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Articles 1 - 30 of 216
Full-Text Articles in Medicine and Health Sciences
An Investigation Of The Anti-Stemness Actions Of Two Mirnas After Their Induction By Aminoflavone In Luminal A Breast Cancer, Nicole Ursula Rumbidzai Mavingire
An Investigation Of The Anti-Stemness Actions Of Two Mirnas After Their Induction By Aminoflavone In Luminal A Breast Cancer, Nicole Ursula Rumbidzai Mavingire
Loma Linda University Electronic Theses, Dissertations & Projects
Approximately 40% of estrogen receptor positive breast cancer (BC) patients develop resistance to endocrine therapy (ET) agents like tamoxifen (Tam). Resistance promotes metastasis, recurrence, and death since metastatic BC is often incurable. Breast cancer stem cells (CSCs) greatly contribute to disease progression and drug resistance. We previously showed that aryl hydrocarbon receptor (AhR) agonist aminoflavone (AF) inhibits the expression of CSC biomarker α6-integrin (ITGA6) to disrupt the formation of endocrine-sensitive and -resistant luminal A mammospheres. In this study, we performed miRNAsequencing analysis of luminal A MCF-7 and MCF-7TamR mammospheres before and after AF treatment to further develop the mechanism of …
Phytochemical And Synthetic Ahr Ligands As Novel Therapy For Refractory Breast Cancer, Jonathan V. Wooten
Phytochemical And Synthetic Ahr Ligands As Novel Therapy For Refractory Breast Cancer, Jonathan V. Wooten
Loma Linda University Electronic Theses, Dissertations & Projects
Patients with triple-negative breast cancer (TNBC) possess tumors that lack estrogen receptor, progesterone receptor, and human growth factor receptor 2 expression. Such patients have lower survival rates than those diagnosed with other breast cancer subtypes in part, due to the scarcity of targeted therapy for TNBC. In addition to chemotherapy, patients with TNBC often consume natural remedies, which has led us and others to evaluate the ability of plant isolates to confer anticancer and chemopreventive actions. Poly-ADP ribose polymerase (PARP) is an enzyme that promotes DNA single-strand break repair. PARP inhibitor olaparib exploits DNA repair enzyme deficiency in tumors to …
Development And Maturation Of The Brain Following Pediatric Mtbi, Jeong Bin Lee
Development And Maturation Of The Brain Following Pediatric Mtbi, Jeong Bin Lee
Loma Linda University Electronic Theses, Dissertations & Projects
Pediatric mild traumatic brain injury (mTBI) is a major public health concern with the potential to produce long-lasting cognitive, adaptive, and socio-behavioral outcomes. However, our understanding of how TBI pathophysiology evolves in the developing brain is lacking. Our central hypothesis was that pediatric mTBI results in evolving microstructural dysregulation that leads to functional and structural deficits late in life. To test this hypothesis, we first sought to assess the influence of pediatric mTBI on white matter (WM) dysregulation in early adulthood. To accomplish this, we investigated the effects of single and repeated pediatric mTBI on white matter, focusing on the …
Neuroprotective Functions Of Docosahexaenoic Acid And Epidermal Fatty Acid Binding Protein, Manuel Luis Montero
Neuroprotective Functions Of Docosahexaenoic Acid And Epidermal Fatty Acid Binding Protein, Manuel Luis Montero
Loma Linda University Electronic Theses, Dissertations & Projects
Lipotoxicity (LTx) is involved in mostly every process of neuronal injury. Using NGFDPC12 cells we show that palmitic acid (PA) induces the expression of stress response genes HIF-1α and BNIP3, increases the accumulation of reactive oxygen species, and decreases cell viability by apoptosis. Inhibition of cathepsins does not rescue neurons from PA-LTx but inhibition of necroptosis and promotion of autophagy do. DHA decreases the expression of HIF-1α and BNIP3 and rescues PA-induced cell death by inhibiting apoptosis and necroptosis. Besides DHA stimulates the mRNA expression, phosphorylation and conjugation of autophagy controlling proteins. Inhibiting autophagy during DHA treatment decreases its capacity …
A Novel Exo-Proteomic Approach To The Study Of Traumatic Brain Injury, Ron B. Moyron
A Novel Exo-Proteomic Approach To The Study Of Traumatic Brain Injury, Ron B. Moyron
Loma Linda University Electronic Theses, Dissertations & Projects
