Browsing by Subject "Department of Pediatrics"
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Item Absence of Twisted Gastrulation (Twsg1) Limits the Population of Cranial Neural Crest Cells(2009-04-08) Mittelstaedt, GinaCraniofacial defects are among the most common birth defects with cranial neural crest cells (NCCs) playing a fundamental role in craniofacial development. The cranial NCCs migrate from dorsal neural folds to populate the branchial arches. Then they differentiate into the cells that form facial structures. For example, the mandible forms from the first branchial arch (BA1). Twisted gastrulation (Twsg1) is a gene that has been found to influence craniofacial development. A mutation in Twsg1 in mice produces a spectrum of craniofacial defects ranging from normal appearance to underdevelopment of the mandible, midline facial defects, and forebrain defects resulting in holoprosencephaly. Previous research has shown that Twsg1 acts as a bone morphogenetic protein (BMP) antagonist and thereby limits apoptosis in BA1, a key destination of cranial NCCs. Apoptosis is increased in BA1 in the absence of Twsg1, leading to a loss of BA1 derivatives. The hypothesis of this work is that the absence of Twsg1 also increases apoptosis in the cranial NCCs and thereby limits the population of NCCs prior to their migration to BA1. This study focused on determining whether the NCC population was depleted in Twsg1 knockout mice and whether the midbrain region itself was affected. We found that the midbrain markers were normal, but the markers specific for NCCs were significantly reduced. This reduction is consistent with a depletion of the NCC population. Future research will directly study proliferation, apoptosis, and BMP signaling in NCC populations in the absence of Twsg1.Item Characterizing Endothelin-1 and ABO Blood Type in Cerebral Malaria(2009-04-08) Ireland, KathleenMalaria remains one of the most life-threatening problems in the world today. Cerebral Malaria (CM) caused by Plasmodium falciparum infection is a severe form of malarial disease that kills more than two million people annually, most of which are children. CM affects the brain and is associated with cognitive impairments, coma, and death. Left untreated, it is fatal with 24-72 hours. Quicker diagnosis is needed to provide adequate and superior treatment. In order to do so, a better understanding of the disease pathogenesis is needed. The goal of my proposed research was to further characterize endothelial cell activation in children with cerebral malaria, as well as the role of blood type as possible clinical markers that may play a role in the disease. The first aim of the project was to measure endothelin-1 levels in samples previously obtained at Mulago Hospital in Kampala, Uganda. Samples were comprised of children ages 4-12 with varying levels of disease severity. Endothelin-1 levels were measured by an immunoassay and analyzed with relation to known clinical outcomes. My second aim was to develop a polymerase chain reaction assay to determine ABO blood type from the Ugandan children's genomic DNA. I have developed a protocol using positive and negative controls that I will apply toward genotyping samples from the patients. Though this project is still in progress, I expect my results will help to characterize the role of endothelin-1 and blood type in cerebral malaria pathogenesis.Item Cytogenetics Worldwide(2012-04-18) Selinger, JessieWith the advance of molecular technology in the past thirty years, cytogenetic analysis has become essential for making an appropriate diagnosis, prognosis, and treatment plan for children with acute leukemia. It is now a regular practice to document the frequencies of chromosomal translocations that are found in children with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), but a comparison of the different frequencies of chromosomal translocations throughout the world has not yet been undertaken. Differing frequencies of chromosomal translocations in pediatric leukemia in populations worldwide could have large implications for the study of genetics and pediatric leukemia.Item Effects of Iron Deficiency on Social-Emotional Behavior of Internationally Adopted Children(2010-04-21) Zuck, TaylorIron Deficiency Anemia affects 20-25% of infants around the world, and even more are experiencing iron deficiency without anemia. Iron Deficiency has been reported in internationally adopted children, including those from Eastern Europe, China and Guatemala. Infants with iron deficiencies are known to test lower on various measures of development as well as show differences in affect. Infants' social-emotional behavior has been shown to be adversely affected by iron deficiency with or without anemia. The aim of this study is to assess the differences between post-institutionalized