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金沢大学大学院医学系研究科, Left ventricular (LV) systolic function in hypertrophic cardiomyopathy (HCM) is usually normal. Late in the disease, however, LV systolic dysfunction and dilatation are recognized. Although abnormalities in cardiac sympathetic nerve activity in patients with HCM have been demonstrated using 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, the changes of cardiac sympathetic nerve activity throughout the clinical course from typical to end-stage HCM are unclear. The objective of this study was to evaluate the relationship between abnormalities on 123I-MIBG myocardial scintigraphy and pathophysiologic changes in patients with HCM. Methods: We performed 123I-MIBG scintigraphy on 46 patients with HCM and 18 age-matched control subjects. The patients were categorized into 3 groups: 28 patients with normal LV systolic function (group A), 9 patients with LV systolic dysfunction (group B), and 9 patients with LV systolic dysfunction and dilatation (group C). With planar 123I-MIBG imaging, the heart-to-mediastinum ratio for early and delayed acquisitions and the washout rate were calculated. With SPECT, polar maps of the LV myocardium were divided into 20 segments. The regional uptake and washout rate were calculated from semiquantitative 20-segment bull's-eye analysis. Results: The early uptake was significantly lower in group C than in the control group (P < 0.01). The washout rate was progressively higher in group A, group B, and group C (P < 0.01). Reduced regional early uptake was found in 2.9 ± 3.4 (group A), 4.1 ± 4.7 (group B), and 7.4 ± 4.3 (group C) segments, respectively. In group C, regional early uptake was significantly reduced, predominantly in the interventricular septal wall, and regional washout rate was increased in the apex and lateral wall. Conclusion: These results suggest that cardiac sympathetic nerve abnormalities in patients with HCM may advance with development of LV systolic dysfunction and dilatation and that 123I-MIBG myocardial scintigraphy may be a useful tool for the evaluation of pathophysiologic changes in HCM.

金沢大学大学院医学系研究科, Congenital long QT syndrome (LQTS) is caused by mutations in various cardiac potassium or sodium channel genes, with 6 different genotypes thus far identified. However, it is unknown whether these genotypes can be differentiated by QT variables. The electrocardiograms obtained from 16 patients with a mutation in KCNQ1 (LQT1), 7 patients with a mutation in HERG (LQT2) and 20 control subjects were analyzed. The corrected QT interval (QTc), Q-T peak interval (QTpc) and dispersion of QTc or QTpc were measured in 6 precordial leads. The corrected interval from T peak to T end (Tpec) was measured in lead V5. The maximum QTc, QTc dispersion, and Tpec were significantly increased in the LQT1 and LQT2 patients than in the controls. However, there were no significant differences in these indices between the LQT1 and LQT2 patients. In contrast, QTpc dispersion was significantly increased in the LQT2 patients (78±25 ms) compared with the LQT1 patients (29±15 ms) and controls (26±19 ms). These results suggest that increased lag of the peak of the T wave in each precordial lead (QTpc dispersion) may be a possible index to differentiate LQTS patients with HERG mutation from those with KCNQ1 mutation.

金沢大学大学院医学系研究科, Cardiac sympathetic nerve activity is changed in patients with hypertrophic cardiomyopathy (HCM). However, the relationship between heterogeneity of this activity and systolic left ventricular dysfunction in patients with HCM is not well established. This study was performed to evaluate the sympathetic nerve activity in various cardiac regions and to investigate the relationship between cardiac dysfunction and heterogeneity of the cardiac sympathetic nerve activity in patients with HCM. Methods: Cardiac sympathetic nerve activity was evaluated in 25 patients with HCM and 10 control subjects using planar imaging and SPECT by 123l-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. With planar 123I-MIBG imaging, the heart-to-mediastinum activity ratios (H/M), at early (20 min) and delayed (3 h) acquisition, and the washout rate were calculated. Polar maps of the left ventricular myocardium were divided into 20 segments, and the dispersion (maximal to minimal values) and SD of uptake and the washout rate in 20 segments were calculated. Results: The early H/M did not differ between the 2 groups. The delayed H/M was significantly lower and the washout rate of the whole heart was significantly higher in the HCM group than those in the control group. In patients with HCM, the delayed H/M, early uptake dispersion, and SD of early uptake showed good correlation with the left ventricular end-diastolic and end-systolic dimensions and the percentage of fractional shortening. A stepwise regression analysis revealed that the SD of early uptake was a powerful determinant for the percentage of fractional shortening in patients with HCM. Conclusion: These results suggest that the heterogeneity of regional cardiac sympathetic nerve activity may be correlated with cardiac dysfunction in patients with HCM.

Publication in the conference proceedings of EUSIPCO, Lisbon, Portugal, 2014

天然の高分子多糖であるグルコマンナン(GM)およびスラブ電気泳動の支持体として用いられている市販の試薬を含むいくつかの多糖類を,キャピラリー電気泳動(CE)用ポリマー溶液として,それらの分子ふるい添加物としての高分子分離特性について比較,検討した。その結果,溶液濃度および測定条件を統一し,分離対象物質として制限酵素消化 DNA フラグメントを用いた場合, GM が最も高い分離度を示した。これは GM が他の多糖類と比較して分子量が大きいこと,分岐の少ない直鎖状の構造を持ち慣性半径が大きいことなどにより,キャピラリー内で安定な網目を形成するためと考えた。一般に DNA フラグメントの分離度は, GM 濃度を調整することで改善が可能であった。しかし,オリゴヌクレオチドのような低分子試料,また数千 bp といったかなり大きな DNA フラグメントの分離には, GM 濃度の調整だけでは十分には対臨できないことがわかった。この場合,GMの分子量が分離度に大きく影響しており,分離対象物質の分子量に応じて,分離媒体であるGMの分子量を適切に選択することが重要であることがわかった。また,分離度以外に GM 溶液は,(1) 毒性がない,(2) 長期保存安定性にすぐれている,(3) 分析の再現性が良好であり自動化がはかれる,といった CE 用ポリマー溶液として好ましい特徴をいくつか持っていることが確認できた。本研究の成果は,将来 PCR 産物の分析,遺伝子解析など生命科学領域への適用が可能であると考える。

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Glucomannan, a natural polysaccharide extracted from Amorphophallus konjac, was employed as a sieving additive for the separation of restriction DNA fragments in capillary electrophoresis. A stable solution of entangled glucomannan was successfully prepared under mild conditions. The separation capillary filled with 0.25% glucomannan exhibited excellent resolution and reproducibility on separation of DNA fragments over the range of ca. 1400 base pairs. The separation was dependent on the size of the fragments, which allowed the determination of the size of separated DNAs directly from the migration time. In addition to these separation characteristics, glucomannan has practical advantages in its chemical stability, non-toxicity and ease of handling. Because the method is applicable to the separation and characterization of the DNA fragments generated by digestion with restriction enzymes or produced by polymerase chain reactions, it is concluded that glucomannan is a good alternative to the conventional sieving additives for capillary electrophoresis, such as polyacrylamide and hydroxymethylcellulose.

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