Medical Sciences Commons^™

Identification And Characterization Of Spcu, A Chaperone Required For Efficient Secretion Of The Exou Cytotoxin, Viviane Finck-Barbançon, Timothy L. Yahr, Dara W. Frank

Dartmouth Scholarship

In recent studies, we have shown that Pseudomonas aeruginosa strains that are acutely cytotoxic in vitro damage the lung epithelium in vivo. Genetic analysis indicated that the factor responsible for acute cytotoxicity was controlled by ExsA and therefore was part of the exoenzyme S regulon. The specific virulence determinant responsible for epithelial damage in vivo and cytotoxicity in vitro was subsequently mapped to the exoU locus. The present studies are focused on a genetic characterization of the exoU locus. Northern blot analyses and complementation experiments indicated that a region downstream of exoU was expressed and that the expression of this …

Regeneration Of Hair Cell Epithelia In The Chick And Salamander, Kenneth Detwiler

Masters Theses & Specialist Projects

The acousticolateralis sensory system is characterized by a specific receptor cell type called the sensory hair cell and is found in all vertebrates. There are two types of hair cell sensory epithelia based on location: those of the inner ear, such as the organs for hearing and balance, and the lateral line system located within the epidermis. In mammals, including humans, loss or damage of the hair cells of the auditorysystem results in permanent hearing loss. However, this is not the case with birds and amphibians. Amphibians, with a lateral line system, are capable of replacing lost or damaged hair …

The Role Of Gap Junctions In Congenital Diseases Of The Heart, Scott Henry Britz-Cunningham

Loma Linda University Electronic Theses, Dissertations & Projects

Background. Gap junctions are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. Connexin43, the major protein of gap junctions in the heart, is targeted by several protein kinases that regulate myocardial cell-cell coupling. We hypothesized that mutations altering sites critical to this regulation would lead to functional or developmental abnormalities of the heart.

Methods. Connexin43 DNA from 25 normal subjects and 30 children with a variety of congenital heart diseases was amplified by the polymerase chain reaction and sequenced. Mutant DNA was expressed in cell culture and examined for its effect …

The Isolation And Partial Purification Of Dna Polymerase-Beta From Soybean, Lesa Dill

Masters Theses & Specialist Projects

5 kilodaltons). Its activation and inhibition spectra were similar to those previously determined for animal polymerase-beta. Therefore, since the structure of polymerase-beta shows significant evolutionary conservation in both plant and animal species and given strong functional correlations among species, polymerase-beta performs a vital role in plants in the repair of newly synthesized DNA just as it does in animal systems.

Projections Of Alzheimer's Disease In The United States And The Public Health Impact Of Delaying Disease Onset., Ron Brookmeyer, Sarah Gray, Claudia Kawas

Ron Brookmeyer

OBJECTIVES: The goal of this study was to project the future prevalence and incidence of Alzheimer's disease in the United States and the potential impact of interventions to delay disease onset.

METHODS: The numbers of individuals in the United States with Alzheimer's disease and the numbers of newly diagnosed cases that can be expected over the next 50 years were estimated from a model that used age-specific incidence rates summarized from several epidemiological studies, US mortality rates, and US Bureau of the Census projections.

RESULTS: in 1997, the prevalence of Alzheimer's disease in the United States was 2.32 million (range: …

The Seca Subunit Of Escherichia Coli Preprotein Translocase Is Exposed To The Periplasm, Jerry Eichler, William Wickner

Dartmouth Scholarship

SecA undergoes conformational changes during translocation, inserting domains into and across the membrane or enhancing the protease resistance of these domains. We now show that some SecA bound at SecYEG is accessible from the periplasm to a membrane-impermeant probe in cells with a permeabilized outer membrane but an intact plasma membrane.

Exoy, An Adenylate Cyclase Secreted By The Pseudomonas Aeruginosa Type Iii System, Timothy L. Yahr, Amy J. Vallis, Michael Hancock, Joseph T. Barbieri, Dara W. Frank

Dartmouth Scholarship

The exoenzyme S regulon is a set of coordinately regulated virulence genes of Pseudomonas aeruginosa. Proteins encoded by the regulon include a type III secretion and translocation apparatus, regulators of gene expression, and effector proteins. The effector proteins include two enzymes with ADP-ribosyltransferase activity (ExoS and ExoT) and an acute cytotoxin (ExoU). In this study, we identified ExoY as a fourth effector protein of the regulon. ExoY is homologous to the extracellular adenylate cyclases of Bordetella pertussis (CyaA) and Bacillus anthracis (EF). The homology among the three adenylate cyclases is limited to two short regions, one of which possesses an …

