Chemicals and Drugs Commons^™

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 …

The Effect Of Mtad On Eight Strains Of E. Faecalis In Contaminated Root Canals, Bradley M. Newberry

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this investigation was to determine the antimicrobial effect of Biopure MTAD (a mixture of a tetracycline isomer, an acid, and a detergent) as a final irrigant on eight strains of Enterococcus faecalis (E. faecalis) in contaminated root canals of extracted human teeth. In addition, the Minimum Inhibitory Concentration (MIC) and Minimum Lethal Concentration (MLC) of MTAD were also measured on the same strains of bacteria. Two-hundred and forty extracted human teeth were instrumented using 1.3% NaOCl followed by 17% EDTA to remove the smear layer. The teeth were randomly contaminated with one of eight strains of E. …

Biochemical Characteristics Of Inconsistent Free T₄ Assays, Kristofer S. Fritz

Loma Linda University Electronic Theses, Dissertations & Projects

Serum levels of free thyroxine (T₄) are helpful in the clinical evaluation of patients who are suspected of having thyroid disease, since free T₄ (unbound) is known to closely relate to hyper, eu and hypothyroidism. There are documented inconsistencies among commercially available direct free thyroxine immunoassays. The biochemical basis for these inconsistencies is not understood and has not been characterized. Direct free T₄ measurements have been linked to both T₄-binding serum protein concentrations and protein-bound T₄ concentrations. A free T₄ reference method using direct equilibrium dialysis radioimmunoassay has been well characterized. New …

The Effect Of Radiation And Repeated Sub-Culturing On Tgf-Β1 Signaling In Frtl-5 Cells, Cheryl G. Burrell

Loma Linda University Electronic Theses, Dissertations & Projects

From our ongoing in vitro studies using the Fisher Rat Thyroid cell line-5 (FRTL-5) we recorded accelerated growth, reduced follicularization and reduction in thyroxin release that occurred as the cells were repeatedly sub-cultured. We also recorded that these changes occurred earlier and more rapidly following radiation exposure. We determined that TGF-β1 production increased under both conditions. We hypothesized that alteration in the TGF-β1 signaling pathway contributed to the changes observed in the cellular properties of FRTL-5 cells. Our objective was to examine some of the players in the TGF-β1 signaling pathway to determine whether radiation and/or repeated subculturing promoted 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 …

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 …

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 …

The Dose Response Effect Of Almonds On Serum Vitamin E, Plasma Lipid Fractions And Erythrocyte Phospholipids, Pera Jambazian

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to determine if two different amounts of almonds added to a heart healthy diet would increase vitamin E concentrations in healthy men and women, and reflect positive fatty acid profiles in serum lipids and erythrocytes. Twenty three subjects participated in a crossover metabolic study for a 14 week period. Subjects consumed one of three diets for 4 weeks each, a control diet, a low almond diet and a high almond diet after a 2 week run-in period. All meals were prepared in the test kitchen, and almonds were added to the experimental diets by …

Effects Of A Serine 364 To Proline Mutation Of The Connexin43 Protein In Transgenic Mice, Chia-Ling Nhan-Chang

Loma Linda University Electronic Theses, Dissertations & Projects

[Abstract Not Included]

Study Of The Hiv-1 Gene Regulatory Proteins Tat And Rev By The Two-Hybrid System In Yeast, David Allen Elkins

Loma Linda University Electronic Theses, Dissertations & Projects

Tat and Rev, small proteins encoded by the Human Immunodeficiency Virus type 1 (HIV-1), regulate its pattern of gene expression within infected cells. Tat increases transcription from the integrated pro virus by approximately a thousand-fold; Rev effects a shift in the pattern of splicing of the viral mRNA. Both are likely to interact with cellular proteins in executing their respective functions. Tat has additional activities (including neurotoxicity and inhibition of lymphocyte activation) which may be extraneous to its viral functions.

