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Sample records for adult human hemoglobin

  1. 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.

  2. Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells.

    PubMed

    Emara, Marwan; Turner, A Robert; Allalunis-Turner, Joan

    2014-02-01

    Hemoglobin is a hemoprotein, produced mainly in erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell types including human and rodent neurons of embryonic and adult brain, but not astrocytes and oligodendrocytes. Human glioblastoma multiforme (GBM) is the most aggressive tumor among gliomas. However, despite extensive basic and clinical research studies on GBM cells, little is known about glial defence mechanisms that allow these cells to survive and resist various types of treatment. We have shown previously that the newest members of vertebrate globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are expressed in human GBM cells. In this study, we sought to determine whether hemoglobin is also expressed in GBM cells. Conventional RT-PCR, DNA sequencing, western blot analysis, mass spectrometry and fluorescence microscopy were used to investigate globin expression in GBM cell lines (M006x, M059J, M059K, M010b, U87R and U87T) that have unique characteristics in terms of tumor invasion and response to radiotherapy and hypoxia. The data showed that α, β, γ, δ, ζ and ε globins are expressed in all tested GBM cell lines. To our knowledge, we are the first to report expression of fetal, embryonic and adult hemoglobin in GBM cells under normal physiological conditions that may suggest an undefined function of those expressed hemoglobins. Together with our previous reports on globins (Ngb and Cygb) expression in GBM cells, the expression of different hemoglobins may constitute a part of series of active defence mechanisms supporting these cells to resist various types of treatments including chemotherapy and radiotherapy.

  3. 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.

  4. Heme orientational disorder in human adult hemoglobin reconstituted with a ring fluorinated heme and its functional consequences

    SciTech Connect

    Nagao, Satoshi; Hirai, Yueki; Kawano, Shin; Imai, Kiyohiro; Suzuki, Akihiro; Yamamoto, Yasuhiko . E-mail: yamamoto@chem.tsukuba.ac.jp

    2007-03-16

    A ring fluorinated heme, 13,17-bis(2-carboxylatoethyl)-3,8-diethyl-2-fluoro-7,12, 18-trimethyl-porphyrin-atoiron(III), has been incorporated into human adult hemoglobin (Hb A). The heme orientational disorder in the individual subunits of the protein has been readily characterized using {sup 19}F NMR and the O{sub 2} binding properties of the protein have been evaluated through the oxygen equilibrium analysis. The equilibrated orientations of hemes in {alpha}- and {beta}- subunits of the reconstituted protein were found to be almost completely opposite to each other, and hence were largely different from those of the native and the previously reported reconstituted proteins [T. Jue, G.N. La Mar, Heme orientational heterogeneity in deuterohemin-reconstituted horse and human hemoglobin characterized by proton nuclear magnetic resonance spectroscopy, Biochem. Biophys. Res. Commun. 119 (1984) 640-645]. Despite the large difference in the degree of the heme orientational disorder in the subunits of the proteins, the O{sub 2} affinity and the cooperativity of the protein reconstituted with 2-MF were similar to those of the proteins reconstituted with a series of hemes chemically modified at the heme 3- and 8-positions [K. Kawabe, K. Imaizumi, Z. Yoshida, K. Imai, I. Tyuma, Studies on reconstituted myoglobins and hemoglobins II. Role of the heme side chains in the oxygenation of hemoglobin, J. Biochem. 92 (1982) 1713-1722], whose O{sub 2} affinity and cooperativity were higher and lower, respectively, relative to those of native protein. These results indicated that the heme orientational disorder could exert little effect, if any, on the O{sub 2} affinity properties of Hb A. This finding provides new insights into structure-function relationship of Hb A.

  5. Reactivating Fetal Hemoglobin Expression in Human Adult Erythroblasts Through BCL11A Knockdown Using Targeted Endonucleases

    PubMed Central

    Bjurström, Carmen F; Mojadidi, Michelle; Phillips, John; Kuo, Caroline; Lai, Stephen; Lill, Georgia R; Cooper, Aaron; Kaufman, Michael; Urbinati, Fabrizia; Wang, Xiaoyan; Hollis, Roger P; Kohn, Donald B

    2016-01-01

    We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34+ progenitor cells. ZFNs and TALENs were delivered as in vitro transcribed mRNA through electroporation; CRISPR/Cas9 was codelivered by Cas9 mRNA with plasmid-encoded guideRNA (gRNA) (pU6.g1) or in vitro transcribed gRNA (gR.1). Analyses of efficacy revealed that for these specific reagents and the delivery methods used, the ZFNs gave rise to more allelic disruption in the targeted locus compared to the TALENs and CRISPR/Cas9, which was associated with increased levels of fetal hemoglobin in erythroid cells produced in vitro from nuclease-treated CD34+ cells. Genome-wide analysis to evaluate the specificity of the nucleases revealed high specificity of this specific ZFN to the target site, while specific TALENs and CRISPRs evaluated showed off-target cleavage activity. ZFN gene-edited CD34+ cells had the capacity to engraft in NOD-PrkdcSCID-IL2Rγnull mice, while retaining multi-lineage potential, in contrast to TALEN gene-edited CD34+ cells. CRISPR engraftment levels mirrored the increased relative plasmid-mediated toxicity of pU6.g1/Cas9 in hematopoietic stem/progenitor cells (HSPCs), highlighting the value for the further improvements of CRISPR/Cas9 delivery in primary human HSPCs.

  6. Protonation states of histidine and other key residues in deoxy normal human adult hemoglobin by neutron protein crystallography

    SciTech Connect

    Kovalevsky, Andrey; Chatake, Toshiyuki; Shibayama, Naoya; Park, Sam-Yong; Ishikawa, Takuya; Mustyakimov, Marat; Fisher, S. Zoe; Langan, Paul; Morimoto, Yukio

    2010-11-01

    Using neutron diffraction analysis, the protonation states of 35 of 38 histidine residues were determined for the deoxy form of normal human adult hemoglobin. Distal and buried histidines may contribute to the increased affinity of the deoxy state for hydrogen ions and its decreased affinity for oxygen compared with the oxygenated form. The protonation states of the histidine residues key to the function of deoxy (T-state) human hemoglobin have been investigated using neutron protein crystallography. These residues can reversibly bind protons, thereby regulating the oxygen affinity of hemoglobin. By examining the OMIT F{sub o} − F{sub c} and 2F{sub o} − F{sub c} neutron scattering maps, the protonation states of 35 of the 38 His residues were directly determined. The remaining three residues were found to be disordered. Surprisingly, seven pairs of His residues from equivalent α or β chains, αHis20, αHis50, αHis58, αHis89, βHis63, βHis143 and βHis146, have different protonation states. The protonation of distal His residues in the α{sub 1}β{sub 1} heterodimer and the protonation of αHis103 in both subunits demonstrates that these residues may participate in buffering hydrogen ions and may influence the oxygen binding. The observed protonation states of His residues are compared with their ΔpK{sub a} between the deoxy and oxy states. Examination of inter-subunit interfaces provided evidence for interactions that are essential for the stability of the deoxy tertiary structure.

  7. Upstream promoter mutation associated with a modest elevation of fetal hemoglobin expression in human adults.

    PubMed

    Gilman, J G; Mishima, N; Wen, X J; Kutlar, F; Huisman, T H

    1988-07-01

    In hereditary persistence of fetal hemoglobin, Hb F (alpha 2 gamma 2) is elevated after birth. Screening of sickle cell patients has revealed a family with elevated Hb F and high A gamma values. The propositus was a sickle cell patient with approximately 25% Hb F and 68.4% A gamma. He was heterozygous for the Benin (#19) and Mor beta S haplotypes. Five AS relatives with the Mor haplotype had 2.5% +/- 0.9% fetal hemoglobin and 92.8% +/- 2.8% A gamma, whereas two with the Benin haplotype had normal fetal hemoglobin (0.5%). The Mor haplotype is thus associated with the elevated Hb F in this family. The 13-kilobase (kb) Bg/II fragment containing the G gamma and A gamma genes of the Mor haplotype was cloned, and the G gamma and A gamma promoters sequenced from -383 to beyond the Cap sites. The Mor G gamma gene was normal, but the A gamma gene had a unique C----T mutation at -202. A different mutation at -202 of G gamma (C----G) was previously detected by other researchers in association with considerably higher Hb F in AS cases (15% to 25%). These data suggest either that -202 mutations affect the G gamma and A gamma promoters differently or that different nucleotide substitutions at -202 have divergent effects. Alternatively, additional unknown mutations could cause the differences in gene expression.

  8. LIN28B-mediated expression of fetal hemoglobin and production of fetal-like erythrocytes from adult human erythroblasts ex vivo

    PubMed Central

    Lee, Y. Terry; de Vasconcellos, Jaira F.; Yuan, Joan; Byrnes, Colleen; Noh, Seung-Jae; Meier, Emily R.; Kim, Ki Soon; Rabel, Antoinette; Kaushal, Megha; Muljo, Stefan A.

    2013-01-01

    Reactivation of fetal hemoglobin (HbF) holds therapeutic potential for sickle cell disease and β-thalassemias. In human erythroid cells and hematopoietic organs, LIN28B and its targeted let-7 microRNA family, demonstrate regulated expression during the fetal-to-adult developmental transition. To explore the effects of LIN28B in human erythroid cell development, lentiviral transduction was used to knockdown LIN28B expression in erythroblasts cultured from human umbilical cord CD34+ cells. The subsequent reduction in LIN28B expression caused increased expression of let-7 and significantly reduced HbF expression. Conversely, LIN28B overexpression in cultured adult erythroblasts reduced the expression of let-7 and significantly increased HbF expression. Cellular maturation was maintained including enucleation. LIN28B expression in adult erythroblasts increased the expression of γ-globin, and the HbF content of the cells rose to levels >30% of their hemoglobin. Expression of carbonic anhydrase I, glucosaminyl (N-acetyl) transferase 2, and miR-96 (three additional genes marking the transition from fetal-to-adult erythropoiesis) were reduced by LIN28B expression. The transcription factor BCL11A, a well-characterized repressor of γ-globin expression, was significantly down-regulated. Independent of LIN28B, experimental suppression of let-7 also reduced BCL11A expression and significantly increased HbF expression. LIN28B expression regulates HbF levels and causes adult human erythroblasts to differentiate with a more fetal-like phenotype. PMID:23798711

  9. 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

  10. 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.

  11. 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

  12. Direct determination of protonation states of histidine residues in a 2 A neutron structure of deoxy-human normal adult hemoglobin and implications for the Bohr effect.

    PubMed

    Kovalevsky, Andrey Y; Chatake, Toshiyuki; Shibayama, Naoya; Park, Sam-Yong; Ishikawa, Takuya; Mustyakimov, Marat; Fisher, Zoe; Langan, Paul; Morimoto, Yukio

    2010-04-30

    We have investigated the protonation states of histidine residues (potential Bohr groups) in the deoxy form (T state) of human hemoglobin by direct determination of hydrogen (deuterium) positions with the neutron protein crystallography technique. The reversible binding of protons is key to the allosteric regulation of human hemoglobin. The protonation states of 35 of the 38 His residues were directly determined from neutron scattering omit maps, with 3 of the remaining residues being disordered. Protonation states of 5 equivalent His residues--alpha His20, alpha His50, alpha His89, beta His143, and beta His146--differ between the symmetry-related globin subunits. The distal His residues, alpha His58 and beta His63, are protonated in the alpha 1 beta 1 heterodimer and are neutral in alpha 2 beta 2. Buried residue alpha His103 is found to be protonated in both subunits. These distal and buried residues have the potential to act as Bohr groups. The observed protonation states of His residues are compared to changes in their pK(a) values during the transition from the T to the R state and the results provide some new insights into our understanding of the molecular mechanism of the Bohr effect.

  13. 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.

  14. Genome annotation of a 1.5 Mb region of human chromosome 6q23 encompassing a quantitative trait locus for fetal hemoglobin expression in adults

    PubMed Central

    Close, James; Game, Laurence; Clark, Barnaby; Bergounioux, Jean; Gerovassili, Ageliki; Thein, Swee Lay

    2004-01-01

    Background Heterocellular hereditary persistence of fetal hemoglobin (HPFH) is a common multifactorial trait characterized by a modest increase of fetal hemoglobin levels in adults. We previously localized a Quantitative Trait Locus for HPFH in an extensive Asian-Indian kindred to chromosome 6q23. As part of the strategy of positional cloning and a means towards identification of the specific genetic alteration in this family, a thorough annotation of the candidate interval based on a strategy of in silico / wet biology approach with comparative genomics was conducted. Results The ~1.5 Mb candidate region was shown to contain five protein-coding genes. We discovered a very large uncharacterized gene containing WD40 and SH3 domains (AHI1), and extended the annotation of four previously characterized genes (MYB, ALDH8A1, HBS1L and PDE7B). We also identified several genes that do not appear to be protein coding, and generated 17 kb of novel transcript sequence data from re-sequencing 97 EST clones. Conclusion Detailed and thorough annotation of this 1.5 Mb interval in 6q confirms a high level of aberrant transcripts in testicular tissue. The candidate interval was shown to exhibit an extraordinary level of alternate splicing – 19 transcripts were identified for the 5 protein coding genes, but it appears that a significant portion (14/19) of these alternate transcripts did not have an open reading frame, hence their functional role is questionable. These transcripts may result from aberrant rather than regulated splicing. PMID:15169551

  15. Amino acid sequences of the alpha and beta chains of adult hemoglobin of the slender loris, Loris tardigradus.

    PubMed

    Maita, T; Goodman, M; Matsuda, G

    1978-08-01

    alpha and beta chains from adult hemoglobin of the slender loris (Loris tardigradus) were isolated by Amberlite CG-50 column chromatography. After S-aminoethylation, both chains were digested with trypsin and the amino acid sequences of the tryptic peptides obtained were analyzed. Further, the order of these tryptic peptides in each chain was deduced from their homology with the primary structures of alpha and beta chains of human adult hemoglobin. Comparing the primary structures of the alpha and beta chains of adult hemoglobin of the slender loris thus obtained with those of adult hemoglobin of the slow loris, 4 amino acid substitutions in the alpha chains and 2 in the beta chains were recognized.

  16. 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.

  17. 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.

  18. An Origin of Cooperative Oxygen Binding of Human Adult Hemoglobin: Different Roles of the α and β Subunits in the α2β2 Tetramer

    PubMed Central

    Sakurai, Hiroshi; Imai, Kiyohiro; Mizusawa, Naoki; Ogura, Takashi

    2015-01-01

    Human hemoglobin (Hb), which is an α2β2 tetramer and binds four O2 molecules, changes its O2-affinity from low to high as an increase of bound O2, that is characterized by ‘cooperativity’. This property is indispensable for its function of O2 transfer from a lung to tissues and is accounted for in terms of T/R quaternary structure change, assuming the presence of a strain on the Fe-histidine (His) bond in the T state caused by the formation of hydrogen bonds at the subunit interfaces. However, the difference between the α and β subunits has been neglected. To investigate the different roles of the Fe-His(F8) bonds in the α and β subunits, we investigated cavity mutant Hbs in which the Fe-His(F8) in either α or β subunits was replaced by Fe-imidazole and F8-glycine. Thus, in cavity mutant Hbs, the movement of Fe upon O2-binding is detached from the movement of the F-helix, which is supposed to play a role of communication. Recombinant Hb (rHb)(αH87G), in which only the Fe-His in the α subunits is replaced by Fe-imidazole, showed a biphasic O2-binding with no cooperativity, indicating the coexistence of two independent hemes with different O2-affinities. In contrast, rHb(βH92G), in which only the Fe-His in the β subunits is replaced by Fe-imidazole, gave a simple high-affinity O2-binding curve with no cooperativity. Resonance Raman, 1H NMR, and near-UV circular dichroism measurements revealed that the quaternary structure change did not occur upon O2-binding to rHb(αH87G), but it did partially occur with O2-binding to rHb(βH92G). The quaternary structure of rHb(αH87G) appears to be frozen in T while its tertiary structure is changeable. Thus, the absence of the Fe-His bond in the α subunit inhibits the T to R quaternary structure change upon O2-binding, but its absence in the β subunit simply enhances the O2-affinity of α subunit. PMID:26244770

  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. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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% ...

  13. 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.

  14. 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.

  15. 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.

  16. Hemoglobin E Hemoglobinopathy in an Adult from Assam with Unusual Presentation: A Diagnostic Dilemma

    PubMed Central

    Kiran, Sunitha S; Aithal, Saraswathy; Belagavi, Charalingappa S

    2016-01-01

    Hemoglobin E (HbE) is estimated to affect at least one million people around the world. Carrier frequency of hemoglobin E/β-thalassemia (HbE/β-thalassemia) is highest in Southeast Asia, reaching as high as 60% in parts of Thailand, Laos, and Cambodia. In the Indian subcontinent, highest frequency is observed in The Northeast regions, but relatively rare in rest of the country. Increasing migration of population from highly affected areas is resulting in rising prevalence in The South and other parts of India. HbE/β-thalassemia is characterized by marked clinical diversity, phenotypic instability, and age-related changes in adaptation to anemia. This paper reports a case of HbE disease in an adult immigrant from Assam and documents the difficulties encountered in the definitive subtyping of HbE hemoglobinopathy. Distinguishing between homozygous HbE disease and HbE/β-thalassemia is a challenge to hematopathologist as both are clinically and hematologically similar. PMID:27365922

  17. Absolute measurement of cerebral optical coefficients, hemoglobin concentration and oxygen saturation in old and young adults with near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Hallacoglu, Bertan; Sassaroli, Angelo; Wysocki, Michael; Guerrero-Berroa, Elizabeth; Schnaider Beeri, Michal; Haroutunian, Vahram; Shaul, Merav; Rosenberg, Irwin H.; Troen, Aron M.; Fantini, Sergio

    2012-08-01

    We present near-infrared spectroscopy measurement of absolute cerebral hemoglobin concentration and saturation in a large sample of 36 healthy elderly (mean age, 85±6 years) and 19 young adults (mean age, 28±4 years). Non-invasive measurements were obtained on the forehead using a commercially available multi-distance frequency-domain system and analyzed using a diffusion theory model for a semi-infinite, homogeneous medium with semi-infinite boundary conditions. Our study included repeat measurements, taken five months apart, on 16 elderly volunteers that demonstrate intra-subject reproducibility of the absolute measurements with cross-correlation coefficients of 0.9 for absorption coefficient (μa), oxy-hemoglobin concentration ([HbO2]), and total hemoglobin concentration ([HbT]), 0.7 for deoxy-hemoglobin concentration ([Hb]), 0.8 for hemoglobin oxygen saturation (StO2), and 0.7 for reduced scattering coefficient (). We found significant differences between the two age groups. Compared to young subjects, elderly subjects had lower cerebral [HbO2], [Hb], [HbT], and StO2 by 10±4 μM, 4±3 μM, 14±5 μM, and 6%±5%, respectively. Our results demonstrate the reliability and robustness of multi-distance near-infrared spectroscopy measurements based on a homogeneous model in the human forehead on a large sample of human subjects. Absolute, non-invasive optical measurements on the brain, such as those presented here, can significantly advance the development of NIRS technology as a tool for monitoring resting/basal cerebral perfusion, hemodynamics, oxygenation, and metabolism.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. [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.

  3. Inclusion bodies in loggerhead erythrocytes are associated with unstable hemoglobin and resemble human Heinz bodies.

    PubMed

    Basile, Filomena; Di Santi, Annalisa; Caldora, Mercedes; Ferretti, Luigi; Bentivegna, Flegra; Pica, Alessandra

    2011-08-01

    The aim of this study was to clarify the role of the erythrocyte inclusions found during the hematological screening of loggerhead population of the Mediterranean Sea. We studied the erythrocyte inclusions in blood specimens collected from six juvenile and nine adult specimens of the loggerhead turtle, Caretta caretta, from the Adriatic and Tyrrhenian Seas. Our study indicates that the percentage of mature erythrocytes containing inclusions ranged from 3 to 82%. Each erythrocyte contained only one round inclusion body. Inclusion bodies stained with May Grünwald-Giemsa show that their cytochemical and ultrastructure characteristics are identical to those of human Heinz bodies. Because Heinz bodies originate from the precipitation of unstable hemoglobin (Hb) and cause globular osmotic resistance to increase, we analyzed loggerhead Hb using electrophoresis and high-performance liquid chromatography to detect and quantitate Hb fractions. We also tested the resistance of Hb to alkaline pH, heat, isopropanol denaturation, and globular osmosis. Our hemogram results excluded the occurrence of any infection, which could be associated with an inclusion body, in all the specimens. Negative Feulgen staining indicated that the inclusion bodies are not derived from DNA fragmentation. We hypothesize that amino acid substitutions could explain why loggerhead Hb precipitates under normal physiologic conditions, forming Heinz bodies. The identification of inclusion bodies in loggerhead erythrocytes allow us to better understand the haematological characteristics and the physiology of these ancient reptiles, thus aiding efforts to conserve such an endangered species. PMID:21538919

  4. Using the NCBI Genome Databases to Compare the Genes for Human & Chimpanzee Beta Hemoglobin

    ERIC Educational Resources Information Center

    Offner, Susan

    2010-01-01

    The beta hemoglobin protein is identical in humans and chimpanzees. In this tutorial, students see that even though the proteins are identical, the genes that code for them are not. There are many more differences in the introns than in the exons, which indicates that coding regions of DNA are more highly conserved than non-coding regions.

  5. Multispectroscopic and calorimetric studies on the binding of the food colorant tartrazine with human hemoglobin.

    PubMed

    Basu, Anirban; Suresh Kumar, Gopinatha

    2016-11-15

    Interaction of the food colorant tartrazine with human hemoglobin was studied using multispectroscopic and microcalorimetric techniques to gain insights into the binding mechanism and thereby the toxicity aspects. Hemoglobin spectrum showed hypochromic changes in the presence of tartrazine. Quenching of the fluorescence of hemoglobin occurred and the quenching mechanism was through a static mode as revealed from temperature dependent and time-resolved fluorescence studies. According to the FRET theory the distance between β-Trp37 of hemoglobin and bound tartrazine was evaluated to be 3.44nm. Synchronous fluorescence studies showed that tartrazine binding led to alteration of the microenvironment around the tryptophans more in comparison to tyrosines. 3D fluorescence and FTIR data provided evidence for conformational changes in the protein on binding. Circular dichroism studies revealed that the binding led to significant loss in the helicity of hemoglobin. The esterase activity assay further complemented the circular dichroism data. Microcalorimetric study using isothermal titration calorimetry revealed the binding to be exothermic and driven largely by positive entropic contribution. Dissection of the Gibbs energy change proposed the protein-dye complexation to be dominated by non-polyelectrolytic forces. Negative heat capacity change also corroborated the involvement of hydrophobic forces in the binding process. PMID:27450339

  6. 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

  7. Tyrosine residues as redox cofactors in human hemoglobin: implications for engineering nontoxic blood substitutes.

    PubMed

    Reeder, Brandon J; Grey, Marie; Silaghi-Dumitrescu, Radu-Lucian; Svistunenko, Dimitri A; Bülow, Leif; Cooper, Chris E; Wilson, Michael T

    2008-11-01

    Respiratory proteins such as myoglobin and hemoglobin can, under oxidative conditions, form ferryl heme iron and protein-based free radicals. Ferryl myoglobin can safely be returned to the ferric oxidation state by electron donation from exogenous reductants via a mechanism that involves two distinct pathways. In addition to direct transfer between the electron donor and ferryl heme edge, there is a second pathway that involves "through-protein" electron transfer via a tyrosine residue (tyrosine 103, sperm whale myoglobin). Here we show that the heterogeneous subunits of human hemoglobin, the alpha and beta chains, display significantly different kinetics for ferryl reduction by exogenous reductants. By using selected hemoglobin mutants, we show that the alpha chain possesses two electron transfer pathways, similar to myoglobin. Furthermore, tyrosine 42 is shown to be a critical component of the high affinity, through-protein electron transfer pathway. We also show that the beta chain of hemoglobin, lacking the homologous tyrosine, does not possess this through-protein electron transfer pathway. However, such a pathway can be engineered into the protein by mutation of a specific phenylalanine residue to a tyrosine. High affinity through-protein electron transfer pathways, whether native or engineered, enhance the kinetics of ferryl removal by reductants, particularly at low reductant concentrations. Ferryl iron has been suggested to be a major cause of the oxidative toxicity of hemoglobin-based blood substitutes. Engineering hemoglobin with enhanced rates of ferryl removal, as we show here, is therefore likely to result in molecules better suited for in vivo oxygen delivery.

  8. [Influence of mastication on the amount of hemoglobin in human brain tissue].

    PubMed

    Sasaki, A

    2001-03-01

    The purpose of this study was to investigate the influence of mastication on the amount of hemoglobin in human brain tissue. Nine healthy volunteers (6 males and 3 females) participated in this study. They underwent two tasks: 1) at rest, 2) gum-chewing. In seven of the nine (4 males and 3 females), experimental occlusal interference was applied to the first molar of the mandibule on the habitual masticatory side. They underwent the gum-chewing task. To evaluate the amount of hemoglobin, both the hemoglobin oxygenation state and blood volume during gum-chewing were measured in the frontal region, using near-infrared spectroscopy. The amount of total-hemoglobin (blood volume) and oxyhemoglobin of subjects significantly increased during gum-chewing (p < 0.01). When the subjects finished gum-chewing, both levels returned to the original levels. When experimental occlusal interference was imposed on the subject, the amount of them significantly decreased compared with subjects without experimental occlusal interference (p < 0.05). The results suggested that increases of cerebral blood flow in the frontal region were not due to the mandibular movement, and that human brain activity caused by mastication was not only in the cortical masticatory area but also in the frontal region.

  9. Diabetes knowledge in young adults: associations with hemoglobin A1C.

    PubMed

    Beck, Joni K; Zhang, Ying; Shay, Christina M; Muhamedagic, Cynthia A; Sternlof, Steven A; Ding, Kai; Short, Megan M; Dvorak, Justin D; Lane, James T

    2015-03-01

    The purpose of this study was to quantify associations between hemoglobin A1C (A1C) and diabetes knowledge score using an assessment tool developed to evaluate the level of diabetes knowledge in young adults with Type 1 diabetes (T1DM) and their parent/primary caregiver. Seventy-five participants with T1DM, ages 15-22 years, completed questionnaires. Two 25-item questionnaires were developed: one for patient and one for caregiver. Linear regression quantified associations between correct items on the tools and participant A1C and demographic characteristics. Mean age of participants was 16.7 ± 1.7 years, diabetes duration 5.9 ± 4.2 years, 46.7% male, 74.7% Caucasian, 69.3% on multiple daily injections, and 30.7% on continuous subcutaneous insulin infusion therapy; 78.7% of parents/caregivers completed the questionnaire. A significant interaction was observed between patient and caregiver scores with A1C by diabetes duration. Among patients with diabetes <6 years, higher patient and caregiver scores were associated with lower A1C (-0.25 ± 0.11, p = .03 and -0.59 ± 0.19, p = .005, respectively) accounting for age, gender, race, therapy, and insurance. Neither patient nor caregiver score was associated with A1C in patients with diabetes duration ≥6 years. Better performance on a diabetes knowledge assessment (for both patient and the caregiver) was found to be associated with more favorable levels of glycemic control among young adults with diabetes <6 years. Additional evaluation of these questionnaires and novel interventions to enhance knowledge in this population are needed.

  10. Molecular oxygen migration through the xenon docking sites of human hemoglobin in the R-state.

    PubMed

    Lepeshkevich, Sergei V; Gilevich, Syargey N; Parkhats, Marina V; Dzhagarov, Boris M

    2016-09-01

    A nanosecond laser flash-photolysis technique was used to study bimolecular and geminate molecular oxygen (O2) rebinding to tetrameric human hemoglobin and its isolated α and β chains in buffer solutions equilibrated with 1atm of air and up to 25atm of xenon. Xenon binding to the isolated α chains and to the α subunits within tetrameric hemoglobin was found to cause a decrease in the efficiency of O2 escape by a factor of ~1.30 and 3.3, respectively. A kinetic model for O2 dissociation, rebinding, and migration through two alternative pathways in the hemoglobin subunits was introduced and discussed. It was shown that, in the isolated α chains and α subunits within tetrameric hemoglobin, nearly one- and two-third escaping molecules of O2 leave the protein via xenon docking sites, respectively. The present experimental data support the idea that O2 molecule escapes from the β subunits mainly through the His(E7) gate, and show unambiguously that, in the α subunits, in addition to the direct E7 channel, there is at least one alternative escape route leading to the exterior via the xenon docking sites. PMID:27288155

  11. Separation of human hemoglobins by DEAE-cellulose chromatography using glycine-KCN-NaC1 developers.

    PubMed

    Abraham, E C; Reese, A; Stallings, M; Huisman, T H

    This chromatographic procedure uses DEAE-cellulose as ion exchanger and glycine-KCN-NaC1 solutions as developers. Blood samples from several adults and newborn infants with alpha, beta, delta, or gamma chains variants have been analysed. The hemoglobins are eluted as compact and symmetrical zones, and the separation of many hemoglobin types is greatly improved. The procedure is relatively fast, simple, and inexpensive.

  12. Towards hemerythrin-based blood substitutes: comparative performance to hemoglobin on human leukocytes and umbilical vein endothelial cells.

    PubMed

    Fischer-Fodor, Eva; Mot, Augustin; Deac, Florina; Arkosi, Mariann; Silaghi-Dumitrescu, Radu

    2011-06-01

    Hemerythrin is a dioxygen-carrying protein whose oxidative/nitrosative stress-related reactivity is lower than that of hemoglobin, which may warrant investigation of hemerythrin as raw material for artificial oxygen carriers ('blood substitutes'). We report here the first biological tests for hemerythrin and its chemical derivatives, comparing their performance with that of a representative competitor, glutaraldehyde-polymerized bovine hemoglobin. Hemerythrin (native or derivatized) exhibits a proliferative effect on human umbilical vein endothelial cell (HUVEC) cultures, as opposed to a slight inhibitory effect of hemoglobin. A similar positive effect is displayed on human lymphocytes by glutaraldehyde-polymerized hemerythrin, but not by native or polyethylene glycol-derivatized hemerythrin.

