ADHD患児とその保護者の服薬アドヒアランス調査

【目的】注意欠如・多動症（ADHD）の患児とその保護者が薬物治療をどのように評価し，治療に向き合っているのかを明らかにする。【方法】ADHDの診断を受け，メチルフェニデート徐放剤およびアトモキセチンを処方された小１から高３までの患児94 人と保護者106人に質問紙調査と半構造化面接を行った。【結果】90％以上で服薬は規則正しく行われており，薬物治療に対する肯定的な評価は，患児・保護者で約80 ～ 90％と高かった。一方で，全面的に賛成しているわけではなく，約80％の保護者が否定的な意見も持っていた．否定的評価をする要因は，保護者は副作用を含めた長期的な影響への不安，患児は服薬の煩わしさや胃腸症状が多かった。定期的な薬物治療を続けているにも関わらず，効果と不安等を天秤にかけて治療を継続することへの積極的な支持は，患児・保護者で約50 ～ 60％であった。【結論】小児では，低年齢のため客観的に自身の状況を判断し，見通しをもって治療に参加することが難しい場合がある。患児へは胃腸症状への対処を，保護者へは治療の見通しや副作用について丁寧な説明を繰り返すことによって，薬物治療への否定的評価が軽減され，服薬アドヒアランスが向上する可能性がある

Multi-channel near-infrared spectroscopy reveals reduced prefrontal activation in schizophrenia patients during performance of the kana Stroop task

The purpose of the present study was to investigate the activity of frontal lobe of patients with schizophrenia during performance of two Japanese versions of the Stroop task (kana and kanji) by measuring changes in the concentration of oxygenated hemoglobin (oxyHb) with near-infrared spectroscopy (NIRS). Fourteen schizophrenia patients and 14 age- and gender-matched healthy control subjects participated in the study after giving consent. The relative changes of concentrations of oxyHb were measured by NIRS during performance of the Stroop task. Significant Stroop effects, as measured by the number of correct responses, were observed with both the kana and the kanji versions. Analysis of NIRS data revealed that the schizophrenia patients showed reduced activation in the prefrontal cortex compared to healthy controls during performance of the kana Stroop task, and that both schizophrenia patients and healthy controls showed lack of activity in the prefrontal cortex during performance of the kanji Stroop task. The results of the present study suggest the possibility that the kana Stroop task cause a greater Stroop effect than the kanji Stroop task, and schizophrenia patients show decreased prefrontal vascular reactivity associated with the inhibition required during the performance of the kana Stroop task

Assessment of human stress and depression by DNA microarray analysis

Precise assessment of stress is an imminent issue to deal with stress-related social, medical and psychological problems. Psychological stress is known to stimulate the neuroendocrine, sympathetic nervous, and immune systems. By analyzing mRNA expression levels in leukocytes, which express receptors for hormones, neurotransmitters, growth factors, cytokines, and other stress related signals, levels of stress may be adequately measured. In a series of studies, our group has developed a cDNA microarray specifically designed to measure the mRNA levels of stress-related genes in peripheral blood leukocytes. This microarray enabled us to sensitively detect the response to psychological stress. In addition, our preliminary study suggests that the array could differentiate patients with depression from sex- and age-matched control subjects

A Serine Palmitoyltransferase Inhibitor Blocks Hepatitis C Virus Replication in Human Hepatocytes

