ノックインマウスモデルによるＤＮＭＴ３Ａ変異の造血機構における意義の探索

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 東條 有伸, 東京大学准教授 新井 郷子, 東京大学准教授 瀧本 禎之, 東京大学講師 田中 哲洋, 東京大学特任講師 牛久 綾University of Tokyo(東京大学

Guillain-Barré syndrome complicated by posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome

Introduction: Guillain-Barré syndrome is an immune-mediated inflammatory polyneuritis characterised by rapidly progressive flaccid paralysis. Guillain-Barré syndrome may present with posterior reversible encephalopathy syndrome or reversible cerebral vasoconstriction syndrome in rare cases. Case description: A woman in her 60s with a history of follicular lymphoma presented with a one-week history of difficulty walking and thunderclap headaches. The patient was diagnosed with Guillain-Barré syndrome based on neurological examination, cerebrospinal fluid analysis and nerve conduction findings. Further diagnosis of posterior reversible encephalopathy and reversible cerebral vasoconstriction syndromes was based on imaging findings and headache history. The patient was treated with intravenous immunoglobulin and amlodipine, and symptoms improved. Discussion: We reviewed the literature on Guillain-Barré syndrome associated with posterior reversible encephalopathy and/or reversible cerebral vasoconstriction syndrome. The underlying pathophysiology may involve dysautonomia resulting in unstable blood pressure, and hyponatraemia causing endothelial dysfunction. The SNOOP mnemonic highlights the ‘red flags’. This SNOOP mnemonic suggests the possibility of secondary headaches that require imaging studies. In this case, the patient exhibited three SNOOP symptoms: S (history of malignancy: follicular lymphoma), O (sudden-onset headache) and O (over 50 years old). Conclusion: This case highlights the importance of considering coexisting central neurological disorders in patients with Guillain-Barré syndrome

Attempt to Generate Uniform Magnetic Field by Face-to-Face Magnet System Containing HTS Bulk Magnets

In order to develop small-scale nuclear magnetic resonance devices, the authors have been developing uniform magnetic fields in the space between the face-to-face settled magnetic poles which contain HTS bulk magnets. Since the NMR magnets in general require highly uniform field, it was expected to be difficult to form such homogeneous magnetic-field distribution with use of HTS bulk magnet, because the bulk magnets is characterized by its inhomogeneous magnetic field showing steep gradient. The authors modified the shape of the field distribution from convex to concave by attaching an iron plate on the pole surface. Then, the magnets were then settled face-to-face with various gaps, and the magnetic-field uniformity was estimated in the space. In order to detect the NMR signals, the field uniformity less than 1,500 ppm should be required after the former results on the hollow-type magnets. When we combined the concave and convex field distributions to compensate the uneven field distributions, the best uniformity reached 358 ppm in the 30 mm gaps, which exceeded the target value. In addition, we numerically simulated the feasible performance in this configuration, which resulted in obtaining the best uniformity of 30 ppm at 1.1 T at 7 mm distant from the pole surface in the gap of 30 mm. This result suggested that the concave and convex magnetic field distributions compensate the field uniformity with each other with keeping the magnetic field strength in the gap

Isolated Cardiomyocytes from Transgenic Mouse Hearts Show Tissue-specific mTOR Overexpression

Mechanistic target of rapamycin (mTOR) is a key downstream effector of insulin that plays an important role in glucose uptake and cardioprotection. We previously used transgenic (Tg) mice with cardiac-specific overexpression of mTOR driven by the murine alpha-myosin heavy chain promoter to demonstrate that mTOR protects the heart against acute MI by inhibiting necrosis in cardiac cells (cardiomyocyte, CM). Since the heart consists of multiple cell types, including CMs and fibroblasts, protein assays with tissue lysates from the whole heart alone cannot demonstrate tissue specific protein expression in transgenic mice. To determine whether our hemagglutinin (HA)-tagged rat mTOR transgene is expressed in CMs, we assessed HA-mTOR expression and examined the mTOR signaling pathway in CMs isolated from the heart. Hearts harvested from either wild-type (WT) or mTOR-Tg mice were treated with collagenases using an ex vivo perfused heart system for isolating CMs. The isolated CMs and whole hearts from either WT or Tg mice were homogenized for Western blotting. Western blotting demonstrated a significant increase in mTOR expression in the whole heart and CMs from mTOR-Tg mice. The increase in mTOR expression was more significant in isolated CMs compared to the whole hearts. mTOR-Tg mice showed an increase in phosphorylation of mTOR downstream molecules Akt and S6. HA was only observed in the heart when compared to skeletal muscle, liver, kidney, and spleen samples in Tg mice. We observed cardiac specific mTOR expression and an increase in kinase activity of mTOR in CMs isolated from mTOR-Tg mice

