1, a widely circulating genotype in Japan, and one (1.1%) had that against JEV Beijing-1 strain, vaccine strain, genotype 3. Prevalence rates of JEV Oki431S antibody tended to increase with age and reached 20%. This result indicates that deer are sensitive to JEV, and also strongly suggests that Odaigahara is a JEV-endemic area, with rather low virus activity.

はじめに, ヒトiPS細胞から分化誘導した神経幹細胞(NSC)にウイルスベクターを用いてHSV-tK遺伝子を導入した。脳腫瘍モデルマウスにHSV-tk発現NSCを移植し, Ganciclovir(GCV)を投与したところ, 著明な治療効果が認められた。つぎにゲノム編集によりHSV-tk遺伝子をiPSに導入したところ, 細胞毒性により安定したiPS細胞株が樹立できなかった。そこで, 遺伝子発現誘導システムを用いて, Tet-inducible HSV-tk導入iPS細胞を樹立した。治療用NSCを誘導し, 脳腫瘍モデルマウスに移植後, GCVとDoxycyclineを投与すると, 著明な治療効果が確認された。 In this study, the HSV-tK gene was firstly transduced into neural stem cells (NSCs) differentiated from human iPS cells using a viral vector. HSV-tk expressing iPS-NSCs were transplanted into human brain tumor model mice, and the effectiveness of this therapy by administration of ganciclovir (GCV) was demonstrated. Next, HSV-tk gene was introduced into iPS by genome editing, but HSV-tk expressing iPS cell line could not be established due to cytotoxicity. Then, Tet-inducible HSV-tk transduced iPS cells were established using gene expression induction system. After induction of differentiation into therapeutic NSCs, these NSCs were transplanted into brain tumor model mice. After administration of GCV with Doxycycline, a remarkable therapeutic effect of this therapy using gene expression induction system was confirmed., 研究種目 : 挑戦的萌芽研究 研究期間 : 2016～2017 課題番号 : 16K15648 研究分野 : 脳神経外科学

本研究は重症インフルエンザ感染後肺炎球菌性肺炎にヒストンアセチル化を介したエピジェネティクス制御が関与している仮説のもとに, C57BL/6マウスにインフルエンザA(PR8株)5PFUを点鼻投与し, 7日後に10の4乗CFUの肺炎球菌を点鼻感染させた。ヒストン脱アセチル化酵素(HDAC)阻害薬のTSAを1日1回腹腔内投与を行った(1mg/kg)ところ, HDAC活性は有意に低下し, 生存率も有意に向上し, 細菌の菌量や肺胞洗浄液中の総細胞数は有意に低下した。さらにTSA投与により全肺NK細胞数も有意に低下し, TSAによるインフルエンザ感染後肺炎球菌性肺炎の保護的効果に寄与している可能性が考えられた。 The hypothesis of the study was epigenetic mechanism, especially for histone acetylation, might contribute to the poor outcome of post-influenza pneumonia. Mice were infected intranasally with 1.0×104 CFU of Streptococcus pneumoniae 7 days after intranasal inoculation with 5 PFU of influenza virus A/PR8.The mice were intraperitoneally injected with the histone deacetylase (HDAC) inhibitor TSA. TSA significantly suppressed HDAC activity and significantly improved the survival rate of mice after post-influenza pneumococcal infection, which was associated with a significant decrease in bacterial load and the total cell count of the BALF. The number of natural killer cells in the lungs were significantly lower in the TSA-treated group, which may contribute to the protective effects of TSA. TSA protects mice against post-influenza pneumococcal pneumonia possibly through multiple factors, including a decrease in lung and systemic bacterial load, and suppression of systemic inflammation., 研究種目 : 基盤研究(C)(一般) 研究期間 : 2015～2017 課題番号 : 15K09580 研究分野 : 呼吸器内科学

