Chemicals and Drugs Commons^™

Radiosensitization Of Head & Neck Carcinoma Cells By Linifanib, A Receptor Tyrosine Kinase Inhibitor, Heng-Wei Hsu

Loma Linda University Electronic Theses, Dissertations & Projects

Tumor angiogenesis is a hallmark of advanced cancers and promotes invasion and metastasis. Over 90% of head and neck squamous cell carcinomas (HNSCC) express angiogenic factors such as vascular endothelial growth factor (VEGF). Since radiotherapy is one of the most commonly used treatments for HNSCC, it is imperative to identify the interactions between antiangiogenic therapy and radiotherapy, and to develop combination therapy to improve clinical outcome. The mechanisms between antiangiogenic agents and ionizing radiation are complicated and involve many interactions between the vasculature, tumor stroma and tumor cells. The proliferation and metastasis of tumor cells rely on angiogenesis/blood vessel formation. …

Ricin B Chain-Insulin Fusion Protein Immunomodulation Of Type 1 Diabetes, James Edward Carter Iii

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus (T1D) is a debilitating chronic inflammatory disease of the insulin-producing pancreatic islet β-cells that results from a combination of genetic and environmental factors. Attempts to suppress Th1-mediated autoimmune diseases such as T1D by mucosal delivery of autoantigens for immunotolerization have yielded only partial success. Attainment of satisfactory levels of sustained immunological tolerance remains to be accomplished. To restore self-tolerance requires delivery of sufficient amounts of autoantigen to stimulate regulatory T helper cells that function to survey the gut and induce tolerance to consumed antigens such as food. Oral delivery of autoantigens has previously been shown to …

Postprandial Effects Of Pecans Ingestion On Plasma Level Of Nutrients, Polyphenolic Compounds And Biomarkers Of Antioxidant Status In Human Volunteers, Chatrapa Hudthagosol

Loma Linda University Electronic Theses, Dissertations & Projects

Pecans (Carya illinoinensis) are rich sources of polyphenolic compounds and nutrients, which have antioxidant capacity results in favorable reductions in plasma lipids and lipoproteins. However, the health benefits of pecans may not be limited to blood lipid changes. There has been very little investigation into the contribution of bioactive components found in nuts to antioxidant protection. The purposes of the study were 1) to determine the impact of pecan consumption on concentration of total plasma polyphenols and their peak concentration over time. 2) to measure the effect of a pecan diet on postprandial levels of plasma lipid peroxidation …

Novel Binding Domains Mediate Binding Of Hpv 16 E6 To Fadd And Procaspase 8, Sandy S. Tungteakkhun

Loma Linda University Electronic Theses, Dissertations & Projects

To evade the host response to infection, viruses have developed means to survive and propagate. HPV 16, a causative agent of cervical cancer and of some cases of oropharyngeal cancers, is one example. We have reported that the early viral protein E6 binds to proteins necessary for propagation of the apoptotic signal following receptor/ligand interactions, such as those mediated by FADD DED and procaspase 8 DED. E6 expression leads to the dose-dependent accelerated degradation of FADD and the protection of E6-expressing cells from Fas-induced apoptosis. Surprisingly, the splice isoforms of E6, E6_large and E6*, affect the stability of procaspase …

Radiation-Induced Glutamate Transport Alterations In Neuron-Astrocyte Coupling, Martha Celia Sanchez

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure of the central nervous system (CNS) to ionizing radiation is known to result in behavioral, cognitive, and motor deficits - effects similar to those seen in many neurodegenerative disorders. Neurons and astrocytes, two principal cell types in the brain, coexist as an interdependent metabolic unit via the neurotransmitter glutamate. Disruption of this metabolic coupling would have widespread effects within the CNS, therefore it is hypothesized that ionizing radiation impairs glutamate transport and metabolism, and increases oxidative stress, ultimately impairing neuron-astrocyte coupling. We propose to investigate the mechanism and determine the impetus for radiation-induced neurotoxicity by measuring the temporal sequence …

Gene Expression In The Mouse Placenta: Developmental And Stress Responses, Ciprian P. Gheorghe

Loma Linda University Electronic Theses, Dissertations & Projects

Successful placental development is crucial for optimal growth, maturation, and survival of the embryo/fetus. Placental failure and placental pathology contributes to both morbidity and mortality of the fetus. We sought to understand normal placental development and also placental responses to stress using oligonucleotide microarray technology. To examine genetic aspects of normal placental development, we investigated gene expression patterns in the murine placenta at embryonic day 10.5 (E10.5), E12.5, E15.5, and E17.5. Hypoxia has been identified as a major stressor in placental and fetal development. In order to comprehend more completely hypoxic stress responses we sought to measure gene expression changes …

