Abuse is associated with higher depressive symptoms (DS) and coronary heart disease risk (CHD), lower health-related quality of life (HRQOL), and dysregulated levels of cortisol and norepinephrine (NE). In HIV+ women, abuse relates to higher viral load (VL), lower CD4 count, and nonadherence to highly active antiretroviral therapy (HAART). Resilience (adaptive functioning following trauma) and positive self-esteem (PSE) were hypothesized to buffer the impact of abuse and predict better health outcomes. Three studies tested these hypotheses using self-report measures (for abuse, resilience, DS, HRQOL, and HAART use and adherence), autobiographical narratives (for PSE), Framingham Risk Score (for CHD risk), and blood and urinary specimens for cortisol, NE, and HIV disease markers (VL and CD4 count). Study 1 included 138 HIV+ and 64 HIV- women (87% African-American), and investigated the relationships between childhood sexual abuse (CSA), DS, and HRQOL and whether resilience moderated the relationships between CSA and outcomes. Consistent with the hypothesis, multiple regressions indicated that higher resilience related to lower DS and higher HRQOL across both HIV+ and HIV-women, and CSA related to higher DS only for women scoring low in resilience. Study 2 examined how resilience moderated the relationships between abuse history and HAART adherence, VL, and CD4 count in 138 HIV+ women. As predicted, multiple regressions revealed that resilience related to having undetectable VL. Sexual and multiple abuse histories related to lower HAART adherence only for women scoring low in resilience. Study 3 with 53 HIV+ women investigated the relationships among resilience, PSE, abuse histories, NE, cortisol and CHD risk. In partial support of hypotheses, partial correlations showed that higher resilience related to lower cortisol; higher PSE related to lower NE; higher NE/cortisol ratio related to higher CHD risk; histories of abuse related to higher CHD risk, and lower cortisol related to higher CHD risk. The findings suggest that resilience and PSE relate to better health outcomes for HIV+ and HIV- women, and levels of stress hormones in HIV+ women are related in complex ways to abuse, resilience, PSE, and CHD risk. Promoting resilience and PSE may help HIV+ and HIV- women achieve better health outcomes.

The physiological responses to stressor exposure can be broadly grouped into the organismal and the cellular stress responses. The organismal stress response involves the release of hormones into general circulation, while the cellular stress response involves the synthesis of proteins, the most important being the heat shock proteins (HSPs), which play a role in maintaining protein homeostasis. Elevated HSP70 expression in response to stressors has been demonstrated in trout (Oncorhynchus mykiss) red blood cells (RBCs). The ease of repeated sampling of blood suggests the possibility of using this tissue as a non-lethal marker of cellular stress in fish. This study tested the hypothesis that stressor exposure will elevate HSP70 expression in trout RBCs and the role of stress hormones in mediating this response. Acute heat shock exposure (+12oC) significantly elevated plasma cortisol, glucose and lactate levels in heat shocked fish over 24 h. A tissue-specific response was seen in HSP70 expression in liver, brain, gill and RBCs. To enable measurement of RBC HSP70 concentrations, an enzyme-linked immunosorbent assay (ELISA) was developed using a commercially available rabbit anti-salmon HSP70 and a recombinant chinook salmon (Oncorhynchus tshawytscha) HSP70. To determine effects of chronic exposure, two studies were conducted exposing trout to either cadmium (0, 0.75 or 2.0 µg/L over 28 d) or municipal wastewater effluent (0, 20 or 90% over 14 d). However, neither exposure elicited a significant HSP70 response. Effects of stress hormones on RBC HSP70 levels were tested by exposing cells in vitro to either cortisol (10 and 100 ng/mL) or epinephrine (10 nM) with or without heat shock. Heat shock elevated HSP70 content in trout RBCs but no modulation by stress hormones was seen. It was shown for the first time that RBCs release HSP70 content into the medium in response to an acute heat shock and this release is attenuated by stress hormones. Overall, HSP70 levels in RBCs have the potential to be a reliable non-lethal marker of acute cellular stress effects in fish. The release of HSP70 from RBCs leads to the hypothesis that HSP70 may also have an extracellular role in fish, and warrants further study.

