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DiethyleneglycoxyP(V)tetrakis(p-n-butoxyphenyl)porphyrin (EGP(V)TBPP) forms a self-aggregation in an aqueous solution, and the photoexcited state of this molecule was effectively deactivated. Association with human serum albumin (HSA), a water-soluble protein, causes dissociation of the self-aggregation, resulting in recovery of the photosensitizer activity of EGP(V)TBPP. Under visible light irradiation, EGP(V)TBPP photosensitized HSA oxidation. The photosensitized singlet oxygen-generating activity of EGP(V)TBPP was confirmed by near-infrared emission measurement. A singlet oxygen quencher, sodium azide, partially inhibited the HSA photodamage; however, the quenching effect was estimated to be 57%. Another 43% of the HSA photodamage could be explained by the electron transfer mechanism. The redox potential of EGP(V)TBPP and the calculated Gibbs energy of electron transfer from tryptophan to photoexcited EGP(V)TBPP demonstrated the possibility of HSA oxidation through electron extraction. Fluorescence lifetime measurements of EGP(V)TBPP verified the electron transfer from HSA. The photosensitizer activity of EGP(V)TBPP can be controlled through an association with biomolecules, such as protein, and the electron transfer-mediated biomolecule photooxidation plays an important role in photodynamic therapy under hypoxia.

Purpose: The purpose of this study is to assess the usefulness of liraglutide in elderly patients with type 2 diabetes to prevent progression of dementia. Methods: We retrospectively reviewed 31 outpatients with 65 years of age or older, who have been treated with liraglutide for 6 years (Group G; 12 males/19 females, 73.1 ± 8.6 years-old, HbA1c 7.5 ± 0.4%, 9 patients with cerebrovascular diseases, 8 patients with cardiovascular diseases, 16 patients with insulin therapy). Daily dose of liraglutide was 0.9 mg except 2 patients (0.6 mg). We examined Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) on MRI, max-IMT measured by carotid artery ultrasonography, visceral fat area, concentrations of HbA1c and FPG, serum levels of CRP, HDL/LDL cholesterol, and TG, both before and after the treatment. Age, HbA1c, and VSRAD values-matched 16 patients who were treated with linagliptin were analyzed as a control (Group D). Results: After 6 years, VSRAD was significantly deteriorated in Group D (1.06±0.98→1.39±1.05 (p Conclusion: Liraglutide possibly prevent progression of dementia. The reduction of visceral obesity may contribute to this beneficial effect through anti-arteriosclerosis. Disclosure M. Yoshida: None. A. Yoshida: None. E. Oh: None. N. Yamamoto: None. E. Sasaki: None. S. Yoshida: None. N. Ohsawa: None. M. Sugino: None. I. Koyama: None.

OBJECTIVE Presenteeism is considered to be not only a work-related stressor but also a factor involved in the development of workaholism and error proneness, which is often described as careless. Additionally, increasing health issues arising from aging suggest the possibility that presenteeism in middle-aged nurses is different than that in young ones. Therefore, the present study aimed to identify and tease apart factors involved in presenteeism among young and middle-aged nurses. METHODS An anonymous self-administered questionnaire survey was conducted among 2,006 nurses working at 10 hospitals. In total, 761 nurses aged

Purpose: The aim of this study was to assess the long-term efficacy of liraglutide on diabetic nephropathy in elderly patients with type 2 diabetes. Methods: Liraglutide was administrated to elderly patients with poorly controlled type 2 diabetes in Aino Hospital. We recruited and retrospectively reviewed 31 patients who were treated with liraglutide for 5 years (Group L: 7 males/24 females, 75.4±8.1 years old of age, 16 with cerebrovascular and 8 patients with cardiovascular diseases at baseline) and 25 patients who were not treated with liraglutide (Group N, 9 males/16 females, 74.6±11.6 years old of age). Daily dose of liraglutide was 0.9mg except 2 patients (0.6 mg). Results: After 5 years of treatment, HbA1c, FPG, and 2h-PPG significantly decreased in both groups (7.5±0.4 to 6.8±0.5 vs. 7.4±0.6 to 6.9±0.4%, 138±19 to 120±11 vs. 132±16 to 113±13, 206±31 to 173±18 vs. 186±23 to 163±18mg/dl, respectively(p60, Group B (n=18): eGFR = 30-60, Group C (n=7): eGFR Conclusion: Liraglutide improved glycemic control, lipid profile and BMI of elderly patients with type 2 diabetes. Liraglutide also demonstrated its beneficial effect on renal function. Disclosure M. Yoshida: None. A. Yoshida: None. E. Oh: None. N. Yamamoto: None. E. Sasaki: None. A. Saeki: None. S. Yoshida: None. T. Kuzuya: None. N. Ohsawa: None. M. Sugino: None.

