Animal Experimentation and Research 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 …

Behavior And Physiology Of Hermit Crabs During Burial: Shell Abandonment And Lactate Accumulation, Janelle Allison Shives

Loma Linda University Electronic Theses, Dissertations & Projects

Organisms living in the intertidal zone must adapt to environmental and physical stressors. One physical stressor that these organisms may face, and that may require specific behavioral and physiological responses, is burial by sediment. In this thesis I report the results of experiments in which I subjected the intertidal hermit crab, Pagurus samuelis, to burial and analyzed aspects of subsequent behavior and physiology. In the first set of experiments, hermit crabs were buried with the shell aperture facing either up or down, and at one of three depths (2, 4, or 6 cm). The factors hermit crab weight, shell …

Mnte-2-Pyp And Radiation In A Prostate Cancer Model: Implications For Radiotherapy, Adeola Y. Makinde

Loma Linda University Electronic Theses, Dissertations & Projects

A major limitation of successful radiation therapy in cancer treatment is the increase in normal tissue damage as higher doses are used to achieve greater tumor destruction. Radiation dose optimization in cancer therapy requires achieving maximum tumor destruction with minimal damage to normal tissue Antioxidants have been shown to protect normal tissues against radiation damage, as radiation-induced tissue damage results predominantly from reactive oxygen species that directly damage cellular components. However, for effective use as normal tissue radioprotectants in radiotherapy, these antioxidants must not protect the tumors. Mn (III) tetrakis (N-ethylpyridinium-2-yl) porphyrin (MnTE-2-PyP) is a metalloporphyrin antioxidant that has been …

Role Of No In The Regulation Of Cortisol Synthesis In Long-Term Hypoxic Sheep Fetal Adrenal, Tshepo Rothi Monau

Loma Linda University Electronic Theses, Dissertations & Projects

Our laboratory has demonstrated that sheep fetuses adapt to long-term hypoxia (LTH) by maintaining normal level of basal plasma cortisol despite increased adrenocorticotropic hormone (ACTH). But the mechanisms involved are not fully understood. Studies have shown that nitric oxide (NO) inhibits synthesis of steroid hormones in a variety of tissues, and in different animal species. Studies also showed that hypoxia increases both expression and activity levels of the nitric oxide (NO) generating enzyme, nitric oxide synthase (NOS), in certain tissues. We have here investigated the expression level and localization of NOS isoforms in sheep fetal adrenals. We also investigated the …

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 …

Radiation-Induced Increases In Pkc Modulate Integrin Expression And Contribute To Fibrotic Changes, Pinal Rushikesh Pandya

Loma Linda University Electronic Theses, Dissertations & Projects

The sequences of events in fibrosis are similar to those in wound healing; however, the normal termination and resolution stages do not take place. The initial cellular response following ionizing radiation involves accumulation of the ECM (extracellular matrix) including collagen, fibronectin and the interaction of many growth factors (cytokines) with their receptors. There are a number of unanswered questions regarding many aspects of radiation-induced fibrosis, including the initial triggers and physical changes that initiate the process. We have confirmed that elevated pKC and other cellular changes following radiation are similar to those found at sites of inflammation. This information leads …

Effects Of Diabetes Mellitus On The Healing Of The Dental Pulp, Stuart Evan Garber

Loma Linda University Electronic Theses, Dissertations & Projects

Diabetes Mellitus (DM) has been implicated as a factor affecting healing. The purpose of this study was to use the healing of experimentally exposed pulps subsequent to pulp capping as a model to determine the effect of DM on healing.

Twenty-two Sprague-Dawley rats were divided into two groups of eleven animals each. In one group, DM was induced by injection of 70 mg/KG of streptozotocin. In the other group, the animals were injected with sterile saline. Under anesthesia with Ketamine and Xylazine, the pulps of the maxillary first molars of all rats were exposed using a 1/16 round bur under …

Histological Comparison Of White And Gray Mta In Repair Of Furcation Perforations, Miguel Elias Mego

Loma Linda University Electronic Theses, Dissertations & Projects

Mineral trioxide aggregate (MTA) has been shown to promote regeneration of the periodontal apparatus when used as a repair material in furcation perforations. Two variations of MTA (Gray and White) have been introduced to the dental market. The purpose of this study was to histologically compare the in vivo response to immediate furcation perforation repair using gray or white MTA in beagle dogs.

