数サイクルレーザーパルスによる C2D2 の非対称 C-D 結合切断における搬送波位相依存性

学位の種別:課程博士University of Tokyo(東京大学

Menkes Kinky Hair Disease Presenting with Pseudoperiodic Tonic Spasms during the Clinical Course

A case of Menkes kinky hair disease presenting with pseudoperiodic tonic spasms during the clinical course is described. The reported case had been treated by parenteral copper administration since 10 days of age. Although he gradually appeared to deteriorated mentally and developmentally and developed West syndrome at eight months of age, he had no convulsive seizures until four years of age. At four years of age, tonic spasms, which tended to be i.e. pseudoperiodic appeared. He had two types of tonic spasms, flexor spasms and extensor spasms. An ictal EEG also revealed different patterns, including diffuse desynchronization superimposed over the low voltage fast activities of during the flexor spasms and fast activities appeared only during extensor spasms. Both of these ictal events were dominantly in the left hemisphere on a EEG and each of the tonic spasms was easily controlled with phenytoin. The possibility must be entertained that the presented tonic spasms may have been partial seizures

Evolution of the Genus Camellia Based on the Biological Interaction and the Historical Background

departmental bulletin pape

KLHDC10 Activates ASK1 by Suppressing PP5

Reactive oxygen species (ROS)-induced activation of Apoptosis signal-regulating kinase 1 (ASK1) plays crucial roles in oxidative stress-mediated cell death through the activation of the JNK and p38 MAPK pathways. However, the regulatory mechanism of ASK1 in the oxidative stress response remains to be elucidated. Here, we identified the kelch repeat protein, Slim, as an activator of ASK1 through a Drosophila misexpression screen. We also performed a proteomics screen and revealed that Kelch domain containing 10 (KLHDC10), a mammalian ortholog of Slim, interacted with Protein phosphatase 5 (PP5), which has been shown to inactivate ASK1 in response to ROS. KLHDC10 bound to the phosphatase domain of PP5 and suppressed its phosphatase activity. Moreover, KLHDC10 was required for H2O2-induced sustained activation of ASK1 and cell death in Neuro2A cells. These findings suggest that Slim/KLHDC10 is an activator of ASK1, contributing to oxidative stress-induced cell death through the suppression of PP5

Risk factors of recurrent tricuspid regurgitation after valve repair with three-dimensional ring

Objective: The purpose of this study was to investigate the results of tricuspid valve (TV) repair with three-dimensional ring (3DR) and risk factors of recurrent tricuspid regurgitation (TR).Methods: We retrospectively investigated 171 patients who underwent TV repair with a 3DR for TR from 2007 to 2016 at our institution. The patients were divided into the non-Recurrence group (<2+ TR) and Recurrence group (≥2+ TR), and compared to identify the cause of recurrent TR. The mean follow-up period was 58±35 months.Results: The preoperative TR grade was 3.0±0.8. A total of 22 patients had at least ≥2+ TR in the follow-up period. Freedom from ≥2+ TR and re-operation at 5 years were 83.6±3.3% and 97.9±2.1%. Comparison of the non-Recurrence and Recurrence groups revealed significant differences in the preoperative TR grade (2.9±0.8 and 3.4±0.6, p=0.008), proportion of the patients with left ventricular ejection fraction (LVEF) <40% (9% and 32%, p=0.003) and right ventricular end-systolic dimension (RVDs, 22.8±7.1 mm and 31.1±12.3 mm, P=0.001). In the multivariate analysis, LVEF <40% (hazard ratio: 12.65, 95% confidence interval: 2.66–60.18; p=0.002) and RVDs (hazard ratio: 1.08, 95% confidence interval: 1.02–1.14; p=0.02) were identified as risk factors for recurrent TR.Conclusion: Our results of TV repair with 3DR were of satisfactory. However, patients with preoperative lower LVEF and larger RVDs were identified at risk of recurrent TR. This result suggests the limitation to use of 3DR alone for TV repair and need for additional procedure

Delocalization of vortex in SmBa2Cu3O7−δ superconducting films with BaHfO3 nano-rods

Transport measurements revealed flux pinning properties and vortex phases in SmBa2Cu3O7−δ (Sm123) superconducting films with BaHfO3 nano-rods on LaAlO3 substrates. The films have large matching fields BΦ up to 9.9 T, nano-rod diameters of ∼6 nm, and a slight Tc degradation with Tc ∼ 91.8 K by using the low temperature growth technique. According to the transport results, a small critical exponent ∼4 indicates the presence of a Bose-glass phase in the films. Double peaks of the flux pinning force density are unexpectedly observed at high temperatures over 80 K, which is accompanied by steep drops of the crossover magnetic fields between the single vortex pinning and the collective pinning states. The drops are explained by the delocalization of the vortex where the vortex is pinned by many nano-rods in the single vortex pinning state. From the viewpoint of the vortex delocalization, we conclude that BΦ should be less than 11 T for applications at liquid nitrogen temperature

p62/SQSTM1-droplet serves as a platform for autophagosome formation and anti-oxidative stress response