Recent schizophrenia (SCZ) studies have reported an increased burden of de novo copy number variants (CNVs) and identified specific high-risk CNVs, although with variable phenotype expressivity. However, the pathogenesis of SCZ has not been fully elucidated. Using array comparative genomic hybridization, we performed a high-resolution genome-wide CNV analysis on a mainly (92%) Japanese population (1699 SCZ cases and 824 controls) and identified 7066 rare CNVs, 70.0% of which were small (

Purpose: The aim of this study was to assess the efficacy of liraglutide on prevention of dementia in elderly patients with type 2 diabetes (T2DM). Subjects and methods: We studied 34 (male 8/female 26) outpatients with 65 years or older, whose HbA1c was over 7.0% by other antidiabetic treatment. We administrated liraglutide 0.3mg before breakfast for the first week, 0.6mg for the second week, and 0.9mg after the third week. 34 subjects in the liraglutide group (G group) [8 males/ 26 females, 75.7±7.8 years old, HbA1c 7.5 ± 0.38%] were followed-up for 3 years. We examined Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) on MRI, max-IMT measured by carotid artery echo, visceral fat area, HbA1c, FPG, serum HDL/LDL level, and TG, both before and after the treatment.10 patients in the linagliptin group (D group) in which ages, HbA1c, visceral fat, and VSRAD were matched with G group were used as controls. Result: After 3 years, VSRAD was not changed in G group and was significantly deteriorated in D group (G group: 1.22±0.73→1.19±0.73 (NS) vs. G group: 1.36±0.87→1.53±0.99 (p = 0.022)). Max IMT was significantly improved in G group (2.42±1.65→2.14±1.40 (p =0.035) vs. 2.25±1.19→2.19±1.01(NS)). Visceral fat was significantly reduced in G group (137.1±54.0→128.0±59.3 (p Conclusion: Liraglutide improved the glycemic control, lipid profile, and visceral obesity of elderly patients with T2DM for 3 years. In addition, the hippocampal atrophy and arteriosclerosis were not deteriorated, suggesting the possibility of being effective for prevention of dementia. Disclosure M. Yoshida: None. T. Morimoto: None. E. Oh: None. N. Yamamoto: None. K. Nagata: None. A. Saeki: None. E. Sasaki: None. S. Yoshida: None. T. Kuzuya: None. N. Ohsawa: None. M. Sugino: None.

Due to the accident of Fukushima Daiichi Nuclear Power Plant, some areas were contaminated by released radioisotopes (mainly 137Cs and 134Cs). Effective decontamination is demanded to encourage eva...

DNA damage by oxidative stress has been extensively investigated, but the effect of interaction with histone protein on the DNA oxidation has not been well-understood. The effects of amino acids on DNA oxidation induced by one-electron oxidants were examined by ab initio molecular orbital calculation at Hartree-Fock 6-31G* level. The calculated ionization potentials of nucleobases suggest that guanine is protected by interaction with amino acids from oxidative damage, whereas oxidation of adenine is enhanced through interaction with several kinds of amino acids. These findings suggest that adenine can be easily oxidized under the interaction with certain amino acid in chromatin rather than guanine, which can be most easily oxidized in isolated DNA. The effect of amino acids on DNA oxidation may explain the mutation at adenine residue induced by oxidative stress due to ultraviolet A irradiation.

