Blood vessel injury was found to release intracellular pools of protein D-aspartyl/L-isoaspartyl carboxyl methyltransferase (PIMT) into the extracellular milieu, where it became trapped. Trapped PIMT was able to utilize radiolabeled S-adenosyl-L-methionine (AdoMet) introduced into the circulation to methylate blood vessel proteins containing altered aspartyl residues specifically at the site of injury. In vitro studies more fully characterized this endogenous PIMT activity in thoracic aorta and inferior vena cava. At least 50% of the PIMT activity released during injury, was resistant to non-ionic detergent extraction, suggesting that the enzyme activity can become trapped within or behind the extracellular matrix (ECM). Analysis of inferior vena cava, found that 90% of the altered aspartyl residues in blood vessels are inaccessible to methylation by intracellular PIMT under physiological conditions. Subfractionation of inferior vena cava on the basis of solubility found that at least 40% of the altered aspartyl containing proteins in blood vessels are insoluble in non-ionic detergent containing buffers and are highly resistant to extraction by protein denaturants. Analysis of peptides revealed that the majority of the altered aspartyl groups in blood vessels are located extracellularly. Digestion of these extracellular matrix proteins with cyanogen bromide (CNBr), followed by methylation with (PIMT), found that about 60% of the altered aspartyl residues in the ECM are solubilized by this treatment. The presence of hydroxyproline in amino acid hydrosolates of this fraction and acidic pH gel electrophoresis of methylated peptides, allowed the identification of collagen as the major PIMT substrate in the CNBr-soluble material. CNBr peptides derived from both type I and type III collagen were found to methylated. It is estimated that one centimeter of blood vessel contains on the order of 5 x 10����� altered aspartyl residues involving 1% to 5% of the total extracellular protein. / Graduation date: 1997

This investigation was conducted to determine the effectiveness of Personal Achievement Skills (PAS), a structured group psychotherapy approach, on the productivity, social functioning, self-esteem, locus of control, and life satisfaction of individuals with traumatic spinal cord injury. Subjects for the study were recruited through disability advocacy organizations, state disability service agencies, and local colleges, universities, and rehabilitation centers. The research design utilized was a randomized, pretest, posttest control group design with 15 experimental and 14 control group subjects. A behavioral Activity Questionnaire was specially designed for the study to assess productivity. It included activities such as employment, educational pursuits, social and community involvement, volunteer work, and family responsibilities. Other measures included: (a) the Affiliative Tendency Scale, (b) the Rosenberg Self-Esteem Scale, (c) the Nowicki-Strickland Locus of Control Scale, and (d) the Life Satisfaction Index. The results of the investigation indicated that PAS group participants, in comparison to the control group, improved significantly on the self-esteem measure. No such improvement was found on the other measures in the study. With regard to the self-esteem finding, male subjects responded more favorably to the PAS approach than female subjects. The issues and concerns of using the PAS approach with individuals with physical limitations were discussed along with recommendations and modifications for future research. / Graduation date: 1992

Thesis (M.D.)--Friedrich-Wilhelms-Universität zu Berlin, 1898. / "Inaugural-Dissertation, welche zur Erlangung der Doctorwürde in der Medicin und Chirurgie mit zustimmung der medicinischen Facultät der Friedrich-Wilhelms-Universität zu Berlin am 15. Juli 1898." Includes bibliographical references.

Thesis (M.S.), Biology--University of Central Oklahoma, 2009. / Includes bibliographical references (leaves 53-57).

