Chemicals and Drugs Commons^™

Expression And Requirement Of Epithelial Fatty Acid- Binding Protein In Neuronal Axon Growth, Gregory William Allen

Loma Linda University Electronic Theses, Dissertations & Projects

Epithelial fatty acid-binding protein (E-FABP) is expressed in the dorsal root ganglia following sciatic nerve injury and in migrating and differentiating neurons during neuronal development. It was hypothesized that E-FABP expression is required for the robust outgrowth of axons from developing and regenerating neurons. To test this hypothesis, E-FABP expression in both PC12 cells and primary retinal neurons was examined. In PC12 cells, NGF induces E-FABP mRNA and protein during the period of neurite outgrowth, and E-FABP localizes to the perinuclear cytoplasm, nucleus, and growth cone. Furthermore, E-FABP-deficient cell lines exposed to NGF were less differentiated and had shorter neurites …

Regulation Of Connexin43 By Phosphorylation, Maithili M. Shah

Loma Linda University Electronic Theses, Dissertations & Projects

Gap junctions play a crucial role in embryogenesis, especially of the heart where connexin43 is thought to be important for its formation as well as synchronized contraction. Several reports have shown that connexin43 protein is phosphorylated on serine residues in vitro and in vivo.

Studies performed in our laboratory have demonstrated that cell-to-cell communication in cells expressing connexin43 can be controlled rapidly and reversibly by microinjection of active protein kinases or phosphatases that target serine or threonine residues. Phosphorylation by cAMP-dependent protein kinase (PKA) seems to favor channel opening, whereas the effect of protein kinase C (PKC) on channel gating …

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 …

Localization Of Sodium, Potassium-Adenosine Triphosphatase In The Cerebral Cortex Of Developing Rats, Maki Ujiie

Loma Linda University Electronic Theses, Dissertations & Projects

Active transport via Na⁺, K⁺-ATPase plays an important role in establishing and maintaining proper ionic gradient across all mammalian cell membranes. A strict regulation of Na⁺, and K⁺ ion levels is especially important in excitable cells such as neurons and myocytes. Inhibition of the enzyme is associated with several pathological conditions and has serious detrimental effects on cerebral cortical cells. Yet the enzyme appears to be limited in amount and distribution in newborn rats. In this study, Na_⁺, K⁺- ATPase expression and distribution in early postnatal rats were studied …

A Model Using Radiation And Pws4-Htnf-Α Gene Therapy For Treatment Of Glioblastomas, Angelo G. Baher

Loma Linda University Electronic Theses, Dissertations & Projects

The efficacy of radiotherapy for cancer is limited by the dose that can be safely delivered to the tumor without causing debilitating side effects. In addition, successful treatment of highly malignant tumors such as glioblastomas is likely to require adjunctive therapies to enhance tumor response to radiation. Previous studies have shown immunomodulation and a synergestic reduction in tumor volume of malignant tumors when tumor necrosis factor-α (TNF-α) protein is administered prior to radiation. The major goal of the present investigation was to evaluate the efficacy of pWS4-human TNF-α (pWS4-hTNF-α), a new plasmid construct that expresses human TNF-α protein, together with …

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 …

Regeneration In Periodontal Defects With Rhbmp-2 : A Dosage Study, Paola Guglielmoni

Loma Linda University Electronic Theses, Dissertations & Projects

Bone morphogenetic proteins (BMPs) have been shown to induce bone formation in ectopic and orthotopic sites. This inductive capability has led to their evaluation as possible adjuncts in periodontal reconstructive therapy. Indeed, studies have reported periodontal regeneration following surgical implantation of recombinant human BMP-2. This study evaluated regeneration of alveolar bone and cementum following periodontal reconstructive surgery including implantation of a construct consisting of sterile lyophilized rhBMP-2 in buffer adsorbed onto an absorbable collagen sponge. Critical size mandibular supra-alveolar periodontal defects were surgically created, and an incomplete block design was used to evaluate the regenerative potential of rhBMP-2 at 0.05, …

A Cytochemical Evaluation Of Blood-Brain Barrier Sodium, Potassium- And Calcium-Adenosine Triphosphatase Polarity, Panya Steve Manoonkitiwongsa

Loma Linda University Electronic Theses, Dissertations & Projects

The blood-brain barrier (BBB) is formed by cerebral vascular endothelial cells. Brain ion and fluid homeotasis essential for proper neural functioning is due to the BBB. Sodium-potassium and calcium-activated adenosine triphosphatase (Na⁺, K⁺-ATPase and Ca²⁺-ATPase) serve as one of the main mechanisms controlling brain Na⁺, K⁺, and Ca²⁺ concentrations. The present accepted concept is that both of these enzymes are localized to the abluminal plasma membrane of endothelial cells although there have been contrary results from some studies. Because of these discrepancies, further work was needed. Various cytochemical procedures …

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 …

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 …

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 …

Transcriptional Regulation Of Insulin-Like Growth Factor : Binding Protein-4 By Protein Kinase A And Protein Kinase C Signal Transduction Pathways In Human Bone Cells, Kuk-Wha Lee

Loma Linda University Electronic Theses, Dissertations & Projects

The Insulin-like Growth Factor (IGF) system is an important local regulator of osteoblast proliferation, the primary determinant of bone formation. Six IGF Binding Proteins (IGFBPs) either inhibit or enhance IGF actions. Previous studies have shown that IGFBP-4 is an important negative regulator of osteoblast cell proliferation and that agents such as PTH which increase intracellular cAMP significantly increase expression of IGFBP-4 at the protein and mRNA levels. The underlying molecular mechanism which accounted for IGFBP-4 expression had not been determined and was the focus of my dissertation. Agents which increase intracellular cAMP rapidly increased IGFBP-4 mRNA levels. Nuclear run-off experiments …

