Browsing by Subject "Respiratory System"
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Item A Study of the Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for Three Months Versus Daily Isoniazid for Nine Months for the Treatment of Latent Tuberculosis Infection(2004-11-01) Lemp, Jessie; Patricia Gwirtz; Walter McConathy; Richard EasomLemp, Jessie M. A Study of the Effectiveness and Tolerability of Weekly Rifapentine/Isoniazid for Three Months Versus Daily Isoniazid for Nine Months for the Treatment of Latent Tuberculosis Infection. Master of Science, November, 2004, 107 pp., 4 tables, 4 figures, references, 29 titles. The standard treatment for latent tuberculosis infection, nine months of daily isoniazid, is effective at preventing active tuberculosis; however, its full benefits are limited by non-adherence. A shorter intermittent regimen of rifapentine plus isoniazid once weekly for three months is equally effective as the standard regimen in animal models. This regimen facilitates the use of directly observed therapy, a method that significantly improves adherence. The Center for Disease Control is sponsoring Study 26 to test the effectiveness and tolerability the three-month rifapentine based regimen in latently infected persons with risk factors for progression to active tuberculosis. This thesis will describe the background rationale and methods for the clinical trial, and the internship experience.Item Association Between Breastfeeding and Asthma: A Cross-Sectional Study(2003-08-01) Trombley, Ann M.; Manuel Bayona; Raghbir SandhuTrombley, Ann M., Association Between Breastfeeding and Asthma: A Cross-Sectional Study. Master of Public Health (Epidemiology), August 2003, 17 pp., 12 tables, bibliography, 54 titles. Controversy has surrounded the topic of breastfeeding and if it provides a protective effect against childhood asthma. The objective of this study was to assess whether a relationship exists between breastfeeding and childhood asthma. This study also examined several significant predictors of childhood asthma. A cross-sectional study was conducted using NHANES 1999-2000 data to identify and assess the crude and multivariate associations between the above mentioned variables and asthma and the effect that breastfeeding has on these relationships. Prevalence of asthma in this study was 12.5 per 100. Mexican Americans were found to have a protective association with the development of asthma. A strong protective association was found for those who were breastfed and the development of childhood asthma (OR=0.693, p-value=0.014).Item Cardiovascular Fitness and Lung Function of Adult Men and Women in the United States: NHANES 1999-2002.(2008-12-01) Jackson, HannahThere is a distinct disparity between adult males and females in lung function and cardiovascular fitness in the United States. This study utilizes a nationally representative sample in order to determine predictors of lung function between men and women. Simple means analysis, logistic and linear regressions were utilized in order to determine predictors of lung function between genders. Continuous analyses of lung function reveal that sex and BMI are the most important predictors of VO2 max. However, analyses of clinical cut-points of cardiovascular fitness indicate that gender was not a significant predictor.Item Combined Chemo/Anti-Angiogenic Cancer Therapy in Lewis Lung Metastases(2002-05-01) Sinha-Datta, Anjuli; Goldfarb, Ronald H.; Agarwal, Neeraj; Mathew, Porunelloor A.Datta, Anjuli. Combined Chemo/Anti-Angiogenic Cancer Therapy in Lewis Lung Metastases. Master of Science (Microbiology and Immunology), May 2002. 41 pp., 17 illustrations, bibliography. The focus of my dissertation studies is an eight amino acid peptide (Å6) derived from the non-receptor binding region of urokinase plasminogen activator (uPA), which partially inhibits the binding of uPA to its receptor (uPAR). Å6 has been synthesized as a potential novel anti-cancer agent and kindly provided by Ångstrom Pharmaceuticals, Inc. (San Diego, CA). We further examined potential therapeutic properties of Å6 in vivo and in vitro. Å6 appeared to directly inhibit the invasion of Lewis lung carcinoma cells through Matrigel by approximately 40-45% compared to control. In addition, Å6 had a morphological effect resulting in thicker tubes on small vessel endothelial tube formation compared to no treatment. Interestingly, doxorubicin had similar effects when added to growing endothelial cells. Moreover, Å6 was administered alone and in combination with a standard clinically