  13. Probing the energetics of proteins through structural perturbation: sites of regulatory energy in human hemoglobin.

    PubMed Central

    Pettigrew, D W; Romeo, P H; Tsapis, A; Thillet, J; Smith, M L; Turner, B W; Ackers, G K

    1982-01-01

    The sites of energy transduction within the human hemoglobin molecule for the regulation of oxygen affinity have been determined by an extensive study of the molecule's energetic response to structural alteration at individual amino acid residues. For 22 mutant and chemically modified hemoglobins we have determined the total free energy used by the tetrameric molecule for alteration of oxygen affinity at the four binding steps. The results imply that the regulation of oxygen binding affinity is due to energy changes which are mostly localized at the alpha 1 beta 2 interface. They also indicate a high degree of "internal cooperativity" within this contact region--i.e., the structural perturbations at individual residue sites are energetically coupled. Cooperativity in ligand binding is thus a reflection of cooperativity at a deeper level--that of the protein-protein interactions within the alpha 1 beta 2 interfacial domain. Images PMID:6952235

  14. Analytical determination of specific 4,4'-methylene diphenyl diisocyanate hemoglobin adducts in human blood.

    PubMed

    Gries, Wolfgang; Leng, Gabriele

    2013-09-01

    4,4'-Methylene diphenyl diisocyanate (MDI) is one of the most important isocyanates in the industrial production of polyurethane and other MDI-based synthetics. Because of its high reactivity, it is known as a sensitizing agent, caused by protein adducts. Analysis of MDI is routinely done by determination of the nonspecific 4,4'-methylenedianiline as a marker for MDI exposure in urine and blood. Since several publications have reported specific adducts of MDI and albumin or hemoglobin, more information about their existence in humans is necessary. Specific adducts of MDI and hemoglobin were only reported in rats after high-dose MDI inhalation. The aim of this investigation was to detect the hemoglobin adduct 5-isopropyl-3-[4-(4-aminobenzyl)phenyl]hydantoin (ABP-Val-Hyd) in human blood for the first time. We found values up to 5.2 ng ABP-Val-Hyd/g globin (16 pmol/g) in blood samples of workers exposed to MDI. Because there was no information available about possible amounts of this specific MDI marker, the analytical method focused on optimal sensitivity and selectivity. Using gas chromatography-high-resolution mass spectrometry with negative chemical ionization, we achieved a detection limit of 0.02 ng ABP-Val-Hyd/g globin (0.062 pmol/g). The robustness of the method was confirmed by relative standard deviations between 3.0 and 9.8 %. Combined with a linear detection range up to 10 ng ABP-Val-Hyd/g globin (31 pmol/g), the enhanced precision parameter demonstrates that the method described is optimized for screening studies of the human population. PMID:23839327

  15. A biochemical--biophysical study of hemoglobins from woolly mammoth, Asian elephant, and humans.

    PubMed

    Yuan, Yue; Shen, Tong-Jian; Gupta, Priyamvada; Ho, Nancy T; Simplaceanu, Virgil; Tam, Tsuey Chyi S; Hofreiter, Michael; Cooper, Alan; Campbell, Kevin L; Ho, Chien

    2011-08-30

    This study is aimed at investigating the molecular basis of environmental adaptation of woolly mammoth hemoglobin (Hb) to the harsh thermal conditions of the Pleistocene ice ages. To this end, we have carried out a comparative biochemical-biophysical characterization of the structural and functional properties of recombinant hemoglobins (rHb) from woolly mammoth (rHb WM) and Asian elephant (rHb AE) in relation to human hemoglobins Hb A and Hb A(2) (a minor component of human blood). We have obtained oxygen equilibrium curves and calculated O(2) affinities, Bohr effects, and the apparent heat of oxygenation (ΔH) in the presence and absence of allosteric effectors [inorganic phosphate and inositol hexaphosphate (IHP)]. Here, we show that the four Hbs exhibit distinct structural properties and respond differently to allosteric effectors. In addition, the apparent heat of oxygenation (ΔH) for rHb WM is less negative than that of rHb AE, especially in phosphate buffer and the presence of IHP, suggesting that the oxygen affinity of mammoth blood was also less sensitive to temperature change. Finally, (1)H NMR spectroscopy data indicates that both α(1)(β/δ)(1) and α(1)(β/δ)(2) interfaces in rHb WM and rHb AE are perturbed, whereas only the α(1)δ(1) interface in Hb A(2) is perturbed compared to that in Hb A. The distinct structural and functional features of rHb WM presumably facilitated woolly mammoth survival in the Arctic environment.

  16. A biochemical--biophysical study of hemoglobins from woolly mammoth, Asian elephant, and humans.

    PubMed

    Yuan, Yue; Shen, Tong-Jian; Gupta, Priyamvada; Ho, Nancy T; Simplaceanu, Virgil; Tam, Tsuey Chyi S; Hofreiter, Michael; Cooper, Alan; Campbell, Kevin L; Ho, Chien

    2011-08-30

    This study is aimed at investigating the molecular basis of environmental adaptation of woolly mammoth hemoglobin (Hb) to the harsh thermal conditions of the Pleistocene ice ages. To this end, we have carried out a comparative biochemical-biophysical characterization of the structural and functional properties of recombinant hemoglobins (rHb) from woolly mammoth (rHb WM) and Asian elephant (rHb AE) in relation to human hemoglobins Hb A and Hb A(2) (a minor component of human blood). We have obtained oxygen equilibrium curves and calculated O(2) affinities, Bohr effects, and the apparent heat of oxygenation (ΔH) in the presence and absence of allosteric effectors [inorganic phosphate and inositol hexaphosphate (IHP)]. Here, we show that the four Hbs exhibit distinct structural properties and respond differently to allosteric effectors. In addition, the apparent heat of oxygenation (ΔH) for rHb WM is less negative than that of rHb AE, especially in phosphate buffer and the presence of IHP, suggesting that the oxygen affinity of mammoth blood was also less sensitive to temperature change. Finally, (1)H NMR spectroscopy data indicates that both α(1)(β/δ)(1) and α(1)(β/δ)(2) interfaces in rHb WM and rHb AE are perturbed, whereas only the α(1)δ(1) interface in Hb A(2) is perturbed compared to that in Hb A. The distinct structural and functional features of rHb WM presumably facilitated woolly mammoth survival in the Arctic environment. PMID:21806075

  17. Hydroxyurea-Increased Fetal Hemoglobin Is Associated with Less Organ Damage and Longer Survival in Adults with Sickle Cell Anemia

    PubMed Central

    Fitzhugh, Courtney D.; Hsieh, Matthew M.; Allen, Darlene; Coles, Wynona A.; Seamon, Cassie; Ring, Michael; Zhao, Xiongce; Minniti, Caterina P.; Rodgers, Griffin P.; Schechter, Alan N.; Tisdale, John F.; Taylor, James G.

    2015-01-01

    Background Adults with sickle cell anemia (HbSS) are inconsistently treated with hydroxyurea. Objectives We retrospectively evaluated the effects of elevating fetal hemoglobin with hydroxyurea on organ damage and survival in patients enrolled in our screening study between 2001 and 2010. Methods An electronic medical record facilitated development of a database for comparison of study parameters based on hydroxyurea exposure and dose. This study is registered with ClinicalTrials.gov, number NCT00011648. Results Three hundred eighty-three adults with homozygous sickle cell disease were analyzed with 59 deaths during study follow-up. Cox regression analysis revealed deceased subjects had more hepatic dysfunction (elevated alkaline phosphatase, Hazard Ratio = 1.005, 95% CI 1.003–1.006, p<0.0.0001), kidney dysfunction (elevated creatinine, Hazard Ratio = 1.13, 95% CI 1.00–1.27, p = 0.043), and cardiopulmonary dysfunction (elevated tricuspid jet velocity on echocardiogram, Hazard Ratio = 2.22, 1.23–4.02, p = 0.0082). Sixty-six percent of subjects were treated with hydroxyurea, although only 66% of those received a dose within the recommended therapeutic range. Hydroxyurea use was associated with improved survival (Hazard Ratio = 0.58, 95% CI 0.34–0.97, p = 0.040). This effect was most pronounced in those taking the recommended dose of 15–35 mg/kg/day (Hazard Ratio 0.36, 95% CI 0.17–0.73, p = 0.0050). Hydroxyurea use was not associated with changes in organ function over time. Further, subjects with higher fetal hemoglobin responses to hydroxyurea were more likely to survive (p = 0.0004). While alkaline phosphatase was lowest in patients with the best fetal hemoglobin response (95.4 versus 123.6, p = 0.0065 and 96.1 versus 113.6U/L, p = 0.041 at first and last visits, respectively), other markers of organ damage were not consistently improved over time in patients with the highest fetal hemoglobin levels. Conclusions Our data suggest that adults should be

  18. [Identification of rat and human hemoglobin acetilation sites after its interaction with acetylsalicylic acid].

    PubMed

    Shreĭner, E V; Murashko, E A; Dubrovskiĭ, Ia D; Krasnov, N V; Podol'skaia, E P; Babakov, V N

    2012-01-01

    The possibility of interaction of 0.1 mg/mL acetylsalicylic acid with purified human and rat globin in vitro during 24 h at 37 degrees C was investigated. The rat globin can be modified with acetylsalicylic acid on aminoacid residues K-17, K-57, K-91, K-140 in alpha subunit as well as on K-18, K-77 in beta subunit. The human globin can be modified with acetylsalicylic acid on aminoacid residues K-17, K-41, K-57 and K-91 in alpha subunit as well as on K-18, K-96 and K- 133 in beta subunit. We identified of acetetylated lysines K-17 and K-57 in alpha subunit of human hemoglobin after incubation whole blood with 0.1 mg/mL acetylsalicylic acid during 3 h.

  19. Biocompatibility study of protein capped and uncapped silver nanoparticles on human hemoglobin

    NASA Astrophysics Data System (ADS)

    Bhunia, Amit Kumar; Kanti Samanta, Pijus; Aich, Debasish; Saha, Satyajit; Kamilya, Tapanendu

    2015-06-01

    The interactions of human hemoglobin with protein capped silver nanoparticles and bare silver nanoparticles were studied to understand fundamental perspectives about the biocompatibility of protein capped silver nanoparticles compared with bare silver nanoparticles. Bare silver (Ag) nanoparticles (NPs) were prepared by the chemical reduction method. High resolution transmission electron microscopy (HRTEM) analysis along with absorption at ~390 nm indicated the formation of bare Ag NPs. Protein coated Ag NPs were prepared by a green synthesis method. Absorption at ~440 nm along with ~280 nm indicated the formation of protein coated Ag NPs. The biocompatibility of the above mentioned Ag NPs was studied by interaction with human hemoglobin (Hb) protein. In presence of bare Ag NPs, the Soret band of Hb was red shifted. This revealed the distortion of iron from the heme pockets of Hb. Also, the fluorescence peak of Hb was quenched and red shifted which indicated that Hb became unfolded in the presence of bare Ag NPs. No red shift of the absorption of Soret, along with no shift and quenching of the fluorescence peak of Hb were observed in the presence of protein coated Ag NPs. A hemolysis assay suggested that protein coated Ag NPs were more biocompatible than bare one.

  20. Luminol chemiluminescence biosensor for glycated hemoglobin (HbA1c) in human blood samples.

    PubMed

    Ahn, Kwang-Soo; Lee, JungHoon; Park, Jong-Myeon; Choi, Han Nim; Lee, Won-Yong

    2016-01-15

    Luminol chemiluminescence (CL) biosensor based on boronic acid modified gold substrate has been developed for the determination of glycated hemoglobin (HbA1c) in human blood samples. In order to selectively capture HbA1c in sample, carboxy-EG6-undecanethiol was self-assembled on a gold thin-film substrate, followed by covalent coupling of 3-aminophenyl boronic acid (3-APBA). The captured HbA1c containing four iron heme groups plays as a catalyst for luminol CL reaction in the presence of hydrogen peroxide, and thus the luminol CL response is linearly proportional to the amount of HbA1c captured on the biosensor surface. The present biosensor showed linear dynamic range of HbA1c from 2.5% to 17.0%, which well covers the clinically important concentration range. In addition, the present biosensor exhibited negligible response to interfering species such as hemoglobin, fructose, and sorbitol. The present HbA1c biosensor was applied to the determination of HbA1c in human blood samples and the results were well agreed with that obtained with a conventional method.

  1. [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

  2. Mutual effects of proton and sodium chloride on oxygenation of liganded human hemoglobin.

    PubMed

    Lepeshkevich, Sergei V; Dzhagarov, Boris M

    2005-12-01

    The different effects of pH and NaCl on individual O2-binding properties of alpha and beta subunits within liganded tetramer and dimer of human hemoglobin (HbA) were examined in a number of laser time-resolved spectroscopic measurements. A previously proposed approach [Dzhagarov BM & Lepeshkevich SV (2004) Chem Phys Lett390, 59-64] was used to determine the extent of subunit dissociation rate constant difference and subunit affinity difference from a single flash photolysis experiment. To investigate the effect of NaCl concentration on the association and dissociation rate constants we carried out a series of experiments at four different concentrations (0.1, 0.5, 1.0 and 2.0 m NaCl) over the pH range of the alkaline Bohr effect. As the data suggest, the individual properties of the alpha and beta subunits within the completely liganded tetrameric hemoglobin did not depend on pH under salt-free conditions. However, different effects NaCl on the individual kinetic properties of the alpha and beta subunits were revealed. Regulation of the O2-binding properties of the alpha and beta subunits within the liganded tetramer is proposed to be attained in two quite different ways.

  3. Oxygenated hemoglobin diffuse reflectance ratio for in vitro detection of human gastric pre-cancer

    NASA Astrophysics Data System (ADS)

    Li, L. Q.; Wei, H. J.; Guo, Z. Y.; Yang, H. Q.; Wu, G. Y.; Xie, S. S.; Zhong, H. Q.; Li, X. Y.; Zhao, Q. L.; Guo, X.

    2010-07-01

    Oxygenated hemoglobin diffuse reflectance (DR) ratio (R540/R575) method based on DR spectral signatures is used for early diagnosis of malignant lesions of human gastric epithelial tissues in vitro. The DR spectra for four different kinds of gastric epithelial tissues were measured using a spectrometer with an integrating sphere detector in the spectral range from 400 to 650 nm. The results of measurement showed that the average DR spectral intensity for the epithelial tissues of normal stomach is higher than that for the epithelial tissues of chronic and malignant stomach and that for the epithelial tissues of chronic gastric ulcer is higher than that for the epithelial tissues of malignant stomach. The average DR spectra for four different kinds of gastric epithelial tissues show dips at 542 and 577 nm owing to absorption from oxygenated Hemoglobin (HbO2). The differences in the mean R540/R575 ratios of HbO2 bands are 6.84% between the epithelial tissues of normal stomach and chronic gastric ulcer, 14.7% between the epithelial tissues of normal stomach and poorly differentiated gastric adenocarcinoma and 22.6% between the epithelial tissues of normal stomach and undifferentiated gastric adenocarcinoma. It is evident from results that there were significant differences in the mean R540/R575 ratios of HbO2 bands for four different kinds of gastric epithelial tissues in vitro ( P < 0.01).

  4. Arts & Humanities in Adult Education.

    ERIC Educational Resources Information Center

    Word's Worth: A Quarterly Newsletter of the Lifelong Learning Network, 1998

    1998-01-01

    This issue of a quarterly newsletter on lifelong learning focuses on the theme of the arts and humanities in adult literacy education. The following articles are included: (1) "In Defense of a Practical Education" (Earl Shorris); (2) "From the Program Director" (Elizabeth Bryant McCrary); (3) "Vermont Council on the Humanities: Book Discussion…

  5. Nitroreduction and formation of hemoglobin adducts in rats with a human intestinal microflora

    SciTech Connect

    Scheepers, P.T.J.; Straetemans, M.M.E.; Koopman, J.P.; Bos, R.P.

    1994-10-01

    In the covalent binding of nitroarenes to macromolecules, nitroreduction is an important step. The intestinal microflora represents an enormous potential of bacterial nitroreductase activity. As a consequence, the in vivo nitroreduction of orally administerednitroarenes is primarily located in the intestine. In this study, we have investigated the nitroreduction of 2-nitrofluorene (2-NF) by a human microflora in female Wistar rats. Germ-free (FG) rats were equipped with a bacterial flora derived from human feces. Nontreated GF rats and GF animals equipped with a conventional rat flora were used as controls. The composition of the human and the conventional microflora isolated from the rats were consistent with the microflora of the administered feces. In the rats receiving only sunflower seed oil, no adducts were detected. The animals equipped with a human or rat microflora that received 2-aminofluorene (2-AF) formed 2-AF hemoglobin (Hb)-adducts at average levels mean {+-} 0.003 and 0.043 {+-} 0.010 {mu}mole/g Hb, respectively. In the FG rats, an adduct level of 0.57 {+-} 0.09 was determined after 2-AF administration and non adducts were detected after 2-NF administration. The results show that nitroreduction by an acquired human intestinal microflora and subsequent adduct formation can be studied in the rate in vivo. 21 refs., 3 tabs.

  6. Absolute measurement of cerebral optical coefficients, hemoglobin concentration and oxygen saturation in old and young adults with near-infrared spectroscopy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We present near-infrared spectroscopy measurement of absolute cerebral hemoglobin concentration and saturation in a large sample of 36 healthy elderly (mean age, 85 ± 6 years) and 19 young adults (mean age, 28 ± 4 years). Non-invasive measurements were obtained on the forehead using a commercially a...

  7. 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 ...

  8. Variations in the distribution of selenium between erythrocyte glutathione peroxidase and hemoglobin in different human populations

    SciTech Connect

    Whanger, P.D.; Robinson, M.F.; Feldman, E.B.; Beilstein, M.A.; Butler, J.A.

    1986-03-01

    The majority of erythrocyte (RBC) selenium (Se) is associated with glutathione peroxidase (GPx) in animals, but most of it is with hemoglobin (Hb) in human RBCs. Dietary forms of Se may influence this distribution since a rat study showed that selenite promoted the deposition of Se in GPx but selenomethionine (SeMet) resulted in greater amounts with Hb. Three different populations of people were chosen to investigate some possible reasons for the Se distribution in human RBC proteins. An average of 12% of the RBC Se (0.71 ng Se/mg Hb) was associated with GPx in people living in Oregon, but nearly 30% of the Se was associated with GPx in RBC (0.26 ng Se/mg Hb) from New Zealanders. Georgia residents with low RBC Se levels (0.35 ng Se/mg Hb) had 38% of the Se associated with GPx as compared to 29% for those with higher RBC levels (0.56 ng Se/mg Hb). In a third group of people the amount of Se tended to be higher in RBC GPx from non-vegetarian OSU students than from vegetarians. The predominant form of Se in meat appears to be selenocysteine, which is metabolized similarly to selenite, and presumably contributes to this difference since many plant foods contain Se as SeMet. These are examples of many possible factors affecting the relative distribution of Se in human RBC proteins.

  9. Hemoglobin and hemin induce DNA damage in human colon tumor cells HT29 clone 19A and in primary human colonocytes.

    PubMed

    Glei, Michael; Klenow, Stefanie; Sauer, Julia; Wegewitz, Uta; Richter, Konrad; Pool-Zobel, Beatrice L

    2006-02-22

    Epidemiological findings have indicated that red meat increases the likelihood of colorectal cancer. Aim of this study was to investigate whether hemoglobin, or its prosthetic group heme, in red meat, is a genotoxic risk factor for cancer. Human colon tumor cells (HT29 clone 19A) and primary colonocytes were incubated with hemoglobin/hemin and DNA damage was investigated using the comet assay. Cell number, membrane damage, and metabolic activity were measured as parameters of cytotoxicity in both cell types. Effects on cell growth were determined using HT29 clone 19A cells. HT29 clone 19A cells were also used to explore possible pro-oxidative effects of hydrogen peroxide (H2O2) and antigenotoxic effects of the radical scavenger dimethyl sulfoxide (DMSO). Additionally we determined in HT29 clone 19A cells intracellular iron levels after incubation with hemoglobin/hemin. We found that hemoglobin increased DNA damage in primary cells (> or =10 microM) and in HT29 clone 19A cells (> or =250 microM). Hemin was genotoxic in both cell types (500-1000 microM) with concomitant cytotoxicity, detected as membrane damage. In both cell types, hemoglobin and hemin (> or =100 microM) impaired metabolic activity. The growth of HT29 clone 19A cells was reduced by 50 microM hemoglobin and 10 microM hemin, indicating cytotoxicity at genotoxic concentrations. Hemoglobin or hemin did not enhance the genotoxic activity of H2O2 in HT29 clone 19A cells. On the contrary, DMSO reduced the genotoxicity of hemoglobin, which indicated that free radicals were scavenged by DMSO. Intracellular iron increased in hemoglobin/hemin treated HT29 clone 19A cells, reflecting a 40-50% iron uptake for each compound. In conclusion, our studies show that hemoglobin is genotoxic in human colon cells, and that this is associated with free radical mechanisms and with cytotoxicity, especially for hemin. Thus, hemoglobin/hemin, whether available from red meat or from bowel bleeding, may pose genotoxic and

  10. Hemoglobin adducts of the human bladder carcinogen o-toluidine after treatment with the local anesthetic prilocaine.

    PubMed

    Gaber, Kerstin; Harréus, Ulrich A; Matthias, Christoph; Kleinsasser, Norbert H; Richter, Elmar

    2007-01-01

    Prilocaine, a widely used local anesthetic, is metabolized to o-toluidine which is classified as human carcinogen. We aimed to assess the impact of prilocaine-treatment on hemoglobin adducts from o-toluidine. Blood samples were obtained before and 24h after receiving prilocaine local anesthesia (Xylonest, 100mg) from 20 head and neck surgery patients and 6 healthy volunteers. Hemoglobin adducts of o-toluidine and 4-aminobiphenyl were determined by gas chromatography/mass spectrometry. Hemoglobin adducts of o-toluidine were significantly increased 24h after 100mg prilocaine-treatment by 21.6+/-12.8ng/g hemoglobin (mean+/-S.D., N=26; P<0.0001). This corresponds to a 6-360-fold increase of o-toluidine adduct levels in 25 patients from 0.54+/-0.95ng/g before treatment to 22.0+/-13.2ng/g 24h after surgery (mean+/-S.D.). Because of an extremely high background level the increase was only 1.6-fold in one patient (40.9ng/g before and 64.4ng/g 24h after prilocaine injection). Current smoking had no influence on background values and on the increase of o-toluidine adducts. No treatment-related differences were seen in mean hemoglobin adduct levels of 4-aminobiphenyl which were significantly higher in smokers, 0.149+/-0.096ng/g (mean+/-S.D., N=8) as compared to nonsmokers 0.036+/-0.035ng/g (mean+/-S.D., N=16; P<0.01). In conclusion, prilocaine anesthesia leads to a massive increase of hemoglobin adducts of the carcinogenic arylamine o-toluidine. This implies a carcinogenic risk which should be taken into account in preventive hazard minimization.

  11. Transfection of the Human Heme Oxygenase Gene Into Rabbit Coronary Microvessel Endothelial Cells: Protective Effect Against Heme and Hemoglobin Toxicity

    NASA Astrophysics Data System (ADS)

    Abraham, N. G.; Lavrovsky, Y.; Schwartzman, M. L.; Stoltz, R. A.; Levere, R. D.; Gerritsen, M. E.

    1995-07-01

    Heme oxygenase (HO) is a stress protein and has been suggested to participate in defense mechanisms against agents that may induce oxidative injury such as metals, endotoxin, heme/hemoglobin, and various cytokines. Overexpression of HO in cells might therefore protect against oxidative stress produced by certain of these agents, specifically heme and hemoglobin, by catalyzing their degradation to bilirubin, which itself has antioxidant properties. We report here the successful in vitro transfection of rabbit coronary microvessel endothelial cells with a functioning gene encoding the human HO enzyme. A plasmid containing the cytomegalovirus promoter and the human HO cDNA complexed to cationic liposomes (Lipofectin) was used to transfect rabbit endothelial cells. Cells transfected with human HO exhibited an ≈3.0-fold increase in enzyme activity and expressed a severalfold induction of human HO mRNA as compared with endogenous rabbit HO mRNA. Transfected and nontransfected cells expressed factor VIII antigen and exhibited similar acetylated low-density lipoprotein uptake (two important features that characterize endothelial cells) with >85% of cells staining positive for each marker. Moreover, cells transfected with the human HO gene acquired substantial resistance to toxicity produced by exposure to recombinant hemoglobin and heme as compared with nontransfected cells. The protective effect of HO overexpression against heme/hemoglobin toxicity in endothelial cells shown in these studies provides direct evidence that the inductive response of human HO to such injurious stimuli represents an important tissue adaptive mechanism for moderating the severity of cell damage produced by these blood components.

  12. Evidence by chromatography and mass spectrometry that inorganic nitrite induces S-glutathionylation of hemoglobin in human red blood cells.

    PubMed

    Böhmer, Anke; Pich, Andreas; Schmidt, Mario; Haghikia, Arash; Tsikas, Dimitrios

    2016-04-15

    Previously we found by HPLC with fluorescence detection that inorganic nitrite induces oxidation of glutathione (GSH) to its disulfide (GSSG) in intact and more abundantly in lyzed red blood cells (RBCs) from healthy humans. In the present work, we performed MS-based protein analysis and observed that nitrite (range, 0-20mM) induces formation of S-glutathionyl hemoglobin (HbSSG) at cysteine (Cys) β93 and β112 of oxyhemoglobin (HbO2) in lyzed human RBCs (range, 6-8mM HbO2). Hemoglobin species were isolated from incubation mixtures of nitrite in lyzed RBCs by ultrafiltration or affinity chromatography and analyzed by HPLC and LC-MS/MS. The mechanism likely involves inhibition of catalase activity by nitrite (IC50, 9 μM), which allows H2O2 to accumulate and oxidize Cys moieties of oxyhemoglobin and erythrocytic GSH to form HbSSG in addition to GSSG. In freshly prepared hemolysate samples, nitrite induced release of superoxide and molecular oxygen. In the presence of paracetamol and nitrite in hemolysate samples, 3-nitro-paracetamol was detected. Nitrite also induced S-nitroso hemoglobin (HbSNO) formation in low yield (i.e., 0.1%). Synthetic cysteine (Cys), glutathione (GSH), N-acetylcysteine (NAC) and N-acetylcysteine ethyl ester (NACET) inhibited nitrite-induced modifications of oxyhemoglobin including methemoglobin, HbSSG (CysSH > NACET > GSH ≈ NAC; thiol concentration, 50 μM) and HbSNO. Nitrite-induced oxidative modifications may alter physiological hemoglobin functions and may require alternative treatments for conditions associated with oxidized hemoglobin like in nitrite-induced methemoglobinemia. Accumulation of soluble Cys in RBCs via oral administration of NACET could be a new promising strategy to prevent nitrite-induced methemoglobinemia by nitrite and other oxidants. PMID:26830534

  13. Binding of dihydromyricetin to human hemoglobin: Fluorescence and circular dichroism studies

    NASA Astrophysics Data System (ADS)

    Chen, Tingting; Zhu, Shajun; Shang, Yanfang; Ge, Cunwang; Jiang, Guoqing

    The binding reaction between dihydromyricetin (DMY) and human hemoglobin (HHb) was investigated systematically with various spectroscopic methods including fluorescence quenching technique, ultraviolet (UV)-vis absorption, synchronous fluorescence, circular dichroism (CD) spectroscopy. The experimental results showed that DMY effectively quenched the intrinsic fluorescence of HHb via static quenching. DMY binds to HHb with a stoichiometry that varies from 0.972:1 to 0.906:1 as the temperature increases from 296 to 304 K. The DMY-HHb binding constants were determined to be K296 = 2.79 × 104 and K304 = 1.18 × 104 L mol-1. The reaction is characterized by negative enthalpy (ΔH = -80.46 kJ mol-1) and negative entropy (ΔS = -186.72 kJ mol-1), indicating that the predominant forces in the DMY-HHb complex are van der Waals and hydrogen bonding forces. Based on the Förster's theory of non-radiative energy transfer, the binding distance between DMY and the inner tryptophan residues of HHb was determined to be 3.15 nm. Furthermore, the CD spectroscopy indicated the secondary structure of HHb is not changed in the presence of DMY.

  14. Non-site-specific allosteric effect of oxygen on human hemoglobin under high oxygen partial pressure

    PubMed Central

    Takayanagi, Masayoshi; Kurisaki, Ikuo; Nagaoka, Masataka

    2014-01-01

    Protein allostery is essential for vital activities. Allosteric regulation of human hemoglobin (HbA) with two quaternary states T and R has been a paradigm of allosteric structural regulation of proteins. It is widely accepted that oxygen molecules (O2) act as a “site-specific” homotropic effector, or the successive O2 binding to the heme brings about the quaternary regulation. However, here we show that the site-specific allosteric effect is not necessarily only a unique mechanism of O2 allostery. Our simulation results revealed that the solution environment of high O2 partial pressure enhances the quaternary change from T to R without binding to the heme, suggesting an additional “non-site-specific” allosteric effect of O2. The latter effect should play a complementary role in the quaternary change by affecting the intersubunit contacts. This analysis must become a milestone in comprehensive understanding of the allosteric regulation of HbA from the molecular point of view. PMID:24710521

  15. Staphylococcus aureus uses a novel multidomain receptor to break apart human hemoglobin and steal its heme.

    PubMed

    Spirig, Thomas; Malmirchegini, G Reza; Zhang, Jiang; Robson, Scott A; Sjodt, Megan; Liu, Mengyao; Krishna Kumar, Kaavya; Dickson, Claire F; Gell, David A; Lei, Benfang; Loo, Joseph A; Clubb, Robert T

    2013-01-11

    Staphylococcus aureus is a leading cause of life-threatening infections in the United States. It requires iron to grow, which must be actively procured from its host to successfully mount an infection. Heme-iron within hemoglobin (Hb) is the most abundant source of iron in the human body and is captured by S. aureus using two closely related receptors, IsdH and IsdB. Here we demonstrate that each receptor captures heme using two conserved near iron transporter (NEAT) domains that function synergistically. NMR studies of the 39-kDa conserved unit from IsdH (IsdH(N2N3), Ala(326)-Asp(660)) reveals that it adopts an elongated dumbbell-shaped structure in which its NEAT domains are properly positioned by a helical linker domain, whose three-dimensional structure is determined here in detail. Electrospray ionization mass spectrometry and heme transfer measurements indicate that IsdH(N2N3) extracts heme from Hb via an ordered process in which the receptor promotes heme release by inducing steric strain that dissociates the Hb tetramer. Other clinically significant Gram-positive pathogens capture Hb using receptors that contain multiple NEAT domains, suggesting that they use a conserved mechanism.