[要旨]青枯病菌に感染した植物体から分離した細菌、KRsL-001，KRsL-003 およびKRsL-004 に感染するバクテリオファージ（ファージ）を土壌より分離した。分離したファージのうち、KRsL-001 に感染するファージは17 種類、KRsL-003 に感染するファージは1種類、KRsL-004 に感染するファージは84種類であった。これらファージが形成するプラーク形状は、周縁輪郭が明瞭なもの、および不明瞭なものの2種類に分類され、ファージの種類と使用する宿主菌によって形成されるプラークの特徴は異なることが明らかとなった。[Abstract] This study isolated bacteriophages（phages）from field soil for use in the biological control of the bacterial wilt disease pathogen Ralstonia solanacearum. Soil collected from the field was mixed with host bacteria culture solution（KRsL-001, -003, and -004）to increase the numbers of infectious phages, and incubated at room temperature for 24 h. The supernatant collected from the mixture was spotted on phage-detection plates and incubated at room temperature for 16 h. Plaques that formed on the plateswere isolated as phages that could infect KRsL-001, -003, and -004. More than 100 phages were obtained from the phage-detection plates. These phages were classified into transparent or turbid plaque types based on their plaque morphology., 近畿大学先端技術総合研究所紀要編集委員会

Herpes zoster is caused by the infection of Varicella-Zoster virus. The anatomical distribution of herpes zoster in the sacral area is only6. 9%1). Moreover, the onset rate of herpes zoster with urinary dysfunction is 0.6%1). The lesion sites of herpes zoster which cause urinary dysfunction are almost lumber and sacral areas. We describe four cases of sacral herpes zoster with urinary dysfunction in this report. All patients were elderly people (66-84 years old), and all patients were administered anti-virus drugs and alpha 1-adrenergic receptor blockers. Because of urinary retention, three patients have performed clean intermittent self-catheterization (CIC) for several weeks. As the lesions of herpes zoster healed, each patient recovered from urinary dysfunction.

Since Takatsuki’s group noticed a new disease, adult T-cell leukemia (ATL), caused by retroviral infection, many researchers tried to figure out how to prevent the transmission and how to treat the neoplasm of mature T lymphocyte for 35 years. Blood borne infection was controlled and stopped after the screening of HTLV‐1 antibody started in 1986. However, once HTLV‐1 carriers develop to aggressive type of ATL including acute type and lymphoma-type, the median survival time is about one year and the patients relapse and die even during chemotherapy. It has been hard time for patients and families more than 25 years. Then, over the last 10 years, nation-wide studies resulted in the progression of treatment strategy for improvement of ATL patients’ survival. One is allogeneic stem cell transplantation undergone in patients available for and the other is a novel monoclonal antibody against chemokine receptor CCR4 on the surface of ATL cells. The new era of ATL treatment has come. Furthermore, novel predictive marker of ATL development and biomarker of ATL treatment are investigated to release patients from this incurable disease.

Chemo-resistance to anti-cancer drugs is a major obstacle in efforts to develop a successful treatment of cancer.Resveratrol(RSV)facilitates the cellular uptake of doxorubicin through an induced down-regulation of multidrug resistance -associated protein-1(MRP1)expression.We studied whether RSV enhances the cytotoxic effect of vinblastine,vincristine,irinotecan,and etoposide in MRP1-expressing Burkitt's lymphoma Raji cells.Treatment with RSV caused decrease of cell viability in a time-and dose-dependent manner,and down-regulation of MRP1 expression in Raji cells.The cytotoxic effects of vinblastine,vincristine,and etoposide increased in RSV-pretreated Raji cells,but the effect of irinotecan did not change in the cells.These results indicate that RSV enhances the cellular uptake of vinblastine,and etoposide in Raji cell.

