11, together with Rad50 and Xrs2/NBS, plays pivotal roles in homologous recombination, repair of DNA double strand breaks (DSBs), activation of damage-induced checkpoint, and telomere maintenance. Here we demonstrate that the absence of 11 in yeast causes specific effects on regulation of a class of meiotic genes for spore development. Using DNA microarray assays to analyze yeast mutants defective for meiotic DSB formation, we revealed that the meiotic expression profile in the cells was generally unaffected when compared to the one in the wild-type strain, although the activation of about 90 meiotic genes were severely and specifically impaired in early meiosis. These defects were confirmed by northern and lacZ reporter gene assays. Interestingly, a substantial portion of the severely affected genes includes genes responsible for spore wall biogenesis, the defects of which may account for the fragile spore wall phenotype of the strain. The transcriptional deficiency was not observed in other DSB mutants such as rad50Δ, xrs2Δ, spo11Δ, and spo11Y135F, suggesting the transcriptional defect in is due to neither lack of meiotic DSB formation, nor disintegrity of 11-Rad50-Xrs2 complex. In addition, the deficiency of in gene activation was not alleviated by the deletion of RAD24. Therefore, it is unlikely that DNA damage checkpoint activation by caused transcriptional deficiency. We also found that a C-terminus DNA binding domain truncation mutant (), which has meiosis-specific defects, exhibited transcriptional defects as observed in , whereas an N-terminal phosphoesterase mutant () does not. Taken together, we propose that 11 is involved in the regulation of a specific class of genes during spore development through its C-terminus domain.

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Purpose: This study aimed to facilitate research progress in MR elastography (

) by providing a versatile and convenient application for reconstruction, namely the research tool (-rTool). It can be used for a series of image analyses, including phase unwrapping, arbitrary bandpass and directional filtering, noise assessment of the wave propagation image (motion SNR), and reconstruction of the elastogram in both 2D and 3D acquisitions. To reinforce the versatility of -rTool, the conventional method of motion SNR was modified into a new method that reflects the effects of image filtering.

Methods:

tests of the phantom and liver were performed using different estimation algorithms for stiffness value (algebraic inversion of the differential equation [AIDE], local frequency estimation [LFE] in -rTool, and multimodel direct inversion [MMDI] in clinical reconstruction) and acquiring dimensions (2D and 3D acquisitions). This study also tested the accuracy of masking low SNR regions using modified and conventional motion SNR under various mechanical vibration powers.

Results: The stiffness values estimated using AIDE/LFE in

-rTool were comparable to that of MMDI (phantom, 3.71 ± 0.74, 3.60 ± 0.32, and 3.60 ± 0.54 kPa in AIDE, LFE, and MMDI; liver, 2.26 ± 0.31, 2.74 ± 0.16, and 2.21 ± 0.26 kPa in AIDE, LFE, and MMDI). The stiffness value in 3D acquisition was independent of the direction of the motion-encoding gradient and was more accurate than that of 2D acquisition. The masking of low SNR regions using the modified motion SNR worked better than that in the conventional motion SNR for each vibration power, especially when using a directional filter.

Conclusion: The performance of

-rTool on test data reached the level required in clinical studies. -rTool has the potential to facilitate research, contribute to the future development of , and has been freely released online.

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The magneto rheological elastomer (

) is composed of silicone elastomers and ferromagnetic powders that are responsible for its ferromagnetic and viscoelastic properties. The shape and the stiffness of the change depending on the magnetic field. Therefore, it is expected to be used for artificial muscle or damping material. We developed a coupled analysis method by combining the moving particle semi-implicit/simulation (MPS) method with the finite element method (FEM) for the design of the actuator. However, this method does not take into account a rigid body. Therefore, when analyzing the coil embedded in the , it was difficult to calculate parameters such as the coil rotation and position. Therefore, this paper presents a numerical method for actuator analysis by coupling MPS method with FEM to arrive at a calculation method for a rigid body. The numerical algorithm is described, and the calculated results are shown.