Staphylococcal Enterotoxin B Primes Cytokine Secretion And Lytic Activity In Response To Native Bacterial Antigens, K. M. Mason, T. D. Dryden, Nancy J. Bigley, P. S. Fink

Neuroscience, Cell Biology & Physiology Faculty Publications

Superantigens stimulate T-lymphocyte proliferation and cytokine production, but the effects of superantigen exposure on cell function within a complex, highly regulated immune response remain to be determined. In this study, we demonstrate that superantigen exposure significantly alters the murine host response to bacterial antigens in an in vitro coculture system. Two days after exposure to the superantigen staphylococcal enterotoxin B, splenocytes cultured with Streptococcus mutans produced significantly greater amounts of gamma interferon (IFN-gamma) and interleukin-12 than did sham-injected controls. The majority of IFN-gamma production appeared to be CD8(+) T-cell derived since depletion of this cell type dramatically reduced the levels …

Animal Organs In Humans: Uncalculated Risks And Unanswered Questions, Gillian R. Langley, Joyce D'Silva

Biomedicine and Animal Models in Research Collection

This report, produced jointly by the British Union for the Abolition of Vivisection and Compassion in World Farming, fills a number of significant gaps in the current debate about xenotransplantation.

In this report we also summarise the ethical and welfare issues concerning experiments on animals for xenotransplant research and their possible use as source animals for organs. Both these aspects are responsible for much pain and distress caused to many animals. We prefer the term “source animals” to “donor animals”, because animals do not choose to donate their organs for xenotransplantation.

Influence Of Physical Setting On Seagrass Landscapes Near Beaufort, North Carolina, Usa, Mark S. Fonseca, Susan S. Bell

Integrative Biology Faculty and Staff Publications

Field surveys were conducted in Core and Back Sounds, North Carolina, USA, to relate the physical setting of seagrass beds, as measured by a wave exposure index (REI), tidal current speed and water depth, to various measures of the sedimentary environment, spatial heterogeneity of seagrass distribution and measures of seagrass abundance. Seagrass beds in this area form patterns ranging from continuous to semi-continuous to widely dispersed, discrete patches across a gradient of increasing hydrodynamic activity. Tidal current speeds, exposure to waves and relative water depths revealed strong correlative evidence that physical processes influenced landscape-scale (50 x 50 m range with …

Assessment Of Side Effects Induced By Injection Of Different Adjuvant/Antigen Combinations In Rabbits And Mice, P.P.A.M. Leenaars, M. A. Koedam, P. W. Wester, V. Baumans, E. Claassen, C. F.M. Hendriksen

Biomedicine and Animal Models in Research Collection

We evaluated the side effects induced by injection of Freund's adjuvant (FA)and alternative adjuvants combined with different antigens. Rabbits and mice were injected subcutaneously, intramuscularly (rabbits) and intraperitoneally (mice)with different adjuvants (FA, Specol, RIBI,TiterMax, Montanide ISA50)in combination with several types of antigens (synthetic peptides, autoantigen, glycolipid, protein, mycoplasma or viruses). The effects of treatment on the animals' well-being were assessed by clinical and behavioural changes (POTand LABORASassays) and gross and histopathological changes. In rabbits, treatment did not appear to induce acute or prolonged pain and distress. Mice showed behavioural changes immediately after (predominantly secondary) immunization. Injection of several adjuvant/antigen mixtures …

Identifying Swelling-Activated Channels From Ion Selectivity Patterns, Dan R. Halm

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.

The Location Of The Carboxy-Terminal Region Of Γ Chains In Fibrinogen And Fibrin D Domains, Michael W. Mosesson, Kevin R. Siebenlist, David A. Meh, Joseph S. Wall, James F. Hainfeld

Biomedical Sciences Faculty Research and Publications

Elongated fibrinogen molecules are comprised of two outer “D” domains, each connected through a “coiled-coil” region to the central “E” domain. Fibrin forms following thrombin cleavage in the E domain and then undergoes intermolecular end-to-middle D:E domain associations that result in double-stranded fibrils. Factor XIIIa mediates crosslinking of the C-terminal regions of γ chains in each D domain (the γXL site) by incorporating intermolecular ɛ-(γ-glutamyl)lysine bonds between amine donor γ406 lysine of one γ chain and a glutamine acceptor at γ398 or γ399 of another. Several lines of evidence show that crosslinked γ chains extend “transversely” between the strands of …

