知能検査による自閉症児と精神遅滞児の鑑別

本研究では,自閉症スペクトラム障害(ASD;Autism Spectrum Disorder)の能力のばらつきについて定量的に解明することを目的とし,ASD児と精神遅滞(MR;Mental Retardation)児に対して日本版ウエクスラー式児童用知能検査第3版を実施し,それぞれの言語性知能指数(VIQ;Verbal Intelligence Quotient)と動作性知能指数(PIQ;Performance Intelligence Quotient)の傾向を統計的手法を用いて調べた.その結果,(1)ASD群はMR群と比べ,言語性能力と非言語性能力がともに有意に高い,(2)ASD群は言語性能力が非言語性能力と比べて有意に低い,(3)MR群は言語性能力と非言語性能力に有意な差がない,(4)両群のVIQとPIQの差(VIQ-PIQ)の平均値には有意な差がある,(5)両群を鑑別する値,すなわちカットオフポイントはVIQ-PIQ=-6であることが明らかになった.以上から,個人内の言語性能力と非言語性能力の差,つまり両者のばらつきの傾向を調べることは,ASD児とMR児の鑑別診断に役立つことが示唆された

Comparisons among the complete genomes of four betanodavirus genotypes.

Betanodaviruses, the causative agents of viral nervous necrosis in marine fish, have bipartite positive-sense RNA genomes and have been classified (based on analysis of RNA2 sequences) into 4 genotypes: tiger puffer nervous necrosis virus (TPNNV), barfin flounder nervous necrosis virus (BFNNV), striped jack nervous necrosis virus (SJNNV), and redspotted grouper nervous necrosis virus (RGNNV). Full-length genomes of TPNNV and BFNNV were sequenced for the first time in this study. Their sequence data and those of SJNNV and RGNNV retrieved from GenBank were compared in order to investigate the relationships among the 4 genotypes. Between TPNNV and BFNNV, sequence identities were relatively high in RNA1 and encoded Protein A, but were not significantly high in RNA2 or the coat protein (CP). Similarly, between BFNNV and RGNNV, the amino acid sequences of CP were highly similar, but identities of RNA1, RNA2, and Protein A sequences were not especially high. Furthermore, multiple alignment data of the 4 genotypes of RNA2 sequences revealed that the TPNNV and SJNNV sequences have the same sizes of gaps and extra sequences at the same positions. Collectively, these apparent contradictions in sequence identity suggest that betanodavirus genomes have been constructed via complex evolutionary processes

RETROPERITONEAL FIBROSARCOMA WITH DISTINCTIVE CHARACTERISTICS ON GROWTH P ATTERN AND FINDINGS IN DIAGNOSTIC IMAGING

A 47-year-old man with lumbago had been found to have a perirenal hematoma at the lower pole of the left kidney on CT. MR imaging also demonstrated a hematoma，8 X8X9αn in size. After 1-month observation，the mass had very rapidly increased in size，suggesting it to be a neoplasm. Consequent surgery resulted in noncurative tumor extirpation，because of invasion to the descending colon，left kidney and surrounding tissues. Histlogically，the tumor consisted of uniform spindle-shaped cells with interlacing solid and bundle forms，showing a herring-bone pattern. Immunohistochemical studies finally led to the diagnosis of fibrosarcoma with markedly high malignant potential. Additional therapy was not performed. Rapid local spread of the tumor was demonstrated when bowel obstruction developed 2 months later. The patient died of the disease 3 months after surgery. No distant metastasis was observed throughout the clinical course