家畜防疫に用いられている消毒用資材の現場の使用条件下での口蹄疫ウイルスに対する消毒効果の指標とするために，口蹄疫ウイルスと同様の性状を持つ牛鼻炎B ウイルス（BRBV）とエンベロープを持たない牛アデノウイルス7 型（BAdVh7）を用いて検討した．8 種類の消毒薬（消石灰，炭酸ナトリウム，クエン酸，ヨウ素系，塩素系，アルデヒド系，複合及び水酸化ナトリウム添加消毒薬）を用いた．スラリー処理で両ウイルスに効果を示したのは消石灰と炭酸ナトリウムであった．生乳処理では，BAdVh7 に対する塩素系消毒薬以外はすべて効果を示した．土壌散布と堆肥散布後のBRBV に対する効果は消石灰と炭酸ナトリウムでみられ，BAdVh7 に対しては消石灰のみが効果を示した．以上の成績より，口蹄疫ウイルスの土壌や堆肥における消毒には消石灰と炭酸ナトリウム，生乳に対してはすべての消毒薬の有効性が示唆された. To estimate the effects on foot-and-mouth disease virus (FMDV) of disinfectants used on Japanese farms, we investigated the effects on bovine rhinitis B virus (BRBV) and bovine adenovirus type 7 (BAdVh7), instead of FMDV, under conditions that mimicked field usage. We employed eight disinfectants : calcium hydroxide, sodium carbonate, citric acid, iodine, chlorine, aldehyde, disinfectant complex and quaternary ammonium compounds with a 0.1% sodium hydroxide. Among the disinfectants mixed with bovine excreta slurry, calcium hydroxide and sodium carbonate inactivated both viruses. After mixing them with bovine raw milk, all disinfectants could inactivate both viruses except for chlorine on BAdVh7. After sprinkling the disinfectants on soil and compost, calcium hydroxide and sodium carbonate could inactivate BRBV, and only calcium hydroxide could inactivate BAdV. These results suggested that FMDV on soil and compost might be inactivated by calcium hydroxide and sodium carbonate and that all disinfectants might inactivate FMDV in raw milk.

本研究課題では, KSHVウイルスによる直接的な免疫抑制性サイトカインIL-10の発現誘導メカニズムの解明を目的とした。その結果, IL-10遺伝子プロモーター上でのK-RTA反応性のDNA領域が同定された。また, ここに結合すると報告されている他の転写因子がK-RTAと協調的にIL-10プロモーターの活性化を引き起こすことが初めて明らかになった。さらに, 間接的な作用として, アセチル化因子による転写複合体がK-RTAのIL-10 プロモーター活性化に関与する事が明らかになった。今後はこれらの転写因子とK-RTAとの機能的協調メカニズムの解明が期待される。 In this study, we have investigated molecular mechanism involved in KSHV K-RTA-mediated regulation of IL-10. At the specific region on IL-10 gene promoter 256 base upstream from first ATG codon, we identified K-RTA-responsive region, and in addition, we found that some host cell factor (s) seemed to modulate K-RTA-mediated IL-10 promoter activation. We found when K-RTA was co-expressed with some transcriptional factor, synergistic activation of IL-10 promoter was induced, and interestingly, posttranslational modification including protein acetylation had some impact on K-RTA. For protein acetylation modification, there are many members of histone acetylase and deacetylase families known to regulate various transcriptional mechanism so that we would like to determine which molecules were involved in K-RTA-mediated IL-10 promoter activation., 研究種目 : 基盤研究(C)(一般) 研究期間 : 2014～2016 課題番号 : 26460076 研究分野 : 生物系薬学

The present study was aimed to develop rapid diagnostic systems of Bovine viral diarrhea-mucosal disease (BVD-MD). This study was composed of three works: collection of Japanese Bovine viral diarrhea virus (BVDV) isolates, analysis of domestic distribution of BVDV subgenotypes, and development of anti-BVDV antibodies. Because of the affinities of the antibodies produced were too low, any diagnostic system did not developed. However, it was revealed that most of the Japanese isolates were non-cytopathogenic and almost 100% of domestic outbreaks were caused by the viruses classified in 4 subgenotypes of 1a, 1b, 1c, and 2a. We are planning to continue these investigations and hope the results contribute to control of BVD-MD., 本研究では, 国内における牛ウイルス性下痢ウイルス（BVDV）分離株の収集および亜型分布の解析を行うと共に, 牛ウイルス性下痢・粘膜病の迅速診断法の開発を目指して抗BVDV 抗体の作出を行った. 収集した分離株の解析では, 非細胞病原性株が大部分であること, 国内における発生は1a, 1b, 1c および2a の4 亜型でほぼ100%を占めることが明らかとなった. 一方, 本研究で作出した抗体は抗原との結合力が不十分であり, 診断系の開発には至らなかった. 今後も国内分離株の収集と解析を継続すると共に, 解析結果を活用して有用な診断系の開発を目指す.

