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Mitostatin, A Putative Tumor Suppressor On Chromosome 12q24.1, Is Downregulated In Human Bladder And Breast Cancer., A Vecchione, M Fassan, V Anesti, A Morrione, S Goldoni, G Baldassarre, D Byrne, D D'Arca, J P Palazzo, J Lloyd, L Scorrano, L G Gomella, R V Iozzo, R Baffa

Department of Urology Faculty Papers

Allelic deletions on human chromosome 12q24 are frequently reported in a variety of malignant neoplasms, indicating the presence of a tumor suppressor gene(s) in this chromosomal region. However, no reasonable candidate has been identified so far. In this study, we report the cloning and functional characterization of a novel mitochondrial protein with tumor suppressor activity, henceforth designated MITOSTATIN. Human MITOSTATIN was found within a 3.2-kb transcript, which encoded a approximately 62 kDa, ubiquitously expressed protein with little homology to any known protein. We found homozygous deletions and mutations of MITOSTATIN gene in approximately 5 and approximately 11% of various cancer-derived …

Genetic And Hormonal Factors Modulate Spreading Depression And Transient Hemiparesis In Mouse Models Of Familial Hemiplegic Migraine Type 1, Katharina Eikermann-Haerter, Ergin Dileköz, Chiho Kudo, Sean I Savitz, Christian Waeber, Michael J Baum, Michel D Ferrari, Arn M J M Van Den Maagdenberg, Michael A Moskowitz, Cenk Ayata

Faculty, Staff and Student Publications

Familial hemiplegic migraine type 1 (FHM1) is an autosomal dominant subtype of migraine with aura that is associated with hemiparesis. As with other types of migraine, it affects women more frequently than men. FHM1 is caused by mutations in the CACNA1A gene, which encodes the alpha1A subunit of Cav2.1 channels; the R192Q mutation in CACNA1A causes a mild form of FHM1, whereas the S218L mutation causes a severe, often lethal phenotype. Spreading depression (SD), a slowly propagating neuronal and glial cell depolarization that leads to depression of neuronal activity, is the most likely cause of migraine aura. Here, we have …

Successional Change In Phosphorus Stoichiometry Explains The Inverse Relationship Between Herbivory And Lupin Density On Mount St. Helens, Jennifer L. Apple, Michael Wink, Shannon E. Wills, John G. Bishop

Biology

Background: The average nitrogen-to-phosphorus ratio (N:P) of insect herbivores is less than that of leaves, suggesting that P may mediate plant-insect interactions more often than appreciated. We investigated whether succession-related heterogeneity in N and P stoichiometry influences herbivore performance on N-fixing lupin (Lupinus lepidus) colonizing primary successional volcanic surfaces, where the abundances of several specialist lepidopteran herbivores are inversely related to lupin density and are known to alter lupin colonization dynamics. We examined larval performance in response to leaf nutritional characteristics using gelechiid and pyralid leaf-tiers, and a noctuid leaf-cutter. Methodology/Principal Findings: We conducted four studies. First, growth of larvae …

Functional Interleukin-17 Receptor A Is Expressed In Central Nervous System Glia And Upregulated In Experimental Autoimmune Encephalomyelitis., Jayasri Das Sarma, Bogoljub Ciric, Ryan Marek, Sanjoy Sadhukhan, Michael L. Caruso, Jasmine Shafagh, Denise C. Fitzgerald, Kenneth S. Shindler, Am Rostami

Department of Neurology Faculty Papers

BACKGROUND: Interleukin-17A (IL-17A) is the founding member of a novel family of inflammatory cytokines that plays a critical role in the pathogenesis of many autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-17A signals through its receptor, IL-17RA, which is expressed in many peripheral tissues; however, expression of IL-17RA in the central nervous system (CNS) and its role in CNS inflammation are not well understood.