used chemotherapeutic agent, doxorubicin, in a Lewis lung carcinoma mouse model to test possible synergy between an anti-angiogenic compound (Å6) and a chemotherapeutic agent. This is the first observation that Å6 has the potential to display a direct anti-metastatic therapeutic effect for established pulmonary metastases in this model. Therefore, we believe that Å6 in combination with doxorubicin has the potential to provide better therapy to cancer patients with tumor metastases than potent chemotherapeutics agents alone, by increasing the dose of non-toxic Å6 and reducing the recommended dose of doxorubicin.Item Does Osteopathic Manipulative Treatment Improve Dyspnea and Exercise Tolerance Subjects with Stable Chronic Obstructive Pulmonary Disease?(2006-05-01) Pickett, Carolyn M.; Stoll, Scott; Cruser, des Anges; Licciardone, John C.Pickett, Carolyn M., D.O., M.S. Does Osteopathic Manipulative Treatment Improve Dyspnea and Exercise Tolerance in Subjects with Stable Chronic Obstructive Pulmonary Disease? Master of Science (Clinical Research and Education – OMM), May 2006, 54 pages, 10 tables, 4 figures, references 48 titles. Chronic Obstructive Pulmonary Disease (COPD) is the fourth leading cause of death globally and is projected to increase. This highly prevalent and costly disease causes reduced physical and social functioning, and none of the existing medications for COPD seem to modify long-term decline in lung function. COPD patients with the severe dyspnea have more deficits in the health status and energy. Reduced functional status has been significantly correlated with health related quality of life. Osteopathic Manipulative Treatment (OMT) has been suggested for treatment of COPD as early as 1902, some research indicates that OMT may improve dyspnea and exercise tolerance, yet there are few published studies on OMT and COPD. Study goals were to increase scientific knowledge about how OMT may immediately improve dyspnea and exercise tolerance in stable COPD following exertion. This RCT was approved by the Institutional Review Board at the University of North Texas Health Science Center (UNTHSC) in Fort Worth and funded by the Osteopathic Research Center (ORC) at UNTHSC. –Hypothesis 1: A single intervention of OMT will improve dyspnea in a stable COPD subject, as measured by response to the Borg scale with exertion, when compared to no treatment. –Hypothesis: a single intervention of OMT will improve exercise tolerance in a stable COPD subject, as measured by distance walked during the six-minute walk test, when compared to no treatment. Twenty-one subjects completed the trial, 10 in the OMT group and 11 in the no-treatment group. No significant differences were found in the Borg scale or 6MWT following OMT. This study is limited by a small sample size and single OMT intervention design; however, it does demonstrate the feasibility of this research at this institution and may lead to a larger, more definitive and funded clinical trial.Item Environmental Tobacco Smoke Exposure in Children: Compliance with a Home Smoking Ban Among Texas Households(2007-12-01) Rodriguez, Lori A.; Cardarelli, Kathryn; Ramisetty-Mikler, Suhasini; Lin, Yu-ShengRodriguez, Lori A., Environmental Tobacco Smoke Exposure in Children: Compliance With a Home Smoking Ban Among Texas Households. Master of Public Health (Epidemiology), December, 2007, 72 pp., 10 tables, bibliography, 75 titles. This general population study explores characteristics influencing non-compliance with a home smoking ban among Texas households with children, particularly those with asthmatic children. Over 17% of adults reported non-compliance, with the highest rate in African Americans. Adults who currently smoke (25%) had higher reports of having an asthmatic child in the household and were more likely to not comply. Child asthma status was not a significant predictor of non-compliance; however, African Americans with no asthmatic children were more likely than African Americans with an asthmatic child to not comply. The role of race/ethnicity should be further investigated to improve interventions and home smoking bans should continue to be promoted in an effort to reduce environmental tobacco smoke exposure.Item For Better or for Worse: The Influence of NK Cells, IFN-y and IL-4 on the Development of Protective Adaptive Immunity in Mycoplasma Respiratory Disease(2008-08-01) Bodhankar, Sheetal; Porunelloor A. Mathew; Stephen R. Grant; Rance E. BergSheetal Bodhankar, For better or for worse: The influence of NK cells, IFN-y and IL-4 on the generation