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Community Medicine / Master / Master of Public Health

Liver is one of the most important organs in the body that maintains the homeostasis of metabolism, immunity, detoxification and hematopoiesis. A large number of acute and chronic intoxications and diseases can influence the normal functions of the liver, leading to irreversible liver damage and even cancer. Currently, applying herbs or herbal derivatives in the prevention and therapy of acute and chronic liver injury receive numerous attentions since they hold great potentials as food supplements in the treatment strategy of liver injuries. There were two major hypotheses of this current work namely: a)In CCl4-inducedacute liver injury animal model, whether pre-treatment with garlic derived S-allylmercaptocysteine (SAMC)or Wolfberry derived Lycium barbarum polysaccharides (LBP)could reduce liver injury, oxidative stress and inflammation partly through a NF-κB-dependent pathway. SAMC or LBP could also promote liver regeneration after acute damage. b)In non-alcoholic steatohepatitis (NASH)-induced chronic liver injury animal model, whether administration of SAMC or LBP along with high-fat diet induction could attenuate liver injury, lipid metabolism dysfunction, fibrosis, oxidative stress, inflammation, apoptosis and transcription factors activities in the liver. In this study, SAMC and LBP were applied in a carbon tetrachloride (CCl4) induced mice acute liver injury model and a high-fat diet induced non-alcoholic steatohepatitis model. In the acute model, an eight-hour CCl4treatment induced severe acute liver injury. Pre-treatment with SAMC or LBP (1) attenuated hepatic histological injury; (2) reduced serum ALT level; (3) ameliorated oxidative stress; (4) reduced expression of inflammatory mediators and chemokines; (5) promoted liver regeneration; and (6) decreased NF-κB activity. Vehicle-treated SAMC or LBP did not exhibit obvious adverse effects on healthy mice. In the chronic NASH model, when compared with control rats, NASH rats showed typical clinical features of human NASH patients, including increased liver injury, lipid content, oxidative stress, inflammation, and apoptosis. In comparison, SAMC or LBP co-treated NASH rats showed (1) reduced fat accumulation, cellular necrosis, collagen formation, as well as reduced serum ALT and free fatty acids levels; (2) restored insulin resistance related kinase phosphorylation status which had been altered during NASH; (3) reduced pro-fibrogenic factors; (4) restored antioxidant enzymes, as well as attenuated end-products of lipid peroxidation and NO production through a cytochrome P450 2E1-dependent pathway; (5) reduced hepatic pro-inflammatory mediators and chemokines production; (6) diminished activities of nuclear transcription factors (NF-κB and AP-1); and (7) ameliorated hepatic cellular apoptosis through a p53-dependentpathwaywhich was under the regulation of LKB1/AMPK axis and PI3K/Akt axis. In conclusion, our data demonstrated that SAMC or LBP consumption protects the liver from acute injury caused by CCl4and chronic damages caused by a high-fat diet. These effects were mainly mediated by the amelioration of hepatic oxidative stress, inflammation, and cell death. In the NASH model, SAMC or LBP also improved hepatic lipid metabolism, fibrosis, and apoptosis. Therefore, the present study proposed that both garlic and Wolfberry, which are novel hepatoprotective herbal products, can be taken as part of the daily dietary supplements in the prevention of acute and chronic liver injury. / published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Hypothermia is commonly found in injured victims who suffer from central nervous system injury, hypovolemic shock, exposure to environment, administration of anesthetic drugs and cold intravenous fluid. All these factors decrease the abilities of trauma victims to maintain normothermia and conserve body heat. Hypothermia in injured victim is a significant contributor to a well known cycle—triad of death and associated with increased mortality, morbidity and length of hospital stay. Hypothermia is one of the preventable complications in trauma patients. Therefore nurse plays a vital role to evaluate the methods of preventing hypothermia. However, there is no systematic review of effectiveness of different warming methods in local setting. The purpose of this dissertation is to develop an evidence-based guideline to prevent hypothermia in trauma patients by reviewing existing evidence, to assess the feasibility and transferability of implementing the guideline and to develop its implementation and evaluation plan. Five articles meeting the inclusion and exclusion criteria are identified after a systematic research of six electronic databases. Among these articles, four of them are randomized controlled trials while the remaining one is quasi-experimental design with prospective randomized assignment. The quality of these identified articles is evaluated with the methodology checklist for randomized controlled trials which is developed by Scottish Intercollegiate Guideline Network (SIGN). All studies of medium and high quality would be considered as sufficient evidence to support the proposed innovation in preventing hypothermia for trauma patients in Accident & Emergency Department. After assessing the implementation potential, an evidence-based guideline in preventing hypothermia for adult trauma patients is established. The proposed innovation is necessary and beneficial for adult trauma patients to prevent hypothermia. The grade of recommendation in the guideline is rated based on the SIGN grading system from A to D. Communication plans with stakeholders and 3-month pilot study on 20 patients are conducted before implementing the innovation into clinical setting. Evaluation is made to assess the effectiveness of the proposed guideline after the end of pilot study and the end of implementation of guideline. The effectiveness of the proposed innovation is determined by change of core temperature as + 1.1 °C/hr and at least 90% reduction in shivering and thermal discomfort which are reported in the reviewed articles. The guideline is considered as clinical effective when similar outcome is obtained. / published_or_final_version / Nursing Studies / Master / Master of Nursing

