The purpose of this study was to determine if an association exists between housing characteristics and demographic characteristics of Tennessee neighborhoods (census tracts) and the rate of child fatalities (violent, accidental, and natural) in the neighborhoods reporting child fatalities for the years 1996-2003. The child fatalities, for the eight years, reported to each Tennessee Judicial District Child Fatality Review Team required by the Tennessee Department of Health’s Maternal and Child Health Division were selected for use in the study. Data was selected from the Bureau of the Census’ 2000 United States Census to obtain the housing characteristics and demographic characteristics of heads of households by census tract. The data were analyzed using descriptive statistics, Spearman Rho, and Chi-Square Cross-tabulation analyses. The descriptive profile showed the under one year of age had the most child fatalities for the eight years. The children aged 15 - 18 years old were the second largest group of child fatalities for the years 1996-2003. Children aged one to four years made up the third largest group of fatalities in Tennessee for the years 1996-2003. More male children died than female children in Tennessee from 1996-2003. The top six most frequently reported causes of death were illness or other natural causes, prematurity, vehicular, Sudden Infant Death Syndrome (SIDS), and firearm fatalities. In Tennessee, the top two reported manners of death were natural and accidental. The following conclusions were drawn from the findings of the study; the neighborhood housing characteristics of the percent of rental housing and household size was associated with the rate of Tennessee child fatalities classified as violent and accidental deaths; the neighborhood demographic characteristic of Non-white heads of households was associated with the rate of Tennessee violent and natural child fatalities; and the neighborhood housing characteristics of the percent of rental housing, vacancy status, household size, and urban location were associated with the rate of Tennessee child fatalities classified as natural deaths. More research needs to be conducted to determine the nature of the weak associations between the neighborhood housing and demographic characteristics and the rate of child fatalities.

The two cellular components of B cell memory are antibody (Ab)-secreting cells (ASCs) and memory B cells (BMem). BMem are quiescent cells that respond to “recall” antigen and contribute substantially to vaccine effectiveness. The rational evaluation of vaccination strategies is dependent on quantitative information on the state of B cell memory. Despite the importance of BMem in resistance to infection, there is little information on the nature of BMem populations generated by influenza infection or vaccination. The major goal of this dissertation was a comprehensive quantitative analysis of the frequency and distribution of influenza-specific BMem generated by influenza infection of the respiratory tract, or by vaccination with inactivated virus. To achieve this, a prerequisite was the development of a sensitive and reproducible limiting dilution assay (LDA) for determining influenza-specific BMem frequencies. The results in Chapter 2 demonstrated that a strategy utilizing BPL-inactivated virus particles was effective for the in vitro activation of virus-specific BMem. This strategy selectively activates virus-specific BMem and, importantly, achieves this without a requirement for CD4+ T cell associated factors. Using this strategy, the frequency of Influenza specific BMem in different anatomical sites was measured and we also tested three different forms of influenza virus immunization strategy; (i) intranasal (i.n.) infection, (ii) i.n. vaccination, (iii) intramuscular (i.m.) vaccination. The results in Chapter III, IV showed that following different forms of immunization, BMem dispersed broadly to organized lymphoid tissues throughout the body, and a population of ASCs was established in the bone marrow. ASC and BMem frequencies in these locations reflected the magnitude of the primary B cell response to the form of immunization. Thus, the frequencies were higher following i.n. infection. Interestingly, the state of B cell memory in the lung was profoundly influenced by the form of immunization. The lung was a preferential site of BMem localization after i.n. infection. However, this was not the case after i.m. immunization when BMem frequencies in the lung were considerably lower than in other sites. Our findings point to an effect of influenza infection on the lung environment that profoundly influences ASC and BMem trafficking to this site.

