本邦における中鎖アシルCoA脱水素酵素欠損症新生児スクリーニングより発見されたACADM遺伝子変異の重要性

内容の要旨 , 審査の要旨広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

Velocity Structure of Jets in Coronal Hole

Velocity structures of jets in a coronal hole have been derived for the first time. Hinode observations revealed the existence of many bright points in coronal holes. They are loop-shaped and sometimes associated with coronal jets. Spectra obtained with the Extreme ultraviolet Imaging Spectrometer (EIS) on board Hinode are analyzed to infer Doppler velocity of bright loops and jets in a coronal hole of the north polar region. Elongated jets above bright loops are found to be blue-shifted by 30 km/s at maximum, while foot points of bright loops are red-shifted. Blue-shifts detected in coronal jets are interpreted as upflows produced by magnetic reconnection between emerging flux and the ambient field in the coronal hole.Comment: 11 pages, 7 figures, accepted for publication in PASJ Hinode special issu

2D Slice-driven Physics-based 3D Motion Estimation Framework for Pancreatic Radiotherapy

Pancreatic diseases are difficult to treat with high doses of radiation, as they often present both periodic and aperiodic deformations. Nevertheless, we expect that these difficulties can be overcome, and treatment results may be improved with the practical use of a device that can capture 2D slices of organs during irradiation. However, since only a few 2D slices can be taken, the 3D motion needs to be estimated from partially observed information. In this study, we propose a physics-based framework for estimating the 3D motion of organs, regardless of periodicity, from motion information obtained by 2D slices in one or more directions and a regression model that estimates the accuracy of the proposed framework to select the optimal slice. Using information obtained by slice-to-slice registration and setting the surrounding organs as boundaries, the framework drives the physical models for estimating 3D motion. The R2 score of the proposed regression model was greater than 0.9, and the RMSE was 0.357 mm. The mean errors were 5.11 $\pm$ 1.09 mm using an axial slice and 2.13 $\pm$ 0.598 mm using concurrent axial, sagittal, and coronal slices. Our results suggest that the proposed framework is comparable to volume-to-volume registration, and is feasible

Molecular phylogeny of the higher and lower taxonomy of the Fusarium genus and differences in the evolutionary histories of multiple genes

<p>Abstract</p> <p>Background</p> <p>Species of the <it>Fusarium </it>genus are important fungi which is associated with health hazards in human and animals. The taxonomy of this genus has been a subject of controversy for many years. Although many researchers have applied molecular phylogenetic analysis to examine the taxonomy of <it>Fusarium </it>species, their phylogenetic relationships remain unclear only few comprehensive phylogenetic analyses of the <it>Fusarium </it>genus and a lack of suitable nucleotides and amino acid substitution rates. A previous stugy with whole genome comparison among <it>Fusairum </it>species revealed the possibility that each gene in <it>Fusarium </it>genomes has a unique evolutionary history, and such gene may bring difficulty to the reconstruction of phylogenetic tree of <it>Fusarium</it>. There is a need not only to check substitution rates of genes but also to perform the exact evaluation of each gene-evolution.</p> <p>Results</p> <p>We performed phylogenetic analyses based on the nucleotide sequences of the rDNA cluster region (rDNA cluster), and the β-tubulin gene (<it>β-tub</it>), the elongation factor 1α gene (<it>EF-1α</it>), and the aminoadipate reductase gene (<it>lys2</it>). Although incongruence of the tree topologies between <it>lys2 </it>and the other genes was detected, all genes supported the classification of <it>Fusarium </it>species into 7 major clades, I to VII. To obtain a reliable phylogeny for <it>Fusarium </it>species, we excluded the <it>lys2 </it>sequences from our dataset, and re-constructed a maximum likelihood (ML) tree based on the combined data of the rDNA cluster, <it>β-tub</it>, and <it>EF-1α</it>. Our ML tree indicated some interesting relationships in the higher and lower taxa of <it>Fusarium </it>species and related genera. Moreover, we observed a novel evolutionary history of <it>lys2</it>. We suggest that the unique tree topologies of <it>lys2 </it>are not due to an analytical artefact, but due to differences in the evolutionary history of genomes caused by positive selection of particular lineages.</p> <p>Conclusion</p> <p>This study showed the reliable species tree of the higher and lower taxonomy in the lineage of the <it>Fusarium </it>genus. Our ML tree clearly indicated 7 major clades within the <it>Fusarium </it>genus. Furthermore, this study reported differences in the evolutionary histories among multiple genes within this genus for the first time.</p

