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Increased circulating fibrocytes are associated with higher reticulocyte percent in children with sickle cell anemia.
Karafin MS, Dogra S, Rodeghier M, Burdick M, Mehrad B, Rose CE, Strieter RM, DeBaun MR, Strunk RC, Field JJ
(2016) Pediatr Pulmonol 51: 295-9
MeSH Terms: Adolescent, Anemia, Sickle Cell, Asthma, Child, Child, Preschool, Cohort Studies, Cross-Sectional Studies, Female, Forced Expiratory Volume, Humans, Lung Diseases, Interstitial, Male, Pulmonary Fibrosis, Reticulocytes, Young Adult
Show Abstract · Added July 14, 2015
BACKGROUND - Interstitial lung disease is common in patients with sickle cell anemia (SCA). Fibrocytes are circulating cells implicated in the pathogenesis of pulmonary fibrosis and airway remodeling in asthma. In this study, we tested the hypotheses that fibrocyte levels are: (1) increased in children with SCA compared to healthy controls, and (2) associated with pulmonary disease.
PROCEDURE - Cross-sectional cohort study of children with SCA who participated in the Sleep Asthma Cohort Study.
RESULTS - Fibrocyte levels were obtained from 45 children with SCA and 24 controls. Mean age of SCA cases was 14 years and 53% were female. In children with SCA, levels of circulating fibrocytes were greater than controls (P < 0.01). The fibrocytes expressed a hierarchy of chemokine receptors, with CXCR4 expressed on the majority of cells and CCR2 and CCR7 expressed on a smaller subset. Almost half of fibrocytes demonstrated α-smooth muscle actin activation. Increased fibrocyte levels were associated with a higher reticulocyte count (P = 0.03) and older age (P = 0.048) in children with SCA. However, children with increased levels of fibrocytes were not more likely to have asthma or lower percent predicted forced expiratory volume in 1 sec/forced vital capacity (FEV1 /FVC) or FEV1 than those with lower fibrocyte levels.
CONCLUSIONS - Higher levels of fibrocytes in children with SCA compared to controls may be due to hemolysis. Longitudinal studies may be able to better assess the relationship between fibrocyte level and pulmonary dysfunction.
© 2015 Wiley Periodicals, Inc.
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15 MeSH Terms
Neonatal CD71+ Erythroid Cells Do Not Modify Murine Sepsis Mortality.
Wynn JL, Scumpia PO, Stocks BT, Romano-Keeler J, Alrifai MW, Liu JH, Kim AS, Alford CE, Matta P, Weitkamp JH, Moore DJ
(2015) J Immunol 195: 1064-70
MeSH Terms: Adoptive Transfer, Animals, Antibodies, Antigens, CD, Bone Marrow Cells, CD11b Antigen, Endotoxins, Erythroid Cells, Female, Fetal Blood, Humans, Male, Mice, Mice, Inbred C57BL, Receptors, Transferrin, Reticulocytes, Sepsis, Spleen
Show Abstract · Added June 24, 2015
Sepsis is a major cause of neonatal mortality and morbidity worldwide. A recent report suggested that murine neonatal host defense against infection could be compromised by immunosuppressive CD71(+) erythroid splenocytes. We examined the impact of CD71(+) erythroid splenocytes on murine neonatal mortality to endotoxin challenge or polymicrobial sepsis and characterized circulating CD71(+) erythroid (CD235a(+)) cells in human neonates. Adoptive transfer or an Ab-mediated reduction in neonatal CD71(+) erythroid splenocytes did not alter murine neonatal survival to endotoxin challenge or polymicrobial sepsis challenge. Ex vivo immunosuppression of stimulated adult CD11b(+) cells was not limited to neonatal splenocytes; it also occurred with adult and neonatal bone marrow. Animals treated with anti-CD71 Ab showed reduced splenic bacterial load following bacterial challenge compared with isotype-treated mice. However, adoptive transfer of enriched CD71(+) erythroid splenocytes to CD71(+)-reduced animals did not reduce bacterial clearance. Human CD71(+)CD235a(+) cells were common among cord blood mononuclear cells and were shown to be reticulocytes. In summary, a lack of effect on murine survival to polymicrobial sepsis following adoptive transfer or diminution of CD71(+) erythroid splenocytes under these experimental conditions suggests that the impact of these cells on neonatal infection risk and progression may be limited. An unanticipated immune priming effect of anti-CD71 Ab treatment, rather than a reduction in immunosuppressive CD71(+) erythroid splenocytes, was likely responsible for the reported enhanced bacterial clearance. In humans, the well-described rapid decrease in circulating reticulocytes after birth suggests that they may have a limited role in reducing inflammation secondary to microbial colonization.
