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Sample records for hemoglobins abnormal

  1. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415...

  2. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415...

  3. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415...

  4. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415...

  5. 21 CFR 864.7415 - Abnormal hemoglobin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Abnormal hemoglobin assay. 864.7415 Section 864.7415 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7415...

  6. Improved screening test for abnormal hemoglobins from dried blood samples.

    PubMed

    Altland, K; Kaempfer, M; Granda, H

    1979-01-01

    A method is described wherein blood samples taken from adults or newborns and dried on filter paper can be used for hemoglobin analysis within 2 years after sampling. The samples are eluted in 8 M urea in the presence of 5% 2-mercaptoethanol and 2% of the neutral detergent Nonidet P-40. Then the individual alpha, beta, gamma, and epsilon chains are separated by means of electrofocusing in 8 M urea-PAA gels. Up to 96 samples can be applied to a gel using multiple syringes. Several hundred samples can be analyzed daily by one person. This method may be especially useful for preventive programs against sickle cell anemia as well as for human mutation monitoring systems.

  7. Hemoglobin Agenogi--A rare abnormal beta globin chain variant.

    PubMed

    Sharma, Sunita; Sharma, Geetika; Chandra, Jagdish; Colah, Roshan

    2016-01-01

    Haemoglobin (Hb) Agenogi is clinically asymptomatic, rare β-globin chain variant characterized by a substitution of glutamic acid by lysine at position 90 of β-chain. It elutes in the C-window on high-performance liquid chromatography (HPLC). We report a 10-year-old male with easy fatigability, lethargy, pallor, and mild splenomegaly. Hematological parameters revealed microcytic hypochromic anemia and mildly raised red blood cells count, suggestive of thalassemia trait. On HPLC, a predominant peak was observed in the C-window (82.6%) along with raised HbA 2 level (9.3%). Based on these findings, a possibility of HbC disease/β-thalassemia trait doubly heterozygous was considered. Family studies were advised. HPLC findings in father were suggestive of β-thalassemia trait, while both his mother and brother had an abnormal peak in the C-window of 42.7% and 40.8%, respectively, with elevated HbA 2 values of 5% and 4.9%, respectively. Direct DNA sequencing revealed intervening sequences 1-5 (G ; C) in father, confirming β-thalassemia trait. His mother and brother had heterozygous gene mutation at codon 90 of β-globin chain (G ; A) suggestive of Hb Agenogi. The child carried mutations for both β-thalassemia trait as well as Hb Agenogi. PMID:26960650

  8. Prevalence of β-thalassemia trait and abnormal hemoglobins in Sanliurfa Province in southeast Turkey.

    PubMed

    Incebiyik, Adnan; Genc, Ahmet; Hilali, Nese Gul; Camuzcuoglu, Aysun; Camuzcuoglu, Hakan; Kilic, Avni; Vural, Mehmet

    2014-01-01

    Thalassemia is one of the most common hereditary disorders in Turkey, especially in the Mediterranean region of the country. The purpose of this study was to determine the frequency of the β-thalassemia (β-thal) trait and abnormal hemoglobins (Hbs) in couples who applied for premarital screening in Sanliurfa Province, in the southeastern region of Turkey, a province with the first reported incidence of β-thal and abnormal Hbs. In the present study, in order to detect the prevalence of the β-thal trait and abnormal Hbs in Sanliurfa Province, Turkey, a total of 37,962 couples who applied for premarital screening were analyzed. From January 2011 through March 2014, red blood cell (RBC) counts and Hb fractionation were carried out by a cell counter and high performance liquid chromatography (HPLC), respectively. The prevalence of β-thal with high Hb A2 (>3.5%) values was found at rates of 2.44% (n = 1853) in Sanliurfa Province. Additionally, the abnormal Hb rate was 1.57% (1193/75,924), and Hb S (HBB: c.20T > A), Hb C (HBB: c.19G > A) and Hb D-Punjab (HBB: c.364G > C) were reported as 0.50, 0.38 and 0.69, respectively. This study is the first to establish the frequency of β-thal and abnormal Hbs in Sanliurfa Province, which has the highest birth frequency. We report that the frequency of the β-thal trait is at a high-risk level compared to other cities in Turkey. Due to the high risk of β-thal in Sanliurfa Province, a premarital screening program would be of great value in informing parents about offspring with β-thal.

  9. Hemoglobin (image)

    MedlinePlus

    Hemoglobin is the most important component of red blood cells. It is composed of a protein called ... exchanged for carbon dioxide. Abnormalities of an individual's hemoglobin value can indicate defects in the normal balance ...

  10. Hemoglobin C disease

    MedlinePlus

    Clinical hemoglobin C ... Hemoglobin C is an abnormal type of hemoglobin, the protein in red blood cells that carries oxygen. It is ... Americans. You are more likely to have hemoglobin C disease if someone in your family has had ...

  11. Hemoglobin electrophoresis

    MedlinePlus

    ... sickle cell anemia. Other, less common, abnormal Hb molecules cause other types of anemia . ... adults, these are normal percentages of different hemoglobin molecules: Hb A: 95% to 98% Hb A2: 2% ...

  12. Hemoglobin derivatives

    MedlinePlus

    ... in red blood cells that moves oxygen and carbon dioxide between the lungs and body tissues. This article ... attached to carbon monoxide instead of oxygen or carbon dioxide. High amounts of this type of abnormal hemoglobin ...

  13. Hemoglobin substitutes.

    PubMed

    Anbari, Kevin K; Garino, Jonathan P; Mackenzie, Colin F

    2004-10-01

    Orthopaedic patients frequently require blood transfusions to treat peri-operative anemia. Research in the area of hemoglobin substitutes has been of great interest since it holds the promise of reducing the reliance on allogeneic blood transfusions. The three categories of hemoglobin substitutes are (1) cell-free, extracellular hemoglobin preparations made from human or bovine hemoglobin (hemoglobin-based oxygen carriers or HBOCs); (2) fluorine-substituted linear or cyclic carbon chains with a high oxygen-carrying capacity (perfluorocarbons); and (3) liposome-encapsulated hemoglobin. Of the three, HBOCs have been the most extensively studied and tested in preclinical and clinical trials that have shown success in diminishing the number of blood transfusions as well as an overall favorable side-effect profile. This has been demonstrated in vascular, cardiothoracic, and orthopaedic patients. HBOC-201, which is a preparation of cell-free bovine hemoglobin, has been approved for clinical use in South Africa. These products may well become an important tool for physicians treating peri-operative anemia in orthopaedic patients.

  14. Serum free hemoglobin test

    MedlinePlus

    Blood hemoglobin; Serum hemoglobin ... Hemoglobin (Hb) is the main component of red blood cells. It is a protein that carries oxygen. ... people may contain up to 5 mg/dL hemoglobin. Normal value ranges may vary slightly among different ...

  15. Structure-function relations of human hemoglobins

    PubMed Central

    2006-01-01

    In 1949 Pauling and his associates showed that sickle cell hemoglobin (HbS) belonged to an abnormal molecular species. In 1958 Ingram, who used a two-dimensional system of electrophoresis and chromatography to break down the hemoglobin molecule into a mixture of smaller peptides, defined the molecular defect in HbS by showing that it differed from normal adult hemoglobin by only a single peptide. Since then, more than 200 variant and abnormal hemoglobins have been described. Furthermore, the construction of an atomic model of the hemoglobin molecule based on a high-resolution x-ray analysis by Dr. Max Perutz at Cambridge has permitted the study of the stereochemical part played by the amino acid residues, which were replaced, deleted, or added to in each of the hemoglobin variants. Some of the variants have been associated with clinical conditions. The demonstration of a molecular basis for a disease was a significant turning point in medicine. A new engineered hemoglobin derived from crocodile blood, with markedly reduced oxygen affinity and increased oxygen delivery to the tissues, points the way for future advances in medicine. PMID:17252042

  16. Hemoglobin variant (hemoglobin Aalborg) mimicking interstitial pulmonary disease.

    PubMed

    Panou, Vasiliki; Jensen, Peter-Diedrich Mathias; Pedersen, Jan Freddy; Thomsen, Lars Pilegaard; Weinreich, Ulla Møller

    2014-01-01

    Hemoglobin Aalborg is a moderately unstable hemoglobin variant with no affiliation to serious hematological abnormality or major clinical symptoms under normal circumstances. Our index person was a healthy woman of 58, not previously diagnosed with hemoglobinopathy Aalborg, who developed acute respiratory failure after a routine cholecystectomy. Initially she was suspected of idiopathic interstitial lung disease, yet a series of tests uncovered various abnormal physiological parameters and set the diagnosis of hemoglobinopathy Aalborg. This led us to examine a group of the index person's relatives known with hemoglobinopathy Aalborg in order to study whether the same physiological abnormalities would be reencountered. They were all subjected to spirometry and body plethysmography, six-minute walking test, pulse oximetry, and arterial blood gas samples before and after the walking test. The entire study population presented the same physiological anomalies: reduction in diffusion capacity, and abnormalities in P(a)O2 and p50 values; the latter could not be presented by the arterial blood gas analyzer; furthermore there was concordance between pulse oximetry and arterial blood gas samples regarding saturation. These data suggest that, based upon the above mentioned anomalies in physiological parameters, the diagnosis of hemoglobinopathy Aalborg should be considered.

  17. Hemoglobin Variant (Hemoglobin Aalborg) Mimicking Interstitial Pulmonary Disease

    PubMed Central

    Panou, Vasiliki; Jensen, Peter-Diedrich Mathias; Pedersen, Jan Freddy; Thomsen, Lars Pilegaard; Weinreich, Ulla Møller

    2014-01-01

    Hemoglobin Aalborg is a moderately unstable hemoglobin variant with no affiliation to serious hematological abnormality or major clinical symptoms under normal circumstances. Our index person was a healthy woman of 58, not previously diagnosed with hemoglobinopathy Aalborg, who developed acute respiratory failure after a routine cholecystectomy. Initially she was suspected of idiopathic interstitial lung disease, yet a series of tests uncovered various abnormal physiological parameters and set the diagnosis of hemoglobinopathy Aalborg. This led us to examine a group of the index person's relatives known with hemoglobinopathy Aalborg in order to study whether the same physiological abnormalities would be reencountered. They were all subjected to spirometry and body plethysmography, six-minute walking test, pulse oximetry, and arterial blood gas samples before and after the walking test. The entire study population presented the same physiological anomalies: reduction in diffusion capacity, and abnormalities in PaO2 and p50 values; the latter could not be presented by the arterial blood gas analyzer; furthermore there was concordance between pulse oximetry and arterial blood gas samples regarding saturation. These data suggest that, based upon the above mentioned anomalies in physiological parameters, the diagnosis of hemoglobinopathy Aalborg should be considered. PMID:25400945

  18. The Hemoglobin E Thalassemias

    PubMed Central

    Fucharoen, Suthat; Weatherall, David J.

    2012-01-01

    Hemoglobin E (HbE) is an extremely common structural hemoglobin variant that occurs at high frequencies throughout many Asian countries. It is a β-hemoglobin variant, which is produced at a slightly reduced rate and hence has the phenotype of a mild form of β thalassemia. Its interactions with different forms of α thalassemia result in a wide variety of clinical disorders, whereas its coinheritance with β thalassemia, a condition called hemoglobin E β thalassemia, is by far the most common severe form of β thalassemia in Asia and, globally, comprises approximately 50% of the clinically severe β-thalassemia disorders. PMID:22908199

  19. Phylogeny of Echinoderm Hemoglobins

    PubMed Central

    Christensen, Ana B.; Herman, Joseph L.; Elphick, Maurice R.; Kober, Kord M.; Janies, Daniel; Linchangco, Gregorio; Semmens, Dean C.; Bailly, Xavier; Vinogradov, Serge N.; Hoogewijs, David

    2015-01-01

    Background Recent genomic information has revealed that neuroglobin and cytoglobin are the two principal lineages of vertebrate hemoglobins, with the latter encompassing the familiar myoglobin and α-globin/β-globin tetramer hemoglobin, and several minor groups. In contrast, very little is known about hemoglobins in echinoderms, a phylum of exclusively marine organisms closely related to vertebrates, beyond the presence of coelomic hemoglobins in sea cucumbers and brittle stars. We identified about 50 hemoglobins in sea urchin, starfish and sea cucumber genomes and transcriptomes, and used Bayesian inference to carry out a molecular phylogenetic analysis of their relationship to vertebrate sequences, specifically, to assess the hypothesis that the neuroglobin and cytoglobin lineages are also present in echinoderms. Results The genome of the sea urchin Strongylocentrotus purpuratus encodes several hemoglobins, including a unique chimeric 14-domain globin, 2 androglobin isoforms and a unique single androglobin domain protein. Other strongylocentrotid genomes appear to have similar repertoires of globin genes. We carried out molecular phylogenetic analyses of 52 hemoglobins identified in sea urchin, brittle star and sea cucumber genomes and transcriptomes, using different multiple sequence alignment methods coupled with Bayesian and maximum likelihood approaches. The results demonstrate that there are two major globin lineages in echinoderms, which are related to the vertebrate neuroglobin and cytoglobin lineages. Furthermore, the brittle star and sea cucumber coelomic hemoglobins appear to have evolved independently from the cytoglobin lineage, similar to the evolution of erythroid oxygen binding globins in cyclostomes and vertebrates. Conclusion The presence of echinoderm globins related to the vertebrate neuroglobin and cytoglobin lineages suggests that the split between neuroglobins and cytoglobins occurred in the deuterostome ancestor shared by echinoderms and

  20. THE RENAL HANDLING OF HEMOGLOBIN

    PubMed Central

    Bunn, H. Franklin; Esham, William T.; Bull, Robert W.

    1969-01-01

    The glomerular filtration of hemoglobin (α2β2) was studied under conditions in which its dissociation into αβ dimers was experimentally altered. Rats receiving hemoglobin treated with the sulfhydryl reagent bis(N-maleimidomethyl) ether (BME) showed a much lower renal excretion and prolonged plasma survival as compared with animals injected with untreated hemoglobin. Plasma disappearance was also prolonged in dogs receiving BME hemoglobin. Gel filtration data indicated that under physiological conditions, BME hemoglobin had impaired subunit dissociation. In addition, BME hemoglobin showed a very high oxygen affinity and a decreased rate of auto-oxidation. Glomerular filtration was enhanced under conditions which favor the dissociation of hemoglobin into dimers. Cat hemoglobin, which forms subunits much more extensively than canine hemoglobin, was excreted more readily by the rat kidney. The renal uptake of 59Fe hemoglobin injected intra-arterially into rabbits varied inversely with the concentration of the injected dose. PMID:5778789

  1. Rice (Oryza) hemoglobins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hemoglobins (Hbs) corresponding to non-symbiotic (nsHb) and truncated (tHb) Hbs have been identified in rice (Oryza). This review discusses the major findings from the current studies on rice Hbs. At the molecular level, a family of the nshb genes, consisting of hb1, hb2, hb3, hb4 and hb5, and a sin...

  2. Sickle cell anemia: targeting the role of fetal hemoglobin in therapy.

    PubMed

    Coleman, Emma; Inusa, Baba

    2007-06-01

    Sickle cell anemia results from the single amino acid substitution of valine for glutamic acid in the beta-chain owing to a nucleotide defect that causes the production of abnormal beta-chains in hemoglobin S. Abnormal hemoglobin chains form polymers in the deoxygenated state, leading to the characteristic sickle cells. The polymerization of deoxygenated hemoglobin S accounts for the pathologic changes in sickle cell disease. The main-stay of therapy in sickle cell disease aims to reduce the amount of sickled hemoglobin present through the prevention of polymerization and reversal of this process. One way of discouraging polymerization is to increase the level of fetal hemoglobin, which because of its high oxygen affinity, does not participate in the polymerization process. Fetal hemoglobin production may be induced pharmacologically or by the use of gene therapy and genetic engineering techniques. PMID:17556734

  3. Temperature modulation of bovine hemoglobins.

    PubMed

    Condò, S G; el-Sherbini, S; Giardina, B

    1991-06-28

    The functional properties of hemoglobin from Egyptian water buffalo have been characterized as a function of pH, temperature and chloride concentration. Alongside overall similarities shared with ox and Arctic ruminant hemoglobins, hemoglobin from buffalo shows significant differences with respect to the effect of temperature. The results obtained may suggest that the limited effect of temperature on oxygen binding recently reported for ox hemoglobin could be regarded as an interesting case of a reminiscence of a past glacial age.

  4. Hemoglobin interacting proteins and implications of spectrin hemoglobin interaction.

    PubMed

    Basu, Avik; Chakrabarti, Abhijit

    2015-10-14

    In this report we have analyzed interacting partners of hemoglobin inside erythrocyte and sought possible implications of hemoglobin-spectrin interaction. Our list of identified cytosolic hemoglobin interacting proteins includes redox regulators like peroxiredoxin-2, Cu-Zn superoxide dismutase, catalase, aldehyde dehydrogenase-1, flavin reductase and chaperones like HSP70, α-hemoglobin stabilizing protein. Others include metabolic enzymes like carbonic anhydrase-1, selenium binding protein-1, purine nucleoside phosphorylase and nucleoside diphosphate kinase. Additionally, various membrane proteins like α and β spectrin, ankyrin, band3, protein4.1, actin and glyceraldehyde 3 phosphate dehydrogenase have been shown to interact with hemoglobin. Our result indicates that major membrane skeleton protein spectrin, that also has a chaperone like activity, helps to fold the unstable alpha-globin chains in vitro. Taken together our results could provide insight into a protein network evolved around hemoglobin molecule inside erythrocyte that may add a new perspective in understanding the hemoglobin function and homeostasis.

  5. Antimicrobial properties of hemoglobin.

    PubMed

    Sheshadri, Preethi; Abraham, Jayanthi

    2012-12-01

    Hemoglobin consists of a heme containing component and a globin unit. It exists as a tetramer with 2 α subunits and 2 β subunits in adults and with 2 α subunits and 2 γ chains in infants. On proteolytic cleavage, hemoglobin breaks down to produce many biologically active compounds, among which are hemocidins, those which exhibit antimicrobial property. The generation of these peptides does not depend on the blood group, Rhesus factor, age and sex of the healthy donors. The microbicidal activity has been observed against a variety of gram positive and Gram-negative bacteria, and against filamentous fungi, yeast and even certain parasites. The discovery of hemocidins opens a new field for research into the details of the peptides acting as second line of defence in boosting the innate immune system of the organisms.

  6. Studies of hemoglobin denaturation and Heinz body formation in the unstable hemoglobins.

    PubMed

    Winterbourn, C C; Carrell, R W

    1974-09-01

    The sequential changes that occur during the precipitation on mild heating of the unstable hemoglobins, Hb Christchurch, Hb Sydney, Hb Köln, and Hb A, were examined with particular attention to the possibility of an accompanying oxidative process. Hb Christchurch, Hb Sydney, and Hb A precipitated with equal amounts of alpha- and beta-chains and full heme complement. Hb Köln, however, was one-half hemedepleted and showed a slight excess of precipitated beta-chains. In all cases the spectrum of the precipitated material was typical of a hemichrome. There was no evidence that sulfhydryl oxidation contributed to the precipitation process. Reduced glutathione was unable to protect the hemoglobin against precipitation, and mixed disulfide formation between the precipitating hemoglobin and glutathione was insignificant, even in the presence of excess glutathione. No blockade of beta93 cysteines could be demonstrated in the unstable hemoglobins. Precipitation of oxyhemoglobin and carboxyhemoglobin in all cases gave nonspecific oxidation of approximately two of the six hemoglobin sulfhydryl groups to give intra- and intermolecular disulfide bonds. Single alpha- and beta-chains, plus polymers of up to five or six chains linked by disulfide bridges, were demonstrated by polyacrylamide gel electrophoresis. This disulfide oxidation was not observed with deoxy- or methemoglobin and did not appear to influence the rate of precipitation. These findings fit the theoretical prediction that autoxidation of oxy- and carboxyhemoglobin is accompanied by formation of a free radical, with the reactions of this free radical being confined intramolecularly.Together, these results are in keeping with predictions based on the known structural abnormalities of the unstable hemoglobins, all of which result in greater molecular flexibility. Our findings support the conclusion that the usual precipitating event is altered bonding at the heme to give the formation of hemichromes. There is no

  7. Unexpectedly low pulse oximetry measurements associated with variant hemoglobins: a systematic review.

    PubMed

    Verhovsek, Madeleine; Henderson, Matthew P A; Cox, Gerard; Luo, Hong-yuan; Steinberg, Martin H; Chui, David H K

    2010-11-01

    Pulse oximetry estimates arterial blood oxygen saturation based on light absorbance of oxy- and deoxy-hemoglobin at 660 and 940 nm wavelengths. Patients with unexpectedly low SpO₂ often undergo cardio-pulmonary testing to ascertain the cause of their hypoxemia. However, in a subset of patients, a variant hemoglobin is responsible for low SpO₂ measurements. The extent of this problem is unclear. We performed a systematic literature review for reports of low SpO₂ associated with variant hemoglobins. We also reviewed unpublished cases from an academic hemoglobin diagnostic reference laboratory. Twenty-five publications and four unpublished cases were identified, representing 45 patients with low SpO₂ and confirmed variant hemoglobin. Fifty-seven family members of patients had confirmed or suspected variant hemoglobin. Three low oxygen affinity variant hemoglobins had concordantly low SpO₂ and SaO₂. Eleven variant hemoglobins were associated with unexpectedly low SpO₂ measurements but normal SaO₂. Hemoglobin light absorbance testing was reported in three cases, all of which showed abnormal absorption spectra between 600 and 900 nm. Seven other variant hemoglobins had decreased SpO₂, with unreported or uncertain SaO₂. Twenty-one variant hemoglobins were found to be associated with low SpO₂. Most variant hemoglobins were associated with spuriously low SpO₂. Abnormal absorption spectra explain the discrepancy between SpO₂ and SaO(2) for some variants. The differential diagnosis of possible variant hemoglobin ought to be considered in asymptomatic patients found to have unexpectedly low SpO₂. The correct diagnosis will help to spare patients from unnecessary investigations and anxiety.

  8. Disorders of Human Hemoglobin

    NASA Astrophysics Data System (ADS)

    Bank, Arthur; Mears, J. Gregory; Ramirez, Francesco

    1980-02-01

    Studies of the human hemoglobin system have provided new insights into the regulation of expression of a group of linked human genes, the γ -δ -β globin gene complex in man. In particular, the thalassemia syndromes and related disorders of man are inherited anemias that provide mutations for the study of the regulation of globin gene expression. New methods, including restriction enzyme analysis and cloning of cellular DNA, have made it feasible to define more precisely the structure and organization of the globin genes in cellular DNA. Deletions of specific globin gene fragments have already been found in certain of these disorders and have been applied in prenatal diagnosis.

  9. Subunit dissociation in fish hemoglobins.

    PubMed

    Edelstein, S J; McEwen, B; Gibson, Q H

    1976-12-10

    The tetramer-dimer dissociation equilibria (K 4,2) of several fish hemoglobins have been examined by sedimentation velocity measurements with a scanner-computer system for the ultracentrifuge and by flash photolysis measurements using rapid kinetic methods. Samples studied in detail included hemoglobins from a marine teleost, Brevoortia tyrannus (common name, menhaden); a fresh water teleost, Cyprinus carpio, (common name, carp); and an elasmobranch Prionace glauca (common name, blue shark). For all three species in the CO form at pH 7, in 0.1 M phosphate buffer, sedimentation coefficients of 4.3 S (typical of tetrameric hemoglobin) are observed in the micromolar concentration range. In contrast, mammalian hemoglobins dissociate appreciably to dimers under these conditions. The inability to detect dissociation in three fish hemoglobins at the lowest concentrations examined indicates that K 4,2 must have a value of 10(-8) M or less. In flash photolysis experiments on very dilute solutions in long path length cells, two kinetic components were detected with their proportions varying as expected for an equilibrium between tetramers (the slower component) and dimers (the faster component); values of K 4,2 for the three fish hemoglobins in the range 10(-9) to 10(-8) M were calculated from these data. Thus, the values of K 4,2 for liganded forms of the fish hemoglobins appear to be midway between the value for liganded human hemoglobin (K 4,2 approximately 10(-6) M) and unliganded human hemoglobin (K 4,2 approximately 10(-12) M). This conclusion is supported by measurements on solutions containing guanidine hydrochloride to enhance the degree of dissociation. All three fish hemoglobins are appreciably dissociated at guanidine concentrations of about 0.8 M, which is roughly midway between the guanidine concentrations needed to cause comparable dissociation of liganded human hemoglobin (about 0.4 M) and unliganded human hemoglobin (about 1.6 M). Kinetic measurements on

  10. Meiotic abnormalities

    SciTech Connect

    1993-12-31

    Chapter 19, describes meiotic abnormalities. These include nondisjunction of autosomes and sex chromosomes, genetic and environmental causes of nondisjunction, misdivision of the centromere, chromosomally abnormal human sperm, male infertility, parental age, and origin of diploid gametes. 57 refs., 2 figs., 1 tab.

  11. Insights into Hemoglobin Assembly through in Vivo Mutagenesis of α-Hemoglobin Stabilizing Protein*

    PubMed Central

    Khandros, Eugene; Mollan, Todd L.; Yu, Xiang; Wang, Xiaomei; Yao, Yu; D'Souza, Janine; Gell, David A.; Olson, John S.; Weiss, Mitchell J.

    2012-01-01

    α-Hemoglobin stabilizing protein (AHSP) is believed to facilitate adult Hemoglobin A assembly and protect against toxic free α-globin subunits. Recombinant AHSP binds multiple forms of free α-globin to stabilize their structures and inhibit precipitation. However, AHSP also stimulates autooxidation of αO2 subunit and its rapid conversion to a partially unfolded bishistidyl hemichrome structure. To investigate these biochemical properties, we altered the evolutionarily conserved AHSP proline 30 in recombinantly expressed proteins and introduced identical mutations into the endogenous murine Ahsp gene. In vitro, the P30W AHSP variant bound oxygenated α chains with 30-fold increased affinity. Both P30W and P30A mutant proteins also caused decreased rates of αO2 autooxidation as compared with wild-type AHSP. Despite these abnormalities, mice harboring P30A or P30W Ahsp mutations exhibited no detectable defects in erythropoiesis at steady state or during induced stresses. Further biochemical studies revealed that the AHSP P30A and P30W substitutions had minimal effects on AHSP interactions with ferric α subunits. Together, our findings indicate that the ability of AHSP to stabilize nascent α chain folding intermediates prior to hemin reduction and incorporation into adult Hemoglobin A is physiologically more important than AHSP interactions with ferrous αO2 subunits. PMID:22287545

  12. Insights into hemoglobin assembly through in vivo mutagenesis of α-hemoglobin stabilizing protein.

    PubMed

    Khandros, Eugene; Mollan, Todd L; Yu, Xiang; Wang, Xiaomei; Yao, Yu; D'Souza, Janine; Gell, David A; Olson, John S; Weiss, Mitchell J

    2012-03-30

    α-Hemoglobin stabilizing protein (AHSP) is believed to facilitate adult Hemoglobin A assembly and protect against toxic free α-globin subunits. Recombinant AHSP binds multiple forms of free α-globin to stabilize their structures and inhibit precipitation. However, AHSP also stimulates autooxidation of αO(2) subunit and its rapid conversion to a partially unfolded bishistidyl hemichrome structure. To investigate these biochemical properties, we altered the evolutionarily conserved AHSP proline 30 in recombinantly expressed proteins and introduced identical mutations into the endogenous murine Ahsp gene. In vitro, the P30W AHSP variant bound oxygenated α chains with 30-fold increased affinity. Both P30W and P30A mutant proteins also caused decreased rates of αO(2) autooxidation as compared with wild-type AHSP. Despite these abnormalities, mice harboring P30A or P30W Ahsp mutations exhibited no detectable defects in erythropoiesis at steady state or during induced stresses. Further biochemical studies revealed that the AHSP P30A and P30W substitutions had minimal effects on AHSP interactions with ferric α subunits. Together, our findings indicate that the ability of AHSP to stabilize nascent α chain folding intermediates prior to hemin reduction and incorporation into adult Hemoglobin A is physiologically more important than AHSP interactions with ferrous αO(2) subunits.

  13. Hemoglobin variants in Cyprus.

    PubMed

    Kyrri, Andreani R; Felekis, Xenia; Kalogerou, Eleni; Wild, Barbara J; Kythreotis, Loukas; Phylactides, Marios; Kleanthous, Marina

    2009-01-01

    Cyprus, located at the eastern end of the Mediterranean region, has been a place of eastern and western civilizations, and the presence of various hemoglobin (Hb) variants can be considered a testimony to past colonizations of the island. In this study, we report the structural Hb variants identified in the Cypriot population (Greek Cypriots, Maronites, Armenians, and Latinos) during the thalassemia screening of 248,000 subjects carried out at the Thalassaemia Centre, Nicosia, Cyprus, over a period of 26 years. A sample population of 65,668 people was used to determine the frequency and localization of several of the variants identified in Cyprus. The localization of some of the variants in regions where the presence of foreign people was most prevalent provides important clues to the origin of the variants. Twelve structural variants have been identified by DNA sequencing, nine concerning the beta-globin gene and three concerning the alpha-globin gene. The most common beta-globin variants identified were Hb S (0.2%), Hb D-Punjab (0.02%), and Hb Lepore-Washington-Boston (Hb Lepore-WB) (0.03%); the most common alpha-globin variant was Hb Setif (0.1%). The presence of some of these variants is likely to be directly linked to the history of Cyprus, as archeological monuments have been found throughout the island which signify the presence for many years of the Greeks, Syrians, Persians, Arabs, Byzantines, Franks, Venetians, and Turks. PMID:19373583

  14. Oxygen transport by hemoglobin.

    PubMed

    Mairbäurl, Heimo; Weber, Roy E

    2012-04-01

    Hemoglobin (Hb) constitutes a vital link between ambient O2 availability and aerobic metabolism by transporting oxygen (O2) from the respiratory surfaces of the lungs or gills to the O2-consuming tissues. The amount of O2 available to tissues depends on the blood-perfusion rate, as well as the arterio-venous difference in blood O2 contents, which is determined by the respective loading and unloading O2 tensions and Hb-O2-affinity. Short-term adjustments in tissue oxygen delivery in response to decreased O2 supply or increased O2 demand (under exercise, hypoxia at high altitude, cardiovascular disease, and ischemia) are mediated by metabolically induced changes in the red cell levels of allosteric effectors such as protons (H(+)), carbon dioxide (CO2), organic phosphates, and chloride (Cl(-)) that modulate Hb-O2 affinity. The long-term, genetically coded adaptations in oxygen transport encountered in animals that permanently are subjected to low environmental O2 tensions commonly result from changes in the molecular structure of Hb, notably amino acid exchanges that alter Hb's intrinsic O2 affinity or its sensitivity to allosteric effectors. Structure-function studies of animal Hbs and human Hb mutants illustrate the different strategies for adjusting Hb-O2 affinity and optimizing tissue oxygen supply.

  15. Nonlinear photoacoustic spectroscopy of hemoglobin

    SciTech Connect

    Danielli, Amos; Maslov, Konstantin; Favazza, Christopher P.; Xia, Jun; Wang, Lihong V.

    2015-05-18

    As light intensity increases in photoacoustic imaging, the saturation of optical absorption and the temperature dependence of the thermal expansion coefficient result in a measurable nonlinear dependence of the photoacoustic (PA) signal on the excitation pulse fluence. Here, under controlled conditions, we investigate the intensity-dependent photoacoustic signals from oxygenated and deoxygenated hemoglobin at varied optical wavelengths and molecular concentrations. The wavelength and concentration dependencies of the nonlinear PA spectrum are found to be significantly greater in oxygenated hemoglobin than in deoxygenated hemoglobin. These effects are further influenced by the hemoglobin concentration. These nonlinear phenomena provide insights into applications of photoacoustics, such as measurements of average inter-molecular distances on a nm scale or with a tuned selection of wavelengths, a more accurate quantitative PA tomography.

  16. More Refined Experiments with Hemoglobin.

    ERIC Educational Resources Information Center

    Morin, Phillippe

    1985-01-01

    Discusses materials needed, procedures used, and typical results obtained for experiments designed to make a numerical stepwise study of the oxygenation of hemoglobin, myoglobin, and other oxygen carriers. (JN)

  17. Rice ( Oryza) hemoglobins

    PubMed Central

    Arredondo-Peter, Raúl; Moran, Jose F.; Sarath, Gautam

    2014-01-01

    Hemoglobins (Hbs) corresponding to non-symbiotic (nsHb) and truncated (tHb) Hbs have been identified in rice ( Oryza). This review discusses the major findings from the current studies on rice Hbs. At the molecular level, a family of the nshb genes, consisting of hb1, hb2, hb3, hb4 and hb5, and a single copy of the thb gene exist in Oryza sativa var. indica and O. sativa var. japonica, Hb transcripts coexist in rice organs and Hb polypeptides exist in rice embryonic and vegetative organs and in the cytoplasm of differentiating cells. At the structural level, the crystal structure of rice Hb1 has been elucidated, and the structures of the other rice Hbs have been modeled. Kinetic analysis indicated that rice Hb1 and 2, and possibly rice Hb3 and 4, exhibit a very high affinity for O 2, whereas rice Hb5 and tHb possibly exhibit a low to moderate affinity for O 2. Based on the accumulated information on the properties of rice Hbs and data from the analysis of other plant and non-plant Hbs, it is likely that Hbs play a variety of roles in rice organs, including O 2-transport, O 2-sensing, NO-scavenging and redox-signaling. From an evolutionary perspective, an outline for the evolution of rice Hbs is available. Rice nshb and thb genes vertically evolved through different lineages, rice nsHbs evolved into clade I and clade II lineages and rice nshbs and thbs evolved under the effect of neutral selection. This review also reveals lacunae in our ability to completely understand rice Hbs. Primary lacunae are the absence of experimental information about the precise functions of rice Hbs, the properties of modeled rice Hbs and the cis-elements and trans-acting factors that regulate the expression of rice hb genes, and the partial understanding of the evolution of rice Hbs. PMID:25653837

  18. Rice ( Oryza) hemoglobins.

    PubMed

    Arredondo-Peter, Raúl; Moran, Jose F; Sarath, Gautam

    2014-01-01

    Hemoglobins (Hbs) corresponding to non-symbiotic (nsHb) and truncated (tHb) Hbs have been identified in rice ( Oryza). This review discusses the major findings from the current studies on rice Hbs. At the molecular level, a family of the nshb genes, consisting of hb1, hb2, hb3, hb4 and hb5, and a single copy of the thb gene exist in Oryza sativa var. indica and O. sativa var. japonica, Hb transcripts coexist in rice organs and Hb polypeptides exist in rice embryonic and vegetative organs and in the cytoplasm of differentiating cells. At the structural level, the crystal structure of rice Hb1 has been elucidated, and the structures of the other rice Hbs have been modeled. Kinetic analysis indicated that rice Hb1 and 2, and possibly rice Hb3 and 4, exhibit a very high affinity for O 2, whereas rice Hb5 and tHb possibly exhibit a low to moderate affinity for O 2. Based on the accumulated information on the properties of rice Hbs and data from the analysis of other plant and non-plant Hbs, it is likely that Hbs play a variety of roles in rice organs, including O 2-transport, O 2-sensing, NO-scavenging and redox-signaling. From an evolutionary perspective, an outline for the evolution of rice Hbs is available. Rice nshb and thb genes vertically evolved through different lineages, rice nsHbs evolved into clade I and clade II lineages and rice nshbs and thbs evolved under the effect of neutral selection. This review also reveals lacunae in our ability to completely understand rice Hbs. Primary lacunae are the absence of experimental information about the precise functions of rice Hbs, the properties of modeled rice Hbs and the cis-elements and trans-acting factors that regulate the expression of rice hb genes, and the partial understanding of the evolution of rice Hbs.

  19. Craniofacial Abnormalities

    MedlinePlus

    ... of the skull and face. Craniofacial abnormalities are birth defects of the face or head. Some, like cleft ... palate, are among the most common of all birth defects. Others are very rare. Most of them affect ...

  20. Chromosome Abnormalities

    MedlinePlus

    ... decade, newer techniques have been developed that allow scientists and doctors to screen for chromosomal abnormalities without using a microscope. These newer methods compare the patient's DNA to a normal DNA ...

  1. Walking abnormalities

    MedlinePlus

    ... include: Arthritis of the leg or foot joints Conversion disorder (a psychological disorder) Foot problems (such as a ... injuries. For an abnormal gait that occurs with conversion disorder, counseling and support from family members are strongly ...

  2. Nail abnormalities

    MedlinePlus

    Beau's lines; Fingernail abnormalities; Spoon nails; Onycholysis; Leukonychia; Koilonychia; Brittle nails ... Just like the skin, the fingernails tell a lot about your health: ... the fingernail. These lines can occur after illness, injury to ...

  3. Reactions of arsine with hemoglobin

    SciTech Connect

    Hatlelid, K.M.; Brailsford, C.; Carter, D.E.

    1996-02-09

    The mechanism of arsine (AsH{sub 3}) induced hemolysis was studied in vitro using isolated red blood cells (RBCs) from the rat or dog. AsH{sub 3}-induced hemolysis of dog red blood cells was completely blocked by carbon monoxide (CO) preincubation and was reduced by pure oxygen (O{sub 2}) compared to incubations in air. Since CO and O{sub 2} bind to heme and also reduced hemolysis, these results suggested a reaction between AsH{sub 3} and hemoglobin in the hemeligand binding pocket or with the heme iron. Further, sodium nitrite induction of methemoglobin (metHb) to 85% and 34% of total Hb in otherwise intact RBCs resulted in 56% and 16% decreases in hemolysis, respectively, after incubation for 4 h. This provided additional evidence for the involvement of hemoglobin in the AsH{sub 3}-induced hemolysis mechanism. Reactions between AsH{sub 3} and hemoglobin were studied in solutions of purified dog hemoglobin. Spectrophotometric studies of the reaction of AsH{sub 3} with various purified hemoglobin species revealed that AsH{sub 3} reacted with HbO{sub 2} to produce metHb and, eventually, degraded Hb characterized by gross precipitation of the protein. AsH{sub 3} did not alter the spectrum of deoxyHb and did not cause degradation of metHb in oxygen, but bound to and reduced metHb in the absence of oxygen. These data indicate that a reaction of AsH{sub 3} with oxygenated hemoglobin, HbO{sub 2}, may lead to hemolysis, but there are reactions between AsH{sub 3} and metHb that may not be directly involved in the hemolytic process. 17 refs., 6 figs.

  4. [Homozygous hemoglobin-E (Hb-EE) disease].

    PubMed

    Amendola, G; Danise, P; Di Palma, A; Franzese, M; Avino, D; D'Arco, A M

    2004-01-01

    The Authors report on a 16 year-old girl, of Cambodian descent, who was admitted to the hospital for hematuria. She showed a mild microcytic, hypochromic anemia with a normal iron balance; clinical examination was normal with neither pallor nor icterus nor splenomegaly; electrophoresis of hemoglobin yielded no hemoglobin A, a sligtly increased amount of HbF and a single band with a mobility similar to that of HbA2; the patient showed no evidence of overt increased hemolysis. With the DNA technology a final diagnosis of homozygous hemoglobin E was made. Hemoglobin E is the most common Hb variant among Southeast Asian populations. The Authors discuss on the benign nature of Hb-EE disease, pointing out that the presence of a single HbE gene in combination with that for beta-thalassemia leads generally to a disorder often comparable in severity to that of homozygous beta-thalassemia. With the recent migration of a high number of people from the countries, where HbE is extremely frequent, to the Western world (including Italy), this thalassemia syndrome is now a global health problem; therefore its knowledge is an important diagnostic challenge to all the experts involved in the care of thalassemic patients.

  5. Identification of the Presence of Variant Hemoglobin Using a Measurement of the Labile HbA1c (#C) Fraction.

    PubMed

    Koga, Masafumi; Inada, Shinya; Miyazaki, Ayako

    2016-07-01

    Labile HbA1c migrates in the #C fraction together with modified hemoglobin (such as carbamylated hemoglobin, acetaldehyde hemoglobin, and acetylated hemoglobin) when HbA1c is measured by Arkray's high-performance liquid chromatography (HPLC). It is assumed that most of the labile glycation products of variant hemoglobin do not migrate in #C fraction; in addition, a part of the stable glycation products of variant hemoglobin migrates in #C fraction. We hypothesized that subjects with variant hemoglobin are likely to show abnormally low or high values of #C fraction. In this study, we investigated this hypothesis. Twenty-one non-diabetic subjects with nine types of variant hemoglobin, and 103 non-diabetic subjects without variant hemoglobin were used. HbA1c and #C fraction were measured by Arkray's HPLC (HA-8180) using standard mode. The values of #C fraction in the control group were 1.75 ± 0.15% (range: 1.5-2.1%). The variant hemoglobin group reported #C fraction values of ≤1.3% in twelve subjects, ≥2.3% in five subjects, and within the reference range (1.4-2.2%) in three subjects. When the cutoff values of #C fraction were set at ≤1.3% and ≥2.3%, sensitivity and specificity were 86% and 100%, respectively. Most non-diabetic subjects with variant hemoglobin showed abnormal values of #C fraction. Measurement of #C fraction is a useful screening test for variant hemoglobin in non-diabetic subjects. PMID:27466298

  6. Influence of hemoglobin on non-invasive optical bilirubin sensing

    NASA Astrophysics Data System (ADS)

    Jiang, Jingying; Gong, Qiliang; Zou, Da; Xu, Kexin

    2012-03-01

    Since the abnormal metabolism of bilirubin could lead to diseases in the human body, especially the jaundice which is harmful to neonates. Traditional invasive measurements are difficult to be accepted by people because of pain and infection. Therefore, the real-time and non-invasive measurement of bilirubin is of great significance. However, the accuracy of currently transcutaneous bilirubinometry(TcB) is generally not high enough, and affected by many factors in the human skin, mostly by hemoglobin. In this talk, absorption spectra of hemoglobin and bilirubin have been collected and analyzed, then the Partial Least Squares (PLS) models have been built. By analyzing and comparing the Correlation and Root Mean Square Error of Prediction(RMSEP), the results show that the Correlation of bilirubin solution model is larger than that of the mixture solution added with hemoglobin, and its RMSEP value is smaller than that of mixture solution. Therefore, hemoglobin has influences on the non-invasive optical bilirubin sensing. In next step, it is necessary to investigate how to eliminate the influence.

  7. THE PREPARATION OF COMPLETELY COAGULATED HEMOGLOBIN

    PubMed Central

    Anson, M. L.; Mirsky, A. E.

    1929-01-01

    As a preliminary to the study of the reversal of the coagulation of hemoglobin several methods are described for the preparation of completely denatured and coagulated hemoglobin and the evidence is given that hemoglobin is a typical coagulable protein. PMID:19872511

  8. Hemoglobin

    MedlinePlus

    ... the anemia is severe Some conditions affect RBC production in the bone marrow and may cause an ... there is a problem with red blood cell production and/or lifespan, but it cannot determine the ...

  9. Hemoglobin

    MedlinePlus

    ... disease ) Failure of the right side of the heart ( cor pulmonale ) Severe chronic obstructive pulmonary disease (COPD) Scarring or thickening of the lungs ( pulmonary fibrosis ) and other severe lung disorders Other reasons for ...

  10. Determination Of Ph Including Hemoglobin Correction

    DOEpatents

    Maynard, John D.; Hendee, Shonn P.; Rohrscheib, Mark R.; Nunez, David; Alam, M. Kathleen; Franke, James E.; Kemeny, Gabor J.

    2005-09-13

    Methods and apparatuses of determining the pH of a sample. A method can comprise determining an infrared spectrum of the sample, and determining the hemoglobin concentration of the sample. The hemoglobin concentration and the infrared spectrum can then be used to determine the pH of the sample. In some embodiments, the hemoglobin concentration can be used to select an model relating infrared spectra to pH that is applicable at the determined hemoglobin concentration. In other embodiments, a model relating hemoglobin concentration and infrared spectra to pH can be used. An apparatus according to the present invention can comprise an illumination system, adapted to supply radiation to a sample; a collection system, adapted to collect radiation expressed from the sample responsive to the incident radiation; and an analysis system, adapted to relate information about the incident radiation, the expressed radiation, and the hemoglobin concentration of the sample to pH.

  11. Hemoglobin Variants: Biochemical Properties and Clinical Correlates

    PubMed Central

    Thom, Christopher S.; Dickson, Claire F.; Gell, David A.; Weiss, Mitchell J.

    2013-01-01

    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples. PMID:23388674

  12. Hemoglobin variants: biochemical properties and clinical correlates.

    PubMed

    Thom, Christopher S; Dickson, Claire F; Gell, David A; Weiss, Mitchell J

    2013-03-01

    Diseases affecting hemoglobin synthesis and function are extremely common worldwide. More than 1000 naturally occurring human hemoglobin variants with single amino acid substitutions throughout the molecule have been discovered, mainly through their clinical and/or laboratory manifestations. These variants alter hemoglobin structure and biochemical properties with physiological effects ranging from insignificant to severe. Studies of these mutations in patients and in the laboratory have produced a wealth of information on hemoglobin biochemistry and biology with significant implications for hematology practice. More generally, landmark studies of hemoglobin performed over the past 60 years have established important paradigms for the disciplines of structural biology, genetics, biochemistry, and medicine. Here we review the major classes of hemoglobin variants, emphasizing general concepts and illustrative examples.

  13. Hemoglobin Labeled by Radioactive Lysine

    DOE R&D Accomplishments Database

    Bale, W. F.; Yuile, C. L.; DeLaVergne, L.; Miller, L. L.; Whipple, G. H.

    1949-12-08

    This paper reports on the utilization of tagged epsilon carbon of DL-lysine by a dog both anemic and hypoproteinemic due to repeated bleeding plus a diet low in protein. The experiment extended over period of 234 days, a time sufficient to indicate an erythrocyte life span of at least 115 days based upon the rate of replacement of labeled red cell proteins. The proteins of broken down red cells seem not to be used with any great preference for the synthesis of new hemoglobin.

  14. Hemoglobin potentiates central nervous system damage.

    PubMed Central

    Sadrzadeh, S M; Anderson, D K; Panter, S S; Hallaway, P E; Eaton, J W

    1987-01-01

    Iron and iron compounds--including mammalian hemoglobins--catalyze hydroxyl radical production and lipid peroxidation. To determine whether hemoglobin-mediated lipid peroxidation might be important in hemorrhagic injuries to the central nervous system (CNS), we studied the effects of purified hemoglobin on CNS homogenates and injected hemoglobin into the spinal cords of anesthetized cats. Hemoglobin markedly inhibits Na/K ATPase activity in CNS homogenates and spinal cords of living cats. Hemoglobin also catalyzes substantial peroxidation of CNS lipids. Importantly, the potent iron chelator, desferrioxamine, blocks these adverse effects of hemoglobin, both in vitro and in vivo. Because desferrioxamine is not known to interact with heme iron, these results indicate that free iron, derived from hemoglobin, is the proximate toxic species. Overall, our data suggest that hemoglobin, released from red cells after trauma, can promote tissue injury through iron-dependent mechanisms. Suppression of this damage by desferrioxamine suggests a rational therapeutic approach to management of trauma-induced CNS injury. Images PMID:3027133

  15. Net charge and oxygen affinity of human hemoglobin are independent of hemoglobin concentration

    PubMed Central

    1978-01-01

    The dependence of net charge and oxygen affinity of human hemoglobin upon hemoglobin concentration was reinvestigated. In contrast to earlier reports from various laboratories, both functional properties of hemoglobin were found to be independent of hemoglobin concentration. Two findings indicate a concentration-independent net charge of carbonmonoxy hemoglobin at pH 6.6: (A) The pH value of a given carbonmonoty hemoglobin solution remains constant at 6.6 when the hemoglobin concentration is raised from 10 to 40 g/dl, indicating that there is no change in protonation of titratable groups of hemoglobin: (b) the net charge of carbonmonoxy hemoglobin as estimated from the Donnan distribution of 22Na+ shows no dependence on hemoglobin concentration in this concentration range. The oxygen affinity of human hemoglobin was determined from measurements of oxygen concentrations in equilibrated samples using a Lex-O2-Con apparatus (Lexington Instruments, Waltham, Mass.). P50 averaged 11.4 mm Hg at 37 degrees C, pH = 7.2, and ionic strength approximately 0.15. Neither P50 nor Hill's n showed any variation with hemoglobin concentrations increasing from 10 to 40 g/dl. PMID:32221

  16. Capillary zone electrophoresis: an additional technique for the identification of hemoglobin variants.

    PubMed

    Lin, C; Cotton, F; Fontaine, B; Gulbis, B; Janssens, J; Vertongen, F

    1999-05-01

    Two capillary zone electrophoresis kits (Hb A2 and Hb A1c) were tested for confirmation and identification of hemoglobin variants. The capillary zone electrophoresis experiments were performed at pH 4.7 (Hb A1c kit) and 8.7 (Hb A2 kit) in a 24 cm uncoated fused silica capillary tube (25 microm I.D.). Normal hemoglobins and common hemoglobin variants, including Hbs S, D-Punjab, C, E, O-Arab, and G-Philadelphia, were successfully separated by both methods within a few minutes. Both systems provided completely different elution profiles of normal and abnormal hemoglobin fractions tested and were complementary. The inter-assay coefficient of variations of the migration times of hemoglobin variants were less than 1.0 and 1.3% by the Hb A2 and Hb A1c, respectively. This permits a higher resolution of some hemoglobin variants in low concentrations, like Hb S in newborns, compared with conventional electrophoresis methods. The present capillary zone electrophoresis methods are sensitive, rapid, not labor intensive, and highly selective for the separation of hemoglobin variants. Combination of both methods with some conventional methods, such as isoelectrofocusing, allows identification of Hbs C, E, O-Arab, S, and D-Punjab, as well as their quantification. We have demonstrated that the conventional electrophoresis methods (electrophoresis at pH 6.5 in citrate agar gel and electrophoresis at pH 8.6 on cellulose acetate) can be advantageously replaced by the present capillary zone electrophoresis methods in a clinical laboratory practice for the detection and quantification of hemoglobin variants. PMID:10335978

  17. Effects of Hemoglobin Variants on Hemoglobin A1c Values Measured Using a High-Performance Liquid Chromatography Method

    PubMed Central

    De-La-Iglesia, Silvia; Ropero, Paloma; Nogueira-Salgueiro, Patricia; Santana-Benitez, Jesus

    2014-01-01

    Hemoglobin A1c (HbA1c) is routinely used to monitor long-term glycemic control and for diagnosing diabetes mellitus. However, hemoglobin (Hb) gene variants/modifications can affect the accuracy of some methods. The potential effect of Hb variants on HbA1c measurements was investigated using a high-performance liquid chromatography (HPLC) method compared with an immunoturbimetric assay. Fasting plasma glucose (FPG) and HbA1c levels were measured in 42 371 blood samples. Samples producing abnormal chromatograms were further analyzed to characterize any Hb variants. Fructosamine levels were determined in place of HbA1c levels when unstable Hb variants were identified. Abnormal HPLC chromatograms were obtained for 160 of 42 371 samples. In 26 samples HbS was identified and HbA1c results correlated with FPG. In the remaining 134 samples HbD, Hb Louisville, Hb Las Palmas, Hb N-Baltimore, or Hb Porto Alegre were identified and HbA1c did not correlate with FPG. These samples were retested using an immunoturbidimetric assay and the majority of results were accurate; only 3 (with the unstable Hb Louisville trait) gave aberrant HbA1c results. Hb variants can affect determination of HbA1c levels with some methods. Laboratories should be aware of Hb variants occurring locally and choose an appropriate HbA1c testing method. PMID:25355712

  18. Spectrophotometric Properties of Hemoglobin: Classroom Applications.

    ERIC Educational Resources Information Center

    Frary, Roger

    1997-01-01

    Discusses simple and safe techniques that can be used in the educational laboratory to study hemoglobin. Discusses the spectral properties of hemoglobin, spectral-absorbence curves of oxyhemoglobin and carboxyhemoglobin, tracking the conversion of oxyhemoglobin to methemoglobin, and changing from the oxyhemoglobin to deoxyhemoglobin conformation.…

  19. Blood glycated hemoglobin evaluation in sick dogs.

    PubMed Central

    Marca, M C; Loste, A; Unzueta, A; Pérez, M

    2000-01-01

    Blood glycated hemoglobin concentration reflects long-term serum glucose levels in dogs. In this study, the effects of several diseases on blood glycated hemoglobin levels have been evaluated. For this study, blood samples were drawn from 93 unhealthy dogs. The animals were distributed into 10 groups according to pathological process (group 1, digestive problems; group 2, leishmaniasis; group 3, anemia; group 4, dermatological disorders; group 5, urinary problems; group 6, cardiorespiratory problems; group 7, diabetes mellitus; group 8, insulinoma; group 9, general diseases; group 10, control group). Blood glucose and glycated hemoglobin concentrations and hemoglobin and hematocrit values were analyzed in all the animals. In diabetic dogs, a strong increase in blood glycated hemoglobin was observed when compared with the other groups (P < 0.01). In contrast, dogs with insulinoma showed a decrease in blood glycated hemoglobin, though significant differences were not reported in all cases. No change in blood glycated hemoglobin concentrations were reported in dogs affected by other diseases. So, we can suppose that only the chronic alterations in glucose metabolism (chronic hyper- or hypoglycemia) can induce significant changes on the blood glycated hemoglobin concentrations in dogs. PMID:10805256

  20. Determination of Human Hemoglobin Derivatives.

    PubMed

    Attia, Atef M M; Ibrahim, Fatma A A; Abd El-Latif, Noha A; Aziz, Samir W; Abdelmottaleb Moussa, Sherif A; Elalfy, Mohsen S

    2015-01-01

    The levels of the inactive hemoglobin (Hb) pigments [such as methemoglobin (metHb), carboxyhemoglobin (HbCO) and sulfohemoglobin (SHb)] and the active Hb [in the oxyhemoglobin (oxyHb) form] as well as the blood Hb concentration in healthy non pregnant female volunteers were determined using a newly developed multi-component spectrophotometric method. The results of this method revealed values of SHb% in the range (0.0727-0.370%), metHb% (0.43-1.0%), HbCO% (0.4-1.52%) and oxyHb% (97.06-98.62%). Furthermore, the results of this method revealed values of blood Hb concentration in the range (12.608-15.777 g/dL). The method is highly sensitive, accurate and reproducible.

  1. Monoclonal antibodies specific for sickle cell hemoglobin

    SciTech Connect

    Jensen, R.H.; Vanderlaan, M.; Grabske, R.J.; Branscomb, E.W.; Bigbee, W.L.; Stanker, L.H.

    1985-01-01

    Two mouse hybridoma cell lines were isolated which produce monoclonal antibodies that bind hemoglobin S. The mice were immunized with peptide-protein conjugates to stimulate a response to the amino terminal peptide of the beta chain of hemoglobin S, where the single amino acid difference between A and S occurs. Immunocharacterization of the antibodies shows that they bind specifically to the immunogen peptide and to hemoglobin S. The specificity for S is high enough that one AS cell in a mixture with a million AA cells is labeled by antibody, and such cells can be analyzed by flow cytometry. Immunoblotting of electrophoretic gels allows definitive identification of hemoglobin S as compared with other hemoglobins with similar electrophoretic mobility. 12 references, 4 figures.

  2. The Biochemistry of Vitreoscilla hemoglobin

    PubMed Central

    Stark, Benjamin C.; Dikshit, Kanak L.; Pagilla, Krishna R.

    2012-01-01

    The hemoglobin (VHb) from Vitreoscilla was the first bacterial hemoglobin discovered. Its structure and function have been extensively investigated, and engineering of a wide variety of heterologous organisms to express VHb has been performed to increase their growth and productivity. This strategy has shown promise in applications as far-ranging as the production of antibiotics and petrochemical replacements by microorganisms to increasing stress tolerance in plants. These applications of “VHb technology” have generally been of the “black box” variety, wherein the endpoint studied is an increase in the levels of a certain product or improved growth and survival. Their eventual optimization, however, will require a thorough understanding of the various functions and activities of VHb, and how VHb expression ripples to affect metabolism more generally. Here we review the current knowledge of these topics. VHb's functions all involve oxygen binding (and often delivery) in one way or another. Several biochemical and structure-function studies have provided an insight into the molecular details of this binding and delivery. VHb activities are varied. They include supply of oxygen to oxygenases and the respiratory chain, particularly under low oxygen conditions; oxygen sensing and modulation of transcription factor activity; and detoxification of NO, and seem to require interactions of VHb with “partner proteins”. VHb expression affects the levels of ATP and NADH, although not enormously. VHb expression may affect the level of many compounds of intermediary metabolism, and, apparently, alters the levels of expression of many genes. Thus, the metabolic changes in organisms engineered to express VHb are likely to be numerous and complicated. PMID:24688662

  3. Oxygen Measurements in Liposome Encapsulated Hemoglobin

    NASA Astrophysics Data System (ADS)

    Phiri, Joshua Benjamin

    Liposome encapsulated hemoglobins (LEH's) are of current interest as blood substitutes. An analytical methodology for rapid non-invasive measurements of oxygen in artificial oxygen carriers is examined. High resolution optical absorption spectra are calculated by means of a one dimensional diffusion approximation. The encapsulated hemoglobin is prepared from fresh defibrinated bovine blood. Liposomes are prepared from hydrogenated soy phosphatidylcholine (HSPC), cholesterol and dicetylphosphate using a bath sonication method. An integrating sphere spectrophotometer is employed for diffuse optics measurements. Data is collected using an automated data acquisition system employing lock-in -amplifiers. The concentrations of hemoglobin derivatives are evaluated from the corresponding extinction coefficients using a numerical technique of singular value decomposition, and verification of the results is done using Monte Carlo simulations. In situ measurements are required for the determination of hemoglobin derivatives because most encapsulation methods invariably lead to the formation of methemoglobin, a nonfunctional form of hemoglobin. The methods employed in this work lead to high resolution absorption spectra of oxyhemoglobin and other derivatives in red blood cells and liposome encapsulated hemoglobin (LEH). The analysis using singular value decomposition method offers a quantitative means of calculating the fractions of oxyhemoglobin and other hemoglobin derivatives in LEH samples. The analytical methods developed in this work will become even more useful when production of LEH as a blood substitute is scaled up to large volumes.

  4. Hemoglobin Abraham Lincoln, β32 (B14) Leucine → Proline AN UNSTABLE VARIANT PRODUCING SEVERE HEMOLYTIC DISEASE

    PubMed Central

    Honig, George R.; Green, David; Shamsuddin, Mir; Vida, Loyda N.; Mason, R. George; Gnarra, David J.; Maurer, Helen S.

    1973-01-01

    An unstable hemoglobin variant was identified in a Negro woman with hemolytic anemia since infancy. A splenectomy had been performed when the patient was a child. The anemia was accompanied by erythrocyte inclusion bodies and excretion of darkly pigmented urine. Neither parent of the proposita demonstrated any hematologic abnormality, and it appeared that this hemoglobin variant arose as a new mutation. Erythrocyte survival in the patient was greatly reduced: the erythrocyte t½ using radiochromium as a tag was 2.4 days, and a reticulocyte survival study performed after labeling the cells with L-[14C]leucine indicated a t½ of 7.2 days. When stroma-free hemolysates were heated at 50°C, 16-20% of the hemoglobin precipitated. The thermolability was prevented by the addition of hemin, carbon monoxide, or dithionite, suggesting an abnormality of heme binding. An increased rate of methemoglobin formation was also observed after incubation of erythrocytes at 37°C. The abnormal hemoglobin could not be separated from hemoglobin A by electrophoresis or chromatography, but it was possible to isolate the variant β-chain by precipitation with p-hydroxymercuribenzoate. Purification of the β-chain by column chromatography followed by peptide mapping and amino acid analysis demonstrated a substitution of proline for β32 leucine. It appears likely that a major effect of this substitution is a disruption of the normal orientation of the adjacent leucine residue at β31 to impair heme stabilization. Images PMID:4352462

  5. Hemoglobin Abraham Lincoln, beta32 (B14) leucine leads to proline. An unstable variant producing severe hemolytic disease.

    PubMed

    Honig, G R; Green, D; Shamsuddin, M; Vida, L N; Mason, R G; Gnarra, D J; Maurer, H S

    1973-07-01

    An unstable hemoglobin variant was identified in a Negro woman with hemolytic anemia since infancy. A splenectomy had been performed when the patient was a child. The anemia was accompanied by erythrocyte inclusion bodies and excretion of darkly pigmented urine. Neither parent of the proposita demonstrated any hematologic abnormality, and it appeared that this hemoglobin variant arose as a new mutation. Erythrocyte survival in the patient was greatly reduced: the erythrocyte t(1/2) using radiochromium as a tag was 2.4 days, and a reticulocyte survival study performed after labeling the cells with L-[(14)C]leucine indicated a t(1/2) of 7.2 days. When stroma-free hemolysates were heated at 50 degrees C, 16-20% of the hemoglobin precipitated. The thermolability was prevented by the addition of hemin, carbon monoxide, or dithionite, suggesting an abnormality of heme binding. An increased rate of methemoglobin formation was also observed after incubation of erythrocytes at 37 degrees C. The abnormal hemoglobin could not be separated from hemoglobin A by electrophoresis or chromatography, but it was possible to isolate the variant beta-chain by precipitation with p-hydroxymercuribenzoate. Purification of the beta-chain by column chromatography followed by peptide mapping and amino acid analysis demonstrated a substitution of proline for beta32 leucine. It appears likely that a major effect of this substitution is a disruption of the normal orientation of the adjacent leucine residue at beta31 to impair heme stabilization.

  6. Hemoglobin-based red blood cell substitutes.

    PubMed

    Chang, Thomas Ming Swi

    2004-09-01

    Polyhemoglobin is already well into the final stages of clinical trials in humans with one approved for routine clinical use in South Africa. Conjugated hemoglobin is also in ongoing clinical trials. Meanwhile, recombinant Hb has been modified to modulate the effects of nitric oxide. Other systems contain antioxidant enzymes for those clinical applications that may have potential problems related to ischemia-reperfusion injuries. Other developments are based on hemoglobin-lipid vesicles and also the use of nanotechnology and biodegradable copolymers to prepare nanodimension artificial red blood cells containing hemoglobin and complex enzyme systems.

  7. Variant hemoglobin phenotypes may account for differential erythropoiesis-stimulating agent dosing in African-American hemodialysis patients.

    PubMed

    Derebail, Vimal K; Nachman, Patrick H; Key, Nigel S; Ansede, Heather; Falk, Ronald J; Rosamond, Wayne D; Kshirsagar, Abhijit V

    2011-11-01

    African-American patients with end-stage renal disease have historically lower hemoglobin concentrations and higher requirements of erythropoiesis-stimulating agent (ESA). While disparities in health-care access may partially explain these findings, the role of variant hemoglobin, such as sickle trait, has not been investigated. To clarify this, we evaluated 154 African-American patients receiving in-center hemodialysis with available hemoglobin phenotyping. The primary exposure was any abnormal hemoglobin variant and the primary outcome of higher-dose ESA was defined as a dose of 6500 or more units per treatment. Logistic regression assessed the association between variant hemoglobin and higher-dose ESA. Covariates included age, gender, diabetes, iron parameters, intravenous iron dose, parathyroid hormone, albumin, phosphorus, body mass index, vascular access type, hospitalization/missed treatments, smoking status, alcohol abuse, and gastrointestinal bleeding. Of 33 patients with variant hemoglobin, 24 had HbAS and 9 had HbAC. Univariate odds of higher-dose ESA among those with hemoglobin variants were twice that of those with the normal HbAA phenotype (odds ratio 2.05). In multivariate models, the likelihood of higher-dose ESA had an odds ratio of 3.31 and the nature of this relationship did not change in Poisson regression or sensitivity analyses. Hence, our findings may explain, in part, the difference in ESA dosing between Caucasians and African-Americans with end-stage renal disease but await further study.

  8. [Research on Early Diagnosis of Gastric Cancer by the Surface Enhanced Raman Spectroscopy of Human Hemoglobin].

    PubMed

    Wang, Wei; Pan, Zhi-feng; Tang, Wei-yue; Li, Yun-tao; Fan, Chun-zhen

    2015-12-01

    Early diagnosis have great positive effect on the treatment of gastric cancer patients. Raman spectroscopy can provide a useful monitor for hemoglobin dynamics. Besides, Raman spectroscopy has notable advantages in the fields of abnormal hemoglobin diagnosis, hemoglobin oxygen saturation deter mination and blood methemoglobin analysis. In this paper, novel silver colloid was synthesized by microwave heated method. The surface enhanced Raman spectrums of hemoglobin from 11 normal persons and 20 gastric cancer patients are measured and analyzed in order to obtain spectrums which are high repeatability and characteristic peaks protruding. By analyzing the assignations of the SERS bands, it found that the content of asparagine, tyrosine and phenylalanine in the hemoglobin are significantly lower than healthy people. Discussing the structure of hemoglobin, when hemoglobin combines with oxygen, Fe²⁺ is in a low spin state, ionic radius shrinks and moves 0. 075 nm and fall into the pore in the middle of the heme porphyrin ring plane. This spatial variation affects F8His connected with the iron, will narrow the gap between the globin in the two strands of the helix, as a result, HC2 tyrosine pushed out of the void. Using this mechanism, the absorption peak of 1 560 cm⁻¹ confirmed that the tyrosine content in patients with gastric cancer was lower than that of normal people. Principal component analysis(PCA) is employed to get a three-dimensional scatter plot of PC scores for the health and cancer groups, and it can be learned that they are distributed in separate areas. By using the method of discriminate analysis, it is found that the diagnostic algorithm separates the two groups with sensitivity of 90.0% and diagnostic specificity of 90.9%, the overall diagnostic accuracy was 90.3%. The results from this exploratory study demonstrate that, SERS detection of oxyhemoglobin combined with multivariate analysis would be an effective method for early diagnosis of gastric

  9. [Research on Early Diagnosis of Gastric Cancer by the Surface Enhanced Raman Spectroscopy of Human Hemoglobin].

    PubMed

    Wang, Wei; Pan, Zhi-feng; Tang, Wei-yue; Li, Yun-tao; Fan, Chun-zhen

    2015-12-01

    Early diagnosis have great positive effect on the treatment of gastric cancer patients. Raman spectroscopy can provide a useful monitor for hemoglobin dynamics. Besides, Raman spectroscopy has notable advantages in the fields of abnormal hemoglobin diagnosis, hemoglobin oxygen saturation deter mination and blood methemoglobin analysis. In this paper, novel silver colloid was synthesized by microwave heated method. The surface enhanced Raman spectrums of hemoglobin from 11 normal persons and 20 gastric cancer patients are measured and analyzed in order to obtain spectrums which are high repeatability and characteristic peaks protruding. By analyzing the assignations of the SERS bands, it found that the content of asparagine, tyrosine and phenylalanine in the hemoglobin are significantly lower than healthy people. Discussing the structure of hemoglobin, when hemoglobin combines with oxygen, Fe²⁺ is in a low spin state, ionic radius shrinks and moves 0. 075 nm and fall into the pore in the middle of the heme porphyrin ring plane. This spatial variation affects F8His connected with the iron, will narrow the gap between the globin in the two strands of the helix, as a result, HC2 tyrosine pushed out of the void. Using this mechanism, the absorption peak of 1 560 cm⁻¹ confirmed that the tyrosine content in patients with gastric cancer was lower than that of normal people. Principal component analysis(PCA) is employed to get a three-dimensional scatter plot of PC scores for the health and cancer groups, and it can be learned that they are distributed in separate areas. By using the method of discriminate analysis, it is found that the diagnostic algorithm separates the two groups with sensitivity of 90.0% and diagnostic specificity of 90.9%, the overall diagnostic accuracy was 90.3%. The results from this exploratory study demonstrate that, SERS detection of oxyhemoglobin combined with multivariate analysis would be an effective method for early diagnosis of gastric

  10. Structure of Hemoglobin M Boston, a Variant with a Five-Coordinated Ferric Heme

    PubMed Central

    Pulsinelli, P. D.; Perutz, M. F.; Nagel, R. L.