of protective adaptive immunity in mycoplasma respiratory disease, Doctor of Philosophy (Microbiology and Immunology) August 2008, 136 pp., 13 illustrations, 3 tables, bibliography, 176 titles. The purpose of these studies was to evaluate the contribution of NK cells and the polarizing cytokines, IFN-y and IL-4, in the generation of protective adaptive immunity against mycoplasma infection. Presence of NK cells during the generation of adaptive immunity resulted in detrimental immune responses. However, upon depletion of NK cells, prior to nasal-pulmonary immunizations, mice demonstrated better clearance of mycoplasma from the respiratory tracts. That the NK cells hindered with the beneficial development of adaptive immune responses via lymphoid cells was demonstrated, since no protection was demonstrated in SCID mice. Furthermore, purified pulmonary T and B lymphocytes primed in a NK cell depleted environment as opposed to one’s primed in a versus non-depleted environment could transfer protection to naïve mice. Interestingly, this is the first time that a favorable role of functional CD4 T cells in mediating protection in mycoplasma respiratory disease was demonstrated. The presence of NK cells at the time of nasal-pulmonary immunization also modulated mycoplasma-specific IFN-y and IL-4 responses in lungs and lower respiratory nodes. In evaluating the roles of IFN-y and IL-4, it was demonstrated that the absence of a single cytokine alters a vast array of chemokines and cytokines produced in response to mycoplasma infection. Corresponding to the higher numbers of mycoplasma and severity in disease due to the loss of IFN-y, altered cytokine and chemokine responses in the lungs to mycoplasma infection were demonstrated. Nasal-pulmonary immunization of IFN-y mice exacerbated, rather than reduced, mycoplasma disease and infection, whereas immunization of IL-4 mice significantly enhanced protection along the respiratory tract particularly in the lungs. Prominent Th-2 type immune responses in the lungs of IFN-y mice corresponded to the severe immunopathologic reactions developed after mycoplasma infection and immunization. These studies demonstrated diverse but crucial functions for NK cells, IFN-y and IL-4 vital towards the development of protective adaptive immune responses against mycoplasma respiratory infection that will have a significant impact on future studies on respiratory immunology.Item Immune and Inflammatory Responses Differ Between the Upper and Lower Respiratory Tract(2001-05-01) Hodge, Lisa M.; Simecka, Jerry; Goldfarb, Ronald H.; Mathew, Porunelloor A.The purpose of these studies was to evaluate the role of upper and lower respiratory immune responses during immunization against respiratory disease antigens, and to characterize which immune responses during immunization against respiratory disease antigens, and to characterize which immune responses contribute to protection in the respiratory tract during infection. After nasal immunization, antigen-specific IgA antibody forming cells dominated throughout the respiratory tract. However, IgG responses were significant in lungs, but not in nasal passages. Furthermore, parental immunization did not enhance humoral immunity in the upper respiratory tract even after a nasal challenge, whereas extrapulmonary lymphoid responses enhanced responses in the lung. After nasal immunization, inflammatory reactions developed within the lungs of mice, but not in nasal passages. Lowering dosages of CT reduced, but did not eliminate, these adverse reactions without compromising immunogenicity. Serum IgE responses were also enhanced in a dose dependent manner by inclusion of CT. During infection, mRNA expression for IL-4 was greater in the nasal passages, while both mRNAs for IL-4 and IFN-y were increased in the lungs. As well, we found increased mycoplasma organisms in the lungs of IFN-y-/- mice, suggesting a protective role for cell-mediated immunity in the lung. In contrast, IL-4-/- mice had greater mycoplasma organisms in the nasal passages, indicating IL-4 responses are crucial for upper respiratory tract protection. Consistent with antigen deposition, nasal inoculation with 10 μl volume of antigen plus CT resulted in significant IgA responses in the nasal passages compared to mice given 24 μl immunizations; however, lower respiratory tract immunizations generated antibody responses in both nasal passages and lungs. In addition, both immunizations resulted in equivalent serum antibody responses. Upper and total respiratory tract immunizations provided protection