Chemicals and Drugs Commons^™

Transcriptional Regulation Of Azole Antifungal Resistance In Candida Albicans, Teresa T. Liu

Theses and Dissertations (ETD)

Candida albicans is a pathogenic fungi found in the mucosa, gastrointestinal, and urogenital tracts of humans. Oropharyngeal candidiasis (OPC), an opportunistic mucosal infection caused by C. albicans, occurs most frequently in patients infected with human immunodeficiency virus (HIV). OPC is usually treated with azole antifungals, a class of antifungals that target ergosterol biosynthesis, at low doses over long periods of time. This course of treatment allows for the development of azole resistance.

Two major mechanisms of azole resistance exist in C. albicans, the up-regulation of genes encoding efflux pumps and the up-regulation of ERG11, a gene encoding the azole drug …

The Role Of Multi-Drug Resistance Associated Protein 4 And P-Glycoprotein In Resistance Of Neuroblastoma To Topotecan And Irinotecan, Patricia Kellie Turner

Theses and Dissertations (ETD)

High-risk neuroblastoma presents a significant therapeutic challenge because the 5-year survival rate remains less than 30% despite the use of surgery, multi-agent chemotherapy, radiation, and autologous bone marrow transplant. Novel therapeutic modalities are under development. The camptothecin analogs topotecan and irinotecan have been identified as successful cytotoxic agents. For topotecan, pharmacokinetically guided dosing to achieve a systemic exposure associated with preclinical anti-tumor activity in neuroblastoma xenograft models is feasible and has elicited favorable responses in children with high-risk neuroblastoma. However, some children with high-risk disease did not respond to the putatively effective topotecan systemic exposure. These children represent a subset …

The Association Between Lifestyle Factors And Inflammatory Markers, Kerry Ann Stonebrook

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Cardiovascular disease (CVD) is the leading cause of death for both men and women in the United States. While smoking, high blood pressure, and elevated cholesterol levels are established risk factors for CVD, inflammation is being evaluated as a potential independent risk factor. A key cytokine regulator of the inflammatory response, interleukin-1 (IL-1), has emerged as playing a particularly important role at the genetic level in determining the degree to which the inflammation pathway is turned on. How an individual’s genetic make-up affects inflammation, CVD risk, and response to lifestyle intervention is an area of research that is in …

What Is The Safety And Efficacy Of Biobrane Versus Silver Sulfadiazine In The Treatment Of Low Body Surface Area Partial-Thickness Burns?, Gregory Wanner

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: To determine how the synthetic skin substitute Biobrane compares to silver sulfadiazine (SSD, silvadine) in the treatment of patients with low body surface area partial thickness burns.

The Potential Role Of Ledgf/P75 In Prostate Cancer, Tracy Ruth Daniels

Loma Linda University Electronic Theses, Dissertations & Projects

The serum autoantibody repertoire from cancer patients is currently being exploited for the identification of tumor associated antigens (TAA) and the design of TAA arrays. Such arrays would facilitate autoantibody profiling and potentially aid in the serological diagnosis and prognosis of tumors. The goal of this study was to identify and characterize prostate-specific TAA. We observed that while the general frequency and titers of autoantibodies in PCa patients were relatively similar to those in matched controls, significant differences could be detected between the two groups in the autoantibody response to the lens epithelial-derived growth factor p75 (LEDGF/p75). LEDGF/p75 is a …

Il-10 And Alveolar Bone Loss, Abdulaziz Saud Al-Rasheed

Loma Linda University Electronic Theses, Dissertations & Projects

Interleukin-10 (IL-10) is a cytokine with anti-inflammatory activities. IL-10 knockout (KO) mice exhibit severe intestinal inflammation in the presence of normal gut flora. We hypothesized that IL-10 KO mice would also be susceptible to inflammatory periodontal disease resulting in alveolar bone loss (ABL). The purpose of this study was to compare naturally occurring ABL in IL-10 KO and wild type (WT) mice. Twelve IL-10 KO and 12 WT mice, age-(7 months) and sex-(male) matched, were used. Half of the mice were on 129/SvEv and half on C57BL/6J background. Animal heads were defleshed and treated to remove all organic material. ABL …