    1973-01-01

    X-ray analysis of the natural valency hybrid α2+M Bostonβ2deoxy shows that the ferric iron atoms in the abnormal α subunits are bonded to the phenolate side chains of the tyrosines that have replaced the distal histidines; the iron atoms are displaced to the distal side of the porphyrin ring and are not bonded to the proximal histidines. The resulting changes in tertiary structure of the α subunits stabilize the hemoglobin tetramer in the quaternary deoxy structure, which lowers the oxygen affinity of the normal β subunits and causes cyanosis. The strength of the bond from the ferric iron to the phenolate oxygen appears to be the main factor responsible for the many abnormal properties of hemoglobin M Boston. Images PMID:4521212

  11. Blood Test: Hemoglobin A1C

    MedlinePlus

    ... the person's average blood sugar levels over that time. Why It's Done Doctors use the hemoglobin A1c test to determine if your child's diabetes management plan needs to be adjusted. Typically the test ...

  12. Nanobiotechnology for hemoglobin-based blood substitutes.

    PubMed

    Chang, T M S

    2009-04-01

    Nanobiotechnology is the assembling of biological molecules into nanodimension complexes. This has been used for the preparation of polyhemoglobin formed by the assembling of hemoglobin molecules into a soluble nanodimension complex. New generations of this approach include the nanobiotechnological assembly of hemoglobin, catalase, and superoxide dismutase into a soluble nanodimension complex. This acts as an oxygen carrier and an antioxidant for those conditions with potential for ischemiareperfusion injuries. Another recent novel approach is the assembling of hemoglobin and fibrinogen into a soluble nanodimension polyhemoglobin-fibrinogen complex that acts as an oxygen carrier with platelet-like activity. This is potentially useful in cases of extensive blood loss requiring massive replacement using blood substitutes, resulting in the need for the replacement of platelets and clotting factors. A further step is the preparation of nanodimension artificial red blood cells that contain hemoglobin and all the enzymes present in red blood cells.

  13. Hemoglobins, programmed cell death and somatic embryogenesis.

    PubMed

    Hill, Robert D; Huang, Shuanglong; Stasolla, Claudio

    2013-10-01

    Programmed cell death (PCD) is a universal process in all multicellular organisms. It is a critical component in a diverse number of processes ranging from growth and differentiation to response to stress. Somatic embryogenesis is one such process where PCD is significantly involved. Nitric oxide is increasingly being recognized as playing a significant role in regulating PCD in both mammalian and plant systems. Plant hemoglobins scavenge NO, and evidence is accumulating that events that modify NO levels in plants also affect hemoglobin expression. Here, we review the process of PCD, describing the involvement of NO and plant hemoglobins in the process. NO is an effector of cell death in both plants and vertebrates, triggering the cascade of events leading to targeted cell death that is a part of an organism's response to stress or to tissue differentiation and development. Expression of specific hemoglobins can alter this response in plants by scavenging the NO, thus, interrupting the death process. Somatic embryogenesis is used as a model system to demonstrate how cell-specific expression of different classes of hemoglobins can alter the embryogenic process, affecting hormone synthesis, cell metabolite levels and genes associated with PCD and embryogenic competence. We propose that plant hemoglobins influence somatic embryogenesis and PCD through cell-specific expression of a distinct plant hemoglobin. It is based on the premise that both embryogenic competence and PCD are strongly influenced by cellular NO levels. Increases in cellular NO levels result in elevated Zn(2+) and reactive-oxygen species associated with PCD, but they also result in decreased expression of MYC2, a transcription factor that is a negative effector of indoleacetic acid synthesis, a hormone that positively influences embryogenic competence. Cell-specific hemoglobin expression reduces NO levels as a result of NO scavenging, resulting in cell survival.

  14. Cloned Hemoglobin Genes Enhance Growth Of Cells

    NASA Technical Reports Server (NTRS)

    Khosla, Chaitan; Bailey, James E.

    1991-01-01

    Experiments show that portable deoxyribonucleic acid (DNA) sequences incorporated into host cells make them produce hemoglobins - oxygen-binding proteins essential to function of red blood cells. Method useful in several biotechnological applications. One, enhancement of growth of cells at higher densities. Another, production of hemoglobin to enhance supplies of oxygen in cells, for use in chemical reactions requiring oxygen, as additive to serum to increase transport of oxygen, and for binding and separating oxygen from mixtures of gases.

  15. Evolution of ruminant hemoglobins. Thermodynamic divergence of ox and buffalo hemoglobins.

    PubMed

    Giardina, B; Arevalo, F; Clementi, M E; Ferrara, L; Di Luccia, A; Lendaro, E; Bellelli, A; Condò, S G

    1992-03-01

    The ligand-binding properties of hemoglobins from two homozygote phenotypes (AA and BB) of water buffalo (Bubalus bubalis) have been characterized by equilibrium and kinetic techniques. In the case of the BB phenotype, the two constituent hemoglobins have been purified and separately analysed. Buffalo hemoglobins display the reduced sensitivity to organic phosphates characteristic of ruminant hemoglobins, their physiological effector probably being the chloride ion. In contrast to the other known hemoglobins from ruminants, all the hemoglobins from the water buffalo display a significant temperature sensitivity, the delta H for oxygen binding in the presence of physiological effectors approaching that of human hemoglobin (delta H = -30.5 kJ/mol O2). This discrepancy with the other ruminant hemoglobins (e.g. ox, delta H = -10.4 kJ/mol O2), whose primary structure is very similar to that of buffalo, hemoglobins might be correlated to the different habitat and phylogenetic history of the two subfamilies (Bos and Bubalus) of Bovidae.

  16. Enteral and parenteral feeding influences mortality after hemoglobin-E. coli peritonitis in normal rats.

    PubMed

    Kudsk, K A; Stone, J M; Carpenter, G; Sheldon, G F

    1983-07-01

    Enteral feeding with 25% dextrose-4.25% Freamine II (TPN) improves the survival of malnourished animals to normal levels after hemoglobin-E. coli adjuvant peritonitis, whereas intravenous feeding does not. To determine whether intravenous feeding maintained a high survival rate in previously well-nourished animals, 81 rats received TPN via gastrostomy or intravenous infusion for 12 days. They were then fasted for 24 hours and given a septic challenge. Gastrostomy-fed animals survived the challenge significantly better than intravenously fed animals. Enteral feeding appears to be important in producing a high survival rate after hemoglobin-E. coli adjuvant peritonitis.

  17. Hemoglobin parameters from diffuse reflectance data

    PubMed Central

    Mourant, Judith R.; Marina, Oana C.; Hebert, Tiffany M.; Kaur, Gurpreet; Smith, Harriet O.

    2014-01-01

    Abstract. Tissue vasculature is altered when cancer develops. Consequently, noninvasive methods of monitoring blood vessel size, density, and oxygenation would be valuable. Simple spectroscopy employing fiber optic probes to measure backscattering can potentially determine hemoglobin parameters. However, heterogeneity of blood distribution, the dependence of the tissue-volume-sampled on scattering and absorption, and the potential compression of tissue all hinder the accurate determination of hemoglobin parameters. We address each of these issues. A simple derivation of a correction factor for the absorption coefficient, μa, is presented. This correction factor depends not only on the vessel size, as others have shown, but also on the density of blood vessels. Monte Carlo simulations were used to determine the dependence of an effective pathlength of light through tissue which is parameterized as a ninth-order polynomial function of μa. The hemoglobin bands of backscattering spectra of cervical tissue are fit using these expressions to obtain effective blood vessel size and density, tissue hemoglobin concentration, and oxygenation. Hemoglobin concentration and vessel density were found to depend on the pressure applied during in vivo acquisition of the spectra. It is also shown that determined vessel size depends on the blood hemoglobin concentration used. PMID:24671524

  18. Subunit dissociations in natural and recombinant hemoglobins.

    PubMed

    Manning, L R; Jenkins, W T; Hess, J R; Vandegriff, K; Winslow, R M; Manning, J M

    1996-04-01

    A precise and rapid procedure employing gel filtration on Superose-12 to measure the tetramer-dimer dissociation constants of some natural and recombinant hemoglobins in the oxy conformation is described. Natural sickle hemoglobin was chosen to verify the validity of the results by comparing the values with those reported using an independent method not based on gel filtration. Recombinant sickle hemoglobin, as well as a sickle double mutant with a substitution at the Val-6(beta) receptor site, had approximately the same dissociation constant as natural sickle hemoglobin. Of the two recombinant hemoglobins with amino acid replacements in the alpha 1 beta 2 subunit interface, one was found to be extensively dissociated and the other completely dissociated. In addition, the absence of an effect of the allosteric regulators DPG and IHP on the dissociation constant was demonstrated. Thus, a tetramer dissociation constant can now be determined readily and used together with other criteria for characterization of hemoglobins and their interaction with small regulatory molecules. PMID:8845768

  19. AMINO ACIDS AND HEMOGLOBIN PRODUCTION IN ANEMIA

    PubMed Central

    Whipple, G. H.; Robscheit-Robbins, F. S.

    1940-01-01

    Certain individual amino acids when given to standard anemic dogs cause an increase in new hemoglobin production. Occasional negative experiments are recorded. Glycine, glutamic acid, aspartic acid, cystine, histidine, phenylalanine, and proline when given in 1 gm. doses daily for 2 weeks, increase hemoglobin output on the average 23 to 25 gm. above the control level. This reaction amounts to 25 to 30 per cent of the new hemoglobin produced by the feeding of 300 gm. liver daily for 2 weeks—a standard liver test. Alanine, valine, isoleucine, and arginine in the same dosage increase the hemoglobin output on the average 13 to 17 gm. per 2 weeks over the control level. Leucine, methionine, lysine, tryptophane, and tyrosine fall in a middle group with hemoglobin output of about 20 gm. Isovaleric acid, β-hydroxybutyric acid, glutaric acid, and asparagine have shown positive effects and the butyrate is unusually potent for hemoglobin production (Table 2). The isomeric and dl-synthetic forms of the amino acids are as effectively utilized in this reaction as are the natural forms. PMID:19870982

  20. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  1. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  2. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  3. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  4. 21 CFR 864.7500 - Whole blood hemoglobin assays.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Whole blood hemoglobin assays. 864.7500 Section... blood hemoglobin assays. (a) Identification. A whole blood hemoglobin assay is a device consisting or... hemoglobin content of whole blood for the detection of anemia. This generic device category does not...

  5. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  6. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  7. Hemoglobin, nitric oxide and molecular mechanisms of hypoxic vasodilation

    PubMed Central

    Allen, Barry W.; Stamler, Jonathan S.; Piantadosi, Claude A.

    2009-01-01

    The protected transport of nitric oxide (NO) by hemoglobin (Hb) links the metabolic activity of working tissue to the regulation of its local blood supply through hypoxic vasodilation. This physiologic mechanism is allosterically coupled to the O2 saturation of Hb and involves the covalent binding of NO to a cysteine residue in the β-chain of Hb (Cys β93) to form S-nitrosohemoglobin (SNO-Hb). Subsequent S-transnitrosation, the transfer of NO groups to thiols on the RBC membrane and then in the plasma, preserves NO vasodilator activity for delivery to the vascular endothelium. This SNO-Hb paradigm provides insight into the respiratory cycle and a new therapeutic focus for diseases involving abnormal microcirculatory perfusion. In addition, the formation of S-nitrosothiols in other proteins may regulate an array of physiological functions. PMID:19781996

  8. The renal handling of hemoglobin. I. Glomerular filtration.

    PubMed

    Bunn, H F; Esham, W T; Bull, R W

    1969-05-01

    The glomerular filtration of hemoglobin (alpha(2)beta(2)) was studied under conditions in which its dissociation into alphabeta dimers was experimentally altered. Rats receiving hemoglobin treated with the sulfhydryl reagent bis(N-maleimidomethyl) ether (BME) showed a much lower renal excretion and prolonged plasma survival as compared with animals injected with untreated hemoglobin. Plasma disappearance was also prolonged in dogs receiving BME hemoglobin. Gel filtration data indicated that under physiological conditions, BME hemoglobin had impaired subunit dissociation. In addition, BME hemoglobin showed a very high oxygen affinity and a decreased rate of auto-oxidation. Glomerular filtration was enhanced under conditions which favor the dissociation of hemoglobin into dimers. Cat hemoglobin, which forms subunits much more extensively than canine hemoglobin, was excreted more readily by the rat kidney. The renal uptake of (59)Fe hemoglobin injected intra-arterially into rabbits varied inversely with the concentration of the injected dose.

  9. Protein characterization by LC-MS/MS may be required for the DNA identification of a fusion hemoglobin: the example of Hb P-Nilotic.

    PubMed

    Zanella-Cleon, Isabelle; Delolme, Frédéric; Lacan, Philippe; Garcia, Caroline; Vinatier, Isabelle; Francina, Alain; Joly, Philippe

    2012-02-01

    DNA analysis is currently the easiest way to identify a hemoglobin variant in most cases. Nevertheless, in case of complex gene rearrangements, mass spectrometry studies may be required to orientate the DNA diagnosis. The present report shows the use of mass spectrometry techniques prior to DNA analysis for the identification of the rare P-Nilotic fusion hemoglobin. Complete protein analysis is performed by liquid chromatography-tandem mass spectrometry on the abnormal globin chain isolated by reversed-phase liquid chromatography.

  10. Anion Bohr effect of human hemoglobin.

    PubMed

    Bucci, E; Fronticelli, C

    1985-01-15

    The pH dependence of oxygen affinity of hemoglobin (Bohr effect) is due to ligand-linked pK shifts of ionizable groups. Attempt to identify these groups has produced controversial data and interpretations. In a further attempt to clarify the situation, we noticed that hemoglobin alkylated in its liganded form lost the Bohr effect while hemoglobin alkylated in its unliganded form showed the presence of a practically unmodified Bohr effect. In spite of this difference, analyses of the extent of alkylation of the two compounds failed to identify the presence of specific preferential alkylations. In particular, the alpha 1 valines and beta 146 histidines appeared to be alkylated to the same extent in the two proteins. Focusing our attention on the effect of the anions on the functional properties of hemoglobin, we measured the Bohr effect of untreated hemoglobin in buffers made with HEPES [N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid], MES [2-(N-morpholino)ethanesulfonic acid], and MOPS [3-(N-morpholino)propanesulfonic acid], which being zwitterions do not need addition of chlorides or other anions for reaching the desired pH. The shape acquired by the Bohr effect curves, either as pH dependence of oxygen affinity or as pH dependence of protons exchanged with the solution, was irreconcilable with that of the Bohr effect curves in usual buffers. This indicated the relevance of solvent components in determining the functional properties of hemoglobin. A new thermodynamic model is proposed for the Bohr effect that includes the interaction of hemoglobin with solvent components. The classic proton Bohr effect is a special case of the new theory.

  11. Properties of Hemoglobin Solutions in Red Cells

    PubMed Central

    Gary-Bobo, C. M.; Solomon, A. K.

    1968-01-01

    The present studies are concerned with a detailed examination of the apparent anomalous osmotic behavior of human red cells. Red cell water has been shown to behave simultaneously as solvent water for nonelectrolytes and nonsolvent water, in part, for electrolytes. The nonsolvent properties are based upon assumptions inherent in the conventional van't Hoff equation. However, calculations according to the van't Hoff equation give osmotic volumes considerably in excess of total cell water when the pH is lowered beyond the isoelectric point for hemoglobin; hence the van't Hoff equation is inapplicable for the measurement of the solvent properties of the red cell. Furthermore, in vitro measurements of osmotic and other properties of 3.7 millimolal solutions of hemoglobin have failed to reveal the presence of any salt exclusion. A new hypothesis has been developed from thermodynamic principles alone, which predicts that, at constant pH, the net charge on the hemoglobin molecule decreases with increased hemoglobin concentration. The existence of such cooperative interaction may be inferred from the effect of pH on the changes in hemoglobin net charge as the spacing between the molecules decreases. The resultant movement of counterions across the cell membrane causes the apparent anomalous osmotic behavior. Quantitative agreement has been found between the anion shift predicted by the equation and that observed in response to osmotic gradients. The proposed mechanism appears to be operative in a variety of tissues and could provide an electrical transducer for osmotic signals. PMID:5688085

  12. NHANES III: influence of race on GFR thresholds and detection of metabolic abnormalities.

    PubMed

    Foley, Robert N; Wang, Changchun; Ishani, Areef; Collins, Allan J

    2007-09-01

    Whether the creatinine-based glomerular filtration rate (GFR) thresholds used to define chronic kidney disease (CKD) identify metabolic abnormalities similarly in minority and nonminority populations is unknown. We addressed this question among adult participants in the Third National Health and Nutrition Examination Survey (NHANES III) (n = 15,837). GFR was estimated from serum creatinine values and metabolic abnormalities were defined by 5th or 95th percentile values. After adjustment for age, demographic characteristics, and GFR, black participants were significantly more likely than white participants to have abnormal levels of systolic and diastolic blood pressure, hemoglobin, phosphorus, and uric acid. Hispanic subjects were significantly more likely to have abnormal levels of systolic blood pressure, hemoglobin, bicarbonate, and phosphorus. Among participants with GFR < 60 mL/min per 1.73 m(2), black participants were significantly more likely to have abnormal levels of systolic and diastolic blood pressure, hemoglobin, and uric acid; Hispanic subjects were significantly more likely to have abnormal systolic blood pressure levels. Metabolic abnormalities were more common in minority populations, and low GFR appeared to have a multiplicative effect. Defining CKD using a single GFR threshold may be disadvantageous for minority populations because metabolic abnormalities are present at higher levels of GFR.

  13. Hemoglobin Cranston, an unstable variant having an elongated beta chain due to nonhomologous crossover between two normal beta chain genes.

    PubMed Central

    Bunn, H F; Schmidt, G J; Haney, D N; Dluhy, R G

    1975-01-01

    An asymptomatic woman was found to have a compensated hemolytic state due to an unstable hemoglobin variant, comprising 35% of the total. Peptide maps of tryptic digests of the abnormal beta chain were identical to those of beta A except that tryptic peptide 15 (Tyr-His-COOH) was absent and a new peptide was detected, containing equivalent amounts of Ser, Ile, Thr, and Lys. Its sequence was determined by manual Edman degradation. An additional hydrophobic peptide isolated by counter-current distribution contained: Asx, Ser, Ala, Tyr, 2 Phe, and 3 Leu. Its sequence was determined on an automatic solid phase sequencer. Digestion with carboxypeptidase A confirmed the C-terminal sequence. Hemoglobin Cranston has an elongated beta chain with the following structure: (see article). This variant is the first "adult" human hemoglobin known to contain isoleucine. It is likely that hemoglobin Cranston arose because of a nonhomologous crossover of two normal beta chain genes, probably during meiosis, with the insertion of two nucleotides (AG) at position 144, resulting in a frame shift. Hemoglobin Cranston provides new information on the structure of the beta chain gene as well as an explanation of both the structure and genetic basis of hemoglobin Tak, the only other elongated beta chain variant that has been described. Images PMID:1059149

  14. Classification of the Disorders of Hemoglobin

    PubMed Central

    Forget, Bernard G.; Bunn, H. Franklin

    2013-01-01

    Over the years, study of the disorders of hemoglobin has served as a paradigm for gaining insights into the cellular and molecular biology, as well as the pathophysiology, of inherited genetic disorders. To date, more than 1000 disorders of hemoglobin synthesis and/or structure have been identified and characterized. Study of these disorders has established the principle of how a mutant genotype can alter the function of the encoded protein, which in turn can lead to a distinct clinical phenotype. Genotype/phenotype correlations have provided important understanding of pathophysiological mechanisms of disease. Before presenting a brief overview of these disorders, we provide a summary of the structure and function of hemoglobin, along with the mechanism of assembly of its subunits, as background for the rationale and basis of the different categories of disorders in the classification. PMID:23378597

  15. Characterization of Polyethylene Glycol Modified Hemoglobins

    NASA Astrophysics Data System (ADS)

    Salazar, Gil; Barr, James; Morgan, Wayne; Ma, Li

    2011-03-01

    Polyethylene glycol modified hemoglobins (PEGHbs) was characterized by liquid chromatography and fluorescence methods. We prepared four samples of two different molecular weight PEG, 5KDa and 20KDa, modified bovine and human hemoglobin. We studied the oxygen affinities, stabilities, and peroxidase activities of PEGHbs. We have related oxygen affinities with different degrees of modifications. The data showed that the modification on the beta subunits was less stable than that of the alpha subunits on the human Hb based samples especially. We also compared peroxidase activities among different modified PEGHbs.

  16. In vitro study of the direct effect of extracellular hemoglobin on myelin components.

    PubMed

    Bamm, Vladimir V; Lanthier, Danielle K; Stephenson, Erin L; Smith, Graham S T; Harauz, George

    2015-01-01

    There is a relationship between cerebral vasculature and multiple sclerosis (MS) lesions: abnormal accumulations of iron have been found in the walls of dilated veins in MS plaques. The sources of this iron can be varied, but capillary and venous hemorrhages leading to blood extravasation have been recorded, and could result in the release of hemoglobin extracellularly. Extracellular hemoglobin oxidizes quickly and is known to become a reactive molecule that triggers low-density lipoprotein oxidation and plays a pivotal role in atherogenesis. In MS, it could lead to local oxidative stress, inflammation, and tissue damage. Here, we investigated whether extracellular hemoglobin and its breakdown products can cause direct oxidative damage to myelin components in a peroxidative environment such as occurs in inflamed tissue. Oxidation of lipids was assessed by the formation of fluorescent peroxidized lipid-protein covalent adducts, by the increase in conjugated diene and malondialdehyde. Oxidation of proteins was analyzed by the change in protein mass. The results suggest that the globin radical could be a trigger of myelin basic protein oxidative cross-linking, and that heme transferred to the lipids is involved in lipid peroxidation. This study provides new insight into the mechanism by which hemoglobin exerts its pathological oxidative activity towards myelin components. This work supports further research into the vascular pathology in MS, to gain insight into the origin and role of iron deposits in disease pathogenesis, or in stimulation of different comorbidities such as cardiovascular disease.

  17. Asymptomatic child heterozygous for hemoglobin S and hemoglobin Pôrto Alegre.

    PubMed

    Lojo, Liliana; Santiago-Borrero, Pedro; Rivera, Enid; Renta, Jessicca; Cadilla, Carmen L

    2011-03-01

    Hemoglobin Pôrto Alegre (PA) is a rare hemoglobin resulting from a mutation in β9(A6)Ser → Cys. We describe an asymptomatic Puerto Rican female with combined heterozygosity for Hb PA and Hb S. Since birth, she has maintained normal hemoglobin, bilirubin, LDH levels, and reticulocyte count. Peripheral smear evaluation has revealed normal erythrocyte morphology with no changes suggestive of hemolysis. We conclude that the presence of Hb PA does not increase the risk of red blood cell sickling in patients who carry the Hb S mutation.

  18. Asymptomatic Child Heterozygous for Hemoglobin S and Hemoglobin Pôrto Alegre

    PubMed Central

    Lojo, Liliana; Santiago-Borrero, Pedro; Rivera, Enid; Renta, Jessicca; Cadilla, Carmen L

    2013-01-01

    Hemoglobin Pôrto Alegre (PA) is a rare hemoglobin resulting from a mutation in β9(A6)Ser→Cys. We describe an asymptomatic Puerto Rican female with combined heterozygosity for Hb PA and Hb S. Since birth, she has maintained normal hemoglobin, bilirubin, LDH levels, and reticulocyte count. Peripheral smear evaluation has revealed normal erythrocyte morphology with no changes suggestive of hemolysis. We conclude that the presence of Hb PA does not increase the risk of red blood cell sickling in patients who carry the Hb S mutation. PMID:21225927

  19. Unrecognized hemoglobin SE disease as microcytosis

    PubMed Central

    Cooper, Barry; Guileyardo, Joseph; Mora, Adan

    2016-01-01

    Hemoglobin SE disease was first described during the 1950s as a relatively benign microcytosis, but increasing prevalence has revealed a predisposition towards vasoocclusive sickling. Recognition of SE hemoglobinopathies’ potential complications is crucial so medical measures can be utilized to avoid multiorgan injury. PMID:27365881

  20. Metastable Polymerization of Sickle Hemoglobin in Droplets

    PubMed Central

    Aprelev, Alexey; Weng, Weijun; Zakharov, Mikhail; Rotter, Maria; Yosmanovich, Donna; Kwong, Suzanna; Briehl, Robin W.; Ferrone, Frank A.

    2007-01-01

    Sickle cell disease arises from a genetic mutation of one amino acid in each of the two hemoglobin β chains, leading to the polymerization of hemoglobin in the red cell upon deoxygenation, and is characterized by vascular crises and tissue damage due to the obstruction of small vessels by sickled cells. It has been an untested assumption that, in red cells that sickle, the growing polymer mass would consume monomers until the thermodynamically well-described monomer solubility was reached. By photolyzing droplets of sickle hemoglobin suspended in oil we find that polymerization does not exhaust the available store of monomers, but stops prematurely, leaving the solutions in a supersaturated, metastable state typically 20% above solubility at 37°C, though the particular values depend on the details of the experiment. We propose that polymer growth stops because the growing ends reach the droplet edge, whereas new polymer formation is thwarted by long nucleation times, since the hemoglobin concentration is lowered by depletion of monomers into the polymers that have formed. This finding suggests a new aspect to the pathophysiology of sickle cell disease, namely, that cells deoxygenated in the microcirculation are not merely undeformable, but will actively wedge themselves tightly against the walls of the microvasculature by a ratchet-like mechanism driven by the supersaturated solution. PMID:17493634

  1. Circular dichroism and conformation of fish hemoglobins.

    PubMed

    Greenwood, C; Gibson, Q H

    1983-04-10

    The circular dichroism spectrum of fully liganded CO hemoglobin from the Atlantic bluefin tuna (Tunnus thynnus) shows a pH- and temperature-dependent feature at 416 nm. It is half-developed at pH 5.9 and 20 degrees C and its change with temperature corresponds to a heat of 34 kcal/mol (tetramer) for the transition. Correlation with studies on function (Morris, R. J., and Gibson, Q. H. (1982) J. Biol. Chem. 257, 4869-4874) shows that the dichroism feature changes at about 1 pH unit below the R-T transition. There is a close correlation between the 416 nm band and changes in circular dichroism at 287 nm. The new 416 nm band is seen in several fish hemoglobins, but not with human hemoglobin. With hemoglobin from Brevoortia tyrannus, which has been sufficiently studied to permit the comparison, there is a smaller gap between the change in dichroism spectrum and the functional R-T transition. So far, no change in function has been associated with the appearance of the 416 nm circular dichroism band. PMID:6833248

  2. Hemoglobin: A Nitric-Oxide Dioxygenase

    PubMed Central

    Gardner, Paul R.

    2012-01-01

    Members of the hemoglobin superfamily efficiently catalyze nitric-oxide dioxygenation, and when paired with native electron donors, function as NO dioxygenases (NODs). Indeed, the NOD function has emerged as a more common and ancient function than the well-known role in O2 transport-storage. Novel hemoglobins possessing a NOD function continue to be discovered in diverse life forms. Unique hemoglobin structures evolved, in part, for catalysis with different electron donors. The mechanism of NOD catalysis by representative single domain hemoglobins and multidomain flavohemoglobin occurs through a multistep mechanism involving O2 migration to the heme pocket, O2 binding-reduction, NO migration, radical-radical coupling, O-atom rearrangement, nitrate release, and heme iron re-reduction. Unraveling the physiological functions of multiple NODs with varying expression in organisms and the complexity of NO as both a poison and signaling molecule remain grand challenges for the NO field. NOD knockout organisms and cells expressing recombinant NODs are helping to advance our understanding of NO actions in microbial infection, plant senescence, cancer, mitochondrial function, iron metabolism, and tissue O2 homeostasis. NOD inhibitors are being pursued for therapeutic applications as antibiotics and antitumor agents. Transgenic NOD-expressing plants, fish, algae, and microbes are being developed for agriculture, aquaculture, and industry. PMID:24278729

  3. Trematode hemoglobins show exceptionally high oxygen affinity.

    PubMed

    Kiger, L; Rashid, A K; Griffon, N; Haque, M; Moens, L; Gibson, Q H; Poyart, C; Marden, M C

    1998-08-01

    Ligand binding studies were made with hemoglobin (Hb) isolated from trematode species Gastrothylax crumenifer (Gc), Paramphistomum epiclitum (Pe), Explanatum explanatum (Ee), parasitic worms of water buffalo Bubalus bubalis, and Isoparorchis hypselobagri (Ih) parasitic in the catfish Wallago attu. The kinetics of oxygen and carbon monoxide binding show very fast association rates. Whereas oxygen can be displaced on a millisecond time scale from human Hb at 25 degrees C, the dissociation of oxygen from trematode Hb may require a few seconds to over 20 s (for Hb Pe). Carbon monoxide dissociation is faster, however, than for other monomeric hemoglobins or myoglobins. Trematode hemoglobins also show a reduced rate of autoxidation; the oxy form is not readily oxidized by potassium ferricyanide, indicating that only the deoxy form reacts rapidly with this oxidizing agent. Unlike most vertebrate Hbs, the trematodes have a tyrosine residue at position E7 instead of the usual distal histidine. As for Hb Ascaris, which also displays a high oxygen affinity, the trematodes have a tyrosine in position B10; two H-bonds to the oxygen molecule are thought to be responsible for the very high oxygen affinity. The trematode hemoglobins display a combination of high association rates and very low dissociation rates, resulting in some of the highest oxygen affinities ever observed.

  4. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  5. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  6. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Hemoglobin glutamer-200 (bovine). 522.1125 Section... § 522.1125 Hemoglobin glutamer-200 (bovine). (a) Specifications. Each 125 milliliter bag contains 13 grams per deciliter of polymerized hemoglobin of bovine origin in modified Lactated Ringer's...

  7. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  8. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  9. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  10. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... hemoglobin polypeptide chains). The hemoglobin determination may be made by methods such as...

  11. Bioimaging techniques for subcellular localization of plant hemoglobins and measurement of hemoglobin-dependent nitric oxide scavenging in planta.

    PubMed

    Hebelstrup, Kim H; Østergaard-Jensen, Erik; Hill, Robert D

    2008-01-01

    Plant hemoglobins are ubiquitous in all plant families. They are expressed at low levels in specific tissues. Several studies have established that plant hemoglobins are scavengers of nitric oxide (NO) and that varying the endogenous level of hemoglobin in plant cells negatively modulates bioactivity of NO generated under hypoxic conditions or during cellular signaling. Earlier methods for determination of hemoglobin-dependent scavenging in planta were based on measuring activity in whole plants or organs. Plant hemoglobins do not contain specific organelle localization signals; however, earlier reports on plant hemoglobin have demonstrated either cytosolic or nuclear localization, depending on the method or cell type investigated. We have developed two bioimaging techniques: one for visualization of hemoglobin-catalyzed scavenging of NO in specific cells and another for visualization of subcellular localization of green fluorescent protein-tagged plant hemoglobins in transformed Arabidopsis thaliana plants.

  12. Tooth - abnormal shape

    MedlinePlus

    Hutchinson incisors; Abnormal tooth shape; Peg teeth; Mulberry teeth; Conical teeth ... The appearance of normal teeth varies, especially the molars. ... conditions. Specific diseases can affect tooth shape, tooth ...

  13. The Folate-Vitamin B12 Interaction, Low Hemoglobin, and the Mortality Risk from Alzheimer's Disease.

    PubMed

    Min, Jin-Young; Min, Kyoung-Bok

    2016-03-21

    Abnormal hemoglobin levels are a risk factor for Alzheimer's disease (AD). Although the mechanism underlying these associations is elusive, inadequate micronutrients, particularly folate and vitamin B12, may increase the risk for anemia, cognitive impairment, and AD. In this study, we investigated whether the nutritional status of folate and vitamin B12 is involved in the association between low hemoglobin levels and the risk of AD mortality. Data were obtained from the 1999-2006 National Health and Nutrition Examination Survey (NHANES) and the NHANES (1999-2006) Linked Mortality File. A total of 4,688 participants aged ≥60 years with available baseline data were included in this study. We categorized three groups based on the quartiles of folate and vitamin B12 as follows: Group I (low folate and vitamin B12); Group II (high folate and low vitamin B12 or low folate and high vitamin B12); and Group III (high folate and vitamin B12). Of 4,688 participants, 49 subjects died due to AD. After adjusting for age, sex, ethnicity, education, smoking history, body mass index, the presence of diabetes or hypertension, and dietary intake of iron, significant increases in the AD mortality were observed in Quartile1 for hemoglobin (HR: 8.4, 95% CI: 1.4-50.8), and the overall risk of AD mortality was significantly reduced with increases in the quartile of hemoglobin (p for trend = 0.0200), in subjects with low levels of both folate and vitamin B12 at baseline. This association did not exist in subjects with at least one high level of folate and vitamin B12. Our finding shows the relationship between folate and vitamin B12 levels with respect to the association between hemoglobin levels and AD mortality. PMID:27003215

  14. Structurally abnormal human autosomes

    SciTech Connect

    1993-12-31

    Chapter 25, discusses structurally abnormal human autosomes. This discussion includes: structurally abnormal chromosomes, chromosomal polymorphisms, pericentric inversions, paracentric inversions, deletions or partial monosomies, cri du chat (cat cry) syndrome, ring chromosomes, insertions, duplication or pure partial trisomy and mosaicism. 71 refs., 8 figs.

  15. Universal metastability of sickle hemoglobin polymerization

    NASA Astrophysics Data System (ADS)

    Weng, Weijun

    Sickle hemoglobin (HbS) is a natural mutation of the normal hemoglobin (HbA) found in the red blood cells of human body. Polymerization of HbS occurs when the concentration of deoxyHbS exceeds a well-defined solubility, which is the underlying cause of the Sickle Cell Disease. It has long been assumed that thermodynamic equilibrium is reached when polymerization comes to an end. However, in this thesis we demonstrate that in confined volume as well as in bulk solution, HbS polymerization terminates prematurely, leaving the solution in a metastable state. A newly developed Reservoir method as well as modulated excitation method were adopted for the study. This discovery of universal metastability gives us new insights into understanding the mechanism of sickle cell disease.

  16. Morphological abnormalities among lampreys

    USGS Publications Warehouse

    Manion, Patrick J.

    1967-01-01

    The experimental control of the sea lamprey (Petromyzon marinus) in the Great Lakes has required the collection of thousands of lampreys. Representatives of each life stage of the four species of the Lake Superior basin were examined for structural abnormalities. The most common aberration was the presence of additional tails. The accessory tails were always postanal and smaller than the normal tail. The point of origin varied; the extra tails occurred on dorsal, ventral, or lateral surfaces. Some of the extra tails were misshaped and curled, but others were normal in shape and pigment pattern. Other abnormalities in larval sea lampreys were malformed or twisted tails and bodies. The cause of the structural abnormalities is unknown. The presence of extra caudal fins could be genetically controlled, or be due to partial amputation or injury followed by abnormal regeneration. Few if any lampreys with structural abnormalities live to sexual maturity.

  17. Serum ferritin levels in hemoglobin H disease.

    PubMed

    Galanello, R; Melis, M A; Paglietti, E; Cornacchia, G; de Virgiliis, S; Cao, A

    1983-01-01

    This study shows that hemoglobin H disease patients aged between 0.5 and 44 years, usually (27 out of 30) have normal serum ferritin levels according to age. This reconfirms that in this disease there are usually normal iron stores. However, in a few patients (3 out of 30) increased levels were found. This may be due to inappropriate iron medication, transfusions or associated idiopathic hereditary hemocromatosis gene.

  18. Free heme and sickle hemoglobin polymerization

    NASA Astrophysics Data System (ADS)

    Uzunova, Veselina V.

    This work investigates further the mechanism of one of the most interesting of the protein self-assembly systems---the polymerization of sickle hemoglobin and the role of free heme in it. Polymerization of sickle hemoglobin is the primary event in the pathology of a chronic hemolytic condition called sickle cell anemia with complex pathogenesis, unexplained variability and symptomatic treatment. Auto-oxidation develops in hemoglobin solutions exposed to room temperature and causes release of ferriheme. The composition of such solutions is investigated by mass spectrometry. Heme dimers whose amount corresponds to the initial amounts of heme released from the protein are followed. Differences in the dimer peak height are established for hemoglobin variants A, S and C and depending on the exposure duration. The effects of free heme on polymerization kinetics are studied. Growth rates and two characteristic parameters of nucleation are measured for stored Hb S. After dialysis of polymerizing solutions, no spherulites are detected at moderately high supersaturation and prolonged exposure times. The addition of 0.16-0.26 mM amounts of heme to dialyzed solutions leads to restoration of polymerization. The measured kinetic parameters have higher values compared to the ones before dialysis. The amount of heme in non-dialyzed aged solution is characterized using spectrophotometry. Three methods are used: difference in absorbance of dialyzed and non-dialyzed solutions, characteristic absorbance of heme-albumin complex and absorbance of non-dialyzed solutions with added potassium cyanide. The various approaches suggest the presence of 0.12 to 0.18 mM of free ferriheme in such solutions. Open questions are whether the same amounts of free heme are present in vivo and whether the same mechanism operates intracellulary. If the answer to those questions is positive, then removal of free heme from erythrocytes can influence their readiness to sickle.

  19. Imidazolidinone adducts of peptides and hemoglobin

    SciTech Connect

    San George, R.C.; Hoberman, H.D.

    1986-05-01

    Acetaldehyde reacts selectively with the terminal amino groups of the ..cap alpha.. and ..beta.. chains of hemoglobin to form stable adducts, the structures of which, based on /sup 13/C NMR studies, are proposed to be diastereomeric 2-methyl imidazolidin-4-ones. In this scheme, acetaldelhyde forms a reversible Schiff base with the ..cap alpha..-amino groups of the polypeptide chains which cyclize with the amide nitrogen of the first peptide bond to form the stable imidazolidinone adducts. In support of this mechanism, the authors found that in following the reaction of the peptide val-gly-gly with (1,2-/sup 13/C) acetaldehyde, /sup 13/C NMR resonances attributed to a Schiff base (delta = 170 ppm) were observed which slowly disappeared prior to appearance of resonances from a pair of stable adducts (delta = 70 and 71 ppm) believed to be the diastereomeric imidazolidinones. Schiff base formation appeared to limit the overall rate. Tetraglycine reacted in a similar manner but with a resonance from a single stable adduct observed representing the enantiomeric imidazolidinone adducts of this peptide. Peptides with proline in position 2 should be incapable of forming imidazolidinones, and the authors found that ala-pro-gly did in fact fail to form a stable adduct with acetaldehyde. The 2-methyl imidazolidin-4-one adducts of hemoglobin may be useful in determining the contribution of the amino terminal groups to the structure and functional properties of hemoglobins.

  20. Hemoglobin concentration in men with type 2 diabetes mellitus.

    PubMed

    Harusato, Ichiko; Fukui, Michiaki; Tanaka, Muhei; Shiraishi, Emi; Senmaru, Takafumi; Sakabe, Kazumi; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto

    2010-06-01

    Anemia is a common but often overlooked complication of diabetes. We investigated the relationship between hemoglobin concentration and various factors as well as markers of subclinical atherosclerosis in men with type 2 diabetes mellitus. Hemoglobin concentration was measured in 319 men with type 2 diabetes mellitus. We evaluated the relationship between hemoglobin concentration and various factors including age, body mass index, and glycemic control, as well as between hemoglobin concentration and pulse wave velocity or ankle-brachial index (n = 209) and between hemoglobin concentration and carotid intima-media thickness or plaque score (n = 125). Mean hemoglobin concentration was 14.2 +/- 0.80 g/dL. Body mass index (r = 0.340, P < .0001) and estimated glomerular filtration rate (r = 0.219, P = .0011) were positively associated with hemoglobin concentration, whereas age (r = -0.388, P < .0001), glycated albumin (r = -0.148, P = .0121), serum creatinine concentration (r = -0.206, P = .0019), and log (urinary albumin excretion) (r = -0.188, P = .0010) were negatively associated with hemoglobin concentration. Multiple regression analysis identified age (beta = -0.222, P = .0019), body mass index (beta = 0.145, P = .0432), systolic blood pressure (beta = 0.214, P = .0015), total cholesterol concentration (beta = 0.170, P = .0077), and serum creatinine concentration (beta = -0.181, P = .0045) as independent determinants of hemoglobin concentration. No significant association was observed between hemoglobin concentration and serum erythropoietin concentration (r = -0.079, P = .2980). Negative correlations were found between hemoglobin concentration and pulse wave velocity (r = -0.289, P < .0001) and between hemoglobin concentration and plaque score (r = -0.275, P = .0024). In conclusion, hemoglobin concentration was associated with various factors; and decreased hemoglobin concentration was associated with subclinical markers of atherosclerosis in men with type 2

  1. Cardiac abnormalities in children with sickle cell anemia.

    PubMed

    Lester, L A; Sodt, P C; Hutcheon, N; Arcilla, R A

    1990-11-01

    The cardiac status of 64 children (ages 0.2 to 18 yr) with sickle cell anemia documented by hemoglobin electrophoresis was evaluated by echocardiography. Left atrial, left ventricular and aortic root dimensions were significantly increased in over 60 percent of these children at all ages compared to values for 99 normal black (non-SCA) control subjects. Left ventricular wall thickness was increased in only 20 percent of older children with sickle cell anemia. Estimated LV mass/m2 and left ventricular cardiac index were increased compared to control subjects (p less than 0.001). Left heart abnormalities expressed as a single composite function, derived from multivariate regression analysis, correlated well with severity of anemia expressed as grams of hemoglobin (r = -0.52, p = less than 0.001) and with percentage of hemoglobin S (r = 0.51, p less than 0.001), but not to the same extent with age. Echocardiographically assessed left ventricular function at rest was comparable to that of control subjects. These data suggest that the major cardiac abnormalities in children are related to the volume overload effects of chronic anemia, and that in this age group, there is no evidence for a distinct "sickle cell cardiomyopathy" or cardiac dysfunction.

  2. Abnormal uterine bleeding.

    PubMed

    Jennings, J C

    1995-11-01

    Physicians who care for female patients cannot avoid the frequent complaint of abnormal uterine bleeding. Knowledge of the disorders that cause this problem can prevent serious consequences in many patients and improve the quality of life for many others. The availability of noninvasive and minimally invasive diagnostic studies and minimally invasive surgical treatment has revolutionized management of abnormal uterine bleeding. Similar to any other disorder, the extent to which a physician manages abnormal uterine bleeding depends on his or her own level of comfort. When limitations of either diagnostic or therapeutic capability are encountered, consultation and referral should be used to the best interest of patients.

  3. Possibilities of Using Fetal Hemoglobin as a Platform for Producing Hemoglobin-Based Oxygen Carriers (HBOCs).

    PubMed

    Ratanasopa, Khuanpiroon; Cedervall, Tommy; Bülow, Leif

    2016-01-01

    The expression levels of fetal hemoglobin (HbF) in bacterial recombinant systems are higher compared with normal adult hemoglobin (HbA). However, heme disorientation in globins are often observed in recombinant production processes, both for HbA and HbF, although the degree of heme oriental disorder is much lower for HbF. In addition, the heme disorientation can be converted to a normal conformation by an oxidation-reduction process. A chromatographic cleaning process involving a strong anion exchanger can be utilized to remove such unstable and nondesirable forms of Hb.

  4. "Jeopardy" in Abnormal Psychology.

    ERIC Educational Resources Information Center

    Keutzer, Carolin S.

    1993-01-01

    Describes the use of the board game, Jeopardy, in a college level abnormal psychology course. Finds increased student interaction and improved application of information. Reports generally favorable student evaluation of the technique. (CFR)

  5. Abnormal Uterine Bleeding

    MedlinePlus

    ... Abnormal uterine bleeding is any bleeding from the uterus (through your vagina) other than your normal monthly ... or fibroids (small and large growths) in the uterus can also cause bleeding. Rarely, a thyroid problem, ...

  6. Abnormal Uterine Bleeding FAQ

    MedlinePlus

    ... as cancer of the uterus, cervix, or vagina • Polycystic ovary syndrome How is abnormal bleeding diagnosed? Your health care ... before the fetus can survive outside the uterus. Polycystic Ovary Syndrome: A condition characterized by two of the following ...

  7. Mini-hemoglobins from nemertean worms.

    PubMed

    Vandergon, Thomas L; Riggs, Austen F

    2008-01-01

    Hemoglobins (Hbs) found in members of the phylum Nemertea are smaller than any other known Hb molecules. These mini-Hbs have been of great interest because of their unique three-dimensional structure and their stable ligand-binding properties. Also of interest is the expression of mini-Hb in neural tissue, body wall muscle tissue, and red blood cells. This chapter outlines methods that may be used to isolate and purify functional mini-Hbs from all three tissue types in nemertean worms.

  8. Neutral changes during divergent evolution of hemoglobins

    NASA Technical Reports Server (NTRS)

    Jukes, T. H.

    1978-01-01

    A comparison of the mRNAs for rabbit and human beta-hemoglobins shows that synonymous changes in codons have accumulated three times as rapidly as nucleotide replacements that produced changes in amino acids. This agrees with predictions based on the so-called neutral theory. In addition, seven codon changes that appear to be single-base changes (according to maximum parsimony) are actually two-base changes. This indicates that the construction of primordial sequences is of limited significance when based on inferences that assume minimum base changes for amino acid replacements.

  9. ECK FISTULA LIVER SUBNORMAL IN PRODUCING HEMOGLOBIN AND PLASMA PROTEINS ON DIETS RICH IN LIVER AND IRON

    PubMed Central

    Whipple, G. H.; Robscheit-Robbins, F. S.; Hawkins, W. B.

    1945-01-01

    The Eck fistula shunts the portal blood around the liver which receives its blood only by way of the hepatic artery. There are slight gross and histological changes in the Eck fistula liver of the dog. There is evidence at times of some functional abnormalities of the liver due to the Eck fistula but the dog can tolerate this fistula for 1 to 8 years and appear normal. Chloroform is tolerated by the Eck fistula dog, which may take twice a lethal dose for the control dog without evidence of significant liver injury. Acacia given by vein is deposited in the Eck fistula liver and impairs further its functional capacity to contribute to hemoglobin production. The stress of anemia brings out the fact that the anemic Eck fistula animal cannot utilize standard diet factors and iron as efficiently as the anemic non-Eck control dog. The output of new hemoglobin in some instances may drop to one-fourth of normal. When hypoproteinemia alone or combined with anemia is produced in the Eck fistula dog, we observe at times very low production of plasma protein—seven a drop to one-tenth of normal. This interrelation of liver abnormality, liver dysfunction, and lessened plasma protein and hemoglobin production is significant. It is generally accepted that the liver is concerned with the production of several plasma proteins—fibrinogen, prothrombin, and albumin. The experiments above indicate that the liver is concerned directly or indirectly with the production of new hemoglobin. Our belief is that the liver contributes to the fabrication of hemoglobin by means of the mobile plasma proteins which to a large extent derive from the liver. PMID:19871451

  10. Polymeric nanoparticles for hemoglobin-based oxygen carriers.

    PubMed

    Piras, Anna Maria; Dessy, Alberto; Chiellini, Federica; Chiellini, Emo; Farina, Claudio; Ramelli, Massimiliano; Della Valle, Elena

    2008-10-01

    This article reports on the current status of the research on blood substitutes with particular attention on hemoglobin-based oxygen carriers (HBOCs). Insights on the physiological role of hemoglobin are reported in the view of the development of both acellular and cellular hemoglobin-based oxygen carriers. Attention is then focused on biocompatible polymeric materials that find application as matrices for cellular based HBOCs and on the strategies employed to avoid methemoglobin formation. Results are reported regarding the use of bioerodible polymeric matrices based on hemiesters of alternating copolymer (maleic anhydride-co-butyl vinyl ether) for the preparation of hemoglobin loaded nanoparticles.

  11. WAXS studies of the structural diversity of hemoglobin in solution.

    SciTech Connect

    Makowski, L.; Bardhan, J.; Gore, D.; Lal, J.; Mandava, S.; Park, S.; Rodi, D. J.; Ho, N. T.; Ho, C.; Fischetti, R. F.

    2011-01-01

    Specific ligation states of hemoglobin are, when crystallized, capable of taking on multiple quaternary structures. The relationship between these structures, captured in crystal lattices, and hemoglobin structure in solution remains uncertain. Wide-angle X-ray solution scattering (WAXS) is a sensitive probe of protein structure in solution that can distinguish among similar structures and has the potential to contribute to these issues. We used WAXS to assess the relationships among the structures of human and bovine hemoglobins in different liganded forms in solution. WAXS data readily distinguished among the various forms of hemoglobins. WAXS patterns confirm some of the relationships among hemoglobin structures that have been defined through crystallography and NMR and extend others. For instance, methemoglobin A in solution is, as expected, nearly indistinguishable from HbCO A. Interestingly, for bovine hemoglobin, the differences between deoxy-Hb, methemoglobin and HbCO are smaller than the corresponding differences in human hemoglobin. WAXS data were also used to assess the spatial extent of structural fluctuations of various hemoglobins in solution. Dynamics has been implicated in allosteric control of hemoglobin, and increased dynamics has been associated with lowered oxygen affinity. Consistent with that notion, WAXS patterns indicate that deoxy-Hb A exhibits substantially larger structural fluctuations than HbCO A. Comparisons between the observed WAXS patterns and those predicted on the basis of atomic coordinate sets suggest that the structures of Hb in different liganded forms exhibit clear differences from known crystal structure.

  12. Characterization of the hemoglobin of the backswimmer Anisops deanei (Hemiptera).

    PubMed

    Wawrowski, Agnes; Matthews, Philip G D; Gleixner, Eva; Kiger, Laurent; Marden, Michael C; Hankeln, Thomas; Burmester, Thorsten

    2012-09-01

    While O(2)-binding hemoglobin-like proteins are present in many insects, prominent amounts of hemoglobin have only been found in a few species. Backswimmers of the genera Anisops and Buenoa (Notonectidae) have high concentrations of hemoglobin in the large tracheal cells of the abdomen. Oxygen from the hemoglobin is delivered to a gas bubble and controls the buoyant density, which enables the bugs to maintain their position without swimming and to remain stationary in the mid-water zone where they hunt for prey. We have obtained the cDNA sequences of three Anisops deanei hemoglobin chains by RT-PCR and RACE techniques. The deduced amino acid sequences show an unusual insertion of a single amino acid in the conserved helix E, but this does not affect protein stability or ligand binding kinetics. Recombinant A. deanei hemoglobin has an oxygen affinity of P(50) = 2.4 kPa (18 torr) and reveals the presence of a dimeric fraction or two different conformations. The absorption spectra demonstrate that the Anisops hemoglobin is a typical pentacoordinate globin. Phylogenetic analyses show that the backswimmer hemoglobins evolved within Heteroptera and most likely originated from an intracellular hemoglobin with divergent function. PMID:22575160

  13. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  14. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  15. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  16. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  17. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient. (b) Classification. Class II (performance standards)....

  18. A review of variant hemoglobins interfering with hemoglobin A1c measurement.

    PubMed

    Little, Randie R; Roberts, William L

    2009-05-01

    Hemoglobin A1c (HbA1c) is used routinely to monitor long-term glycemic control in people with diabetes mellitus, as HbA1c is related directly to risks for diabetic complications. The accuracy of HbA1c methods can be affected adversely by the presence of hemoglobin (Hb) variants or elevated levels of fetal hemoglobin (HbF). The effect of each variant or elevated HbF must be examined with each specific method. The most common Hb variants worldwide are HbS, HbE, HbC, and HbD. All of these Hb variants have single amino acid substitutions in the Hb beta chain. HbF is the major hemoglobin during intrauterine life; by the end of the first year, HbF falls to values close to adult levels of approximately 1%. However, elevated HbF levels can occur in certain pathologic conditions or with hereditary persistence of fetal hemoglobin. In a series of publications over the past several years, the effects of these four most common Hb variants and elevated HbF have been described. There are clinically significant interferences with some methods for each of these variants. A summary is given showing which methods are affected by the presence of the heterozygous variants S, E, C, and D and elevated HbF. Methods are divided by type (immunoassay, ion-exchange high-performance liquid chromatography, boronate affinity, other) with an indication of whether the result is artificially increased or decreased by the presence of a Hb variant. Laboratorians should be aware of the limitations of their method with respect to these interferences.

  19. Alkaline Bohr effect of human hemoglobin Ao.

    PubMed

    Di Cera, E; Doyle, M L; Gill, S J

    1988-04-01

    Differential oxygen binding measurements obtained over the pH range 6.95 to 9.10 at 25 degrees C have allowed a detailed description of the alkaline Bohr effect of human hemoglobin Ao. Phenomenological analysis of the data in terms of the Adair equation shows that: (1) the oxygen binding curves are asymmetrical with the population of the triply oxygenated species being negligible throughout the pH range studied: (2) the shape of the oxygen binding curve is affected by pH, especially at low saturation; and (3) the maximum O2-proton linkage is -0.52 mole of proton per mole of oxygen at pH 7.4. A possible molecular mechanism of the Bohr effect is proposed within the framework of an allosteric model which accounts for the low population of triply oxygenated hemoglobin species. At least three Bohr groups are necessary for a quantitative description of the alkaline Bohr effect. Two of these groups titrate in the range of the His146 beta and Vall alpha residues, which have long been identified as the main alkaline Bohr groups, and altogether contribute 84% of the alkaline Bohr effect at physiological pH. A third ionizable group, linked to oxygenation presumably at the beta chains, is implicated and is titrated in a pH range characteristic of a surface histidyl residue.

  20. Hemoglobin alpha in the blood vessel wall

    PubMed Central

    Butcher, Joshua T.; Johnson, Tyler; Beers, Jody; Columbus, Linda; Isakson, Brant E

    2014-01-01

    Hemoglobin has been studied and well haracterized in red blood cells for over one hundred years. However, new work has indicated that the hemoglobin alpha subunit (Hbα) is also found within the blood vessel wall, where it appears to localize at the myoendothelial junction (MEJ) and plays a role in regulating nitric oxide (NO) signaling between endothelium and smooth muscle. This discovery has created a new paradigm for control of endothelial nitric oxide synthase activity, nitric oxide diffusion, and ultimately, control of vascular tone and blood pressure. This review will discuss the current knowledge of hemoglobin’s properties as a gas exchange molecule in the blood stream, and extrapolate the properties of Hbα biology to the MEJ signaling domain. Specifically, we propose that Hbα is present at the MEJ to regulate NO release and diffusion in a restricted physical space, which would have powerful implications for the regulation of blood flow in peripheral resistance arteries. PMID:24832680

  1. Rare hemoglobin variants in Tunisian population.

    PubMed

    Zorai, A; Moumni, I; Mosbahi, I; Douzi, K; Chaouachi, D; Guemira, F; Abbes, S

    2015-04-01

    During the last 30 years, many studies concerning hemoglobinopathies were realized among Tunisians. More than twenty different thalassemic alleles were detected on the β-globin gene, and less are affecting the α-globin genes. Unusual hemoglobin (Hb) variants other than Hb S, Hb C, and Hb O-arab, which are the most frequent variants in Tunisia, were also detected. Eight Tunisian subjects were studied at phenotypic and molecular levels. Hematological indices and hemoglobin (Hb) pattern were performed by alkaline electrophoresis and isoelectric focusing (IEF),and the Hb fractions were quantitated by cation exchange HPLC. On genomic level, coding regions were amplified by polymerase chain reaction (PCR) followed by a sequencing of the purified PCR products using the dye terminator method. Seven uncommon Hb variants were detected and described for the first time among Tunisians. HbA2-Tunis [δ46(CD5), Gly → Glu, GGG → GAG] is the newly described δ-chain variant in our laboratory, and some other variants (Hb Constant Spring, G San Jose, and Hb J-Bangkok) are very uncommon in the Mediterranean region. We present here an updated review of the Hb variants detected among Tunisians. Twenty-one rare Hb variants were detected affecting the α1-, α2-, δ-, γ-, and β-globin genes, leading in some cases to a severe phenotype especially when the stability is completely altered. The ethnical history of Tunisia could explain this important variability of the observed rare Hb variants. PMID:24905386

  2. Liposome-encapsulated hemoglobin processing methods.

    PubMed

    Zheng, S; Zheng, Y; Beissinger, R L; Fresco, R

    1992-01-01

    An effective and safe red blood cell substitute is being developed based on double emulsion/evaporation techniques followed by high pressure homogenization to form liposome-encapsulated hemoglobin (LEH). Formulations are made up of hydrogenated phosphatidylcholine (PC, soy or egg), cholesterol, phosphatidylinositol (PI), and alpha-tocopherol in a molar ratio of 1:1:0.2:0.02, respectively. Resulting LEH-encapsulated hemoglobin (Hb) concentrations are greater than 80% of precursor Hb solutions. Met-Hb generation accompanying LEH processing appears to be small with only a 3% increase for encapsulated over precursor. These results correspond to an oxygen content for an LEH suspension sample (50% by volume LEH) of 15 volume% oxygen. Oxygen affinity and cooperativity values for LEH suspensions appear to be near the normal values expected for whole blood. The viscosity of LEH suspension samples (50% by volume LEH in phosphate-buffered saline containing 7.5 wt% albumin) were slightly higher than that of whole blood. The effect of shear rate on leakage of encapsulated Hb from LEH was small, i.e. 0.5% or less. Nearly total isovolemic exchange transfusion using a cannulated rat model demonstrates efficacy of LEH suspension samples. There appears to be no difference in rat internal organ weights between rats exchanged with control compared to rats exchanged with LEH. Circulation half-life following 50% isovolemic exchange-transfusion is about 15 to 18 hours. PMID:1391451

  3. Hemoglobin switching in sheep and goats: occurrence of hemoglobins A and C in the same red cell.

    PubMed

    Nienhuis, A W; Bunn, H F

    1974-09-13

    Sheep and goats switch from the synthesis of hemoglobin A (alpha(2)beta(2)(A)) to hemoglobin C (alpha(2)beta(2)(C)) when made anemic. We have demonstrated the existence of the asymmetrical hybrid hemoglobin, alpha(2)beta(A)beta(C), in the circulating red cells of anemic sheep. These erythroid cells, therefore, synthesized both A and C hemoglobin simultaneously. Thus, the switch appears to be mediated by selective gene expression rather than by a clonal or cellular selective mechanism. PMID:4469671

  4. [Hair shaft abnormalities].

    PubMed

    Itin, P H; Düggelin, M

    2002-05-01

    Hair shaft disorders may lead to brittleness and uncombable hair. In general the hair feels dry and lusterless. Hair shaft abnormalities may occur as localized or generalized disorders. Genetic predisposition or exogenous factors are able to produce and maintain hair shaft abnormalities. In addition to an extensive history and physical examination the most important diagnostic examination to analyze a hair shaft problem is light microscopy. Therapy of hair shaft disorders should focus to the cause. In addition, minimizing traumatic influences to hair shafts, such as dry hair with an electric dryer, permanent waves and dyes is important. A short hair style is more suitable for such patients with hair shaft disorders.

  5. Interpreting elevated fetal hemoglobin in pathology and health at the basic laboratory level: new and known γ- gene mutations associated with hereditary persistence of fetal hemoglobin.

    PubMed

    Amato, A; Cappabianca, M P; Perri, M; Zaghis, I; Grisanti, P; Ponzini, D; Di Biagio, P

    2014-02-01

    Fetal hemoglobin may be slightly or significantly elevated in post-natal life due to a number of causes. We report two novel mutations found on the promoter of the Aγ gene and summarize all common and rare determinants associated with hereditary persistence of fetal hemoglobin (HPFH) described thus far. Hematological and molecular analysis of the Aγ globin gene in two cases of HPFH. Comparison of the novel cases with all those described in the literature. We have found two novel mutations in three Italian patients with HbF values between 5.9% and 6.5% without an elevated HbA(2) and with normal hemoglobin parameters. In two probands (mother and son), a -197 C>T transition was observed, while in a single individual, a -113 A>G transition was present on the distal CCAAT box of the Aγ gene. As no other abnormalities were present in both γ-gene promoters and the changes are located on regulatory sequences, we may conclude that these mutations are responsible for the HPFH phenotype shown by the carriers. The laboratory should be able to discriminate between elevated HbF due to artifacts or to serious causes including bone marrow malignancies, aplastic anemia, and β-thalassemia major or recessive traits such as β-thalassemia minor, δβ-thalassemia, or nonpathological conditions induced by mutations or polymorphisms of the γ-gene promoters that may even be beneficial when present in patients with thalassemia major or sickle cell disease and, in particular, when these patients are treated with hydroxyurea.

  6. A study of membrane protein defects and alpha hemoglobin chains of red blood cells in human beta thalassemia

    SciTech Connect

    Rouyer-Fessard, P.; Garel, M.C.; Domenget, C.; Guetarni, D.; Bachir, D.; Colonna, P.; Beuzard, Y. )

    1989-11-15

    The soluble pool of alpha hemoglobin chains present in blood or bone marrow cells was measured with a new affinity method using a specific probe, beta A hemoglobin chain labeled with ({sup 3}H)N-ethylmaleimide. This pool of soluble alpha chains was 0.067 {plus minus} 0.017% of hemoglobin in blood of normal adult, 0.11 {plus minus} 0.03% in heterozygous beta thalassemia and ranged from 0.26 to 1.30% in homozygous beta thalassemia intermedia. This elevated pool of soluble alpha chains observed in human beta thalassemia intermedia decreased 33-fold from a value of 10% of total hemoglobin in bone marrow cells to 0.3% in the most dense red blood cells. The amount of insoluble alpha chains was measured by using the polyacrylamide gel electrophoresis in urea and Triton X-100. In beta thalassemia intermedia the amount of insoluble alpha chains was correlated with the decreased spectrin content of red cell membrane and was associated with a decrease in ankyrin and with other abnormalities of the electrophoretic pattern of membrane proteins. The loss and topology of the reactive thiol groups of membrane proteins was determined by using ({sup 3}H)N-ethylmaleimide added to membrane ghosts prior to urea and Triton X-100 electrophoresis. Spectrin and ankyrin were the major proteins with the most important decrease of thiol groups.

  7. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body fluids. Measurements of free hemoglobin aid in the diagnosis of various hematologic disorders, such as sickle cell anemia, Fanconi's anemia (a rare inherited disease), aplastic anemia (bone marrow does not produce...

  8. Hemoglobin Screening Independently Predicts All-Cause Mortality.

    PubMed

    Fulks, Michael; Dolan, Vera F; Stout, Robert L

    2015-01-01

    Objective .- Determine if the addition of hemoglobin testing improves risk prediction for life insurance applicants. Method .- Hemoglobin results for insurance applicants tested from 1993 to 2007, with vital status determined by Social Security Death Master File follow-up in 2011, were analyzed by age and sex with and without accounting for the contribution of other test results. Results .- Hemoglobin values ≤12.0 g/dL (and possibly ≤13.0 g/dL) in females age 50+ (but not age <50) and hemoglobin values ≤13.0 g/dL in all males are associated with progressively increasing mortality risk independent of the contribution of other test values. Increased risk is also noted for hemoglobin values >15.0 g/dL (and possibly >14.0 g/dL) for all females and for hemoglobin values >16.0 g/dL for males. Conclusion .- Hemoglobin testing can add additional independent risk assessment to that obtained from other laboratory testing, BP and build in this relatively healthy insurance applicant population. Multiple studies support this finding at older ages, but data (and the prevalence of diseases impacting hemoglobin levels) are limited at younger ages. PMID:27584842

  9. Computation Of Facilitated Transport of O2 In Hemoglobin

    NASA Technical Reports Server (NTRS)

    Davis, Sanford

    1991-01-01

    Report describes computations of unsteady facilitated transport of oxygen through liquid membrane of hemoglobin. Used here, "facilitated transport" means diffusion of permeant through membrane in which that diffusion enhanced by reversible chemical reaction between permeant and membrane. In this case, reversible reactions between hemoglobin and oxygen.

  10. Hemoglobin Screening Independently Predicts All-Cause Mortality.

    PubMed

    Fulks, Michael; Dolan, Vera F; Stout, Robert L

    2015-01-01

    Objective .- Determine if the addition of hemoglobin testing improves risk prediction for life insurance applicants. Method .- Hemoglobin results for insurance applicants tested from 1993 to 2007, with vital status determined by Social Security Death Master File follow-up in 2011, were analyzed by age and sex with and without accounting for the contribution of other test results. Results .- Hemoglobin values ≤12.0 g/dL (and possibly ≤13.0 g/dL) in females age 50+ (but not age <50) and hemoglobin values ≤13.0 g/dL in all males are associated with progressively increasing mortality risk independent of the contribution of other test values. Increased risk is also noted for hemoglobin values >15.0 g/dL (and possibly >14.0 g/dL) for all females and for hemoglobin values >16.0 g/dL for males. Conclusion .- Hemoglobin testing can add additional independent risk assessment to that obtained from other laboratory testing, BP and build in this relatively healthy insurance applicant population. Multiple studies support this finding at older ages, but data (and the prevalence of diseases impacting hemoglobin levels) are limited at younger ages.

  11. On the fate of extracellular hemoglobin and heme in brain.

    PubMed

    Lara, Flavio A; Kahn, Suzana A; da Fonseca, Anna Cc; Bahia, Carlomagno P; Pinho, João Pc; Graca-Souza, Aurélio V; Houzel, Jean C; de Oliveira, Pedro L; Moura-Neto, Vivaldo; Oliveira, Marcus F

    2009-06-01

    Intracerebral hemorrhage (ICH) is a major cause of disability in adults worldwide. The pathophysiology of this syndrome is complex, involving both inflammatory and redox components triggered by the extravasation of blood into the cerebral parenchyma. Hemoglobin, heme, and iron released therein seem be important in the brain damage observed in ICH. However, there is a lack of information concerning hemoglobin traffic and metabolism in brain cells. Here, we investigated the fate of hemoglobin and heme in cultured neurons and astrocytes, as well as in the cortex of adult rats. Hemoglobin was made traceable by conjugation to Alexa 488, whereas a fluorescent heme analogue (tin-protoporphyrin IX) was prepared to allow heme tracking. Using fluorescence microscopy we observed that neurons were more efficient in uptake hemoglobin and heme than astrocytes. Exposure of cortical neurons to hemoglobin or heme resulted in an oxidative stress condition. Viability assays showed that neurons were more susceptible to both hemoglobin and heme toxicity than astrocytes. Together, these results show that neurons, rather than astrocytes, preferentially take up hemoglobin-derived products, indicating that these cells are actively involved in the ICH-associated brain damage.

  12. Combinatorics of giant hexagonal bilayer hemoglobins.

    PubMed

    Hanin, L G; Vinogradov, S N

    2000-01-01

    The paper discusses combinatorial and probabilistic models allowing to characterize various aspects of spacial symmetry and structural heterogeneity of the giant hexagonal bilayer hemoglobins (HBL Hb). Linker-dodecamer configurations of HBL are described for two and four linker types (occurring in the two most studied HBL Hb of Arenicola and Lumbricus, respectively), and the most probable configurations are found. It is shown that, for HBL with marked dodecamers, the number of 'normal-marked' pairs of dodecamers in homological position follows a binomial distribution. The group of symmetries of the dodecamer substructure of HBL is identified with the dihedral group D6. Under natural symmetry assumptions, the total dipole moment of the dodecamer substructure of HBL is shown to be zero. Biological implications of the mathematical findings are discussed.

  13. Stroma-free hemoglobin from bovine blood.

    PubMed

    Lima, Maria Celiana P; Andrade, Cristina T

    2007-01-01

    Isolation and purification of bovine hemoglobin (HbBv) was carried out after reaction of whole blood with carbon monoxide. Washing/centrifugation steps were used to eliminate leukocytes, platelets, and plasma proteins. Hypotonic media and ultrasound radiation were used to lyse red blood cells. Lyse by ultrasound was shown to lead to solutions at the highest concentrations in HbBv, and the least concentrations in major phospholipids contaminants. Additional purification procedures were performed to remove membrane proteins and phospholipids. In the first case, proteins were denatured by thermal treatment, and filtered. To eliminate phospholipids, liquid chromatography was used with strong anion exchangers. Purity of HbBv was evaluated by normal phase high performance liquid chromatography (HPLC), electrophoresis, and size-exclusion HPLC. PMID:17701489

  14. Separation and characterization of Menhaden hemoglobin components.

    PubMed

    Pokrywka, G S; Gold, F

    1980-01-01

    Hemolysate from Brevoortia tyrannus (Atlantic Menhaden) consists of two major and two minor components, as determined by ion-exchange chromatography. Oxygen equilibria, flash photolysis and rapid mixing techniques are used to detect functional differences between the two major components, revealing a system analogous to the Trout I-IV system. Menhaden IV exhibits a moderate Root effect and is sensitive to organic phosphate inhibition. Menhaden I exhibits little sensitivity to pH changes or the presence of organic phosphates. These differences are probably based on contrasting kinetic behavior, subunit heterogeneity and replacement of a COOH-terminal histidine residue. Theories accounting for the significance of functional hemoglobin multiplicity are reviewed. By bypassing the normal physiological unloading mechanisms, Menhaden I may be functioning as an oxygen reservoir, perhaps for red muscle during periods of high activity. PMID:7353958

  15. Computational Study on Hemoglobin Protein Family

    NASA Astrophysics Data System (ADS)

    Craciun, Dana; Isvoran, Adriana; Avram, Nicolae M.

