Animal Experimentation and Research Commons^™

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 …

Chimpanzees In Laboratories: Distribution And Types Of Research, Martin L. Stephens

Laboratory Experiments Collection

This review presents the results of an informal 1993 survey of the distribution of chimpanzees (Pan troglodytes) in the world's laboratories, and the types of research conducted on them. Based on the available information, there are over 2200 chimpanzees in.laboratories, most of which are located in several US facilities. Europe apparently has less than 200 chimpanzees housed in two facilities. Worldwide, an estimated 80% of the chimpanzees in laboratories are used in studies on AIDS and hepatitis. It is concluded that, if Europe terminated its use of chimpanzees in research, for either financial, moral or political reasons, the impact on …

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 Animal Research Controversy: Protest, Process & Public Policy, Andrew N. Rowan, Franklin M. Loew, Joan C. Weer

eBooks

The controversy today regarding the use of animals in research appears on the surface to be a strongly polarized struggle between the scientific community and the animal protection movement. However, there is a wide range of opinions and philosophies on both sides. Mistrust between the factions has blossomed while communication has withered. Through the 1960s, 1970s and early 1980s, the animal movement grew in numbers and financial resources, and developed much greater public recognition and political clout. The research community paid relatively little attention to the animal movement for much of this period but, alarmed by several public relations coups …

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 …

The Next Decade: A Shifting Focus, Henry Spira

Commentaries and Editorials

No abstract provided.

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 …

Alternatives In The 90'S: What's Next?, Henry Spira

Conference Presentations

The 80's was a decade of remarkable and innovative research and development of alternatives. We see the 90’s as the decade of validation and implementation.

From an activist's perspective, the 80's was very encouraging,-- alternatives gained acceptance, legitimacy and credibility within the toxicology, corporate and regulatory communities. And The Center for Alternatives to Animal Testing (CAAT) at Johns Hopkins University played a significant role in making this acceptance possible.

But these new technologies have yet to realize their full potential; the focus to date has been on development more than on bringing these technologies into routine usage. And the public, …

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 …

Catecholamines And The Regulation Of Uterine Contractions In The Pregnant Rhesus Macaque, Cahleen Mae Mcnutt

Loma Linda University Electronic Theses, Dissertations & Projects

This study was designed to test the hypothesis that: 1) maternal and/or amniotic fluid catecholamines or prostaglandins display nocturnal activity rhythms similar to those of the myometrial contractility in the pregnant rhesus macaque and, 2) catecholamines stimulate prostaglandin production by fetal membranes. Paired maternal arterial blood and amniotic fluid samples were collected at 0900 h (AM) and 2100 h (PM) from chronically catheterized rhesus macaques until delivery and analyzed for prostaglandin metabolites (PGFM and PGEM-II) and catecholamines (norepinephrine, epinephrine, and dopamine). Uterine activity data was continuously recorded. A rhythm in uterine contractility was observed, with peak activity between 1900 and …

Pharmacokinetics And Effects On Blood Chemistry Of Cyclosporine In Human Infants And Kid Goats, Floyd A. Beierle

Loma Linda University Electronic Theses, Dissertations & Projects

Kid goats (newborn) have been used in transplantation protocols to study the techniques and problems of infant human cardiac transplantation. Immunosuppression has been by cyclosporine in both species. However, the pharmacokinetics of cyclosporine (CSA) in both the kid goat and human infant were unknown. Therefore, the pharmacokinetics of CSA were investigated. A single dose study and a long term chronic administration study were undertaken in the goat. Six Nubian goats, ages 60-90 days, were given a single IV dose of CSA, 0.25 mg/kg, over a 10 minute period and 72 hr later an oral cyclosporine dose of 20 mg/kg. The …

The Effect Of An Anti-Osteoclastic Agent And A Collagen Sponge On Root Resorption Following Regenerative Periodontal Surgery In The Dog, Rudolf Hahn

