PhD

thesisThe mechanisms of natural resistance to neoplastic disease are unknown. The hypothesis has been established that in a system involving white mice (albino Mus musculus) and Ehrlich ascites tumor (EAT) a mechanism of normal resistance exists against the establishment of the neoplasm. The concept of natural resistance to establishment of neoplasia in the models employed is derived from experiments yielding dose-response relationships; that is, reproducible LD50 values can be determined by different routes of challenge with counted numbers of viable cells. The LD50 values differed markedly among the intraperitoneal (ip), subcutaneous (sc), and intravenous (iv) routes indicating differences in the degree of resistance by these routes. Furthermore, the degree of resistance could be significantly increased by iv immunization with a sublethal dose of viable tumor cells. An avenue of approach that deserves exploration is the potential role of cellular defenses in such natural resistance. Although much work has been done with respect to humoral defenses, relatively few data exist concerning cellular defenses and neoplastic diseases. The role played in living cells in the induction of increased resistance was investigated. By Whole body x-irradiation at varying intervals of time after iv injection with EAT cells did not result in increased incidence of lung tumors in mice. The experimental results obtained did not support the hypothesis that dormant tumor cells mediate some mechanism by which living cells induce increased resistance to subsequent tumor challenge. Indirect evidence for the existence of cellular defenses in natural resistance was exhibited by x-irradiated animals. Whole body x-irradiation (300 r, LD0) of normal mice 4 days prior to ip or sc challenge with EAT cells resulted in depressed resistance compared to nonirradiated animals. Irradiation of immunized mice, to the same extent as normals, did not depress resistance to challenge with EAT cell, indicating the role of humoral defenses in induced resistance. There was no evidence of agglutination, phagocytosis or tumor cell destruction in the peritoneal fluid from either immune or normal animals. In contrast, macrophages from immunized animals adhered to EAT cells when incubated in vitro at 37? C. This effect could not be demonstrated with S-37 tumor cells. Rabbit antibody or guinea pig complement significantly reduced tumor cell viability when incubated in vitro prior to ip inoculation into normal mice. Under similar condition rabbit antibody plus complement completely neutralized EAT cells. Neither homologous serum nor lysates of macrophages demonstrated any capacity to neutralize EAT cells. No difference in mortality ratios were observed in mice challenged ip with a mixture of normal or immune mouse peritoneal macrophages and EAT cells. The ratio employed was 4 macrophages to 1 tumor cell and the time incubation prior to challenge was 2.5 and 5 hours. Macrophages from immunized or normal mice incubated with tumor cells in the ratio 1200 macrophages to 1 tumor cell and subsequently injected into normal mice showed an increase in survival time over animals receiving EAT cells alone. No difference was noted, however, between the effects of normal and immune macrophages. Immune lymph cells extended the survival time of mice receiving a mixture of lymph node cell and EAT cells via the sc route. This effect could not be demonstrated via the ip route. Ehrlich ascites tumor cells were injected ip or sc into mice acclimatized to low ambient temperatures following challenge. The viability of EAT cells was not affected, and acclimatized mice showed significant delays in mortality compared to the control animals kept at room temperature; however, the final mortalities were similar in the acclimatized and room temperature exposed mice. Mice kept at low temperature and challenged with S-37 tumor cells showed a significant difference in the mortality and survival time with challenged via the sc route

Dysregulation of Iron Metabolism in Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis

Dysregulation of iron metabolism has been observed in patients with neurodegenerative diseases (NDs). Utilization of several importers and exporters for iron transport in brain cells helps maintain iron homeostasis. Dysregulation of iron homeostasis leads to the production of neurotoxic substances and reactive oxygen species, resulting in iron-induced oxidative stress. In Alzheimer's disease (AD) and Parkinson's disease (PD), circumstantial evidence has shown that dysregulation of brain iron homeostasis leads to abnormal iron accumulation. Several genetic studies have revealed mutations in genes associated with increased iron uptake, increased oxidative stress, and an altered inflammatory response in amyotrophic lateral sclerosis (ALS). Here, we review the recent findings on brain iron metabolism in common NDs, such as AD, PD, and ALS. We also summarize the conventional and novel types of iron chelators, which can successfully decrease excess iron accumulation in brain lesions. For example, iron-chelating drugs have neuroprotective effects, preventing neural apoptosis, and activate cellular protective pathways against oxidative stress. Glial cells also protect neurons by secreting antioxidants and antiapoptotic substances. These new findings of experimental and clinical studies may provide a scientific foundation for advances in drug development for NDs

Supplemental Cellular Protection by a Carotenoid Extends Lifespan via Ins/IGF-1 Signaling in Caenorhabditis elegans

Astaxanthin (AX), which is produced by some marine animals, is a type of carotenoid that has antioxidative properties. In this study, we initially examined the effects of AX on the aging of a model organism C. elegans that has the conserved intracellular pathways related to mammalian longevity. The continuous treatments with AX (0.1 to 1 mM) from both the prereproductive and young adult stages extended the mean lifespans by about 16–30% in the wild-type and long-lived mutant age-1 of C. elegans. In contrast, the AX-dependent lifespan extension was not observed even in a daf-16 null mutant. Especially, the expression of genes encoding superoxide dismutases and catalases increased in two weeks after hatching, and the DAF-16 protein was translocated to the nucleus in the AX-exposed wild type. These results suggest that AX protects the cell organelle mitochondria and nucleus of the nematode, resulting in a lifespan extension via an Ins/IGF-1 signaling pathway during normal aging, at least in part

Improving a Course Based on the LTD Teaching Mode : Practice in First Year Experience Course at a Nursing School

本実践報告では，看護専門学校の初年次教育科目を対象に試みた，LTD 授業モデルに依拠した授業改善について報告する。参加学生は122名であり，30の小グループにランダムに割り当てられた。授業科目は基礎段階，習熟段階，応用段階で構成されていた。基礎段階では協同学習の基本的な考え方と技法を教えた。習熟段階では基礎段階で獲得した学習技法の熟達を意図し，論理的な言語技術と絵図の読解法を指導した。応用段階では，前2段階の学習内容を活用した問題解決型学習を実践した。授業を評価するたために協同認識尺度とディスカッション= スキル尺度，授業記録紙および最終レポートを用いた。これらの資料を検討した結果，授業全体として期待する方向の成果を得ることができた。特に，基礎段階では協同を基盤とした学びの姿勢と技法の獲得が確認できた。また，基礎段階と習熟段階での学びが応用段階での学びを促す可能性が示唆された。This case report describes an attempt to improve a first-year experience course at a nursing school using the LTD teaching model. The 122 participating students were randomly assigned to 30 small groups. The course consisted of a foundation stage, a proficiency stage, and an application stage. In the foundation stage, the students were taught the basic concepts and techniques of cooperative learning. In the proficiency stage, students were taught logical language skills and pictorial reading comprehension skills with the intention of mastering the learning techniques acquired in the foundation stage. In the application stage, problem-solving learning was practiced using the learning content of the previous two stages. To evaluate the lessons, we used the Cooperative Awareness Scale, the Discussion Skills Scale, class notes, and the final report. The results showed that the class as a whole achieved the expected results. In particular, the acquisition of cooperative learning attitudes and techniques was confirmed. It was also suggested that learning in the foundation and proficiency stages could promote learning in the application stage