  16. Staphylococcus aureus Uses a Novel Multidomain Receptor to Break Apart Human Hemoglobin and Steal Its Heme*

    PubMed Central

    Spirig, Thomas; Malmirchegini, G. Reza; Zhang, Jiang; Robson, Scott A.; Sjodt, Megan; Liu, Mengyao; Krishna Kumar, Kaavya; Dickson, Claire F.; Gell, David A.; Lei, Benfang; Loo, Joseph A.; Clubb, Robert T.

    2013-01-01

    Staphylococcus aureus is a leading cause of life-threatening infections in the United States. It requires iron to grow, which must be actively procured from its host to successfully mount an infection. Heme-iron within hemoglobin (Hb) is the most abundant source of iron in the human body and is captured by S. aureus using two closely related receptors, IsdH and IsdB. Here we demonstrate that each receptor captures heme using two conserved near iron transporter (NEAT) domains that function synergistically. NMR studies of the 39-kDa conserved unit from IsdH (IsdHN2N3, Ala326–Asp660) reveals that it adopts an elongated dumbbell-shaped structure in which its NEAT domains are properly positioned by a helical linker domain, whose three-dimensional structure is determined here in detail. Electrospray ionization mass spectrometry and heme transfer measurements indicate that IsdHN2N3 extracts heme from Hb via an ordered process in which the receptor promotes heme release by inducing steric strain that dissociates the Hb tetramer. Other clinically significant Gram-positive pathogens capture Hb using receptors that contain multiple NEAT domains, suggesting that they use a conserved mechanism. PMID:23132864

  17. Induction of human fetal hemoglobin via the NRF2 antioxidant response signaling pathway

    PubMed Central

    Macari, Elizabeth R.

    2011-01-01

    Although hematopoietic stem cell transplantation and gene therapy have the potential to cure β-thalassemia and sickle cell disease, they are not currently available to most people with these diseases. In the near term, pharmacologic induction of fetal hemoglobin (HbF) may offer the best possibility for safe, effective, and widely available therapy. In an effort to define new pathways for targeted drug development for HbF induction, we evaluated the nuclear factor erythroid 2–related factor 2 (NRF2) antioxidant response element signaling pathway. We found that 3 well-known activators of this pathway increased γ-globin mRNA at nontoxic doses in K562 cells. Tert-butylhydroquinone (tBHQ), the most active of these compounds, increased cellular levels and nuclear translocation of NRF2 and binding of NRF2 to the γ-globin promoter. siRNA knockdown of NRF2 inhibited γ-globin induction by tBHQ. When tested in human primary erythroid cells, tBHQ induced NRF2 binding to the γ-globin promoter, increased γ-globin mRNA and HbF, and suppressed β-globin mRNA and HbA, resulting in a > 3-fold increase in the percentage of HbF. These results suggest that drugs that activate the NRF2/antioxidant response element signaling pathway have the potential to induce therapeutic levels of HbF in people with β-hemoglobinopathies. PMID:21464371

  18. Induction of human fetal hemoglobin via the NRF2 antioxidant response signaling pathway.

    PubMed

    Macari, Elizabeth R; Lowrey, Christopher H

    2011-06-01

    Although hematopoietic stem cell transplantation and gene therapy have the potential to cure β-thalassemia and sickle cell disease, they are not currently available to most people with these diseases. In the near term, pharmacologic induction of fetal hemoglobin (HbF) may offer the best possibility for safe, effective, and widely available therapy. In an effort to define new pathways for targeted drug development for HbF induction, we evaluated the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant response element signaling pathway. We found that 3 well-known activators of this pathway increased γ-globin mRNA at nontoxic doses in K562 cells. Tert-butylhydroquinone (tBHQ), the most active of these compounds, increased cellular levels and nuclear translocation of NRF2 and binding of NRF2 to the γ-globin promoter. siRNA knockdown of NRF2 inhibited γ-globin induction by tBHQ. When tested in human primary erythroid cells, tBHQ induced NRF2 binding to the γ-globin promoter, increased γ-globin mRNA and HbF, and suppressed β-globin mRNA and HbA, resulting in a > 3-fold increase in the percentage of HbF. These results suggest that drugs that activate the NRF2/antioxidant response element signaling pathway have the potential to induce therapeutic levels of HbF in people with β-hemoglobinopathies.

  19. Refractive index of solutions of human hemoglobin from the near-infrared to the ultraviolet range: Kramers-Kronig analysis.

    PubMed

    Sydoruk, Oleksiy; Zhernovaya, Olga; Tuchin, Valery; Douplik, Alexandre

    2012-11-01

    Because direct measurements of the refractive index of hemoglobin over a large wavelength range are challenging, indirect methods deserve particular attention. Among them, the Kramers-Kronig relations are a powerful tool often used to derive the real part of a refractive index from its imaginary part. However, previous attempts to apply the relations to solutions of human hemoglobin have been somewhat controversial, resulting in disagreement between several studies. We show that this controversy can be resolved when careful attention is paid not only to the absorption of hemoglobin but also to the dispersion of the refractive index of the nonabsorbing solvent. We present a Kramers-Kroning analysis taking both contributions into account and compare the results with the data from several studies. Good agreement with experiments is found across the visible and parts of near-infrared and ultraviolet regions. These results reinstate the use of the Kramers-Kronig relations for hemoglobin solutions and provide an additional source of information about their refractive index.

  20. Hemoglobin: a gas transport molecule that is hormonally regulated in the ovarian follicle in mice and humans.

    PubMed

    Brown, Hannah M; Anastasi, Marie R; Frank, Laura A; Kind, Karen L; Richani, Dulama; Robker, Rebecca L; Russell, Darryl L; Gilchrist, Robert B; Thompson, Jeremy G

    2015-01-01

    An increasing number of nonerythroid tissues are found to express hemoglobin mRNA and protein. Hemoglobin is a well-described gas transport molecule, especially for O2, but also for NO, CO2, and CO, and also acts as a reactive oxygen species scavenger. We previously found Hba-a1 and Hbb mRNA and protein at high levels within mouse periovulatory cumulus cells, but not in cumulus following in vitro maturation. This led us to investigate the temporal and spatial regulation in follicular cells during the periovulatory period. Cumulus-oocyte complexes were collected from equine chorionic gonadotropin/human chorionic gonadotropin-treated peripubertal SV129 female mice and collected and analyzed for gene expression and protein localization at a variety of time points over the periovulatory period. A further cohort matured in vitro with different forms of hemoglobin (ferro- and ferrihemoglobin) under different O2 atmospheric conditions (2%, 5%, and 20% O2) were subsequently fertilized in vitro and cultured to the blastocyst stage. Murine mRNA transcripts for hemoglobin were regulated by stimulation of the ovulatory cascade, in both granulosa and cumulus cells, and expression of HBA1 and HBB was highly significant in human granulosa and cumulus, but erythrocyte cell marker genes were not. Several other genes involved in hemoglobin function were similarly luteinizing hormone-regulated, including genes for heme biosynthesis. Immunohistochemistry revealed a changing localization pattern of HBA-A1 protein in murine cumulus cells and oocytes following the ovulatory signal. Significantly, no positive staining for HBA-A1 protein was observed within in vitro-matured oocytes, but, if coincubated with ferro- or ferrihemoglobin, cytoplasmic HBA-A1 was observed, similar to in vivo-derived oocytes. Addition of ferro-, but not ferrihemoglobin, had a small, positive effect on blastocyst yield, but only under either 2% or 20% O2 gas atmosphere. The identification of hemoglobin within

  1. 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

  2. [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

  3. [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

  4. 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.

  5. Reaction of benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide with human hemoglobin and chromatographic resolution of the covalent adducts

    SciTech Connect

    Haugen, D.A.; Myers, S.R.

    1990-01-01

    The formation of hemoglobin-carcinogen adducts has been proposed as a measure of human exposure to carcinogens. Hemoglobin-carcinogen adducts have been detected in carcinogen-treated animals and in human populations. Although polycyclic aromatic hydrocarbons (PAH) are ubiquitous in the human environment and DNA-PAH adducts have been detected in human tissues, the occurrent of hemoglobin-PAH adducts in humans has not been described. In this study we examined the effects of reaction conditions on the extent of in vitro reaction of human hemoglobin and (+)(anti)-({sup 3}H)benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE), a metabolite largely responsible for the carcinogenic effect of benzo(a)pyrene. The chromatographic properties of the resulting hemoglobin-BPDE adducts were examined by conventional DEAE-cellulose ion-exchange liquid chromatography and by reversed-phase high-performance liquid chromatography. Several adducts were chromatographically resolved from hemoglobin and from the individual globins.

  6. Spectroscopic investigations of the interactions of tramadol hydrochloride and 5-azacytidine drugs with human serum albumin and human hemoglobin proteins.

    PubMed

    Tunç, Sibel; Cetinkaya, Ahmet; Duman, Osman

    2013-03-01

    The interactions of tramadol hydrochloride (THC) and 5-azacytidine (AZA) drugs with human serum albumin (HSA) and human hemoglobin (HMG) proteins were investigated by fluorescence, UV absorption and circular dichroism (CD) spectroscopy at pH 7.4 and different temperatures. The UV absorption spectra and the fluorescence quenching of HSA and HMG proteins indicated the formation of HSA-THC and HMG-THC complexes via static quenching mechanism. AZA did not interact with HSA and HMG proteins. It was found that the formation of HMG-THC complex was stronger than that of HSA-THC complex. The stability of HSA-THC and HMG-THC complexes decreased with increasing temperature. The number of binding site was found as one for HSA-THC and HMG-THC systems. Negative enthalpy change (ΔH) and Gibbs free energy change (ΔG) and positive entropy change (ΔS) values were obtained for these systems. The binding of THC-HSA and HMG proteins was spontaneous and exothermic. In addition, electrostatic interactions between protein and drug molecules played an important role in the binding processes. The results of CD analysis revealed that the addition of THC led to a significant conformational change in the secondary structure of HSA protein, on the contrary to HMG protein. PMID:23428887

  7. FORMATION OF HEMOGLOBIN AND ALBUMIN ADDUCTS OF BENZENE OXIDE IN MOUSE, RAT, AND HUMAN BLOOD

    EPA Science Inventory

    Little is known about the formation and disposition of benzene oxide (BO), the initial metabolite arising from oxidation of benzene by cytochrome P450. In this study, reactions of BO with hemoglobin (Hb) and albumin (Alb) were investigated in blood from B6C3F1 mice, F344 rats, ...

  8. Bohr effect of human hemoglobin A: magnitude of negative contributions determined by the equilibrium between two tertiary structures.

    PubMed

    Okonjo, Kehinde O; Olatunde, Abimbola M; Fodeke, Adedayo A; Babalola, J Oyebamiji

    2014-06-01

    We have measured the affinity of the CysF9[93]β sulfhydryl group of human deoxyhemoglobin and oxyhemoglobin for 5,5'-dithiobis(2-nitrobenzoate), DTNB, between pH ≈5.6 and 9 in order to understand the basis of the reported reduction of the Bohr effect induced by chemical modification of the sulfhydryl. We analyzed the results quantitatively on the basis of published data indicating that the sulfhydryl exists in two conformations that are coupled to the transition between two tertiary structures of hemoglobin in dynamic equilibrium. Our analyses show that the ionizable groups linked to the DTNB reaction have lower pKas of ionization in deoxyhemoglobin compared to oxyhemoglobin. So these ionizable groups should make negative contributions to the Bohr effect. We identify these groups as HisNA2[2]β, HisEF1[77]β and HisH21[143]β. We provide explanations for the finding that hemoglobin, chemically modified at CysF9[93]β, has a lower Bohr effect and a higher oxygen affinity than unmodified hemoglobin.

  9. Cysteines beta93 and beta112 as probes of conformational and functional events at the human hemoglobin subunit interfaces.

    PubMed Central

    Vásquez, G B; Karavitis, M; Ji, X; Pechik, I; Brinigar, W S; Gilliland, G L; Fronticelli, C

    1999-01-01

    Three variants of tetrameric human hemoglobin, with changes at the alpha1beta2/alpha2beta1-interface, at the alpha1beta1/alpha2beta2-interface, and at both interfaces, have been constructed. At alpha1beta2/alpha2beta1-interface the beta93 cysteine was replaced by alanine (betaC93A), and at the alpha1beta1/alpha2beta2-interface the beta112 cysteine was replaced by glycine (betaC112G). The alpha1beta2 interface variant, betaC93A, and the alpha1beta1/alpha1beta2 double mutant, beta(C93A+C112G), were crystallized in the T-state, and the structures determined at 2. 0 and 1.8 A resolution, respectively. A comparison of the structures with that of natural hemoglobin A shows the absence of detectable changes in the tertiary folding of the protein or in the T-state quaternary assembly. At the beta112 site, the void left by the removal of the cysteine side chain is filled by a water molecule, and the functional characteristics of betaC112G are essentially those of human hemoglobin A. At the beta93 site, water molecules do not replace the cysteine side chain, and the alanine substitution increases the conformational freedom of beta146His, weakening the important interaction of this residue with beta94Asp. As a result, when Cl- is present in the solution, at a concentration 100 mM, the Bohr effect of the two mutants carrying the beta93Cys-->Ala substitution, betaC93A and beta(C93A+C112G), is significantly modified being practically absent below pH 7.4. Based on the crystallographic data, we attribute these effects to the competition between beta94Asp and Cl- in the salt link with beta146His in T-state hemoglobin. These results point to an interplay between the betaHis146-betaAsp94 salt bridge and the Cl- in solution regulated by the Cys present at position beta93, indicating yet another role of beta93 Cys in the regulation of hemoglobin function. PMID:9876125

  10. 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 ...

  11. 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.

  12. Fluorescence line-narrowing spectral analysis of in vivo human hemoglobin-benzo(a)pyrene adducts: Comparison to synthetic analogues

    SciTech Connect

    Jankowiak, R.; Small, G.J. ); Day, B.W.; Skipper, P.L.; Tannenbaum, S.R.; Lu, Peiqi; Doxtader, M.M. )

    1990-07-18

    In order to gain insight as to the structure(s) of the adduct formed in vivo between human hemoglobin and the anti-diol epoxide (anti-BPDE) of benzo(a)pyrene (BaP), a series of model compounds was synthesized to investigate the effect on the fluorescence line-narrowing (FLN) spectra of heteroatom substitution at C-10 in BaP tetrahydrotetrol analogues. Spectra taken at 4.2 K by vibronic laser excitation at both 356.9 and 363.4 nm revealed marked differences between BaP tetrahydrotetrols and synthetic thioether, amino, and ester adducts of anti-BPDE. Use of these same excitation wavelengths on intact human globin samples obtained from individual s environmentally exposed to ambient levels of BaP yielded vibronic FLN spectra that were virtually indistinguishable from those of a synthetic C-10 carboxylic ester derived from anti-BPDE.

  13. 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.

  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. 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 ...

  16. Enhancing stability and expression of recombinant human hemoglobin in E. coli: Progress in the development of a recombinant HBOC source.

    PubMed

    Graves, Philip E; Henderson, Douglas P; Horstman, Molly J; Solomon, Brian J; Olson, John S

    2008-10-01

    The commercial feasibility of recombinant human Hb (rHb) as an O(2) delivery pharmaceutical is limited by the production yield of holoprotein in E. coli. Currently the production of rHb is not cost effective for use as a source in the development of third and fourth generation Hb-based oxygen carriers (HBOCs). The major problems appear to be aggregation and degradation of apoglobin at the nominal expression temperatures, 28-37 degrees C, and the limited amount of free heme that is available for holohemoglobin assembly. One approach to solve the first problem is to inhibit apoglobin precipitation by a comparative mutagenesis strategy to improve apoglobin stability. alpha Gly15 to Ala and beta Gly16 to Ala mutations have been constructed to increase the stability of the alpha helices of both subunits of HbA, based on comparison with the sequences of the more stable sperm whale hemoglobin subunits. Fetal hemoglobin is also known to be more stable than human HbA, and sequence comparisons between human beta and gamma (fetal Hb) chains indicate several substitutions that stabilize the alpha1beta1 interface, one of which, beta His116 to Ile, increases resistance to denaturation and enhances expression in E. coli. These favorable effects of enhanced globin stability can be augmented by co-expression of bacterial membrane heme transport systems to increase the rate and extent of heme uptake through the bacterial cell membranes. The combination of increased apoglobin stability and active heme transport appear to enhance holohemoglobin production to levels that may make rHb a plausible starting material for all extracellular Hb-based oxygen carriers.

  17. Prostacyclin receptor expression on platelets of humans with type 2 diabetes is inversely correlated with hemoglobin A1c levels.

    PubMed

    Knebel, Stephanie M; Sprague, Randy S; Stephenson, Alan H

    2015-01-01

    Inappropriate platelet aggregation can result in thrombosis and tissue ischemia. When compared to healthy human platelets, those of humans with type 2 diabetes (DM2) exhibit increased aggregation when stimulated. Activation of the platelet prostacyclin receptor (IPR) results in cAMP accumulation and inhibition of platelet aggregation. We hypothesized that DM2 platelets express decreased IPR when compared to platelets of healthy humans, resulting in decreased IPR agonist-induced cAMP accumulation. We measured IPR expression with radioligand binding of [(3)H]-iloprost, a stable prostacyclin analog, and with Western blotting of the IPR protein. Iloprost-stimulated platelet cAMP levels were used to identify the functional response to IPR activation. IPR binding, expression of the IPR protein and the levels of cAMP in platelets incubated with iloprost were significantly decreased in DM2 platelets when compared to platelets of healthy humans. IPR expression decreased in platelets as glycemic control of the subjects worsened, as indicated by increased hemoglobin A1c levels. Taken together, these findings suggest that reduced IPR expression in DM2 platelets may contribute to platelet hyperactivity in humans with type 2 diabetes. PMID:25617843

  18. Probing the binding of anticancer drug topotecan with human hemoglobin: Structural and thermodynamic studies.

    PubMed

    Khan, Asma Yasmeen; Kumar, Gopinatha Suresh

    2016-10-01

    Protein - ligand interactions play pivotal role in almost all the biological processes occurring in living organisms, and therefore such studies hold immense importance from the standpoint of rational drug design and development. In this study the binding of the topoisomerase I inhibitor drug, topotecan to hemoglobin was probed using various biophysical and microcalorimetry techniques. Spectrofluorimetric data confirmed the static nature of the quenching mechanism of the protein induced by the drug. Significant conformational changes in the protein were ascertained from circular dichroism and three dimensional fluorescence results. Synchronous fluorescence study revealed an increase in the polarity around the Trp residues of the protein while atomic force microscopy study enabled to obtain images of the bound molecules. Isothermal titration calorimetry studies indicated an exothermic binding with a negative Gibbs energy change; ionic strength variation suggested a greater contribution from non-polyelectrolytic forces in the binding process. Differential scanning calorimetry studies indicated an increased thermal stabilization of the protein upon topotecan binding which is also in close agreement with the results obtained from absorbance and circular dichroism melting studies. Overall this manuscript presents results on the molecular interaction from structural and energetic perspectives providing an in depth insight into drug-protein interaction. PMID:27585365

  19. The interaction of actinide and lanthanide ions with hemoglobin and its relevance to human and environmental toxicology.

    PubMed

    Kumar, Amit; Ali, Manjoor; Ningthoujam, Raghumani S; Gaikwad, Pallavi; Kumar, Mukesh; Nath, Bimalendu B; Pandey, Badri N

    2016-04-15

    Due to increasing use of lanthanides/actinides in nuclear and civil applications, understanding the impact of these metal ions on human health and environment is a growing concern. Hemoglobin (Hb), which occurs in all the kingdom of living organism, is the most abundant protein in human blood. In present study, effect of lanthanides and actinides [thorium: Th(IV), uranium: U(VI), lanthanum: La(III), cerium: Ce(III) and (IV)] on the structure and function of Hb has been investigated. Results showed that these metal ions, except Ce(IV) interacted with carbonyl and amide groups of Hb, which resulted in the loss of its alpha-helix conformation. However, beyond 75μM, these ions affected heme moiety. Metal-heme interaction was found to affect oxygen-binding of Hb, which seems to be governed by their closeness with the charge-to-ionic-radius ratio of iron(III). Consistently, Ce(IV) being closest to iron(III), exhibited a greater effect on heme. Binding constant and binding stoichiometry of Th(IV) were higher than that of U(VI). Experiments using aquatic midge Chironomus (possessing human homologous Hb) and human blood, further validated metal-Hb interaction and associated toxicity. Thus, present study provides a biochemical basis to understand the actinide/lanthanide-induced interference in heme, which may have significant implications for the medical and environmental management of lanthanides/actinides toxicity. PMID:26799219

  20. MicroRNA-15a and -16-1 act via MYB to elevate fetal hemoglobin expression in human trisomy 13.

    PubMed

    Sankaran, Vijay G; Menne, Tobias F; Šćepanović, Danilo; Vergilio, Jo-Anne; Ji, Peng; Kim, Jinkuk; Thiru, Prathapan; Orkin, Stuart H; Lander, Eric S; Lodish, Harvey F

    2011-01-25

    Many human aneuploidy syndromes have unique phenotypic consequences, but in most instances it is unclear whether these phenotypes are attributable to alterations in the dosage of specific genes. In human trisomy 13, there is delayed switching and persistence of fetal hemoglobin (HbF) and elevation of embryonic hemoglobin in newborns. Using partial trisomy cases, we mapped this trait to chromosomal band 13q14; by examining the genes in this region, two microRNAs, miR-15a and -16-1, appear as top candidates for the elevated HbF levels. Indeed, increased expression of these microRNAs in primary human erythroid progenitor cells results in elevated fetal and embryonic hemoglobin gene expression. Moreover, we show that a direct target of these microRNAs, MYB, plays an important role in silencing the fetal and embryonic hemoglobin genes. Thus we demonstrate how the developmental regulation of a clinically important human trait can be better understood through the genetic and functional study of aneuploidy syndromes and suggest that miR-15a, -16-1, and MYB may be important therapeutic targets to increase HbF levels in patients with sickle cell disease and β-thalassemia.

  1. 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

  2. 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.

  3. Association of Estimated Glomerular Filtration Rate with Hemoglobin Level in Korean Adults: The 2010–2012 Korea National Health and Nutrition Examination Survey

    PubMed Central

    Han, Sang Youb; Oh, Se Won; Hong, Jae Won; Yi, Seong Yoon; Noh, Jung Hyun; Lee, Hye Ran; Kim, Dong-Jun

    2016-01-01

    Purpose Little is known about anemia in patients with early renal dysfunction. We aimed to investigate the association of hemoglobin level and anemia prevalence with estimated glomerular filtration rate (eGFR) decline using a nation-wide representative sample of the adult Korean population. Methods In total, 17,373 participants (7,296 men; weighted n = 18,330,187; mean age, 44.2±0.3 years; 9,886 women, weighted n = 18,317,454; mean age, 46.9±0.3 years) were included. eGFR was divided into 5 groups: Group 1, ≥105; Group 2, 90–104; 75–89; Group 4, 60–74; and Group 5, <60 mL/min/1.73m2. Results The weighted anemia prevalence rates were 2.6% in men and 12.8% in women. In men, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked at an eGFR of 60–89 mL/min/1.73m2 and decreased thereafter at an eGFR of <60 mL/min/1.73m2 (15.19±0.03, 15.35±0.03, 15.53±0.03, 15.52±0.06, and 14.90±0.12 g/dL from Groups 1 to 5) after adjustment for age, college graduation, cancer history, current smoking, waist circumference, serum cholesterol level, serum triglyceride level, and diastolic blood pressure. In women, the weighted hemoglobin level increased with a decrease in eGFR; this value peaked with an eGFR of 75–89 mL/min/1.73m2 and decreased thereafter (12.90±0.03, 13.08±0.02, 13.20±0.04, 13.14±0.05, and 12.47±0.11 g/dL from Groups 1 to 5) after adjustment for menstruation, pregnancy, estrogen replacement, and the above-mentioned variables. In both sexes, the weighted prevalence of anemia with an eGFR of 60–104 mL/min/1.73m2 was significantly lower than that with an eGFR of ≥105 mL/min/1.73m2 (men, 3.2±0.4%, 1.9±0.3%, 1.8±0.3%, 2.0±0.9%, and 18.1±3.1%; women, 14.0±0.8%, 11.2±0.7%, 10.5±1.0%, 13.2±1.6%, and 32.3±3.2% from Groups 1 to 5). Conclusions We noted a compensatory increase in the hemoglobin level with a minor decline in kidney function (in the range of eGFR ≥60 mL/min/1.73m2) prior to a marked decrease in

  4. [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.

  5. Glycidol exposure evaluation of humans who have ingested diacylglycerol oil containing glycidol fatty acid esters using hemoglobin adducts.

    PubMed

    Honda, Hiroshi; Fujii, Kenkichi; Yamaguchi, Tohru; Ikeda, Naohiro; Nishiyama, Naohiro; Kasamatsu, Toshio

    2012-11-01

    Glycidol fatty acid esters (GEs) have been found as impurities in refined edible oils including diacylglycerol (DAG) oil, and concerns of possible exposure to glycidol (G), a known animal carcinogen, during digestion have been raised. We previously measured N-(2,3-dihydroxy-propyl)valine (diHOPrVal), a G hemoglobin adduct, for DAG oil exposed and non-exposed groups and showed there was no significant difference between them. In the present study, we conducted an additional analysis to verify the outcome of the previous report. The first experiment was designed as a matched case-control study to adjust variables with an increased sample size. The average levels of diHOPrVal were 6.9 pmol/g-globin (95%CI: 4.9-9.0) for 14 DAG oil exposed subjects and 7.3 pmol/g-globin (95%CI: 6.1-8.5) for 42 non-exposed volunteers, and no significant difference in levels was found between the two groups. In a second experiment, we compared the adduct levels of 12 DAG oil exposed subjects before and after discontinuing use of DAG oil, and found there was no significant change in diHOPrVal levels (from 7.1±1.1 to 7.5±1.4 pmol/g-globin). These results suggest that there was no increased exposure to G for humans who ingested DAG oil daily, although the evaluated population was limited.

  6. Measurement of glycidol hemoglobin adducts in humans who ingest edible oil containing small amounts of glycidol fatty acid esters.

    PubMed

    Honda, Hiroshi; Onishi, Masayuki; Fujii, Kenkichi; Ikeda, Naohiro; Yamaguchi, Tohru; Fujimori, Taketoshi; Nishiyama, Naohiro; Kasamatsu, Toshio

    2011-10-01

    Hemoglobin (Hb) adducts are frequently used to address and/or monitor exposure to reactive chemicals. Glycidol (G), a known animal carcinogen, has been reported to form Hb adducts. Here, we measure G adduct levels in humans who daily ingest DAG oil, an edible oil consisting mainly of diacylglycerol. Since DAG oil contains a small amount of glycidol fatty acid esters (GEs), possible exposure to G released from GEs has been raised as a possible concern. For measurement of Hb adducts, we employed the N-alkyl Edman method reported by Landin et al. (1996) using gas chromatography-tandem mass spectrometry with minor modifications to detect G-Hb adducts as N-(2,3-dihydroxy-propyl)valine (diHOPrVal). Blood samples were collected from 7 DAG oil users and 6 non-users, and then G-Hb adduct levels were measured. G-Hb adducts were detected in all samples. The average level of diHOPrVal was 3.5±1.9pmol/g globin in the DAG oil users and 7.1±3.1pmol/g globin in the non-users. We conclude that there is no increased exposure to G in individuals who daily ingest DAG oil.

  7. Binding of the alkaloid aristololactam-β-D-glucoside and daunomycin to human hemoglobin: spectroscopy and calorimetry studies.

    PubMed

    Das, Abhi; Suresh Kumar, Gopinatha

    2016-01-01

    The interaction of the plant alkaloid aristololactam-β-D-glucoside (ADG) and the anticancer agent daunomycin (DAN) with human hemoglobin was studied by different spectroscopic and calorimetric methods. The binding affinity values of ADG and DAN, estimated from spectroscopic experiments, were 3.79 × 10(4) and 6.68 × 10(4) M(-1), respectively. From circular dichroism, 3D fluorescence, and FTIR studies it was observed that, DAN induced stronger conformational changes than ADG in the protein. From synchronous fluorescence spectroscopy results, a pronounced shift in the maximum emission wavelength of tyrosine residues was observed in both cases suggesting that the drugs changed the polarity around tyrosine residues with marginal change around the tryptophan residues. The thermodynamics of the binding interaction analyzed using microcalorimetry presented single binding events that were exothermic in nature in both cases. The binding was driven by large positive standard molar entropy changes with small favorable enthalpy contributions. Negative heat capacity changes in both cases are correlated to the involvement of significant hydrophobic forces in the complexation process. The affinity of DAN to Hb was higher than that of ADG. PMID:26065442

  8. Variation in hemoglobin F production among normal and sickle cell adults is not related to nucleotide substitutions in the gamma promoter regions.

    PubMed

    Economou, E P; Antonarakis, S E; Kazazian, H H; Serjeant, G R; Dover, G J

    1991-01-01

    Single nucleotide substitutions in the promoter regions of the A gamma- and G gamma-globin genes have been associated with increased fetal hemoglobin (HbF) production. We wished to determine whether these or other unrecognized substitutions in the gamma promoter regions are responsible for the 20-fold variation in HbF production in sickle cell patients or normal adults. From a random sampling of 250 sickle cell (SS) patients and 125 normal adults, 17 individuals representing the highest and lowest HbF producers were selected for study. All three common restriction fragment length polymorphism beta-globin region haplotypes (Benin, Central African Republic, and Senegal) were found in both the highest and lowest HbF producers with SS disease. Using the polymerase chain reaction amplification and direct sequencing of the amplified DNA product, we examined the promoter regions of both the A gamma and G gamma genes from -350 bp to +50 bp of the CAP site. No mutations were found in either gamma gene promoter region. We conclude that nucleotide substitutions in the promoter regions (-350 to +50 bp) of both gamma genes are not responsible for the marked variation in HbF production among SS or normal individuals.

  9. Highly Selective Fluorescence Determination of the Hematin Level in Human Erythrocytes with No Need for Separation from Bulk Hemoglobin.

