Medical Sciences Commons^™

The Anti-Proliferation Effects Of Lycopene On Breast Cancer Cells, Tixieanna Dissmore

Loma Linda University Electronic Theses, Dissertations & Projects

Background: The incidence and deaths from breast cancer represent the most cause of all cancer deaths among women. Lycopene, the carotenoid in tomatoes has been associated with decreasing risk of prostate, breast, and digestive tract cancers. Various mechanisms of lycopene action have been proposed, including antioxidant activity and pro-differentiation activities. Identifying changes in the expression of proteins modified by lycopene can provide information to study the modulating effects of lycopene carcinogenesis and tumorigenesis development.

Objective: The objective was to study the anti-proliferative effects of lycopene on MCF- 7 human breast cancer cells and to identify changes in protein expression patterns. …

Ionizing Radiation And Endostatin Gene Therapy Against Lung Tumor, Xian Luo

Loma Linda University Electronic Theses, Dissertations & Projects

Although many advances have been made in radiotherapy, tumor radioresistance and normal tissue damage continue to always be important issues for radiation oncologists. Numerous reports have also documented that radiation exposure increases the risk for malignancy and suppresses immune mechanisms. However, increasing evidence has suggested that anti-angiogenic therapy that targets tumor blood supply may alter abnormal tumor vasculature, thus synergizing radiotherapy. The governing hypothesis of the present study was that modification of tumor vasculature by antiangiogenic gene therapy can increase the efficacy of radiotherapy and that radiation can also improve DNA transfection efficiency by increasing expression of the administered gene. …

Update - March 2004, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- Christians Contemplating New Developments in Biomedicine
-- Editorial
-- Christian Principals of Genetic Intervention
-- Statement on Ethical Considerations Regarding Human Cloning
-- Honoring the Religious Impulse Within the Arena of Genetic Counseling

Prediction Of Fetal Sheep Brain Metabolic Rate During Hypoxia And Cord Occlusion, Adam D. Hickerson

Loma Linda University Electronic Theses, Dissertations & Projects

Many investigators have observed that fetal and neonatal animals are remarkably tolerant to hypoxia compared to the adult. The precise mechanisms however are still unclear. In order to better characterize the hemodynamic and metabolic responses of the fetal brain to hypoxic stress, we have designed a mathematical model to predict tissue oxygenation and metabolic rate of the fetal brain during both moderate hypoxia and severe asphyxia.

The model is based on the Krogh cylinder concept and is similar to one previously published by our lab. Several new concepts were added including the ability to run the model over time using …

Validation Of A Serotonin Checklist In A Parkinson’S Disease Population, Kelly Diane Darby-Holder

Loma Linda University Electronic Theses, Dissertations & Projects

Although the distinctive pathological marker of Parkinson’s Disease is the progressive death of neurons that produce dopamine, there are also alterations in the production of quantities of other neurotransmitters, such as norepinephrine and serotonin that contribute to the disease. Parkinson’s Disease (PD) can be divided into two distinct classes based on the manifestation of motor symptoms, Type A and Type B Parkinson’s Disease. Type B PD patients often manifest symptoms in which serotonin deficiency plays an important role, which often includes a history of depression. Within the brain and spinal cord serotonin has wide spread projections, acting as an important …

Interaction Between Adrenergic And Nitric Oxide-Releasing Nerves In Cerebral Arteries, Emmanuel Ngu Mbaku

Loma Linda University Electronic Theses, Dissertations & Projects

Of all body tissues, the brain is the least tolerant of ischemia so much that interruption of cerebral blood flow by 5 sec can cause syncope, with irreversible tissue damage if the ischemia last a few minutes. In this respect, the body has an imperative duty of ensuring constant and adequate blood supply to the brain. It does so through a series of intrinsic and extrinsic control factors of which adrenergic and nitric oxide-releasing nerves are components. My research examined the interaction between these two nerve-types with emphasis on the mechanisms involved as well as on changes in their functions …

Prevalence Of Various Upper Extremity Disorders In Patients With Carpal Tunnel Syndrome Versus Patients Without Carpal Tunnel Syndrome, Daniel C. Buda

Loma Linda University Electronic Theses, Dissertations & Projects

Background and Purpose: Increasingly larger numbers of patients present with repetitive strain injuries of the upper extremities, especially carpal tunnel syndrome (CTS). A large number of these patients appear to have more than one upper extremity condition. The purpose of this study was to determine the probability that a patient diagnosed with carpal tunnel syndrome will also be diagnosed with other upper extremity and/or cervical spine disorders.

