Medical Sciences Commons^™

Mechanisms Of Brain Edema Formation In Mouse Models Of Intracerebral Hemorrhage, Qingyi Ma

Loma Linda University Electronic Theses, Dissertations & Projects

Perihematomal edema causes major neurologic deterioration following intracerebral hemorrhage (ICH), mainly resulting from the disruption of the blood-brain barrier (BBB) by multiple mediators, including inflammatory mediators and thrombin. The objective of our study was to investigate the mechanisms by which inflammation and thrombin respectively lead to the formation of brain edema following ICH. Our long-term goal is to develop new therapeutic strategies against ICH-induced brain edema by targeting: (1) VAP-1 mediated inflammatory response and (2) PDGFR-α orchestrated BBB impairment. Vascular adhesion protein-1 (VAP-1) was previously shown to promote leukocyte adhesion and transmigration. Additionally, PDGFR-α was also found to play a …

Mechanisms Of Erythropoietin-Induced Neuroprotection In: In-Vivo And In-Vitro Models Of Hypoxia Ischema, Rhonda Andrea Souvenir

Loma Linda University Electronic Theses, Dissertations & Projects

Hypoxic ischemic brain injury (HIBI) is a common cause of neonatal mortality and morbidity. Approximately 60 % of preterm babies and 2% of full term infants suffer from asphyxia. Asphyxia related death accounts for approximately 23% of neonatal mortality annually. Many therapeutic interventions show promise in the laboratory but fail in clinics. A thorough understanding of mechanisms by which promising therapeutic intervention confers its neuroprotection is necessary to promote smoother transitions from bench to the bedside. Erythropoietin (EPO), a hematopoietic growth factor that increases oxygen availability during hypoxia/ischemia is associated with cell survival and neuroprotection in: in vivo and in …

Characterization Of Palmitic Acid Induced Lipotoxicity In Schwann Cells, Amelia Padilla

Loma Linda University Electronic Theses, Dissertations & Projects

Lipotoxicity is a response to lipid overload that has been associated with cellular dysfunction leading to cellular death. The mechanism of lipotoxicity and its impact on the nervous system is critical as it can lead to debilitating neurological conditions. This study examines key cellular events induced by palmitic acid lipotoxicity (PA-LTx) in Schwann cells cultured in euglycemic and hyperglycemic conditions. The data show that immortalized Schwann cell (iSC), as well as primary Schwann cell (pSC) cultures exposed to elevated levels of PA induced an apoptotic cell death that is dose and time-dependent. The earliest indication of cellular dysfunction was a …

Role Of Vima In Cell Surface Biogenesis In Porphyromonas Gingivalis, Devon Osbourne Jr.

Loma Linda University Electronic Theses, Dissertations & Projects

Porphyromonas gingivalis is an important etiological agent of periodontal disease - a disease that affects an estimated 49,000,000 people in the United States of America. Periodontal disease includes gingivitis – inflammation of the gums, and periodontitis – destruction of the teeth and their supporting tissues. Porphyromonas gingivalis is associated with the chronic form of periodontal disease in addition to several systemic diseases.

The vimA gene of P. gingivalis has been previously shown to play a significant role in the biogenesis of gingipains (trypsin-like cysteine proteases). The vimA has also been demonstrated to play a role in hemolysis, hemagglutination, autoaggregation, posttranslational …

Chronic Hypoxia Induces Epigenetic Modifications In The Fetal Rat Heart, Andrew James Grant Patterson

Loma Linda University Electronic Theses, Dissertations & Projects

Heart disease remains the leading cause of death worldwide. As a result of studies done by Barker and associates, our awareness of the significance of stress during gestation as a risk factor for heart diseases has expanded. We now know that events in utero can significantly alter gene expression patterns in heart tissue leading to increase susceptibility to ischemia reperfusion injury in adulthood. The focus of this project was to elucidate the role of chronic hypoxia in the programming of the cardio-protective gene, Protein Kinase C epsilon (PKCε) in fetal rat heart. We used an animal, organ base, and cell …