N-ブチル-N-（4-ヒドロキシブチル）ニトロソアミン誘発膀胱癌マウスモデルを用いた膀胱内化学療法による局所及び全身の免疫応答

Intravesical bacillus Calmette-Guerin (BCG) treatment is the most common therapy to prevent progression and recurrence of non-muscle invasive bladder cancer (NMIBC). Although the immunoreaction elicited by BCG treatment is well documented, those induced by intravesical treatment with chemotherapeutic agents are much less known. We investigated the immunological profiles caused by mitomycin C, gemcitabine, adriamycin and docetaxel in the N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced orthotopic bladder cancer mouse model. Ninety mice bearing orthotopic bladder cancer induced by BBN were randomly divided into six groups and treated with chemotherapeutic agents once a week for four weeks. After last treatment, bladder and serum samples were analyzed for cell surface and immunological markers (CD4, CD8, CD56, CD204, Foxp3, and PD-L1) using immunohistochemistry staining. Serum and urine cytokine levels were evaluated by ELISA. All chemotherapeutic agents presented anti-tumor properties similar to those of BCG. These included changes in immune cells that resulted in fewer M2 macrophages and regulatory T cells around tumors. This result was compatible with those in human samples. Intravesical chemotherapy also induced systemic changes in cytokines, especially urinary interleukin (IL)-17A and granulocyte colony stimulating factor (G-CSF), as well as in the distribution of blood neutrophils, lymphocytes, and monocytes. Our findings suggest that intravesical treatment with mitomycin C and adriamycin suppresses protumoral immunity while enhancing anti-tumor immunity, possibly through the action of specific cytokines. A better understanding of the immunoreaction induced by chemotherapeutic agents can lead to improved outcomes and fewer side effects in intravesical chemotherapy against NMIBC.博士（医学）・甲第695号・平成31年3月15日Copyright: © 2017 Hori et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Vibrio splendidus biovar II as the causative agent of bacillary necrosis of Japanese oyster Crassostrea gigas.

Recurrent outbreaks of a disease leading to mass mortalities in an oyster (Crassostrea gigas) hatchery located in western Japan were investigated. The disease occurred regularly in 2- to 8-d-old larvae and has been experimentally controlled in the hatchery by treating the larval rearing water with streptomycin, without ascertaining the etiological agent. The signs of the disease and the course of infection resembled bacillary necrosis reported in oysters and other bivalve molluscs in the USA and Europe. Quantitative and qualitative examinations of the bacterial flora of hatchery samples including source water, broodstock, larval feed and larvae revealed a very high total bacterial load and presumptive vibrios in diseased larvae. Further, the bacterial profile revealed that Vibrio spp. constituted approximately 60 to 95% of the bacteria isolated from infected larvae and most isolates were identified as V. splendidus biovar II and V. harveyi, suggesting their possible role in the disease. However, experimental challenges proved the pathogenicity of V. splendidus II. Several isolates of V. splendidus II from infected larvae were highly pathogenic, producing 100% mortality at levels of 105 cfu ml-1 in 24 h, while isolates from other sources demonstrated a low degree of virulence. Detection of V. splendidus II from broodstock, especially in the gonad of a few breeders, suggests the probability that broodstock could be the source and route of transmission of this pathogen

非小細胞肺がんと非小細胞肺がんから発生した転移性脳腫瘍における光線力学的測定によりPEPT1の発現は5-ALAから代謝されるプロトポルフィリンⅨの蓄積において正の相関をする

BACKGROUND: Recently, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX fluorescence was reported to be a useful tool during total surgical resection of high-grade gliomas. However, the labeling efficacy of protoporphyrin IX fluorescence is lower in metastatic brain tumors compared to that in high-grade gliomas, and the mechanism underlying protoporphyrin IX fluorescence in metastatic brain tumors remains unclear. Lung cancer, particularly non-small cell lung cancer (NSCLC), is the most common origin for metastatic brain tumor. Therefore, we investigated the mechanism of protoporphyrin IX fluorescence in NSCLC and associated metastatic brain tumors. METHODS: Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the protein and mRNA levels of five transporters and enzymes involved in the porphyrin biosynthesis pathway: peptide transporter 1 (PEPT1), hydroxymethylbilane synthase (HMBS), ferrochelatase (FECH), ATP-binding cassette 2 (ABCG2), and heme oxygenase 1 (HO-1). The correlation between protein, mRNA, and protoporphyrin IX levels in NSCLC cells were evaluated in vitro. Immunohistochemistry was used to determine proteins that played a key role in intraoperative protoporphyrin IX fluorescence in clinical samples from patients with NSCLC and pathologically confirmed metastatic brain tumors. RESULTS: A significant correlation between PEPT1 expression and protoporphyrin IX accumulation in vitro was identified by western blotting (P = 0.003) and qRT-PCR (P = 0.04). Immunohistochemistry results indicated that there was a significant difference in PEPT1 between the intraoperative protoporphyrin IX fluorescence-positive and protoporphyrin IX fluorescence-negative groups (P = 0.009). CONCLUSION: Expression of PEPT1 was found to be positively correlated with 5-ALA-induced protoporphyrin IX accumulation detected by photodynamic reaction in metastatic brain tumors originating from NSCLC.博士（医学）・甲第714号・令和元年年6月26日Copyright © 2019 Elsevier B.V. All rights reserved

