Research Topics
Species | A N SchechterSummaryAffiliation: National Institutes of Health Country: USA Publications
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Publications
NO solutions?Alan N Schechter
Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA
J Clin Invest 109:1149-51. 2002
Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilatorChristian J Hunter
Critical Care Medicine Department, Clinical Center, National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892-1662, USA
Nat Med 10:1122-7. 2004....- Hemolysis-associated endothelial dysfunction mediated by accelerated NO inactivation by decompartmentalized oxyhemoglobinPeter C Minneci
Critical Care Medicine Department, NIH, Bethesda, Maryland 20892, USA
J Clin Invest 115:3409-17. 2005.... - Translational medicine--doing it backwardsRobert B Nussenblatt
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Transl Med 8:12. 2010..Its mission is science in pursuit of fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to extend healthy life and reduce the burdens of illness and disability 1... - Prematurity in gene therapyAlan N Schechter
Laboratory of Chemical Biology/NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA
Mol Ther 5:217-9. 2002 - Hemoglobin and the paracrine and endocrine functions of nitric oxideAlan N Schechter
National Institute of Diabetes and Digestive and Kidney Diseases, and the Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892-1822, USA
N Engl J Med 348:1483-5. 2003 - Hemoglobin research and the origins of molecular medicineAlan N Schechter
Molecular Medicine Branch, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
Blood 112:3927-38. 2008..It is likely that current research will also have significant clinical implications, as well as lessons for other aspects of molecular medicine, the origin of which can be largely traced to this research tradition... - Why is revitalizing clinical research so important, yet so difficult?Alan N Schechter
Laboratory of Chemical Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892 1822, USA
Perspect Biol Med 47:476-86. 2004..Discussion of alternate conceptual frameworks for biomedical research should help lead to changes in funding and organizational structures that might finally revitalize clinical research... - Inhaled nitric oxide augments nitric oxide transport on sickle cell hemoglobin without affecting oxygen affinityM T Gladwin
Critical Care Medicine Department, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892, USA
J Clin Invest 104:937-45. 1999..The levels of nitrosylated hemoglobin are too low to affect overall hemoglobin oxygen affinity, but augmented NO transport to the microvasculature seems a promising strategy for improving microvascular perfusion... - Nitric oxide transport on sickle cell hemoglobin: where does it bind?M T Gladwin
Critical Care Medicine Department, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
Free Radic Res 35:175-80. 2001.... - Effects of inhaled nitric oxide on regional blood flow are consistent with intravascular nitric oxide deliveryR O Cannon
Cardiology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, Maryland 20892 1650, USA
J Clin Invest 108:279-87. 2001..This effect may have application for the treatment of diseases characterized by endothelial dysfunction... - Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humansM T Gladwin
Critical Care Medicine Department of the Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 97:11482-7. 2000.... - Increasing hemoglobin oxygen saturation levels in sickle trait donor whole blood prevents hemoglobin S polymerization and allows effective white blood cell reduction by filtrationDavid F Stroncek
Department of Tranfusion Medicine, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Transfusion 44:1293-9. 2004..Techniques were investigated to successfully filter Hb AS donor blood by increasing the Hb oxygen saturation with storage bags and conditions suitable for transfusion products... - Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formationAndre Dejam
Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Circulation 116:1821-31. 2007..However, important questions of potency, kinetics, mechanism of action, and possible induction of tolerance remain unanswered... - Erythropoietin and hypoxia stimulate erythropoietin receptor and nitric oxide production by endothelial cellsBojana B Beleslin-Cokic
Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892 1822, USA
Blood 104:2073-80. 2004..This effect of EPO on eNOS may be a physiologically relevant mechanism to counterbalance the hypertensive effects of increased hemoglobin-related NO destruction resulting from hypoxia-induced increased red cell mass... - Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric controlZhi Huang
Vascular Therapeutics Section, Cardiovascular Branch, National Heart, Lung and Blood Institute, and Laboratory of Chemical Biology, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892-1662, USA
J Clin Invest 115:2099-107. 2005..These data suggest that the oxygen sensor for hypoxic vasodilation is determined by Hb oxygen saturation and quaternary structure and that the nitrite reductase activity of Hb generates NO gas under allosteric and pH control... - Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulationKenyatta Cosby
Cardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 7B15 Bethesda, Maryland 20892, USA
Nat Med 9:1498-505. 2003..These results suggest that nitrite represents a major bioavailable pool of NO, and describe a new physiological function for hemoglobin as a nitrite reductase, potentially contributing to hypoxic vasodilation... - Erythrocytes are the major intravascular storage sites of nitrite in human bloodAndre Dejam
Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, MD 20892, USA
Blood 106:734-9. 2005..These studies suggest a dynamic intravascular NO metabolism in which endothelial NOS-derived NO is stabilized as nitrite, transported by erythrocytes, and consumed during arterial-to-venous transit... - Pathophysiology of a sickle cell trait mouse model: human alpha(beta)(S) transgenes with one mouse beta-globin alleleC T Noguchi
Laboratory of Chemical Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892 1822, USA
Blood Cells Mol Dis 27:971-7. 2001..Analyses of parameters such as P(50), red cell indices, and genetic background are necessary in establishing potential relevance of any mouse model of the sickle cell syndromes... - Linderstrom-Lang-Schellman's model for protein stabilization revisitedHiroshi Taniuchi
Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Curr Protein Pept Sci 5:275-86. 2004.... - Nitric oxide's reactions with hemoglobin: a view through the SNO-stormMark T Gladwin
Critical Care Medicine Department of the Warren G. Magnuson Clinical Center, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
Nat Med 9:496-500. 2003 - The emerging biology of the nitrite anionMark T Gladwin
Vascular Medicine Branch, National Heart, Lung, and Blood Institute, US National Institutes of Health, Bethesda, Maryland, USA
Nat Chem Biol 1:308-14. 2005..A recent two-day symposium at the US National Institutes of Health highlighted recent advances in the understanding of nitrite biochemistry, physiology and therapeutics... - Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailabilityLewis L Hsu
Marian Anderson Sickle Cell Center at St Christopher s Hospital for Children, Drexel University College of Medicine, Philadelphia, PA 19134, USA
Blood 109:3088-98. 2007..Although the time course is shorter than typical pulmonary hypertension in human sickle cell disease, these results demonstrate that hemolytic anemia is sufficient to produce endothelial dysfunction and global dysregulation of NO... - Pulmonary hypertension as a risk factor for death in patients with sickle cell diseaseMark T Gladwin
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892 1662, USA
N Engl J Med 350:886-95. 2004..The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism of its development, and its prospective prognostic significance are unknown... - Measurement of nitrite in blood samples using the ferricyanide-based hemoglobin oxidation assayBarbora Piknova
Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Methods Mol Biol 704:39-56. 2011..We also explain how to preserve the original physiological nitrite concentration in nitrite-hostile environments, such as an excess of hemoglobin in blood... - Increasing oxygen tension improves filtration of sickle trait donor bloodKaren M Byrne
Department of Transfusion Medicine, National Institute of Diabetes and Digestive and Kidney Diseases NIH, Warren G Magnuson Clinical Center, Building 10, Room 1C711, 10 Center Drive MSC 1184, Bethesda, MD 20892 2284, USA
Br J Haematol 122:678-81. 2003..Bags with added air had increased sO2 levels (from 49 +/- 10% to 76 +/- 6%). Filtration was successful for nine of 10 components with air, and one of 10 without air. Successful filtration of RBC components occurs when sO2 is increased... - Nitric oxide donor properties of hydroxyurea in patients with sickle cell diseaseMark T Gladwin
Critical Care Medicine Department of the Warren G Magnuson Clinical Center, Bethesda, MD 20892 1662, USA
Br J Haematol 116:436-44. 2002..The role of NO in the induction of fetal haemoglobin and possible synergy between NO donor therapy and classic cytostatic and differentiating medications should be explored... - Sickle Hb polymerization in RBC components from donors with sickle cell trait prevents effective WBC reduction by filtrationDavid F Stroncek
Department of Transfusion Medicine, Warren G Magnuson Clinical Center, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 1184, USA
Transfusion 42:1466-72. 2002..RBC components collected from donors with sickle cell trait frequently occlude WBC-reduction filters. In vitro, sickle trait RBCs have the potential for sickle Hb (Hb S) polymerization at low oxygen saturations and high Hb concentrations... - Cell-free hemoglobin limits nitric oxide bioavailability in sickle-cell diseaseChristopher D Reiter
Critical Care Medicine Department of the Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA
Nat Med 8:1383-9. 2002..Decompartmentalization of hemoglobin and subsequent dioxygenation of nitric oxide may explain the vascular complications shared by acute and chronic hemolytic disorders... - S-Nitrosohemoglobin is unstable in the reductive erythrocyte environment and lacks O2/NO-linked allosteric functionMark T Gladwin
Critical Care Medicine Department, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, Maryland 20892 1662, USA
J Biol Chem 277:27818-28. 2002.... - Divergent nitric oxide bioavailability in men and women with sickle cell diseaseMark T Gladwin
Critical Care Medicine Department, Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892 1662, USA
Circulation 107:271-8. 2003..Although reduced endothelial nitric oxide (NO) bioavailability has been demonstrated in arteriosclerotic vascular disease, the integrity of this system in sickle cell disease remains uncertain... - Exogenous reference RNA for normalization of real-time quantitative PCRReginald D Smith
Laboratory of Chemical Biology, NIDDK, NIH, Building 10, Room 9N318, 10 Center Drive, MSC 1822, Bethesda, MD 20892 1822, USA
Biotechniques 34:88-91. 2003..The use of an exogenous reference such as in vitro transcribed mRNA for the RuBisCO plant gene provides a robust and sample-independent method for the normalization of quantitative PCR data in bacterial and animal cells... - Biological action of nitric oxide donor compounds on platelets from patients with sickle cell diseaseT H Mondoro
Laboratory of Cellular Hematology and Laboratory of Plasma Derivatives, Center for Biologics Evaluation and Research, Food and Drugs Administration, National Institutes of Health, Bethesda, MD 20892, USA
Br J Haematol 112:1048-54. 2001..Taken together, these data suggest that the mode of NO delivery to platelets may produce various physiological responses and the optimization of NO delivery may contribute to reducing platelet aggregation in sickle cell disease... - Nitric oxide therapy in sickle cell diseaseM T Gladwin
Critical Care Medicine Department, Warren G. Magnuson Clinical Center, NIH, Bethesda, MD 20892-1662, USA
Semin Hematol 38:333-42. 2001..While direct evidence for a clinical benefit of NO therapy in sickle cell disease has not been reported, studies are underway to determine if inhaled NO will reduce the substantial morbidity and mortality suffered by these patients... 