N-methyl-d-aspartate receptors (NMDARs) play a critical role in excitatory synaptic transmission and plasticity in the central nervous systems. Recent genetics studies in schizophrenia (SCZ) show that SCZ is susceptible to NMDARs and the NMDAR signaling complex. In autism spectrum disorder (ASD), several studies report dysregulation of NMDARs as a risk factor for ASD. To further examine the association between NMDARs and SCZ/ASD development, we conducted a mutation screening study of GRIN2B which encodes NR2B subunit of NMDARs, to identify rare mutations that potentially cause diseases, in SCZ and ASD patients (n = 574 and 152, respectively). This was followed by an association study in a large sample set of SCZ, ASD, and normal healthy controls (n = 4145, 381, and 4432, respectively). We identified five rare missense mutations through the mutation screening of GRIN2B. Although no statistically significant association between any single mutation and SCZ or ASD was found, one of its variant, K1292R, is found only in the patient group. To further examine the association between mutations in GRIN2B and SCZ/ASD development, a larger sample size and functional experiments are needed.

Sanguinarine, a plant alkaloid, was identified as a potent and specific protein phosphatase (PP) 2C inhibitor. It inhibited PP2C competitively with respect to alpha-casein (Ki=0.68 microM) and showed selectivity for PP2C as compared with PP1, PP2A, and PP2B in vitro. In vivo, sanguinarine showed cytotoxicity toward human promyelocytic leukemia cell line HL60, with an IC(50) value of 0.37 microM, and induced apoptosis through a caspase-3/7-dependent mechanism involving the phosphorylation of p38, a PP2Calpha substrate. The apoptosis activity induced by sanguinarine was partially inhibited by a p38 inhibitor, SB203580, and was involved in the phospho-p38 protein in HL60 cells.

我々は, バセドウ病発症に伴い, 精神変調を来した, もしくは精神変調が悪化し, 西洋医学的治療により甲状腺機能が正常化したにも関わらず精神変調の改善が無く, 漢方治療を併用することで改善を認めた2症例を経験した。症例1は, 24歳女性。2000年にバセドウ病と診断され, 抗甲状腺剤による治療が開始され, 機能正常となったが, イライラ感, 不安感, 絶望感等の精神変調が改善しないため2005年2月来院。症例2は, 26歳女性。高校卒業後, 就職を契機にバセドウ病を発症。抗甲状腺剤による治療が開始されたが, 甲状腺機能は不安定で軽度の亢進と低下を繰り返し, その間にイライラ感, 疲れやすい, 気力減退, 脱毛等の症状が悪化し, 2005年1月来院。2例とも桂枝甘草竜骨牡蠣湯合半夏厚朴湯を処方 (症例1は経過中変方有り) し, それぞれ16週, 9週後には症状は著明に改善した。精神変調を併発したバセドウ病に対する漢方治療の有用性が示唆された。

Four 81Br NQR lines in 4-NH2C5H4NHBiBr4·H2O were observed in the temperature range between 77 and ca. 380 K; with increasing temperatures the respective sets of higher and lower two resonance lines coalesced into single lines discontinuously at 274 K, showing the occurrence of a first-order type phase transition of this crystal. The transition was confirmed with heat anomaly on a DTA curve. Each higher and lower line of high-temperature phase is assignable to the terminal Br atoms and the bridging ones of one-dimensional poly anions (BiBr4 −)n in the crystal structure (C2/c), which was investigated by a X-ray structure analysis at room temperature. The 1/T 1 temperature dependence of 81Br NQR follows the usual T 2 law in the temperature range between 77 and ca. 140 K, being explained by fluctuation of the EFG at Br nucleus due to lattice vibrations. The T1 vs. 1/T curve in the temperature range between about 160 and 190 K was describable by the exponential curves, allowing us the estimation of activation energies. These exponential behaviors of T 1 of 81Br NQR are attributable to the fluctuations caused by the thermal motion of 4-NH2C5H4H+ ions. Echo signals of the 81Br NQR could not be detected above 190 K owing to poor S/N with very short T 2.

This study was undertaken to identify the temporal characteristics of corticospinal excitability of tibialis anterior muscle during the observation of the initial phase of gait. For this purpose, using transcranial magnetic stimulation, we recorded motor evoked potentials (MEPs) during the observation of the second step of an actor's first three steps of gait initiation with (complex gait) or without (normal gait) an obstacle and unstable surface. The results demonstrate that (1) MEPs during the observation of the initial phase of normal gait were significantly increased only at early swing phase, but not other phases (mid-swing, heel contact, mid-stance, and heel off) and (2) MEPs during the observation of the initial phase of complex gait were significantly increased at early swing and also at mid-swing and heel contact phases. These findings provide the first evidence that corticospinal excitability during the observation of gait, especially the initial phase, is modulated in phase- and motor-demanded-dependent manners.