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 …

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 …

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, …

A Physical Map Of The Klebsiella Pneumoniae M5a1 Genome, Alexandrine Randriamahefa

Loma Linda University Electronic Theses, Dissertations & Projects

Klebsiella pneumoniae is an enteric opportunistic pathogen which commonly causes pulmonary, urinary tract and kidney infections. It has also been widely used for the study of nitrogen fixation. In this study, a macrorestriction map of K. pneumoniae M5a1 chromosomal DNA was constructed using pulsed field gel electrophoresis (PFGE) and Southern hybridization techniques. The genome DNA was digested with two rare cutting restriction enzymes (XbaI and BlnI) and the genome size was estimated from the sum of the fragment sizes as 5,121 Kb (+2.8%). A tentative order of fragments was deduced using Southern hybridization with purified restriction fragments. …

Aerotaxis In Bacillus Subtilis, Laurence Samuel Wong

Loma Linda University Electronic Theses, Dissertations & Projects

B. subtilis, like Escherichia coli and Salmonella typhimurium, responded to a step increase in oxygen concentration by swimming smoothly (~ 35 s duration) and to a decrease in oxygen by tumbling. In a spatial gradient of oxygen in liquid media, a band of cells congregated near the air interface. Aerotaxis required a functioning respiratory chain. Adaptation of B. subtilis, E. coli and S. typhimurium to media containing amino acids requires methylation of receptors/methyl-accepting chemotaxis proteins. Adaptation to oxygen and phosphotransferase sugar substrates in B. subtilis was dependent on methylation, unlike similar adaptation in E. coli and S. typhimurium. …

Plasticity Of The Gnrh Neuronal System During Sexual Maturation Of The Male Djungarian Hamster, Kevin L. Buchanan

Loma Linda University Electronic Theses, Dissertations & Projects

Onset of puberty in male Djungarian hamsters is characterized by increased pituitary gonadotropin secretion and testes maturation, and is controlled by neurons within the brain which secrete gonadotropin-releasing hormone (GnRH). Puberty is associated with increased numbers of morphologically unipolar, but not bipolar, GnRH neurons in the medial preoptic area (MPOA) and diagonal band of Broca (DBB). To test the hypothesis that delayed sexual maturation arrests this increase, males were exposed to short days or administered melatonin. Males with delayed puberty had significantly fewer unipolar GnRH neuron numbers in the MPOA and DBB comparable to pubertal controls in long days. Unipolar …

The Expression And Regulation Of The Hsdk Genes Of Escherichia Coli K-12, Ainu Parkash

Loma Linda University Electronic Theses, Dissertations & Projects

The DNA restriction and modification (R-M) genes in bacteria play a defensive role in the organism, offering protection to the host from invaders such as bacteriophages. The expression of these genes in E. coli K-12 had not previously been studied due to the complexity of the EcoK R-M enzymes. The use of lacZ gene fusion techniques allowed studies of the expression of the hsdK genes for the first time. Operon fusions of Mu(/ac) to the hsdK genes show that the two hsdK promoters, p _res and p _mod, are weak (50 Miller units) and that …

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 Disulfiram On The Urinary Excretion Of 5-Hydroxytryptophol And 5-Hydroxyindoleacetic Acid In Subjects Consuming Serotonin Rich Foods, Amy G. Tordecilla

Loma Linda University Electronic Theses, Dissertations & Projects

The effect of disulfiram and/or serotonin rich foods (SRF) on the urinary excretion of 5-hydroxytryptophol (5-HTOL) and 5-hydroxyindoleacetic acid (5-HIAA) in normal male subjects was investigated. Urine collections were obtained on 1) regular serotonin free diet, 2) SRF, 3) serotonin free diet with disulfiram, and 4) SRF with disulfiram. Urinary excretion of 5-HTOL in ug/gm creatinine during disulfiram administration was 112.0 ± 24.1. Five HTOL (ug/gm creatinine) with disulfiram and SRF increased to 1532 ± 352.0 (p < 0.001). Five-HIAA (mg/g creatinine) before and after SRF was 3.4 ± .44 and 33.1 ± 6.1 respectively, p < 0.001. With disulfiram and SRF the excretion of was 24.2 ± 3.2 mg/g creatinine which was significantly greater than when on the regular diet (p < 0.001) than the excretion on SRF alone (p < 0.05)

Key words: Disulfiram, serotonin, 5-hydroxytryptophol, 5-hydroxyindoleacetic acid, urinary excretion, high performance liquid chromatography, alcoholism

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 …

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 …

Dietary And Hormonal Evaluation Of Men At Risk For Prostate Cancer, Donald J. Pusateri

Loma Linda University Electronic Theses, Dissertations & Projects

Relationships between dietary nutrients and plasma and fecal estrone, estradiol-17β, testosterone, and plasma prolactin levels were studied in young Seventh-day Adventist men: 18 nonvegetarians (NV), 20 lacto-ovovegetarians (LOV), and 15 vegans (V). Blood samples and 3 d dietary records were obtained. Contemporaneously collected diet composites and stool samples were analyzed for fiber. The vegetarians consumed significantly more fiber than the omnivores, while NVs and LOVs consumed more saturated fat than the Vs. Although plasma steroid hormone status did not differ, the Vs had significantly higher fecal estrogen levels than the NVs or LOVs. Plasma prolactin levels were significantly higher in …