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In eukaryotes, together with the 11/Rad50/Xrs2 (or Nbs1) complex, a family of related protein kinases (the ATM family) is involved in checkpoint activation in response to DNA double-strand breaks. In Saccharomyces cerevisiae, two members of this family, MEC1 and TEL1, have functionally redundant roles in DNA damage repair. Strains with mutations in their mec1 as well as genes are very sensitive to DNA damaging agents, show defective induction of damage-induced cell-cycle checkpoints, and defective damage-induced homologous recombination. However, the fact that both the mec1Δ and strains exhibit the spontaneous hyper-recombination phenotype is paradoxical in light of the homologous recombination defects in these strains. In this study, we constructed yeast mec1, tel1, and null mutations and characterized their genome stability properties. Spontaneous and methylmethane sulfonate (MMS)-induced point mutations, base-substitutions, and frameshifts occurred to an almost equal extent in the wild-type, mec1Δ, tel1Δ, and strains. Thus, Mec1, Tel1, and 11 do not play roles in the point mutation response. We then found that the mec1Δ, , and mec1Δ tel1Δ strains demonstrated increased rates of spontaneous loss of heterozygosity (LOH), which includes crossover, gene conversion, and chromosome loss, compared with the wild-type strain. In the tel1Δ strain, the rate of spontaneous LOH was as low as that in the wild-type strain. Finally, no induction of LOH by MMS was observed in the mec1Δ, , or mec1Δ tel1Δ strain; however, it was detected in the wild-type and tel1Δ strains upon exposure to MMS. The elevated level of spontaneous LOH but not MMS-induced LOH in the mec1Δ, , and mec1Δ tel1Δ strains suggests the presence of high levels of spontaneous recombinogenic DNA damage, which differs from the damage induced by MMS treatment, in these strains.

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The purpose of this study was to explicate the mechanism of transition storage modulus and loss modulus under external magnetic field. Magneto-rheological elastomer (

) is expected to be used as damping material and actuator controlled by an external magnetic field. However, magnetic particles' behavior inside of has not been explained completely. Especially, the mechanisms of loss modulus transition under external magnetic field has not been known well. We constructed a simple model with two magnetic particles, and try to make behavior clear. In this report, we show a data of the viscoelastic property of which consists of magnetic particles and polydimethylsiloxane (PDMS). The obtained viscoelastic property is explained by using two magnetic particles model.

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　Magnetic resonance elastography (

) is a relatively new technology for quantitatively assessing the mechanical properties of tissues. It can be considered an imaging-based virtual palpation. The purpose of this review is to introduce this technology to clinicians/technologists and summarize its basic mechanism. First, a brief overview of is provided. Second, the method of is explained. Finally, an example of psoas major is introduced.

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Metallothioneins (MTs) are small metal-binding proteins that have a role in the defense against heavy metals. Mammalian MT genes are transcriptionally activated by metals such as Cd and Zn through multiple copies of the metal responsive element () present in the 5'-flanking region. To examine whether each in a single promoter has a distinct role, we characterized seven MREs located upstream of the human MT-IIA gene. By transient transfection experiments using -driven reporter gene constructs, individual MREs were assayed for the activity to mediate transcription in response to several heavy metal species. Four MREs including MREs a, b, e and g independently mediated reporter gene expression in response to Zn, Cd and Hg, while other MREs were not responsive to any of these metals. These results suggest that the multiplicity of contributes to enhancing its activity, rather than providing functional diversity.

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本の研究グループが、 データ解析として培ってきた修正積分法やそのほかのデータ解析手法とその適用に関して、進捗状況を報告する。

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データより生体・ファントムの粘弾性率を再構成することは逆問題に他ならない。この逆問題の解決には，生体・ファントム内部波動場を記述する偏微分方程式モデルを必要とする。のデータ解析には、この偏微分方程式モデルと測定されたデータに基づいて、理論的・数値的逆解析を行うことが必要である。特に，今回は北海道大学のMicro-計測データによるファントム粘弾性率の逆解析が可能となった。

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Palpation is a standard clinical tool to diagnose abnormal stiffness changes in soft tissues. However, it is difficult to palpate the supraspinatus muscle because it locates under the trapezius muscle. The magnetic resonance elastography (

) uses harmonic mechanical excitation to quantitatively measure the stiffness (shear modulus) of both the superficial and deep tissues. The purpose of this study was to build a vibration system for applying the to the supraspinatus muscle. In this study, a power amplifier and a pneumatic pressure generator were used to supply vibrations to a vibration pad. Six healthy volunteers underwent . We investigated the effects of position (the head of the humerus and the trapezius muscle) of the vibration pad on the patterns of wave propagation (wave image). When the vibration pad was placed in the trapezius muscle, the wave images represented clear wave propagation. On the other hand, when the vibration pad was placed in the head of the humerus, the wave images represented unclear wave propagation. This result might be caused by wave interferences resulting from the vibrations from bones and an intramuscular tendon of the supraspinatus muscle. The mean shear modulus also was 8.12 ± 1.83 (mean ± SD) kPa, when the vibration pad was placed in the trapezius muscle. Our results demonstrated that the vibration pad should be placed in the trapezius muscle in the of the supraspinatus muscle.