    2009-05-01

    We have analyzed 19 proteins belonging to hemoglobin protein family: 3 for plants, 4 for invertebrates and the others for vertebrates. For every protein we have determined the following parameters: the fractal dimension of its backbone, the fractal dimension of its surface, the radius of gyration, the area of its molecular surface and the area of the surface of its cavities. At global level, we did not notice significant differences for the fractal parameters for proteins belonging to different organisms and it underlines that all these proteins perform the same biological function. We have obtained different values of the local and global surface fractal dimensions reflecting distinct roughness of protein pockets in comparison to the entire surface, also in good correlation with the biological function. The geometric characteristics are distinct for the three investigated families of proteins.

  16. Effect of hydrostatic pressure on ligand binding to hemoglobin.

    PubMed

    Carey, F G; Knowles, F; Gibson, Q H

    1977-06-25

    Increase in hydrostatic pressure to 1000 atm increased the affinity of human and menhaden (Brevoortia tyrannus) hemoglobins for oxygen. With necessary assumptions about the form of the equilibrium curve, and after correction for changes in pH and volume due to pressure, the increase in affinity is about 2-fold for both hemoglobins. At pH 6.5, Hill's n for menhaden hemoglobin is near 1, and it is believed to remain in the T state, whereas human hemoglobin undergoes a T to R transition. This suggests that the R-T equilibrium is not disturbed by pressure. In direct experiments the binding of a fluorescent effector (8 hydroxy-1,3,6-pyrene (trisulfonic acid) to deoxyhemoglobin was not changed by pressure. The binding of n-butylisocyanide to hemoglobin and to myoglobin is also greater at high pressures, similarly suggesting that the R-T transition is not involved in the pressure effect. PMID:16924

  17. Hydroxylation and dealkylation reactions catalyzed by hemoglobin.

    PubMed

    Mieyal, J J; Starke, D W

    1994-01-01

    Red blood cells contain many enzymes that are akin to those that catalyze xenobiotic metabolism in liver and other tissues. An obvious exception is the cytochrome P-450 system that is found in virtually all other tissues. In vitro studies, however, have shown that hemoglobin can be a broad monooxygenase catalyst, exhibiting the properties of a monooxygenase enzyme. Thus, catalysis by Hb displays typical Michaelis-Menten kinetics, dependence on the native protein, coupling to NADPH-dependent flavoprotein reductases, and inhibition by carbon monoxide. The reconstituted system containing Hb along with P-450 reductase utilizes NADPH and O2 to catalyze typical monooxygenase reactions, including O- and N-demethylations as well as aromatic and aliphatic hydroxylations, and the catalytic cycle appears to mimic the typical P-450 mechanism. Turnover numbers for aniline hydroxylation are similar for Hb and P-450 reconstituted systems, whereas P-450 systems are more effective for other reactions. Catalysis by Hb seems to be restricted to the beta-heme sites of the tetramer, reflecting more facile substrate access. Overall the similarities and differences between Hb and P-450 provide an opportunity to examine the basis for their differential monooxygenase or peroxidase/peroxygenase activities in a comparative manner. Hb may be especially useful in delineating the early events in the respective reaction schemes, because it can be studied in various stable redox/ligand states, including the oxyferrous form. Similar hemoglobin-catalyzed oxidative biotransformations occur within intact erythrocytes, but apparent turnover numbers are much lower than those with the reconstituted Hb system, suggesting different mechanisms of catalysis. Although Hb-mediated oxidase activity in erythrocytes is low relative to other sites of xenobiotic metabolism, it may contribute to in situ activation of xenobiotics leading to oxidative stress, disruption of sulfhydryl homeostasis in the erythrocytes

  18. Bohr effect of hemoglobins: Accounting for differences in magnitude.

    PubMed

    Okonjo, Kehinde O

    2015-09-01

    The basis of the difference in the Bohr effect of various hemoglobins has remained enigmatic for decades. Fourteen amino acid residues, identical in pairs and located at specific 'Bohr group positions' in human hemoglobin, are implicated in the Bohr effect. All 14 are present in mouse, 11 in dog, eight in pigeon and 13 in guinea pig hemoglobin. The Bohr data for human and mouse hemoglobin are identical: the 14 Bohr groups appear at identical positions in both molecules. The dog data are different from the human because three Bohr group positions are occupied by non-ionizable groups in dog hemoglobin; the pigeon data are vastly different from the human because six Bohr group positions are occupied by non-ionizable groups in pigeon hemoglobin. The guinea pig data are quite complex. Quantitative analyses showed that only the pigeon data could be fitted with the Wyman equation for the Bohr effect. We demonstrate that, apart from guinea pig hemoglobin, the difference between the Bohr effect of each of the other hemoglobins and of pigeon hemoglobin can be accounted for quantitatively on the basis of the occupation of some of their Bohr group positions by non-ionizable groups in pigeon hemoglobin. We attribute the anomalous guinea pig result to a new salt-bridge formed in its R2 quaternary structure between the terminal NH3(+) group of one β-chain and the COO(-) terminal group of the partner β-chain in the same molecule. The pKas of this NH3(+) group are 6.33 in the R2 and 4.59 in the T state.

  19. Morphological abnormalities in elasmobranchs.

    PubMed

    Moore, A B M

    2015-08-01

    A total of 10 abnormal free-swimming (i.e., post-birth) elasmobranchs are reported from The (Persian-Arabian) Gulf, encompassing five species and including deformed heads, snouts, caudal fins and claspers. The complete absence of pelvic fins in a milk shark Rhizoprionodon acutus may be the first record in any elasmobranch. Possible causes, including the extreme environmental conditions and the high level of anthropogenic pollution particular to The Gulf, are briefly discussed.

  20. Chromosome abnormalities in glioma

    SciTech Connect

    Li, Y.S.; Ramsay, D.A.; Fan, Y.S.

    1994-09-01

    Cytogenetic studies were performed in 25 patients with gliomas. An interesting finding was a seemingly identical abnormality, an extra band on the tip of the short arm of chromosome 1, add(1)(p36), in two cases. The abnormality was present in all cells from a patient with a glioblastoma and in 27% of the tumor cells from a patient with a recurrent irradiated anaplastic astrocytoma; in the latter case, 7 unrelated abnormal clones were identified except 4 of those clones shared a common change, -Y. Three similar cases have been described previously. In a patient with pleomorphic astrocytoma, the band 1q42 in both homologues of chromosome 1 was involved in two different rearrangements. A review of the literature revealed that deletion of the long arm of chromosome 1 including 1q42 often occurs in glioma. This may indicate a possible tumor suppressor gene in this region. Cytogenetic follow-up studies were carried out in two patients and emergence of unrelated clones were noted in both. A total of 124 clonal breakpoints were identified in the 25 patients. The breakpoints which occurred three times or more were: 1p36, 1p22, 1q21, 1q25, 3q21, 7q32, 8q22, 9q22, 16q22, and 22q13.

  1. [Congenital foot abnormalities].

    PubMed

    Delpont, M; Lafosse, T; Bachy, M; Mary, P; Alves, A; Vialle, R

    2015-03-01

    The foot may be the site of birth defects. These abnormalities are sometimes suspected prenatally. Final diagnosis depends on clinical examination at birth. These deformations can be simple malpositions: metatarsus adductus, talipes calcaneovalgus and pes supinatus. The prognosis is excellent spontaneously or with a simple orthopedic treatment. Surgery remains outstanding. The use of a pediatric orthopedist will be considered if malposition does not relax after several weeks. Malformations (clubfoot, vertical talus and skew foot) require specialized care early. Clubfoot is characterized by an equine and varus hindfoot, an adducted and supine forefoot, not reducible. Vertical talus combines equine hindfoot and dorsiflexion of the forefoot, which is performed in the midfoot instead of the ankle. Skew foot is suspected when a metatarsus adductus is resistant to conservative treatment. Early treatment is primarily orthopedic at birth. Surgical treatment begins to be considered after walking age. Keep in mind that an abnormality of the foot may be associated with other conditions: malposition with congenital hip, malformations with syndromes, neurological and genetic abnormalities. PMID:25524290

  2. The role of hemoglobin heme loss in Heinz body formation: studies with a partially heme-deficient hemoglobin and with genetically unstable hemoglobins

    PubMed Central

    Jacob, Harry S.; Winterhalter, Kaspar H.

    1970-01-01

    A number of mutant hemoglobins are inordinately unstable, denaturing in circulating red cells into Heinz bodies, resulting in congenital Heinz body hemolytic anemia (CHBHA). We have emphasized that most such hemoglobins involve amino acid substitutions at sites neighboring the heme group of the β-polypeptide chain, and have shown that heme binding to globin is diminished thereby. Thus, hemes were progressively lost from four unstable hemoglobins (Köln, Hammersmith, San Francisco, and Zürich) as they precipitated into Heinz bodies at 50°C. The role of heme loss, especially from beta chains, in Heinz body formation was supported by studies with a hemoglobin synthesized to contain hemes only on its alpha chains (α2hemeβ20). The behavior of this compound, postulated to be an intermediary in the formation of Heinz bodies, mimicked that of the genetically unstable hemoglobins in several ways: (a) it precipitated at 50°C into typical coccoid Heinz bodies; (b) as also observed with CHBHA hemoglobins this denaturation was virtually prevented by the heme ligands, cyanide or carbon monoxide, which inhibit further heme loss; it was potentiated by oxidation of hemes to the ferri- state, which accentuates heme loss; (c) the thiol groups of α2hemeβ20 were hyperreactive, forming mixed disulfides with glutathione and membrane sulfhydryls at rates similar to those of CHBHA hemoglobins and 10 or more times that of normal hemoglobin A; (d) heme repletion of the protein molecules by the addition of crystalline hemin to either α2hemeβ20 or to the genetically unstable hemoglobins, prevented their precipitation into Heinz bodies and normalized their aberrant electrophoretic behaviors; and (e) during Heinz body formation at 50°C both α2hemeβ20 and the genetically unstable hemoglobins released free αheme-chains into solution, suggesting that the bulk of the whitish, Heinz body precipitate is naked β8-chains. We conclude that heme loss from mutant beta chains is an early step

  3. Abnormal pressures as hydrodynamic phenomena

    USGS Publications Warehouse

    Neuzil, C.E.

    1995-01-01

    So-called abnormal pressures, subsurface fluid pressures significantly higher or lower than hydrostatic, have excited speculation about their origin since subsurface exploration first encountered them. Two distinct conceptual models for abnormal pressures have gained currency among earth scientists. The static model sees abnormal pressures generally as relict features preserved by a virtual absence of fluid flow over geologic time. The hydrodynamic model instead envisions abnormal pressures as phenomena in which flow usually plays an important role. This paper develops the theoretical framework for abnormal pressures as hydrodynamic phenomena, shows that it explains the manifold occurrences of abnormal pressures, and examines the implications of this approach. -from Author

  4. Two-photon excited fluorescence emission from hemoglobin

    NASA Astrophysics Data System (ADS)

    Sun, Qiqi; Zeng, Yan; Zhang, Wei; Zheng, Wei; Luo, Yi; Qu, Jianan Y.

    2015-03-01

    Hemoglobin, one of the most important proteins in blood, is responsible for oxygen transportation in almost all vertebrates. Recently, we discovered two-photon excited hemoglobin fluorescence and achieved label-free microvascular imaging based on the hemoglobin fluorescence. However, the mechanism of its fluorescence emission still remains unknown. In this work, we studied the two-photon excited fluorescence properties of the hemoglobin subunits, heme/hemin (iron (II)/(III) protoporphyrin IX) and globin. We first studied the properties of heme and the similar spectral and temporal characteristics of heme and hemoglobin fluorescence provide strong evidence that heme is the fluorophore in hemoglobin. Then we studied the fluorescence properties of hemin, globin and methemoglobin, and found that the hemin may have the main effect on the methemoglobin fluorescence and that globin has tryptophan fluorescence like other proteins. Finally, since heme is a centrosymmetric molecule, that the Soret band fluorescence of heme and hemoglobin was not observed in the single photon process in the previous study may be due to the parity selection rule. The discovery of heme two-photon excited fluorescence may open a new window for heme biology research, since heme as a cofactor of hemoprotein has many functions, including chemical catalysis, electron transfer and diatomic gases transportation.

  5. Development of an immunoassay to detect benzene adducts in hemoglobin

    SciTech Connect

    Grassman, J.A.

    1993-01-01

    The purpose of this project was to develop an immunoassay to detect the adducts formed in hemoglobin after exposure to benzene, which is known to cause bone marrow degeneration and acute myelogenous leukemia. The use of benzene-adduct detection as a biological monitoring method would permit measurement of low exposures and exposures sustained weeks earlier. The reactivity of hydroquinone, an important benzene metabolite, with blood proteins and amino acids was investigated in order to decide which antigens and analytes were likely to be suitable for immunoassay development. The second section determined the combination of benzene-metabolite and antigen need to produce an immunoassay with the requisite low detection limit and specificity. The immunoassays with the best performance were tested on hemoglobin from benzene-exposed mice. In vitro studies showed that hydroquinone efficiently formed adducts with erythrocyte membranes and hemoglobin but not with albumin. Adduction efficiency was greater in incubations using purified hemoglobin than whole blood. Cysteine accounted for 15 to 27% of the adducts formed by hydroquinone. The site of the other adducts were not identified although there was evidence that the hemoglobin heme was adducted. Adducts were found on only 1 of the 2 globin chains. Tryptic digestion of the globin failed to associate the adducts with a specific peptide. Antigens made from hydroquinone-adducted hemoglobin but not hydroquinone-adducted cysteines coupled to carrier proteins effectively elicited adduct-specific antibodies. Interference due to reactivity to hemoglobin was controlled by using uniform quantities of hemoglobin in all wells. The mid-range of the best assays were approximately 12 pmoles HQ per well. Antibodies directed toward hemoglobin adducted with the benzene metabolites phenol, catechol and 1,2,4-trihydroxybenzene were also made. The performance of the anti-1,2,4-trihydroxybenzene were suitable for quantitative immunoassays.

  6. Functional differentiation in trematode hemoglobin isoforms.

    PubMed

    Rashid, A K; Weber, R E

    1999-03-01

    The Hbs and the major electrophoretic Hb components (isoHbs) were isolated from three species of the trematodes, Explanatum explanatum (Ee), Gastrothylax crumenifer (Gc) and Paramphistomum epiclitum (Pe), that parasitise the common Indian water buffalo Bubalus bubalis. The Hbs are monomeric and resemble the so-called nonfunctional mutant hemoglobins that have Tyr at B10 or E7 positions (replacing Leu and the His residues, respectively). However, they are capable of binding with O2 and CO. O2 equilibrium studies of trematode Hb isoforms reveal extremely high O2 affinities, with half-saturation O2 tension (P50) values up to 800 times lower than those of human hemoglobins. This correlates with Tyr residues at B10 and at the distal position (E7) that decrease the O2 dissociation rate by contributing hydrogen bonds (H-bonds) to the bound O2. These substitutions also increase the O2 association rates either due to orientation of E7-Tyr towards the solvent and/or by sterically hindering the entry of water molecules into the heme pocket. The latter may account for the low rate of autoxidation of trematode Hbs. The Hbs and their isoforms from different species exhibited pronounced variation in O2 affinity, which may relate to subtle differences in the structure of the heme pocket. The O2 affinities of the composite (unfractionated) Hbs were intermediate to those of the individual Hb isoform. The P50 values of Hbs here obtained by direct O2 equilibrium measurements differed from those calculated from kinetic data already published [Kiger, L., Rashid, A. K., Griffon, N., Haque, M., Moens, L.,Gibson, Q. H., Poyart, C., & Marden, M. C. (1998). Biophys. J. 75, 990-998.] Intermediate state(s) due to slow reorientation of E7-Tyr may account for this difference. Some Hb isoforms showed slight (either normal or reverse) Bohr effects. The hyperbolic O2 equilibrium curve, Hill coefficient (n) values near unity accord with a monomeric nature of trematode Hbs. In marked contrast to

  7. Feeling Abnormal: Simulation of Deviancy in Abnormal and Exceptionality Courses.

    ERIC Educational Resources Information Center

    Fernald, Charles D.

    1980-01-01

    Describes activity in which student in abnormal psychology and psychology of exceptional children classes personally experience being judged abnormal. The experience allows the students to remember relevant research, become sensitized to the feelings of individuals classified as deviant, and use caution in classifying individuals as abnormal.…

  8. Biophysical basis of hypoxic radioprotection by deoxygenated dextran-hemoglobin

    SciTech Connect

    Wong, J.T.; Hill, R.P.

    1986-08-01

    Perfusion with deoxygenated dextran-hemoglobin provides an effective method for inducing hypoxic radioprotection of normal tissues during radiation treatment of tumors. In this study, the dependence of P50, the half-saturation pressure of oxygen binding to dextran-hemoglobin, was analyzed as a function of solution temperature and pH. The variation of attainable radioprotection with P50, and with the amount of collateral blood entering into the perfused region, was calculated. Upon perfusion of canine gracilis muscle with deoxygenated dextran-hemoglobin, a rapid onset of extensive venous hypoxia was observed.

  9. Abnormal human sex chromosome constitutions

    SciTech Connect

    1993-12-31

    Chapter 22, discusses abnormal human sex chromosome constitution. Aneuploidy of X chromosomes with a female phenotype, sex chromosome aneuploidy with a male phenotype, and various abnormalities in X chromosome behavior are described. 31 refs., 2 figs.

  10. Exercises to Improve Gait Abnormalities

    MedlinePlus

    ... Home About iChip Articles Directories Videos Resources Contact Exercises to Improve Gait Abnormalities Home » Article Categories » Exercise and Fitness Font Size: A A A A Exercises to Improve Gait Abnormalities Next Page The manner ...

  11. Hemoglobin Yoshizuka (G10(108)β asparagine→aspartic acid): a new variant with a reduced oxygen affinity from a Japanese family

    PubMed Central

    Imamura, Takashi; Fujita, Shigeru; Ohta, Yoshiro; Hanada, Motosuke; Yanase, Toshiyuki

    1969-01-01

    During the course of a survey, a new hemoglobin, designated hemoglobin Yoshizuka, has been encountered in a Japanese family. Clinically, mild anemia was noted in five of six heterozygous individuals but no other significant abnormalities were found. Hemoglobin Yoshizuka is characterized by the substitution of aspartic acid for asparagine at the tenth residue of the G helix in the β-chain. Reduced oxygen affinity with almost normal heme-heme interaction was found to be a property of this abnormal hemoglobin. The asparagine residue G10(108)β lies in the internal cavity of the tetrameric molecule and its main chain carbonyl is thought to be hydrogen bonded to histidine G10(103)α at the region of contact between α- and β-chains. It would appear likely that the introduction of a carboxyl group into the central cavity might result in interactions between the polar groups and the substituted side chain, disrupting the system of hydrogen bonds which contribute to the stability of the contacts between unlike subunits. Images PMID:5355345

  12. Effects of cerebral ischemia on neuronal hemoglobin

    PubMed Central

    He, Yangdong; Hua, Ya; Liu, Wenquan; Hu, Haitao; Keep, Richard F.; Xi, Guohua

    2009-01-01

    Summary The present study examined whether or not neuronal hemoglobin (Hb) is present in rats. It then examined whether cerebral ischemia or ischemic preconditioning (IPC) affects neuronal Hb levels in vivo and in vitro. In vivo, male Sprague-Dawley rats were subjected to either 15 minutes of transient middle cerebral artery occlusion with 24 hours of reperfusion, an IPC stimulus, or 24 hours of permanent middle cerebral artery occlusion (pMCAO), or IPC followed three days later by 24 hours of pMCAO. In vitro, primary cultured neurons were exposed to 2 hours of oxygen-glucose deprivation with 22 hours of reoxygenation. Results showed that Hb is widely expressed in rat cerebral neurons but not astrocytes. Hb expression was significantly upregulated in the ipsilateral caudate and the cortical core of the middle cerebral artery territory after IPC. Hb levels also increased in more penumbral cortex and the contralateral hemisphere 24 hours after pMCAO, but expression in the ipsilateral caudate and cortical core area were decreased. Ischemic preconditioning modified pMCAO-induced brain Hb changes. Neuronal Hb levels in vitro were increased by 2 hours of oxygen-glucose deprivation and 22 hours of reoxygenation. These results indicate that Hb is synthesized in neurons and can be upregulated by ischemia. PMID:19066615

  13. Influences of genetic variation on fetal hemoglobin.

    PubMed

    He, Yunyan; Lin, Weixiong; Luo, Jianming

    2011-11-01

    Fetal hemoglobin (HbF) plays a dominant role in ameliorating morbidity and mortality of hemoglobinopathies. The authors performed a replicated study following the genome-wide association study (GWAS) guidelines to identify the genetic mechanics that influence HbF. The authors recruited and phenotyped 312 unrelated β-thalassemia subjects. Single-nucleotide polymorphism (SNP) analysis was performed by using polymerase chain reaction (PCR)/restriction enzymes. Four independent regions of interest were identified: HBS1L-MYB intergenic region, BCL11A locus, β-globin gene cluster, and the CSNK2A1 gene. There were 10 SNPs associated with HbF levels. In addition, haplotypes of HBS1L-MYB and BCL11A were identified and showed association with HbF production. Three independent regions, including HBS1L-MYB intergenic region, BCL11A locus, and β-globin gene cluster, were associated with HbF levels. This study can significantly improve the GWAS findings in Chinese cohorts and is useful for further research in the field of common predictors of the erythropoiesis.

  14. Structure and evolution of Paramecium hemoglobin genes.

    PubMed

    Yamauchi, K; Tada, H; Usuki, I

    1995-10-17

    Hemoglobin (Hb) genes have been cloned from three different species of ciliated protists, P. multimicronucleatum, P. triaurelia and P. jenningsi. Southern blotting of the genomic DNAs using the P. caudatum Hb cDNA showed both intraspecies variation in different stocks of P. caudatum and interspecies variation within the genus Paramecium. The isolated Hb genes were composed of 118, 117 and 117 codons, and interrupted by a short intron with 27, 29 and 29 bp at the same position, in P. multimicronucleatum, P. triaurelia and P. jenningsi, respectively. This suggests that the one-intron and two-exon structure has been conserved in the Hb genes in this genus. The amino acid sequences of the Paramecium Hbs were more than 87% identical to one another and homologous to those from the other ciliated protists Tetrahymena thermophila and T. pyriformis, the green alga Chlamydomonas eugametos, and the cyanobacterium Nostoc commune Hbs, all of which consist of about 120 amino acid residues (120-aa group). In particular, the amino acid sequences of the P. triaurelia and P. jenningsi Hbs were the same, although there were 20 nucleotide differences between the coding regions in the two genes. A maximum likelihood inference as to the phylogenetic relationships among these genes suggests that the Paramecium Hbs genes have evolved more rapidly than the other genes in the 120-aa group, and that P. triaurelia and P. genningsi are sibling species and the P. aurelia complex became a small cell after it separated from P. jenningsi.

  15. Abnormal ionization in sonoluminescence

    NASA Astrophysics Data System (ADS)

    Zhang, Wen-Juan; An, Yu

    2015-04-01

    Sonoluminescence is a complex phenomenon, the mechanism of which remains unclear. The present study reveals that an abnormal ionization process is likely to be present in the sonoluminescing bubble. To fit the experimental data of previous studies, we assume that the ionization energies of the molecules and atoms in the bubble decrease as the gas density increases and that the decrease of the ionization energy reaches about 60%-70% as the bubble flashes, which is difficult to explain by using previous models. Project supported by the Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20120002110031) and the National Natural Science Foundation of China (Grant No. 11334005).

  16. Abnormal hematological indices in cirrhosis

    PubMed Central

    Qamar, Amir A; Grace, Norman D

    2009-01-01

    Abnormalities in hematological indices are frequently encountered in cirrhosis. Multiple causes contribute to the occurrence of hematological abnormalities. Recent studies suggest that the presence of hematological cytopenias is associated with a poor prognosis in cirrhosis. The present article reviews the pathogenesis, incidence, prevalence, clinical significance and treatment of abnormal hematological indices in cirrhosis. PMID:19543577

  17. Spirometric abnormalities among welders

    SciTech Connect

    Rastogi, S.K.; Gupta, B.N.; Husain, T.; Mathur, N.; Srivastava, S. )

    1991-10-01

    A group of manual welders age group 13-60 years having a mean exposure period of 12.4 {plus minus} 1.12 years were subjected to spirometry to evaluate the prevalence of spirometric abnormalities. The welders showed a significantly higher prevalence of respiratory impairment than that observed among the unexposed controls as a result of exposure to welding gases which comprised fine particles of lead, zinc, chromium, and manganese. This occurred despite the lower concentration of the pollutants at the work place. In the expose group, the smoking welders showed a prevalence of respiratory impairment significantly higher than that observed in the nonsmoking welders. The results of the pulmonary function tests showed a predominantly restrictive type of pulmonary impairment followed by a mixed ventilatory defect among the welders. The effect of age on pulmonary impairment was not discernible. Welders exposed for over 10 years showed a prevalence of respiratory abnormalities significantly higher than those exposed for less than 10 years. Smoking also had a contributory role.

  18. Solid hemoglobin-polymer phantoms for evaluation of biophotonic systems.

    PubMed

    Jang, Hyounguk; Pfefer, T Joshua; Chen, Yu

    2015-09-15

    Stable tissue phantoms that incorporate the spectral absorption properties of hemoglobin would benefit a wide range of biophotonic technologies. Toward this end, we have developed and validated a novel polymer material incorporating hemoglobin. Our solid hemoglobin-polymer (SHP) material is fabricated by mixing liquid silicone base with a hemoglobin solution, followed by sonication and low temperature curing. The optical properties of samples were determined over 450-1000 nm using the inverse adding-doubling method and the Beer-Lambert law. Measurements indicated SHP optical stability over four months. Near-infrared spectroscopy and hyperspectral imaging measurements of SHP samples were performed to demonstrate the utility of this approach. SHP materials have the potential to improve tissue-simulating phantoms used for development, evaluation, and standardization of optical devices for oximetry and other applications. PMID:26371926

  19. Reverse engineering the cooperative machinery of human hemoglobin.

    PubMed

    Ren, Zhong

    2013-01-01

    Hemoglobin transports molecular oxygen from the lungs to all human tissues for cellular respiration. Its α2β2 tetrameric assembly undergoes cooperative binding and releasing of oxygen for superior efficiency and responsiveness. Over past decades, hundreds of hemoglobin structures were determined under a wide range of conditions for investigation of molecular mechanism of cooperativity. Based on a joint analysis of hemoglobin structures in the Protein Data Bank (Ren, companion article), here I present a reverse engineering approach to elucidate how two subunits within each dimer reciprocate identical motions that achieves intradimer cooperativity, how ligand-induced structural signals from two subunits are integrated to drive quaternary rotation, and how the structural environment at the oxygen binding sites alter their binding affinity. This mechanical model reveals the intricate design that achieves the cooperative mechanism and has previously been masked by inconsistent structural fluctuations. A number of competing theories on hemoglobin cooperativity and broader protein allostery are reconciled and unified.

  20. Weak binding gases as modulators of hemoglobin function

    SciTech Connect

    Schoenborn, B P; Saxena, A; North, B E

    1980-01-01

    Studies are reported in which the mechanisms of binding of inert gaseous agents to hemoglobin and myoglobin are investigated. Specific binding sites are mapped. Possible effects on sickle cell formation and oxygen binding are discussed. (ACR)

  1. The Stepwise Mutation Model: An Experimental Evaluation Utilizing Hemoglobin Variants

    PubMed Central

    Fuerst, Paul A.; Ferrell, Robert E.

    1980-01-01

    The stepwise mutation model of Ohta and Kimura (1973) was proposed to explain patterns of genetic variability revealed by means of electrophoresis. The assumption that electrophoretic mobility was principally determined by unit changes in net molecular charge has been criticized by Johnson (1974, 1977). This assumption has been tested directly using hemoglobin. Twenty-seven human hemoglobin variants with known amino acid substitutions, and 26 nonhuman hemoglobins with known sequences were studied by starch gel electrophoresis. Of these hemoglobins, 60 to 70% had electrophoretic mobilities that could be predicted solely on the basis of net charge calculated from the amino acid composition alone, ignoring tertiary structure. Only four hemoglobins showed a mobility that was clearly different from an expected mobility calculated using only the net charge of the molecule. For the remaining 30% of hemoglobins studied, mobility was determined by a combination of net charge and other unidentified components, probably reflecting changes in ionization of some amino acid residues as a result of small alterations in tertiary structure due to the amino acid substitution in the variant. For the nonhuman hemoglobins, the deviation of a sample from its expected mobility increased with increasing amino acid divergence from human hemoglobin A.—It is concluded that the net electrostatic charge of a molecule is the principal determinant of electrophoretic mobility under the conditions studied. However, because of the significant deviation from strict stepwise mobility detected for 30 to 40% of the variants studied, it is further concluded that the infinite-allele model of Kimura and Crow (1964) or a "mixed model" such as that proposed by Li (1976) may be more appropriate than the stepwise mutation model for the analysis of much of the available electrophoretic data from natural populations. PMID:17248992

  2. Monoclonal antibodies recognizing single amino acid substitutions in hemoglobin

    SciTech Connect

    Stanker, L.H.; Branscomb, E.; Vanderlaan, M.; Jensen, R.H.

    1986-06-01

    Four monoclonal antibodies (mAb) to non-human primate hemoglobin referred to as Cap-4, Cap-5, Rh-2, and Rh-4, and two mAb to human hemoglobin, referred to as H-1 and H-3 were isolated and were partially characterized. Binding studies with these mAb on a panel of hemoglobins and isolated ..cap alpha.. and ..beta.. globin chains revealed a unique reactivity pattern for each mAb. Amino acid sequence analysis of the antigens used to generate the binding data suggests that the specific recognition of certain hemoglobin antigens by each mAb is controlled by the presence of a particular amino acid at a specific position within the epitope. The use of synthetic peptides as antigens confirmed this observation for five of the mAb. No synthetic peptides were tested with the sixth mAb, Rh-2. The amino acids required for binding of mAb Cap-4, Cap-5, Rh-4, and Rh-2 to hemoglobin are alanine at ..beta..5, threonine at ..beta..13, glutamine at ..beta..125, and leucine at ..cap alpha..68. The non-human primate hemoglobin antibodies require a specific amino acid that is not present in human hemoglobin. The amino acid required for binding of Cap-4, Cap-5, and Rh-4 could arise by a single base change in the ..beta.. globin gene, whereas the amino acid required for Rh-2 binding could only occur if two base changes occurred. Thus these mAb are candidate probes for a somatic cell mutation assay on the basis of the detection of peripheral blood red cells that possess single amino acid substituted hemoglobin as a result of single base substitutions in the globin genes of precursor cells.

  3. [Rare variants of Hb D Punjab, Hb O Arab and polymorphism of human hemoglobins].

    PubMed

    Spivak, V A; Tasheva, E S; Aseeva, E A; Tokarev, Iu N

    1986-03-01

    This report describes the occurrence, study and molecular diagnostics of 40 Hb O Arab beta 121 Glu Lys cases and 4 Hb D punjab beta 121 Glu Gln cases in Bulgaria. Hematological, morphological and clinical data for 12 patients with Hb O arab are listed. Among them we observed 7 simple heterozygotes for Hb O Arab/Hb A, two double heterozygotes-compounds for Hb O/beta+-thalassemia and three compounds for Hb O/beta 0-thalassemia (the latter assumed). Also, general hematological, morphological and clinical data are presented for 4 Hb D Punjab carriers, from which two are simple heterozygotes and two are assumed, as compounds for Hb D/beta 0-thalassemia. The consideration of heterozygosity, homozygosity for both abnormal hemoglobins and of the compound state of Hb O or Hb D/beta-thalassemia or HbS types let us suggest the relative neutrality of the variants and the limitation in their distribution, depending on genetic structure of populations, where they spread. It may be concluded that human hemoglobin is characterized by marked monomorphism. At the same time, the high frequency of HbS, HbE and HbC in some populations can be well explained by contemporary selectionism; the distribution of relatively neutral Hb D Punjab and Hb O Arab with some limitations can follow Kimura's neutralism concept. PMID:3957034

  4. Hemoglobin uptake by Paracoccidioides spp. is receptor-mediated.

    PubMed

    Bailão, Elisa Flávia Luiz Cardoso; Parente, Juliana Alves; Pigosso, Laurine Lacerda; de Castro, Kelly Pacheco; Fonseca, Fernanda Lopes; Silva-Bailão, Mirelle Garcia; Báo, Sônia Nair; Bailão, Alexandre Melo; Rodrigues, Marcio L; Hernandez, Orville; McEwen, Juan G; Soares, Célia Maria de Almeida

    2014-05-01

    Iron is essential for the proliferation of fungal pathogens during infection. The availability of iron is limited due to its association with host proteins. Fungal pathogens have evolved different mechanisms to acquire iron from host; however, little is known regarding how Paracoccidioides species incorporate and metabolize this ion. In this work, host iron sources that are used by Paracoccidioides spp. were investigated. Robust fungal growth in the presence of the iron-containing molecules hemin and hemoglobin was observed. Paracoccidioides spp. present hemolytic activity and have the ability to internalize a protoporphyrin ring. Using real-time PCR and nanoUPLC-MSE proteomic approaches, fungal growth in the presence of hemoglobin was shown to result in the positive regulation of transcripts that encode putative hemoglobin receptors, in addition to the induction of proteins that are required for amino acid metabolism and vacuolar protein degradation. In fact, one hemoglobin receptor ortholog, Rbt5, was identified as a surface GPI-anchored protein that recognized hemin, protoporphyrin and hemoglobin in vitro. Antisense RNA technology and Agrobacterium tumefaciens-mediated transformation were used to generate mitotically stable Pbrbt5 mutants. The knockdown strain had a lower survival inside macrophages and in mouse spleen when compared with the parental strain, which suggested that Rbt5 could act as a virulence factor. In summary, our data indicate that Paracoccidioides spp. can use hemoglobin as an iron source most likely through receptor-mediated pathways that might be relevant for pathogenic mechanisms. PMID:24831516

  5. Hemoglobin Uptake by Paracoccidioides spp. Is Receptor-Mediated

    PubMed Central

    Bailão, Elisa Flávia Luiz Cardoso; Parente, Juliana Alves; Pigosso, Laurine Lacerda; de Castro, Kelly Pacheco; Fonseca, Fernanda Lopes; Silva-Bailão, Mirelle Garcia; Báo, Sônia Nair; Bailão, Alexandre Melo; Rodrigues, Marcio L.; Hernandez, Orville; McEwen, Juan G.; Soares, Célia Maria de Almeida

    2014-01-01

    Iron is essential for the proliferation of fungal pathogens during infection. The availability of iron is limited due to its association with host proteins. Fungal pathogens have evolved different mechanisms to acquire iron from host; however, little is known regarding how Paracoccidioides species incorporate and metabolize this ion. In this work, host iron sources that are used by Paracoccidioides spp. were investigated. Robust fungal growth in the presence of the iron-containing molecules hemin and hemoglobin was observed. Paracoccidioides spp. present hemolytic activity and have the ability to internalize a protoporphyrin ring. Using real-time PCR and nanoUPLC-MSE proteomic approaches, fungal growth in the presence of hemoglobin was shown to result in the positive regulation of transcripts that encode putative hemoglobin receptors, in addition to the induction of proteins that are required for amino acid metabolism and vacuolar protein degradation. In fact, one hemoglobin receptor ortholog, Rbt5, was identified as a surface GPI-anchored protein that recognized hemin, protoporphyrin and hemoglobin in vitro. Antisense RNA technology and Agrobacterium tumefaciens-mediated transformation were used to generate mitotically stable Pbrbt5 mutants. The knockdown strain had a lower survival inside macrophages and in mouse spleen when compared with the parental strain, which suggested that Rbt5 could act as a virulence factor. In summary, our data indicate that Paracoccidioides spp. can use hemoglobin as an iron source most likely through receptor-mediated pathways that might be relevant for pathogenic mechanisms. PMID:24831516

  6. Automated quantitation of hemoglobin-based blood substitutes in whole blood samples.

    PubMed

    Kunicka, J; Malin, M; Zelmanovic, D; Katzenberg, M; Canfield, W; Shapiro, P; Mohandas, N

    2001-12-01

    It is necessary to develop methods for accurate monitoring of cell-free hemoglobin in circulation. Routine monitoring of circulating cell-free hemoglobin will be useful for evaluating the efficacy of blood substitute administration andfor determining the clearance rates of the blood substitute from circulation. In addition, discriminating between cell-free hemoglobin and cell-associated hemoglobin will enable accurate determination of RBC indices, mean cell hemoglobin and mean corpuscular hemoglobin concentration, in individuals receiving hemoglobin-based blood substitutes. As colorimetric methods used by hematology analyzers to quantitate the hemoglobin value of a blood sample cannot distinguish between cell-associated and cell-free hemoglobin, it is currently not feasible to quantitate the levels of hemoglobin substitutes in circulation. The advent of a technology that measures volume and hemoglobin concentration of individual RBCs provides an alternative strategy for quantitating the cell-associated hemoglobin in a blood sample. We document that the combined use of cell-based and colorimetric hemoglobin measurements provides accurate discrimination between cell-associated and cell-free hemoglobin over a wide range of hemoglobin levels. This strategy should enable rapid and accurate monitoring of the levels of cell-free hemoglobin substitutes in the circulation of recipients of these blood substitutes.

  7. Iron nitrosyl hemoglobin formation from the reaction of hydroxylamine and hemoglobin under physiological conditions.

    PubMed

    Lockamy, Virginia L; Shields, Howard; Kim-Shapiro, Daniel B; King, S Bruce

    2004-11-01

    Sickle cell disease patients receiving hydroxyurea (HU) therapy have shown increases in the production of nitric oxide (NO) metabolites, which include iron nitrosyl hemoglobin (HbNO), nitrite, and nitrate. However, the exact mechanism by which HU forms HbNO in vivo is not understood. Previous studies indicate that the reaction of oxyhemoglobin (oxyHb) or deoxyhemoglobin (deoxyHb) with HU are too slow to account for in vivo HbNO production. In this study, we show that the reaction of methemoglobin (metHb) with HU to form HbNO could potentially be fast enough to account for in vivo HbNO formation but competing reactions of either excess oxyHb or deoxyHb during the reaction reduces the likelihood that HbNO will be produced from the metHb-HU reaction. Using electron paramagnetic resonance (EPR) spectroscopy we have detected measurable amounts of HbNO and metHb during the reactions of oxyHb, deoxyHb, and metHb with excess hydroxylamine (HA). We also demonstrate HbNO and metHb formation from the reactions of excess oxyHb, deoxyHb, or metHb and HA, conditions that are more likely to mimic those in vivo. These results indicate that the reaction of hydroxylamine with hemoglobin produces HbNO and lend chemical support for a potential role for hydroxylamine in the in vivo metabolism of hydroxyurea.

  8. Relative phase of oscillations of cerebral oxy-hemoglobin and deoxy-hemoglobin concentrations during sleep

    NASA Astrophysics Data System (ADS)

    Pierro, Michele L.; Sassaroli, Angelo; Bergethon, Peter R.; Fantini, Sergio

    2012-02-01

    We present a near-infrared spectroscopy study of the instantaneous phase difference between spontaneous oscillations of cerebral deoxy-hemoglobin and oxy-hemoglobin concentrations ([Hb] and [HbO], respectively) in the low-frequency range, namely 0.04-0.12 Hz. We report phase measurements during the transitions between different sleep stages in a whole-night study of a human subject. We have found that the phase difference between [Hb] and [HbO] low-frequency oscillations tends to be greater in deep sleep (by ~96° on average) and REM sleep (by ~77° on average) compared to the awake state. In particular, we have observed progressive phase increases as the subject transitions from awake conditions into non-REM sleep stages N1, N2, and N3. Corresponding phase decreases were recorded in the reversed transitions from sleep stages N3 to N2, and N2 to awake. These results illustrate the physiological information content of phase measurements of [Hb] and [HbO] oscillations that reflect the different cerebral hemodynamic conditions of the different sleep stages, and that can find broader applicability in a wide range of near-infrared spectroscopy brain studies.

  9. Toxicity of hemoglobin solutions: hemoglobin is a lipopolysaccharide (LPS) binding protein which enhances LPS biological activity.

    PubMed

    Roth, R I; Kaca, W

    1994-01-01

    Administration of alpha alpha-crosslinked stroma-free hemoglobin (SFH) as a cell-free resuscitation fluid is associated with multiple organ toxicities. Many of these toxicities are characteristic of the pathophysiological effects of bacterial endotoxins (lipopolysaccharide, LPS). To better understand the potential role of LPS in the observed in vivo toxicities of SFH, we examined mixtures of SFH and E. coli LPS for evidence of LPS-SFH complex formation. LPS-SFH complexes were demonstrated by three techniques: ultrafiltration through 300 kDa cut-off membranes, which distinguished LPS in complexes (87-89% < 300 kDa) from LPS alone (90% > 300 kDa); density centrifugation through 5% sucrose, which distinguished denser LPS alone from LPS-SFH complexes; and precipitation by 67% ethanol, which demonstrated 2-3 fold increased precipitability of complexes compared to SFH alone. Interaction of LPS with SFH was also associated with markedly increased biological activity of LPS, as manifested by enhancement of LPS activation of Limulus amebocyte lysate (LAL), increased release of human mononuclear cell tissue factor, and enhanced production of cultured human endothelial cell tissue factor. These results demonstrated that hemoglobin can serve as an endotoxin binding protein, and that this interaction results in the alteration of several LPS physical characteristics and enhancement of LPS biological activities.

  10. Glycosylated hemoglobin and hyperbaric oxygen coverage denials.

    PubMed

    Moffat, A D; Worth, E R; Weaver, L K

    2015-01-01

    Some Medicaid and Medicare fiscal intermediaries are denying hyperbaric oxygen (HBO2) therapy for diabetic foot ulcer (DFU) patients if the glycosylated hemoglobin (HbA1c) > 7.0%. We performed multiple PubMed searches for any diabetic wound healing clinical trial that documented HbA1c and had a wound healing endpoint. We scrutinized 30 peer-reviewed clinical trials, representing more than 4,400 patients. The average HbA1c from the intervention side of the studies was 8.6% (7.2% - 9.9%) and the control/sham side was 8.3% (6.0% - 10.6%). Twelve studies made a direct attempt to link HbA1c and wound healing. Four retrospective studies and one prospective cohort study assert that lower HbA1c favors wound healing, but review of the studies reveal design flaws that invalidate these conclusions. In total, 25 studies showed no direct correlation between HbA1c levels and wound healing. There was no randomized controlled trial (RCT) data demonstrating that HbA1c < 7.0% improves diabetic wound healing. In every study reviewed, wounds healed with high HbA1c levels that would be considered poorly controlled by the American Diabetes Association (ADA). Frequently, patients lack optimal blood glucose control when they have a limb-threatening DFU. The evidence supports that denying hyperbaric oxygen to those with HbA1c > 7.0% is unfounded. PMID:26152104

  11. Glycosylated hemoglobin and hyperbaric oxygen coverage denials.

    PubMed

    Moffat, A D; Worth, E R; Weaver, L K

    2015-01-01

    Some Medicaid and Medicare fiscal intermediaries are denying hyperbaric oxygen (HBO2) therapy for diabetic foot ulcer (DFU) patients if the glycosylated hemoglobin (HbA1c) > 7.0%. We performed multiple PubMed searches for any diabetic wound healing clinical trial that documented HbA1c and had a wound healing endpoint. We scrutinized 30 peer-reviewed clinical trials, representing more than 4,400 patients. The average HbA1c from the intervention side of the studies was 8.6% (7.2% - 9.9%) and the control/sham side was 8.3% (6.0% - 10.6%). Twelve studies made a direct attempt to link HbA1c and wound healing. Four retrospective studies and one prospective cohort study assert that lower HbA1c favors wound healing, but review of the studies reveal design flaws that invalidate these conclusions. In total, 25 studies showed no direct correlation between HbA1c levels and wound healing. There was no randomized controlled trial (RCT) data demonstrating that HbA1c < 7.0% improves diabetic wound healing. In every study reviewed, wounds healed with high HbA1c levels that would be considered poorly controlled by the American Diabetes Association (ADA). Frequently, patients lack optimal blood glucose control when they have a limb-threatening DFU. The evidence supports that denying hyperbaric oxygen to those with HbA1c > 7.0% is unfounded.

  12. Photoacoustic imaging of human lymph nodes with endogenous lipid and hemoglobin contrast

    NASA Astrophysics Data System (ADS)

    Guggenheim, James A.; Allen, Thomas J.; Plumb, Andrew; Zhang, Edward Z.; Rodriguez-Justo, Manuel; Punwani, Shonit; Beard, Paul C.

    2015-05-01

    Lymph nodes play a central role in metastatic cancer spread and are a key clinical assessment target. Abnormal node vascularization, morphology, and size may be indicative of disease but can be difficult to visualize with sufficient accuracy using existing clinical imaging modalities. To explore the potential utility of photoacoustic imaging for the assessment of lymph nodes, images of ex vivo samples were obtained at multiple wavelengths using a high-resolution three-dimensional photoacoustic scanner. These images showed that hemoglobin based contrast reveals nodal vasculature and lipid-based contrast reveals the exterior node size, shape, and boundary integrity. These two sources of complementary contrast may allow indirect observation of cancer, suggesting a future role for photoacoustic imaging as a tool for the clinical assessment of lymph nodes.

  13. A Rare Stapes Abnormality

    PubMed Central

    Kanona, Hala; Virk, Jagdeep Singh; Kumar, Gaurav; Chawda, Sanjiv; Khalil, Sherif

    2015-01-01

    The aim of this study is to increase awareness of rare presentations, diagnostic difficulties alongside management of conductive hearing loss and ossicular abnormalities. We report the case of a 13-year-old female reporting progressive left-sided hearing loss and high resolution computed tomography was initially reported as normal. Exploratory tympanotomy revealed an absent stapedius tendon and lack of connection between the stapes superstructure and footplate. The footplate was fixed. Stapedotomy and stapes prosthesis insertion resulted in closure of the air-bone gap by 50 dB. A review of world literature was performed using MedLine. Middle ear ossicular discontinuity can result in significant conductive hearing loss. This can be managed effectively with surgery to help restore hearing. However, some patients may not be suitable or decline surgical intervention and can be managed safely conservatively. PMID:25628909

  14. Interaction of the chlorite-based drug WF10 and chlorite with hemoglobin, methemoglobin and ferryl hemoglobin.

    PubMed

    Pichert, Annelie; Arnhold, Jürgen

    2015-11-01

    The interaction of the chlorite-based drug solution WF10 with human oxyhemoglobin and oxidized hemoglobin forms was investigated monitoring the corresponding spectral changes in heme states. The chlorite component of WF10 converts oxyhemoglobin into methemoglobin with a rate of 35.4 M(-1)s(-1). Methemoglobin is also formed upon the interaction of ferryl hemoglobin and WF10/chlorite. The rate of this interconversion depends on the oxidation state of ferryl hemoglobin. This rate is 114 M(-1)s(-1), when ferryl hemoglobin was generated upon reaction of oxyhemoglobin and hydrogen peroxide. A considerable higher rate (6600 M(-1)s(-1)) is measured between the chlorite components of WF10 and ferryl hemoglobin after formation of the latter species from methemoglobin. WF10/chlorite inactivates also methemoglobin as evidenced by the continuous decrease of the Soret band and all other absorbances with a rate of 8.3 M(-1)s(-1). In all interconversions, the chlorite component of WF10 was the active principle as shown in experiments applying pure chlorite at the same concentration as in WF10. Thus, WF10 is able to diminish efficiently the yield of cytotoxic hemoglobin species that might appear after excessive hemolysis of red blood cells under pathologic situations.

  15. Detection of Abnormal Glucose Tolerance in Africans Is Improved by Combining A1C With Fasting Glucose: The Africans in America Study

    PubMed Central

    Thoreson, Caroline K.; O'Connor, Michelle Y.; Ricks, Madia; Chung, Stephanie T.; Tulloch-Reid, Marshall K.; Lozier, Jay N.; Sacks, David B.

    2015-01-01

    OBJECTIVE Abnormal glucose tolerance is rising in sub-Saharan Africa. Hemoglobin A1c by itself and in combination with fasting plasma glucose (FPG) is used to diagnose abnormal glucose tolerance. The diagnostic ability of A1C in Africans with heterozygous variant hemoglobin, such as sickle cell trait or hemoglobin C trait, has not been rigorously evaluated. In U.S.-based Africans, we determined by hemoglobin status the sensitivities of 1) FPG ≥5.6 mmol/L, 2) A1C ≥ 5.7% (39 mmol/mol), and 3) FPG combined with A1C (FPG ≥5.6 mmol/L and/or A1C ≥5.7% [39 mmol/mol]) for the detection of abnormal glucose tolerance. RESEARCH DESIGN AND METHODS An oral glucose tolerance test (OGTT) was performed in 216 African immigrants (68% male, age 37 ± 10 years [mean ± SD], range 20–64 years). Abnormal glucose tolerance was defined as 2-h glucose ≥7.8 mmol/L. RESULTS Variant hemoglobin was identified in 21% (46 of 216). Abnormal glucose tolerance occurred in 33% (72 of 216). When determining abnormal glucose tolerance from the OGTT (2-h glucose ≥7.8 mmol/L), sensitivities of FPG for the total, normal, and variant hemoglobin groups were 32%, 32%, and 33%, respectively. Sensitivities for A1C were 53%, 54%, and 47%. For FPG and A1C combined, sensitivities were 64%, 63%, and 67%. Sensitivities for FPG and A1C and the combination did not vary by hemoglobin status (all P > 0.6). For the entire cohort, sensitivity was higher for A1C than FPG and for both tests combined than for either test alone (all P values ≤ 0.01). CONCLUSIONS No significant difference in sensitivity of A1C by variant hemoglobin status was detected. For the diagnosis of abnormal glucose tolerance in Africans, the sensitivity of A1C combined with FPG is significantly superior to either test alone. PMID:25338926

  16. Expression of fully functional tetrameric human hemoglobin in Escherichia coli.

    PubMed Central

    Hoffman, S J; Looker, D L; Roehrich, J M; Cozart, P E; Durfee, S L; Tedesco, J L; Stetler, G L

    1990-01-01

    Synthetic genes encoding the human alpha- and beta-globin polypeptides have been expressed from a single operon in Escherichia coli. The alpha- and beta-globin polypeptides associate into soluble tetramers, incorporate heme, and accumulate to greater than 5% of the total cellular protein. Purified recombinant hemoglobin has the correct stoichiometry of alpha- and beta-globin chains and contains a full complement of heme. Each globin chain also contains an additional methionine as an extension to the amino terminus. The recombinant hemoglobin has a C4 reversed-phase HPLC profile essentially identical to that of human hemoglobin A0 and comigrates with hemoglobin A0 on SDS/PAGE. The visible spectrum and oxygen affinity are similar to that of native human hemoglobin A0. The recombinant protein shows a reduction in Bohr and phosphate effects, which may be attributed to the presence of methionine at the amino termini of the alpha and beta chains. We have also expressed the alpha- and beta-globin genes separately and found that the expression of the alpha-globin gene alone results in a marked decrease in the accumulation of alpha-globin in the cell. Separate expression of the beta-globin gene results in high levels of insoluble beta-globin. These observations suggest that the presence of alpha- and beta-globin in the same cell stabilizes alpha-globin and aids the correct folding of beta-globin. This system provides a simple method for expressing large quantities of recombinant hemoglobin and allows facile manipulation of the genes encoding hemoglobin to produce functionally altered forms of this protein. Images PMID:2236062

  17. Resveratrol: Antioxidant activity and induction of fetal hemoglobin in erythroid cells from normal donors and β-thalassemia patients.

    PubMed

    Fibach, Eitan; Prus, Eugenia; Bianchi, Nicoletta; Zuccato, Cristina; Breveglieri, Giulia; Salvatori, Francesca; Finotti, Alessia; Lipucci di Paola, Michele; Brognara, Eleonora; Lampronti, Ilaria; Borgatti, Monica; Gambari, Roberto

    2012-06-01

    Thalassemia and sickle-cell anemia (SCA) present a major public health problem in countries where the number of carriers and affected individuals is high. As a result of the abnormalities in hemoglobin production, cells of thalassemia and SCA patients exhibit oxidative stress, which ultimately is responsible for the chronic anemia observed. Therefore, identification of compounds exhibiting both antioxidant and hemoglobin-inducing activities is highly needed. Our results demonstrate resveratrol to be such a compound. This was shown both in the human K562 cell line, as well as in erythroid precursors derived from normal donors and β-thalassemia patients. Resveratrol was shown to exhibit antioxidant activity and to stimulate the expression of the γ-globin genes and the accumulation of fetal hemoglobin (HbF). To the best of our knowledge, this is the first report pointing to such a double effect of resveratrol. Since this natural product is already marketed as an antioxidant, future investigations should concentrate on demonstrating its potential to augment HbF production in experimental animal models (e.g., thalassemia and SCA mice) as well as in patients. We believe that the potential of clinical use of resveratrol as an antioxidant and HbF stimulator may offer a simple and inexpensive treatment to patients.

  18. Studies in red blood cell preservation: 4. Plasma vesicle hemoglobin exceeds free hemoglobin.

    PubMed

    Greenwalt, T J; McGuinness, C G; Dumaswala, U J

    1991-01-01

    Studies were designed to find out how much of the plasma hemoglobin ( Hb) in whole blood was in microvesicles and how much was free Hb after 21 days of storage in citrate-phosphate-dextrose anticoagulant and to determine the effect of the plasticizer, di-(2-ethylhexyl)phthalate (DEHP). The total plasma Hb in polyolefin (PO) containers without DEHP was much higher than in polyvinyl chloride (PVC) with the plasticizer (p = 0.004). Less than 30% of the Hb was in free solution in either type of container. The addition of 300 micrograms/ml of DEHP to the plasma in the PO containers resulted in marked reduction in the microvesiculation (p less than 0.01) but did not affect the level of free Hb. RBC hypotonic fragility and morphology scores were significantly improved. It is concluded that microvesiculation contributes more to plasma Hb concentration than free Hb during storage. Some hemolysis of red blood cells (RBC) is expected during blood bank storage. It has been shown that part of the hemoglobin (Hb) in the suspending medium is free and part is encapsulated in microvescicles shed by the RBC [1]. The amount of hemolysis and microvesiculation that occurs has been noted to be less when blood is stored in polyvinyl chloride (PVC) containers in which di-(2-ethylhexyl)phthalate (DEHP) is used as the plasticizer [1]. The DEHP that leaches into the plasma has been shown to decrease hemolysis, microvesiculation, and the increase in osmotic fragility which RBC undergo during refrigerated storage [2-9].(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1949704

  19. Ictal Cardiac Ryhthym Abnormalities

    PubMed Central

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic–clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  20. Ictal Cardiac Ryhthym Abnormalities.

    PubMed

    Ali, Rushna

    2016-01-01

    Cardiac rhythm abnormalities in the context of epilepsy are a well-known phenomenon. However, they are under-recognized and often missed. The pathophysiology of these events is unclear. Bradycardia and asystole are preceded by seizure onset suggesting ictal propagation into the cortex impacting cardiac autonomic function, and the insula and amygdala being possible culprits. Sudden unexpected death in epilepsy (SUDEP) refers to the unanticipated death of a patient with epilepsy not related to status epilepticus, trauma, drowning, or suicide. Frequent refractory generalized tonic-clonic seizures, anti-epileptic polytherapy, and prolonged duration of epilepsy are some of the commonly identified risk factors for SUDEP. However, the most consistent risk factor out of these is an increased frequency of generalized tonic-clonic seizures (GTC). Prevention of SUDEP is extremely important in patients with chronic, generalized epilepsy. Since increased frequency of GTCS is the most consistently reported risk factor for SUDEP, effective seizure control is the most important preventive strategy. PMID:27347227

  1. Communication and abnormal behaviour.

    PubMed

    Crown, S

    1979-01-01

    In this paper the similarities between normal and abnormal behaviour are emphasized and selected aspects of communication, normal and aberrant, between persons are explored. Communication in a social system may be verbal or non-verbal: one person's actions cause a response in another person. This response may be cognitive, behavioural or physiological. Communication may be approached through the individual, the social situation or social interaction. Psychoanalysis approaches the individual in terms of the coded communications of psychoneurotic symptoms or psychotic behaviour; the humanist-existential approach is concerned more with emotional expression. Both approaches emphasize the development of individual identity. The interaction between persons and their social background is stressed. Relevant are sociological concepts such as illness behaviour, stigma, labelling, institutionalization and compliance. Two approaches to social interactions are considered: the gamesplaying metaphor, e.g. back pain as a psychosocial manipulation--the 'pain game'; and the 'spiral of reciprocal perspectives' which emphasizes the interactional complexities of social perceptions. Communicatory aspects of psychological treatments are noted: learning a particular metaphor such as 'resolution' of the problem (psychotherapy), learning more 'rewarding' behaviour (learning theory) or learning authenticity or self-actualization (humanist-existential).

  2. Communication and abnormal behaviour.

    PubMed

    Crown, S

    1979-01-01

    In this paper the similarities between normal and abnormal behaviour are emphasized and selected aspects of communication, normal and aberrant, between persons are explored. Communication in a social system may be verbal or non-verbal: one person's actions cause a response in another person. This response may be cognitive, behavioural or physiological. Communication may be approached through the individual, the social situation or social interaction. Psychoanalysis approaches the individual in terms of the coded communications of psychoneurotic symptoms or psychotic behaviour; the humanist-existential approach is concerned more with emotional expression. Both approaches emphasize the development of individual identity. The interaction between persons and their social background is stressed. Relevant are sociological concepts such as illness behaviour, stigma, labelling, institutionalization and compliance. Two approaches to social interactions are considered: the gamesplaying metaphor, e.g. back pain as a psychosocial manipulation--the 'pain game'; and the 'spiral of reciprocal perspectives' which emphasizes the interactional complexities of social perceptions. Communicatory aspects of psychological treatments are noted: learning a particular metaphor such as 'resolution' of the problem (psychotherapy), learning more 'rewarding' behaviour (learning theory) or learning authenticity or self-actualization (humanist-existential). PMID:261653

  3. Abnormal uterine bleeding.

    PubMed

    Whitaker, Lucy; Critchley, Hilary O D

    2016-07-01

    Abnormal uterine bleeding (AUB) is a common and debilitating condition with high direct and indirect costs. AUB frequently co-exists with fibroids, but the relationship between the two remains incompletely understood and in many women the identification of fibroids may be incidental to a menstrual bleeding complaint. A structured approach for establishing the cause using the Fédération International de Gynécologie et d'Obstétrique (FIGO) PALM-COEIN (Polyp, Adenomyosis, Leiomyoma, Malignancy (and hyperplasia), Coagulopathy, Ovulatory disorders, Endometrial, Iatrogenic and Not otherwise classified) classification system will facilitate accurate diagnosis and inform treatment options. Office hysteroscopy and increasing sophisticated imaging will assist provision of robust evidence for the underlying cause. Increased availability of medical options has expanded the choice for women and many will no longer need to recourse to potentially complicated surgery. Treatment must remain individualised and encompass the impact of pressure symptoms, desire for retention of fertility and contraceptive needs, as well as address the management of AUB in order to achieve improved quality of life. PMID:26803558

  4. Abortion for fetal abnormality.

    PubMed

    Maclean, N E

    1979-07-25

    I wish to thank Dr. Pauline Bennett for her reply (NZ Med J, 13 June). She has demonstrated well that in dealing with sensitive difficult issues such as abortion for fetal abnormality, the one thing the doctor is not recommended to do is to speak the truth] I am prompted to write this letter for 2 reasons. Firstly, the excellent letter written by Dr. A. M. Rutherford (NZ Med J, 13 June) on the subject of abortion stated, "The most disturbing feature about the whole controversy is the 'blunting of our conscience'." When the doctors are not encouraged to be honest with patients then indeed our conscience has been blunted. Secondly, I watched Holocaust last night, and cannot refrain from stating that I see frightening parallels between our liberal abortion policy and the activities of the Nazis. As I watched the "mental patients" being herded into the shed for gassing by the polite, tidy, white coated medical staff, and then heard the compassionate, sensitive, letter of the hospital authorities to the relatives of the deceased, the parallel became obvious. The mental patients were weak, defenseless, burdensome, and uneconomic; the unborn are weak, defenseless, burdensome, and uneconomic. The hospital authority's letter was acceptable in many ways, acceptable except that its words bore no relation to the truth. It is said that the "first casualty of war is the truth". Whether that war involves the Jews, or the insane, or the unborn, the statement would seem correct.

  5. Hemoglobin variability after renal transplantation is associated with mortality

    PubMed Central

    Kainz, Alexander; Wilflingseder, Julia; Függer, Reinhold; Kramar, Reinhard; Oberbauer, Rainer

    2012-01-01

    Summary Anemia is a common problem after renal transplantation. Therefore, the patients are treated with erythropoietin stimulating agents (ESAs). The varying response to treatment contributes to hemoglobin variability, which might be associated with mortality. We conducted a retrospective cohort study of first kidney allograft recipients between 1990 and 2008 represented in the Austrian Transplant Registry. We included 1441 patients of whom 683 received ESAs at any time after transplantation. Cox regression with cubic splines and linear estimates and the purposeful selection algorithm of covariables were used. The measure of variability was the moving standard deviation computed at three monthly intervals for the entire graft life. The hazard ratio (HR) of mortality and graft loss in the spline models increased with hemoglobin variability. The linear HR for mortality was 2.35 (95% confidence interval 1.75–3.17, P < 0.001) and functional graft loss 2.45 (1.76–3.40, P < 0.001). In an adjusted Cox model (ESA use, hemoglobin, age, diabetes, days on dialysis, eGFR, biopsy confirmed acute rejection and year of transplantation), hemoglobin variability was associated with mortality (HR: 2.11; 1.51–2.94; P < 0.001). No association with functional graft loss could be detected (HR: 1.34; 0.93-1.93; P = 0.121). These findings suggest that hemoglobin variability is associated with mortality of renal allograft recipients. PMID:22313094

  6. COPPER AND COBALT RELATED HEMOGLOBIN PRODUCTION IN EXPERIMENTAL ANEMIA

    PubMed Central

    Robscheit-Robbins, F. S.; Whipple, G. H.

    1942-01-01

    Copper added to a standard diet often effects a moderate increase in hemoglobin production in anemia due to blood loss. The copper response is quite irregular in contrast to the iron response. In these dogs there is no lack of copper held in reserve stores (liver and spleen) so the reaction is not related to an actual deficiency of the element. An effect upon enzyme complexes related to globin and hemoglobin production is to be considered. Cobalt under similar conditions causes no stimulus to hemoglobin production, rather an inhibitory effect when more than minimal doses are given. The claim that cobalt causes a polycythemia in dogs receives no support from our experiments. PMID:19871199

  7. Hemoglobin - a novel ligand of hepatocyte ectopic F1-ATPase.

    PubMed

    Gburek, J; Konopska, B; Juszczynska, K; Piwowar, A; Dziegiel, P; Borska, S; Tolosano, E; Golab, K

    2015-12-01

    The liver is largely responsible for free hemoglobin uptake, but the molecular mechanism of this phenomenon has never been revealed. This paper presents the results of the study on hemoglobin binding components of the hepatocyte membrane that were purified using affinity chromatography on a hemoglobin matrix and identified by peptide mass fingerprinting. Both F1-ATPase alpha and beta subunits were retrieved. The binding was confirmed via an intrinsic fluorescence quenching study using a purified recombinant F1-ATPase beta subunit, and the dissociation constant for the complex was estimated from the saturation binding curve (Kd = 7.5 x 10(-7) M). The results indicate that haemoglobin binds to hepatocyte ectopic F1-ATPase. We suggested the plausible role of the receptor in endocytosis of haemoglobin by the hepatocyte.

  8. Conformational changes monitored by fluorescence study on reconstituted hemoglobins

    NASA Astrophysics Data System (ADS)

    Venkateshrao, S.; Manoharan, P. T.

    2004-09-01

    Intrinsic steady state fluorescence measurements were performed on a series of reconstituted metal ion and hybrid hemoglobins (Hbs). At 296 nm excitation, the spectrum exhibits a broad and asymmetric feature in the case of copper and nickel reconstituted hemoglobins. Deconvolution of the fluorescence bands clearly reveals the existence of two definite peaks. A similar trend was also observed for hybrid hemoglobins (CuNi, NiCu, CuFe-CO, and NiFe-CO). A guassian fit of the fluorescence bands in these proteins again yields two prominent peaks, which are assigned as due to two different tryptophan (Trp) environments. A relative ratio of the amplitudes of these peaks indicates the percentage of T-character in these molecules. This is in support to our previous findings by other spectroscopic studies on the same molecules. These studies therefore, suggest the presence of two different environments of a tryptophan thereby revealing structural heterogeneity among the subunits.

  9. Haem degradation in abnormal haemoglobins.

    PubMed Central

    Brown, S B; Docherty, J C

    1978-01-01

    The coupled oxidation of certain abnormal haemoglobins leads to different bile-pigment isomer distributions from that of normal haemoglobin. The isomer pattern may be correlated with the structure of the abnormal haemoglobin in the neighbourhood of the haem pocket. This is support for haem degradation by an intramolecular reaction. PMID:708385

  10. Systemic abnormalities in liver disease

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases. PMID:19554648

  11. Abnormal pressure in hydrocarbon environments

    USGS Publications Warehouse

    Law, B.E.; Spencer, C.W.

    1998-01-01

    Abnormal pressures, pressures above or below hydrostatic pressures, occur on all continents in a wide range of geological conditions. According to a survey of published literature on abnormal pressures, compaction disequilibrium and hydrocarbon generation are the two most commonly cited causes of abnormally high pressure in petroleum provinces. In young (Tertiary) deltaic sequences, compaction disequilibrium is the dominant cause of abnormal pressure. In older (pre-Tertiary) lithified rocks, hydrocarbon generation, aquathermal expansion, and tectonics are most often cited as the causes of abnormal pressure. The association of abnormal pressures with hydrocarbon accumulations is statistically significant. Within abnormally pressured reservoirs, empirical evidence indicates that the bulk of economically recoverable oil and gas occurs in reservoirs with pressure gradients less than 0.75 psi/ft (17.4 kPa/m) and there is very little production potential from reservoirs that exceed 0.85 psi/ft (19.6 kPa/m). Abnormally pressured rocks are also commonly associated with unconventional gas accumulations where the pressuring phase is gas of either a thermal or microbial origin. In underpressured, thermally mature rocks, the affected reservoirs have most often experienced a significant cooling history and probably evolved from an originally overpressured system.

  12. Electrocardiograph abnormalities revealed during laparoscopy.

    PubMed

    Nijjer, Sukhjinder; Dubrey, Simon William

    2010-01-01

    This brief case presents a well patient in whom an electrocardiograph abnormality consistent with an accessory pathway was found during a routine procedure. We present the electrocardiographs, explain the underlying condition, and consider why the abnormality was revealed in this manner.

  13. Erythrocyte phosphates and hemoglobin function in monotremes and some marsupials.

    PubMed

    Isaacks, R; Nicol, S; Sallis, J; Zeidler, R; Kim, H D

    1984-02-01

    Hematologic values, red blood cell (RBC) organic phosphate composition, hemoglobin function, and hemoglobin composition have been determined on blood from the monotremes, the duckbill platypus and the echidna, and three species of marsupials, the Tasmanian devil, the wallaby, and the brush-tail possum. Blood from the platypus had a RBC count of 8.63 X 10(6)/mm3, a mean corpuscular volume of 49.1 millemicron3, and a white blood cell count of 26.0 X 10(3)/mm3. The RBCs from the monotremes and the three marsupials exhibited hemoglobin polymorphism, each with three hemoglobin components. Addition of ATP, 2,3-bisphosphoglycerate (2,3-P2-glycerate), or inositol pentakisphosphate (inositol-P5) to phosphate-free hemoglobin from each species decreased hemoglobin oxygen affinity; the order of effect of these compounds was ATP less than 2,3-P2-glycerate less than inositol-P5. The RBCs of all species had concentrations of 2,3-P2-glycerate ranging from 6.02 mumol/ml RBCs in the wallaby to 10.39 mumol/ml RBCs in the possum. The RBCs from the three species of marsupials had concentrations of ATP ranging from 0.24 mumol/ml RBCs in the possum to 0.80 mumol/ml RBCs in the Tasmanian devil. The level of ATP in RBCs of the platypus and echidna were 0.06 and 0.03 mumol/ml RBCs, respectively.