children with iron deficiency and those without on measures of social-emotional behavior.Item ¡Encuentro! A Healthy Youth Development Project Adolescent Contraceptive Use: Perspectives of Local Latina Youth(2011-04-13) Rosas-Lee, MairaIn the United States and in Minnesota, Latina youth have the highest rates of teen pregnancy and birth of all major racial/ethnic groups. Latina girls are also less likely to use contraception than their non-Latina peers. Thus, it is imperative to develop pregnancy prevention programs tailored to Latina youth and their social and cultural contexts. As part of the ¡Encuentro! study, conducted with funds from the CDC, the purpose of this research is to examine influences on Latina teens’ decisions around contraceptive use, using data from focus groups conducted with Twin Cities Latina youth ages 14-22. This poster presents preliminary findings, from analysis of data from two female focus groups. Preliminary findings suggest cultural, social and individual-level influences on local Latinas decisions related to contraceptive use.Item Examining the Effects of Iron Deficiency on Developing Hippocampal Axon Growth and Complexity(2023-12-13) Devgun, Karishma; Monko, Timothy; Bastian, ThomasItem Exploration and Social Communication Inhibition in Internationally Adopted Children(2011-12-16) Shao, Ruxue; Fuglestad, Anita; Kroupina, MariaItem Expression of Surfactant Protein-A (SP-A) in the Developing MurineIntestinal Tract(2011-04-13) Theisen, ErinSurfactant protein-A (SP-A) plays a critical role in the innate immune system and has well characterized effects in the lung where it attenuates inflammatory responses and controls invasion of bacteria. Extra-pulmonary sources of SP-A have also been indentified : SP-A mRNA has been detected in the murine neonatal and adult gastrointestinal (GI) tract, while significant levels of SP-A protein have been detected in amniotic fluid. A novel finding by the George research lab showed that SP-A knockout (-/-) newborn mice raised in a bacterial laden corn dust environment exhibited intestinal inflammation-- instead of pulmonary inflammation--and higher rates of death. Further studies have shown that SP-A -/- mice exhibit abnormal bacterial colonization patterns in the GI tract compared to their wild-type counterparts, indicating a role for SP-A in the newborn intestinal tract. To date it is not clear if newborn intestinal exposure to SP-A comes from ingested amniotic fluid or from production in the newborn intestinal tract. RT-qPCR showed low levels of SP-A gene expression in the newborn murine GI tract; yet, we and others have had mixed results regarding the detection of SP-A protein via immunohistochemistry. To address the question of intestinal exposure of SP-A in the newborn, I will perform RNA in situ hybridization to identify gene expression in specific cells of the GI tract. I have designed a 438 bp digoxigenin-labeled antisense RNA probe specific for the SP-A gene. This probe will be used on flash-frozen GI and lung tissue sections of mice at post-natal days of life 5 and 6 with an in situ hybridization protocol designed by the Panoskaltsis-Mortari laboratory.Item Human Total Tau and its Role as a Possible Biomarker for Cognitive Deficits in Cerebral Malaria(2010-04-21) Ireland, Kathleen F.Cerebral malaria (CM) caused by Plasmodium falciparum infection is a major cause of death in children of developing countries, yet the costs of CM are not just death alone. Recent studies have indicated that children who survive the disease have an increased risk of persistent neurological deficits and cognitive impairments. In this study we investigated the cerebral spinal fluid (CSF) levels of the protein tau as a potential predicative measure of the severity of these deficits. Tau is associated with the stabilization and assembly of neuronal microfilaments and is found in the CSF after neuron damage. Elevated levels of tau have been found in children with CM. We hypothesized that levels of tau in CM children would be higher in those children who had neurologic deficits and higher in those who had long-term cognitive impairments, compared to those who did not. We measured tau in the CSF of 142 CM Ugandan children and compared levels to the children’s cognitive and neurologic test scores in areas such as working memory, executive attention and learning. Working memory was negatively correlated to tau levels at both time of enrollment and at six months later (P=0.01 rho=-0.3; P=0.02 rho=-0.3). Executive attention and learning were not correlated to tau levels (all P>0.05), and there was no significant difference between those children who had neurologic deficits and those who did not (P=0.5). Investigations of tau levels with cognitive impairments are ongoing, as cognitive testing is still being performed on some