Autophagy contributes to the selective degradation of liquid droplets, including the P-Granule, Ape1-complex and p62/SQSTM1-body, although the molecular mechanisms and physiological relevance of selective degradation remain unclear. In this report, we describe the properties of endogenous p62-bodies, the effect of autophagosome biogenesis on these bodies, and the in vivo significance of their turnover. p62-bodies are low-liquidity gels containing ubiquitin and core autophagy-related proteins. Multiple autophagosomes form on the p62-gels, and the interaction of autophagosome-localizing Atg8-proteins with p62 directs autophagosome formation toward the p62-gel. Keap1 also reversibly translocates to the p62-gels in a p62-binding dependent fashion to activate the transcription factor Nrf2. Mice deficient for Atg8-interaction-dependent selective autophagy show that impaired turnover of p62-gels leads to Nrf2 hyperactivation in vivo. These results indicate that p62-gels are not simple substrates for autophagy but serve as platforms for both autophagosome formation and anti-oxidative stress. Liquid-liquid phase separation of p62/SQSTM1 has been previously described, although the significance in vivo remains unclear. Here the authors show p62 droplets contain ubiquitin, autophagy-related proteins and Keap1 to serve as platform of not only autophagosome formation but also Nrf2 activation.Peer reviewe

Evaluation of Source Generators in Partial Seizures : Availability of Neuroradiological Images Superimposed on the Dipole Tracing

To clarify the anatomical localization of epileptic foci in childhood partial seizures, the source generators of interictal focal spikes were analyzed using a dipole tracing method and the effectiveness of a composite image diagnostic technique using neuroradiological images obtained by magnetic resonance imaging and single photon emission computed tomography was evaluated. The localization of electric source generators approximately reflects the abnormal lesions on neuroradiological images. However, the source generators tended to be located in the deep and/or peripheral parts of the abnormal regions. Even though systemic shifts in the position of optimal dipoles from their true positions is a limitation that must be taken into consideration, composite image diagnostic technique may be useful for evaluating the epileptogenic regions in partial seizures, and particularly, in children where noninvasive methods are preferable

Physical inactivity is associated with decreased growth differentiation factor 11 in chronic obstructive pulmonary disease

Rie Tanaka,1 Hisatoshi Sugiura,1 Mitsuhiro Yamada,1 Tomohiro Ichikawa,1 Akira Koarai,1 Naoya Fujino,1 Satoru Yanagisawa,1 Katsuhiro Onodera,1 Tadahisa Numakura,1 Kei Sato,1 Yorihiko Kyogoku,1 Hirohito Sano,1 Shun Yamanaka,1 Tatsuma Okazaki,1 Tsutomu Tamada,1 Motohiko Miura,2 Tsuneyuki Takahashi,3 Masakazu Ichinose1 1Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Aoba-ku, Sendai, Japan; 2Department of Respiratory Medicine, Tohoku Rosai Hospital, Aoba-ku, Sendai, Japan; 3Department of Internal Medicine, Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Wakabayashi-ku, Sendai, Japan Background: Growth differentiation factor 11 (GDF11) is reported to possess anti-aging and rejuvenating effects, including muscle regeneration and to be highly expressed in skeletal muscle. Recently, we demonstrated that the levels of plasma GDF11 were decreased in COPD. However, the effect of decreased circulating GDF11 in the pathophysiology of COPD remains unknown. The aim of this study is to investigate the association between the plasma GDF11 levels and various clinical parameters in patients with COPD. Patients and methods: Eighteen ex-smokers as control subjects and 70 COPD patients participated in the current study. We measured the levels of plasma GDF11 using immunoblotting, lung function, physical activity using a triaxial accelerometer, quadriceps strength, exercise capacity, and systemic inflammatory markers. We investigated the association between the levels of plasma GDF11 and these clinical parameters. Results: The levels of plasma GDF11 in the COPD patients had significant positive correlations with the data of lung function. Furthermore, the levels of plasma GDF11 were significantly correlated with the physical activity, quadriceps strength, and exercise capacity. Moreover, the levels of plasma GDF11 were significantly correlated with the data of inflammatory markers. Although various factors were related to GDF11, the multiple regression analysis showed that physical activity was significantly associated with the levels of plasma GDF11. Conclusion: Physical inactivity was significantly related to the decreased GDF11 levels in COPD, which might be useful for understanding the pathogenesis of COPD. Clarifying the relationships between the physical inactivity and GDF11 may reveal a potentially attractive therapeutic approach in COPD via increasing the plasma levels of GDF11. Keywords: physical activity, muscle strength, rejuvenating factor, COP

Operative Outcome of Cardiac Surgery in Patients with Liver Cirrhosis

Introduction: A retrospective study was performed to investigate the relationship between the severity of liver cirrhosis and the outcome of cardiac surgery. Methods and Results: Twenty-one patients with liver cirrhosis underwent cardiac surgery in our institution. According to the Child-Pugh classification, 13 patients were in class A, 7 in class B, and 1 in class C. Coronary artery bypass grafting was performed in 7 patients, surgery for valvular disease in 10 and other procedures in 4. Major postoperative complications occurred in 8%, 29%, and 100% for Child-Pugh class A, B, and C, respectively. Preoperative hemoglobin level was significantly lower in the patients with postoperative complications. None of 4 patients underwent coronary revascularization using off-pump procedure or mini-pump system experienced major complication. The operative mortality was 0%, 14%, and 0% for Child-Pugh class A, B, and C, respectively. Conclusions: Although the overall mortality rate in patients with liver cirrhosis was acceptable in our study, the incidence of severe complications, such as prolonged ventilation, mediastinitis and irreversible hepatic insufficiency was problematic in Child-Pugh class B and class C patients. Application of less invasive cardiac surgery, such as mini-pump system or off-pump procedure will improve the operative outcome in such patient group.長崎大学学位論文 学位記番号:博（医）甲第1,272号学位授与年月日:平成20年7月16