in the nasal passages when CT was added. However, in the lung, all immunizations resulted in protection against mycoplasma infection, regardless of the inclusion of CT, suggesting a different role for CT as an adjuvant in upper and lower respiratory tract immune protection. In conclusion, we found immune responses generated during immunization and infection are different between the upper and lower respiratory tracts, and the contribution of these responses to clearance of respiratory infection differs.Item Investigating the Role of Stress in a Murine Model of Asthma(2008-07-01) Deshmukh, Aniket; Harlan Jones; P. Mathew; Jerry SimeckaThe mechanisms by which stress can exacerbate asthma are still unknown. The purpose of this study was to examine the immunological links between stress controllability and asthma pathogenesis. Our studies reveal specificity of stress control and immune activation resulting in hyper-inflammatory reactions in response to allergic airway challenge. We anticipate that these studies can serve as a translational piece to facilitate clinical studies of stress and asthma prevalence. The purpose of this project was to establish a murine model of stress controllability and demonstrate the impact of stress on the development of immune allergic airway hypersensitivity as a major feature of asthma. I hypothesized that given the ability to control the degree of stress would translate into less severe allergic airway hypersensitivity. We also hypothesized that distinct changes in immune responses generated in response to uncontrolled stress would reflect the extent of airway hypersensitivity. Mice were exposed to daily regimen of uncontrollable stress, controllable stress or no stress concurrently with allergen exposure. Behavioral disposition to stress was monitored in conjunction with evaluation of severity of asthma and immune status. Our results demonstrate that exerting control over stress conditions leads to distinct changes in immunological status corresponding with positive behavioral responses and less disease severity. We anticipate that our studies will facilitate application of stress management in control of immune status as a biomarker for asthma progression.Item Lethality of Staphylococcus in Murine Pneumonia is Due to Alpha-Toxin and Other Secreted Factors Regulated by AGR and SAR(2003-08-01) Overheim, Katie A.; Dan Dimitrijevich; Glenn Dillon; James CaffreyOverheim, Katie A., Lethality of Staphlococcus aureus in Murine Pneumonia is Due to Alpha-Toxin and Other Secreted Factors Regulated by agr and sar. Doctor of Philosophy (Biomedical Sciences), August, 2003, 91 pp, 6 Tables, 9 illustrations, bibliography, 106. The purpose of these studies was to determine if the S. aureus global regulators agr and sar play a role in staphylococcal pneumonia and if the virulence factors regulated by them contributed to the severity of staphylococcal pneumonia. To determine this, we established a pneumonia model in mice in order to identify if S. aureus global regulators agr and sar play a role in the pathogenesis of staphylococcal pneumonia. As well, we took steps to identify the extracellular factors responsible for the lethality in a murine model of staphylococcal pneumonia and determine if these factors involved in disease process could be used as targets for immune therapy. My work revealed that lethal pneumonia in a mouse model is dependent on the S. aureus global regulators agr and sar. This study also revealed that the lethality associated with our model is due to secreted factors, regulated by S. aureus global regulators agr and sar. Further investigation demonstrated the alpha-toxin is a major virulence factor involved in the lethality in our model. By generating an alpha-toxin deficient strain in S. aureus RN6390, we show a reduced virulence in our disease model. As well, antiserum to alpha-toxin, when administered with a lethal dose of S. aureus RN6390, we show a reduced virulence in our disease model. As well, antiserum to alpha-toxin, when administered a lethal dose of S. aureus RN6390, we show a reduced virulence in our disease model. As well, antiserum to alpha-toxin, when administered with a lethal dose of S. aureus RN6390 protected animals from death. By evaluating the role of alpha-toxin’s ability to contribute to lethality, we assessed numerous strains of S. aureus in our pneumonia model. We discovered that there was a correlation to alpha-toxin production levels and lethality in our pneumonia model. However, our study also demonstrated that alpha-toxin is not the only