The physiological responses to stressor exposure can be broadly grouped into the organismal and the cellular stress responses. The organismal stress response involves the release of hormones into general circulation, while the cellular stress response involves the synthesis of proteins, the most important being the heat shock proteins (HSPs), which play a role in maintaining protein homeostasis. Elevated HSP70 expression in response to stressors has been demonstrated in trout (Oncorhynchus mykiss) red blood cells (RBCs). The ease of repeated sampling of blood suggests the possibility of using this tissue as a non-lethal marker of cellular stress in fish. This study tested the hypothesis that stressor exposure will elevate HSP70 expression in trout RBCs and the role of stress hormones in mediating this response. Acute heat shock exposure (+12oC) significantly elevated plasma cortisol, glucose and lactate levels in heat shocked fish over 24 h. A tissue-specific response was seen in HSP70 expression in liver, brain, gill and RBCs. To enable measurement of RBC HSP70 concentrations, an enzyme-linked immunosorbent assay (ELISA) was developed using a commercially available rabbit anti-salmon HSP70 and a recombinant chinook salmon (Oncorhynchus tshawytscha) HSP70. To determine effects of chronic exposure, two studies were conducted exposing trout to either cadmium (0, 0.75 or 2.0 µg/L over 28 d) or municipal wastewater effluent (0, 20 or 90% over 14 d). However, neither exposure elicited a significant HSP70 response. Effects of stress hormones on RBC HSP70 levels were tested by exposing cells in vitro to either cortisol (10 and 100 ng/mL) or epinephrine (10 nM) with or without heat shock. Heat shock elevated HSP70 content in trout RBCs but no modulation by stress hormones was seen. It was shown for the first time that RBCs release HSP70 content into the medium in response to an acute heat shock and this release is attenuated by stress hormones. Overall, HSP70 levels in RBCs have the potential to be a reliable non-lethal marker of acute cellular stress effects in fish. The release of HSP70 from RBCs leads to the hypothesis that HSP70 may also have an extracellular role in fish, and warrants further study.

The present study considers the versatile role of adipokinetic hormones (AKHs). Using the firebug Pyrrhocoris apterus as a model insect, the hypothesis that AKHs mediate stress response mechanisms was explored. The outcome indicated that there is a positive feedback regulation between an oxidative stressor action and the level of AKH in insect body, and that AKHs might be involved in the activation of antioxidant protection mechanism. Further results revealed a functional homology between AKH and the mammalian hormone glucagon. The possible effects of glucagon on mobilisation of energy reserves and on elicitation of an antioxidant response to oxidative stress were investigated. As a result, glucagon-immunoreactive material was detected for the first time in the firebug central nervous system and gut. Antioxidant mechanisms are elicited after glucagon treatment but it did not involve mobilization of energy reserves or AKH level changes. As a complement, the existence of a feedback between juvenile hormone and AKH was investigated by topical application of the juvenile hormone analogue methoprene, which influenced the release of AKH from the central nervous system into the haemolymph and induced a partial reduction of lipid content in haemolymph.

付記する学位プログラム名: 霊長類学・ワイルドライフサイエンス・リーディング大学院 / 京都大学 / 0048 / 新制・課程博士 / 博士(理学) / 甲第20964号 / 理博第4416号 / 新制||理||1634(附属図書館) / 京都大学大学院理学研究科生物科学専攻 / (主査)准教授 Michael Alan Huffman, 准教授 足立 幾磨, 教授 友永 雅己 / 学位規則第4条第1項該当 / Doctor of Science / Kyoto University / DGAM

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Prolonged strenuous exercise affects the circulating numbers and functions of immune cells. These effects are thought to be largely mediated by the actions of elevated circulating stress hormones and alterations in regulatory cytokines. Although the effects of a single acute bout of exercise on immune system function are quite well established, it is still not clear how time of day and repeated bouts of prolonged exercise on the same day influence immune function. It is of particular interest to understand the effects of nutritional supplementation on immunoendocrine responses. Therefore, the aims of the studies described in this thesis were to determine the effects of two bouts of prolonged cycling and carbohydrate supplementation on immunoendocrine responses. The saliva collection study showed that the use of a swab for collecting saliva is not an ideal method because it affects the results of saliva composition (Chapter 4). The comparison of the effects of exercise at different times of day on immunoendocrine responses showed that a single bout of prolonged exercise performed in the afternoon induces a larger perturbation in the redistribution of leukocytes into the circulation than an identical bout of morning exercise, which maybe due to higher hypothalamic-pituitaryadrenal (HP A) activation and. circadian rhythms. However, in terms of oral mucosal immunity, performing prolonged cycling at different times of day does not differently affect the salivary responses. The second compared with the first of two bouts of prolonged exercise on the same day induces a greater HP A activation, a larger leukocyte trafficking into the circulation, a decreased neutrophil degranulation response to lipopolysaccharide (LPS) on per cell basis and a lower saliva flow rate, but does not increase plasma interleukin-6 (IL-6), or change saliva immunoglobulin A (slgA) secretion rate (Chapter 5). Furthermore, carbohydrate (CHO) ingestion during any period of two bouts of prolonged exercise shows limited beneficial effect in blunting these higher responses in the second exercise bout compared with the first identical exercise bout on the same day (Chapter 6, 7 and 8). The determination of the effects of CHO ingestion on exercise-induced immunoendocrine responses showed that when two bouts of exercise are performed on the same day, the greater benefit in terms of circulating immunoendocrine responses is obtained by feeding CHO at the earliest opportunity (Chapter 6, 7 and 8). A 3-h interval is insufficient for recovery of leukocyte mobilisation and neutrophil function from the impact of previous exercise whether subjects consumed placebo or CHO during exercise or recovery (Chapter 5, 6, 7 and 8). However, an 18-h interval is sufficient for full recovery of all immunoendocrine variables that were measured in this thesis from the impact of two bouts of prolonged exercise (Chapter 8).

