Second Language Attrition ：Selected Bibliography

持っていた言語を失う事,すなわち「言語喪失」(language attrition)の現象はさまざまである.病理学的理由による失語症のような場合もあれば,歴史的,政治的,社会的理由による言語の消滅もある.また,自然な状況下でも言語は失われる.授業で習った外国語を使わないでいると忘れてしまうのも,言語喪失の現象の一環である.言語の喪失を,主として心理言語学的な立場から研究するという分野は,1980年にペンシルベニア大学で開催された会議に端を発するが,この20余年来,研究分野も細分化され,研究者も地域的に広がって急速に発展を見せている.本稿は言語喪失の心理言語学的研究の中で,「第二言語喪失」(second language attrition)に焦点を当て,主要な文献をリストしている.心理言語学的な立場から構成されているので,社会学的な文献,例えば「言語の取り替え」(language shift)や「言語の死」(language death)に関するもの,さらに,病理学的なもの,加齢によるものなどは含まれていない.また,心理言語学的なものでも「第一言語の喪失」(first language attrition)及び「言語の再学習」(language relearning)はその範疇外である.しかしながら,第二言語喪失にも深いかかわりのある知見が得られる文献は「第一言語の喪失」の分野に限って掲載した.言語喪失の分野にあまり造詣の深くない読者を念頭に置き,一部を除き,入手しやすい文献の掲載を留意してある

高齢者のための「ADL体力アップ教室と食事実習」の講座（平成21年度，平成22年度）実施における企画内容の報告

　地域の高齢者を対象に，調理実習を実施する食事講座が料理への関心や健康管理意識，および人とのつながりにどのような影響をもたらすかを検討した。方法は，運動実技の講座参加者のうち希望した者を対象として，運動実技講座終了後，1～2か月に1回，健康に関連したテーマを設定して調理実習を実施した。その結果，料理が楽しくなった，地域の友達が増えたなどの傾向がみられた。食事をテーマにした講座は，自身の健康に対する意識の向上と，受講者間の交流による日常生活への意欲の高まりに役立ち，長期的にはADL「日常生活動作（Activities of Daily Living，ADL）」によい影響をもたらす可能性が示唆された。また，健康福祉学部　健康スポーツ栄養学科の学生が指導スタッフとして参加したことで，異世代交流が図れ，双方に好ましい結果が生じた

野菜の摂取状況に関する研究

　2000年に健康づくりを推進する目的で「健康日本21－21世紀における国民健康づくり運動」を立ち上げた。その指導項目の1つである「野菜の摂取量」が，平成28年度国民健康・栄養調査の資料等からも国が定めた到達ポイントの350gに達していないということが報告されている。　野菜の目標摂取量等は，国民に対し行政がパンフレット等，広く配信されているが，その情報が行き渡っているか不明である。そこで，神戸市主催の「こうべ食育フェア」に，野菜摂取の意識を高める目的で野菜ブースを出店し，当ブースに立ち寄った来場者に対し，野菜摂取状況や野菜の栄養に関する関心度等，現状を知る目的でアンケート調査を実施した。　調査の結果，人々の1日あたりの野菜摂取量目標値350gが，十分浸透していないことが判った。また，野菜を摂取する必要性にっいての認識も低いことが伺われた。以上のことより行政からの配信が，人々に広く伝わっていない可能性が考えられた