Activating mutations of ras genes are frequently found in human cancers. Since Ras proteins and their functions play an important role in tumorigenesis, it is important to develop targeted anticancer therapeutics against Ras-related human cancers. We observed that in addition to tumorigenic ability, oncogenic H-Ras possesses a novel proapoptotic ability to facilitate the induction of apoptosis by histone deacetylase inhibitors (HDACIs), such as FR901228 and trichostatin A (TSA). HDACIs make up a new class of structurally diverse anticancer agents and have been shown to exhibit antimetastatic and antiangiogenic activities toward malignantly transformed cells. We detected that expression of oncogenic H-Ras potentiated intracellular reactive oxygen species (ROS) in human and mouse cells to enhance HDACI-induced ROS, thereby contributing to the induction of selective apoptosis and caspase activation. The first part (Part I) of this dissertation focuses on the understanding of Ras proteins, their role in normal and transformed cell physiology, and current treatment options against Ras-related human cancers, as well as the role of HDACIs and ROS in anticancer therapeutics. The next three parts (Part II-IV) focus on revealing the mechanisms for the novel pro-apoptotic ability of oncogenic H-Ras that allow HDACIs to induce selective apoptosis of the oncogenic H-Ras expressing cells. Results in Part II & III verify the pro-apoptotic activity of oncogenic H-Ras in the increased susceptibility of human cancer cells to HDACIs. The caspase pathways, the B-Raf and extracellular signal regulated kinase pathway, p21Cip1 and p27Kip1, and core histone contents are regulated differently by FR901228 in oncogenic H-Ras–expressed cells than their counterparts in parental cells, contributing to the increased susceptibility to the induction of selective apoptosis. Results in Part IV describe the role of reactive oxygen species in the pro-apoptotic ability ofoncogenic H-Ras to enhance the cell susceptibility to HDACIs. Intracellular ROS was cooperatively up-regulated by oncogenc H-Ras and HDACI treatment to induce selective apoptosis of oncogenic H-Ras-expressing cells. The last section (Part V) summarizes the findings with their importance and discusses future directions.

Campylobacteriosis is caused by the gram-negative bacteria Campylobacter and is a leading cause of gastrointestinal illness worldwide. In the United States an estimated 2.4 million cases occur annually with approximately $8.0 billion in associated costs. Due to the high cost of morbidity, understanding the epidemiology and risk factors of campylobacteriosis is important. It is unclear if the prevalence of campylobacteriosis is higher or lower in East Tennessee than other parts of the state or country or if the clinical characteristics of patients in the area are similar to the rest of the country. Therefore, the purpose of the study was to describe clinical and epidemiological characteristics of campylobacteriosis patients in East Tennessee to assist in health planning to control campylobacteriosis. Data from the Foodborne Disease Active Surveillance Network was analyzed for 2003-2006 in 16 counties in East Tennessee. The data was first assessed for its quality, then descriptive statistics were calculated and spatial and temporal patterns of reported cases and risk factors were assessed. The overall error rate in the data quality analysis was 6.5% although in the last year of the study it was only 2.6%. The mean annual prevalence of campylobacteriosis in East Tennessee was 10.4 cases per 100,000 population, which was 1.6 times higher than all of Tennessee (7.4 cases/100,000). Grainger and Jefferson Counties had higher age- and sex-adjusted prevalence estimates than the region and nation. It is yet unclear why this region has a higher prevalence of campylobacteriosis than the rest of the nation. The highest age-specific prevalence (41.6 cases/100,000) was observed in children under 5. Disease prevalence was consistently higher in the summer months compared to the other seasons. The median age of patients was lower in the most rural counties. More patients in East Tennessee were hospitalized than the rest of the nation. The most commonly reported risk factors were animal and raw meat exposure. Improvement in data collection and entry is necessary to improve the quality and application of this surveillance data. Educational efforts on proper hygiene following animal handling, and proper well protection and disinfection should be targeted at high risk groups.