  14. Independency of Fe ions in hemoglobin on immunomagnetic reduction assay

    NASA Astrophysics Data System (ADS)

    Yang, S. Y.; Lan, C. B.; Chen, C. H.; Horng, H. E.; Hong, Chin-Yih; Yang, H. C.; Lai, Y. K.; Lin, Y. H.; Teng, K. S.

    2009-10-01

    Immunomagnetic reduction (IMR), which involves measuring the reduction in the ac magnetic susceptibility of magnetic reagents, is due to the association between bio-functionalized magnetic nanoparticles and target bio-molecules. This has been demonstrated for assaying proteins in solutions free of Fe ions, such as serum. In this work, the validity of IMR assay for samples rich in Fe ions like hemoglobin (Hb) is investigated. According to the results, there is no magnetic signal contributed by Fe-ion-rich Hb. Furthermore, the results show a high sensitivity in assaying hemoglobin A1c (HbA1c) by using IMR.

  15. Structural significance of the amino terminal residues in human hemoglobin

    SciTech Connect

    Hefta, S.A.

    1986-01-01

    The amino terminal valine residues on the alpha chains of human hemoglobin are known to be important for the function of the molecule. Allosteric effectors such as protons, chloride ions and metabolic anions such as 2,3-diphosphoglycerate bind or associate with these residues and facilitate the release of oxygen. Carbon dioxide also functions as an effector as it is partly transported from the tissues to the lungs by binding to the amino terminal residues. This research describes the semisynthetic alteration of this region and the hemoglobin analogs produced were analyzed by /sup 13/C NMR.

  16. [Hemoglobins, XLVIII: the primary structure of hemoglobin of the Indian elephant (Elephas maximus, Proboscidea): beta 2 = Asn].

    PubMed

    Braunitzer, G; Jelkmann, W; Stangl, A; Schrank, B; Krombach, C

    1982-07-01

    The primary structure of the hemoglobin of the Indian Elephant (Elephas maximus) is given. The sequence was determined automatically in a sequenator. By homologous comparison with adult human HbA, the alpha-chains differ by 24 exchanges and the beta-chains by 27 exchanges. Furthermore, we report p(O2)50 values with regard to altered contact sites with 2,3-bisphosphoglycerate in Indian elephant hemoglobin. Our findings explain the low p(O2)50 and the reduced interaction with 2,3-bisphosphoglycerate. Elephant hemoglobin has, like that of the Llama, only five phosphate binding sites. In addition, we have made an attempt to relate these results to aspects of respiratory physiology. Some implications of these biochemical and physiological results, concerning the Second Punic War and Hannibal's Alp transition, are given.

  17. A recombinant human hemoglobin with anti-sickling properties greater than fetal hemoglobin.

    PubMed

    Levasseur, Dana N; Ryan, Thomas M; Reilly, Michael P; McCune, Steven L; Asakura, Toshio; Townes, Tim M

    2004-06-25

    A new recombinant, human anti-sickling beta-globin polypeptide designated beta(AS3) (betaGly(16) --> Asp/betaGlu(22) --> Ala/betaThr(87) --> Gln) was designed to increase affinity for alpha-globin. The amino acid substitutions at beta22 and beta87 are located at axial and lateral contacts of the sickle hemoglobin (HbS) polymers and strongly inhibit deoxy-HbS polymerization. The beta16 substitution confers the recombinant beta-globin subunit (beta(AS3)) with a competitive advantage over beta(S) for interaction with the alpha-globin polypeptide. Transgenic mouse lines that synthesize high levels of HbAS3 (alpha(2)beta(AS3)(2)) were established, and recombinant HbAS3 was purified from hemolysates and then characterized. HbAS3 binds oxygen cooperatively and has an oxygen affinity that is comparable with fetal hemoglobin. Delay time experiments demonstrate that HbAS3 is a potent inhibitor of HbS polymerization. Subunit competition studies confirm that beta(AS3) has a distinct advantage over beta(S) for dimerization with alpha-globin. When equal amounts of beta(S)- and beta(AS3)-globin monomers compete for limiting alpha-globin chains up to 82% of the tetramers formed is HbAS3. Knock-out transgenic mice that express exclusively human HbAS3 were produced. When these mice were bred with knock-out transgenic sickle mice the beta(AS3) polypeptides corrected all hematological parameters and organ pathology associated with the disease. Expression of beta(AS3)-globin should effectively lower the concentration of HbS in erythrocytes of patients with sickle cell disease, especially in the 30% percent of these individuals who coinherit alpha-thalassemia. Therefore, constructs expressing the beta(AS3)-globin gene may be suitable for future clinical trials for sickle cell disease. PMID:15084588

  18. Abnormal pulmonary function and associated risk factors in children and adolescents with sickle cell anemia.

    PubMed

    Arteta, Manuel; Campbell, Andrew; Nouraie, Mehdi; Rana, Sohail; Onyekwere, Onyinye C; Ensing, Gregory; Sable, Craig; Dham, Niti; Darbari, Deepika; Luchtman-Jones, Lori; Kato, Gregory J; Gladwin, Mark T; Castro, Oswaldo L; Minniti, Caterina P; Gordeuk, Victor R

    2014-04-01

    Obstructive and restrictive pulmonary changes develop in children with sickle cell disease, but reports conflict as to the type of change that predominates. We prospectively performed spirometry, plethysmography, and lung diffusing capacity in 146 children aged 7 to 20 years with hemoglobin SS or Sβ(0)-thalassemia. Nineteen percent of the patients had obstructive physiology as defined according to guidelines of the American Thoracic Society. In addition, 9% had restrictive physiology and 11% had abnormal but not categorized physiology. Increasing age, patient-reported or family-reported history of asthma or wheezing, and higher lactate dehydrogenase concentration were independent predictors of obstruction as reflected in lower forced expiratory volume in the first second/forced vital capacity. In conclusion, abnormal pulmonary function, most often obstructive, is common in children with hemoglobin SS and Sβ(0)-thalassemia. Full pulmonary function testing should be performed in children with hemoglobin SS or Sβ(0)-thalassemia, especially with history of asthma or wheezing and accentuated elevations in hemolytic markers.

  19. Chromosomal abnormalities in human sperm

    SciTech Connect

    Martin, R.H.

    1985-01-01

    The ability to analyze human sperm chromosome complements after penetration of zona pellucida-free hamster eggs provides the first opportunity to study the frequency and type of chromosomal abnormalities in human gametes. Two large-scale studies have provided information on normal men. We have studied 1,426 sperm complements from 45 normal men and found an abnormality rate of 8.9%. Brandriff et al. (5) found 8.1% abnormal complements in 909 sperm from 4 men. The distribution of numerical and structural abnormalities was markedly dissimilar in the 2 studies. The frequency of aneuploidy was 5% in our sample and only 1.6% in Brandriff's, perhaps reflecting individual variability among donors. The frequency of 24,YY sperm was low: 0/1,426 and 1/909. This suggests that the estimates of nondisjunction based on fluorescent Y body data (1% to 5%) are not accurate. We have also studied men at increased risk of sperm chromosomal abnormalities. The frequency of chromosomally unbalanced sperm in 6 men heterozygous for structural abnormalities varied dramatically: 77% for t11;22, 32% for t6;14, 19% for t5;18, 13% for t14;21, and 0% for inv 3 and 7. We have also studied 13 cancer patients before and after radiotherapy and demonstrated a significant dose-dependent increase of sperm chromosome abnormalities (numerical and structural) 36 months after radiation treatment.

  20. Hemoglobin Birmingham and hemoglobin Galicia: two unstable beta chain variants characterized by small deletions and insertions.

    PubMed

    Wilson, J B; Webber, B B; Hu, H; Kutlar, A; Kutlar, F; Codrington, J F; Prchal, J T; Hall, K M; de Pablos, J M; Rodriguez, I

    1990-05-01

    Two unstable hemoglobins (Hbs) causing rather severe hemolytic anemia have been characterized. The beta chain of Hb Birmingham, found in an adult black man, is characterized by the loss of -Leu-Ala-His-Lys- at positions 141, 142, 143, and 144 and their replacement by one Gln residue. These changes are the result of a deletion of nine nucleotides, namely two base pairs (bp) of codon 141, all of codons 142 and 143, and one bp of codon 144; the remaining CAG triplet (C from codon 141 and AG from codon 144) codes for the inserted glutamine. In the beta chain of Hb Galicia from a Spanish patient, His and Val at positions 97 and 98 are replaced by one Leu residue. This is due to an ACG deletion in codons 97 and 98, which causes the removal of one His and one Val residue, while the remaining CTG triplet (C from codon 97 and TG from codon 98) codes for the inserted leucine residue. Two mechanisms, namely slipped mispairing in the presence of short repeats, and misreading by DNA polymerase due to a local distortion of the DNA helix, are considered in explaining the origin of the small deletions.

  1. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Electrophoretic hemoglobin analysis system. 864.7440 Section 864.7440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  2. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Automated hemoglobin system. 864.5620 Section 864.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices §...

  3. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated hemoglobin system. 864.5620 Section 864.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices §...

  4. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Electrophoretic hemoglobin analysis system. 864.7440 Section 864.7440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  5. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Automated hemoglobin system. 864.5620 Section 864.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices §...

  6. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Electrophoretic hemoglobin analysis system. 864.7440 Section 864.7440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  7. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Automated hemoglobin system. 864.5620 Section 864.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices §...

  8. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Electrophoretic hemoglobin analysis system. 864.7440 Section 864.7440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  9. 21 CFR 864.7440 - Electrophoretic hemoglobin analysis system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Electrophoretic hemoglobin analysis system. 864.7440 Section 864.7440 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  10. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automated hemoglobin system. 864.5620 Section 864.5620 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices §...

  11. 21 CFR 864.7455 - Fetal hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal hemoglobin assay. 864.7455 Section 864.7455 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal...

  12. Ultrasonic processing for recovery of chicken erythrocyte hemoglobin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hemoglobin from chicken blood has been shown to be a good substitute for synthetic polymeric flocculants. One stage of processing the blood entails breaking open the cells and releasing the cytoplasmic contents; in the present study, we investigate the use of ultrasonic processing at this stage. Was...

  13. Rapid and sensitive quantitation of heme in hemoglobinized cells.

    PubMed

    Marcero, Jason R; Piel Iii, Robert B; Burch, Joseph S; Dailey, Harry A

    2016-01-01

    Rapid and accurate heme quantitation in the research lab has become more desirable as the crucial role that intracellular hemoproteins play in metabolism continues to emerge. Here, the time-honored approaches of pyridine hemochromogen and fluorescence heme assays are compared with direct absorbance-based technologies using the CLARiTY spectrophotometer. All samples tested with these methods were rich in hemoglobin-associated heme, including buffered hemoglobin standards, whole blood from mice, and murine erythroleukemia (MEL) and K562 cells. While the pyridine hemochromogen assay demonstrated the greatest linear range of heme detection, all 3 methods demonstrated similar analytical sensitivities and normalized limits of quantitation of ∼1 µM. Surprisingly, the fluorescence assay was only shown to be distinct in its ability to quantitate extremely small samples. Using the CLARiTY system in combination with pyridine hemochromogen and cell count data, a common hemoglobin extinction coefficient for blood and differentiating MEL and K562 cells of 0.46 µM-1 cm-1 was derived. This value was applied to supplemental experiments designed to measure MEL cell hemoglobinization in response to the addition or removal of factors previously shown to affect heme biosynthesis (e.g., L-glutamine, iron). PMID:27528073

  14. Human macrophage hemoglobin-iron metabolism in vitro

    SciTech Connect

    Custer, G.; Balcerzak, S.; Rinehart, J.

    1982-01-01

    An entirely in vitro technique was employed to characterize hemoglobin-iron metabolism by human macrophages obtained by culture of blood monocytes and pulmonary alveolar macrophages. Macrophages phagocytized about three times as many erythrocytes as monocytes and six times as many erythrocytes as pulmonary alveolar macrophages. The rate of subsequent release of /sup 59/Fe to the extracellular transferrin pool was two- to fourfold greater for macrophages as compared to the other two cell types. The kinetics of /sup 59/Fe-transferrin release were characterized by a relatively rapid early phase (hours 1-4) followed by a slow phase (hours 4-72) for all three cell types. Intracellular movement of iron was characterized by a rapid shift from hemoglobin to ferritin that was complete with the onset of the slow phase of extracellular release. A transient increase in /sup 59/Fe associated with an intracellular protein eluting with transferrin was also observed within 1 hour after phagocytosis. The process of hemoglobin-iron release to extracellular transferrin was inhibited at 4 degrees C but was unaffected by inhibitory of protein synthesis, glycolysis, microtubule function, and microfilament function. These data emphasize the rapidity of macrophage hemoglobin iron metabolism, provide a model for characterization of this process in vitro, and in general confirm data obtained utilizing in vivo animal models.

  15. Effect of Some High Consumption Spices on Hemoglobin Glycation

    PubMed Central

    Naderi, G. H.; Dinani, Narges J.; Asgary, S.; Taher, M.; Nikkhoo, N.; Boshtam, M.

    2014-01-01

    Formation of glycation products is major factor responsible in complications of diabetes. Worldwide trend is toward the use of natural additives in reducing the complications of diseases. Therefore, there is a growing interest in natural antiglycation found in plants. Herbs and spices are one of the most important targets to search for natural antiglycation from the point of view of safety. This study investigated the ability of some of the spices to inhibit glycation process in a hemoglobin/glucose model system and compared their potency with each other. For this subject the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of extracts by the three concentrations 0.25, 0.5 and 1 μg/ml was measured colorimetrically at 520 nm. Results represent that some of extracts such as wild caraway, turmeric, cardamom and black pepper have inhibitory effects on hemoglobin glycation. But some of the extracts such as anise and saffron have not only inhibitory effects but also aggravated this event and have proglycation properties. In accordance with the results obtained we can conclude that wild caraway, turmeric, cardamom and black pepper especially wild caraway extracts are potent antiglycation agents, which can be of great value in the preventive glycation-associated complications in diabetes. PMID:25593391

  16. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Indications for use. For the treatment of anemia in dogs by increasing systemic oxygen content (plasma hemoglobin concentration) and improving the clinical signs associated with anemia, regardless of the cause of anemia (hemolysis, blood loss, or ineffective erythropoiesis). (3) Limitations. For intravenous use...

  17. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Indications for use. For the treatment of anemia in dogs by increasing systemic oxygen content (plasma hemoglobin concentration) and improving the clinical signs associated with anemia, regardless of the cause of anemia (hemolysis, blood loss, or ineffective erythropoiesis). (3) Limitations. For intravenous use...

  18. Effect of some high consumption spices on hemoglobin glycation.

    PubMed

    Naderi, G H; Dinani, Narges J; Asgary, S; Taher, M; Nikkhoo, N; Boshtam, M

    2014-01-01

    Formation of glycation products is major factor responsible in complications of diabetes. Worldwide trend is toward the use of natural additives in reducing the complications of diseases. Therefore, there is a growing interest in natural antiglycation found in plants. Herbs and spices are one of the most important targets to search for natural antiglycation from the point of view of safety. This study investigated the ability of some of the spices to inhibit glycation process in a hemoglobin/glucose model system and compared their potency with each other. For this subject the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of extracts by the three concentrations 0.25, 0.5 and 1 μg/ml was measured colorimetrically at 520 nm. Results represent that some of extracts such as wild caraway, turmeric, cardamom and black pepper have inhibitory effects on hemoglobin glycation. But some of the extracts such as anise and saffron have not only inhibitory effects but also aggravated this event and have proglycation properties. In accordance with the results obtained we can conclude that wild caraway, turmeric, cardamom and black pepper especially wild caraway extracts are potent antiglycation agents, which can be of great value in the preventive glycation-associated complications in diabetes.

  19. Correlations between oxygen affinity and sequence classifications of plant hemoglobins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plants express three phylogenetic classes of hemoglobins (Hb) based on sequence analyses. Class 1 and 2 Hbs are full length globins with the classical 8 helix Mb-like fold, whereas Class 3 plant Hbs resemble the truncated globins found in bacteria. With the exception of the specialized leghemoglobin...

  20. Occult hemoglobin as an indicator of impingement stress in fishes

    SciTech Connect

    Not Available

    1980-01-01

    During the process of impingement on cooling system intake screens, fish may be subject to different types of stress, the total of which often results in the death of individual fish. This report assesses the use of occult hemoglobin in fish demand mucus as an indicator of impingement stress. (ACR)

  1. Using a Poetry Reading on Hemoglobin to Enhance Subject Matter

    ERIC Educational Resources Information Center

    Herrick, Richard S.; Cording, Robert K.

    2013-01-01

    student interest in the beauty and mystery of chemistry. A reading of the poem "Jerry-Built Forever" (on various aspects of hemoglobin) is used as an example; the poem is included in the article. Details of how the reading was performed and reactions of the…

  2. The Relationship Between Hemoglobin Level and Intellectual Function.

    ERIC Educational Resources Information Center

    Munro, Nancy

    In a study to learn whether or not poor nutrition, as indicated by low hemoglobin levels, affects intelligence and behavior, 113 Head Start children in Missoula, Montana took part. Group testing with the Lorge Thorndike Intelligence Test and individual testing with the Wechsler and Primary Scale of Intelligence or Wechsler Intelligence Scale for…

  3. Effect of some high consumption spices on hemoglobin glycation.

    PubMed

    Naderi, G H; Dinani, Narges J; Asgary, S; Taher, M; Nikkhoo, N; Boshtam, M

    2014-01-01

    Formation of glycation products is major factor responsible in complications of diabetes. Worldwide trend is toward the use of natural additives in reducing the complications of diseases. Therefore, there is a growing interest in natural antiglycation found in plants. Herbs and spices are one of the most important targets to search for natural antiglycation from the point of view of safety. This study investigated the ability of some of the spices to inhibit glycation process in a hemoglobin/glucose model system and compared their potency with each other. For this subject the best concentration and time to incubate glucose with hemoglobin was investigated. Then the glycosylation degree of hemoglobin in the presence of extracts by the three concentrations 0.25, 0.5 and 1 μg/ml was measured colorimetrically at 520 nm. Results represent that some of extracts such as wild caraway, turmeric, cardamom and black pepper have inhibitory effects on hemoglobin glycation. But some of the extracts such as anise and saffron have not only inhibitory effects but also aggravated this event and have proglycation properties. In accordance with the results obtained we can conclude that wild caraway, turmeric, cardamom and black pepper especially wild caraway extracts are potent antiglycation agents, which can be of great value in the preventive glycation-associated complications in diabetes. PMID:25593391

  4. 21 CFR 864.7400 - Hemoglobin A2 assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Hemoglobin A2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... polypeptide chains). (b) Classification. Class II (performance standards)....

  5. 21 CFR 864.7400 - Hemoglobin A 2 assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hemoglobin A 2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... polypeptide chains). (b) Classification. Class II (performance standards)....

  6. 21 CFR 864.7400 - Hemoglobin A2 assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Hemoglobin A2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... polypeptide chains). (b) Classification. Class II (performance standards)....

  7. 21 CFR 864.7400 - Hemoglobin A2 assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hemoglobin A2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... polypeptide chains). (b) Classification. Class II (performance standards)....

  8. 21 CFR 864.7400 - Hemoglobin A 2 assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hemoglobin A 2 assay. 864.7400 Section 864.7400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... polypeptide chains). (b) Classification. Class II (performance standards)....

  9. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hemoglobin immunological test system. 866.5470 Section 866.5470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  10. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Hemoglobin immunological test system. 866.5470 Section 866.5470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems §...

  11. Hemoglobin, Growth, and Attention of Infants in Southern Ethiopia

    ERIC Educational Resources Information Center

    Aubuchon-Endsley, Nicki L.; Grant, Stephanie L.; Berhanu, Getenesh; Thomas, David G.; Schrader, Sarah E.; Eldridge, Devon; Kennedy, Tay; Hambidge, Michael

    2011-01-01

    Male and female infants from rural Ethiopia were tested to investigate relations among hemoglobin (Hb), anthropometry, and attention. A longitudinal design was used to examine differences in attention performance from 6 (M = 24.9 weeks, n = 89) to 9 months of age (M = 40.6 weeks, n = 85), differences hypothesized to be related to changes in iron…

  12. Liposome-encapsulated hemoglobin: an oxygen-carrying fluid.

    PubMed

    Rabinovici, R; Rudolph, A S; Ligler, F S; Yue, T L; Feuerstein, G

    1990-09-01

    From the original concept of encapsulating hemoglobin in an inert shell, LEH has evolved into a fluid proven to carry oxygen, capable of surviving for reasonable periods in the circulation, and amenable to large-scale production. The formula for the outer shell evolved from synthetic, nonlipid materials, to egg-lecithin-based lipid mixtures, to distearoyl-phosphatidylcholine-based blends. The fabrication technology started with the production of milliliter quantities and methods detrimental to the hemoglobin and developed into high-pressure extrusion systems producing multi-liter quantities without damaging the hemoglobin. The development of methods for analysis and quality control of LEH has been difficult: even techniques for measuring basic characteristics of size and methemoglobin are still being standardized. In vivo studies have established that LEH has a circulation half-life of 16-20 hr and can carry oxygen sufficient to sustain life, but safety has yet to be proven. In each of the general areas mentioned above, there are opportunities for further improvement and characterization. The source of the hemoglobin and the coencapsulation of hemoglobin modifiers needs to be reassessed now that human hemoglobin has been cloned and functional hemoglobin can be produced by using fermentation techniques. The development of routine methods for quality control and assurance must accompany the production of large quantities of LEH for preclinical studies. Whether or not the LEH can and should be manufactured as a lyophilized product must be assessed. Animal studies must done to prove safety as well as efficacy in a variety of clinical models, including hemorrhagic and septic shock as well as various levels of isovolemic exchange. One approach toward the improvement of the LEH is to alter the liposome surface to increase its biocompatibility. The evolution of biocompatible liposome surfaces has included carbohydrate moieties, as carbohydrates are expressed on the

  13. Plant hemoglobins: a molecular fossil record for the evolution of oxygen transport.

    PubMed

    Hoy, Julie A; Robinson, Howard; Trent, James T; Kakar, Smita; Smagghe, Benoit J; Hargrove, Mark S

    2007-08-01

    The evolution of oxygen transport hemoglobins occurred on at least two independent occasions. The earliest event led to myoglobin and red blood cell hemoglobin in animals. In plants, oxygen transport "leghemoglobins" evolved much more recently. In both events, pentacoordinate heme sites capable of inert oxygen transfer evolved from hexacoordinate hemoglobins that have unrelated functions. High sequence homology between hexacoordinate and pentacoordinate hemoglobins in plants has poised them for potential structural analysis leading to a molecular understanding of this important evolutionary event. However, the lack of a plant hexacoordinate hemoglobin structure in the exogenously ligand-bound form has prevented such comparison. Here we report the crystal structure of the cyanide-bound hexacoordinate hemoglobin from barley. This presents the first opportunity to examine conformational changes in plant hexacoordinate hemoglobins upon exogenous ligand binding, and reveals structural mechanisms for stabilizing the high-energy pentacoordinate heme conformation critical to the evolution of reversible oxygen binding hemoglobins.

  14. Plant Hemoglobins: A Molecular Fossil Record for the Evolutin of Oxygen Transport

    SciTech Connect

    Hoy,J.; Robinson, H.; Trent, lll, J.; Kakar, S.; Smagghe, B.; Hargrove, M.

    2007-01-01

    The evolution of oxygen transport hemoglobins occurred on at least two independent occasions. The earliest event led to myoglobin and red blood cell hemoglobin in animals. In plants, oxygen transport 'leghemoglobins' evolved much more recently. In both events, pentacoordinate heme sites capable of inert oxygen transfer evolved from hexacoordinate hemoglobins that have unrelated functions. High sequence homology between hexacoordinate and pentacoordinate hemoglobins in plants has poised them for potential structural analysis leading to a molecular understanding of this important evolutionary event. However, the lack of a plant hexacoordinate hemoglobin structure in the exogenously ligand-bound form has prevented such comparison. Here we report the crystal structure of the cyanide-bound hexacoordinate hemoglobin from barley. This presents the first opportunity to examine conformational changes in plant hexacoordinate hemoglobins upon exogenous ligand binding, and reveals structural mechanisms for stabilizing the high-energy pentacoordinate heme conformation critical to the evolution of reversible oxygen binding hemoglobins.

  15. Purification of diverse hemoglobins by metal salt precipitation.

    PubMed

    Zimmerman, Devon; Dienes, Jack; Abdulmalik, Osheiza; Elmer, Jacob J

    2016-09-01

    Although donated blood is the preferred material for transfusion, its limited availability and stringent storage requirements have motivated the development of blood substitutes. The giant extracellular hemoglobin (aka erythrocruorin) of the earthworm Lumbricus terrestris (LtEc) has shown promise as a blood substitute, but an efficient purification method for LtEc must be developed to meet the potential large demand for blood substitutes. In this work, an optimized purification process that uses divalent and trivalent metal salts to selectively precipitate human, earthworm, and bloodworm hemoglobin (HbA, LtEc, and GdHb, respectively) from crude solutions was developed. Although several metal ions were able to selectively precipitate LtEc, Zn(2+) and Ni(2+) provided the lowest heme oxidation and highest overall yield of LtEc. In contrast, Zn(2+) was the only metal ion that completely precipitated HbA and GdHb. Polyacrylamide gel electrophoresis (PAGE) analysis shows that metal precipitation removes several impurities to provide highly pure hemoglobin samples. Heme oxidation levels were relatively low for Zn(2+)-purified HbA and LtEc (2.4±1.3% and 5.3±2.1%, respectively), but slightly higher for Ni(2+)-purified LtEc (8.4±1.2%). The oxygen affinity and cooperativity of the precipitated samples are also identical to samples purified with tangential flow filtration (TFF) alone, indicating the metal precipitation does not significantly affect the function of the hemoglobins. Overall, these results show that hemoglobins from several different species can be highly purified using a combination of metal (Zn(2+)) precipitation and tangential flow filtration. PMID:26363116

  16. Purification of diverse hemoglobins by metal salt precipitation.

    PubMed

    Zimmerman, Devon; Dienes, Jack; Abdulmalik, Osheiza; Elmer, Jacob J

    2016-09-01

    Although donated blood is the preferred material for transfusion, its limited availability and stringent storage requirements have motivated the development of blood substitutes. The giant extracellular hemoglobin (aka erythrocruorin) of the earthworm Lumbricus terrestris (LtEc) has shown promise as a blood substitute, but an efficient purification method for LtEc must be developed to meet the potential large demand for blood substitutes. In this work, an optimized purification process that uses divalent and trivalent metal salts to selectively precipitate human, earthworm, and bloodworm hemoglobin (HbA, LtEc, and GdHb, respectively) from crude solutions was developed. Although several metal ions were able to selectively precipitate LtEc, Zn(2+) and Ni(2+) provided the lowest heme oxidation and highest overall yield of LtEc. In contrast, Zn(2+) was the only metal ion that completely precipitated HbA and GdHb. Polyacrylamide gel electrophoresis (PAGE) analysis shows that metal precipitation removes several impurities to provide highly pure hemoglobin samples. Heme oxidation levels were relatively low for Zn(2+)-purified HbA and LtEc (2.4±1.3% and 5.3±2.1%, respectively), but slightly higher for Ni(2+)-purified LtEc (8.4±1.2%). The oxygen affinity and cooperativity of the precipitated samples are also identical to samples purified with tangential flow filtration (TFF) alone, indicating the metal precipitation does not significantly affect the function of the hemoglobins. Overall, these results show that hemoglobins from several different species can be highly purified using a combination of metal (Zn(2+)) precipitation and tangential flow filtration.

  17. Manipulation of hemoglobin expression affects Arabidopsis shoot organogenesis.

    PubMed

    Wang, Yaping; Elhiti, Mohamed; Hebelstrup, Kim H; Hill, Robert D; Stasolla, Claudio

    2011-10-01

    Over the past few years non-symbiotic plant hemoglobins have been described in a variety of plant species where they fulfill several functions ranging from detoxification processes to basic aspects of plant growth and post-embryonic development. To date no information is available on the role of hemoglobins during in vitro morphogenesis. Shoot organogenesis was induced in Arabidopsis lines constitutively expressing class 1, 2 and 3 hemoglobins (GLB1, 2 and 3) and lines in which the respective genes were either downregulated by RNAi (GLB1) or knocked out (GLB2 and GLB3). The process was executed by culturing root explants on an initial auxin-rich callus induction medium (CIM) followed by a transfer onto a cytokinin-containing shoot induction medium (SIM). While the repression of GLB2 inhibited organogenesis the over-expression of GLB1 or GLB2 enhanced the number of shoots produced in culture, and altered the transcript levels of genes participating in cytokinin perception and signalling. The up-regulation of GLB1 or GLB2 activated CKI1 and AHK3, genes encoding cytokinin receptors and affected the transcript levels of cytokinin responsive regulators (ARRs). The expression of Type-A ARRs (ARR4, 5, 7, 15, and 16), feed-back repressors of the cytokinin pathway, was repressed in both hemoglobin over-expressors whereas that of several Type-B ARRs (ARR2, 12, and 13), transcription activators of cytokinin-responsive genes, was induced. Such changes enhanced the sensitivity of the root explants to cytokinin allowing the 35S::GLB1 and 35S::GLB2 lines to produce shoots at low cytokinin concentrations which did not promote organogenesis in the WT line. These results show that manipulation of hemoglobin can modify shoot organogenesis in Arabidopsis and possibly in those systems partially or completely unresponsive to applications of exogenous cytokinins. PMID:21741261

  18. Near-infrared absorbance measurements of hemoglobin solutions incubated with glucose

    NASA Astrophysics Data System (ADS)

    Zhernovaya, Olga S.; Tuchin, Valery V.; Meglinski, Igor; Ritchie, Laurie

    2007-02-01

    It is known that glucose influences on spectral properties of blood and hemoglobin and interacts with plasma proteins and hemoglobin in erythrocytes. Changes of optical properties of blood and hemoglobin at glucose concentration within physiological level are important for diagnosis and monitoring of diabetes. The purpose of this study is to investigate the effect of presence of glucose and glycation of hemoglobin on absorbance of aqueous hemoglobin solutions with different glucose concentrations. Measurements were taken using spectrophotometer EQUINOX 55 (Bruker Optic GmbH) in a range 1000-1800 nm. Water has absorption bands in the near-infrared region which may be influenced by glucose presence. We have hypothesized that glucose and hemoglobin, especially glycated hemoglobin, may influence the absorption band of water in solution. The hemoglobin solutions with different amount of glucose (from 0 to 1000 mg/dl with a step 100 mg/dl) were incubated up to 28 days. Our measurements show that presence of glucose affects the spectra of aqueous hemoglobin solutions. The magnitude of absorbance depends on glucose concentration. At the beginning of incubation hemoglobin solution without glucose has the lowest absorbance magnitude, but after a rather long time of incubation (28 days) the absorbance of hemoglobin solutions with glucose become smaller compared to the absorbance of hemoglobin solution without glucose. This fact may be explained by assumption of hemoglobin glycation, when glucose molecules chemically bind to hemoglobin, and water binding to hemoglobin. In the case of water binding to hemoglobin molecules the amount of free water molecules in solution decreases, so the water aborbance is excepted to decrease.

  19. Abnormal rheology of oxygenated blood in sickle cell anemia

    PubMed Central

    Chien, Shu; Usami, Shunichi; Bertles, John F.

    1970-01-01

    The viscosity of oxygenated blood from patients with sickle cell anemia (Hb SS disease) was found to be abnormally increased, a property which contrasts with the well recognized viscous aberration produced by deoxygenation of Hb SS blood. Experiments designed to explain this finding led to considerations of deformation and aggregation, primary determinants of the rheologic behavior of erythrocytes as they traverse the microcirculation. Deformability of erythrocytes is in turn dependent upon internal viscosity (i.e. the state and concentration of hemoglobin in solution) and membrane flexibility. Definition of the contribution made by each of these properties to the abnormal viscosity of oxygenated Hb SS blood was made possible by analysis of viscosity measurements, made over a wide range of shear rates and cell concentrations, on Hb SS erythrocytes and normal erythrocytes suspended in Ringer's solution (where aggregation does not occur) and in plasma. Similar measurements were made on the two cell types separated by ultracentrifugation of Hb SS erythrocytes: high density erythrocytes composed of 50 to 70% irreversibly “sickled” cells (ISC) and low density erythrocytes composed of over 95% non-ISC. Under all experimental conditions (hematocrit, shear rate, and suspending medium) the viscosity of ISC exceeds that of normal erythrocytes. The viscosity of non-ISC is elevated only in the absence of aggregation and over intermediate ranges of hematocrit. Analyses of the data reveal (a) an elevated internal viscosity of ISC: (b) a reduced membrane flexibility of both ISC and non-ISC, particularly at low shear rates; and (c) a reduced tendency for aggregation displayed by both cell types. The abnormal viscosity of oxygenated Hb SS blood can be attributed to the altered rheology of ISC and, to a lesser extent, of non-ISC. These studies assign a role to the abnormal rheology of Hb SS erythrocytes in the pathogenesis of sickle cell anemia, even under conditions of complete

  20. Identification of chloride-binding sites in hemoglobin by nuclear-magnetic-resonance quadrupole-relaxation studies of hemoglobin digests.

    PubMed

    Chiancone, E; Norne, J E; Forsén, S; Bonaventura, J; Brunori, M; Antonini, E; Wyman, J

    1975-07-01

    35Cl minus-nuclear magnetic resonance (NMR) studies indicate that various digests of human hemoglobin with carboxypeptidase A and B, or a combination of the two, may be used for the identification of chloride binding sites. All the digestion products contain, like hemoglobin itself, at least two classes of binding sites, one of high, the others of low affinity. The pH dependence of the excess linewidth of the 35Cl minus NMR signal indicates that in the simple digests with either carboxypeptidase A or B, chloride is bound with high affinity at or near His-beta146-Asp-beta94 and at or near Val-alpha1-Arg-alpha141. The high-affinity sites show, in the case of the simple digests, a strong oxygen linkage which is lost in the forms digested with both carboxypeptidase A and B; this linkage may thus be correlated to the presence of conformational changes. Organic phosphates, like inositol hexaphosphate, show competition for some of the high-affinity chloride binding sites in hemoglobin and in the simple digests. This competition is likewise lost in the doubly digested hemoglobins. PMID:236

  1. Phase characterization of oscillatory components of the cerebral concentrations of oxy-hemoglobin and deoxy-hemoglobin

    NASA Astrophysics Data System (ADS)

    Pierro, Michele; Sassaroli, Angelo; Zheng, Feng; Fantini, Sergio

    2011-02-01

    We present a study of the relative phase of oscillations of cerebral oxy- and deoxy-hemoglobin concentrations in the low-frequency range, namely 0.04-0.12 Hz. We have characterized the potential contributions of noise to the measured phase distributions, and we have performed phase measurements on the brain of a human subject at rest, and on the brain of a human subject during stage I sleep. While phase distributions of pseudo hemodynamic oscillations generated from noise (obtained by applying to two independent sets of random numbers the same linear transformation that converts absorption coefficients at 690 and 830 nm into concentrations of oxy- and deoxy-hemoglobin) are peaked at 180º, those associated with real hemodynamic changes can be peaked around any value depending on the underlying physiology and hemodynamics. In particular, preliminary results reported here indicate a greater phase lead of deoxy-hemoglobin vs. oxy-hemoglobin low-frequency oscillations during stage I sleep (82º +/- 55º) than while the subject is awake (19º +/- 58º).

  2. ESA frequency and hemoglobin levels in patients on peritoneal dialysis: 2002 vs. 2008.

    PubMed

    Kruger, Ann; Trowbridge, Lynette; York, Jane; Butcher, Belinda; Bradley, Jennifer

    2013-01-01

    This study examined whether a change infrequency of administration of erythropoietin-stimulating agent affected hemoglobin levels in patients on peritoneal dialysis. Data were extracted from the Australian Renal Anaemia Management database for the years 2002 and 2008. Less frequent dosing and increasing age were associated with higher hemoglobin levels, while increasing ferritin levels and later years were associated with lower hemoglobin levels.

  3. Comparable application of the OCT and Abbe refractometers for measurements of glycated hemoglobin portion in blood

    NASA Astrophysics Data System (ADS)

    Zhernovaya, Olga S.; Tuchin, Valery V.; Wang, Ruikang K.

    2006-02-01

    It is known that glucose interacts with plasma proteins and hemoglobin in erythrocytes. Glycated (glycosylated) hemoglobin is the result of an irreversible non-enzymatic fixation of glucose on the beta chain of hemoglobin A. The amount of glycated hemoglobin depends on blood glucose concentration and reflects the mean glycemia of about the previous 2-3 months. Glycated hemoglobin is a useful marker for long-term glucose control in diabetic patients. Therefore, the search of quick and high sensitive methods for measurement of glycated hemoglobin portion in blood is important. This study is focused on the determination of refractive index of hemoglobin solution at different glucose concentrations. Measurements were performed using Abbe refractometer at 589 nm and optical coherence tomography (OCT) at 820 nm. The different amount of glucose (from 0 to 1000 mg/dl with a step 100 mg/dl) was added to hemoglobin solution. Theoretical values of refractive index of hemoglobin solutions with glucose were calculated supposing non-interacting hemoglobin and glucose molecules. There is a difference between measured and calculated values of refractive index. This difference is due to glucose binding to hemoglobin. It is shown that the refractive index measurements can be applied for the evaluation of glycated hemoglobin amount.

  4. MR Imaging-derived Oxygen-Hemoglobin Dissociation Curves and Fetal-Placental Oxygen-Hemoglobin Affinities.

    PubMed

    Avni, Reut; Golani, Ofra; Akselrod-Ballin, Ayelet; Cohen, Yonni; Biton, Inbal; Garbow, Joel R; Neeman, Michal

    2016-07-01

    Purpose To generate magnetic resonance (MR) imaging-derived, oxygen-hemoglobin dissociation curves and to map fetal-placental oxygen-hemoglobin affinity in pregnant mice noninvasively by combining blood oxygen level-dependent (BOLD) T2* and oxygen-weighted T1 contrast mechanisms under different respiration challenges. Materials and Methods All procedures were approved by the Weizmann Institutional Animal Care and Use Committee. Pregnant mice were analyzed with MR imaging at 9.4 T on embryonic days 14.5 (eight dams and 58 fetuses; imprinting control region ICR strain) and 17.5 (21 dams and 158 fetuses) under respiration challenges ranging from hyperoxia to hypoxia (10 levels of oxygenation, 100%-10%; total imaging time, 100 minutes). A shorter protocol with normoxia to hyperoxia was also performed (five levels of oxygenation, 20%-100%; total imaging time, 60 minutes). Fast spin-echo anatomic images were obtained, followed by sequential acquisition of three-dimensional gradient-echo T2*- and T1-weighted images. Automated registration was applied to align regions of interest of the entire placenta, fetal liver, and maternal liver. Results were compared by using a two-tailed unpaired Student t test. R1 and R2* values were derived for each tissue. MR imaging-based oxygen-hemoglobin dissociation curves were constructed by nonlinear least square fitting of 1 minus the change in R2*divided by R2*at baseline as a function of R1 to a sigmoid-shaped curve. The apparent P50 (oxygen tension at which hemoglobin is 50% saturated) value was derived from the curves, calculated as the R1 scaled value (x) at which the change in R2* divided by R2*at baseline scaled (y) equals 0.5. Results The apparent P50 values were significantly lower in fetal liver than in maternal liver for both gestation stages (day 14.5: 21% ± 5 [P = .04] and day 17.5: 41% ± 7 [P < .0001]). The placenta showed a reduction of 18% ± 4 in mean apparent P50 values from day 14.5 to day 17.5 (P = .003

  5. [Hemoglobins, XLVII. Hemoglobins of the bar-headed goose (Anser indicus): primary structure and physiology of respiration, systematic and evolution].

    PubMed

    Oberthür, W; Braunitzer, G; Würdinger, I

    1982-06-01

    The primary structures of the alpha- and beta-chains of the main component of Bar-headed Goose (Anser indicus) are given. By homologous comparison with the hemoglobin of the Grey-Lag Goose (Anser anser) 3 differences were found in the alpha-chains, 1 difference in the beta-chains. In position alpha 119 H2Ala and beta 125 H3Asp alpha 1 beta 2-contact points are changed. The mutation alpha 63 E12Val brings a drastic change in tertiary structure of the alpha-chains of Bar-headed Goose: the helices E and B are moved apart by 1.5 A as there is no room for the larger side chain. This is probably the reason for a slightly higher intrinsic oxygen affinity of Bar-headed Goose hemoglobin. The bindings of inositol pentaphosphate on hemoglobin are identical in Grey-Lag Goose and Bar-headed Goose (contact points are not mutated). The reason for the increased difference in oxygen affinity by binding of inositol pentaphosphate is probably caused by two mutations in alpha 1 beta 2-contact points. It suggests that these two mutations are the reason for a different interaction between alpha- and beta-chains under the influence of inositol pentaphosphate by Grey-Lag and Bar-headed Goose hemoglobins. The difference in the primary structure of the Grey-Lag and Bar-headed Goose hemoglobins suggests that the Bar-headed Goose is not the genus of anser. Unfinished experiments (about 80% of the sequences) of White-fronted Goose (Anser albifrons a.) and Snow Goose (Anser caerulescens c.) show no exchanges with Grey-Lag Goose hemoglobin. The Canada Goose (Branta canadensis), however, which belongs to the genus Branta, has a number of substitutions similar to the Bar-headed Goose hemoglobin. These changes in primary structure suggest that Grey-Lag Goose and Bar-headed Goose are separated by a period of 9-15 Million years. This would support the hypothesis that the two species of goose became geographically separated by the elevation of the Himalayas. PMID:7106705

  6. Phenotypic expression of hemoglobins A₂, E and F in various hemoglobin E related disorders.

    PubMed

    Sae-ung, Nattaya; Srivorakun, Hataichanok; Fucharoen, Goonnapa; Yamsri, Supawadee; Sanchaisuriya, Kanokwan; Fucharoen, Supan

    2012-01-15

    Study on the phenotypic expression of hemoglobin (Hb) A(2) and Hb E in Hb E disorders has been difficult due to the co-separation of Hb A(2) and Hb E in most Hb analysis assays. Because these two Hbs are separated on capillary electrophoresis, we studied phenotypic expression of Hbs A(2), E and F in various Hb E disorders using this system. This was done on 362 subjects with several Hb E disorders including heterozygous Hb E, homozygous Hb E, β-thalassemia/Hb E, δβ-thalassemia/Hb E, and Hb Lepore/Hb E and those of these disorders with several forms of α-thalassemia. Normal controls showed Hb A(2) of 2.7 ± 0.3%. Heterozygous Hb E and homozygous Hb E had elevated Hb A(2) i.e. 3.8 ± 0.3% and 4.8 ± 0.5%, respectively. Further elevations were observed for β(0)-thalassemia/Hb E (6.1 ± 1.9%) and β(+)-thalassemia/Hb E (7.1 ± 1.2%). Interestingly, no elevation of Hb A(2) was found in the δβ-thalassemia/Hb E, and Hb Lepore/Hb E (2.3 ± 0.3%) but higher Hb F levels were noted which could be useful diagnostic markers. The levels of Hb E were variable. Co-inheritance of these Hb E disorders with α-thalassemia were associated with lower outputs of Hb E and Hb F but the levels of Hb A(2) were not altered. Different phenotypic expression of Hb A(2), Hb E and Hb F could help in differential diagnosis of these Hb E related disorders commonly encountered in the regions where access to molecular techniques is limited.

  7. Association between Elevated Hemoglobin A1c Levels and the Outcomes of Patients with Small-Artery Occlusion: A Hospital-Based Study

    PubMed Central

    Gao, Yuan; Jiang, Lihong; Wang, Hui; Yu, Changshen; Wang, Wanjun; Liu, Shoufeng; Gao, Chunlin; Tong, Xiaoguang; Wang, Jinhuan; Jin, Yi; Wu, Jialing

    2016-01-01

    Introduction Abnormal glucose metabolism is an independent risk factor for poor outcome following acute ischemic stroke. However, the relationship between initial hemoglobin A1c level and functional outcome (defined by modified Rankin Scale scores) following small-artery occlusion, a subtype of ischemic stroke, is unknown. The aim of the present study was to evaluate this association among patients diagnosed with small-artery occlusion. Materials and Methods Data on 793 patients diagnosed with small-artery occlusion from October 25, 2012 to June 30, 2015 were collected from the stroke registry of the Department of Neurorehabilitation of HuanHu Hospital. Hemoglobin A1c values at admission were classified into three groups according to tertiles (<5.9,5.9to<6.7, and≥6.7). We used receiver operating characteristics curves to investigate the predictive value of hemoglobin A1c and examined the relationship between hemoglobin A1c levels at admission and modified Rankin Scale scores using univariate and multivariate analyses. Results The area under the curve was 0.570 (95%CI, 0.509–0.631; P = 0.023). Patients in the highest HbA1c stratification (≥6.7) had a significantly higher risk of an unfavorable outcome than patients in the lowest stratification (<5.9; adjusted odds ratio, 2.099; 95%CI, 1.160–3.798; P = 0.014). However, a significant association was not seen in the middle stratification (5.9 to <6.7; P = 0.115). Conclusions Elevated hemoglobin A1c level on admission was adversely associated with functional outcomes 3 months after stroke onset among patients presenting with small-artery occlusion. PMID:27486868

  8. Kidney transplantation in abnormal bladder

    PubMed Central

    Mishra, Shashi K.; Muthu, V.; Rajapurkar, Mohan M.; Desai, Mahesh R.

    2007-01-01

    Structural urologic abnormalities resulting in dysfunctional lower urinary tract leading to end stage renal disease may constitute 15% patients in the adult population and up to 20-30% in the pediatric population. A patient with an abnormal bladder, who is approaching end stage renal disease, needs careful evaluation of the lower urinary tract to plan the most satisfactory technical approach to the transplant procedure. Past experience of different authors can give an insight into the management and outcome of these patients. This review revisits the current literature available on transplantation in abnormal bladder and summarizes the clinical approach towards handling this group of difficult transplant patients. We add on our experience as we discuss the various issues. The outcome of renal transplant in abnormal bladder is not adversely affected when done in a reconstructed bladder. Correct preoperative evaluation, certain technical modification during transplant and postoperative care is mandatory to avoid complications. Knowledge of the abnormal bladder should allow successful transplantation with good outcome. PMID:19718334

  9. Noninvasive investigation of skin local hypothermia influence upon local oxygenation and hemoglobin concentration

    NASA Astrophysics Data System (ADS)

    Douplik, Alexandre Y.; Kessler, Manfred D.; Kakihana, Yasuyuki; Krug, Alfons

    1997-08-01

    Functional evaluation of local hemoglobin concentration and hemoglobin oxygenation based on back scattering spectra from human skin in vivo have been obtained in visible range (502 - 628 nm) by a rapid microlightguide spectrometer (EMPHO II) with step 250 micrometer. Analysis of received results has shown that during local cooling there is two nearly simultaneous reactions: reduction of hemoglobin concentration and increase of hemoglobin oxygenation level. In a case when one has used previous heating of planning place for cooling, reduction of hemoglobin concentration is expressed higher by 22 - 33%.

  10. Concurrent measurement of cellular turbidity and hemoglobin to evaluate the antioxidant activity of plants.

    PubMed

    Bellik, Yuva; Iguer-Ouada, Mokrane

    2016-01-01

    In past decades, a multitude of analytical methods for measuring antioxidant activity of plant extracts has been developed. However, when using methods to determine hemoglobin released from human erythrocytes treated with ginger extracts, we found hemoglobin concentrations were significantly higher than in untreated control samples. This suggests in the presence of antioxidants that measuring hemoglobin alone is not sufficient to determine hemolysis. We show concurrent measurement of erythrocyte concentration and hemoglobin is essential in such assays, and describe a new protocol based on simultaneous measurement of cellular turbidity and hemoglobin.

  11. Abnormal expression of inflammatory genes in placentas of women with sickle cell anemia and sickle hemoglobin C disease.

    PubMed

    Baptista, Letícia C; Costa, Maria Laura; Ferreira, Regiane; Albuquerque, Dulcinéia M; Lanaro, Carolina; Fertrin, Kleber Y; Surita, Fernanda G; Parpinelli, Mary A; Costa, Fernando F; Melo, Mônica Barbosa de

    2016-10-01

    Sickle cell disease (SCD) is a complex disease that is characterized by the polymerization of deoxyhemoglobin S, altered red blood cell membrane biology, endothelial activation, hemolysis, a procoagulant state, acute and chronic inflammation, and vaso-occlusion. Among the physiological changes that occur during pregnancy, oxygen is consumed by fetal growth, and pregnant women with SCD are more frequently exposed to low oxygen levels. This might lead to red blood cells sickling, and, consequently, to vaso-occlusion. The mechanisms by which SCD affects placental physiology are largely unknown, and chronic inflammation might be involved in this process. This study aimed to evaluate the gene expression profile of inflammatory response mediators in the placentas of pregnant women with sickle cell cell anemia (HbSS) and hemoglobinopathy SC (HbSC). Our results show differences in a number of these genes. For the HbSS group, when compared to the control group, the following genes showed differential expression: IL1RAP (2.76-fold), BCL6 (4.49-fold), CXCL10 (-2.12-fold), CXCR1 (-3.66-fold), and C3 (-2.0-fold). On the other hand, the HbSC group presented differential expressions of the following genes, when compared to the control group: IL1RAP (4.33-fold), CXCL1 (3.05-fold), BCL6 (4.13-fold), CXCL10 (-3.32-fold), C3 (-2.0-fold), and TLR3 (2.38-fold). Taken together, these data strongly suggest a differential expression of several inflammatory genes in both SCD (HbSS and HbSC), indicating that the placenta might become an environment with hypoxia, and increased inflammation, which could lead to improper placental development. PMID:27546026

  12. Prevalence and mutations of β-thalassemia trait and abnormal hemoglobins in premarital screening in Çanakkale province, Turkey

    PubMed Central

    Uludağ, A; Uludağ, A; Ertekin, YH; Tekin, M; Kütük, B; Silan, F; Özdemir, Ö

    2016-01-01

    Abstract The prevalence of β-thalassemia (β-thal) carriers in Turkey varies according to region but in general it is 2.0%. Çanakkale is a city in the Aegean region of Turkey but no study about β-thal frequency in Çanakkale has been published to date. In this study, we aimed to investigate the frequency of β-thal mutations in this province. A total of 4452 couples (8904 individuals) applied for premarital thalassemia scans at the Çanakkale State Health Directorate Laboratory between January 2008 and June 2012 and scanning was done with high performance liquid chromatography (HPLC). Of 125 β-thal carriers seen at the Medical Genetics Clinic, Çanakkale Onsekiz Mart University, Çanakkale, Turkey, for genetic counseling, 46 participated in the study. The remaining 79 patients could not be reached. The prevalence for β-thal carriers in Çanakkale was identified as 1.4% (125/8904). One couple were both β-thal carriers. β-Globin gene analysis of 46 carriers found the total frequency of the three most common mutations was 45.6%. These mutations were found to be HBB: c.93-21G>A [IVS-I-110 (G>A)], 26.08% (12/46); HBB: c.17_ 18delCT [codon 5 (‒CT)], 10.85% (5/46); HBB: c.20delA [codon 6 (‒A)] 8.69% (4/46). This is the first report on the frequency and mutation profiles of β-thal for Çanakkale. The incidence of β-thal carriers in Çanakkale is below the average for Turkey. The most frequently observed mutation profile and rate of β-thal in our region is different from the other regions of Turkey.

  13. Virucidal levels of ozone induce hemolysis and hemoglobin degradation

    SciTech Connect

    Wagner, S.J.; Wagner, K.F.; Friedman, L.I.; Benade, L.F. )

    1991-10-01

    The animal virus, vesicular stomatitis virus (VSV), and the bacterial virus, phi 6, were inactivated by greater than 4 log10 in response to incubation with 13 to 14 mL of 1.4 mmol per L (65 micrograms/mL) to 1.6 mmol per L (75 micrograms/mL) of overlaid ozone in virus-spiked, dilute, red cell suspensions. Virus inactivation was greatly inhibited when ozone was overlaid in the presence of high-hematocrit red cells or, to a lesser degree, high levels of plasma. At hematocrits at which 5 to 6 log10 of VSV were inactivated, ozone caused 30-percent hemolysis, as measured by the loss of total cellular hemoglobin. Unexpectedly, this level of hemolysis could not be observed in supernatants because of the ozone-induced destruction (bleaching) of extracellular hemoglobin. These results suggest that ozone may have little biological specificity for damaging viruses over red cells.

  14. Vitreoscilla hemoglobin promotes Salecan production by Agrobacterium sp. ZX09*

    PubMed Central

    Chen, Yun-mei; Xu, Hai-yang; Wang, Yang; Zhang, Jian-fa; Wang, Shi-ming

    2014-01-01

    Salecan is a novel exopolysaccharide produced by the strain Agrobacterium sp. ZX09, and it is composed of only glucose monomers. The unique chemical composition and excellent physicochemical properties make Salecan a promising material for applications in coagulation, lubrication, protection against acute liver injury, and alleviating constipation. In this study, we cloned the Vitreoscilla hemoglobin gene into a broad-host-range plasmid pCM158. Without antibiotic selection, there was negligible loss of the plasmid in the host Agrobacterium sp. ZX09 after one passage of cultivation. The expression of Vitreoscilla hemoglobin was demonstrated by carbon monoxide (CO) difference spectrum. The engineered strain Agrobacterium sp. ZX09 increased Salecan yield by 30%. The other physiological changes included its elevated respiration rate and cellular invertase activity. PMID:25367790

  15. First Reported Case of Proliferative Retinopathy in Hemoglobin SE Disease

    PubMed Central

    Yang, Christopher; Fantin, Aldo; Darnley-Fisch, Deborah; Desai, Uday

    2014-01-01

    We report the first case of proliferative sickle cell retinopathy in a patient with hemoglobin SE (Hb SE) disease. Only a few dozen cases of Hb SE disease have been reported previously, and none had evidence of proliferative retinopathy. A 56-year-old African American man presented to our clinic for routine examination and was found to have sea-fan peripheral neovascularization bilaterally without maculopathy. Hemoglobin analysis revealed Hb SE heterozygosity. Sector laser photocoagulation to areas of nonperfusion in both eyes resulted in regression of the peripheral neovascularization over a period of 6 months. Although Hb SE disease is rare, the incidence of Hb SE disease is postulated to rise in the future. Awareness of its potential ocular complications is needed to appropriately refer these patients for screening. PMID:25210638

  16. Neonatal Cyanosis Due to Hemoglobin Variant: Hb F-Sarajevo.

    PubMed

    Lozar-Krivec, Jana; Stepic, Maja; Hovnik, Tinka; Krsnik, Mladen; Paro-Panjan, Darja

    2016-10-01

    Neonatal cyanosis is rarely due to hemoglobin variants with low oxygen affinity. We describe the clinical course and results of molecular genetic analysis of a boy who presented after birth with severe cyanosis. Arterial blood-gas analysis demonstrated a pronounced shift of the oxygen-hemoglobin dissociation curve to the right and molecular genetic analysis revealed a γ-globin variant, Hb F-Sarajevo. The patient presented is the second reported case of neonatal cyanosis due to this mutation, which was first described in 2012 by Zimmermann-Baer and coauthors. With the introduction of universal screening for congenital heart disease, the finding of low oxygen saturation will uncover more neonates with hemoglobinopathies with low oxygen affinity. PMID:27571121

  17. The Linkage Between Oxygenation and Subunit Dissociation in Human Hemoglobin

    PubMed Central

    Ackers, Gary K.; Halvorson, Herbert R.

    1974-01-01

    The use of subunit dissociation as a means of probing intersubunit contact energy changes which accompany cooperative ligand binding has been studied for the case of human hemoglobin. An analysis is presented delineating the information that can be obtained from the linkage relationships between ligand binding and subunit dissociation of hemoglobin tetramers into dimers. The analysis defines (a) the variation of the saturation function, Ȳ, with total protein concentration, (b) the variation of the subunit dissociation constant xK2 with ligand concentration (X) and (c) the correlations between changes in dimer-dimer contact energy and the sequential ligand binding steps. Sensitivity of the linkage function has been explored by numerical simulation. It is shown that subunit dissociation may appreciably affect oxygenation curves under usual conditions of measurement and that relying solely on either xK2 or Ȳ may lead to incorrect picutres of the energetics, whereas the combination defines the system much more exactly. PMID:4530985

  18. Double filaments in fibers and crystals of deoxygenated hemoglobin S

    SciTech Connect

    Magdoff-Fairchild, B.; Chiu, C.C.

    1980-10-01

    Sickle cell hemoglobin (HbS) molecules in solution or in SS erythrocytes (those from individuals homozygous for the sickle hemoglobin gene), when deoxygenated, aggregate to form fibers that pack into paracrystalline arrays. The diminished oxygen affinity of HbS is produced by the polymerization, and the distortion of the pliant erythrocyte membrane is produced by the polymerization, and the distortion of the pliant erythrocyte membrane in sickle cell disease results from the elongation of polymers and their subsequent alignment. One of the important problems to be solved in sickle cell disease is the definition of the intermolecular interactions that stabilize the fiber structure. Knowledge of these interactions might lead to the design of stereospecific antisickling agents for clinical use that could inhibit polymerization or could at least destabilize the fiber.

  19. Bitter peptide from hemoglobin hydrolysate: isolation and characterization.

    PubMed

    Aubes-Dufau, I; Capdevielle, J; Seris, J L; Combes, D

    1995-05-01

    Two separation methods, ultrafiltration and 2-butanol extraction, have shown that a peptide is the major agent responsible for bitterness in peptic hemoglobin hydrolysates. It was easily purified from these complex mixtures by specific hydrophobic adsorption on Superose 12, a gel-filtration column, which could constitute an original and interesting method for bitterness detection. The bitter peptide which corresponded to VV-hemorphin 7, the fragment 32-40 of the beta chain of bovine hemoglobin, is first generated during proteolysis, then hydrolysed by pepsin. It exhibited a strong bitterness at 0.25 mM equivalent to 0.073 mM quinine sulfate or 21 mM caffeine.

  20. Water buffalo (Bubalus bubalis) hemoglobins: an electrophoretic and chromatographic study.

    PubMed

    Di Luccia, A; Iannibelli, L; Ferranti, P; Iorio, M; Annunziata, M; Ferrara, L

    1989-01-01

    1. Hemoglobins from three phenotypes of Italian water buffalo (Bubalus bubalis), named AA, AB and BB, were selected by starch gel electrophoresis at alkaline pH and analyzed using polyacrylamide gel isoelectric focusing and subsequent analysis of titration curves to reveal differences between two types of hemoglobin identified as Hb fast and Hb slow. 2. Globins from Hb fast and Hb slow were purified by fast protein liquid chromatography (FPLC). Electrophoretic differences were found in the respective alpha-chains using polyacrylamide gel disc-electrophoresis at acid pH, polyacrylamide gel isoelectric focusing and by subsequently analyzing titration curves. 3. The results suggest that the alpha chains of Hb fast and Hb slow, called I alpha and II alpha, respectively, differ in at least two aminoacid residues. Subsequently, these amino acids were identified as lysine and cysteine.

  1. Complex patterns of abnormal heartbeats

    NASA Technical Reports Server (NTRS)

    Schulte-Frohlinde, Verena; Ashkenazy, Yosef; Goldberger, Ary L.; Ivanov, Plamen Ch; Costa, Madalena; Morley-Davies, Adrian; Stanley, H. Eugene; Glass, Leon

    2002-01-01

    Individuals having frequent abnormal heartbeats interspersed with normal heartbeats may be at an increased risk of sudden cardiac death. However, mechanistic understanding of such cardiac arrhythmias is limited. We present a visual and qualitative method to display statistical properties of abnormal heartbeats. We introduce dynamical "heartprints" which reveal characteristic patterns in long clinical records encompassing approximately 10(5) heartbeats and may provide information about underlying mechanisms. We test if these dynamics can be reproduced by model simulations in which abnormal heartbeats are generated (i) randomly, (ii) at a fixed time interval following a preceding normal heartbeat, or (iii) by an independent oscillator that may or may not interact with the normal heartbeat. We compare the results of these three models and test their limitations to comprehensively simulate the statistical features of selected clinical records. This work introduces methods that can be used to test mathematical models of arrhythmogenesis and to develop a new understanding of underlying electrophysiologic mechanisms of cardiac arrhythmia.

  2. A Membrane-bound Hemoglobin from Gills of the Green Shore Crab Carcinus maenas*

    PubMed Central

    Ertas, Beyhan; Kiger, Laurent; Blank, Miriam; Marden, Michael C.; Burmester, Thorsten

    2011-01-01

    Most hemoglobins serve for the transport or storage of O2. Although hemoglobins are widespread in “entomostracan” Crustacea, malacostracans harbor the copper-containing hemocyanin in their hemolymph. Usually, only one type of respiratory protein occurs within a single species. Here, we report the identification of a hemoglobin of the shore crab Carcinus maenas (Malacostraca, Brachyura). In contrast to the dodecameric hemocyanin of this species, C. maenas hemoglobin does not reside in the hemolymph but is restricted to the gills. Immunofluorescence studies and cell fractioning showed that C. maenas hemoglobin resides in the membrane of the chief cells of the gill. To the best of our knowledge, this is the first time that a membrane-bound hemoglobin has been identified in eukaryotes. Bioinformatic evaluation suggests that C. maenas hemoglobin is anchored in the membrane by N-myristoylation. Recombinant C. maenas hemoglobin has a hexacoordinate binding scheme at the Fe2+ and an oxygen affinity of P50 = 0.5 Torr. A rapid autoxidation rate precludes a function as oxygen carrier. We rather speculate that, analogous to prokaryotic membrane-globins, C. maenas hemoglobin carries out enzymatic functions to protect the lipids in cell membrane from reactive oxygen species. Sequence comparisons and phylogenetic studies suggested that the ancestral arthropod hemoglobin was most likely an N-myristoylated protein that did not have an O2 supply function. True respiratory hemoglobins of arthropods, however, evolved independently in chironomid midges and branchiopod crustaceans. PMID:21118803

  3. IsdB-dependent hemoglobin binding is required for acquisition of heme by Staphylococcus aureus.

    PubMed

    Pishchany, Gleb; Sheldon, Jessica R; Dickson, Claire F; Alam, Md Tauqeer; Read, Timothy D; Gell, David A; Heinrichs, David E; Skaar, Eric P

    2014-06-01

    Staphylococcus aureus is a Gram-positive pathogen responsible for tremendous morbidity and mortality. As with most bacteria, S. aureus requires iron to cause disease, and it can acquire iron from host hemoglobin. The current model for staphylococcal hemoglobin-iron acquisition proposes that S. aureus binds hemoglobin through the surface-exposed hemoglobin receptor IsdB. IsdB removes heme from bound hemoglobin and transfers this cofactor to other proteins of the Isd system, which import and degrade heme to release iron in the cytoplasm. Here we demonstrate that the individual components of the Isd system are required for growth on low nanomolar concentrations of hemoglobin as a sole source of iron. An in-depth study of hemoglobin binding by IsdB revealed key residues that are required for hemoglobin binding. Further, we show that these residues are necessary for heme extraction from hemoglobin and growth on hemoglobin as a sole iron source. These processes are found to contribute to the pathogenicity of S. aureus in a murine model of infection. Together these results build on the model for Isd-mediated hemoglobin binding and heme-iron acquisition during the pathogenesis of S. aureus infection.

  4. IsdB-dependent Hemoglobin Binding Is Required for Acquisition of Heme by Staphylococcus aureus

    PubMed Central

    Pishchany, Gleb; Sheldon, Jessica R.; Dickson, Claire F.; Alam, Md Tauqeer; Read, Timothy D.; Gell, David A.; Heinrichs, David E.; Skaar, Eric P.

    2014-01-01

    Staphylococcus aureus is a Gram-positive pathogen responsible for tremendous morbidity and mortality. As with most bacteria, S. aureus requires iron to cause disease, and it can acquire iron from host hemoglobin. The current model for staphylococcal hemoglobin-iron acquisition proposes that S. aureus binds hemoglobin through the surface-exposed hemoglobin receptor IsdB. IsdB removes heme from bound hemoglobin and transfers this cofactor to other proteins of the Isd system, which import and degrade heme to release iron in the cytoplasm. Here we demonstrate that the individual components of the Isd system are required for growth on low nanomolar concentrations of hemoglobin as a sole source of iron. An in-depth study of hemoglobin binding by IsdB revealed key residues that are required for hemoglobin binding. Further, we show that these residues are necessary for heme extraction from hemoglobin and growth on hemoglobin as a sole iron source. These processes are found to contribute to the pathogenicity of S. aureus in a murine model of infection. Together these results build on the model for Isd-mediated hemoglobin binding and heme-iron acquisition during the pathogenesis of S. aureus infection. PMID:24338348

  5. Comparison of the hemoglobins of the platyhelminths Gastrothylax crumenifer and Paramphistomum epiclitum (Trematoda: Paramphistomatidae).

    PubMed

    Haque, M; Rashid, K A; Stern, M S; Sharma, P K; Siddiqi, A H; Vinogradov, S N; Walz, D A

    1992-04-01

    1. Gastrothylax crumenifer and Paramphistomum epiclitum parasitize the water buffalo Bubalus bubalis. 2. Gastrothylas hemoglobin consisted of two fractions of ca 30,000 and ca 18,000 by gel filtration. SDS-electrophoresis showed both to be single, ca 15,000 chains. 3. Paramphistomum hemoglobin was ca 16,000 by both gel filtration and SDS-electrophoresis. 4. Reversed-phase chromatography of carboxymethylated trematode and buffalo globins gave single peaks and two peaks, respectively. Although Paramphistomum hemoglobin provided and N-terminal sequence, Gastrothylax hemoglobin did not, suggesting blocked N-terminals. The buffalo sequences were found to be identical to the sequences of the alpha and beta chains of bovine hemoglobin. 5. Although Paramphistomum hemoglobin consists of only one chain, Gastrothylax hemoglobin consists either of one chain which aggregates to a dimer or of two different chains, only one of which aggregates to a dimer.