    PubMed

    Ji, Lijuan; Chen, Li; Wu, Ping; Gervasio, Dominic F; Cai, Chenxin

    2016-04-01

    Hematin-induced fluorescence quenching of boron-doped graphene quantum dots (BGQDs) allows for determination of hematin concentration in human erythrocytes with no need for separating hematin from hemoglobin before performing the assay. The BGQDs are made by oxidizing a graphite anode by holding the voltage between a graphite rod and a Pt cathode at 3 V for 2 h in an aqueous borax solution at pH 7; then, the borate solution was filtered with BGQDs, and the borate was dialyzed from the filtrate, leaving a solution of BGQDs in water. The fluorescence intensity of BGQDs is measurable in real time, and its quenching is very sensitive to the concentration of hematin in the system but not to other coexisting biological substances. The analytical signal is defined as ΔF = 1 - F/F0, where F0 and F are the fluorescence intensities of the BGQDs before and after interaction with hematin, respectively. There is a good linear relationship between ΔF and hematin concentration, ranging from 0.01 to 0.92 μM, with the limit of detection (LOD) being ∼0.005 ± 0.001 μM at a signal-to-noise ratio of 3. This new method is sensitive, label-free, simple, and inexpensive, and many tedious procedures related to sample separation and preparation can be omitted, implying that this method has potential for applications in clinical examinations and disease diagnoses. For example, the determination of the hematin levels in two kind of red blood cell samples, healthy human and sickle cell erythrocytes, gives average concentrations of hematin of ∼(23.1 ± 4.9) μM (average of five samples) for healthy red cell cytosols and ∼(52.5 ± 9.5) μM (average of two samples) for sickle red cell cytosols. PMID:26942664

  10. Evidence for Association between SH2B1 Gene Variants and Glycated Hemoglobin in Nondiabetic European American Young Adults: The Add Health Study.

    PubMed

    Lange, Leslie A; Graff, Mariaelisa; Lange, Ethan M; Young, Kristin L; Richardson, Andrea S; Mohlke, Karen L; North, Kari E; Harris, Kathleen M; Gordon-Larsen, Penny

    2016-09-01

    Glycated hemoglobin (HbA1c) is used to classify glycaemia and type 2 diabetes (T2D). Body mass index (BMI) is a predictor of HbA1c levels and T2D. We tested 43 established BMI and obesity loci for association with HbA1c in a nationally representative multiethnic sample of young adults from the National Longitudinal Study of Adolescent to Adult Health [Add Health: age 24-34 years; n = 5641 European Americans (EA); 1740 African Americans (AA); 1444 Hispanic Americans (HA)] without T2D, using two levels of covariate adjustment (Model 1: age, sex, smoking, and geographic region; Model 2: Model 1 covariates plus BMI). Bonferroni adjustment was made for 43 SNPs and we considered P < 0.0011 statistically significant. Means (SD) for HbA1c were 5.4% (0.3) in EA, 5.7% (0.4) in AA, and 5.5% (0.3) in HA. We observed significant evidence for association with HbA1c for two variants near SH2B1 in EA (rs4788102, P = 2.2 × 10(-4) ; rs7359397, P = 9.8 × 10(-4) ) for Model 1. Both results were attenuated after adjustment for BMI (rs4788102, P = 1.7 × 10(-3) ; rs7359397, P = 4.6 × 10(-3) ). No variant reached Bonferroni-corrected significance in AA or HA. These results suggest that SH2B1 polymorphisms are associated with HbA1c, largely independent of BMI, in EA young adults. PMID:27530450

  11. Evidence for Association between SH2B1 Gene Variants and Glycated Hemoglobin in Nondiabetic European American Young Adults: The Add Health Study.

    PubMed

    Lange, Leslie A; Graff, Mariaelisa; Lange, Ethan M; Young, Kristin L; Richardson, Andrea S; Mohlke, Karen L; North, Kari E; Harris, Kathleen M; Gordon-Larsen, Penny

    2016-09-01

    Glycated hemoglobin (HbA1c) is used to classify glycaemia and type 2 diabetes (T2D). Body mass index (BMI) is a predictor of HbA1c levels and T2D. We tested 43 established BMI and obesity loci for association with HbA1c in a nationally representative multiethnic sample of young adults from the National Longitudinal Study of Adolescent to Adult Health [Add Health: age 24-34 years; n = 5641 European Americans (EA); 1740 African Americans (AA); 1444 Hispanic Americans (HA)] without T2D, using two levels of covariate adjustment (Model 1: age, sex, smoking, and geographic region; Model 2: Model 1 covariates plus BMI). Bonferroni adjustment was made for 43 SNPs and we considered P < 0.0011 statistically significant. Means (SD) for HbA1c were 5.4% (0.3) in EA, 5.7% (0.4) in AA, and 5.5% (0.3) in HA. We observed significant evidence for association with HbA1c for two variants near SH2B1 in EA (rs4788102, P = 2.2 × 10(-4) ; rs7359397, P = 9.8 × 10(-4) ) for Model 1. Both results were attenuated after adjustment for BMI (rs4788102, P = 1.7 × 10(-3) ; rs7359397, P = 4.6 × 10(-3) ). No variant reached Bonferroni-corrected significance in AA or HA. These results suggest that SH2B1 polymorphisms are associated with HbA1c, largely independent of BMI, in EA young adults.

  12. Automated quantitative analysis of 3D morphology and mean corpuscular hemoglobin in human red blood cells stored in different periods.

    PubMed

    Moon, Inkyu; Yi, Faliu; Lee, Yeon H; Javidi, Bahram; Boss, Daniel; Marquet, Pierre

    2013-12-16

    Quantitative phase (QP) images of red blood cells (RBCs), which are obtained by off-axis digital holographic microscopy, can provide quantitative information about three-dimensional (3D) morphology of human RBCs and the characteristic properties such as mean corpuscular hemoglobin (MCH) and MCH surface density (MCHSD). In this paper, we investigate modifications of the 3D morphology and MCH in RBCs induced by the period of storage time for the purpose of classification of RBCs with different periods of storage by using off-axis digital holographic microscopy. The classification of RBCs based on the duration of storage is highly relevant because a long storage of blood before transfusion may alter the functionality of RBCs and, therefore, cause complications in patients. To analyze any changes in the 3D morphology and MCH of RBCs due to storage, we use data sets from RBC samples stored for 8, 13, 16, 23, 27, 30, 34, 37, 40, 47, and 57 days, respectively. The data sets consist of more than 3,300 blood cells in eleven classes, with more than 300 blood cells per class. The classes indicate the storage period of RBCs and are listed in chronological order. Using the RBCs donated by healthy persons, the off-axis digital holographic microscopy reconstructs several quantitative phase images of RBC samples stored for eleven different periods. We employ marker-controlled watershed transform to remove the background in the RBC quantitative phase images obtained by the off-axis digital holographic microscopy. More than 300 single RBCs are extracted from the segmented quantitative phase images for each class. Such a large number of RBC samples enable us to obtain statistical distributions of the characteristic properties of RBCs after a specific period of storage. Experimental results show that the 3D morphology of the RBCs, in contrast to MCH, is essentially related to the aging of the RBCs.

  13. Hemodynamic Measurements of the Human Adult Head in Transmittance Mode by Near-Infrared Time-Resolved Spectroscopy.

    PubMed

    Suzuki, Hiroaki; Oda, Motoki; Ohmae, Etsuko; Suzuki, Toshihiko; Yamashita, Daisuke; Yoshimoto, Kenji; Homma, Shu; Yamashita, Yutaka

    2016-01-01

    Using a near-infrared time-resolved spectroscopy (TRS) system, we measured the human head in transmittance mode to obtain the optical properties and the hemodynamic changes of deep brain tissues in seven healthy adult volunteers during hyperventilation. For six out of seven volunteers, we obtained the optical signals with sufficient intensity within 10 sec. of sampling. We confirmed that it is possible to non-invasively measure the hemodynamic changes of the human head during hyperventilation, even in the transmittance measurements by the developed TRS system. These results showed that the level of deoxygenated hemoglobin was significantly increased, and the level of oxygenated and total hemoglobin and tissue oxygen saturation were also significantly decreased during hyperventilation. We expect that this TRS technique will be applied to clinical applications for measuring deep brain tissues and deep biological organs. PMID:26782238

  14. Angiogenic properties of adult human thymus fat.

    PubMed

    Salas, Julián; Montiel, Mercedes; Jiménez, Eugenio; Valenzuela, Miguel; Valderrama, José Francisco; Castillo, Rafael; González, Sergio; El Bekay, Rajaa

    2009-11-01

    The endogenous proangiogenic properties of adipose tissue are well recognized. Although the adult human thymus has long been known to degenerate into fat tissue, it has never been considered as a potential source of angiogenic factors. We have investigated the expression of diverse angiogenic factors, including vascular endothelial growth factor A and B, angiopoietin 1, and tyrosine-protein kinase receptor-2 (an angiopoietin receptor), and then analyzed their physiological role on endothelial cell migration and proliferation, two relevant events in angiogenesis. The detection of the gene and protein expression of the various proteins has been performed by immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction. We show, for the first time, that adult thymus fat produces a variety of angiogenic factors and induces the proliferation and migration of human umbilical cord endothelial cells. Based on these findings, we suggest that this fat has a potential angiogenic function that might affect thymic function and ongoing adipogenesis within the thymus.

  15. Detection of total and A1c-glycosylated hemoglobin in human whole blood using sandwich immunoassays on polydimethylsiloxane-based antibody microarrays.

    PubMed

    Chen, Huang-Han; Wu, Chih-Hsing; Tsai, Mei-Ling; Huang, Yi-Jing; Chen, Shu-Hui

    2012-10-16

    The percentage of glycosylated hemoglobin A1c (%GHbA1c) in human whole blood indicates the average plasma glucose concentration over a prolonged period of time and is used to diagnose diabetes. However, detecting GHbA1c in the whole blood using immunoassays has limited detection sensitivity due to its low percentage in total hemoglobin (tHb) and interference from various glycan moieties in the sample. We have developed a sandwich immunoassay using an antibody microarray on a polydimethylsiloxane (PDMS) substrate modified with fluorinated compounds to detect tHb and glycosylated hemoglobin A1c (GHbA1c) in human whole blood without sample pretreatment. A polyclonal antibody against hemoglobin (Hb) immobilized on PDMS is used as a common capture probe to enrich all forms of Hb followed by detection via monoclonal anti-Hb and specific monoclonal anti-GHbA1c antibodies for tHb and GHbA1c detection, respectively. This method prevents the use of glycan binding molecules and dramatically reduces the background interference, yielding a detection limit of 3.58 ng/mL for tHb and 0.20 ng/mL for GHbA1c. The fluorinated modification on PDMS is superior to the glass substrate and eliminates the need for the blocking step which is required in commercial enzyme linked immunosorbent assay (ELISA) kits. Moreover, the detection sensitivity for GHbA1c is 4-5 orders of magnitude higher, but the required sample amount is 25 times less than the commercial method. On the basis of patient sample data, a good linear correlation between %GHbA1c values determined by our method and the certified high performance liquid chromatography (HPLC) standard method is shown with R(2) > 0.98, indicating the great promise of the developed method for clinical applications.

  16. Effect of Metformin Glycinate on Glycated Hemoglobin A1c Concentration and Insulin Sensitivity in Drug-Naive Adult Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Martínez-Abundis, Esperanza; Robles-Cervantes, José A.; Ramos-Zavala, Maria G.; Barrera-Durán, Carmelita; González-Canudas, Jorge

    2012-01-01

    Abstract Aim This study evaluated the effect of metformin glycinate on glycated hemoglobin A1c (A1C) concentration and insulin sensitivity in drug-naive adult patients with type 2 diabetes mellitus (T2DM). Subjects and Methods A randomized, double-blind, placebo-controlled clinical trial was carried out in 20 patients with drug-naive T2DM. Ten subjects received metformin glycinate (1,050.6 mg) once daily during the first month and force-titrated twice daily during the second month. Ten additional patients received placebo as the control group. Before and after the intervention, metabolic profile including A1C and insulin sensitivity (euglycemic-hyperinsulinemic clamp technique) was estimated. Results A1C concentrations decreased significantly with metformin glycinate administration (8.0±0.7% vs. 7.1±0.9%, P=0.008) before and after the intervention, respectively. There were significant differences in changes from baseline of A1C between groups (0.0±0.7% vs. −1.0±0.5% for placebo and metformin glycinate groups, respectively; P=0.004). A reduction of ≥1% in A1C levels was reached in 60.0% of patients with metformin glycinate administration (P=0.02). Insulin sensitivity was not modified by the intervention. Conclusions Administration of metformin glycinate during a 2-month period showed a greater decrease in A1C concentrations than placebo in a selected group of drug-naive adult patients with T2DM. PMID:22974412

  17. Calibration of NIRS-measured hemodynamics with best-matched hemoglobin extinction coefficients and group statics on human-blood-model data

    NASA Astrophysics Data System (ADS)

    Li, Ting; Zhao, Yue; Sun, Yunlong; Li, Kai; Li, Wenjie; Zhang, Chi; Liu, Junpeng

    2015-03-01

    Near-infrared spectroscopy (NIRS) has been extensively developed for in-vivo measurements of tissue vascular oxygenation, breast tumor detection, and functional brain imaging, by groups of physicists, biomedical engineers, and mathematicians. To quantify concentrations of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin (hemodynamics), extinction coefficients of hemoglobin (ɛ) have to be employed. However, it is still controversial what ɛ values should be used and relatively what calibration should be done in NIRS quantification to achieve the highest precision, although that the differences in ɛ values among published data resulted in ~20% variation in quantification of hemoglobin concentration is reported based a single human blood test. We collected 12 blood samples from 12 healthy people, and with each blood sample performed blood tissue model experiments. 4 teams of published extinction value widely used in NIRS fields were employed respectively in our quantification. Calibrations based least square analysis and regression between real and estimated hemodynamics for 12 subjects were performed with each team of ɛ values respectively. We found that: Moaveni's ɛ values contributed to highest accuracy; Regression method produced quite effective calibration, and when it combined with Moaveni's ɛ values, the calibration reduced the std/mean of estimation by two orders of magnitude. Thus Moaveni's ɛ values are most recommended to use in NIRS quantification, especially with our calibration matrix based on regression analysis with a group of subjects' blood sample.

  18. Mass Spectrometric Analysis of Glyoxal and Methylglyoxal-Induced Modifications in Human Hemoglobin from Poorly Controlled Type 2 Diabetes Mellitus Patients.

    PubMed

    Chen, Hauh-Jyun Candy; Chen, Yu-Chin; Hsiao, Chiung-Fong; Chen, Pin-Fan

    2015-12-21

    Glyoxal and methylglyoxal are oxoaldehydes derived from the degradation of glucose-protein conjugates and from lipid peroxidation, and they are also present in the environment. This study investigated the site-specific reaction of glyoxal and methylglyoxal with the amino acid residues on human hemoglobin using a shot-gun proteomic approach with nanoflow liquid chromatography/nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS). In human hemoglobin incubated with glyoxal, modification on 8 different sites, including lysine residues at α-Lys-11, α-Lys-16, α-Lys-56, β-Lys-17, β-Lys-66, β-Lys-144, and arginine residues at α-Arg-92 and β-Arg-30, was observed using a data-dependent scan. In methylglyoxal-treated hemoglobin, there were specific residues, namely, α-Arg-92, β-Lys-66, β-Arg-30, and β-Lys-144, forming carboxyethylation as well as the dehydrated product hydroimidazolone at α-Arg-92 and β-Arg-30. These lysine and arginine modifications were confirmed by accurate mass measurement and the MS(2) and MS(3) spectra. The most intensive signal of each modified peptide was used as the precursor ion to perform the product ion scan. The relative extent of modifications was semiquantified simultaneously relative to the native reference peptide by nanoLC-NSI/MS/MS under the selected reaction monitoring (SRM) mode. The extent of these modifications increased dose-dependently with increasing concentrations of glyoxal or methylglyoxal. Six out of the eight modifications induced by glyoxal and three out of the six modifications induced by methylglyoxal were detected in hemoglobin freshly isolated from human blood samples. The relative extent of modification of these post-translational modifications was quantified in poorly controlled type 2 diabetes mellitus patients (n = 20) and in nondiabetic control subjects (n = 21). The results show that the carboxymethylated peptides at α-Lys-16, α-Arg-92, β-Lys-17, β-Lys-66, and the peptide at α-Arg-92

  19. Mass Spectrometric Analysis of Glyoxal and Methylglyoxal-Induced Modifications in Human Hemoglobin from Poorly Controlled Type 2 Diabetes Mellitus Patients.

    PubMed

    Chen, Hauh-Jyun Candy; Chen, Yu-Chin; Hsiao, Chiung-Fong; Chen, Pin-Fan

    2015-12-21

    Glyoxal and methylglyoxal are oxoaldehydes derived from the degradation of glucose-protein conjugates and from lipid peroxidation, and they are also present in the environment. This study investigated the site-specific reaction of glyoxal and methylglyoxal with the amino acid residues on human hemoglobin using a shot-gun proteomic approach with nanoflow liquid chromatography/nanospray ionization tandem mass spectrometry (nanoLC-NSI/MS/MS). In human hemoglobin incubated with glyoxal, modification on 8 different sites, including lysine residues at α-Lys-11, α-Lys-16, α-Lys-56, β-Lys-17, β-Lys-66, β-Lys-144, and arginine residues at α-Arg-92 and β-Arg-30, was observed using a data-dependent scan. In methylglyoxal-treated hemoglobin, there were specific residues, namely, α-Arg-92, β-Lys-66, β-Arg-30, and β-Lys-144, forming carboxyethylation as well as the dehydrated product hydroimidazolone at α-Arg-92 and β-Arg-30. These lysine and arginine modifications were confirmed by accurate mass measurement and the MS(2) and MS(3) spectra. The most intensive signal of each modified peptide was used as the precursor ion to perform the product ion scan. The relative extent of modifications was semiquantified simultaneously relative to the native reference peptide by nanoLC-NSI/MS/MS under the selected reaction monitoring (SRM) mode. The extent of these modifications increased dose-dependently with increasing concentrations of glyoxal or methylglyoxal. Six out of the eight modifications induced by glyoxal and three out of the six modifications induced by methylglyoxal were detected in hemoglobin freshly isolated from human blood samples. The relative extent of modification of these post-translational modifications was quantified in poorly controlled type 2 diabetes mellitus patients (n = 20) and in nondiabetic control subjects (n = 21). The results show that the carboxymethylated peptides at α-Lys-16, α-Arg-92, β-Lys-17, β-Lys-66, and the peptide at α-Arg-92

  20. 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

  1. 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.

  2. X-ray diffraction study of the binding of the antisickling agent 12C79 to human hemoglobin

    SciTech Connect

    Wireko, R.C.; Abraham, D.J. )

    1991-03-15

    The hemoglobin binding site of the antisickling agent 12C79 has been determined by x-ray crystallography. 12C79 is recognized as one of the first molecules to reach clinical trials that was designed, de novo, from x-ray-determined atomic coordinates of a protein. Several previous attempts to verify the proposed Hb binding sites via crystallographic studies have failed. Using revised experimental procedures, the authors obtained 12C79-deoxhemoglobin crystals grown after reaction with oxyhemoglobin and cyanoborohydride reduction to stabilize the Schiff base linkage. The difference electron-density Fourier maps show that two 12C79 molecules bind covalently to both symmetry-related N-terminal amino groups of the hemoglobin {alpha} chains. This is in contrast to the original design that proposed the binding of one drug molecule that spans the molecular dyad to interact with both N-terminal {alpha}-amino groups.

  3. Thiamin requirement of the adult human.

    PubMed

    Sauberlich, H E; Herman, Y F; Stevens, C O; Herman, R H

    1979-11-01

    Young adult male subjects maintained on a metabolic ward were fed diets providing controlled intakes of thiamin and either 2800 or 3600 kcal. The higher level of calories was attained by an increased intake of carbohydrates. Constant weights were maintained by the subjects by adjusting daily activity and exercise schedules. Thiamin requirements were evaluated in terms of erythrocyte transketolase activity and urinary excretion of the vitamin. The results of the study revealed that a relationship exists between thiamin requirement and caloric intake and expenditure. Thus, when the calories being utilized were derived primarily from carbohydrate sources, the minimum adult male requirement for thiamin appeared to be 0.30 mg of thiamin per 1000 kcal. Urinary excretion of thiamin and erythrocyte transketolase activity appear to be reasonably reliable reflections of thiamin intakes and thiamin nutritional status. The use of these measurements in nutrition surveys appears justified. The microbiological assay (Lactobacillus viridescens) for measuring thiamin levels in urine samples appears to be a somewhat more sensitive but valid procedure as an alternate for the thiochrome method. Judged from the results of this study, the recommended intake for the adult human of 0.40 mg of thiamin per 1000 kcal by FAO/WHO and the recommended allowance of 0.5 mg per 1000 kcal by the Food and Nutrition Board of the NAS-NRC appear reasonable and amply allow for biological variations and other factors that may influence the requirement for this vitamin.

  4. Characterization of the binding of metoprolol tartrate and guaifenesin drugs to human serum albumin and human hemoglobin proteins by fluorescence and circular dichroism spectroscopy.

    PubMed

    Duman, Osman; Tunç, Sibel; Kancı Bozoğlan, Bahar

    2013-07-01

    The interactions of metoprolol tartrate (MPT) and guaifenesin (GF) drugs with human serum albumin (HSA) and human hemoglobin (HMG) proteins at pH 7.4 were studied by fluorescence and circular dichroism (CD) spectroscopy. Drugs quenched the fluorescence spectra of HSA and HMG proteins through a static quenching mechanism. For each protein-drug system, the values of Stern-Volmer quenching constant, bimolecular quenching constant, binding constant and number of binding site on the protein molecules were determined at 288.15, 298.15, 310.15 and 318.15 K. It was found that the binding constants of HSA-MPT and HSA-GF systems were smaller than those of HMG-MPT and HMG-GF systems. For both drugs, the affinity of HMG was much higher than that of HSA. An increase in temperature caused a negative effect on the binding reactions. The number of binding site on blood proteins for MPT and GF drugs was approximately one. Thermodynamic parameters showed that MPT interacted with HSA through electrostatic attraction forces. However, hydrogen bonds and van der Waals forces were the main interaction forces in the formation of HSA-GF, HMG-MPT and HMG-GF complexes. The binding processes between protein and drug molecules were exothermic and spontaneous owing to negative ∆H and ∆G values, respectively. The values of binding distance between protein and drug molecules were calculated from Förster resonance energy transfer theory. It was found from CD analysis that the bindings of MPT and GF drugs to HSA and HMG proteins altered the secondary structure of HSA and HMG proteins. PMID:23471625

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. Enhancing actions of peptides derived from the γ-chain of fetal human hemoglobin on the immunostimulant activities of monophosphoryl lipid A.

    PubMed

    Ulmer, Artur J; Kaconis, Yani; Heinbockel, Lena; Correa, Wilmar; Alexander, Christian; Rietschel, Ernst Th; Mach, Jean-Pierre; Gorczynski, Reginald M; Heini, Adrian; Rössle, Manfred; Richter, Walter; Gutsmann, Thomas; Brandenburg, Klaus

    2016-04-01

    Hemoglobin and its structures have been described since the 1990s to enhance a variety of biological activities of endotoxins (LPS) in a dose-dependent manner. To investigate the interaction processes in more detail, the system was extended by studying the interactions of newly designed peptides from the γ-chain of human hemoglobin with the adjuvant monophosphoryl lipid A (MPLA), a partial structure of lipid A lacking its 1-phosphate. It was found that some selected Hbg peptides, in particular two synthetic substructures designated Hbg32 and Hbg35, considerably increased the bioactivity of MPLA, which alone was only a weak activator of immune cells. These findings hold true for human mononuclar cells, monocytes and T lymphocytes. To understand the mechanisms of action in more detail, biophysical techniques were applied. These showed a peptide-induced change of the MPLA aggregate structure from multilamellar into a non-lamellar, probably inverted, cubic structure. Concomitantly, the peptides incorporated into the tightly packed MPLA aggregates into smaller units down to monomers. The fragmentation of the aggregates was an endothermic process, differing from a complex formation but rather typical for a catalytic reaction. PMID:26921253

  10. Crystallographic analysis of human hemoglobin elucidates the structural basis of the potent and dual antisickling activity of pyridyl derivatives of vanillin

    SciTech Connect

    Abdulmalik, Osheiza; Ghatge, Mohini S.; Musayev, Faik N.; Parikh, Apurvasena; Chen, Qiukan; Yang, Jisheng; Nnamani, Ijeoma; Danso-Danquah, Richmond; Eseonu, Dorothy N.; Asakura, Toshio; Abraham, Donald J.; Venitz, Jurgen; Safo, Martin K.

    2011-11-01

    Pyridyl derivatives of vanillin increase the fraction of the more soluble oxygenated sickle hemoglobin and/or directly increase the solubility of deoxygenated sickle hemoglobin. Crystallographic analysis reveals the structural basis of the potent and dual antisickling activity of these derivatives. Vanillin has previously been studied clinically as an antisickling agent to treat sickle-cell disease. In vitro investigations with pyridyl derivatives of vanillin, including INN-312 and INN-298, showed as much as a 90-fold increase in antisickling activity compared with vanillin. The compounds preferentially bind to and modify sickle hemoglobin (Hb S) to increase the affinity of Hb for oxygen. INN-312 also led to a considerable increase in the solubility of deoxygenated Hb S under completely deoxygenated conditions. Crystallographic studies of normal human Hb with INN-312 and INN-298 showed that the compounds form Schiff-base adducts with the N-terminus of the α-subunits to constrain the liganded (or relaxed-state) Hb conformation relative to the unliganded (or tense-state) Hb conformation. Interestingly, while INN-298 binds and directs its meta-positioned pyridine-methoxy moiety (relative to the aldehyde moiety) further down the central water cavity of the protein, that of INN-312, which is ortho to the aldehyde, extends towards the surface of the protein. These studies suggest that these compounds may act to prevent sickling of SS cells by increasing the fraction of the soluble high-affinity Hb S and/or by stereospecific inhibition of deoxygenated Hb S polymerization.

  11. Production and characterization of monoclonal antibodies against α-globin chain-containing human hemoglobins for detecting α-thalassemia disease.

    PubMed

    Pakdeepak, Kanet; Pata, Supansa; Chiampanichayakul, Sawitree; Kasinrerk, Watchara; Tatu, Thanusak

    2016-01-01

    Monoclonal antibodies against α-globin containing human Hbs, named AMS-Alpha1 and AMS-Alpha 2, were produced by the hybridoma technique using spleen cells enriched by the newly developed B lymphocyte enrichment protocol. These two monoclonal antibodies were of IgM class, reacting to only intact form of human Hbs A, A2, E, and F, which contain α-globin chain. By the indirect ELISA, the AMS-Alpha1 and AMS-Alpha 2 quantified less amount of α-globin chain containing hemoglobins in HbH disease than the SEA-α thalassemia 1 carriers and normal individuals. It was thus anticipated that these monoclonal antibodies can be used for detecting Hb Bart's hydrops fetalis in which no α-globin chain is produced. PMID:27050832

  12. Rethinking Adult Literacy Programs: A Humanities-Based Curriculum.

    ERIC Educational Resources Information Center

    Anania, Joanne

    The Roosevelt University Humanities Enrichment Program tries to acknowledge the adult part of adult literacy. Its instructional materials are of interest and value to the adult student and, therefore, provide incentives for reading and discussion instead of serving merely as skill-building exercises. The materials are drawn from literature,…

  13. Naphthalene biomarkers and relationship with hemoglobin and hematocrit in White, Black, and Hispanic adults: results from the 2003-2004 National Health and Nutrition Examination Survey.

    PubMed

    Sudakin, Daniel L; Smit, Ellen; Cardenas, Andres; Harding, Anna

    2013-06-01

    Naphthalene is an important contaminant in indoor and outdoor air. Acute overexposure can have toxic effects, resulting in hemolysis. There have been no studies evaluating the impact of environmental exposure on red blood cell indices. We examined 1- and 2-hydroxynaphthalene urinary metabolites (NAP1 and NAP2) in non-Hispanic White, non-Hispanic Black, and Mexican-American adults in the USA and their relationship with hemoglobin (Hb) and hematocrit (HCT). Using the 2003-2004 National Health and Nutrition Examination Survey data, weighted generalized linear regression analyses were used to examine the association between Hb (in grams per deciliter) and HCT (in percent) with NAP1 and NAP2 (per 100,000 ng/L). Beta coefficients ± SE are reported. NAP1 and NAP2 were highest in non-Hispanic Blacks, followed by non-Hispanic Whites, and lowest in Mexican-American adults. There was a positive association between NAP1 and Hb (0.39 ± 0.11, p = 0.0034) and HCT (1.14 ± 0.28, p = 0.0009) after adjusting for age, gender, race, education, and smoking. Stratified analysis by smoking showed similar results with the association being stronger for smokers (Hb 0.63 ± 0.23, p = 0.02; HCT 1.43 ± 0.79, p = 0.09) than nonsmokers (Hb 0.34 ± 0.14, p = 0.03; HCT 1.08 ± 0.42, p = 0.02). The association was also stronger for non-Hispanic blacks (Hb 0.54 ± 0.20, p = 0.02; HCT 1.43 ± 0.55, p = 0.02) than for non-Hispanic whites (Hb 0.37 ± 0.18, p = 0.06; HCT 1.20 ± 0.51, p = 0.03) and was not significant for Mexican-Americans (Hb 0.30 ± 1.7, p = 0.10; HCT 0.99 ± 0.52, p = 0.08). NAP2 was not significantly associated with Hb or HCT. The observed disparity in NAP1 and NAP2 levels by race/ethnicity is consistent with published literature. The origin of these differences in exposure is unclear but may reflect differences in environmental exposure as well as genetic susceptibility. The

  14. 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

  15. Properties of a recombinant human hemoglobin with aspartic acid 99(beta), an important intersubunit contact site, substituted by lysine.

    PubMed Central

    Yanase, H.; Cahill, S.; Martin de Llano, J. J.; Manning, L. R.; Schneider, K.; Chait, B. T.; Vandegriff, K. D.; Winslow, R. M.; Manning, J. M.

