A Functional Polymorphism in B and T Lymphocyte Attenuator Is Associated with Susceptibility to Rheumatoid Arthritis

Inhibitory coreceptors are thought to play important roles in maintaining immunological homeostasis, and a defect in the negative signals from inhibitory coreceptors may lead to the development of autoimmune diseases. We have recently identified B and T lymphocyte attenuator (BTLA), a new inhibitory coreceptor expressed on immune cells, and we suggest that BTLA may be involved in the development of autoimmune diseases using BTLA-deficient mice. However, the role of BTLA in the pathogenesis of autoimmune diseases in humans remains unknown. We, therefore, examined the possible association between BTLA and rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS) by conducting a case-control genetic association study. We found that 590C single-nucleotide polymorphism (SNP) of BTLA gene was significantly associated with susceptibility to RA, but not to SLE or SS. Furthermore, RA patients bearing this 590C SNP developed the disease significantly earlier than the patients without this allele. We also found that BTLA with 590C allele lacked the inhibitory activity on concanavalin A- and anti-CD3 Ab-induced IL-2 production in Jurkat T cells. These results suggest that BTLA is an RA-susceptibility gene and is involved in the protection from autoimmunity in humans

A case report of Homalogaster paloniae from the cecum of a bull in Fukuyama City

広島県福山市のとちく場で1頭の牛の盲腸より22匹の吸虫を検出し､形態的特徴より総て平腹双口吸虫Homalogaster paloniaeの成虫と同定した｡この牛は岡山県真庭郡川上村で生まれ､そこで約10ヶ月飼育されていた｡福山市の牧場内には､この吸虫の中間宿主であるヒラマキモドキガイが生息するような環境はなく､岡山県で飼育されていた時にこの吸虫に感染した可能性が高いと推察された｡Twenty-two worms were taken out from the cecum of a bull at the slaughterhouse in Fukuyama City. These worms were identified as adult Homalogaster paloniae by its morphological features. However, we were unable to determine the infection route of these worms. It was suggested that the bull was infected with Homalogaster paloniae in the birthplace, Okayama Prefecture

A postmortem study suggests a revision of the dual-hit hypothesis of Parkinson's disease

The dual-hit hypothesis of Parkinson's disease (PD) originally postulated that a neurotropic pathogen leads to formation of alpha-synuclein pathology in the olfactory bulb (OB) and dorsal motor nucleus of the vagus (DMV) and then invades the brain from these two entry points. Little work has been conducted to validate an important underlying premise for the dual-hit hypothesis, namely that the initial Lewy pathology does arise simultaneously in the OB and the enteric nervous system (ENS) plexuses and DMV at the earliest disease stage. We conducted a focused re-analysis of two postmortem datasets, which included large numbers of mild Lewy body disease (LBD) cases. We found that cases with alpha-synuclein pathology restricted to the peripheral autonomic nervous system and/or lower brainstem (early body-first LBD cases) very rarely had any OB pathology, suggesting that Lewy pathology commonly arises in the ENS without concomitant involvement of the OB. In contrast, cases with mild amygdala-predominant Lewy pathology (early brain-first LBD cases) nearly always showed OB pathology. This is compatible with the first pathology being triggered in the OB or amygdala followed by secondary spreading to connected structures, but without early involvement of the ENS or lower brainstem. These observations support that the pathologic process starts in either the olfactory bulb or the ENS, but rarely in the olfactory bulb and gut simultaneously. More studies on neuropathological datasets are warranted to reproduce these findings. The agreement between the revised single-hit hypothesis and the recently proposed brain-first vs. body-first model of LBD is discussed.Peer reviewe

Cross-talk between autoimmunity and tumor immunity

Both autoimmunity and tumor immunity are immune responses against self-tissues or cells. However, the precise similarity or difference between them remains unclear. In this study, to understand a novel mechanism of tumor immunity, we performed transplantation experiments with a murine autoimmune model, C57BL/6J (B6)/lpr mice. A melanoma cell line, B16F10 cells, or granulocyte macrophage colony-stimulating factor- overexpressing B16F10 (B16F10/mGM) cells were transplanted into B6 or B6/lpr mice. Tumor growth by transplanted B16F10/mGM cells was significantly accelerated in B6/lpr mice compared with that in B6 mice. The accumulation of M1 macrophages in the tumor tissues of B6/lpr recipient mice was significantly lower compared with that in the control mice. In vitro co-culture experiment showed that impaired differentiation into M1 macrophages was observed in B6/lpr mice. The number of tumor vessels and vascular endothelial growth factor (VEGF) expression were also significantly enhanced in the tumor tissues of B6/lpr mice compared with those in the B6 mice. Moreover, VEGF expression was correlated with the increased expression of hypoxia-inducible factor-1α in the tumor tissues of B6/lpr mice. These results suggest that dysfunctional tumor immunity and enhanced angiogenesis in autoimmunity influence tumor growth