[Abstract] Herein we described the synthesis of siRNA-NES (nuclear export signal) peptide conjugates by solid phase fragment coupling (SPFC) and application of them to silencing of bcr/abl chimeric gene in human leukemia cell line K562. Synthesis of siRNA-NES conjugates was achieved by SPFC. As a result, two types of siRNA-NES conjugates C1 and C2 were prepared in which 5' -end of sense strand was covalently linked to N-terminus of the NES peptides derived from TFIIIA and HIV-1rev, respectively. Silencing effects of C1 and C2 against bcr/abl mRNA in human leukemia cell line K562 were evaluated by quantitative PCR. The expression of bcr/abl gene was suppressed to 30.2％ at 200nM and 36.3％ at 50 nM by native siRNA. Significant enhancement of silencing efficiency was observed with C1 and C2. siRNA-TFIIIA NES (C1) suppressed the expression of bcr/abl gene to 8.3％ at 200 nM and 11.6％ at 50nM and siRNA-HIV-1rev NES (C2) suppressed to 4.0％ at 200 nM and 6.3％ at 50nM. Previously, we reported that DNA-HIV-1 rev NES peptide conjugate was localized in cytoplasm of Jurkat cell. The large enhancement of the silencing efficiency of siRNA-NES conjugates could be reasonably ascribed to the localization of siRNA-NES conjugates in cytoplasm. It can be also pointed out that modification of 5' -endo of sense strand reduced off-target effect by minimizing the extent of the sense strand incorporation into RISC. (3) Unfortunately, siRNA-NES conjugates could not penetrate the cellular membrane by itself and required a transfection reagent to be taken up into cells, while oligodeoxyribonucleotide-NES conjugates were internalized into cells without any transfection reagents. It can be elucidated the double stranded structure of siRNA retarded the penetration through cellular membrane.

Varicella-zoster virus (VZV) infection is a common complication of cancer, which is particularly high for patients with hematological malignancies. However, little data has been reported on VZV infection about its frequency of onset and risk factors during chemotherapy for malignant lymphoma. Here, we wish to report a retrospective analysis of complications of VZV infection in patients with malignant lymphoma after their first chemotherapy treatment at our department. Out of 188 patients, 23 cases (12.2％) developed complications of VZV infection. In non-Hodgkin lymphoma (NHL), VZV infection was found in 18 patients out of 173 (8.4％), whereas in Hodgkin lymphoma (HL) it was found in 5 patients out of 16 (35.3％). Although in all cases, response to the treatment showed improvements, postherpetic neuralgia was found in 5 patients. According to univariate analysis, gender (female, P＝0.0261), histology (HL, P＝0.0152), duration of steroids administration (≧ 61 days, P＝0.0075) were considered as significant factors relating to the risk factors of VZV infection. In conclusion, these findings suggested that initiating prophylactic oral administration from the start of chemotherapy with patients with higher risk for VZV infection requires examination.

It is thought that virus diseases in plants can not to be cured by application of chemicals. Removal of diseased plants from the field is the sole practical counter-measure to prevent diffusion of virus disease. In agriculture as well as medicine, attenuated viruses are used preventively as vaccines to protect plants from damage caused by viruses. We found that an attenuated virus having a satellite RNA reduced symptoms on diseased tomato plants infected with Cucumber mosaic virus (CMV). Inoculation tests under various conditions were performed to investigate the ability of the attenuated CMV to reduce mosaic symptoms on CMV-diseased tomato plants. Mosaic symptoms were alleviated from the top leaf of the diseased plants about 3 weeks after inoculation by post-inoculation of an attenuated virus having a satellite RNA. Furthermore, the attenuated virus improved the quality and quantity of tomato fruits. Symptoms were reduced more effectively if the interval between infection with the CMV strain and inoculation of the attenuated virus was short. The effect was more pronounced on young plants. Challenge inoculation exclusively with satellite RNA molecules resulted in cure of the CMV-diseased tomato plants, indicating that the alleviation of symptoms was due to the satellite RNA. These results show the possibility of plant virus disease protection by satellite RNA that attenuates CMV, i.e., therapy for plant virus disease.