children.Item Investigation of the Novel Peptide TUF1 in Context Conditioning(2011-08-11) Reise, Kathryn• TUF1 is a newly discovered peptide expressed in the hippocampus, amygdala, hypothalamus, and endocrine tissues (Figure 1B). These regions are crucial for the integration of external stimuli and play an important role in necessary responses for survival, such as fear acquisition to environments. •This study will measure the role of TUF1 in context and will measure whether TUF1 expression is altered after contextual conditioning. •Figure 1A shows the predicted structure of TUF1. Illustrated is the signal peptide (SP) and transmembrane region (TM). •TUF has a p75 receptor-binding domain, a domain commonly found in neurotrophins such as brain-derived neurotrophic factor (BDNF). This indicates that TUF1 could have possible effects on neuronal plasticity.Item The Investigation of the Novel Peptide TUF1 in Fear Potentiated Startle(2011-03-16) Reise, KathrynThe goal of this study is to determine the role of TUF1 and to measure if the administration of this peptide into the ventricles alters fear responses by affecting the acquisition and/or expression of acoustic startle.Item The Role of p53 and MDM2 Expression in Pediatric Rhabdomyosarcoma(2010-04-21) Antolick, AshleyRhabdomyosarcoma is a highly malignant and fast growing tumor that accounts for over half of the soft tissue sarcomas diagnosed in children. Seventy percent of all cases of this cancer are diagnosed in a child’s first ten years of life. This study focused on the alveolar and embryonal classifications of rhabdomyosarcoma. Embryonal rhabdomyosarcoma is the most common but also most treatable form of RMS. Conversely, alveolar rhabdomyosarcoma is the most aggressive and elusive form. My research examined the make-up of these tumors. Specifically, I measured the expression of cellular and nuclear components in human tumor tissues using immunohistochemistry staining. I focused on identifying the presence of three different proteins: 1) p53 tumor suppressor gene/protein, 2) MDM2 regulator of p53, and 3) NFkB nuclear transcription factor. It is expected that there should be an increased expression of the three investigated proteins in the tissue if they do indeed play a role in the proliferation of tumor cells. The results of this research are very important in the search for a cure to this devastating childhood cancer. Based upon the revealed composition of this specific type of tumor and the correlation between protein/gene pathways, new treatment and prevention methods could be discovered for rhabdomyosarcoma and other similar cases.Item The Role of Sema3E in Optic Fissure Closure of the Eye in Zebrafish(2011-04-13) Agamawi, Yusuf; Hatler, Julia; Lerach, Stephanie; Spahn, SchimmentiMicrophthalmia, anophthalmia, and coloboma are significant birth defects causing up to ten percent of childhood blindness that can be identified in two per ten thousand newborns. Up to seventy percent of microphthalmia, anophthalmia, and coloboma are associated with optic fissure (OF) closure defects and fall into a category of developmental eye defects. One of the goals of our laboratory is to determine the genetic mechanism of developmental eye defects. We are investigating the role of SEMA3E, a gene associated with colobomas in two unrelated children. Class three semaphorins (Sema3s) are a family of molecules known to direct cell movement (Callander et al. 2007). We hypothesized that Sema3E is required for cell movement during OF closure. Following morpholino (MO) knockdown of Sema3E expression in zebrafish embryos, a significant and dose dependent reduction in eye size was observed. Additionally, inverted pear shaped pupils, evidence of defective optic fissure closure, were seen in some of the Sema3E-deficient embryos. A reporter transgenic line of zebrafish expressing green fluorescent protein (GFP) expression at the edges of the OF was used to evaluate OF closure. MO injected embryos had greater GFP intensity at the OF closure line in comparison to un-injected zebrafish, suggesting delayed OF closure. These results indicate that Sema3E plays a critical role in OF closure. Currently, retinal layers of the zebrafish eye are being examined by immunohistochemistry and hematoxylin and eosin (H&E) staining to understand the mechanism(s) by which Sema3E is involved in eye development.Item Social-Communication Skills (Status) of Post-Institutionalized Children(2010-04-21) Wert, LindsayThe aim of this study is to assess the differences between postinstitutionalized children and the controls on measures social communication skills. Hypothesis: Post-institutionalized children will be significantly lower in initiating social interactions associated with positive emotions including joint attention and social referencing compared to the control group.