Concussions and Traumatic Brain Injuries (TBI) are significant health concerns and affect a wide cross section of society. Current diagnostic criteria and modalities, such as brain imaging and subjective measures of consciousness such as the Glasgow Coma Scale (GCS) score, are insufficient to properly diagnose the full spectrum of head injuries. Assessment of injury severity and outcome are further complicated by the vast array of symptoms, many of which mimic those displayed by other disorders. It is important to possess a better diagnostic tool for head injury triage and outcome prediction. One current line of inquiry seeks to discover a …
Aminoflavone Inhibits Α6-Integrin And Growth Of Tamoxifen Resistant Breast Cancer, Petreena S. Campbell
Aminoflavone Inhibits Α6-Integrin And Growth Of Tamoxifen Resistant Breast Cancer, Petreena S. Campbell
Loma Linda University Electronic Theses, Dissertations & Projects
Approximately 40% of estrogen receptor positive (ER+) breast cancer patients develop resistance to standard of care agent tamoxifen, while ER negative (ER-) breast cancer patients are intrinsically resistant to tamoxifen. Resistance often promotes metastasis, recurrence and death. Tumor-initiating cells (TICs) represent key contributors to resistance and adhesion protein α6-integrin is a putative TIC biomarker. Investigational agent Aminoflavone (AF) demonstrates efficacy against breast cancer cells irrespective of ER status. Interestingly, we found tamoxifen resistant (TamR) cells and tumors exhibited elevated α6-integrin expression in comparison to their tamoxifen sensitive counterparts. AF effectively disrupted mammospheres enriched for TICs and reduced α6-integrin levels in …
Rna-Seq Reveals Transcriptomic Program Associated With Stemness In Taxane Resistant Prostate Cancer, Christina K. Cajigas-Du Ross
Rna-Seq Reveals Transcriptomic Program Associated With Stemness In Taxane Resistant Prostate Cancer, Christina K. Cajigas-Du Ross
Loma Linda University Electronic Theses, Dissertations & Projects
There is no cure for advanced prostate cancer (PCa), and taxane chemotherapy is the only treatment option once other therapies have failed. However, this is problematic since all patients eventually develop chemoresistance. Emerging treatments for advanced PCa have shown promise at the benchside, but clinical trials have not resulted in newly approved drugs due in part to redundant survival pathways utilized by prostate tumor cells to maintain therapy-resistance. Using RNAsequencing—an innovative approach for quantifying gene expression changes—this dissertation sought to elucidate chemoresistance-associated molecular pathways as a catalyst to develop new therapeutic targets. Results revealed a differential upregulation of stemness-associated genes …
Microgravity Exerts An Age-Dependent Effect On Cardiovascular Progenitor Cell Development, Jonathan Baio
Microgravity Exerts An Age-Dependent Effect On Cardiovascular Progenitor Cell Development, Jonathan Baio
Loma Linda University Electronic Theses, Dissertations & Projects
The heart and its cellular components are profoundly altered by missions to space and injury on Earth. Increasing evidence has identified that one such alteration induced by spaceflight is the promotion of the efficacious use of stem cells in therapies on Earth. For this reason, neonatal and adult human cardiovascular progenitor cells (CPCs) were cultured aboard the International Space Station (ISS). Subsequently, we assessed the effects of mechanical unloading on developmental properties and signaling. Spaceflight induced the expression of genes that are typically associated with an earlier state of cardiovascular development. In particular, in neonatal CPCs, we measured increased expression …
The Role Of Wnt3a In Ischemic Stroke, Nathanael Matei
The Role Of Wnt3a In Ischemic Stroke, Nathanael Matei
Loma Linda University Electronic Theses, Dissertations & Projects
After ischemic stroke, apoptosis of neurons is a primary factor in determining outcome. Wnt3a is a naturally occurring protein that has been shown to have protective effects in the brain for traumatic brain injury. Although wnt3a has been investigated in the phenomena of neurogenesis, anti-apoptosis, and anti-inflammation, it has never been investigated as a therapy for stroke. We hypothesized that the potential neuroprotective agent wnt3a would reduce infarction and improve behavior following ischemic stroke by attenuating neuronal apoptosis and promoting cell survival through the Frizzled-1/PIWI1a/FOXM1 pathway in MCAO rats. 229 Sprague-Dawley rats were assigned to male, female, and aged 9-month …
Effects Of Omega-3s And Vitamin E Prophylactic Diets And The Implications Of Lipid Transport In Spinal Cord Injury, Kathia Cordero-Caban
Effects Of Omega-3s And Vitamin E Prophylactic Diets And The Implications Of Lipid Transport In Spinal Cord Injury, Kathia Cordero-Caban