Bovine papillomaviruses (BPV) are a group of small, spherical DNA viruses that cause bovine papillomatosis. Six types of BPV (BPV-1 to BPV-6) had been known for some time, but recently four new types (BPV-7 to BPV-10) have been identified. Studies from Japan, Sweden and Brazil now also suggest the existence of other new BPV types. It has therefore become increasingly clear that BPV constitutes a very large group of viruses. The diversity of diseases known to be associated with BPV has increased along with increasing knowledge of the diversity of these viruses. One such example is the recent occurrence of intractable bovine papillomatosis caused by BPV-9 at grazing facilities in northern Japan, which has been causing milking-related problems there. Here, we discuss how the new BPVs have been identified as well as the latest findings on the characteristics of diseases related to infection with these viruses., 牛パピローマウイルス（BPV）は, 牛乳頭腫症の原因となる小型球形のDNA ウイルスである. BPV は従来, 遺伝子型によって6 種類（BPV-1 ～ BPV-6）に分類されていたが, 近年新たに4 種類のBPV（BPV-7 ～ BPV-10）が同定された. また更なる新型BPV の存在を示唆する報告が日本やスウェーデン, ブラジルから出されている. これによりBPV はより幅広い型を含むウイルス群であることが分かってきた. ウイルスの多様性が分かるにつれて, BPV が関与する疾病の多様性も次第に明らかになりつつある. その一例が北日本の放牧施設で流行し搾乳障害の原因となっている「BPV-9 による難治性牛乳頭腫症」である. 本稿では, 新型BPV 発見の経緯と, それらが関与する疾病の特徴について最新の知見を紹介する.

In this study, the efect of exposure to an electric field on activation of lymphocytes in the peripheral blood in FIV positive or negative cats was investigated, using an electrical stimulating device which is used for 'electrostatic potential therapy'. In human cases and in a few species of animals, exposure to an electric field generated by an altemating current has been found to improve the physiological conditions. In our experiments, we used 8 cats infected by feline immunodeficiency virus(FIV) and 5 cats without FIV, each of which was exposed to an electric field for 30 minutes per day for 2 weeks, and we measured the activation of lymphocytes after adding Concanavalin A, a stimulator of T cells. In the FIV positive cats, electric field exposure significantly activated blastogenesis of lymphocytes. Induction of lymphocyte blastogenesis in the FIV positive cats required a longer exposure than in the FIV negative cats. In addition, lymphocytes in the peripheral blood increased in some of the FIV positive cats. These results suggest that electeic field exposure is effective in stimulating immunological responses in FIV cats., 電位治療器とは,安全な高圧交流電位を身体に与えて身体周囲に電界を発生させ,電気－生体作用を身体に与える物理療法機器である｡本研究では,電位治療器が生体の免疫能を活性化する作用に着目し,猫免疫不全ウイルス感染症(FIV)陰性猫5頭,FIV陽性猫8頭を用いて,電位治療器による電位負荷(電界エクスポジャー)を実施し,そのリンパ球機能を活性化するかどうか検討した｡電界エクスポジャーはFIV陽性猫のConA刺激に対する末梢血リンパ球幼若化能を増加させ,一部のFIV陽性猫では末梢血リンパ球数も増加することが示された｡このことから,FIV陽性猫に 対する電界エクスポジャー刺激は,そのT細胞機能を活性化することが示唆されFIV感染症治療法の1つとして応用できる可能性があると考えられた｡また,FIV陽性猫の電界エクスポジャー後のリンパ球幼若化能変動パターンはFIV陰性猫と明らかに異なっており,そのリンパ球機能を活性化するためにはFIV陰性猫より長期間エクスポジャーを実施する必要があると思われた。

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic progressive myelopathy characterized by spastic paraparesis and sphincter dysfunction observed in a minority of HTLV-1 infected individuals. Previously studies indicated that HTLV-1 Tax subtype, several HLA and non-HLA genes are closely associated with the development of HAM/TSP. Two HAM/TSP associated alleles, HLA-A^*02 and HLA-DRB1^*0101 can recognize immunodominant HTLV-1 epitopes, and some HAM/TSP associated non-HLA genes are trans-activated by HTLV-1 Tax protein. Namely, complex virus-host interactions play an important role in determining the risk of HAM/TSP.