    1994-01-01

    Site-directed mutagenesis of an important subunit contact site, Asp-99(beta), by a Lys residue (D99K(beta)) was proven by sequencing the entire beta-globin gene and the mutant tryptic peptide. Oxygen equilibrium curves of the mutant hemoglobin (Hb) (2-15 mM in heme) indicated that it had an increased oxygen affinity and a lowered but significant amount of cooperativity compared to native HbA. However, in contrast to normal HbA, oxygen binding of the recombinant mutant Hb was only marginally affected by the allosteric regulators 2,3-diphosphoglycerate or inositol hexaphosphate and was not at all responsive to chloride. The efficiency of oxygen binding by HbA in the presence of allosteric regulators was limited by the mutant Hb. At concentrations of 0.2 mM or lower in heme, the mutant D99K(beta) Hb was predominantly a dimer as demonstrated by gel filtration, haptoglobin binding, fluorescence quenching, and light scattering. The purified dimeric recombinant Hb mutant exists in 2 forms that are separable on isoelectric focusing by about 0.1 pH unit, in contrast to tetrameric hemoglobin, which shows 1 band. These mutant forms, which were present in a ratio of 60:40, had the same masses for their heme and globin moieties as determined by mass spectrometry. The elution positions of the alpha- and beta-globin subunits on HPLC were identical. Circular dichroism studies showed that one form of the mutant Hb had a negative ellipticity at 410 nm and the other had positive ellipticity at this wavelength. The findings suggest that the 2 D99K(beta) recombinant mutant forms have differences in their heme-protein environments. PMID:7987216

  16. Have you got any cholesterol? Adults' views of human nutrition

    NASA Astrophysics Data System (ADS)

    Schibeci, Renato; Wong, Khoon Yoong

    1994-12-01

    The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

  17. Adult Education & Human Resource Development: Overlapping and Disparate Fields

    ERIC Educational Resources Information Center

    Watkins, Karen E.; Marsick, Victoria J.

    2014-01-01

    Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

  18. Global allostery model of hemoglobin. Modulation of O(2) affinity, cooperativity, and Bohr effect by heterotropic allosteric effectors.

    PubMed

    Yonetani, Takashi; Park, Sung-Ick; Tsuneshige, Antonio; Imai, Kiyohiro; Kanaori, Kenji

    2002-09-13

    The O(2) equilibria of human adult hemoglobin have been measured in a wide range of solution conditions in the presence and absence of various allosteric effectors in order to determine how far hemoglobin can modulate its O(2) affinity. The O(2) affinity, cooperative behavior, and the Bohr effect of hemoglobin are modulated principally by tertiary structural changes, which are induced by its interactions with heterotropic allosteric effectors. In their absence, hemoglobin is a high affinity, moderately cooperative O(2) carrier of limited functional flexibility, the behaviors of which are regulated by the homotropic, O(2)-linked T/R quaternary structural transition of the Monod-Wyman-Changeux/Perutz model. However, the interactions with allosteric effectors provide such "inert" hemoglobin unprecedented magnitudes of functional diversities not only of physiological relevance but also of extreme nature, by which hemoglobin can behave energetically beyond what can be explained by the Monod-Wyman-Changeux/Perutz model. Thus, the heterotropic effector-linked tertiary structural changes rather than the homotropic ligation-linked T/R quaternary structural transition are energetically more significant and primarily responsible for modulation of functions of hemoglobin.

  19. Could adult hippocampal neurogenesis be relevant for human behavior?

    PubMed Central

    Snyder, Jason S.; Cameron, Heather A.

    2011-01-01

    Although the function of adult neurogenesis is still unclear, tools for directly studying the behavioral role of new hippocampal neurons now exist in rodents. Since similar studies are impossible to do in humans, it is important to assess whether the role of new neurons in rodents is likely to be similar to that in humans. One feature of adult neurogenesis that varies tremendously across species is the number of neurons that are generated, so a key question is whether there are enough neurons generated in humans to impact function. In this review we examine neuroanatomy and circuit function in the hippocampus to ask how many granule neurons are needed to impact hippocampal function and then discuss what is known about numbers of new neurons produced in adult rats and humans. We conclude that relatively small numbers of neurons could affect hippocampal circuits and that the magnitude of adult neurogenesis in adult rats and humans is probably larger than generally believed. PMID:21736900

  20. 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.

  1. 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.

  2. Phytoestrogen Metabolism by Adult Human Gut Microbiota.

    PubMed

    Gaya, Pilar; Medina, Margarita; Sánchez-Jiménez, Abel; Landete, José Mᵃ

    2016-08-09

    Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed.

  3. Comparative study of the effect of BPA and its selected analogues on hemoglobin oxidation, morphological alterations and hemolytic changes in human erythrocytes.

    PubMed

    Maćczak, Aneta; Bukowska, Bożena; Michałowicz, Jaromir

    2015-01-01

    Bisphenol A (BPA) has been shown to provoke many deleterious impacts on human health, and thus it is now successively substituted by BPA analogues, whose effects have been poorly investigated. Up to now, only one study has been realized to assess the effect of BPA on human erythrocytes, which showed its significant hemolytic and oxidative potential. Moreover, no study has been conducted to evaluate the effect of BPA analogues on red blood cells. The purpose of the present study was to compare the impact of BPA and its selected analogues such as bisphenol F (BPF), bisphenol S (BPS) and bisphenol AF (BPAF) on hemolytic and morphological changes and hemoglobin oxidation (methemoglobin formation) of human erythrocytes. The erythrocytes were incubated with different bisphenols concentrations ranging from 0.5 to 500μg/ml for 1, 4 and 24h. The compounds examined caused hemolysis in human erythrocytes with BPAF exhibiting the strongest effect. All bisphenols examined caused methemoglobin formation with BPA inducing the strongest oxidative potential. Flow cytometry analysis showed that all bisphenols (excluding BPS) induced significant changes in erythrocytes size. Changes in red blood cells shape were conducted using phase contrast microscopy. It was noticed that BPA and BPAF induced echinocytosis, BPF caused stomatocytosis, while BPS did not provoke significant changes in shape of red blood cells. Generally, the results showed that BPS, which is the main substituent of bisphenol A in polymers and thermal paper production, exhibited significantly lower disturbance of erythrocyte functions than BPA.

  4. Adult Human Neurogenesis: From Microscopy to Magnetic Resonance Imaging

    PubMed Central

    Sierra, Amanda; Encinas, Juan M.; Maletic-Savatic, Mirjana

    2011-01-01

    Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases. PMID:21519376

  5. Phytoestrogen Metabolism by Adult Human Gut Microbiota.

    PubMed

    Gaya, Pilar; Medina, Margarita; Sánchez-Jiménez, Abel; Landete, José Mᵃ

    2016-01-01

    Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed. PMID:27517891

  6. Anemia, Blood Transfusion Requirements and Mortality Risk in Human Immunodeficiency Virus-Infected Adults Requiring Acute Medical Admission to Hospital in South Africa

    PubMed Central

    Kerkhoff, Andrew D.; Lawn, Stephen D.; Schutz, Charlotte; Burton, Rosie; Boulle, Andrew; Cobelens, Frank J.; Meintjes, Graeme

    2015-01-01

    Background. Morbidity and mortality remain high among hospitalized patients infected with human immunodeficiency virus (HIV) in sub-Saharan Africa despite widespread availability of antiretroviral therapy. Severe anemia is likely one important driver, and some evidence suggests that blood transfusions may accelerate HIV progression and paradoxically increase short-term mortality. We investigated the relationship between anemia, blood transfusions, and mortality in a South African district hospital. Methods. Unselected consecutive HIV-infected adults requiring acute medical admission to a Cape Town township district hospital were recruited. Admission hemoglobin concentrations were used to classify anemia severity according to World Health Organization/AIDS Clinical Trials Group criteria. Vital status was determined at 90 days, and Cox regression analyses were used to determine independent predictors of mortality. Results. Of 585 HIV-infected patients enrolled, 578 (98.8%) were included in the analysis. Anemia was detected in 84.8% of patients and was severe (hemoglobin, 6.5–7.9 g/dL) or life-threatening (hemoglobin, <6.5 g/dL) in 17.3% and 13.3%, respectively. Within 90 days of the date of admission, 13.5% (n = 78) patients received at least 1 blood transfusion with red cell concentrate and 77 (13.3%) patients died. In univariable analysis, baseline hemoglobin and receipt of blood transfusion were associated with increased mortality risk. However, in multivariable analysis, neither hemoglobin nor receipt of a blood transfusion were independently associated with greater mortality risk. Acquired immune deficiency syndrome-defining illnesses other than tuberculosis and impaired renal function independently predicted mortality. Conclusions. Newly admitted HIV-infected adults had a high prevalence of severe or life-threatening anemia and blood transfusions were frequently required. However, after adjustment for confounders, blood transfusions did not confer an

  7. Gustofacial and olfactofacial responses in human adults.

    PubMed

    Weiland, Romy; Ellgring, Heiner; Macht, Michael

    2010-11-01

    Adults' facial reactions in response to tastes and odors were investigated in order to determine whether differential facial displays observed in newborns remain stable in adults who exhibit a greater voluntary facial control. Twenty-eight healthy nonsmokers (14 females) tasted solutions of PROP (bitter), NaCl (salty), citric acid (sour), sucrose (sweet), and glutamate (umami) differing in concentration (low, medium, and high) and smelled different odors (banana, cinnamon, clove, coffee, fish, and garlic). Their facial reactions were video recorded and analyzed using the Facial Action Coding System. Adults' facial reactions discriminated between stimuli with opponent valences. Unpleasant tastes and odors elicited negative displays (brow lower, upper lip raise, and lip corner depress). The pleasant sweet taste elicited positive displays (lip suck), whereas the pleasant odors did not. Unlike newborns, adults smiled with higher concentrations of some unpleasant tastes that can be regarded as serving communicative functions. Moreover, adults expressed negative displays with higher sweetness. Except for the "social" smile in response to unpleasant tastes, adults' facial reactions elicited by tastes and odors mostly correspond to those found in newborns. In conclusion, adults' facial reactions to tastes and odors appear to remain stable in their basic displays; however, some additional reactions might reflect socialization influences.

  8. Adult Literacy Education and Human Rights: A View from Afghanistan

    ERIC Educational Resources Information Center

    Andersen, Susan M.; Kooij, Christina S.

    2007-01-01

    In this article, we argue that adult literacy as part of international development is an issue of both human rights and women's rights. We explore this by presenting a case study of the effects of one innovative adult literacy program in Afghanistan that places men and women, as well as various ethnicities, together in the same classroom as…

  9. 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.

  10. 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

  11. BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations

    PubMed Central

    Basak, Anindita; Hancarova, Miroslava; Ulirsch, Jacob C.; Balci, Tugce B.; Trkova, Marie; Pelisek, Michal; Vlckova, Marketa; Muzikova, Katerina; Cermak, Jaroslav; Trka, Jan; Dyment, David A.; Orkin, Stuart H.; Daly, Mark J.; Sedlacek, Zdenek; Sankaran, Vijay G.

    2015-01-01

    A transition from fetal hemoglobin (HbF) to adult hemoglobin (HbA) normally occurs within a few months after birth. Increased production of HbF after this period of infancy ameliorates clinical symptoms of the major disorders of adult β-hemoglobin: β-thalassemia and sickle cell disease. The transcription factor BCL11A silences HbF and has been an attractive therapeutic target for increasing HbF levels; however, it is not clear to what extent BCL11A inhibits HbF production or mediates other developmental functions in humans. Here, we identified and characterized 3 patients with rare microdeletions of 2p15-p16.1 who presented with an autism spectrum disorder and developmental delay. Moreover, these patients all exhibited substantial persistence of HbF but otherwise retained apparently normal hematologic and immunologic function. Of the genes within 2p15-p16.1, only BCL11A was commonly deleted in all of the patients. Evaluation of gene expression data sets from developing and adult human brains revealed that BCL11A expression patterns are similar to other genes associated with neurodevelopmental disorders. Additionally, common SNPs within the second intron of BCL11A are strongly associated with schizophrenia. Together, the study of these rare patients and orthogonal genetic data demonstrates that BCL11A plays a central role in silencing HbF in humans and implicates BCL11A as an important factor for neurodevelopment. PMID:25938782

  12. BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations.

    PubMed

    Basak, Anindita; Hancarova, Miroslava; Ulirsch, Jacob C; Balci, Tugce B; Trkova, Marie; Pelisek, Michal; Vlckova, Marketa; Muzikova, Katerina; Cermak, Jaroslav; Trka, Jan; Dyment, David A; Orkin, Stuart H; Daly, Mark J; Sedlacek, Zdenek; Sankaran, Vijay G

    2015-06-01

    A transition from fetal hemoglobin (HbF) to adult hemoglobin (HbA) normally occurs within a few months after birth. Increased production of HbF after this period of infancy ameliorates clinical symptoms of the major disorders of adult β-hemoglobin: β-thalassemia and sickle cell disease. The transcription factor BCL11A silences HbF and has been an attractive therapeutic target for increasing HbF levels; however, it is not clear to what extent BCL11A inhibits HbF production or mediates other developmental functions in humans. Here, we identified and characterized 3 patients with rare microdeletions of 2p15-p16.1 who presented with an autism spectrum disorder and developmental delay. Moreover, these patients all exhibited substantial persistence of HbF but otherwise retained apparently normal hematologic and immunologic function. Of the genes within 2p15-p16.1, only BCL11A was commonly deleted in all of the patients. Evaluation of gene expression data sets from developing and adult human brains revealed that BCL11A expression patterns are similar to other genes associated with neurodevelopmental disorders. Additionally, common SNPs within the second intron of BCL11A are strongly associated with schizophrenia. Together, the study of these rare patients and orthogonal genetic data demonstrates that BCL11A plays a central role in silencing HbF in humans and implicates BCL11A as an important factor for neurodevelopment.

  13. 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

  14. A comparative study of bifidobacteria in human babies and adults

    PubMed Central

    KHONSARI, Shadi; SUGANTHY, Mayuran; BURCZYNSKA, Beata; DANG, Vu; CHOUDHURY, Manika; PACHENARI, Azra

    2015-01-01

    The composition and diversity of the gut microbiota are known to be different between babies and adults. The aim of this project was to compare the level of bifidobacteria between babies and adults and to investigate the influence of lifestyle factors on the level of this bacterium in the gut. During this study, the levels of bifidobacteria in 10 human babies below 2 years of age were compared with that of 10 human adults above 40 years. The level of bifidobacteria proved to be significantly higher in babies in comparison with adults. This investigation concluded that a combination of several factors, such as age, diet, and BMI, has an important effect on the level of bifidobacteria in adults, while in babies, a combination of diet and age may influence the level of intestinal bifidobacteria. PMID:27200263

  15. 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

  16. Coexpression of Human α- and Circularly Permuted β-Globins Yields a Hemoglobin with Normal R State but Modified T State Properties†

    PubMed Central

    Asmundson, Anna L.; Taber, Alexandria M.; van der Walde, Adella; Lin, Danielle H.; Olson, John S.; Anthony-Cahill, Spencer J.

    2009-01-01

    For the first time, a circularly permuted human β-globin (cpβ) has been coexpressed with human α-globin in bacterial cells and shown to associate to form α-cpβ hemoglobin in solution. Flash photolysis studies of α-cpβ show markedly biphasic CO and O2 kinetics with the amplitudes for the fast association phases being dominant due the presence of large amounts of high-affinity liganded hemoglobin dimers. Extensive dimerization of liganded but not deoxygenated α-cpβ was observed by gel chromatography. The rate constants for O2 and CO binding to the R state forms of α-cpβ are almost identical to those of native HbA (k′R(CO) ≈ 5.0 μM−1 s−1; k′R(O2) ≈ 50 μM−1 s−1), and the rate of O2 dissociation from fully oxygenated α-cpβ is also very similar to that observed for HbA (kR(O2) ≈ 21–28 s−1). When the equilibrium deoxyHb form of α-cpβ is reacted with CO in rapid mixing experiments, the observed time courses are monophasic and the observed bimolecular association rate constant is ∼1.0 μM−1 s−1, which is intermediate between the R state rate measured in partial photolysis experiments (∼5 μM−1 s−1) and that observed for T state deoxyHbA (k′T(CO) ≈ 0.1 to 0.2 μM−1 s−1). Thus the deoxygenated permutated β subunits generate an intermediate, higher affinity, deoxyHb quaternary state. This conclusion is supported by equilibrium oxygen binding measurements in which α-cpβ exhibits a P50 of ∼1.5 mmHg and a low n-value (∼1.3) at pH 7, 20 °C, compared to 8.5 mmHg and n ≈ 2.8 for native HbA under identical, dilute conditions. PMID:19397368

  17. 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

  18. Neural stem cells in the adult human brain

    PubMed Central

    Gonzalez-Perez, Oscar

    2012-01-01

    For decades, it was believed that the adult brain was a quiescent organ unable to produce new neurons. At the beginning of the1960's, this dogma was challenged by a small group of neuroscientists. To date, it is well-known that new neurons are generated in the adult brain throughout life. Adult neurogenesis is primary confined to the subventricular zone (SVZ) of the forebrain and the subgranular zone of the dentate gyrus within the hippocampus. In both the human and the rodent brain, the primary progenitor of adult SVZ is a subpopulation of astrocytes that have stem-cell-like features. The human SVZ possesses a peculiar cell composition and displays important organizational differences when compared to the SVZ of other mammals. Some evidence suggests that the human SVZ may be not only an endogenous source of neural precursor cells for brain repair, but also a source of brain tumors. In this review, we described the cytoarchitecture and cellular composition of the SVZ in the adult human brain. We also discussed some clinical implications of SVZ, such as: stem-cell-based therapies against neurodegenerative diseases and its potential as a source of malignant cells. Understanding the biology of human SVZ and its neural progenitors is one of the crucial steps to develop novel therapies against neurological diseases in humans. PMID:23181200

  19. Humanities and the Adult Learner in an Information Society.

    ERIC Educational Resources Information Center

    Myers, Dale; Kamholtz, Jonathan

    Humanities courses have often been given little attention in continuing education for adults, possibly because they have been viewed as not "practical" or not "job-oriented" enough in our career-oriented, technologically advanced society. However, the humanities should be an integral part of our culture and of the lives of educated persons--a…

  20. Teaching Human Rights: Grades 7 through Adult.

    ERIC Educational Resources Information Center

    Shiman, David A.

    This curriculum resource on human rights is rooted in the United Nations Universal Declaration of Human Rights and seeks to help students understand the issues involved. Using the rights categories suggested by the Universal Declaration, this book offers new ways of teaching about familiar themes. The book contains activities to encourage students…

  1. 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.

  2. 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.

  3. Directly observed reversible shape changes and hemoglobin stratification during centrifugation of human and Amphiuma red blood cells.

    PubMed

    Hoffman, Joseph F; Inoué, Shinya

    2006-02-21

    This paper describes changes that occur in human and Amphiuma red blood cells observed during centrifugation with a special microscope. Dilute suspensions of cells were layered, in a centrifuge chamber, above an osmotically matched dense solution, containing Nycodenz, Ficoll, or Percoll (Pharmacia) that formed a density gradient that allowed the cells to slowly settle to an equilibrium position. Biconcave human red blood cells moved downward at low forces with minimum wobble. The cells oriented vertically when the force field was increased and Hb sedimented as the lower part of each cell became bulged and assumed a "bag-like" shape. The upper centripetal portion of the cell became thinner and remained biconcave. These changes occurred rapidly and were completely reversible upon lowering the centrifugal force. Bag-shaped cells, upon touching red cells in rouleau, immediately reverted to biconcave disks as they flipped onto a stack. Amphiuma red cells displayed a different type of reversible stratification and deformation at high force fields. Here the cells became stretched, with the nucleus now moving centrifugally, the Hb moving centripetally, and the bottom of the cells becoming thinner and clear. Nevertheless, the distribution of the marginal bands at the cells' rim was unchanged. We conclude that centrifugation, per se, while changing a red cell's shape and the distribution of its intracellular constituents, does so in a completely reversible manner. Centrifugation of red cells harboring altered or missing structural elements could provide information on shape determinants that are still unexplained. PMID:16477016

  4. New neurons in the adult striatum: from rodents to humans

    PubMed Central

    Inta, Dragos; Cameron, Heather A.; Gass, Peter

    2015-01-01

    Most neurons are generated during development and are not replaced during adulthood, even if they are lost to injury or disease. It is firmly established, however, that new neurons are generated in the dentate gyrus of the hippocampus of virtually all adult mammals, including humans [1]. Many questions still remain, however, regarding adult neurogenesis in other brain regions and particularly in humans, where standard birthdating methods are not generally feasible. Exciting recent evidence indicates that calretinin-expressing interneurons are added to the adult human striatum at a substantial rate [2]. The role of new neurons is unknown, but studies in rodents will be able to further elucidate their identity and origin and then begin to understand their regulation and function. PMID:26298770

  5. 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.

  6. Adult human metapneumonovirus (hMPV) pneumonia mimicking Legionnaire's disease.

    PubMed

    Cunha, Burke A; Irshad, Nadia; Connolly, James J

    2016-01-01

    In adults hospitalized with viral pneumonias the main differential diagnostic consideration is influenza pneumonia. The respiratory viruses causing viral influenza like illnesses (ILIs), e.g., RSV may closely resemble influenza. Rarely, extrapulmonary findings of some ILIs may resemble Legionnaire's disease (LD), e.g., adenovirus, human parainfluenza virus (HPIV-3). We present a most unusual case of human metapneumonovirus pneumonia (hMPV) with some characteristic extrapulmonary findings characteristic of LD, e.g., relative bradycardia, as well as mildly elevated serum transaminases and hyphosphatemia. We believe this is the first reported case of hMPV pneumonia in a hospitalized adult that had some features of LD.

  7. Adult human metapneumonovirus (hMPV) pneumonia mimicking Legionnaire's disease.

    PubMed

    Cunha, Burke A; Irshad, Nadia; Connolly, James J

    2016-01-01

    In adults hospitalized with viral pneumonias the main differential diagnostic consideration is influenza pneumonia. The respiratory viruses causing viral influenza like illnesses (ILIs), e.g., RSV may closely resemble influenza. Rarely, extrapulmonary findings of some ILIs may resemble Legionnaire's disease (LD), e.g., adenovirus, human parainfluenza virus (HPIV-3). We present a most unusual case of human metapneumonovirus pneumonia (hMPV) with some characteristic extrapulmonary findings characteristic of LD, e.g., relative bradycardia, as well as mildly elevated serum transaminases and hyphosphatemia. We believe this is the first reported case of hMPV pneumonia in a hospitalized adult that had some features of LD. PMID:26988110

  8. 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...

  9. In-vitro correlation between reduced scattering coefficient and hemoglobin concentration of human blood determined by near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Paunescu, Lelia A.; Michalos, Antonios; Choi, Jee H.; Wolf, Ursula; Wolf, Martin; Gratton, Enrico

    2001-06-01

    We study the correlation between (mu) s' and THC obtained in vitro, in a highly scattering medium containing human blood. We used a frequency domain near infrared spectrometer (modulation frequency: 110 MHz, wavelengths: 758 and 830 nm) to measure in real time (acquisition time: 0.64 s) (mu) s' and THC. We used Liposyn suspension and red blood cells in saline buffer solution. After a couple of minutes of baseline acquisition, several consecutive increments of 3-5 ml blood were added to the solution yielding THC equals 15-100 (mu) M and (mu) a equals 0.03-0.3 1/cm. At the last amount of blood added, increments of glucose in the range of 0.5-20 g/L were added. For each step of blood and glucose added, data were acquired for a couple of minutes. This was repeated 6 times. Average of data was calculated for both (mu) s' and THC for each of the red blood cells and glucose increments added. We found a high correlation between (mu) s' and THC (0.018 X THC + 4.51, R2 equals 0.98 at 758 nm and 0.012 X THC + 4.86, R2 equals 0.97 at 830 nm). We studied the effect of glucose on (mu) s' and we found a high correlation between the glucose added to the suspension and the decrease in (mu) s' for the case of high glucose concentrations. The slope of this correlation is -0.011 at both wavelengths and the correlation factors were R2 X 0.96 at 830 nm and R2 equals 0.91 at 758 nm (case shown). The effect of glucose was less significant at 830 nm than at 758 nm in general. This work is a proof of principle for detection of (mu) s' changes with glucose. This approach also establishes limits for glucose detection in physiological conditions.

  10. 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.

  11. Late Pleistocene adult mortality patterns and modern human establishment

    PubMed Central

    Trinkaus, Erik

    2011-01-01

    The establishment of modern humans in the Late Pleistocene, subsequent to their emergence in eastern Africa, is likely to have involved substantial population increases, during their initial dispersal across southern Asia and their subsequent expansions throughout Africa and into more northern Eurasia. An assessment of younger (20–40 y) versus older (>40 y) adult mortality distributions for late archaic humans (principally Neandertals) and two samples of early modern humans (Middle Paleolithic and earlier Upper Paleolithic) provides little difference across the samples. All three Late Pleistocene samples have a dearth of older individuals compared with Holocene ethnographic/historical samples. They also lack older adults compared with Holocene paleodemographic profiles that have been critiqued for having too few older individuals for subsistence, social, and demographic viability. Although biased, probably through a combination of preservation, age assessment, and especially Pleistocene mobility requirements, these adult mortality distributions suggest low life expectancy and demographic instability across these Late Pleistocene human groups. They indicate only subtle and paleontologically invisible changes in human paleodemographics with the establishment of modern humans; they provide no support for a life history advantage among early modern humans. PMID:21220336

  12. Probing the biological evaluations of a new designed Pt(II) complex using spectroscopic and theoretical approaches: human hemoglobin as a target.

    PubMed

    Abazari, Omid; Shafaei, Zahra; Divsalar, Adeleh; Eslami-Moghadam, Mahbubeh; Ghalandari, Behafarid; Saboury, Ali Akbar

    2016-05-01

    In recent years, using heavy metal compounds such as platinum as anticancer agent is one of the common ways in chemical therapy. In this study, a new anticancer compound of glycine derivatives of Pt(II) complex (amyl-glycine1, 10-phenanthroline Platinum nitrate) was designed, and the biological effects of this novel compound on the alterations in the function and structure of human hemoglobin (Hb) at different temperatures of 25 and 37°C were assessed by applying various spectroscopic (fluorescence and circular dichroism (CD)) and theoretical methods. Fluorescence data indicated the strong ability of Pt(II) complex to quench the intrinsic fluorescence of Hb. The binding constant, number of binding sites, and thermodynamic parameters at two temperatures were calculated, and the results indicated the major possibility of occurring van der Waals force or hydrogen bond interactions in the Pt(II) complex-Hb interaction. For evaluating the alteration of secondary structure of Hb upon interaction with various concentrations of complex, far-UV CD spectra were used and it was observed that in high dose of complex, significant changes were occurred which is indicative of some side effects in overdosing of this complex. On the other hand, the molecular docking results illustrate that are well in agreement in obtaining data with spectroscopy. Above results suggested that using Pt(II) complex as an anticancer agent, model drug in high-dose usage might cause some disordering in structure and function of Hb as well as improve understanding of the side effects of newly designed metal anticancer drugs undergoing. PMID:26274094

  13. The Human Endogenous Protection System against Cell-Free Hemoglobin and Heme Is Overwhelmed in Preeclampsia and Provides Potential Biomarkers and Clinical Indicators

    PubMed Central

    Johansson, Maria E.; Edström-Hägerwall, Anneli; Larsson, Irene; Jälmby, Maya; Hansson, Stefan R.; Åkerström, Bo

    2015-01-01

    Preeclampsia (PE) complicates 3–8% of all pregnancies and manifests clinically as hypertension and proteinuria in the second half of gestation. The pathogenesis of PE is not fully understood but recent studies have described the involvement of cell-free fetal hemoglobin (HbF). Hypothesizing that PE is associated with prolonged hemolysis we have studied the response of the cell-free Hb- and heme defense network. Thus, we have investigated the levels of cell-free HbF (both free, denoted HbF, and in complex with Hp, denoted Hp-HbF) as well as the major human endogenous Hb- and heme-scavenging systems: haptoglobin (Hp), hemopexin (Hpx), α1-microglobulin (A1M) and CD163 in plasma of PE women (n = 98) and women with normal pregnancies (n = 47) at term. A significant increase of the mean plasma HbF concentration was observed in women with PE. Plasma levels of Hp and Hpx were statistically significantly reduced, whereas the level of the extravascular heme- and radical scavenger A1M was significantly increased in plasma of women with PE. The Hpx levels significantly correlated with maternal blood pressure. Furthermore, HbF and the related scavenger proteins displayed a potential to be used as clinical biomarkers for more precise diagnosis of PE and are candidates as predictors of identifying pregnancies with increased risk of obstetrical complications. The results support that PE pathophysiology is associated with increased HbF-concentrations and an activation of the physiological Hb-heme defense systems. PMID:26368565

  14. Probing the biological evaluations of a new designed Pt(II) complex using spectroscopic and theoretical approaches: human hemoglobin as a target.

    PubMed

    Abazari, Omid; Shafaei, Zahra; Divsalar, Adeleh; Eslami-Moghadam, Mahbubeh; Ghalandari, Behafarid; Saboury, Ali Akbar

    2016-05-01

    In recent years, using heavy metal compounds such as platinum as anticancer agent is one of the common ways in chemical therapy. In this study, a new anticancer compound of glycine derivatives of Pt(II) complex (amyl-glycine1, 10-phenanthroline Platinum nitrate) was designed, and the biological effects of this novel compound on the alterations in the function and structure of human hemoglobin (Hb) at different temperatures of 25 and 37°C were assessed by applying various spectroscopic (fluorescence and circular dichroism (CD)) and theoretical methods. Fluorescence data indicated the strong ability of Pt(II) complex to quench the intrinsic fluorescence of Hb. The binding constant, number of binding sites, and thermodynamic parameters at two temperatures were calculated, and the results indicated the major possibility of occurring van der Waals force or hydrogen bond interactions in the Pt(II) complex-Hb interaction. For evaluating the alteration of secondary structure of Hb upon interaction with various concentrations of complex, far-UV CD spectra were used and it was observed that in high dose of complex, significant changes were occurred which is indicative of some side effects in overdosing of this complex. On the other hand, the molecular docking results illustrate that are well in agreement in obtaining data with spectroscopy. Above results suggested that using Pt(II) complex as an anticancer agent, model drug in high-dose usage might cause some disordering in structure and function of Hb as well as improve understanding of the side effects of newly designed metal anticancer drugs undergoing.