Spinal Cord Compression: Histologic Spectrum Of Lesions, I. N. Soomro, N.Kayani N.Kayani, Shahid Pervez, A. S. Hussainy, R. Ahmed, S. Muzaffar, S. A. Aziz, S. H. Hasan

Department of Pathology and Laboratory Medicine

Histologic diagnosis ultimately determines the prognosis and treatment of lesions causing spinal cord compression. Modem imaging techniques have revolutionized the procedure of localizing lesions pre¬senting with signs and symptoms of spinal cord compression. As a result, these lesions are more accessible for fine needle aspiration and biopsy. A quick diagnosis is possible if cytologic preparation is made. Similarly, intraoperative frozen section facility not only provides rapid diagnosis, but also offers oppor tunity of appropriate management decision there and then. Histology in many cases needs help of special stains and immunocytochemistry. This study looks at the histologic spectrum of these lesions, …

Soft Tissue Sarcomas: Pattern Diagnosis Or Entity, Naasha Talati, Shahid Pervez

Department of Pathology and Laboratory Medicine

Soft tissue sarcomas (STS) are a diverse and heterogeneous group of tumours The sub-classification of these tumours is of importance for both prognosis and treatment. Classically, sub- categorization is based purely on histomorphological grounds, but as new techniques evolve, a more, conclusive and accurate diagnosis can be made. This study describes the prevalence of soft tissue sarcomas in adults diagnosed at The Aga Khan University Hospital (AKUH) and the impact of immunohistochemistry(IHC) on the precise sub-categorization of these tumours. The study included 364 adults (age 16+) who were diagnosed as soft tissue sarcoma in the past six years (May 1991 …

Variability Of Target Volume Delineation In Cervical Esophageal Cancer, Patricia Tai, Jake Van Dyk, Edward Yu, Jerry Battista, Larry Stitt, Terry Coad

Edward Yu

PURPOSE: Three-dimensional (3D) conformal radiation therapy (CRT) assumes and requires the precise delineation of the target volume. To assess the consistency of target volume delineation by radiation oncologists, who treat esophageal cancers, we have performed a transCanada survey. MATERIALS AND METHODS: One of three case presentations, including CT scan images, of different stages of cervical esophageal cancer was randomly chosen and sent by mail. Respondents were asked to fill in questionnaires regarding treatment techniques and to outline boost target volumes for the primary tumor on CT scans, using ICRU-50 definitions. RESULTS: Of 58 radiation oncologists who agreed to participate, 48 …

Identification Of Putative Cytoskeletal Protein Homologues In The Protozoan Host Hartmannella Vermiformis As Substrates For Induced Tyrosine Phosphatase Activity Upon Attachment To The Legionnaires' Disease Bacterium, Legionella Pneumophila, Chandrasekar Venkataraman, Lian-Yang Gao, Subbarao Bondada, Yousef Abu Kwaik

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The Legionnaires' disease bacterium, Legionella pneumophila, is a facultative intracellular pathogen that invades and replicates within two evolutionarily distant hosts, free living protozoa and mammalian cells. Invasion and intracellular replication within protozoa are thought to be major factors in the transmission of Legionnaires' disease. We have recently reported the identification of a galactose/N-acetyl-d-galactosamine (Gal/GalNAc) lectin in the protozoan host Hartmannella vermiformis as a receptor for attachment and invasion by L. pneumophila (Venkataraman, C., B.J. Haack, S. Bondada, and Y.A. Kwaik. 1997. J. Exp. Med. 186:537–547). In this report, we extended our studies to the …

Expression Of Toxoplasma Gondii-Specific Heat Shock Protein 70 During In Vivo Conversion Of Bradyzoites To Tachyzoites, Neide M. Silva, Ricardo T. Gazzinelli, Deise A. O. Silva, Eloisa A. V. Ferro, Lloyd H. Kasper, Jose R. Mineo

Dartmouth Scholarship

Stage conversion between bradyzoites and tachyzoites was investigated in C57BL/6 mice chronically infected with the ME-49 strain of Toxoplasma gondii. In order to promote bradyzoite-tachyzoite conversion, mice were treated in vivo with neutralizing doses of anti-gamma interferon (IFN-gamma) or anti-tumor necrosis factor alpha (TNF-alpha) antibodies. Expression of parasite-specific antigens SAG-1, SAG-2, and heat shock protein 70 (Hsp-70) was visualized in the central nervous system by immunocytochemistry and measured by photometric assay. The immunosuppressive effect of anti-IFN-gamma or anti-TNF-alpha treatment was immediate, leading to parasite stage conversion as indicated by the increased expression of tachyzoite-specific antigens (SAG-1 and SAG-2) and by …

2,4-Disulfo Phenyl Butyl Nitrone, Its Salt And Their Use As Pharmaceuticals, John M. Carney

Pharmacology and Nutritional Sciences Faculty Patents

2,4-disulfonyl α-phenyl-tert-butyl nitrone and its pharmaceutically acceptable salts are disclosed. These materials are useful as pharmaceutical agents for oral or parenteral, e.g. intravenous administration to patients suffering from acute central nervous system oxidation as occurs in a stroke or from gradual central nervous system oxidation which can exhibit itself as progressive central nervous system function loss. The materials are also used to ameliorate the side effects of oxidative-damage causing antineoplastic disease treatments.

