The relation analysis between periodontal disease and diabetes mellitus using the severity classification of periodontal disease

【背景と目的】現在，国際糖尿病連合によると，世界では3億8,670万人の糖尿病患者がいるといわれている．また，2012年の国民健康・栄養調査結果によると，日本人で糖尿病が強く疑われる者は950万人，さらに糖尿病の可能性を否定できない者が1,100万人いると報告されている．このように，糖尿病は日本においても非常に罹患率の高い疾患であり，歯科医院に通院中の患者の中にも多くの糖尿病罹患者が存在することが予想される．すでに，歯周病は，網膜症，腎症，神経障害，末梢血管障害，大血管障害に続く糖尿病の第6番目の合併症とされている．20年ほど前より，ペリオドンタルメディシンという概念のもと，歯周病と糖尿病との関連性が疫学研究を中心に数多く報告されているが，日本人における両疾患の関連性に関する統一見解，あるいは詳細なデータはほとんど存在しない．その理由の1つに，歯周病を評価する統一基準がなかったことがあげられる．そこで，2011年に特定非営利活動法人日本歯周病学会ペリオドンタルメディシン委員会は，より簡便で，医科と情報共有が可能な分類であることを目標とし，歯周病の臨床指標である歯槽骨吸収率と，炎症マーカーである高感度C-reactive protein (CRP)値を用いた歯周病の重症度別分類を作成した．本研究では，この重症度別分類に用いられ，指標となっている歯槽骨吸収率，および高感度CRP値と，糖尿病の関係を明らかにすることを目的とした．さらに，歯槽骨吸収率および高感度CRP値から糖尿病を予測しうるかどうかも検討した．【材料と方法】研究には，松本歯科大学病院健診センターに人間ドック，および同大学病院歯周病科を受診した糖尿病罹患者50名を含む患者374人（男性253名，女性121名）を対象とし，すべての被験者の撮影されたパノラマエックス線写真，あるいはデンタルエックス線写真から，歯槽骨吸収率を求めた．また，末梢血を採取し，高感度CRP値の測定を行った．その後，上述の重症度別分類を用いて，各々の被験者における歯周病の重症度程度を分類した．本研究で用いる重症度別分類とは，歯槽骨吸収率が25％以下を臨床的軽度：Ⅰ，25％以上を中等度：Ⅱ，35％以上を重度：Ⅲとし，高感度CRP値が440ng/ml以下を炎症度軽度：A，440ng/ml以上を中等度：B，1,020ng/ml以上を重度：Cとして，それぞれ3段階に分け，9つの群に分類するものである．解析方法は，性別，年齢，Body Mass Index(BMI)，喫煙の既往，現在歯数，歯槽骨吸収率（3分類），高感度CRP値（3分類）を独立変数とし，糖尿病の有無を従属変数とするロジスティック回帰分析（変数増加法）により評価した．さらに，歯槽骨吸収率および高感度CRP値により，糖尿病のスクリーニングができるか否かをROC（Receiver Operating Characteristic curve；受信者動作特性曲線）解析で検討した．【結果】解析結果より，糖尿病の有無に関連する因子は，年齢，BMI，歯槽骨吸収率，高感度CRP値であることが判明した．また，歯槽骨吸収率および高感度CRP値が高いほど糖尿病のリスクが高くなることが分かった．そこでROC解析を行ったところ，歯槽骨吸収率，および高感度CRP値と糖尿病のArea under the Receiver Operatorating Characteristic curve (AUROC)値は各々，0.76と0.71であり，歯槽骨吸収率と高感度CRP値が糖尿病のスクリーニング指標として有用であることが判明した．【結論】本研究により，糖尿病の有無に関連する因子は年齢，BMI，歯槽骨吸収率，高感度CRP値であることが判明した．さらに歯槽骨吸収率，および高感度CRP値が糖尿病のスクリーニング指標として有用であることがわかり，この事から，歯科受診時のエックス線写真撮影，あるいは健診時の高感度CRP値を測定することで，糖尿病のスクリーニングができ，早期発見，早期治療につながる可能性が示唆された．2015博士（歯学）松本歯科大

Overexpression of the JmjC histone demethylase KDM5B in human carcinogenesis: involvement in the proliferation of cancer cells through the E2F/RB pathway.

BACKGROUND: Although an increasing number of histone demethylases have been identified and biochemically characterized, their biological functions largely remain uncharacterized, particularly in the context of human diseases such as cancer. We investigated the role of KDM5B, a JmjC histone demethylase, in human carcinogenesis. Quantitative RT-PCR and microarray analyses were used to examine the expression profiles of histone demethylases in clinical tissue samples. We also examined the functional effects of KDM5B on the growth of cancer cell lines treated with small interfering RNAs (siRNAs). Downstream genes and signal cascades induced by KDM5B expression were identified from Affymetrix Gene Chip experiments, and validated by real-time PCR and reporter assays. Cell cycle-dependent characteristics of KDM5B were identified by immunofluorescence and FACS. RESULTS: Quantitative RT-PCR analysis confirmed that expression levels of KDM5B are significantly higher in human bladder cancer tissues than in their corresponding non-neoplastic bladder tissues (P < 0.0001). The expression profile analysis of clinical tissues also revealed up-regulation of KDM5B in various kinds of malignancies. Transfection of KDM5B-specific siRNA into various bladder and lung cancer cell lines significantly suppressed the proliferation of cancer cells and increased the number of cells in sub-G1 phase. Microarray expression analysis indicated that E2F1 and E2F2 are downstream genes in the KDM5B pathway. CONCLUSIONS: Inhibition of KDM5B may affect apoptosis and reduce growth of cancer cells. Further studies will explore the pan-cancer therapeutic potential of KDM5B inhibition.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Possible involvement of iron-induced oxidative insults in neurodegeneration.

