Life Sciences Commons^™

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 …

Expression, Isolation And Purification Of Human Zona Pellucida Protein 3, Ting-Fung Chi

Theses and Dissertations in Biomedical Sciences

Mammalian fertilization involves interactions of sperm surface receptors with the ligands of the zona pellucida, an extracellular matrix surrounding the ovulated oocytes. In humans, the zona pellucida is composed of three major glycoproteins. One of them, ZP3, participates in the primary sperm binding and in the subsequent triggering of the spermatozoa's acrosome reaction. Studies on the role of this specific protein in the human fertilization process are hampered by the limited amount of available biologically functional proteins.

By use of a pcDNA 3.1(+) expression vector, a transfecting-vector was constructed containing a 1.3 kb histidine tagged hZP3 cDNA. This histidine tagged …

Leukemia Inhibitory Factor (Lif): Murine Preimplantation Embryo Development, Implantation Rates, And Skeletal Development, Michael Hayes Mitchell

Theses and Dissertations in Biomedical Sciences

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine which demonstrates perplexing physiological effects. It has been demonstrated that LIF is essential for implantation in mice. Little is known relating to the manner by which LIF effects pre-implantation and post-implantation development. The objectives of this project were to determine the effects LIF on pre-implantation development, to determine the effects that it may have on implantation rates, successful pregnancy rates, and resorption rates, and to determine the effects that LIF has on the skeletal development of mice. For the embryo transfer experiments, embryos were exposed to test compounds in the transfer medium …

Mouse Embryo Development In The Presence Of Capsaicin, Carlos Santiago Villar-Gosalvez

Theses and Dissertations in Biomedical Sciences

Capsaicin is the pungent agent found in hot peppers of the Capsicum genus. It is a potent neurotoxin that stimulates the degranulation and degeneration of C-afferent neurons. Capsaicin is widely used as a food condiment and medicine. Human exposure of capsaicin can exceed levels shown to be neurotoxic in laboratory animals. Additionally, capsaicin can cross the blood/placenta barrier and affect an embryo in utero. In order to assay the potential for toxicity to human embryos, mouse embryos were exposed to capsaicin and the effect of the capsaicin on embryo development was measured. Embryos were co-cultured in Krebs medium with 1% …

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 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 …

Pressure-Induced Intracellular Signaling In Isolated Arteries, Victor A. Miriel

Theses and Dissertations in Biomedical Sciences

The ability of cells to respond to mechanical stimuli has been studied through a variety of techniques in numerous cell types. The cells of the vascular wall have adapted to specific mechanical stresses through the activation of intracellular signaling pathways which result in cell-specific responses such as hypertrophy, hyperplasia, proliferation, and migration. Vascular smooth muscle of the arteries have been shown to be sensitive to mechanical stimuli such as stretch, and pressure.

This study attempts to add to the current knowledge of mechanotransduction by utilizing the isolated artery preparation. This preparation allows for the study of vascular smooth muscle signal …

The Role Of Glycoconjugates In Mediating Human Fertilization And Induction Of Fetomaternal Tolerance, Manish S. Patankar

Theses and Dissertations in Biomedical Sciences

Using the hemizona assay (HZA), a in vitro sperm-egg binding assay, we show that specific glycoconjugates known to inhibit immune cell interactions mediated by the selectins, potently block human sperm-egg binding. The selectin ligand sialyl Lewis^x inhibits sperm binding in the HZA by 60% at a concentration of 1 mg/ml. Our data indicates that glycodelin-A, a endometrial glycoprotein known to block sperm-egg binding in the HZA at low concentrations expresses unusual fucosylated lacdiNAc type glycans. The fucosylated lacdiNAc type sugars have been previously shown to be 15-20 fold more potent ligands of E-selectin. Glycodelin-S a seminal plasma glycoform of …

Reaction-Diffusion Models Of Cancer Dispersion, Kim Yvette Ward

Mathematics & Statistics Theses & Dissertations

The phenomenological modeling of the spatial distribution and temporal evolution of one-dimensional models of cancer dispersion are studied. The models discussed pertain primarily to the transition of a tumor from an initial neoplasm to the dormant avascular state, i.e. just prior to the vascular state, whenever that may occur. Initiating the study is the mathematical analysis of a reaction-diffusion model describing the interaction between cancer cells, normal cells and growth inhibitor. The model leads to several predictions, some of which are supported by experimental data and clinical observations $\lbrack25\rbrack$. We will examine the effects of additional terms on these characteristics. …

Evaluation Of The Role Of Fructosamine As An Indicator Of Diabetic Control, Katherine Hooley

Theses

Diabetes mellitus, a common metabolic disease, is characterised by excess circulating glucose concentrations. Such a hyperglycaemic status provides the stimulus for irreversible glycation (non-enzymatically post-translational) of structural and functional proteins. Protein glycation, although a cause of complication (neuropathy, micro/macrovascular disease), provides a time-averaged index of diabetes status and control. In particular, glycated plasma proteins analysis, i.e., the fructosamine assay, has received favourable response due to its speed, simplicity, low cost, and ease of automation. However, lack of standardisation and a universally-accepted calibrant has limited technical and subsequent clinical confidence in fructosamine analysis. In response, a comprehensive technical evaluation (including novel …