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Tubular injury and interstitial fibrosis are the hallmarks of chronic kidney disease. While recent studies have verified that proximal tubular injury triggers interstitial fibrosis, the impact of fibrosis on tubular injury and regeneration remains poorly understood. We generated a novel mouse model expressing diphtheria toxin receptor on renal fibroblasts to allow for the selective disruption of renal fibroblast function. Administration of diphtheria toxin induced upregulation of the tubular injury marker Ngal and caused tubular proliferation in healthy kidneys, whereas administration of diphtheria toxin attenuated tubular regeneration in fibrotic kidneys. Microarray analysis revealed down-regulation of the retinol biosynthesis pathway in diphtheria toxin-treated kidneys. Healthy proximal tubules expressed retinaldehyde dehydrogenase 2 (RALDH2), a rate-limiting enzyme in retinoic acid biosynthesis. After injury, proximal tubules lost RALDH2 expression, whereas renal fibroblasts acquired strong expression of RALDH2 during the transition to myofibroblasts in several models of kidney injury. The retinoic acid receptor (RAR) RARγ was expressed in proximal tubules both with and without injury, and αB-crystallin, the product of an RAR target gene, was strongly expressed in proximal tubules after injury. Furthermore, BMS493, an inverse agonist of RARs, significantly attenuated tubular proliferation in vitro. In human biopsy tissue from patients with IgA nephropathy, detection of RALDH2 in the interstitium correlated with older age and lower kidney function. These results suggest a role of retinoic acid signaling and cross-talk between fibroblasts and tubular epithelial cells during tubular injury and regeneration, and may suggest a beneficial effect of fibrosis in the early response to injury., 腎障害における線維化の正の側面の発見 --線維化が腎臓を修復する--. 京都大学プレスリリース. 2019-01-18.

Evidence-based nursing (EBN) ensures the science of nursing practice, while the philosophical and ethical aspects of nursing practice are based on caring. Caring not only leads to the patient and their family’s healing but also to the nurse’s professional and personal growth since caring includes mutual approval and reciprocity. In the latter half of the chapter, we explain how to establish Dr. Jean Watson’s transpersonal caring using the following two events: ① case study: An expert nurse unintentionally says, “Your mother continues to be near and protect you,” to a crying daughter beside her mother’s deathbed; and ② our project: sanatorium’s nurses listen to Hansen’s disease survivors’ life review.

There have been suicides at the Hansen’s disease sanatoria in the past. What is the level of suffering that makes a person think of suicide? Through the analysis of a Hansen’s disease survivor’s life, we clarified that the nature of sufferings is spiritual pain that is brought by the “loss of autonomy and independence for carving out my life.” The patient was stuck in a negative cycle for about 20 years: All my dreams and hopes cut off → Despair → I want to die but cannot die easily → Lethargy∙Desperation∙Nihilistic → Momentary pleasure by gambling → I do not feel like living → I ask myself why am I alive → Self-criticism → Repeat again. Recovery from spiritual pain was achieved with time and by reflection. The bellwethers led to a turning point that helped to change the flow of his life. He also started using time effectively. Spiritual well-being of aging survivors has a trilaminar structure, comprising the following: (1) establishing the existential foundation of a sustained self; (2) living in the moment while contemplating the future; and (3) dovetailing within the society and transcending space and time. It indicates that they can achieve the developmental tasks related to old age, personal integration containing spirituality, and the wisdom and strength to get over difficulties. This study consists of the first report and the second report.

早大学位記番号:新8310

There have been suicides at the Hansen’s disease sanatoria in the past. What is the level of suffering that makes a person think of suicide? This study is divided into two reports. In the first report, we demonstrate the conceptual structure of spirituality and the relationship between quality of life (QOL) and spirituality, and the history of Hansen’s disease. In the second report, based on the first report, we will show spiritual pain and spiritual well-being experienced by Hansen’s disease survivors through an analysis of their life reviews. When our daily lives are calm and mundane, we do not notice spirituality. However, when we confront hardships of life, for example, diagnosed with leprosy and isolated in a sanatorium for lifetime, we notice spirituality as an existential distress. On the other hand, the development of individuality and imperturbability by overcoming hardship is spiritual well-being. Spirituality serves as the existential foundation for human existence and is important for the relationship with “something greater than self.” Spiritual well-being is one of multiple dimensions of QOL.

Historically, Hansen’s disease patients suffered from discrimination because their physical features changed due to the bacterium Mycobacterium leprae (M. leprae) and made them “ugly” in the eyes of society. Former Japanese governments saw them as a national disgrace and forced them to reside in leprosaria. Since the law requiring isolation continued after the silver bullet was developed, survivors could not leave the leprosaria and return to society. Currently, survivors’ average age is 82 and they live in 13 national sanatoriums. When they pass away, the history of Hansen’s disease in Japan will end, so we must record their experiences. We conducted qualitative and inductive studies with survivors. In this chapter, we reconstruct them from the perspective of bioethics and propose several theories surrounding them: (1) How former leprosaria and medical administrations in Japan threatened bioethical principles; (2) the wisdom of aging survivors, who lived through extreme situations, and what real restoration of their rights might look like; and (3) the ethical dilemmas of how we will care for the survivors—who have multiple severe sequelae—until they all pass away. Finally, we will introduce our ethical nursing practices in relation to caring and understanding via holism.