The Acute Effects Of Nut Ingestion On Plasma Levels Of Polyphenol Compounds, Biomarkers Of Antioxidant Status, And Lipid Peroxidation, Setareh Torabian Esfahani

Loma Linda University Electronic Theses, Dissertations & Projects

Nuts are rich sources of polyphenolic compounds and nutrients, which have antioxidant capacity. To assess the acute effect of treatment diet (75% of energy from nuts (walnut or almond) and control diet (habitual diet with no nut consumption) in healthy subjects on plasma total phenol content, antioxidant capacity and plasma lipid peroxidation. Thirteen subjects participated in the crossover design study. After an overnight fast, walnut, almond and a control diet, in form of smoothies, were consumed by the study subjects. Each subject participated on three occasions one week apart, consuming one of the smoothies each time. Blood samples were obtained …

Effects Of Feeding Regular Eggs, N-3 Fatty Acid Enriched Eggs, And Walnuts, On Blood Lipids, Membrane Incorporation Of Fatty Acids, And Serum Lutein, In Free-Living Lacto-Ovo Vegetarians, Bonny Burns-Whitmore

Loma Linda University Electronic Theses, Dissertations & Projects

Americans do not receive enough n-3 fatty acids (F. A.) in their diets. Walnuts are good source of α-linolenic acid (ALA), while n-3 F.A. enriched eggs provide a dietary source of DHA. Whether ALA and DHA have equivalent effects modifying cardiovascular risk factors is not known. This study compared the changes in blood and erythrocyte membrane lipids in twenty free-living lacto-ovo vegetarians following the consumption of regular eggs (6/wk), n-3 F.A. enriched eggs (6/wk), or walnuts (6 oz/wk) in a triple crossover design.

Results indicate significant differences between treatments for serum triacylglycerols (TAGs), total cholesterol (TC), apo B, apo B: …

Enterotoxin B Subunit Lectins As Adjuvants For Improvement Of Mucosal Vaccine, Nak-Won Choi

Loma Linda University Electronic Theses, Dissertations & Projects

In comparison with whole organism vaccines, subunit vaccines may be safer for immunization but may lack sufficient immunogenicity to provide complete immunity to the pathogen. To resolve this problem, bacterial and plant enterotoxin B subunit adjuvants containing a variety of receptor-binding properties were used to enhance the immunogenicity of rotavirus subunit vaccines. Enterotoxin B subunit adjuvants were employed to enhance protection against virus infection. Pentameric cholera toxin B subunit (CTB), shiga toxin-1 B subunit (STB) and monomeric ricin toxin B subunit (RTB) molecules were genetically linked to a 90 amino acid peptide from the simian rotavirus (SA11) nonstructural protein NSP4 …

Effect Of Monounsaturated Fat Rich Almonds On Hemostatic And Inflammatory Factors In Healthy Adults, Kristianne M. Connell

Loma Linda University Electronic Theses, Dissertations & Projects

Background: The frequent consumption of nuts is inversely associated with the incidence of cardiovascular disease. Nuts are known to decrease the risk of cardiovascular disease by reducing serum total and low-density lipoprotein (LDL) cholesterol. Markers of inflammation including C-reactive protein, E-selectin and interleukin-6 have been proposed to be newer risk factors for cardiovascular disease. However, the influence of nuts such as almonds on markers of inflammation and hemostasis that influence cardiovascular disease risk is not currently known.

Objective: The objective of this study was to determine the effect of almond consumption on markers of inflammation and hemostatic factors in healthy …

Glucocorticoid Regulation Of Insulin Like Growth Factor Binding Protein-5 Gene Transcription In Human Osteoblasts, Xiaoying Wang

Loma Linda University Electronic Theses, Dissertations & Projects

Glucocorticoids (GCs) inhibit bone formation in vivo and inhibit osteoblast proliferation and collagen synthesis in vitro. These effects may be mediated by alterations in the insulin-like growth factor (IGF) system. In the present study of normal human osteoblast-like (HOB) cells, we tested the hypothesis that dexamethasone (Dex) inhibits the expression of IGF binding protein-5 (IGFBP-5). Dex decreased IGFBP-5 mRNA levels to 54% of control after 4 hr. Dex did not modify the decay of IGFBP-5 mRNA in transcriptionally arrested osteoblast cells. Dex decreased IGFBP-5 hnRNA levels to 67% of control after 2 hr, and the activity of the human IGFBP- …

The Role Of Gap Junctions In Congenital Diseases Of The Heart, Scott Henry Britz-Cunningham

Loma Linda University Electronic Theses, Dissertations & Projects

Background. Gap junctions are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. Connexin43, the major protein of gap junctions in the heart, is targeted by several protein kinases that regulate myocardial cell-cell coupling. We hypothesized that mutations altering sites critical to this regulation would lead to functional or developmental abnormalities of the heart.