  15. Novel surface markers directed against adult human gallbladder.

    PubMed

    Galivo, Feorillo H; Dorrell, Craig; Grompe, Maria T; Zhong, YongPing; Streeter, Philip R; Grompe, Markus

    2015-07-01

    Novel cell surface-reactive monoclonal antibodies generated against extrahepatic biliary cells were developed for the isolation and characterization of different cell subsets from normal adult human gallbladder. Eleven antigenically distinct gallbladder subpopulations were isolated by fluorescence-activated cell sorting. They were classified into epithelial, mesenchymal, and pancreatobiliary (PDX1(+)SOX9(+)) subsets based on gene expression profiling. These antigenically distinct human gallbladder cell subsets could potentially also reflect different functional properties in regards to bile physiology, cell renewal and plasticity. Three of the novel monoclonal antibodies differentially labeled archival sections of primary carcinoma of human gallbladder relative to normal tissue. The novel monoclonal antibodies described herein enable the identification and characterization of antigenically diverse cell subsets within adult human gallbladder and are putative tumor biomarkers.

  16. Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults

    PubMed Central

    Tong, Ann-Jay; Kollmann, Tobias R.; Smale, Stephen T.

    2015-01-01

    A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development. PMID:26147648

  17. [The existence vomeronasal organ in adult humans].

    PubMed

    Rapiejko, Piotr; Zielnik-Jurkiewicz, Beata; Wojdas, Andrzej; Ratajczak, Jan; Jurkiewicz, Dariusz

    2007-01-01

    The influence of chemical substances (feromones) on human emotional and physical condition has fascinated psychologists, sexuologists and laryngologists since centurie. Literature conveys inconsistent information on vomeronasal organ (VNO) occurrence in humans. This organ is often called Jacobson's, and 2 symmetrical openings leading into it, located on both sides of septum, are called Ruyasch's ducts. The aim of the study was to analyze vomeronasal organ occurrence in humans in relation to age and sex. The study was conducted in a group of 634 patients, aged 18-80 years. All patients underwent routine ENT examination including rhinoscopy, nasal cavity examination with usage of 2.5x magnification lens (surgical glasses) and surgical microscope with 10x magnification. All persons had nasal cavities examined endoscopically. Every time presence of vomeronasal organ openings, along with localization, size and symmetry of these was noted. Subjects, who presented Jacobson's organ, were asked to fill a questionnaire concerning influence of smells on erotic sensations. Vomeronasal organ was fund in 312 persons, that is 49.21%. In 83.65% of cases vomeronasal organ opening size was smaller than 0.2 mm, what restricted its visibility to usage of magnifying lens, microscope, or endoscope. In 16.34% of cases only vomeronasal organ ducts openings were well visible in routine rhinoscopy without magnification. Vomeronasal organ was found more often in men than women. VNO was significantly more rare in patients with nasal septal deviation. In these cases, vomeronasal organ was usually found unilaterally, in all the cases on the concave side of deviated nasal septum. PMID:18260256

  18. 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.

  19. 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

  20. 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.

  1. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  2. 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

  3. Characterization and comparative analysis of 2,4-toluene diisocyanate and 1,6-hexamethylene diisocyanate haptenated human serum albumin and hemoglobin.

    PubMed

    Mhike, Morgen; Hettick, Justin M; Chipinda, Itai; Law, Brandon F; Bledsoe, Toni A; Lemons, Angela R; Nayak, Ajay P; Green, Brett J; Beezhold, Donald H; Simoyi, Reuben H; Siegel, Paul D

    2016-04-01

    Diisocyanates (dNCOs) are low molecular weight chemical sensitizers that react with autologous proteins to produce neoantigens. dNCO-haptenated proteins have been used as immunogens for generation of dNCO-specific antibodies and as antigens to screen for dNCO-specific antibodies in exposed individuals. Detection of dNCO-specific antibodies in exposed individuals for diagnosis of dNCO asthma has been hampered by poor sensitivities of the assay methods in that specific IgE can only be detected in approximately 25% of the dNCO asthmatics. Apart from characterization of the conjugates used for these immunoassays, the choice of the carrier protein and the dNCO used are important parameters that can influence the detection of dNCO-specific antibodies. Human serum albumin (HSA) is the most common carrier protein used for detection of dNCO specific-IgE and -IgG but the immunogenicity and/or antigenicity of other proteins that may be modified by dNCO in vivo is not well documented. In the current study, 2,4-toluene diisocyanate (TDI) and 1,6-hexamethylene diisocyanate (HDI) were reacted with HSA and human hemoglobin (Hb) and the resultant adducts were characterized by (i) HPLC quantification of the diamine produced from acid hydrolysis of the adducts, (ii) 2,4,6-trinitrobenzene sulfonic acid (TNBS) assay to assess extent of cross-linking, (iii) electrophoretic migration in polyacrylamide gels to analyze intra- and inter-molecular cross-linking, and (iv) evaluation of antigenicity using a monoclonal antibody developed previously to TDI conjugated to Keyhole limpet hemocyanin (KLH). Concentration-dependent increases in the amount of dNCO bound to HDI and TDI, cross-linking, migration in gels, and antibody-binding were observed. TDI reactivity with both HSA and Hb was significantly higher than HDI. Hb-TDI antigenicity was approximately 30% that of HSA-TDI. In conclusion, this data suggests that both, the extent of haptenation as well as the degree of cross-linking differs

  4. Human pancreatic polypeptide in children and young adults.

    PubMed

    Hanukoglu, A; Chalew, S; Kowarski, A A

    1990-01-01

    Measurement of human pancreatic polypeptide may be useful for assessment of gastrointestinal function, integrity of the parasympathetic nervous system or screening for endocrine neoplasia. In adults hPP levels have been reported to increase with age. However hPP levels throughout childhood have not been well characterized in comparison with the adult range. We studied fasting human pancreatic polypeptide (hPP) from 45 pediatric patients, from infancy - 15 years, and 18 older adolescents and adults aged 16-45 years. The mean hPP level of children (233 +/- 147 pg/ml) was significantly higher than that (113 +/- 35 pg/ml) of adults (P less than .0001). There was no difference in mean hPP levels of children with normal growth hormone secretion compared to growth hormone deficient patients. There was no effect of gender or body mass index on hPP levels. We conclude that fasting hPP levels must be interpreted with respect to the age of the subject, children particularly, in that preteens may have higher fasting levels than older teenagers and adults.

  5. Human pancreatic polypeptide in children and young adults.

    PubMed

    Hanukoglu, A; Chalew, S; Kowarski, A A

    1990-01-01

    Measurement of human pancreatic polypeptide may be useful for assessment of gastrointestinal function, integrity of the parasympathetic nervous system or screening for endocrine neoplasia. In adults hPP levels have been reported to increase with age. However hPP levels throughout childhood have not been well characterized in comparison with the adult range. We studied fasting human pancreatic polypeptide (hPP) from 45 pediatric patients, from infancy - 15 years, and 18 older adolescents and adults aged 16-45 years. The mean hPP level of children (233 +/- 147 pg/ml) was significantly higher than that (113 +/- 35 pg/ml) of adults (P less than .0001). There was no difference in mean hPP levels of children with normal growth hormone secretion compared to growth hormone deficient patients. There was no effect of gender or body mass index on hPP levels. We conclude that fasting hPP levels must be interpreted with respect to the age of the subject, children particularly, in that preteens may have higher fasting levels than older teenagers and adults. PMID:2307392

  6. 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.

  7. Predictors of food preferences in adult humans.

    PubMed

    Logue, A W; Smith, M E

    1986-06-01

    Predictors of preferences for a wide variety of foods were examined in 303 male and female human subjects ranging from 14-68 years of age. The subjects completed questionnaires which requested information on the subject's sex, age, thinness, sensation seeking and ethnic background, as well as on the subjects' food preferences. Largely consistent with previous studies, female subjects reported higher preferences for low-calorie foods, candy and wine, and lower preferences for meat, beer, spicy foods and milk. Younger subjects reported higher preferences for sweet foods and lower preferences for foods such as chili pepper that are considered acquired tastes. Thinner subjects tended to rate both sweet foods and meat lower than did other subjects. Preferences for spicy foods or foods likely to cause illness were positively correlated with sensation seeking while preferences for sweet or bland foods or foods unlikely to cause illness were negatively correlated with sensation seeking. Subjects for whom the primary cuisine on which they were raised was Oriental cuisine preferred alcoholic beverages and non-Oriental foods less than did other subjects. A factor analysis of the food preferences yielded ten factors including those for meat and potatoes, alcohol, spices and junk food. Data on predictors of food preferences can assist research on the determinants of food preferences, however much of the variance in food preferences remains to be explained.

  8. Human Adult Cortical Reorganization and Consequent Visual Distortion

    PubMed Central

    Dilks, Daniel D.; Serences, John T.; Rosenau, Benjamin J.; Yantis, Steven; McCloskey, Michael

    2009-01-01

    Neural and behavioral evidence for cortical reorganization in the adult somatosensory system after loss of sensory input (e.g., amputation) has been well documented. In contrast, evidence for reorganization in the adult visual system is far less clear: neural evidence is the subject of controversy, behavioral evidence is sparse, and studies combining neural and behavioral evidence have not previously been reported. Here, we report converging behavioral and neuroimaging evidence from a stroke patient (B.L.) in support of cortical reorganization in the adult human visual system. B.L.’s stroke spared the primary visual cortex (V1), but destroyed fibers that normally provide input to V1 from the upper left visual field (LVF). As a consequence, B.L. is blind in the upper LVF, and exhibits distorted perception in the lower LVF: stimuli appear vertically elongated, toward and into the blind upper LVF. For example, a square presented in the lower LVF is perceived as a rectangle extending upward. We hypothesized that the perceptual distortion was a consequence of cortical reorganization in V1. Extensive behavioral testing supported our hypothesis, and functional magnetic resonance imaging (fMRI) confirmed V1 reorganization. Together, the behavioral and fMRI data show that loss of input to V1 after a stroke leads to cortical reorganization in the adult human visual system, and provide the first evidence that reorganization of the adult visual system affects visual perception. These findings contribute to our understanding of the human adult brain’s capacity to change and has implications for topics ranging from learning to recovery from brain damage. PMID:17804619

  9. New Insight on Biological Interaction Analysis: New Nanocrystalline Mixed Metal Oxide SPME Fiber for GC-FID Analysis of BTEX and Its Application in Human Hemoglobin-Benzene Interaction Studies

    PubMed Central

    Hosseinzadeh, Reza; Moosavi Movahedi, Ali Akbar; Ghourchian, Hedayatollah

    2014-01-01

    Nanocrystalline mixed metal oxides (MMO) of various metal cations were synthesized and were used for coating a piece of copper wire as a new high sensitive solid phase micro extraction (SPME) fiber in extraction and determination of BTEX compounds from the headspace of aqueous samples prior to GC-FID analysis. Under optimum extraction conditions, the proposed fiber exhibited low detection limits, and quantification limits, good reproducibility, simple and fast preparation method, high fiber capacity and high thermal and mechanical durability. These are some of the most important advantages of the new fiber. The proposed fiber was used for human hemoglobin upon interaction with benzene. Binding isotherm, Scatchard and Klotz logarithmic plots were constructed using HS-SPME-GC data, accurately. The obtained binding isotherm analyzed using Hill method. The Hill parameters have been obtained by calculating saturation parameter from the ratio of measured chromatographic peak areas in the presence and absence of hemoglobin. In this interaction, Hill coefficient and Hill constant determined as (nH = 6.14 and log KH = 6.47) respectively. These results reveal the cooperativity of hemoglobin upon interaction with benzene. PMID:25068260

  10. Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin

    PubMed Central

    Masuda, Takeshi; Wang, Xin; Maeda, Manami; Canver, Matthew C.; Sher, Falak; Funnell, Alister P. W.; Fisher, Chris; Suciu, Maria; Martyn, Gabriella E.; Norton, Laura J.; Zhu, Catherine; Kurita, Ryo; Nakamura, Yukio; Xu, Jian; Higgs, Douglas R.; Crossley, Merlin; Bauer, Daniel E.; Orkin, Stuart H.; Kharchenko, Peter V.; Maeda, Takahiro

    2016-01-01

    Genes encoding human β-type globin undergo a developmental switch from embryonic to fetal to adult-type expression. Mutations in the adult form cause inherited hemoglobinopathies or globin disorders, including sickle cell disease and thalassemia. Some experimental results have suggested that these diseases could be treated by induction of fetal-type hemoglobin (HbF). However, the mechanisms that repress HbF in adults remain unclear. We found that the LRF/ZBTB7A transcription factor occupies fetal γ-globin genes and maintains the nucleosome density necessary for γ-globin gene silencing in adults, and that LRF confers its repressive activity through a NuRD repressor complex independent of the fetal globin repressor BCL11A. Our study may provide additional opportunities for therapeutic targeting in the treatment of hemoglobinopathies. PMID:26816381

  11. Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin.

    PubMed

    Masuda, Takeshi; Wang, Xin; Maeda, Manami; Canver, Matthew C; Sher, Falak; Funnell, Alister P W; Fisher, Chris; Suciu, Maria; Martyn, Gabriella E; Norton, Laura J; Zhu, Catherine; Kurita, Ryo; Nakamura, Yukio; Xu, Jian; Higgs, Douglas R; Crossley, Merlin; Bauer, Daniel E; Orkin, Stuart H; Kharchenko, Peter V; Maeda, Takahiro

    2016-01-15

    Genes encoding human β-type globin undergo a developmental switch from embryonic to fetal to adult-type expression. Mutations in the adult form cause inherited hemoglobinopathies or globin disorders, including sickle cell disease and thalassemia. Some experimental results have suggested that these diseases could be treated by induction of fetal-type hemoglobin (HbF). However, the mechanisms that repress HbF in adults remain unclear. We found that the LRF/ZBTB7A transcription factor occupies fetal γ-globin genes and maintains the nucleosome density necessary for γ-globin gene silencing in adults, and that LRF confers its repressive activity through a NuRD repressor complex independent of the fetal globin repressor BCL11A. Our study may provide additional opportunities for therapeutic targeting in the treatment of hemoglobinopathies. PMID:26816381

  12. Visualizing the Bohr effect in hemoglobin: neutron structure of equine cyanomethemoglobin in the R state and comparison with human deoxyhemoglobin in the T state.

    PubMed

    Dajnowicz, Steven; Seaver, Sean; Hanson, B Leif; Fisher, S Zoë; Langan, Paul; Kovalevsky, Andrey Y; Mueser, Timothy C

    2016-07-01

    Neutron crystallography provides direct visual evidence of the atomic positions of deuterium-exchanged H atoms, enabling the accurate determination of the protonation/deuteration state of hydrated biomolecules. Comparison of two neutron structures of hemoglobins, human deoxyhemoglobin (T state) and equine cyanomethemoglobin (R state), offers a direct observation of histidine residues that are likely to contribute to the Bohr effect. Previous studies have shown that the T-state N-terminal and C-terminal salt bridges appear to have a partial instead of a primary overall contribution. Four conserved histidine residues [αHis72(EF1), αHis103(G10), αHis89(FG1), αHis112(G19) and βHis97(FG4)] can become protonated/deuterated from the R to the T state, while two histidine residues [αHis20(B1) and βHis117(G19)] can lose a proton/deuteron. αHis103(G10), located in the α1:β1 dimer interface, appears to be a Bohr group that undergoes structural changes: in the R state it is singly protonated/deuterated and hydrogen-bonded through a water network to βAsn108(G10) and in the T state it is doubly protonated/deuterated with the network uncoupled. The very long-term H/D exchange of the amide protons identifies regions that are accessible to exchange as well as regions that are impermeable to exchange. The liganded relaxed state (R state) has comparable levels of exchange (17.1% non-exchanged) compared with the deoxy tense state (T state; 11.8% non-exchanged). Interestingly, the regions of non-exchanged protons shift from the tetramer interfaces in the T-state interface (α1:β2 and α2:β1) to the cores of the individual monomers and to the dimer interfaces (α1:β1 and α2:β2) in the R state. The comparison of regions of stability in the two states allows a visualization of the conservation of fold energy necessary for ligand binding and release.

  13. Visualizing the Bohr effect in hemoglobin: neutron structure of equine cyanomethemoglobin in the R state and comparison with human deoxyhemoglobin in the T state.

    PubMed

    Dajnowicz, Steven; Seaver, Sean; Hanson, B Leif; Fisher, S Zoë; Langan, Paul; Kovalevsky, Andrey Y; Mueser, Timothy C

    2016-07-01

    Neutron crystallography provides direct visual evidence of the atomic positions of deuterium-exchanged H atoms, enabling the accurate determination of the protonation/deuteration state of hydrated biomolecules. Comparison of two neutron structures of hemoglobins, human deoxyhemoglobin (T state) and equine cyanomethemoglobin (R state), offers a direct observation of histidine residues that are likely to contribute to the Bohr effect. Previous studies have shown that the T-state N-terminal and C-terminal salt bridges appear to have a partial instead of a primary overall contribution. Four conserved histidine residues [αHis72(EF1), αHis103(G10), αHis89(FG1), αHis112(G19) and βHis97(FG4)] can become protonated/deuterated from the R to the T state, while two histidine residues [αHis20(B1) and βHis117(G19)] can lose a proton/deuteron. αHis103(G10), located in the α1:β1 dimer interface, appears to be a Bohr group that undergoes structural changes: in the R state it is singly protonated/deuterated and hydrogen-bonded through a water network to βAsn108(G10) and in the T state it is doubly protonated/deuterated with the network uncoupled. The very long-term H/D exchange of the amide protons identifies regions that are accessible to exchange as well as regions that are impermeable to exchange. The liganded relaxed state (R state) has comparable levels of exchange (17.1% non-exchanged) compared with the deoxy tense state (T state; 11.8% non-exchanged). Interestingly, the regions of non-exchanged protons shift from the tetramer interfaces in the T-state interface (α1:β2 and α2:β1) to the cores of the individual monomers and to the dimer interfaces (α1:β1 and α2:β2) in the R state. The comparison of regions of stability in the two states allows a visualization of the conservation of fold energy necessary for ligand binding and release. PMID:27377386

  14. Visualizing the Bohr effect in hemoglobin: neutron structure of equine cyanomethemoglobin in the R state and comparison with human deoxyhemoglobin in the T state

    PubMed Central

    Dajnowicz, Steven; Seaver, Sean; Hanson, B. Leif; Fisher, S. Zoë; Langan, Paul; Kovalevsky, Andrey Y.; Mueser, Timothy C.

    2016-01-01

    Neutron crystallography provides direct visual evidence of the atomic positions of deuterium-exchanged H atoms, enabling the accurate determination of the protonation/deuteration state of hydrated biomolecules. Comparison of two neutron structures of hemoglobins, human deoxyhemoglobin (T state) and equine cyanomethemoglobin (R state), offers a direct observation of histidine residues that are likely to contribute to the Bohr effect. Previous studies have shown that the T-state N-terminal and C-terminal salt bridges appear to have a partial instead of a primary overall contribution. Four conserved histidine residues [αHis72(EF1), αHis103(G10), αHis89(FG1), αHis112(G19) and βHis97(FG4)] can become protonated/deuterated from the R to the T state, while two histidine residues [αHis20(B1) and βHis117(G19)] can lose a proton/deuteron. αHis103(G10), located in the α1:β1 dimer interface, appears to be a Bohr group that undergoes structural changes: in the R state it is singly protonated/deuterated and hydrogen-bonded through a water network to βAsn108(G10) and in the T state it is doubly protonated/deuterated with the network uncoupled. The very long-term H/D exchange of the amide protons identifies regions that are accessible to exchange as well as regions that are impermeable to exchange. The liganded relaxed state (R state) has comparable levels of exchange (17.1% non-exchanged) compared with the deoxy tense state (T state; 11.8% non-exchanged). Interestingly, the regions of non-exchanged protons shift from the tetramer interfaces in the T-state interface (α1:β2 and α2:β1) to the cores of the individual monomers and to the dimer interfaces (α1:β1 and α2:β2) in the R state. The comparison of regions of stability in the two states allows a visualization of the conservation of fold energy necessary for ligand binding and release. PMID:27377386

  15. 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.

  16. 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

  17. Ultrastructural characteristics of human adult and infant cerebral cortical neurons.

    PubMed Central

    Ong, W Y; Garey, L J

    1991-01-01

    Biopsy specimens of human cerebral cortex from three adults and two infants were studied by correlating their light microscopic features in semithin sections with their ultrastructural characteristics. There was good tissue preservation, due to a minimum delay between obtaining the specimens and fixation. Pyramidal cells had a prominent apical dendrite, fine heterochromatin clumps in the nucleus and generally small numbers of cytoplasmic organelles, except for numerous free ribosomes in some of the large pyramids of Layers III to VI. Non-pyramidal cells lacked an apical dendrite and were further classified, on size and ultrastructure, into small, medium and large types. Large numbers of asymmetrical and symmetrical synapses were present in the neuropil but very few axosomatic synapses were found in the human cerebral cortex compared with subhuman primates and other mammals. Some symmetrical synapses were characterised by the presence of wide pre- and postsynaptic densities. The same general features of the adult cortex were also encountered in the infant, with certain exceptions. Many of the infant neurons had less densely packed heterochromatin, but greater numbers of free ribosomes, compared with the adult, and lipofuscin was absent. There was a total absence of myelinated fibres from the infant cortex; more large diameter dendrites were present than in the adult and axosomatic synapses were commoner. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 PMID:2050578

  18. [Generation of new nerve cells in the adult human brain].

    PubMed

    Poulsen, Frantz Rom; Meyer, Morten; Rasmussen, Jens Zimmer

    2003-03-31

    Generation of new nerve cells (neurogenesis) is normally considered to be limited to the fetal and early postnatal period. Thus, damaged nerve cells are not expected to be replaced by generation of new cells. The brain is, however, more plastic than previously assumed. This also includes neurogenesis in the adult human brain. In particular two brain regions show continuous division of neural stem and progenitor cells generating neurons and glial cells, namely the subgranular zone of the dentate gyrus and the subventricular zones of the lateral ventricles. From the latter region newly generated neuroblasts (immature nerve cells) migrate toward the olfactory bulb where they differentiate into neurons. In the dentate gyrus the newly generated neurons become functionally integrated in the granule cell layer, where they are believed to be of importance to learning and memory. It is at present not known whether neurogenesis in the adult human brain can be manipulated for specific repair after brain damage.

  19. Interaction of toxic azo dyes with heme protein: biophysical insights into the binding aspect of the food additive amaranth with human hemoglobin.

    PubMed

    Basu, Anirban; Kumar, Gopinatha Suresh

    2015-05-30

    A biophysical study on the interaction of the food colorant amaranth with hemoglobin was undertaken. Spectrophotometric and spectrofluorimetric studies proposed for an intimate binding interaction between the dye and the protein. The dye quenched the fluorescence of the protein remarkably and the mechanism of quenching was found to be static in nature. Synchronous fluorescence studies suggested that the polarity around the tryptophan residues was altered in the presence of amaranth whereas the polarity around tyrosine residues remained largely unaltered. 3D fluorescence, FTIR and circular dichroism results suggested that the binding reaction caused conformational changes in hemoglobin. The negative far-UV CD bands exhibited a significantly large decrease in magnitude in the presence of amaranth. From calorimetry studies it was established that the binding was driven by a large positive entropic contribution and a small but favorable enthalpy change.

  20. Interaction of toxic azo dyes with heme protein: biophysical insights into the binding aspect of the food additive amaranth with human hemoglobin.

    PubMed

    Basu, Anirban; Kumar, Gopinatha Suresh

    2015-05-30

    A biophysical study on the interaction of the food colorant amaranth with hemoglobin was undertaken. Spectrophotometric and spectrofluorimetric studies proposed for an intimate binding interaction between the dye and the protein. The dye quenched the fluorescence of the protein remarkably and the mechanism of quenching was found to be static in nature. Synchronous fluorescence studies suggested that the polarity around the tryptophan residues was altered in the presence of amaranth whereas the polarity around tyrosine residues remained largely unaltered. 3D fluorescence, FTIR and circular dichroism results suggested that the binding reaction caused conformational changes in hemoglobin. The negative far-UV CD bands exhibited a significantly large decrease in magnitude in the presence of amaranth. From calorimetry studies it was established that the binding was driven by a large positive entropic contribution and a small but favorable enthalpy change. PMID:25725343

  1. Epidermal growth factor receptor in adult human dorsal root ganglia.

    PubMed

    Huerta, J J; Diaz-Trelles, R; Naves, F J; Llamosas, M M; Del Valle, M E; Vega, J A

    1996-09-01

    Transforming growth factor-alpha (TGFalpha) enhances neuronal survival and neurite outgrowth in cultured dorsal root ganglia (DRG) sensory neurons. It binds a membrane protein, denominated epidermal growth factor receptor (EGFr). EGFr has been localized in developing and adult human DRG. However, it remains to be elucidated whether all DRG neurons express EGFr or whether differences exist among neuronal subtypes. This study was undertaken to investigate these topics in adult human DRG using immunoblotting, and combined immunohistochemistry and image analysis techniques. A mouse monoclonal antibody (clone F4) mapping within the intracytoplasmic domain of EGFr was used. Immunoblotting revealed two main proteins with estimated molecular masses of approximately/equal to 65 kDa and 170 kDa, and thus consistent with the full-length EGFr. Additional protein bands were also encountered. Light immunohistochemistry revealed specific immunoreactivity (IR) for EGFr-like proteins in most (86%) primary sensory neurons, the intensity of immunostaining being stronger in the small- and intermediate-sized ones. Furthermore, EGFr-like IR was also observed in the satellite glial cells of the ganglia as well as in the intraganglionic and dorsal root Schwann cells. Taken together, our findings demonstrate that EGFr, and other related proteins containing the epitope labeled with the antibody F4, are responsible for the EGFr IR reported in DRG. Furthermore, we demonstrated heterogeneity in the expression of EGFr-like IR in adult human primary sensory neurons, which suggests different responsiveness to their ligands.

  2. 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

  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. Association of diabetes-related distress, depression, medication adherence, and health-related quality of life with glycated hemoglobin, blood pressure, and lipids in adult patients with type 2 diabetes: a cross-sectional study

    PubMed Central

    Chew, Boon-How; Sherina, Mohd-Sidik; Hassan, Noor-Hasliza

    2015-01-01

    This study examined the associations of diabetes-related distress (DRD), depressive symptoms, health-related quality of life (HRQoL), and medication adherence with glycemia, blood pressure (BP), and lipid biomarkers in adults with type 2 diabetes mellitus (T2D). This cross-sectional study was conducted in three Malaysian public health clinics in 2012–2013, recruited adult patients (aged ≥30 years) with T2D who had been diagnosed for more than one year, were on active follow-up, and had recent blood test results. Univariable and multivariable analyses were performed to identify significant associated factors for glycated hemoglobin (HbA1c) BP, and lipids. The response rate was 93.1% (700/752). The majority were females (52.8%), Malay (52.4%), and married (78.7%). DRD correlated with systolic BP (r= −0.16); depressive symptoms correlated with low-density lipoprotein cholesterol (r=0.12) and total cholesterol (r=0.13); medication adherence correlated with HbA1c (r= −0.14) and low-density lipoprotein cholesterol (r= −0.11); and HRQoL correlated with casual blood glucose (r= −0.11), high-density lipoprotein cholesterol (r= −0.13), and total cholesterol (r= −0.08). Multivariable analyses showed that HRQoL was significantly associated with casual blood glucose (adjusted B= −0.06, P=0.024); DRD was associated with systolic BP (adjusted B= −0.08, P=0.066); depressive symptoms were associated with low-density lipoprotein cholesterol (adjusted B=0.02, P=0.061), and medication adherence was associated with HbA1c (adjusted B= −0.11, P=0.082) and total cholesterol (adjusted B= −0.06, P=0.086). There were significant and distinctive associations of DRD, depressive symptoms, HRQoL, and medication adherence with glycemia, BP, and lipid biomarkers. Unexpected beneficial therapeutic effects of DRD on BP require further study. A multidisciplinary approach may be needed for risk management in adults with T2D at the primary care level. PMID:25995640

  5. Therapeutic hemoglobin levels after gene transfer in β-thalassemia mice and in hematopoietic cells of β-thalassemia and sickle cells disease patients.

    PubMed

    Breda, Laura; Casu, Carla; Gardenghi, Sara; Bianchi, Nicoletta; Cartegni, Luca; Narla, Mohandas; Yazdanbakhsh, Karina; Musso, Marco; Manwani, Deepa; Little, Jane; Gardner, Lawrence B; Kleinert, Dorothy A; Prus, Eugenia; Fibach, Eitan; Grady, Robert W; Giardina, Patricia J; Gambari, Roberto; Rivella, Stefano

    2012-01-01

    Preclinical and clinical studies demonstrate the feasibility of treating β-thalassemia and Sickle Cell Disease (SCD) by lentiviral-mediated transfer of the human β-globin gene. However, previous studies have not addressed whether the ability of lentiviral vectors to increase hemoglobin synthesis might vary in different patients.We generated lentiviral vectors carrying the human β-globin gene with and without an ankyrin insulator and compared their ability to induce hemoglobin synthesis in vitro and in thalassemic mice. We found that insertion of an ankyrin insulator leads to higher, potentially therapeutic levels of human β-globin through a novel mechanism that links the rate of transcription of the transgenic β-globin mRNA during erythroid differentiation with polysomal binding and efficient translation, as reported here for the first time. We also established a preclinical assay to test the ability of this novel vector to synthesize adult hemoglobin in erythroid precursors and in CD34(+) cells isolated from patients affected by β-thalassemia and SCD. Among the thalassemic patients, we identified a subset of specimens in which hemoglobin production can be achieved using fewer copies of the vector integrated than in others. In SCD specimens the treatment with AnkT9W ameliorates erythropoiesis by increasing adult hemoglobin (Hb A) and concurrently reducing the sickling tetramer (Hb S).Our results suggest two major findings. First, we discovered that for the purpose of expressing the β-globin gene the ankyrin element is particularly suitable. Second, our analysis of a large group of specimens from β-thalassemic and SCD patients indicates that clinical trials could benefit from a simple test to predict the relationship between the number of vector copies integrated and the total amount of hemoglobin produced in the erythroid cells of prospective patients. This approach would provide vital information to select the best candidates for these clinical trials

  6. [Multipotency of adult stem cells derived from human amnion].