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従来ＭＳＧを使用して収集されたデータを元にが行われてきている．本研究では臨床における画像収集用シーケンスを用いて，つまりＭＳＧを用いないで，が行えることを確認し，その限界について明らかにしたので報告する．

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Metallothionein genes are known to be transcriptionally regulated by a variety of factors such as heavy metals, glucocorticoids and cytokines, and have multiple regulatory elements in their 5'-flanking region. To study the interactions between these sequences and regulatory factors, HeLa cell nuclear proteins were analyzed by band-shift assay using a 95-base pair (bp) DNA probe containing a part of the human MT-IIA gene upstream sequences. Consequently, two Zn-dependent DNA-binding proteins were detected. One of these showed properties almost identical with those of zinc regulatory factor (ZRF), which had been detected using an oligonucleotide probe containing the metal responsive element (); namely, this protein is activated only by Zn, and requires not only but also its flanking sequences for optimal DNA-binding. The other protein appears to be Spl, based on its recognition sequences specificity. In addition, by South-western blotting analysis of nuclear extracts using the 95-bp probe or oligonucleotide probe, we detected a Zn-dependent DNA-binding protein with a molecular mass of 116 kDa, which is likely to be ZRF. Analysis of HeLa cell nuclear proteins fractionated by glycerol gradient centrifugation showed that ZRF is distinct from another -binding protein, MREBP.

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Background: Critical hyperthermia targets in cancer cells have to be clearly identified.
Method: To determine if the DNA double strand break (DSB)-recognizing proteins, phospho-Nbs1 and 11, co-localize with phospho-H2AX (γH2AX), immunohistochemical methods were used with multiple antibodies. After a heat treatment at 45.5°C for 20 min, human normal fibroblasts were analyzed with a laser scanning confocal microscope at 0.5 h and 8 h post-heat treatment.
Results: At 0.5 h after a heat treatment, γH2AX formed foci in the nucleus, but phospho-Nbs1 and 11 were scattered over the nucleus and cytoplasm, and did not co-localize with γH2AX. At 8 h after a heat-treatment, and also after X-irradiation, both phospho-Nbs1 and 11 co-localized with γH2AX foci, which were already present, in the nucleus. Moreover, both phospho-Nbs1 and 11 which were observed at 0.5 h after a heat treatment in the cytoplasm, were no longer observed in the cytoplasm at 8 h after a heat treatment.
Conclusion: These findings provide support for the concept that heat, like X-rays, may lead to the induction of DSBs.

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Purpose: We evaluated the validity and reliability of magnetic resonance elastography () for staging hepatic fibrosis in patients with chronic hepatitis B.
Methods: The study included 73 patients with chronic hepatitis B and confirmed stages of pathological fibrosis. Two radiologists measured liver stiffness using in all cases. We compared the area under the receiver operating characteristic (ROC) curve (Az) for distinguishing stages of fibrosis compared with liver stiffness measurements and serum fibrosis markers. We used intraclass correlation coefficients to analyze interobserver agreement for measurements of liver stiffness and 2 one-sided t-tests to test the equivalence of the measurements by the 2 observers.
Results: ROC analyses revealed the significantly superior discrimination abilities of for liver fibrosis staging (Az = 0.945 to 0.978 [Observer 1] and 0.936 to 0.967 [Observer 2]) to those of serum fibrosis markers (0.491 to 0.742) for both observers (P < 0.0004). The intraclass correlation coefficient between the 2 observers was excellent (ρ = 0.971), and the measurements of liver stiffness by the 2 observers were statistically equivalent within a 0.1-kPa difference (P = 0.0157)
Conclusion: is a valid and reliable technique for discriminating the stage of hepatic fibrosis in patients with chronic hepatitis B.