Methods. Connexin43 DNA from 25 normal subjects and 30 children with a variety of congenital heart diseases was amplified by the polymerase chain reaction and sequenced. Mutant DNA was expressed in cell culture and examined for its effect …

Cellular Responses In Escherichia Coli To Lethal And Sublethal Doses Of Ozone, Indira Ruth Komanapalli

Loma Linda University Electronic Theses, Dissertations & Projects

Ozone is a major component of photochemical smog. High levels of this pollutant, sufficient to affect human health are found in many urban areas worldwide. Though limited studies in humans are supported by extensive findings from animal experiments, a difficulty in interpreting the results of these experiments has lead to an ambiguity on the biochemical mechanism of ozone toxicity. To elucidate the mechanism by which ozone causes cell damage and eventual cell death we conducted a comprehensive study using Escherichia coli K-12 as a model.

Studies on the comparative inactivation of bacteriophage lambda (λ), Escherichia coli, and Candida albicans …

Cerebral Microcirculatory Effects Of Maturation, Scott R. Elliott

Loma Linda University Electronic Theses, Dissertations & Projects

The present studies demonstrate that in the second (2B) and fourth (4B) branches of newborn and adult sheep middle cerebral arteries, 5-HT2 serotonergic receptors mediate contractile responses to serotonin and that alpha-1 adrenergic receptors mediate contractile responses to norepinephrine. In addition, tissue sensitivity to 5-HT and NE decreases significantly with maturation, but does not vary with branch order. These age-related changes were associated with a decrease in affinity and maximum response in 2B and 4B segments of 5-HT and NE contracted arteries, respectively. Norepinephrine and 5-HT occupancy at the pD₂ rose significantly in 2B segments, but did not change …

Signal Transduction In Bacterial Chemotaxis, Edward Heath Rowsell

Loma Linda University Electronic Theses, Dissertations & Projects

This study investigated the site of ATP utilization in the signal transduction pathway of bacterial chemotaxis and localized the point of convergence of a methylation-independent system of chemotaxis with the methylation-dependent system. The identity of the signal originating from the phosphotransferase system was investigated by substituting the fructose-inducible HPr-like protein FPr for HPr in transport and chemotaxis. In addition, a novel chemoattractant, glycerol, was identified for Salmonella typhimurium. Histidine-auxotrophic S. typhimurium strains ST23 (hisF) and ST171 (hisF cheB) were depleted for ATP. The times required for the bacteria to adapt to a step increase in serine, …

Catecholamines And The Regulation Of Uterine Contractions In The Pregnant Rhesus Macaque, Cahleen Mae Mcnutt

Loma Linda University Electronic Theses, Dissertations & Projects

This study was designed to test the hypothesis that: 1) maternal and/or amniotic fluid catecholamines or prostaglandins display nocturnal activity rhythms similar to those of the myometrial contractility in the pregnant rhesus macaque and, 2) catecholamines stimulate prostaglandin production by fetal membranes. Paired maternal arterial blood and amniotic fluid samples were collected at 0900 h (AM) and 2100 h (PM) from chronically catheterized rhesus macaques until delivery and analyzed for prostaglandin metabolites (PGFM and PGEM-II) and catecholamines (norepinephrine, epinephrine, and dopamine). Uterine activity data was continuously recorded. A rhythm in uterine contractility was observed, with peak activity between 1900 and …

Effect Of Glucose Administration On Hamster Liver S9-Mediated Mutagenesis, Metabolism And Dna-Binding Of Benzo[A]Pyrene And Aflatoxin B1, Daniel C. Rubano