「前立腺癌に対する herpes simplex virus-thymidine kinase遺伝子発現アデノウイルスベクター及びガンシクロビルを用いた遺伝子治療臨床研究」を実施した．対象となる被験者は内分泌療法中に再燃してきた臨床的に遠隔転移を認めない局所再燃前立腺癌とした．まず herpes simplex virus-thymidine kinase（HSV-tk）遺伝子発現アデノウイルスベクターを単独で腫瘍内に直接投与し，その後ガンシクロビル（ganciclovir：GCV）を全身投与した． 本研究は2001年3月より第1例目の被験者の治療を開始し，平成17年7月に最終登録例である9例目の被験者の治療を実施し，6ヶ月以上観察し，臨床試験を終了とした（8名のべ9症例）． 9症例すべてにおいて有意な副作用を認めなかった．また，ウイルスベクター投与後の抗アデノウイルス中和抗体価の上昇は軽度でかつ一過性であった．ウイルスベクター投与後，48時間において採取した組織において ｍRNA レベルでの HSV-tk 遺伝子の発現が確認された．治療効果の指標として腫瘍マーカーである PSA は9例中6例において低下した． 結論として局所再燃前立腺癌に対し，HSV-tk 遺伝子発現アデノウイルスベクターを単独で局所内投与し，その後ガンシクロビルを全身投与することの安全性および治療効果が確認された．

(Abstract)Phage display is emerging as a promising strategy for the discovery of peptide ligands that are used for analytical tools, drug discovery, and target validations. Phage display technology can produce a huge number of peptides and generate novel peptide ligands. Phage display technology has successfully managed to create some peptide ligand. The structural analysis of ligands shows that the conformational desigh of peptides in library is important for structural relationship among peptides on phage, synthetic peptides and non-peptidic compounds as well as for selecting high-affinity ligands that bind to every target from a phage peptide library. Key issues concern constraints on the conformation of peptides on the phage and the development of chemically synthesized peptides derived from peptides on pharge. This review dis-cusses studies related to the conformation of peptides selected from phage display peptide libraries in addition to the conversion from peptides to non-peptides.

This paper is a review of psychological studies on Identity and TAT (Thematic Apperception Test) and also examines the possibility of TAT for concepts of Identity, and from the viewpoint of "Individuation" and "Relatedness". The theory of Identity is constructed from the viewpoint of "Individuation" and "Relatedness". Especially, it is necessary to study Identity taking account of "Relatedness" with infants at an early stage. The TAT is recommended as an assessment to test for "Relatedness" at an early stage of development. The analysis of TAT is a recommended approach toward analyzing an interpersonal world. TAT seems to establish a theory of Identity from the viewpoint of "Individuation" and "Relatedness".

Infection with a variety of viruses induces apoptosis in host cells. This phenomenon may be considered to be a self-defense mechanism to avoid viral propagation. However, the growth of influenza virus is completed before host cells become dysfunctional due to apoptosis. To clarify the physiologic consequences of influenza virus-induced apoptosis, the fate of influenza virus-infected cells was examined in vitro as well as in vivo. Influenza virus-infected cells were engulfed by macrophages in vitro, and virus propagation was almost completely inhibited. This phagocytosis was dependent on the specific recognition of the membrane phospholipid phosphatidylserine exposed on the surface of virus-infected apoptotic cells by macrophages. In addition, the activity of viral neuraminidase expressed at the surface of virus-infected cells was necessary for the maximal level of phagocytosis. When mice infected with influenza virus were administered phagocytosis inhibitors, the level of lethality and inflammation in the lung were augmented. These results show that apoptosis makes influenza virus-infected cells susceptible to phagocytosis by macrophages, and that this leads to a reduction in the extent of influenza pathology.

In late years, there are many reports about increasing of virus infections. It is necessary to be careful not to become lacking in fatigue and sleeping for viral infections such as herpesvirus, coxsackievirus and enterovirus (case 1,5). Even if merely insect is said to stick by outdoor activity (insect bite), the quick treatment is expected in the case of a face without having a scar, and knowledge about a rare disorder to need appropriate judgment is demanded (case 2,3). As for the cervical adenitis (case 4) with pyrexia, many causes are thought about, but it is necessary for infectious mononucleosis to know that it is causal one with a young woman.