Copyright © 2015 by The American Association of Immunologists, Inc.
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18 MeSH Terms
Type I transforming growth factor beta receptor binds to and activates phosphatidylinositol 3-kinase.
Yi JY, Shin I, Arteaga CL
(2005) J Biol Chem 280: 10870-6
MeSH Terms: Activin Receptors, Type I, Animals, COS Cells, Cell Line, Culture Media, Serum-Free, DNA-Binding Proteins, Enzyme Activation, Enzyme Inhibitors, Genes, Dominant, Genetic Vectors, Humans, Immunoblotting, Ligands, Mice, Mutation, Phosphatidylinositol 3-Kinases, Phosphorylation, Plasmids, Protein Binding, Protein Structure, Tertiary, Protein-Serine-Threonine Kinases, Rabbits, Receptor, Transforming Growth Factor-beta Type I, Receptors, Transforming Growth Factor beta, Reticulocytes, Smad7 Protein, Trans-Activators, Transcriptional Activation, Transfection
Show Abstract · Added March 5, 2014
We have examined the interaction of transforming growth factor (TGF)beta receptors with phosphatidylinositol 3-(PI3) kinase in epithelial cells. In COS7 cells, treatment with TGFbeta increased PI3 kinase activity as measured by the ability of p85-associated immune complexes to phosphorylate inositides in vitro. Both type I and type II TGFbeta receptors (TbetaR) associated with p85, but the association of TbetaRII appeared to be constitutive. The interaction of TbetaRI with p85 was induced by treatment with TGFbeta. The receptor association with PI3 kinase was not direct as (35)S-labeled rabbit reticulocyte p85 did not couple with fusion proteins containing type I and type II receptors. A kinase-dead, dominant-negative mutant of TbetaRII blocked ligand-induced p85-TbetaRI association and PI3 kinase activity. In TbetaRI-null R1B cells, TGFbeta did not stimulate PI3 kinase activity. This stimulation was restored upon reconstitution of TbetaRI by transfection. In R1B and NMuMG epithelial cells, overexpression of a dominant active mutant form of TbetaRI markedly enhanced ligand-independent PI3 kinase activity, which was blocked by the addition of the TbetaRI kinase inhibitor LY580276, suggesting a causal link between TbetaRI function and PI3 kinase. Overexpressed Smad7 also prevented ligand-induced PI3 kinase activity. Taken together, these data suggest that 1) TGFbeta receptors can indirectly associate with p85, 2) both receptors are required for ligand-induced PI3 kinase activation, and 3) the activated TbetaRI serine-threonine kinase can potently induce PI3 kinase activity.
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29 MeSH Terms
Neocytolysis on descent from altitude: a newly recognized mechanism for the control of red cell mass.
Rice L, Ruiz W, Driscoll T, Whitley CE, Tapia R, Hachey DL, Gonzales GF, Alfrey CP
(2001) Ann Intern Med 134: 652-6
MeSH Terms: Adaptation, Physiological, Adult, Altitude, Cell Count, Erythrocytes, Erythropoietin, Ferritins, Hematocrit, Hemoglobins, Hemolysis, Humans, Male, Middle Aged, Polycythemia, Prospective Studies, Reticulocytes
Show Abstract · Added March 20, 2014
BACKGROUND - Studies of space-flight anemia have uncovered a physiologic process, neocytolysis, by which young red blood cells are selectively hemolyzed, allowing rapid adaptation when red cell mass is excessive for a new environment.
OBJECTIVES - 1) To confirm that neocytolysis occurs in another situation of acute plethora-when high-altitude dwellers with polycythemia descend to sea level; and 2) to clarify the role of erythropoietin suppression.
DESIGN - Prospective observational and interventional study.