Characterization Of Host-Bacteria Interactions Contributing To Group B Streptococcus Colonization, Jennifer Marie Smith

Theses, Dissertations and Capstones

Group B streptococcus (GBS) is the leading cause of life-threatening bacterial infections during the first three months of life. GBS is also a frequent cause of maternal postpartum infections. Both types of infections stem from maternal vaginal and/or rectal colonization with GBS in the perinatal period. Limited information is available concerning how the colonization process occurs and what role the host immune system may play in the establishment of persistent colonization by GBS. The complex interactions between the immune system and GBS normally should end in clearance of the bacteria. However, since colonization by GBS occurs in a large number …

Ritalin And The Child, Valerie Vickers

Theses, Dissertations and Capstones

This study focuses on Attention Deficit Hyperactivity Disorder (ADHD) the history of the disease, sufferers, individual accounts from sufferers, and both positive outcomes and negative repercussions of its treatment. Extensive secondary research and the collection of a personal account form the body of the work. The information focuses attention on key points regarding the historical background of ADHD, including: the discovery of the disease, change in categories of drugs used to control it, and the rate of evolution in thoughts on and treatment of the disease. Also researched are the various guidelines as well as ignored factors in the diagnosing …

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 …

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 …

The Relationship Between Tamoxifen And Depressive Symptoms In Women With Breast Cancer, Terry Marie Lynn

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to determine whether women with breast cancer and the presence of the drug tamoxifen, are more severely depressed than women with breast cancer and the absence of tamoxifen. Average Beck Depression Inventory (BDI) scores did not differ between the two sub-groups; however, two significant group differences were found. First, 10 women in the tamoxifen group had scores of zero (versus 4 in the absence of prescribed tamoxifen group). Research has shown that scores of zero do not always reflect an absence of depression. Second, the most severely depressed women (BDI scores in the 25 …

Analysis Of Serotonin And Postural Instability In Parkinson’S Disease, Sandra Kuniyoshi

Loma Linda University Electronic Theses, Dissertations & Projects

Postural instability is one of the most debilitating symptoms of Parkinson’s disease and the best clinical prognostic indicator of progressive disease. Significant differences in neuropathology, neurochemistry, response to L-dopa therapy and stereotactic surgery as well as prognosis have been identified in subtypes when patients with predominant postural instability and gait difficulty (PIGD)/Type B were differentiated from those with predominant symptoms of tremor and rigidity/Type A. Postural instability is resistant to the therapeutic effects of L-dopa, despite its continued efficacy on other Parkinson’s symptomatology, implicating the nondopaminergic mechanism of postural instability in Parkinson’s disease. Patients with significant postural instability and gait …

Progestin Stimulation Of The Protooncogene C-̲M̲Y̲C In T47d Human Breast Cancer Cells, Kristy Ann Blankenship

Theses, Dissertations and Capstones

Moore and co-workers have previously demonstrated that progestins stimulate the growth of T47D human breast cancer cells. We now investigate the possibility that progestins might transactivate the protooncogcne c-myc as part of the mechanism for growth stimulation. Treatment of T47D cells with the synthetic progestin R5020 results in a rapid, dose-dependent increase in c-myc mRNA. This stimulation is evident as early as 5 minutes, increases up to 4-fold at 1 hour, and then returns toward basal levels. The optimal concentration of R5020 for induction of c-myc gene expression is 10 nM, which is within the physiologically relevant range of hormone …

Periodontal Repair In Dogs : Effect Of Recombinant Human Transforming Growth Factor Beta-1 On Guided Tissue Regeneration, Saghi Shayan Razi