In order to identify cellular proteins interacting with Tat and Rev, the genes for both were cloned into plasmid vectors …

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 …

Bone Morphogenetic Proteins And Periodontal Repair, Michael B. Lee

Loma Linda University Electronic Theses, Dissertations & Projects

For over thirty years now, research has been carried out to isolate and purify bone morphogenetic protein (BMP), a substance which has been shown to induce heterotopic bone formation in various animal species. Recent advances in the fields of developmental biology, molecular biology and genetics, have shown that the BMPs not only are responsible for postfetal bone induction (including normal bone remodeling, healing and repair), but are also critical during embryogenesis - not only in regards to the skeletal system, but quite possibly in the morphogenesis and pattern formation of other tissues and organs as well.

Due to their bone …

Ornithine Decarboxylase And Polyamines In Perinatal Hypoxia, Satyaseelan Packianathan

Loma Linda University Electronic Theses, Dissertations & Projects

Hypoxic and hypoxic/ischemic episodes contribute to various neurological aberrations, learning disabilities, et cetera in surviving infants. Despite major advances in understanding the pathophysiology of hypoxia, the cellular basis for hypoxic-mediated injury remains poorly understood. In addition, the role of developmentally essential enzymes vis á vis their contributions, or lack thereof, to hypoxic-mediated injury has not been adequately investigated. In the series of studies comprising this dissertation, we tested the hypothesis that acute and/or chronic hypoxia affect the activity of omithine decarboxylase (ODC; E.C. 4.1.1.17), the developmentally essential enzyme in polyamine biosynthesis, in the fetal and newborn rat brain. Fetal and …

Effects Of Furosemide And Oleic Acid On Thyroxine Binding To Isolated Pairs Of Thyroxine Binding Serum Proteins, Deborah Hustead

Loma Linda University Electronic Theses, Dissertations & Projects

Dosage dependent binding inhibition and redistribution of thyroxine (T₄) between three pairs of thyroxine binding serum proteins, TBG-TTR, TBG-albumin and TTR-albumin, by furosemide (0.0 to 1.0 mol/L) and oleic acid (0.0 to 0.10 mol/L) were studied using equilibrium dialysis with purified binding proteins at concentrations 1/200 of levels in normal human sera, separated across the dialysis membrane and competing for T₄.

Furosemide (1.0 mol/L) reduced TBG bound T₄ in both the TBG-TTR system and TBG-albumin system (>90% decrease) and inhibited T₄ binding to TTR in the TTR-albumin system (68% decrease) and to albumin …

The Production And Characterization Of A Monoclonal Antibody To A Naturally Occurring Aminomalonic Acid Epitope And A Comparison With An Antibody To A Synthetically Derived Aminomalonic Acid Epitope, James L. Gulley

Loma Linda University Electronic Theses, Dissertations & Projects

The goal for this project is to undertake the first step in the study of blocking metastasis by a monoclonal antibody. The long range goal of this line of research is to study a novel mechanism for the blocking of tumor metastasis in general and prostatic cancer metastasis in particular. The problem that this addresses is the growing number of cases of prostatic cancer in the increasingly aging male population. This cancer is not lethal unless it metastasizes, yet there is no cure for the metastatic disease. The inherent specificity of a monoclonal antibody combined with the uniqueness of the …

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 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 …

Regulation Of Epidermal Growth Factor Receptor Synthesis By Retinoic Acid And Dexamethasone, Kerby C. Oberg

Loma Linda University Electronic Theses, Dissertations & Projects

Fetal rat lung (FRL) cells incubated in the presence of retinoic acid or dexamethasone exhibit altered ¹²⁵I-epidermal growth factor (EOF) binding capacity. Retinoic acid enhances ¹²⁵I-EGF binding 3-fold following 24 hours of 37° incubation. In contrast, FRL cells incubated in the presence of dexamethasone display a 2-fold reduction in ¹²⁵I-EGF binding capacity. The change in binding capacity, induced by either hormone, was due to alterations in the average number of receptors per cell as determined by Scatchard analysis of ¹²⁵I-EGF binding. In the absence of retinoic acid or dexamethasone, FRL cells were calculated to have approximately …

Decreased Triiodothyronine Binding To The Hepatic Nuclear Thyroid Hormone Receptor In The Diabetic Mouse, Thomas J. Dewind