[資料]「ピアサポーター養成講座」実施報告

要旨：学生の自殺予防対策の一環として、また、看護師や介護福祉士に必要な援助的対人関係スキルを身に着ける機会として「ピアサポーター養成講座」を企画実施した。参加者は、看護学生８名（２年生　男子１名、女子２名、３年生　女子５名）であった。研修内容は、①講座開催の経緯、②ピアサポートとは、③アイスブレイク、④感情活用、⑤傾聴と共感、⑥ロールプレイであった。　質問紙による学生からのフィードバックによれば、学生たちは、研修内容を理解し、この研修が役に立ったと全員が回答している。また、全員が今後も講座が続けられることを望んでいた。Abstract：A “Training Seminar for Peer Supporters” was planned and implemented as a part of the measures for suicide prevention and as an opportunity to acquire supportive interpersonal skills required of nurses and care workers. The participants were eight nursing students （one male and two female second year students and five female third year students）. The contents of the training seminar were（ 1） background for this seminar,（ 2） what is peer support?（ 3） how to “break the ice,”（ 4） emotional leveraging,（ 5） listening and empathy and（ 6） role play.　According to the feedback through the questionnaires from the participants, they well understood the contents of the seminar, all of them responded that this seminar was very useful, and all of them hoped that this seminar would continue in the future

大都市団地居住高齢者の社会関係と生活ニーズ充足のためのソーシャルサポート ─ライフコースとケアリング関係の視点からの分析─

本研究の目的は,ライフコースとケアリング関係の視点から,大都市団地居住高齢者の社会関係と生活ニーズ充足のためのソーシャルサポートとの関連を分析し,地域包括ケアの課題を検討することである。東京都A 市B 団地居住高齢者429 名への訪問調査を2011 年5-6 月に実施した(有効N=196 名,有効回答率:46.0%)。主な結果として,1)生活ニーズのある人(全体の1 割弱)の2-4 割に支援者がおらず,有支援者の2 割弱が家事,買い物,ゴミだし,当番の場合に近所の人を担い手としてあげた(複数回答),2)困りごとの相談相手がいない人は2 割弱で,男性の方が女性よりいない割合が高い,3)ロジスティック回帰分析の結果,独居,男性,近隣ネットワークが小さい方が相談者がいない確率が高いことがわかった。独居や男性など既存の社会ネットワークを活用したソーシャルサポートの活用可能性が乏しいグループには適切な支援策が必要であることが示唆された。小規模調査の限界もあるが,団地居住高齢者の多様な社会関係とソーシャルサポートの現状をふまえての地域包括ケアの課題があきらかになった。The purpose of this study is two-fold: 1) to examine the association between social relationships and support for meeting the daily life needs of elderly people in an urban housing complex from the lifecourse and caring-relations perspectives and 2) to discuss the challenges of community comprehensive care. Structured home-visit interviews were conducted among 429 elderly people at Housing Complex B in City A, in the Tokyo Metropolitan area, from May to June, 2011. Valid responses were obtained from 196 persons, for a response rate of 46.0%. The results are as follows: 1) among the elderly who had daily-life needs (less than ten percent of total respondents), twenty percent relied on neighbors for doing housework, shopping, taking out garbage, and performing duties in the housing complex (multiple answer); 2) less than twenty percent of respondents had no one they could turn to for advice regarding their day-to-day difficulties; and 3) as a result of logistic regression analysis, single people, males, and respondents with small networks of neighbors were found to be less likely than couples, females, and those with large networks of neighbors to have anyone to turn to for advice. Our findings indicate thatit is necessary to have an appropriate support system for those who have limited support available in their existing social network (e.g. single people, males). In spite of the limitation of a small sample, we could clarify some of the challenges for community comprehensive care for elderly people by considering the diverse social relations and social support available to them in a housing complex

Impact of Tunnel Excavation Muck dumped along the canyon on Streamwater Chemistry