Update - July 1998, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- Christianity and Human Cloning - A Seventh-day Adventist Declaration of Ethical Principles
-- Cloning: Dolly's Mother is Her Sister!?
-- Hello, Dolly! Dolly! Dolly!

Expression Of Constitutively Active Raf-1 In The Mitochondria Restores Antiapoptotic And Leukemogenic Potential Of A Transformation-Deficient Bcr/Abl Mutant., P Salomoni, M A Wasik, R F Riedel, K Reiss, J K Choi, T Skorski, B Calabretta

Department of Microbiology and Immunology Faculty Papers

The oncogenic BCR/ABL protein protects hematopoietic cells from apoptosis induced by growth factor deprivation, but the mechanisms are only partially understood. A BCR/ABL mutant lacking amino acids 176-426 in the BCR domain (p185DeltaBCR) failed to protect interleukin 3-deprived 32Dcl3 myeloid precursor cells from apoptosis, although it possessed tyrosine kinase activity and was capable of activating the Ras-Raf-MAP kinase pathway. Compared to p185 wild-type transfectants, p185DeltaBCR-transfected cells showed markedly reduced levels of Bcl-2 and expressed the hypophosphorylated, proapoptotic form of BAD. Bcl-2 expression in the mitochondrial fraction of p185DeltaBCR cells was also markedly diminished and mitochondrial RAF was undetectable. In p185DeltaBCR …

Developmental Expression Of Rat Target Of The Antiproliferative Antibody (Rtapa) Protein In The Brain, Clyde Dale Sullivan

Theses and Dissertations (ETD)

The present study defines the expression pattern of rTAPA (CD81) in the developing rat brain. rTAPA is a member of the tetramembrane spanning family of proteins, and like other members of this family, appears to be associated with the stabilization of cellular contacts. On immunoblots of the brain, rTAPA is present in higher levels than any other tissue examined: muscle, tendon, peripheral nerve, cartilage, liver, kidney, skin, and testicle. Immunohistochemical methods were used to define the distribution of rTAPA in the brain. This protein is expressed by ependyma, choroid plexus, astrocytes, and oligodendrocytes, and rTAPA is dramatically upregulated at the …

The “Spot 14” Gene Resides On The Telomeric End Of The 11q13 Amplicon And Is Expressed In Lipogenic Breast Cancers: Implications For Control Of Tumor Metabolism, Joel T. Moncur, Jonathan P. Park, Vincent A. Memoli, T. K. Mohandas, William B. Kinlaw

Dartmouth Scholarship

Enhanced long chain fatty acid synthesis may occur in breast cancer, where it is necessary for tumor growth and predicts a poor prognosis. “Spot 14” (S14) is a carbohydrate- and thyroid hormone-inducible nuclear protein specific to liver, adipose, and lactating mammary tissues that functions to activate genes encoding the enzymes of fatty acid synthesis. Amplification of chromosome region 11q13, where the S14 gene (THRSP) resides, also predicts a poor prognosis in breast tumors. We localized the S14 gene between markers D11S906 and D11S937, at the telomeric end of the amplified region at 11q13, and found that it was …

Knowledge, Attitudes And Behavior Of African American Undergraduate College Students Concerning Primary Preventative Health, Lionas Mayes

McCabe Thesis Collection

African Americans' knowledge about primary preventive health and their attitudes toward primary preventive health influence their health behavior. Primary preventive health behavior is also affected by the individuals' definition of health and the significance they ascribe to their health status. Attitudes toward primary preventive health determine whether health assessment is important in preventing disease. African Americans have a myriad of views about health and general well being. The purpose of this study is to determine the relationship between primary preventive health knowledge, primary preventive health attitudes and primary preventive health behavior in African American undergraduate students. A survey will be …

Evaluation Of The Success Of Adoptive Versus Passive Transfer Of Immunity Against Trypanosoma Cruzi, Karen Powell

Masters Theses & Specialist Projects

Several investigators have demonstrated an increased resistance to the protozoal parasite Trypanosoma cruzi (the causative agent of Chagas' disease) in highly susceptible C3H mice when maintained at an environmental temperature of 36°C. This increased resistance is manifested as delay in onset of parasitemia, decreased parasitemia, decreased pathology, and increased longevity with eventual clearing of the parasite from the bloodstream. In addition, this enhanced resistance has been shown to be an immunologic phenomenon and not due to the direct effects of elevated temperature on the parasite itself. To ascertain the possible contributions of humoral vs. cellular immunity to the above phenomenon, …

Ca2+ Signaling Modulates Cytolytic T Lymphocyte Effector Functions, Mark T. Esser, Doris M. Haverstick, Claudette L. Fuller, Charles A. Gullo Phd, Vivian Lam Braciale

Biochemistry and Microbiology

Cytolytic T cells use two mechanisms to kill virally infected cells, tumor cells, or other potentially autoreactive T cells in short-term in vitro assays. The perforin/granule exocytosis mechanism uses preformed cytolytic granules that are delivered to the target cell to induce apoptosis and eventual lysis. FasL/Fas (CD95 ligand/CD95)–mediated cytolysis requires de novo protein synthesis of FasL by the CTL and the presence of the death receptor Fas on the target cell to induce apoptosis. Using a CD8⁺ CTL clone that kills via both the perforin/granule exocytosis and FasL/Fas mechanisms, and a clone that kills via the FasL/Fas mechanism only, …

The Sequential Role Of Lymphotoxin And B Cells In The Development Of Splenic Follicles, Mercedes Gonzalez, Fabienne Mackay, Jeffrey L. Browning, Marie H. Kosco-Vilbois, Randolph J. Noelle

Dartmouth Scholarship

The transfer of lymphocytes into severe combined immunodeficiency (SCID) mice induces a series of histological changes in the spleen, including the appearance of mature follicular dendritic cells (FDCs). Studies were undertaken to clarify the role of lymphotoxin (LT) in this process. The results show that SCID mice have a small and partially differentiated white pulp containing marginal zone and interdigitating dendritic cells, but lacking FDCs. Transferred spleen cells can segregate into T and B cell areas shortly after their injection to SCID mice. This ability is dependent on signaling through LT-β receptor (LT-βR), since blocking ligand–receptor interaction in recipient SCID …

Predicting Future Years Of Healthy Life For Older Adults, Paula Diehr

Paula Diehr

Cost-effectiveness studies often need to compare the cost of a program to the lifetime benefits of the program, but estimates of lifetime benefits are not routinely available, especially for older adults. We used data from two large longitudinal studies of older adults (ages 65-100) to estimate transition probabilities from one health state to another, and used those probabilities to estimate the mean additional years of healthy life that an older adult of specified age, sex, and health status would experience. We found, for example, that 65-year-old women in excellent health can expect 16.8 years of healthy life in the future, …

An Exploration Of Possibly Using Anti-Angiogenic Therapy As A Treatment For Lung Cancer, Peter Alan Middleton

Mahurin Honors College Capstone Experience/Thesis Projects

Controlling angiogenesis in vivo is strongly being considered by pathologists and experimenters due to the recent success of using anti-angiogenic therapy for cancer patients in clinical trials. The apparent nature and overwhelming number of cases of lung cancer (bronchogenic carcinoma) are leading some clinicians to using anti-angiogenic pharmaceuticals with lung-cancer patients. Pre-clinical and experimental evidence supporting the use of anti-angiogenic therapy for lung cancer is apparently increasing. The literature research here attempts to point out specific relationships between lung tumor growth and the mechanisms by which the body reacts to such. Macrophages, lymphocytes, fibroblasts, vascular smooth muscle cells, lung alveolar, …

Antigen-Specific Cd8+ T Cells Protect Against Lethal Toxoplasmosis In Mice Infected With Neospora Caninum, Lloyd H. Kasper, Imtiaz A. Khan

Dartmouth Scholarship

Neospora caninum is a coccidial protozoan parasite that appears morphologically indistinguishable from Toxoplasma gondii and that infects a large range of mammals. Both inbred and outbred strains of mice exhibit a high degree of resistance to infection with N. caninum. Three inbred strains of mice (A/J, BALB/c, and C57BL/6) that were infected intraperitoneally with N. caninum were protected against a lethal challenge from T. gondii. Vaccine-induced protection was Neospora dose dependent. A rise in the CD8+ T-cell population in mice that had been vaccinated with N. caninum and challenged with T. gondii was observed. Adoptive transfer of CD8+ T-cell splenocytes …