  6. Chemical modifications that inhibit gelation of sickle hemoglobin.

    PubMed

    Benesch, R; Benesch, R E; Yung, S

    1974-04-01

    Substitution of the N-terminal amino groups with pyridoxal compounds inhibits gelation and increases the solubility of deoxy sickle hemoglobin (Hb S). Pyridoxylation of the alpha chains has considerably more effect than that of the beta chains. The increase in minimum gelling concentration of Hb S that results from modification of the alpha N-termini is the same as that produced by dilution of Hb S with an equal amount of Hb A. PMID:4524653

  7. Hemoglobin Status and Externalizing Behavioral Problems in Children

    PubMed Central

    Su, Jianhua; Cui, Naixue; Zhou, Guoping; Ai, Yuexian; Sun, Guiju; Zhao, Sophie R.; Liu, Jianghong

    2016-01-01

    Background: Still considered one of the most prevalent nutritional problems in the world, anemia has been shown in many studies to have deleterious effects on neurobehavioral development. While most research efforts have focused on investigating the effects of anemia on social and emotional development of infants by using a cross-sectional design, research is still needed to investigate whether early childhood anemia, beyond infantile years, is linked with behavioral problems. Objective: This study assessed whether (1) hemoglobin (Hb) levels in early childhood are associated with externalizing behavior; and (2) this relationship is confounded by social adversity. Methods: Hemoglobin levels were taken from children (N = 98) of the China Jintan Cohort Study at age 4 years, and externalizing behaviors (attention and aggression) were assessed with the Child Behavior Checklist (ASEBA-CBCL) at age 6 years (mean age 5.77 ± 0.39 years old). Results: Compared with other children in the sample, children with relatively lower Hb levels at age 4 had more behavioral problems in both attention and aggression at age 6, independent of social adversity. For boys, this association was significant for attention problems, which did not interact with social adversity. For girls, the association was significant for aggression, which interacted with social adversity. While girls on average exhibited higher social adversity than boys, the main effect of Hb was only significant in girls with low social adversity. Conclusions: These results indicate that there is an inverse association between hemoglobin levels and later behavioral problems. Findings of this study suggest that regular monitoring of children’s hemoglobin levels and appropriate intervention may help with early identification of behavioral problems. PMID:27472352

  8. Multimeric hemoglobin of the Australian brine shrimp Parartemia.

    PubMed

    Coleman, M; Matthews, C M; Trotman, C N

    2001-04-01

    The hemoglobin molecule of the commercially important brine shrimp Artemia sp. has been used extensively as a model for the study of molecular evolution. It consists of nine globin domains joined by short linker sequences, and these domains are believed to have originated through a series of duplications from an original globin gene. In addition, in Artemia, two different polymers of hemoglobin, called C and T, are found which differ by 11.7% at the amino acid level and are believed to have diverged about 60 MYA. This provides a set of data of 18 globin domain sequences that have evolved in the same organism. The pattern of amino acid substitution between these two polymers is unusual, with pairs of equivalent domains displaying differences of up to 2.7-fold in total amino acid substitution. Such differences would reflect a similar range of molecular-clock rates in what appear to be duplicate, structurally equivalent domains. In order to provide a reference outgroup, we sequenced the cDNA for a nine-domain hemoglobin (P) from another genus of brine shrimp, Parartemia zietziana, which differs morphologically and ecologically from Artemia and is endemic to Australia. Parartemia produces only one hundredth the amount of hemoglobin that Artemia produces and does not upregulate production in response to low oxygen partial pressure. Comparison of the globin domains at the amino acid and DNA levels suggests that the Artemia globin T gene has accumulated substitutions differently from the Parartemia P and Artemia C globin genes. We discuss the questions of accelerated evolution after duplication and possible functions for the Parartemia globin. PMID:11264409

  9. Hemoglobin-based red blood cell substitutes and nitric oxide.

    PubMed

    Yu, Binglan; Bloch, Kenneth D; Zapol, Warren M

    2009-04-01

    Hemoglobin-based oxygen carriers (HBOCs) have been studied for decades as red blood cell substitutes. Profound vasoconstrictor effects have limited the clinical utility of HBOCs and are attributable to avid scavenging of nitric oxide (NO). Inhaling NO can charge the body's stores of NO metabolites without producing hypotension and can prevent systemic hypertension induced when HBOCs are subsequently infused. Concurrent breathing of low NO doses can prevent pulmonary vasoconstriction after HBOC infusion without augmenting plasma methemoglobinemia.

  10. Initial studies of hypoxic radioprotection by deoxygenated dextran-hemoglobin

    SciTech Connect

    Hill, R.P.; Porter, L.S.; Ives, S.A.; Wong, J.T.F.

    1984-03-01

    Initial studies were performed to examine the potential of perfused dextran-hemoglobin to protect pig skin or mouse bone marrow cells against radiation damage. Some protection was indicated in both systems. In the pig skin a protection factor of 1.5 was observed for moist desquamation, and 2.0 for necrosis. These results suggest the possibility of using blood substitutes to induce tissue hypoxia for therapeutic purposes.

  11. Hemoglobin s polymerization and red cell membrane changes.

    PubMed

    Kuypers, Frans A

    2014-04-01

    Different pathways lead from the simple point mutation in hemoglobin to the membrane changes that characterize the altered interaction of the sickle red blood cell with its environment, including endothelial cells, white blood cells, and platelets. Polymerization and oxidation-induced damage to both lipid and protein components of the red cell membrane, as well as the generation of bioreactive membrane material (microparticles), has a profound effect on all tissues and organs, and defines the vasculopathy of the patient with sickle cell disease.

  12. [Emotion Disorders and Abnormal Perspiration].

    PubMed

    Umeda, Satoshi

    2016-08-01

    This article reviewed the relationship between emotional disorders and abnormal perspiration. First, I focused on local brain areas related to emotional processing, and summarized the functions of the emotional network involving those local areas. Functional disorders followed by the damage in the amygdala, orbitofrontal cortex, and insular cortex were reviewed, including related abnormal perspiration. I then addressed the mechanisms of how autonomic disorders influence emotional processing. Finally, possible future directions for integrated understanding of the connection between neural activities and bodily reactions were discussed. PMID:27503817

  13. [Emotion Disorders and Abnormal Perspiration].

    PubMed

    Umeda, Satoshi

    2016-08-01

    This article reviewed the relationship between emotional disorders and abnormal perspiration. First, I focused on local brain areas related to emotional processing, and summarized the functions of the emotional network involving those local areas. Functional disorders followed by the damage in the amygdala, orbitofrontal cortex, and insular cortex were reviewed, including related abnormal perspiration. I then addressed the mechanisms of how autonomic disorders influence emotional processing. Finally, possible future directions for integrated understanding of the connection between neural activities and bodily reactions were discussed.

  14. Direct estimation of evoked hemoglobin changes by multimodality fusion imaging

    PubMed Central

    Huppert, Theodore J.; Diamond, Solomon G.; Boas, David A.

    2009-01-01

    In the last two decades, both diffuse optical tomography (DOT) and blood oxygen level dependent (BOLD)-based functional magnetic resonance imaging (fMRI) methods have been developed as noninvasive tools for imaging evoked cerebral hemodynamic changes in studies of brain activity. Although these two technologies measure functional contrast from similar physiological sources, i.e., changes in hemoglobin levels, these two modalities are based on distinct physical and biophysical principles leading to both limitations and strengths to each method. In this work, we describe a unified linear model to combine the complimentary spatial, temporal, and spectroscopic resolutions of concurrently measured optical tomography and fMRI signals. Using numerical simulations, we demonstrate that concurrent optical and BOLD measurements can be used to create cross-calibrated estimates of absolute micromolar deoxyhemoglobin changes. We apply this new analysis tool to experimental data acquired simultaneously with both DOT and BOLD imaging during a motor task, demonstrate the ability to more robustly estimate hemoglobin changes in comparison to DOT alone, and show how this approach can provide cross-calibrated estimates of hemoglobin changes. Using this multimodal method, we estimate the calibration of the 3 tesla BOLD signal to be −0.55% ± 0.40% signal change per micromolar change of deoxyhemoglobin. PMID:19021411

  15. Evolutionary and Functional Relationships in the Truncated Hemoglobin Family

    PubMed Central

    Bustamante, Juan P.; Radusky, Leandro; Boechi, Leonardo; Estrin, Darío A.; ten Have, Arjen; Martí, Marcelo A.

    2016-01-01

    Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural properties and the relevant properties can be computed using the sequence as the starting point, it should in principle be possible to predict function in detail. The truncated hemoglobin family presents an interesting benchmark study due to their ubiquity, sequence diversity in the context of a conserved fold and the number of characterized members. Their functions are tightly related to O2 affinity and reactivity, as determined by the association and dissociation rate constants, both of which can be predicted and analyzed using in-silico based tools. In the present work we have applied a strategy, which combines homology modeling with molecular based energy calculations, to predict and analyze function of all known truncated hemoglobins in an evolutionary context. Our results show that truncated hemoglobins present conserved family features, but that its structure is flexible enough to allow the switch from high to low affinity in a few evolutionary steps. Most proteins display moderate to high oxygen affinities and multiple ligand migration paths, which, besides some minor trends, show heterogeneous distributions throughout the phylogenetic tree, again suggesting fast functional adaptation. Our data not only deepens our comprehension of the structural basis governing ligand affinity, but they also highlight some interesting functional evolutionary trends. PMID:26788940

  16. Modulating hemoglobin nitrite reductase activity through allostery: a mathematical model.

    PubMed

    Rong, Zimei; Alayash, Abdu I; Wilson, Michael T; Cooper, Chris E

    2013-11-30

    The production of nitric oxide by hemoglobin (Hb) has been proposed to play a major role in the control of blood flow. Because of the allosteric nature of hemoglobin, the nitrite reductase activity is a complex function of oxygen partial pressure PO2. We have previous developed a model to obtain the micro rate constants for nitrite reduction by R state (kR) and T state (kT) hemoglobin in terms of the experimental maximal macro rate constant kNmax and the corresponding oxygen concentration PO2max. However, because of the intrinsic difficulty in obtaining accurate macro rate constant kN, from available experiments, we have developed an alternative method to determine the micro reaction rate constants (kR and kT) by fitting the simulated macro reaction rate curve (kN versus PO2) to the experimental data. We then use our model to analyze the effect of pH (Bohr Effect) and blood ageing on the nitrite reductase activity, showing that the fall of bisphosphoglycerate (BPG) during red cell storage leads to increase NO production. Our model can have useful predictive and explanatory power. For example, the previously described enhanced nitrite reductase activity of ovine fetal Hb, in comparison to the adult protein, may be understood in terms of a weaker interaction with BPG and an increase in the value of kT from 0.0087M(-1)s(-1) to 0.083M(-1)s(-1).

  17. Vibrational modes of hemoglobin in red blood cells.

    PubMed

    Martel, P; Calmettes, P; Hennion, B

    1991-02-01

    Equine red blood cells were washed in saline heavy water (2H2O) to exchange the hydrogen atoms of the non-hemoglobin components with deuterons. This led to novel neutron scattering measurements of protein vibrations within a cellular system and permitted a comparison with inelastic neutron scattering measurements on purified horse hemoglobin, either dry or wetted with 2H2O. As a function of wavevector transfer Q and the frequency transfer v the neutron response typified by the dynamic structure factor S(Q, v) was found to be similar for extracted and cellular hemoglobin at low and high temperatures. At 77 K, in the cells, a peak in S(Q, v) due to the protein was found near 0.7 THz, approximately half the frequency of a strong peak in the aqueous medium. Measurements at higher temperatures (170 and 230 K) indicated similar small shifts downwards in the peak frequencies of both components. At 260 K the low frequency component became predominantly quasielastic, but a significant inelastic component could still be ascribed to the aqueous scattering. Near 295 K the frequency responses of both components were similar and centered near zero. When scattering due to water is taken into account it appears that the protein neutron response in, or out of, red blood cells is little affected by hydration in the low frequency regime where Van der Waals forces are thought to be effective. PMID:1849028

  18. Evolutionary and Functional Relationships in the Truncated Hemoglobin Family.

    PubMed

    Bustamante, Juan P; Radusky, Leandro; Boechi, Leonardo; Estrin, Darío A; Ten Have, Arjen; Martí, Marcelo A

    2016-01-01

    Predicting function from sequence is an important goal in current biological research, and although, broad functional assignment is possible when a protein is assigned to a family, predicting functional specificity with accuracy is not straightforward. If function is provided by key structural properties and the relevant properties can be computed using the sequence as the starting point, it should in principle be possible to predict function in detail. The truncated hemoglobin family presents an interesting benchmark study due to their ubiquity, sequence diversity in the context of a conserved fold and the number of characterized members. Their functions are tightly related to O2 affinity and reactivity, as determined by the association and dissociation rate constants, both of which can be predicted and analyzed using in-silico based tools. In the present work we have applied a strategy, which combines homology modeling with molecular based energy calculations, to predict and analyze function of all known truncated hemoglobins in an evolutionary context. Our results show that truncated hemoglobins present conserved family features, but that its structure is flexible enough to allow the switch from high to low affinity in a few evolutionary steps. Most proteins display moderate to high oxygen affinities and multiple ligand migration paths, which, besides some minor trends, show heterogeneous distributions throughout the phylogenetic tree, again suggesting fast functional adaptation. Our data not only deepens our comprehension of the structural basis governing ligand affinity, but they also highlight some interesting functional evolutionary trends.

  19. Short-lived intermediates in hemoglobin/O2 systems.

    PubMed

    Czerlinski, G; Levin, R; Ypma, T

    1998-01-01

    The kinetics of the reaction of hemoglobin with molecular oxygen, in which rapid mixing is followed by a very fast temperature jump, is numerically simulated. Values for rate constants are used to the extent known, otherwise interpolated or extrapolated. It is shown that reaction steps not resolvable by rapid mixing can be resolved by subsequent chemical relaxation at appropriate points in time. Four different mechanisms are considered, all assuming no distinction between the two kinds of chains of hemoglobin. Bimolecular rate constants for oxygen binding are either the same for all four sites, or are governed by "frequency factors" (the kinetic equivalent of statistical factors for equilibrium constants in allosteric models). Furthermore, either the third or the fourth measured (Adair) dissociation constant is composed of the product of a "local" dissociation constant and an allosteric interconversion constant. These two pairs of choices give rise to four different mechanisms. Can these mechanisms be distinguished experimentally? As the final parameter values are so similar for the first two binding steps, discrimination is essentially impossible at low oxygen concentration levels (less than 100 microM with 50 microM hemoglobin). Discrimination becomes possible at higher oxygen concentrations, but high resolution in time and concentration amplitude are required. Much depends upon the differences in molar extinction coefficients of components over the accessible wave length range. Some of these values are as yet unknown or not known to a sufficient precision. Nevertheless, distinction between mechanistic alternatives is possible in principle.

  20. Pancreatic ascites hemoglobin contributes to the systemic response in acute pancreatitis.

    PubMed

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-04-01

    Upon hemolysis extracellular hemoglobin causes oxidative stress and cytotoxicity due to its peroxidase activity. Extracellular hemoglobin may release free hemin, which increases vascular permeability, leukocyte recruitment, and adhesion molecule expression. Pancreatitis-associated ascitic fluid is reddish and may contain extracellular hemoglobin. Our aim has been to determine the role of extracellular hemoglobin in the local and systemic inflammatory response during severe acute pancreatitis in rats. To this end we studied taurocholate-induced necrotizing pancreatitis in rats. First, extracellular hemoglobin in ascites and plasma was quantified and the hemolytic action of ascitic fluid was tested. Second, we assessed whether peritoneal lavage prevented the increase in extracellular hemoglobin in plasma during pancreatitis. Third, hemoglobin was purified from rat erythrocytes and administered intraperitoneally to assess the local and systemic effects of ascitic-associated extracellular hemoglobin during acute pancreatitis. Extracellular hemoglobin and hemin levels markedly increased in ascitic fluid and plasma during necrotizing pancreatitis. Peroxidase activity was very high in ascites. The peritoneal lavage abrogated the increase in extracellular hemoglobin in plasma. The administration of extracellular hemoglobin enhanced ascites; dramatically increased abdominal fat necrosis; upregulated tumor necrosis factor-α, interleukin-1β, and interleukin-6 gene expression; and decreased expression of interleukin-10 in abdominal adipose tissue during pancreatitis. Extracellular hemoglobin enhanced the gene expression and protein levels of vascular endothelial growth factor (VEGF) and other hypoxia-inducible factor-related genes in the lung. Extracellular hemoglobin also increased myeloperoxidase activity in the lung. In conclusion, extracellular hemoglobin contributes to the inflammatory response in severe acute pancreatitis through abdominal fat necrosis and inflammation

  1. Fasting serum glucose and glycosylated hemoglobin level in obesity.

    PubMed

    Das, R K; Nessa, A; Hossain, M A; Siddiqui, N I; Hussain, M A

    2014-04-01

    Obesity is a condition in which the body fat stores are increased to an extent which impairs health and leads to serious health consequences. The amount of body fat is difficult to measure directly, and is usually determined from an indirect measure - the body mass index (BMI). Increased BMI in obese persons is directly associated with an increase in metabolic disease, such as type 2 diabetes mellitus. This Analytical cross sectional study was undertaken to assess the relation between obesity and glycemic control of body by measuring fasting serum glucose and glycosylated hemoglobin. This study was carried out in the Department of Physiology, Mymensingh Medical College, Mymensingh from 1st July 2011 to 30th June 2012 on 120 equally divided male and female persons within the age range of 25 to 55 years. Age more than 55 years and less than 25 years and diagnosed case of Hypothyroidism, Cushing's syndrome, polycystic ovary, Antipsychotic drug user and regular steroid users were excluded. Non probability purposive type of sampling technique was used for selecting the study subjects. Measurement of body mass index was done as per procedure. Fasting serum glucose was estimated by glucose oxidase method and Glycosylated hemoglobin by Boronate Affinity method. Statistical analysis was done by SPSS (version 17.0). Data were expressed as Mean±SE and statistical significance of difference among the groups were calculated by unpaired student's 't' test and Pearson's correlation coefficient tests were done as applicable. The Mean±SE of fasting serum glucose was significant at 1% level (P value <0.001) for obese group of BMI. There was no significant difference of glycosylated hemoglobin level between control and study groups. But there was positive correlation within each group. Fasting serum glucose also showed a bit stronger positive correlation with BMI. Both obese male and female persons showed higher levels of fasting serum glucose and glycosylated hemoglobin. The

  2. Safety Evaluation of Hemoglobin-Albumin Cluster “HemoAct” as a Red Blood Cell Substitute

    PubMed Central

    Haruki, Risa; Kimura, Takuya; Iwasaki, Hitomi; Yamada, Kana; Kamiyama, Ikuo; Kohno, Mitsutomo; Taguchi, Kazuaki; Nagao, Saori; Maruyama, Toru; Otagiri, Masaki; Komatsu, Teruyuki

    2015-01-01

    A hemoglobin (Hb) wrapped covalently by human serum albumins (HSAs), a core–shell structured hemoglobin-albumin cluster designated as “HemoAct”, is an O2-carrier designed for use as a red blood cell (RBC) substitute. This report describes the blood compatibility, hemodynamic response, and pharmacokinetic properties of HemoAct, and then explains its preclinical safety. Viscosity and blood cell counting measurements revealed that HemoAct has good compatibility with whole blood. Intravenous administration of HemoAct into anesthetized rats elicited no unfavorable increase in systemic blood pressure by vasoconstriction. The half-life of 125I-labeled HemoAct in circulating blood is markedly longer than that of HSA. Serum biochemical tests conducted 7 days after HemoAct infusion yielded equivalent values to those observed in the control group with HSA. Histopathologic inspections of the vital organs revealed no marked abnormality in their tissues. All results indicate that HemoAct has sufficient preclinical safety as an alternative material for RBC transfusion. PMID:26220366

  3. [Susceptibility of induced sickle in samples of heterozygous hemoglobin S patients (sickle cell trait) suffering diabetes mellitus type 2].

    PubMed

    Díaz-Piedra, Pablo; Cervantes-Villagrana, Alberto Rafael; Ramos-Jiménez, Raúl; Presno-Bernal, José Miguel; Cervantes-Villagrana, Rodolfo Daniel

    2015-01-01

    Hemoglobin S is an abnormal protein that induces morphological changes in erythrocyte in low-oxygen conditions. In Mexico, it is reported that up to 13.7% of the population with mutation in one allele are considered asymptomatic (sickle cell trait). The sickle cell trait and diabetes mellitus are conditions that occur together in more than one million patients worldwide. Both diseases possibly produce microvascular changes in retinopathy and acute chest syndrome. The aim of this study was to evaluate the induction of sickle cells in samples of diabetic patients with sickle cell trait to identify altered red cell parameters. We obtained samples of diabetic patients to determine hemoglobin A1c and S; furthermore, red blood cell biometrics data were analyzed. We found that older men with diabetes were susceptible to generate sickle cells and this correlated with reduced red blood cell count and an increase in media cell volume. In samples of women diabetes, there were no differences. We conclude that samples from patients with sickle cell trait and diabetes can cause sickle cells with high frequency in men, with lower red blood cells count and increased mean corpuscular volume as susceptibility parameters.

  4. Effects of PEG-PLA-nano artificial cells containing hemoglobin on kidney function and renal histology in rats.

    PubMed

    Liu, Zun Chang; Chang, Thomas M S

    2008-01-01

    This study is to investigate the long-term effects of PEG-PLA nano artificial cells containing hemoglobin (NanoRBC) on renal function and renal histology after 1/3 blood volume top loading in rats. The experimental rats received one of the following infusions: NanoRBC in Ringer lactate, Ringer lactate, stroma-free hemoglobin (SFHB), polyhemoglobin (PolyHb), autologous rat whole blood (rat RBC). Blood samples were taken before infusions and on days 1, 7 and 21 after infusions for biochemistry analysis. Rats were sacrificed on day 21 after infusions and kidneys were excised for histology examination. Infusion of SFHB induced significant decrease in renal function damage evidenced by elevated serum urea, creatinine and uric acid throughout the 21 days. Kidney histology in SFHb infusion group revealed focal tubular necrosis and intraluminal cellular debris in the proximal tubules, whereas the glomeruli were not observed damaged. In all the other groups, NanoRBC, PolyHb, Ringer lactate and rat RBC, there were no abnormalities in renal biochemistry or histology. In conclusion, injection of NanoRBC did not have adverse effects on renal function nor renal histology.

  5. Electrocardiograph abnormalities in intracerebral hemorrhage.

    PubMed

    Takeuchi, Satoru; Nagatani, Kimihiro; Otani, Naoki; Wada, Kojiro; Mori, Kentaro

    2015-12-01

    This study investigated the prevalence and type of electrocardiography (ECG) abnormalities, and their possible association with the clinical/radiological findings in 118 consecutive patients with non-traumatic, non-neoplastic intracerebral hemorrhage (ICH). ECG frequently demonstrates abnormalities in patients with ischemic stroke and subarachnoid hemorrhage, but little is known of ECG changes in ICH patients. Clinical and radiological information was retrospectively reviewed. ECG recordings that were obtained within 24 hours of the initial hemorrhage were analyzed. Sixty-six patients (56%) had one or more ECG abnormalities. The most frequent was ST depression (24%), followed by left ventricular hypertrophy (20%), corrected QT interval (QTc) prolongation (19%), and T wave inversion (19%). The logistic regression analysis demonstrated the following: insular involvement was an independent predictive factor of ST depression (p<0.001; odds ratio OR 10.18; 95% confidence interval [CI] 2.84-36.57); insular involvement (p<0.001; OR 23.98; 95% CI 4.91-117.11) and presence of intraventricular hemorrhage (p<0.001; OR 8.72; 95% CI 2.69-28.29) were independent predictive factors of QTc prolongation; deep hematoma location (p<0.001; OR 19.12; 95% CI 3.82-95.81) and hematoma volume >30 ml (p=0.001; OR 6.58; 95% CI 2.11-20.46) were independent predictive factors of T wave inversion. We demonstrate associations between ECG abnormalities and detailed characteristics of ICH.

  6. Evaluation of Hemoglobin A1c Criteria to Assess Preoperative Diabetes Risk in Cardiac Surgery Patients

    PubMed Central

    Saberi, Sima; Zrull, Christina A.; Patil, Preethi V.; Jha, Leena; Kling-Colson, Susan C.; Gandia, Kenia G.; DuBois, Elizabeth C.; Plunkett, Cynthia D.; Bodnar, Tim W.; Pop-Busui, Rodica

    2011-01-01

    Abstract Objective Hemoglobin A1c (A1C) has recently been recommended for diagnosing diabetes mellitus and diabetes risk (prediabetes). Its performance compared with fasting plasma glucose (FPG) and 2-h post-glucose load (2HPG) is not well delineated. We compared the performance of A1C with that of FPG and 2HPG in preoperative cardiac surgery patients. Methods Data from 92 patients without a history of diabetes were analyzed. Patients were classified with diabetes or prediabetes using established cutoffs for FPG, 2HPG, and A1C. Sensitivity and specificity of the new A1C criteria were evaluated. Results All patients diagnosed with diabetes by A1C also had impaired fasting glucose, impaired glucose tolerance, or diabetes by other criteria. Using FPG as the reference, sensitivity and specificity of A1C for diagnosing diabetes were 50% and 96%, and using 2HPG as the reference they were 25% and 95%. Sensitivity and specificity for identifying prediabetes with FPG as the reference were 51% and 51%, respectively, and with 2HPG were 53% and 51%, respectively. One-third each of patients with prediabetes was identified using FPG, A1C, or both. When testing A1C and FPG concurrently, the sensitivity of diagnosing dysglycemia increased to 93% stipulating one or both tests are abnormal; specificity increased to 100% if both tests were required to be abnormal. Conclusions In patients before cardiac surgery, A1C criteria identified the largest number of patients with diabetes and prediabetes. For diagnosing prediabetes, A1C and FPG were discordant and characterized different groups of patients, therefore altering the distribution of diabetes risk. Simultaneous measurement of FGP and A1C may be a more sensitive and specific tool for identifying high-risk individuals with diabetes and prediabetes. PMID:21854260

  7. Hemoglobin redux: combining neutron and X-ray diffraction with mass spectrometry to analyse the quaternary state of oxidized hemoglobins

    PubMed Central

    Mueser, Timothy C.; Griffith, Wendell P.; Kovalevsky, Andrey Y.; Guo, Jingshu; Seaver, Sean; Langan, Paul; Hanson, B. Leif

    2010-01-01

    Improvements in neutron diffraction instrumentation are affording the opportunity to re-examine the structures of vertebrate hemoglobins and to interrogate proton and solvent position changes between the different quaternary states of the protein. For hemoglobins of unknown primary sequence, structural studies of cyanomethemoglobin (CNmetHb) are being used to help to resolve sequence ambiguity in the mass spectra. These studies have also provided additional structural evidence for the involvement of oxidized hemoglobin in the process of erythrocyte senescence. X-ray crystal studies of Tibetan snow leopard CNmetHb have shown that this protein crystallizes in the B state, a structure with a more open dyad, which possibly has relevance to RBC band 3 protein binding and erythrocyte senescence. R-state equine CNmetHb crystal studies elaborate the solvent differences in the switch and hinge region compared with a human deoxyhemoglobin T-­state neutron structure. Lastly, comparison of histidine protonation between the T and R state should enumerate the Bohr-effect protons. PMID:21041946

  8. Hemoglobin redux: combining neutron and X-ray diffraction with mass spectrometry to analyse the quaternary state of oxidized hemoglobins

    SciTech Connect

    Mueser, Timothy C. Griffith, Wendell P.; Kovalevsky, Andrey Y.; Guo, Jingshu; Seaver, Sean; Langan, Paul; Hanson, B. Leif

    2010-11-01

    X-ray and neutron diffraction studies of cyanomethemoglobin are being used to evaluate the structural waters within the dimer–dimer interface involved in quaternary-state transitions. Improvements in neutron diffraction instrumentation are affording the opportunity to re-examine the structures of vertebrate hemoglobins and to interrogate proton and solvent position changes between the different quaternary states of the protein. For hemoglobins of unknown primary sequence, structural studies of cyanomethemoglobin (CNmetHb) are being used to help to resolve sequence ambiguity in the mass spectra. These studies have also provided additional structural evidence for the involvement of oxidized hemoglobin in the process of erythrocyte senescence. X-ray crystal studies of Tibetan snow leopard CNmetHb have shown that this protein crystallizes in the B state, a structure with a more open dyad, which possibly has relevance to RBC band 3 protein binding and erythrocyte senescence. R-state equine CNmetHb crystal studies elaborate the solvent differences in the switch and hinge region compared with a human deoxyhemoglobin T-state neutron structure. Lastly, comparison of histidine protonation between the T and R state should enumerate the Bohr-effect protons.

  9. Hemoglobin redux: combining neutron and X-ray diffraction with mass spectrometry to analyse the quaternary state of oxidized hemoglobins.

    PubMed

    Mueser, Timothy C; Griffith, Wendell P; Kovalevsky, Andrey Y; Guo, Jingshu; Seaver, Sean; Langan, Paul; Hanson, B Leif

    2010-11-01

    Improvements in neutron diffraction instrumentation are affording the opportunity to re-examine the structures of vertebrate hemoglobins and to interrogate proton and solvent position changes between the different quaternary states of the protein. For hemoglobins of unknown primary sequence, structural studies of cyanomethemoglobin (CNmetHb) are being used to help to resolve sequence ambiguity in the mass spectra. These studies have also provided additional structural evidence for the involvement of oxidized hemoglobin in the process of erythrocyte senescence. X-ray crystal studies of Tibetan snow leopard CNmetHb have shown that this protein crystallizes in the B state, a structure with a more open dyad, which possibly has relevance to RBC band 3 protein binding and erythrocyte senescence. R-state equine CNmetHb crystal studies elaborate the solvent differences in the switch and hinge region compared with a human deoxyhemoglobin T-state neutron structure. Lastly, comparison of histidine protonation between the T and R state should enumerate the Bohr-effect protons.

  10. Lipid peroxidation and hemoglobin degradation in red blood cells exposed to t-butyl hydroperoxide. Dependence on glucose metabolism and hemoglobin status.

    PubMed

    Trotta, R J; Sullivan, S G; Stern, A

    1981-12-01

    Changes in hemoglobin status and lipid peroxidation were followed in red cells containing either oxy-met-, or carbonmonoxyhemoglobin, incubated with t-butyl hydroperoxide in a medium with or without glucose. Loss of intact hemoglobin (the sum of oxyhemoglobin and methemoglobin) was inversely proportional to the degree of lipid peroxidation in red cells containing either oxy- or methemoglobin. When glucose was added to the medium, lipid peroxidation increased while there was a decreased loss of intact hemoglobin in red cells containing either oxy- or methemoglobin, while both lipid peroxidation and changes in hemoglobin decreased in red cells containing carbonmonoxyhemoglobin. Methemoglobin formation and loss of intact hemoglobin were directly proportional to the degree of lipid peroxidation in red cells containing carbonmonoxyhemoglobin. The greatest amount of lipid peroxidation occurred in red cells containing carbonmonoxyhemoglobin, incubated without glucose. These results indicate that methemoglobin and non-intact hemoglobin may protect the membrane against lipid peroxidation. We propose that, depending on the availability of glucose and the liganded state of hemoglobin, lipid peroxidation and hemoglobin alterations represent extremes of a spectrum of oxidative damage.

  11. Correlation Between the Severity of Diabetic Peripheral Polyneuropathy and Glycosylated Hemoglobin Levels: A Quantitative Study

    PubMed Central

    Lee, Won-Jae; Jang, Sol; Lee, Seung-Hwa

    2016-01-01

    Objective To investigate risk factors for diabetic peripheral polyneuropathy and their correlation with the quantified severity of nerve dysfunction in patients with diabetes mellitus (DM). Methods A total of 187 diabetic patients with clinically suspected polyneuropathy (PN) were subclassified into 2 groups according to electrodiagnostic testing: a DM-PN group of 153 diabetic patients without electrophysiological abnormality and a DM+PN group of 34 diabetic patients with polyneuropathy. For all patients, age, sex, height, weight, duration of DM, and plasma glycosylated hemoglobin (HbA1c) level were comparatively investigated. A composite score was introduced to quantitatively analyze the results of the nerve conduction studies. Logistic regression analysis and multiple regression analysis were used to evaluate correlations between significant risk factors and severity of diabetic polyneuropathy. Results The DM+PN group showed a significantly higher HbA1c level and composite score, as compared with the DM-PN group. Increased HbA1c level and old age were significant predictive factors for polyneuropathy in diabetic patients (odds ratio=5.233 and 4.745, respectively). In the multiple linear regression model, HbA1c and age showed a significant positive association with composite score, in order (β=1.560 and 0.253, respectively). Conclusion Increased HbA1c level indicative of a state of chronic hyperglycemia was a risk factor for polyneuropathy in diabetic patients and a quantitative measure of its severity. PMID:27152276

  12. Accelerated autoxidation and heme loss due to instability of sickle hemoglobin

    SciTech Connect

    Hebbel, R.P.; Morgan, W.T.; Eaton, J.W.; Hedlund, B.E.

    1988-01-01

    The pleiotropic effect of the sickle gene suggests that factors in addition to polymerization of the mutant gene product might be involved in sickle disease pathobiology. The authors have examined rates of heme transfer to hemopexin from hemoglobin in dilute aqueous solution at 37/sup 0/C. HbO/sub 2/ S loses heme 1.7 times faster than HbO/sub 2/ A. In contrast, Hb A and Hb S behave identically in their MetHb forms and their HbCO forms. This indicates that the faster heme loss from HbO/sub 2/ S is due to accelerated autoxidation (HbO/sub 2/ ..-->.. MetHb) rather than to some other type of instability inherent in the relationship of sickle heme to its pocket in globin. This interpretation is supported by spectrophotometric measurement of initial rates of MetHb formation during incubation at 37/sup 0/C. This directly shows 1.7 times faster autoxidation, with apparent rate constants of 0.050 hr/sup -1/ for HbO/sub 2/ S and 0.029 hr/sup -1/ for HbO/sub 2/. While the participation of this process in the cellular pathobiology of sickle erythrocytes remains unproven, the present data are consistent with, and perhaps help explain, two prio observations: the excessive spontaneous generation of superoxide by sickle erythrocytes; and the abnormal deposition of heme and heme proteins on membranes of sickle erythrocytes.

  13. Morphology and chirality control self-assembly of sickle hemoglobin inside red blood cells

    NASA Astrophysics Data System (ADS)

    Li, Xuejin; Lei, Huan; Caswell, Bruce; Karniadakis, George

    2012-02-01

    Sickle cells exhibit abnormal morphology and membrane mechanics in the deoxygenated state due to the polymerization of the interior sickle hemoglobin (HbS). In this study, the dynamics of self-assembly behavior of HbS in solution and corresponding induced cell morphologies have been investigated by dissipative particle dynamics approach. A coarse-grained HbS model, which contains hydrophilic and hydrophobic particles, is constructed to match the structural properties and physical description (including crowding effects) of HbS. The hydrophobic interactions are shown to be necessary with chirality being the main driver for the formation of HbS fibers. In the absence of chain chirality, only the self-assembled small aggregates are observed whereas self-assembled elongated step-like bundle microstructures appear when we consider the chain chirality. Several typical cell morphologies (sickle, granular, elongated shapes), induced by the growth of HbS fibers, are revealed and their deviations from the biconcave shape are quantified by the asphericity and elliptical shape factors.

  14. Occipital lobe seizures related to marked elevation of hemoglobin A1C: report of two cases.

    PubMed

    Hung, Wan-Ling; Hsieh, Peiyuan F; Lee, Yi-Chung; Chang, Ming-Hong

    2010-07-01

    Occipital lobe seizures caused by nonketotic hyperglycemia (NKH) have been reported in only a few cases and are not fully characterized. We report two cases of NKH-related occipital lobe seizures with high hemoglobin A1C (HbA1C), epileptiform electroencephalograph (EEG) and MRI abnormalities. Both patients had moderate hyperglycemia (310-372 mg/dl) and mildly elevated serum osmolarity (295-304 mOsm/kg) but markedly elevated HbA1C (13.8-14.4%). One patient had a clinico-EEG seizure originating from the right occipital region during sleep. The other patient had an interictal epileptiform discharge consisting of unilateral occipital beta activity in sleep. None of the previously reported cases fulfilled the criteria of a nonketotic hyperglycemic hyperosmolar (NKHH) state, or showed any interictal beta paroxysms, spikes, sharp waves, or spike/sharp-slow wave complexes. We suggest that prolonged exposure to uncontrolled hyperglycemia, as indicated by HbA1C, rather than an acute NKHH state is crucial in the development of this peculiar seizure. We also suggest clinicians look for the presence of interictal focal beta paroxysms in addition to the usual epileptiform discharges while reading the EEG of these patients.

  15. Specific induction of fibronectin binding activity by hemoglobin in Candida albicans grown in defined media.

    PubMed

    Yan, S; Nègre, E; Cashel, J A; Guo, N; Lyman, C A; Walsh, T J; Roberts, D D

    1996-08-01

    Fibronectin (FN) is a major component of host extracellular matrix that may play an important role in the initiation and dissemination of Candida albicans infections. Expression of FN binding requires growth of C albicans blastoconidia in complex medium, and the regulation of FN receptor expression is poorly understood. We now demonstrate that hemoglobin is a potent and specific inducer of FN receptor expression and describe a defined medium supplemented with hemoglobin that greatly and stably enhances the binding activity of C. albicans for soluble FN. Enhancement of FN binding by hemoglobin in strain 44807 was concentration dependent and was maximal at 0.1% hemoglobin with 20- to 80-fold enhancement. The hemoglobin-induced FN binding to C. albicans was saturable, with a Kd of 2.7 X 10(-8) M. Enhancement required growth of C. albicans in hemoglobin-containing medium, since simply exposing blastoconidia to hemoglobin in a nongrowing status did not enhance binding. Induction was reversible following removal of hemoglobin from the growth medium and not associated with germination. Inorganic or protein-bound iron was not sufficient for the induction, since other iron-containing proteins or inorganic iron salts were inactive. Growth in the simple medium yeast nitrogen base supplemented with hemoglobin increased cell adhesion to immobilized FN and to cultured monolayers of bovine corneal endothelial cells. These data suggest that hemoglobin may be an important regulator of FN binding activity in C. albicans and thus may play a role in its pathogenesis. PMID:8757815

  16. Hemoglobin E: a common hemoglobinopathy among children of Southeast Asian origin.

    PubMed

    Katsanis, E; Luke, K H; Hsu, E; Yates, J R

    1987-07-01

    With the recent immigration of Southeast Asians to Canada, hemoglobin E has become a frequent diagnosis. The clinical and hematologic findings in 42 children (mean age 4.3 years) with hemoglobin E are presented. There were 33 heterozygotes (having hemoglobin E trait), 6 homozygotes (having hemoglobin EE) and 3 double heterozygotes (having hemoglobin E-beta-thalassemia). The heterozygotes had low-normal hemoglobin levels and mean corpuscular volumes; coexisting iron deficiency, present in 62% of these children, resulted in substantially lower hemoglobin levels, very low mean corpuscular volumes and lower than expected levels of hemoglobin E on electrophoresis. The children with hemoglobin EE were only slightly anemic, but those with hemoglobin E-beta-thalassemia had severe anemia and required long-term transfusion therapy. Nutritional factors and parasitic infestations were the main causes of iron depletion, which was common, particularly in children less than 2 years old (87%). Physicians of patients of Southeast Asian origin should be aware of the clinical and hematologic presentation of these hemoglobinopathies.

  17. Laboratory Abnormalities Among HIV-Exposed, Uninfected Infants: IMPAACT Protocol P1025

    PubMed Central

    Read, Jennifer S.; Huo, Yanling; Patel, Kunjal; Mitchell, Marcia; Scott, Gwendolyn B.

    2012-01-01

    Background. Infant laboratory abnormalities have been associated with exposure to antiretrovirals and to trimethoprim/sulfamethoxazole (TMP/SMX). Methods. We analyzed data from International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) Protocol P1025, a prospective cohort study of human immunodeficiency virus type 1 (HIV)–infected women and their infants. Live-born, singleton, HIV-uninfected infants with at least 6 months of follow-up who represented the first pregnancy on study of HIV-infected mothers with at least 1 prenatal visit, CD4 count, and viral load during pregnancy and who used at least 1 antiretroviral during pregnancy were eligible for inclusion in this analysis. Results. The study population comprised 1524 infants. During the first 6 months of life, 7.4% of laboratory serious adverse events (SAEs) were related to glucose, 7.2% were related to hemoglobin, 8.7% were related to absolute neutrophil count, and 4.0% were related to total lymphocyte count. The likelihood of laboratory SAEs decreased with increasing age for hemoglobin, absolute neutrophil count, and glucose. Infant preterm birth and current receipt of antiretroviral(s) were the factors with the strongest associations with laboratory SAEs. Conclusions. The overall frequency of laboratory SAEs was low and decreased with age. Preterm infants are at higher risk of hemoglobin- and total lymphocyte count–related SAEs. PMID:23687574

  18. [Transient abnormal Q-waves].

    PubMed

    Godballe, C; Hoeck, H C; Sørensen, J A

    1990-01-01

    We present a case of transient abnormal Q-waves (TAQ) and a review of the literature. TAQ are defined as abnormal Q-waves, which disappear within ten days. They are most often seen in patients with ischemic heart disease (IHD) but are also seen in other conditions. Brief episodes of myocardial ischemia giving rise to reversible biochemical and ultrastructural myocardial changes, resulting in transient ECG changes, provide an accepted theory for the pathogenesis of TAO. Investigations have shown that the occurrence of exercise-induced TAQ may be a symptom of IHD. It is impossible to distinguish TAQ from Q-waves induced by myocardial infarction. Appearance of TAQ during exercise-testing frequently indicates IHD. PMID:2301045

  19. [Chromosome abnormalities in human cancer].

    PubMed

    Salamanca-Gómez, F

    1995-01-01

    Recent investigation on the presence of chromosome abnormalities in neoplasias has allowed outstanding advances in the knowledge of malignant transformation mechanisms and important applications in the clinical diagnosis and prognosis of leukaemias, lymphomas and solid tumors. The purpose of the present paper is to discuss the most relevant cytogenetic aberrations, some of them described at the Unidad de Investigación Médica en Genética Humana, Instituto Mexicano del Seguro Social, and to correlate these abnormalities with recent achievements in the knowledge of oncogenes, suppressor genes or antioncogenes, their chromosome localization, and their mutations in human neoplasia; as well as their perspectives in prevention and treatment of cancer that such findings permit to anticipate.

  20. Ultrasound screening for fetal abnormalities.

    PubMed

    Chitty, L S

    1995-12-01

    Ultrasound screening for fetal abnormalities is increasingly becoming part of routine antenatal care in Europe and the UK. However, there has been very little formal evaluation of this practice. In this article reports of routine ultrasound screening are reviewed and the advantages and disadvantages discussed. The majority of routine anomaly scanning is done in the second trimester but there may be a case for screening at other times in pregnancy and alternative anomaly screening policies are discussed. PMID:8710765

  1. Oxygen equilibria of ectotherm blood containing multiple hemoglobins.

    PubMed

    Maginniss, L A; Song, Y K; Reeves, R B

    1980-12-01

    Complete isocapnic O2 equilibrium curves (O2EC's) and related blood-gas properties are reported for whole blood of the bullfrog (Rana catesbeiana) and the aquatic turtle (Pseudemys scripta) at temperatures ranging from 5 to 35 degrees C. P50's for bullfrog and turtle blood at physiological pH and 25 degrees C were 36.6 Torr (pH 7.83) and 19.3 Torr (pH 7.55), respectively. Elevation of blood temperature significantly reduced hemoglobin oxygen affinity in both species (delta H = -8.1 and -7.8 kcal/mol O2 for Rana and Pseudemys, respectively). Bullfrog and turtle oxygen equilibrium data revealed non-standard curve shapes when compared with the Severinghaus curve for human blood (1979); ectotherm O2EC's rose more steeply below P50 (less sigmoid) and were distinctly flattened (linear) above 50% saturation. The CO2-Bohr effect for bullfrog and turtle blood varied significantly as a function of saturation. In addition, both species exhibited non-linear Hill relationships (logS/1-s vs. log PO2). These results indicate that the oxygen binding properties of the multiple hemoglobin bloods of Rana and Pseudemys (demonstrated by isoelectric focusing) are more complex than those exhibited by normal human blood. As a consequence, these ectotherm blood oxygen data are not well characterized by the limited number of simple descriptive parameters (P50, Hill's n and delta log P50/delta pH) commonly used to delineate predominantly single hemoglobin systems.

  2. Mass Spectra and Ion Collision Cross Sections of Hemoglobin

    NASA Astrophysics Data System (ADS)

    Kang, Yang; Terrier, Peran; Douglas, D. J.

    2011-02-01

    Mass spectra of commercially obtained hemoglobin (Hb) show higher levels of monomer and dimer ions, heme-deficient dimer ions, and apo-monomer ions than hemoglobin freshly prepared from blood. This has previously been attributed to oxidation of commercial Hb. Further, it has been reported that that dimer ions from commercial bovine Hb have lower collision cross sections than low charge state monomer ions. To investigate these effects further, we have recorded mass spectra of fresh human Hb, commercial human and bovine Hb, fresh human Hb oxidized with H2O2, lyophilized fresh human Hb, fresh human Hb both lyophilized and chemically oxidized, and commercial human Hb oxidized with H2O2. Masses of α-monomer ions of all hemoglobins agree with the masses expected from the sequences within 3 Da or better. Mass spectra of the β chains of commercial Hb and oxidized fresh human Hb show a peak or shoulder on the high mass side, consistent with oxidation of the protein. Both commercial proteins and oxidized fresh human Hb produce heme-deficient dimers with masses 32 Da greater than expected and higher levels of monomer and dimer ions than fresh Hb. Lyophilization or oxidation of Hb both produce higher levels of monomer and dimer ions in mass spectra. Fresh human Hb, commercial human Hb, commercial bovine Hb, and oxidized commercial human Hb all give dimer ions with cross sections greater than monomer ions. Thus, neither oxidation of Hb or the difference in sequence between human and bovine Hb make substantial differences to cross sections of ions.

  3. New-old hemoglobin-like proteins of symbiotic dinoflagellates

    PubMed Central

    Rosic, Nedeljka N; Leggat, William; Kaniewska, Paulina; Dove, Sophie; Hoegh-Guldberg, Ove

    2013-01-01

    Symbiotic dinoflagellates are unicellular photosynthetic algae that live in mutualistic symbioses with many marine organisms. Within the transcriptome of coral endosymbionts Symbiodinium sp. (type C3), we discovered the sequences of two novel and highly polymorphic hemoglobin-like genes and proposed their 3D protein structures. At the protein level, four isoforms shared between 87 and 97% sequence identity for Hb-1 and 78–99% for Hb-2, whereas between Hb-1 and Hb-2 proteins, only 15–21% sequence homology has been preserved. Phylogenetic analyses of the dinoflagellate encoding Hb sequences have revealed a separate evolutionary origin of the discovered globin genes and indicated the possibility of horizontal gene transfer. Transcriptional regulation of the Hb-like genes was studied in the reef-building coral Acropora aspera exposed to elevated temperatures (6–7°C above average sea temperature) over a 24-h period and a 72-h period, as well as to nutrient stress. Exposure to elevated temperatures resulted in an increased Hb-1 gene expression of 31% after 72 h only, whereas transcript abundance of the Hb-2 gene was enhanced by up to 59% by both 1-day and 3-day thermal stress conditions. Nutrient stress also increased gene expression of Hb-2 gene by 70%. Our findings describe the differential expression patterns of two novel Hb genes from symbiotic dinoflagellates and their polymorphic nature. Furthermore, the inducible nature of Hb-2 gene by both thermal and nutrient stressors indicates a prospective role of this form of hemoglobin in the initial coral–algal responses to changes in environmental conditions. This novel hemoglobin has potential use as a stress biomarker. PMID:23610627

  4. Differential expression of murine adult hemoglobins in early ontogeny

    SciTech Connect

    Wawrzyniak, C.J.; Lewis, S.E.; Popp, R.A.

    1985-01-01

    A hemoglobin mutation is described that permits study of the expression of the two adult ..beta..-globin genes throughout fetal and postnatal development. Mice with a mutation at the Hbb/sup s/, ..beta..-globin locus, were used to study the relative levels of ..beta..-s2major and ..beta..-sminor globins specified by the mutant Hbb/sup s2/ haplotype during development. At 11.5 days of gestation ..beta..-sminor comprised over 80% and ..beta..-s2major under 20% of the adult beta-globin. The relative level of ..beta..-sminor decreased through fetal development; at birth ..beta..-sminor represented 33.7% of the ..beta..-globin. The adult values of 71.0% ..beta..-s2major and 29.0% ..beta..-sminor globin are expressed in mice six days after birth. Because the two ..beta..-globin genes are expressed in mice of the Hbb/sup 2s/ haplotype, both the ..beta..-smajor and ..beta..-sminor genes must be expressed in mice of the Hbb/sup s/ haplotype. Expression of the ..beta..-sminor gene is elevated to 35.6% in Hbb/sup s2/ mice that have been bled repeatedly. Thus, the 5' ..beta..-s2major and 3' ..beta..-sminor genes of the Hbb/sup s2/ haplotype and, presumably the 5' ..beta..-smajor and 3' ..beta..-sminor genes of the Hbb/sup s/ haplotype, are regulated independently and are homologous to the 5' ..beta..-dmajor and 3' ..beta..-dminor genes of the Hbb/sup d/ haplotype. Mice of the Hbb/sup s2/ haplotype are better than mice of the Hbb/sup d/ haplotytpe for studying the mechanisms of hemoglobin switching because the Hbb/sup s2/ each of the three embryonic and two adult hemoglobins can be separated by electrophoresis. 17 refs., 3 figs.

  5. [Endocrine abnormalities in HIV infections].

    PubMed

    Verges, B; Chavanet, P; Desgres, J; Kisterman, J P; Waldner, A; Vaillant, G; Portier, H; Brun, J M; Putelat, R

    The finding of endocrine gland lesions at pathological examination in AIDS and reports of several cases of endocrine disease in patients with this syndrome have prompted us to study endocrine functions in 63 patients (51 men, 12 women) with HIV-1 infection. According to the Center for Disease Control (CDC) classification system, 13 of these patients were stage CDC II, 27 stage CDC III and 23 stage CDC IV. We explored the adrenocortical function (ACTH, immediate tetracosactrin test) and the thyroid function (free T3 and T4 levels, TRH on TSH test) in all 63 patients. The hypothalamic-pituitary-gonadal axis (testosterone levels, LHRH test) and prolactin secretion (THR test) were explored in the 51 men. The results obtained showed early peripheral testicular insufficiency at stage CDC II and early pituitary gland abnormalities with hypersecretion of ACTH and prolactin also at stage CDC II. On the other hand, adrenocortical and pituitary abnormalities were not frequently found. The physiopathology of the endocrine abnormalities observed in HIV-1-infected patients remains unclear, but one may suspect that it involves interleukin-1 since this protein factor has recently been shown to stimulate the corticotropin-releasing hormone secretion and to act directly on the glycoprotein capsule of the virus (gp 120) whose structure is similar to that of some neurohormones.

  6. Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

    DOEpatents

    Jensen, R.H.; Vanderlaan, M.; Bigbee, W.L.; Stanker, L.H.; Branscomb, E.W.; Grabske, R.J.

    1984-11-29

    The present invention provides monoclonal antibodies specific to and distinguishing between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype. 4 figs.

  7. Long-term variation in hemoglobin concentration in nestling great tits Parus major.

    PubMed

    Kaliński, Adam; Bańbura, Mirosława; Glądalski, Michał; Markowski, Marcin; Skwarska, Joanna; Wawrzyniak, Jarosław; Zieliński, Piotr; Cyżewska, Iwona; Bańbura, Jerzy

    2015-07-01

    Several studies have previously proposed that blood hemoglobin concentration in nestling passerines is a reliable index of individual condition and nutritional state. In this paper we present results concerning variation in hemoglobin concentration in the blood of ca. 14-day-old nestling great tits Parus major in central Poland in an 11-year-long period, 2003-2013, in two distinct habitat types: urban park and deciduous forest. The most important findings of the study were: (i) variation in hemoglobin concentration was consistent within broods, (ii) hemoglobin concentration of nestlings varied markedly across years, (iii) hemoglobin concentration was significantly higher in the forest study site which is richer in terms of food abundance during the short period of tits breeding season and (iv) high hemoglobin level was a predictor of nestling survival from hatching to fledging.

  8. Monoclonal antibodies to human hemoglobin S and cell lines for the production thereof

    DOEpatents

    Jensen, Ronald H.; Vanderlaan, Martin; Bigbee, William L.; Stanker, Larry H.; Branscomb, Elbert W.; Grabske, Robert J.

    1988-01-01

    The present invention provides monoclonal antibodies specific to and distinguish between hemoglobin S and hemoglobin A and methods for their production and use. These antibodies are capable of distinguishing between two hemoglobin types which differ from each other by only a single amino acid residue. The antibodies produced according to the present method are useful as immunofluorescent markers to enumerate circulating red blood cells which have the property of altered expression of the hemoglobin gene due to somatic mutation in stem cells. Such a measurement is contemplated as an assay for in vivo cellular somatic mutations in humans. Since the monoclonal antibodies produced in accordance with the instant invention exhibit a high degree of specificity to and greater affinity for hemoglobin S, they are suitable for labeling human red blood cells for flow cytometric detection of hemoglobin genotype.

  9. Modeling hemoglobin at optical frequency using the unconditionally stable fundamental ADI-FDTD method.

    PubMed

    Heh, Ding Yu; Tan, Eng Leong

    2011-04-12

    This paper presents the modeling of hemoglobin at optical frequency (250 nm - 1000 nm) using the unconditionally stable fundamental alternating-direction-implicit finite-difference time-domain (FADI-FDTD) method. An accurate model based on complex conjugate pole-residue pairs is proposed to model the complex permittivity of hemoglobin at optical frequency. Two hemoglobin concentrations at 15 g/dL and 33 g/dL are considered. The model is then incorporated into the FADI-FDTD method for solving electromagnetic problems involving interaction of light with hemoglobin. The computation of transmission and reflection coefficients of a half space hemoglobin medium using the FADI-FDTD validates the accuracy of our model and method. The specific absorption rate (SAR) distribution of human capillary at optical frequency is also shown. While maintaining accuracy, the unconditionally stable FADI-FDTD method exhibits high efficiency in modeling hemoglobin.

  10. Electron Transfer Dissociation Mass Spectrometry of Hemoglobin on Clinical Samples

    NASA Astrophysics Data System (ADS)

    Coelho Graça, Didia; Lescuyer, Pierre; Clerici, Lorella; Tsybin, Yury O.; Hartmer, Ralf; Meyer, Markus; Samii, Kaveh; Hochstrasser, Denis F.; Scherl, Alexander

    2012-10-01

    A mass spectrometry-based assay combining the specificity of selected reaction monitoring and the protein ion activation capabilities of electron transfer dissociation was developed and employed for the rapid identification of hemoglobin variants from whole blood without previous proteolytic cleavage. The analysis was performed in a robust ion trap mass spectrometer operating at nominal mass accuracy and resolution. Subtle differences in globin sequences, resulting with mass shifts of about one Da, can be unambiguously identified. These results suggest that mass spectrometry analysis of entire proteins using electron transfer dissociation can be employed on clinical samples in a workflow compatible with diagnostic applications.

  11. Computation of the unsteady facilitated transport of oxygen in hemoglobin

    NASA Technical Reports Server (NTRS)

    Davis, Sanford

    1990-01-01

    The transport of a reacting permeant diffusing through a thin membrane is extended to more realistic dissociation models. A new nonlinear analysis of the reaction-diffusion equations, using implicit finite-difference methods and direct block solvers, is used to study the limits of linearized and equilibrium theories. Computed curves of molecular oxygen permeating through hemoglobin solution are used to illustrate higher-order reaction models, the effect of concentration boundary layers at the membrane interfaces, and the transient buildup of oxygen flux.

  12. Carbon monoxide binding to a fish hemoglobin under photostationary conditions.

    PubMed

    Torkelson, S J; Gibson, Q H

    1978-10-25

    Determinations of carbon monoxide binding curves for hemoglobin from Brevoortia tyrannus under equilibrium and photostationary conditions show that in the light, the curve is shifted to the right and altered in shape. The Bohr effect is much less in the light. The kinetics of the transition between equilibrium and photostationary states has been examined. All of the results are satisfactorily described using the two-state model of Monod, J. Wyman, J., and Changeux, J.P. (1965) J. Mol. Biol. 12, 88-118 with the assumption that light produces an additive increase in the rate of dissociation of ligand from the R and T states. PMID:701255

  13. Broadband diffuse optical spectroscopy assessment of hemorrhage- and hemoglobin-based blood substitute resuscitation

    NASA Astrophysics Data System (ADS)

    Lee, Jangwoen; Kim, Jae G.; Mahon, Sari; Tromberg, Bruce J.; Mukai, David; Kreuter, Kelly; Saltzman, Darin; Patino, Renee; Goldberg, Robert; Brenner, Matthew

    2009-07-01

    Hemoglobin-based oxygen carriers (HBOCs) are solutions of cell-free hemoglobin (Hb) that have been developed for replacement or augmentation of blood transfusion. It is important to monitor in vivo tissue hemoglobin content, total tissue hemoglobin [THb], oxy- and deoxy-hemoglobin concentrations ([OHb], [RHb]), and tissue oxygen saturation (StO2=[OHb]/[THb]×100%) to evaluate effectiveness of HBOC transfusion. We designed and constructed a broadband diffuse optical spectroscopy (DOS) prototype system to measure bulk tissue absorption and scattering spectra between 650 and 1000 nm capable of accurately determining these tissue hemoglobin component concentrations in vivo. Our purpose was to assess the feasibility of using DOS to optically monitor tissue [OHb], [RHb], StO2, and total tissue hemoglobin concentration ([THb]=[OHb]+[RHb]) during HBOC infusion using a rabbit hypovolemic shock model. The DOS prototype probe was placed on the shaved inner thigh muscle of the hind leg to assess concentrations of [OHb], [RHb], [THb], as well as StO2. Hemorrhagic shock was induced in intubated New Zealand white rabbits (N=6) by withdrawing blood via a femoral arterial line to 20% blood loss (10-15 cc/kg). Hemoglobin glutamer-200 (Hb-200) 1:1 volume resuscitation was administered following the hemorrhage. These values were compared against traditional invasive measurements, serum hemoglobin concentration (sHGB), systemic blood pressure, heart rate, and blood gases. DOS revealed increases of [THb], [OHb], and tissue hemoglobin oxygen saturation after Hb-200 infusion, while blood total hemoglobin values continued did not increase; we speculate, due to hyperosmolality induced hemodilution. DOS enables noninvasive in vivo monitoring of tissue hemoglobin and oxygenation parameters during shock and volume expansion with HBOC and potentially enables the assessment of efficacy of resuscitation efforts using artificial blood substitutes.

  14. Genetic and developmental variation of hemoglobin in the deermouse, Peromyscus maniculatus.

    PubMed

    Maybank, K M; Dawson, W D

    1976-04-01

    A genetic investigation of electrophoretic hemoglobin variants of the deermouse, Peromyscus maniculatus, shows three alleles, Hblf, Hblr, and Hblo, at a duplicated site controlling the six adult phenotypes. The Hblf allele has not been described previously. The hemoglobin locus is not closely linked to the albino locus. Fetal hemoglobin is distinct from any of the adult components and has a slower electrophoretic mobility. The fetal phenotype changes to the adult type between the days 15 and 18 of prenatal life. PMID:962849

  15. Do high blood folate concentrations exacerbate metabolic abnormalities in people with low vitamin B-12 status?123

    PubMed Central

    Mills, James L; Carter, Tonia C; Scott, John M; Troendle, James F; Gibney, Eileen R; Shane, Barry; Kirke, Peadar N; Ueland, Per M; Brody, Lawrence C; Molloy, Anne M

    2011-01-01

    Background: In elderly individuals with low serum vitamin B-12, those who have high serum folate have been reported to have greater abnormalities in the following biomarkers for vitamin B-12 deficiency: low hemoglobin and elevated total homocysteine (tHcy) and methylmalonic acid (MMA). This suggests that folate exacerbates vitamin B-12–related metabolic abnormalities. Objective: We determined whether high serum folate in individuals with low serum vitamin B-12 increases the deleterious effects of low vitamin B-12 on biomarkers of vitamin B-12 cellular function. Design: In this cross-sectional study, 2507 university students provided data on medical history and exposure to folic acid and vitamin B-12 supplements. Blood was collected to measure serum and red blood cell folate (RCF), hemoglobin, plasma tHcy, and MMA, holotranscobalamin, and ferritin in serum. Results: In subjects with low vitamin B-12 concentrations (<148 pmol/L), those who had high folate concentrations (>30 nmol/L; group 1) did not show greater abnormalities in vitamin B-12 cellular function in any area than did those with lower folate concentrations (≤30 nmol/L; group 2). Group 1 had significantly higher holotranscobalamin and RCF, significantly lower tHcy, and nonsignificantly lower (P = 0.057) MMA concentrations than did group 2. The groups did not differ significantly in hemoglobin or ferritin. Compared with group 2, group 1 had significantly higher mean intakes of folic acid and vitamin B-12 from supplements and fortified food. Conclusions: In this young adult population, high folate concentrations did not exacerbate the biochemical abnormalities related to vitamin B-12 deficiency. These results provide reassurance that folic acid in fortified foods and supplements does not interfere with vitamin B-12 metabolism at the cellular level in a healthy population. PMID:21653798

  16. Oxidative stress in preeclampsia and the role of free fetal hemoglobin

    PubMed Central

    Hansson, Stefan R.; Nääv, Åsa; Erlandsson, Lena

    2015-01-01

    Preeclampsia is a leading cause of pregnancy complications and affects 3–7% of pregnant women. This review summarizes the current knowledge of a new potential etiology of the disease, with a special focus on hemoglobin-induced oxidative stress. Furthermore, we also suggest hemoglobin as a potential target for therapy. Gene and protein profiling studies have shown increased expression and accumulation of free fetal hemoglobin in the preeclamptic placenta. Predominantly due to oxidative damage to the placental barrier, fetal hemoglobin leaks over to the maternal circulation. Free hemoglobin and its metabolites are toxic in several ways; (a) ferrous hemoglobin (Fe2+) binds strongly to the vasodilator nitric oxide (NO) and reduces the availability of free NO, which results in vasoconstriction, (b) hemoglobin (Fe2+) with bound oxygen spontaneously generates free oxygen radicals, and (c) the heme groups create an inflammatory response by inducing activation of neutrophils and cytokine production. The endogenous protein α1-microglobulin, with radical and heme binding properties, has shown both ex vivo and in vivo to have the ability to counteract free hemoglobin-induced placental and kidney damage. Oxidative stress in general, and more specifically fetal hemoglobin-induced oxidative stress, could play a key role in the pathology of preeclampsia seen both in the placenta and ultimately in the maternal endothelium. PMID:25628568

  17. An “acquired” hemoglobin J variant in a sickle cell disease patient

    PubMed Central

    Swedan, Nawwar; Nicol, Kathleen; Moder, Phylis; Kahwash, Samir

    2008-01-01

    We report the case of a rare hemoglobin variant, “Hemoglobin J”, discovered while performing hemoglobin electrophoresis following exchange transfusion of a sickle cell disease patient. It is usual practice in our institution to confirm the hemoglobin S level in sickle cell disease patients after red cell exchange. The patient had received 5 red cell units and the source of this variant was traced back to two of those units. Due to the uncertain clinical impact of this variant, and the lack of specific guidelines, the two donors were deferred from future donations to our institution. PMID:18827863

  18. Molecular analysis of the high-hemoglobin-F phenotype in Saudi Arabian sickle cell anemia.

    PubMed

    Miller, B A; Olivieri, N; Salameh, M; Ahmed, M; Antognetti, G; Huisman, T H; Nathan, D G; Orkin, S H

    1987-01-29

    Patients from the eastern province of Saudi Arabia who have sickle cell anemia have high circulating levels of fetal hemoglobin (hemoglobin F, 17 percent), and they therefore have a mild form of the disease. To examine the molecular basis of the elevated production of hemoglobin F, we searched for mutations in the promoter regions of the two hemoglobin F gamma-globin genes (G gamma and A gamma). The DNA sequences 450 bp (base pairs) upstream of both the G gamma and A gamma globin genes were normal except for a single-base cytosine-to-thymidine (C----T) substitution at -158 bp 5' to the cap (preinitiation) site of the G gamma-globin gene of the high-hemoglobin-F chromosome. We searched for an association between this -158 C----T substitution and the production of hemoglobin F and G gamma in normal Saudis and Saudis with sickle cell disease or trait. The substitution was present in nearly 100 percent of the patients with sickle cell disease or trait, and in 22 percent of the normal Saudis. Homozygosity for this mutation had no demonstrable effect on hemoglobin F production in the normal Saudi population. We conclude that this mutation is not uniquely responsible for the increase in hemoglobin F in Saudi patients. It may nevertheless have an important role in regulating hemoglobin F production, but its expression is complex and requires interaction with additional factors, such as hemolytic stress or other molecular determinants, possibly linked to the sickle cell gene.

  19. The temperature dependence of refractive index of hemoglobin at the wavelengths 930 and 1100 nm

    NASA Astrophysics Data System (ADS)

    Lazareva, Ekaterina N.; Tuchin, Valery V.

    2016-04-01

    In this study, the refractive index of hemoglobin was measured at different temperatures within a physiological range and above that is characteristic to light-blood interaction at laser therapy. Measurements were carried out using the multi-wavelength Abbe refractometer (Atago, Japan). The refractive index was measured at two NIR wavelengths of 930 nm and 1100 nm. Samples of hemoglobin solutions with concentration of 80, 120 and 160 g/l were investigated. The temperature was varied between 25 and 55 °C. It was shown that the dependence of the refractive index of hemoglobin is nonlinear with temperature, which may be associated with changes in molecular structure of hemoglobin.

  20. The crystal structure of oxy hemoglobin from high oxygen affinity bird emu (Dromaius novaehollandiae).

    PubMed

    Mohamed Abubakkar, Mohamed H; Saraboji, Kadhirvel; Ponnuswamy, Mon Nanjappa G

    2014-01-01

    Hemoglobin is an honorary enzyme, a two-way respiratory carrier, transporting oxygen from the lungs to the tissues and facilitating the return transport of carbon dioxide. Hemoglobin has high affinity for oxygen and low affinity for carbon dioxide and other substances in the arterial circulation, whereas in the venous circulation these relative affinities are upturned. The oxygen affinity of hemoglobin increases with the fall in temperature and decreases with the increase in pH and 2, 3-bisphosphoglycerate; point mutations also affect the tetrameric arrangement and alter the oxygen affinity. Though several studies have revealed the specific reasons for the adaptation of increased oxygen affinity of avian hemoglobins at high-altitudes, further structural insights on hemoglobins from high oxygen affinity species are required to understand the detailed oxygen adaptation at the molecular level. Herein, we describe the structural investigation of hemoglobin from emu (Dromaius novaehollandiae), a high oxygen affinity bird. Hemoglobin from emu was purified using anion-exchange chromatography, crystallized and determined the structure in the oxy form at a resolution of 2.3 Å; the R-factor of the model was 19.2%. The structure was compared with other oxy hemoglobins of high oxygen affinity avian species; significant changes are noted at intra-subunit contacts which provide the clues for increased oxygen affinity of emu hemoglobin. PMID:25146185

  1. Hemoglobin aggregates studied under static and dynamic conditions involving the formation of nanobacteria-like structures.

    PubMed

    Baum, Jeramy L R; Jones, Riland L; Manning, Thomas J; Nienow, James; Phillips, Dennis

    2012-06-01

    Laser light scattering and scanning electron microscopy (SEM) are used to study hemoglobin in the aqueous phase. The impact that salts [NaCl, Ca₃(PO₄)₂] and iron oxide nanoparticles have on the hemoglobin size are also studied. The first set of experiments examined hemoglobin aggregates in the aqueous phases in the presence of salts and nanoparticles. Aqueous phase samples were then dehydrated and examined using SEM. The resulting structures resemble those observed in nanobacteria studies conducted in other labs. This study demonstrates that aggregates of hemoglobin and various salts found in a physiological environment can produce structures that resemble nanobacteria. PMID:22750818

  2. Structural and redox behavior of OxyVita, a zero-linked polymeric hemoglobin: comparison with natural acellular polymeric hemoglobins.

    PubMed

    Harrington, John P; Orlik, Kseniya; Orlig, Kseniya; Zito, Samantha L; Wollocko, Jacek; Wollocko, Hanna

    2010-04-01

    A zero-linked polymeric hemoglobin (OxyVita Hb) has been developed for application as an acellular therapeutic hemoglobin-based-oxygen-carrier (HBOC). For effective and safe oxygen binding, transport and delivery, an HBOC must meet essential molecular requirements related to its structural integrity and redox stability. OxyVita is a super polymer possessing an average M.wt. of 17 x 10(6) Da. Structural integrity was determined by unfolding studies of OxyVita in the presence of increasing concentrations of urea. The unfolding midpoints (D(1/2)) of different preparations of OxyVita (solution and powder forms) were compared to Lumbricus Hb (LtHb) and Arenicola Hb (ArHb), natural acellular polymeric hemoglobins, which are serving as models for an effective and safe acellular HBOC. Reduction studies of OxyVita Hb using endogenous reducing agents were also investigated. Results from these studies indicate that: 1) OxyVita Hb exhibits greater resistance to conformational change than either LtHb or ArHb in the reduced (oxyHb) state; and 2) the reduction of met OxyVita Hb to oxyHb occurs slowly in the presence of either ascorbic acid (70% reduction in 560 min.) or beta-NADH (40% reduction in 90 min.). These studies provide consistent evidence that OxyVita Hb possesses physiochemical properties that exhibit structural integrity and redox behavior necessary for functioning as an effective and safe HBOC within clinical applications. These results are in agreement with observations made by other investigators as to the reduction in heme-loss of OxyVita Hb, essential for the reversible binding/release of molecular oxygen within the circulatory system. PMID:20196683

  3. Structural and redox behavior of OxyVita, a zero-linked polymeric hemoglobin: comparison with natural acellular polymeric hemoglobins.

