腸管内微生物による免疫応答調節機構の解析

学位の種別: 課程博士審査委員会委員 : （主査）東京大学教授 清野 宏, 東京大学教授 畠山 昌則, 東京大学教授 小池 和彦, 東京大学准教授 渡邊 洋一, 東京大学准教授 牛久 哲男University of Tokyo(東京大学

Novel CHD7 mutation in CHARGE syndrome

CHARGE syndrome is a rare autosomal dominant developmental disorder involving multiple organs. CHD7 is a major causative gene of CHARGE syndrome. We performed targeted-exome sequencing using a next-generation sequencer for molecular diagnosis of a 4-month-old male patient who was clinically suspected to have CHARGE syndrome, and report a novel monoallelic mutation in CHD7, NM_017780.3(CHD7_v001):c.2966del causing a reading frameshift [p.(Cys989Serfs*3)]

Angiotensinogen expression in neonates

Background We recently demonstrated that preterm neonates have higher urinary angiotensinogen (AGT) levels than full-term neonates. Here, we tested the hypothesis that enhanced neonatal AGT expression is associated with intrarenal renin-angiotensin system (RAS) status during kidney development. Methods We prospectively recruited neonates born at our hospital and healthy children with minor glomerular abnormalities between April 2013 and March 2017. We measured neonatal plasma and urinary AGT levels at birth and one year later and assessed renal AGT expression in kidney tissues from neonates and healthy children using immunohistochemical (IHC) analysis. Results Fifty-four neonates and eight children were enrolled. Although there were no changes in plasma AGT levels, urinary AGT levels were significantly decreased one year after birth. Urinary AGT levels at birth were inversely correlated with gestational age, and urinary AGT levels at birth and one year later were inversely correlated with estimated glomerular filtration rate one year after birth. IHC analysis showed that renal AGT expression in neonates was higher than that in healthy children and inversely correlated with gestational age. Conclusions Enhanced AGT expression and urinary AGT excretion may reflect intrarenal RAS activation associated with kidney development in utero

Serum biotin level during pregnancy

Background : Biotin is a water-soluble vitamin that plays various biological roles through histone modification, such as immune functions and fetal growth. Mammalian maternal biotin deficiency during gestation induces fetal growth restriction. Preterm infants are known to be marginal biotin deficiency. However, studies on the biotin status of pregnant women under various conditions are lacking. Method : This was a retrospective case control study to analyze serum biotin concentration during pregnancy and cord blood in normal pregnancy, preterm delivery and small-for-gestational-age (SGA). Results : Twenty pregnant women with normal term delivery, 35 with preterm delivery, 24 with SGA, and 10 non-pregnant adult women were enrolled. Serum biotin concentrations of pregnant women remained low from first to third trimester. The levels of serum biotin in cord blood showed a significant positive correlation with gestational age, and that of pregnant women showed a weak positive correlation with gestational age. The maternal serum biotin levels during second and third trimester of SGA group were significantly lower than those of normal term delivery. Conclusion : This study suggests that maternal biotin deficiency during pregnancy might be the risk of preterm labor or fetal growth restriction. Further studies are required to clarify the roles of biotin in perinatal medicine

Simultaneous in-situ multi-element analysis of minerals on thin section using LA-ICP-MS

Department of Earth Sciences, Faculty of Science, Kanazawa University:Graduate School of Natural Science and Technology, Kanazawa UniversityDepartment of Earth Sciences, Faculty of Science, Kanazawa University:Graduate School of Natural Science and Technology, Kanazawa UniversityDepartment of Earth Sciences, Faculty of Science, Kanazawa University:Graduate School of Natural Science and Technology, Kanazawa UniversityDepartment of Earth Sciences, Faculty of Science, Kanazawa University:Graduate School of Natural Science and Technology, Kanazawa UniversityIn-situ trace-element analyses on minerals are especially useful for characterization of geological materials. We explored optimistic conditions of a inductively coupled plasma mass spectroscopy with laser-ablation sample introduction method (LA-ICP-MS) for in-situ quantitative trace-element analysis of geological materials on thin section. The sampling with an excimer laser with energy density of 8 J/cm^2 is appropriate for in-situ analysis of minerals on thin section based on ablation hole morphology. The rate of material removal is estimated from deep holes on a glass after 500 shots with energy on sample surface of 8 J/cm^2 to be approximately 0.2ƒﾊm/pulse. 150-200 shots might be available for a sample prepared as normal thin section (30ƒﾊm in thickness). All data were obtained by ablating in He gas prior to combination with the dominant Ar carrier flow because ablation in He minimized post-ablation surface condensation, resulting in high sensitivity. We examined the relationship between the size of laser-ablation hole and sensitivity of analysis in conducting in-situ simultaneous quantitative LA-ICP-MS analysis of 37 elements including rare earth elements (REEs). The diameter of laser beam can be as small as 30ƒﾊm to obtain sufficiently good dataset for trace-element concentrations of minerals from thin section

Validating Variational Bayes Linear Regression Method With Multi-Central Datasets.