We investigated whether polymorphisms of the renin-angiotensin system genes are involved in IgA nephropathy in Japanese children. We identified the M235T polymorphism of the angiotensinogen (AGT) gene, the I/D polymorphisms of the angiotensin-converting enzyme (ACE) gene, and the A1166C polymorphism of the angiotensin II type 1 receptor gene in 95 Japanese children with IgA nephropathy and 99 healthy Japanese adults. There were no differences in the genotype and allele frequencies of these genes between patients with IgA nephropathy and controls. Urinary protein excretion at the time of biopsy was significantly greater in patients with the TT genotype of the AGT gene than in those with the MM/MT genotypes of the AGT gene (1.32 +/- 1.42 versus 0.75 +/- 0.78 g/day; P = 0.01) and in patients with the ID/DD genotypes of the ACE gene than in those with the II genotype of the ACE gene (1.45 +/- 1.50 versus 0.63 +/- 0.56 g/day; P = 0.001). Thus, the TT genotype of the AGT gene and the ID/DD genotype of the ACE gene are associated with increased severity of proteinuria, suggesting that AGT and ACE gene polymorphisms may play a significant role in the progression of IgA nephropathy in Japanese children.

本稿では,2000年度から平安女学院短期大学英語コミュニケーション学科において英語プログラムを改変するにあたって,旧プログラムの問題点分析を行い,その問題点の対処策及びその他の改善方法を具体的に提案した。まず最初に,先行研究から語学教育のカリキュラム刷新において重要な理論を紹介し,Skilbeckの枠組みに沿ってカリキュラム刷新を計画した。旧プログラムにおいて最大の問題なであった各授業間のコーディネーションの欠如は,統一のトピックでリーディング,ライティング,スピーキング,リスニングの各授業を展開できるようにシラパスや教材を作成することで改善されることを提案した。さらに,発音練習や口頭発表などを積極的に促すことで,あらゆる場面でスピーキング能力向上を第一に目指した指導法を使用することの必然性も指摘した。

In many experimental systems, antisense nucleic acids of various compositions, including antisense oligodeoxynucleotides, ribozymes, and DNAzymes, have been shown to perturb gene expression in a sequence specific manner. Nevertheless, we have employed need to be optimized with regard to intracellular delivery, targeting, chemical composition, and efficiency of mRNA destruction. These sequence-specific inhibitors of gene expression may have therapeutic potential in the treatment of a wide range of diseases. We have addressed these critical issues lead to the development of practical and effective nucleic acid drugs within this review.

肥満を伴うインスリン非依存性糖尿病 (NIDDM) 患者19例に対し, 運動療法が可能な9例では, 160Calorie/日の有酸素運動 (速歩) 療法を6ヵ月間施行, 実施困難な身体状況にある11例には, 防已黄耆湯を6ヵ月間投与した。運動療法は内臓脂肪型肥満に有効とされているが, 運動療法群では, 治療前後で, CTスキャンを用い測定した内臓脂肪面積と皮下脂肪面積の比 (V/S比) が0.77±0.26から0.65±0.30へ低下したが, 肥満度及び血糖, 脂質についても有意な改善をみなかった。一方, 防已黄耆湯投与群では, 血清コレステロール値が197±31mg/dlから180±19mg/dl(P

A major purpose of this article is to examine past research devoted to the 'inferential process' in first language (LI) reading and second language (L2) reading and, in so doing, to uncover significant research voids related to L2 reading research and suggest further research possibilities. The article first demonstrates current development on inference study in both LI and L2 reading research. It then discusses five fundamental dimensions to L2 inference research from the perspectives of cognitive process required in reading and unique problems encountered by L2 reading research. The five fundamental dimensions discussed here are: 1) types of inference 2) automatization of the process and assessment methodologies 3) the effect of background knowledge 4) the effect of L2 proficiency 5) the transferability of LI reading skill. This article also proposes how these five dimensions should be incorporated in the L2 inference research, in order to establish adequate theoretical ground for L2 reading research.