Background & AimsHost cell lipid rafts form a scaffold required for replication of hepatitis C virus (HCV). Serine palmitoyltransferases (SPTs) produce sphingolipids, which are essential components of the lipid rafts that associate with HCV nonstructural proteins. Prevention of the de novo synthesis of sphingolipids by an SPT inhibitor disrupts the HCV replication complex and thereby inhibits HCV replication. We investigated the ability of the SPT inhibitor NA808 to prevent HCV replication in cells and mice.MethodsWe tested the ability of NA808 to inhibit SPT’s enzymatic activity in FLR3-1 replicon cells. We used a replicon system to select for HCV variants that became resistant to NA808 at concentrations 4- to 6-fold the 50% inhibitory concentration, after 14 rounds of cell passage. We assessed the ability of NA808 or telaprevir to inhibit replication of HCV genotypes 1a, 1b, 2a, 3a, and 4a in mice with humanized livers (transplanted with human hepatocytes). NA808 was injected intravenously, with or without pegylated interferon alfa-2a and HCV polymerase and/or protease inhibitors.ResultsNA808 prevented HCV replication via noncompetitive inhibition of SPT; no resistance mutations developed. NA808 prevented replication of all HCV genotypes tested in mice with humanized livers. Intravenous NA808 significantly reduced viral load in the mice and had synergistic effects with pegylated interferon alfa-2a and HCV polymerase and protease inhibitors.ConclusionsThe SPT inhibitor NA808 prevents replication of HCV genotypes 1a, 1b, 2a, 3a, and 4a in cultured hepatocytes and in mice with humanized livers. It might be developed for treatment of HCV infection or used in combination with pegylated interferon alfa-2a or HCV polymerase or protease inhibitors

Characterization of autonomous Dart1 transposons belonging to the hAT superfamily in rice

An endogenous 0.6-kb rice DNA transposon, nDart1-0, was found as an active nonautonomous element in a mutable virescent line, pyl-v, displaying leaf variegations. Here, we demonstrated that the active autonomous element aDart in pyl-v corresponds to Dart1-27 on chromosome 6 in Nipponbare, which carries no active aDart elements, and that aDart and Dart1-27 are identical in their sequences and chromosomal locations, indicating that Dart1-27 is epigenetically silenced in Nipponbare. The identification of aDart in pyl-v was first performed by map-based cloning and by detection of the accumulated transposase transcripts. Subsequently, various transposition activities of the cloned Dart1-27 element from Nipponbare were demonstrated in Arabidopsis. Dart1-27 in Arabidopsis was able to excise nDart1-0 and Dart1-27 from cloned sites, generating footprints, and to integrate into new sites, generating 8-bp target site duplications. In addition to Dart1-27, Nipponbare contains 37 putative autonomous Dart1 elements because their putative transposase genes carry no apparent nonsense or frameshift mutations. Of these, at least four elements were shown to become active aDart elements in transgenic Arabidopsis plants, even though considerable sequence divergence arose among their transposases. Thus, these four Dart1 elements and Dart1-27 in Nipponbare must be potential autonomous elements silenced epigenetically. The regulatory and evolutionary implications of the autonomous Dart1 elements and the development of an efficient transposon-tagging system in rice are discussed

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

ADHD患児とその保護者の服薬アドヒアランス調査

【目的】注意欠如・多動症（ADHD）の患児とその保護者が薬物治療をどのように評価し，治療に向き合っているのかを明らかにする。【方法】ADHDの診断を受け，メチルフェニデート徐放剤およびアトモキセチンを処方された小１から高３までの患児94 人と保護者106人に質問紙調査と半構造化面接を行った。【結果】90％以上で服薬は規則正しく行われており，薬物治療に対する肯定的な評価は，患児・保護者で約80 ～ 90％と高かった。一方で，全面的に賛成しているわけではなく，約80％の保護者が否定的な意見も持っていた．否定的評価をする要因は，保護者は副作用を含めた長期的な影響への不安，患児は服薬の煩わしさや胃腸症状が多かった。定期的な薬物治療を続けているにも関わらず，効果と不安等を天秤にかけて治療を継続することへの積極的な支持は，患児・保護者で約50 ～ 60％であった。【結論】小児では，低年齢のため客観的に自身の状況を判断し，見通しをもって治療に参加することが難しい場合がある。患児へは胃腸症状への対処を，保護者へは治療の見通しや副作用について丁寧な説明を繰り返すことによって，薬物治療への否定的評価が軽減され，服薬アドヒアランスが向上する可能性がある