    PubMed

    Shi, Mingxia; Li, Weijia; Li, Bingzong; Li, Jing; Zhao, Chunhua

    2009-05-01

    Adult stem cells are drawing more and more attention due to the potential application in degenerative medicine without posing any moral problem. There is growing evidence showing that the human amnion contains various types of adult stem cell. Since amniotic tissue is readily available, it has the potential to be an important source of regenerative medicine material. In this study we tried to find multipotent adult stem cells in human amnion. We isolated stem cells from amniotic mesenchymal cells by limiting dilution assay. Similar to bone marrow derived mesenchymal stem cells, these cells displayed a fibroblast like appearance. They were positive for CD105, CD29, CD44, negative for haematopoietic (GlyA, CD31, CD34, CD45) and epithelial cell (pan-CK) markers. These stem cells had the potential to differentiate not only into osteogenic, adipogenic and endothelial lineages, but also hepatocyte-like cells and neural cells at the single-cell level depending on the culture conditions. They had the capacity for self-renewal and multilineage differentiation even after being expanded for more than 30 population doublings in vitro. So they may be an ideal stem cell source for inherited or degenerative diseases treatment.

  7. How long have adult humans been consuming milk?

    PubMed

    Gerbault, Pascale; Roffet-Salque, Mélanie; Evershed, Richard P; Thomas, Mark G

    2013-12-01

    Lactase is the enzyme that breaks down the milk sugar lactose, and in most mammals, including most humans, lactase activity is down-regulated after the weaning period is completed. However, in about 35% of adults worldwide, lactase continues to be expressed throughout adulthood, a feature termed lactase persistence (LP). Genetic evidence indicates that LP is a recent human adaptation, and its current geographic distribution correlates with the relative historical importance of dairying in different human populations. Investigating archaeological evidence for fresh milk consumption has proved crucial in building an account of the joint evolution of LP and dairying. A powerful technique for investigating food processing, including milk processing, in ancient populations is lipid residue analysis on archaeological pottery. We review here the archaeological and genetic evidence available that have contributed to a better understanding of the gene-culture co-evolution of LP and dairying. PMID:24339181

  8. How long have adult humans been consuming milk?

    PubMed

    Gerbault, Pascale; Roffet-Salque, Mélanie; Evershed, Richard P; Thomas, Mark G

    2013-12-01

    Lactase is the enzyme that breaks down the milk sugar lactose, and in most mammals, including most humans, lactase activity is down-regulated after the weaning period is completed. However, in about 35% of adults worldwide, lactase continues to be expressed throughout adulthood, a feature termed lactase persistence (LP). Genetic evidence indicates that LP is a recent human adaptation, and its current geographic distribution correlates with the relative historical importance of dairying in different human populations. Investigating archaeological evidence for fresh milk consumption has proved crucial in building an account of the joint evolution of LP and dairying. A powerful technique for investigating food processing, including milk processing, in ancient populations is lipid residue analysis on archaeological pottery. We review here the archaeological and genetic evidence available that have contributed to a better understanding of the gene-culture co-evolution of LP and dairying.

  9. Neurons in the White Matter of the Adult Human Neocortex

    PubMed Central

    Suárez-Solá, M. Luisa; González-Delgado, Francisco J.; Pueyo-Morlans, Mercedes; Medina-Bolívar, O. Carolina; Hernández-Acosta, N. Carolina; González-Gómez, Miriam; Meyer, Gundela

    2009-01-01

    The white matter (WM) of the adult human neocortex contains the so-called “interstitial neurons”. They are most numerous in the superficial WM underlying the cortical gyri, and decrease in density toward the deep WM. They are morphologically heterogeneous. A subgroup of interstitial neurons display pyramidal-cell like morphologies, characterized by a polarized dendritic tree with a dominant apical dendrite, and covered with a variable number of dendritic spines. In addition, a large contingent of interstitial neurons can be classified as interneurons based on their neurochemical profile as well as on morphological criteria. WM- interneurons have multipolar or bipolar shapes and express GABA and a variety of other neuronal markers, such as calbindin and calretinin, the extracellular matrix protein reelin, or neuropeptide Y, somatostatin, and nitric oxide synthase. The heterogeneity of interstitial neurons may be relevant for the pathogenesis of Alzheimer disease and schizophrenia. Interstitial neurons are most prominent in human brain, and only rudimentary in the brain of non-primate mammals. These evolutionary differences have precluded adequate experimental work on this cell population, which is usually considered as a relict of the subplate, a transient compartment proper of development and without a known function in the adult brain. The primate-specific prominence of the subplate in late fetal stages points to an important role in the establishment of interstitial neurons. Neurons in the adult WM may be actively involved in coordinating inter-areal connectivity and regulation of blood flow. Further studies in primates will be needed to elucidate the developmental history, adult components and activities of this large neuronal system. PMID:19543540

  10. 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%.

  11. 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.

  12. 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

  13. 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.

  14. Ontogeny of morningness-eveningness across the adult human lifespan

    NASA Astrophysics Data System (ADS)

    Randler, Christoph

    2016-02-01

    Sleep timing of humans can be classified alongside a continuum from early to late sleepers, with some people (larks) having an early activity, early bed, and rise times and others (owls) with a more nocturnally orientated activity. Only a few studies reported that morningness-eveningness changes significantly during the adult lifespan based on community samples. Here, I applied a different methodological approach to seek for evidence for the age-related changes in morningness-eveningness preferences by using a meta-data from all available studies. The new aspect of this cross-sectional approach is that only a few studies themselves address the age-related changes of the adult lifespan development, but that many studies are available that provide exactly the data needed. The studies came from 27 countries and included 36,939 participants. Age was highly significantly correlated with scores on the Composite Scale of Morningness ( r = 0.70). This relationship seems linear, because a linear regression explained nearly the same amount of variance compared to other models such as logarithmic, quadratic, or cubic models. The standard deviation of age correlated with the standard deviation of CSM scores ( r = 0.55), suggesting when there is much variance in age in a study; in turn, there is much variance in morningness. This meta-analytical approach shows that morningness-eveningness changes across the adult lifespan and that older age is related to higher morningness.

  15. Investigating the adduct formation of organic mercury species with carbonic anhydrase and hemoglobin from human red blood cell hemolysate by means of LC/ESI-TOF-MS and LC/ICP-MS.

    PubMed

    Hogeback, Jens; Schwarzer, Miriam; Wehe, Christoph A; Sperling, Michael; Karst, Uwe

    2016-01-01

    The interaction of mercury species with human erythrocytes is studied to investigate possible high molecular binding partners for mercury species. Human blood hemolysate was spiked with methylmercury and investigated by means of liquid chromatography (LC) coupled to electrospray ionization time of flight mass spectrometry (ESI-ToF-MS) and inductively coupled plasma mass spectrometry (ICP-MS). Beside adduct formation of mercury species with hemoglobin, the main compound of the erythrocytes, mercury binding to the enzyme carbonic anhydrase was revealed. Due to an enzymatic digest of the protein-mercury adduct, the binding site at the free thiol group of the protein was identified. These results indicate that carbonic anhydrase might play a role in mercury toxicity.

  16. Multipotent progenitor cells isolated from adult human pancreatic tissue.

    PubMed

    Todorov, I; Nair, I; Ferreri, K; Rawson, J; Kuroda, A; Pascual, M; Omori, K; Valiente, L; Orr, C; Al-Abdullah, I; Riggs, A; Kandeel, F; Mullen, Y

    2005-10-01

    The supply of islet cells is a limiting factor for the widespread application of islet transplantation of type-1 diabetes. Islets constitute 1% to 2% of pancreatic tissue, leaving approximately 98% as discard after islet isolation and purification. In this report we present our data on the isolation of multipotent progenitor cells from discarded adult human pancreatic tissue. The collected cells from discarded nonislet fractions, after enzymatic digestion and gradient purification of islets, were dissociated for suspension culture in a serum-free medium. The cell clusters grown to a size of 100 to 150 mum contained cells staining for stage-specific embryonic antigens, but not insulin or C-peptide. To direct cell differentiation toward islets, clusters were recultured in a pancreatic differentiation medium. Insulin and C-peptide-positive cells by immunocytochemistry appeared within a week, reaching over 10% of the cell population. Glucagon and somatostatin-positive cells were also detected. The cell clusters were found to secrete insulin in response to glucose stimulation. Cells from the same clusters also had the capacity for differentiation into neural cells, as documented by staining for neural and glial cell markers when cultured as monolayers in media containing neurotrophic factors. These data suggest that multipotent pancreatic progenitor cells exist within the human pancreatic tissue that is typically discarded during islet isolation procedures. These adult progenitor cells can be successfully differentiated into insulin-producing cells, and thus they have the potential for treatment of type-1 diabetes mellitus. PMID:16298614

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. Erythrocyte enrichment in hematopoietic progenitor cell cultures based on magnetic susceptibility of the hemoglobin.

    PubMed

    Jin, Xiaoxia; Abbot, Stewart; Zhang, Xiaokui; Kang, Lin; Voskinarian-Berse, Vanessa; Zhao, Rui; Kameneva, Marina V; Moore, Lee R; Chalmers, Jeffrey J; Zborowski, Maciej

    2012-01-01

    Using novel media formulations, it has been demonstrated that human placenta and umbilical cord blood-derived CD34+ cells can be expanded and differentiated into erythroid cells with high efficiency. However, obtaining mature and functional erythrocytes from the immature cell cultures with high purity and in an efficient manner remains a significant challenge. A distinguishing feature of a reticulocyte and maturing erythrocyte is the increasing concentration of hemoglobin and decreasing cell volume that results in increased cell magnetophoretic mobility (MM) when exposed to high magnetic fields and gradients, under anoxic conditions. Taking advantage of these initial observations, we studied a noninvasive (label-free) magnetic separation and analysis process to enrich and identify cultured functional erythrocytes. In addition to the magnetic cell separation and cell motion analysis in the magnetic field, the cell cultures were characterized for cell sedimentation rate, cell volume distributions using differential interference microscopy, immunophenotyping (glycophorin A), hemoglobin concentration and shear-induced deformability (elongation index, EI, by ektacytometry) to test for mature erythrocyte attributes. A commercial, packed column high-gradient magnetic separator (HGMS) was used for magnetic separation. The magnetically enriched fraction comprised 80% of the maturing cells (predominantly reticulocytes) that showed near 70% overlap of EI with the reference cord blood-derived RBC and over 50% overlap with the adult donor RBCs. The results demonstrate feasibility of label-free magnetic enrichment of erythrocyte fraction of CD34+ progenitor-derived cultures based on the presence of paramagnetic hemoglobin in the maturing erythrocytes.

  3. 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.

  4. 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)

  5. 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

  6. 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

  7. 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.

  8. Neuropeptide Y in the adult and fetal human pineal gland.

    PubMed

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  9. Gustatory reaction time to various sweeteners in human adults.

    PubMed

    Yamamoto, T; Kato, T; Matsuo, R; Kawamura, Y; Yoshida, M

    1985-09-01

    Reaction times to recognize the sweet taste of 12 sweeteners at various concentrations were measured in 48 human adults. The reaction time (T) decreased with increasing concentration (C) of each sweetener applied to the anterior dorsal tongue. The relationships between T and C, and T and logC were well described by a rectangular hyperbola formula for each of the 12 sweeteners. Reaction times to discriminate sweet taste quality between pairs of sweeteners were measured, then a similarity index was calculated. Factor analysis based on correlation coefficients between pairs of sweeteners which were obtained by the similarity indices has indicated classification of the sweeteners. Sucrose, fructose, glucose, maltose, sorbitol and aspartame tend to group together. Na-cyclamate and Na-saccharin form another group. DL-alanine, stevioside and neohesperidin dihydrochalcone are rather independent and do not belong to any group.

  10. Real-time tracking of CO migration and binding in the α and β subunits of human hemoglobin via 150-ps time-resolved Laue crystallography

    PubMed Central

    Schotte, Friedrich; Cho, Hyun Sun; Soman, Jayashree; Wulff, Michael; Olson, John S.; Anfinrud, Philip A.

    2014-01-01

    We have developed the method of picosecond Laue crystallography and used this capability to probe ligand dynamics in tetrameric R-state hemoglobin (Hb). Time-resolved, 2 Å-resolution electron density maps of photolyzed HbCO reveal the time-dependent population of CO in the binding (A) and primary docking (B) sites of both α and β subunits from 100 ps to 10 μs. The proximity of the B site in the β subunit is about 0.25 Å closer to its A binding site, and its kBA rebinding rate (~300 μs−1) is six times faster, suggesting distal control of the rebinding dynamics. Geminate rebinding in the β subunit exhibits both prompt and delayed geminate phases. We developed a microscopic model to quantitatively explain the observed kinetics, with three states for the α subunit and four states for the β subunit. This model provides a consistent framework for interpreting rebinding kinetics reported in prior studies of both HbCO and HbO2. PMID:24839343

  11. Glucocorticoid treatment skews human monocyte differentiation into a hemoglobin-clearance phenotype with enhanced heme-iron recycling and antioxidant capacity.

    PubMed

    Vallelian, Florence; Schaer, Christian A; Kaempfer, Theresa; Gehrig, Peter; Duerst, Elena; Schoedon, Gabriele; Schaer, Dominik J

    2010-12-01

    Glucocorticoids are used extensively to treat autoimmune hemolytic anemias. Some beneficial effects of glucocorticoid pulse therapy have also been reported in sickle cell disease and paroxysmal nocturnal hemoglobinuria. Based on established concepts of hemoglobin (Hb) toxicity and physiologic Hb scavenger systems, we evaluated whether glucocorticoids could support an adaptive response to extracellular Hb independently of their immunosuppressive activities. Using global proteome and transcriptome analysis with mass-spectrometry (isobaric tag for relative and absolute quantitation and liquid chromatography-mass spectrometry) and gene-array experiments, we found that glucocorticoid treatment in vitro and in patients on glucocorticoid-pulse therapy polarized monocytes into a M2/alternatively activated phenotype with high Hb-scavenger receptor (CD163) expression and enhanced Hb-clearance and detoxification capability. Monocytes concurrently exposed to the interactive activity of glucocorticoids and extracellular Hb were characterized by high expression of a group of antioxidant enzymes known to be regulated by the conserved oxidative response transcription factor nuclear factor E2-related factor. Further, suppressed transferrin receptor, together with high ferroportin expression, pointed to a shift in iron homeostasis directed toward an increased cellular export of heme-derived iron. Therefore, stimulating Hb-endocytosis by CD163 and enhancing antioxidative homeostasis and iron recycling may be an essential activity of glucocorticoids that helps alleviate the adverse effects of extracellular Hb. PMID:20739658

  12. A biokinetic model for systemic technetium in adult humans

    DOE PAGES

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection.more » Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.« less

  13. Comprehensive cellular‐resolution atlas of the adult human brain

    PubMed Central

    Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

    2016-01-01

    ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  14. Comprehensive cellular-resolution atlas of the adult human brain.

    PubMed

    Ding, Song-Lin; Royall, Joshua J; Sunkin, Susan M; Ng, Lydia; Facer, Benjamin A C; Lesnar, Phil; Guillozet-Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A; Koch, Christof; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Zielke, H Ronald; Hohmann, John G; Jones, Allan R; Bernard, Amy; Hawrylycz, Michael J; Hof, Patrick R; Fischl, Bruce; Lein, Ed S

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  15. Comprehensive cellular-resolution atlas of the adult human brain.

    PubMed

    Ding, Song-Lin; Royall, Joshua J; Sunkin, Susan M; Ng, Lydia; Facer, Benjamin A C; Lesnar, Phil; Guillozet-Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A; Koch, Christof; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Zielke, H Ronald; Hohmann, John G; Jones, Allan R; Bernard, Amy; Hawrylycz, Michael J; Hof, Patrick R; Fischl, Bruce; Lein, Ed S

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  16. A biokinetic model for systemic technetium in adult humans

    SciTech Connect

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection. Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.

  17. Determinants of Anemia Among Human Immunodeficiency Virus-Positive Adults at Care and Treatment Clinics in Dar es Salaam, Tanzania.

    PubMed

    Petraro, Paul; Duggan, Christopher; Spiegelman, Donna; Hertzmark, Ellen; Makubi, Abel; Chalamilla, Guerino; Siril, Helen; Sando, David; Aboud, Said; Fawzi, Wafaie W

    2016-02-01

    Anemia is often a comorbidity of human immunodeficiency virus (HIV) infection. Many cross-sectional studies have been conducted on anemia and HIV, but few, if any, have addressed incidence of anemia prospectively. A longitudinal analysis was conducted in 48,068 nonpregnant HIV-infected adults in Dar es Salaam, Tanzania, seen at Management and Development for Health-U.S. President's Emergency Plan for AIDS Relief HIV care and treatment programs between 2004 and 2011. Almost 56% (N = 27,184) of study participants had anemia (hemoglobin < 11 g/dL) at the time of enrollment at the clinic. Female gender, low body mass index (BMI), low CD4 T-cell count, high levels of liver enzyme alanine aminotransferase, antiretroviral treatment (ART) regimens, and concurrent tuberculosis treatment were all independently significantly associated with an increased risk of anemia. Low BMI and low CD4 T-cell count were independently significantly associated with an increased risk for iron deficiency anemia (IDA). Higher BMI status and ART use were associated with recovery from anemia. Anemia, including IDA, is a comorbidity that is associated with other adverse consequences (e.g., low BMI and CD4 T-cell count) among individuals with HIV infection, including those on ART. Interventions to prevent anemia and its complications need to be examined in the context of future studies. PMID:26666698

  18. 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.

  19. 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.

  20. AltitudeOmics: rapid hemoglobin mass alterations with early acclimatization to and de-acclimatization from 5260 m in healthy humans.

    PubMed

    Ryan, Benjamin J; Wachsmuth, Nadine B; Schmidt, Walter F; Byrnes, William C; Julian, Colleen G; Lovering, Andrew T; Subudhi, Andrew W; Roach, Robert C

    2014-01-01

    It is classically thought that increases in hemoglobin mass (Hbmass) take several weeks to develop upon ascent to high altitude and are lost gradually following descent. However, the early time course of these erythropoietic adaptations has not been thoroughly investigated and data are lacking at elevations greater than 5000 m, where the hypoxic stimulus is dramatically increased. As part of the AltitudeOmics project, we examined Hbmass in healthy men and women at sea level (SL) and 5260 m following 1, 7, and 16 days of high altitude exposure (ALT1/ALT7/ALT16). Subjects were also studied upon return to 5260 m following descent to 1525 m for either 7 or 21 days. Compared to SL, absolute Hbmass was not different at ALT1 but increased by 3.7 ± 5.8% (mean ± SD; n = 20; p<0.01) at ALT7 and 7.6 ± 6.6% (n = 21; p<0.001) at ALT16. Following descent to 1525 m, Hbmass was reduced compared to ALT16 (-6.0 ± 3.7%; n = 20; p = 0.001) and not different compared to SL, with no difference in the loss in Hbmass between groups that descended for 7 (-6.3 ± 3.0%; n = 13) versus 21 days (-5.7 ± 5.0; n = 7). The loss in Hbmass following 7 days at 1525 m was correlated with an increase in serum ferritin (r =  -0.64; n = 13; p<0.05), suggesting increased red blood cell destruction. Our novel findings demonstrate that Hbmass increases within 7 days of ascent to 5260 m but that the altitude-induced Hbmass adaptation is lost within 7 days of descent to 1525 m. The rapid time course of these adaptations contrasts with the classical dogma, suggesting the need to further examine mechanisms responsible for Hbmass adaptations in response to severe hypoxia.

  1. 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.

  2. The Adult Learner. The Definitive Classic in Adult Education and Human Resource Development. Fifth Edition.

    ERIC Educational Resources Information Center

    Knowles, Malcolm S.; Holton, Elwood F., III; Swanson, Richard A.

    This book examines the core principles of adult learning and the roots of andragogy, advances in adult learning, and practice in adult learning. The following are among the topics discussed in the book's 17 chapters: importance of learning theory; theories of learning (concept of part and whole models of development, theories based on elemental…

  3. [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.

  4. 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.

  5. Adult somatic stem cells in the human parasite, Schistosoma mansoni

    PubMed Central

    Collins, James J.; Wang, Bo; Lambrus, Bramwell G.; Tharp, Marla; Iyer, Harini; Newmark, Phillip A.

    2013-01-01

    Summary Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide1. The etiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades2, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms3,4 (e.g., planarians), and neoblast-like cells have been described in some parasitic tapeworms5, little is known about whether similar cell types exist in any trematode species. Here, we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources6,7 and RNAseq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor ortholog. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations suggest that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes likely contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites. PMID:23426263

  6. A biokinetic model for systemic technetium in adult humans.

    PubMed

    Leggett, R; Giussani, A

    2015-06-01

    This paper reviews biokinetic data for technetium and proposes a biokinetic model for systemic technetium in adult humans. The development of parameter values focuses on data for pertechnetate TcO(-)(4) the most commonly encountered form of technetium and the form expected to be present in body fluids. The model is intended as a default model for occupational or environmental intake of technetium, i.e. applicable in the absence of form- or site-specific information. Tissues depicted explicitly in the model include thyroid, salivary glands, stomach wall, right colon wall, liver, kidneys, and bone. Compared with the ICRP's current biokinetic model for occupational or environmental intake of technetium (ICRP 1993, 1994), the proposed model provides a more detailed and biologically realistic description of the systemic behaviour of technetium and is based on a broader set of experimental and medical data. For acute input of (99m)Tc (T(1/2) = 6.02 h) to blood, the ratios of cumulative (time-integrated) activity predicted by the current ICRP model to that predicted by the proposed model range from 0.4-7 for systemic regions addressed explicitly in both models. For acute input of (99)Tc (T(1/2) = 2.1 × 10(5) year) to blood, the corresponding ratios range from 0.2-30.

  7. Metric analysis of basal sphenoid angle in adult human skulls

    PubMed Central

    Netto, Dante Simionato; Nascimento, Sergio Ricardo Rios; Ruiz, Cristiane Regina

    2014-01-01

    Objective To analyze the variations in the angle basal sphenoid skulls of adult humans and their relationship to sex, age, ethnicity and cranial index. Methods The angles were measured in 160 skulls belonging to the Museum of the Universidade Federal de São Paulo Department of Morphology. We use two flexible rules and a goniometer, having as reference points for the first rule the posterior end of the ethmoidal crest and dorsum of the sella turcica, and for the second rule the anterior margin of the foramen magnum and clivus, measuring the angle at the intersection of two. Results The average angle was 115.41°, with no statistical correlation between the value of the angle and sex or age. A statistical correlation was noted between the value of the angle and ethnicity, and between the angle and the horizontal cranial index. Conclusions The distribution of the angle basal sphenoid was the same in sex, and there was correlation between the angle and ethnicity, being the proportion of non-white individuals with an angle >125° significantly higher than that of whites with an angle >125°. There was correlation between the angle and the cranial index, because skulls with higher cranial index tend to have higher basiesfenoidal angle too. PMID:25295452

  8. Bone-forming capacity of adult human nasal chondrocytes

    PubMed Central

    Pippenger, Benjamin E; Ventura, Manuela; Pelttari, Karoliina; Feliciano, Sandra; Jaquiery, Claude; Scherberich, Arnaud; Walboomers, X Frank; Barbero, Andrea; Martin, Ivan

    2015-01-01

    Nasal chondrocytes (NC) derive from the same multipotent embryological segment that gives rise to the majority of the maxillofacial bone and have been reported to differentiate into osteoblast-like cells in vitro. In this study, we assessed the capacity of adult human NC, appropriately primed towards hypertrophic or osteoblastic differentiation, to form bone tissue in vivo. Hypertrophic induction of NC-based micromass pellets formed mineralized cartilaginous tissues rich in type X collagen, but upon implantation into subcutaneous pockets of nude mice remained avascular and reverted to stable hyaline-cartilage. In the same ectopic environment, NC embedded into ceramic scaffolds and primed with osteogenic medium only sporadically formed intramembranous bone tissue. A clonal study could not demonstrate that the low bone formation efficiency was related to a possibly small proportion of cells competent to become fully functional osteoblasts. We next tested whether the cues present in an orthotopic environment could induce a more efficient direct osteoblastic transformation of NC. Using a nude rat calvarial defect model, we demonstrated that (i) NC directly participated in frank bone formation and (ii) the efficiency of survival and bone formation by NC was significantly higher than that of reference osteogenic cells, namely bone marrow-derived mesenchymal stromal cells. This study provides a proof-of-principle that NC have the plasticity to convert into bone cells and thereby represent an easily available cell source to be further investigated for craniofacial bone regeneration. PMID:25689393

  9. AltitudeOmics: Rapid Hemoglobin Mass Alterations with Early Acclimatization to and De-Acclimatization from 5260 m in Healthy Humans

    PubMed Central

    Ryan, Benjamin J.; Wachsmuth, Nadine B.; Schmidt, Walter F.; Byrnes, William C.; Julian, Colleen G.; Lovering, Andrew T.; Subudhi, Andrew W.; Roach, Robert C.

    2014-01-01

    It is classically thought that increases in hemoglobin mass (Hbmass) take several weeks to develop upon ascent to high altitude and are lost gradually following descent. However, the early time course of these erythropoietic adaptations has not been thoroughly investigated and data are lacking at elevations greater than 5000 m, where the hypoxic stimulus is dramatically increased. As part of the AltitudeOmics project, we examined Hbmass in healthy men and women at sea level (SL) and 5260 m following 1, 7, and 16 days of high altitude exposure (ALT1/ALT7/ALT16). Subjects were also studied upon return to 5260 m following descent to 1525 m for either 7 or 21 days. Compared to SL, absolute Hbmass was not different at ALT1 but increased by 3.7±5.8% (mean ± SD; n = 20; p<0.01) at ALT7 and 7.6±6.6% (n = 21; p<0.001) at ALT16. Following descent to 1525 m, Hbmass was reduced compared to ALT16 (−6.0±3.7%; n = 20; p = 0.001) and not different compared to SL, with no difference in the loss in Hbmass between groups that descended for 7 (−6.3±3.0%; n = 13) versus 21 days (−5.7±5.0; n = 7). The loss in Hbmass following 7 days at 1525 m was correlated with an increase in serum ferritin (r = −0.64; n = 13; p<0.05), suggesting increased red blood cell destruction. Our novel findings demonstrate that Hbmass increases within 7 days of ascent to 5260 m but that the altitude-induced Hbmass adaptation is lost within 7 days of descent to 1525 m. The rapid time course of these adaptations contrasts with the classical dogma, suggesting the need to further examine mechanisms responsible for Hbmass adaptations in response to severe hypoxia. PMID:25271637

  10. 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.

  11. Adult Education and the Human Environment: Transactions of a Celebration.

    ERIC Educational Resources Information Center

    Jones-Quartey, K. A. B., Ed.; And Others

    The document comprises a collection of speeches and seminar reports arising from the 25th anniversary celebration of the Institute of Adult Education at the University of Ghana. The theme of the celebration, introduced in the first chapter, was Adult Education and Man's Environment--the Next Quarter-Century. The second chapter comprises the…

  12. 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

  13. Transcriptional profiling of adult neural stem-like cells from the human brain.

    PubMed

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  14. Transcriptional Profiling of Adult Neural Stem-Like Cells from the Human Brain

    PubMed Central

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O.; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A.

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33–60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate. PMID

  15. 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...

  16. 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 §...

  17. 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 §...

  18. 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 §...

  19. 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 §...

  20. 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...

  1. 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 §...

  2. 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 §...

  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. 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 §...

  7. 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 §...

  8. 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 §...

  9. 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 §...

  10. 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...

  11. 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)....

  12. 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)....

  13. 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)....

  14. 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)....

  15. 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)....

  16. 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 §...

  17. 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 §...

  18. Germline stem cells and neo-oogenesis in the adult human ovary.

    PubMed

    Liu, Yifei; Wu, Chao; Lyu, Qifeng; Yang, Dongzi; Albertini, David F; Keefe, David L; Liu, Lin

    2007-06-01

    It remains unclear whether neo-oogenesis occurs in postnatal ovaries of mammals, based on studies in mice. We thought to test whether adult human ovaries contain germline stem cells (GSCs) and undergo neo-oogenesis. Rather than using genetic manipulation which is unethical in humans, we took the approach of analyzing the expression of meiotic marker genes and genes for germ cell proliferation, which are required for neo-oogenesis, in adult human ovaries covering an age range from 28 to 53 years old, compared to testis and fetal ovaries served as positive controls. We show that active meiosis, neo-oogenesis and GSCs are unlikely to exist in normal, adult, human ovaries. No early meiotic-specific or oogenesis-associated mRNAs for SPO11, PRDM9, SCP1, TERT and NOBOX were detectable in adult human ovaries using RT-PCR, compared to fetal ovary and adult testis controls. These findings are further corroborated by the absence of early meiocytes and proliferating germ cells in adult human ovarian cortex probed with markers for meiosis (SCP3), oogonium (OCT3/4, c-KIT), and cell cycle progression (Ki-67, PCNA), in contrast to fetal ovary controls. If postnatal oogenesis is confirmed in mice, then this species would represent an exception to the rule that neo-oogenesis does not occur in adults.

  19. A comparison of erythrocyte glutathione S-transferase activity from human foetuses and adults.

    PubMed Central

    Strange, R C; Johnston, J D; Coghill, D R; Hume, R

    1980-01-01

    Glutathione S-transferase activity was measured in partially purified haemolysates of erythrocytes from human foetuses and adults. Enzyme activity was present in erythrocytes obtained between 12 and 40 weeks of gestation. The catalytic properties of the enzyme from foetal cells were similar to those of the enzyme from adult erythrocytes, indicating that probably only one form of the erythrocytes enzyme exists throughout foetal and adult life. PMID:7396875

  20. Brain stem auditory evoked responses in human infants and adults

    NASA Technical Reports Server (NTRS)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  1. Adult Continuing Education and Human Resource Development: Present Competitors, Potential Partners

    ERIC Educational Resources Information Center

    Smith, Douglas H.

    2006-01-01

    Adult Continuing Education (ACE) and Human Resource Development (HRD) have grown tremendously in the last quarter century. ACE experienced tremendous growth in the 60s and 70s, with over 17 million attending colleges and universities, and local school and community adult education programs by the end of the 1970s. More ACE programs were started…

  2. Reaching beyond the United States: Adventures in International Adult Education and Human Resource Development

    ERIC Educational Resources Information Center

    Henschke, John A.

    2005-01-01

    In this article, the author shares his experience of how travel and adult education merged, for him, into a major emphasis in international adult education (AE) and human resource development (HRD). International ventures have been some of the most exciting and learning-filled aspects of the author's career in AE and HRD. His involvement in…

  3. Role of β/δ101Gln in regulating the effect of temperature and allosteric effectors on oxygen affinity in woolly mammoth hemoglobin.