    PubMed

    Harrington, John P; Orlik, Kseniya; Orlig, Kseniya; Zito, Samantha L; Wollocko, Jacek; Wollocko, Hanna

    2010-04-01

    A zero-linked polymeric hemoglobin (OxyVita Hb) has been developed for application as an acellular therapeutic hemoglobin-based-oxygen-carrier (HBOC). For effective and safe oxygen binding, transport and delivery, an HBOC must meet essential molecular requirements related to its structural integrity and redox stability. OxyVita is a super polymer possessing an average M.wt. of 17 x 10(6) Da. Structural integrity was determined by unfolding studies of OxyVita in the presence of increasing concentrations of urea. The unfolding midpoints (D(1/2)) of different preparations of OxyVita (solution and powder forms) were compared to Lumbricus Hb (LtHb) and Arenicola Hb (ArHb), natural acellular polymeric hemoglobins, which are serving as models for an effective and safe acellular HBOC. Reduction studies of OxyVita Hb using endogenous reducing agents were also investigated. Results from these studies indicate that: 1) OxyVita Hb exhibits greater resistance to conformational change than either LtHb or ArHb in the reduced (oxyHb) state; and 2) the reduction of met OxyVita Hb to oxyHb occurs slowly in the presence of either ascorbic acid (70% reduction in 560 min.) or beta-NADH (40% reduction in 90 min.). These studies provide consistent evidence that OxyVita Hb possesses physiochemical properties that exhibit structural integrity and redox behavior necessary for functioning as an effective and safe HBOC within clinical applications. These results are in agreement with observations made by other investigators as to the reduction in heme-loss of OxyVita Hb, essential for the reversible binding/release of molecular oxygen within the circulatory system.

  4. Tyrosine can protect against oxidative stress through ferryl hemoglobin reduction.

    PubMed

    Lu, Naihao; He, Yingjie; Chen, Chao; Tian, Rong; Xiao, Qiang; Peng, Yi-Yuan

    2014-08-01

    The toxic mechanism of hemoglobin (Hb) under oxidative stress is linked to the formations of highly cytotoxic ferryl species and subsequently heme-to-protein cross-linked derivative of Hb (Hb-X). In this study, we have examined the effects of free tyrosine and its analogues (3-chlorotyrosine, phenylalanine) on the stability of ferryl hemoglobin and the formation of Hb-X. The results showed that free tyrosine (not phenylalanine, 10-500 μM) was an efficient reducing agent of ferryl species and also effective at preventing the formation of cytotoxic Hb-X. Meanwhile, the dimeric tyrosine was formed as the oxidation product of tyrosine during Hb redox reaction. Compared with free tyrosine, 3-chlorotyrosine, an oxidation product of tyrosine and a proposed biomarker for hypochlorous acid (HOCl) in vivo, exhibited stronger antioxidant properties in Hb-induced oxidative stress, which was consistent with its more efficient ability in the reduction of ferryl species. These results showed that the presence of tyrosine and its derivative in vivo and vitro could ameliorate oxidative damage through ferryl heme reduction. The antioxidant ability, therefore, may provide new insights into the nutritional and physiological significance of free tyrosine with redox active heme proteins-related oxidative stress.

  5. Effectors of hemoglobin. Separation of allosteric and affinity factors.

    PubMed Central

    Marden, M C; Bohn, B; Kister, J; Poyart, C

    1990-01-01

    The relative contributions of the allosteric and affinity factors toward the change in p50 have been calculated for a series of effectors of hemoglobin (Hb). Shifts in the ligand affinity of deoxy Hb and the values for 50% ligand saturation (p50) were obtained from oxygen equilibrium data. Because the high-affinity parameters (liganded conformation) are poorly determined from the equilibrium curves, they were determined from kinetic measurements of the association and dissociation rates with CO as ligand. The CO on-rates were obtained by flash photolysis measurements. The off-rates were determined from the rate of oxidation of HbCO by ferricyanide, or by replacement of CO with NO. The partition function of fully liganded hemoglobin for oxygen and CO is only slightly changed by the effectors. Measurements were made in the presence of the effectors 2,3-diphosphoglycerate (DPG), inositol hexakisphosphate (IHP), bezafibrate (Bzf), and two recently synthesized derivatives of Bzf (LR16 and L35). Values of p50 change by over a factor of 60; the on-rates decrease by nearly a factor of 8, with little change in the off-rates for the liganded conformation. The data indicate that both allosteric and affinity parameters are changed by the effectors; the changes in ligand affinity represent the larger contribution toward shifts in p50. PMID:2306490

  6. Multiwavelength pulse oximetry in the measurement of hemoglobin fractions

    NASA Astrophysics Data System (ADS)

    Manzke, Bernd; Schwider, Johannes; Lutter, Norbert O.; Engelhardt, Kai; Stork, Wilhelm

    1996-04-01

    The two wavelength design of the majority of pulse oximeters assumes only two absorbing hemoglobin fractions, oxyhemoglobin (O2Hb), and reduced hemoglobin (HHb) irrespective of the presence of methemoglobin (MetHb) and carboxyhemoglobin (COHb). If MetHb or COHb is present, it contributes to the pulse-added absorbance signal and will be interpreted as either HHb or O2Hb or some combination of the two. In this paper we describe a noninvasive multi-wavelength pulse oximeter measuring O2Hb, HHb, MetHb, and COHb at a specified accuracy of 1.0%. The system was designed with respect to the results of numerical simulations. It consists of 9 laserdiodes (LDs) and 7 light emitting diodes (LEDs), a 16-bit analog-digital converter (ADC) and has a sampling rate of 16 kHz. The laser didoes and LEDs were coupled into multi-mode fibers and led with a liquid lightguide to the finger clip and then the photodiode. It also presents the results of a clinical study, including a setup with a quartz tungsten halogen lamp (with fiber output) and a diode array spectrometer, a standard pulse oximeter and two in-vitro oximeters (radiometer OSM3 and radiometer ABL 520) as references.

  7. Autofluorescence characterization of advanced glycation end products of hemoglobin

    NASA Astrophysics Data System (ADS)

    Vigneshwaran, Nadanathangam; Bijukumar, Gopalakrishnapillai; Karmakar, Nivedita; Anand, Sneh; Misra, Anoop

    2005-01-01

    This article describes the analysis of autofluorescence of advanced glycation end products of hemoglobin (Hb-AGE). Formed as a result of slow, spontaneous and non-enzymatic glycation reactions, Hb-AGE possesses a characteristic autofluorescence at 308/345 nm ( λex/ λem). Even in the presence of heme as a quenching molecule, the surface presence of the glycated adduct gave rise to autofluorescence with the quantum yield of 0.19. The specificity of monoclonal antibody developed against common AGE structure with Hb-AGE was demonstrated using reduction in fluorescence polarization value due to increased molecular volume while binding. The formation of fluorescent adduct in hemoglobin in the advanced stage of glycation and the non-fluorescent HbA 1c will be of major use in distinguishing and to know the past status of diabetes mellitus. While autofluorescence correlated highly with HbA 1c value under in vivo condition ( r=0.85), it was moderate in the clinical samples ( r=0.55). The results suggest a non-linear relation between glycemia and glycation, indicating the application of Hb-AGE as a measure of susceptibility to glycation rather than glycation itself.

  8. Carnivora: primary structure of the hemoglobins from ratel (Mellivora capensis).

    PubMed

    Rodewald, K; Braunitzer, G; Göltenboth, R

    1988-10-01

    The erythrocytes of adult ratel contain two hemoglobin components, with two alpha- and one beta-chains. In this paper, their complete amino acid sequences are presented. The two alpha-chains differ in one residue at position 34 (Ala----Val) only. The primary structure of the chains was determined by sequencing the N-terminal regions (45 steps) and the tryptic peptides after their isolation from the digests by reversed-phase high-performance liquid chromatography. The alignment of these peptides was deduced from homology with other carnivora globins. The alpha-chains show 21 and the beta-chains 11 exchanges compared with human globin chains. In the alpha-chains, one heme- and two alpha 1/beta 1 contacts are exchanged. In the beta-chains there are three exchanges which involve one alpha 1/beta 1-, one alpha 1/beta 2- and one heme-contact. Between the ratel hemoglobin and those of carnivora a high degree of homology was found. PMID:3242544

  9. Screening for Structural Hemoglobin Variants in Bahia, Brazil

    PubMed Central

    Silva, Wellington Santos; de Oliveira, Roberto Ferreira; Ribeiro, Sanzia Bezerra; da Silva, Isabel Batista; de Araújo, Edna Maria; Baptista, Abrahão Fontes

    2016-01-01

    Brazil was the country that received the largest number of Africans during the time of colonization, and Bahia was the Brazilian state that received the largest number of slaves from Africa. The purpose of this study was to evaluate the coverage of the newborn screening program for sickle cell disease in the Recôncavo Baiano region of the state of Bahia, and to show the frequency of the subjects with hemoglobin variants in the 2006–2009 period. Blood samples from neonates in twelve cities in the Recôncavo Baiano region were analyzed by High Performance Liquid Chromatography. A total of 16,402 children were born in this period, 14,773 of which underwent newborn screening. In this period 1416 children were born carrying hemoglobin variants HbS and HbC. Forty-seven patients—20 HbSS genotype and 27 HbSC genotype—were diagnosed in eleven of the twelve cities surveyed. The proportion of children born with sickle cell disease in the Recôncavo Baiano region was 1/314, which was higher than the 1/650 rate for the state of Bahia. The data presented in this study confirm the high frequency of sickle cell disease in Recôncavo Baiano, demonstrating the need to create a referral center for the care of patients with sickle cell diseases in the region. PMID:26901212

  10. Vitreoscilla hemoglobin gene ( vgb) improves lutein production in Chlorella vulgaris

    NASA Astrophysics Data System (ADS)

    Ma, Ruijuan; Lin, Xiangzhi

    2014-03-01

    Vitreoscilla hemoglobin is an oxygen-binding protein that promotes oxygen delivery and reduces oxygen consumption under low oxygen conditions to increase the efficiency of cell respiration and metabolism. In this study, we introduced a Vitreoscilla hemoglobin gene ( vgb) into Chlorella vulgaris by Agrobacterium tumefaciens -mediated transformation (ATMT). PCR analysis confirmed that the vgb gene was successfully integrated into the Chlorella vulgaris genome. Analysis of biomass obtained in shake flasks revealed transformant biomass concentrations as high as 3.28 g/L, which was 38.81% higher than that of the wild-type strain. Lutein content of transformants also increased slightly. Further experiments recovered a maximum lutein yield of 2.91 mg/L from the transformants, which was 36.77% higher than that of the wild-type strain. The above results suggest that integrated expression of the vgb gene may improve cell growth and lutein yield in Chlorella vulgaris, with applications to lutein production from Chlorella during fermentation.

  11. Biphasic Oxidation of Oxy-Hemoglobin in Bloodstains

    PubMed Central

    Bremmer, Rolf H.; de Bruin, Daniel M.; de Joode, Maarten; Buma, Wybren Jan; van Leeuwen, Ton G.; Aalders, Maurice C. G.

    2011-01-01

    Background In forensic science, age determination of bloodstains can be crucial in reconstructing crimes. Upon exiting the body, bloodstains transit from bright red to dark brown, which is attributed to oxidation of oxy-hemoglobin (HbO2) to met-hemoglobin (met-Hb) and hemichrome (HC). The fractions of HbO2, met-Hb and HC in a bloodstain can be used for age determination of bloodstains. In this study, we further analyze the conversion of HbO2 to met-Hb and HC, and determine the effect of temperature and humidity on the conversion rates. Methodology The fractions of HbO2, met-Hb and HC in a bloodstain, as determined by quantitative analysis of optical reflectance spectra (450–800 nm), were measured as function of age, temperature and humidity. Additionally, Optical Coherence Tomography around 1300 nm was used to confirm quantitative spectral analysis approach. Conclusions The oxidation rate of HbO2 in bloodstains is biphasic. At first, the oxidation of HbO2 is rapid, but slows down after a few hours. These oxidation rates are strongly temperature dependent. However, the oxidation of HbO2 seems to be independent of humidity, whereas the transition of met-Hb into HC strongly depends on humidity. Knowledge of these decay rates is indispensable for translating laboratory results into forensic practice, and to enable bloodstain age determination on the crime scene. PMID:21789186

  12. Stability of blood carbon monoxide and hemoglobins during heating.

    PubMed

    Seto, Y; Kataoka, M; Tsuge, K

    2001-09-15

    The effects of heating on hemoglobin (Hb) and carbon monoxide (CO) levels in human blood were investigated by in vitro experiments. Head-space gas chromatography (HS-GC) using a molecular sieve 5A stationary phase and thermal conductivity detection was adopted for the measurement of CO gas, and spectrophotometric methods were used for the measurement of various Hb forms, protein and heme contents. Deteriorated absorbance spectra were observed for heat-treated blood samples, and double wavelength spectrophotometry was proven to give wrong percent saturation of carboxyhemoglobin content (% CO-Hb). The blood sample taken from one fatal fire casualty gave significantly higher % CO-Hb measured spectrophotometrically, compared to that by HS-GC. Control blood or purified Hb solution, which was saturated with CO in designated extent, was heated in a sealed vial. Under the incubation below 54 degrees C, all Hb forms were stable, except for oxyhemoglobin (Hb-O(2)), which was partially oxidized to met-hemoglobin (Met-Hb). In contrast, under the incubation at 65 degrees C, Met-Hb was denatured completely to be insoluble, and Hb-O(2) was partially denatured via Met-Hb formation. CO-Hb was resistant against heating. The difference of heat susceptibility and precipitability among Hb forms resulted in artificial increase of % CO-Hb. During heating, spontaneous CO was produced from blood.

  13. [Hemoglobin and testosterone: importance on high altitude acclimatization and adaptation].

    PubMed

    Gonzales, Gustavo F

    2011-03-01

    The different types of response mechanisms that the organism uses when exposed to hypoxia include accommodation, acclimatization and adaptation. Accommodation is the initial response to acute exposure to high altitude hypoxia and is characterized by an increase in ventilation and heart rate. Acclimatization is observed in individuals temporarily exposed to high altitude, and to some extent, it enables them to tolerate the high altitudes. In this phase, erythropoiesis is increased, resulting in higher hemoglobin and hematocrit levels to improve oxygen delivery capacity. Adaptation is the process of natural acclimatization where genetical variations and acclimatization play a role in allowing subjects to live without any difficulties at high altitudes. Testosterone is a hormone that regulates erythropoiesis and ventilation and could be associated to the processes of acclimatization and adaptation to high altitude. Excessive erythrocytosis, which leads to chronic mountain sickness, is caused by low arterial oxygen saturation, ventilatory inefficiency and reduced ventilatory response to hypoxia. Testosterone increases during acute exposure to high altitude and also in natives at high altitude with excessive erythrocytosis. Results of current research allow us to conclude that increase in serum testosterone and hemoglobin is adequate for acclimatization, as they improve oxygen transport, but not for high altitude adaptation, since high serum testosterone levels are associated to excessive erythrocytosis.

  14. Redox reactions of hemoglobin: mechanisms of toxicity and control.

    PubMed

    Mollan, Todd L; Alayash, Abdu I

    2013-06-10

    In the last several years, significant work has been done studying hemoglobin (Hb) oxidative reactions and clearance mechanisms using both in vitro and in vivo model systems. One active research area involves the study of molecular chaperones and other proteins that are thought to mitigate the toxicity of acellular Hb. For example, the plasma protein haptoglobin (Hp) and the pre-erythroid protein alpha-hemoglobin-stabilizing protein (AHSP) bind to acellular Hb and alpha-subunits of Hb, respectively, to reduce these adverse effects. Moreover, there has been significant work studying hemopexin and alpha-1 microglobulin, both of which are thought to be involved with hemin degradation. These studies have coincided with the timely publication of the first crystal structure of the Hb-Hp complex. In constructing this Forum, we have invited a number of researchers in the area of Hb and myoglobin (Mb) redox biochemistry, as well as those who have contributed fundamentally to our knowledge of Hp function. Our goal has been to update this critically important research area, because we believe that it will ultimately impact the practice of transfusion medicine in a number of important ways.

  15. Interaction of recombinant octameric hemoglobin with endothelial cells.

    PubMed

    Gaucher, Caroline; Domingues-Hamdi, Élisa; Prin-Mathieu, Christine; Menu, Patrick; Baudin-Creuza, Véronique

    2015-02-01

    Hemoglobin-based oxygen carriers (HBOCs) may generate oxidative stress, vasoconstriction and inflammation. To reduce these undesirable vasoactive properties, we increased hemoglobin (Hb) molecular size by genetic engineering with octameric Hb, recombinant (r) HbβG83C. We investigate the potential side effects of rHbβG83C on endothelial cells. The rHbβG83C has no impact on cell viability, and induces a huge repression of endothelial nitric oxide synthase gene transcription, a marker of vasomotion. No induction of Intermolecular-Adhesion Molecule 1 and E-selectin (inflammatory markers) transcription was seen. In the presence of rHbβG83C, the transcription of heme oxygenase-1 (oxidative stress marker) is weakly increased compared to the two other HBOCs (references) or Voluven (control). This genetically engineered octameric Hb, based on a human Hb βG83C mutant, leads to little impact at the level of endothelial cell inflammatory response and thus appears as an interesting molecule for HBOC development.

  16. Electrophoretic analysis of PEGylated hemoglobin-based blood substitutes.

    PubMed

    Ronda, Luca; Pioselli, Barbara; Bruno, Stefano; Faggiano, Serena; Mozzarelli, Andrea

    2011-01-01

    Polyethylene glycol (PEG)-conjugated hemoglobins, a novel class of blood substitutes, were investigated by a combination of native and denaturing one- and two-dimensional polyacrylamide gel electrophoresis (PAGE) coupled with the microspectrophotometric characterization of single bands and the functional analysis of electrophoretically separated fractions. For these intrinsically heterogeneous products, the molecular mass, the size distribution, and the degree of PEGylation are strictly correlated to their side effects and, therefore, are crucial pieces of information to evaluate their safety and efficacy. The PEGylation pattern was shown to strongly depend on the quaternary conformation of hemoglobin during the reaction, and the degree of conjugation was shown to correlate with the oxygen binding properties of the individual electrophoretically separated fractions. Moreover, small but not negligible fractions of underivatized tetramers, known to be responsible for serious side effects, were detected even in preparations with a high average degree of PEGylation. Overall, this approach might be exploited to characterize other products of protein PEGylation, an increasingly relevant technology for the optimization of the pharmacokinetic properties of protein-based drugs.

  17. Light Scattering and Absorption Studies of Sickle Cell Hemoglobin

    NASA Astrophysics Data System (ADS)

    Kim-Shapiro, Daniel

    1997-11-01

    The use of physical techniques has been very important in understanding the pathophysiology of sickle cell disease. In particular, light scattering and absorption studies have been used to measure the kinetics of sickle cell hemoglobin polymerization and depolymerization (melting). The theory of sickle cell polymerization that has been derived and tested by these methods has not only led to an increased understanding of the pathophysiology of the disease but has also led to improved treatment strategies. Sickle cell disease effects about 1 out of 600 people of African descent born in the United States. The disease is caused by a mutant form of hemoglobin (the oxygen transporting molecule in the blood), hemoglobin S (HbS), which differs from normal adult hemoglobin by the substitution of a single amino acid for another. The polymerization of HbS, which occurs under conditions of low oxygen pressure, causes distortion and increased rigidity of the sickle red blood cell that leads to blockage of the capillaries and a host of resulting complications. The disease is associated with tissue damage, severe painful crises and a high degree of mortality. Light scattering studies of purified HbS and whole cells (conducted by F.A. Ferrone, J. Hofrichter, W.A. Eaton, and their associates) have been used to determine the mechanism of HbS polymerization. Polymerization will generally not occur when the hemoglobin is in an oxygen-rich environment. The question is, when HbS is rapidly deoxygenated (as it is when going from the lungs to the tissues) what is the kinetics of polymerization? Photolysis methods were used to rapidly deoxygenate HbS and light scattering was used as a function of time to measure the kinetics of polymerization. Polarized light scattering may be a more effective way to measure polymer content than total intensity light scattering. It was found that no polymerization occurs during a period of time called the delay time and subsequent polymerization occurs

  18. Making chromosome abnormalities treatable conditions.

    PubMed

    Cody, Jannine DeMars; Hale, Daniel Esten

    2015-09-01

    Individuals affected by the classic chromosome deletion syndromes which were first identified at the beginning of the genetic age, are now positioned to benefit from genomic advances. This issue highlights five of these conditions (4p-, 5p-, 11q-, 18p-, and 18q-). It focuses on the increased in understanding of the molecular underpinnings and envisions how these can be transformed into effective treatments. While it is scientifically exciting to see the phenotypic manifestations of hemizygosity being increasingly understood at the molecular and cellular level, it is even more amazing to consider that we are now on the road to making chromosome abnormalities treatable conditions.

  19. [Erythrocyte membrane abnormalities - hereditary elliptocytosis].

    PubMed

    Kvezereli-Kopadze, M; Kvezereli-Kopadze, A; Mtvarelidze, Z; Bubuteishvili, A

    2015-04-01

    This study was designed to investigate the 4 year old boy with Hereditary Elliptocitosis (HE). The diagnosis of this rare hemolytic anemia was based on detailed family history (positive in the 4-th generation), physical examination and Para-clinical data analyses. The vast majority of patients with HE are asymptomatic, severe forms are rare. The most important is examination of blood films, which is helpful to detect the morphology abnormalities of red cells. In case of HE a different approach is required. Positive family history and series of investigations should be conducted to determine the HE.

  20. Abnormalities of the erythrocyte membrane.

    PubMed

    Gallagher, Patrick G

    2013-12-01

    Primary abnormalities of the erythrocyte membrane are characterized by clinical, laboratory, and genetic heterogeneity. Among this group, hereditary spherocytosis patients are more likely to experience symptomatic anemia. Treatment of hereditary spherocytosis with splenectomy is curative in most patients. Growing recognition of the long-term risks of splenectomy has led to re-evaluation of the role of splenectomy. Management guidelines acknowledge these considerations and recommend discussion between health care providers, patient, and family. The hereditary elliptocytosis syndromes are the most common primary disorders of erythrocyte membrane proteins. However, most elliptocytosis patients are asymptomatic and do not require therapy.

  1. Foot abnormalities of wild birds

    USGS Publications Warehouse

    Herman, C.M.; Locke, L.N.; Clark, G.M.

    1962-01-01

    The various foot abnormalities that occur in birds, including pox, scaly-leg, bumble-foot, ergotism and freezing are reviewed. In addition, our findings at the Patuxent Wildlife Research Center include pox from dove, mockingbird, cowbird, grackle and several species of sparrows. Scaly-leg has been particularly prevalent on icterids. Bumble foot has been observed in a whistling swan and in a group of captive woodcock. Ergotism is reported from a series of captive Canada geese from North Dakota. Several drug treatments recommended by others are presented.

  2. Cardiac abnormalities in children with sickle cell anemia.

    PubMed

    Batra, Anjan S; Acherman, Ruben J; Wong, Wing-yen; Wood, John C; Chan, Linda S; Ramicone, Emily; Ebrahimi, Mahmood; Wong, Pierre C

    2002-08-01

    Sickle cell anemia (SCA) results in chronic volume overload of the heart due to hemodilution. Previous echocardiographic studies of cardiac function in children with SCA have not accounted for these abnormal loading conditions. The objectives of this study were to (1) determine how the degree of anemia and transfusion status relate to cardiac findings and (2) evaluate cardiac function using load-independent parameters of function. We evaluated 77 patients with SCA, ages 2 to 22 years (mean +/- SD = 11.7 +/- 4.7), using physical examination, electrocardiography, and echocardiography. We compared two groups of patients. Group 1 consisted of 57 non-transfused patients, and Group 2 consisted of 20 patients on a chronic transfusion protocol. Group 1 patients exhibited a significantly lower hemoglobin, higher cardiac output, and larger left ventricular (LV) end-diastolic dimension and LV mass than groups 2 (P < 0.05). However, the velocity of circumferential fiber shortening-wall stress index (a load-independent measure of systolic function) was normal and not statistically different between the two groups. Conversely, the LV myocardial performance index (a measure of combined systolic and diastolic function) was significantly higher in Group 2 (P < 0.001), possibly indicating impaired myocardial diastolic function. SCA in children results in a volume-overloaded heart with a significant increase in LV dimensions and mass, both proportional to the degree of anemia. Despite these abnormal loading conditions, systolic function is preserved. Patients on a chronic transfusion protocol may develop diastolic dysfunction despite iron chelation therapy. PMID:12210812

  3. A cis-proline in alpha-hemoglobin stabilizing protein directs the structural reorganization of alpha-hemoglobin.

    PubMed

    Gell, David A; Feng, Liang; Zhou, Suiping; Jeffrey, Philip D; Bendak, Katerina; Gow, Andrew; Weiss, Mitchell J; Shi, Yigong; Mackay, Joel P

    2009-10-23

    alpha-Hemoglobin (alphaHb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with alphaHb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting alphaHb to a conformation in which the heme is coordinated at both axial positions by histidine side chains (bis-histidyl coordination). Currently, the detailed mechanism by which AHSP induces structural changes in alphaHb has not been determined. Here, we present x-ray crystallography, NMR spectroscopy, and mutagenesis data that identify, for the first time, the importance of an evolutionarily conserved proline, Pro(30), in loop 1 of AHSP. Mutation of Pro(30) to a variety of residue types results in reduced ability to convert alphaHb. In complex with alphaHb, AHSP Pro(30) adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in alphaHb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the alphaHb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of alphaHb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops.

  4. A cis-Proline in α-Hemoglobin Stabilizing Protein Directs the Structural Reorganization of α-Hemoglobin*

    PubMed Central

    Gell, David A.; Feng, Liang; Zhou, Suiping; Jeffrey, Philip D.; Bendak, Katerina; Gow, Andrew; Weiss, Mitchell J.; Shi, Yigong; Mackay, Joel P.

    2009-01-01

    α-Hemoglobin (αHb) stabilizing protein (AHSP) is expressed in erythropoietic tissues as an accessory factor in hemoglobin synthesis. AHSP forms a specific complex with αHb and suppresses the heme-catalyzed evolution of reactive oxygen species by converting αHb to a conformation in which the heme is coordinated at both axial positions by histidine side chains (bis-histidyl coordination). Currently, the detailed mechanism by which AHSP induces structural changes in αHb has not been determined. Here, we present x-ray crystallography, NMR spectroscopy, and mutagenesis data that identify, for the first time, the importance of an evolutionarily conserved proline, Pro30, in loop 1 of AHSP. Mutation of Pro30 to a variety of residue types results in reduced ability to convert αHb. In complex with αHb, AHSP Pro30 adopts a cis-peptidyl conformation and makes contact with the N terminus of helix G in αHb. Mutations that stabilize the cis-peptidyl conformation of free AHSP, also enhance the αHb conversion activity. These findings suggest that AHSP loop 1 can transmit structural changes to the heme pocket of αHb, and, more generally, highlight the importance of cis-peptidyl prolyl residues in defining the conformation of regulatory protein loops. PMID:19706593

  5. Medical management of abnormal pregnancy.

    PubMed

    Ratnam, S S; Prasad, R N

    1990-06-01

    Medical termination of abnormal pregnancy requires specific techniques since some conditions make therapy more effective, e.g., missed abortion intrauterine death and molar pregnancy, and others less so, e.g. anencephalic pregnancy. In all cases it is best to terminate the pregnancy as soon as possible to reduce anguish and risks of complications such as consumptive coagulopathy. Oxytocin is not consistently effective, but intraamniotic rivanol has oxytocic properties, and prostaglandins (PGs) are effective by several routes. Surgical methods are more popular in Japan and the US. A diagnostic flow chart is included and described. For missed abortion and fetal death vacuum aspiration or dilatation and evacuation are appropriate for early pregnancy, or PGs are used for later pregnancy, unless there are medical contraindications. Anencephalic pregnancy, usually diagnoses in 2nd or 3rd trimester, is resistant to medical therapy and must often be terminated by cesarean section. Molar pregnancy can be managed with vacuum aspiration at any length of gestation, but must be completed by curettage. Intraamniotic PGs are not advised for mole or fetal death. PG analogs can be administered intramuscularly, or vaginally in gel form. Other types of abnormal pregnancy that can be managed with PGs are spina bifida, hydrocephalus, hydrops fetalis, Dandy-Walker syndrome and Down's syndrome. Tubal pregnancy can be evacuated with intratubally administered PGs under laparoscopic control, thereby preserving tubal integrity. PMID:2225605

  6. Hemoglobin Aggregation in Single Red Blood Cells of Sickle Cell Anemia

    NASA Astrophysics Data System (ADS)

    Nishio, Izumi; Tanaka, Toyoichi; Sun, Shao-Tang; Imanishi, Yuri; Tsuyoshi Ohnishi, S.

    1983-06-01

    A laser light scattering technique was used to observe the extent of hemoglobin aggregation in solitary red blood cells of sickle cell anemia. Hemoglobin aggregation was confirmed in deoxygenated cells. The light scattering technique can also be applied to cytoplasmic studies of any biological cell.

  7. Effect of deep breathing on extracted oxygen and cerebral hemoglobin levels.

    PubMed

    Kennedy, Patrick M; Zarbock, Christopher M; Burke, Broc A; Diamond, Solomon G

    2011-01-01

    This study examines the relationship between oxygen expired and functional near infrared spectroscopy (fNIRS) measured hemoglobin levels in the brain. Analysis of these two signals during normal versus deep breathing provides insight into the dynamics of cerebral physiology. Intersubject variation suggests the existence of two distinct groups with respect to oxygen extraction and hemoglobin levels. PMID:22254486

  8. Molecular Cloning and Sequencing of Hemoglobin-Beta Gene of Channel Catfish, Ictalurus Punctatus Rafinesque

    Technology Transfer Automated Retrieval System (TEKTRAN)

    : Hemoglobin-y gene of channel catfish , lctalurus punctatus, was cloned and sequenced . Total RNA from head kidneys was isolated, reverse transcribed and amplified . The sequence of the channel catfish hemoglobin-y gene consists of 600 nucleotides . Analysis of the nucleotide sequence reveals one o...

  9. Using the Cascade Model to Improve Antenatal Screening for the Hemoglobin Disorders

    ERIC Educational Resources Information Center

    Gould, Dinah; Papadopoulos, Irena; Kelly, Daniel

    2012-01-01

    Introduction: The inherited hemoglobin disorders constitute a major public health problem. Facilitators (experienced hemoglobin counselors) were trained to deliver knowledge and skills to "frontline" practitioners to enable them to support parents during antenatal screening via a cascade (train-the-trainer) model. Objectives of evaluation were to…

  10. Hemoglobin oxidation products extract phospholipids from the membrane of human erythrocytes.

    PubMed

    Moxness, M S; Brunauer, L S; Huestis, W H

    1996-06-01

    Hydrogen peroxide oxidation of human erythrocytes induces a transfer of phospholipid from the membrane into the cytosol [Brunauer, L.S., Moxness, M.S., & Huestis, W.H. (1994) Biochemistry 33, 4527-4532]. The current study examines the mechanism of lipid reorganization in oxidized cells. Exogenous phosphatidylserine was introduced into the inner monolayer of erythrocytes, and its distribution was monitored by microscopy and radioisotopic labeling. Pretreatment of cells with carbon monoxide prevented both hemoglobin oxidation and the transfer of phosphatidyserine into the cytosolic compartment. The roles of the various hemoglobin oxidation products in lipid extraction were investigated using selective oxidants. Nitrite treatment of intact cells produced almost complete conversion to methemoglobin, but no detectable lipid extraction. Treatments designed to produce the green hemoglobin derivatives, sulfhemoglobin and choleglobin, resulted in cytosolic extraction of phosphatidylserine. Ion exchange and size exclusion chromatography of oxidized cytosolic components revealed a lipid-hemoglobin complex. The interaction between lipid and hemoglobin oxidation products was verified in a model system. Purified hemoglobin, enriched in sulfhemoglobin and choleglobin by treatment with H2O2, H2S, or ascorbate, extracted phospholipid from small unilamellar phospholipid vesicles. Electron paramagnetic resonance studies demonstrated that hemoglobin oxidation products also adsorb fatty acids from solution. This newly described activity of hemoglobin may play a role in the clearance of oxidatively damaged and senescent cells from circulation.

  11. Band assignment in hemoglobin porphyrin ring spectrum: using four-orbital model of Gouterman.

    PubMed

    Dayer, Mohammad Reza; Moosavi-Movahedi, Ali Akbar; Dayer, Mohammad Saaid

    2010-04-01

    Band assignment for oxy, deoxy and methemoglobin using orbital promotion is crucial to understanding inter-relation of electronic transitions. Spectral changes may be correlated with conformational alteratiions. Conformational changes of hemoglobin were interpreted using four-orbital model of Gouterman. Our results indicated that Goutherman model can predict the predominant conformations of hemoglobin.

  12. Iron bioavailability of maize hemoglobin in a Caco-2 cell culture model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maize is an important staple crop in many parts of the world but has low iron bioavailability, in part due to its high phytate content. Hemoglobin is a form of iron that is highly bioavailable and its bioavailability is not inhibited by phytate. We hypothesize that maize hemoglobin is a highly bioav...

  13. Prevalence of common hemoglobin variants in an afro-descendent Ecuadorian population

    PubMed Central

    2013-01-01

    Background Hemoglobinopathies are among the most studied and frequent pathologies. These genetic disorders are considered a very important health care threat in many tropical countries. Ecuador is a tropical Latin-American country with an important presence of afro-descendants (7.2%). Afro-descendants are among the ethnic groups with higher frequency of hemoglobinopathies reported. Ambuqui is a region within the Imbabura province with an important presence of afro-descendants (>50%). The present study analyzed the frequency of the most common hemoglobin variants in an asymptomatic afro-descendent population using capillary electrophoresis. Findings From 114 individuals, 25 (22%) reported a hemoglobin variant. All individuals that presented hemoglobin variants were heterozygotes (asymptomatic). Hemoglobin S (sickle cell trait) was the most frequent variant found (14%), followed by hemoglobin E (4.4%), Fetal (2.6%) and C (1%). Conclusion Prevalence of hemoglobin S was consistent with populations from other countries, but it was lower than other Ecuadorian afro-descendent populations. Frequency of hemoglobin C was lower than other afro-descendent populations. This data suggests the possibility of gene flow from Native American individuals to the Ambuqui population there by lowering the frequency of their hemoglobin variants compared with other afro-descendant populations. Evaluating the frequency of hemoglobinopathies in Ecuadorian populations is essential. Despite the high frequency of these disorders, very few health care facilities implement hemoglobinopathies tests as a routine practice. PMID:23557107

  14. A Simple Question to Think about When Considering the Hemoglobin Function

    ERIC Educational Resources Information Center

    Ruiz-Larrea, M. Begona

    2002-01-01

    Hemoglobin is a complex protein formed by various subunits interacting with each other. These noncovalent interactions, quaternary structure, are responsible for hemoglobin functioning as an excellent oxygen transporter, loading up with oxygen in the lungs and delivering it to tissues, where the oxygen pressure is lower. The communications between…

  15. Transition of hemoglobin between two tertiary conformations: The transition constant differs significantly for the major and minor hemoglobins of the Japanese quail (Cortunix cortunix japonica).

    PubMed

    Okonjo, Kehinde Onwochei; Bello, Olugbenga S; Babalola, J Oyebamiji

    2008-03-01

    We demonstrate that 5,5'-dithiobis(2-nitrobenzoate) - DTNB - reacts with only CysF9[93]beta and CysB5[23]beta among the multiple sulfhydryl groups of the major and minor hemoglobins of the Japanese quail (Cortunix cortunix japonica). K(equ), the equilibrium constant for the reaction, does not differ very significantly between the two hemoglobins. It decreases 430-fold between pH approximately 5.6 and pH approximately 9: from a mean of 7+/-1 to a mean of 0.016+/-0.003. Quantitative analyses of the K(equ) data based on published X-ray and temperature-jump evidence for a tertiary structure transition in liganded hemoglobin enable the calculation of K(rt), the equilibrium constant for the r<---->t tertiary structure transition. K(rt) differs significantly between the two hemoglobins: 0.744+/-0.04 for the major, 0.401+/-0.01 for the minor hemoglobin. The mean pK(a)s of the two groups whose ionizations are coupled to the DTNB reaction are about the same as previously reported for mammalian hemoglobins.

  16. Probing confined and unconfined hemoglobin molecules with photoacoustics

    NASA Astrophysics Data System (ADS)

    Saha, Ratan K.; Karmakar, Subhajit; Roy, Madhusudan

    2014-03-01

    Photoacoustic (PA) measurements on confined and unconfined hemoglobin molecules are presented. In vitro experiments were performed with porcine red blood cells (RBCs) at 532 and 1064 nm at various laser fluences. Fluence was gradually changed from 8 to 21 mJ/cm2/pulse for 532 nm and 353 to 643 mJ/cm2/pulse for 1064 nm. PA signals from suspended RBCs (SRBCs) and hemolyzed RBCs (HRBCs) were measured using a needle hydrophone at hematocrits ranging from 10 to 60%. PA amplitude was found to be varied linearly with the laser fluence for each type of samples at the above two optical radiations. At 532 nm, PA signals from SRBCs and HRBCs were measured to be nearly equal, whereas, at 1064 nm, signal amplitude for SRBCs was approximately 2 times higher than that of HRBCs. The results suggest that it may be feasible to detect hemolysis with PAs.

  17. Effects of Hemoglobin-Based Oxygen Carriers on Blood Coagulation

    PubMed Central

    Roghani, Kimia; Holtby, Randall J.; Jahr, Jonathan S.

    2014-01-01

    For many decades, Hemoglobin-based oxygen carriers (HBOCs) have been central in the development of resuscitation agents that might provide oxygen delivery in addition to simple volume expansion. Since 80% of the world population lives in areas where fresh blood products are not available, the application of these new solutions may prove to be highly beneficial (Kim and Greenburg 2006). Many improvements have been made to earlier generation HBOCs, but various concerns still remain, including coagulopathy, nitric oxide scavenging, platelet interference and decreased calcium concentration secondary to volume expansion (Jahr et al. 2013). This review will summarize the current challenges faced in developing HBOCs that may be used clinically, in order to guide future research efforts in the field. PMID:25514567

  18. Noninvasive hemoglobin oxygenation monitor and computed tomography by NIR spectrophotometry

    NASA Astrophysics Data System (ADS)

    Oda, Ichiro; Ito, Yasunobu; Eda, Hideo; Tamura, Tomomi; Takada, Michinosuke; Abumi, Rentaro; Nagai, Katumi; Nakagawa, Hachiro; Tamura, Masahide

    1991-05-01

    Using a near infrared (NIR) spectrophotometry, a compact instrument for monitoring the hemoglobin (Hb) oxygenation state in human brain was developed. Brian oxygen metabolism was non-invasively studied by simultaneous measurement of oxygenated Hb, deoxygnated Hb and total Hb content in rat and human head. After evaluating our method using anesthetized and artificially ventilated rats, this instrument was applied for clinical use, and was useful for the management of clinical patients. The same method was applied to develope the NIR computed tomography (CT). Human X-ray CT was modified for NIR-CT, and CT images were obtained using the back-projection (BP) method. NIR-CT could measure the oxygenation map of the tissues of anesthetized rats.

  19. Brownian dynamics simulation of sickle hemoglobin bundle formation

    NASA Astrophysics Data System (ADS)

    Liu, Ya; Gunton, James; Chakrabarti, Amit

    2010-03-01

    The physical properties of biopolymer fibers, such as their stability and degree of aggregation, are implicated in many diseases, including sickle cell anemia. The natural chirality of protofilaments plays a crucial role in the formation of sickle hemoglobin fiber which leads to the permanent blockage of microvessels. We use Brownian dynamics to investigate the kinetics of fiber aggregation. The geometrical helical structure and chirality of the filaments are modeled by anisotropic patch-like interactions. We present the kinetics of fiber formation and study the possibility of a finite critical fiber bundle size. We compare our results with various experimental and theoretical results. This work is supported by grants from the NSF and the G. Harold and Leila Y. Mathers Foundation.

  20. SANS studies of interacting hemoglobin in intact erythrocytes

    SciTech Connect

    Krueger, S.; Nossal, R.

    1988-01-01

    Small angle neutron scattering (SANS) was used to investigate interaction forces between hemoglobin (Hb) molecules contained within human red cells. The scattering separately attributable to cell membranes and intracellular Hb was identified. A series of D/sub 2/O-H/sub 2/O contrast variation measurements were made in order to establish conditions for which scattering from the cell membrane is minimized (approximately 15% D/sub 2/O). Measurements then were performed to examine changes in intermolecular Hb interactions occurring when the cells are contracted or swollen by varying the ionic strength of the suspension buffer. The scattering cross-sections were fitted to structure factors computed by a mean spherical approximation, and molecular parameters thereby extracted. Oxygenation studies on normal cells were performed, and results contrasted with those of similar studies of erythrocytes obtained from sickle cell disease patients.

  1. A Journey in Science: Early Lessons from the Hemoglobin Field

    PubMed Central

    Weatherall, David J

    2014-01-01

    Real innovations in medicine and science are historic and singular; the stories behind each occurrence are precious. At Molecular Medicine we have established the Anthony Cerami Award in Translational Medicine to document and preserve these histories. The monographs recount the seminal events as told in the voice of the original investigators who provided the crucial early insight. These essays capture the essence of discovery, chronicling the birth of ideas that created new fields of research; and launched trajectories that persisted and ultimately influenced how disease is prevented, diagnosed, and treated. In this volume, the Cerami Award Monograph is by David J Weatherall, Founder, Weatherall Institute of Molecular Medicine, Oxford University, John Radcliffe Hospital. A visionary in the field of hemoglobin, this is the story of Professor Weatherall’s scientific journey. PMID:25548947

  2. Mitochondrial Respiration and Hemoglobin Gene Expression in Barley Aleurone Tissue.

    PubMed Central

    Nie, X.; Hill, R. D.

    1997-01-01

    Previous studies have shown that plant hemoglobin (Hb) mRNA is expressed in barley (Hordeum vulgare L.) aleurone layers during hypoxia. We have examined the effect of a number of respiratory inhibitors on barley aleurone layers to determine the factors that influence Hb gene expression. Respiratory inhibitors that reduce O2 consumption, such as CO, cyanide, and antimycin A, strongly enhanced Hb mRNA levels. Treatment with the oxidative phosphorylation uncoupler 2,4-dinitrophenol markedly increased O2 consumption and had a similar positive effect on Hb gene expression. Hb transcript levels were also stimulated by the ATP synthase inhibitor oligomycin. The results suggest that the expression of Hb is not directly influenced by O2 usage or availability but is influenced by the availability of ATP in the tissue. PMID:12223746

  3. A new polyethyleneglycol-derivatized hemoglobin derivative with decreased oxygen affinity and limited toxicity.

    PubMed

    Zolog, Oana; Mot, Augustin; Deac, Florina; Roman, Alina; Fischer-Fodor, Eva; Silaghi-Dumitrescu, Radu

    2011-01-01

    A new protocol is described for derivatization of hemoglobin with polyethyleneglycol (PEG) via reaction of the unmodified native hemoglobin with an activated amine-reacting polyethylene glycol derivative which, unlike protocols previously described, leads to formation of a peptide bond between hemoglobin and PEG. Dioxygen binding and peroxide reactivities of the derivatized hemoglobin are examined, and found to be within reasonable limits, with the particular observation that, unlike with a few other derivatization protocols, the dioxygen affinity is slightly lower than that of native Hb. In cell culture tests (human umbilical vein epithelial cells, HUVEC), the derivatization protocol induces no toxic effect. These results show promise towards applicability for production of hemoglobin-based blood substitutes. PMID:21161348

  4. A new polyethyleneglycol-derivatized hemoglobin derivative with decreased oxygen affinity and limited toxicity.

    PubMed

    Zolog, Oana; Mot, Augustin; Deac, Florina; Roman, Alina; Fischer-Fodor, Eva; Silaghi-Dumitrescu, Radu

    2011-01-01

    A new protocol is described for derivatization of hemoglobin with polyethyleneglycol (PEG) via reaction of the unmodified native hemoglobin with an activated amine-reacting polyethylene glycol derivative which, unlike protocols previously described, leads to formation of a peptide bond between hemoglobin and PEG. Dioxygen binding and peroxide reactivities of the derivatized hemoglobin are examined, and found to be within reasonable limits, with the particular observation that, unlike with a few other derivatization protocols, the dioxygen affinity is slightly lower than that of native Hb. In cell culture tests (human umbilical vein epithelial cells, HUVEC), the derivatization protocol induces no toxic effect. These results show promise towards applicability for production of hemoglobin-based blood substitutes.

  5. Identification of hemoglobin variants by top-down mass spectrometry using selected diagnostic product ions.

    PubMed

    Coelho Graça, Didia; Hartmer, Ralf; Jabs, Wolfgang; Beris, Photis; Clerici, Lorella; Stoermer, Carsten; Samii, Kaveh; Hochstrasser, Denis; Tsybin, Yury O; Scherl, Alexander; Lescuyer, Pierre

    2015-04-01

    Hemoglobin disorder diagnosis is a complex procedure combining several analytical steps. Due to the lack of specificity of the currently used protein analysis methods, the identification of uncommon hemoglobin variants (proteoforms) can become a hard task to accomplish. The aim of this work was to develop a mass spectrometry-based approach to quickly identify mutated protein sequences within globin chain variants. To reach this goal, a top-down electron transfer dissociation mass spectrometry method was developed for hemoglobin β chain analysis. A diagnostic product ion list was established with a color code strategy allowing to quickly and specifically localize a mutation in the hemoglobin β chain sequence. The method was applied to the analysis of rare hemoglobin β chain variants and an (A)γ-β fusion protein. The results showed that the developed data analysis process allows fast and reliable interpretation of top-down electron transfer dissociation mass spectra by nonexpert users in the clinical area.

  6. Oxidation of dibenzothiophene catalyzed by hemoglobin and other hemoproteins in various aqueous-organic media

    SciTech Connect

    Klyachko, N.L. Klibanov, A.M. )

    1992-10-01

    Biocatalytic oxidation of dibenzothiophene (a model of organic sulfur in coal) with hydrogen peroxide was investigated. It was found that various hemoproteins, both enzymic (e.g., horseradish peroxidase) and nonenzymic (e.g., bovine blood hemoglobin), readily oxidized dibensothiophene to its S-oxide and, to a minor extent, further to its S-dioxide (sulfone). This process catalyzed by hemoglobin was competent as an oxidation catalyst even in nearly dry organic solvents (with protic, acidic solvents being optimal), the highest conversions were observed in predominantly aqueous media. The hemoglobin-catalyzed oxidation of dibenzothiophene at low concentrations of the protein stopped long before all the substrate was oxidized. This phenomenon was caused by inactivation of hemoglobin by hydrogen peroxide that destroyed the heme moiety. The maximal degree of the hemoglobin-catalyzed dibenzothiophene oxidation was predicted, and found, to be strongly dependent on the reaction medium composition. 24 refs., 7 figs., 3 tabs.

  7. Radiation-induced changes in the optical properties of hemoglobin molecule

    NASA Astrophysics Data System (ADS)

    Selim, Nabila S.; El-Marakby, Seham M.

    2010-06-01

    Adult male Albino rats were exposed to different doses of gamma radiation from Cs-137 source. Hemoglobin samples were analyzed 24 h after irradiation. The UV-visible spectrum of hemoglobin molecule was measured in the range 200-700 nm. The overall spectrum of the hemoglobin molecule showed hypochromicity that increased with dose increase. To investigate the effect of radiation on the hemoglobin molecule, different parameters of the spectrum were calculated: molar absorption coefficient, absorption cross-section, transition dipole moment, dipole length, the optical energy gap and activation energy for each characteristic peak. The obtained results revealed that the radiation effect can induce rearrangement of the transition dipole moments and change molecular energy levels of the hemoglobin molecule.

  8. Facile heme vinyl posttranslational modification in a hemoglobin.

    PubMed

    Preimesberger, Matthew R; Wenke, Belinda B; Gilevicius, Lukas; Pond, Matthew P; Lecomte, Juliette T J

    2013-05-21

    Iron-protoporphyrin IX, or b heme, is utilized as such by a large number of proteins and enzymes. In some cases, notably the c-type cytochromes, this group undergoes a posttranslational covalent attachment to the polypeptide chain, which adjusts the physicochemical properties of the holoprotein. The hemoglobin from the cyanobacterium Synechocystis sp. PCC 6803 (GlbN), contrary to the archetypical hemoglobin, modifies its b heme covalently. The posttranslational modification links His117, a residue that does not coordinate the iron, to the porphyrin 2-vinyl substituent and forms a hybrid b/c heme. The reaction is an electrophilic addition that occurs spontaneously in the ferrous state of the protein. This apparently facile type of heme modification has been observed in only two cyanobacterial GlbNs. To explore the determinants of the reaction, we examined the behavior of Synechocystis GlbN variants containing a histidine at position 79, which is buried against the porphyrin 4-vinyl substituent. We found that L79H/H117A GlbN bound the heme weakly but nevertheless formed a cross-link between His79 Nε2 and the heme 4-Cα. In addition to this linkage, the single variant L79H GlbN also formed the native His117-2-Cα bond yielding an unprecedented bis-alkylated protein adduct. The ability to engineer the doubly modified protein indicates that the histidine-heme modification in GlbN is robust and could be engineered in different local environments. The rarity of the histidine linkage in natural proteins, despite the ease of reaction, is proposed to stem from multiple sources of negative selection. PMID:23607716

  9. Sickle hemoglobin gelation. Reaction order and critical nucleus size.

    PubMed Central

    Behe, M J; Englander, S W

    1978-01-01

    Sickle hemoglobin (Hb S) gelation displays kinetics consistent with a rate-limiting nucleation step. The approximate size of the critical nucleus can be inferred from the order of the reaction with respect to Hb S activity, but determination of the reaction order is complicated by the fact that Hb S activity is substantially different from Hb S concentration at the high protein concentrations required for gelation. Equilibrium and kinetic experiments on Hb S gelation were designed to evaluate the relative activity coefficient of Hb S as a function of concentration. These experiments used non-Hb S proteins to mimic, and thus evaluate, the effect on activity coefficients of increasing Hb S concentration. At Hb S concentrations near 20% the change in Hb S activity coefficient generates two-thirds of the apparent dependence of nucleation rate on Hb S concentration. When this effect is explicitly accounted for, the nucleation reaction is seen to be approximately 10th-order with respect to effective number concentration of Hb S. The closeness of the reaction order to the number of strands in models of Hb S fibers suggests a nucleus close to the size of one turn of the Hb S fiber. These experiments introduce a new approach to the study of Hb S gelation, the equal activity isotherm, used here also to show that Hb S.Hb A (normal adult hemoglobin) hybrids do incorporate into growing nuclei and stable microtubules but that A.S hybridization is neutral with respect to promotion of Hb S nucleation and the sol-gel equilibrium. PMID:667302

  10. Hemoglobin: a newly recognized binding protein for bacterial endotoxins (LPS).

    PubMed

    Roth, R I; Kaca, W; Levin, J

    1994-01-01

    Administration of purified hemoglobin (Hb) as a cell-free resuscitation fluid is associated with multiple organ toxicities. Many of these toxicities are characteristic of the pathophysiological effects of bacterial endotoxins (lipopolysaccharide, LPS). To better understand the potential role of LPS in the observed in vivo toxicities of Hb, we examined mixtures of Hb and LPS for evidence of LPS-Hb complex formation. LPS-Hb complexes were demonstrated by three techniques: ultrafiltration through 300 kDa cut-off membranes, which distinguished LPS in complexes (87-89% < 300 kDa) from LPS alone (90% > 300 kDa); density centrifugation through sucrose, which distinguished denser LPS alone from LPS-Hb complexes; and precipitation by 67% ethanol, which demonstrated 2-3 fold increased precipitability of Hb in complexes compared to Hb alone. Interaction of LPS with Hb was also associated with markedly increased biological activity of LPS, as manifested by enhancement of LPS activation of Limulus amebocyte lysate (LAL), increased release of human mononuclear cell tissue factor, and enhanced production of human endothelial cell tissue factor. These results demonstrated that hemoglobin can serve as an endotoxin binding protein, and that this interaction results in the alteration of several of the physical characteristics of LPS and enhancement of the biological activities of LPS. These findings suggest that a mechanism for the toxicity of infused Hb in vivo may involve potentiation of the biological effects of LPS. In addition, these observations suggest a mechanism by which LPS-related morbidity during sepsis could be enhanced by erythrocyte hemolysis.

  11. Treatment of periodontal disease in diabetics reduces glycated hemoglobin.

    PubMed

    Grossi, S G; Skrepcinski, F B; DeCaro, T; Robertson, D C; Ho, A W; Dunford, R G; Genco, R J

    1997-08-01

    Periodontal disease is a common infection-induced inflammatory disease among individuals suffering from diabetes mellitus. The purpose of this study was to assess the effects of treatment of periodontal disease on the level of metabolic control of diabetes. A total of 113 Native Americans (81 females and 32 males) suffering from periodontal disease and non-insulin dependent diabetes mellitus (NIDDM) were randomized into 5 treatment groups. Periodontal treatment included ultrasonic scaling and curettage combined with one of the following antimicrobial regimens: 1) topical water and systemic doxycycline, 100 mg for 2 weeks; 2) topical 0.12% chlorhexidine (CHX) and systemic doxycycline, 100 mg for 2 weeks; 3) topical povidone-iodine and systemic doxycycline, 100 mg for 2 weeks; 4) topical 0.12% CHX and placebo; and 5) topical water and placebo (control group). Assessments were performed prior to and at 3 and 6 months after treatment and included probing depth (PD), clinical attachment level (CAL), detection of Porphyromonas gingivalis in subgingival plaque and determination of serum glucose and glycated hemoglobin (HbA1c). After treatment all study groups showed clinical and microbial improvement. The doxycycline-treated groups showed the greatest reduction in probing depth and subgingival Porphyromonas gingivalis compared to the control group. In addition, all 3 groups receiving systemic doxycycline showed, at 3 months, significant reductions (P < or = 0.04) in mean HbA1c reaching nearly 10% from the pretreatment value. Effective treatment of periodontal infection and reduction of periodontal inflammation is associated with a reduction in level of glycated hemoglobin. Control of periodontal infections should thus be an important part of the overall management of diabetes mellitus patients.

  12. Hemoglobin Constant Spring among Southeast Asian Populations: Haplotypic Heterogeneities and Phylogenetic Analysis

    PubMed Central

    Jomoui, Wittaya; Fucharoen, Goonnapa; Sanchaisuriya, Kanokwan; Nguyen, Van Hoa; Fucharoen, Supan

    2015-01-01

    Background Hemoglobin Constant Spring (Hb CS) is an abnormal Hb caused by a mutation at the termination codon of α2-globin gene found commonly among Southeast Asian and Chinese people. Association of Hb CS with α°-thalassemia leads to a thalassemia intermedia syndrome commonly encountered in the region. We report chromosome background and addressed genetic origins of Hb CS observed in a large cohort of Hb CS among Southeast Asian populations. Materials and Methods A study was done on 102 Vietnamese (aged 15–49 year-old) and 40 Laotian (aged 18–39 year-old) subjects with Hb CS and results compared with 120 Hb CS genes in Thailand. Hematological parameters were recorded and Hb analysis was performed using capillary electrophoresis. Hb CS mutation and thalassemia genotypes were defined by DNA analysis. Six DNA polymorphisms within α-globin gene cluster including 5’Xba I, Bgl I, Inter-zeta HVR, AccI, RsaI and αPstI 3’, were determined using PCR-RFLP assay. Results Nine different genotypes of Hb CS were observed. In contrast to the Thai Hb CS alleles which are mostly linked to haplotype (+—S + + -), most of the Vietnamese and the Laotian Hb CS genes were associated with haplotype (+—M + + -), both of which are different from that of the European Hb CS. Conclusions Hb CS is commonly found in combination with other thalassemias among Southeast Asian populations. Accurate genotyping of the cases requires both hematologic and DNA analyses. At least two independent origins are associated with the Hb CS gene which could indirectly explain the high prevalence of this Hb variant in the region. PMID:26683994

  13. Adults with Chromosome 18 Abnormalities.

    PubMed

    Soileau, Bridgette; Hasi, Minire; Sebold, Courtney; Hill, Annice; O'Donnell, Louise; Hale, Daniel E; Cody, Jannine D

    2015-08-01

    The identification of an underlying chromosome abnormality frequently marks the endpoint of a diagnostic odyssey. However, families are frequently left with more questions than answers as they consider their child's future. In the case of rare chromosome conditions, a lack of longitudinal data often makes it difficult to provide anticipatory guidance to these families. The objective of this study is to describe the lifespan, educational attainment, living situation, and behavioral phenotype of adults with chromosome 18 abnormalities. The Chromosome 18 Clinical Research Center has enrolled 483 individuals with one of the following conditions: 18q-, 18p-, Tetrasomy 18p, and Ring 18. As a part of the ongoing longitudinal study, we collect data on living arrangements, educational level attained, and employment status as well as data on executive functioning and behavioral skills on an annual basis. Within our cohort, 28 of the 483 participants have died, the majority of whom have deletions encompassing the TCF4 gene or who have unbalanced rearrangement involving other chromosomes. Data regarding the cause of and age at death are presented. We also report on the living situation, educational attainment, and behavioral phenotype of the 151 participants over the age of 18. In general, educational level is higher for people with all these conditions than implied by the early literature, including some that received post-high school education. In addition, some individuals are able to live independently, though at this point they represent a minority of patients. Data on executive function and behavioral phenotype are also presented. Taken together, these data provide insight into the long-term outcome for individuals with a chromosome 18 condition. This information is critical in counseling families on the range of potential outcomes for their child.

  14. Impact of higher hemoglobin targets on blood pressure and clinical outcomes: a secondary analysis of CHOIR

    PubMed Central

    Inrig, Jula K.; Sapp, Shelly; Barnhart, Huiman; Patel, Uptal D.; Reddan, Donal; Singh, Ajay; Califf, Robert M.; Szczech, Lynda

    2012-01-01

    Background Targeting a higher hemoglobin in patients with chronic kidney disease leads to adverse cardiovascular outcomes, yet the reasons remain unclear. Herein, we sought to determine whether changes in erythropoiesis-stimulating agent (ESA) dose and in hemoglobin were predictive of changes in blood pressure (BP) and whether these changes were associated with cardiovascular outcomes. Methods In this secondary analysis of 1421 Correction of Hemoglobin and Outcomes in Renal Disease (CHOIR) participants, mixed model analyses were used to describe monthly changes in ESA dose and hemoglobin with changes in diastolic BP (DBP) and systolic BP (SBP). Poisson modeling was performed to determine whether changes in hemoglobin and BP were associated with the composite end point of death or cardiovascular outcomes. Results Monthly average DBP, but not SBP, was higher in participants in the higher hemoglobin arm. Increases in ESA doses and in hemoglobin were significantly associated with linear increases in DBP, but not consistently with increases in SBP. In models adjusted for demographics and comorbid conditions, increases in ESA dose (>0 U) and larger increases in hemoglobin (>1.0 g/dL/month) were associated with poorer outcomes [event rate ratio per 1000 U weekly dose per month increase 1.05, (1.02–1.08), P = 0.002 and event rate ratio 1.70 (1.02–2.85), P = 0.05, respectively]. However, increasing DBP was not associated with adverse outcomes [event rate ratio 1.01 (0.98–1.03), P = 0.7]. Conclusion Among CHOIR participants, higher hemoglobin targets, increases in ESA dose and in hemoglobin were associated both with increases in DBP and with higher event rates; however, increasing DBP was not associated with adverse outcomes. PMID:22573238

  15. Development of a method to produce hemoglobin in a bioreactor culture of Escherichia coli BL21(DE3) transformed with a plasmid containing Plesiomonas shigelloides heme transport genes and modified human hemoglobin genes.

    PubMed

    Smith, B J Z; Gutierrez, P; Guerrero, E; Brewer, C J; Henderson, D P

    2011-09-01

    We describe a method for production of recombinant human hemoglobin by Escherichia coli grown in a bioreactor. E. coli BL21(DE3) transformed with a plasmid containing hemoglobin genes and Plesiomonas shigelloides heme transport genes reached a cell dry weight of 83.64 g/liter and produced 11.92 g/liter of hemoglobin in clarified lysates.

  16. Phenotypic abnormalities: terminology and classification.

    PubMed

    Merks, Johannes H M; van Karnebeek, Clara D M; Caron, Hubert N; Hennekam, Raoul C M

    2003-12-15

    Clinical morphology has proved essential for the successful delineation of hundreds of syndromes and as a powerful instrument for detecting (candidate) genes (Gorlin et al. [2001]; Syndromes of the Head and Neck; Oxford: Oxford University Press. 1 p]. The major approach to reach this has been careful clinical evaluations of patients, focused on congenital anomalies. A similar careful physical examination performed in patients, who have been treated for childhood cancer, may allow detection of concurrent patterns of anomalies and provide clues for causative genes. In the past, several studies were performed describing the prevalence of anomalies in patients with cancer. However, in most studies, it was not possible to indicate the biologic relevance of the recorded anomalies, or to judge their relative importance. Are the detected anomalies common variants, and should they thus be regarded as normal, or are they minor anomalies or true abnormalities, indicating a possible developmental cause? Classification of items in the categories of common variants (disturbances of phenogenesis with a prevalence >4%), minor anomalies (disturbances of phenogenesis with a prevalence abnormal physical findings by a nomenclature for errors of morphogenesis detectable on surface examination, and secondly a uniform classification system. This should allow investigators to evaluate systematically the presence of patterns in phenotypic anomalies, in the general population, and in patients with various disorders, suspected to be a developmental anomaly. Also

  17. Hemoglobin system of Sparus aurata: changes in fishes farmed under extreme conditions.

    PubMed

    Campo, Salvatore; Nastasi, Giancarlo; D'Ascola, Angela; Campo, Giuseppe M; Avenoso, Angela; Traina, Paola; Calatroni, Alberto; Burrascano, Emanuele; Ferlazzo, Alida; Lupidi, Giulio; Gabbianelli, Rosita; Falcioni, Giancarlo

    2008-09-15

    In order to gain more knowledge on the stress responses of gilhead seabream (Sparus aurata) under extreme conditions, this study investigated the functional properties of the hemoglobin system and globin gene expression under hypoxia and low salinity. The oxygen affinity for the two hemoglobin components present inside the S. aurata erythrocyte was practically identical as was the influence of protons and organic phosphates (Root effect). The quantification of S. aurata hemoglobin fractions performed by HPLC and the data on gene expression of globin chains assayed by PCR indicate that under hypoxia and low salinity there is a change in the ratio between the two different hemoglobin components. The result indicating that the distinct hemoglobins present in S. aurata erythrocyte have almost identical functional properties, does not explain the adaptive response (expression change) following exposure of the animal to hypoxia or low salinity on the basis of their function as oxygen transporter. We hypothesize that other parallel biological functions that the hemoglobin molecule is known to display within the erythrocyte are involved in adaptive molecular mechanisms. The autoxidation-reduction cycle of hemoglobin could be involved in the response to particular living conditions.

  18. Effect of the N-terminal residues on the quaternary dynamics of human adult hemoglobin

    NASA Astrophysics Data System (ADS)

    Chang, Shanyan; Mizuno, Misao; Ishikawa, Haruto; Mizutani, Yasuhisa

    2016-05-01

    The protein dynamics of human hemoglobin following ligand photolysis was studied by time-resolved resonance Raman spectroscopy. The time-resolved spectra of two kinds of recombinant hemoglobin expressed in Escherichia coli, normal recombinant hemoglobin and the α(V1M)/β(V1M) double mutant, were compared with those of human adult hemoglobin (HbA) purified from blood. A frequency shift of the iron-histidine stretching [ν(Fe-His)] band was observed in the time-resolved spectra of all three hemoglobin samples, indicative of tertiary and quaternary changes in the protein following photolysis. The spectral changes of the α(V1M)/β(V1M) double mutant were distinct from those of HbA in the tens of microseconds region, whereas the spectral changes of normal recombinant hemoglobin were similar to those of HbA isolated from blood. These results demonstrated that a structural change in the N-termini is involved in the second step of the quaternary structure change of hemoglobin. We discuss the implications of these results for understanding the allosteric pathway of HbA.

  19. Engineering the oxygen sensing regulation results in an enhanced recombinant human hemoglobin production by Saccharomyces cerevisiae.

    PubMed

    Martínez, José L; Liu, Lifang; Petranovic, Dina; Nielsen, Jens

    2015-01-01

    Efficient production of appropriate oxygen carriers for transfusions (blood substitutes or artificial blood) has been pursued for many decades, and to date several strategies have been used, from synthetic polymers to cell-free hemoglobin carriers. The recent advances in the field of metabolic engineering also allowed the generation of different genetically modified organisms for the production of recombinant human hemoglobin. Several studies have showed very promising results using the bacterium Escherichia coli as a production platform, reporting hemoglobin titers above 5% of the total cell protein content. However, there are still certain limitations regarding the protein stability and functionality of the recombinant hemoglobin produced in bacterial systems. In order to overcome these limitations, yeast systems have been proposed as the eukaryal alternative. We recently reported the generation of a set of plasmids to produce functional human hemoglobin in Saccharomyces cerevisiae, with final titers of active hemoglobin exceeding 4% of the total cell protein. In this study, we propose a strategy for further engineering S. cerevisiae by altering the oxygen sensing pathway by deleting the transcription factor HAP1, which resulted in an increase of the final recombinant active hemoglobin titer exceeding 7% of the total cellular protein.

  20. Trypanosomatid parasites rescue heme from endocytosed hemoglobin through lysosomal HRG transporters.

    PubMed

    Cabello-Donayre, María; Malagarie-Cazenave, Sophie; Campos-Salinas, Jenny; Gálvez, Francisco J; Rodríguez-Martínez, Alba; Pineda-Molina, Estela; Orrego, Lina M; Martínez-García, Marta; Sánchez-Cañete, María P; Estévez, Antonio M; Pérez-Victoria, José M

    2016-09-01

    Pathogenic trypanosomatid parasites are auxotrophic for heme and they must scavenge it from their human host. Trypanosoma brucei (responsible for sleeping sickness) and Leishmania (leishmaniasis) can fulfill heme requirement by receptor-mediated endocytosis of host hemoglobin. However, the mechanism used to transfer hemoglobin-derived heme from the lysosome to the cytosol remains unknown. Here we provide strong evidence that HRG transporters mediate this essential step. In bloodstream T. brucei, TbHRG localizes to the endolysosomal compartment where endocytosed hemoglobin is known to be trafficked. TbHRG overexpression increases cytosolic heme levels whereas its downregulation is lethal for the parasites unless they express the Leishmania orthologue LmHR1. LmHR1, known to be an essential plasma membrane protein responsible for the uptake of free heme in Leishmania, is also present in its acidic compartments which colocalize with endocytosed hemoglobin. Moreover, LmHR1 levels modulated by its overexpression or the abrogation of an LmHR1 allele correlate with the mitochondrial bioavailability of heme from lysosomal hemoglobin. In addition, using heme auxotrophic yeasts we show that TbHRG and LmHR1 transport hemoglobin-derived heme from the digestive vacuole to the cytosol. Collectively, these results show that trypanosomatid parasites rescue heme from endocytosed hemoglobin through endolysosomal HRG transporters, which could constitute novel drug targets. PMID:27328668

  1. Radiologic atlas of pulmonary abnormalities in children

    SciTech Connect

    Singleton, E.B.; Wagner, M.L.; Dutton, R.V.

    1988-01-01

    This book is an atlas about thoracic abnormalities in infants and children. The authors include computed tomographic, digital subtraction angiographic, ultrasonographic, and a few magnetic resonance (MR) images. They recognize and discuss how changes in the medical treatment of premature infants and the management of infection and pediatric tumors have altered some of the appearances and considerations in these diseases. Oriented toward all aspects of pulmonary abnormalities, the book starts with radiographic techniques and then discusses the normal chest, the newborn, infections, tumors, and pulmonary vascular diseases. There is comprehensive treatment of mediastinal abnormalities and a discussion of airway abnormalities.

  2. [Renal abnormalities in ankylosing spondylitis].