Loma Linda University Electronic Theses, Dissertations & Projects
Traumatic injury to the central nervous system (CNS) presents a devastating problem to our society. Although current interventions are promising, no effective treatments are available. The neural membrane fatty acid composition is markedly altered during the first few days after spinal cord injury (SCI). SCI results in autonomic dysfunction, paralysis, spasticity, and significant chronic neuropathic pain. The trauma leads to significantly increased levels of free radical and oxidative stress that contribute to obstructing tissue healing and recovery. A growing body of evidence shows that administration of hydrophobic molecules such as Vitamin E and long-chain omega-3 polyunsaturated fatty acids (ω3PUFAs) are …
Gene Delivery Of Adenoviral-Tmbim6 Vector Protects The Neonatal Brain After Hypoxic-Ischemic Injury, Desislava Doycheva
Gene Delivery Of Adenoviral-Tmbim6 Vector Protects The Neonatal Brain After Hypoxic-Ischemic Injury, Desislava Doycheva
Loma Linda University Electronic Theses, Dissertations & Projects
Neonatal hypoxia ischemia (HI) is an injury caused to the immature brain due to reduced cerebral blood flow which is associated with life-long neurological impairments. HI causes oxidative protein folding in the endoplasmic reticulum (ER), which results in ER stress. Generation of reactive oxygen species (ROS), from cytochrome P450 members (CYP) and NADPH-P450 reductases (NPR), in combination with activation of the unfolded protein response (UPR) are two major consequences of ER stress that cause oxidative damage and cell death. Herein we identified the role of Bax Inhibitor-1 (BI-1), an evolutionary conserved protein encoded by the Transmembrane Bax inhibitor Motif Containing …
Changes In The Morphology Of Hypoglossal Motor Neurons In The Brainstem Of Developing Rats, Paul Allen Williams
Changes In The Morphology Of Hypoglossal Motor Neurons In The Brainstem Of Developing Rats, Paul Allen Williams
Loma Linda University Electronic Theses, Dissertations & Projects
The autonomic brainstem generates and modifies breathing rhythm by integrating inputs from chemo- and mechanosensors in the viscera while coordinating descending outputs from higher CNS structures. Hypoglossal motoneurons (XII MNs) receive inputs from respiratory premotor neurons in the medulla. Previous studies in rodents have demonstrated significant changes in breathing control during the first three weeks of life, with a sensitive period at 10 to 13 days post-birth (P10–P13) characterized by pronounced changes in neurotransmitters, receptors, excitation-inhibition balance, and breathing. However, age-dependent morphological changes of XII MNs during the first three weeks post-birth and especially during this sensitive period, have not …
The Role Of Glucocorticoid Signaling In Prostate Cancer Health Disparities, Leanne W. Burnham
The Role Of Glucocorticoid Signaling In Prostate Cancer Health Disparities, Leanne W. Burnham
Loma Linda University Electronic Theses, Dissertations & Projects
African-American men are more likely to develop aggressive prostate cancer (PCa) and die from the disease than other ethnic groups. Glucocorticoid signaling is a contributing biological factor to worse PCa prognosis, and is emerging as a key driver of PCa progression in the absence of androgens. The mechanism involves glucocorticoids binding to glucocorticoid receptor (GR) and bypassing the androgen receptor (AR) signaling pathway to activate AR-target genes that promote tumor aggressiveness and therapy-resistance. This is problematic as African-American men have hypersensitive GR signaling and chronically-elevated levels of glucocorticoids linked to cumulative stressful life events. To explore the role of glucocorticoid …
Epidemiological, Environmental, And Biological Risk Factors For Gastroschisis, Arti Ketan Desai
Epidemiological, Environmental, And Biological Risk Factors For Gastroschisis, Arti Ketan Desai
Loma Linda University Electronic Theses, Dissertations & Projects
Gastroschisis, a congenital defect of the abdominal wall, manifests as external herniation of viscera, most commonly the fetal bowel. The worldwide prevalence of gastroschisis continues to rise, and this increase can also be seen in California with an overall birth prevalence of 2-3 per 10,000 births. While the etiology and pathogenesis of gastroschisis remains unknown, previous studies indicate several risk factors including young maternal age, nulliparity, and low maternal body mass index, in addition to environmental factors and exposure, given the increase in global prevalence with a predisposition of cases to occur in clusters, and absence of a genetic link. …