METHODS: EAE was induced in C57Bl/6 mice by immunization with myelin oligodendroglial glycoprotein. IL-17RA expression in the CNS was compared between control and EAE mice using RT-PCR, in situ …

Mutation I810n In The Α3 Isoform Of Na+,K +-Atpase Causes Impairments In The Sodium Pump And Hyperexcitability In The Cns, Steven J. Clapcote, Steven Duffy, Gang Xie, Greer Kirshenbaum, Allison R. Bechard, Vivien Rodacker Schack, Janne Petersen, Laleh Sinai, Bechara J. Saab, Jason P. Lerch, Berge A. Minassian, Cameron A. Ackerley, John G. Sled, Miguel A. Cortez, Jeffrey T. Henderson, Bente Vilsen, John C. Roder

Psychology

In a mouse mutagenesis screen,weisolated a mutant, Myshkin (Myk), with autosomal dominant complex partial and secondarily generalized seizures, a greatly reduced threshold for hippocampal seizures in vitro, posttetanic hyperexcitability of the CA3-CA1 hippocampal pathway, and neuronal degeneration in the hippocampus. Positional cloning and functional analysis revealed that Myk/+ mice carry a mutation (I810N) which renders the normally expressed Na +,K+-. ATPase α3 isoform inactive. Total Na +,K+-ATPase activity was reduced by 42% in Myk/+ brain. The epilepsy in Myk/+ mice and in vitro hyperexcitability could be prevented by delivery of additional copies of wild-type Na+,K+-ATPase α3 by transgenesis, which also …

Behavioral Changes In Aging But Not Young Mice After Neonatal Exposure To The Polybrominated Flame Retardant Decabde, Deborah C. Rice, W. Douglas Thompson, Elizabeth A. Reeve, Kristen D. Onos, Mina Assadollahzadeh, Vincent P. Markowski

Psychology

BACKGROUND: After several decades of commercial use, the flame-retardant chemicals polybrominated diphenyl ethers (PBDEs) and their metabolites are pervasive environmental contaminants and are detected in the human body. Decabrominated diphenyl ether (decaBDE) is currently the only PBDE in production in the United States. oBjectives: Little is known about the health effects of decaBDE. In the present study we examined the effects of neonatal decaBDE exposure on behavior in mice at two ages. METHODS: Neonatal male and female C57BL6/J mice were exposed to a daily oral dose of 0, 6, or 20 mg/kg decaBDE from postnatal days 2 through 15. Two …

Regulation Of The Fibrosis And Angiogenesis Promoter Sparc/Osteonectin In Human Adipose Tissue By Weight Change, Leptin, Insulin, And Glucose., Katrina Kos, Steve Wong, Bee Tan, Anders Gummesson, Margareta Jernas, Niclas Franck, David Kerrigan, Fredrik H. Nystrom, Lena M.S. Carlsson, Harpal S. Randeva, Jonathan H. Pinkney, John P.H. Wilding

Peninsula Medical School

OBJECTIVE: Matricellular Secreted Protein, Acidic and Rich in Cysteine (SPARC), originally discovered in bone as osteonectin, is a mediator of collagen deposition and promotes fibrosis. Adipose tissue collagen has recently been found to be linked with metabolic dysregulation. Therefore, we tested the hypothesis that SPARC in human adipose tissue is influenced by glucose metabolism and adipokines. RESEARCH DESIGN AND METHODS: Serum and adipose tissue biopsies were obtained from morbidly obese nondiabetic subjects undergoing bariatric surgery and lean control subjects for analysis of metabolic markers, SPARC, and various cytokines (RT-PCR). Additionally, 24 obese subjects underwent a very-low-calorie diet of 1,883 kJ …

Noninvasive Measurement Of Aminolevulinic Acid-Induced Protoporphyrin Ix Fluorescence Allowing Detection Of Murine Glioma In Vivo, Summer L. Gibbs-Strauss, Julia A. O'Hara, P Jack Hoopes, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

Aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence is studied as a contrast agent for noninvasive detection of murine glioma, using the fluorescence-to-transmission ratio measured through the cranium. Signals measured prior to administration of ALA are very similar between control animals, 9L-GFP, and U251 tumor-bearing animals. However, 2 h after ALA administration, the PpIX signal from both tumor-bearing groups is significantly higher than the control group (9L-GFP group p-value=0.016, and U251 group p-value=0.004, relative to the control group). The variance in signal from the 9L-GFP group is much larger than either the control group or the U251 group, which is consistent …

Quantitative Imaging Of Scattering Changes Associated With Epithelial Proliferation, Necrosis And Fibrosis In Tumors Using Microsampling Reflectance Spectroscopy, Venkataramanan Krishnaswamy, P Jack Hoopes, Kimberley S. Samkoe, Julia A. O'Hara, Tayyaba Hasan, Brian W. Pogue

Dartmouth Scholarship

Highly localized reflectance measurements can be used to directly quantify scatter changes in tissues. We present a microsampling approach that is used to raster scan tumors to extract parameters believed to be related to the tissue ultrastructure. A confocal reflectance imager was developed to examine scatter changes across pathologically distinct regions within tumor tissues. Tissue sections from two murine tumors, AsPC-1 pancreas tumor and the Mat-LyLu Dunning prostate tumor, were imaged. After imaging, histopathology-guided region-of-interest studies of the images allowed analysis of the variations in scattering resulting from differences in tissue ultra-structure. On average, the median scatter power of tumor …

What Determines Auditory Similarity? The Effect Of Stimulus Group And Methodology., Kirsteen M. Aldrich, Elizabeth J. Hellier, Judy Edworthy

School of Psychology

Two experiments on the internal representation of auditory stimuli compared the pairwise and grouping methodologies as means of deriving similarity judgements. A total of 45 undergraduate students participated in each experiment, judging the similarity of short auditory stimuli, using one of the methodologies. The experiments support and extend Bonebright's (1996) findings, using a further 60 stimuli. Results from both methodologies highlight the importance of category information and acoustic features, such as root mean square (RMS) power and pitch, in similarity judgements. Results showed that the grouping task is a viable alternative to the pairwise task with N > 20 sounds whilst …

Revealing Genes Associated With Vitellogenesis In The Liver Of The Zebrafish (Danio Rerio) By Transcriptome Profiling., Liraz Levi, Irena Pekarski, Ellen Gutman, Paolo Fortina, Terry Hyslop, Jakob Biran, Berta Levavi-Sivan, Esther Lubzens

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: In oviparous vertebrates, including fish, vitellogenesis consists of highly regulated pathways involving 17beta-estradiol (E2). Previous studies focused on a relatively small number of hepatic expressed genes during vitellogenesis. This study aims to identify hepatic genes involved in vitellogenesis and regulated by E2, by using zebrafish microarray gene expression profiling, and to provide information on functional distinctive genes expressed in the liver of a vitellogenic female, using zebrafish as a model fish. RESULTS: Genes associated with vitellogenesis were revealed by the following paired t-tests (SAM) comparisons: a) two-month old vitellogenic (Vit2) females were compared with non-vitellogenic (NV) females, showing 825 …

Elevated Expression Of L-Selectin Ligand In Lymph Node-Derived Human Prostate Cancer Cells Correlates With Increased Tumorigenicity., Prakash Radhakrishnan, Ming-Fong Lin, Pi-Wan Cheng

Journal Articles: Biochemistry & Molecular Biology

Human prostate cancer LNCaP cells including C-33 and C-81 cells were originally derived from the lymph nodes of a patient with metastatic prostate cancer. These two cells were employed for characterization of L-selectin ligand and in vitro tumorigenicity, because they mimic the clinical conditions of early and late-stage human prostate cancer. C-81 cells exhibit higher in vitro migratory and invasive properties as compared with C-33 cells. We find that the L-selectin ligand and mucin glycan-associated MECA-79 epitope were elevated in C-81 cells. An increase of these glycotopes positively correlates with elevated tumorigenicity and expression of key glycosyl- and sulfotransferase genes. …