    PubMed

    Samia, Barbouch; Hazgui, Faiçal; Abdelghani, Khaoula Ben; Hamida, Fethi Ben; Goucha, Rym; Hedri, Hafedh; Taarit, Chokri Ben; Maiz, Hedi Ben; Kheder, Adel

    2012-07-01

    We will study the epidemiologic, clinical, biological, therapeutic, prognostic characteristics and predictive factors of development of nephropathy in ankylosing spondylitis patients. We retrospectively reviewed the medical record of 32 cases with renal involvement among 212 cases of ankylosing spondylitis followed in our service during the period spread out between 1978 and 2006. The renal involvement occurred in all patients a mean of 12 years after the clinical onset of the rheumatic disease. Thirty-two patients presented one or more signs of renal involvement: microscopic hematuria in 22 patients, proteinuria in 23 patients, nephrotic syndrome in 11 patients and decreased renal function in 24 patients (75%). Secondary renal amyloidosis (13 patients), which corresponds to a prevalence of 6,1% and tubulointerstitial nephropathy (7 patients) were the most common cause of renal involvement in ankylosing spondylitis followed by IgA nephropathy (4 patients). Seventeen patients evolved to the end stage renal disease after an average time of 29.8 ± 46 months. The average follow-up of the patients was 4,4 years. By comparing the 32 patients presenting a SPA and renal disease to 88 with SPA and without nephropathy, we detected the predictive factors of occurred of nephropathy: tobacco, intense inflammatory syndrome, sacroileite stage 3 or 4 and presence of column bamboo. The finding of 75% of the patients presented a renal failure at the time of the diagnosis of renal involvement suggests that evidence of renal abnormality involvement should be actively sought in this disease. PMID:22520483

  3. [Renal abnormalities in ankylosing spondylitis].

    PubMed

    Samia, Barbouch; Hazgui, Faiçal; Abdelghani, Khaoula Ben; Hamida, Fethi Ben; Goucha, Rym; Hedri, Hafedh; Taarit, Chokri Ben; Maiz, Hedi Ben; Kheder, Adel

    2012-07-01

    We will study the epidemiologic, clinical, biological, therapeutic, prognostic characteristics and predictive factors of development of nephropathy in ankylosing spondylitis patients. We retrospectively reviewed the medical record of 32 cases with renal involvement among 212 cases of ankylosing spondylitis followed in our service during the period spread out between 1978 and 2006. The renal involvement occurred in all patients a mean of 12 years after the clinical onset of the rheumatic disease. Thirty-two patients presented one or more signs of renal involvement: microscopic hematuria in 22 patients, proteinuria in 23 patients, nephrotic syndrome in 11 patients and decreased renal function in 24 patients (75%). Secondary renal amyloidosis (13 patients), which corresponds to a prevalence of 6,1% and tubulointerstitial nephropathy (7 patients) were the most common cause of renal involvement in ankylosing spondylitis followed by IgA nephropathy (4 patients). Seventeen patients evolved to the end stage renal disease after an average time of 29.8 ± 46 months. The average follow-up of the patients was 4,4 years. By comparing the 32 patients presenting a SPA and renal disease to 88 with SPA and without nephropathy, we detected the predictive factors of occurred of nephropathy: tobacco, intense inflammatory syndrome, sacroileite stage 3 or 4 and presence of column bamboo. The finding of 75% of the patients presented a renal failure at the time of the diagnosis of renal involvement suggests that evidence of renal abnormality involvement should be actively sought in this disease.

  4. The XXXXY Sex Chromosome Abnormality

    PubMed Central

    Barr, M. L.; Carr, D. H.; Pozsonyi, J.; Wilson, R. A.; Dunn, H. G.; Jacobson, T. S.; Miller, J. R.; Chown, B.

    1962-01-01

    The most common sex chromosome complex in sex chromatin-positive males with Klinefelter's syndrome is XXY. When the complex is XXYY or XXXY, the clinical findings do not seem to differ materially from those seen in XXY subjects, although more patients with these intersexual chromosome complements need to be studied to establish possible phenotypical expressions of the chromosomal variants. Two male children with an XXXXY sex chromosome abnormality are described. The data obtained from the study of these cases and five others described in the literature suggest that the XXXXY patient is likely to have congenital defects not usually seen in the common form of the Klinefelter syndrome. These include a triad of (1) skeletal anomalies (including radioulnar synostosis), (2) hypogenitalism (hypoplasia of penis and scrotum, incomplete descent of testes and defective prepubertal development of seminiferous tubules), and (3) greater risk of severe mental deficiency. That the conclusions are based on data from a small number of patients is emphasized, together with the need for a cytogenetic survey of a large control or unselected population. ImagesFig. 1Fig. 2Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7Fig. 8Fig. 9Fig. 10 PMID:13969480

  5. [Analytical problems in determination of hemoglobin A1c and the different ways of its interpretation].

    PubMed

    Góth, László

    2009-04-19

    Glycated proteins are formed during the nonenzymatic reaction of glucose and amino groups of proteins. Hemoglobin A1c is formed by the condensation of glucose with the N-terminal valine residue of each beta-chain of hemoglobin A. The amount of glycated hemoglobin in blood depends on both life-span of red blood cells and blood glucose concentration. As the rate of formation of hemoglobin A1c is directly proportional to the concentration of glucose in the blood, it represent the integrated values for glucose over the preceding 6 to 8 weeks. Hemoglobin A1c determination is widely used for monitoring long-term glycemic control, and it is a risk factor for complications of diabetes. The concentration of blood hemoglobin A1c depends on further factors such as half-life of hemoglobin, blood carbohydrates, blood analytes, methods of determination and calibration. Committees were established under the auspices of the American Association of Clinical Chemistry, American Diabetes Association, International Federation of Clinical Chemistry (IFCC) to standardize HbA1c assays (DCCT: Diabetes Control and Complications Trial, NGSP: National Glycohemoglobin Standardization Program, IFCC reference method for measurement of HbA1c). The NGSP recommends to report HbA1c result in % (g HbA1c/g hemoglobin) while IFCC suggests mmol HbA1c/mol hemoglobin A. Reports are presenting mathematical relationship between HbA1c and average glucose concentration in blood, however, the clinical usefulness of estimating average serum glucose from HbA1c level is under discussion. PMID:19362928

  6. Maternal HIV status affects the infant hemoglobin level

    PubMed Central

    Feleke, Berhanu Elfu

    2016-01-01

    Abstract Children, especially infants, are highly vulnerable to iron-deficiency anemia because of their rapid growth of the brain and the rest of the body. The objectives of this study were to compare the prevalence of iron-deficiency anemia in infants born from HIV-positive mothers and HIV-negative mothers and to identify the determinants of iron-deficiency anemia in infants. A comparative cross-sectional study was conducted in Bahir Dar city. Simple random sampling technique was used to select the study participants. Mothers were interviewed; blood samples were collected from mothers and infants to measure the hemoglobin level and anthropometric indicators were obtained from the infants using world health organization standards. Descriptive statistics were used to estimate the prevalence of infantile anemia. Binary logistic regression and multiple linear regressions were used to identify the determinants of infant anemia. A total of 1459 infants born from HIV-positive and HIV-negative mothers were included. The prevalence of iron-deficiency anemia in infants born from HIV-positive and HIV-negative mothers was 41.9% (95% CI: 39–44). Infantile iron-deficiency anemia was associated with maternal HIV infection (adjusted odds ratio [AOR] 2.54 [95% CI: 1.65–3.9]), stunting (AOR 3.46 [95% CI: 2.41–4.97]), low income (AOR 2.72 [95% CI: 2–3.73]), maternal malaria during pregnancy (AOR 1.81 [95% CI: 1.33–2.47]), use of cow milk before 6 month (AOR 1.82 [95% CI: 1.35–2.45]), residence (AOR 0.09 [95% CI: 0.06–0.13]), history of cough or fever 7 days preceding the survey (AOR 2.71 [95% CI: 1.99–3.69]), maternal hemoglobin (B 0.65 [95% CI: 0.61–0.68]), educational status of mother (B 0.22 [95% CI: 0.2–0.23]), age of the mother (B –0.03 [95% CI: –0.03, –0.02]), and family size (B –0.14 [95% CI: –0.18,–0.11]). PMID:27495044

  7. Heme degradation upon production of endogenous hydrogen peroxide via interaction of hemoglobin with sodium dodecyl sulfate.

    PubMed

    Salehi, N; Moosavi-Movahedi, A A; Fotouhi, L; Yousefinejad, S; Shourian, M; Hosseinzadeh, R; Sheibani, N; Habibi-Rezaei, M

    2014-04-01

    In this study the hemoglobin heme degradation upon interaction with sodium dodecyl sulfate (SDS) was investigated using UV-vis and fluorescence spectroscopy, multivariate curve resolution analysis, and chemiluminescence method. Our results showed that heme degradation occurred during interaction of hemoglobin with SDS producing three fluorescent components. We showed that the hydrogen peroxide, produced during this interaction, caused heme degradation. In addition, the endogenous hydrogen peroxide was more effective in hemoglobin heme degradation compared to exogenously added hydrogen peroxide. The endogenous form of hydrogen peroxide altered oxyHb to aquamethemoglobin and hemichrome at low concentration. In contrast, the exogenous hydrogen peroxide lacked this ability under same conditions.

  8. Long Range Correlation of Hydrophilicity and Flexibility Along the Hemoglobin Chain

    SciTech Connect

    Craciun, D.; Isvoran, A.; Avram, N. M.

    2010-08-04

    Within this study, we reveal the long range correlation concerning hydrophilicity and flexibility along sequences of hemoglobins belonging to different organisms and we compare them with the long range correlations properties obtained for other protein families. For all hemoglobins considered, we investigate two discrete spatial series: the hydrophilicity and flexibility respectively. We apply the nonlinear analysis methods to analyze the two spatial series by calculating the spectral coefficient {beta}, the scaling exponent {alpha} and Hurst exponent H. The obtained values for the mentioned coefficients suggest long range correlation within the analyzed sequences of hemoglobins in good agreement with those obtained for the calcium binding proteins and hydrolases.

  9. Comparison of Hemoglobin Levels Before and After Hemodialysis and Their Effects on Erythropoietin Dosing and Cost

    PubMed Central

    Sagheb, Mohammad Mahdi; Fallahzadeh, Mohammad Amin; Moaref, Alireza; Fallahzadeh, Mohammad Hossein; Dormanesh, Banafshe

    2016-01-01

    Background Hemoglobin levels measured after hemodialysis, as compared to hemoglobin levels measured before hemodialysis, are suggested to be a more accurate reflection of the hemoglobin levels between hemodialysis sessions, and to be a better reference point for adjusting erythropoietin dosing. Objectives The aim of this study was to compare the hemoglobin levels before and after hemodialysis, to calculate the required erythropoietin doses based on these levels, and to develop a model to predict effective erythropoietin dosing. Patients and Methods In this cross-sectional study, the hemoglobin levels of 52 patients with end-stage renal disease were measured before and after hemodialysis. The required erythropoietin doses and the differences in cost were calculated based on the hemoglobin levels before and after hemodialysis. A model to predict the adjusted erythropoietin dosages based on post-hemodialysis hemoglobin levels was proposed. Results Hemoglobin levels measured after hemodialysis were significantly higher than the hemoglobin levels before hemodialysis (11.1 ± 1.1 vs. 11.9 ± 1.2 g/dL, P < 0.001, 7% increase). The mean required erythropoietin dose based on post-hemodialysis hemoglobin levels was significantly lower than the corresponding erythropoietin dose based on pre-hemodialysis hemoglobin levels (10947 ± 6820 vs. 12047 ± 7542 U/week, P < 0.001, 9% decrease). The cost of erythropoietin was also significantly lower when post-hemodialysis levels were used (15.96 ± 9.85 vs. 17.57 ± 11.00 dollars/patient/week, P < 0.001). This translated into 83.72 dollars/patient/year in cost reduction. The developed model for predicting the required dosage is: Erythropoietin (U/week) = 43540.8 + (-2734.8) × Post-hemodialysis Hb* (g/dL). [(R2) = 0.221; *P < 0.001]. Conclusions Using post-hemodialysis hemoglobin levels as a reference point for erythropoietin dosing can result in significant dose and cost reduction, and can protect hemodialysis patients from

  10. A Theoretical Study of some Rheological Properties of the Aggregation of the Molecules Deoxy- Hemoglobin S

    NASA Astrophysics Data System (ADS)

    Mensah, Francis; Grant, Julius; Thorpe, Arthur

    2010-02-01

    Sickle cell disease is a serious public health problem that affects many people worldwide. In this paper, the Langevin equation is used for hemoglobin's aggregation in sickle cell anemia. Several parameters are explored such as the time-dependent deformation of the aggregates whose plot gives a sigmoid, the time-dependent expressions obtained for the coefficient of viscosity and the elastic modulus which characterize the aggregation of the sickle hemoglobin. Other properties such as the viscoelastic and the elasto-thixotropic properties of the sickle hemoglobin polymer are also described. An attempt is made to approach the polymerization process in terms of a dynamical system. )

  11. Direct electrochemistry of hemoglobin in egg-phosphatidylcholine films and its catalysis to H(2)O(2).

    PubMed

    Han, Xiaojun; Huang, Weimin; Jia, Jianbo; Dong, Shaojun; Wang, Erkang

    2002-09-01

    Direct electrochemistry of hemoglobin was observed in stable thin film composed of a natural lipid (egg-phosphatidylcholine) and hemoglobin on pyrolytic graphite (PG) electrode. Hemoglobin in lipid films shows thin layer electrochemistry behavior. The formal potential E degrees ' of hemoglobin in the lipid film was linearly varied with pH in the range from 3.5 to 7.0 with a slope of -46.4 mV pH(-1). Hemoglobin in the lipid film exhibited elegant catalytic activity for electrochemical reduction of H(2)O(2), based which a unmediated biosensor for H(2)O(2) was developed.

  12. Human bulbar conjunctival hemodynamics in hemoglobin SS and SC disease.

    PubMed

    Wanek, Justin; Gaynes, Bruce; Lim, Jennifer I; Molokie, Robert; Shahidi, Mahnaz

    2013-08-01

    The known biophysical variations of hemoglobin (Hb) S and Hb C may result in hemodynamic differences between subjects with SS and SC disease. The purpose of this study was to measure and compare conjunctival hemodynamics between subjects with Hb SS and SC hemoglobinopathies. Image sequences of the conjunctival microcirculation were acquired in 9 healthy control subjects (Hb AA), 24 subjects with SC disease, and 18 subjects with SS disease, using a prototype imaging system. Diameter (D) and blood velocity (V) measurements were obtained in multiple venules of each subject. Data were categorized according to venule caliber by averaging V and D for venules with diameters less than (vessel size 1) or greater than (vessel size 2) 15 µm. V in vessel size 2 was significantly greater than V in vessel size 1 in the AA and SS groups (P ≥ 0.009), but not in the SC group (P = 0.1). V was significantly lower in the SC group as compared to the SS group (P = 0.03). In AA and SS groups, V correlated with D (P ≤ 0.005), but the correlation was not statistically significant in the SC group (P = 0.08). V was inversely correlated with hematocrit in the SS group for large vessels (P = 0.03); however, no significant correlation was found in the SC group (P ≥ 0.2). Quantitative assessment of conjunctival microvascular hemodynamics in SS and SC disease may advance understanding of sickle cell disease pathophysiology and thereby improve therapeutic interventions.

  13. Hemoglobin Bohr effects: atomic origin of the histidine residue contributions.

    PubMed

    Zheng, Guishan; Schaefer, Michael; Karplus, Martin

    2013-11-26

    The Bohr effect in hemoglobin, which refers to the dependence of the oxygen affinity on the pH, plays an important role in its cooperativity and physiological function. The dominant contribution to the Bohr effect arises from the difference in the pKa values of His residues of the unliganded (deoxy) and liganded (carbonmonoxy) structures. Using recent high resolution structures, the residue pKa values corresponding to the two structures are calculated. The method is based on determining the electrostatic interactions between residues in the protein, relative to those of the residue in solution, by use of the linearized finite difference Poisson-Boltzmann equation and Monte Carlo sampling of protonation states. Given that good agreement is obtained with the available experimental values for the contribution of His residues in HbA to the Bohr effect, the calculated results are used to determine the atomic origin of the pKa shift between deoxy and carbonmonoxy HbA. The contributions to the pKa shift calculated by means of the linear response approximation show that the salt bridge involving His146 plays an important role in the alkaline Bohr effect, as suggested by Perutz but that other interactions are significant as well. A corresponding analysis is made for the contribution of His143 to the acid Bohr effect for which there is no proposed explanation. The method used is summarized and the program by which it is implemented is described in the Appendix .

  14. Nitrite attenuated hypochlorous acid-mediated heme degradation in hemoglobin.

    PubMed

    Lu, Naihao; Li, Jiayu; Ren, Xiaoming; Tian, Rong; Peng, Yi-Yuan

    2015-08-01

    Hypochlorous acid (HOCl) is elevated in many inflammatory diseases and causes the accumulation of free iron. Through the Fenton reaction, free iron has the ability to generate free radicals and subsequently is toxic. Recent studies have demonstrated that HOCl participates in heme destruction of hemoglobin (Hb) and free iron release. In this study, it was showed that nitrite (NO2(-)) could prevent HOCl-mediated Hb heme destruction and free iron release. Also, NO2(-) prevented HOCl-mediated loss of Hb peroxidase activity. After the NO2(-)/HOCl treatment, Tyr 42 in α-chain was found to be nitrated in Hb, attenuating the electron transferring abilities of phenolic compounds. The protective effects of NO2(-) on HOCl-induced heme destruction were attributed to its reduction of ferryl Hb and/or direct scavenging of HOCl. Therefore, NO2(-) could show protective effects in some inflammatory diseases by preventing HOCl-mediated heme destruction of hemoproteins and free iron release. PMID:26051522

  15. Effects of rutin on the redox reactions of hemoglobin.

    PubMed

    Lu, Naihao; Ding, Yun; Yang, Zhen; Gao, Pingzhang

    2016-08-01

    Flavonoids are widely used to attenuate oxidative damage in vitro and in vivo. In this study, we investigated the influence of rutin (quercetin-3-rhamnosylglucoside) on hemoglobin (Hb)- dependent redox reactions, i.e. oxidative stability of Hb and its cytotoxic ferryl intermediate. It was found that rutin induced generation of H2O2, which in turn oxidized Hb rapidly. Meanwhile, rutin exhibited anti-oxidant effect by effectively reducing ferryl intermediate back to ferric Hb at physiological pH. In comparison with quercetin, rutin had stronger capability on reducing ferryl species while lesser pro-oxidant effect on H2O2 generation, thus it exhibited more protective effect on H2O2-induced Hb oxidation. Circular dichroism spectrum showed no significant change in the secondary structure of Hb after flavonoid addition, while molecular docking revealed different binding modes of quercetin and rutin with Hb. These results might provide new insights into the potential nutritional and physiological implications of rutin and quercetin with redox active heme proteins regarding their ani- and pro-oxidant effects.

  16. Resuscitation with increasing doses of diaspirin crosslinked hemoglobin in swine.

    PubMed

    Marchand, G; Dunlap, E; Farrell, L; Nigro, C; Burhop, K

    1996-09-01

    This study examined the effects of administering 0.5, 4, 10, and 30 mL/kg of Diaspirin Crosslinked Hemoglobin (DCLHb) in a swine model of non-lethal hemorrhagic shock. Thirty unanesthetized animals were bled (30 mL/kg, 1 mL/kg/min) and either recovered without treatment (Untreated Control, UC) or infused with 10 g/dL DCLHb (0.5, 4.0, 10 or 30 mL/kg at 1 mL/kg/min) or Lactated Ringer (LR, 90 mL/kg at 3 mL/kg/min). DCLHb caused dose-related increases in MAP. Both the 10 and 30 mL/kg doses of DCLHb increased MAP more than UC or LR. Lower doses of DCLHb and LR had effects on MAP similar to UC. After hemorrhage, CO increased in all groups. The effect of DCLHb on CO was dose-related. Only LR and 30 mL/kg of DCLHb transiently (through 90 min) increased CO more than UC. CO in animals given lower doses of DCLHb was comparable to UC. DCLHb (10 and 30 mL/kg) improved base excess and lactate concentrations, two indices of global perfusion, more rapidly and to a greater extent than either UC or LR. In this swine model of hemorrhage, even small doses of DCLHb exerted measurable beneficial effects on blood pressure and perfusion.

  17. Erythrocyte differentiation during the metamorphic hemoglobin switch of Rana catesbeiana.

    PubMed Central

    Dorn, A R; Broyles, R H

    1982-01-01

    Anurans (frogs and toads) switch from tadpole to adult hemoglobin synthesis during metamorphosis. A number of workers have attempted to determine whether tadpole and adult Hb types are expressed in the same or different erythroid cells during the switch. If the different Hb types are found in different cells during the transition, the switch in globin gene expression occurs at an early stage of cellular differentiation. Previous studies, in which immunocytochemical techniques were used to approach this question, are in conflict in regard to the metamorphic Hb switch of the North American bullfrog Rana catesbeiana. We have purified newly differentiating erythroid cells from the blood of metamorphosing tadpoles by using Percoll gradients. These new cells have an immature morphology, are very active in the synthesis of adult Hb, and contain no detectable tadpole Hb. The tadpole cells have no detectable adult Hb, are synthetically inactive, increase in density during the switch, and are then cleared from the circulation. Thus, only adult Hb expression is detected in newly differentiating erythroid cells during metamorphosis. Images PMID:6182567

  18. Quantification of hemoglobin variants by capillary isoelectric focusing.

    PubMed

    Hempe, J M; Craver, R D

    1994-12-01

    Capillary isoelectric focusing (cIEF) was used to identify and quantify major and minor hemoglobin (Hb) variants. Whole blood (approximately 10 microL required) hemolysate was analyzed with a commercial instrument equipped with a 50 microns (i.d.) x 27 cm coated capillary filled with 20 g/L ampholytes (pH 6-8) in 4 g/L methylcellulose (MC). Cathode and anode solutions were 20 mol/L NaOH and 100 mol/L H3PO4 in MC, respectively. Samples (approximately 40 nL) were applied via autosampler by low-pressure injection, focused for 3 min at 30 kV, and mobilized by simultaneous voltage and low pressure past the detector, where absorbance at 415 nm was analyzed by an automated data acquisition system. Blood from subjects with sickle cell trait, Hb S/C disease, and various beta-thalassemias were analyzed by cIEF in < 15 min. cIEF was used to separate Hb S from Hb D-Los Angeles. Assay precision determined with commercial controls gave CV < 2% for Hb A and S, and 1-11% for minor Hb variants A2, F, and A1c. Results obtained by cIEF for patients' samples agreed well with values determined by conventional assays (r2 > 0.95). The results demonstrate that cIEF is a rapid, sensitive, high-resolution automated method for routine quantitative clinical analysis of Hb variants.

  19. The interaction between hemoglobin and two surfactants with different charges.

    PubMed

    Liu, Wenjie; Guo, Xia; Guo, Rong

    2007-12-01

    The interactions of hemoglobin (Hb) with sodium dodecyl sulfate (SDS) and dodecyl trimethylammonium bromide (DTAB) are investigated by several methods. We observed the formation of hemichrome below the critical micelle concentration (cmc) of surfactant and the release of heme from Hb above the cmc. When pH value of Hb/surfactant system is lower than isoelectric point (pI) of Hb, the interaction of SDS with Hb is both electrostatic and hydrophobic, while the interaction of DTAB with Hb is hydrophobic mainly. On the contrary, when pH>pI, the interaction of SDS with Hb is hydrophobic mainly, while the interaction of DTAB with Hb is both electrostatic and hydrophobic. In the case where both the electrostatic interaction and hydrophobic interaction exist, the electrostatic interaction plays a more important role. Thus, SDS tends to interact with Hb more obviously than DTAB does when pHpI.

  20. Five Rare β Globin Chain Hemoglobin Variants in India.

    PubMed

    Colah, Roshan B; Nadkarni, Anita; Gorakshakar, Ajit; Sawant, Pratibha; Gorivale, Manju; Mehta, Pallavi; Sawant, Madhavi; Ghosh, Kanjaksha

    2016-06-01

    Thalassemias as well as structural hemoglobin (Hb) variants are common monogenic inherited disorders of Hb in India. In this paper we describe 5 rare β-chain Hb variants identified in the Indian population on the basis of high performance liquid chromatography (HPLC). Of these 3 were identified during antenatal screening of β-thalassemia while the other 2 cases were referred to us for a diagnostic work up. These 5 Hb variants were Hb British Columbia (β CD 101 GAG → AAG), Hb Saint Louis (β CD28 CTG → CAG), Hb G Coushatta (β CD 22 GAA → GCA), Hb Pyrgos (β CD 83 GGC → GAC) and Hb Agenogi (β CD 90 GAG → AAG). Hb Saint Louis and Hb G Coushatta eluted in the HbA2 window, Hb British Columbia and Hb Agenogi eluted in the Hb C window while Hb Pyrgos eluted in an unknown window on HPLC. They were all identified by DNA sequencing. The child having Hb St. Louis had hepatosplenomegaly and anemia while the individuals with the other 4 variants were asymptomatic. Rare Hb variants are diagnostic curiosities that may be encountered by laboratories. Correct identification requires the application of more than one technique to avoid misdiagnosing them as more common variants (e.g. St. Louis and G Coushatta as E or D Iran on HPLC. Some, like G Coushatta may interfere with HPLC-based HbA1c estimation). PMID:27408413

  1. Variant subunit specificity in the quaternary structure of Artemia hemoglobin.

    PubMed

    Vandenberg, Cassandra J; Matthews, Charles M; Trotman, Clive N A

    2002-08-01

    The brine shrimp Artemia has three extracellular hemoglobins (Hbs) that are developmentally expressed and exhibit distinct oxygen-binding characteristics (Heip, Moens, and Kondo 1978; Heip et al. 1978 ). These Hbs are composed of two polymers, each of which comprises nine covalently linked globin domains. Although the cDNA sequences of two nine-domain globins from Artemia have been published, there is evidence for the existence of further expressed globin genes (Manning, Trotman, and Tate 1990 ). In the present study extensive analysis at the cDNA and genomic levels was performed in order to determine the globin gene copy number in Artemia. Sequence and Southern analysis suggest that four Hb polymers (T1, T2, C1, and C2) are expressed in Artemia. In addition, there is also at least one globin pseudogene. Protein sequencing of the native Hbs revealed that there are limitations on which two polymers can associate. The composition of the Hbs has been determined to be: Hb I, C1C2; Hb II, C1T2; and Hb III, T1T2. These pairings allow the levels of the three Artemia Hbs to be regulated independently by polymer expression alone, therefore explaining the previously inconsistent developmental and hypoxia-induced expression patterns. PMID:12140240

  2. Differential sensitivity of Chironomus and human hemoglobin to gamma radiation.

    PubMed

    Gaikwad, Pallavi S; Panicker, Lata; Mohole, Madhura; Sawant, Sangeeta; Mukhopadhyaya, Rita; Nath, Bimalendu B

    2016-08-01

    Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study.

  3. Erythrocyte differentiation during the metamorphic hemoglobin switch of Rana catesbeiana.

    PubMed

    Dorn, A R; Broyles, R H

    1982-09-01

    Anurans (frogs and toads) switch from tadpole to adult hemoglobin synthesis during metamorphosis. A number of workers have attempted to determine whether tadpole and adult Hb types are expressed in the same or different erythroid cells during the switch. If the different Hb types are found in different cells during the transition, the switch in globin gene expression occurs at an early stage of cellular differentiation. Previous studies, in which immunocytochemical techniques were used to approach this question, are in conflict in regard to the metamorphic Hb switch of the North American bullfrog Rana catesbeiana. We have purified newly differentiating erythroid cells from the blood of metamorphosing tadpoles by using Percoll gradients. These new cells have an immature morphology, are very active in the synthesis of adult Hb, and contain no detectable tadpole Hb. The tadpole cells have no detectable adult Hb, are synthetically inactive, increase in density during the switch, and are then cleared from the circulation. Thus, only adult Hb expression is detected in newly differentiating erythroid cells during metamorphosis.

  4. [On the modified process of human hemoglobin based blood substitutes].

    PubMed

    Li, Fengjuan; Zhang, Honghui; Wang, Jinfeng; Yang, Chengmin

    2009-10-01

    Purified hemoglobin was modified with pyridoxal 5-phosphate(PLP) and polymerized with glutaric dialdehyde(GDA) to get the products. By comparison of the physical, chemical and biological properties of different procedures for modification before and after polymerization, there is no significant difference in molecular distribution, methemoglobin(MetHb) concentration, oxygen carrier capacity, P50 and spectra. Furthermore, the procedure of modification after polymerization can save PLP greatly and decrease cost greatly. So the procedure of modification after polymerization is a better way in research and production. The addition of GDA could control the increasing of MetHb. By comparison on the physical, chemical and biological properties of different procedures, there is no significant difference in molecular distribution, MetHb concentration, oxygen carrier capacity and spectra between the procedure of adding GDA before PLP and that after PLP. But the P50 of adding GDA before PLP is much lower than that after PLP. So the procedure of adding GDA after PLP is a better way.

  5. Extracellular hemoglobin: the case of a friend turned foe

    PubMed Central

    Quaye, Isaac K.

    2015-01-01

    Hemoglobin (Hb) is a highly conserved molecule present in all life forms and functionally tied to the complexity of aerobic organisms on earth in utilizing oxygen from the atmosphere and delivering to cells and tissues. This primary function sustains the energy requirements of cells and maintains cellular homeostasis. Decades of intensive research has presented a paradigm shift that shows how the molecule also functions to facilitate smooth oxygen delivery through the cardiovascular system for cellular bioenergetic homeostasis and signaling for cell function and defense. These roles are particularly highlighted in the binding of Hb to gaseous molecules carbon dioxide (CO2), nitric oxide (NO) and carbon monoxide (CO), while also serving indirectly or directly as sources of these signaling molecules. The functional activities impacted by Hb outside of bioenergetics homeostasis, include fertilization, signaling functions, modulation of inflammatory responses for defense and cell viability. These activities are efficiently executed while Hb is sequestered safely within the confines of the red blood cell (rbc). Outside of rbc confines, Hb disaggregates and becomes a danger molecule to cell survival. In these perpectives, Hb function is broadly dichotomous, either a friend in its natural environment providing and facilitating the means for cell function or foe when dislocated from its habitat under stress or pathological condition disrupting cell function. The review presents insights into how this dichotomy in function manifests. PMID:25941490

  6. Intermolecular interactions, nucleation, and thermodynamics of crystallization of hemoglobin C.

    PubMed Central

    Vekilov, Peter G; Feeling-Taylor, Angela R; Petsev, Dimiter N; Galkin, Oleg; Nagel, Ronald L; Hirsch, Rhoda Elison

    2002-01-01

    The mutated hemoglobin HbC (beta 6 Glu-->Lys), in the oxygenated (R) liganded state, forms crystals inside red blood cells of patients with CC and SC diseases. Static and dynamic light scattering characterization of the interactions between the R-state (CO) HbC, HbA, and HbS molecules in low-ionic-strength solutions showed that electrostatics is unimportant and that the interactions are dominated by the specific binding of solutions' ions to the proteins. Microscopic observations and determinations of the nucleation statistics showed that the crystals of HbC nucleate and grow by the attachment of native molecules from the solution and that concurrent amorphous phases, spherulites, and microfibers are not building blocks for the crystal. Using a novel miniaturized light-scintillation technique, we quantified a strong retrograde solubility dependence on temperature. Thermodynamic analyses of HbC crystallization yielded a high positive enthalpy of 155 kJ mol(-1), i.e., the specific interactions favor HbC molecules in the solute state. Then, HbC crystallization is only possible because of the huge entropy gain of 610 J mol(-1) K(-1), likely stemming from the release of up to 10 water molecules per protein intermolecular contact-hydrophobic interaction. Thus, the higher crystallization propensity of R-state HbC is attributable to increased hydrophobicity resulting from the conformational changes that accompany the HbC beta 6 mutation. PMID:12124294

  7. Differential sensitivity of Chironomus and human hemoglobin to gamma radiation.

    PubMed

    Gaikwad, Pallavi S; Panicker, Lata; Mohole, Madhura; Sawant, Sangeeta; Mukhopadhyaya, Rita; Nath, Bimalendu B

    2016-08-01

    Chironomus ramosus is known to tolerate high doses of gamma radiation exposure. Larvae of this insect possess more than 95% of hemoglobin (Hb) in its circulatory hemolymph. This is a comparative study to see effect of gamma radiation on Hb of Chironomus and humans, two evolutionarily diverse organisms one having extracellular and the other intracellular Hb respectively. Stability and integrity of Chironomus and human Hb to gamma radiation was compared using biophysical techniques like Dynamic Light Scattering (DLS), UV-visible spectroscopy, fluorescence spectrometry and CD spectroscopy after exposure of whole larvae, larval hemolymph, human peripheral blood, purified Chironomus and human Hb. Sequence- and structure-based bioinformatics methods were used to analyze the sequence and structural similarities or differences in the heme pockets of respective Hbs. Resistivity of Chironomus Hb to gamma radiation is remarkably higher than human Hb. Human Hb exhibited loss of heme iron at a relatively low dose of gamma radiation exposure as compared to Chironomus Hb. Unlike human Hb, the heme pocket of Chironomus Hb is rich in aromatic amino acids. Higher hydophobicity around heme pocket confers stability of Chironomus Hb compared to human Hb. Previously reported gamma radiation tolerance of Chironomus can be largely attributed to its evolutionarily ancient form of extracellular Hb as evident from the present study. PMID:27237970

  8. Low hemoglobin levels are associated with upper gastrointestinal bleeding

    PubMed Central

    Tomizawa, Minoru; Shinozaki, Fuminobu; Hasegawa, Rumiko; Shirai, Yoshinori; Motoyoshi, Yasufumi; Sugiyama, Takao; Yamamoto, Shigenori; Ishige, Naoki

    2016-01-01

    Upper gastrointestinal (GI) bleeding can be fatal. Blood test variables were reviewed in search of threshold values to detect the presence of occult upper GI bleeding. The records of 1,023 patients who underwent endoscopy at the National Hospital Organization Shimoshizu Hospital from October 2014, to September 2015, were retrospectively reviewed. Of those, 95 had upper GI bleeding. One-way analysis of variance was applied to blood test variables comparing patients with and without upper GI bleeding. Logistic regression analysis was applied to detect the association of blood test parameters with upper GI bleeding, and receiver-operator characteristics were applied to establish threshold values. White blood cell count (WBC), platelet (Plt) count, and blood urea nitrogen (BUN) levels were higher, and hemoglobin (Hb) and albumin (Alb) levels were lower in patients with upper GI bleeding. Logistic regression analysis showed that low Hb was significantly associated with upper GI bleeding and a Hb value of 10.8 g/dl was established as the threshold for the diagnosis. In patients with upper GI bleeding, WBC, Plt count, and BUN levels were higher and Hb and Alb levels were reduced. Hb at 10.8 g/dl was established as a threshold value to detect upper GI bleeding. PMID:27588176

  9. Dual targeted poplar ferredoxin NADP(+) oxidoreductase interacts with hemoglobin 1.

    PubMed

    Jokipii-Lukkari, Soile; Kastaniotis, Alexander J; Parkash, Vimal; Sundström, Robin; Leiva-Eriksson, Nélida; Nymalm, Yvonne; Blokhina, Olga; Kukkola, Eija; Fagerstedt, Kurt V; Salminen, Tiina A; Läärä, Esa; Bülow, Leif; Ohlmeier, Steffen; Hiltunen, J Kalervo; Kallio, Pauli T; Häggman, Hely

    2016-06-01

    Previous reports have connected non-symbiotic and truncated hemoglobins (Hbs) to metabolism of nitric oxide (NO), an important signalling molecule involved in wood formation. We have studied the capability of poplar (Populus tremula × tremuloides) Hbs PttHb1 and PttTrHb proteins alone or with a flavin-protein reductase to relieve NO cytotoxicity in living cells. Complementation tests in a Hb-deficient, NO-sensitive yeast (Saccharomyces cerevisiae) Δyhb1 mutant showed that neither PttHb1 nor PttTrHb alone protected cells against NO. To study the ability of Hbs to interact with a reductase, ferredoxin NADP(+) oxidoreductase PtthFNR was characterized by sequencing and proteomics. To date, by far the greatest number of the known dual-targeted plant proteins are directed to chloroplasts and mitochondria. We discovered a novel variant of hFNR that lacks the plastid presequence and resides in cytosol. The coexpression of PttHb1 and PtthFNR partially restored NO resistance of the yeast Δyhb1 mutant, whereas PttTrHb coexpressed with PtthFNR failed to rescue growth. YFP fusion proteins confirmed the interaction between PttHb1 and PtthFNR in plant cells. The structural modelling results indicate that PttHb1 and PtthFNR are able to interact as NO dioxygenase. This is the first report on dual targeting of central plant enzyme FNR to plastids and cytosol. PMID:27095407

  10. Severe central nervous system thrombotic events in hemoglobin Sabine patient.

    PubMed

    Pavlovic, Sonja; Kuzmanovic, Milos; Urosevic, Jelena; Poznanic, Jelena; Zoranovic, Tamara; Djordjevic, Valentina; Rasovic, Nada; Bunjevacki, Gordana; Cvorkov-Drazic, Milica; Colovic, Milica

    2004-01-01

    Hemoglobin (Hb) Sabine is a rare, unstable Hb variant resulting from the point mutation in codon 91 (CTG --> CCG) of beta-globin gene. We report a case of Hb Sabine patient with mild hemolytic anemia, unusually high Hb F level and severe central nervous system thrombotic disturbances. We have tried to elucidate possible genetic background of this unusual Hb Sabine phenotype. Extremely high level of Hb F and rather mild anemia in our patient could be partially explained by the presence of G gamma Xmn I polymorphism. This case of Hb Sabine, unlike all other reported to date, shows extremely severe thromboembolic complications. It is our opinion that the hypercoagulable state described in thalassemia is not the only factor responsible for this specific clinical state. The presence of MTHFR C677T mutation in heterozygous state found in our patient and unstable Hb Sabine molecules could contribute to development of thromboembolic phenomena. However, it remains unclear whether other factors participate in pathogenesis of the disease. In this paper we emphasize different genetic background of father and son both affected with Hb Sabine, but with markedly different severity of the disease.

  11. Noninvasive in vivo monitoring of total blood hemoglobin

    NASA Astrophysics Data System (ADS)

    Wuori, Edward; Gmitter, Mary

    2003-07-01

    Blood hemoglobin (Hb) level is an important health parameter for a large segment of the population. Low Hb can indicate anemia due to chemotherapy, HIV, alcoholism, internal bleeding or other blood loss. There is a great need for noninvasive Hb measurement. A total blood Hb measurement method is shown which does not disturb the subject's skin. Results were obtained using MinforMed's noninvasive blood analyzer prototype (patent pending). A light is shined onto a body part, through the skin, engaging the blood. The emerging light is analyzed for Hb's signature strength in the visible and infrared ranges. Orthogonal decomposition methods are used to extract the Hb data from the complete spectrum. Results were compared to a laboratory-grade instrument that uses a drop of blood. A Hb range from 11 g/dL through 19 g/dL shows excellent correlation, r2=0.97. Other characteristics of the complete spectrum give indication of additional blood analytes, most notably bilirubin and water. Initial results are also shown indicating how light scattering varies with Hb concentration. Approximate residual skin and tissue spectrum is found by removing the spectral signature of the four Hb components (oxy-Hb, deoxy-Hb, carboxy-Hb and met-Hb) from the complete spectrum. This procedure yields the least squares concentrations of the individual Hb components. An SBIR grant from NIH is currently in progress on related work.

  12. Inherited hemoglobin disorders in an Afro-Amazonian community: Saracura

    PubMed Central

    Cardoso, Greice Lemos; Takanashi, Silvania Yukiko Lins; Guerreiro, João Farias

    2012-01-01

    The most common hemoglobinopathies, viz, hemoglobins S and C, and α- and β-thalassemias, were investigated through the molecular screening of 116 subjects from the community of Saracura, comprising fugitive African slaves from farms of the municipality of Santarém, in the west of Pará State, Brazilian Amazon. The observed frequency of the HBB*S gene (0.9%) was significantly lower than that encountered in other Afro-derived communities in the region. Concomitantly, the absence of the HBB*C allele has been reported for most of the Afro-Amazonian communities thus far studied. As remnant populations of quilombos are generally small, the heterogeneous distribution of HBB*S and HBB*C alleles among them is probably due to genetic drift and/or founder effect. The observed frequency of 3.7 kb deletion in Saracura (8.5%) was consistent with the African origin of the population, with a certain degree of local differentiation and admixture with individuals of Caucasian ancestry, placed in evidence by the occurrence of - -(MED) deletion (1.2%), a common mutation in Mediterranean regions. As regards β-thalassemia, among the seven different mutations found in Saracura, three βo and two β+ mutations were of Mediterranean origin, and two β+ of African. Thus, only 28% of the local β-thalassemia mutations found in Saracura were of African origin. PMID:23055791

  13. Association of Hemoglobin Concentration With Total and Cause-Specific Mortality in a Cohort of Postmenopausal Women.

    PubMed

    Kabat, Geoffrey C; Kim, Mimi Y; Verma, Amit K; Manson, JoAnn E; Lessin, Lawrence S; Kamensky, Victor; Lin, Juan; Wassertheil-Smoller, Sylvia; Rohan, Thomas E

    2016-05-15

    Anemia and low and high levels of hemoglobin have been associated with increased mortality and morbidity. However, most studies have measured hemoglobin at only 1 time point, and few studies have considered possible reverse causation. We used data from the Women's Health Initiative, in which baseline hemoglobin was measured in 160,081 postmenopausal women and year 3 hemoglobin was measured in 75,658 participants, to examine the associations of hemoglobin concentration with total mortality, coronary heart disease mortality, and cancer mortality. Women were enrolled from 1993 to 1998 and followed for a median of 16 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline hemoglobin and the mean of baseline + year 3 hemoglobin. Both low and high deciles of baseline hemoglobin were positively associated with all 3 outcomes in the total cohort. In analyses restricted to women with 2 measurements, a low mean hemoglobin level was robustly and positively associated with all 3 outcomes, after exclusion of the early years of follow-up. High mean hemoglobin was also associated with increased risk of total mortality, whereas associations with heart disease mortality and cancer mortality were weaker and inconsistent. Our results provide evidence that low and high levels of hemoglobin are associated with increased risk of mortality in otherwise healthy women. PMID:27076671

  14. Immune Abnormalities in Patients with Autism.

    ERIC Educational Resources Information Center

    Warren, Reed P.; And Others

    1986-01-01

    A study of 31 autistic patients (3-28 years old) has revealed several immune-system abnormalities, including decreased numbers of T lymphocytes and an altered ratio of helper-to-suppressor T cells. Immune-system abnormalities may be directly related to underlying biologic processes of autism or an indirect reflection of the actual pathologic…

  15. An Abnormal Psychology Community Based Interview Assignment

    ERIC Educational Resources Information Center

    White, Geoffry D.

    1977-01-01

    A course option in abnormal psychology involves students in interviewing and observing the activities of individuals in the off-campus community who are concerned with some aspect of abnormal psychology. The technique generates student interest in the field when they interview people about topics such as drug abuse, transsexualism, and abuse of…

  16. Detection of Structural Abnormalities Using Neural Nets

    NASA Technical Reports Server (NTRS)

    Zak, M.; Maccalla, A.; Daggumati, V.; Gulati, S.; Toomarian, N.

    1996-01-01

    This paper describes a feed-forward neural net approach for detection of abnormal system behavior based upon sensor data analyses. A new dynamical invariant representing structural parameters of the system is introduced in such a way that any structural abnormalities in the system behavior are detected from the corresponding changes to the invariant.

  17. Nail abnormalities in patients with vitiligo*

    PubMed Central

    Topal, Ilteris Oguz; Gungor, Sule; Kocaturk, Ozgur Emek; Duman, Hatice; Durmuscan, Mustafa

    2016-01-01

    Background Vitiligo is an acquired pigmentary skin disorder affecting 0.1-4% of the general population. The nails may be affected in patients with an autoimmune disease such as psoriasis, and in those with alopecia areata. It has been suggested that nail abnormalities should be apparent in vitiligo patients. Objective We sought to document the frequency and clinical presentation of nail abnormalities in vitiligo patients compared to healthy volunteers. We also examined the correlations between nail abnormalities and various clinical parameters. Methods This study included 100 vitiligo patients and 100 healthy subjects. Full medical histories were collected from the subjects, who underwent thorough general and nail examinations. All nail changes were noted. In the event of clinical suspicion of a fungal infection, additional mycological investigations were performed. Results Nail abnormalities were more prevalent in the patients (78%) than in the controls (55%) (p=0.001). Longitudinal ridging was the most common finding (42%), followed by (in descending order): leukonychia, an absent lunula, onycholysis, nail bed pallor, onychomycosis, splinter hemorrhage and nail plate thinning. The frequency of longitudinal ridging was significantly higher in patients than in controls (p<0.001). Conclusions Nail abnormalities were more prevalent in vitiligo patients than in controls. Systematic examination of the nails in such patients is useful because nail abnormalities are frequent. However, the causes of such abnormalities require further study. Longitudinal ridging and leukonychia were the most common abnormalities observed in this study. PMID:27579738

  18. Skeletal Muscle Abnormalities in Heart Failure.

    PubMed

    Kinugawa, Shintaro; Takada, Shingo; Matsushima, Shouji; Okita, Koichi; Tsutsui, Hiroyuki

    2015-01-01

    Exercise capacity is lowered in patients with heart failure, which limits their daily activities and also reduces their quality of life. Furthermore, lowered exercise capacity has been well demonstrated to be closely related to the severity and prognosis of heart failure. Skeletal muscle abnormalities including abnormal energy metabolism, transition of myofibers from type I to type II, mitochondrial dysfunction, reduction in muscular strength, and muscle atrophy have been shown to play a central role in lowered exercise capacity. The skeletal muscle abnormalities can be classified into the following main types: 1) low endurance due to mitochondrial dysfunction; and 2) low muscle mass and muscle strength due to imbalance of protein synthesis and degradation. The molecular mechanisms of these skeletal muscle abnormalities have been studied mainly using animal models. The current review including our recent study will focus upon the skeletal muscle abnormalities in heart failure. PMID:26346520

  19. Binding of hydroxylated single-walled carbon nanotubes to two hemoproteins, hemoglobin and myoglobin.

    PubMed

    Wang, Yan-Qing; Zhang, Hong-Mei; Cao, Jian

    2014-12-01

    Herein, we studied the binding interactions between hydroxylated single-walled carbon nanotubes and hemoglobin and myoglobin by the use of multi-spectral techniques and molecular modeling. The ultraviolet-vis absorbance and circular dichroism spectral results indicated that the binding interactions existed between hydroxylated single-walled carbon nanotubes and hemoglobin/myoglobin. These binding interactions partially affected the soret/heme bands of hemoglobin and myoglobin. The secondary structures of hemoproteins were partially destroyed by hydroxylated single-walled carbon nanotubes. Fluorescence studies suggested that the complexes formed between hydroxylated single-walled carbon nanotubes and hemoglobin/myoglobin by hydrogen bonding, hydrophobic, and π-π stacking interactions. In addition, molecular modeling analysis well supported the experimental results.

  20. Oxygen binding properties of hemoglobin from the white rhinoceros (beta 2-GLU) and the tapir.

    PubMed

    Baumann, R; Mazur, G; Braunitzer, G

    1984-04-01

    The beta-chain of rhinoceros hemoglobin contains glutamic acid at position beta 2, and important site for the binding of organic phosphates. We have investigated the oxygen binding properties of this hemoglobin and its interaction with ATP, 2,3-diphosphoglycerate, CO2 and chloride. The results show that the presence of GLU at position beta 2 nearly abolishes the effect of organic phosphates and CO2, whereas the oxygen-linked binding of chloride is not affected. Thus rhinoceros hemoglobin has only protons and chloride anions as major allosteric effectors for the control of its oxygen affinity. From the results obtained with hemoglobin solutions it can be calculated that the blood oxygen affinity of the rhinoceros must be rather high with a P50 of about 20 torr at pH 7.4 and 37 degrees C, which conforms with observations obtained for other large mammals.

  1. Towards erythropoietin equations that estimate oxygen delivery rather than static hemoglobin targets.

    PubMed

    Diskin, Charles J

    2012-01-01

    Although we have known since the 19th century that oxygen tension affects erythrocyte production, we have only recently begun to understand many subtleties of erythropoietin physiology. The unanticipated increase in mortality associated with erythropoietin use found in recent randomized studies is prompting a reassessment of static hemoglobin targets. Hemoglobin levels in dialysis patients do not correlate with endogenous erythropoietin production and may be related to differences in oxygen delivery resulting from shifts in the oxygen-hemoglobin dissociation curve. The time may have arrived to develop more physiologic targets such as oxygen delivery that would mimic the natural response to hypoxia. There are several equations that already exist that can compensate for the effects of the concentration of inorganic and organic phosphates as well as pH, carbon dioxide, and temperature on the delivery of oxygen. However, since the shape and dispersion of the oxygen-hemoglobin dissociation curve may actually change in different disease states, more work is needed.

  2. Substitution of Fingertip Blood for Venous Blood in the Measurement of Hematocrit and Hemoglobin Following Exercise

    ERIC Educational Resources Information Center

    Fahey, Thomas D.; And Others

    1977-01-01

    Results from comparative testing indicate that fingertip blood is a valid indicator of antecubital venous hematocrit (hct) and hemoglobin (hgb), and that hct ratios determined on the Coulter counter are comparable to those found by the microhematocrit method. (MB)

  3. Effects of Iron Supplementation and Activity on Serum Iron Depletion and Hemoglobin Levels in Female Athletes

    ERIC Educational Resources Information Center

    Cooter, G. Rankin; Mowbray, Kathy W.

    1978-01-01

    Research revealed that a four-month basketball training program did not significantly alter serum iron, total iron binding capacity, hemoglobin, and percent saturation levels in female basketball athletes. (JD)

  4. Glycosylated hemoglobin determination from capillary blood samples. Utility in an epidemiologic survey of diabetes.

    PubMed

    Ferrell, R E; Hanis, C L; Aguilar, L; Tulloch, B; Garcia, C; Schull, W J

    1984-02-01

    Total glycosylated hemoglobin was measured from capillary blood specimens obtained from a sample of 1880 individuals of Mexican-American ancestry residing in Starr County, Texas, between January 1981 and February 1982, as part of an epidemiologic survey to assess the prevalence of noninsulin-dependent diabetes mellitus (Type II). No significant difference was found between males and females. Diabetics were found to have significantly higher levels of glycosylated hemoglobin than nondiabetics. However, among diabetics, there was no significant difference between newly diagnosed and known diabetics, and known diabetics taking medication did not differ significantly from those not taking medication. An analysis of the specificity and sensitivity of glycosylated hemoglobin, fasting blood glucose, and casual blood glucose determinations as screening devices in a survey of diabetes prevalence reveals that glycosylated hemoglobin is superior to casual blood glucose determination. The conditions under which various screening devices might be more effective are discussed. PMID:6695895

  5. Assessment of hemoglobin dynamics in traumatic bruises using temperature depth profiling

    NASA Astrophysics Data System (ADS)

    Vidovič, Luka; Milanič, Matija; Majaron, Boris

    2013-11-01

    Perceived color of traumatic bruise depends strongly on depth of the spilled blood, natural skin tone, ambient light conditions, etc., which prevents an accurate and reliable determination of the time of the injury. Pulsed photothermal radiometry (PPTR) allows noninvasive determination of the laser-induced temperature depth profile in human skin. We have applied this technique to characterize dynamics of extravasated hemoglobin in the bruise. Next, we use simple model of mass diffusion and biochemical transformation kinetics to simulate bruise dynamics. By applying Monte Carlo simulation of laser energy deposition, comparison with measured temperature profiles is possible. However, parameters of the model were previously not determined directly. Instead, biologically plausible values were assumed. We show how temperature depth profiling enables accurate monitoring of hemoglobin diffusion and degradation. Parameters of the model, hemoglobin mass diffusivity, hemoglobin degradation time, and skin geometry, can be estimated rather accurately. Derivation of bruise evolution parameters will be a valuable addition to existing bruise age determination techniques.

  6. Fetal hemoglobin in sickle cell anemia: molecular characterization of the unusually high fetal hemoglobin phenotype in African Americans.

    PubMed

    Akinsheye, Idowu; Solovieff, Nadia; Ngo, Duyen; Malek, Anita; Sebastiani, Paola; Steinberg, Martin H; Chui, David H K

    2012-02-01

    Fetal hemoglobin (HbF) is a major modifier of disease severity in sickle cell anemia (SCA). Three major HbF quantitative trait loci (QTL) are known: the Xmn I site upstream of (G)γ- globin gene (HBG2) on chromosome 11p15, BCL11A on chromosome 2p16, and HBS1L-MYB intergenic polymorphism (HMIP) on chromosome 6q23. However, the roles of these QTLs in patients with SCA with uncharacteristically high HbF are not known. We studied 20 African American patients with SCA with markedly elevated HbF (mean 17.2%). They had significantly higher minor allele frequencies (MAF) in two HbF QTLs, BCL11A, and HMIP, compared with those with low HbF. A 3-bp (TAC) deletion in complete linkage disequilibrium (LD) with the minor allele of rs9399137 in HMIP was also present significantly more often in these patients. To further explore other genetic loci that might be responsible for this high HbF, we sequenced a 14.1 kb DNA fragment between the (A)γ-(HBG1) and δ-globin genes (HBD). Thirty-eight SNPs were found. Four SNPs had significantly higher major allele frequencies in the unusually high HbF group. In silico analyses of these four polymorphisms predicted alteration in transcription factor binding sites in 3.

  7. Inducible heme oxygenase in the kidney: a model for the homeostatic control of hemoglobin catabolism

    PubMed Central

    Pimstone, Neville R.; Engel, Peter; Tenhunen, Raimo; Seitz, Paul T.; Marver, Harvey S.; Schmid, Rudi

    1971-01-01

    We have recently identified and characterized NADPH-dependent microsomal heme oxygenase as the major enzymatic mechanism for the conversion of hemoglobin-heme to bilirubin-IXα in vivo. Enzyme activity is highest in tissues normally involved in red cell breakdown, that is, spleen, liver, and bone marrow, but it usually is negligible in the kidney. However, renal heme oxygenase activity may be transiently increased 30- to 100-fold following hemoglobinemia that exceeded the plasma haptoglobin-binding capacity and consequently resulted in hemoglobinuria. Maximal stimulation of enzyme activity in rats is reached 6-16 hr following a single intravenous injection of 30 mg of hemoglobin per 100 g body weight; activity returns to basal levels after about 48 hr. At peak level, total enzyme activity in the kidneys exceeds that of the spleen or liver. Cyclohexamide, puromycin, or actinomycin D, given just before, or within a few hours after, a single intravenous injection of hemoglobin minimizes or prevents the rise in renal enzyme activity; this suggests that the increase in enzyme activity is dependent on continued synthesis of ribonucleic acid and protein. The apparent biological half-life of renal heme oxygenase is about 6 hr. These observations indicate that functional adaptation of renal heme oxygenase activity reflects enzyme induction either directly or indirectly by the substrate, hemoglobin. Filtered rather than plasma hemoglobin appears to regulate renal heme oxygenase activity. Thus, stabilization of plasma hemoglobin in its tetrameric form with bis (N-maleimidomethyl) ether, which diminishes its glomerular filtration and retards it plasma clearance, results in reduced enzyme stimulation in the kidney, but enhances its activity in the liver. These findings suggest that the enzyme is localized in the tubular epithelial cells rather than in the glomeruli and is activated by luminal hemoglobin. Direct support for this concept was obtained by the demonstration of heme

  8. Hemoglobin and hip fracture risk in older non-Hispanic white adults1

    PubMed Central

    Looker, Anne C.

    2016-01-01

    Purpose The few studies to date that have examined the relationship between hemoglobin and fracture risk have focused on low hemoglobin values. The present study examined hip fracture risk across the hemoglobin distribution in older non-Hispanic white adults from the third National Health and Nutrition Examination Survey (NHANES III, 1988–1994). Methods Hemoglobin was measured using a Coulter S-plus Jr.® (Coulter Electronics, Hialeah, FL) in 2122 non-Hispanic whites age 65 years and older. Hip fracture cases were identified using linked Medicare and mortality records obtained through 2007. Cox proportional hazards models were used to assess the best-fitting model and to estimate the hazards ratio (HR) for hip fracture by hemoglobin decile before and after adjusting for selected confounders. Results There were 239 hip fracture cases in the analytic sample. The best fitting model was quadratic. When compared to values in the middle of the distribution, those with hemoglobin in the lowest and highest deciles had increased hip fracture risk (HRlowest decile =2.96, 95% CI 1.44–6.08; HRhighest decile = 2.06, 95% CI 1.09–3.92) after adjusting for age and sex. Both HRs remained significant after adjusting for additional confounders (HRlowest decile =2.24, 95% CI 1.09–3.92; HRhighest decile = 2.37, 95% CI 1.35–4.16). Conclusions Both low and high hemoglobin values were associated with increased hip fracture risk. The mechanism underlying the relationship is not clear, but there was some suggestion that it may differ for low versus high hemoglobin. PMID:24938506

  9. Association of hemoglobin with ankle-brachial index in general population

    PubMed Central

    Chenglong, Zhang; Jing, Lei; Xia, Ke; Yang, Tianlun

    2016-01-01

    OBJECTIVES: Previous studies have demonstrated that both low and high hemoglobin concentrations are predictive of adverse cardiovascular outcomes in various populations. However, an association of hemoglobin with the ankle-brachial index, which is widely used as a screening test for peripheral arterial disease, has not yet been identified. METHODS: We examined 786 subjects (236 women and 550 men) who received routine physical check-ups. The ankle-brachial index and several hematological parameters, including the hemoglobin level, hematocrit and red blood cell count and other demographic and biochemical characteristics were collected. Univariate and multivariate linear regression analyses were performed to assess the relationships between the ankle-brachial index and the independent determinants. Receiver operating characteristic curve analysis was conducted to calculate the cut-off level of hemoglobin for a relatively low ankle-brachial index (less than 20% of all subjects, which was 1.02). RESULTS: The hemoglobin level, hematocrit and red blood cell count were correlated with the ankle-brachial index in the males (r=-0.274, r=-0.224 and r=-0.273, respectively, p<0.001 for all), but these associations were not significant in the females. Multivariate linear regression analysis revealed that the independent determinants of the ankle-brachial index included age, total cholesterol, high-density lipoprotein cholesterol and the white blood cell count for the females and age, hypertension, total cholesterol and hemoglobin (β=-0.001, p<0.001) for the males after adjusting for confounding factors. Receiver operating characteristic curve analysis revealed that the cut-off level of hemoglobin for predicting a low ankle-brachial index was 156.5 g/L in the males. CONCLUSIONS: A high hemoglobin concentration was independently correlated with a low ankle-brachial index in the healthy males, indicating that an elevation in this level may be associated with an increased

  10. The hemoglobin system of the brown moray Gymnothorax unicolor: structure/function relationships.

    PubMed

    Tamburrini, M; Verde, C; Olianas, A; Giardina, B; Corda, M; Sanna, M T; Fais, A; Deiana, A M; di Prisco, G; Pellegrini, M

    2001-07-01

    The Gymnothorax unicolor hemoglobin system is characterized by two components, called cathodic and anodic on the basis of their isoelectric point, which were separated by ion-exchange chromatography. The oxygen-binding properties of the purified components were studied in the absence and presence of chloride and/or GTP or ATP in the pH range 6.5-8.0. Stripped cathodic hemoglobin showed a small reverse Bohr effect, high oxygen affinity, and low co-operativity; the addition of chloride only caused a small decrease in oxygen affinity. In the presence of GTP or ATP, the oxygen affinity was dramatically reduced, the co-operativity increased, and the reverse Bohr effect abolished. Stripped anodic hemoglobin is characterized by both low oxygen affinity and co-operativity, and displayed a normal Bohr effect; the addition of chloride increased co-operativity, whereas ATP and GTP significantly modulated oxygen affinity at acidic pH values, enhancing the Bohr effect and giving rise to the Root effect. The complete amino-acid sequences of the alpha and beta chains of both hemoglobins were established; the molecular basis of the functional properties of the hemoglobins is discussed in the light of the primary structure and compared with those of other fish hemoglobins.

  11. Comparison of two iron supplementation methods on Hemoglobin level and Menstrual Bleeding in Tabriz students

    PubMed Central

    Bani, S; Hassanpour- Siahestalkhi, A; Hassanpour, Sh; Mommad- Alizadeh- Charandabi, S; Mirghafourvand, M; Javadzadeh, Y

    2014-01-01

    Background Iron deficiency anemia is a global health problem, and approximately 50% of anemia is caused by iron deficiency. According to studies, iron supplementation in young females improves iron status by increasing concentration of hemoglobin. To compare of prescribing two methods of iron supplementation administered either on a weekly basis or during menstruation, on hemoglobin level and menstrual blood¸ this double blind Randomized clinical trial study was carried out among female students in Tabriz, Iran. Materials and Methods In this double-blind randomized clinical trial, 150 female students allocated randomly in two groups. (75 students took an iron tablet weekly and 75 students took an iron tablet for first four days during their menstruation cycle for 16 weeks). Before and after intervention, the level of hemoglobin was measured and Higham chart was completed by participants in each group. Chi-square, independent t-Test, paired t-Test and ANCOVA were used for data analysis. Results There was no significant difference between two groups in terms of demographic characteristics, hemoglobin level and amount of menstrual bleeding before and after intervention (p>0.05). Taking iron supplement increased significantly the level of hemoglobin in each group (p<0.001). However, there was no significant difference in amount of menstrual bleeding (p>0.05) when comparing the data before and after intervention in each group. Conclusion The two iron supplementation methods (menstrual bleeding period and weekly) have similar results on Hemoglobin level and menstrual bleeding. PMID:24734158

  12. Investigation of Hemoglobin/Gold Nanoparticle Heterolayer on Micro-Gap for Electrochemical Biosensor Application

    PubMed Central

    Lee, Taek; Kim, Tae-Hyung; Yoon, Jinho; Chung, Yong-Ho; Lee, Ji Young; Choi, Jeong-Woo

    2016-01-01

    In the present study, we fabricated a hemoglobin/gold nanoparticle (Hb/GNP) heterolayer immobilized on the Au micro-gap to confirm H2O2 detection with a signal-enhancement effect. The hemoglobin which contained the heme group catalyzed the reduction of H2O2. To facilitate the electron transfer between hemoglobin and Au micro-gap electrode, a gold nanoparticle was introduced. The Au micro-gap electrode that has gap size of 5 µm was fabricated by conventional photolithographic technique to locate working and counter electrodes oppositely in a single chip for the signal sensitivity and reliability. The hemoglobin was self-assembled onto the Au surface via chemical linker 6-mercaptohexanoic acid (6-MHA). Then, the gold nanoparticles were adsorbed onto hemoglobin/6-MHA heterolayers by the layer-by-layer (LbL) method. The fabrication of the Hb/GNP heterolayer was confirmed by atomic force microscopy (AFM) and surface-enhanced Raman spectroscopy (SERS). The redox property and H2O2 detection of Hb/GNP on the micro-gap electrode was investigated by a cyclic voltammetry (CV) experiment. Taken together, the present results show that the electrochemical signal-enhancement effect of a hemoglobin/nanoparticle heterolayer was well confirmed on the micro-scale electrode for biosensor applications. PMID:27171089

  13. A spectroscopic study on the interaction between gold nanoparticles and hemoglobin

    SciTech Connect

    Garabagiu, Sorina

    2011-12-15

    Highlights: Black-Right-Pointing-Pointer The interaction was studied using UV-vis and fluorescence spectroscopy. Black-Right-Pointing-Pointer Gold nanoparticles quench the fluorescence emission of hemoglobin solution. Black-Right-Pointing-Pointer The binding and thermodynamic constants were calculated. Black-Right-Pointing-Pointer Major impact: electrochemical applications of the complex onto a substrate. -- Abstract: The interaction between horse hemoglobin and gold nanoparticles was studied using optical spectroscopy. UV-vis and fluorescence spectra show that a spontaneous binding process occurred between hemoglobin and gold nanoparticles. The Soret band of hemoglobin in the presence of gold nanoparticles does not show significant changes, which proves that the protein retained its biological function. A shift to longer wavelengths appears in the plasmonic band of gold nanoparticles upon the attachment of hemoglobin molecules. Gold nanoparticles quench the fluorescence emission of tryptophan residues in the structure of hemoglobin. The Stern-Volmer quenching constant, the binding constant and the number of binding sites were also calculated. Thermodynamic parameters indicate that the binding was mainly due to hydrophobic interactions.

  14. Increased hemoglobin-oxygen affinity ameliorates bleomycin-induced hypoxemia and pulmonary fibrosis.

    PubMed

    Geng, Xin; Dufu, Kobina; Hutchaleelaha, Athiwat; Xu, Qing; Li, Zhe; Li, Chien-Ming; Patel, Mira P; Vlahakis, Nicholas; Lehrer-Graiwer, Josh; Oksenberg, Donna

    2016-09-01

    Although exertional dyspnea and worsening hypoxia are hallmark clinical features of idiopathic pulmonary fibrosis (IPF), no drug currently available could treat them. GBT1118 is a novel orally bioavailable small molecule that binds to hemoglobin and produces a concentration-dependent left shift of the oxygen-hemoglobin dissociation curve with subsequent increase in hemoglobin-oxygen affinity and arterial oxygen loading. To assess whether pharmacological modification of hemoglobin-oxygen affinity could ameliorate hypoxemia associated with lung fibrosis, we evaluated GBT1118 in a bleomycin-induced mouse model of hypoxemia and fibrosis. After pulmonary fibrosis and hypoxemia were induced, GBT1118 was administered for eight consecutive days. Hypoxemia was determined by monitoring arterial oxygen saturation, while the severity of pulmonary fibrosis was assessed by histopathological evaluation and determination of collagen and leukocyte levels in bronchoalveolar lavage fluid. We found that hemoglobin modification by GBT1118 had strong antihypoxemic therapeutic effects with improved arterial oxygen saturation to near normal level. Moreover, GBT1118 treatment significantly attenuated bleomycin-induced lung fibrosis, collagen accumulation, body weight loss, and leukocyte infiltration. This study is the first to suggest the beneficial effects of hemoglobin modification in fibrotic lungs and offers a promising and novel therapeutic strategy for the treatment of hypoxemia associated with chronic fibrotic lung disorders in human, including IPF. PMID:27624688

  15. EHMT1 and EHMT2 inhibition induces fetal hemoglobin expression

    PubMed Central

    Renneville, Aline; Van Galen, Peter; Canver, Matthew C.; McConkey, Marie; Krill-Burger, John M.; Dorfman, David M.; Holson, Edward B.; Bernstein, Bradley E.; Orkin, Stuart H.; Bauer, Daniel E.

    2015-01-01

    Fetal hemoglobin (HbF, α2γ2) induction is a well-validated strategy for sickle cell disease (SCD) treatment. Using a small-molecule screen, we found that UNC0638, a selective inhibitor of EHMT1 and EHMT2 histone methyltransferases, induces γ-globin expression. EHMT1/2 catalyze mono- and dimethylation of lysine 9 on histone 3 (H3K9), raising the possibility that H3K9Me2, a repressive chromatin mark, plays a role in silencing γ-globin expression. In primary human adult erythroid cells, UNC0638 and EHMT1 or EHMT2 short hairpin RNA–mediated knockdown significantly increased γ-globin expression, HbF synthesis, and the percentage of cells expressing HbF. At effective concentrations, UNC0638 did not alter cell morphology, proliferation, or erythroid differentiation of primary human CD34+ hematopoietic stem and progenitor cells in culture ex vivo. In murine erythroleukemia cells, UNC0638 and Ehmt2 CRISPR/Cas9-mediated knockout both led to a marked increase in expression of embryonic β-globin genes Hbb-εy and Hbb-βh1. In primary human adult erythroblasts, chromatin immunoprecipitation followed by sequencing analysis revealed that UNC0638 treatment leads to genome-wide depletion in H3K9Me2 and a concomitant increase in the activating mark H3K9Ac, which was especially pronounced at the γ-globin gene region. In RNA-sequencing analysis of erythroblasts, γ-globin genes were among the most significantly upregulated genes by UNC0638. Further increase in γ-globin expression in primary human adult erythroid cells was achieved by combining EHMT1/2 inhibition with the histone deacetylase inhibitor entinostat or hypomethylating agent decitabine. Our data provide genetic and pharmacologic evidence that EHMT1 and EHMT2 are epigenetic regulators involved in γ-globin repression and represent a novel therapeutic target for SCD. PMID:26320100

  16. Hemoglobin enhances tissue factor expression on human malignant cells.

    PubMed

    Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

    2001-04-01

    Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined.