Loma Linda University Electronic Theses, Dissertations & Projects

The objective of this study was to evaluate bone and cementum regeneration in the critical size, supraalveolar, periodontal defect model following surgical implantation of recombinant human transforming growth factor beta-1 (rhTGFß-1) in conjunction with guided tissue regeneration (GTR). Five male beagle dogs were used in a split-mouth design. Alternate jaw quadrants in consecutive animals received GTR with rhTGFß-1 in a resorbable calcium carbonate carrier. Contralateral jaw quadrants received GTR with carrier only (control). The healing interval was 4 weeks. Clinical healing was generally uneventful, however, minor membrane exposures were observed for both treatments with limited gingival inflammation. All defects with …

An Enzyme-Linked Immunosorbent Assay For The Detection Of Cardiac Myoglobin Using Monoclonal Antibodies, Deborah F. Kelly

Chemistry & Biochemistry Theses & Dissertations

The most prevalent life-threatening disease worldwide, secondary to coronary artery thrombosis is Acute Myocardial Infarction (AMI). Increases in three clinical markers have been explored as an early means of AMI detection: Cardiac myoglobin, and the two specific cardiac isoforms of Creatine Kinase, CK-MM and CK-MB. However, myoglobin levels have shown to give a more accurate correlation (R = 0.89) than does Creatine Kinase evaluation. Therefore, we have developed a two-site Enzyme-Linked Immunosorbent Assay (ELISA) using monoclonal antibodies against myoglobin isolated from human heart tissue. This assay is based on specific anti-genantibody interactions and is sensitive at the nanogram level. We …

Longitudinal Study Of Plasma And Erythrocyte Selenium Levels In Type I Diabetic Children During Development And Treatment Of Ketoacidosis, Pi-Hsia Fan

Chemistry & Biochemistry Theses & Dissertations

Most studies on the biological activity of selenium have focused on its role at the active site in the ubiquitous enzyme, glutathione peroxidase (GSH-Px) which catalyzes the removal of hydrogen peroxide and organic hydroperoxides (1). A connection between selenium deficiency and a wide range of diseases in animals and humans has been reviewed (2). Development of various forms of human cancer (3), failure of the immune system (4), as well as some cardiovascular diseases (5) have been reported or suspected to correlate with selenium deficiency. However, the physiological function of selenium in these different diseases is not fully understood, and …

Kinetic Characterization Of A Recombinant C-Terminal Mutant Of Reverse Transcriptase From The Human Immunodeficiency Virus, Thomas S. Heard

Chemistry & Biochemistry Theses & Dissertations

The human immunodeficiency virus (HIV) reverse transcriptase (RT) (EC 2.7.7.49) is the central replication enzyme for HIV. In general, the kinetic mechanism for this and all other polymerases involves the ordered binding of two substrates: a primer-template (PT) followed by a deoxyribonucleoside triphosphate (dNTP). Previous investigations prompted this research when it was discovered that the substrate dNTP, in absence of PT, could protect a recombinant c-terminal mutant HIV-1 RT from inhibition by pyridoxal-5'-monophosphate (PLP), an active-site dNTP inhibitor. In contrast, the non-mutant recombinant HIV-1 RT required both substrates for protection from PLP inhibition. This investigation sought to determine if this …

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 …

Insulin And Glucagon Responses To Dietary Protein In Diabetic And Nondiabetic Men, Monica L. Blomstedt

Loma Linda University Electronic Theses, Dissertations & Projects

Five men with non-insulin-dependent diabetes mellitus and fourteen nondiabetic men, were given test meals with soy protein, casein or additional carbohydrate in place of protein. Blood levels of insulin, glucagon, glucose and lipids were measured at fasting, one-half hour and two hours postprandial. To all meals, the nondiabetic subjects responded with a quick rise of the insulin level which decreased at two hours. In contrast, the diabetics showed a significantly lower insulin response at one-half hour (p < 0.05), but a tendency to higher levels at two hours. The same pattern was observed in the insulin to glucagon ratio. No significant difference between the meals was found in regard to insulin or glucagon responses, suggests that a sustained, although delayed postprandial insulin response, may be a precursor to the higher cholesterol and increased risk for cardiovascular disease among diabetics.