Effector Memory T Cell Responses Are Associated With Protection Of Rhesus Monkeys From Mucosal Simian Immunodeficiency Virus Challenge., Scott G. Hansen, Cassandra Vieville, Nathan Whizin, Lia Coyne-Johnson, Don C. Siess, Derek D. Drummond, Alfred W. Legasse, Michael K. Axthelm, Kelli Oswald, Charles M. Trubey, Michael Piatak, Jeffrey D. Lifson, Jay A. Nelson, Michael A. Jarvis, Louis J. Picker

School of Biomedical Sciences

The rapid onset of massive, systemic viral replication during primary HIV or simian immunodeficiency virus (SIV) infection and the immune evasion capabilities of these viruses pose fundamental problems for vaccines that depend upon initial viral replication to stimulate effector T cell expansion and differentiation. We hypothesized that vaccines designed to maintain differentiated effector memory T cell (TEM cell) responses at viral entry sites might improve efficacy by impairing viral replication at its earliest stage, and we have therefore developed SIV protein-encoding vectors based on rhesus cytomegalovirus (RhCMV), the prototypical inducer of life-long TEM cell responses. RhCMV vectors expressing SIV Gag, …

Aluminum Bioavailability From Tea Infusion, Robert A. Yokel, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

The objective was to estimate oral Al bioavailability from tea infusion in the rat, using the tracer ²⁶Al. ²⁶Al citrate was injected into tea leaves. An infusion was prepared from the dried leaves and given intra-gastrically to rats which received concurrent intravenous ²⁷Al infusion. Oral Al bioavailability (F) was calculated from the area under the ²⁶Al, compared to ²⁷Al, serum concentration × time curves. Bioavailability from tea averaged 0.37%; not significantly different from water (F = 0.3%), or basic sodium aluminum phosphate (SALP) in cheese (F = 0.1 to 0.3%), but greater than acidic SALP …

Increased Myocardial Susceptibility To Repetitive Ischemia With High-Fat–Diet-Induced Obesity, Geeta D Thakker, Nikolaos G Frangogiannis, Pawel T Zymek, Saumya Sharma, Joe L Raya, Philip M Barger, Heinrich Taegtmeyer, Mark L Entman, Christie M Ballantyne

Faculty, Staff and Student Publications

Obesity and diabetes are frequently associated with cardiovascular disease. When a normal heart is subjected to brief/sublethal repetitive ischemia and reperfusion (I/R), adaptive responses are activated to preserve cardiac structure and function. These responses include but are not limited to alterations in cardiac metabolism, reduced calcium responsiveness, and induction of antioxidant enzymes. In a model of ischemic cardiomyopathy inducible by brief repetitive I/R, we hypothesized that dysregulation of these adaptive responses in diet-induced obese (DIO) mice would contribute to enhanced myocardial injury. DIO C57BL/6J mice were subjected to 15 min of daily repetitive I/R while under short-acting anesthesia, a protocol …

Medial Temporal Lobe Bold Activity At Rest Predicts Individual Differences In Memory Ability In Hhealthy Young Adults, Gagan S. Wig, Scott T. Grafton, Kathryn E. Demos, George L. Wolford, Steven E. Petersen, William M. Kelley

Dartmouth Scholarship

Human beings differ in their ability to form and retrieve lasting long-term memories. To explore the source of these individual differences, we used functional magnetic resonance imaging to measure blood-oxygen-level-dependent (BOLD) activity in healthy young adults (n = 50) during periods of resting fixation that were interleaved with periods of simple cognitive tasks. We report that medial temporal lobe BOLD activity during periods of rest predicts individual differences in memory ability. Specifically, individuals who exhibited greater magnitudes of task-induced deactivations in medial temporal lobe BOLD signal (as compared to periods of rest) demonstrated superior memory during offline testing. This relationship …

Focal Cerebral Ischemia In The Tnfalpha-Transgenic Rat, L. Creed Pettigrew, Mark S. Kindy, Stephen W. Scheff, Joe E. Springer, Richard J. Kryscio, Yizhao Li, David S. Grass

Sanders-Brown Center on Aging Faculty Publications

BACKGROUND: To determine if chronic elevation of the inflammatory cytokine, tumor necrosis factor-alpha (TNFalpha), will affect infarct volume or cortical perfusion after focal cerebral ischemia.

