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application/pdf英米言語文化研究. 1995, 43othe

旧海洋イスラーム王国キルワ島にみるスワヒリ海村の構造

名古屋大学博士(文学)名古屋大学博士学位論文 学位の種類:博士(文学) 学位授与年月日:平成20年3月25日doctoral thesi

Association between mu opioid receptorgene polymorphisms and alcohol dependence in a Japanese population

Alcohol dependence is an addiction that causes psychological and physical dependence and makes it difficult for those affected to control their intake of alcohol. The μ (mu), δ (delta) and κ (kappa) opioid receptors are thought to be associated with the development of alcohol dependence. Research has shown that μ opioid receptor knockout mice exhibit reduced alcohol consumption and reduced preference for alcohol. In this study, we confirmed whether mu opioid receptor (OPRM1) polymorphisms (IVS2+691C/G, −172G/T and −1748G/A) indeed have an effect on alcohol dependence formation in 64 patients, with 73 healthy people used as a control group. We compared the genotype, allele, carrier (minor allele carriers versus major allele homozygous carriers) and haplotype frequencies between these groups. In addition, the 1510A allele of acetaldehyde dehydrogenase 2 (ALDH2) polymorphism (1510G/A) causes poor metabolism of acetaldehyde, a major metabolite of alcohol. We also focused on ALDH2 1510G/G (ALDH2 *1/*1) carriers in the subjects. Three OPRM1 and one ALDH2 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. No significant differences were found in the frequency of OPRM1 polymorphisms between those suffering from alcohol dependence and the control group. We concluded that the three OPRM1 polymorphisms (IVS2+691C/G, −172G/T and −1748G/A) were not likely to be risk factors for alcohol dependence in a Japanese population. This report is the first in a Japanese population. Nevertheless, further analysis of the opioid receptor gene in a large sample size is required.アルコール依存症とは，飲酒の自制が困難となる薬物中毒であり，オピオイド受容体との関連が考えられている。μオピオイド受容体欠損マウスは，アルコール自己投与の減少とアルコールに対する嫌悪を示すことが確認されている。本研究では，μオピオイド受容体（OPRM1）遺伝子多型IVS2+691C/G，−172G/Tおよび −1748G/Aがアルコール依存形成に与える影響を調べるため，遺伝子型，アレルおよびマイナーアレル保持者別頻度，ハプロタイプ解析，連鎖不平衡解析を含めた検討を行った。なお，OPRM1遺伝子多型の影響についてより詳細に検討するため，アルコール感受性に関わる2型アルデヒド脱水素酵素遺伝子多型ALDH2 *1/*1を有する対象者に着目した解析も行った。アルコール依存症患者64人，コントロール75人を対象とした。遺伝子多型の解析には，制限酵素断片長多型法（PCR-RFLP）を用いた。解析の結果，患者群および健常者群間における遺伝子型，アレルおよびマイナーアレル保持者別，全てのハプロタイプ頻度において，有意な差異は認められなかった。今回の結果より，着目した3つのOPRM1遺伝子多型がアルコール依存症発症の危険因子となる可能性は低いことが示唆された。今後は，同遺伝子上の他の多型や，他のオピオイド受容体にも着目し，アルコール依存症との関与についてより詳細に検討する必要があると考えられる。journal articl

Nursing of tube feeding for the patients of postoperative head and neck cancer

頭頸部腫瘍術後の患者の食の満足感に対する、日常生活における病前の食の満足感と、経管栄養法に対する思いを明らかにすることを目的に、半構成的面接法で調査を行なった。その結果、頭頸部腫瘍患者の食事の満足感に影響する重要項目は、「嗜好性」「環境」であった。また食事形態によっても違いがみられ、最も食の楽しみを与えるのはミキサー食(患者に配膳し献立を確認後、ミキサーにかける)の可能性が示唆された。Article信州大学医学部附属病院看護研究集録 36(1): 135-144(2007)departmental bulletin pape

