Research Methods in Life Sciences Commons^™

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 …

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, …

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, …

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. …

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 …

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 …

Stability In Mechanical Expansion Of The Maxilla With Surgical/Mechanical Expansion Of The Mandible In An Adult Baboon, Robert D. Mitchell

Loma Linda University Electronic Theses, Dissertations & Projects

Expansion of the maxilla at the midpalatal suture has had much investigation and is a recognized option in orthodontic therapy. Lateral expansions of the mandible through surgical separation at the symphysis have been done in animal studies. A combination of these procedures has not yet been done together.

The purpose of this study was to expand both the maxilla and the mandible of a baboon simultaneously while maintaining occlusion. The amount of expansion and stability was studied using photographs, models, cephalograms, and tetracycline bone labels using U.V. microscopy.

A young adult baboon with full dentition and normal occlusion was used. …

Age-Related Changes Of Neurites In Meissner Corpuscles Of Diabetic, Vicky R. Ras

Loma Linda University Electronic Theses, Dissertations & Projects

This thesis is based on a qualitative and quantitative study of the neural component of Meissner corpuscles of diabetic and non-diabetic mice. Age-related changes were also documented in these mechanoreceptors. Corpuscles from forty-six diabetic mice and forty-six non-diabetic mice ranging from 2.5 to 17 months old were studied. Forepaw index digital pads were formalin-fixed and frozen-sectioned parallel to each digit and perpendicular to the skin. Serial sections were then silver-impregnated to allow light microscopic examination of the neurites in the corpuscles.

Neurites became more coarse, tortuous, branched, varicose, and thus more complex until middle age. Corpuscle size appeared greatest at …

Observation Of Bone Formation In The Mandibular Symphysis Following Surgical Separation And Slow Mechanical Expansion In A Baboon, Robert J. Homer

Loma Linda University Electronic Theses, Dissertations & Projects

Mechanical expansion of the maxilla, at the midline suture, is a widely accepted orthodontic procedure used to gain arch width in certain types of maxillary deficient arches.

In animal research on the mandible, techniques using surgical separation at the symphysis with immediate expansion up to 12 mm, fixation with a metal splint, and autogenous bone transplanted into the expanded area, have been reported to be successful.

To date, no experiment utilizing slow mechanical expansion of the mandible at the symphysis has been reported.

In this pilot study, the mandible of a female baboon was surgically separated A-P at the symphysis. …

The Effect Of Escherichia Coli Endotoxin On The Cat Periapical Tissues, Thomas G. Dwyer

Loma Linda University Electronic Theses, Dissertations & Projects

The periapical tissue reaction to three concentrations of endotoxin solutions and to a sterile saline control solution was examined in six adult cats. The maxillary and mandibular cuspids were isolated and the pulps extirpated with barbed broaches. The four solutions (1, 10, 100 μg/ml endotoxin, and saline) were then injected into the four prepared teeth for each cat and the access cavities sealed with IRM.

At two week intervals, two cats were sacrificed and the specimens removed, while the remaining animals were retreated as previously described. The block tissue sections were radiographed, fixed in 10% buffered formalin, and prepared for …

Cell Mediated Immunity By Cytotoxicity Assay And The Effect Of Corynebacterium Parvum And Radiation On Mice Bearing Herpes-Induced Tumors, Robert B. Stagg

Loma Linda University Electronic Theses, Dissertations & Projects

Cell mediated immune (CMI) cytotoxic reactivity of Balb/c mice against H238 cells, a Herpes simplex virus (HSV) Type 2 - induced sarcoma, was measured by the ¹²⁵IUdR release assay. The Balb/c mouse response to the growing HSV-induced tumor, treated with radiation and , was measured by survival rate, tumor growth and immune cytotoxicity of spleen and peritoneal exudate cells (PEC) as determined by ¹²⁵IUdR release assay. Subcutaneous (s.c.) inoculation of 1 x 10⁶ H238 cells (high dose) produced progressive tumor growth while s.c. inoculation of 1 x 10⁴ H238 cells (low dose) produced no tumors. A …

The Effect Of Endodontic Therapy On The Incidence Of Radiation Caries In Dogs, James A. Abbott

Loma Linda University Electronic Theses, Dissertations & Projects

Endodontic therapy was evaluated as a possible control or prevention modality of radiation type dental caries in dogs. Two adult male dogs with permanent dentitions had endodontic therapy performed on alternating teeth in each jaw. The nontreated teeth served as controls.

The dogs were irradiated with 7000 rad Cobalt-60 radiation fractionated over an eight week period. The dogs were killed at 60 and 182 days post-irradiation. The teeth were removed from the jaws and immersed in methylene blue dye, sectioned, and the dye penetration pattern photographed. Diffusion of the dye into the tooth structure was quantified and statistically analyzed.