Involvement of iron in the development of neurodegenerative disorders has long been suggested, and iron that cannot be stored properly is suggested to induce iron toxicity. To enhance iron uptake and suppress iron storage in neurons, we generated transgenic (Tg) mice expressing iron regulatory protein 2 (IRP2), a major regulator of iron metabolism, in a neuron-specific manner. Although very subtle, IRP2 was expressed in all regions of brain examined. In the Tg mice, mitochondrial oxidative insults were observed including generation of 4-hydroxynonenal modified proteins, which appeared to be removed by a mitochondrial quality control protein Parkin. Inter-crossing of the Tg mice to Parkin knockout mice perturbed the integrity of neurons in the substantia nigra and provoked motor symptoms. These results suggest that a subtle, but chronic increase in IRP2 induces mitochondrial oxidative insults and accelerates neurodegeneration in a mouse model of Parkinson's disease. Thus, the IRP2 Tg may be a useful tool to probe the roles of iron-induced mitochondrial damages in neurodegeraration research

Comprehensive analysis including the nutritional point of view on the pathogenesis of periodontal disease

To clarify risk factors for periodontal disease from the viewpoints of physiology, blood biochemistry, and nutrition, a survey involving 364 persons (224 males, 140 females) who consulted the Medical Examination Center of Matsumoto Dental University Hospital was conducted. The pathogenesis of periodontal disease was investigated using the maximum Community Periodontal Index (CPI) and Attachment Loss (AL) values, and their distributions with respect to the sex were analyzed using Wilcoxonʼs rank sum test. Based on the CPI and AL values, the subjects were divided into 3 groups: healthy (0), mild (1–2), and severe (3–4). The mean values obtained from the physiological, dental, blood biochemical, and nutritional findings in the 3 groups were analyzed using the multiple comparison test. Furthermore, their distributions with respect to sex and smoking in the 3 groups were analyzed using Fisherʼs direct probability test. A p–value of 0.05 was regarded as significant. Factors influencing the CPI included the sex (male), body mass index (BMI), abdominal circumference, diastolic blood pressure, AL, alanine aminotransferase (ALT), fasting blood glucose, neutral fat, HDL cholesterol, and smoking. Factors influencing the AL included the sex (male), age, current number of teeth, CPI, lipid intake, manganese intake, vitamin C intake, monounsaturated fatty acid intake, polyunsaturated fatty acid intake, n–6 fatty acid intake, fruit intake, and smoking. The results suggest that the physiological, blood biochemical, and nutritional states are involved in the pathogenesis of periodontal disease. The CPI was associated with metabolic error in the presence of metabolic syndrome. There was an association between the AL and diet as an environmental factor

Factors related to the number of missing teeth from a physiological, blood biochemical, and nutritional point of view

The aim of this study was to clarify the risk factors for tooth loss from a physiological, blood biochemical, and nutritional point of view. The subjects of this study were 364 people (224 males, 140 females). They were examinees of a medical examination center in Matsumoto Dental University Hospital. Using the number of teeth present (including sound, decayed, and filled teeth) as the response variable, a multiple regression analysis was conducted using parameters in the mouth, physiological parameters, blood biochemical parameters, and nutritional parameters as covariates. In the multiple regression analysis with the response variable as the number of teeth present, the significant influence of attachment loss, sugar–sweetener intake, age, and sodium intake was noted on a decreasing number of teeth in the study subjects. Thus, the number of teeth present was influenced by the physiological, blood biochemical, and nutritional condition. In the future, increasing the number of cases will be necessary along with long–term follow–up

Global Landscape of a Co-Expressed Gene Network in Barley and its Application to Gene Discovery in Triticeae Crops

