Research Methods in Life Sciences Commons^™

Microct Study Of Critical-Sized Defects Restored With A New Rhbmp-2 Carrier, Joanne S. Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Regenerating bone in critical-sized maxillofacial osseous defects remains a challenge. The utilization of recombinant human bone morphogenetic protein-2 (rhBMP-2) to form new bone has been shown to be a promising alternative to autogenous bone grafts, and the development of a carrier matrix to effectively deliver the rhBMP-2 has been identified as the critical factor necessary for the successful clinical application of rhBMP-2. The objective of this study was to perform a microCT analysis to examine the density of reconstructed bone using different rhBMP-2 carriers in critical-sized defects.

Material and Methods: Critical-sized defects (approximately 2.5 cm) were created in the …

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 …

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 …

Anti-Inflammatory Effects Of Ppar-Gamma In Surgical Brain Injury (Sbi), Amy Hyong

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Brain injury can be caused by neurosurgical procedures themselves, due to direct trauma, retractor stretch, intraoperative hemorrhage and electrocautery damage. As a result of this surgical brain injury (SBI) postoperative complications such as inflammation, brain edema, and cell death can occur in the susceptible brain areas. Cerebral inflammation is a known contributor to the pathophysiology of brain injury. Following brain injury, the release of inflammatory mediators facilitates the development of BBB breakdown, cerebral edema, oxidative stress and neuronal death, resulting in further tissue damage in the brain and poor neurological outcomes. This study evaluates whether the use of a …

Neuronal Connections From The Cervix To The Spinal Cord Before Parturition, Mary Medina Groves

Loma Linda University Electronic Theses, Dissertations & Projects

By the day before birth, the density of nerve fibers in the cervix has increased compared to earlier in pregnancy or in nonpregnant mice. Similar findings are reported in parturient women. To test the hypothesis that connections between the cervix and spinal cord are enhanced by term, the cervix of nonpregnant and time-dated pregnant mice (day 15 or 18 post-breeding) was injected with pseudorabies virus (PRV), a trans-synaptic retrograde neural tract tracer. Mice were euthanized and perfused 5 days later. The spinal cord and cervix were removed and postfixed overnight, immersed in sucrose, and cryostat sections through the thoracic to …

Mechanisms Of T Helper Cell Modulation In A Simulated Space Radiation Environment, Asma Rizvi

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure to solar particle events (SPEs) poses the most serious threat to astronaut health. Due to this radiation environment, exploration of the solar system beyond Earth’s orbit entails many risks for the crew on these deep space missions. Depression or dysfunction of the immune system is a major concern due to its high radio-sensitivity; potential consequences include overwhelming infection, development of cancer, fibrosis, and poor wound healing. Astronauts are also exposed to low dose/low dose rate (LDR) radiation. A three month stay at the international space station exposes them to ~ 0.05 Gy of radiation.

C57BL/6 mice received LDR gamma-radiation …

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 …

Mechanisms Of Hbo-Induced Neuroprotection In A Neonatal Hypoxia-Ischemia Model, John Winter Calvert

Loma Linda University Electronic Theses, Dissertations & Projects

With an incidence approaching 1/4000 live births and as high as 60% in low birth weight infants, cerebral hypoxia-ischemia during the perinatal period is the single most important cause of acute mortality and chronic disability in newborns. Herein, we tested the hypothesis that following a hypoxic-ischemic insult hyperbaric oxygen (HBO) treatment can restore high energy metabolite levels in the affected regions of the brain and through this increase in energy levels ameliorate the spread of cell death following the insult. We also investigated if an additional mechanism by which HBO affords its neuroprotection is by altering the expression of the …

Stability Of The Miniscrew-Bone Interface: Reverse Torque Values In Rabbits, Daniel John Drye

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Miniscrews are used in orthodontics as practical temporary anchorage devices (TAD's). The purpose of this animal study was to measure reverse torque values for Absoanchor 1.2 mm and Micerium 1.5mm miniscrews at 0, 2, and 12 weeks under loaded and unloaded conditions.

Methods: Ninety-six miniscrews were placed in the femora of twelve rabbits and allowed to heal for either two or twelve weeks. Half of the fixtures were loaded immediately with NiTi open coil springs producing a force of 150-200g and the other half served as unloaded controls. For each of the healing times, two and twelve weeks, …

Bone Formation Using Platelet-Rich Plasma + Allograft: An Experimental Study In Sheep, Edgar Grageda

Loma Linda University Electronic Theses, Dissertations & Projects

Recently Platelet-Rich Plasma has been proven to be an effective regeneration adjunct when combined with autogenous bone in the reconstruction of mandibular defects. However, little is known about the effect of PRP when combined with a bone allograft in the maxillary sinus.