Aging And Sympathetic Neurotransmission In Two Strains Of Rats That Differ In Longevity And Immune Profiles, Sam David Perez

Loma Linda University Electronic Theses, Dissertations & Projects

Age-related changes in sympathetic neurotransmission in immune organs may be associated with immunosenescence; however no causal relationship has been established. From previous studies in Fischer rats (F344), we have found that during middle age, sympathetic nerve activity (SNA) rises in the spleen followed by a decline in noradrenergic (NA) innervation. Also, increased sympathetic signaling via betaadrenergic receptor (β-AR) and reduced proliferation of lymphocytes are evident with increasing age. Although SNA progressively rises with age, effects of age on sympathetic factors may be different across rat strains. If causal relationships exist between sympathetic activity and immune function, they may be related …

Lateralization Of Emotion, Reaction Time, And Skin Conductance Responsiveness, Kimberley Erin Rose

Loma Linda University Electronic Theses, Dissertations & Projects

Bilateral presentations of brief (250 ms), unmasked emotional and neutral stimuli were examined in two experiments with primarily female samples. Reaction time and accuracy data were used to measure perception of emotion and skin conductance response (SCR) was used to measure experience of emotion. Both words and pictures were used to account for hemispheric differences in language and visuospatial dominance. Response time was faster to emotional pictures than words. Reaction time and speeded accuracy data did not support right hemisphere hypothesis (RHH) or valence hypothesis (VH) in the expected manner. Data suggested emotion caused greater interference under speeded conditions in …

Biochemical And Functional Characterization Of The Ledgf/P75-Mecp2 Interaction In Tumor Cells, Lai Sum Leoh

Loma Linda University Electronic Theses, Dissertations & Projects

The lens epithelial derived growth factor p75 (LEDGF/p75) is a novel pro-survival and stress-inducible transcription co-activator that protects mammalian cells from various environmental stresses such as oxidative stress, heat shock, and serum starvation. This emerging cancer-related protein is highly expressed in prostate tumors and other tumor types and promotes resistance to chemotherapy in cancer cells. LEDGF/p75 is also involved in acquired immunodeficiency syndrome (AIDS) since it interacts with HIV-1 integrase to facilitate the integration and replication of the HIV virus in human cells. In addition, LEDGF/p75 has been shown to interact with MLL (mixed lineage leukemia)/menin transcription complex in leukemia …

Nanomaterials And Block Copolymers For Overcoming Multidrug Resistance In Cancer, Wesley Livingstone

Loma Linda University Electronic Theses, Dissertations & Projects

The development of multidrug resistance in cancer is one of the leading causes for decreased chemotherapy efficacy and is particularly threatening to aggressive cancers such as that of the pancreas. In cancers where chemotherapy is amongst the few treatment options, it is crucial to develop chemotherapeutics that either bypass or control the development of multidrug resistance. Polymeric nanomaterials such as Pluronics® are of current interest due to their ability to perform these functions in addition to enhancing pro-apoptotic mechanisms. Using the respectively known chemosensitive and chemoresistant pancreatic adenocarcinoma cell lines MiaPaCa-2 and PANC-1, an in vitro analysis of the synergistic …

Cholera Toxin B Subunit-Diabetes Autoantigen Fusion Proteins Modulate Dendritic Cell Function And T Cell Morphogenesis, Oludare Jeremiah Odumosu

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus is a chronic inflammatory disease in which the insulin and glutamic acid decarboxylase producing β-cells of the pancreatic islets are killed by autoreactive cells of the immune system in response to a loss of tolerance. Early experiments showed that self-tolerance could be partially restored by oral inoculation with small amounts of insulin. Later experiments showed that insulin autoantigen induced immune tolerance could be greatly enhanced by linkage of β-cell autoantigens (Auto Ag) to adjuvant molecules such as the non-toxic cholera enterotoxin B subunit (CTB). To identify mechanisms responsible for CTB-autoantigen fusion protein suppression of diabetes autoimmunity, …

Dna Repair Of 8-Oxo-7,8-Dihydroguanine Lesions In Porphyromonas Gingivalis, Leroy G. Henry Jr.