Haplotypes and a Novel Defective Allele of CES2 Found in a Japanese Population

ABSTRACT: Human carboxylesterase 2 (hCE-2) is a member of the serine esterase superfamily and is responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. hCE-2 also activates an anticancer drug, irinotecan (7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxycamptothecin, CPT-11), into its active metabolite, 7-ethyl-10-hydroxycamptothecin (SN-38). In this study, a comprehensive haplotype analysis of the CES2 gene, which encodes hCE-2, in a Japanese population was conducted. Human carboxylesterases are members of the serine esterase superfamily and are responsible for hydrolysis of a wide variety of xenobiotic and endogenous esters. They metabolize esters, thioesters, carbamates, and amides to yield soluble acids and alcohols or amines Although both hCE-1 and hCE-2 show broad substrate specificities, hCE-2 is relatively specific for heroin, cocaine (benzoyl ester), 6-acetylmorphine, procaine, and oxybutynin 1865 camptothecin (SN-38), a topoisomerase inhibitor, by carboxylesterases Previously, 12 exons and their flanking regions of CES2 were sequenced from 153 Japanese subjects, who received irinotecan or steroidal drugs, and 12 novel SNPs, including the nonsynonymous SNP, 100CϾT (Arg 34 Trp), and the SNP at the splice acceptor site of intron 8 (IVS8-2AϾG) were found Materials and Methods Chemicals. Irinotecan, SN-38, and SN-38G were kindly supplied by Yakult Honsha Co. Ltd. (Tokyo, Japan). Patients. A total of 262 Japanese subjects analyzed in this study consisted of 85 patients with allergies who received steroidal drugs and 177 patients with cancer who received irinotecan. The ethical review boards of the National Cancer Center, National Center for Child Health and Development, and National Institute of Health Sciences approved this study. Written informed consent was obtained from all participants. DNA Sequencing. Total genomic DNA was extracted from blood leukocytes or Epstein-Barr virus-transformed lymphocytes and used as a template in the polymerase chain reaction (PCR). Sequence data of the CES2 gene from 72 patients and 81 cancer patients were described previously Linkage Disequilibrium and Haplotype Analyses. LD analysis was performed by the SNPAlyze software (version 5.1; Dynacom Co., Yokohama, Japan), and a pairwise two-dimensional map between SNPs was obtained for the DЈ and rho square (r 2 ) values. All allele frequencies were in HardyWeinberg equilibrium. Some haplotypes were unambiguously assigned in the subjects with homozygous variations at all sites or a heterozygous variation at only one site. Separately, the diplotype configurations (combinations of haplotypes) were inferred by LDSUPPORT software, which determines the posterior probability distribution of the diplotype configuration for each subject on the basis of estimated haplotype frequencies Administration of Irinotecan and Pharmacokinetic Analysis. The demographic data and eligibility criteria for 177 cancer patients who received irinotecan in the National Cancer Center Hospitals (Tokyo and Chiba, Japan) were described elsewhere Each patient received a 90-min i.v. infusion at doses of 60 to 150 mg/m 2 , which varied depending on regimens/coadministered drugs: i.e., irinotecan dosages were 100 or 150 mg/m 2 for monotherapy and combination with 5-FU, 150 mg/m 2 for combination with mitomycin C (MMC), and 60 (or 70) mg/m 2 for combination with platinum anticancer drugs. Heparinized blood was collected before administration of irinotecan and at 0 min (end of infusion), 20 min, 1 h, 2 h, 4 h, 8 h, and 24 h after infusion. Plasma concentrations of irinotecan, SN-38, and SN-38G were determined as described previously Expression of Wild-Type and Variant CES2 Proteins in COS-1 Cells. Expression of wild-type and variant CES2 proteins in COS-1 cells was examined as described previously and ZERO-Dscan software (Raytest, Straubenhardt, Germany). The relative expression levels are shown as the means Ϯ S.D. of three separate transfection experiments. Determination of CES2 mRNA by Real-Time RT-PCR. Total RNA was isolated from transfected COS-1 cells using the RNeasy Mini Kit (QIAGEN, Tokyo, Japan). After RNase-free DNase treatment of samples to minimize plasmid DNA contamination, first-strand cDNA was prepared from 1 g of total RNA using the High-Capacity cDNA Archive Kit (Applied Biosystems, Foster City, CA) with random primers. Real-time PCR assays were performed with the ABI7500 Real Time PCR System (Applied Biosystems) using the TaqMan Gene Expression Assay for CES2 (Hs01077945_m1; Applied Biosystems) according to the manufacturer's instructions. The relative mRNA levels were determined using calibration curves obtained from serial dilutions of the pooled wild-type CES2 cDNA. Samples without reverse transcriptase were routinely included in the RT-PCR reactions to measure possible contributions of contaminating DNA, which was usually less than 1% of the mRNA-derived amplification. Transcripts of ␤-actin were quantified as internal controls using TaqMan ␤-Actin Control Reagent (Applied Biosystems), and normalization of CES2 mRNA levels were based on ␤-actin concentrations. Enzyme Assay. CPT-11 hydrolyzing activity of the postmitochondrial supernatants (microsomal fraction plus cytosol) was assayed over the substrate concentration range of 0.25 to 50 M as described previously Statistical Analysis. Statistical analysis of the differences in the AUC ratios among CES2 diplotypes, coadministered drugs. or irinotecan dosages was performed using the Kruskal-Wallis test, Mann-Whitney test, or Spearman rank correlation test (Prism 4.0, GraphPad Software, Inc., San Diego, CA). The t test (Prism 4.0) was applied to the comparison of the average values of protein expression and mRNA levels between wild-type and variant CES2. Results CES2 Variations Detected in a Japanese Population. Previously, the promoter region, all 12 exons, and their flanking introns of the CES2 gene were sequenced from 72 allergic patients and 81 cancer patients and resulted in the identification of 12 novel SNPs The nonsynonymous SNP 424GϾA (V142M) reported by our group LD and Haplotype Analysis. Using the detected SNPs, LD analysis was performed, and the pairwise values of r 2 and DЈ were obtained. A perfect linkage (r 2 ϭ 1.00) was observed between SNPs Ϫ363CϾG and IVS10-87GϾA. A close association (r 2 ϭ 0.85) was found between SNPs IVS10-108GϾA and 1749AϾG. Other associations were much lower (r 2 Ͻ 0.1). Therefore, the entire CES2 gene was analyzed as one LD block. The determined/inferred haplotypes are summarized i

