Laboratory and Basic Science 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 …

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 …

The Comparative Radiopacity Between Primary And Permanent Teeth, Robert C. Lee

Loma Linda University Electronic Theses, Dissertations & Projects

Purpose: This in vitro study compared the radiopacity between human primary and permanent enamel and dentin. It also compared the radiopacity between human anterior and posterior teeth.

Methods: Extracted primary and permanent teeth were used in this study. One mm enamel and one mm dentin slices were cut from each extracted tooth. Radiographs were taken of each enamel and dentin specimen 1 mm in thickness along with an aluminum step-wedge using procedures specified in International Standards Organization (ISO) 4049:2000. A densitometer was used to measure the Optical Density (OD) of the radiographs of the specimen and the accompanying aluminum step-wedge. …

Response Of Endothelial Cells To Stressors: The Impact Of Aging And Diabetes, Katie Mclellan

Loma Linda University Electronic Theses, Dissertations & Projects

Preliminary research indicates there is some impairment of the endothelial cells to respond to single stressors such as local heat, shear stress, and global heat in older people and people who have diabetes. The response of the skin blood flow to local heat is an indicator of the endothelial cells ability to cope with stress. In addition, factors such as thicker subcutaneous fat and skin moisture may impair the skin’s ability to dissipate heat. For older people and people with diabetes, this endothelial dysfunction may cause an even more diminished response to multiple stressors. However, no studies have examined the …

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 …

An In Vitro Model Of Ovarian Cancer: Studying The Effects Of Talc And Pycnogenol®, Amber Renée Buz'zard

Loma Linda University Electronic Theses, Dissertations & Projects

Ovarian cancer is the sixth most common cancer and accounts for more deaths than any other cancer of the female reproductive system. The American Cancer Society has suggested that poor diet, talc and industrial pollutants may increase the risk of developing ovarian cancer. Talc is ubiquitous and concern is raised about its safety, role as a possible carcinogen and known ability to cause irritation and inflammation. Due to the silent nature of ovarian cancer, chemoprevention is a high priority. The most useful chemopreventive compounds will inhibit, delay or reverse carcinogenesis, and can be taken for long periods of time with …

The Acute Effects Of Nut Ingestion On Plasma Levels Of Polyphenol Compounds, Biomarkers Of Antioxidant Status, And Lipid Peroxidation, Setareh Torabian Esfahani

Loma Linda University Electronic Theses, Dissertations & Projects

Nuts are rich sources of polyphenolic compounds and nutrients, which have antioxidant capacity. To assess the acute effect of treatment diet (75% of energy from nuts (walnut or almond) and control diet (habitual diet with no nut consumption) in healthy subjects on plasma total phenol content, antioxidant capacity and plasma lipid peroxidation. Thirteen subjects participated in the crossover design study. After an overnight fast, walnut, almond and a control diet, in form of smoothies, were consumed by the study subjects. Each subject participated on three occasions one week apart, consuming one of the smoothies each time. Blood samples were obtained …

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 …

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 …

Connexin-32 Contributes To Radiation Resistance In Thyroid Follicles, Da-Thao Dinh Tran

Loma Linda University Electronic Theses, Dissertations & Projects

The objective of this study was to examine the role of gap junctions in the radiation resistance of thyroid follicles. The question of whether gap junctional intercellular communication plays an important role in the “contact effect”, wherein cells in direct apposition are more resistant to the damaging effects of radiation, has been debated for years. We used the Fischer rat thyroid cell line (FRTL-5) to carry out our experiments. This thesis is divided into two parts: 1) characterization of gap junctional properties in FRTL-5 cells and, 2) exposure of these cells to radiation.

We found that, unlike primary thyroid cells, …

The Immunology Of Parturition, Ari Mayer Mackler

Loma Linda University Electronic Theses, Dissertations & Projects

Macrophage-derived factors have been implicated in the etiology of preterm labor but little is known about trafficking of this immune cell into the uterus or its regulation of uterine contractility in mice. Enhanced number and activation of macrophages was hypothesized to precede parturition. Studies characterized contractile activity and the distribution of macrophages in the uterus of C3/HeN mice before and after term (=day 19). Contractile activity by uterine strips on days 15 and 18 of pregnancy, the day of delivery, and 1 day postpartum indicate that an endogenous oscillator sustains high frequency contractions. Modest acceleration of the pacemaker occurred before …

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, …

Molecular Mechanism Of The Stimulation Of Alkaline Phosphatase Activity In Human Bone Cells By 1,25(Oh)2 D3, Eru Kyeyune-Nyombi

Loma Linda University Electronic Theses, Dissertations & Projects

To facilitate this study an in vitro human model system was established that exhibited many aspects of normal osteoblasts. The human osteosarcoma cell line (TE85 cells) expressed a skeletal alkaline phosphatase activity (an accepted bone cell differentiation marker) which was stimulated by 1,25(OH)₂D₃ (a potent differentiating agent), under serum-free conditions in a dose-dependent, time-dependent, and cell density-dependent manner. Cytochemical analysis of the stimulation of ALP activity by 1,25(OH)₂D₃ showed that 1,25(OH)₂D₃ increased the number of TE85 cells that expressed detectable ALP activity, suggesting that 1,25(OH)₂D₃ promoted the process …

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 …

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 …

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.

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 …

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 …

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 …

Endodontic Sealing Properties Of Cavit, Chloro-Rosin Gutta Percha, N2, And Silver Cones Using Radioisotopes, Frank H. Beal

Loma Linda University Electronic Theses, Dissertations & Projects

The main purpose of this investigation was to test the endodontic sealing abilities of silver cones, N2, warm gutta percha, chemically softened gutta percha, laterally condensed gutta percha and Cavit under carefully controlled conditions. Evaluations were done by radiographic, macroscopic, microscopic, and autoradiographic examinations.

The four points which must be considered when evaluating the efficacy of sealing root canal systems, in vivo, were presented and discussed.

Cavit as a total endodontic filling material was presented, investigated and discussed.

An improvement of the chloro-rosin - gutta percha diffusion technique was presented.

The concept of surface as well as marginal leakage was …

The Degree And Time-Course Of Stress In The Patient Undergoing Cardiac Surgery, Hulda Esther Serra, Patricia Jo Yvonne Tygret

Loma Linda University Electronic Theses, Dissertations & Projects

An important nursing objective is to assist patients through stressful experiences. It has been assumed that cardiac surgery constitutes such a stress situation. For this reason, twenty-two patients undergoing cardiac surgery at Loma Linda University Hospital studied for the purpose of exploring the degree and time-course of were psychological stress.

The methodology consisted of administration of psychological tests before and after surgery; determination of urine catecholamines (UCA) before, during and after surgery; administration of a coping assessment tool before surgery, and a recall interview on the fifth day after surgery. The Multiple Affect Adjective Check List (MAACL)-Today form, and the …

Bacteriuria As A Precursor Of Intracatheter Encrustation, Namcy Moll

Loma Linda University Electronic Theses, Dissertations & Projects

The problem with which this study was concerned was the development of criteria that could be used to determine when urinary catheter changes were necessary. By determining when encrustation occurred, it was felt that some complications could be eliminated by changing catheters before obstruction occurred due to encrustation.

It was the purpose of this study to: 1) explore some indications for catheter change, 2) determine if encrustation of urinary catheters necessitates catheter change, and 3) estimate potential criteria for a routine time for catheter changes.

Forty-five catheters were examined after their removal from patients. Flow rates were determined on 33 …

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 …

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 …

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 …