METHODS: Transgenic (TNFalpha-Tg) rats overexpressing the murine TNFalpha gene in brain were prepared by injection of mouse DNA into rat oocytes. Brain levels of TNFalpha mRNA and protein were measured and compared between TNFalpha-Tg and non-transgenic (non-Tg) littermates. Mean infarct volume was calculated 24 hours or 7 days after one hour of reversible middle cerebral artery occlusion (MCAO). Cortical perfusion was monitored by laser-Doppler flowmetry (LDF) during MCAO. Cortical vascular density was quantified by stereology. …

Speaking The Right Language: The Scientific Method As A Framework For A Continuous Quality Improvement Program Within Academic Medical Research Compliance Units, Kurt B. Nolte, Douglas M. Stewart, Kevin C. O'Hair, William L. Gannon, Michael S. Briggs, A Marie Barron, Judy Pointer, Richard S. Larson

Pathology Research and Scholarship

The authors developed a novel continuous quality improvement (CQI) process for academic biomedical research compliance administration. A challenge in developing a quality improvement program in a nonbusiness environment is that the terminology and processes are often foreign. Rather than training staff in an existing quality improvement process, the authors opted to develop a novel process based on the scientific method--a paradigm familiar to all team members. The CQI process included our research compliance units. Unit leaders identified problems in compliance administration where a resolution would have a positive impact and which could be resolved or improved with current resources. They …

Characteristics Of A Spina Bifida Population Including North American Caucasian And Hispanic Individuals, Kit Sing Au, Phong X Tran, Chester C Tsai, Michelle R O'Byrne, Jone-Ing Lin, Alanna C Morrison, Amy W Hampson, Paul Cirino, Jack M Fletcher, Kathryn K Ostermaier, Gayle H Tyerman, Sabine Doebel, Hope Northrup

Faculty, Staff and Student Publications

BACKGROUND: Meningomyelocele (MM) is a common human birth defect. MM is a disorder of neural development caused by contributions from genes and environmental factors that result in the NTD and lead to a spectrum of physical and neurocognitive phenotypes.

METHODS: A multidisciplinary approach has been taken to develop a comprehensive understanding of MM through collaborative efforts from investigators specializing in genetics, development, brain imaging, and neurocognitive outcome. Patients have been recruited from five different sites: Houston and the Texas-Mexico border area; Toronto, Canada; Los Angeles, California; and Lexington, Kentucky. Genetic risk factors for MM have been assessed by genotyping and …

Molecular And Macromolecular Alterations Of Recombinant Adenoviral Vectors Do Not Resolve Changes In Hepatic Drug Metabolism During Infection, Shellie M Callahan, Piyanuch Wonganan, Maria A Croyle

Faculty, Staff and Student Publications

In this report we test the hypothesis that long-term virus-induced alterations in CYP occur from changes initiated by the virus that may not be related to the immune response. Enzyme activity, protein expression and mRNA of CYP3A2, a correlate of human CYP3A4, and CYP2C11, responsive to inflammatory mediators, were assessed 0.25, 1, 4, and 14 days after administration of several different recombinant adenoviruses at a dose of 5.7 x 1012 virus particles (vp)/kg to male Sprague Dawley rats. Wild type adenovirus, containing all viral genes, suppressed CYP3A2 and 2C11 activity by 37% and 39%, respectively within six hours. Levels fell …

Co-Up-Regulation Of Three P450 Genes In Response To Permethrin Exposure In Permethrin Resistant House Flies, Musca Domestica, Fang Zhu, Ting Li, Lee Zhang, Nannan Liu