Loma Linda University Electronic Theses, Dissertations & Projects

The persistence of Porphyromonas gingivalis in the inflammatory environment of the periodontal pocket requires an ability to overcome oxidative stress. DNA damage is a major consequence of oxidative stress. Unlike other organisms, a non-base excision repair mechanism for the removal of 8-oxo-7,8-dihydroguanine (8-oxoG) in P. gingivalis was suggested. Because the uvrB gene is known to be important in nucleotide excision repair, the role of this gene in the repair of oxidative stress-induced DNA damage was investigated. A 3.1 kb fragment containing the uvrB gene was PCR-amplified from the chromosomal DNA of P. gingivalis W83. This gene was insertionally inactivated using …

Dynamic Contrast-Enhanced Mri Of Pancreatic Islet Transplants, Nathaniel K. Chan

Loma Linda University Electronic Theses, Dissertations & Projects

Since its discovery in 1922, insulin has been the life-saving treatment for type 1 diabetes mellitus. As the disease is caused by the loss of insulin-producing pancreatic islets, transplantation of donor islets has the potential to not only supplement insulin replacement therapy but to cure type 1 diabetes. However, long-term insulin independence (> 2 years post-transplant) remains a challenge partly due to low islet blood flow immediately following transplantation leading to hypoxic stress on islets. The goal of our studies is to improve islet engraftment by monitoring and promoting the regrowth and maturation of new islet blood vessels in a …

Influence Of Gender And Aerobic Training Background On Exercise-Induced Increase In Adiponectin, Pooja Pratap Mujumdar

Loma Linda University Electronic Theses, Dissertations & Projects

Adipose tissue secretes the adipokine, adiponectin (ADPN), which is insulinsensitizing, anti-inflammatory, and anti-atherogenic. Exercise training improves insulin sensitivity and lowers the risk of cardiovascular complications. As some of the metabolic effects of exercise training and ADPN overlap, exercise training has been proposed to increase ADPN. However, most single bout exercise, or short-term (ï‚£3 months) and constant-effort (fixed session duration, fixed number of sessions/week, and fixed intensity) exercise protocols do not produce increases in ADPN in untrained and trained cohorts. Furthermore, most exercise studies were conducted on male-female mixed gender cohorts or male/female single gender cohorts. As a result, no direct …

Novel Molecules That Regulate Bone Formation And Bone Resorption, Gabriel Robert Linares

Loma Linda University Electronic Theses, Dissertations & Projects

Osteoporosis is a disease characterized by decreased bone mass and microarchitectural deterioration of bone. Bone loss occurs when the increased bone resorption that occurs with age is not compensated by a corresponding increase in bone formation. Therefore, understanding the mechanisms which regulate bone formation and bone resorption is important for developing diagnostic and treatment strategies for osteoporosis. In my dissertation, we investigated the role of Glutaredoxin 5 (Grx5), Diabetes and Obesity Related protein (DOR), and Claudin 18 (Cldn-18), novel molecules involved in regulating bone formation and bone resorption. We demonstrated that Grx5 protects osteoblasts from oxidative stress induced apoptosis via …

Igf2 Promotes Activation Of Estrogen Receptors In Basal-Like Breast Cancer Cells, Angelique Richardson

Loma Linda University Electronic Theses, Dissertations & Projects

The autocrine-paracrine effects of IGF2 are important in the growth and differentiation of normal breast. In breast cancer (BC), IGF2 is initially stimulated by estrogen, progesterone and prolactin to regulate proliferation and cancer progression. These actions are mediated by the IGF-1R and insulin receptor A (IR-A) both members of the tyrosine- kinase receptors family. The activation of Estrogen Receptor (ER) is also very important in BC growth and progression. As BC progresses to estrogen-independent growth, the IGF-1R and the estrogen receptor (ER) interact in crosstalk mechanisms that are synergistic and results in enhanced activation of both receptors signaling cascades. This …