Under general anesthesia, non-surgical root canal therapy and furcal perforations were performed on sixteen mandibular premolars of eight 2-year old beagle dogs. The perforations were immediately repaired with either white (n=8) or gray (n=8) MTA. The animals …

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 …

Effect Of Anti-Tgfß1 And Pycnogenol® On Scar Formation In Rats, Pilseong Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Wound healing is a complex biologic process that involves chemotaxis and division of cells, neovascularization, synthesis of extracellular matrix proteins, and remodeling of the repaired tissues. Of equal importance is the restoration of normal tissue structure and function without scar formation. The aim of this study was to find out the clinical effects of anti-TGFß1 and Pycnogenol® on scarless wound healing on rat skin.

An acute incision wound model was used with 20 healthy rats. Four incisions were made on each rat's skin and 4 different variables were applied by local infiltration. The four variables were anti-TGFß1, Pycnogenol®, PBS, and …

Effects Of Various Hemostatic Agents On Bone, David Daryl Roland

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies have evaluated the effects of various hemostatic agents on radicular tissues following apical surgery. The purpose of this study was to examine the early osseous responses to seven hemostatic agents under identical conditions in rabbits. Sixteen adult male New Zealand white rabbits were used for this study. Following anesthesia, utilizing a midline submandibular incision, standardized bony defects were prepared on the lateral-superior regions of the mandible. Test materials were placed using standardized volumes and exposure times. Bone wax, Surgicel, Capset, alginate, Cut-Trol, Hemogin-L, and silver nitrate were compared to control sites irrigated with saline. Test materials or controls …

Identification Of Hard Tissue Using Dentin Sialoprotein (Dsp) As A Marker, Wallis E. Andeline

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to identify the early hard tissue formed in experimental pulp exposures capped with calcium hydroxide, mineral trioxide aggregate (MTA) or bone morphogenetic protein-7 (BMP-7) using dentin sialoprotein (DSP) as a marker. The pulps of eighty-five maxillary first, second and third molar teeth from twenty male rats were experimentally exposed. The exposed pulps were capped with calcium hydroxide followed by restoration with amalgam (n = 20), with MTA alone as a pulp capping agent and final restoration (n = 20) or with BMP-7 followed by restoration with MTA (n = 20). Ten teeth with Class …

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]

Effects Of Liposome-Encapsulated Tnf-Alpha And Radiation Against Colon Cancer, Dong Won Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies have shown that tumor necrosis factor-α (TNF-α) can augment the antitumor effects of radiation, inhibiting tumor progression to a greater extent than either modality alone. However, nonspecific toxicities associated with TNF-α have limited its use as an adjuvant. This limitation is potentially resolved with the encapsulation of TNF-α in sterically stabilized, PEGylated liposomes (STEALTH®). Thus, the overall hypothesis of the research was that the combination of radiation with STEALTH® liposome encapsulated TNF-α (SL-TNF-α) will have greater efficacy and fewer dose-limiting side effects in the LS174T human colorectal tumor xenograft model compared to the combination of free TNF-α and …

The Effect Of Chronic Hypoxia On Cardiac Function In The Fetal Ovine Heart, Rodney David Rodrigo

Loma Linda University Electronic Theses, Dissertations & Projects

It has been shown that long-term high altitude hypoxia during pregnancy was associated with a decrease in cardiac contractility in fetal sheep. Given that hypoxia caused apoptotic cell death in fetal and neonatal rat cardiomyocytes, the present study tested the hypothesis that chronic hypoxia during pregnancy increases apoptosis in the fetal sheep heart. Pregnant (d 30) sheep were divided between normoxic control and chronically hypoxic (maintained at high altitude, 3,820 m, PaO₂: 60 Torr for 110 days) groups. Hearts were isolated from near-term (d 140) fetal sheep, and samples from all four chambers, right and left atria, and …

Periradicular Response Of Immunodeficient Rats To Mechanical Pulpal Exposure, James E. Stich