Gliosarcoma arising from a fibrillary astrocytoma

We report a 67-year-old woman who was diagnosed with a gliosarcoma at a second operation after diagnosis of a fibrillary astrocytoma 5 months previously. Initially, she underwent a CT-guided stereotactic biopsy. Histological examination showed fibrillary astrocytoma (World Health Organization [WHO] grade II). Loss of heterozygosity (LOH) on 1 p, 10q, and 19q was not detected. She received chemotherapy, but no radiotherapy. Five months after the biopsy, MRI revealed rapid tumor growth. Tissue obtained from partial removal of the tumor revealed gliosarcoma (WHO grade IV), and LOH on 10q and 19q was detected. The history, histopathology, and genetic alterations of this patient are discussed.ArticleJOURNAL OF CLINICAL NEUROSCIENCE. 18(9):1251-1254 (2011)journal articl

A Randomized Phase 2 Trial of Antibiotic Prophylaxis Versus No Intervention for Muscle Biopsy in A Neurology Department

Muscle biopsy can be used to confirm the diagnosis of neuromuscular diseases. However, it is unclear whether antibiotic prophylaxis prior to muscle biopsy is needed to prevent surgical site infection (SSI). We are conducting a phase 2, single-center, open-labeled, prospective randomized trial to clarify the need for antibiotic prophylaxis in patients at low risk for SSI undergoing muscle biopsy. Patients will be randomized to an antibiotic prophylaxis group or a control group, and the incidence of SSI will be compared between the groups. Our findings will clarify the need for antibiotic prophylaxis in this patient population

The outcome and a new ISN/RPS 2003 classification of lupus nephritis in Japanese

The outcome and a new ISN/RPS 2003 classification of lupus nephritis in Japanese.BackgroundA considerable diversity in prognosis is seen with lupus glomerulonephritis (LGN). Hence, the clinical usefulness of a recent International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification to judge the long-term outcome of human LGN has been investigated.MethodsWe studied retrospectively 60 subjects with LGN (7 males, 53 females, mean age of 33 years old) who underwent renal biopsies and were followed from 1 to 366 months, with a mean of 187 months. We diagnosed renal pathology as classes, active and sclerosing lesions, according to the new and WHO1995 classification of LGN, and analyzed the clinicopathologic factors affecting to the prognosis of LGN.ResultsNew classification got much higher consensus in the judgment of classes (98% vs. 83%, P = 0.0084). The group of Class IV-S (N = 6) or IV-G (N = 17) at initial biopsies showed higher rate of end-stage renal failure (ESRF) compared with that of Class I, II, III or V (40.9% vs. 2.6%, P < 0.001). The mean 50% renal survival time of Class IV was 189 ± 29 months, and patients with Class IV-S tended to have a poorer prognosis (95 ± 22 months for IV-S vs. 214 ± 35 months for IV-G, P = 0.1495). Class IV was also selected as the most significant risk factor for ESRF by stepwise model (P = 0.002). In subanalysis for ESRF in Class IV (-S or –G), treatment including methylprednisolone pulse therapy was only selected as a significant improving factor for primary outcome (P = 0.034). In addition, activity index was the significant risk factor of death and/or ESRF after initial renal biopsies (P = 0.043). As for actuarial patient death during all follow-up periods, complications with anti-phospholipid syndrome or nephrotic syndrome were significant risk factors (P = 0.013, P = 0.041, respectively).ConclusionNew ISN/RPS 2003 classification provided beneficial pathologic information relevant to the long-term renal outcome and the optimal therapy preventing ESRF and/or death in patients with LGN