The purpose of this study was to quantitatively evaluate the ability of PRP to enhance bone regeneration in the maxillary sinus of sheep when combined with DFDBA + CCFDBA. Ten sheep were selected for bilateral sinus augmentation DFDBA + CCFDBA + PRP (test) and DFDBA + CCFDBA (control). Five were sacrificed at 3 months and the other five …

The Histological Effects Of Mandibular Distraction Osteogenesis On Rabbit Condyles, Eunice Jungmin Hong

Loma Linda University Electronic Theses, Dissertations & Projects

The present study is a histological evaluation of condyles taken from rabbits that underwent either a midline or paramedian distraction osteogenesis procedure on the mandibles. Fifteen rabbits were originally operated on and eight of these fifteen successfully made it through both the distraction osteogenesis procedure and the 1 month holding period that followed. There was one control animal.

In the present study, the condyles from these nine rabbits (1 control, 2 midline distraction osteogenesis, 6 paramedian distraction osteogenesis) were prepared for histological evaluation (18 total). Step serial sections were cut along the coronal plane and the sections from the anterior …

Radiation Effects On Dopamine-Mediated Prepulse Inhibition In The C57bl/6 Mouse, Cara Nicole Zuccarelli Miller

Loma Linda University Electronic Theses, Dissertations & Projects

This study examined the effects of proton and gamma radiation on a dopamine-dependent sensory gating mechanism: prepulse inhibition of the startle reflex. The purpose of this research was to describe potential hazards of proton radiation to the central nervous system in long-term space fight and for proton therapy patients. Results from previous research indicate that startle behavior is modified by proton and iron radiation. Forty-eight 10-½ week old, male C57BL/6 mice were used to characterize the optimal parameters for the model (prepulse duration, probe duration, and stimulus-onset-asynchrony). Three hundred and fifty two mice were used to characterize the time course …

Distraction Osteogenesis In Edentulous Alveolar Bone With Rhbmp-2 Enhancement, Liviu F. Eftimie

Loma Linda University Electronic Theses, Dissertations & Projects

Distraction osteogenesis, a unique system of affecting rapid bone healing in fractures, realigning malformed bones, and lengthening congenitally short and traumatically shortened bones has become an increasingly utilized technique for the maxillofacial region. The use of distraction osteogenesis has been described for increasing the height of edentulous mandibular alveolar ridges while concurrently forming new bone within the ridge to allow for adequate reconstruction. A standard protocol for performing distraction osteogenesis in the maxillofacial region has been well documented in the literature. Standard distraction osteogenesis requires an initial surgery to place the distraction osteogenesis device and mobilize the segment to be …

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 …

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 …

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 …

Stab Wounds To Rat Brains : Demyelination, Remyelination And The Cellular Response, Particularly Of Oligodendrocytes, Xie Dangci

Loma Linda University Electronic Theses, Dissertations & Projects

The present body of knowledge concerning the results of central nervous system injury is incomplete and controversial. The role of oligodendrocytes, the cells involved in phagocytosis, the stages of demyelination, and the evidence for remyelination are of interest. Following stab wounds to rat brain cortex, corpus callosum and hippocampus, the animals were examined at 4,7,11,18,23,29,45,60 and 70 days postoperation (dpo). To help in the identification of cells immunocytochemical markers for astrocytes and immature oligodendrocytes were used. These were labels for glial fibrillary acidic protein (GFAP) and myelin/oligodendrocyte specific protein (MOSP) respectively. Light and electron microscopy were correlated using conventionally prepared …

Short And Long Term Effects Of Proton Microbeam Irradiation : In The Lateral Geniculate Nucleus Of Felis Domesticus, Chad Sherwood Reder

Loma Linda University Electronic Theses, Dissertations & Projects

Little is known of the effects of proton irradiation on neural tissue. A 1.0 mm microbeam was used on the cat lateral geniculate nucleus (LGN) to quantify the short term (< 3 months) and long term (< 9 months) effects of radiation damage. The LGN is a large structure with well defined afferent, efferent, and receptive field properties.