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　AT様疾患(ATLD)は、放射線高感受性、染色体不安定性、チェックポイント異常といった特徴を持つ遺伝病である。ATLDの原因遺伝子11はNBS1とRAD50と複合体(MRN複合体)を作り、放射線や他のストレスによって誘導されるDNA二重鎖切断の際の相同組み換え（HR）修復に関与することが知られている。ATLD細胞は染色体不安定性を示すがその理由として、11遺伝子欠損によるDNA修復能破綻が挙げられている。 　今回、我々は11が中心体と共局在していることを発見し、11がDNA修復だけでなく、中心体の制御にも関与している可能性を見いだした。中心体とは1組の中心小体と中心体周辺物質からなり、細胞周期の間期において微小管形成中心として細胞内の極性を維持し、M期には双極紡錘体の極を形成する中心器官となる。複製異常や細胞質分裂の失敗によって生じる中心体の過剰状態は多極紡錘体の原因となり、染色体の不等分配を起こす。よって、中心体の数の制御は染色体分配の重要なポイントである。放射線を照射した細胞では中心体の過剰複製が起こるといった現象が報告されている。また、最近ではDNA損傷応答に関わるBRCA1が染色体の維持に重要である事が報告され、他にも多数のDNA修復因子が中心体に局在することがわかってきている。特にDNA損傷応答因子のチェックポイントが中心体制御と何らかの関わりがあると考えられているが、詳細は不明である。 　今回、11が中心体と共局在することから11が中心体制御に関与している可能性が示唆されたので、siRNAによる11のノックダウン実験を中心に中心体制御の機構を解析した結果を報告する。

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目的：MRIによる肝の弾性率測定法（MR Elastography［］）を用いた肝線維化診断の有用性を検討する．
対象と方法：対象は当院でが施行されかつ組織学的に肝線維化スコアが確定した56例．用に開発された振動発生装置により体表から弱い振動を加え，この波をMRIの位相画像で検出し弾性率に変換した．得られた弾性率と組織学的肝線維化スコアを比較し受動者動作特性曲線（ROC曲線）で解析した．
結果：F1以上，F2以上，F3以上，F4以上を診断するための最適カットオフ値（ROC曲線下面積）はそれぞれ，2.6 kPa（0.97），3.6 kPa（0.95），4.1 kPa（0.96），4.2 kPa（0.96）であった．この値を用いF3以上の肝線維化をで診断した場合，感度80％，特異度100％であった．
結論：MR Elastographyは肝線維化を予測する有用な検査法である．

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近年，magnetic resonance imaging（MRI）により非侵襲的に物体の物理的属性である粘弾性率分布を定量的に測定する手法としてMR elastography（）が提案されており，臨床用MRIや高磁場MRIを用いたシステム開発が進められている．経験ある医師は疾病や機能障害をおこした生体組織の硬さが正常組織と異なることを利用して触診により疾患を発見したり機能障害の程度を定性的評価している．は生体深部組織の硬さを粘弾性率という客観的指標として定量的に求められることから臨床上有用と期待されている．本講演では，の原理と実際に構築したシステムについて紹介する．

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顕微鏡データ解析を行って、様々定常型粘弾性方程式がモデル方程式の適切性を検証する。

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医師は触診により，疾患の存在や進展による組織の力学的性質の変化を評価することができる．生体組織の力学的性質を磁気共鳴画像装置（magnetic resonance imaging; MRI）を用いて非侵襲的かつ定量的に画像化する手法として，MRエラストグラフィ（MR elastography; ）がある．典型的なシステムでは，外部加振装置により生体組織内に弾性波を発生させ，位相コントラスト法により時間的に変化する組織内の弾性波分布を速写し，弾性算出法により弾性波画像から粘弾性分布を画像化する．これらを構成する3つの要素は，発表から20年をかけて改良されており，互いに深く依存している．また，改良によりさまざまな器官を撮像対象とした検討が進み，力学的性質が疾患の病期判定や鑑別に有効であることが示されている．本稿では，の原理と技術，臨床応用について述べる．

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Metallothionein (MT) is thought to play a central role in the detoxification of heavy metals, and thus studies on its regulation are toxicologically important. Heavy metal-dependent induction of MT genes is mediated by metal responsive elements (MREs) located upstream of the genes. Zinc regulatory factor (ZRF) is a zinc-dependent -bind-ing protein that was originally detected in HeLa cell nuclear extracts using the most proximal of the human MT-IIA gene (hMREa) as a probe. We show that ZRF in HeLa cell nuclear extracts can also bind to the most potent of the mouse MT-I gene (mMREd). This finding was further confirmed by using partially purified ZRF. Moreover, cadmium could not promote complex formation between ZRF and mMREd at any concentra-tion tested, as is also the case with ZRF and hMREa. These observations suggest that the transcriptional regulatory system of MT genes by zinc is conserved beyond species.

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