Research Topics
Species | Paul W BuehlerSummaryAffiliation: Food and Drug Administration Country: USA Publications
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Detail Information
Publications
O-raffinose crosslinked hemoglobin lacks site-specific chemistry in the central cavity: structural and functional consequences of beta93Cys modificationRobert A Boykins
Laboratory of Biophysics, Division of Bacterial, Parasitic and Allergenic Products, Bethesda, Maryland 20892, USA
Proteins 59:840-55. 2005..Structural data presented here when taken together with the oxidative instability of O-R-PolyHbA0 may provide some basis for the reported toxicity of this oxygen carrier...
Effects of endogenous ascorbate on oxidation, oxygenation, and toxicokinetics of cell-free modified hemoglobin after exchange transfusion in rat and guinea pigPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
J Pharmacol Exp Ther 323:49-60. 2007..The present findings suggest the importance of plasma AA in maintaining the stability of acellular Hb susceptible to oxidation, and they may be relevant to humans, which display a similar plasma/tissue antioxidant status to guinea pig...
Toxicological consequences of extracellular hemoglobin: biochemical and physiological perspectivesPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
Antioxid Redox Signal 12:275-91. 2010....
Down selection of polymerized bovine hemoglobins for use as oxygen releasing therapeutics in a guinea pig modelJin Hyen Baek
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research CBER, Food and Drug Administration FDA, Bethesda, Maryland 20892, USA
Toxicol Sci 127:567-81. 2012..Moreover, the approach to down selection described could be applied to enhance the early predictability of human safety for this class of biological therapeutics to optimize for specific indications...
Hemoglobin-driven pathophysiology is an in vivo consequence of the red blood cell storage lesion that can be attenuated in guinea pigs by haptoglobin therapyJin Hyen Baek
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland 20892, USA
J Clin Invest 122:1444-58. 2012..Hb sequestration by Hp might therefore be a therapeutic modality for enhancing transfusion safety in severely ill or massively transfused patients...
Induction of hypoxia inducible factor (HIF-1α) in rat kidneys by iron chelation with the hydroxypyridinone, CP94Jin Hyen Baek
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Biochim Biophys Acta 1809:262-8. 2011..In conclusion, we have identified the inhibition of iron-binding pocket of PHD as an underlying mechanism of HIF induction in vivo and in vitro by a bidentate hydroxypyridinone...
Differential induction of renal heme oxygenase and ferritin in ascorbate and nonascorbate producing species transfused with modified cell-free hemoglobinOmer I Butt
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
Antioxid Redox Signal 12:199-208. 2010..These findings suggest significant differences in the renal handling of HbG which may be important for understanding how endogenous antioxidant defenses may modulate the renal response to extracellular Hb...
Structural and functional characterization of glutaraldehyde-polymerized bovine hemoglobin and its isolated fractionsPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research (CBER, Food and Drug Administration (FDA, Bethesda, Maryland 20892, USA
Anal Chem 77:3466-78. 2005..Structural modification imparted by glutaraldehyde resulted in nearly identical functional characteristics of PolyHbBv and its fractions with regard to oxygen equilibrium, ligand binding, and autoxidative kinetics...
First-generation blood substitutes: what have we learned? Biochemical and physiological perspectivesAbdu I Alayash
Center for Biologics Evaluation and Research, Food and Drug Administration, Laboratory of Biochemistry and Vascular Biology, Division of Hematology, National Institutes of Health Campus, Bethesda, MD 20892, USA
Expert Opin Biol Ther 7:665-75. 2007..Here the authors provide an overview of their research experiences, novel insights into the molecular basis of toxicities of these products and some lessons learned...
Structural basis of peroxide-mediated changes in human hemoglobin: a novel oxidative pathwayYiping Jia
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
J Biol Chem 282:4894-907. 2007....
Free hemoglobin induction of pulmonary vascular disease: evidence for an inflammatory mechanismPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Office of Blood Research and Review, Center for Biologics Evaluation and Research, U S Food and Drug Administration, Bethesda, MD, USA
Am J Physiol Lung Cell Mol Physiol 303:L312-26. 2012..Tempol demonstrated a modest effect on the attenuation of Hb-induced pulmonary vascular disease. NO bioavailability was found to be of minimal importance in this model...
Hemoglobin-based oxygen carriers: From mechanisms of toxicity and clearance to rational drug designPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research CBER, Food and Drug Administration FDA, Bethesda, MD 20892, USA
Trends Mol Med 16:447-57. 2010..Together with novel animal models and biomarkers tailored to monitor the effects of extracellular Hb, a new generation of HBOCs can be envisioned...
Blood-brain barrier disruption and oxidative stress in guinea pig after systemic exposure to modified cell-free hemoglobinOmer I Butt
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA
Am J Pathol 178:1316-28. 2011....
Synthesis, biophysical properties and pharmacokinetics of ultrahigh molecular weight tense and relaxed state polymerized bovine hemoglobinsPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Biomaterials 31:3723-35. 2010..Our findings also demonstrate that T-state PolybHb exhibited a longer circulating half-life, slower clearance and longer systemic exposure time compared to R-state PolybHb...
Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobinPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Biochem Biophys Res Commun 409:412-7. 2011..These CNS changes were not observed in animals treated with Hb or NaNO(2) alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity...
Acellular haemoglobin attenuates hypoxia-inducible factor-1alpha (HIF-1alpha) and its target genes in haemodiluted ratsDominador J Manalo
LBVB Laboratory of Biochemistry and Vascular Biology, Division of Hematology, CBER Center for Biologics Evaluation and Research, FDA Food and Drug Administration, NIH National Institutes of Health, Bethesda, MD 20892, USA
Biochem J 414:461-9. 2008....
Inactivation of prolyl hydroxylase domain (PHD) protein by epigallocatechin (EGCG) stabilizes hypoxia-inducible factor (HIF-1α) and induces hepcidin (Hamp) in rat kidneyDominador J Manalo
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Biochem Biophys Res Commun 416:421-6. 2011..These data demonstrate EGCG's therapeutic potential in modulating hepcidin expression in diseases associated with altered iron metabolism...
Blood aging, safety, and transfusion: capturing the "radical" menacePaul W Buehler
Division of Hematology, Center for Biologics Evaluation and Research, U S Food and Drug Administration, Bethesda, Maryland 20892, USA
Antioxid Redox Signal 14:1713-28. 2011..Furthermore, some of the same naturally occurring protective mechanisms can potentially be employed to oxidatively inactivate this redox active protein and control its damaging side reactions when released outside of the RBC...
All hemoglobin-based oxygen carriers are not created equallyPaul W Buehler
Laboratory of Biochemistry and Vascular Biology LBVB, Division of Hematology, Center for Biologics Evaluation and Research CBER, Food and Drug Administration FDA, Maryland 20892, USA
Biochim Biophys Acta 1784:1378-81. 2008....
Oxygen sensing in the circulation: "cross talk" between red blood cells and the vasculaturePaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration, Bethesda, MD 20892, USA
Antioxid Redox Signal 6:1000-10. 2004..We believe that there are important and yet unexplored mechanisms by which RBCs can directly or indirectly communicate via redox intermediates with extravascular sites as part of the global O(2) sensing mechanism...
Chemical characterization of diaspirin cross-linked hemoglobin polymerized with poly(ethylene glycol)Paul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research (CBER, Food and Drug Administration (FDA, Bethesda, Maryland 20892, USA
Anal Chem 78:4634-41. 2006..e., 64 kDa) has a direct influence on HBOC-mediated vasoactivity and that other protective strategies should be considered to control blood pressure imbalances...
Redox biology of blood revisited: the role of red blood cells in maintaining circulatory reductive capacityPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892, USA
Antioxid Redox Signal 7:1755-60. 2005..In the current short review, we have revisited the topic of redox biology of blood and focused on yet another emerging area of research, which deals with the reductive power of blood and the physiological Redox Signal...
Structural stabilization in tetrameric or polymeric hemoglobin determines its interaction with endogenous antioxidant scavenger pathwaysPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research CBER, U S Food and Drug Administration FDA, Rockville, Maryland, USA
Antioxid Redox Signal 10:1449-62. 2008..Based on these results, a rational and systematic approach to HBOC design may be used to optimize interaction with endogenous Hb clearance and detoxification pathways...
Toxicities of hemoglobin solutions: in search of in-vitro and in-vivo model systemsPaul W Buehler
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Bethesda, Maryland, USA
Transfusion 44:1516-30. 2004....
Synthesis and characterization of a novel DTPA polymerized hemoglobin based oxygen carrierChad R Haney
Department of Bioengineering, The University of Illinois at Chicago, Chicago, IL 60612, USA
Biochim Biophys Acta 1725:358-69. 2005..Cyclic-diethylenetriaminepentaacetic acid (DTPA) was used to polymerize stroma free Hb (SF-Hb)...
Polynitroxyl hemoglobin: a pharmacokinetic study of covalently bound nitroxides to hemoglobin platformsPaul W Buehler
Department of Biopharmaceutical Sciences, University of Illinois at Chicago, Chicago, IL 60612, USA
Free Radic Biol Med 37:124-35. 2004..The therapeutic potential of polynitroxylation of HBOCs as it relates to observations from the current and previously reported studies is discussed...
Ascorbate removes key precursors to oxidative damage by cell-free haemoglobin in vitro and in vivoJacqueline Dunne
Department of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, UK
Biochem J 399:513-24. 2006..g. haemolytic anaemias, subarachnoid haemorrhage, rhabdomyolysis...
Gating the radical hemoglobin to macrophages: the anti-inflammatory role of CD163, a scavenger receptorDominik J Schaer
Medical Clinic B Research Unit, University of Zurich, Switzerland
Antioxid Redox Signal 9:991-9. 2007..Here, an overview and novel insights into the role of CD163 in Hb redox inactivation and clearance are provided...
CD163 is the macrophage scavenger receptor for native and chemically modified hemoglobins in the absence of haptoglobinDominik J Schaer
Medical Clinic B Research Unit, University Hospital, CH 8091 Zurich, Switzerland
Blood 107:373-80. 2006..These results identify CD163 as a scavenger receptor for native Hb and small-molecular-weight Hb-based blood substitutes after Hp depletion...
