ゲンチョ チョウセイ ノウカン ハンノウ ケンサ ノ リンショウテキ ケンキュウ 5ネンカン 273レイ ニ ツイテノ ケントウ

聴性脳幹反応(Auditory Brainstem Response,以下ABRと略す)は音刺激により誘発される聴覚伝導路由来の脳波であり,1970年にJewettらにより報告されて以来,他覚的聴力検査及び脳幹部の神経学的検査として臨床的に広く活用されている。我々は3kHzサイン波一波のクリックを刺激音とするABRを施行しているが,今回1985年から1989年までの5年間に施行した273例について検討した。症例は男性147例,女性126例であり,年齢的に純音聴力検査が不可能である0-4歳の幼児に多く施行した。幼児に対し施行した聴力検査症例152例のうち,85例に主訴となった聴力障害以外の何等かの基礎疾患があり,その半数が閾値上昇を示した。これらの疾患を有する症例では,難聴の合併率が高いばかりでなく,脳幹部を始めとする中枢神経系に異常を持つことがあるため,ABRがスクリーニング検査として非常に有用であり,早期及び経時的に施行することが必要であると思われた。また聴神経腫瘍を主とする小脳橋角部腫瘍の診断にあたっては,ABRのV波潜時の延長所見の検索は極めて有用であり,診断学的に高い特異性と感受性を有する検査手段のひとつとみなされる。さらに,他覚的聴力検査としてABRの記録は,機能性難聴の確定診断にも不可欠である事が確かめられた。journal articl

Measurement of the e+e-→D(*)+D(*)- cross sections

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Structures of indole–CBI conjugated Py–Im polyamides –, and schematic representations of their DNA alkylation

<p><b>Copyright information:</b></p><p>Taken from "Alkylation of template strand of coding region causes effective gene silencing"</p><p>Nucleic Acids Research 2006;34(4):1189-1195.</p><p>Published online 25 Feb 2006</p><p>PMCID:PMC1383623.</p><p>© The Author 2006. Published by Oxford University Press. All rights reserved</p> Open circles, filled circles and ellipses indicate pyrroles, imidazoles and indoles, respectively. W indicates A or T. CBI, which is an alkylating moiety, adducts to the adenine N3 position

Results of real-time quantification of PCR GFP () and β-actin () mRNAs in HCT116 cells treated with polyamides A–C

<p><b>Copyright information:</b></p><p>Taken from "Alkylation of template strand of coding region causes effective gene silencing"</p><p>Nucleic Acids Research 2006;34(4):1189-1195.</p><p>Published online 25 Feb 2006</p><p>PMCID:PMC1383623.</p><p>© The Author 2006. Published by Oxford University Press. All rights reserved</p> To evaluate the amount of transcribed GFP mRNA, TaqMan real-time PCR was performed with the 7300 Real-Time PCR System. The amount of GFP and β-actin mRNAs in the HCT116 cells were measured using pairs of primers with the TaqMan probes for each gene. The amount of mRNAs in HCT116 cells treated with 100 nM polyamides for 24 h was calculated with reference to the cells treated with 0.1% DMF (Control), set as 100%. Compared with the control, HCT116 cells treated with polyamide C showed significantly decreased GFP mRNA expression. The cells which the GFP vectors were not transfected (Mock) did not express GFP mRNA. Error bars, standard deviation of the means of triplicate samples. * < 0.05 by unpaired Student's -test compared with control

Application of Support Vector Machine to Three-Dimensional Shape-Based Virtual Screening Using Comprehensive Three-Dimensional Molecular Shape Overlay with Known Inhibitors

In this study, machine learning using support vector machine was combined with three-dimensional (3D) molecular shape overlay, to improve the screening efficiency. Since the 3D molecular shape overlay does not use fingerprints or descriptors to compare two compounds, unlike 2D similarity methods, the application of machine learning to a 3D shape-based method has not been extensively investigated. The 3D similarity profile of a compound is defined as the array of 3D shape similarities with multiple known active compounds of the target protein and is used as the explanatory variable of support vector machine. As the measures of 3D shape similarity for our new prediction models, the prediction performances of the 3D shape similarity metrics implemented in ROCS, such as ShapeTanimoto and ScaledColor, were validated, using the known inhibitors of 15 target proteins derived from the ChEMBL database. The learning models based on the 3D similarity profiles stably outperformed the original ROCS when more than 10 known inhibitors were available as the queries. The results demonstrated the advantages of combining machine learning with the 3D similarity profile to process the 3D shape information of plural active compounds