Endothelin-1 And Hypoxic Vascular Remodeling In Ovine Fetal Cerebral Arteries, Jinjutha Silpanisong
Endothelin-1 And Hypoxic Vascular Remodeling In Ovine Fetal Cerebral Arteries, Jinjutha Silpanisong
Loma Linda University Electronic Theses, Dissertations & Projects
Intrauterine hypoxia resulting from decreased maternal oxygen uptake, insufficient oxygen carrying capacity, or compromised oxygen delivery to the fetus jeopardizes fetal oxygen delivery, detrimentally affecting growth and development of the immature vasculature. Hypoxia transiently increases Hypoxia Inducible Factor-1α (HIF- 1α), which complexes with HIF-1β to form the active HIF-1 dimer that can affect transcription. This temporary rise in HIF-1 can promote gene transcription of ligands such as Vascular Endothelial Growth Factor (VEGF) and Endothelin-1 (ET-1), which rises and falls with HIF levels. The absence of chronic elevation of these ligands prompted the question of how long-term effects of hypoxia is …
The Role Of Vegf And Smooth Muscle Phenotype In Hypoxic Remodeling Of Ovine Carotid And Cerebral Arteries, Margaret C. Hubbell
The Role Of Vegf And Smooth Muscle Phenotype In Hypoxic Remodeling Of Ovine Carotid And Cerebral Arteries, Margaret C. Hubbell
Loma Linda University Electronic Theses, Dissertations & Projects
Arteries are a dynamic tissue with multiple cell types that incorporate systemic and local factors to maintain homeostasis. Hypoxia stimulates capillary angiogenesis to effectively match metabolic demand with perfusion. With chronic hypoxia, vascular remodeling of even large vessels can occur. This predisposes to pathologic states as seen with atherosclerosis, hypoxic brain injury, myocardial ischemia, diabetes, and developmental anomalies. With this remodeling comes changes in vessel structure including medial thickness and organization of contractile proteins as well as changes in myogenic tone. All of these factors culminate in changes in status or behavior of the vascular smooth muscle within the vessel …
Effect Of Extracellular Survivin And Lymphoma Exosomes On Natural Killer Cells, Heather R. Ferguson Bennit
Effect Of Extracellular Survivin And Lymphoma Exosomes On Natural Killer Cells, Heather R. Ferguson Bennit
Loma Linda University Electronic Theses, Dissertations & Projects
Tumors alter their microenvironment to promote survival using methods such as angiogenesis promotion, growth signals, and immune suppression. The immune system becomes unresponsive to transformed neoplastic cells through a variety of methods including T cell suppression, increased myeloid-derived suppressor cells (MDSCs), and reduced natural killer (NK) cell activity. NK cells have inherent killing capabilities and thus are among the first responders in recognizing and destroying abnormal cells. However, many types of cancers inhibit the surveillance and cytotoxic abilities of NK cells by releasing exosomes, vesicles that can modulate the tumor microenvironment (TME) and intercellular communication for the purpose of enhancing …
The Role Of Tgf-Β In Ctb-Insulin Regulated Human Dendritic Cell Tolerance, Grace Edosewe Esebanmen
The Role Of Tgf-Β In Ctb-Insulin Regulated Human Dendritic Cell Tolerance, Grace Edosewe Esebanmen
Loma Linda University Electronic Theses, Dissertations & Projects
Cholera toxin B subunit fusion to autoantigen vaccines such as proinsulin (CTB-INS) down regulates dendritic cell (DC) activation and induces the synthesis of DC immunosuppressive cytokines. Recent studies of CTB-INS induction of immune tolerance in human DCs indicate that increased IDO1 biosynthesis may play an important role in CTB-INS vaccine inhibition of DC activation. Previous studies suggest transforming growth factor beta (TGF-β) may play a role in the stimulation of IDO1 biosynthesis for induction of immunological tolerance in murine DCs. To elucidate the mechanisms by which CTB-INS may stimulate IDO1 biosynthesis and mediate tolerance in human DCs, we investigated the …
Targeting Ledgf/P75 To Sensitize Chemoresistant Prostate Cancer Cells To Taxanes, Leslimar Rios-Colón
Targeting Ledgf/P75 To Sensitize Chemoresistant Prostate Cancer Cells To Taxanes, Leslimar Rios-Colón
Loma Linda University Electronic Theses, Dissertations & Projects