A recently identified phospholipid translocase, Atp10c, may be involved in the modulation of glucose and lipid metabolism in mouse adipocytes. Aminophospholipid translocases have previously been associated with cell signaling and intracellular protein trafficking. In this study, the role of Atp10c in the insulin signaling pathway and adipogenesis was investigated using the murine 3T3-L1 cell line. Atp10c mRNA is highly expressed in undifferentiated cells and 2-fold down-regulated during adipogenesis. Interestingly, Western blotting showed a band for ATP10C protein at 70 kDa, a lower molecular weight than expected; ATP10C expression increased during differentiation. Possible reasons for these discrepancies will be discussed. Since PPARgamma is considered to be the master regulator of adipogenesis and controls the expression of adipocyte genes, the effect of PPARgamma agonists on Atp10c expression was examined. The PPARgamma agonists and anti-diabetic drugs MCC555 and troglitazone both promoted adipogenesis and consequently reduced Atp10c expression by 5-fold and 3-fold, respectively. When used in combination with the PPARgamma antagonist GW9662, treatment rescued some of the decrease in Atp10c due to MCC555 or troglitazone alone. The pattern of Atp10c expression is shown to be opposite to that of PPARgamma. Additionally, the correlation between effectors of glucose and lipid metabolism and Atp10c was investigated. Treatment of 3T3-L1 adipocytes with insulin and dexamethasone showed significantly increased expression of Atp10c; treatment with the β-adrenergic factor isoproterenol slightly decreased expression. This suggests transcriptional control of Atp10c by hormonal factors, but not β-adrenergic factors, during differentiation. To further explore the function of Atp10c in lipid metabolism, ATP10C silencing through transient transfection of 3T3-L1 cells was first optimized to ultimately allow the assessment of changes in proteins related to obesity and diabetes. An 84% and 77% knockdown of Atp10c gene expression in preadipocytes and adipocytes, respectively, was achieved. To elucidate a potential role for Atp10c/ATP10C in the insulin signaling pathway, glucose uptake was investigated. Following Atp10c silencing in 3T3-L1 adipocytes, glucose uptake was significantly increased at both 24 and 48 hours. Based on the results presented herein, the Atp10c gene and ATP10C protein have an important role in the insulin signaling pathway and may be involved in adipogenesis.,/p>

Purpose: To examine the validity of the SenseWear Pro3 armband in estimating energy expenditure during a wide range of field-based activities. Methods: 41 participants (mean age = 34.5 + 11.7 yrs.) performed one of two routines with 6 activities each, Routine 1 (Outdoor Aerobic Activities) or Routine 2 (Indoor Home-based Activities), while wearing the SenseWear Pro3 (SW) and the Cosmed K4b2 portable metabolic unit. Routine 1 (n=16) included road walking, track walking, walking with 6.8 kg (15 lb.) bag, singles tennis, track running, and road running. Routine 2 (n=25) included TV watching, reading, doing laundry, ironing, light cleaning, and aerobics. Each activity was done for approximately 10 min with a 3-5 min break between activities with resting measurements taken for all participants before routines. Results: The mean differences (Cosmed-SW) in average MET values for Routine 1 were: road walking (-1.0, p<0.001), track walking (-0.9, p<0.001), walking with bag (-0.7, p<0.01), tennis (1.7, p<0.001), track running (2.7, p<0.001), road running (2.7, p<0.001). For Routine 2, mean differences were: watching TV (-0.1, p>0.05), reading (-0.1, p>0.1), laundry (0.1, p>0.1), ironing (-1.3, p<0.001), light cleaning (-0.4, p<0.01), and aerobics (0.4, p>0.1). Discussion: Compared to indirect calorimetry, significant differences in average MET levels by the SW Pro3 armband were found for several activities with a trend for EE underestimation at higher intensities (r=0.72, p<0.01). The SW significantly overestimated MET levels of ironing, light cleaning, and all three walking variations, and it significantly underestimated tennis and both running bouts. Algorithms need to be refined for more accurate EE estimations at high intensities and in different field-based activities.