Thermally induced strand cleavage of 5′-Texas Red-labeled DNA fragments of GFP former ( and ) and latter ( and ) sequences of GFP alkylated by polyamides A, B and C

<p><b>Copyright information:</b></p><p>Taken from "Alkylation of template strand of coding region causes effective gene silencing"</p><p>Nucleic Acids Research 2006;34(4):1189-1195.</p><p>Published online 25 Feb 2006</p><p>PMCID:PMC1383623.</p><p>© The Author 2006. Published by Oxford University Press. All rights reserved</p> Results in the sequence of complementary strand (a–c) and coding strand (d-f) are displayed. Lanes 1–4: 100, 50, 25, 12.5 nM of A; lanes 5–8: 100, 50, 25, 12.5 nM of B, lanes 9–12: 100, 50, 25, 12.5 nM of C and lane 13: DNA control. Lanes G, C, T and A contain Sanger-sequencing products ( and ). Sequences containing alkylation sites are represented. Mismatched sequences are indicated by gray letters

Sequence-Specific Alkylation of Double-Strand Human Telomere Repeat Sequence by Pyrrole-Imidazole Polyamides with Indole Linkers

We designed and synthesized pyrrole (Py)−imidazole (Im) hairpin polyamide 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) conjugates 1 and 2, which target both strands of the double-stranded region of the human telomere repeat sequences, 5‘-d(TTAGGG)n-3‘/5‘-d(CCCTAA)n-3‘. High-resolution denaturing polyacrylamide gel electrophoresis demonstrated that conjugates 1 and 2 alkylated DNA at the 3‘ A of 5‘-ACCCTA-3‘ and 5‘-AGGGTTA-3‘, respectively. Cytotoxicities of conjugates 1 and 2 were evaluated using 39 human cancer cell lines; averages of log IC50 values for conjugates 1 and 2 were −6.96 (110 nM) and −7.24 (57.5 nM), respectively. Conjugates 1 and 2 have potential as antitumor drugs capable of targeting telomere repeat sequence

Application of Support Vector Machine to Three-Dimensional Shape-Based Virtual Screening Using Comprehensive Three-Dimensional Molecular Shape Overlay with Known Inhibitors

In this study, machine learning using support vector machine was combined with three-dimensional (3D) molecular shape overlay, to improve the screening efficiency. Since the 3D molecular shape overlay does not use fingerprints or descriptors to compare two compounds, unlike 2D similarity methods, the application of machine learning to a 3D shape-based method has not been extensively investigated. The 3D similarity profile of a compound is defined as the array of 3D shape similarities with multiple known active compounds of the target protein and is used as the explanatory variable of support vector machine. As the measures of 3D shape similarity for our new prediction models, the prediction performances of the 3D shape similarity metrics implemented in ROCS, such as ShapeTanimoto and ScaledColor, were validated, using the known inhibitors of 15 target proteins derived from the ChEMBL database. The learning models based on the 3D similarity profiles stably outperformed the original ROCS when more than 10 known inhibitors were available as the queries. The results demonstrated the advantages of combining machine learning with the 3D similarity profile to process the 3D shape information of plural active compounds

DNA Alkylation by Pyrrole−Imidazole <i>seco</i>-CBI Conjugates with an Indole Linker: Sequence-Specific DNA Alkylation with 10-Base-Pair Recognition through Heterodimer Formation

The sequence-specific DNA alkylation by conjugates 4 and 5, which consist of N-methylpyrrole (Py)−N-methylimidazole (Im) polyamides and 1-(chloromethyl)-5-hydroxy-1,2-dihydro-3H-benz[e]indole (seco-CBI) linked with an indole linker, was investigated in the absence or presence of partner Py−Im polyamide 6. High-resolution denaturing polyacrylamide gel electrophoresis revealed that conjugate 4 alkylates DNA at the sequences 5‘-(A/T)GCCTA-3‘ through hairpin formation, and alkylates 5‘-GGAAAGAAAA-3‘ through an extended binding mode. However, in the presence of partner Py−Im polyamide 6, conjugate 4 alkylates DNA at a completely different sequence, 5‘-AGGTTGTCCA-3‘. Alkylation of 4 in the presence of 6 was effectively inhibited by a competitor 7. Surface plasmon resonance (SPR) results indicated that conjugate 4 does not bind to 5‘-AGGTTGTCCA-3‘, whereas 6 binds tightly to this sequence. The results suggest that alkylation proceeds through heterodimer formation, indicating that this is a general way to expand the recognition sequence for DNA alkylation by Py−Im seco-CBI conjugates