As a model for studying apoptosis associated with pathogenesis of congenital rubella syndrome, bicistronic rubella virus (RUBV) replicons expressing an antibiotic resistance gene in the presence (925-IN) or absence (IN-IN) of RUBV capsid protein (C) were constructed. Apoptosis was assessed by detection of caspase activation, chromatin fragmentation, and flow cytometry. 925-IN cells grew similarly to Vero, but IN-IN cells demonstrated caspase activation, chromatin fragmentation and cell cycle arrest. Whereas Vero cells transfected with P150 exhibited rapid apoptosis not detected in transfected Vero cells stably expressing C, neither exhibited cell cycle alterations, indicating a cell cycle stall not associated with apoptosis. Finally, two human epithelial cells, HEK293 and A549, transfected with P150 failed to exhibit apoptosis, indicating that while replicon-transfected Vero cells are useful for studying apoptosis and cell cycle arrest, the results are not applicable to other cell types.

No description available.

Congenital heart defects due to the aberrant development of the atrioventricular (AV) valves and septum are among the most common developmental abnormality in newborns and cause significant neonatal morbidity and mortality. A key point in cardiac morphogenesis occurs when cells within the endocardial cushions (ECCs), the precursors for the AV valvoseptal complex, delaminate and undergo an epithelial-to-mesenchymal transformation (EMT). The mesenchymal cells then proliferate and the cushion area elongates to form the AV valves and portions of the AV septae. The signals that initiate region-specific EMT during heart development are unknown. Cilia, known for their role in establishing left-right (LR) asymmetry, function to receive and integrate extracellular signals, including fluid flow, in a range of other organ systems. We hypothesize that cilia could also have a direct role in heart development outside of their role in LR development. Using immunohistochemistry, we demonstrated the presence of cilia on the myocardium, epicardium, and ECCs of wild-type mouse hearts at embryonic day (e) 9.5 and e12.5. To characterize the potential role of these cilia, we compared mice with mutations affecting ciliary biogenesis, motility, and mechanosensation. Using bright field microscopy and in situ hybridization, we analyzed the embryonic heart structure and the expression pattern of Gata4, an EMT transcription factor. We showed that compared to mice with immotile but structurally normal cilia, the mice without cilia had hypocellular ECCs, a thinned compact myocardium (CM), and an up-regulated expression of Gata4. These observations suggest that a subset of cilia called cardiac cilia have a role in cardiogenesis outside of their role in LR development and affect Gata4 expression. One possible function of cardiac cilia is as mechanosensors, integrating fluid flow and influencing cardiac morphogenesis including EMT and development of the CM.

Thesis (M. Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 68-75).

Source: Masters Abstracts International, Volume: 47-06, page: 3501. Advisers: Irwin B. Horwitz; Jacqueline T. Hecht. Includes bibliographical references.

Thesis--University of Kentucky (M.S.), 2003. / Title from document title page. Document formatted into pages; contains viii, 86 p. : ill. Includes abstract and vita. Includes bibliographical references (p. 82-85).

Infant health is an important comprehensive measure of the health in a society. Experiences during infancy can create durable and heritable patterns of social deprivation and illness ultimately producing health disparities in a population. This thesis sought to determine the relationship between maternal circumstances and infant mortality, morbidity and congenital anomaly rates in Winnipeg, Manitoba, Canada. Using logistic regression models the study explored provincial program screening data and administrative data held. The study found higher rates of congenital anomalies within two parent families and male infants. There was a relationship between hospital readmission rates and social and economic factors. Newborn hospital readmissions were associated with social support factors, while post-neonatal hospital readmissions were associated with contextual factors. Understanding the odds of infant mortality, morbidity and congenital anomaly in relation to different maternal socioeconomic factors may contribute to future health planning and the development of interventions that can improve health equity. / October 2015

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Purpose: Infants born with Heterotaxy Syndrome (HS) often have intestinal malrotation in addition to severe congenital heart disease (CHD). Given the catastrophic risk of midgut volvulus, where the vascular supply to the gut is cut off causing necrotic bowel and possible future short‐gut syndrome following surgery, an elective Ladd procedure is recommended at the first diagnosis of malrotation. In patients with severe CHD, however, the risk of complications from prophylactic surgery is high, especially in infancy prior to stable cardiac palliation. This study sought to determine whether deferring a Ladd procedure during the first six months of life in infants with CHD is safe by focusing on the incidence of volvulus in the HS population, morbidity of volvulus and morbidity of an elective Ladd procedure. Methods: Medical records of patients with HS and intestinal malrotation at Phoenix Children’s Hospital from 2006‐2011 were reviewed. Stage of heart surgery, severity of heart disease, diagnosis of intestinal malrotation, and timing of Ladd procedure if applicable were recorded. Results: 31 patients with HS and intestinal malrotation were identified. Of the 31, 9 had a Ladd procedure prior to six months of age, 2 for volvulus and the other 7 either electively or for less severe GI symptoms that were not suggestive of volvulus. The other 22 did not have a Ladd procedure prior to six months of age. There was one death (1/22) from a non‐gastrointestinal cause in a patient who had not undergone a Ladd procedure. There were no deaths in the 9 patients who underwent a Ladd procedure (0/9). Conclusions: Given the low overall incidence of volvulus in HS, and with continued vigilance for obstructive symptoms, this study suggests that delaying the Ladd procedure in asymptomatic patients with HS and CHD and intestinal malrotation is safe. Watchful waiting may reduce the incidence of cardiac complications during the Ladd procedure by allowing for stabilizing cardiac surgical palliation prior to elective abdominal surgery.

Caffeine, a mild central nervous system stimulant, is a natural component of common hot and cold beverages like coffee, tea, sodas and cocoa. Animal studies have demonstrated caffeine’s teratogenic effects when administered at high concentrations; however, epidemiologic studies have yielded inconsistent results in humans. Because caffeine containing beverages are commonly consumed by pregnant women, we examined the prevalence of use and explored possible associations of maternal caffeine consumption with cardiovascular malformations in 3,274 cases matched with 3,519 controls enrolled in the 1981-89 “Baltimore-Washington Infant Study,” a population-based case-control investigation. We explored several key aspects of the quality of and distribution of measurements of caffeine consumption among mothers in the study population. We concluded with recommendations for refining data collection to reduce potential bias associated with assessing both caffeine content and changes in caffeine consumption during pregnancy in order to inform future research studies and birth defects/adverse birth outcomes surveillance programs.