factor involved in the disease process.Item Mechanisms of Post-Apneic Symathoinhibition in Humans(2002-08-01) Swift, Nicolette Muenter; Michael Smith; David Barker; John R BurkMuenter Swift, Nicolette, Mechanisms of Post-Apneic Sympathoinhibition in Humans. Doctor of Philosophy (Biomedical Sciences), August, 2002, 110 pp., 14 figures, references. Apnea is accompanied by a concomitant rise in arterial pressure and muscle sympathetic nerve activity (MSNA), the latter primarily due to chemoreflex stimulation and possibly the lack of sympathoinhibitory input from pulmonary stretch receptors. The progressive sympathoexcitation during apnea suggests a possible overriding of arterial baroreflex sympathoinhibitory input to sympathoregulatory centers by apnea-induced sympathoexcitatory mechanisms. Nevertheless, it is unknown whether apnea attenuates baroreflex control of MSNA. Apnea termination is accompanied by a profound and immediate sympathoinhibition, the mechanisms of which are unclear; however, potential mediators include normalization of blood gases (i.e. chemoreflex unloading), the lung inflation reflex, and arterial baroreflex stimulation. Therefore, the purpose of the current studies was to: i) determine the contribution of chemoreflex unloading to post-apneic sympathoinhibition, ii) determine the contribution of the lung inflation reflex to post-apneic sympathoinhibition, and iii) determine whether carotid baroreflex control of MSNA is altered by apnea and its termination. The first study compared MSNA during post-apneic administration of room air versus a gas mixture designed to maintain the subjects’ end-apneic alveolar gas levels. Regardless of post-apneic gas administration, post-apneic MSNA was at or below baseline pre-apneic levels; thus; chemoreflex unloading does not contribute to post-apneic sympathoinhibition. Furthermore, quantification of post-apneic MSNA associated only with the low lung volume phase of respiration, when sympathoinhibitory input from the lung inflation reflex is minimal, demonstrated that post-apneic sympathoinhibition persists even during the low lung volume phase of respiration, when sympathoinhibitory input from the lung inflation reflex is minimal, demonstrated that post-apneic sympathoinhibition persists even during the low lung volume phase of respiration. Therefore, the lung inflation reflex does not appear to be the primary mediator of post-apneic sympathoinhibition. The second study utilized neck suction (NS) and neck pressure (NP) to assess carotid baroreflex function during and following sleep apnea. The sympathoinhibitory response to -60 Torr NS was maintained throughout apnea; conversely, the sympathoexcitatory response to +30 Torr NP was attenuated for nearly one minute post-apnea. Thus, carotid baroreflex control of MSNA is not altered by apnea but is transiently attenuated by apnea termination. We propose that the carotid baroreflex-MSNA function curve resets rightward and upward during apnea. Return of the function curve to baseline upon apnea termination may partly explain the reduced MSNA response to NP post-apnea.Item Molecular Characterization of a Second Superoxide Dismutase Gene (sodM) of Staphylococcus Aureus and Effects of SodM and SodA on Oxidative Stress Resistance and Virulence(2001-11-01) Valderas, Michele Wright; Porunelloor A. Mathew; Richard Easom; Jerry SimeckaValderas, Michelle Wright., Molecular Characterization of a Second Superoxide Dismutase Gene(sodM) of Staphylococcus aureus and Effects of SodM and SodA on Oxidative Stress Resistance and Virulence. Doctor of Philosophy (Biomedical Sciences), November, 2001, 191 pp., 4 tables, 20 illustrations, bibliography, 389 titles. A second gene for superoxide dismutase (SOD) in S. aureus (sodM) was cloned and characterized. This gene was found to be unique to S. aureus among the staphylococci. S. aureus is the first gram-positive bacterium reported to contain two or more SOD activities. The three native SOD enzymes observed for S. aureus can be accounted for by two distinct genes, sodM and sodA. The SodM and SodA proteins form homodimers, but their subunits also interact to form an active heterodimeric SOD. The deduced amino acid sequence from each gene and the relative insensitivity to hydrogen peroxide and potassium cyanide indicated that the S. aureus SODs utilize manganese as a metal ion cofactor. Additionally, viabilities of the soda and sod double mutants, but not the sodM mutant were drastically reduced under conditions of oxidative stress in early exponential growth. However, only the double