  17. The pathophysiology of extracellular hemoglobin associated with enhanced oxidative reactions

    PubMed Central

    Rifkind, Joseph M.; Mohanty, Joy G.; Nagababu, Enika

    2015-01-01

    Hemoglobin (Hb) continuously undergoes autoxidation producing superoxide which dismutates into hydrogen peroxide (H2O2) and is a potential source for subsequent oxidative reactions. Autoxidation is most pronounced under hypoxic conditions in the microcirculation and for unstable dimers formed at reduced Hb concentrations. In the red blood cell (RBC), oxidative reactions are inhibited by an extensive antioxidant system. For extracellular Hb, whether from hemolysis of RBCs and/or the infusion of Hb-based blood substitutes, the oxidative reactions are not completely neutralized by the available antioxidant system. Un-neutralized H2O2 oxidizes ferrous and ferric Hbs to Fe(IV)-ferrylHb and OxyferrylHb, respectively. FerrylHb further reacts with H2O2 producing heme degradation products and free iron. OxyferrylHb, in addition to Fe(IV) contains a free radical that can undergo additional oxidative reactions. Fe(III)Hb produced during Hb autoxidation also readily releases heme, an additional source for oxidative stress. These oxidation products are a potential source for oxidative reactions in the plasma, but to a greater extent when the lower molecular weight Hb dimers are taken up into cells and tissues. Heme and oxyferryl have been shown to have a proinflammatory effect further increasing their potential for oxidative stress. These oxidative reactions contribute to a number of pathological situations including atherosclerosis, kidney malfunction, sickle cell disease, and malaria. The toxic effects of extracellular Hb are of particular concern with hemolytic anemia where there is an increase in hemolysis. Hemolysis is further exacerbated in various diseases and their treatments. Blood transfusions are required whenever there is an appreciable decrease in RBCs due to hemolysis or blood loss. It is, therefore, essential that the transfused blood, whether stored RBCs or the blood obtained by an Autologous Blood Recovery System from the patient, do not further increase

  18. Relationship between periodontal status and levels of glycated hemoglobin.

    PubMed

    Morita, I; Inagaki, K; Nakamura, F; Noguchi, T; Matsubara, T; Yoshii, S; Nakagaki, H; Mizuno, K; Sheiham, A; Sabbah, W

    2012-02-01

    The objective of this study was to assess whether there is a bi-directional relationship between periodontal status and diabetes. Study 1 included 5,856 people without periodontal pockets of ≥ 4 mm at baseline. Relative risk was estimated for the 5-year incidence of periodontal pockets of ≥ 4 mm (CPI scores 3 and 4, with the CPI probe), in individuals with glycated hemoglobin (HbA1c) levels of ≥ 6.5% at baseline. Study 2 included 6,125 people with HbA1c < 6.5% at baseline. The relative risk was assessed for elevation of HbA1c levels in 5 years, with baseline periodontal status, assessed by CPI. Relative risk of developing a periodontal pocket was 1.17 (p = 0.038) times greater in those with HbA1c of ≥ 6.5% at baseline, adjusted for body mass index (BMI), smoking status, sex, and age. Relative risks for having HbA1c ≥ 6.5% at 5-year follow-up in groups with periodontal pockets of 4 to 5 mm and ≥ 6 mm at baseline were 2.47 (p = 0.122) and 3.45 (p = 0.037), respectively, adjusted for BMI, alcohol consumption, smoking status, sex, and age. The risk of developing periodontal disease was associated with levels of HbA1c, and the risk of elevations of HbA1c was associated with developing periodontal pockets of more than 4 mm. PMID:22157098

  19. [Glycosylated hemoglobin (HbA1) in pregnancy].

    PubMed

    Partida Hernández, G; Gómez García, A; Arreola Ortíz, J F

    2000-10-01

    The life style, genetic predisposition and metabolic changes occurring during pregnancy can modify the percent value of glycated hemoglobins (HbA1 and HbA1c). In addition, research papers from different laboratories in the world have reported contradictory results on this respect. The purpose of this trial was to know the percent value of HbA1 in healthy women, during the different trimesters of pregnancy. 206 pregnant (E) healthy women who came over for prenatal control to UMF No 80 IMSS in Morelia, Michoacan with no previous history of Diabetes mellitus or Essential Hypertension were classified by trimesters of pregnancy (1T, 2T, 3T) and chronological age (I, 18-24; 11, 25-30; III, 31-35 years). Their chronological and gestational ages, weight, height, body mass index and parity were recorded. % HbA1 (ion exchange chromatography) was determined on each patient. Control group was formed by 187 non pregnant healthy women (NE) chosen with same criterion that pregnant women. % HbA1 was lower in E during pregnancy (7.11 +/- 1.53 vs 7.78 +/- 1.12%, p < 0.0001) than NE group. % HbA1 in E group was lower in the 1T and 2T than in the 3T (p < 0.001), same situation was observed in 18 to 24 (group I) and 25 to 30 (group II) years old. In the other hand, in E from group II on the 2T the weeks of gestation were correlated with % HbA1 (r = 0.72, p < 0.05). This results show a diminished HbA1 percent in E group with a lower values in the 1T and 2T. Moreover, these results will allow us to know HbA1 appearance in diabetic pregnant women and to evaluate the degree of metabolic control.

  20. Oxygenation properties and isoform diversity of snake hemoglobins.

    PubMed

    Storz, Jay F; Natarajan, Chandrasekhar; Moriyama, Hideaki; Hoffmann, Federico G; Wang, Tobias; Fago, Angela; Malte, Hans; Overgaard, Johannes; Weber, Roy E

    2015-11-01

    Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer-dimer dissociation. However, standardized comparative data are lacking for snake Hbs, and the Hb isoform composition of snake red blood cells has not been systematically characterized. Here we present the results of an integrated analysis of snake Hbs and the underlying α- and β-type globin genes to characterize 1) Hb isoform composition of definitive erythrocytes, and 2) the oxygenation properties of isolated isoforms as well as composite hemolysates. We used species from three families as subjects for experimental studies of Hb function: South American rattlesnake, Crotalus durissus (Viperidae); Indian python, Python molurus (Pythonidae); and yellow-bellied sea snake, Pelamis platura (Elapidae). We analyzed allosteric properties of snake Hbs in terms of the Monod-Wyman-Changeux model and Adair four-step thermodynamic model. Hbs from each of the three species exhibited high intrinsic O2 affinities, low cooperativities, small Bohr factors in the absence of phosphates, and high sensitivities to ATP. Oxygenation properties of the snake Hbs could be explained entirely by allosteric transitions in the quaternary structure of intact tetramers, suggesting that ligation-dependent dissociation of Hb tetramers into αβ-dimers is not a universal feature of snake Hbs. Surprisingly, the major Hb isoform of the South American rattlesnake is homologous to the minor HbD of other amniotes and, contrary to the pattern of Hb isoform differentiation in birds and turtles, exhibits a lower O2 affinity than the HbA isoform. PMID:26354849

  1. Oxygenation properties and isoform diversity of snake hemoglobins.

    PubMed

    Storz, Jay F; Natarajan, Chandrasekhar; Moriyama, Hideaki; Hoffmann, Federico G; Wang, Tobias; Fago, Angela; Malte, Hans; Overgaard, Johannes; Weber, Roy E

    2015-11-01

    Available data suggest that snake hemoglobins (Hbs) are characterized by a combination of unusual structural and functional properties relative to the Hbs of other amniote vertebrates, including oxygenation-linked tetramer-dimer dissociation. However, standardized comparative data are lacking for snake Hbs, and the Hb isoform composition of snake red blood cells has not been systematically characterized. Here we present the results of an integrated analysis of snake Hbs and the underlying α- and β-type globin genes to characterize 1) Hb isoform composition of definitive erythrocytes, and 2) the oxygenation properties of isolated isoforms as well as composite hemolysates. We used species from three families as subjects for experimental studies of Hb function: South American rattlesnake, Crotalus durissus (Viperidae); Indian python, Python molurus (Pythonidae); and yellow-bellied sea snake, Pelamis platura (Elapidae). We analyzed allosteric properties of snake Hbs in terms of the Monod-Wyman-Changeux model and Adair four-step thermodynamic model. Hbs from each of the three species exhibited high intrinsic O2 affinities, low cooperativities, small Bohr factors in the absence of phosphates, and high sensitivities to ATP. Oxygenation properties of the snake Hbs could be explained entirely by allosteric transitions in the quaternary structure of intact tetramers, suggesting that ligation-dependent dissociation of Hb tetramers into αβ-dimers is not a universal feature of snake Hbs. Surprisingly, the major Hb isoform of the South American rattlesnake is homologous to the minor HbD of other amniotes and, contrary to the pattern of Hb isoform differentiation in birds and turtles, exhibits a lower O2 affinity than the HbA isoform.

  2. Hemoglobin enhances tissue factor expression on human malignant cells.

    PubMed

    Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

    2001-04-01

    Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined. PMID:11414630

  3. Hemoglobin O2 Saturation with Mild Hypoxia and Microgravity

    NASA Technical Reports Server (NTRS)

    Conkin, J.; Wessel, J. H., III; Norcross, J. R.; Bekdash, O. S.; Abercromby, A. J. F.; Koslovsky, M. D.; Gernhardt, M. L.

    2017-01-01

    INTRODUCTION: The increase in the alveolar-arterial oxygen (O2) partial pressure gradient during increasing hypoxia may further increase in microgravity (microG). METHODS: Four male astronauts on STS-69 (1995) and 4 on STS-72 (1996) submitted to an acute sequential hypoxic challenge by breathing for 4 minutes at 18.0%, 14.9%, 13.5%, 12.9%, and 12.2% O2 - balance nitrogen at sea level. The 18.0% O2 mixture was equivalent to an inspired O2 partial pressure (PIO2) of 127 mm Hg when exposed to 527 mm Hg while breathing 26.5% O2 for several days in ?G. A Novametrix CO2SMO Model 7100 recorded heart rate (HR, beats × min-1) and hemoglobin (Hb) O2 saturation through finger pulse oximetry (SpO2, %), end-tidal carbon dioxide partial pressure (PETCO2, mm Hg), and respiration rate (RR, breaths/min) through an infrared capnograph positioned in a mouthpiece. Measurements were also taken the day of return to Earth (R+0) and at R+2. Linear mixed effects models assessed changes in SpO2 after exposure to ?microG. Interactions between measurement condition and available physiologic measurements were also explored. RESULTS: Astronaut SpO2 levels at baseline, R+0, and R+2 were not significantly different from in flight, about 97% given a PIO2 of 127 mm Hg. There was no difference in astronaut SpO2 levels between baseline and R+0 or R+2 over the hypoxic challenge. Additionally, no significant interactions were identified. CONCLUSIONS: While microG did not affect astronaut Hb O2 saturation in this study, large within- and between-subject variability in SpO2 at increasingly hypoxic doses require a deeper understanding of subject-specific factors that influence O2 transfer onto Hb.

  4. Development of Recombinant Hemoglobin-Based Oxygen Carriers

    PubMed Central

    Varnado, Cornelius L.; Mollan, Todd L.; Birukou, Ivan; Smith, Bryan J.Z.; Henderson, Douglas P.

    2013-01-01

    Abstract Significance: The worldwide blood shortage has generated a significant demand for alternatives to whole blood and packed red blood cells for use in transfusion therapy. One such alternative involves the use of acellular recombinant hemoglobin (Hb) as an oxygen carrier. Recent Advances: Large amounts of recombinant human Hb can be expressed and purified from transgenic Escherichia coli. The physiological suitability of this material can be enhanced using protein-engineering strategies to address specific efficacy and toxicity issues. Mutagenesis of Hb can (i) adjust dioxygen affinity over a 100-fold range, (ii) reduce nitric oxide (NO) scavenging over 30-fold without compromising dioxygen binding, (iii) slow the rate of autooxidation, (iv) slow the rate of hemin loss, (v) impede subunit dissociation, and (vi) diminish irreversible subunit denaturation. Recombinant Hb production is potentially unlimited and readily subjected to current good manufacturing practices, but may be restricted by cost. Acellular Hb-based O2 carriers have superior shelf-life compared to red blood cells, are universally compatible, and provide an alternative for patients for whom no other alternative blood products are available or acceptable. Critical Issues: Remaining objectives include increasing Hb stability, mitigating iron-catalyzed and iron-centered oxidative reactivity, lowering the rate of hemin loss, and lowering the costs of expression and purification. Although many mutations and chemical modifications have been proposed to address these issues, the precise ensemble of mutations has not yet been identified. Future Directions: Future studies are aimed at selecting various combinations of mutations that can reduce NO scavenging, autooxidation, oxidative degradation, and denaturation without compromising O2 delivery, and then investigating their suitability and safety in vivo. Antioxid. Redox Signal. 18, 2314–2328. PMID:23025383

  5. Expression and Purification of Recombinant Hemoglobin in Escherichia coli

    PubMed Central

    Natarajan, Chandrasekhar; Jiang, Xiaoben; Fago, Angela; Weber, Roy E.; Moriyama, Hideaki; Storz, Jay F.

    2011-01-01

    Background Recombinant DNA technologies have played a pivotal role in the elucidation of structure-function relationships in hemoglobin (Hb) and other globin proteins. Here we describe the development of a plasmid expression system to synthesize recombinant Hbs in Escherichia coli, and we describe a protocol for expressing Hbs with low intrinsic solubilities. Since the α- and β-chain Hbs of different species span a broad range of solubilities, experimental protocols that have been optimized for expressing recombinant human HbA may often prove unsuitable for the recombinant expression of wildtype and mutant Hbs of other species. Methodology/Principal Findings As a test case for our expression system, we produced recombinant Hbs of the deer mouse (Peromyscus maniculatus), a species that has been the subject of research on mechanisms of Hb adaptation to hypoxia. By experimentally assessing the combined effects of induction temperature, induction time and E. coli expression strain on the solubility of recombinant deer mouse Hbs, we identified combinations of expression conditions that greatly enhanced the yield of recombinant protein and which also increased the efficiency of post-translational modifications. Conclusion/Significance Our protocol should prove useful for the experimental study of recombinant Hbs in many non-human animals. One of the chief advantages of our protocol is that we can express soluble recombinant Hb without co-expressing molecular chaperones, and without the need for additional reconstitution or heme-incorporation steps. Moreover, our plasmid construct contains a combination of unique restriction sites that allows us to produce recombinant Hbs with different α- and β-chain subunit combinations by means of cassette mutagenesis. PMID:21625463

  6. Measuring and modeling hemoglobin aggregation below the freezing temperature.

    PubMed

    Rosa, Mónica; Lopes, Carlos; Melo, Eduardo P; Singh, Satish K; Geraldes, Vitor; Rodrigues, Miguel A

    2013-08-01

    Freezing of protein solutions is required for many applications such as storage, transport, or lyophilization; however, freezing has inherent risks for protein integrity. It is difficult to study protein stability below the freezing temperature because phase separation constrains solute concentration in solution. In this work, we developed an isochoric method to study protein aggregation in solutions at -5, -10, -15, and -20 °C. Lowering the temperature below the freezing point in a fixed volume prevents the aqueous solution from freezing, as pressure rises until equilibrium (P,T) is reached. Aggregation rates of bovine hemoglobin (BHb) increased at lower temperature (-20 °C) and higher BHb concentration. However, the addition of sucrose substantially decreased the aggregation rate and prevented aggregation when the concentration reached 300 g/L. The unfolding thermodynamics of BHb was studied using fluorescence, and the fraction of unfolded protein as a function of temperature was determined. A mathematical model was applied to describe BHb aggregation below the freezing temperature. This model was able to predict the aggregation curves for various storage temperatures and initial concentrations of BHb. The aggregation mechanism was revealed to be mediated by an unfolded state, followed by a fast growth of aggregates that readily precipitate. The aggregation kinetics increased for lower temperature because of the higher fraction of unfolded BHb closer to the cold denaturation temperature. Overall, the results obtained herein suggest that the isochoric method could provide a relatively simple approach to obtain fundamental thermodynamic information about the protein and the aggregation mechanism, thus providing a new approach to developing accelerated formulation studies below the freezing temperature.

  7. Hemoglobin Variability Does Not Predict Mortality in European Hemodialysis Patients

    PubMed Central

    Kim, Joseph; Kronenberg, Florian; Aljama, Pedro; Anker, Stefan D.; Canaud, Bernard; Molemans, Bart; Stenvinkel, Peter; Schernthaner, Guntram; Ireland, Elizabeth; Fouqueray, Bruno; Macdougall, Iain C.

    2010-01-01

    Patients with CKD exhibit significant within-patient hemoglobin (Hb) level variability, especially with the use of erythropoiesis stimulating agents (ESAs) and iron. Analyses of dialysis cohorts in the United States produced conflicting results regarding the association of Hb variability with patient outcomes. Here, we determined Hb variability in 5037 European hemodialysis (HD) patients treated over 2 years to identify predictors of high variability and to evaluate its association with all-cause and cardiovascular disease (CVD) mortality. We assessed Hb variability with various methods using SD, residual SD, time-in-target (11.0 to 12.5 g/dl), fluctuation across thresholds, and area under the curve (AUC). Hb variability was significantly greater among incident patients than prevalent patients. Compared with previously described cohorts in the United States, residual SD was similar but fluctuations above target were less frequent. Using logistic regression, age, body mass index, CVD history, dialysis vintage, serum albumin, Hb, angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) use, ESA use, dialysis access type, dialysis access change, and hospitalizations were significant predictors of high variability. Multivariable adjusted Cox regression showed that SD, residual SD, time-in-target, and AUC did not predict all-cause or CVD mortality during a median follow-up of 12.4 months (IQR: 7.7 to 17.4). However, patients with consistently low levels of Hb (<11 g/dl) and those who fluctuated between the target range and <11 g/dl had increased risks for death (RR 2.34; 95% CI: 1.24 to 4.41 and RR 1.74; 95% CI: 1.00 to 3.04, respectively). In conclusion, although Hb variability is common in European HD patients, it does not independently predict mortality. PMID:20798262

  8. Non-symbiotic hemoglobins in the life of seeds.

    PubMed

    Matilla, Angel J; Rodríguez-Gacio, María del Carmen

    2013-03-01

    Non-symbiotic hemoglobins (nsHbs), ancestors of symbiotic-Hbs, are hexacoordinated dimeric proteins, for which the crystal structure is well described. According to the extent of hexacoordination, nsHbs are classified as belonging to class-1 (nsHbs1) or class-2 (nsHbs2). The nsHbs1 show weak hexacoordination, moderate rates of O(2)-binding, very small rates of O(2) dissociation, and a remarkably high affinity for O(2), all suggesting a function involving O(2) scavenging. In contrast, the nsHbs2 exhibit strong hexacoordination, low rates of O(2)-binding and moderately low O(2) dissociation and affinity, suggesting a sensing role for sustained low (μM) levels of O(2). The existence of spatial and specific expression of nsHbs1 suggests that nsHbs play tissue-specific rather than housekeeping functions. The permeation of O(2) into seeds is usually prevented during the desiccation phase and early imbibition, generating an internal hypoxic environment that leads to ATP limitation. During evolution, the seed has acquired mechanisms to prevent or reduce this hypoxic stress. The nsHbs1/NO cycle appear to be involved in modulating the redox state in the seed and in maintaining an active metabolism. Under O(2) deficit, NADH and NO are synthesized in the seed and nsHbs1 scavenges O(2), which is used to transform NO into NO(3)(-) with concomitant formation of Fe(3+)-nsHbs1. Expression of nsHbs1 is not detectable in dry viable seeds. However, in the seeds cross-talk occurs between nsHbs1 and NO during germination. This review considers the current status of our knowledge of seed nsHbs and considers key issues of further work to better understand their role in seed physiology. PMID:23286879

  9. Distribution, adaptation and physiological meaning of thiols from vertebrate hemoglobins.

    PubMed

    Reischl, Evaldo; Dafre, Alcir Luiz; Franco, Jeferson Luis; Wilhelm Filho, Danilo

    2007-01-01

    In the present review, the sequences of hemoglobins (Hb) of 267 adult vertebrate species belonging to eight major vertebrate taxa are examined for the presence and location of cysteinyl residues in an attempt at correlation with their ecophysiology. Essentially, all vertebrates have surface cysteinyl residues in Hb molecules whereby their thiol groups may become highly reactive. Thiol-rich Hbs may display eight or more thiols per tetramer. In vertebrates so far examined, the cysteinyl residues occur in 44 different sequence positions in alpha chains and 41 positions in beta chains. Most of them are conservatively located and occur in only a few positions in Teleostei, Aves and Mammalia, whereas they are dispersed in Amphibia. The internal cysteinyl residue alpha104 is ubiquitous in vertebrates. Residue beta93 is highly conserved in reptiles, birds and mammals. The number of cysteine residues per tetramer with solvent access varies in vertebrates, mammalians and bony fish having the lowest number of external residues, whereas nearly all external cysteine residues in Aves and Lepidosauria are of the surface crevice type. In cartilaginous fish, amphibians, Crocodylidae and fresh water turtles, a substantial portion of the solvent accessible thiols are of the totally external type. Recent evidence shows that some Hb thiol groups are highly reactive and undergo extensive and reversible S-thiolation, and that they may be implicated in interorgan redox equilibrium processes. Participation of thiol groups in nitric oxide ((*)NO) metabolism has also been proved. The evidence argues for a new physiologically relevant role for Hb via involvement in free radical and antioxidant metabolism. PMID:17368111

  10. Functional and Spectroscopic Characterization of Chlamydomonas reinhardtii Truncated Hemoglobins.

    PubMed

    Ciaccio, Chiara; Ocaña-Calahorro, Francisco; Droghetti, Enrica; Tundo, Grazia R; Sanz-Luque, Emanuel; Polticelli, Fabio; Visca, Paolo; Smulevich, Giulietta; Ascenzi, Paolo; Coletta, Massimo

    2015-01-01

    The single-cell green alga Chlamydomonas reinhardtii harbors twelve truncated hemoglobins (Cr-TrHbs). Cr-TrHb1-1 and Cr-TrHb1-8 have been postulated to be parts of the nitrogen assimilation pathway, and of a NO-dependent signaling pathway, respectively. Here, spectroscopic and reactivity properties of Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4, all belonging to clsss 1 (previously known as group N or group I), are reported. The ferric form of Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 displays a stable 6cLS heme-Fe atom, whereas the hexa-coordination of the ferrous derivative appears less strongly stabilized. Accordingly, kinetics of azide binding to ferric Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are independent of the ligand concentration. Conversely, kinetics of CO or NO2- binding to ferrous Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are ligand-dependent at low CO or NO2- concentrations, tending to level off at high ligand concentrations, suggesting the presence of a rate-limiting step. In agreement with the different heme-Fe environments, the pH-dependent kinetics for CO and NO2-binding to ferrous Cr-TrHb1-1, Cr-TrHb1-2, and Cr-TrHb1-4 are characterized by different ligand-linked protonation events. This raises the question of whether the simultaneous presence in C. reinhardtii of multiple TrHb1s may be related to different regulatory roles. PMID:25993270

  11. Human bulbar conjunctival hemodynamics in hemoglobin SS and SC disease

    PubMed Central

    Wanek, Justin; Gaynes, Bruce; Lim, Jennifer I.; Molokie, Robert; Shahidi, Mahnaz

    2014-01-01

    The known biophysical variations of hemoglobin (Hb) S and Hb C may result in hemodynamic differences between subjects with SS and SC disease. The purpose of this study was to measure and compare conjunctival hemodynamics between subjects with Hb SS and SC hemoglobinopathies. Image sequences of the conjunctival microcirculation were acquired in 9 healthy control subjects (Hb AA), 24 subjects with SC disease, and 18 subjects with SS disease, using a prototype imaging system. Diameter (D) and blood velocity (V) measurements were obtained in multiple venules of each subject. Data were categorized according to venule caliber by averaging V and D for venules with diameters less than (vessel size 1) or greater than (vessel size 2) 15 µm. V in vessel size 2 was significantly greater than V in vessel size 1 in the AA and SS groups (P ≥ 0.009), but not in the SC group (P = 0.1). V was significantly lower in the SC group as compared to the SS group (P = 0.03). In AA and SS groups, V correlated with D (P ≥ 0.005), but the correlation was not statistically significant in the SC group (P = 0.08). V was inversely correlated with hematocrit in the SS group for large vessels (P = 0.03); however, no significant correlation was found in the SC group (P ≥ 0.2). Quantitative assessment of conjunctival microvascular hemodynamics in SS and SC disease may advance understanding of sickle cell disease pathophysiology and thereby improve therapeutic interventions. PMID:23657867

  12. Two new hemoglobin variants: Hb Brem-sur-Mer [beta9(A6)Ser-->Tyr] and Hb Passy [alpha81(F2)Ser-->Pro (alpha2)].

    PubMed

    Lacan, Philippe; Moreau, Mathieu; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Louis, Jean-Jacques; Couprie, Nicole; Francina, Alain

    2005-01-01

    Two new hemoglobin (Hb) variants: Hb Brem-sur-Mer [codon 9 (TCT-->TAT); beta9(A6)Ser-->Tyr] on the first exon of the beta-globin gene and Hb Passy [codon 81 (TCC-->CCC); alpha81(F2)Ser-->Pro (alpha2)] on the second exon of the alpha2-globin gene, are described. The two variants were characterized by DNA sequencing and mass spectrometry (MS). Hematological abnormalities: microcytosis and hypochromia were found only in the carrier of Hb Passy. In the absence of an association with an alpha-thalassemic deletion or mutation, the mutation 81(F2)Pro could induce a possible alpha-thalassemia (thal).

  13. Sleep Physiology, Abnormal States, and Therapeutic Interventions

    PubMed Central

    Wickboldt, Alvah T.; Bowen, Alex F.; Kaye, Aaron J.; Kaye, Adam M.; Rivera Bueno, Franklin; Kaye, Alan D.

    2012-01-01

    Sleep is essential. Unfortunately, a significant portion of the population experiences altered sleep states that often result in a multitude of health-related issues. The regulation of sleep and sleep-wake cycles is an area of intense research, and many options for treatment are available. The following review summarizes the current understanding of normal and abnormal sleep-related conditions and the available treatment options. All clinicians managing patients must recommend appropriate therapeutic interventions for abnormal sleep states. Clinicians' solid understanding of sleep physiology, abnormal sleep states, and treatments will greatly benefit patients regardless of their disease process. PMID:22778676

  14. Numerically abnormal chromosome constitutions in humans

    SciTech Connect

    1993-12-31

    Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.

  15. Channel catfish hemoglobin genes: identification, phylogenetic and syntenic analysis, and specific induction in response to heat stress.

    PubMed

    Feng, Jianbin; Liu, Shikai; Wang, Xiuli; Wang, Ruijia; Zhang, Jiaren; Jiang, Yanliang; Li, Chao; Kaltenboeck, Ludmilla; Li, Jiale; Liu, Zhanjiang

    2014-03-01

    Hemoglobins transport oxygen from gill to inner organs in fish, and this process is affected by temperature, one of the major environmental factors for fish. The hemoglobin gene clusters have been well studied in humans and several model fish species, but remain largely unknown in catfish. Here, eight α- and six β-hemoglobin genes were identified and characterized in channel catfish. Genomic synteny analysis showed that these hemoglobin genes were separated into two unlinked clusters, the MN cluster containing six α- and six β-hemoglobin genes, and the LA cluster consisting of two α-hemoglobin genes. Channel catfish hemoglobin genes were ubiquitously expressed in all the 10 tested tissues from healthy fish, but exhibited higher expression level in spleen, head kidney, and trunk kidney. In response to heat stress, hemoglobin genes, especially MN Hbα4, MN Hbα5, MN Hbα6, MN Hbβ4, MN Hbβ5, MN Hbβ6, LA Hbα1, and LA Hbα2, presumably the embryonic hemoglobin genes, were drastically up-regulated in the gill and head kidney of heat-tolerant fishes, but not in these tissues of the heat-intolerant fish, suggesting the importance of the embryonic hemoglobin genes in coping with the low oxygen conditions under heat stress.

  16. Structural characterization of hemoglobins from Monilifera and Frenulata tubeworms (Siboglinids): first discovery of giant hexagonal-bilayer hemoglobin in the former "Pogonophora" group.

    PubMed

    Meunier, Cédric; Andersen, Ann C; Bruneaux, Matthieu; Le Guen, Dominique; Terrier, Peran; Leize-Wagner, Emmanuelle; Zal, Franck

    2010-01-01

    Siboglinids are symbiotic polychete annelids having hemoglobins as essential oxygen- and sulfide-carriers for their endosymbiotic bacteria. We analyzed the structure of the hemoglobins from two species of siboglinids: the monilifera Sclerolinum contortum and the frenulata Oligobrachia webbi (i.e. haakonmosbiensis) from Norwegian cold seeps. Measured by Multi-Angle Laser Light Scattering (MALLS), Sclerolinum shows a 3190+/-50 kDa hexagonal bilayer hemoglobin (HBL-Hb) and a 461+/-46 kDa ring-Hb, just as vestimentifera, whereas Oligobrachia has a 409+/-3.7 kDa ring-Hb only. Electrospray Ionization-Mass Spectrometry (ESI-MS) showed Sclerolinum HBL-Hb composed of seven monomeric globins (15-16 kDa), three disulfide-bonded globin heterodimers and three linkers. The heterodimers always contain globin-b (15814.4+/-1.5 Da). Sclerolinum ring-Hb is composed of globins and dimers with identical masses as its HBL-Hb, but lacks linkers. Oligobrachia ring-Hb has three globin monomers (14-15 kDa) only, with no disulfide-bonded dimers. Comparison of Sclerolinum hemoglobins between Storegga and Haakon Mosby Mud Volcano, using the normalized height of deconvoluted ESI-MS peaks, shows differences in globin monomers abundances that could reflect genetic differences or differential gene expression between distinct seep populations. The discovery of HBL-Hb in Sclerolinum is a new element supporting the hypothesis of monilifera being phylogenetically more closely related to vestimentifera, than to frenulata.

  17. Hematologic and hemorheological determinants of resting and exercise-induced hemoglobin oxygen desaturation in children with sickle cell disease

    PubMed Central

    Waltz, Xavier; Romana, Marc; Lalanne-Mistrih, Marie-Laure; Machado, Roberto F.; Lamarre, Yann; Tarer, Vanessa; Hardy-Dessources, Marie-Dominique; Tressières, Benoît; Divialle-Doumdo, Lydia; Petras, Marie; Maillard, Frederic; Etienne-Julan, Maryse; Connes, Philippe

    2013-01-01

    The aim of the study was to determine the factors associated with resting and exercise-induced hemoglobin oxygen desaturation. The well-established six-minute walk test was conducted in 107 sickle cell children (50 with sickle hemoglobin C disease and 57 with sickle cell anemia) at steady state. Hemoglobin oxygen saturation was measured before and immediately after the six-minute walk test. Blood samples were obtained on the same day to measure hematologic and hemorheological parameters. Exercise-induced hemoglobin oxygen desaturation was defined as a drop in hemoglobin oxygen saturation of 3% or more at the end of the six-minute walk test compared to resting levels. No children with sickle hemoglobin C disease, but approximately 50% of children with sickle cell anemia showed mild or moderate oxygen desaturation at rest, which was independently associated with the percentage of reticulocytes. Exercise-induced hemoglobin oxygen desaturation was observed in 18% of children with sickle hemoglobin C disease and 34% of children with sickle cell anemia, and was independently associated with the six-minute walk test, acute chest syndrome rate and the strength of red blood cell aggregates in children with sickle cell anemia. No association was found in children with sickle hemoglobin C disease between exercise-induced hemoglobin oxygen desaturation and the measured parameters. Hemoglobin oxygen desaturation at rest was common in children with sickle cell anemia but not in children with sickle hemoglobin C disease, and was mainly associated with greater hemolysis. Physiological strain during exercise and red blood cell aggregation properties may predict the occurrence of exercise-induced hemoglobin oxygen desaturation in children with sickle cell anemia. PMID:23539539

  18. Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital heinz body hemolytic anemia

    PubMed Central

    Jacob, Harry S.; Brain, Michael C.; Dacie, John V.

    1968-01-01

    The mechanisms of hemoglobin precipitation into Heinz bodies and hemolytic anemia that characterize congenital Heinz body hemolytic anemia (CHBHA) were studied in patients with the unstable hemoglobins, Köln (β-98 valine → methionine) and Hammersmith (β-42 phenylalanine → serine). The cysteines in the 93rd position of the β-chains of CHBHA hemoglobins bound glutathione excessively in mixed disulfide linkage. The resulting diminished “free” GSH within the cell accelerated hexose monophosphate shunt metabolism. The unique precipitability of CHBHA hemoglobins when heated at 50°C could be induced in normal hemoglobin A by artificially blockading its sulfhydryl groups with paramercuribenzoate (PMB). Reflecting the previously reported excessive flux of hemes from hemoglobin Köln, the expected heme/globin ratio in this hemoglobin was reduced by 30%. The further increment in heme loss that occurs with heat (50°C) underlies the unique heat precipitability of CHBHA hemoglobins; it was retarded if detachment of heme was inhibited by cyanide or carbon monoxide. Heinz bodies were attached to red cell membrane thiol groups presumably through mixed disulfide bonds, being released by mercaptoethanol. Binding of hemoglobin Köln-59Fe to red cell ghosts, which was markedly enhanced when Heinz bodies were generated at 50°C, was inhibited if membrane thiols were preblockaded by PMB. The depletion of membrane thiols by their reaction with Heinz bodies rendered CHBHA red cells hypersusceptible to membrane sulfhydryl inhibitors, as manifested by inordinate cation leakage, osmotic fragility, and autohemolysis. We conclude that both cellular and membrane thiols bind β-93 sulfhydryls of CHBHA hemoglobins as mixed disulfides. Concomitantly, heme avidity to β-92 lessens, suggesting that degradation of the resulting excessively freed heme may produce the pigmented dipyrroluria of this syndrome. Heinz bodies, reflecting the heightend precipitability of heme-deficient globin

  19. Maternal hemoglobin level and fetal outcome at low and high altitudes

    PubMed Central

    Steenland, Kyle; Tapia, Vilma

    2009-01-01

    Both, low (<7 g/dl) and high (>14.5 g/dl), maternal hemoglobin (Hb) levels have been related to poor fetal outcome. Most studies have been done at low altitude (LA). Here, we have sought to determine whether this relationship exists at both high and low altitude, and also whether there is an adverse effect of high altitude (HA) on fetal outcome independent of level of maternal hemoglobin. The study is based on a retrospective multicenter analysis of 35,449 pregnancies at LA and six other cities above 3000 meters. In analyses of all women at both LA and HA, those with Hb <9 g/dl had odds ratios (ORs) and 95% confidence intervals (CI) of 4.4 (CI: 2.8–6.7), 2.5 (CI: 1.9–3.2), and 1.4 (CI: 1.1–1.9) for stillbirths, preterm, and small for gestational age (SGA) births, respectively, compared with women with 11–12.9 g/dl of Hb, after adjustment for confounders. These risks by hemoglobin level differed little between women at LA and HA, suggesting that no correction of the definition of anemia is necessary for women at HA. Women living at high altitude with hemoglobin >15.5 g/dl had higher risks for stillbirths (OR: 1.3; CI: 1.05–1.3), preterm (OR: 1.5; CI 1.3–1.8), and SGA births (OR: 2.1, CI 1.8–2.3). There was also a significant adverse effect of living at HA, independent of hemoglobin level for all three outcomes (OR: 3.9, 1.7, and 2.3; CI: 2.8–5.2, 1.5–1.9, and 2.1–2.5) for stillbirths, preterms, and SGA respectively, after adjusting for hemoglobin level. Both, high and low maternal hemoglobin levels were related to poor pregnancy outcome, with similar effect of low hemoglobin in both LA and HA. Our data suggest, that maternal hemoglobin above 11 g/dl but below 13 g/dl is the area of minimal risk of poor adverse outcomes. Living at HA had an adverse effect independent of hemoglobin level. PMID:19741055

  20. Development of severe anemia during fever episodes in patients with hemoglobin E trait and hemoglobin H disease combinations.

    PubMed

    Jetsrisuparb, Arunee; Sanchaisuriya, Kanokwan; Fucharoen, Goonnapa; Fucharoen, Supan; Wiangnon, Surapon; Jetsrisuparb, Charoon; Sirijirachai, Jittima; Chansoong, Kanchana

    2006-04-01

    Globin chain imbalance and tissue hypoxia are important determinants of the clinical severity of thalassemias. Phenotypic expression may be further modified by interactions between alpha- and beta-thalassemia defects. We retrospectively and prospectively studied the clinical and hematologic features in children and adults with hemoglobin (Hb) E trait/Hb H disease (SEA/Paksé) (seven cases) and Hb E trait/Hb H disease (SEA/Constant Spring) (29 cases) and found that they had similar presentations. The severity of these two intermediate thalassemic manifestations ranged from very mild to severe. Severe anemia developed in accordance with very high fever, whereupon the range of Hb and hematocrit (Hct) levels declined to 5.2-5.8 g/dL and 13%-19%, respectively. In one case, during a hemoconcentrated state as occurs in dengue hemorrhagic fever, the Hb and Hct were 10 g/dL and 31%; the latter rose to 35% after fluid therapy. In some patients, the range of Hb and Hct levels was constantly low (4.3-5.8 g/dL and 15%-19%, respectively). (If dengue hemorrhagic fever is misdiagnosed, a fatal outcome may occur for thalassemic patients.) After a hemodiluted condition as in acute post-streptococcal glomerulonephritis, the respective Hb and Hct were 5.4 g/dL and 19%. These observations suggest that the instability of Hb E, especially during fever, may play an important role in the clinical manifestations of Hb E trait/Hb H disease with Hb Paksé and with Hb Constant Spring.

  1. Pharmacokinetic study of enclosed hemoglobin and outer lipid component after the administration of hemoglobin vesicles as an artificial oxygen carrier.

    PubMed

    Taguchi, Kazuaki; Urata, Yukino; Anraku, Makoto; Maruyama, Toru; Watanabe, Hiroshi; Sakai, Hiromi; Horinouchi, Hirohisa; Kobayashi, Koichi; Tsuchida, Eishun; Kai, Toshiya; Otagiri, Masaki

    2009-07-01

    The hemoglobin vesicle (HbV) is an artificial oxygen carrier that encapsulates a concentrated Hb solution in lipid vesicles (liposomes). The pharmacokinetic properties of HbV were investigated in mice and rats. With use of HbV in which the internal Hb was labeled with (125)I ((125)I-HbV) and cell-free (125)I-Hb, it was found that encapsulation of Hb increased the half-life by 30 times, accompanied by decreased distribution in both the liver and kidney. The half-life of HbV was increased, and the uptake clearance for the liver and spleen were decreased with increasing doses of HbV. In an in vitro study, the specific uptake and degradation of HbV in RAW 264.7 cells were found, but this was not the case for parenchymal and endothelial cells. The pharmacokinetics of HbV components (internal Hb and liposomal lipid) were also investigated using (125)I-HbV and (3)H-HbV (liposomal cholesterol was radiolabeled with tritium-3). The time courses for the plasma concentration curves of (125)I-HbV, (3)H-HbV, and iron derived from HbV suggest that HbV maintain an intact structure in the blood circulation up to 24 h after injection. (125)I-HbV and (3)H-HbV were distributed mainly to the liver and spleen. Internal Hb disappeared from both the liver and spleen 5 days after injection, and the liposomal cholesterol disappeared at approximately 14 days. Internal Hb was excreted into the urine and cholesterol into feces via biliary excretion. These results suggest that the HbV has a reasonable blood retention and metabolic and excretion performance and could be used as an oxygen carrier.

  2. Four families with immunodeficiency and chromosome abnormalities.

    PubMed Central

    Candy, D C; Hayward, A R; Hughes, D T; Layward, L; Soothill, J F

    1979-01-01

    Six children, with severe deficiency of some or all of the immunoglobulins and minor somatic abnormalities, had chromosomal abnormalities: (1) 45,XY,t(13q/18q), (2) 46,XY,21ps +, (3) two brothers 46,XY (inv. 7) (4) 45,X,t(11p/10p)/46X,iXq,t(11p/10p) and, (5) in addendum, 45,XX,-18;46,XX, r18. The chromosome abnormalities were detected in B- as well as T-lymphocytes (as evidenced by using both PHA- and PWM-stimulated cultures) in all probands, but one was mosaic in PHA culture, although all his PWM-stimulated cells were abnormal. Chromosomal variants were also detected in relatives of three and immunodeficiency in relatives of two. Images Fig. 1 Fig. 3 PMID:314782

  3. Abnormal Uterine Bleeding (Beyond the Basics)

    MedlinePlus

    ... Approach to abnormal uterine bleeding in nonpregnant reproductive-age women Differential diagnosis of genital tract bleeding in women Postmenopausal uterine bleeding The following organizations also provide reliable health information. ● National Library of Medicine ( www.nlm.nih.gov/ ...

  4. Low-set ears and pinna abnormalities

    MedlinePlus

    Low-set ears; Microtia; "Lop" ear; Pinna abnormalities; Genetic defect-pinna; Congenital defect-pinna ... The outer ear or "pinna" forms when the baby is growing in the mother's womb. The growth of this ear part ...

  5. Quantitative, single-step dual measurement of hemoglobin A1c and total hemoglobin in human whole blood using a gold sandwich immunochromatographic assay for personalized medicine.

    PubMed

    Ang, Shu Hwang; Rambeli, Musalman; Thevarajah, T Malathi; Alias, Yatimah Binti; Khor, Sook Mei

    2016-04-15

    We describe a gold nanoparticle-based sandwich immunoassay for the dual detection and measurement of hemoglobin A1c (HbA1c) and total hemoglobin in the whole blood (without pretreatment) in a single step for personalized medicine. The optimized antibody-functionalized gold nanoparticles immunoreact simultaneously with HbA1c and total hemoglobin to form a sandwich at distinctive test lines to transduce visible signals. The applicability of this method as a personal management tool was demonstrated by establishing a calibration curve to relate % HbA1c, a useful value for type 2 diabetes management, to the signal ratio of captured HbA1c to all other forms of hemoglobin. The platform showed excellent selectivity (100%) toward HbA1c at distinctive test lines when challenged with HbA0, glycated HbA0 and HbA2. The reproducibility of the measurement was good (6.02%) owing to the dual measurement of HbA1c and total hemoglobin. A blood sample stability test revealed that the quantitative measurement of % HbA1c was consistent and no false-positive results were detected. Also, this method distinguished the blood sample with elevated HbF from the normal samples and the variants. The findings of this study highlight the potential of a lateral flow immunosensor as a simple, inexpensive, consistent, and convenient strategy for the dual measurement of HbA1c and total Hb to provide useful % HbA1c values for better on-site diabetes care.

  6. Electrocardiography series. Electrocardiographic T wave abnormalities.

    PubMed

    Lin, Weiqin; Teo, Swee Guan; Poh, Kian Keong

    2013-11-01

    The causes of abnormal T waves on electrocardiography are multiple and varied. Careful clinical history taking and physical examination are necessary for accurate identification of the cause of such abnormalities. Subsequent targeted specialised cardiac investigations, such as echocardiography or coronary angiography, may be of importance in the diagnosis of the underlying cardiac pathology. We present two cases of T wave inversions with markedly different aetiologies.

  7. Prevalence of asymptomatic urinary abnormalities among adolescents.

    PubMed

    Fouad, Mohamed; Boraie, Maher

    2016-05-01

    To determine the prevalence of asymptomatic urinary abnormalities in adolescents, first morning clean mid-stream urine specimens were obtained from 2500 individuals and examined by dipstick and light microscopy. Adolescents with abnormal screening results were reexamined after two weeks and those who had abnormal results twice were subjected to systemic clinical examination and further clinical and laboratory investigations. Eight hundred and three (32.1%) individuals had urinary abnormalities at the first screening, which significantly decreased to 345 (13.8%) at the second screening, (P <0.001). Hematuria was the most common urinary abnormalities detected in 245 (9.8%) adolescents who had persistent urine abnormalities; 228 (9.1%) individuals had non glomerular hematuria. The hematuria was isolated in 150 (6%) individuals, combined with leukocyturia in 83 (3.3%) individuals, and combined with proteinuria in 12 (0.5%) individuals. Leukocyturia was detected in 150 (6%) of all studied adolescents; it was isolated in 39 (1.6%) individuals and combined with proteinuria in 28 (1.1%) of them. Asymptomatic bacteriuria was detected in 23 (0.9%) of all studied adolescents; all the cases were females. Proteinuria was detected in 65 (2.6%) of all the studied adolescents; 45 (1.8%) individuals had <0.5 g/day and twenty (0.8%) individuals had 0.5-3 g/day. Asymptomatic urinary abnormalities were more common in males than females and adolescents from rural than urban areas (P <0.01) and (P <0.001), respectively. The present study found a high prevalence of asymptomatic urinary abnormalities among adolescents in our population.

  8. Thermodynamic aspects of the linkage between binding of chloride and oxygen to human hemoglobin

    PubMed Central

    Haire, Robert N.; Hedlund, Bo E.

    1977-01-01

    Oxygen isotherms of human hemoglobin measured in distilled water and in solutions of sodium chloride in the concentration range from 0.02 to 3.0 M indicate that the oxygen affinity decreases up to about 1 M salt and then begins to increase. The isotherms obtained in the range from 0.02 to 0.6 M sodium chloride, at 37° and pH 7.4, have been analyzed in terms of changes in Gibbs free energy of heme ligation, resulting from the differential interaction between the chloride ion and the two forms of hemoglobin. The maximal theoretical change in Gibbs free energy that chloride ion can exert on the oxygen binding of hemoglobin amounts to 4.9 ± 0.2 kcal/mol (21 ± 0.8 kJ/mol) of hemoglobin tetramer. A plot of the logarithm of oxygen concentration at half saturation versus the logarithm of the chloride concentration has a slope of 0.40, suggesting 1.6 apparent chloride sites per hemoglobin tetramer. Because the interaction between chloride and hemoglobin is dependent on pH, the apparent thermodynamic linkage between chloride and oxygen binding will also include the salt dependence of the Bohr effect at pH 7.4. The fractional change in Gibbs free energy, measured as a function of the chloride concentration, can be approximated by the binding isotherm between a protein and a ligand, using an association constant of 11 M-1. Thus, if the number of oxygen-linked chloride sites is more than one per hemoglobin tetramer, these sites must be considered independent. PMID:270660

  9. Capacity of reductants and chelators to prevent lipid oxidation catalyzed by fish hemoglobin.

    PubMed

    Maestre, Rodrigo; Pazos, Manuel; Iglesias, Jacobo; Medina, Isabel

    2009-10-14

    The efficiency of different reductants (reduced glutathione, ascorbic acid, and catalase) and metal chelators [ethylenediaminetetraacetic acid (EDTA), citric acid, sodium tripolyphosphate (STPP), and adenosine-5'-triphosphate (ATP)] to inhibit lipid oxidation promoted by fish hemoglobin was investigated. The inhibitory activity on hemoglobin-catalyzed lipid oxidation was also evaluated for grape oligomeric catechins (proanthocyanidins), which have both reducing and chelating properties. The antioxidant activity was studied in two different lipid oxidation models, liposomes and washed minced fish muscle. Grape proanthocyanidins were found to be significantly more effective than other reductants to prevent hemoglobin-mediated lipid oxidation in both liposomes and washed fish muscle. Reduced glutathione was also efficient to retard lipid oxidation at the same molarity in washed fish muscle, whereas catalase and ascorbic acid showed a lower antioxidant activity. Metal chelators were less active than reductants, and consequently, the former were necessarily evaluated at much higher concentration than grape proanthocyanidins and reducing compounds. STPP was found to be the iron chelator with the strongest efficiency to delay hemoglobin-mediated lipid oxidation followed by EDTA. Citric acid and ATP were ineffective in retarding lipid oxidation in both systems. Grape proanthocyanidins provided the most extensive protection to preserve hemoglobin at ferrous state in washed fish muscle. Our results draw attention to the greater capacity of reducing compounds to prevent fish hemoglobin-mediated lipid oxidation in comparison with iron chelators, suggesting that the free radical scavenging and/or reduction of ferrylHb species are crucial actions to avoid the pro-oxidant capacity of fish hemoglobin.

  10. Extraction of Phospholipids from Human Erythrocyte Membranes by Hemoglobin Oxidation Products.

    PubMed

    Brunauer, Linda S; Chen, James Y; Koontz, M Zachary; Davis, Kathryn K; O'Brien, Laura E; Wright, Emily M; Huestis, Wray H

    2016-06-01

    This investigation examines oxidation conditions under which hemoglobin extracts membrane phospholipid from erythrocytes and model membranes. In erythrocytes made echinocytic with exogenous phospholipid, addition of hemoglobin oxidized with hydrogen peroxide (H2O2) or Vitamin C (conditions that result in the formation of significant quantities of choleglobin), but not ferricyanide (which produces predominantly methemoglobin), induced dose-dependent shape reversion to less echinocytic forms, consistent with extraction of phospholipids from the exofacial side of the membrane. Erythrocytes preloaded with radiolabeled phosphatidylcholine or NBD-labeled phosphatidylcholine, phosphatidylglycerol or phosphatidic acid, exhibited greatest extraction of radiolabel or fluorescence signal with exogenous hemoglobin oxidized via H2O2 or Vitamin C, but not ferricyanide. However, with NBD-phosphatidylserine (a preferential inner monolayer intercalator), significantly less extraction of labeled lipid occurred with oxidized hemoglobin prepared under all three oxidizing conditions. In dimyristoylphosphatidylcholine liposomes containing radiolabeled phosphatidylcholine, phosphatidylserine or phosphatidylethanolamine, subsequent addition of hemoglobin oxidized with H2O2 or Vitamin C extracted radiolabeled lipid with significantly greater efficiency than ferricyanide-treated hemoglobin, with enhanced extraction detectable at levels approaching physiological plasma oxidant concentrations. Radiolabeled lipid extraction was comparable for phospholipids containing saturated acyl chains between 12 and 18 carbons but diminished significantly for oleoyl-containing phospholipids. Hemoglobin dimerization occurred at very low levels with H2O2 treatment, and even lower levels with Vitamin C treatment, and thus did not correlate to the high efficiency and consistent levels of lipid extraction observed with these treatments. These findings indicate that choleglobin extracts lipids from cell

  11. Ex vivo hemoglobin status study using photoacoustic computed tomography small animal scanner

    NASA Astrophysics Data System (ADS)

    Liu, Bo; Kruger, Robert; Reinecke, Daniel; Stantz, Keith M.

    2010-02-01

    Purpose: The purpose of this study is to calibrate the PCT scanner to quantify the hemoglobin status utilizing a blood flow phantom. Materials and Methods: A blood circulation system was designed and constructed to control the oxygen saturation and hemoglobin concentration of blood. As a part of the circulation system, a 1.1mm FEP tube was placed in the center of imaging tank of PCT scanner as the imaging object. Photoacoustic spectra (690-950 nm) was acquired for different hemoglobin concentrations (CtHb) and oxygen saturation levels (SaO2), where the formers was formed by diluting blood samples with PBS and the latter by mixing blood with gases at different oxygen content. Monte Carlo simulations were performed to calculate the photon energy depositions in the phantom tube, which took into account photon losses in water and blood. A Kappa value which represents the energy transfer efficiency of hemoglobin molecule was calculated based on the PCT measurement and simulation result. The final SaO2 value of each blood sample was calculated based on the PCT spectrum and Kappa value. These oxygen saturation results were compared with co-oximeter measurements to obtain systematic errors. Results and Conclusion: The statistic error of calculating Kappa value from hemoglobin concentration experiment was less than 5%. The systematic error between PCT spectra analysis and co-oximeter analysis for hemoglobin oxygen saturation was -4.5%. These calibration techniques used to calculate Kappa and hemoglobin absorption spectra would be used in hypoxia measurements in tumors as well as for endogenous biomarkers studies.

  12. Kinetics of the polymerization of hemoglobin in high and low phosphate buffers.

    PubMed

    Adachi, K; Asakura, T

    1982-01-01

    Diluted solutions of deoxyhemoglobin S in concentrated phosphate buffer form aggregates or gels with a clear exhibition of a delay time. The aggregates can be liquified by cooling, bubbling with O2 or CO gas, or the dilution of phosphate buffer with water. These properties can be used as a simple method for studying the mechanism of polymerization and depolymerization of hemoglobins. The advantages of this method are: 1) The amount of hemoglobin sample required is only 1% to 5% of that required for the gelation of deoxy-Hb S in low phosphate buffer. 2) The kinetics can be measured turbidimetrically using an ordinary spectrophotometer. 3) The solubility of hemoglobin can be directly determined by taking the absorption spectrum of the supernatant solution after polymerization. 4) The polymer phase can be easily separated from the solution so that the amount and composition of the polymers can be analyzed. 5) The volume of the polymer phase is so small that excluded volume effect can be neglected. 6) The method can be applied to the study of polymerization of non-sickle hemoglobins and that of mixtures of sickle and non-sickle hemoglobins. The major question is whether the polymerization of hemoglobin in concentrated phosphate buffer is the same as that of deoxy-Hb S in low phosphate buffer. To answer this question, we studied the polymerization of Hb S, Hb A, Hb C Harlem, and Hb C in phosphate buffers of different molarities. We also studied the mechanism of the conversion of gels of these hemoglobins into crystals.

  13. Capacity of reductants and chelators to prevent lipid oxidation catalyzed by fish hemoglobin.

    PubMed

    Maestre, Rodrigo; Pazos, Manuel; Iglesias, Jacobo; Medina, Isabel

    2009-10-14

    The efficiency of different reductants (reduced glutathione, ascorbic acid, and catalase) and metal chelators [ethylenediaminetetraacetic acid (EDTA), citric acid, sodium tripolyphosphate (STPP), and adenosine-5'-triphosphate (ATP)] to inhibit lipid oxidation promoted by fish hemoglobin was investigated. The inhibitory activity on hemoglobin-catalyzed lipid oxidation was also evaluated for grape oligomeric catechins (proanthocyanidins), which have both reducing and chelating properties. The antioxidant activity was studied in two different lipid oxidation models, liposomes and washed minced fish muscle. Grape proanthocyanidins were found to be significantly more effective than other reductants to prevent hemoglobin-mediated lipid oxidation in both liposomes and washed fish muscle. Reduced glutathione was also efficient to retard lipid oxidation at the same molarity in washed fish muscle, whereas catalase and ascorbic acid showed a lower antioxidant activity. Metal chelators were less active than reductants, and consequently, the former were necessarily evaluated at much higher concentration than grape proanthocyanidins and reducing compounds. STPP was found to be the iron chelator with the strongest efficiency to delay hemoglobin-mediated lipid oxidation followed by EDTA. Citric acid and ATP were ineffective in retarding lipid oxidation in both systems. Grape proanthocyanidins provided the most extensive protection to preserve hemoglobin at ferrous state in washed fish muscle. Our results draw attention to the greater capacity of reducing compounds to prevent fish hemoglobin-mediated lipid oxidation in comparison with iron chelators, suggesting that the free radical scavenging and/or reduction of ferrylHb species are crucial actions to avoid the pro-oxidant capacity of fish hemoglobin. PMID:19736927

  14. Maternal Hemoglobin Levels during Pregnancy and their Association with Birth Weight of Neonates

    PubMed Central

    Moghaddam Tabrizi, F; Barjasteh, S

    2015-01-01

    Back ground Anemia in pregnancy is associated with increased rates of maternal and perinatal mortality, premature delivery, low birth weight, and other adverse outcomes Materials and Methods A prospective study was conducted on 1405 Iranian pregnant women who delivered during 2015. Blood was collected from all the subjects to measure the hemoglobin (Hb) during 16-19 weeks, 22-24 weeks, and 34-36 weeks of gestation. According to the level of hemoglobin, it is divided into 4 groups. Group 1; Hb > 10.1 gm/100ml (control group), Group 2; Hb= 8.1-10 gm/100ml (mild anemia) Group 3; Hb= 6.5-8 gm/100ml (moderate anemia) Group 4; Hb <6.5 gm/100ml (severe anemia). After delivery, the neonates were weighted within 24 hours after birth. Maternal hemoglobin and birth weights were compared. Results The anemia prevalence was 20.2% (Hb<10g/dl). Out of them, 16.2 % hadmoderate anemia (Hb=6.5-8 g/dl) and 83.8% had mild anemia (Hb=8.1-10 g/dl). Severe anemia did not detect in pregnant women. The hemoglobin levels in non anemic group showed a drop in the second trimester. Pregnant women with hemoglobin less than 10 g/dl, considered as anemic gave birth to neonates with birth weight of 2.6kg, while pregnant women with higher hemoglobin level (>10 g/dl), considered as normal gave birth to heavier and normal babies (3.3 kg). The severity of anemia during three trimesters was closely associated with birth weight of newborns. Conclusion The low hemoglobin values during three trimesters of pregnancy were associated with low birth weight in Iran. The anemia can lead to intra uterine growth retardation. PMID:26985354

  15. Reaction of dehydropyrrolizidine alkaloids with valine and hemoglobin.

    PubMed

    Zhao, Yuewei; Wang, Shuguang; Xia, Qingsu; Gamboa da Costa, Gonçalo; Doerge, Daniel R; Cai, Lining; Fu, Peter P

    2014-10-20

    Pyrrolizidine alkaloid-containing plants are probably the most common poisonous plants affecting livestock, wildlife, and humans. Pyrrolizidine alkaloids exert toxicity through metabolism to dehydropyrrolizidine alkaloids that bind to cellular protein and DNA, leading to hepatotoxicity, genotoxicity, and tumorigenicity. To date, it is not clear how dehydropyrrolizidine alkaloids bind to cellular constituents, including amino acids and proteins, resulting in toxicity. Metabolism of carcinogenic monocrotaline, riddelliine, and heliotrine produces dehydromonocrotaline, dehyroriddelliine, and dehydroheliotrine, respectively, as primary reactive metabolites. In this study, we report that reaction of dehydromonocrotaline with valine generated four highly unstable 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-derived valine (DHP-valine) adducts. For structural elucidation, DHP-valine adducts were derivatized with phenyl isothiocyanate (PITC) to DHP-valine-PITC products. After HPLC separation, their structures were characterized by mass spectrometry, UV-visible spectrophotometry, (1)H NMR, and (1)H-(1)H COSY NMR spectral analysis. Two DHP-valine-PITC adducts, designated as DHP-valine-PITC-1 and DHP-valine-PITC-3, had the amino group of valine linked to the C7 position of the necine base, and the other two DHP-valine-PITC products, DHP-valine-PITC-2 and DHP-valine-PITC-4, linked to the C9 position of the necine base. DHP-valine-PITC-1 was interconvertible with DHP-valine-PITC-3, and DHP-valine-PITC-2 was interconvertible with DHP-valine-PITC-4. Reaction of dehydroriddelliine and dehydroheliotrine with valine provided similar results. However, reaction of valine and dehydroretronecine (DHR) under similar experimental conditions did not produce DHP-valine adducts. Reaction of dehydromonocrotaline with rat hemoglobin followed by derivatization with PITC also generated the same four DHP-valine-PITC adducts. This represents the first full structural elucidation of

  16. Hemoglobin and Ferritin Concentrations in Subjects with Metabolic Syndrome

    PubMed Central

    Adediran, Adewumi; Uche, Ebele; Akinbami, Akinsegun; Dada, Akin; Wakama, Tamunomieibi; Damulak, Dapus; Ajibola, Sarah; Okwegbuna, Oluwakemi

    2015-01-01

    BACKGROUND Metabolic syndrome (MetS), a clinical condition characterized by insulin resistance, glucose intolerance, dyslipidemia, hypertension, and obesity, has been linked with raised levels of serum ferritin (Sfr) concentrations. OBJECTIVES This study was carried out to compare hemoglobin (Hb) and Sfr concentrations in patients with MetS, regular donors and first-time donors. MATERIALS AND METHODS A total of 102 subjects who were between 18 and 60 years were enrolled for the study. They were divided into three groups. The first group (n = 20) was made up of 5 males and 15 females, all who met the criteria that define MetS. The second group (n = 52; M = 34, F = 18) were regular donors, while the last group (n = 30; M = 16, F = 14) were first-time donors or those who had not donated before. Following an overnight fast, 20 mL of venous blood was drawn from each subject. About 5 mL of this was put into sodium ethylenediaminetetraacetate (EDTA) specimen bottles for the full blood count parameters with Sysmex KX-21N hematology analyzer (made in Japan). The remaining 15 mL had serum separated for Sfr assay using enzyme-linked immunosorbent assay (ELISA) with a commercial assay kit manufactured by Teco Diagnostics. RESULTS Significant difference was found in the mean Sfr concentration of subjects with MetS (163 ± 136.92 ng/mL) and regular donors (41.46 ± 40.33 ng/mL), P = 0.001. The mean Sfr concentrations of subjects with MetS (163 ± 136.92 ng/mL) were also higher than that of first-time donors (102.46 ± 80.26 ng/mL), but it was not statistically significant, P = 0.053. The Hb concentrations of the three groups were not significantly different. CONCLUSION Sfr concentrations of regular donors were lower than that of subjects with MetS and first-time donors. The difference between regular donors and subjects with MetS was statistically significant. However, there is no significant difference in the Hb concentrations in the three groups. MetS is not associated with

  17. Lamprey hemoglobin. Structural basis of the bohr effect.

    PubMed

    Qiu, Y; Maillett, D H; Knapp, J; Olson, J S; Riggs, A F

    2000-05-01

    Lampreys, among the most primitive living vertebrates, have hemoglobins (Hbs) with self-association and ligand-binding properties very different from those that characterize the alpha(2)beta(2) tetrameric Hbs of higher vertebrates. Monomeric, ligated lamprey Hb self-associates to dimers and tetramers upon deoxygenation. Dissociation to monomers upon oxygenation accounts for the cooperative binding of O(2) and its pH dependence. Honzatko and Hendrickson (Honzatko, R. B., and Hendrickson, W. A. (1986) Proc. Natl. Acad. Sci. U. S. A 83, 8487-8491) proposed that the dimeric interface of the Hb resembles either the alpha(1)beta(2) interface of mammalian Hbs or the contacts in clam Hb where the E and F helices form the interface. Perutz (Perutz, M. F. (1989) Quart. Rev. Biophys. 2, 139- 236) proposed a version of the clam model in which the distal histidine swings out of the heme pocket upon deoxygenation to form a bond with a carboxyl group of a second monomer. The sedimentation behavior and oxygen equilibria of nine mutants of the major Hb component, PMII, from Petromyzon marinus have been measured to test these models. The results strongly support a critical role of the E helix and the AB corner in forming the subunit interface in the dimer and rule out the alpha(1)beta(2) model. The pH dependence of both the sedimentation equilibrium and the oxygen binding of the mutant E75Q indicate that Glu(75) is one of two groups responsible for the Bohr effect. Changing the distal histidine 73 to glutamine almost completely abolishes the self-association of the deoxy-Hb and causes a large increase in O(2) affinity. The recent x-ray crystallographic determination of the structure of deoxy lamprey Hb, reported after the completion of this work (Heaslet, H. A., and Royer, W. E. (1999) Structure 7, 517-526), shows that the dimer interface does involve the E helix and the AB corner, supporting the measurements and interpretations reported here.

  18. Site-Selective Glycosylation of Hemoglobin on Cys β93

    PubMed Central

    Zhang, Yalong; Bhatt, Veer S.; Sun, Guoyong; Wang, Peng G.; Palmer, Andre F.

    2009-01-01

    In this work, we describe the synthesis and characterization of a novel glycosylated hemoglobin (Hb) with high oxygen affinity as a potential Hb-based oxygen carrier. Site-selective glycosylation of bovine Hb was achieved by conjugating a lactose derivative to Cys 93 on the β subunit of Hb. LC-MS analysis indicates that the reaction was quantitative, with no unmodified Hb present in the reaction product. The glycosylation site was identified by chymotrypsin digestion of the glycosylated bovine Hb followed with LC-MS/MS and from the X-ray crystal structure of the glycosylated Hb. The chemical conjugation of the lactose derivative at Cys β93 yields an oxygen carrier with a high oxygen affinity (P50 of 4.94 mmHg) and low cooperativity coefficient (n) of 1.20. Asymmetric flow field-flow fractionation (AFFFF) coupled with multi-angle static light scattering (MASLS) was used to measure the absolute molecular weight of the glycosylated Hb. AFFFF-MASLS analysis indicates that glycosylation of Hb significantly altered the α2β2-αβ equilibrium compared to native Hb. Subsequent X-ray analysis of the glycosylated Hb crystal showed that the covalently linked lactose derivative is sandwiched between the β1 and α2 (and hence by symmetry the β2 and α1) subunits of the tetramer, and the interaction between the saccharide and amino acid residues located at the interface is apparently stabilized by hydrogen bonding interactions. The resultant structural analysis of the glycosylated Hb helps to explain the shift in the α2β2-αβ equilibrium in terms of the hydrogen bonding interactions at the β1α2/β2α1 interface. Taken together, all of these results indicate that it is feasible to site-specifically glycosylate Hb. This work has great potential in developing an oxygen carrier with defined chemistry that can target oxygen delivery to low pO2 tissues and organs. PMID:18925771

  19. Hemoglobin induces inflammation after preterm intraventricular hemorrhage by methemoglobin formation

    PubMed Central

    2013-01-01

    Background Cerebral intraventricular hemorrhage (IVH) is a major cause of severe neurodevelopmental impairment in preterm infants. To date, no therapy is available that prevents infants from developing serious neurological disability following IVH. Thus, to develop treatment strategies for IVH, it is essential to characterize the initial sequence of molecular events that leads to brain damage. In this study, we investigated extracellular hemoglobin (Hb) as a causal initiator of inflammation in preterm IVH. Methods Using a preterm rabbit pup model, we investigated the molecular mechanisms and events following IVH. We also characterized the concentrations of cell-free Hb metabolites and pro-inflammatory mediators in the cerebrospinal fluid (CSF) of preterm human infants and rabbit pups. Finally, Hb metabolites were evaluated as causal initiators of inflammation in primary rabbit astrocyte cell cultures. Results Following IVH in preterm rabbit pups, the intraventricular CSF concentration of cell-free methemoglobin (metHb) increased from 24 to 72 hours and was strongly correlated with the concentration of TNFα at 72 hours (r2 = 0.896, P <0.001). Also, the mRNA expression of TNFα, IL-1β, and Toll-like receptor-4 and TNFα protein levels were significantly increased in periventricular tissue at 72 hours, which was accompanied by extensive astrocyte activation (that is, glial fibrillary acidic protein (GFAP)staining). Furthermore, exposure of primary rabbit astrocyte cell cultures to metHb caused a dose-dependent increase in TNFα mRNA and protein levels, which was not observed following exposure to oxyhemoglobin (oxyHb) or hemin. Finally, a positive correlation (r2 = 0.237, P <0.03) between metHb and TNFα concentrations was observed in the CSF of preterm human infants following IVH. Conclusions Following preterm IVH, increased metHb formation in the intraventricular space induces expression of pro-inflammatory cytokines. Thus, the formation of metHb might be a

  20. Human hemoglobin structural and functional alterations and heme degradation upon interaction with benzene: A spectroscopic study

    NASA Astrophysics Data System (ADS)

    Hosseinzadeh, Reza; Moosavi-Movahedi, Ali Akbar

    2016-03-01

    Here, the effect of benzene on hemoglobin structure, stability and heme prosthetic group integrity was studied by different methods. These included UV-vis absorption spectrophotometry, normal and synchronous fluorescence techniques, and differential scanning calorimetry (DSC). Our results indicated that benzene has high hemolytic potential even at low concentrations. The UV-vis spectroscopic results demonstrated that benzene altered both the globin chain and the heme prosthetic group of hemoglobin increasing met- and deoxy-Hb, while decreasing oxy-Hb. However, with increasing benzene the concentration of all species decreased due to heme destruction. The spectrophotometric results show that benzene has a high potential for penetrating the hydrophobic pocket of hemoglobin. These results were consistent with the molecular docking simulation results of benzene-hHb. Aggregation and thermal denaturation studies show that the increased benzene concentration induced hemoglobin aggregation with a decrease in stability, which is consistent with the DSC results. Conventional fluorescence spectroscopy revealed that the heme degradation species were produced in the presence of benzene. The results of constant wavelength synchronous fluorescence spectroscopy (CWSFS) indicated that at least five heme-degraded species were produced. Together, our results indicated that benzene has adverse effects on hemoglobin structure and function, and heme degradation.