Electrophysiological and histological techniques were used to examine the effects of the microbeam at 60, 40, and 16 Gy, administered as a single bolus. Recordings of light evoked responses in the LGN were obtained using microelectrodes in nine animals within 12 weeks of irradiation, and 6 animals within 36 weeks of irradiation. Receptive fields were mapped onto a tangent screen using standard receptive field techniques. Histological measures included afferent …

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, …

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 …

In Vitro Evaluation Of Cancer Patient Immune Responses Following Infusion Of Radiolabeled Murine Monoclonal Antibody, Kelly A. King

Loma Linda University Electronic Theses, Dissertations & Projects

Several monoclonal antibody (MAb) types derived from mice have been developed specifically for the use of targeting human tumors. The specificity of these murine MAb’s for their respective tumor antigens is very high making them potentially good immunotherapeutic agents for cancer treatment and diagnosis. A limiting factor in using these murine MAb’s in patients is the development of human anti-mouse antibody (HAMA). The presence of HAMA may reduce the effectiveness of MAb for tumor targeting. If patient sensitization could be quickly detected following the initial infusion of MAb, then future infusion could be altered or terminated to prevent further sensitization. …

Regeneration Of Meissner Corpuscles In Diabetic Mice Following Median Nerve Crush, Bonnie J. Forrester

Loma Linda University Electronic Theses, Dissertations & Projects

The hyperglycemic metabolic condition found in diabetes mellitus leads to the development of sensory neuropathies and causes delayed and incomplete neuronal regeneration. Diabetic sensory neuropathy has been shown to contribute to the impairment of light touch and low frequency vibratory perception. It is proposed that the regeneration of receptors that detect these sensations will be delayed and incomplete in diabetic animals with uncontrolled hyperglycemia. This study addresses the effects of diabetes on the regeneration of Meissner corpuscles, distal sensory endings that perceive light touch and low frequency vibration.

Corpuscles from 60 diabetic mice, and their age-matched, non-diabetic littermates, were examined …

The Inhibition Of Bone Formation Occurring Under Weightlessness : The Effect Of Skeletal Unloading On Serum Levels Of A Bone-Derived Growth Factor, Jean D. Sibonga

Loma Linda University Electronic Theses, Dissertations & Projects

A deleterious effect of spaceflight on human health is the loss of bone associated with the prolonged lack of gravitational stress on the skeleton. A potential for bone loss is indicated by the hypercalciuria and decreased heel bone density determined in Skylab astronauts. Histological studies of juvenile laboratory rats in actual spaceflight and in simulation models document a suppression of bone formation with little alteration of bone resorption. The mechanism for net bone loss needs to be defined in order to develop measures for its prevention or correction.

Skeletal growth factors, which may mediate coupling and locally regulate bone volume …

Age-Related Changes In Meissner Corpuscles Of Diabetic Mice As Observed By Electron Microscopy, Vicky R. Ras

Loma Linda University Electronic Theses, Dissertations & Projects

Light touch and low-frequency vibration sense are often impaired in diabetic patients. Meissner corpuscles are distally located mechanoreceptors that respond to these stimuli. Peripheral sensory neuropathy in diabetes progresses from distal to proximal, therefore, Meissner corpuscles are ideally suited to study diabetic neuropathy in the C57BL/Ks (db/db) mouse.

Corpuscles from the forepaw digital pads of 9 diabetic and 9 nondiabetic littermates were studied by electron microscopy. These were divided into 3 age groups; 2.5 months, 10 months, and 17 months old.

Ultrastructural changes observed within various receptor components were myelin figures, multivesicular bodies, vacuoles, basal lamina duplication, abnormal and enlarged …

A [6-14c] Glucose Autoradiographic Study Of The Rat Brainstem Under Hypercapnic And Hypocapnic Conditions: Identification Of Respiratory-Related Regions, Tobey M. Leung

Loma Linda University Electronic Theses, Dissertations & Projects

The effects of systemic hypercapnia on brainstem metabolism were studied with the [6-¹⁴C] glucose autoradiography method. Neuronal pools which are metabolically active take up more [6-¹⁴C] glucose and maybe revealed pictorially as darker areas on autoradiograms. Since a high concentration of carbon dioxide stimulates central chemoreceptors and hence enhances respiratory drive, the darker regions on the autoradiograms may represent regions concentrated with respiratory-related neurons. Two discrete regions in the ventrolateral medulla (a column near nucleus ambiguus and a column in the lateral reticular nucleus) appeared dark and were analyzed with an image processing system, which converted …

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 …

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 …