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies indicate that root resorption is a frequent sequela to significant amounts of periodontal repair following experimental regenerative periodontal surgical procedures in animal models. To study if root resorption can be reduced or prevented, periodontal repair was evaluated in large horizontal circumferential defects in the dog in the absence of influence from the oral environment. Diphosphonate (Cl₂ MDP) applied topically to the root surfaces prior to wound closure as well as the use of a collagen sponge membrane (Helistat®) draped over the root surfaces and a control with no additional treatment after defect creation were the modalities employed. …

Effect Of Photoperiod On Developmental Morphology And Enolase Isoenzyme Immunohistochemistry In Rat And Djungarian Hamster Superficial Pineal Glands, Chalmer D. Mcclure

Loma Linda University Electronic Theses, Dissertations & Projects

The best understood functional activity of the pineal gland is its diurnal production of melatonin in response to environmental lighting cues. Several enzymes of the melatonin pathway respond to daily photoperiod changes, for example hydroxyindole-O-methyltransferase (HIOMT) and serotonin N-acetyltransferase (SNAT). Increased levels of the glycolytic enzyme neuron-specific enolase (NSE) are thought to reflect increased physiological demands placed on neurons and neuroendocrine tissues. Homodimer non-neuronal enolase isoenzyme (NNE) is immunolocalized to cells, and the hybrid enolase (consisting of subunits from NSE and NNE) has been seen in cerebellar stellate and basket cells. Although not rate limiting, concentrations of both NSE and …

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. …

Enhancement Of Intratumor Antibody Distribution With A Bifunctional Antibody Delivery System And With Hyperthermia, Karen Lynn King

Loma Linda University Electronic Theses, Dissertations & Projects

The intratumor distribution of a new monoclonal antibody-hapten-based delivery system was examined. From two marine antibodies, Hybritech, Inc. has developed a bifunctional antibody (BPA) with specificities against CEA (ZCE-025 or GEM 231) and against one of two derivatives of [¹¹¹In]-benzyl-EDTA (CHA 255), EOTUBE or BLEDTA IV, to form ZCE/CHA or CEM/CHA. BFA accumulates in CEA-expressing tissue and clears from non-antigenic tissues prior to administration of an [¹¹¹In]-hapten.

Using five groups of nude mice bearing human colon tumor xenografts (T380), we evaluated different carriers of [¹¹¹In]-EOTUBE to prelocalized ZCE/CHA. We administered all antibodies and haptens …

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 Prenatal Development Of The "Synaptic" Structures In The Guinea Pig Pineal Gland, Zhongrong Luo

Loma Linda University Electronic Theses, Dissertations & Projects

Pineal "synaptic" ribbons are a heterogeneous population of organelles. In addition to "synaptic" ribbons (SR) sensu stricto, which are electron-dense rods, "synaptic" spherules (SS) and intermediate forms (IMF) are present. The SS are electron-dense spherical structures, the diameter of which is two to three times the width of the SR. The IMF appear as irregularly formed structures. The SR, SS and IMF are surrounded by electron-lucent vesicles. Their function and origin are unknown and also a knowledge of their prenatal development is lacking. In order to gain an insight into the development of the "synaptic structures, the pineal glands …

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 …

Electromagnetic Field Variations In The Activation Of Bone Cell Synthesis, Gary Ketcherside

Loma Linda University Electronic Theses, Dissertations & Projects

[Abstract Not Included]

Inventing The Skin You Love To Test, Rick Weiss

Popular Press Items

No abstract provided.

Hyperosmotic Modification Of Brain Extracellular Space And Blood-Brain Barrier In The Rat As Observed By Electron Microscopy, Susan A. Meacham

Loma Linda University Electronic Theses, Dissertations & Projects

The highly selective permeability of cerebral blood vessels, termed the blood-brain barrier, is due to endothelial tight junctions (zonulae occludentes). Hyperosmotic solutions reversibly open the blood-brain barrier. The purpose of this study is to determine the immediate effect of hyperosmotic arabinose perfusion upon the cerebrovascular endothelium, the morphology of the cerebral cortex, and the cortical extracellular space.

Twelve adult male Sprague-Dawley rats were separated into three groups of four animals each: control, intermediate, and extreme. Controls were perfused with a Tyrode's solution prewash followed by trialdehyde fixative. The intermediate group received a prewash of 740 mmol/kg arabinose followed by the …