Loma Linda University Electronic Theses, Dissertations & Projects

Periradicular lesions develop as a result of the interaction between root canal irritants and the immune system. The purpose of this study was to investigate the periradicular response of immunodeficient rats to their oral flora. Twenty Sprague-Dawley rats received a total body irradiation dose of 750 cGy one week prior to the investigation. The pulps of the mandibular first molars of these animals and six nonirradiated rats were exposed mechanically with a ½ round bur and left open to the oral cavity. Additional irradiation (350 cGy) was administered bi-weekly to maintain immunosuppression. Periradicular specimens were obtained after two and four …

The Role Of Brn-3.2 In Retinal Ganglion Cell Differentiation, Jerin Marie Wright

Loma Linda University Electronic Theses, Dissertations & Projects

Within the retina, the POU domain of transcription factors brn-3.0, brn-3.1, and brn-3.2 are present only in retinal ganglion cells. These genes are believed to be involved in establishing neural cell lineages in mammals. In this study brn-3.2 was examined by comparing the number of ganglion cells present during postnatal development in normal mice (+/+), in mice homozygous (-/-) for the brn-3.2 gene, and in adult mice with a heterozygous gene deletion (+/-) for brn-3.2. Optic nerve cross sections were imaged by electron microscopy, and axon profiles counted systematically by hand. These counts were then related to the nerve cross …

The Effect Of Root End Demineralization On Cementogenesis : A Long Term Investigation, Hamid R. Abedi

Loma Linda University Electronic Theses, Dissertations & Projects

Craig and Harrison¹² examined the effect of demineralization of resected root ends on wound healing following periradicular surgery. Based on its microscopic evaluations from 4-45 days, it was proposed that demineralization of resected root ends enhances cementogenesis. The purpose of this study was to investigate the longer term effects of demineralization on cementogenesis using Mineral Trioxide Aggregate (MTA) or amalgam as root end filling materials. After completion of root canal therapy and endodontic surgery on seventy-two roots of mandibular second, third and fourth premolars of six beagle dogs, 32/72 of the root ends at random were etched with 50% …

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 …

An Animal Model For Development Of Pulpal Inflammation, John W. Masters

Loma Linda University Electronic Theses, Dissertations & Projects

Several animal models have been proposed to develop pulpal inflammation. Procedures recommended in these models have many variables and have not produced consistent results. The purpose of this study was to create pulpal inflammation using the Nd:YAG laser.

Forty-five cuspids of 12-18 month old beagle dogs were lased at 5, 7.5, and 10 watts (W) for 20 seconds with a 600 micron contact probe. Five cuspids were not lased but were used as controls. Following laser application, the teeth were extracted at intervals of 3, 7, and 30 days. They were then fixed in 10% formalin, decalcified, sectioned, and stained …

The Effect Of Guidor™ And Hop-1 On Hard Tissue Healing : Following Periradicular Surgery In Cats, Hugh Maguire

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to evaluate the effects of the resorbable membrane Guidor™ and the osteogenic protein hOP-1 on hard tissue healing following periradicular surgery in cats.

Surgical endodontic therapy was performed on the maxillary canine teeth of twelve cats. After orthograde root canal therapy, flap reflection, osteotomy, resection of the root end, root end cavity preparation and the placement of a root end filling, eight of the surgical sites were treated with Guidor™ and eight with hOP-1. The remaining eight sites received no further treatment and served as controls.

The animals were sacrificed at twelve weeks following …

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 …

Periodontal Repair In Dogs : Evaluation Of Rhbmp-2 Carriers, Lauralee Nygaard

Loma Linda University Electronic Theses, Dissertations & Projects

This study evaluated candidate carriers for recombinant human bone morphogenic protein-2 (rhBMP-2) in periodontal reconstructive surgery.