Cord Blood Transplantation from Unrelated Donors for Children with Acute Lymphoblastic Leukemia in Japan: The Impact of Methotrexate on Clinical Outcomes

Cord blood transplantation (CBT) from an unrelated donor is recognized as one of the major treatment modalities in allogeneic stem cell transplantation (SCT) for children with hematologic malignancies. We analyzed the clinical outcomes of CBT for children with acute lymphoblastic leukemia (ALL) in Japan and identified the risk factors for the transplant outcomes. From 1997 to 2006, 332 children with ALL underwent CBT from unrelated donors, 270 of which had no prior transplant. Their disease statuses at transplant were first complete remission (CR) (n = 120), second CR (n = 71), and more advanced stages (n = 75). As preconditioning for SCT, total body irradiation (TBI) was given to 194 patients and, for the prophylaxis of graft-versus-host disease (GVHD), methotrexate (MTX) was given to 159 patients. The cumulative incidents of neutrophil and platelet recovery (>20 K) were 88.5% and 78.4%, respectively. The incidents of grade II-IV, III-IV acute GVHD (aGVHD), and chronic GVHD (cGVHD) were 45.6%, 20.4%, and 19.2%, respectively, and treatment-related mortality was 22.6%. The 5-year event-free survival (EFS) and overall survival (OS) at CR1, CR2, and advanced status were 47.4%, 45.5%, 15.0%, and 63.7%, 59.7%, and 20.7%, respectively. Multivariate analysis revealed that MTX with calcineurin inhibitor (CNI) was associated with decreased incidence of grade II-IV GVHD (CNI alone: hazard ratio [HR] = 1.74, 95% confidence interval [CI] = 1.06-2.83, P = .027; CNI + prednisolone (PSL), HR = 1.61, 95% CI = 1.03-2.50, P = .036), III-IV aGVHD (CNI alone: HR = 3.02, 95% CI = 1.55-5.91, P = 0.001; CNI + PSL, HR = 1.89, 95% CI = 0.93-3.83, P = .078), or cGVHD (CNI alone: HR = 1.78, 95% CI = 0.83-3.82, P = .143; CNI + PSL, HR = 2.44, 95% CI = 1.24-4.82, P = .01), compared with CNI alone or CNI + PSL. At an advanced stage of disease, GVHD prophylaxis with MTX + CNI is associated with improved OS compared with CNI alone (CNI alone: HR = 3.20, 95% CI = 1.43-7.15, P = .005; CNI + PSL, HR = 1.47, CI = 0.67-3.20, P = .332). Our retrospective study showed that CBT for children with ALL is feasible and GVHD prophylaxis with MTX + CNI is associated with significant favorable outcomes in prevention of aGVHD and cGVHD as well as survival advantage in advanced cases

Improved Sendai viral system for reprogramming to naive pluripotency

優れた多分化能を持つヒトのナイーブ型iPS細胞を迅速に作製する方法を発明. 京都大学プレスリリース. 2022-10-18.A novel method for generating naive human iPS cells with significantly higher differentiation potency. 京都大学プレスリリース. 2022-11-15.Naive human induced pluripotent stem cells (iPSCs) can be generated by reprogramming somatic cells with Sendai virus (SeV) vectors. However, only dermal fibroblasts have been successfully reprogrammed this way, and the process requires culture on feeder cells. Moreover, SeV vectors are highly persistent and inhibit subsequent differentiation of iPSCs. Here, we report a modified SeV vector system to generate transgene-free naive human iPSCs with superior differentiation potential. The modified method can be applied not only to fibroblasts but also to other somatic cell types. SeV vectors disappear quickly at early passages, and this approach enables the generation of naive iPSCs in a feeder-free culture. The naive iPSCs generated by this method show better differentiation to trilineage and extra-embryonic trophectoderm than those derived by conventional methods. This method can expand the application of iPSCs to research on early human development and regenerative medicine