ラット膀胱での水吸収におけるアクアポリン-2の役割

AIM: We investigated the role of the bladder wall in permeating water, focusing on aquaporins. METHODS: Female Sprague-Dawley rats weighing 300 g were used to investigate the role of the bladder wall in saline permeation. Changes in intravesical fluid volume and sodium concentration were measured in the desmopressin acetate hydrate-loaded and control groups 3 h after administration. Bladders were resected to measure aquaporin-1, 2, and 3 gene expression using qRT-PCR. Additionally, the change of aquaporin-2 expression was measured using Western blotting and immunohistochemistry in intravesical aquaporin-2 siRNA-treated and control groups. RESULTS: Although the intravesical fluid volume and sodium concentration significantly decreased from 0 to 3 h (1.00 ± 0.00 vs 0.83 ± 0.08 mL, 157.80 ± 1.30 vs 146.8 ± 1.92 mEq/mL, P < 0.01, respectively in the control group), administration of desmopressin did not affect the extent of volume change. Aquaporin-2 expression was significantly higher in the 3-h distended bladders than in the empty bladder. Aquaporin-2 siRNA treatment suppressed aquaporin-2 expression and the change of intravesical fluid volume from 0 to 3 h (1.00 ± 0.00 and 0.99 ± 0.02 mL), which was related to the suppression of sodium concentration change in comparison with control siRNA treatment (149.6 ± 2.4 vs 143.6 ± 3.67 mEq/mL, P < 0.05). CONCLUSIONS: The rat urinary bladder absorbs water and salts under the full-filled condition. Aquaporin-2 plays an important role in the transport of water, accompanied by sodium concentration change. We demonstrated a part of the bladder absorption mechanism, which may lead to development of a new method for regulating bladder storage function.博士（医学）・甲第697号・平成31年3月15日© 2018 Wiley Periodicals, Inc.This is the pre-peer reviewed version of the following article: [https://onlinelibrary.wiley.com/doi/full/10.1002/nau.23715], which has been published in final form at [http://dx.doi.org/10.1002/nau.23715]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions

Life sciences

Aims: To examine the circadian expression changes in bladder clock genes in Dahl salt-sensitive rats following high salt intake. Main methods: Eighteen rats were divided into three groups: the high-salt diet group (HS group), the normal-salt diet group (NS group), and the salt-load interruption group (from a 4 % salt diet to a normal diet; salt-load interruption group [SI group]). Each rat was placed in an individual metabolic cage for 24 h twice weekly. Water intake, urine production, voiding frequency, and voided volume per micturition were recorded. Furthermore, 108 control rats were prepared. Bladders were harvested every 4 h at six time points. Furthermore, the mRNA expression of clock genes and mechanosensors was analyzed. Key findings: In the HS group, the bladder clock genes showed lower mRNA levels than in the NS group. The amplitude of circadian expression changes in bladder clock genes in the HS group was lower than that in the NS group. However, after changing from a 4 % salt diet to a normal diet, the waveforms of the clock gene expression in the SI group were closer to those of the NS group. The 24-h water intake and urinary volume of the SI group decreased to levels comparable to those of the NS group. Significance: Reduced salt intake partially restored the circadian rhythms of bladder clock genes.博士（医学）・甲第857号・令和4年12月22日Copyright © 2022 Elsevier Inc. All rights reserved

保育者養成における子どもの「ことば」を育てる視点の理解についての研究

子どもは,絵本や物語の内容に想像を巡らしたりイメージを膨らませたりすることによって「ことば」を育んでいく.保育者は,子どもの「ことば」への興味関心や「ことば」と言葉をつなげていくことを支援する必要がある.本研究では,保育者養成校の学生が,絵本を紙芝居に作り替えるという体験学習を通して,子どもの「ことば」を育てる視点を理解することができたかどうかを検討した.その結果,この学習を通してほとんどの学生が,絵本や紙芝居の構造が子どもの「ことば」の意味の理解を促進したり「ことば」の使途を広げたりする役割を担っていることに気付くことができ,そこから更に,保育における「ことば」の指導の視点まで理解を深めることができていたことが分かった