Medicine and Health Sciences Commons^™

Attachment Of Toxoplasma Gondii To A Specific Membrane Fraction Of Cho Cells, Chaitali Dutta, Jane Grimwood, Lloyd H. Kasper

Dartmouth Scholarship

We have observed previously that attachment of Toxoplasma gondii to synchronized host cells is considerably increased at the mid-S phase (4 h postrelease). Synchronized CHO host cells at the mid-S phase were fractionated by molecular weight, and the antigens were used to produce a panel of polyclonal mouse antisera. The polyclonal antisera raised against fraction 4 with molecular mass ranging approximately from 18 to 40 kDa significantly reduced attachment to mid-S-phase host cells. Immunofluorescence assays demonstrated strong reactivity to mid-S-phase host cells and identified a number of potential receptors on Western blots. These data indicate that there is a specific …

Microbial Biofilms: From Ecology To Molecular Genetics, Mary Ellen Davey, George A. O'Toole

Dartmouth Scholarship

Biofilms are complex communities of microorganisms attached to surfaces or associated with interfaces. Despite the focus of modern microbiology research on pure culture, planktonic (free-swimming) bacteria, it is now widely recognized that most bacteria found in natural, clinical, and industrial settings persist in association with surfaces. Furthermore, these microbial communities are often composed of multiple species that interact with each other and their environment. The determination of biofilm architecture, particularly the spatial arrangement of microcolonies (clusters of cells) relative to one another, has profound implications for the function of these complex communities. Numerous new experimental approaches and methodologies have been …

Vaccinia Virus-Mediated Glioma Gene Therapy Using P53, Il-2 And Il-12, Bing Chen

Loma Linda University Electronic Theses, Dissertations & Projects

Malignant brain tumors are generally lethal soon after their diagnosis, and the five-year survival rate for the patient is low in spite of neurosurgery, radiation therapy, and/or chemotherapy. Gene therapy has the potential to improve patient survival and quality of life by delivering specific combinations of therapeutic genes directly to the tumor for localized treatment.

We have based our cancer gene therapy for glioma on a highly attenuated variant of the Lister strain of vaccinia virus (VV) which has been proven to be a safe and effective vaccine vector. Other advantages include a wide host range, a strong promoter system, …

Technology Evaluation: Pro-542, Progenics Pharmaceuticals Inc., Muhammad Mukhtar, Zahida Parveen, Roger J Pomerantz

Department of Medicine Faculty Papers

Progenics's rCD4-IgG2 (PRO-542) is a recombinant fusion protein, which has been developed using the company's Universal Antiviral Binding (UnAB) technology, and is in phase I/II clinical trials for the treatment of human immunodeficiency virus type I (HIV-1) infection [273391]. At the beginning of 1997, Progenics received a Phase II Small Business Innovation Research Program (SBIR) grant from the National Institute of Allergy and Infectious diseases (NIAID) to fund the development of PRO-542 [236048]. A further grant of $2.7 million was awarded in August 1998 for the clinical evaluation of PRO-542 and other anti-HIV therapies [294200]. Progenics is collaborating with the …

Glucocorticoid Regulation Of Insulin Like Growth Factor Binding Protein-5 Gene Transcription In Human Osteoblasts, Xiaoying Wang

Loma Linda University Electronic Theses, Dissertations & Projects

Glucocorticoids (GCs) inhibit bone formation in vivo and inhibit osteoblast proliferation and collagen synthesis in vitro. These effects may be mediated by alterations in the insulin-like growth factor (IGF) system. In the present study of normal human osteoblast-like (HOB) cells, we tested the hypothesis that dexamethasone (Dex) inhibits the expression of IGF binding protein-5 (IGFBP-5). Dex decreased IGFBP-5 mRNA levels to 54% of control after 4 hr. Dex did not modify the decay of IGFBP-5 mRNA in transcriptionally arrested osteoblast cells. Dex decreased IGFBP-5 hnRNA levels to 67% of control after 2 hr, and the activity of the human IGFBP- …

Chronic Hypoxia, Exercise Training, And Skeletal Muscle Capillarity: Angiogenic Regulation And Morphological Consequences, Ivan Mark Olfert

Loma Linda University Electronic Theses, Dissertations & Projects

Angiogenesis is important in health and disease. In particular, exercise training is known to increase skeletal muscle capillarity, providing there is sufficient training intensity. The stimulus for this may be intracellular hypoxia activating angiogenic growth factor gene expression. Acute hypoxia alone has been shown to increase the gene expression of several key angiogenic regulators, e.g. vascular endothelial growth factor (VEGF) and to a lesser degree transforming growth factor-β1 (TGF-β1), basic fibroblast growth factor (bFGF), and thrombospondin-1 (TSP-1), an endogenous negative angiogenic regulator. Paradoxically, however, chronic hypoxia is generally not found to increase mammalian skeletal muscle capillarity. Accordingly, we hypothesized that …

Hybridization Of Dna By Sequential Immobilization Of Oligonucleotides At The Air-Water Interface, Murali Sastry, Vidya Ramakrishnan, Mrunalini Pattarkine, Anand Gole, K. N. Ganesh

Faculty Works

The hybridization of DNA by sequential electrostatic and hydrogen-bonding immobilization of single-stranded complementary oligonucleotides at the air-water interface with cationic Langmuir monolayers is demonstrated. The complexation of the single-stranded DNA molecules with octadecylamine (ODA) Langmuir monolayers was followed in time by monitoring the pressure-area isotherms. A large (and slow) expansion of the ODA monolayer was observed during each stage of complexation in the following sequence: primary single-stranded DNA followed by complementary single-stranded DNA followed by the intercalator, ethidium bromide. Langmuir-Blodgett (LB) films of the ODA-DNA complex were formed on different substrates and characterized using quartz-crystal microgravimetry (QCM), Fourier transform infrared …

Prenatal Cocaine Exposure And Prematurity: Neurodevelopmental Growth, K. A. Espy, D. J. Francis, M. L. Riese

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

The consequences of prematurity and prenatal cocaine exposure on early neurobehavior and physical growth were examined longitudinally in a sample of 20 cocaine-exposed and 20 nonexposed preterm neonates. The magnitude of the difference in physical growth acceleration related to prenatal cocaine exposure increased with increasing birth gestational age, whereas growth rate differences in irritability decreased. In contrast, prenatal cocaine exposure, independent of prematurity, was related to reduced attention skills at 36 wks conceptional age and increased rates of neurobehavioral change. The effects of prenatal cocaine exposure differed with respect to the degree of prematurity, depending on the nature of the …

Cognitive Consequences And Central Nervous System Injury Following Treatment For Childhood Leukemia, I. M. Moore, K. A. Espy, P. Kaufmann, J. Kramer, K. Kaemingk, P. Miketova, N. Mollova, M. Kaspar, A. Pasvogel, K. Schram, W. Wara, J. Hutter, K. Matthay

Developmental Cognitive Neuroscience Laboratory: Faculty and Staff Publications

OBJECTIVES: To determine the relationship between membrane damage and intellectual and academic abilities in children with acute lymphoblastic leukemia (ALL) and pilot test a math intervention for children with ALL who were affected. DATA SOURCES: Research studies and review articles. CONCLUSIONS: Despite the prophylactic central nervous system (CNS) treatment for long-term disease-free survival, many children with ALL subsequently experience declines in intellectual and academic skills. IMPLICATIONS FOR NURSING PRACTICE: Improving academic abilities in children who have received CNS treatment is of high priority and may have longlasting implications on quality of life.

Lack Of Cd4+ T Cells Does Not Affect Induction Of Cd8+ T-Cell Immunity Against Encephalitozoon Cuniculi Infection, Magali Moretto, Lori Casciotti, Brigit Durell, Imtiaz A. Khan

Dartmouth Scholarship

Cell-mediated immunity has been reported to play an important role in defense against Encephalitozoon cuniculi infection. Previous studies from our laboratory have underlined the importance of cytotoxic CD8⁺ T lymphocytes (CTL) in survival of mice infected with E. cuniculi. In the present study, immune response against E. cuniculi infection in CD4⁺T-cell-deficient mice was evaluated. Similar to resistant wild-type animals, CD4^−/− mice were able to resolve E. cuniculi infection even at a very high challenge dose (5 × 10⁷ spores/mouse). Tissues from infected CD4^−/−mice did not exhibit higher parasite loads in comparison to …

Position Of Γ-Chain Carboxy-Terminal Regions In Fibrinogen/Fibrin Cross-Linking Mixtures, Kevin R. Siebenlist, David A. Meh, Michael W. Mosesson

Biomedical Sciences Faculty Research and Publications

There are conflicting ideas regarding the location of the carboxyl-terminal regions of cross-linked γ-chain dimers in double-stranded fibrin fibrils. Some investigators believe that the chains are always oriented longitudinally along each fibril strand and traverse the contacting ends of abutting fibrin D domains (“DD-long” cross-linking). Other investigations have indicated instead that the chains are situated transversely between adjacent D domains in opposing fibril strands (transverse cross-linking). To distinguish between these two possibilities, the γ dimer composition of factor XIIIa-cross-linked fibrin/fibrinogen complexes that had been formed through noncovalent D/E interactions between fibrinogen D domains and fibrin E domains was examined. Two …

Amino Acid Osmolytes In Regulatory Volume Decrease And Isovolumetric Regulation In Brain Cells: Contribution And Mechanisms, Herminia Pasantes-Morales, Rodrigo Franco, M. Eugenia Torres-Marquez, Karla Hernandez-Fonseca, Arturo Ortega

School of Veterinary and Biomedical Sciences: Faculty Publications

Brain adaptation to hyposmolarity is accomplished by loss of both electrolytes and organic osmolytes, including amino acids, polyalcohols and methylamines. In brain in vivo, the organic osmolytes account for about 35% of the total solute loss. This review focus on the role of amino acids in cell volume regulation, in conditions of sudden hyposmosis, when cells respond by active regulatory volume decrease (RVD) or after gradual exposure to hyposmotic solutions, a condition where cell volume remains unchanged, named isovolumetric regulation (IVR). The amino acid efflux pathway during RVD is passive and is similar in many respects to the volume-activated anion …

Genomic Structure Of Murine Mitochondrial Dna Polymerase-Gamma., Justin L. Mott, Grace Denniger, Steve J. Zullo, H. Peter Zassenhaus

Journal Articles: Biochemistry & Molecular Biology

We have sequenced a genomic clone of the gene encoding the mouse mitochondrial DNA polymerase. The gene consists of 23 exons, which span approximately 13.2 kb, with exons ranging in size from 53 to 768 bp. All intron-exon boundaries conform to the GT-AG rule. By comparison with the human genomic sequence, we found remarkable conservation of the gene structure; the intron-exon borders are in almost identical locations for the 22 introns. The 5' upstream region contains approximately 300 bp of homology between the mouse and human sequences that presumably contain the promoter element. This region lacks any obvious TATA domain …

Immunologic Effects Of Gliotoxin In Rats: Mechanisms For Prevention Of Autoimmune Diabetes Mellitus, Honggang Liu, Susan H. Jackman, Henry Driscoll, Bryan Larsen

Biochemistry and Microbiology

Various fungal products, such as gliotoxin (GT), have immunomodulating activity, a fact exploited previously by our group for prevention of autoimmune diabetes mellitus in BB/Wor rats. To understand better the immunologic effects in GT-treated rats, splenocytes from 65-day-old prediabetic diabetes-prone rats were phenotypically characterized after chronic treatment with GT. A parallel study examined the direct effects of GT on splenocyte preparations incubated with the mycotoxin. In vitro treatment of splenocytes with GT revealed relative decreases in CD4+ and increases in CD8+ T-cell subsets, whereas in vivo treatment with GT did not result in detectable alterations in relative CD4+ and CD8+ …

Single Channel Properties And Regulated Expression Of Ca2+ Release-Activated Ca2+ (Crac) Channels In Human T Cells, Alla F. Fomina, Christopher M. Fanger, J. Ashot Kozak, Michael D. Cahalan

Neuroscience, Cell Biology & Physiology Faculty Publications

Although the crucial role of Ca²⁺ influx in lymphocyte activation has been well documented, little is known about the properties or expression levels of Ca²⁺ channels in normal human T lymphocytes. The use of Na⁺ as the permeant ion in divalent-free solution permitted Ca²⁺ release-activated Ca²⁺ (CRAC) channel activation, kinetic properties, and functional expression levels to be investigated with single channel resolution in resting and phytohemagglutinin (PHA)-activated human T cells. Passive Ca²⁺ store depletion resulted in the opening of 41-pS CRAC channels characterized by high open probabilities, voltage-dependent block by extracellular Ca²⁺ in …

Update - September 2000, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- Takanobu Kinjo, Scott Winters and Nicole Wurscher graduate with degrees in Ethics and Ministry
-- Robert and Joyce Orr return to Vermont
-- Medical Theodicy Today
-- Changing our Genes: Medical Promises and Ethical Threats

Helicobacter Pylori Serology And The Diagnosis Of H. Pylori Infection In Children, Yoram Elitsur, Rafah Aflak, Cheryl Neace, W. E. Triest

Biochemistry and Microbiology

Serological screening accuracy rate may be dependent on clinical and pathological determinants. The aim of this study was to evaluate the accuracy of Hp serology test (Roche Biomedical Lab., Labcorp), In the diagnosis of Hp infection in 121 children who were seen in the Pediatric Gastoenterology Clinic at the Marshall University Joan C. Edwards School of Medicine In Huntington. Positive serology detected children with Hpassociated gastritis with a sensitivity of 51.6%. Positive serology significantly correlated with the degree of gastric inflammation and density of Hp organisms in the gastric mucosa (ANOVA p < 0.001). The Labcorp. Hp-ELISA test had a poor accuracy rate for the detection of Hp-gastritis in children. Gastric biopsies should always be performed to establish the diagnosis of Hp infection in children.

Staphylococcus Aureus Rn6390 Replicates And Induces Apoptosis In A Pulmonary Epithelial Cell Line, Barbara C. Kahl, Mark Goulian, Willem Van Wamel, Mathias Herrmann, Sanford M. Simon, Gilla Kaplan, Georg Peters, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus frequently colonizes the airways of patients with compromised airway defenses (e.g., cystic fibrosis [CF] patients) for extended periods. Persistent and relapsing infections may be related to live S. aureus bacteria actively residing inside epithelial cells. In this study, we infected a respiratory epithelial cell line, which was derived from a CF patient, with S. aureus RN6390. Internalization of S. aureus was found to be time and dose dependent and could be blocked by cytochalasin D. Transmission electron microscopy revealed that internalized bacteria resided within endocytic vacuoles without any evidence of lysosomal fusion in a 24-h period. The results …

Low Serum Alpha 1 Antitrypsin In Duodenal Ulcer--A Family Study, Anjum Shahid, Sarwar J, Zuberi Mohammad A, Waqar,Huma Qureshi Waqar,Huma Qureshi Waqar,Huma Qureshi, Anwar Ali Siddiqui, Taranum Sultana

Department of Biological & Biomedical Sciences

No abstract provided.

Structured Treatment Interrupion (Sti) With Nevirapine (Nvp) And Two Nucleoside Reverse Transciptase Inhibitors (Nsrti): Is Re-Suppression Achieved Following Treatment Interruption?, Joseph L. Yozviak Do, Facp, R Eric Doerfler Np, Cch, William C. Woodward Do

Department of Medicine

No abstract provided.

Antiretroviral Therapy (Art) In Clinical Practice: Effectiveness And Tolerability Of Necvirapine (Nvp), Stavudine (D4t) And Lamivudine (3tc), Joseph L. Yozviak Do, Facp, R Eric Doerfler Np, Cch, William C. Woodward Do

Department of Medicine

No abstract provided.

Identification And Characterization Of The Cis-Acting Elements Around The Murine Cd4 Cnhancer, Xin Dong

Loma Linda University Electronic Theses, Dissertations & Projects

The cluster determinant 4 (CD4) molecule is a transmembrane glycoprotein. CD4 is essential for normal T helper cell function and plays an important role in T cell development and activation. CD4 is encoded by a single gene located on chromosome 6 in the mouse and chromosome 12 in the human. Both human and murine CD4 genes are divided into ten exons spanning more than 25 kb and have a large non-coding region in the first and third intron. CD4 gene expression is controlled primarily at the transcriptional level during T cell development and activation.

An enhancer has been identified approximately …

Method Of Treatment Of Conditions Associate With Oxidative Tissue Damage, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions containing as the active ingredient a spin-trapping reagent, preferably α-phenyl butyl nitrone (PBN) or spin-trapping derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient are disclosed for treating or preventing symptoms associated with aging or other conditions associated with oxidative tissue damage. Other spin-trapping agents can also be used, such as 5,5-dimethyl pyrroline N-oxide (DMPO) or α-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), and other spin-trapping derivatives thereof. These compositions and methods are useful in the treatment of age-related disorders, pre-surgical and/or pre-anesthetic preparation or administration of chemotherapeutic agents, and in the treatment of disorders or trauma of the brain, …

A Ypt/Rab Effector Complex Containing The Sec1 Homolog Vps33p Is Required For Homotypic Vacuole Fusion, Darren F. Seals, Gary Eitzen, Nathan Margolis, William T. Wickner, Albert Price

Dartmouth Scholarship

Yeast vacuoles undergo priming, docking, and homotypic fusion, although little has been known of the connections between these reactions. Vacuole-associated Vam2p and Vam6p (Vam2/6p) are components of a 65S complex containing SNARE proteins. Upon priming by Sec18p/NSF and ATP, Vam2/6p is released as a 38S subcomplex that binds Ypt7p to initiate docking. We now report that the 38S complex consists of both Vam2/6p and the class C Vps proteins [Reider, S. E. and Emr, S. D. (1997) Mol. Biol. Cell 8, 2307-2327]. This complex includes Vps33p, a member of the Sec1 family of proteins that bind t-SNAREs. We term this …

Eye Position Signal Modulates A Human Parietal Pointing Region During Memory-Guided Movements., J F Desouza, S P Dukelow, J S Gati, R S Menon, R A Andersen, T Vilis

Brain and Mind Institute Researchers' Publications

Using functional magnetic resonance imaging, we examined the signal in parietal regions that were selectively activated during delayed pointing to flashed visual targets and determined whether this signal was dependent on the fixation position of the eyes. Delayed pointing activated a bilateral parietal area in the intraparietal sulcus (rIPS), rostral/anterior to areas activated by saccades. During right-hand pointing to centrally located targets, the left rIPS region showed a significant increase in activation when the eye position was rightward compared with leftward. As expected, activation in motor cortex showed no modulation when only eye position changed. During pointing to retinotopically identical …

Characterization Of 50s Ribosomal Subunit Assembly Inhibition In Erythromycin Treated Escherichia Coli Cells., Jerry Edward Usary

Electronic Theses and Dissertations

Erythromycin has long been recognized for its ability to inhibit protein synthesis by interfering with mRNA translation on the bacterial ribosome. We have recently shown that erythromycin also inhibits the assembly of the 50S ribosomal subunit in growing bacterial cells. The nature of this assembly inhibition has been investigated using ³H-uridine pulse-chase labeling of control and erythromycin treated E. coli cells.

Subunit assembly was examined by sucrose gradient centrifugation of labeled cell lysates. Normal assembly kinetics of subunit assembly were observed in control cells at 37°C. Formation of the 30S subunit was completed by 7.5 minutes and assembly of …

Measuring The "Managedness" And Covered Benefits Of Health Plans, Paula Diehr, David Grembowski

Paula Diehr

STUDY AIMS: (1) To develop indexes measuring the degree of managedness and the covered benefits of health insurance plans, (2) to describe the variation in these indexes among plans in one health insurance market, (3) to assess the validity of the health plan indexes, and (4) to examine the association between patient characteristics and the health plan indexes. Measures of the "managedness" and covered benefits of health plans are requisite for studying the effects of managed care on clinical practice and health system performance, and they may improve people's understanding of our complex health care system. DATA SOURCES/STUDY SETTING: As …

Differential Infectivity And Division Of Toxoplasma Gondii In Human Peripheral Blood Leukocytes, Jacqueline Y. Channon, Rosanne M. Seguin, Lloyd H. Kasper

Dartmouth Scholarship

When tachyzoites were incubated with human peripheral blood leukocytes in vitro, more monocytes and dendritic cells than neutrophils or lymphocytes were infected. Although tachyzoites were able to divide in each of these cell types, monocytes and dendritic cells were more permissive to rapid tachyzoite division than neutrophils or lymphocytes.

Vibrio Cholerae H-Ns Silences Virulence Gene Expression At Multiple Steps In The Toxr Regulatory Cascade, Melinda B. Nye, James D. Pfau, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

H-NS is an abundant nucleoid-associated protein involved in the maintenance of chromosomal architecture in bacteria. H-NS also has a role in silencing the expression of a variety of environmentally regulated genes during growth under nonpermissive conditions. In this study we demonstrate a role for H-NS in the negative modulation of expression of several genes within the ToxR virulence regulon ofVibrio cholerae. Deletion of hns resulted in high, nearly constitutive levels of expression of the genes encoding cholera toxin, toxin-coregulated pilus, and the ToxT virulence gene regulatory protein. For the cholera toxin- and ToxT-encoding genes, elevated expression in an …

A New Role For A Snare Protein As A Regulator Of The Ypt7/Rab-Dependent Stage Of Docking, Christian Ungermann, Albert Price, William Wickner

Dartmouth Scholarship

The homotypic fusion of yeast vacuoles occurs in an ordered cascade of priming, docking, and fusion. The linkage between these steps has so far remained unclear. We now report that Vam7p (the vacuolar SNAP-23/25 homolog) signals from the cis-SNARE complex to Ypt7p (the vacuolar Rab/Ypt) to initiate the docking process. After Vam7p has been released from the cis-SNARE complex by Sec18p-mediated priming, it is still required for Ypt7p-dependent docking and it needs Ypt7p to remain on the vacuole.