Entomology Faculty Publications

BACKGROUND: Insects may use various biochemical pathways to enable them to tolerate the lethal action of insecticides. For example, increased cytochrome P450 detoxification is known to play an important role in many insect species. Both constitutively increased expression (overexpression) and induction of P450s are thought to be responsible for increased levels of detoxification of insecticides. However, unlike constitutively overexpressed P450 genes, whose expression association with insecticide resistance has been extensively studied, the induction of P450s is less well characterized in insecticide resistance. The current study focuses on the characterization of individual P450 genes that are induced in response to permethrin …

Missense Mutation In Exon 2 Of Slc36a1 Responsible For Champagne Dilution In Horses, Deborah Cook, Samantha Brooks, Rebecca Bellone, Ernest Bailey

Veterinary Science Faculty Publications

Champagne coat color in horses is controlled by a single, autosomal-dominant gene (CH). The phenotype produced by this gene is valued by many horse breeders, but can be difficult to distinguish from the effect produced by the Cream coat color dilution gene (CR). Three sires and their families segregating for CH were tested by genome scanning with microsatellite markers. The CH gene was mapped within a 6 cM region on horse chromosome 14 (LOD = 11.74 for theta = 0.00). Four candidate genes were identified within the region, namely SPARC [Secreted protein, acidic, cysteine-rich (osteonectin)], SLC36A1 (Solute Carrier 36 family …

The Fgf System Has A Key Role In Regulating Vascular Integrity, Masahiro Murakami, Loc T. Nguyen, Zhen W. Zhang, Karen L. Moodie, Pater Carmellet, Radu V. Stan, Michael Simons

Dartmouth Scholarship

The integrity of the endothelial monolayer is essential to blood vessel homeostasis and active regulation of endothelial permeability. The FGF system plays important roles in a wide variety of physiologic and pathologic conditions; however, its role in the adult vasculature has not been defined. To assess the role of the FGF system in the adult endothelial monolayer, we disrupted FGF signaling in bovine aortic endothelial cells and human saphenous vein endothelial cells in vitro and in adult mouse and rat endothelial cells in vivo using soluble FGF traps or a dominant inhibitor of all FGF receptors. The inhibition of FGF …

Spatiotemporally Distributed Frontotemporal Networks For Sentence Reading, Sidney R. Lehky, Xinmiao Peng, Carrie J. Mcadams, Anne B. Sereno

Faculty, Staff and Student Publications

BACKGROUND: A key aspect of representations for object recognition and scene analysis in the ventral visual stream is the spatial frame of reference, be it a viewer-centered, object-centered, or scene-based coordinate system. Coordinate transforms from retinocentric space to other reference frames involve combining neural visual responses with extraretinal postural information.

METHODOLOGY/PRINCIPAL FINDINGS: We examined whether such spatial information is available to anterior inferotemporal (AIT) neurons in the macaque monkey by measuring the effect of eye position on responses to a set of simple 2D shapes. We report, for the first time, a significant eye position effect in over 40% of …

Toll-Like Receptor And Il-12 Signaling Control Susceptibility To Contact Hypersensitivity., Stefan F. Martin, Jan C. Dudda, Eva Bachtanian, Annalisa Lembo, Stefanie Liller, Christoph Dürr, Markus M. Heimesaat, Stefan Bereswill, György Fejer, Ralitsa Vassileva, Thilo Jakob, N Freudenberg, Christian C. Termeer, Caroline Johner, Chris Galanos, Ma Freudenberg

School of Biomedical Sciences

Allergic contact hypersensitivity (CHS) is a T cell-mediated inflammatory skin disease. Interleukin (IL)-12 is considered to be important in the generation of the allergen-specific T cell response. Loss of IL-12 function in IL-12Rbeta2-deficient mice, however, did not ameliorate the allergic immune response, suggesting alternate IL-12-independent pathways in the induction of CHS. Because exposure to contact allergens always takes place in the presence of microbial skin flora, we investigated the potential role of Toll-like receptors (TLRs) in the induction of CHS. Using mice deficient in TLR4, the receptor for bacterial lipopolysaccharide (LPS), IL-12 receptor (R) beta2, or both, we show that …