SETTING - Cerro de Pasco (4380 m) and Lima (sea level), Peru.
PARTICIPANTS - Nine volunteers with polycythemia.
INTERVENTIONS - Volunteers were transported to sea level; three received low-dose erythropoietin.
MEASUREMENTS - Changes in red cell mass, hematocrit, hemoglobin concentration, reticulocyte count, ferritin level, serum erythropoietin, and enrichment of administered(13)C in heme.
RESULTS - In six participants, red cell mass decreased by 7% to 10% within a few days of descent; this decrease was mirrored by a rapid increase in serum ferritin level. Reticulocyte production did not decrease, a finding that establishes a hemolytic mechanism.(13)C changes in circulating heme were consistent with hemolysis of young cells. Erythropoietin was suppressed, and administration of exogenous erythropoietin prevented the changes in red cell mass, serum ferritin level, and(13)C-heme.
CONCLUSIONS - Neocytolysis and the role of erythropoietin are confirmed in persons with polycythemia who descend from high altitude. This may have implications that extend beyond space and altitude medicine to renal disease and other situations of erythropoietin suppression, hemolysis, and polycythemia.
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16 MeSH Terms
Arrestin: mutagenesis, expression, purification, and functional characterization.
Gurevich VV, Benovic JL
(2000) Methods Enzymol 315: 422-37
MeSH Terms: Amino Acid Substitution, Animals, Arrestin, Blotting, Western, Cell-Free System, Chromatography, Affinity, Chromatography, Ion Exchange, Cloning, Molecular, Cyclic AMP-Dependent Protein Kinases, Electrophoresis, Polyacrylamide Gel, Escherichia coli, Mutagenesis, Site-Directed, Phosphorylation, Protein Biosynthesis, RNA, Messenger, Rabbits, Recombinant Proteins, Reticulocytes, Rhodopsin, Transcription, Genetic, beta-Adrenergic Receptor Kinases
Added December 10, 2013
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21 MeSH Terms
The bovine CYP17 promoter contains a transcriptional regulatory element cooperatively bound by tale homeodomain proteins.
Bischof LJ, Kagawa N, Waterman MR
(1998) Endocr Res 24: 489-95
MeSH Terms: Animals, Binding Sites, Cattle, Cyclic AMP Response Element-Binding Protein, DNA-Binding Proteins, Homeodomain Proteins, Mice, Myeloid Ecotropic Viral Integration Site 1 Protein, Neoplasm Proteins, Pre-B-Cell Leukemia Transcription Factor 1, Promoter Regions, Genetic, Proto-Oncogene Proteins, Recombinant Proteins, Reticulocytes, Steroid 17-alpha-Hydroxylase, Steroidogenic Factor 1, Transcription Factors, Tumor Cells, Cultured
Show Abstract · Added February 12, 2015
Bovine CYP17 is regulated at the transcriptional level by ACTH acting through the second messenger cAMP in adrenal fasciculata and reticularis cells. Promoter analysis has previously identified two regions, proximal and distal, within the CYP17 promoter important in the cAMP dependent transcriptional regulation of this gene. The proximal (-80 to -40) cAMP responsive sequence (CRS2) has been identified as a binding site for Steroidogenic Factor-1 (SF-1)/Ad4BP. The distal region (-243 to -100) is also important for the cAMP transcriptional response as revealed by deletion analysis. Within this distal region from -243 to -225, an independent cAMP responsive sequence referred to as CRS1 has been described. The transcription factors binding CRS1 have been identified as homeodomain transcription factors belonging to an atypical class of homeodomain proteins referred to as TALE. Two families of homeodomain proteins which bind CRS1 are the Pbx and Meis1 families. Proteins from neither of these families can bind CRS1 individually; however, members of the Pbx family interact with members of the Meis1 family to cooperatively bind this element. CRS1 was the first identified cis-acting target element for members of both the Pbx and Meis1 family. Unlike SF-1, these proteins are not expressed in a steroidogenic tissue-specific manner but rather, appear ubiquitous. A current model for the function of these proteins in CYP17 regulation is that they may enhance the cAMP response through the downstream SF-1 binding site.