芍薬甘草湯によってミオトニーの持続時間が短縮した筋緊張性ジストロフィー症の一例を報告した。本剤は現在一般に使用されている西洋薬と同等の効果を示した。この効果より, 本剤は骨格筋細胞膜のイオンチャンネルにも作用することが明かとなった。その主要機序として glycyrrhizin によるKチャンネルへの作用を考え, 作用部位として apamin-sensitive K channel の可能性を推定した。また, 本剤は5週間連続投与されたが, ミオパチーの悪化は認められなかった。

西洋医学的な対症療法では対応できなくなった HTLV-I-associated myelopathy 症例に小柴胡湯を投与したところ, 瞑眩様症状の後に臨床症状の改善をみた。本例に対する小柴胡湯の効果は, その抗炎症作用と免疫調整作用によるものと考え, 特にサイトカインを介した後者の作用に注目した。本症に対して西洋医学的に有効な治療法がない現在, 症例を集積して漢方治療が検討されるべきである。

本研究では, 早期発症型歯周炎に対する初期治療の効果を評価した。早期発症型歯周炎患者29人 (年齢13～35歳, 男性12人, 女性17人) を対象として初期治療 (ブラッシング指導, スケーリング, ルートプレーニング, 簡単な咬合調整) 前後の各臨床評価項目の推移について比較・検討した。その結果, 歯肉の発赤・腫脹, 出血, 排膿, 動揺の各スコアーおよびプロービングデプスはいずれも初期治療により有意に改善した。初診時に深さが6mm以下であった歯周ポケットでは, 初期治療により4mm以下に改善するものが多くみられたが, 7mm以上のポケットの多くは初期治療後に5mm以上に留った。また, 30代の患者では, 10代, 20代に比べて初期治療によるPDの改善が悪かった。これらのことから, 早期発症型歯周炎においても早期発見が重要であり, 成人性歯周炎同様に初期治療による効果が十分に期待できること, また, 初期治療による効果が少ない症例にはさらに積極的な治療を行う必要性があることが示唆された。

Photosensitized DNA damage participates in solar-UV carcinogenesis, photogenotoxicity and phototoxicity. A chemoprevention of photosensitized DNA damage is one of the most important methods for the above phototoxic effects. In this study, the chemopreventive action of xanthone (XAN) derivatives (bellidifolin [BEL], gentiacaulein [GEN], norswertianin [NOR] and swerchirin [SWE]) on DNA damage photosensitized by riboflavin was demonstrated using [32P]-5'-end-labeled DNA fragments obtained from genes relevant to human cancer. GEN and NOR effectively inhibited the formation of piperidine-labile products at consecutive G residues by photoexcited riboflavin, whereas BEL and SWE did not show significant inhibition of DNA damage. The four XAN derivatives decrease the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), an oxidative product of G, by photoexcited riboflavin. The preventive action for the 8-oxodGuo formation of these XAN derivatives increased in the following order: GENNORBELSWE. A fluorescence spectroscopic study and ab initio molecular orbital calculations suggested that the prevention of DNA photodamage is because of the quenching of the triplet excited state of riboflavin by XAN derivatives through electron transfer. This chemoprevention is based on neither antioxidation nor a physical sunscreen effect; rather, it is based on the quenching of a photosensitizer. In conclusion, XAN derivatives, especially GEN, may act as novel chemopreventive agents by the quenching mechanism of an excited photosensitizer.

