京都大学 / 新制・課程博士 / 博士(医学) / 甲第25199号 / 医博第5085号 / 新制||医||1072(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川口 義弥, 教授 藤田 恭之, 教授 妹尾 浩 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

In previous work, mouse lines were selected for resistance (R) or for susceptibility (S) to fescue toxicosis based upon reductions in post-weaning growth rate caused by an endophyte-infected diet. The first objective of the current experiment was to determine whether long term reproduction of S mice was more severely depressed than that of R mice by the toxic diet. The second objective was to quantify glutathione-S-epoxytransferase (GST) and uridine diphosphate glucuronosyl-transferase (UDPGT) activities in R and S dams form the experiment and to determine whether reproduction during continuous cohabitation and liver detoxification enzyme activities were correlated within line x diet groups. Effects of the toxic diet were detectable within the first litters produced. Reproduction was more seriously influenced by the toxic diet within the S line than within the R line when these measures were compared within four equal time phases. The effects of the toxic diet on reproduction were greatest early in the experiment; by the fourth time phase differences among line x diet groups, with the exception of litter weight, were not significant. Percentage differences in total reproduction were greater between S mice fed the non-toxic diet and S mice fed the toxic diet than those between the R mice fed the non-toxic and toxic diets. Averaged across diets, GST activities were higher in R mice, but UDPGT activities were not significant. Within R line mice, GST was correlated with three reproductive measures, but UDPGT activity was not correlated with reproduction within any line x diet group. / Master of Science

Introdução: A polipose nasal (PN) é considerada uma condição inflamatória crônica da mucosa da cavidade nasal e seios paranasais de etiologia não muito clara. Há poucos dados sobre alterações epiteliais em PN e sua relação com a ação dos radicais livres. Muitas doenças estão ligadas a danos causados por espécies reativas de oxigênio (ROS) e de nitrogênio (RNSS) e ocorrem de um desequilíbrio entre eles e antioxidantes, o que for maior atividade de espécies reativas, o que chamamos de estresse oxidativo. Objetivo: O objetivo principal deste estudo é avaliar o estresse oxidativo em pólipos removidos cirurgicamente em 3 grupos de pacientes com polipose nasal (com PN unicamente, PN associado à asma e PN associado à asma e intolerância ao ácido acetilsalicílico) a fim de elucidar possíveis diferenças no perfil redox nestes grupos. Material e Métodos: Cinquenta e nove pacientes com diagnóstico de polipose nasal foram divididos em três grupos clínicos: um grupo controle PN unicamente, um grupo asma (PN associado à asma) e um grupo Widal (PN associado à asma e intolerância ao ácido acetilsalicílico). Medição e Resultados Principais: Neste trabalho defesas enzimáticas (superóxido dismutase, consumo de peróxido de hidrogênio, glutationa peroxidase e glutationa S-transferase) e defesas não enzimáticas (glutationa total, nitritos e nitratos, vitamina C e E) foram analisados. Também foi realizada a medição de danos em lipídios (malondialdeído) e proteínas (carbonila). No grupo asma, o consumo de peróxido de hidrogênio, atividade da glutationa peroxidase, níveis de malondialdeído e vitamina E foram significativamente menores do que no grupo de controle. Também foi realizada a medição de danos em lipídios (malondialdeído) e proteínas (carbonila). No grupo Widal foram encontrados níveis significativamente maiores de glutationa e nitritos e nitratos em relação ao grupo controle. Não foram encontradas diferenças entre os grupos em relação ao nível de carbonila e glutationa, tamanho dos pólipos, atividades da superóxido dismutase e S-transferase. Conclusões: A classificação redox dos grupos de PN foi parcialmente alcançada. Os pólipos do grupo asma possuem alterações nas defesas enzimáticas relacionadas com o peróxido de hidrogênio e a peroxidação lipídica, enquanto pólipos do grupo Widal apresentaram alterações nos níveis de óxido nítrico e glutationa. / Introduction: Nasal polyposis (NP) is considered a chronic inflammatory condition of the mucosa of the nasal cavity and paranasal sinuses of etiology is not very clear. There are few data on epithelial changes in nasal polyposis and its relation to the action of free radicals. Many diseases are linked to damage caused by reactive oxygen species (ROS) and nitrogen (RNSs) and occur from an imbalance between them and antioxidants, whichever is greater activity of reactive species, what we call oxidative stress. Objective: The primary objective of this study is to evaluate oxidative stress in polyps surgically removed in 3 groups of patients with nasal polyposis, in order to elucidate possible differences in redox profile in these groups. Methods: Fifty nine patients diagnosed with nasal polyposis were divided into three groups: a control group, an asthma group (NP with asthma) and a Widal group (NP with asthma and aspirin intolerance) in which patients had an association of NP, asthma and aspirin intolerance. Measurement and main results: In this work enzymatic defenses (superoxide dismutase, hydrogen peroxide consumption, glutathione peroxidase and glutathione S-transferase) and non-enzymatic defenses (total glutathione, measurement of nitrites and nitrates, vitamin C and E) were analyzed. Also the measurement of damage in lipids (malondialdehyde) and proteins (carbonyl) was conducted. In the asthma group, hydrogen peroxide consumption, glutathione peroxidase activity, malondialdehyde, and vitamin E levels were significantly lower than in the control group. The Widal group showed significant higher glutathione levels, nitrite and nitrate levels than found in the control group. No differences were found among the groups regarding carbonyl level, polyp size, superoxide dismutase, and glutathione S-transferase activities. Conclusions: The redox classification of the groups of NP was partly achieved. Polyps of patients with asthma have changes in enzymatic defense pathways related to hydrogen peroxide and lipid peroxidation while polyps of patients with Widal triad present changes in nitric oxide and glutathione.