Amber is the fossilized resin or sap of pine trees which grew in forests around 45-100 million years ago. Amber is used for jewelry and decorative articles nowadays, but it was also used for healing and health enhancement in Eastern and Western countries in ancient times. In order to investigate the physiological effects of amber when burning it like incense, we analyzed the contingent negative variation(CNV) of electroencepha- lograms(EEG) and autonomic nervous activities such as respiratory interval, heart rate and fluctuation of heart beat interval. Amber used in the present study was mined in Kuji, Iwate Prefecture. Areas of CNV on 19 out of 23 recording spots were increased after amber incense stimulation. On the other hand, the well-known incense agalloch, i.e.Jinko, enhanced the area of CNV less effectively than amber incense. During CNV procedures, the respiratory interval was reduced and the heart rate was increased. These parameters were changed by amber incense. Reduction of amplitude in high frequency fluctuation of the heart rate, which may correspond to activities of the parasympathetic nervous system, was suppressed during exposure to amber incense. It is known that CNV represents activities of expectation, conation, motivation and attention in humans and activation of the parasympathetic activities induces relaxation in the human mind. These data suggested that amber incense enhanced expectation, conation, motivation and attention in humans, and also suggested that a stressful burden such as the CNV trial was alleviated by amber incense in the case of the present subject., 琥珀は、4500万～１億年前のマツ科植物の樹脂や樹液が化石化したものである。現在、琥珀は宝飾品や装飾品として使われているが、古代より洋の東西問わず癒しや健康増進のために使われてきた。琥珀をお香のように燻らせた時に、生体にいかなる生理作用があるかを調べるために、脳波随伴陰性変動（ＣＮＶ）及び自律神経活動を解析した。用いた琥珀は、岩手県久慈産である。琥珀のお香の刺激により、23ヶ所の脳波測定電極のうち、19ヶ所でＣＮＶ面積が増大した。一方、お香として良く知られる沈香の場合には、琥珀に比べＣＮＶ面積の増加はわずかであった。ＣＮＶ試行中に、呼吸数と心拍が増加した。これらの指標は、琥珀お香の刺激中に変化があった。心拍変動の高周波成分（副交感神経の活性）の減少が、琥珀お香の刺激中に抑制された。ＣＮＶは期待感、意志、動機や集中力の程度を表し、また副交感神経活性化はリラックス状態を誘導するとされている。以上の結果は、本研究の被験者において琥珀お香が生体における期待感、意志、動機や集中力を促進し、また琥珀お香の最中にはＣＮＶなどのストレス不負荷を軽減することができたことを示唆した。

The clinical and laboratory findings of 5 adult patients with recent human parvovirus B19 infection in Anan city （from January to February 2005） were reported. They showed local and generalized edema and/or arthritis. Clinical examinations showed relative neutrophilia with lymphcytopenia, anemia, hypocomlementemia in all patients and proteinuria with hematuria in 2 cases （No 2, 3）. Erythema were recognized in only 2 younger cases （No 3, 5）. Mean weight increase due to edema was 2.2Kg. All 5 patients were positive for human parvovirus B19 IgM/IgG antibody. After treatment, CTR decreased 8.0% on an average, and elevated BNP levels markedly declined one month later in 3 cases （No 2, 3, 4）. %FS also reduced in these cases, and one case （No 4） observed slight degree of echo free space （probably pericardial effusion）. When human parvovirus B19 is prevalent, differential diagnosis of the symptoms such as anemia, dyspnea, oligouria and polyarthralgia are mandatory. If human parvovirus B19 infection is suspected, virus-related cardiomyopathy should be considered.

In order to establish infection to host cells, viruses suppress or escape from the host immune response against microorganisms by various strategies. Interferon （IFN） system is an important contributor of innate immunity. IFN is induced by viral infection, and it promotes antiviral state through induction and/or activation of the effector molecules. Many viruses possess the suppression mechanisms for the anti-viral effector molecules, whereas they also perform inhibition of IFN signaling pathway, JAK/STAT pathway. We consider that latter is a most effective strategy counteracting IFN function, because the signaling pathway is an entrance of the system. The strategies counteracting JAK/STAT pathway are varied among virus species. Viruses perform （i） degradation of JAK/STAT components, （ii） suppression of activation （phosphorylation） of the components, （iii） inhibition of nuclear translocation of activated transcription factor, and （iv） induction of host JAK/STAT negative regulator. In this review, we describe details of these strategies, especially our recent results of HSV-1, measles virus and mumps virus.