This study addresses the hypothesis that the following cell adhesion molecules (CAMs): homing-associated cell adhesion molecule (HCAM), very late antigen-4 (VLA-4) and L-selecti I I . . n p ay a ro e m the trafficking of hematopoietic progenitor cells (HPCs) between the bone marrow microenvironment and the peripheral circulation. In order to ascertain differences in CAM expression based on physiologic compartment, the expression of HCAM, VLA-4 or L-selectin per CD34+ myeloid progenitor cell was assessed between paired samples of blood and marrow. CAM expression was flow cytometrically quantitated in paired samples obtained from patients treated with cell than those in circulation. To functionally demonstrate the hematopoietic potential of mobilizing doses of granulocyte-colony stimulating factor (G-CSF) or from normal donors donating for allogeneic transplant. In G-CSF mobilized patients, marrow derived CD34+ myeloid progenitor cells expressed more VLA-4 per cell than those in circulation. In normal donors, marrow derived myeloid progenitor cells expressed more CD34 per CAM expressing (HCAM+, VLA-4+ or L-selectin+) CD34+ myeloid progenitors, colony forming unit (CFU) and long term culture initiating cell (LTCIC) assays of flow cytometrically sorted normal marrow and blood CAM+!-CD34+myeloid progenitors were performed. L-selectin+CD34+ myeloid progenitors formed a greater percentage of BFU-E colonies and a lower percentage of CFU-GM colonies than all other CAM+!- CD34+ myeloid progenitors sorted from norma I bl00d. In normal donors, CAM+!-CD34+ myeloid. progerut.ors sorte d from blood formed significantly more colonies per 10· plated cells than those denv.ed from marrow. L-selectin+CD34+ myeloid progenitors derived . d . .fi antly more L TCIC (per 10· sorted CAM+CD34+myeloid from marrow contame srgni IC x progenitors) than those expressing RCAM or VLA-4. In order to determine whether CD34+ myeloid progenitors utilize VLA-4 to bind to fibronectin (FN), in vitro binding assays were performed Adhesion of normal blood derived VLA-4+ CD34+ myeloid progenitors to FN was blocked by the addition of monoclonal antibodies against the a4 subunit of VLA-4. These data suggest a model ofHPC trafficking, in which HPCs utilize VLA-4 to adhere to components of the bone marrow microenvironment, while HPe modulation of L-selectin affinity plays an important role in HPC homing and a less direct role in hematopoietic reconstitution.

Heart disease is the leading cause of death for both men and women (Kochanek, Xu, Murphy, Miniño & Kung, 2011). Every year in the United States, more than 600,000 people die from heart disease, which amounts to roughly a quarter of all deaths (Kochanek et al., 2011). Heart attacks account for a large portion of the deaths attributed to heart disease, and include sudden cardiac arrest or chronic cases of heart trouble that develop into heart attack after an extended period of time. Heart attacks affect approximately 935,000 Americans each year, with roughly two-thirds of people experiencing them for a first time (Kochanek et al, 2011). With such a high level of incidence, much research into incidence, prevalence, symptoms, and risk factors is being conducted in hopes of altering such somber statistics in the future.

No description available.

This study examines the active presence of folk healing medicines in selected urban, African-American women’s pregnancy experiences. These experiences were found be collectively recognized as gynecological resistance. Furthermore, this study sought to clarify the epistemological frame of knowledge constructed within the African- American women’s cultural base, which motivates, influences, and constructs rationales for pregnancy choices, decision making, and the pursuits of resistance. This study was based on the premise that some African-American women continue to resist control of their reproduction, by empowering themselves using a variety of folk medicines practices. A case study analysis approach was used to analyze data gathered and it reflected that the collective reproductive resistances stemmed from a shared memory known as the African Ancestral Maternal Memory. The researcher found that selected urban African-American women utilized several forms of folk healing medicines to gynecologically resist control of their reproduction. The conclusions drawn from the findings suggest that the need for continued gynecological resistance by African-American women was not only rooted in the reproductive oppression of enslaved African women, but correlated with the systematic gynecological control of urban African-American women.