Brain Fiber Tract Plasticity In Experimental Spinal Cord Injury: Diffusion Tensor Imaging, Jaivijay Ramu, Juan Herrera, Raymond Grill, Tobias Bockhorst, Ponnada Narayana

Faculty, Staff and Student Publications

Diffusion tensor imaging (DTI) and immunohistochemistry were performed in spinal cord injured rats to understand the basis for activation of multiple regions in the brain observed in functional magnetic resonance imaging (fMRI) studies. The measured fractional anisotropy (FA), a scalar measure of diffusion anisotropy, along the region encompassing corticospinal tracts (CST) indicates significant differences between control and injured groups in the 3 to 4 mm area posterior to bregma that correspond to internal capsule and cerebral peduncle. Additionally, DTI-based tractography in injured animals showed increased number of fibers that extend towards the cortex terminating in the regions that were activated …

Obesity And Cardiac Metabolism In Women, Heinrich Taegtmeyer, Mohamed F Algahim

Faculty, Staff and Student Publications

No abstract provided.

Beta3 Integrin Haplotype Influences Gene Regulation And Plasma Von Willebrand Factor Activity, Katie E. Payne, Paul F. Bray, Peter J. Grant, Angela M. Carter

Department of Medicine Faculty Papers

The Leu33Pro polymorphism of the gene encoding beta(3) integrin (ITGB3) is associated with acute coronary syndromes and influences platelet aggregation. Three common promoter polymorphisms have also been identified. The aims of this study were to (1) investigate the influence of the ITGB3 -400C/A, -425A/C and -468G/A promoter polymorphisms on reporter gene expression and nuclear protein binding and (2) determine genotype and haplotype associations with platelet alpha(IIb)beta(3) receptor density. Promoter haplotypes were introduced into an ITGB3 promoter-pGL3 construct by site directed mutagenesis and luciferase reporter gene expression analysed in HEL and HMEC-1 cells. Binding of nuclear proteins was assessed by electrophoretic …

Aluminum Bioavailability From Basic Sodium Aluminum Phosphate, An Approved Food Additive Emulsifying Agent, Incorporated In Cheese, Robert A. Yokel, Clair L. Hicks, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

Oral aluminum (Al) bioavailability from drinking water has been previously estimated, but there is little information on Al bioavailability from foods. It was suggested that oral Al bioavailability from drinking water is much greater than from foods. The objective was to further test this hypothesis. Oral Al bioavailability was determined in the rat from basic [26Al]-sodium aluminum phosphate (basic SALP) in a process cheese. Consumption of approximately 1g cheese containing 1.5% or 3% basic SALP resulted in oral Al bioavailability (F) of approximately 0.1% and 0.3%, respectively, and time to maximum serum 26Al concentration (Tmax) of 8-9h. These Al bioavailability …

Demyelinating And Nondemyelinating Strains Of Mouse Hepatitis Virus Differ In Their Neural Cell Tropism., Jayasri Das Sarma, Kathryn Iacono, Lilli Gard, Ryan Marek, Lawrence C. Kenyon, Michael Koval, Susan R. Weiss

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Some strains of mouse hepatitis virus (MHV) can induce chronic inflammatory demyelination in mice that mimics certain pathological features of multiple sclerosis. We have examined neural cell tropism of demyelinating and nondemyelinating strains of MHV in order to determine whether central nervous system (CNS) cell tropism plays a role in demyelination. Previous studies demonstrated that recombinant MHV strains, isogenic other than for the spike gene, differ in the extent of neurovirulence and the ability to induce demyelination. Here we demonstrate that these strains also differ in their abilities to infect a particular cell type(s) in the brain. Furthermore, there is …