The study aimed to investigate the following: 1. Investigate a putative glutathione peroxidase gene (Glyma17g34110) within Glycine max by an in silico analysis and spatial expression. 2. Determine the effects of exogenously applied nitric oxide on the expression of Glyma17g34110. 3. Investigate the antioxidant mechanism with attention to Glyma17g34110,reactive oxygen species and cell death in the response to salt stress. 4. Establish whether Glyma17g34110 is a glutathione peroxidase or thioredoxindependent peroxidase gene. / Magister Scientiae - MSc

The production of reactive oxygen species (ROS) is prominent in all aerobic metabolisms including plants. For this reason, the redox homeostasis of the production and scavenging of these intermediates is imperative for growth, development and survival during unfavourable conditions. In this study, a putative glutathione peroxidase gene (Glyma17g34110) from Glycine max (soybean) was identified and analyzed. The successful characterisation of Glyma17g34110 provided evidence of it being a glutathione peroxidase using glutathione as its preferred electron donor and substrate. Furthermore, it is known that antioxidant enzymes such as GPX exist in various tissues, performing a diverse set of functions. By a bioinformatic analysis of Glyma17g34110 and its promoter region, it was indicated that Glyma17g34110 could be a putative chloroplast protein that could play an important role in photosynthesis.One of the major factors affecting plant growth and development worldwide is abiotic stresses such as salinity. In the presence of salinity the production of harmful ROS is increased, resulting in detrimental reactions with important biological features (DNA, protein and lipid membranes), leading to cell death. The analysis of Glyma17g34110 under salt stress revealed that it is a salt sensitive gene and thus, the down-regulation of Glyma17g34110 could be due to the lack of known defence and response cis-acting elements present in the promoter region. Furthermore, it was proven in previous studies that the application of exogenous nitric oxide (NO) increases the activity of antioxidant enzymes. In this thesis it was observed that the presence of exogenously applied NO increased the expression of Glyma17g34110 tremendously in all soybean tissues (leaves, roots and nodules) investigated.Studies have found numerous cis-acting elements to be NO responsive, however, none of these elements were found in the promoter region upstream of glyma17g34110. This suggests that novel cis-acting elements could be present in the promoter region of Glyma17g34110.Thus, increasing the expression of Glyma17g34110 during salinity in the presence of NO, as well as the identification of these novel cis-acting elements, could lead to the enhancement of the defence mechanisms against ROS, which could lead to increasing plant tolerance to stress. / >Magister Scientiae - MSc

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Missouri--Columbia, 1998. / Typescript. Vita. Includes bibliographical references (leaves: 138-170). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri-Columbia, 2005. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. "December 2005" Includes bibliographical references.