<p>This thesis presents hormonal, emotional, physical and visual status changes in female fibromyalgia (FMS) patients after treatment with the Creative Art therapy; dance/movement therapy, compared to controls. FMS is a syndrome of chronic pain involving musculoskeletal aches, stiffness and pain where perturbations in the stress-axis and high scores on somatic anxiety and muscular tension also have been found. The study comprises thirty-six female FMS patients divided in treatment- and control group. Serum concentrations of the hormones prolactin, dehydroepiandrosterone sulphate (DHEA-S), cortisol and neuropeptide Y (NPY) in plasma and cortisol in saliva were analysed. Different verbal self-rating scales concerning well-being, pain, personality and life events among other things have been used. Assessments of the condition of the FMS patients affected by video-viewing were evaluated together with interviews about the self-perception phenomenon of video viewing (a phenomenological hermeneutic method). </p><p>The results of the study show that six months of dance/movement therapy appears sufficient to improve both psychological and physical function, as indicated by the visual analyses. The video interpretation technique (VIT) and self-figure drawings captured treatment effects that were not evident from verbal scales or reflected in hormone levels. The biological markers probably need a longer treatment period to activate the HPA axis and its inter-related hormones and peptides. </p><p>The use of different assessment techniques most likely has affected the treatment outcome. Difficulties perceiving information through verbal/cognitive modalities as well as alexithymia are factors discussed. The VIT may be useful for early identification of maladaptive movement patterns and as a mirror of facial and bodily expressions of emotions. In conclusion, this study indicates that both the dance/movement therapy and the VIT have had great influence on the FMS patient’s well-being, self-perception and perception of pain. </p>

The neurological wake-up test, NWT, is a clinical monitoring tool that can be used to evaluate the level of consciousness in patients with traumatic brain injury (TBI) and subarachnoid haemorrhage (SAH) during neurocritical care (NCC). Since patients with severe TBI or SAH are often treated with mechanical ventilation and sedation, the NWT requires that the continuous sedation is interrupted. However, interruption of continuous sedation may induce a stress response and the use of the NWT in NCC is controversial. The effects of the NWT on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) were evaluated in 21 patients with TBI or SAH. Compared to baseline when the patients were sedated with continuous propofol sedation, the NWT resulted in increased ICP and CPP (p&lt;0.05). Next, the effects of the NWT on the stress hormones adrenocorticotrophic hormone (ACTH), cortisol, epinephrine and norepinephrine were evaluated in 24 patients. Compared to baseline, the NWT caused a mild stress response resulting in increased levels of all evaluated stress hormones (p&lt;0.05). To compare the use of routine NCC monitoring tools, the choice of sedation and analgesia and the frequency of NWT in Scandinavian NCC units, a questionnaire was used. The results showed that all 16 Scandinavian NCC units routinely use ICP and CPP monitoring and propofol and midazolam were primary choices for patient sedation in an equal number of NCC units. In 2009, the NWT was not routinely used in eight NCC units whereas others used the test up to six times daily. Finally, intracerebral microdialysis (MD), brain tissue oxygenation (PbtiO2) and jugular bulb oxygenation (SjvO2) were used in 17 TBI patients to evaluate the effect of the NWT procedure on focal neurochemistry and cerebral oxygenation. The NWT did not negatively alter interstitial markers of energy metabolism or cerebral oxygenation. In conclusion, the NWT induced a mild stress response in patients with TBI or SAH that did not result in a detectable, significant secondary insult to the injured brain. These results suggest that the NWT may safely be used as a clinical monitoring tool in the NCC of severe TBI and SAH in a majority of patients.

This thesis presents hormonal, emotional, physical and visual status changes in female fibromyalgia (FMS) patients after treatment with the Creative Art therapy; dance/movement therapy, compared to controls. FMS is a syndrome of chronic pain involving musculoskeletal aches, stiffness and pain where perturbations in the stress-axis and high scores on somatic anxiety and muscular tension also have been found. The study comprises thirty-six female FMS patients divided in treatment- and control group. Serum concentrations of the hormones prolactin, dehydroepiandrosterone sulphate (DHEA-S), cortisol and neuropeptide Y (NPY) in plasma and cortisol in saliva were analysed. Different verbal self-rating scales concerning well-being, pain, personality and life events among other things have been used. Assessments of the condition of the FMS patients affected by video-viewing were evaluated together with interviews about the self-perception phenomenon of video viewing (a phenomenological hermeneutic method). The results of the study show that six months of dance/movement therapy appears sufficient to improve both psychological and physical function, as indicated by the visual analyses. The video interpretation technique (VIT) and self-figure drawings captured treatment effects that were not evident from verbal scales or reflected in hormone levels. The biological markers probably need a longer treatment period to activate the HPA axis and its inter-related hormones and peptides. The use of different assessment techniques most likely has affected the treatment outcome. Difficulties perceiving information through verbal/cognitive modalities as well as alexithymia are factors discussed. The VIT may be useful for early identification of maladaptive movement patterns and as a mirror of facial and bodily expressions of emotions. In conclusion, this study indicates that both the dance/movement therapy and the VIT have had great influence on the FMS patient’s well-being, self-perception and perception of pain.