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18 MeSH Terms
Induction of synthesis of cholesterol side chain cleavage cytochrome P-450 by adrenocorticotropin in cultured bovine adrenocortical cells.
DuBois RN, Simpson ER, Kramer RE, Waterman MR
(1981) J Biol Chem 256: 7000-5
MeSH Terms: Adrenal Cortex, Adrenocorticotropic Hormone, Animals, Cattle, Cell-Free System, Cells, Cultured, Cholesterol Side-Chain Cleavage Enzyme, Cytochrome P-450 Enzyme System, Enzyme Induction, Kinetics, Methionine, Oxidoreductases, Pregnenolone, Protein Biosynthesis, Rabbits, Reticulocytes
Added February 12, 2015
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16 MeSH Terms
[Separation of [3H]dihydroalprenolol, free or bound to solubilized beta-adrenergic receptors, on a cation-exchange resin].
Voeĭkov VL, Gurevich VV
(1983) Bioorg Khim 9: 628-32
MeSH Terms: Alprenolol, Animals, Cattle, Cerebellum, Chromatography, Ion Exchange, Dihydroalprenolol, In Vitro Techniques, Kinetics, Radioligand Assay, Rats, Receptors, Adrenergic, beta, Reticulocytes
Show Abstract · Added December 10, 2013
A new rapid, facile and reliable method based on microcolumn cation-exchange chromatography has been developed for separating free antagonist [3H]dihydroalprenolol from that bound to solubilized beta-adrenergic receptors.
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12 MeSH Terms
Enzymatic lipid peroxidation: a step in the breakdown of mitochondria during the maturation of red blood cells.
Kühn H, Schewe T, Rapoport SM, Brash AR
(1988) Basic Life Sci 49: 945-9
MeSH Terms: Animals, Erythrocyte Aging, Intracellular Membranes, Lipid Peroxidation, Lipoxygenase, Mitochondria, Mitochondria, Liver, Phosphatidylcholines, Rats, Reticulocytes
Added December 10, 2013
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10 MeSH Terms
Rabbit reticulocyte lipoxygenase catalyzes specific 12(S) and 15(S) oxygenation of arachidonoyl-phosphatidylcholine.
Murray JJ, Brash AR
(1988) Arch Biochem Biophys 265: 514-23
MeSH Terms: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid, Animals, Arachidonic Acids, Chromatography, High Pressure Liquid, Erythrocyte Membrane, Gas Chromatography-Mass Spectrometry, Humans, Hydroxyeicosatetraenoic Acids, Lipoxygenase, Oxidation-Reduction, Phosphatidylcholines, Rabbits, Reticulocytes, Spectrophotometry, Ultraviolet
Show Abstract · Added December 10, 2013
The rabbit reticulocyte lipoxygenase is known to display an unusual facility for oxygenation of esterified polyunsaturated fatty acids, yet the precise structures of the products are not known. With free arachidonate as substrate the enzyme is known to catalyze 15S and 12S oxygenations, and demonstration of a facility for catalysis of these reactions on phospholipids would extend the potential scope of lipoxygenase reactions in cells. We elected to study in detail the reaction of the enzyme with a natural phospholipid, palmitoyl/arachidonoyl-phosphatidylcholine. We determined the nature of the products by initial isolation by RP-HPLC, followed by transesterification and identification of the oxygenated products by HPLC, uv, GC-MS, and steric analysis of hydroxyl configuration by HPLC. The major product was identified as a phosphatidylcholine in which the arachidonate component was converted to the 15(S)-hydroperoxy-eicosatetraenoate. A second oxygenated phospholipid was produced in smaller quantities (2-5% of the latter product) and identified as the 12(S)-oxygenated analog. These products were also identified after reaction of the reticulocyte lipoxygenase with human red cell membranes which were radiolabeled by preincubation with [3H]arachidonic acid. The finding of 12S oxygenation represents the first evidence that a lipoxygenase can control a reaction centered on the 10-carbon of an arachidonoyl phospholipid. This is an important precedent, because hydrogen abstraction from carbon-10 is a critical step in the lipoxygenase-catalyzed synthesis of 8- and 12-hydroperoxy-eicosatetraenoates (HPETEs) and for the conversion of 5- and 15-HPETEs to leukotrienes.
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14 MeSH Terms