ingest cdrApp 2018-06-13T19:54:30.466Z 51cd2fe2-3fd7-401f-a923-a97bc3db68a2 modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-06-13T21:15:19.857Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2018-06-13T21:15:31.226Z Adding technical metadata derived by FITS addDatastream MD_FULL_TEXT fedoraAdmin 2018-06-13T21:15:54.003Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2018-06-13T21:16:16.242Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-11T09:16:29.722Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-18T05:21:14.451Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-16T18:28:27.517Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-27T14:10:46.034Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-12T05:27:08.970Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-21T15:12:08.575Z Laurel Kartchner Author Department of Microbiology and Immunology School of Medicine GENERATION OF CLINICALLY RELEVANT MODELS OF BURN-ASSOCIATED COMORBIDITIES FOR ANALYSIS OF IMMUNE DYSFUNCTION AFTER BURN INJURY Burn injury is a significant form of trauma that leads to alterations in the functionality of multiple body systems. One vital system that promotes both healing and protection from invasive pathogens is the immune system. After burn injury the immune system is severely impeded. However, models of burn injury are unable to successfully recapitulate phenotypes seen among burn-injured patient populations. Studies indicate that presence of burn-associated comorbidities can greatly improve the translatability of models and that study of comorbidities is essential for improving treatment of patients. Here we report the development of a model of repeated bacterial exposure after burn injury. This model is able to recapitulate immune cell recruitment and alterations in cytokine production that mimic those seen among patient populations. Namely, we found that repeated infections lead to increased bacterial burden after burn injury, and the loss of a lab-derived burn “protection” phenotype that is common in the literature late after burn injury. We found that this phenotype corresponds with burn-dependent alterations in pulmonary innate immune cell numbers and function. We believe that these cells represent a potential target for therapeutic intervention. Additionally, we have worked to establish a model of inhalation injury to examine inhalation-dependent alterations in the immune profile that take place both independently and concomitant with burn injury. We have found that inhalation and burn injury independently contribute to damage in our murine model of inhalation. We examined the pulmonary compartment and found that burn and inhalation independently affect the recruitment of neutrophils to either the airspace or the lung tissue. We also found that inhibition of nitric oxide production can ameliorate damage that takes place after inhalation injury, representing a potential target for therapeutic intervention among the patient population. Spring 2018 2018 Immunology Burn, Immune Dysfunction, Infection, Inhalation Injury, Model, Neutrophils eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Bruce Cairns Thesis advisor Robert Maile Thesis advisor Janelle Arthur Thesis advisor Brian Conlon Thesis advisor Felicia Williams Thesis advisor Matthew Wolfgang Thesis advisor text Laurel Kartchner Author Department of Microbiology and Immunology School of Medicine GENERATION OF CLINICALLY RELEVANT MODELS OF BURN-ASSOCIATED COMORBIDITIES FOR ANALYSIS OF IMMUNE DYSFUNCTION AFTER BURN INJURY Burn injury is a significant form of trauma that leads to alterations in the functionality of multiple body systems. One vital system that promotes both healing and protection from invasive pathogens is the immune system. After burn injury the immune system is severely impeded. However, models of burn injury are unable to successfully recapitulate phenotypes seen among burn-injured patient populations. Studies indicate that presence of burn-associated comorbidities can greatly improve the translatability of models and that study of comorbidities is essential for improving treatment of patients. Here we report the development of a model of repeated bacterial exposure after burn injury. This model is able to recapitulate immune cell recruitment and alterations in cytokine production that mimic those seen among patient populations. Namely, we found that repeated infections lead to increased bacterial burden after burn injury, and the loss of a lab-derived burn “protection” phenotype that is common in the literature late after burn injury. We found that this phenotype corresponds with burn-dependent alterations in pulmonary innate immune cell numbers and function. We believe that these cells represent a potential target for therapeutic intervention. Additionally, we have worked to establish a model of inhalation injury to examine inhalation-dependent alterations in the immune profile that take place both independently and concomitant with burn injury. We have found that inhalation and burn injury independently contribute to damage in our murine model of inhalation. We examined the pulmonary compartment and found that burn and inhalation independently affect the recruitment of neutrophils to either the airspace or the lung tissue. We also found that inhibition of nitric oxide production can ameliorate damage that takes place after inhalation injury, representing a potential target for therapeutic intervention among the patient population. Spring 2018 2018 Immunology Burn, Immune Dysfunction, Infection, Inhalation Injury, Model, Neutrophils eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Bruce Cairns Thesis advisor Robert Maile Thesis advisor Janelle Arthur Thesis advisor Brian Conlon Thesis advisor Felicia Williams Thesis advisor Matthew Wolfgang Thesis advisor text Laurel Kartchner Author Department of Microbiology and Immunology School of Medicine GENERATION OF CLINICALLY RELEVANT MODELS OF BURN-ASSOCIATED COMORBIDITIES FOR ANALYSIS OF IMMUNE DYSFUNCTION AFTER BURN INJURY Burn injury is a significant form of trauma that leads to alterations in the functionality of multiple body systems. One vital system