Subjects: A group of 188 subjects diagnosed with carpal tunnel syndrome and a group of 203 subjects without carpal tunnel syndrome were selected through a chart review of patients at Loma Linda …

The Role Of Diet And Physical Activity For Ovarian Cancer Results From The Adventist Health Study, Fatemeh Kiani

Loma Linda University Electronic Theses, Dissertations & Projects

A few aspects of the epidemiology of ovarian cancer are well understood, such as the inverse relationship with parity and oral contraceptive (OC) use. The role of other factors such as the potential influence of diet or physical activity is far from being established. A few studies, however, have been able to identify dietary risk factors for ovarian cancer. In this dissertation, I have conducted two studies that investigate the relationship between dietary factors and physical activity and the three endpoints: 1) nonfatal ovarian cancer (1976-1982; time to diagnosis), 2) fatal ovarian cancer (1976-1988; time to death), and 3) total …

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 …

A Novel Strategy Utilizing Co-Expression Of Murine Il-12 And Antisense Tgf-Pl Against H238 Tumor Formation, Craig A. Seheult

Loma Linda University Electronic Theses, Dissertations & Projects

Cytokines have a profound effect on immune modulation, thus playing a significant role in cancer gene therapy. A variety of human carcinomas secrete transforming growth factor-beta (TGF-β), a cytokine with potent immunosuppressive properties. Suppressing TGF-β could be a key to successfully combating malignancies, such as gliomas, mammary, and colon cancers, that over-express TGF-β. Conversely, interleukin-12 (IL-12) is a potent immunostimulatory cytokine capable of regulating T and NK cell-mediated cytotoxic responses (Trinchieri, 1994) during an anti-tumor response. Activation of the immune system with such immunostimulatory cytokines renders it inert to the suppressive effects of TGF-β. To better understand these processes our …

Cocaine Induces Apoptosis In Coronary Artery Endothelial Cells: Cellular And Molecular Mechanisms, Jiale He

Loma Linda University Electronic Theses, Dissertations & Projects

Cocaine abuse has been associated with numerous cardiovascular consequences, such as depressed myocardial contractility, elevated blood pressure, coronary artery vasoconstriction, and myocardial ischemia and infarction. The multifactorial effects of cocaine often contribute to its sympathomimetic function. However, the direct cytotoxic effects of cocaine on the cardiovascular system, especially vascular endothelium, and the cellular and molecular mechanisms remain unknown. The present study was designed to examine the general hypothesis that cocaine induces apoptosis of coronary artery endothelium by suppressing nitric oxide synthesis, stimulating cytochrome c release from mitochondria and subsequently activation of the caspases cascade, which lead to endothelial cell apoptosis. …

Age Related Changes In Contractile Sensitivity To Cyclic Gmp And Intracellular Calcium Compartmentalization In Ovine Arteries, Surya Margono Nauli

Loma Linda University Electronic Theses, Dissertations & Projects

The study examines the hypothesis that maturation changes the ability of cGMP to produce cerebral vasodilatation and alters the relative intracellular calcium pool sizes in ovine arteries. In ovine basilars taken from near-term fetal and young adult sheep, 8- pCPT-cGMP relaxed potassium- and serotonin-induced tone with pD2 values of 4.4±0.1 and 4.9±0.1 (fetal basilar) and 4.0±0.1 and 4.7±0.1 (adult basilar), respectively. In fura-2 loaded arteries, 8-pCPT-cGMP significantly lowered increases in cytosolic calcium concentration induced by serotonin but not potassium regardless of age. When calcium sensitivity was calculated in the same arteries as the slope of the relation between calcium concentration …