Sodium Channelopathy Underlying Familial Sick Sinus Syndrome With Early Onset and Predominantly Male Characteristics

Background-Sick sinus syndrome (SSS) is a common arrhythmia often associated with aging or organic heart diseases but may also occur in a familial form with a variable mode of inheritance. Despite the identifcation of causative genes, including cardiac Na channel (SCN5A), the pathogenesis and molecular epidemiology of familial SSS remain undetermined primarily because of its rarity. Methods and Results-We genetically screened 48 members of 15 SSS families for mutations in several candidate genes and determined the functional properties of mutant Na channels using whole-cell patch clamping. We identifed 6 SCN5A mutations including a compound heterozygous mutation. Heterologously expressed mutant Na channels showed loss-of-function properties of reduced or no Na current density in conjunction with gating modulations. Among 19 family members with SCN5A mutations, QT prolongation and Brugada syndrome were associated in 4 and 2 individuals, respectively. Age of onset in probands carrying SCN5A mutations was signifcantly less (mean±SE, 12.4±4.6 years; n=5) than in SCN5A-negative probands (47.0±4.6 years; n=10; P<0.001) or nonfamilial SSS (74.3±0.4 years; n=538; P<0.001). Meta-analysis of SSS probands carrying SCN5A mutations (n=29) indicated profound male predominance (79.3%) resembling Brugada syndrome but with a considerably earlier age of onset (20.9±3.4 years). Conclusions-The notable pathophysiological overlap between familial SSS and Na channelopathy indicates that familial SSS with SCN5A mutations may represent a subset of cardiac Na channelopathy with strong male predominance and early clinical manifestations

Improvement of Reduced Bone Mineral Density by Intermittent Cyclical Etidronate in Postmenopausal Asthmatic Patients Receiving Inhaled Corticosteroids

Background: We have recently shown that early postmenopausal but not premenopausal asthmatic women treated with inhaled corticosteroids demonstrate reduced bone mineral density(BMD)and decreased serum intact osteocalcin levels. Thus, the development of therapeutic approaches would be desirable for the prevention and intervention of BMD reduction in postmenopausal asthmatic women receiving inhaled corticosteroids. Methods: This study was aimed at examining the effects of etidronate disodium on BMD in 20 postmenopausal asthmatic women with reduced BMD of the lumbar spine(T score ; −1.5 or less). These patients had been managed by inhaled beclomethasone dipropionate or inhaled fluticasone propionate, without regular use of oral or parentheral corticosteroids. They were given a 200 mg/day oral dose of etidronate disodium for 14 days every three months. BMD of the lumbar spine was determined at baseline and at 1 or 3 years after the treatment. Results: The baseline BMD was 0.692±0.018(SE)g/cm2(T score, −3.0±0.8). The BMD significantly increased by 5.2±2.0% at 1 year(P=0.022)and by 7.3±2.9% at 3 years(P=0.037)after the treatment. Conclusions: : Intermittent cyclical treatment with ethidronate improves reduced BMD in postmenopausal asthmatic women on inhaled corticosteroid therapy