犬悪性乳腺腫瘍に対するミトコンドリア呼吸鎖複合体阻害薬の抗腫瘍効果

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 西村 亮平, 東京大学教授 辻本 元, 東京大学特任教授 日下部 守昭, 東京大学准教授 内田 和幸, 東京大学准教授 米澤 智洋University of Tokyo(東京大学

The validation of a Japanese version of the New Freezing of Gait Questionnaire (NFOG-Q)

The version of record of this article, first published in Neurological Sciences, is available online at Publisher’s website: https://doi.org/10.1007/s10072-024-07405-y.Objective: This study aimed to develop a Japanese version of the New Freezing of Gait Questionnaire (NFOG-Q) and investigate its validity and reliability. Methods: After translating the NFOG-Q according to a standardised protocol, 56 patients with Parkinson’s disease (PD) were administered it. Additionally, the MDS-UPDRS parts II and III, Hoehn and Yahr (H&Y) stage, and number of falls over 1 month were evaluated. Spearman’s correlation coefficients (rho) were used to determine construct validity, and Cronbach’s alpha (α) was used to examine reliability. Results: The interquartile range of the NFOG-Q scores was 10.0–25.3 (range 0–29). The NFOG-Q scores were strongly correlated with the MDS-UPDRS part II, items 2.12 (walking and balance), 2.13 (freezing), 3.11 (freezing of gait), and 3.12 (postural stability) and the postural instability and gait difficulty score (rho = 0.515–0.669), but only moderately related to the MDS-UPDRS item 3.10 (gait), number of falls, disease duration, H&Y stage, and time of the Timed Up-and-Go test (rho = 0.319–0.434). No significant correlations were observed between age and the time of the 10-m walk test. The internal consistency was excellent (α = 0.96). Conclusions: The Japanese version of the NFOG-Q is a valid and reliable tool for assessing the severity of freezing in patients with PD

Endometrial Cancer Diagnosed at an Early Stage during Lynch Syndrome Surveillance: A Case Report

Lynch syndrome is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair genes, resulting in multi-organ cancer. Annual transvaginal ultrasonography and endometrial biopsy are recommended for endometrial cancer surveillance in patients with Lynch syndrome in several guidelines; however, evidence is limited. Here, we present the case of a 51-year-old woman with endometrial cancer who underwent robot-assisted laparoscopic simple hysterectomy at an early stage detected by Lynch syndrome surveillance. The patient was a 51-year-old gravida zero woman without any medical history or symptoms. Her sister suffered from bladder, breast, rectal, and endometrial cancer and was diagnosed with Lynch syndrome using a hereditary cancer panel test (VistaSeq®). During gynecologic surveillance, the patient’s endometrial cytology was classified as Papanicolaou class III. Therefore, she underwent endometrial curettage with hysteroscopy and was diagnosed with atypical endometrial hyperplasia. Robot-assisted hysterectomy was performed with a final pathological diagnosis of endometrial cancer (endometrioid carcinoma, Grade 1), stage 1A. She has remained disease-free for more than 12 months. Owing to advances in genetic medicine, prophylactic and therapeutic surgeries for hereditary cancers are increasing. To achieve an early diagnosis and treatment of Lynch syndrome-associated cancers, the importance of Lynch syndrome surveillance should be more widely recognized

Architecture of the complete oxygen-sensing FixL-FixJ two-component signal transduction system

The symbiotic nitrogen-fixing bacterium Bradyrhizobium japonicum is critical to the agro-industrial production of soybean because it enables the production of high yields of soybeans with little use of nitrogenous fertilizers. The FixL and FixJ two-component system (TCS) of this bacterium ensures that nitrogen fixation is only stimulated under conditions of low oxygen. When it is not bound to oxygen, the histidine kinase FixL undergoes autophosphorylation and transfers phosphate from adenosine triphosphate (ATP) to the response regulator FixJ, which, in turn, stimulates the expression of genes required for nitrogen fixation. We purified full-length B. japonicum FixL and FixJ proteins and defined their structures individually and in complex using small-angle x-ray scattering, crystallographic, and in silico modeling techniques. Comparison of active and inactive forms of FixL suggests that intramolecular signal transduction is driven by local changes in the sensor domain and in the coiled-coil region connecting the sensor and histidine kinase domains. We also found that FixJ exhibits conformational plasticity not only in the monomeric state but also in tetrameric complexes with FixL during phosphotransfer. This structural characterization of a complete TCS contributes both a mechanistic and evolutionary understanding to TCS signal relay, specifically in the context of the control of nitrogen fixation in root nodules