that promotes both healing and protection from invasive pathogens is the immune system. After burn injury the immune system is severely impeded. However, models of burn injury are unable to successfully recapitulate phenotypes seen among burn-injured patient populations. Studies indicate that presence of burn-associated comorbidities can greatly improve the translatability of models and that study of comorbidities is essential for improving treatment of patients. Here we report the development of a model of repeated bacterial exposure after burn injury. This model is able to recapitulate immune cell recruitment and alterations in cytokine production that mimic those seen among patient populations. Namely, we found that repeated infections lead to increased bacterial burden after burn injury, and the loss of a lab-derived burn “protection” phenotype that is common in the literature late after burn injury. We found that this phenotype corresponds with burn-dependent alterations in pulmonary innate immune cell numbers and function. We believe that these cells represent a potential target for therapeutic intervention. Additionally, we have worked to establish a model of inhalation injury to examine inhalation-dependent alterations in the immune profile that take place both independently and concomitant with burn injury. We have found that inhalation and burn injury independently contribute to damage in our murine model of inhalation. We examined the pulmonary compartment and found that burn and inhalation independently affect the recruitment of neutrophils to either the airspace or the lung tissue. We also found that inhibition of nitric oxide production can ameliorate damage that takes place after inhalation injury, representing a potential target for therapeutic intervention among the patient population. Spring 2018 2018 Immunology Burn, Immune Dysfunction, Infection, Inhalation Injury, Model, Neutrophils eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Bruce Cairns Thesis advisor Robert Maile Thesis advisor Janelle Arthur Thesis advisor Brian Conlon Thesis advisor Felicia Williams Thesis advisor Matthew Wolfgang Thesis advisor text Laurel Kartchner Author Department of Microbiology and Immunology School of Medicine GENERATION OF CLINICALLY RELEVANT MODELS OF BURN-ASSOCIATED COMORBIDITIES FOR ANALYSIS OF IMMUNE DYSFUNCTION AFTER BURN INJURY Burn injury is a significant form of trauma that leads to alterations in the functionality of multiple body systems. One vital system that promotes both healing and protection from invasive pathogens is the immune system. After burn injury the immune system is severely impeded. However, models of burn injury are unable to successfully recapitulate phenotypes seen among burn-injured patient populations. Studies indicate that presence of burn-associated comorbidities can greatly improve the translatability of models and that study of comorbidities is essential for improving treatment of patients. Here we report the development of a model of repeated bacterial exposure after burn injury. This model is able to recapitulate immune cell recruitment and alterations in cytokine production that mimic those seen among patient populations. Namely, we found that repeated infections lead to increased bacterial burden after burn injury, and the loss of a lab-derived burn “protection” phenotype that is common in the literature late after burn injury. We found that this phenotype corresponds with burn-dependent alterations in pulmonary innate immune cell numbers and function. We believe that these cells represent a potential target for therapeutic intervention. Additionally, we have worked to establish a model of inhalation injury to examine inhalation-dependent alterations in the immune profile that take place both independently and concomitant with burn injury. We have found that inhalation and burn injury independently contribute to damage in our murine model of inhalation. We examined the pulmonary compartment and found that burn and inhalation independently affect the recruitment of neutrophils to either the airspace or the lung tissue. We also found that inhibition of nitric oxide production can ameliorate damage that takes place after inhalation injury, representing a potential target for therapeutic intervention among the patient population. Spring 2018 2018 Immunology Burn, Immune Dysfunction, Infection, Inhalation Injury, Model, Neutrophils eng Doctor of Philosophy Dissertation Microbiology and Immunology Bruce Cairns Thesis advisor Robert Maile Thesis advisor Janelle Arthur Thesis advisor Brian Conlon Thesis advisor Felicia Williams Thesis advisor Matthew Wolfgang Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution Laurel Kartchner Creator Department of Microbiology and Immunology School of Medicine GENERATION OF CLINICALLY RELEVANT MODELS OF BURN-ASSOCIATED COMORBIDITIES FOR ANALYSIS OF IMMUNE DYSFUNCTION AFTER BURN INJURY Burn injury is a significant form of trauma that leads to alterations in the functionality of multiple body systems. One vital system that promotes both healing and protection from invasive pathogens is the immune system. After burn injury the immune system is severely impeded. However, models of burn injury are unable to successfully recapitulate phenotypes seen among burn-injured patient populations. Studies indicate that presence of burn-associated comorbidities can greatly improve the translatability of models and that study of comorbidities is essential for improving treatment of patients. Here we report the development of a model of repeated bacterial exposure after burn injury. This model is able to recapitulate immune cell recruitment and alterations in cytokine production that mimic those seen among patient populations. Namely, we found that repeated infections lead to increased bacterial burden after burn injury, and the loss of a lab-derived burn “protection” phenotype that is common in the literature late after burn injury. We found that this phenotype corresponds with burn-dependent alterations in pulmonary innate immune cell numbers and function. We believe that these cells represent a potential target for therapeutic