Titanium dioxide (TiO2) is a potential photosensitizer for photodynamic therapy. In this study, the mechanism of DNA damage catalyzed by photo-irradiated TiO2 was examined using [32P]-5'-end-labeled DNA fragments obtained from human genes. Photo-irradiated TiO2 (anatase and rutile) caused DNA cleavage frequently at the guanine residue in the presence of Cu(II) after E. coli formamidopyrimidine-DNA glycosylase treatment, and the thymine residue was also cleaved after piperidine treatment. Catalase, SOD and bathocuproine, a chelator of Cu(I), inhibited the DNA damage, suggesting the involvement of hydrogen peroxide, superoxide and Cu(I). The photocatalytic generation of Cu(I) from Cu(II) was decreased by the addition of SOD. These findings suggest that the inhibitory effect of SOD on DNA damage is due to the inhibition of the reduction of Cu(II) by superoxide. We also measured the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an indicator of oxidative DNA damage, and showed that anatase is more active than rutile. On the other hand, high concentration of anatase caused DNA damage in the absence of Cu(II). Typical free hydroxyl radical scavengers, such as ethanol, mannnitol, sodium formate and DMSO, inhibited the copper-independent DNA photodamage by anatase. In conclusion, photo-irradiated TiO2 particles catalyze the copper-mediated site-specific DNA damage via the formation of hydrogen peroxide rather than that of a free hydroxyl radical. This DNA-damaging mechanism may participate in the phototoxicity of TiO2.

Two research groups have thus far reported a significant association between schizophrenia and a promoter polymorphism (-308G > A) of the gene encoding tumor necrosis factor alpha (TNF-alpha), while contradictive negative results have also been reported. We examined the possible association in a Japanese sample of 297 schizophrenia cases and 458 controls. Allele frequencies of both the patients and controls were very low (1.5% and 0.8%, respectively), and the difference was not statistically significant. We conclude that the effect of the -308G > A polymorphism on the development of schizophrenia is, if any, weak and the majority of Japanese schizophrenics are unrelated to the -308G > A polymorphism of the TNF-alpha gene.

UVA contributes to skin cancer by solar UV light. Photosensitizers are believed to play an important role in UVA carcinogenesis. We investigated the mechanism of DNA damage induced by photoexcited xanthone (XAN) analogues (XAN, thioxanthone [TXAN] and acridone [ACR]), exogenous photosensitizers, and the relationship between the DNA-damaging abilities and their highest occupied molecular orbital (HOMO) energies. DNA damage by these photosensitizers was examined using 32P-labeled DNA fragments obtained from the p53 tumor suppressor gene. Photoexcited XAN caused DNA cleavage specifically at 5'-G of the GG sequence in the double-stranded DNA only when the DNA fragments were treated with piperidine, suggesting that DNA cleavage is due to base modification with little or no strand breakage. With denatured single-stranded DNA, the extent of XAN-sensitized photodamage was decreased. An oxidative product of G, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dGuo), was formed by photoexcited XAN, and the 8-oxo-dGuo formation was decreased in single-stranded DNA. TXAN and ACR induced DNA photodamage as did XAN, although the order of DNA-damaging ability was XANTXANACR. These findings suggest that photoexcited XAN analogues induce nucleobase oxidation at 5'-G of GG sequence in double-stranded DNA through electron transfer. The HOMO energies of these photosensitizers, estimated from ab initio molecular orbital (MO) calculation, decreased in the following order: XANTXANACR. Extents of DNA damage increased exponentially with the HOMO energies of XAN analogues. This study suggests that DNA-damaging abilities of photosensitizers can be estimated from their HOMO energies.

The contribution of intestinal mucosal lipid components to the membrane permeation process of water-soluble drugs was examined by using liposomes as a model membrane. Mucosal lipids extracted from the rat small intestine were fractionated into several lipid classes by column chromatography and each lipid fraction was reconstituted into the liposomal membrane. The release rate of drugs incorporated in liposomes was measured (pH 6.5) as an index of the membrane permeability. 6-Carboxyfluorescein (6-CF), procainamide ethobromide (PAEB) and sulfanilic acid (SA) were employed as model drugs. Their absorption percentages from rat small intestine in one hour were 2.4%, 3.2% and 7.5%, respectively, as determined by the in situ recirculation technique (pH 6.5). These drugs were more permeable through the liposomal membranes containing intestinal free fatty acids than egg lecithin liposomes, with the exception of SA. Arrhenius plots of the release rate constants indicated that increased liposomal membrane fluidity was partly responsible for this accelerated release in the case of PAEB, but no significant change was observed in the activation energy for the membrane permeation of 6-CF. From these observations, it is concluded that lipid components, especially free fatty acids of the intestinal mucosa, play an important role in the absorption process of these water-soluble drugs.