Assessment Of Immune System Involvement In Tourette Syndrome, Ashley Dawn Levine

Loma Linda University Electronic Theses, Dissertations & Projects

Tourette syndrome (TS) is currently hypothesized to be the result of genetic and immunological components. This study investigated whether TS subjects produce IgG and IgA antibodies that bind to caudate nucleus, hippocampus, frontal cortex, cerebellum, thalamus, globus pallidus interior, exterior and putamen. Thirty- two children (14 TS, 7 family control, and 11 non-family control) and thirty-nine adults (11 TS, 14 family control, and 14 non-family control) were studied. Immunofluorescent studies were performed on basal ganglia tissue using serum from TS children and their family members. Brain antigens were prepared as two fractions (supernatant and pellet) and used as targets for …

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- …

Chronic Hypoxia, Exercise Training, And Skeletal Muscle Capillarity: Angiogenic Regulation And Morphological Consequences, Ivan Mark Olfert

Loma Linda University Electronic Theses, Dissertations & Projects

Angiogenesis is important in health and disease. In particular, exercise training is known to increase skeletal muscle capillarity, providing there is sufficient training intensity. The stimulus for this may be intracellular hypoxia activating angiogenic growth factor gene expression. Acute hypoxia alone has been shown to increase the gene expression of several key angiogenic regulators, e.g. vascular endothelial growth factor (VEGF) and to a lesser degree transforming growth factor-β1 (TGF-β1), basic fibroblast growth factor (bFGF), and thrombospondin-1 (TSP-1), an endogenous negative angiogenic regulator. Paradoxically, however, chronic hypoxia is generally not found to increase mammalian skeletal muscle capillarity. Accordingly, we hypothesized that …

Vaccinia Virus-Mediated Glioma Gene Therapy Using P53, Il-2 And Il-12, Bing Chen

Loma Linda University Electronic Theses, Dissertations & Projects

Malignant brain tumors are generally lethal soon after their diagnosis, and the five-year survival rate for the patient is low in spite of neurosurgery, radiation therapy, and/or chemotherapy. Gene therapy has the potential to improve patient survival and quality of life by delivering specific combinations of therapeutic genes directly to the tumor for localized treatment.

We have based our cancer gene therapy for glioma on a highly attenuated variant of the Lister strain of vaccinia virus (VV) which has been proven to be a safe and effective vaccine vector. Other advantages include a wide host range, a strong promoter system, …

Update - September 2000, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- Takanobu Kinjo, Scott Winters and Nicole Wurscher graduate with degrees in Ethics and Ministry
-- Robert and Joyce Orr return to Vermont
-- Medical Theodicy Today
-- Changing our Genes: Medical Promises and Ethical Threats

Identification And Characterization Of The Cis-Acting Elements Around The Murine Cd4 Cnhancer, Xin Dong

Loma Linda University Electronic Theses, Dissertations & Projects

The cluster determinant 4 (CD4) molecule is a transmembrane glycoprotein. CD4 is essential for normal T helper cell function and plays an important role in T cell development and activation. CD4 is encoded by a single gene located on chromosome 6 in the mouse and chromosome 12 in the human. Both human and murine CD4 genes are divided into ten exons spanning more than 25 kb and have a large non-coding region in the first and third intron. CD4 gene expression is controlled primarily at the transcriptional level during T cell development and activation.

An enhancer has been identified approximately …

Identification And Characterization Of Control Elements Within The Murine Cd4 Gene, Zhong Deng

Loma Linda University Electronic Theses, Dissertations & Projects

The control of CD4 gene expression is essential for T lymphocyte development. Since the molecular mechanism for the control of CD4 gene expression during T cell development had not been elucidated, a study of the factors that control CD4 gene expression may lead to further. Toward these goals, we have made a series of recombinant DNA constructs to define the cis-acting transcriptional control elements in the murine CD4 locus that control CD4 gene expression during T cell development. In this study, we have identified multiple cis-acting control elements, which are critical for regulating the expression of the murine …

Effects Of Pycnogenol On Microsomal Cytochrome P450 Activity And Apoptosis, Huong Thu Huynh

Loma Linda University Electronic Theses, Dissertations & Projects

Phytochemicals are naturally-occurring compounds found in plants, many of which are consumed as nutritional supplements by humans. Pycnogenol is a mixture of flavonoid compounds extracted from bark of pine trees (Pinus maritima) and is commercially available in several different pharmaceutical preparations as a free radical scavenger.