mutant was affected when oxidative stress was applied in the late-exponential and stationary phases of growth. It was determined, therefore, that while SodA may be the major SOD activity in S. aureus throughout all stages of growth, SodM, under conditions of oxidative stress, becomes a major source of SOD activity during the late-exponential and stationary phases of growth such that the viability of the S. aureus sodA mutant is maintained. Experiments examining the roles of sodM and sodA in virulence determined the ability of S. aureus to cause disease in the mouse lung and subcutaneous abscess formation in mice was unaffected by sod mutation. Lack of SOD activity, however, results in enhanced clearance of S. aureus within the lung and also promotes killing of the organism by mouse macrophage cell lines and human polymorphonuclear leukocytes.Item Population Characteristics Suggest Modifications to Proposed Pediatric Asthma Intervention Program(1998-08-01) DeMoss, Margaret W.; Ramirez, Gilbert; Urrutia-Rojas, Ximena; Coggin, ClaudiaDeMoss, Margaret W., Population Characteristics Suggest Modifications to Proposed Pediatric Asthma Intervention Program. Master of Public Health, August, 1998, 57 pp., 4 tables, 1 illustration, 2 appendices, reference list, 46 titles. Asthma is the most common chronic childhood disease affecting almost 5 million children in this country. The children most as risk for developing asthma come from low income, minority, and urban families. This studies examines a proposed pediatric asthma intervention program targeting Tarrant County area Medicaid clients. The purpose of this study is to define different subgroups and preferences among those clients and to recommend modifications that are likely to improve program outcomes. Recommendations were based on information gathered from interviews with 70 families, all having at least one child with asthma. Specific interests in learning more about asthma as well as learning preferences are tested for association with a variety of family characteristics. Although no statistically significant results were determined for subgroups, descriptive findings reveal that a large minority of respondents are interested in more information about asthma, but not necessarily by the means proposed. The study also suggests special needs for families with very young children, for those with adult asthma, and for Hispanics.Item Predictors for the Severity of Asthma in the Hospital Setting. An Epidemiologic Study Based on Hospital Records from the Texas Health Care Information Council(2005-04-01) Marruffo, MarcoMarruffo, Marco, Predictors for the Severity of Asthma in the Hospital Setting. An Epidemiologic Study Based on Hospital Records from the Texas Health Care Information Council. Doctor of Public Health (Epidemiology), May 2005, 118 pp., 40 tables, 3 figures, bibliography, 62 titles. The purpose of this research was to identify and assess prognostic factors for severity and risk of death among 27,383 hospitalized asthma patients in the state of Texas during 2002, by using the public available Texas Hospital Inpatient data, collected by The Texas Health Care Information Council (TCHIC)(TCHIC, 2002). Data was analyzed by means of multinomial logistic regression using minor risk as the reference group. Among other results severe asthma cases were 20% more likely to be females, 20% more probability to have HIV/AIDS, 5.5 times more chance to be obese, 4.2 times more likely to have esophageal reflux, 1.7 times more likely to be hypertensive, and 11.8 times more likely to have diabetes as compared to those without severe asthma (p [less than] 0.001). Obese were 2.8, diabetics 3.3, those with urinary tract infection 2.3, those with fever 3.1 and those with congestive heart failure 7.5 times more likely to have major risk of death due to asthma (p [less than] 0.001). The results of this study can be used to identify high risk groups to plan and applied control measures for tertiary prevention of severity and death due to asthma.Item T-Helper Cell Responses in Lungs After Immunization and Chronic Respiratory Disease; And Their Association With Pulmonary Inflammation(2001-05-01) Jones, Harlan P.; Simecka, Jerry; Dimitrijevich, S. Dan; Goldfarb, Ronald H.The purpose of these studies was to characterize T helper cell responses in the lungs of mice after immunization and chronic respiratory infection. CD4+ T cells were the major population of T cells resident in the lung in comparison to CD8+ T cells. Polyclonal activation of resident CD4+T cells produced abundant levels