Background and Objective: Severe inflammation resulted from small-for-size liver graft injury provides favorable environment for tumor growth. The oxidative stress not only accelerates the inflammatory response, but also stimulates the proliferation of cancer cells. Therefore, attenuating oxidative stress after liver surgery may not only ameliorate liver injury, but also suppress tumor growth and metastasis. Glutathione peroxidase 3 (GPx3) is an anti-oxidant which has been reported to be down-regulated in several types of cancer. Here, we aimed to investigate the clinical significance of GPx3 and characterize the role of GPx3 in liver graft injury and hepatocellular carcinoma (HCC). Furthermore, we intended to explore the therapeutic value of GPx3 using hiPSC-MSCs as a delivery vehicle in hepatic ischemia-reperfusion injury and HCC. Materials and methods: To investigate the clinical significance of GPx3, the HCC patients underwent liver transplantation (106 recipients) or hepatectomy (113 patients) were recruited to study the correlation of GPx3 with clinical parameters. To explore the mechanism of GPx3 in liver graft injury, simulated IR injury model and rat liver transplantation model were applied. To examine the effect of GPx3 on HCC, rGPx3 administration and forced-expression of GPx3 within HCC cells were performed in vitro and in vivo. To explore the therapeutic value of GPx3, engineered hiPSC-MSCs delivering GPx3 was established and applied in mice hepatic IR injury model and nude mice liver cancer model. Results: I. The role of GPx3 in graft injury. The intra-graft GPx3 expression was significantly down-regulated in small-for-size graft accompanied with severe graft injury in a rat liver transplantation model. Clinically, the lower plasma GPx3 was mainly observed in the recipients with small-for-size liver graft. Furthermore, the lower plasma GPx3 significantly correlated with higher tumor recurrence post-transplantation. The down-regulation of GPx3 was associated with hepatic senescence in small-for-size graft. GPx3 treatment delivered by hiPSC-MSCs could significantly ameliorated hepatic IR injury through inhibition of macrophages activation followed by decreased production of ROS, TNFα and IL-1. II. The role of GPx3 in HCC. Down-regulation of GPx3 in liver tumor was observed in half of HCC patients (56/113). It significantly correlated with advanced pTNM stage (P = 0.024), presence of venous infiltration (P =0.043) and high AFP level (P = 0.006). The one year (P = 0.038) and five year (P = 0.019) recurrence rate were significantly higher in the patients with lower GPx3 expression. In functional study, rGPx3 administration and over-expression of GPx3 significantly suppressed proliferation and invasiveness of HCC cells in vitro and in vivo. The tumor suppressive activity of GPx3 was mediated by inhibition of EMT through Erk-NFκB-SIP1 pathway. The GPx3 treatment delivered by hiPSC-MSCs could significantly inhibit proliferation of MHCC97L. Conclusions: I. Down-regulation of GPx3 was associated with small-for-size graft injury. Low circulating GPx3 at early phase after transplantation predicted higher tumor recurrence of HCC recipients. II. Down-regulation of GPx3 indicated poor prognosis of HCC patients. GPx3 suppressed tumor growth and invasiveness by inhibition of EMT through Erk-NFκB-SIP1 pathway. III. Engineered hiPSC-MSCs delivering GPx3 may possess therapeutic value in liver graft injury and HCC. / published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

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