Predicting the Start of the Aedes albopictus (Diptera: Culicidae) Female Adult Biting Season Using the Spring Temperature in Japan

Aedes albopictus (Skuse) (Diptera: Culicidae) is distributed widely and is common in much of Japan. In Japan, female adults begin to bite in between April and June, except in the southern subtropics where the mosquito has no dormant period. It is difficult to estimate the first Ae. albopictus biting day because it varies annually depending on the location. Over several years, we surveyed the mosquitoes at different locations that covered a range of warmer to cooler areas of Japan. We found an association between the timing of first biting day by Ae. albopictus and spring temperature. In spring months, the strongest correlation was found with mean April temperatures, followed by March. Based on these data, it may, therefore, be possible to apply a simple formula to predict the timing of the first biting day at various geographical locations in Japan. Forecasting maps were created using a simple prediction formula. We found that the first biting day for Ae. albopictus changed depending on early spring temperatures for each year. There was an approximate 20-d difference in first biting day between years with warmer and cooler springs. This prediction model will provide useful insight for planning and practice of Ae. albopictus control programs, targeting larvae and adults, in temperate regions globally.ArticleJournal of Medical Entomology.54(6):1519-1524(2017)journal articl

Three‐dimensional myocardial scarring along myofibers after coronary ischemia–reperfusion revealed by computerized images of histological assays

Abstract Adverse left ventricular (LV) remodeling after acute myocardial infarction is characterized by LV dilatation and development of a fibrotic scar, and is a critical factor for the prognosis of subsequent development of heart failure. Although myofiber organization is recognized as being important for preserving physiological cardiac function and structure, the anatomical features of injured myofibers during LV remodeling have not been fully defined. In a mouse model of ischemia–reperfusion (I/R) injury induced by left anterior descending coronary artery ligation, our previous histological assays demonstrated that broad fibrotic scarring extended from the initial infarct zone to the remote zone, and was clearly demarcated along midcircumferential myofibers. Additionally, no fibrosis was observed in longitudinal myofibers in the subendocardium and subepicardium. However, a histological analysis of tissue sections does not adequately indicate myofiber injury distribution throughout the entire heart. To address this, we investigated patterns of scar formation along myofibers using three‐dimensional (3D) images obtained from multiple tissue sections from mouse hearts subjected to I/R injury. The fibrotic scar area observed in the 3D images was consistent with the distribution of the midcircumferential myofibers. At the apex, the scar formation tracked along the myofibers in an incomplete C‐shaped ring that converged to a triangular shape toward the end. Our findings suggest that myocyte injury after transient coronary ligation extends along myofibers, rather than following the path of coronary arteries penetrating the myocardium. The injury pattern observed along myofibers after I/R injury could be used to predict prognoses for patients with myocardial infarction

TÉCNICAS PARA VISUALIZAR INFORMAÇÃO E EXTRAIR CONHECIMENTO DE BASES DE INFORMAÇÕES: ESTUDO DE CASO DAS PRODUÇÕES DOS PROFESSORES DO PPGI-UFES

A Visualização é uma parte muito importante para conseguir a compreensão real da informação e para extrair conhecimentos relevantes. Portanto, a técnica para visualizar a informação selecionada deve ser compatível com o conteúdo que se vai apresentar. A proposta desta dissertação é apresentar um site que integre diversas Técnicas de Visualização criadas, que sejam fáceis, rápidas, entendíveis, dinâmicas e adaptáveis, dos temas desenvolvidos pelos integrantes de um grupo de pesquisa, durante alguns períodos. Essas técnicas são construídas tomando por base principalmente as palavras-chave e títulos das Produções Bibliográficas, representando assim a evolução dos temas pesquisados ao longo do tempo, entre outras coisas

