Amino Acids, Peptides, and Proteins Commons^™

Effects Of Intranasally Administered Dnsp-11 On The Central Dopamine System Of Normal And Parkinsonian Fischer 344 Rats, James H. Sonne

Theses and Dissertations--Neuroscience

Due to the blood-brain barrier, delivery of many drugs to the brain has required intracranial surgery which is prone to complication. Here we show that Dopamine Neuron Stimulating Peptide 11 (DNSP-11), following non-invasive intranasal administration, protects dopaminergic neurons from a lesion model of Parkinson’s disease in the rat. A significant and dose-dependent increase in an index of dopamine turnover (the ratio of DOPAC to dopamine) was observed in the striatum of normal young adult Fischer 344 rats by whole-tissue neurochemistry compared to vehicle administered controls.

Among animals challenged with a moderate, unilateral 6-hydroxy-dopamine (6-OHDA) lesion of the substantia nigra, those …

The Role Of The Yxxφ Motif In Cd82 Trafficking And Function, Mekel Marie Richardson

Theses and Dissertations (ETD)

CD82, a tetraspanin, is a tumor metastasis suppressor. Tetraspanins are membrane spanning proteins that play critical roles in diverse biological and pathological processes, e.g., the regulation of cancer metastasis. CD82 is ubiquitously expressed in various types of tissues, but its expression becomes down-regulated or lost in a majority of metastatic tumors. It inhibits tumor metastasis without affecting primary tumor growth. Cancer patients whose tumors contain CD82 exhibit minimal metastasis. We know that CD82 functions as a tumor metastasis suppressor but the mechanism by which this occurs is largely unknown. CD82 can be found on the plasma membrane as well as …

Characterization Of The Mechanism Of Pparγ-Mediated Neointima Formation In Rodents, Ryoko Tsukahara

Theses and Dissertations (ETD)

Lysophosphatidic acid (LPA) and its ether analog alkyl glycerophosphate (AGP) elicit arterial wall remodeling when applied intralumenally into the uninjured carotid artery. LPA is the ligand of eight GPCRs and the peroxisome proliferator-activated receptor γ (PPARγ). We pursued a gene knockout strategy to identify the LPA receptor subtypes necessary for the neointimal response in a non-injury model of carotid remodeling and also compared the effects of AGP and the PPARγ agonist rosiglitazone (ROSI) on balloon injury-elicited neointima development. In the balloon injury model AGP significantly increased neointima; however, rosiglitazone application attenuated it. AGP and ROSI were also applied intralumenally for …

Inflammatory Proteins, Genetic Variation, And Environmental Influences On Health Care Associated Infection Development In Sepsis, Reba Antoinette Umberger

Theses and Dissertations (ETD)

The purpose of this study was to determine the impact of baseline systemic inflammation (pro‑inflammatory cytokine, anti‑inflammatory cytokine, and their ratio), genetic variability, and environment on the development of health care associated infections (HAI) among sepsis patients during their ICU stay (up to 28 days).

Methods: A prospective observation study was conducted at the Veterans Affairs Medical Center in the Medical Intensive Care Unit over an 18 month period. A total of 78 patients were enrolled within 72 hours of presenting to the ICU with sepsis. Patient were excluded if they were receiving immunosuppressants (chemotherapy or greater than one mg/kg …

Characterization Of Amino Acid Residues Integral To Neuronal Binding Of Amyloid Beta Protein In Alzheimer’S Disease, Nicole C. Olson

Chemistry and Biochemistry

Purpose: Alzheimer’s Disease is a neurodegenerative disease resulting from over-production and neuronal accumulation of amyloid-beta proteins (Aβ40/Aβ42). The glycine residue at position 33 and histidine residues at positions 13 and 14 are involved with binding and internalization of these proteins, actions potentially inhibited by substituting or sterically hindering these residues with an antibody specific to positions 2-11 (IgG-4.1). Rat pheochromocytoma (PC12) cells differentiated with nerve growth factor were used as a neuronal model to determine whether substitution and/or antibody block amyloid-beta’s neuronal interactions.

Methods: PC12 cells were incubated with fluorescein-labeled-amyloid-beta-40 (F-Aβ40) or substituted F-Aβ40 derivatives (F-Aβ40-H13,14G, F-Aβ40-H13,14G;G33A), with or without …

Does Tranexamic Acid Effectively And Safely Reduce Menstrual Blood Loss (Mbl) In Women With Menorrhagia Or Iud Induced Mbl?, Veronica W. Chang

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: To determine if Tranexamic Acid effectively and safely reduce menstrual blood loss (MBL) in women with Menorrhagia or IUD induced MBL?

The Role Of Interferon Gamma In The Regulation Of Il-18 Binding Protein And The Development Of Autoimmune Arthritis In A Genetically Non-Susceptible Mouse Strain, Timothy Daniel Kayes

Theses and Dissertations (ETD)

The etiology of the autoimmune disease rheumatoid arthritis (RA) is unknown, but the role of cytokines, including IFN-g, as effectors of immune cell function has been established by the examination of cytokine production in RA patients and through the use of animal models. C57BL/6 (B6) mice that express MHC class II molecules of the b haplotype (I-A^b) are not typically susceptible to collagen-induced arthritis (CIA), the most widely studied animal model of RA. When the gene encoding IFN-g is removed by genetic deletion, however, susceptibility to CIA is conferred. In addition, T cell responses against the immunogen that …

Manipulation Of The Moloney Murine Leukemia Virus Envelope Protein In An Effort To Develop Directly And Indirectly Targeted Retroviral Vectors For Use In Human Gene Therapy, Geneva M. Vasser

Theses and Dissertations (ETD)

Highly effective, targeted therapies against cancer would revolutionize the way people recover from this devastating illness. Gone would be the lingering side effects of the current non-specific treatments and in their place would be faster recovery times, better quality of life both during and after treatment, and less ambiguity about whether or not treatment was effective. This concept will elude modern medicine until treatments can be tailored to the patient's individual and unique disease. This concept of a transient, targeted, and tailored vehicle aimed at cancer cells lends itself to the use of replication deficient retroviral gene therapy vectors with …

C-Reactive Protein Polymorphism And Serum Levels As An Independent Risk Factor In Sickle Cell Disease, Elizabeth A. Chismark

Theses and Dissertations (ETD)

This study explored the relationship of a dinucleotide repeat polymorphism in the intron of the CRP gene and serum CRP levels as independent risk factors for end-organ dysfunction (mild vs. severe) in adults with sickle cell disease. The pathogenesis of secondary complications of sickle cell disease is complex and poorly understood. Predicting the severity of these complications could assist in therapeutic decision-making.

The study measured serum CRP levels and the number of CA intron repeats located on the CRP gene in 29 adults (31.74 ± 11.54 years) with sickle cell disease The hemoglobin genotypes were distributed as Hgb SS 48.6% …

Regulation Of The Human Parainfluenza Virus (Hpiv3) Fusion Protein, Amanda Ruth Chapman

Theses and Dissertations (ETD)

Paramyxoviruses include a number of important human pathogens, including measles virus, mumps virus, and the human parainfluenza viruses (hPIV) 1-4, as well as several animal pathogens, such as Sendai virus, Nipah virus and Hendra virus. The creation of effective drugs and vaccines against this family of viruses would play an important role in decreasing the prevalence of these viruses and contributing to the health of both humans and animals worldwide. The purpose of this work was to determine how the fusion (F) protein is regulated with a focus on the heptad repeat B (HRB) region of the F protein located …

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

Loma Linda University Electronic Theses, Dissertations & Projects

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

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 …

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 …

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 …

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.

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 …

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 …