Oxidation of iron-nitrosyl-hemoglobin by dehydroascorbic acid releases nitric oxide to form nitrite in human erythrocytesNathawut Sibmooh
Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Biochemistry 47:2989-96. 2008..These data provide a physiologically robust mechanism for erythrocytic transport of NO bioactivity allowing for hormone-like properties...- Hydroxyurea induces fetal hemoglobin by the nitric oxide-dependent activation of soluble guanylyl cyclaseVladan P Cokic
Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA
J Clin Invest 111:231-9. 2003..These data provide strong evidence for an NO-derived mechanism for HbF induction by hydroxyurea and suggest possibilities for therapies based on NO-releasing or -potentiating agents... - Emerging role of nitrite in human biologyAndre Dejam
Laboratory of Chemical Biology, National Institute of Diabetes, Digestive and Kidney Disease, National Institute of Health, Bethesda, MD 20892, USA
Blood Cells Mol Dis 32:423-9. 2004..This review focuses on the role of nitrite as a circulating NO donor, its potential as an index of NO synthase (NOS) activity and endothelial function, and discusses potential diagnostic and therapeutic applications... - Biomarker and drug-target discovery using proteomics in a new rat model of sepsis-induced acute renal failureM K Holly
Renal Diagnostics and Therapeutics Unit, NIDDK, Bethesda, Maryland, USA
Kidney Int 70:496-506. 2006..This model allowed us to use DIGE to find changes in urinary proteins and this approach identified a potential biomarker and drug target - meprin-1-alpha... - Relative role of heme nitrosylation and beta-cysteine 93 nitrosation in the transport and metabolism of nitric oxide by hemoglobin in the human circulationM T Gladwin
Critical Care Medicine Department of the Warren G Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 97:9943-8. 2000.... - Activation of the human epsilon- and beta-globin promoters by SV40 T antigenS X Cao
Laboratory of Chemical Biology, National Institute of Diabetes, and Digestive and Kidney Diseases, Bethesda, MD 20892
Biochem J 258:769-76. 1989.... - A study of the influence of the hydrophobic core residues of yeast iso-2-cytochrome c on phosphate binding: a probe of the hydrophobic core-surface charge interactionsH Taniuchi
Laboratory of Chemical Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
J Protein Chem 20:203-15. 2001..Such an explanation would be in accord with the observed difference in thermal stability between iso-2 and horse cytochromes c... - The reaction of cell-free oxyhemoglobin with nitrite under physiologically relevant conditions: Implications for nitrite-based therapiesBarbora Piknova
National Institutes of Health, NIH, NIDDK, Molecular Medicine Branch, Bethesda, MD 20892, USA
Nitric Oxide 20:88-94. 2009..Our findings suggest that pharmacological doses of nitrite are unlikely to cause free radical or ferrylhemoglobin formation in plasma originating from the reaction of nitrite with cell-free oxyhemoglobin in vivo... - Fetal hemoglobin silencing in humansPatricia A Oneal
Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bldg 10, Rm 9B17, Bethesda, MD 20892, USA
Blood 108:2081-6. 2006..The silencing phenomenon is mediated by a mechanism of cellular replacement. This novel silencing pattern may be important for the development of HbF-enhancing therapies... - Cloning of the human erythropoietin receptor geneC T Noguchi
Laboratory of Chemical Biology, NIDDK, National Institutes of Health, Bethesda, MD 20892
Blood 78:2548-56. 1991.... - The measurement of blood and plasma nitrite by chemiluminescence: pitfalls and solutionsMildred M Pelletier
Molecular Medicine Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892, USA
Free Radic Biol Med 41:541-8. 2006.... - Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilationJack H Crawford
Department of Pathology, Center for Free Radical Biology, University of Alabama at Birmingham, 35294, USA
Blood 107:566-74. 2006..These data support a function for RBC hemoglobin as an allosterically and redox-regulated nitrite reductase whose "enzyme activity" couples hypoxia to increased NO-dependent blood flow... - The reaction between nitrite and oxyhemoglobin: a mechanistic studyAgnes Keszler
Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
J Biol Chem 283:9615-22. 2008..The consequences of uncoupling the roles of H(2)O(2) and NO(2) in the reaction mechanism for the in vivo reactivity of nitrite are discussed... - Red blood cell magnetophoresisMaciej Zborowski