岩石中に硫化鉄鉱物を含む岩盤にトンネルを掘削し, 残土を周辺の渓谷に埋め立てると, 硫化鉱物が酸素を含んだ降水や地下水と接触し, 酸化・分解することにより硫酸酸性浸出水が発生し, 生物の斃死や有害金属類の流出などにより周辺環境に悪影響を及ぼす可能性がある。掘削残土の中に酸性化を緩衝する能力を有する鉱物が含まれる場合は, 中和作用により浸出水のpHの低下が抑制されるため, 浸出水のpHは, 硫化鉱物の酸化により生ずる硫酸量と, 緩衝鉱物の分解に消費される硫酸量の兼ね合いによって決まると考えられる。本研究では, トンネル掘削残土の埋め立てによる渓流水の溶存物質濃度の長期的な変化を明らかにするために, トンネル掘削残土の埋め立て区間の直上流, 直下流で, 埋め立て前から後まで23年間, 渓流水質をモニタリングし, その結果に基づき検討した。その結果, 1993～94年に埋め立てが終了した後16年が経過しても, 埋め立てによる渓流水質への影響は続いていた。埋め立て区間の下流ではSO4(2-), Ca(2+), アルカリ度が有意に高い状態が続いているが, 渓流水のpHの低下はみられず, Ca(2+)を主とするカチオンが, S含有鉱物の分解によって生じた硫酸を中和し, pHを中性に保ったと考えられる。埋め立てがCa(2+)以外のカチオン濃度を増加させた期間は3～5年間にとどまり, SiO2には埋め立ての影響がなかった。影響の継続期間については, ワサビ沢では31年, トウバク沢では17年から20年と試算された。To show the long-term changes in streamwater quality after dumping tunnel excavation muck along the canyon, streamwater chemistry monitoring was undertaken at points upstream and downstream from the site where rock muck had been dumped in Wasabi and Toubaku Creek over 23 years. The concentrations of SO4(2-) below the dumping site were significantly increased which is consistent with the results found in the previous study that some of the rock muck contained Greigite. The pH of streamwater below the dumping site was, however, not significantly different from that above the dumping site, suggesting that SO4(2-) was neutralized by some cations such as Ca(2+) which was also significantly increased below the dumping site. Although the difference of mean annual SO4(2-) concentration between the points upstream and downstream of the dumping site became smaller, the difference was still significant for 17 years after dumping. It takes about 31 years in the Wasabi creek and from 17 to 20 years in the Toubaku Creek for the SO4(2-) concentration of streamwater downstream of the rock muck to be returned to the level found upstream

EWSR1-ATF1融合遺伝子を持つ歯原性明細胞癌細胞株の樹立と性状解析

Objective: Clear cell odontogenic carcinoma (CCOC) is a rare malignant odontogenic tumor (MOT) characterized by sheets and lobules of vacuolated and clear cells. To understand the biology of CCOC, we established a new cell line, CCOC-T, with EWSR1-ATF1 fusion gene from a mandible tumor with distant metastasis and characterized this cell line. Materials and methods: To detect the EWSR1-ATF1 fusion gene, we used three CCOC cases, including the present case, by RT-PCR and FISH analysis. We characterized established CCOC-T cells by checking cell growth, invasion and the expression of odontogenic factors and bone-related factors. Moreover, the gene expression profile of CCOC-T cells was examined by microarray analysis. Results: Histologically, the primary tumor was comprised of cords and nests containing clear and squamoid cells separated by fibrous septa. In addition, ameloblastomatous islands with palisaded peripheral cells were observed, indicating probable odontogenic origin. This tumor expressed the fusion gene EWSR1-ATF1, which underlies the etiology of hyalinizing clear cell carcinoma (HCCC) and potentially that of CCOC. We found a breakpoint in the EWSR1-ATF1 fusion to be the same as that reported in HCCC. Established CCOC-T cells grew extremely slowly, but the cells showed highly invasive activity. Moreover, CCOC-T cells expressed bone-related molecules, odontogenic factors, and epithelial mesenchymal transition (EMT)-related molecules. Conclusion: To the best of our knowledge, this is the first report on the establishment of a CCOC cell line. CCOC-T cells serve as a useful in vitro model for understanding the pathogenesis and nature of MOT

Pork as a source of human parasitic infection

Foodborne zoonoses have been estimated to annually affect 10% of the global population, among which zoonotic parasites constitute an important class of aetiological agents. The major meatborne parasites include the protozoa Toxoplasma gondii and Sarcocystis spp., and the helminths Trichinella spp. and Taenia spp., all of which may be transmitted by pork. The significance of zoonotic parasites transmitted by pork consumption is emphasized by the prediction by the Food and Agriculture Organization of an 18.5% increase in world pork production over the next 10years. Of all the porkborne parasites, the three T' parasites have been responsible for most porkborne illness throughout history; they are still endemic, and therefore are important public-health concerns, in developing countries. Although the risk of porkborne parasites, particularly helminths, may currently be considered insignificant in developed countries, the modern trend of consuming raw meat favours their re-emergence. This paper overviews the main parasites transmitted to humans by pork, and outlines the main lines of prevention