Accumulated transcriptome data can be used to investigate regulatory networks of genes involved in various biological systems. Co-expression analysis data sets generated from comprehensively collected transcriptome data sets now represent efficient resources that are capable of facilitating the discovery of genes with closely correlated expression patterns. In order to construct a co-expression network for barley, we analyzed 45 publicly available experimental series, which are composed of 1,347 sets of GeneChip data for barley. On the basis of a gene-to-gene weighted correlation coefficient, we constructed a global barley co-expression network and classified it into clusters of subnetwork modules. The resulting clusters are candidates for functional regulatory modules in the barley transcriptome. To annotate each of the modules, we performed comparative annotation using genes in Arabidopsis and Brachypodium distachyon. On the basis of a comparative analysis between barley and two model species, we investigated functional properties from the representative distributions of the gene ontology (GO) terms. Modules putatively involved in drought stress response and cellulose biogenesis have been identified. These modules are discussed to demonstrate the effectiveness of the co-expression analysis. Furthermore, we applied the data set of co-expressed genes coupled with comparative analysis in attempts to discover potentially Triticeae-specific network modules. These results demonstrate that analysis of the co-expression network of the barley transcriptome together with comparative analysis should promote the process of gene discovery in barley. Furthermore, the insights obtained should be transferable to investigations of Triticeae plants. The associated data set generated in this analysis is publicly accessible at http://coexpression.psc.riken.jp/barley/

A Histone-Like Protein of Mycobacteria Possesses Ferritin Superfamily Protein-Like Activity and Protects against DNA Damage by Fenton Reaction

Iron is an essential metal for living organisms but its level must be strictly controlled in cells, because ferrous ion induces toxicity by generating highly active reactive oxygen, hydroxyl radicals, through the Fenton reaction. In addition, ferric ion shows low solubility under physiological conditions. To overcome these obstacles living organisms possess Ferritin superfamily proteins that are distributed in all three domains of life: bacteria, archaea, and eukaryotes. These proteins minimize hydroxyl radical formation by ferroxidase activity that converts Fe2+ into Fe3+ and sequesters iron by storing it as a mineral inside a protein cage. In this study, we discovered that mycobacterial DNA-binding protein 1 (MDP1), a histone-like protein, has similar activity to ferritin superfamily proteins. MDP1 prevented the Fenton reaction and protects DNA by the ferroxidase activity. The Km values of the ferroxidase activity by MDP1 of Mycobacterium bovis bacillus Calmette-Guérin (BCG-3007c), Mycobacterium tuberculosis (Rv2986c), and Mycobacterium leprae (ML1683; ML-LBP) were 0.292, 0.252, and 0.129 mM, respectively. Furthermore, one MDP1 molecule directly captured 81.4±19.1 iron atoms, suggesting the role of this protein in iron storage. This study describes for the first time a ferroxidase-iron storage protein outside of the ferritin superfamily proteins and the protective role of this bacterial protein from DNA damage

Research and Design of a Routing Protocol in Large-Scale Wireless Sensor Networks

无线传感器网络，作为全球未来十大技术之一，集成了传感器技术、嵌入式计算技术、分布式信息处理和自组织网技术，可实时感知、采集、处理、传输网络分布区域内的各种信息数据，在军事国防、生物医疗、环境监测、抢险救灾、防恐反恐、危险区域远程控制等领域具有十分广阔的应用前景。 本文研究分析了无线传感器网络的已有路由协议，并针对大规模的无线传感器网络设计了一种树状路由协议，它根据节点地址信息来形成路由，从而简化了复杂繁冗的路由表查找和维护，节省了不必要的开销，提高了路由效率，实现了快速有效的数据传输。 为支持此路由协议本文提出了一种自适应动态地址分配算——ADAR（AdaptiveDynamicAddre...As one of the ten high technologies in the future, wireless sensor network, which is the integration of micro-sensors, embedded computing, modern network and Ad Hoc technologies, can apperceive, collect, process and transmit various information data within the region. It can be used in military defense, biomedical, environmental monitoring, disaster relief, counter-terrorism, remote control of haz...学位：工学硕士院系专业：信息科学与技术学院通信工程系_通信与信息系统学号：2332007115216

Redox-dependent axial ligand replacement and its functional significance in heme-bound iron regulatory proteins

Iron regulatory proteins (IRPs), regulators of iron metabolism in mammalian cells, control the translation of proteins involved in iron uptake, storage and utilization by binding to specific iron-responsive element (IRE) sequences of mRNAs. Two homologs of IRPs (IRP1 and IRP2) have a typical heme regulatory motif (HRM), a consensus sequence found in "heme-regulated proteins". However, specific heme binding to HRM has been reported only for IRP2, which is essential for oxidative modification and loss of binding to target mRNAs. In this paper, we confirmed that IRP1 also specifically binds two molar equivalents of heme, and found that the absorption and resonance Raman spectra of heme-bound IRP1 were quite similar to those of heme-bound IRP2. This shows that the heme environmental structures in IRP1 are close to those of proteins using heme as a regulatory molecule. Pulse radiolysis experiments, however, dearly revealed an axial ligand exchange from Cys to His immediately after the reduction of the heme iron to form a 5-coordinate His-ligated heme in heme-bound IRP2, whereas the 5-coordinate His-ligated heme was not observed after the reduction of heme-bound IRP1. Considering that the oxidative modification is only observed in heme-bound IRP2, but not IRP1, probably owing to the structural flexibility of IRP2, we propose that the transient 5 -coordinate His-ligated heme is a prerequisite for oxidative modification of heme-bound IRP2, which functionally differentiates heme binding of IRP2 from that of IRP1