Loma Linda University Electronic Theses, Dissertations & Projects

The diabetic C57BL/KsJ-db m mouse has abnormal thyroid hormone levels and indications of thyroid hormone resistance. To investigate the basis of these abnormalities, the hepatic nuclear thyroid hormone receptor was extracted with 0.4 M KCl, 1.1 mM MgCl₂, 20 mM Tris/HCl, pH 7.9 from hepatocyte nuclei of normal C57BL/KsJ, heterozygous C57BL/KsJ-db m (db/m), and diabetic C57BL/KsJ-db m (db/db) mice. Normal and heterozygous mice were grouped together as the controls. Triiodothyronine (T₃) binding studies at 4°C using nitrocellulose filtration to separate free T₃ from receptor bound T₃ demonstrated an …

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.

Effect Of Disulfiram On The Urinary Excretion Of The Serotonin Metabolites 5-Hydroxytryptophol And 5-Hydroxyindoleacetic Acid In Problem Drinkers, Mark D. Harding

Loma Linda University Electronic Theses, Dissertations & Projects

Problem drinkers (N=7) were given 500mg disulfiram daily for one week. Urine was collected before and after disulfiram intake. 5-Hydroxytryptophol (5-HTOL) was determined by a modification of the method of Davis et al. and adapted to high-performance liquid chromatography (HPLC) with an electrochemical detector setting of 0.75V. 5-Hydroxy-indoleacetic acid (5- HIAA) was determined using the HPLC method of Shihabi et al. (1980). Urinary excretion of 5-HTOL in ug/gm creatinine before and after disulfiram was 25.4± 3.3 and 110.5± 27.1 respectively, p < 0.02. 5-HIAA in mg/gm creatinine before and after disulfiram was 4.9±0.9 and 3.6±0.8 respectively, p > 0.16. The data shows that disulfiram administration alters serotonin metabolism resulting in increased 5-HTOL which is known to increase …

Fasting Plasma Amino Acids In Relation To Serum Lipids In Human Male Subjects, Helen G. Mendiola

Loma Linda University Electronic Theses, Dissertations & Projects

The association of fasting plasma amino acids with serum lipids was studied in 23 healthy human male subjects with ages ranging from 31 to 62 years (45±9, mean± SD). There were 12 normocholesterolemic (serum cholesterol = 183±17 mg/dL) and 11 hypercholesterolemic (271±27 mg/dL) subjects. Venous blood samples were drawn three times at weekly intervals. Plasma amino acids were determined by ion-exchange chromatography, and serum cholesterol and triglycerides by enzymatic methods. Hypercholesterolemic subjects had significantly higher lysine and lower serine levels than normocholesterolemic subjects (p < .05). Serum cholesterol levels were positively correlated with plasma levels of lysine, ornithine and the lysine/arginine ratio (p < .04); and negatively correlated with phenylalanine and urea (p < .05). Serum triglyceride levels were positively correlated with plasma levels of lysine, glutamic acid, and valine (p <. 02); and negatively correlated with serine, glutamine, and asparagine (p < .04). These results add support to the hypothesis that specific plasma amino acids are associated with the metabolism of serum lipids.

Sprague-Dawley Rats Fed Milk Or Beef Protein : Differences In Response To 1,2-Dimethylhydrazine Carcinogenesis, Stanley W. L. Ng

Loma Linda University Electronic Theses, Dissertations & Projects

Colon cancer is responsible for a high percentage of cancer deaths in developing countries, and there is convincing epidemiological evidence that meat protein and fat in the diet increase the incidence of this form of cancer. An animal tumor model which has been used by many investigators interested in colon cancer is the 1,2-dimethylhydrazine (DMH)-rat or DMH-mouse tumor model. In previous work done in this laboratory the DMH-BALB/c mouse tumor model was used to compare the production of colon tumors in mice fed a diet using non-fat powdered milk as a source of protein with those in mice fed beef …

The Effect Of Dietary Fat Level On Tumor Development And Immunity In Balb/C Mice Fed Casein Of Wheat Gluten As Protein And Challenged With Herpes Type 2-Transformed Cells, Helen Drakou