The research interest of authors has focused on the risk assessment of environmental pollutants such as cadmium and dioxin-related compounds, and epidemiology of human T-cell lymphotropic virus type-I （HTLV-I） infection. The authors （１） showed that low-molecular weight proteinuria and reduced glomerular filtration rate caused by environmental cadmium were strongly associated with shortened survival， （２） clarified serological risk factors for development of adult T-cell leukemia/lymphoma among asymptomatic HTLV-I carriers （plasma levels of soluble interleukin２-receptor＞＝５００U/ml and HTLV-I antibody titer＞＝１，０２４）， （３） conducted the first prospective study of HTLV-I infection and development of malignances other than ATL, and found a significantly reduced risk of gastric cancer among HTLV-I carriers, and （４） by a cooperative study, clarified a new pathogenicity of HTLV-I （association with Sjögren’s syndrome）.

This article attempts to consider TAT stories as narrative. In the current research 108 subjects were asked to make TAT stories. Then they were to revise stories made by others as well as by themselves. It is compared how they changed stories, and it is clear that own stories are likely 'to be changed less at the ending' or 'not to be changed at all.' This result shows that structural tendencies subjects have in storytelling also appeared in the TAT. One of the TAT stories and its revise are closely examined. In that case the subject re-wrote all his story after revising. However the plot he originally made and used appeared again in the newly made story. In conclusion it is possible that the TAT stories express the plots as claimed to be found in narrative.

The thematic apperception test (TAT) is known to be a personality test in which a subject is asked to make a story for each picture shown. This article aims at re-thinking TAT from its origin how this test was made. This study reveals that when interpreting TAT results it is important to notice the subjective influences on the examiner's side. Concerning psychological tests in general, subjective effects of an examiner is regarded to be undesirable. However, the current study concludes that it is extremely meaningful to notice the usefulness of an examiner's subjective features in TAT. A book written by Murray and Morgan (1938), Exploration in Personality, is a very useful volume to know the starting point of the TAT. This reading informs Murray's and Morgan's attitudes towards TAT practice as well as how TAT was used when it was a newly invented method. This book clarifies two important features of TAT: 1) the same theme told in TAT is repeatedly expressed in many other situations in various; 2) an examiner reads TAT stories imagining freely. When one reads TAT stories, s/he cannot help experiencing numerous sensations, feelings, insights, and thinking. It is almost amazing to find out how often the authors use their own lively senses on interpreting TAT. This early volume suggests the ways to interpret TAT deeply through an examiner's subjective senses.

Age distributions were studied in children with pathogen proven infectious gastroenteritis. Between 1998 and 2002, 214 patients were enrolled in this study. Causative agents include rotavirus (n=141), Norwalk virus (n=23), enteric adenovirus (n=6), Salmonella spp.(n=27), Campylobacter jejini (n=16) and enterohemorrhagic Escherichia coli (n=1). Of the viral agents, rotavirus infections occurred mostly in children younger than 2 yr (but older than 6 mo), with highest frequency in infants from 12 to 24 months of age; none of the patients 8 yr of age or older were affected. On the other hand, Norwalk virus infections were involved not only in infants but also in older children. Enteric adenovirus (serotype 40/41) infections occurred in children under 7 yr of age. Statistical analysis revealed a significant difference in morbid age between rotavirus infections and Norwalk virus infections. Of the bacterial agents, nontyphoidal Salmonellosis was prevalent in younger children, those aged 0 to 6 yr accounted for 85%. In contrast, C. jejuni infections involved school- age children; those 7 yr of age or older accounted for 50%. There was a statistically significant difference in morbid age between Salmonellosis and C. jejuni infections. Age distribution of patients shows a characteristic pattern in each causative agent not only in viral gastroenteritis but also in bacterial enterocolitis; so that analyses of age distribution are useful for empiric therapy in children with infectious gastroenteritis.

Optimum control of the ankle joint actuator is essential for realizing a stable gait when wearing an active ankle foot orthosis (AFO). An optimum timing control system using the monitored load of both feet is designed and examined. A wireless sensor network (WSN) module is used to monitor load. The gait cycle is estimated from the load change of both feet. The WSN module is practical because it is compact, robust and inexpensive.