of IL-4 in comparison to IFN-γ, indicating that Th2 cells were the major sub-population of CD4+ T cells. In contrast, resident CD8+ T cells were the sole producer of IFN-γ by naïve T lymphocytes. Furthermore, the distribution of T cells was similar between BALB/c, C3H/HeN, C57BL/6 and DBA/2N strains of mice. However differences in the distribution of CD8+T cells, as well as the levels of IL-4 and IFN-y production produced by resident T cells were found between C57 and the other strains of mice tested. These results demonstrate that host genetic factors may be involved in determining host susceptibility to respiratory disease. Differences in the intensity of antigenic stimulation provoke changes in the type of T cell response generated. Intranasal immunization with influenza (FLU) vaccine antigen alone initiated solely an antigen-specific Th2-like response. In contrast, the addition of the potent mucosal adjuvant cholera toxin (CT) in combination with FLU antigen induced not only resident Th2 responses, but also induced antigen-specific Th1-like responses. This change corresponded with a dramatic increase in the number of CD4+ T cells in the lung. Thus, intense immunization of respiratory T cells enhanced resident T helper cell responses, but also promoted the activation of Th1 responses. Chronic respiratory infection also elicited changes in the resident population of T cells consistent with pulmonary inflammatory immune responses. At early stages of infection, CD4+, but not CD8+ T cells increased in number within inductive respiratory lymphoid tissues (lower respiratory nodes [LRNs]). Between day 7 and 14 however, there was a dramatic increase in the number of CD4+ T cells in the lung. Interestingly, CD8+ T cells also increased in the lungs, suggesting their activation along mucosal sites during mycoplasma infection. Mycoplasma-specific IL-4 and IFN-γ production also increased in a tissue-specific/time-dependent manner. IL-4 production was initially observed in the LRNs, whereas significant levels of IL-4 and IFN-γ was produced in both tissues 14 days after infection. In comparison, IFN-γ was the predominate cytokine, produce at 14 days coinciding with pulmonary inflammation. Suggesting that intense activation promoted changes in the resident pulmonary Th2 environment, and possible is a major component of pulmonary inflammatory immune responses. Both CD4+ and CD8= T cells were shown to have a role in modulation of disease severity during mycoplasma disease. Observation of gross pulmonary lesions reveal that mycoplasma infected mice treated with anti-CD8 antibody showed increase clinical signs of disease and pronounced gross pulmonary lesions. Additionally the number of total mononuclear cells increased dramatically in the absence of CD8+ T cells. Thus, CD8+ T cells may have a regulatory role in controlling resident CD4+ T cells that increased 14 days after infection. Chemokine production is known to mediate the recruitment of lymphocytes to enhance the initiation of immunity as well as be responsible for modulating inflammatory responses. We find that mycoplasma increase the number of dendritic cells in the lung 14 days after infection, and stimulated the production of dendritic cell-derived ABCD-1 chemokine. Also, β-chemokine MIP-1α and MIB-1β production was observed during intense immunization as well as during mycoplasma infection. These results provide evidence for a potential mechanism through which changes in resident pulmonary T cell responses occur given the intensity of the immune response generated.Item The Characterization of T Cell Responses Along the Respiratory Tract(2004-05-01) Ivey Jr., James A.; Brown, Mary B.; Fling, John; Wu, Ming-ChiIvey, James A., The Characterization of T Cell Responses Along the Respiratory Tract. Masters (Immunology). May, 2004. 63 pages. 2 tables, 10 figures. 55 titles. This research converged on T cell responses to respiratory agents, tobacco smoke and allergens in humans, and T cell responses to an extracellular bacterium, M. bovis, in calves. In the first chapter, we will discuss the basic functions of the immune system. In the second chapter, we will discuss the basic functions of the immune system. In the second chapter, we characterized the impact of tobacco smoke on T cell responses in atopic smokers and atopic nonsmokers. The results were inconclusive and the study was postponed until the proper allergens were found. We also characterized the T cell responses of calves infected with Mycoplasma bovis in the third chapter. The results showed an increase in T