Loma Linda University Electronic Theses, Dissertations & Projects

Hamster liver S9 prepared from control animals and animals given 30% glucose in drinking water 48 h before time of sacrifice was used in studies of benzo[a]pyrene (BaP) and aflatoxin (AFB₁)-induced mutagenesis, metabolism of BaP and AFB₁, and metabolite binding to calf thymus DNA. BaP-induced mutagenesis in Salmonella typhimurium TA100 was reduced 38.5% while AFB₁-induced mutagenesis was increased 36% by S9 from glucose-treated hamsters. The reduction of [³H]BaP metabolite binding to calf thymus DNA in incubations with S9 from glucose-treated hamsters correlated with a decrease in unknown BaP metabolite-deoxyribonucleoside adducts isolated by …

Effect Of Photoperiod On Developmental Morphology And Enolase Isoenzyme Immunohistochemistry In Rat And Djungarian Hamster Superficial Pineal Glands, Chalmer D. Mcclure

Loma Linda University Electronic Theses, Dissertations & Projects

The best understood functional activity of the pineal gland is its diurnal production of melatonin in response to environmental lighting cues. Several enzymes of the melatonin pathway respond to daily photoperiod changes, for example hydroxyindole-O-methyltransferase (HIOMT) and serotonin N-acetyltransferase (SNAT). Increased levels of the glycolytic enzyme neuron-specific enolase (NSE) are thought to reflect increased physiological demands placed on neurons and neuroendocrine tissues. Homodimer non-neuronal enolase isoenzyme (NNE) is immunolocalized to cells, and the hybrid enolase (consisting of subunits from NSE and NNE) has been seen in cerebellar stellate and basket cells. Although not rate limiting, concentrations of both NSE and …

Autonomic Nervous System And Cholesterol Transport, Yuan-Line Hung

Loma Linda University Electronic Theses, Dissertations & Projects

The effect of autonomic nervous system on cholesterol transport is of clinical interest because the relationship between lipoprotein metabolism and atherogenesis is expressed in coronary artery disease.

Generally speaking, beta blockers increase serum VLDL level but decrease both HDL and HDL₂ cholesterol levels without affecting the LDL in humans. We are unaware of reports concerning the effects of metoprolol on lipoprotein metabolism nor comparison of the effects of metoprolol and propranolol in the unhandled rat model. In part I we employed the unhandled rats to compared the effects of these 2 drugs administered with the drinking water in order …

Interaction Of Putative Estrogens And The Estrogen Receptor System In Leydig Cells In The Balb/C Mouse Testis Resulting In The Initiation Of Dna Synthesis, R. Lloyd Juriansz

Loma Linda University Electronic Theses, Dissertations & Projects

Continuous administration of estrogens for 7-9 months, both steroidal and nonsteroidal, to male BALB/c mice, leads to the formation of testicular Leydig cell tumors. Three days following the subcutaneous implantation of a pellet of estrogen in cholesterol, there is a peak in the incorporation of ³H-tymidine into the DNA of the interstitial cells. These effects are hypothesized to be mediated by the estrogen receptor system in the Leydig cell. Common experimental techniques for the measurement of hormone binding, such as dextran coated charcoal treatment, proved to be impossible to employ in this system, therefore a procedure was developed using …

The Effect Of Dietary Alpha - Linolenic Acid On Apparent Risk Factors Of Cardiovascular Disease, Kelvin D. Lindbeck

Loma Linda University Electronic Theses, Dissertations & Projects

Eight healthy male lacto-ovo-vegetarian subjects averaging 28.0 ± 3.6 years of age (22 to 53 years) were fed a diet rich in α-linolenic acid (18:3 ω 3) for four weeks. Arterial blood pressure and body weight were recorded each week. Plasma 6-keto-prostaglandin F_1α (6-keto- PGF_1α ), thromboxane B₂ (TXB₂), total cholesterol, triglyceride, and total phospholipid fatty acid composition were analyzed at 0, 2 and 4 weeks.

Systolic blood pressure increased significantly between weeks 0 and 1 (106.5 ± 2.7 mmHg to 114.0 ± 3.7 mmHg; p < 0.003), but decreased to 107.3 t 2.6 mrHg (p < 0.02) at week 2. There was an insignificant increase in both systolic and diastolic blood pressures after four weeks. There was no significant change in either total cholesterol or triglyceride levels during the four weeks.