PurposeTo validate the prediction accuracy of variational Bayes linear regression (VBLR) with two datasets external to the training dataset.MethodThe training dataset consisted of 7268 eyes of 4278 subjects from the University of Tokyo Hospital. The Japanese Archive of Multicentral Databases in Glaucoma (JAMDIG) dataset consisted of 271 eyes of 177 patients, and the Diagnostic Innovations in Glaucoma Study (DIGS) dataset includes 248 eyes of 173 patients, which were used for validation. Prediction accuracy was compared between the VBLR and ordinary least squared linear regression (OLSLR). First, OLSLR and VBLR were carried out using total deviation (TD) values at each of the 52 test points from the second to fourth visual fields (VFs) (VF2-4) to 2nd to 10th VF (VF2-10) of each patient in JAMDIG and DIGS datasets, and the TD values of the 11th VF test were predicted every time. The predictive accuracy of each method was compared through the root mean squared error (RMSE) statistic.ResultsOLSLR RMSEs with the JAMDIG and DIGS datasets were between 31 and 4.3 dB, and between 19.5 and 3.9 dB. On the other hand, VBLR RMSEs with JAMDIG and DIGS datasets were between 5.0 and 3.7, and between 4.6 and 3.6 dB. There was statistically significant difference between VBLR and OLSLR for both datasets at every series (VF2-4 to VF2-10) (P < 0.01 for all tests). However, there was no statistically significant difference in VBLR RMSEs between JAMDIG and DIGS datasets at any series of VFs (VF2-2 to VF2-10) (P > 0.05).ConclusionsVBLR outperformed OLSLR to predict future VF progression, and the VBLR has a potential to be a helpful tool at clinical settings

NICU・GCUを退院したSGA児の予後

【Background】Small for gestational age (SGA) infants have multiple risk factors for short stature, developmental disorders, and metabolic diseases in adulthood. Our institute which plays central roles in perinatal medicine in Tokushima prefecture has many high risk pregnant women, therefore a relatively large number of SGA infants admitted to neonatal intensive care unit (NICU) and growth care unit (GCU). 【Objective】To elucidate the prognosis such as short stature, neurodevelopmental disorder and mental retardation of SGA infants discharged from NICU and GCU in our hospital. 【Method】SGA patients discharged from NICU and GCU in our hospital between 2012 and 2014 were enrolled in this study. Clinical data were collected from medical charts. 【Results】There were 106 SGA infants (19.5%) discharged from NICU/GCU for 3 years. We excluded patients with congenital malformation syndrome, chromosomal abnormality, neuromuscular disorder, death and lost of follow-up, and finally 75 SGA infants were enrolled. Four SGA infants (5%) required growth hormone (GH) treatment for short stature and all of them were promoted growth significantly. Three SGA infants (4%) showed attention deficit hyperactivity disorder and/or autism spectrum disorder, and 5 SGA infants (6%) presented with mental retardation. 【Conclusion】This study revealed the prognosis of SGA infants discharged from NICU and GCU in our hospital. Further large cohort with long-term observation is required

Novel COL5A2 mutation in Ehlers–Danlos syndrome

Ehlers–Danlos syndrome (EDS) is a group of inherited connective tissue disorders characterized by hyperextensible skin, joint hypermobility and soft tissue fragility. For molecular diagnosis, targeted exome sequencing was performed on a 9-year-old male patient who was clinically suspected to have EDS. The patient presented with progressive kyphoscoliosis, joint hypermobility and hyperextensible skin without scars. Ultimately, classical EDS was diagnosed by identifying a novel, mono-allelic mutation in COL5A2 [NM_000393.3(COL5A2_v001):c.682G>A, p.Gly228Arg]

Lowe syndrome caused by gloss deletion

Lowe syndrome (LS) is an X-linked disorder affecting the eyes, nervous system and kidneys, typically caused by missense or nonsense/frameshift OCRL mutations. We report a 6-month-old male clinically suspected to have LS, but without the Fanconi-type renal dysfunction. Using a targeted-exome sequencing-first approach, LS was diagnosed by the identification of a deletion involving 1.7 Mb at Xq25-q26.1, encompassing the entire OCRL gene and neighboring loci