lymphocytes in the upper respiratory tract of infected calves, which correlated with sites of infection.Item The Effect of Osteopathic Manipulative Medicine on Pulmonary Function and Lung Volumes in Healthy Adults(2004-04-01) Bradbury, Joseph Aaron; Michael SmithBradbury, Joseph Aaron, The Effect of Osteopathic Manipulative Medicine on pulmonary function and lung volumes in healthy adults. Master of Science, April, 2004. Osteopathic Manipulative Medicine (OMM) techniques that address the diaphragm are commonly taught in Osteopathic medical schools. The application of these techniques is based on the theory that the physician can alter the mechanics of respiration. We hypothesized that OMM treatment of the diaphragm will allow greater diaphragmatic excursion of the diaphragm into the chest resulting in decreased residual volume (RV). Study design consisted of two groups; treatment and sham treatment. Pulmonary function tests (PFTs) were administered to each subject upon admission to the study. Our data was collected from a MedGraphics PF/Dx 1085D series whole body plethysmography machine. Following a short rest period, the subject received either an OMM treatment or a sham treatment. A post treatment series of PFTs were then administered to the subject. A Paired T test comparing pre and post values within each group showed that RV, TLC, and TGV significantly decreased after the OMM treatment. There were no significant changes in the sham treatment group. Univariate Analysis of Covariance between groups also showed that changes in RV remained significant. From these data we conclude that OMM treatments addressing diaphragm function are effective in altering the mechanisms of respiration and particularly in decreasing residual volume.Item Toll-like Receptor 2 Mediates the Host's Responses in Murine Respiratory Mycoplasmosis(2008-04-01) Love, Wees JaMar; Jerry W. Simecka; Duncan C. Krause; Stephen R. GrantLove, Wees J., The role of Toll-like receptor 2 in mediating the host’s defenses toward mycoplasma infection in the upper and lower respiratory tracts. Doctor of Philosophy (Microbiology and Immunology), April, 2008, 88 pp., 7 illustrations, bibliography, 144 titles. The purpose of these studies was to investigate the toll-like receptors (TLR) responsible for the recognition of invading mycoplasmas. They were also meant to evaluate the role of Toll-like receptors in the generation of immune responses and disease progression in mycoplasma respiratory disease. To determine the role of TLRs in recognizing viable Mycoplasma pulmonis, we utilized human embryonic kidney (HEK) cell lines that are known to have low basal expression of TLRs. The HEK cell lines used were stably transfected to express various combinations of TLRs. The HEK cell lines used were stably transfected to express various combinations of TLRs including TLR1, 2 and 6. The current paradigm of TLR recognition of mycoplasma is that TLR2 dimerizes with either TLR1 or TLR6 to recognize different subclasses of mycoplasma lipoproteins. However, the recognition of viable M. pulmonis organisms remains unclear. When stimulated with viable M. pulmonis, it was discovered that TLR2 was pivotal in mediating the host’s pro-inflammatory cytokine production and that the co-expression of TLR1 or TLR6 enhanced the response. To study their role in mycoplasma recognition and disease progression, we utilized TLR2 knockout (KO) mice. Bone-marrow derived dendritic cells (BMDC) from TLR2 KO mice showed an impaired ability to produce pro-inflammatory cytokines such as IL-12p40 in response to viable M. pulmonis. In addition, the host’s ability to clear the infection was also impaired in TLR2 KO animals. There were higher numbers of cfu in the lower respiratory tract where alveolar macrophages are known to mediate the host’s intrapulmonary clearance of organism. In the upper respiratory tract, where alveolar macrophages (AM) are absent, the production of anti-microbial peptides (e.g. β defensing) in response to TLR2 agonists has been demonstrated. Thus, TLR2 does mediate the host’s immune response to mycoplasma infection, by interfering with the host’s ability to clear the infection and be interfering with the host’s ability to mount an effective inflammatory response. These results also suggest that the TLR2 mediated anti-mycoplasma effects vary and are compartmentalized along the respiratory tract. These studies demonstrated diverse and novel roles of TLRs in respiratory infections and will serve as a platform for future studies investigating mycoplasma respiratory infections.