Loma Linda University Electronic Theses, Dissertations & Projects

A high percentage of fat in the diet has been implicated through epidemiological studies in several human cancers. Studies in experimental animals have produced evidence that increasing the fat in the diet decreases the animal’s ability to restrict tumor development and growth. In previous work done in this laboratory with BALB/c mice injected with herpes simplex Type 2-transformed mouse cells (H238), the effects of a diet which greatly enhanced tumor growth was compared with one which restricted tumor growth. The latter, a low (5%) fat, low protein diet, in which the protein was casein, was also found to produce a …

An Immunochemical Analysis Of Alcoholic Hyaline And Its Relationship To Keratin Intermediate Filaments, David L. Drexler

Loma Linda University Electronic Theses, Dissertations & Projects

Alcoholic Hyaline (AH) and keratin intermediate filaments possess ultrastructural, biochemical and immunochemical similarities. This study compares human AH, human stratum corneum keratin (HSCK) and normal human liver cytokeratin (HCK) by quantitative immunochemical means, using polyclonal as well as monoclonal antibodies. Enzyme-linked immunosorbent assays (ELISAs) were employed, as well as "immunoblotting" and immunocytochemical techniques. HCK was isolated using Triton X-100 and "high-salt” buffers and exhibited seven major polypeptide bands on SDS-PAGE (41-58 kd). Antisera were made toward HCK and the two major HCK bands. Other immunochemicals included antisera toward AH, the three major AH bands, and HSCK, as well as 3 …

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 Role Of The Salivary Glands In Uptake Of Fluoride In Teeth And Bone, Robin E. Vance

Loma Linda University Electronic Theses, Dissertations & Projects

The cariostatic capability of fluoride is generally recognized, in addition, it may also have a beneficial effect on bone. Fluoride is thought to exercise its cariostasis through a local effect on teeth, however, the possibility exists that fluoride exerts its action through a systemic mechanism. Fluoride uptake by rat teeth and its effectiveness as a cariostatic substance was studied in parotidectomized, submaxillariectomized, and totally sialoadenectomized animals (both parotid and submaxillary glands removed). The uptake of fluoride in bone was also quantitated for comparison purposes.

Rats were injected daily with 15 micromoles of fluoride dissolved in 0.1 ml saline. The rats …

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 ± …

The Effect Of Hypercholesterolemia On The Membrane Lipids, 3-0-[¹⁴C] Methylglucose Transport, And 2,3-Diphosphoglycerate Levels In Rat Erythrocytes, Edwin J. Lester Jr.

Loma Linda University Electronic Theses, Dissertations & Projects

An increase in dietary cholesterol and cholic acid will produce hypercholesterolemia in rats. For ten months, two groups of rats (six in each group) were fed commercial rat pellets (control group) or rat pellets plus cholesterol (1%) and cholic acid (0.25%) (experimental group). A blood sample from each animal was divided into three aliquots for three separate experiments on the erythrocytes: a membrane cholesterol and phospholipid determination, a 3-0-[¹⁴C] methylglucose (30MG) transport determination, and a 2,3-diphosphoglycerate (2,3 DPG) determination. The 30MG transport and 2,3 DPG aliquots were each incubated in the same five concentrations of 30MG and glucose …

The Effect Of Insulin, Fluoride And Methyl Xanthines On The Hypothalamic-Parotid Gland Endocrine Axis, Reagan Ondler

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to determine the effect of insulin and fluoride on dentinal fluid movement (FM) in high-sucrose fed rats as mediated through the hypothalamic-parotid gland endocrine axis. In conjunction with the fluoride study, the possible involvement of cAMP was examined through the use of several methyl xanthines which are recognized as phosphodiesterase inhibitors.

Twenty-one day old, male Sprague Dawley rats were maintained on a high-sugar diet (62% sucrose) for 8-9 days at which time intravenous or arterial infusions of insulin, fluoride or the methyl xanthines were performed. Additional procedures included collecting plasma from rats which had …