Improved Constraints on D0-D̅0 Mixing in D0→K+π- Decays from the Belle Detector

journal articl

Elevated Mutagenesis Does Not Explain the Increased Frequency of Antibiotic Resistant Mutants in Starved Aging Colonies

<div><p>The frequency of mutants resistant to the antibiotic rifampicin has been shown to increase in aging (starved), compared to young colonies of <i>Eschierchia coli</i>. These increases in resistance frequency occur in the absence of any antibiotic exposure, and similar increases have also been observed in response to additional growth limiting conditions. Understanding the causes of such increases in the frequency of resistance is important for understanding the dynamics of antibiotic resistance emergence and spread. Increased frequency of rifampicin resistant mutants in aging colonies is cited widely as evidence of stress-induced mutagenesis (SIM), a mechanism thought to allow bacteria to increase mutation rates upon exposure to growth-limiting stresses. At the same time it has been demonstrated that some rifampicin resistant mutants are relatively fitter in aging compared to young colonies, indicating that natural selection may also contribute to increased frequency of rifampicin resistance in aging colonies. Here, we demonstrate that the frequency of mutants resistant to both rifampicin and an additional antibiotic (nalidixic-acid) significantly increases in aging compared to young colonies of a lab strain of <i>Escherichia coli</i>. We then use whole genome sequencing to demonstrate conclusively that SIM cannot explain the observed magnitude of increased frequency of resistance to these two antibiotics. We further demonstrate that, as was previously shown for rifampicin resistance mutations, mutations conferring nalidixic acid resistance can also increase fitness in aging compared to young colonies. Our results show that increases in the frequency of antibiotic resistant mutants in aging colonies cannot be seen as evidence of SIM. Furthermore, they demonstrate that natural selection likely contributes to increases in the frequency of certain antibiotic resistance mutations, even when no selection is exerted due to the presence of antibiotics.</p></div

Mutations identified in 15 non-starved and 15 starved isolates, untested for resistance.

1<p>Number of reads at which variant allele was called out of total number of reads at that position.</p>2<p>Based on PCR and Sanger re-sequencing from individual strains.</p>3<p>Located within the gene <i>gcd</i>.</p>4<p>Located between the genes <i>yfjI</i> and <i>yfjJ</i>.</p>5<p>Located within the gene <i>mzrA</i>.</p>6<p>Located between the genes <i>yifB</i> and <i>ilvL</i>.</p

Mutations identified in 15 starved, rifampicin resistant isolates.

1<p>Number of reads at which variant allele was called out of total number of reads at that position.</p>2<p>Based on PCR and Sanger re-sequencing from individual strains.</p

Actual number of observed mutations in rifampicin resistant and nalidixic acid resistant starved genomes is much smaller than expected within HMS (hypermutating cell subpopulation) cells.

<p>Drawn is the distribution of the numbers of mutations we would expect to find in 1000 simulated experiments in which we sequence 15 HMS genomes, and each HMS genome is expected to accumulate on average 4.82 mutations (calculated based on a 25-fold increase in mutagenesis across the entire starved population and an HMS size of 10%). The arrows represent the numbers of mutations we actually observed in 15 fully sequenced starved rifampicin (Red), or nalidixic acid (Blue) resistant genomes.</p

The number of non-ribosomal genes affected by selection on codon usage varies greatly between genomes.

<p>For three representative genomes the distributions of overall levels of codon bias of non-ribosomal coding segments (CS, Blue), and Intergenic Control Coding Segments (ICCS, Red) are presented. Codon bias is measured using Nc′, a measure of codon bias that ranges between 20, for extremely biased genes that use only one codon per amino acid, to 61, for genes that use all synonymous codons equally <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0049060#pone.0049060-Novembre1" target="_blank">[19]</a>. Levels of codon bias in ICCS should result from background substitution biases alone, while levels of bias within CS are the result of both background substitution biases and selection on codon usage, if such selection affects a given CS.</p