A …

Apical Closure Induction Using Bone Growth Factors And Mineral Trioxide Aggregate, Kenneth W. Tittle

Loma Linda University Electronic Theses, Dissertations & Projects

This study compared the ability of three different bone growth factor combinations with that of Ca(OH)₂ to stimulate apical closure as well as the effectiveness of Mineral Trioxide Aggregate (MTA) as an apical barrier. Fifty-six roots of second and fourth mandibular premolars of seven six- month old beagle dogs were used. Periradicular lesions were created over a four week period. The canals were cleaned and shaped and filled with Ca(OH)₂ for one week. They were then irrigated and received one of seven different treatments in a balanced design. Growth factors were placed in a carboxymethylcellulose carrier and delivered …

The Effect Of Elevated Glucose On Neutrophilic Phagocytosis In Genetically Diabetic Mice, Larry B. Thompson

Loma Linda University Electronic Theses, Dissertations & Projects

Infiltration to an injury site or area of bacterial contamination by polymorphonuclear leucocytes (or neutrophils) is an early and essential phase of the early inflammatory reaction. Their action on foreign matter is the most critical step taken by body defense mechanisms in the first 24 hours. Anything which interferes with that action, phagocytosis, greatly hampers early inflammation. This study was designed to see the effect of elevated glucose levels on neutrophil phagocytosis in a unique strain of genetically diabetic mice.

Twenty-two diabetic and twenty-four control female mice were used. Blood glucose determinations and total white counts were made on each …

Some Aspects Of Cranial Bone Growth In The Puberal Macaca Mulatta Monkey: As Evidenced By Metallic Implants And Cephalometric Roentgenography And The Application Of A Geological Lapidary Technique For The Semi-Serial Thin Sectioning Of Undecalcified Bone, Lee Eugene Olsen

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to investigate cranial and facial bone growth in the puberal Macaca mulatta monkey over a six month period utilizing the methods of metallic implantation combined with serial cephalometric roentgenography and a bichromatic vital staining method.

The employment of the vital stains, alizarin Red S and anthracene blue, over the six month period of the study, failed to stain the actively growing bone as evidenced by gross and microscopic analysis of the undecalcified bone preparations.

Interimplant measurements were made across certain bone sutures and the following results were obtained: The zygomaticotemporal sutures showed marked growth …

A Cephalometric, Anatomic And Histologic Investigation Of The Effects Resulting From A Heavy Interrupted Orthopedic Force To The Maxilla Of The Macaca Mulatta Monkey, Roger Wayne Triftshauser

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to determine changes that occur in the craniofacial complex, when a heavy interrupted orthopedic force is employed to retract the maxilla in the post puberal rhesus monkey. Cephalometric, histologic and anatomic examinations were utilized to substantiate the findings.

Four female rhesus monkeys were used for experimentation. Two were experimental animals and the other two controls. Cervical retraction with headgear was applied over a period of 313 days and 159 days to the two experimental animals. Forces not exceeding 2.5 lbs. were found most effective.

The findings were as follows:-

1. A total posterior displacement of …

Craniofacial Changes Resulting From Expansion Of The Midpalatal Suture In The Macaca Mulatta Monkey As Revealed By Roentgenographic Analysis, Raymond M. Sugiyama

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to determine the effects of midpalatal suture separation on the craniofacial complex by quantitative roentgenographic analysis.

Ten female Macaca mulatta monkeys were randomly grouped for experimentation. Six animals were paired in groups for two months of treatment, four months of treatment followed by two months of post retention, and six months of treatment. The four remaining monkeys were paired and served as control animals for two and six month periods. Total activation of the expansion appliances in the treated animals was completed over a three week period.

The findings of this study were based …

Pharmacological Studies Of Antidiabetic Chinese Herbs, Mun Fa Lee

Loma Linda University Electronic Theses, Dissertations & Projects

Rehmannia glutinosa, Atractylus ovata, and Polygonatum chinense have all been employed by the Chinese as oral antidiabetic agents and reported by Min (1928), Kin (1931), and Li et al. (1936) to possess hypoglycemic activity. This prompted the pharmacological studies of these herbs.

Materials and methods. Their pharmacognosy was condensed from all available Chinese and scientific literature. Preliminary chemical and physical analyses included determinations for moisture, ash, crude fat, carbohydrates, protein, phosphorus, pH, alkaloids, melting point, and spectroscopy. Employing the Somogyi-Nelson method, their glycemic activity was studied in rats, rabbits, and dogs. Stress reactions were minimized. The effect …

The Effect Of Adrenal Steroid Hormones On The Protein Content Of Tumorous Livers, Duncan W. Martin

Biology ETDs

Protein is basic to the structure and function of protoplasm. Enzyme systems which regulate the rate of cellular reactions are primarily composed of protein and many of these enzymatic systems influence the metabolism of less specialized proteins that form the major structural material of protoplasm. It is believed that experimental procedures which modify protein composition of cells may also influence the activity of intra-cellular enzymes. In experimental live cancer, it has been shown that the activities of a number of oxidative enzymes are modified as the carcinogenic process proceeds (Richmond, 1955, p.38). Furthermore, it has been demonstrated that endocrine function …

Kidney Of The Frog, Felix Taubman

Bachelors’ Theses

The frog has been used exclusively in both high school and college as the main source of experimental biological and zoological studies. Because it is so easily obtained and so finely adapted to our purposes, we chose it as the specimen upon which to do our thesis work. Much has been done experimentally on the kidneys with the frog. The purpose of this thesis is to present a general view of the external and microscopic anatomy of the frog kidney and with this as a groundwork to present the problems of secretion; whether secretion is carried on by the renal …