Canine demineralized bone matrix (DBM), bovine inorganic crystallene bone matrix (Bio-Oss), bovine derived microfibrillar collagen matrix (Helistat), poly (D,L-lactide-coglycolide) micropaiticles (PLGA), and polylactic acid granules (Drilac) were used with rhBMP-2 (20 (µg/100 µl implant volume) in routine critical size canine supraalveolar periodontal defects. Contralateral defects in six beagle dogs were randomly assigned to receive: DBM/rhBMP-2, DBM-control, Bio-Oss/rhBMP-2, Helistat/rhBMP-2, PLGA/rhBMP-2, or Drilac/rhBMP-2, all with autologous blood except for Helistat and PLGA. Animals were sacrificed eight weeks post-surgery and block sections of the defects were processed …

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 …

Healing Potential Of Osteotomies Of The Nasal Sinus In The Dog, Roderick W. Tataryn

Loma Linda University Electronic Theses, Dissertations & Projects

Maxillary sinus osteotomy is sometimes indicated for transantral surgical approaches to palatal roots of maxillary molars. A search of the literature showed an absence of any report on the healing potential of such defects. The purpose of this study was to determine histologically the reparative process of the nasal sinus of dogs following small and large surgical antral perforations. After anesthetizing six beagle dogs, full thickness periosteal flaps were raised overlying the maxillary buccal cortical plates. A 5x5 mm diameter perforation was created with a trephine bur above the second maxillary premolar on one side of each animal. On the …

Suppressive Effects Of Transforming Factor-Β And Interleukin-10 On The Cytolytic Activity Of Murine Macrophages And Reversal By Cytokines, Chin-Hung Lin

Loma Linda University Electronic Theses, Dissertations & Projects

In this study, the suppressive effects of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) on peritoneal macrophage killing of H238 target cells and the potential for reversal of the immunosuppressive effect by IL-4 and interferon-γ (IFN-γ) were investigated. The responsiveness of naive and peptone-activated macrophages was compared. The cytolytic activity for tumor cells of these effector cells was measured by percent lysis of ³H-thymidine labeled Herpes simplex virus type 2-transformed tumor cells (H238). After 18-24 hours of incubation with TGF-β or IL-10, the cytolytic activity of macro-medium alone. The immunosuppressive effect of TGF-β or IL-10 on non-activated macrophages was …

Development Of Periapical Lesions In Immunosuppressed Rats, Phillip A. Waterman Jr.

Loma Linda University Electronic Theses, Dissertations & Projects

The pathogenesis of periapical lesions is the interaction of the oral flora with the existing host defenses. The role of bacteria has been established in endodontic disease but the contribution of the host defenses in periapical lesion formation is less clear. The purpose of this study was to compare periapical lesion development in immunosuppressed rats with that in normal rats. Thirty-five, eight-week old Sprague-Dawley rats were equally divided into seven groups. Groups 1, 2, and 3 were given weekly injections of Cytoxan, an immunosuppressive agent. Groups 4, 5, and 6 received no immunosuppressive therapy. Group 7 served as a control, …

The Role Of T Cells In The Pathogenesis Of Periapical Lesions, John B. Wallstrom

Loma Linda University Electronic Theses, Dissertations & Projects

The pulps of mandibular molars of 15 athymic and 15 conventional rats were surgically exposed and left open to their oral flora. Each group was divided into 3 subgroups of 5 animals each. The rats were sacrificed after their pulps were exposed for 2, 4, or 8 weeks. After fixing, decalcifying, and embedding, the specimens were sectioned and stained with H and E. They were then examined under a microscopic grid and quantified by percentages of surface areas of bone, connective tissue, bone marrow, intrabony spaces, periapical lesions, and numbers of osteoclasts. This was done using a DataVoice computerized data …

Histomorphometric Analysis Of Primate Periodontal Tissues Following Corticotomy In Orthodontics, Wuiteng Koh

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to evaluate the prevalence of specific cell types and structures at the active tooth movement site in corticotomized and non-corticotomized specimens obtained from a previous study, and to consider the hypothesis that corticotomy facilitated orthodontics is efficacious due to an inflammatory response rather than tooth-bone block movement. Specimens from 3 monkeys, each of which had a treatment and control quadrant in each arch, were sectioned, mounted on glass slides, and stained with Giemsa, haematoxylin, and Safranin stains. A histomorphometric analysis was performed with DataVoice™, a voice activated computer system which allowed for digitization of …