• 2015-2024close
• Research data close
• Other research products close
• JP close
• Kagoshima University Repository close
• Digital Humanities and Cultural Her... close

鹿児島大学 博士(医学) Doctor of Philosophy in Medical Science 博士論文全文, 博士論文要旨, 最終試験結果の要旨, 論文審査の要旨 Nursing records are an account of patient condition and treatment during their hospital stay. In this study, we developed a system that can automatically analyze nursing records to predict the occurrence of diseases and incidents (e.g., falls). Text vectorization was performed for nursing records and compared with past case data on aspiration pneumonia, to develop an onset prediction system. Nursing records for a patient group that developed aspiration pneumonia during hospitalization and a non-onset control group were randomly assigned to definitive diagnostic (for learning), preliminary survey, and test datasets. Data from the preliminary survey were used to adjust parameters and influencing factors. The final verification used the test data and revealed the highest compatibility to predict the onset of aspiration pneumonia (sensitivity = 90.9%, specificity = 60.3%) with the parameter values of size = 80 (number of dimensions of the sentence vector), window = 13 (number of words before and after the learned word), and min_count = 2 (threshold of wordcount for word to be included). This method represents the foundation for a discovery/warning system using machine-based automated monitoring to predict the onset of diseases and prevent adverse incidents such as falls. Shotaro Komaki, Fuminori Muranaga, Yumiko Uto, Takashi Iwaanakuchi, Ichiro Kumamoto Supporting the Early Detection of Disease Onset and Change Using Document Vector Analysis of Nursing Observation Records Evaluation & the Health Professions 2021 https://doi.org/10.1177/01632787211014270 doctoral thesis

The major vault protein (MVP) is the main constituent of the vault ribonucleoprotein particle. Although the role in multidrug resistance has been suggested, the physiological function of vaults remains unclear. It has been reported that MVP levels were elevated after treatment with the DNA-damaging agents such as adriamycin (ADR). The aim of this study was to investigate molecular basis for the induction of MVP by ADM, and to investigate the potential role of MVP in drug resistance. Expression levels of both MVP protein and MVP mRNA were increased by ADM. ADM could also enhance MVP promoter activity. Introduction of siRNA against Sp-1 in SW620 cells attenuated the expression of MVP induced by ADM. Down-regulation of MVP expression by MVP RNAi in SW620 cells increased the sensitivity of the cells to ADM. Furthermore, ADM enhanced the activation of caspase 3 and caspase 8 in the MVP knock-down cells, but not in control cells. Our data demonstrate that exposure of cancer cells to DNA-damaging agents induces MVP that might have an important role in the resistance to chemotherapeutic agents. VaultはRNAタンパク質複合体で、その発現量と多剤耐性癌細胞における治療抵抗性との相関が指摘されているが、vault自体の機能については未だ不明な点が多い。これまでに、vaultの構成成分であるmajor vault protein (MVP) は、DNA傷害性抗癌剤により発現が亢進することが報告されている。本研究は、抗癌剤処理下でのMVPの発現亢進機序およびその機能について検討を行うことを目的とした。ヒト大腸癌細胞株SW-620におけるMVP mRNAとMVPタンパク質の発現はアドリアマイシン（ADM）により誘導された。また、ADMにより、MVPプロモーター活性が約2倍上昇した。さらに、ADMによって誘導されるMVPの発現はSp1をknockdownすることにより抑制された。MVPが抗癌剤耐性に関与することが考えられたので、knockdown株を作製し、抗癌剤感受性試験を行ったところ、MVP発現株はMVP knockdown株に比べ、ADMに耐性を示した。さらに、ADM処理下におけるCaspase 8およびCaspase 3の活性化ついて解析したところ、MVP発現株では、MVP knockdown 株に比べ、ADMで誘導されるCaspase 8およびCaspase 3の活性化が抑制されていた。癌細胞はMVPの発現を亢進することにより、抗癌剤によって誘導されるアポトーシスを回避し、vaultが癌の抗癌剤耐性化に重要な役割を担っている可能性が示唆された。 2009-2011年度科学研究費助成事業(科学研究費補助金(基盤研究(C)))研究成果報告書　課題番号：21590168　研究代表者：山田勝士 (鹿児島大学大学院医歯学総合研究科客員研究員)