Introdução: A polipose nasal (PN) é considerada uma condição inflamatória crônica da mucosa da cavidade nasal e seios paranasais de etiologia não muito clara. Há poucos dados sobre alterações epiteliais em PN e sua relação com a ação dos radicais livres. Muitas doenças estão ligadas a danos causados por espécies reativas de oxigênio (ROS) e de nitrogênio (RNSS) e ocorrem de um desequilíbrio entre eles e antioxidantes, o que for maior atividade de espécies reativas, o que chamamos de estresse oxidativo. Objetivo: O objetivo principal deste estudo é avaliar o estresse oxidativo em pólipos removidos cirurgicamente em 3 grupos de pacientes com polipose nasal (com PN unicamente, PN associado à asma e PN associado à asma e intolerância ao ácido acetilsalicílico) a fim de elucidar possíveis diferenças no perfil redox nestes grupos. Material e Métodos: Cinquenta e nove pacientes com diagnóstico de polipose nasal foram divididos em três grupos clínicos: um grupo controle PN unicamente, um grupo asma (PN associado à asma) e um grupo Widal (PN associado à asma e intolerância ao ácido acetilsalicílico). Medição e Resultados Principais: Neste trabalho defesas enzimáticas (superóxido dismutase, consumo de peróxido de hidrogênio, glutationa peroxidase e glutationa S-transferase) e defesas não enzimáticas (glutationa total, nitritos e nitratos, vitamina C e E) foram analisados. Também foi realizada a medição de danos em lipídios (malondialdeído) e proteínas (carbonila). No grupo asma, o consumo de peróxido de hidrogênio, atividade da glutationa peroxidase, níveis de malondialdeído e vitamina E foram significativamente menores do que no grupo de controle. Também foi realizada a medição de danos em lipídios (malondialdeído) e proteínas (carbonila). No grupo Widal foram encontrados níveis significativamente maiores de glutationa e nitritos e nitratos em relação ao grupo controle. Não foram encontradas diferenças entre os grupos em relação ao nível de carbonila e glutationa, tamanho dos pólipos, atividades da superóxido dismutase e S-transferase. Conclusões: A classificação redox dos grupos de PN foi parcialmente alcançada. Os pólipos do grupo asma possuem alterações nas defesas enzimáticas relacionadas com o peróxido de hidrogênio e a peroxidação lipídica, enquanto pólipos do grupo Widal apresentaram alterações nos níveis de óxido nítrico e glutationa. / Introduction: Nasal polyposis (NP) is considered a chronic inflammatory condition of the mucosa of the nasal cavity and paranasal sinuses of etiology is not very clear. There are few data on epithelial changes in nasal polyposis and its relation to the action of free radicals. Many diseases are linked to damage caused by reactive oxygen species (ROS) and nitrogen (RNSs) and occur from an imbalance between them and antioxidants, whichever is greater activity of reactive species, what we call oxidative stress. Objective: The primary objective of this study is to evaluate oxidative stress in polyps surgically removed in 3 groups of patients with nasal polyposis, in order to elucidate possible differences in redox profile in these groups. Methods: Fifty nine patients diagnosed with nasal polyposis were divided into three groups: a control group, an asthma group (NP with asthma) and a Widal group (NP with asthma and aspirin intolerance) in which patients had an association of NP, asthma and aspirin intolerance. Measurement and main results: In this work enzymatic defenses (superoxide dismutase, hydrogen peroxide consumption, glutathione peroxidase and glutathione S-transferase) and non-enzymatic defenses (total glutathione, measurement of nitrites and nitrates, vitamin C and E) were analyzed. Also the measurement of damage in lipids (malondialdehyde) and proteins (carbonyl) was conducted. In the asthma group, hydrogen peroxide consumption, glutathione peroxidase activity, malondialdehyde, and vitamin E levels were significantly lower than in the control group. The Widal group showed significant higher glutathione levels, nitrite and nitrate levels than found in the control group. No differences were found among the groups regarding carbonyl level, polyp size, superoxide dismutase, and glutathione S-transferase activities. Conclusions: The redox classification of the groups of NP was partly achieved. Polyps of patients with asthma have changes in enzymatic defense pathways related to hydrogen peroxide and lipid peroxidation while polyps of patients with Widal triad present changes in nitric oxide and glutathione.