Department of Biomedical Engineering ND20, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44915, USA
Biophys J 84:2638-45. 2003..Magnetophoresis may open up an approach to characterize and separate cells for biochemical analysis based on intrinsic and extrinsic magnetic properties of biological macromolecules... - Effects of nitric oxide on red blood cell development and phenotypeVladan P Cokic
Laboratory of Experimental Hematology, Institute for Medical Research, Belgrade, Serbia
Curr Top Dev Biol 82:169-215. 2008.... - Effects of iron nitrosylation on sickle cell hemoglobin solubilityXiuli Xu
Department of Physics, Wake Forest University, Winston-Salem, North Carolina 27109, USA
J Biol Chem 277:36787-92. 2002..Given the small amounts of NO-ligated hemoglobin achievable through any kind of NO therapy, we conclude that NO therapy does not benefit patients through any direct solubilizing effect... - Nitric oxide from nitrite reduction by hemoglobin in the plasma and erythrocytesKejing Chen
Department of Biomedical Engineering, Johns Hopkins University School of Medicine, 613 Traylor Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
Nitric Oxide 18:47-60. 2008..mM in erythrocyte); (3) intraerythrocytic hemoglobin encapsulated by a NO-resistant membrane is the major source of NO from nitrite reduction, and cell-free hemoglobin is a significant scavenger of both paracrine and endocrine NO... - Identification and characterization of mechanistically distinct inducers of gamma-globin transcriptionJohn D Haley
OSI Pharmaceuticals Inc, Farmingdale, NY 11735, USA
Biochem Pharmacol 66:1755-68. 2003..This screening methodology successfully identifies active compounds for further mechanistic and preclinical evaluation as potential therapeutic agents for sickle cell anemia... - Hydroxyurea increases eNOS protein levels through inhibition of proteasome activityVladan P Cokic
Laboratory of Experimental Hematology, Institute for Medical Research, Dr Subotica 4, P O Box 102, 11129 Belgrade, Serbia
Nitric Oxide 16:371-8. 2007..The NO production induced by hydroxyurea in endothelial cells appears to be mediated by long term posttranscriptional augmentation in eNOS levels via inhibition of the proteasome activity... - NO contest: nitrite versus S-nitroso-hemoglobinMark T Gladwin
Circ Res 94:851-5. 2004 - How do red blood cells dilate blood vessels?--ReplyDaniel B Kim-Shapiro
Circ Res 95:e10. 2004 - Hydroxyurea induces the eNOS-cGMP pathway in endothelial cellsVladan P Cokic
Institute of Medical Research, and the Institute of Endocrinology, Diabetes and Digestive and Diseases of Metabolism, Belgrade, Serbia and Montenegro
Blood 108:184-91. 2006..These studies established an additional mechanism by which rapid and sustained effects of hydroxyurea may affect cellular NO levels and perhaps enhance the effect of NO in myeloproliferative diseases... - Unraveling the reactions of nitric oxide, nitrite, and hemoglobin in physiology and therapeuticsDaniel B Kim-Shapiro
Department of Physics, Wake Forest University, Winston Salem, NC 27109, USA
Arterioscler Thromb Vasc Biol 26:697-705. 2006..As subsequently understood, the hypoxic generation of NO from nitrite is likely to prove important in many aspects of physiology, pathophysiology, and therapeutics... - Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humansPetra Kleinbongard
Division of Cardiology, Pulmonary Diseases and Angiology, Department of Medicine, Heinrich Heine University, , Germany
Free Radic Biol Med 40:295-302. 2006..Future studies are necessary to identify the prognostic relevance of plasma nitrite determination in patients suffering from cardiovascular disease... - Electron paramagnetic resonance analysis of nitrosylhemoglobin in humans during NO inhalationBarbora Piknova
Department of Biophysics and Free Radical Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA
J Biol Chem 280:40583-8. 2005..v) The half-time of HbNO in vivo is approximately 40 min... - Hydroxyurea nitrosylates and activates soluble guanylyl cyclase in human erythroid cellsVladan P Cokic
Laboratory of Experimental Hematology, Institute for Medical Research, Belgrade, Serbia
Blood 111:1117-23. 2008..These data add to an expanding appreciation of the role of hydroxyurea as an inducer of the NO/cGMP pathway in EPCs. These mechanisms may also be involved in the cytostatic effects of hydroxyurea, as well as the induction of HbF... - To publish or not to publish?Alan N Schechter
J Lab Clin Med 145:9-11. 2005