Neuronal apoptosis and inflammatory responses in the central nervous system of a rabbit treated with Shiga toxin-2

<p>Abstract</p> <p>Background</p> <p>Shiga toxins (Stxs) are the major agents responsible for hemorrhagic colitis and hemolytic-uremic syndrome (HUS) during infections caused by Stx-producing <it>Escherichia coli </it>(STEC) such as serotype O157:H7. Central nervous system (CNS) involvement is an important determinant of mortality in diarrhea associated-HUS. It has been suggested that vascular endothelial injuries caused by Stxs play a crucial role in the development of the disease. The current study investigates the relationship between the cytotoxic effects of Stxs and inflammatory responses in a rabbit brain treated with Stx2.</p> <p>Methods</p> <p>In a rabbit model treated with purified Stx2 or PBS(-), we examined the expression of the Stx receptor globotriaosylceramide (Gb3)/CD77 in the CNS and microglial activation using immunohistochemistry. The relationship between inflammatory responses and neuronal cell death was analyzed by the following methods: real time quantitative reverse transcriptase (RT)-polymerase chain reaction (PCR) to determine the expression levels of pro-inflammatory cytokines, and the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method to detect apoptotic changes.</p> <p>Results</p> <p>Gb3/CD77 expression was detected in endothelial cells but not in neurons or glial cells. In the spinal cord gray matter, significant levels of Gb3/CD77 expression were observed. Severe endothelial injury and microvascular thrombosis resulted in extensive necrotic infarction, which led to acute neuronal damage. Conversely, in the brain, Stx receptor expression was much lower. The observed neuropathology was less severe. However, neuronal apoptosis was observed at the onset of neurological symptoms, and the number of apoptotic cells significantly increased in the brain at a later stage, several days after onset. Microglial activation was observed, and tumor necrosis factor (TNF)-α and interleukin (IL)-1β mRNA in the CNS parenchyma was significantly up-regulated. There was significant overexpression of TNF-α transcripts in the brain.</p> <p>Conclusion</p> <p>This study indicates that Stx2 may not directly damage neural cells, but rather inflammatory responses occur in the brain parenchyma in response to primary injury by Stx2 in vascular endothelial cells expressing Gb3/CD77. These findings suggest that neuroinflammation may play a critical role in neurodegenerative processes during STEC infection and that anti-inflammatory intervention may have therapeutic potential.</p

ヒト胃癌においてEBウイルス感染が誘導するエピゲノム異常の解明

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 畠山 昌則, 東京大学教授 瀬戸 泰之, 東京大学教授 伊庭 英夫, 東京大学准教授 藤城 光弘, 東京大学准教授 北山 丈二University of Tokyo(東京大学

Practical Report on the Activities of the EYL Teacher Education Programmes “English Event for Elementary School Students: Let’s Sing Christmas Songs”: Searching a Place for University Students and Elementary School Students to Learn Together

departmental bulletin pape

QTLs for agronomic traits detected in recombinant inbred lines derived from a bread wheat × spelt cross

application/pdfSpelt wheat (Triticum aestivum subsp. spelta), a subspecies of common wheat, is a genetic resource for the breeding of bread wheat (T. aestivum subsp. aestivum); however, genetic analyses of agronomic traits in bread wheat × spelt crosses are insufficient. Here, we conducted QTL analysis in the recombinant inbred lines from a bread wheat × spelt cross. In addition to the major Q locus, QSpd.obu-4D was detected with the spelt allele conferring a higher spikelet density than the bread wheat allele. The effect of QSpd.obu-4D was evident in the presence of the Q allele of bread wheat, suggesting that this variation might be cryptic in spelt wheat with the q allele. Two QTLs with stable effects were identified for grain length, one of which (QGl.obu-1A) has never been detected in a bread wheat × spelt cross. The spelt wheat allele at QHt.obu-7B conferring later heading was identified in the Vrn-B3 region and could be a novel gene source for modifying heading time. Furthermore, QGi.obu-2B, responsible for low grain dormancy of spelt wheat, was detected. Further exploration and identification of useful QTLs could accelerate the utilization of spelt wheat as a genetic resource for bread wheat breeding programs. © 2019, Japanese Society of Breeding. All rights reserved.journal articl

Successful treatment of desmoid tumor of the chest wall with tranilast: a case report

<p>Abstract</p> <p>Introduction</p> <p>Desmoid tumor is characterized by infiltrative growth and local recurrence often occurs after surgery. To reduce the local recurrence rate, adjuvant therapy, such as radiotherapy and pharmacotherapy with cytotoxic agents, anti-estrogen agents and non-steroidal anti-inflammatory drugs, is often applied. In addition, these non-surgical treatments are also performed in patients with unresectable desmoid tumors. We successfully treated a patient with a desmoid tumor with tranilast; an anti-allergic agent.</p> <p>Case presentation</p> <p>A 48-year-old Japanese man with a slow-growing desmoid tumor on his chest wall was treated with an oral administration of tranilast (300 mg per day, three times a day). Two years and two months after the commencement of his therapy, the tumor became impalpable. At this time, the oral administration of tranilast was discontinued. Two years after discontinuation of the treatment, a physical examination showed no recurrence of the tumor and he continued in a state of remission. We were successfully able to reduce the size of the tumor and thereafter maintain the reduced size.</p> <p>Conclusion</p> <p>Tranilast was clinically effective in our case, and is probably comparable to cytotoxic agents or anti-estrogen agents. Because tranilast has substantially fewer adverse effects than cytotoxic agents, it could be a very useful therapeutic agent for desmoid tumor.</p

Biocompatibility of subretinal parylene-based Ti/Pt microelectrode array in rabbit for further artificial vision studies

To evaluate the biocompatibility of subretinal implanted parylene-based Ti/Pt microelectrode arrays (MEA). Eyes were enucleated 3 months after MEAs were implanted into the subretinal space of rabbits. Morphological changes of the retinas were investigated by H&E staining. Immunohistochemical staining for glial fibrillary acidic protein and opsin were performed to evaluate changes in Muller cells and photoreceptors in the retinas. Retina tissue around the array remained intact. Photoreceptor degeneration and glial cell activation were observed in the retina overlaying the MEA implant. However, the cells in the inner retinal layers were preserved. Photoreceptor degeneration and glial cell activation at the MEA–retina interface are expected to be a normal reaction to implantation. Material used in this experiment has good biocompatibility within the subretinal environment and is expected to be promising in the further retinal prosthesis studies