Since few scientific studies have documented the pharmacologic effects of pycnogenol, our objective was to characterize the biological activity of pycnogenol. One study looked at the effects of pycnogenol on the three pathways of NNK metabolism: NNK reduction, N-oxidation and a-hydroxylation. NNK is a lung carcinogen. Lung and liver microsomes from 6 mo and …

Update - March 2000, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- National conference explores the future of faith-based health care
-- Ruth Macklin Judges Bioethical Relativism (Commentary)
-- Conditional Imortality and Cognitive Neuroscience
-- Clinical Ethics Consultation

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 …

Update - July 1998, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- Christianity and Human Cloning - A Seventh-day Adventist Declaration of Ethical Principles
-- Cloning: Dolly's Mother is Her Sister!?
-- Hello, Dolly! Dolly! Dolly!

The Effect Of Systemic Doxycycline On Alveolar Bone Loss Following Periradicular Surgery, G. Reed Cummings

Loma Linda University Electronic Theses, Dissertations & Projects

Studies have shown an average of 0.5 mm to over 1.0 mm of bone loss following full thickness flap reflection. Recent investigations have revealed that the tetracycline family of antibiotics can prevent bone loss. The purpose of this study was to determine the effect of systemic Doxycycline on crestal alveolar bone loss following periradicular surgery in Beagle dogs.

The experiment was divided into two phases. The first phase served as the control (Non-Doxycycline), the second phase as the experiment (Doxycycline). Full thickness flaps were reflected in the mandibular left or right quadrant (control side) of five Beagle dogs. Using a …

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 …

Reference Serum Chemistry And Hematological Values For Spinal Cord Injured Patients, Michael S. Laymon, Antone L. Davis Ii

Loma Linda University Electronic Theses, Dissertations & Projects

Serum chemistry and hematological values from 220 traumatic spinal cord injured patients (157 male and 63 female between the ages of 15-47, with greater than six months from injury) were compiled via chart review. Traumatic spinal cord injured patient’s reference ranges were determined and compared with the general population reference ranges. Reference ranges within the spinal cord population were compared by age, gender, level of injury and chronicity of injury. The reference ranges determined for all groups within this spinal cord population fall within the reference ranges of the general population. This supports recent research which suggests that a decrease …

Effect Of Long-Term Hypoxia On Myocardial Alpha1- Receptors, Bihong T. Chen

Loma Linda University Electronic Theses, Dissertations & Projects

To determine the developmental changes in myocardial α₁-adrenergic receptor system, we employed [³H-Prazosin] binding technique to characterize α₁-adrenergic receptors in both fetal and adult sheep myocardial ventricular membrane preparations. Myocardial α₁-adrenergic receptor density (Bmax) declined during developmental process with both fetal left ventricle(LV) and fetal right ventricle(RV) having significantly more binding sites than respective adult ventricles. We also demonstrated that the positive inotropic response to the α₁-adrenergic agonist phenylephrine did not differ significantly between the fetal and adult ventricles.

The present study also investigated the effect of long-term high-altitude hypoxemia …

The Influence Of Low Dietary Fat Intake On Incidence And Severity Of Migraine Headache, Zuzana Bic

Loma Linda University Electronic Theses, Dissertations & Projects

Migraine headaches are a common and debilitating syndrome causing untold suffering and loss of productivity. A review of the literature indicates that there are two primary factors involved in triggering these headaches: high levels of blood lipids and high levels of free fatty acids. Under these conditions platelet aggregability is increased, which is associated with decreases in serotonin and heightened prostaglandins levels. These conditions may produce vasodilation, the most immediate precursor to migraine headache. A high fat diet is one factor that may directly affect this process. This study was undertaken to evaluate the impact of dietary fat intake on …

Update - March 1997, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- James Walters publishes book on Personhood
-- Prayer and Health Care: An "Altared" Responsibility
-- Conference Report on "Bioethics and Human Destiny: Jewish and Christian Perspectives"

Update - February 1996, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- Adventism and Assisted Procreation: Excerpts from a panel discussion at LLU
-- Adventist Guidelines on Assisted Procreation
-- LLU offers Masters of Arts in Biomedical and Clinical Ethics