ヴァージニア ウルフ ノ トウダイ エ ゲンゴ エノ シツボウ チンモク ソシテ ゲンゴ エノ アラタナル ココロミ

Virginia　Woolf　deals　with　the　problem　of“1anguage”in　her　many ・works．　Among　them　To　T勿Lゴ8配加％5θis　very　interesting　in understanding　her　idea　of　language． 　　It　i6　Mrs．　Ramsay　and　Lily　Briscoe　who　feel　great　interests　in language　in　this　work．　Mrs，　Ramsay　thinks　that　she　is　not　able　to tt　’ express　what　she　fee13　as　it　is　by・means　of　language　and　is　dissatisfled 　with　it．　Lily．also　doubts　about　Ianguage　as　a　sign　with　a mea耳ing．　In　their　disappointment　Woolf’s　disappointment　at　lan－l guage　is　reflected．　Here　we　must　notice　an　important　thing．　It　is that　only．　women　feel　disgusts　towa；d　language．　Why　are　only women　dissatis茸ed　with　languageP　In且1ヒo伽げ0％θ’ε0ωπWoolf defines　language　used　today　as“a　man’s　sentence”，　that　is，　language dominated　by加en　and　alludes　that　it　is　unsuitable　for　women’s　use． Judging　from　this　view，　we　can　say　that　Mrs．　Ramsay　and　Lily　are described　as　the　sプmbol　of　women　who　are　disappointed　at　language ．dominated　by　men．　And　Mrs．　Ramsay　and　Lily　come　to　refuse　to use　it　and　6nt6r　into　thごkingdom　of　silence．． 　　But　do　they．really　give　up　their　coping　with　language　dominated by　men？In　fact，　Li！y　does　so，　but　Mrs．　Ramsay　tries　to丘nd　a new　possibility’of　Ianguage．　Sandra　M．　Gilbert　mentions　that　Woolf does　not　create“a　women，s　selltence”but　tries　to　revise’ 狽??奄秩@relations 　to　Ianguage　dominated　by　men．　This　attitude　of　revising　the relation　to　language　is　shown　in　Mrs．　Ramsay．　Besides　the　conventional 　usage　of　language　that　we　use　words　as　signs　with　meanings， she　tries　to五nd　a　new　relation　to　language．　First　she　sets　language from　meaning．　She　no　longer　uses　language　only　as　a　means　of communication．　She　focuses　on　the　most　essential　element　of　language，“ sound”which　has　been　hidden　behind　meaning　and　in　it she　tries　to　find　a　new　possibility　of　language．　Finally　she　succeeds in　creating　unity　she　has　longed　for　because　of‘“sound”　and“rhythm”． Thus　she　finds　the　new　relation　to　language　by　emphasizing“sound” and“rhythm”，　not　meaning．　We　can　conclude　that　her　approach symbolizes　Woolf’s　attitude　as　the　woman　writer　who　tries　to　find anew　possibility　of　Ianguage　while　she　is　disappointed　at　it

Alterations of circulating endothelial cell and endothelial progenitor cell counts around the ovulation.

Context:Circulating endothelial cells (CECs) and progenitor cells (CEPs) have been intensively studied as a promising tool for treating ischemic diseases and monitoring cancer treatments, but how the menstrual cycle affects the variation in their counts remains unclear. Objective:The aims of the study were to determine the influence of the menstrual cycle on the number of CECs and CEPs and to investigate the association of their counts with circulating hormones and angiogenesis-associated factors. Design:CEP and CEC counts by flow cytometry and the CellSearch system and circulating factor levels were measured eight times during the menstrual cycle in 18 volunteers. The menstrual cycle was divided into six phases based on hormone concentrations. Results:CEP counts peaked in the periovulatory and middle luteal phases with a drop in the early luteal phase. CEC counts showed no significant variation. There were significant correlations between the CEP counts and the serum concentrations of estradiol (E2), LH, and granulocyte colony-stimulating factor (G-CSF) (P < 0.0001, P < 0.0001, and P = 0.01, respectively). The difference in CEP counts between two adjacent phases was significantly correlated with that in E2, LH, G-CSF, and serum vascular endothelial growth factor (P < 0.0001, P < 0.0001, P = 0.02, and P = 0.006, respectively). Conclusion:CEP counts peaked in the periovulatory and middle luteal phases, with a drop in the early luteal phase, and were correlated with serum E2, LH, and G-CSF concentrations. Consideration of the variation in CEP counts would be important for the clinical application of CEPs

ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function

Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression of ADAM12, a disintegrin and metalloprotease, dramatically affects cell morphology in preadipocytes, changing them from a flattened, fibroblastic appearance to a more rounded shape. We showed that the highest levels of ADAM12 mRNA were detected in preadipocytes at the critical stage when preadipocytes become permissive for adipogenic differentiation. Furthermore, as assessed by immunostaining, ADAM12 was transiently expressed at the cell surface concomitant with the reduced activity of beta1 integrin. Co-immunoprecipitation studies indicated the formation of ADAM12/beta1 integrin complexes in these preadipocytes. Overexpression of ADAM12 at the cell surface of 3T3-L1 preadipocytes achieved by transient transfection or retroviral transduction led to the disappearance of the extensive network of actin stress fibers that are characteristic of these cells, and its reorganization into a cortical network located beneath the cell membrane. The cells became more rounded, exhibited fewer vinculin-positive focal adhesions, and adhered less efficiently to fibronectin in attachment assays. Moreover, ADAM12-expressing cells were more prone to apoptosis, which could be prevented by treating the cells with beta1-activating antibodies. A reduced and re-organized fibronectin-rich extracellular matrix accompanied these changes. In addition, beta1 integrin was more readily extracted with Triton X-100 from cells overexpressing ADAM12 than from control cells. Collectively, these results show that surface expression of ADAM12 impairs the function of beta1 integrins and, consequently, alters the organization of the actin cytoskeleton and extracellular matrix. These events may be necessary for early adipocyte differentiation

Long-term efficacy and safety of canagliflozin in combination with insulin in Japanese patients with type 2 diabetes mellitus

Aim: The aim of this study was to assess the long-term efficacy and safety of canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus who had inadequate glycaemic control with insulin. Materials and methods: The study comprised a 16-week, double-blind period in which patients were randomized to either placebo (P; N = 70) or canagliflozin (100 mg, CAN; N = 76), followed by a 36-week open-label period in which all patients received canagliflozin. The efficacy endpoints included the change in HbA1c from baseline to end of treatment. The safety endpoints were adverse events, hypoglycaemic events, and laboratory test values. Results: The changes from baseline (mean ± standard deviation, last observation carried forward) in the P/CAN and CAN/CAN groups, respectively, were −1.09% ± 0.85% and −0.88% ± 0.86% for HbA1c, −1.40% ± 2.54% and −2.14% ± 2.75% for body weight, and 7.84% ± 14.37% and 8.91% ± 10.80% for HOMA2-%B (all, P < .001). Adverse events occurred in 85.1% of the P/CAN group and 92.0% of the CAN/CAN group. Hypoglycaemic events occurred in 43.3% and 54.7%, respectively. All hypoglycaemic events were mild in severity and insulin dose reduction decreased the incidence rate of hypoglycaemic events. Post-hoc ordinal logistic modelling/logistic modelling showed that lower serum C-peptide at Week 0 was a risk factor for hypoglycaemia in both the P and CAN groups in the double-blind period as well as in the canagliflozin all-treatment period. Conclusions: This study demonstrates the long-term efficacy and safety of canagliflozin combined with insulin in Japanese patients

Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1, 995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction

Genetic and clinical landscape of breast cancers with germline BRCA1/2 variants

遺伝性乳癌の遺伝学的・臨床学的特徴を解明 --BRCA1/2 変異乳癌は両アレルの不活化の有無により異なった特徴を持つ--. 京都大学プレスリリース. 2020-10-26.The genetic and clinical characteristics of breast tumors with germline variants, including their association with biallelic inactivation through loss-of-heterozygosity (LOH) and second somatic mutations, remain elusive. We analyzed germline variants of 11 breast cancer susceptibility genes for 1, 995 Japanese breast cancer patients, and identified 101 (5.1%) pathogenic variants, including 62 BRCA2 and 15 BRCA1 mutations. Genetic analysis of 64 BRCA1/2-mutated tumors including TCGA dataset tumors, revealed an association of biallelic inactivation with more extensive deletions, copy neutral LOH, gain with LOH and younger onset. Strikingly, TP53 and RB1 mutations were frequently observed in BRCA1- (94%) and BRCA2- (9.7%) mutated tumors with biallelic inactivation. Inactivation of TP53 and RB1 together with BRCA1 and BRCA2, respectively, involved LOH of chromosomes 17 and 13. Notably, BRCA1/2 tumors without biallelic inactivation were indistinguishable from those without germline variants. Our study highlights the heterogeneity and unique clonal selection pattern in breast cancers with germline variants

マトリックス支援レーザー脱離イオン化質量分析装置による血清IgG Fc領域のN型糖鎖修飾プロファイリングにより非がんコントロールと乳がん患者を識別することができる

Final publication is available at http://dx.doi.org/10.1016/j.bbrc.2015.12.114 CreativeCommonsAttribution Non-Commercial No Derivatives License の記載が必要京都大学0048新制・課程博士博士(医学)甲第19924号医博第4144号新制||医||1017(附属図書館)33010京都大学大学院医学研究科医学専攻(主査)教授 武藤 学, 教授 野田 亮, 教授 小川 修学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA