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Association Of Viral Genome With Graft Loss In Children After Cardiac Transplantation., Girish S. Shirali, J Ni, R E. Chinnock, J K. Johnston, G L. Rosenthal, N E. Bowles, J A. Towbin

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The survival of recipients of cardiac allografts is limited by rejection, lymphoproliferative disease, and coronary vasculopathy. The purpose of this study in children who had received heart transplants was to evaluate the cardiac allografts for myocardial viral infections and to determine whether the presence of viral genome in the myocardium correlates with rejection, coronary vasculopathy, or graft loss.

METHODS: We enrolled heart-transplant recipients 1 day to 18 years old who were undergoing evaluation for possible rejection and coronary vasculopathy. Endomyocardial-biopsy specimens were evaluated for evidence of rejection with the use of standard criteria and were analyzed for the presence …

Clumping Factor A Mediates Binding Of Staphylococcus Aureus To Human Platelets, Ian R. Siboo, Ambrose L. Cheung, Arnold S. Bayer, Paul M. Sullam

Dartmouth Scholarship

The direct binding of bacteria to platelets may be an important virulence mechanism in the pathogenesis of infective endocarditis. We have previously described Staphylococcus aureus strain PS12, a Tn551-derived mutant of strain ISP479, with reduced ability to bind human platelets in vitro. When tested in an animal model of endocarditis, the PS12 strain was less virulent than its parental strain, as measured by bacterial densities in endocardial vegetations and incidence of systemic embolization. We have now characterized the gene disrupted in PS12 and its function in platelet binding. DNA sequencing, Southern blotting, and PCR analysis indicate that PS12 contained two …

Increased Mrna Expression For The Α1 Subunit Of The GabaA Receptor Following Nitrous Oxide Exposure In Mice, Lisa M. Johanek, William E. Cullinan, Linda K. Vaughn

Biomedical Sciences Faculty Research and Publications

The mechanisms by which nitrous oxide (N₂O) produces physical dependence and withdrawal seizures are not well understood, but both N₂O and ethanol exert some of their effects via the GABA_A receptor and several lines of evidence indicate that withdrawal from N₂O and ethanol may be produced through similar mechanisms. Expression levels of mRNA transcripts encoding several GABA_A receptor subunits change with chronic ethanol exposure and, therefore, we hypothesized that N₂O exposure would produce changes in mRNA expression for the α₁ subunit. Male, Swiss–Webster mice, 10–12 weeks of age, were …

Circadian Clock-Specific Roles For The Light Response Protein White Collar-2, Michael A. Collett, Jay C. Dunlap, Jennifer J. Loros

Dartmouth Scholarship

To understand the role of white collar-2 in theNeurospora circadian clock, we examined alleles ofwc-2 thought to encode partially functional proteins. We found that wc-2 allele ER24 contained a conservative mutation in the zinc finger. This mutation results in reduced levels of circadian rhythm-critical clock gene products, frq mRNA and FRQ protein, and in a lengthened period of the circadian clock. In addition, this mutation altered a second canonical property of the clock, temperature compensation: as temperature increased, period length decreased substantially. This temperature compensation defect correlated with a temperature-dependent increase in overall FRQ protein levels, with the …

Association Of Ace Polymorphism And Diabetic Nephropathy In South Indian Patients, Vijay Viswanathan, Yanqing Zhu, Karthik Bala, Stephen Dunn, Chamukuttan Snehalatha, Ambady Ramachandran, Muthu Jayaraman, Kumar Sharma

Department of Medicine Faculty Papers

Objective: To study the association of ACE gene polymorphism and diabetic nephropathy in South Indian subjects.

Setting: Outpatient clinic of a specialized hospital.

Patients: The study included 109 South Indian type 2 diabetic patients (72 males and 37 females; age 56.7±9.0 years, mean±SD). The patients were subdivided into two groups: nephropathic (n=86) and normoalbuminuric patients (n=23).

Interventions: Genomic DNA was isolated from the peripheral blood leukocytes. To determine the ACE genotype, genomic DNA was amplified by PCR initially using a flanking primer pair and, subsequently when necessary, with a primer pair that recognizes the insertion specific sequence for confirmation of …

Assessment Of Immune System Involvement In Tourette Syndrome, Ashley Dawn Levine

Loma Linda University Electronic Theses, Dissertations & Projects

Tourette syndrome (TS) is currently hypothesized to be the result of genetic and immunological components. This study investigated whether TS subjects produce IgG and IgA antibodies that bind to caudate nucleus, hippocampus, frontal cortex, cerebellum, thalamus, globus pallidus interior, exterior and putamen. Thirty- two children (14 TS, 7 family control, and 11 non-family control) and thirty-nine adults (11 TS, 14 family control, and 14 non-family control) were studied. Immunofluorescent studies were performed on basal ganglia tissue using serum from TS children and their family members. Brain antigens were prepared as two fractions (supernatant and pellet) and used as targets for …

Enhanced Expression Of Human Platelet-Derived Growth Factor In Pichia Pastoris, David M. Kaetzel

Pharmacology and Nutritional Sciences Faculty Patents

Enhanced yields of the platelet-derived growth factor (PDGF) B-chain are obtained using the Pichia pastoris yeast system. Yields of both wild-type and mutant human proteins are enhanced when the yeast is transformed with a vector containing the yeast mating factor promoter fused to a sequence encoding the mature protein. The secreted wild-type protein is indistinguishable from mature 29-32 kDa protein isolated from human and Chinese hamster ovary (CHO) cells. An RKK→EEE mutant exhibited reduced association with the cell surface and accumulated in the culture medium as 29-32 kDa forms. Stable transfection of U87 astrocytoma cells with RKK→EEE mutants of either …

Truncated Forms Of The Dual Function Human Asct2 Neutral Amino Acid Transporter/Retroviral Receptor Are Translationally Initiated At Multiple Alternative Cug And Gug Codons, Chetankumar S. Tailor, Mariana Marin, Ali Nouri, Michael Kavanaugh, David Kabat

Biomedical and Pharmaceutical Sciences Faculty Publications

The sodium-dependent neutral amino acid transporter type 2 (ASCT2) was recently identified as a cell surface receptor for endogenously inherited retroviruses of cats, baboons, and humans as well as for horizontally transmitted type-D simian retroviruses. By functional cloning, we obtained 10 full-length 2.9-kilobase pair (kbp) cDNAs and two smaller identical 2.1-kbp cDNAs that conferred susceptibility to these viruses. Compared with the 2.9-kbp cDNA, the 2.1-kbp cDNA contains exonic deletions in its 3′ noncoding region and a 627-bp 5′ truncation that eliminates sequences encoding the amino-terminal portion of the full-length ASCT2 protein. Although expression of the truncated mRNA caused enhanced amino …

A Comparative Clinical And Histopathological Examination Of Hemangioma And Chronic Inflammatory Enlargement Of Gingiva, Umur Sakallioğlu, Gökhan Açikgöz, Tuğrul Kirtiloğlu, Musa Aldikaçti

Turkish Journal of Medical Sciences

Chronic inflammatory gingival enlargement (CIGE) occasionally exhibits some similarities with hemangioma (Hm) by means of the clinical and histopathological features of gingiva. When compared with hemangioma, CIGE is more frequently encountered by the dental profession. However, Hm is rarely seen on gingiva and it has a non-inflammatory nature and mostly congenital origin. The present paper reports the clinic and histopathologic features of CIGE and Hm of gingiva in patients referred to our clinic suffering primarily from gingival overgrowth. Twenty-one patients were diagnosed as having CIGE (in a 4-month period) and 10 patients were diagnosed as having Hm (in a 12-month …

A Rare Cause Of Upper Gastrointestinal System Bleeding: Pancreatic Endocrine Neoplasm, Oral Saygun, Fati̇h Mehmet Avşar, İ. Hakan Özel, Süleyman Hengi̇rmen, Levent Albayrak, Sema Hücümenoğlu

Turkish Journal of Medical Sciences

No abstract provided.

Diabetic Osteopathy: Who Is At Risk?, Serap Demi̇r, Ayşi̇n Öge, Selma Karaahmetoğlu, Osman Müftüoğlu, Seni̇ha Naldöken

Turkish Journal of Medical Sciences

This study was designed to determine the prevalence of osteopathy in diabetic patients, who are at risk of developing osteopathy, and clarify the relationship between osteopathy and other complications of diabetes mellitus. Thirty-four type I and 66 type II diabetic patients admitted to the endocrinology clinic between 1996 and 1997 and 30 nondiabetic subjects as a control group were studied. Bone scintigraphy (Tc 99m methylene diphosphonate) was used for the diagnosis of osteopathy. The body mass index (BMI) of each patient was calculated. Polyneuropathy was assessed by electromyography and the patients, for each of whom BMI was calculated, were asked …

Titrating And Evaluating Multiple Drug Regimens Within Subjects, Margaret Shih

Theses and Dissertations

The dosing of combination therapies is commonly undertaken empirically by practicing physicians, and there is a lack of a coherent algorithm to approach the problem of combination dosing. Current methods of evaluating multiple drug combinations in clinical trials generally do not provide information regarding the location of more effective dosages when the combination is not found to differ from the standard, even though the absence of a difference does not necessarily mean the new combination is ineffective. Additionally, if a new combination is found to be more effective, often a large proportion of the subjects has not benefited from the …

Central Chemosensitivity, Sleep, And Wakefulness, E. E. Nattie, A Li

Dartmouth Scholarship

No abstract provided.

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 …

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

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 …

Morphological, Molecular, And Biogeographical Variation Within The Imperiled Virginia Spiraea, Constance Anders

Masters Theses & Specialist Projects

Spiraea virginiana Britton is a rare federally listed rhizomatous shrub endemic to the southern Blue Ridge and Appalachian Plateau physiographic provinces. Populations of S. virginiana are found restricted to scoured sections of high gradient streams within the Ohio River drainage. Present evidence indicates the species is reproducing asexually, most probably through the deposition of rhizomes from upstream populations forming new downstream ramets. Phenotypic variation was examined through a morphometric evaluation of 25 leaf measurements and analyzed using Principal Components Analysis (PCA) and discriminant function analysis. Identity and structure at the molecular level as examined with Randomly Amplified Polymorphic DNA (RAPDs) …

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 …

Vitamin A And Cancer, Richard M. Niles

Biochemistry and Microbiology

Vitamin A, its physiological metabolites and synthetic derivatives (retinoids) have been shown to have protective effects against the development of certain types of cancer. In addition, pharmacological amounts of retinoids have been used with some success in the treatment of a few human tumors. The chemoprevention effect of retinoids is most likely exerted at the tumor promotion phase of carcinogenesis. Retinoids block tumor promotion by either inhibiting proliferation, inducing apoptosis, inducing differentiation, or a combination of these actions. Clinically, isotretinoin (13-cis-retinoic acid) significantly decreases the incidence of second primary tumors in patients with head and neck cancer and also reduces …

Long-Term Prevention Of Renal Insufficiency, Excess Matrix Gene Expression, And Glomerular Mesangial Matrix Expansion By Treatment With Monoclonal Antitransforming Growth Factor-Ss Antibody In Db/Db Diabetic Mice , Fuad N. Ziyadeh, Brenda B. Hoffman, Dong Cheol Han, M. Carmen Iglesias-De La Cruz, Soon Won Hong, Motohide Isono, Sheldon Chen, Tracy A. Mcgowan, Kumar Sharma

Department of Medicine Faculty Papers

Emerging evidence suggests that transforming growth factor-(TGF-β) is an important mediator of diabetic nephropathy. We showed previously that short-term treatment with a neutralizing monoclonal anti-TGF-antibody (αT) in streptozotocin-diabetic mice prevents early changes of renal hypertrophy and increased matrix mRNA. To establish that overactivity of the renal TGF-system mediates the functional and structural changes of the more advanced stages of nephropathy, we tested whether chronic administration of αT prevents renal insufficiency and glomerulosclerosis in the db/db mouse, model of type 2 diabetes that develops overt nephropathy. Diabetic db/db mice and nondiabetic db/m littermates were treated intraperitoneally with α or control IgG, …

Effects Of Estradiol And Progesterone On Susceptibility And Early Immune Responses To Chlamydia Trachomatis Infection In The Female Reproductive Tract, Charu Kaushic, Fan Zhou, Andrew D. Murdin, Charles R. Wira

Dartmouth Scholarship

We have used a previously described rodent model to examine the influence of hormonal environment on susceptibility and immune responses to genital Chlamydia infection. Ovariectomized rats were administered estradiol, progesterone, or a combination of both, infected with Chlamydia trachomatis via the intrauterine route, and sacrificed 5 days later. Histopathological examination showed severe inflammation in the uteri and vaginae of progesterone-treated animals, whereas animals receiving estradiol or a combination of both hormones showed no inflammation. Large numbers of chlamydiae were found in vaginal secretions of progesterone-treated and combination-treated animals, while estradiol-treated animals had none. Tissue localization showed that numerous chlamydial inclusions …

Effects Of Pycnogenol On Microsomal Cytochrome P450 Activity And Apoptosis, Huong Thu Huynh

Loma Linda University Electronic Theses, Dissertations & Projects

Phytochemicals are naturally-occurring compounds found in plants, many of which are consumed as nutritional supplements by humans. Pycnogenol is a mixture of flavonoid compounds extracted from bark of pine trees (Pinus maritima) and is commercially available in several different pharmaceutical preparations as a free radical scavenger.

Since few scientific studies have documented the pharmacologic effects of pycnogenol, our objective was to characterize the biological activity of pycnogenol. One study looked at the effects of pycnogenol on the three pathways of NNK metabolism: NNK reduction, N-oxidation and a-hydroxylation. NNK is a lung carcinogen. Lung and liver microsomes from 6 mo and …

Efflux Of Osmolyte Amino Acids During Isovolumic Regulation In Hippocampal Slices, Rodrigo Franco, Octavio Quesada, Herminia Pasantes-Morales

School of Veterinary and Biomedical Sciences: Faculty Publications

The efflux of potassium (K⁺) and amino acids from hippocampal slices was measured after sudden exposure to 10% (270 mOsm), 25% (225 mOsm) or 50% (150 mOsm) hyposmotic solutions or after gradual decrease (22.5 mOsm/min) in external osmolarity. In slices suddenly exposed to 50% hyposmotic solutions, swelling was followed by partial (74%) cell volume recovery, suggesting regulatory volume decrease (RVD). With gradual hyposmotic changes, no increase in cell water content was observed even when the solution at the end of the experiment was 50% hyposmotic, showing the occurrence of isovolumic regulation (IVR). The gradual decrease in osmolarity elicited …

Effect Of Receptor-Selective Retinoids On Growth And Differentiation Pathways In Mouse Melanoma Cells, Sejal H. Desai, Goran Boskovic, Linda L. Eastham, Marcia Dawson, Richard M. Niles

Biochemistry and Microbiology

Treatment of B16 mouse melanoma cells with all-trans-retinoic acid (ATRA) results in inhibition of cell proliferation and induction of differentiation. Accompanying these events is an induction of retinoic acid receptor β (RARβ) expression, an increase in protein kinase Cα (PKCα) expression, and enhanced activator protein-1 (AP-1) transcriptional activity. These cells express nuclear RARα and RARγ and nuclear retinoid X receptors (RXR) α and β constitutively. We tested the ability of receptor-selective retinoids to induce the biochemical changes found in ATRA-treated melanoma cells and also tested their effectiveness in decreasing anchorage-dependent and -independent growth. The RXR-selective ligand (2E,4E)-6-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphthalenyl)-3,7-dimethyl-2,4,6-octatrienoic acid (SR11246) was …

Density And Age Distributions Of Trees In Upland And Lowland Oldfields 60 Years After Abandonment: The Role Of Dispersal, Virginia Mcdaniel

Masters Theses & Specialist Projects

I attempted to determine whether the patterns of seedling establishment described in the literature for forests and recently abandoned oldfields are maintained in fields sixty years after abandonment. To determine this distribution pattern, as well as to compare patterns of age and density distribution in upland and lowland oldfields, I conducted research at Mammoth Cave National Park. I studied three species, the seeds of which are dispersed by three different modes: Juniperus virginiana, a predominantly bird-dispersed species; Acer rubrum, a predominantly winddispersed species; and Fagus grandifolia, a predominantly mammal-dispersed species. The establishment patterns observed by others in recently abandoned oldfields …

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

Update

In this issue:

-- National conference explores the future of faith-based health care
-- Ruth Macklin Judges Bioethical Relativism (Commentary)
-- Conditional Imortality and Cognitive Neuroscience
-- Clinical Ethics Consultation

Single-Channel Properties In Endoplasmic Reticulum Membrane Of Recombinant Type 3 Inositol Trisphosphate Receptor., D O Mak, S Mcbride, V Raghuram, Y Yue, Suresh K. Joseph, J K Foskett

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The inositol 1,4,5-trisphosphate receptor (InsP(3)R) is an intracellular Ca(2+)-release channel localized in endoplasmic reticulum (ER) with a central role in complex Ca(2+) signaling in most cell types. A family of InsP(3)Rs encoded by several genes has been identified with different primary sequences, subcellular locations, variable ratios of expression, and heteromultimer formation. This diversity suggests that cells require distinct InsP(3)Rs, but the functional correlates of this diversity are largely unknown. Lacking are single-channel recordings of the recombinant type 3 receptor (InsP(3)R-3), a widely expressed isoform also implicated in plasma membrane Ca(2+) influx and apoptosis. Here, we describe functional expression and single-channel …

Naturally Occurring Tap-Dependent Specific T-Cell Tolerance For A Variant Of An Immunodominant Retroviral Cytotoxic T-Lymphocyte Epitope, Victor Kim, Jonathan W. Yewdell, William R. Green

Dartmouth Scholarship

Upon immunization and restimulation with tumors induced by the endogenous AKR/Gross murine leukemia virus (MuLV), C57BL/6 mice generate vigorous H-2K(b)-restricted cytotoxic T-lymphocyte (CTL) responses to a determinant (KSPWFTTL) derived from the p15E transmembrane portion of the viral envelope glycoprotein. By contrast, the highly homologous determinant RSPWFTTL, expressed by tumor cells induced by Friend/Moloney/Rauscher (FMR) MuLV, is not immunogenic, even when presented to the immune system as vaccinia virus-encoded cytosolic or endoplasmic reticulum (ER)-targeted minigene products. Such minigene products are usually highly immunogenic since they bypass the need for cells to liberate the peptide or transport the peptide into the ER …

Pentameric Assembly Of A Neuronal Glutamate Transporter, Sepehr Eskandari, Michael Kreman, Michael Kavanaugh, Ernest M. Wright, Guido A. Zampighi

Biomedical and Pharmaceutical Sciences Faculty Publications

Freeze-fracture electron microscopy was used to study the structure of a human neuronal glutamate transporter (EAAT3). EAAT3 was expressed in Xenopus laevis oocytes, and its function was correlated with the total number of transporters in the plasma membrane of the same cells. Function was assayed as the maximum charge moved in response to a series of transmembrane voltage pulses. The number of transporters in the plasma membrane was determined from the density of a distinct 10-nm freeze-fracture particle, which appeared in the protoplasmic face only after EAAT3 expression. The linear correlation between EAAT3 maximum carrier-mediated charge and the total number …