Introdução: A polipose nasal (PN) é considerada uma condição inflamatória crônica da mucosa da cavidade nasal e seios paranasais de etiologia não muito clara. Há poucos dados sobre alterações epiteliais em PN e sua relação com a ação dos radicais livres. Muitas doenças estão ligadas a danos causados por espécies reativas de oxigênio (ROS) e de nitrogênio (RNSS) e ocorrem de um desequilíbrio entre eles e antioxidantes, o que for maior atividade de espécies reativas, o que chamamos de estresse oxidativo. Objetivo: O objetivo principal deste estudo é avaliar o estresse oxidativo em pólipos removidos cirurgicamente em 3 grupos de pacientes com polipose nasal (com PN unicamente, PN associado à asma e PN associado à asma e intolerância ao ácido acetilsalicílico) a fim de elucidar possíveis diferenças no perfil redox nestes grupos. Material e Métodos: Cinquenta e nove pacientes com diagnóstico de polipose nasal foram divididos em três grupos clínicos: um grupo controle PN unicamente, um grupo asma (PN associado à asma) e um grupo Widal (PN associado à asma e intolerância ao ácido acetilsalicílico). Medição e Resultados Principais: Neste trabalho defesas enzimáticas (superóxido dismutase, consumo de peróxido de hidrogênio, glutationa peroxidase e glutationa S-transferase) e defesas não enzimáticas (glutationa total, nitritos e nitratos, vitamina C e E) foram analisados. Também foi realizada a medição de danos em lipídios (malondialdeído) e proteínas (carbonila). No grupo asma, o consumo de peróxido de hidrogênio, atividade da glutationa peroxidase, níveis de malondialdeído e vitamina E foram significativamente menores do que no grupo de controle. Também foi realizada a medição de danos em lipídios (malondialdeído) e proteínas (carbonila). No grupo Widal foram encontrados níveis significativamente maiores de glutationa e nitritos e nitratos em relação ao grupo controle. Não foram encontradas diferenças entre os grupos em relação ao nível de carbonila e glutationa, tamanho dos pólipos, atividades da superóxido dismutase e S-transferase. Conclusões: A classificação redox dos grupos de PN foi parcialmente alcançada. Os pólipos do grupo asma possuem alterações nas defesas enzimáticas relacionadas com o peróxido de hidrogênio e a peroxidação lipídica, enquanto pólipos do grupo Widal apresentaram alterações nos níveis de óxido nítrico e glutationa. / Introduction: Nasal polyposis (NP) is considered a chronic inflammatory condition of the mucosa of the nasal cavity and paranasal sinuses of etiology is not very clear. There are few data on epithelial changes in nasal polyposis and its relation to the action of free radicals. Many diseases are linked to damage caused by reactive oxygen species (ROS) and nitrogen (RNSs) and occur from an imbalance between them and antioxidants, whichever is greater activity of reactive species, what we call oxidative stress. Objective: The primary objective of this study is to evaluate oxidative stress in polyps surgically removed in 3 groups of patients with nasal polyposis, in order to elucidate possible differences in redox profile in these groups. Methods: Fifty nine patients diagnosed with nasal polyposis were divided into three groups: a control group, an asthma group (NP with asthma) and a Widal group (NP with asthma and aspirin intolerance) in which patients had an association of NP, asthma and aspirin intolerance. Measurement and main results: In this work enzymatic defenses (superoxide dismutase, hydrogen peroxide consumption, glutathione peroxidase and glutathione S-transferase) and non-enzymatic defenses (total glutathione, measurement of nitrites and nitrates, vitamin C and E) were analyzed. Also the measurement of damage in lipids (malondialdehyde) and proteins (carbonyl) was conducted. In the asthma group, hydrogen peroxide consumption, glutathione peroxidase activity, malondialdehyde, and vitamin E levels were significantly lower than in the control group. The Widal group showed significant higher glutathione levels, nitrite and nitrate levels than found in the control group. No differences were found among the groups regarding carbonyl level, polyp size, superoxide dismutase, and glutathione S-transferase activities. Conclusions: The redox classification of the groups of NP was partly achieved. Polyps of patients with asthma have changes in enzymatic defense pathways related to hydrogen peroxide and lipid peroxidation while polyps of patients with Widal triad present changes in nitric oxide and glutathione.