intervention. Additionally, we have worked to establish a model of inhalation injury to examine inhalation-dependent alterations in the immune profile that take place both independently and concomitant with burn injury. We have found that inhalation and burn injury independently contribute to damage in our murine model of inhalation. We examined the pulmonary compartment and found that burn and inhalation independently affect the recruitment of neutrophils to either the airspace or the lung tissue. We also found that inhibition of nitric oxide production can ameliorate damage that takes place after inhalation injury, representing a potential target for therapeutic intervention among the patient population. Immunology Burn; Immune Dysfunction; Infection; Inhalation Injury; Model; Neutrophils eng Doctor of Philosophy Dissertation Microbiology and Immunology Bruce Cairns Thesis advisor Robert Maile Thesis advisor Janelle Arthur Thesis advisor Brian Conlon Thesis advisor Felicia Williams Thesis advisor Matthew Wolfgang Thesis advisor text University of North Carolina at Chapel Hill Degree granting institution 2018 2018-05 Laurel Kartchner Author Department of Microbiology and Immunology School of Medicine GENERATION OF CLINICALLY RELEVANT MODELS OF BURN-ASSOCIATED COMORBIDITIES FOR ANALYSIS OF IMMUNE DYSFUNCTION AFTER BURN INJURY Burn injury is a significant form of trauma that leads to alterations in the functionality of multiple body systems. One vital system that promotes both healing and protection from invasive pathogens is the immune system. After burn injury the immune system is severely impeded. However, models of burn injury are unable to successfully recapitulate phenotypes seen among burn-injured patient populations. Studies indicate that presence of burn-associated comorbidities can greatly improve the translatability of models and that study of comorbidities is essential for improving treatment of patients. Here we report the development of a model of repeated bacterial exposure after burn injury. This model is able to recapitulate immune cell recruitment and alterations in cytokine production that mimic those seen among patient populations. Namely, we found that repeated infections lead to increased bacterial burden after burn injury, and the loss of a lab-derived burn “protection” phenotype that is common in the literature late after burn injury. We found that this phenotype corresponds with burn-dependent alterations in pulmonary innate immune cell numbers and function. We believe that these cells represent a potential target for therapeutic intervention. Additionally, we have worked to establish a model of inhalation injury to examine inhalation-dependent alterations in the immune profile that take place both independently and concomitant with burn injury. We have found that inhalation and burn injury independently contribute to damage in our murine model of inhalation. We examined the pulmonary compartment and found that burn and inhalation independently affect the recruitment of neutrophils to either the airspace or the lung tissue. We also found that inhibition of nitric oxide production can ameliorate damage that takes place after inhalation injury, representing a potential target for therapeutic intervention among the patient population. Spring 2018 2018 Immunology Burn, Immune Dysfunction, Infection, Inhalation Injury, Model, Neutrophils eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Microbiology and Immunology Bruce Cairns Thesis advisor Robert Maile Thesis advisor Janelle Arthur Thesis advisor Brian Conlon Thesis advisor Felicia Williams Thesis advisor Matthew Wolfgang Thesis advisor text Laurel Kartchner Creator Department of Microbiology and Immunology School of Medicine Burn injury is a significant form of trauma that leads to alterations in the functionality of multiple body systems. One vital system that promotes both healing and protection from invasive pathogens is the immune system. After burn injury the immune system is severely impeded. However, models of burn injury are unable to successfully recapitulate phenotypes seen among burn-injured patient populations. Studies indicate that presence of burn-associated comorbidities can greatly improve the translatability of models and that study of comorbidities is essential for improving treatment of patients. Here we report the development of a model of repeated bacterial exposure after burn injury. This model is able to recapitulate immune cell recruitment and alterations in cytokine production that mimic those seen among patient populations. Namely, we found that repeated infections lead to increased bacterial burden after burn injury, and the loss of a lab-derived burn “protection” phenotype that is common in the literature late after burn injury. We found that this phenotype corresponds with burn-dependent alterations in pulmonary innate immune cell numbers and function. We believe that these cells represent a potential target for therapeutic intervention. Additionally, we have worked to establish a model of inhalation injury to examine inhalation-dependent alterations in the immune profile that take place both independently and concomitant with burn injury. We have found that inhalation and burn injury independently contribute to damage in our murine model of inhalation. We examined the pulmonary compartment and found that burn and inhalation independently affect the recruitment of neutrophils to either the airspace or the lung tissue. We also found that inhibition of nitric oxide production can ameliorate damage that takes place after inhalation injury, representing a potential target for therapeutic intervention among the patient population. 2018-05 2018 Immunology Burn; Immune Dysfunction; Infection; Inhalation Injury; Model; Neutrophils eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Bruce Cairns Thesis advisor Robert Maile Thesis advisor Janelle Arthur Thesis advisor Brian Conlon Thesis advisor Felicia Williams Thesis advisor Matthew Wolfgang Thesis advisor text Kartchner_unc_0153D_17739.pdf uuid:055e78c8-fadd-4066-bad6-a2886ae4909a 2020-06-13T00:00:00 2018-04-20T02:17:42Z proquest application/pdf 1145625