Prostate cancer (PCa) is the second most diagnosed cancer in males. This disease disproportionately affects African American men, with a higher incidence and mortality compared to other ethnic/racial groups. An aging male population and the complexity of addressing the health disparities associated with this disease puts PCa into the spotlight due to its serious public health implications and the imminent fiscal challenge over the next decades. Chronic prostate inflammation resulting in activation of stress and prosurvival pathways contribute to disease progression and the development of chemoresistance. Lens epithelium-derived growth factor p75 (LEDGF/p75) is a stressresponse protein that promotes cellular survival …
Prenatal Undernutrition, Metyrapone, And The Cerebrovasculature, Lara Durrant
Prenatal Undernutrition, Metyrapone, And The Cerebrovasculature, Lara Durrant
Loma Linda University Electronic Theses, Dissertations & Projects
The link between intrauterine environmental conditions and adult cardiovascular system is well established. Independent of lifestyle factors such as poor diet and exercise habits, individuals who have been exposed to stressful conditions in utero show an increased risk of health problems such as hypertension, stroke, and type II diabetes. In support of the Fetal Origin of Adult Disease hypothesis, many labs have reported permanent anatomical and physiological changes associated with fetal stress and nutrient deficiency, with a focus on organ systems such as the kidney and heart. One key idea proposed by many of these studies is the glucocorticoid hypothesis, …
Pas Signaling Mechanisms In Aer And Aer2, Darysbel Garcia
Pas Signaling Mechanisms In Aer And Aer2, Darysbel Garcia
Loma Linda University Electronic Theses, Dissertations & Projects
PAS domains are widespread signal sensors that share a conserved three-dimensional αβ fold that consists of a central β-sheet flanked by several α- helices. The aerotaxis receptor Aer from Escherichia coli and the Aer2 chemoreceptor from Pseudomonas aeruginosa both contain PAS domains. Aer senses oxygen (O2) indirectly via an FAD cofactor bound to its PAS domain, while Aer2 directly binds O2 to its PAS b-type heme cofactor. The Aer and Aer2 PAS domains both interact with a signal transduction domain known as a HAMP domain. The PAS-HAMP arrangement differs between Aer and Aer2, with Aer- PAS residing adjacent to its …
A Novel Population Of Cardiovascular Progenitors Persist In Neonates As Mesendodermal Cells, Julia Kim
A Novel Population Of Cardiovascular Progenitors Persist In Neonates As Mesendodermal Cells, Julia Kim
Loma Linda University Electronic Theses, Dissertations & Projects
The rise in mortality due to cardiovascular disease has increased the need to develop an efficient regenerative therapeutic for heart failure. Numerous cell-based therapies have been investigated for myocardial regeneration; however, an optimal progenitor has yet to be discovered. Identifying a resident cell population with enhanced ability to differentiate into multiple lineages would greatly contribute to the field of stem cell-based regenerative therapy. Evidence suggests that endogenous cardiovascular progenitor cells (CPCs) that have been isolated from the heart itself express ISL1, KDR, and MESP1, and are capable of differentiating into all major cardiac lineages. The earlier developmental stage at which …
Anti-Tumor Mechanisms Of Hpv16 E6*, Whitney S. Evans
Anti-Tumor Mechanisms Of Hpv16 E6*, Whitney S. Evans
Loma Linda University Electronic Theses, Dissertations & Projects
High-risk types of the human papillomavirus (HR-HPV) are the causative agents of nearly all cases of cervical cancer, as well as a significant number of head, neck, penile, vulvar and anal cancers. Like many other viruses with small genomes, HPV (~8 kb) utilizes numerous mechanisms to increase the capacity of its genome to encode the proteins necessary for successful completion of its infectious life cycle, including alternative splicing. Studies over the past few decades have focused intensively on the activities and roles of E6 proteins from HR-HPVs during the process of cellular transformation, clearly implicating E6 as a major transforming …
Neuroprotective Molecules And Strategies In A Rat Model Of Neonatal Hypoxic Ischemic Encephalopathy, Brandon Joseph Dixon
Neuroprotective Molecules And Strategies In A Rat Model Of Neonatal Hypoxic Ischemic Encephalopathy, Brandon Joseph Dixon
Loma Linda University Electronic Theses, Dissertations & Projects
Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. Since there are no established therapies for …
Neuropsychological Effects Of Pomegranate Supplementation Following Ischemic Stroke, John A. Bellone
Neuropsychological Effects Of Pomegranate Supplementation Following Ischemic Stroke, John A. Bellone
Loma Linda University Electronic Theses, Dissertations & Projects