Functional assessment of coronary artery flow using adenosine stress dual-energy CT: a preliminary study

We attempted to assess coronary artery flow using adenosine-stress and dual-energy mode with dual-source CT (DE-CT). Data of 18 patients with suspected coronary arteries disease who had undergone cardiac DE-CT were retrospectively analyzed. The patients were divided into two groups: 10 patients who performed adenosine stress CT, and 8 patients who performed rest CT as controls. We reconstructed an iodine map and composite images at 120 kV (120 kV images) using raw data with scan parameters of 100 and 140 kV. We measured mean attenuation in the coronary artery proximal to the distal portion on both the iodine map and 120 kV images. Coronary enhancement ratio (CER) was calculated by dividing mean attenuation in the coronary artery by attenuation in the aortic root, and was used as an estimate of coronary enhancement. Coronary stenosis was identified as a reduction in diameter of >50% on CT angiogram, and myocardial ischemia was diagnosed by adenosine-stress myocardial perfusion scintigraphy. The iodine map showed that CER was significantly lower for ischemic territories (0.76 ± 0.06) or stenosed coronary arteries (0.77 ± 0.06) than for non-ischemic territories (0.95 ± 0.21, P = 0.02) or non-stenosed coronary arteries (1.07 ± 0.33, P < 0.001). The 120 kV images showed no difference in CER between these two groups. Use of CER on the iodine map separated ischemic territories from non-ischemic territories with a sensitivity of 86% and a specificity of 75%. Our quantification is the first non-invasive analytical technique for assessment of coronary artery flow using cardiac CT. CER on the iodine map is a candidate method for demonstration of alteration in coronary artery flow under adenosine stress, which is related to the physiological significance of coronary artery disease

Reaction of Hypercoordinate Dichlorosilanes Bearing 8-(Dimethylamino)-1-naphthyl Group(s) with Magnesium: Formation of the 1,2-Disilaacenaphthene Skeleton (SYNTHETIC ORGANIC CHEMISTRY-Synthetic Design)

The reaction of a hypercoordinate dichlorosilane bearing an 8-(dimethylamino)-1-naphthyl group(s) with magnesium affords a dimeric product that contains a 1,2-disilaacenaphthene skeleton arising from silicon.silicon and silicon.naphthyl carbon bond formation and amino group migration from the naphthyl carbon atom to the coordinated silicon atom

Anti-neoplastic effects of topoisomerase inhibitors in canine mammary carcinoma, melanoma, and osteosarcoma cell lines

Numerous topoisomerase inhibitors with proven efficacy have been used extensively to treat various human neoplasms. However, among these, only doxorubicin has been used and studied extensively in veterinary oncology. The current study was performed to evaluate the responsiveness of canine osteosarcoma (cOSA), mammary gland tumour (cMGT), and malignant melanoma (cMM) cell lines to several topoisomerase inhibitors. In addition, the correlation between the sensitivity to treatment and multi-drug resistant (MDR) factors was investigated. cOSA cell lines exhibited higher sensitivity than cMGT and cMM cell lines to all the topoisomerase inhibitors tested in vitro; this was associated with the levels of multi-drug resistance protein 1 (MDR1) gene expression in the cOSA cell lines. Treatment of cOSA (HMPOS) and cMGT cell line (CHMp) xenograft mouse models with etoposide markedly delayed tumour progression in HMPOS xenografts, but failed to elicit lasting anti-tumour effects on CHMp xenograft mice. The present findings suggest that MDR1 represents a molecular signature for prediction of treatment efficacy of topoisomerase inhibitors, especially that of etoposide, which may be a clinically useful anti-tumour agent for cOSA; however, further study is necessary to refine the treatment protocol