Odorant-Binding Proteins OBP57d and OBP57e Affect Taste Perception and Host-Plant Preference in Drosophila sechellia

Despite its morphological similarity to the other species in the Drosophila melanogaster species complex, D. sechellia has evolved distinct physiological and behavioral adaptations to its host plant Morinda citrifolia, commonly known as Tahitian Noni. The odor of the ripe fruit of M. citrifolia originates from hexanoic and octanoic acid. D. sechellia is attracted to these two fatty acids, whereas the other species in the complex are repelled. Here, using interspecies hybrids between D. melanogaster deficiency mutants and D. sechellia, we showed that the Odorant-binding protein 57e (Obp57e) gene is involved in the behavioral difference between the species. D. melanogaster knock-out flies for Obp57e and Obp57d showed altered behavioral responses to hexanoic acid and octanoic acid. Furthermore, the introduction of Obp57d and Obp57e from D. simulans and D. sechellia shifted the oviposition site preference of D. melanogaster Obp57d/e(KO) flies to that of the original species, confirming the contribution of these genes to D. sechellia's specialization to M. citrifolia. Our finding of the genes involved in host-plant determination may lead to further understanding of mechanisms underlying taste perception, evolution of plant–herbivore interactions, and speciation

Winter Activity and Diapause of Aedes albopictus(Diptera: Culicidae) in Hanoi, Northern Vietnam

We studied the winter activity of Aedes albopictus (Skuse) from November 2008 to April 2009 in Bat Trang village of Hanoi, Vietnam. We selected 12 houses and collected: 1) adults with BG sentinel traps, 2) pupae from household water containers, and 3) eggs with ovitraps. Aedes albopictus adults, pupae, and eggs were not collected from early January to early February. Though the egg hatching probability tended to be initially high at longer day length, the maximum probability gradually shifted to shorter day length, as the observation period elapsed. When females were reared under long day length and their eggs were immersed 1 or 5 wk after oviposition, >50% of eggs hatched within 20 days. However, when females were reared under short day length and their eggs were immersed after 1 wk, hatching was suppressed for 60 days. When females were reared under short day length, the median hatching day occurred earlier in eggs kept dry for 5 and 10 wk after oviposition than in those dried for only 1 wk. This indicates that the extended dry periods accelerate egg hatching. Our results showed that hatchability gradually changed with day length, suggesting that selection for overwintering is not as strong relative to Ae. albopictus living in the temperate zone, where winter conditions are less favorable than in tropical and subtropical areas

Population Attributable Fraction of Smoking and Metabolic Syndrome on Cardiovascular Disease Mortality in Japan: a 15-Year Follow Up of NIPPON DATA90

<p>Abstract</p> <p>Background</p> <p>Smoking and metabolic syndrome are known to be related to cardiovascular diseases (CVD) risk. In Asian countries, prevalence of obesity has increased and smoking rate in men is still high. We investigated the attribution of the combination of smoking and metabolic syndrome (or obesity) to excess CVD deaths in Japan.</p> <p>Methods</p> <p>A cohort of nationwide representative Japanese samples, a total of 6650 men and women aged 30-70 at baseline without history of CVD was followed for 15 years. Multivariate-adjusted hazard ratio for CVD death according to the combination of smoking status and metabolic syndrome (or obesity) was calculated using Cox proportional hazard model. Population attributable fraction (PAF) of CVD deaths was calculated using the hazard ratios.</p> <p>Results</p> <p>During the follow-up period, 87 men and 61 women died due to CVD. The PAF component of CVD deaths in non-obese smokers was 36.8% in men and 11.3% in women, which were higher than those in obese smokers (9.1% in men and 5.2% in women). The PAF component of CVD deaths in smokers without metabolic syndrome was 40.9% in men and 11.9% in women, which were also higher than those in smokers with metabolic syndrome (7.1% in men and 3.9% in women).</p> <p>Conclusion</p> <p>Our results indicated that a large proportion of excess CVD deaths was observed in smokers without metabolic syndrome or obesity, especially in men. These findings suggest that intervention targeting on smokers, irrespective of the presence of metabolic syndrome, is still important for the prevention of CVD in Asian countries.</p