Plasma 6-keto-PGF_1α levels increased significantly from 60.13 ± …

Muscle Catabolism During A Protein Sparing Modified Fast As Measured By Urinary 3-Methylhistidine, Judith D. Nielsen

Loma Linda University Electronic Theses, Dissertations & Projects

The urinary excretion of 3-Methylhistidine was used as an index of muscle catabolism in four groups of obese persons receiving a Protein Sparing Modified Fast (PSMF). The composition of the supplements were as follows: Group I: 75 g protein, 25 g complex carbohydrate (starch) per day; Group II: 25 g protein, 75 g complex carbohydrate (starch) per day; Group III: 75 g protein, 25 g simple carbohydrate (glucose) per day; Group IV: 25 g protein, 75 g simple carbohydrate (glucose) per day. The PSMF lasted for seven days and a 24-hour urine sample was collected at the beginning of the …

Lipoprotein Lipase Inhibitor Removal During Ultrafiltration Of Renal Failure Patients, Alisa Minear

Loma Linda University Electronic Theses, Dissertations & Projects

Plasma samples were obtained from seven hypertriglyceridemic (>150 mg/dl) chronic renal failure patients before and after regular hemodialysis. The effect of the plasma on the lipolytic activity of bovine milk lipoprotein lipase was investigated. The lipoprotein lipase activity, as measured by release of C¹⁴-labeled free fatty acid from triglyceride, was decreased 8-67% when incubated with uremic plasma as compared to the control plasma (44 mg/dl triglyceride). The inhibition noted prior to hemodialysis did not appear to be alleviated by the dialysis but subsequent treatment with an isolated ultrafiltration technique did appear to remove an inhibitory substance as …

The Relationship Of Alcohol Consumption In Rats To Morphine And Codeine Intake And The Metabolism Of Dopamine, Hsiu Fen Liu

Loma Linda University Electronic Theses, Dissertations & Projects

The effects of morphine and codeine free-choice alcohol consumption in male Sprague-Dawley rats were studied. Intakes of a 10% alcohol solution in milliliters per 100 gm. of body weight were on recorded weekly. No difference was found in the alcohol intake of rats given either a morphine-supplemented diet (0.01% of the diet) or daily injection of morphine sulfate (2 mg./kg.); however, there was a significant lower intake of water (p < .05) in those rats fed the diet with morphine. Total fluid consumption of both groups given the morphine-supplemented diet and daily injection of morphine sulfate was decreased (p < .05). It was found that morphine did not affect the percentage of total fluid consumed as alcohol or the weight gain.

Two levels of codeine phosphate (10 mg./kg. and 20 mg./kg.) were injected subcutaneously into rats twice a day. It was observed that the codeine significantly decreased alcohol intake in rats …

The Duration Of The Effect Of Different Carbohydrates On Neutrophilic Phagocytosis, Judy L. Reeser

Loma Linda University Electronic Theses, Dissertations & Projects

In order to determine the duration of the effect of glucose, fructose, sucrose, honey, starch, and orange juice on neutrophilic phagocytosis, 10 subjects underwent a complete series of carbohydrate tolerance tests. Blood samples were drawn at specific time periods following ingestion of 100 grams of each carbohydrate. Blood was then analyzed for glucose and phagocytic index (the mean number of bacteria engulfed per leukocyte); a red blood cell and white blood cell count and differential white cell count were done also on about 1/2 of the samples. In addition, 7 other subjects participated in a fasting study in which no …

Some Aspects Of Carbohydrate Metabolism In The Cercariae Of Schistosoma Mansoni Sambon, 1907, A. Eugene Dunham Jr.

Loma Linda University Electronic Theses, Dissertations & Projects

Cercariac of Schistosoma mansoni were studied for glycogen utilization, uptake of glucose from solution, lactic acid production, and respiration.

Using the anthrone method of determination of carbohydrate, the amount of glycogen used by a single cercaria in 4 hours is determined as 43.2 x 10^-4 μg ± 6.6 x 10^-4 μg.

Glucose was not observed to have been used from solution under the conditions of the experiment, even in the presence of trehalose. The determinations were made by the Glucostat method.

After deproteinization and desugarization, aliquots of supernatant from cercarial suspensions were analyzed for lactic acid using p-phenylphenol …

The Effect Of Varying Protein Intake On Trichinella Spiralis Infection In Mice, Clare K. Kwan

Loma Linda University Electronic Theses, Dissertations & Projects

Three hundred Swiss Webster albino mice three weeks of age were placed on low (8%), medium (24%), high (48%) protein levels and a commercial laboratory animal feed, Purina Chow for various lengths of time: (1) simultaneously with infection, and four weeks thereafter, (2) three weeks before infection and throughout the four-week infection period, and (3) six weeks prior to infection and during the infection period. The protein source was casein. Sixty of the 300 mice used served as noninfected controls, and the other 240 were each infected with 400 washed, suspended Trichinella spiralis larvae obtained from a rat by the …