Polyphenols are compounds found in fruits and vegetables that have antioxidant and anti-inflammatory properties. Mounting evidence suggests that dietary polyphenol intake can reduce the detrimental effects of various disease processes, and pomegranates have frequently been examined because of their particularly high polyphenol content. Since stroke induces both oxidative stress and inflammation and is currently the leading cause of long-term disability in the U.S., we sought to determine whether dietary supplementation with polyphenols could enhance cognitive recovery in individuals who had suffered an ischemic stroke. We administered polyphenols via 2 POMx pills containing polyphenols derived from pomegranates equivalent to the content …
Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay
Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay
Loma Linda University Electronic Theses, Dissertations & Projects
Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It …
The Role Of Collagen Interacting Proteins In The Pathogenesis Of Filifactor Alocis, Ozioma Salomey Chioma
The Role Of Collagen Interacting Proteins In The Pathogenesis Of Filifactor Alocis, Ozioma Salomey Chioma
Loma Linda University Electronic Theses, Dissertations & Projects
Filifactor alocis is a Gram-positive, asaccharolytic; obligate anaerobe that has emerged as a potential periodontal pathogen due to its presence in high numbers in patients who have periodontal disease and least detection in healthy individuals (Kumar et al., 2003, Kumar et al., 2006, Wade, 2011). There is compelling evidence in the literature that demonstrates that F. alocis has virulence properties that may play an important role in infection-induced periodontitis (Abusleme et al., 2013, Griffen et al., 2012, Hutter et al., 2003, Khader et al., 2006, Siqueira and Rocas, 2003, Siqueira et al., 2009). However, there is a gap in our …
Mechanisms Of Post-Hemorrhagic Hydrocephalus After Germinal Matrix Hemorrhage, Damon William Klebe
Mechanisms Of Post-Hemorrhagic Hydrocephalus After Germinal Matrix Hemorrhage, Damon William Klebe
Loma Linda University Electronic Theses, Dissertations & Projects
The inherently fragile vasculature of the germinal matrix is susceptible to rupture, possibly as a result of hemodynamic and cardiorespiratory instability associated with prematurity. Germinal matrix hemorrhage is a leading cause of morbidity and mortality in preterm and/or very low birthweight infants, and post-hemorrhagic hydrocephalus is major consequence of severe grade hemorrhages. Chronic post-hemorrhagic hydrocephalus treatment involves surgical insertion of shunts, which are costly and prone to complications. Thus, a safe non-invasive therapeutic approach towards post-hemorrhagic hydrocephalus clinical management would significantly improve the quality of life for this patient population. Thrombin, cerebroventricular blood clots, and iron have been identified as …
Role Of Protein Kinase G In Regulating Vascular Tone In Hypoxic Ovine Cerebral Arteries, Richard Burdette Thorpe
Role Of Protein Kinase G In Regulating Vascular Tone In Hypoxic Ovine Cerebral Arteries, Richard Burdette Thorpe
Loma Linda University Electronic Theses, Dissertations & Projects
Nitric oxide (NO) and its precursors have been used clinically to induce vasorelaxation long before the specific mechanism of how this operates was understood. With the discovery in 1977 of the influence of NO on guanylate cyclase, and the subsequent elucidation of the NO pathway, the role of cyclic guanidine monophosphate (cGMP)-dependent protein kinase (PKG) has been shown to be the main mediator of NO-induced vasorelaxation. Less well understood is the behavior of this pathway in conditions of long term hypoxia (LTH). It was later shown that LTH attenuates the ability of PKG to mediate vasorelaxation. How this operates is …
Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue
Mechanism Of Chimeric Vaccine Mediated Immune Suppression Of Human Dendritic Cells, Jacques Christian Mbongue
Loma Linda University Electronic Theses, Dissertations & Projects
Type 1 diabetes mellitus is a chronic inflammatory disease in which insulin producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Dendritic cells (DC) interact predominantly with naïve T cells to regulate the delicate balance between immunity and tolerance required to maintain immunological homeostasis. In this dissertation, immature human dendritic cells (iDC) were inoculated with a chimeric fusion protein vaccine containing the pancreatic β-cell auto-antigen proinsulin linked to a mucosal adjuvant the cholera toxin B subunit (CTB-INS). Proteomic analysis of vaccine inoculated DCs revealed strong up-regulation of …