Relationship Between Dietary Intake And Reproductive Hormones In Premenopausal Vegetarian And Nonvegetarian Seventh-Day Adventist Women, Joan M. Spuehler

Loma Linda University Electronic Theses, Dissertations & Projects

There is evidence that specific nutrients may modify hormonal balance and contribute to breast cancer etiology. To investigate the relationship between dietary nutrients and plasma reproductive hormones and to determine hormone-nutrient interrelationships, we measured plasma estrogens, androgens. progesterone and prolactin levels in 10 premenopausal Seventh-day Adventist (SDA) vegetarian and 10 premenopausal SDA nonvegetarian women. Over three days in each of three consecutive months. diet records and fasting midluteal blood samples were collected. The nonvegetarians consumed significantly more protein, total and saturated fats, oleic and linoleic acids, and cholesterol than did the vegetarians. Hormonal status of the two groups did not …

The Relationship Of Vitamins B-6 And B-12 To Plasma Homocysteine Levels In Men At Low- And High-Risk For Coronary Heart Disease, Marlene E. Swift

Loma Linda University Electronic Theses, Dissertations & Projects

There is evidence that homocysteine may be a factor in increasing the risk of coronary heart disease (CHD). To explore this relationship further, we assessed the interrelation of dietary vitamins B-6, B-12 and folate, and plasma pyridoxal-5'-phosphate and vitamin B-12 with plasma free and protein-bound homocysteine levels. Fasting blood and three-day dietary records were obtained from nine men low-risk (LR) and five at high-risk (HR) for CHD. The HR mean systolic blood pressure, total cholesterol (TC), and TC/cholesterol ratios were significantly higher than LR levels. Groups were comparable by age, weight, height, skinfolds, exercise, and smoking history. No significant difference …

A Quantitative Study Of The Distinctive Proteins Of The Eosinophil: A Comparison Of Normals And Eosinophilic Patients, James M. Olson

Honors Theses

Eosinophils have long been associated with parasitic and allergic diseases. Methods of procurement and purification of eosinophils in the last ten years have allowed intensive investigation into their components, properties, functions, and mechanisms (Gleich et al, 1982). The goals of this project are to separate eosinophils in blood samples taken from patients with eosinophilia and from normals based on density over distontinuous Metrizamide gradients; to determine quantitatively the levels of the three distinctive proteins of the eosinophil, specifically MBP, EDN, and ECP; and to compare the levels of these proteins found in eosinophils of patients with eosinophilia to the amounts …

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 ± …

Development Of A Procedure For Analysis Of High Density Lipoprotein Subclasses, Chan Chin

Chemistry & Biochemistry Theses & Dissertations

Human serum high density lipoprotein subclasses, HDL₂ and HDL₃ , were isolated by preparative salt density gradient ultracentrifugation and further analyzed by electrophoresis on a 4 to 15% concentration gradient polyacrylamide gel.

The separation of the major classes of serum lipoproteins was achieved after a single ultracentrifugation for 272,000 g at 15°c in a swinging bucket rotor. High resolution concentration gradient gel electrophoresis was found to be particularly suitable for the separation of lipoproteins. The isolation of HDL by precipitation methods, heparin-manganese and dextran-magnesium have also been evaluated in this study, and were found not to completely separate …

Antibiotics And The Wasting Disease In Neonatally Thymectomized Rats, Douglas M. Grignon

Loma Linda University Electronic Theses, Dissertations & Projects

The administration of the antibiotic, Chloramphenicol, to pregnant rats just prior to, and for four days after delivery, diminishes the incidence of the so-called "Wasting Disease" in neonatally thymectomized rats.

A total of 50 rats were divided into the following groups:

1. Thymectomy only---nonmedicated 17 rats
2. Thymectomy only---medicated 12 rats
3. Thymectomy-adrenalectomy---nonmedicated 5 rats
4. Thymectomy-adrenalectomy---medicated 8 rats
5. Controls---nonmedicated 4 rats
6. Controls---medicated 4 rats

Chloramphenicol was administered in the drinking water to the mothers of groups 2, 4 and 6 for about 2 days prior to delivery and 4 days after. On the day of birth or within three days after birth, the …