    PubMed

    Yuan, Yue; Byrd, Catherine; Shen, Tong-Jian; Simplaceanu, Virgil; Tam, Tsuey Chyi S; Ho, Chien

    2013-12-10

    The oxygen affinity of woolly mammoth hemoglobin (rHb WM) is less affected by temperature change than that of Asian elephant hemoglobin (rHb AE) or human normal adult hemoglobin (Hb A). We report here a biochemical-biophysical study of Hb A, rHb AE, rHb WM, and three rHb WM mutants with amino acid substitutions at β/δ101 (β/δ101Gln→Glu, Lys, or Asp) plus a double and a triple mutant, designed to clarify the role of the β/δ101 residue. The β/δ101Gln residue is important for responding to allosteric effectors, such as phosphate, inositol hexaphosphate (IHP), and chloride. The rHb WM mutants studied generally have higher affinity for oxygen under various conditions of pH, temperature, and salt concentration, and in the presence or absence of organic phosphate, than do rHb WM, rHb AE, and Hb A. Titrations for the O2 affinity of these mutant rHbs as a function of chloride concentration indicate a lower heterotopic effect of this anion due to the replacement of β/δ101Gln in rHb WM. The alkaline Bohr effect of rHb WM and its mutants is reduced by 20-50% compared to that of Hb A and is independent of changes in temperature, in contrast to what has been observed in the hemoglobins of most mammalian species, including human. The results of our study on the temperature dependence of the O2 affinity of rHb WM and its mutant rHbs illustrate the important role of β/δ101Gln in regulating the functional properties of these hemoglobins.

  4. Role of β/δ101Gln in regulating the effect of temperature and allosteric effectors on oxygen affinity in woolly mammoth hemoglobin.

    PubMed

    Yuan, Yue; Byrd, Catherine; Shen, Tong-Jian; Simplaceanu, Virgil; Tam, Tsuey Chyi S; Ho, Chien

    2013-12-10

    The oxygen affinity of woolly mammoth hemoglobin (rHb WM) is less affected by temperature change than that of Asian elephant hemoglobin (rHb AE) or human normal adult hemoglobin (Hb A). We report here a biochemical-biophysical study of Hb A, rHb AE, rHb WM, and three rHb WM mutants with amino acid substitutions at β/δ101 (β/δ101Gln→Glu, Lys, or Asp) plus a double and a triple mutant, designed to clarify the role of the β/δ101 residue. The β/δ101Gln residue is important for responding to allosteric effectors, such as phosphate, inositol hexaphosphate (IHP), and chloride. The rHb WM mutants studied generally have higher affinity for oxygen under various conditions of pH, temperature, and salt concentration, and in the presence or absence of organic phosphate, than do rHb WM, rHb AE, and Hb A. Titrations for the O2 affinity of these mutant rHbs as a function of chloride concentration indicate a lower heterotopic effect of this anion due to the replacement of β/δ101Gln in rHb WM. The alkaline Bohr effect of rHb WM and its mutants is reduced by 20-50% compared to that of Hb A and is independent of changes in temperature, in contrast to what has been observed in the hemoglobins of most mammalian species, including human. The results of our study on the temperature dependence of the O2 affinity of rHb WM and its mutant rHbs illustrate the important role of β/δ101Gln in regulating the functional properties of these hemoglobins. PMID:24228693

  5. Functional and biochemical properties of the hemoglobins of the burrowing brittle star Hemipholis elongata say (Echinodermata, Ophiuroidea).

    PubMed

    Christensen, Ana Beardsley; Colacino, James M; Bonaventura, Celia

    2003-08-01

    The burrowing brittle star Hemipholis elongata (Say) possesses hemoglobin-containing coelomocytes (RBCs) in its water vascular system. The RBCs, which circulate between the arms and body, are thought to play a role in oxygen transport. The hemoglobin of adult animals has a moderate affinity for oxygen (P(50) = 11.4 mm Hg at pH 8, 20 degrees C, measured in cellulo) and exhibits cooperativity (Hill coefficient > 1.7). The hemoglobin of juveniles has a higher affinity (P(50) = 2.3 mmHg at pH 8.0, 20 degrees C) and also exhibits cooperativity. The oxygen-binding properties of the hemoglobin are relatively insensitive to pH, temperature, and hydrogen sulfide. Adult hemoglobin is a heterogeneous mixture composed of three major fractions. The combined results of electrospray mass spectrometry and oxygen-binding experiments performed on purified fractions indicate that the native hemoglobin is in the form of homopolymers. A partial amino acid sequence (about 40 amino acids) of adult hemoglobin reveals little homology with holothurian hemoglobins.

  6. Newborn human skin fibroblasts senesce in vitro without acquiring adult growth factor requirements

    SciTech Connect

    Wharton, W.

    1984-01-01

    Cultures of human fibroblasts were prepared from chest skin obtained either from newborns (less than 3 months old) or adults (more than 35 years old) and maintained in vitro until they senesced. Adult cells grew logarithmically in medium supplemented with whole blood serum but not with platelet-poor plasma. Early passage cells obtained from newborns grew equally well in either plasma- or serum-supplemented medium. The difference in growth factor requirements between adult and newborn cells persisted through the lifespan of the cells; i.e., newborn cells did not develop adult hormonal requirements when maintained in culture. Thus, in vitro cellular aging can be distinguished from some types of differentiation.

  7. 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.

  8. Induction of fetal hemoglobin through enhanced translation efficiency of γ-globin mRNA.

    PubMed

    Hahn, Cynthia K; Lowrey, Christopher H

    2014-10-23

    Fetal hemoglobin (HbF) induction can ameliorate the clinical severity of sickle cell disease and β-thalassemia. We previously reported that activation of the eukaryotic initiation factor 2α (eIF2α) stress pathway increased HbF through a posttranscriptional mechanism. In this study, we explored the underlying means by which salubrinal, an activator of eIF2α signaling, enhances HbF production in primary human erythroid cells. Initial experiments eliminated changes in globin messenger RNA (mRNA) stability or cellular location and reduction of adult hemoglobin as possible salubrinal mechanisms. We then determined that salubrinal selectively increased the number of actively translating ribosomes on γ-globin mRNA. This enhanced translation efficiency occurred in the recovery phase of the stress response as phosphorylation of eIF2α and global protein synthesis returned toward baseline. These findings highlight γ-globin mRNA translation as a novel mechanism for regulating HbF production and as a pharmacologic target for induction of HbF. PMID:25170120

  9. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention. PMID:26194112

  10. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention.

  11. The Human Function Compunction: Teleological Explanation in Adults

    ERIC Educational Resources Information Center

    Kelemen, Deborah; Rosset, Evelyn

    2009-01-01

    Research has found that children possess a broad bias in favor of teleological--or purpose-based--explanations of natural phenomena. The current two experiments explored whether adults implicitly possess a similar bias. In Study 1, undergraduates judged a series of statements as "good" (i.e., correct) or "bad" (i.e., incorrect) explanations for…

  12. 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 ...

  13. 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 ...

  14. 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

  15. 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.

  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. Teaching Adults with Learning Disabilities. Professional Practices in Adult Education and Human Resource Development Series.

    ERIC Educational Resources Information Center

    Jordan, Dale R.

    This book is designed to show teachers how to reach out to adults and adolescents with learning disabilities and employ specific strategies for helping them to compensate for the disabilities and acquire literacy skills. The ways in which specific differences in brain structure inhibit the mastery of reading, spelling, handwriting, phonics, and…

  19. 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).

  20. 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.

  1. 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.

  2. A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.

    PubMed

    Pastores, Gregory M; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Szer, Jeffrey; Deegan, Patrick B; Amato, Dominick J; Mengel, Eugen; Tan, Ee Shien; Chertkoff, Raul; Brill-Almon, Einat; Zimran, Ari

    2014-12-01

    Taliglucerase alfa is a β-glucosidase enzyme replacement therapy (ERT) approved in the US and other countries for the treatment of Gaucher disease (GD) in adults and is approved in pediatric and adult patients in Australia and Canada. It is the first approved plant cell-expressed recombinant human protein. A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years. Patients with stable disease were offered taliglucerase alfa treatment using the same dose (9-60U/kg body weight) and regimen of administration (every 2weeks) as imiglucerase. This report summarizes results from 26 adult and 5 pediatric patients who participated in the trial. Disease parameters (spleen and liver volumes, hemoglobin concentration, platelet count, and biomarker levels) remained stable through 9months of treatment in adults and children following the switch from imiglucerase. All treatment-related adverse events were mild or moderate in severity and transient in nature. Exploratory parameters of linear growth and development showed positive outcomes in pediatric patients. These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase. This trial was registered at www.clinicaltrials.gov as # NCT00712348. PMID:24950666

  3. A Phase 3, multicenter, open-label, switchover trial to assess the safety and efficacy of taliglucerase alfa, a plant cell-expressed recombinant human glucocerebrosidase, in adult and pediatric patients with Gaucher disease previously treated with imiglucerase.

    PubMed

    Pastores, Gregory M; Petakov, Milan; Giraldo, Pilar; Rosenbaum, Hanna; Szer, Jeffrey; Deegan, Patrick B; Amato, Dominick J; Mengel, Eugen; Tan, Ee Shien; Chertkoff, Raul; Brill-Almon, Einat; Zimran, Ari

    2014-12-01

    Taliglucerase alfa is a β-glucosidase enzyme replacement therapy (ERT) approved in the US and other countries for the treatment of Gaucher disease (GD) in adults and is approved in pediatric and adult patients in Australia and Canada. It is the first approved plant cell-expressed recombinant human protein. A Phase 3, multicenter, open-label, 9-month study assessed safety and efficacy of switching to taliglucerase alfa in adult and pediatric patients with GD treated with imiglucerase for at least the previous 2years. Patients with stable disease were offered taliglucerase alfa treatment using the same dose (9-60U/kg body weight) and regimen of administration (every 2weeks) as imiglucerase. This report summarizes results from 26 adult and 5 pediatric patients who participated in the trial. Disease parameters (spleen and liver volumes, hemoglobin concentration, platelet count, and biomarker levels) remained stable through 9months of treatment in adults and children following the switch from imiglucerase. All treatment-related adverse events were mild or moderate in severity and transient in nature. Exploratory parameters of linear growth and development showed positive outcomes in pediatric patients. These findings provide evidence of the efficacy and safety profile of taliglucerase alfa as an ERT for GD in patients previously treated with imiglucerase. This trial was registered at www.clinicaltrials.gov as # NCT00712348.

  4. The human function compunction: teleological explanation in adults.

    PubMed

    Kelemen, Deborah; Rosset, Evelyn

    2009-04-01

    Research has found that children possess a broad bias in favor of teleological--or purpose-based--explanations of natural phenomena. The current two experiments explored whether adults implicitly possess a similar bias. In Study 1, undergraduates judged a series of statements as "good" (i.e., correct) or "bad" (i.e., incorrect) explanations for why different phenomena occur. Judgments occurred in one of three conditions: fast speeded, moderately speeded, or unspeeded. Participants in speeded conditions judged significantly more scientifically unwarranted teleological explanations as correct (e.g., "the sun radiates heat because warmth nurtures life"), but were not more error-prone on control items (e.g., unwarranted physical explanations such as "hills form because floodwater freezes"). Study 2 extended these findings by examining the relationship between different aspects of adults' "promiscuous teleology" and other variables such as scientific knowledge, religious beliefs, and inhibitory control. Implications of these findings for scientific literacy are discussed. PMID:19200537

  5. 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

  6. 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.

  7. The PRE-Derived NMR Model of the 38.8-kDa Tri-Domain IsdH Protein from Staphylococcus aureus Suggests That It Adaptively Recognizes Human Hemoglobin.

    PubMed

    Sjodt, Megan; Macdonald, Ramsay; Spirig, Thomas; Chan, Albert H; Dickson, Claire F; Fabian, Marian; Olson, John S; Gell, David A; Clubb, Robert T

    2016-03-27

    Staphylococcus aureus is a medically important bacterial pathogen that, during infections, acquires iron from human hemoglobin (Hb). It uses two closely related iron-regulated surface determinant (Isd) proteins to capture and extract the oxidized form of heme (hemin) from Hb, IsdH and IsdB. Both receptors rapidly extract hemin using a conserved tri-domain unit consisting of two NEAT (near iron transporter) domains connected by a helical linker domain. To gain insight into the mechanism of extraction, we used NMR to investigate the structure and dynamics of the 38.8-kDa tri-domain IsdH protein (IsdH(N2N3), A326-D660 with a Y642A mutation that prevents hemin binding). The structure was modeled using long-range paramagnetic relaxation enhancement (PRE) distance restraints, dihedral angle, small-angle X-ray scattering, residual dipolar coupling and inter-domain NOE nuclear Overhauser effect data. The receptor adopts an extended conformation wherein the linker and N3 domains pack against each other via a hydrophobic interface. In contrast, the N2 domain contacts the linker domain via a hydrophilic interface and, based on NMR relaxation data, undergoes inter-domain motions enabling it to reorient with respect to the body of the protein. Ensemble calculations were used to estimate the range of N2 domain positions compatible with the PRE data. A comparison of the Hb-free and Hb-bound forms reveals that Hb binding alters the positioning of the N2 domain. We propose that binding occurs through a combination of conformational selection and induced-fit mechanisms that may promote hemin release from Hb by altering the position of its F helix.

  8. 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.

  9. The Adult Learning Disabled Employee: The Organization's Hidden Human Resource.

    ERIC Educational Resources Information Center

    Macomber, Janet A.

    This paper describes an experiment with background material designed to promote problem (learning disabled) employees as human resources rather than rejects. The material is presented in the form of the transcript of a fictional advisory committee meeting attended by the human resources manager, assistant corporate counsel, training director, line…

  10. Adult Education and Human Capital: Leadership from the Fortune 500.

    ERIC Educational Resources Information Center

    Palmer, Teresa M.

    1992-01-01

    A survey of 333 Fortune 500 firms received 81 replies indicating that (1) two-thirds formally recognized the value of human resources; (2) most had changed corporate policy regarding human capital; and (3) most training was provided in the ares of new employee orientation, current job needs, customer relations, personal development, and…

  11. Alternative Sources of Adult Stem Cells: Human Amniotic Membrane

    NASA Astrophysics Data System (ADS)

    Wolbank, Susanne; van Griensven, Martijn; Grillari-Voglauer, Regina; Peterbauer-Scherb, Anja

    Human amniotic membrane is a highly promising cell source for tissue engineering. The cells thereof, human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC), may be immunoprivileged, they represent an early developmental status, and their application is ethically uncontroversial. Cell banking strategies may use freshly isolated cells or involve in vitro expansion to increase cell numbers. Therefore, we have thoroughly characterized the effect of in vitro cultivation on both phenotype and differentiation potential of hAEC. Moreover, we present different strategies to improve expansion including replacement of animal-derived supplements by human platelet products or the introduction of the catalytic subunit of human telomerase to extend the in vitro lifespan of amniotic cells. Characterization of the resulting cultures includes phenotype, growth characteristics, and differentiation potential, as well as immunogenic and immunomodulatory properties.

  12. 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.

  13. Nasopharyngeal carriage of Streptococcus pneumoniae in adults infected with human immunodeficiency virus in Jakarta, Indonesia.

    PubMed

    Harimurti, Kuntjoro; Saldi, Siti R F; Dewiasty, Esthika; Khoeri, Miftahuddin M; Yunihastuti, Evi; Putri, Tiara; Tafroji, Wisnu; Safari, Dodi

    2016-01-01

    This study investigated the distribution of serotype and antimicrobial susceptibility of Streptococcus pneumoniae carried by adults infected with human immunodeficiency virus (HIV) in Jakarta, Indonesia. Specimens of nasopharyngeal swab were collected from 200 HIV infected adults aged 21 to 63 years. Identification of S. pneumoniae was done by optochin susceptibility test and PCR for the presence of psaA and lytA genes. Serotyping was performed with sequential multiplex PCR and antibiotic susceptibility with the disk diffusion method. S. pneumoniae strains were carried by 10% adults with serotype 6A/B 20% was common serotype among cultured strains in 20 adults. Most of isolates were susceptible to chloramphenicol (80%) followed by clindamycin (75%), erythromycin (75%), penicillin (55%), and tetracycline (50%). This study found resistance to sulphamethoxazole/trimethoprim was most common with only 15% of strains being susceptible. High non-susceptibility to sulphamethoxazole/trimethoprim was observed in S. pneumoniae strains carried by HIV infected adults in Jakarta, Indonesia.

  14. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    PubMed Central

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and brain tumors. PMID:27375363

  15. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases.

    PubMed

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors. PMID:27375363

  16. [Dietary phytoestrogen and its potential benefits in adult human health].

    PubMed

    Garrido, Argelia; de la Maza, María Pía; Valladares, Luis

    2003-11-01

    Human diet contains a series of bioactive vegetal compounds that can improve human health. Among these, there has been a special interest for phytoestrogens. This article reviews the evidence about the potential benefits of phytoestrogens for human health. Forty eight manuscripts were selected for their study design and relevance to human health. The cell growth inhibitory effects of phytoestrogens and their implication in breast cancer are reviewed. Also the effects of these compounds on serum lipid levels and the effectiveness of a phytoestrogen derivate, ipriflavone, on the prevention of osteoporosis are analyzed. Although these compounds have a great potential for improving health, there is still not enough evidence to recommend the routine use of phytoestrogens.

  17. Cold Preservation of Human Adult Hepatocytes for Liver Cell Therapy.

    PubMed

    Duret, Cedric; Moreno, Daniel; Balasiddaiah, Anangi; Roux, Solene; Briolotti, Phillipe; Raulet, Edith; Herrero, Astrid; Ramet, Helene; Biron-Andreani, Christine; Gerbal-Chaloin, Sabine; Ramos, Jeanne; Navarro, Francis; Hardwigsen, Jean; Maurel, Patrick; Aldabe, Rafael; Daujat-Chavanieu, Martine

    2015-01-01

    Hepatocyte transplantation is a promising alternative therapy for the treatment of hepatic failure, hepatocellular deficiency, and genetic metabolic disorders. Hypothermic preservation of isolated human hepatocytes is potentially a simple and convenient strategy to provide on-demand hepatocytes in sufficient quantity and of the quality required for biotherapy. In this study, first we assessed how cold storage in three clinically safe preservative solutions (UW, HTS-FRS, and IGL-1) affects the viability and in vitro functionality of human hepatocytes. Then we evaluated whether such cold-preserved human hepatocytes could engraft and repopulate damaged livers in a mouse model of liver failure. Human hepatocytes showed comparable viabilities after cold preservation in the three solutions. The ability of fresh and cold-stored hepatocytes to attach to a collagen substratum and to synthesize and secrete albumin, coagulation factor VII, and urea in the medium after 3 days in culture was also equally preserved. Cold-stored hepatocytes were then transplanted in the spleen of immunodeficient mice previously infected with adenoviruses containing a thymidine kinase construct and treated with a single dose of ganciclovir to induce liver injury. Engraftment and liver repopulation were monitored over time by measuring the blood level of human albumin and by assessing the expression of specific human hepatic mRNAs and proteins in the recipient livers by RT-PCR and immunohistochemistry, respectively. Our findings show that cold-stored human hepatocytes in IGL-1 and HTS-FRS preservative solutions can survive, engraft, and proliferate in a damaged mouse liver. These results demonstrate the usefulness of human hepatocyte hypothermic preservation for cell transplantation. PMID:25622096

  18. A century of trends in adult human height.

    PubMed

    2016-07-26

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

  19. A century of trends in adult human height

    PubMed Central

    2016-01-01

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5–22.7) and 16.5 cm (13.3–19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8–144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. DOI: http://dx.doi.org/10.7554/eLife.13410.001 PMID:27458798

  20. Resident aerobic microbiota of the adult human nasal cavity.

    PubMed

    Rasmussen, T T; Kirkeby, L P; Poulsen, K; Reinholdt, J; Kilian, M

    2000-10-01

    Recent evidence strongly suggests that the microbiota of the nasal cavity plays a crucial role in determining the reaction patterns of the mucosal and systemic immune system. However, little is known about the normal microbiota of the nasal cavity. The purpose of this study was to determine the microbiota in different parts of the nasal cavity and to develop and evaluate methods for this purpose. Samples were collected from 10 healthy adults by nasal washes and by swabbing of the mucosa through a sterile introduction device. Both methods gave results that were quantitatively and qualitatively reproducible, and revealed significant differences in the density of the nasal microbiota between individuals. The study revealed absence of gram-negative bacteria that are regular members of the commensal microbiota of the pharynx. Likewise, viridans type streptococci were sparsely represented. The nasal microbiota was dominated by species of the genera Corynebacterium, Aureobacterium, Rhodococcus, and Staphylococcus, including S. epidermis, S. capitis, S. hominis, S. haemolyticus, S. lugdunensis and S. warneri. These studies show that the microbiota of the nasal cavity of adults is strikingly different from that of the pharynx, and that the nasal cavity is a primary habitat for several species of diphtheroids recognized as opportunistic pathogens. Under special circumstances, single species, including IgA1 protease-producing bacteria, may become predominant in a restricted area of the nasal mucosa. PMID:11200821

  1. A century of trends in adult human height.

    PubMed

    2016-01-01

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries. PMID:27458798

  2. 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

  3. Hesperetin induces melanin production in adult human epidermal melanocytes.

    PubMed

    Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban

    2015-06-01

    One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p < 0.01) and 1.1-fold (p < 0.01), respectively, and the corresponding increases in the case of 50 µM HSP were 1.9-fold (p < 0.001) and 1.3-fold (p < 0.001). Therefore, HSP could be considered a valuable photoprotective substance if its capacity to increase melanin production in human melanocyte cultures could be reproduced on human skin.

  4. 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.…

  5. 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

  6. The landscape of genomic imprinting across diverse adult human tissues

    PubMed Central

    Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K.; Rivas, Manuel A.; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S.; Kukurba, Kim R.; Zhang, Rui; Eng, Celeste; Torgerson, Dara G.; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R.; Burchard, Esteban G.; Seibold, Max A.; MacArthur, Daniel G.; Montgomery, Stephen B.; Zaitlen, Noah A.; Lappalainen, Tuuli

    2015-01-01

    Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. PMID:25953952

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  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. 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).

  14. Testosterone affects language areas of the adult human brain

    PubMed Central

    Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  15. 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

  16. Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Older Adults.

    PubMed

    Scott, Jake; Goetz, Matthew Bidwell

    2016-08-01

    Improved survival with combination antiretroviral therapy has led to a dramatic increase in the number of human immunodeficiency virus (HIV)-infected individuals 50 years of age or older such that by 2020 more than 50% of HIV-infected persons in the United States will be above this age. Recent studies confirm that antiretroviral therapy should be offered to all HIV-infected patients regardless of age, symptoms, CD4+ cell count, or HIV viral load. However, when compared with HIV-uninfected populations, even with suppression of measurable HIV replication, older individuals are at greater risk for cardiovascular disease, malignancies, liver disease, and other comorbidities.

  17. 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.

  18. Adult human adipose tissue contains several types of multipotent cells.

    PubMed

    Tallone, Tiziano; Realini, Claudio; Böhmler, Andreas; Kornfeld, Christopher; Vassalli, Giuseppe; Moccetti, Tiziano; Bardelli, Silvana; Soldati, Gianni

    2011-04-01

    Multipotent mesenchymal stromal cells (MSCs) are a type of adult stem cells that can be easily isolated from various tissues and expanded in vitro. Many reports on their pluripotency and possible clinical applications have raised hopes and interest in MSCs. In an attempt to unify the terminology and the criteria to label a cell as MSC, in 2006 the International Society for Cellular Therapy (ISCT) proposed a standard set of rules to define the identity of these cells. However, MSCs are still extracted from different tissues, by diverse isolation protocols, are cultured and expanded in different media and conditions. All these variables may have profound effects on the selection of cell types and the composition of heterogeneous subpopulations, on the selective expansion of specific cell populations with totally different potentials and ergo, on the long-term fate of the cells upon in vitro culture. Therefore, specific molecular and cellular markers that identify MSCs subsets as well as standardization of expansion protocols for these cells are urgently needed. Here, we briefly discuss new useful markers and recent data supporting the rapidly emerging concept that many different types of progenitor cells are found in close association with blood vessels. This knowledge may promote the necessary technical improvements required to reduce variability and promote higher efficacy and safety when isolating and expanding these cells for therapeutic use. In the light of the discussed data, particularly the identification of new markers, and advances in the understanding of fundamental MSC biology, we also suggest a revision of the 2006 ISCT criteria.

  19. Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells

    PubMed Central

    Panula, Sarita; Medrano, Jose V.; Kee, Kehkooi; Bergström, Rosita; Nguyen, Ha Nam; Byers, Blake; Wilson, Kitchener D.; Wu, Joseph C.; Simon, Carlos; Hovatta, Outi; Reijo Pera, Renee A.

    2011-01-01

    Historically, our understanding of molecular genetic aspects of human germ cell development has been limited, at least in part due to inaccessibility of early stages of human development to experimentation. However, the derivation of pluripotent stem cells may provide the necessary human genetic system to study germ cell development. In this study, we compared the potential of human induced pluripotent stem cells (iPSCs), derived from adult and fetal somatic cells to form primordial and meiotic germ cells, relative to human embryonic stem cells. We found that ∼5% of human iPSCs differentiated to primordial germ cells (PGCs) following induction with bone morphogenetic proteins. Furthermore, we observed that PGCs expressed green fluorescent protein from a germ cell-specific reporter and were enriched for the expression of endogenous germ cell-specific proteins and mRNAs. In response to the overexpression of intrinsic regulators, we also observed that iPSCs formed meiotic cells with extensive synaptonemal complexes and post-meiotic haploid cells with a similar pattern of ACROSIN staining as observed in human spermatids. These results indicate that human iPSCs derived from reprogramming of adult somatic cells can form germline cells. This system may provide a useful model for molecular genetic studies of human germline formation and pathology and a novel platform for clinical studies and potential therapeutical applications. PMID:21131292

  20. Hemoglobin Concentration and Cognitive Impairment in the Renal REasons for Geographic And Racial Differences in Stroke (REGARDS) Study

    PubMed Central

    Wadley, Virginia G.; Newsome, Britt B.; Zakai, Neil A.; McClure, Leslie A.; Howard, George; Warnock, David G.; McClellan, William

    2010-01-01

    Background. There is growing interest in determining the degree of anemia, which is clinically significant. The goal of this study was to determine the association between hemoglobin concentration and cognitive impairment in a large sample of U.S. adults. Methods. We used cross-sectional data from 19,701 adults participating in the REasons for Geographic And Racial Differences in Stroke study. Cognitive impairment was defined as a score of 4 or less on the six-item screener. Hemoglobin was analyzed in 1 g/dL increments relative to the World Health Organization (WHO) threshold (<13 g/dL for men and <12 g/dL for women). Results. The mean hemoglobin concentration was 13.7 ± 1.5 g/dL. The prevalence of cognitive impairment increased from 4.3% among individuals with a hemoglobin >3 g/dL above the WHO threshold to 16.8% for those with a hemoglobin ≥2 g/dL below the WHO threshold. After adjustment for demographics, chronic health conditions, health status, and inflammation, the association between reduced hemoglobin and cognitive impairment was attenuated and no longer significant, including among those with hemoglobin ≥2 g/dL below the WHO threshold (odds ratio 1.39, 95% confidence interval = 0.94–2.04). A test for linear trend was of borderline significance (p value = .06). For 94% of the sample within 2 g/dL of the WHO threshold, there was no relationship between hemoglobin concentration and the odds of cognitive impairment. The associations did not differ by sex and race. Conclusions. Within a large sample of community-dwelling adults, there was no significant association between hemoglobin concentration and cognitive impairment after multivariable adjustment. PMID:20634281

  1. Treatment of Human-Caused Trauma: Attrition in the Adult Outcomes Research

    ERIC Educational Resources Information Center

    Matthieu, Monica; Ivanoff, Andre

    2006-01-01

    Attrition or dropout is the failure of a participant to complete, comply, or the prematurely discontinuation or discharge from treatment, resulting in lost data and affecting outcomes. This review of 10 years of adult posttraumatic stress disorder (PTSD) treatment outcome literature specific to Criterion A events of human origin examines how…

  2. Adult attachment style is associated with cerebral μ-opioid receptor availability in humans.

    PubMed

    Nummenmaa, Lauri; Manninen, Sandra; Tuominen, Lauri; Hirvonen, Jussi; Kalliokoski, Kari K; Nuutila, Pirjo; Jääskeläinen, Iiro P; Hari, Riitta; Dunbar, Robin I M; Sams, Mikko

    2015-09-01

    Human attachment behavior mediates establishment and maintenance of social relationships. Adult attachment characteristically varies on anxiety and avoidance dimensions, reflecting the tendencies to worry about the partner breaking the social bond (anxiety) and feeling uncomfortable about depending on others (avoidance). In primates and other mammals, the endogenous μ-opioid system is linked to long-term social bonding, but evidence of its role in human adult attachment remains more limited. We used in vivo positron emission tomography to reveal how variability in μ-opioid receptor (MOR) availability is associated with adult attachment in humans. We scanned 49 healthy subjects using a MOR-specific ligand [(11) C]carfentanil and measured their attachment avoidance and anxiety with the Experiences in Close Relationships-Revised scale. The avoidance dimension of attachment correlated negatively with MOR availability in the thalamus and anterior cingulate cortex, as well as the frontal cortex, amygdala, and insula. No associations were observed between MOR availability and the anxiety dimension of attachment. Our results suggest that the endogenous opioid system may underlie interindividual differences in avoidant attachment style in human adults, and that differences in MOR availability are associated with the individuals' social relationships and psychosocial well-being. PMID:26046928

  3. Perspectives on Adult Education, Human Resource Development, and the Emergence of Workforce Development

    ERIC Educational Resources Information Center

    Jacobs, Ronald L.

    2014-01-01

    This article presents a perspective on the relationship between adult education and human resource development of the past two decades and the subsequent emergence of workforce development. The lesson taken from the article should be more than simply a recounting of events related to these fields of study. Instead, the more general lesson may be…

  4. Concept Maps: Practice Applications in Adult Education and Human Resource Development

    ERIC Educational Resources Information Center

    Daley, Barbara J.

    2010-01-01

    Concept maps can be used as both a cognitive and constructivist learning strategy in teaching and learning in adult education and human resource development. The maps can be used to understand course readings, analyze case studies, develop reflective thinking and enhance research skills. The creation of concept maps can also be supported by the…

  5. Emotions and Human Concern: Adult Education and the Philosophical Thought of Martha Nussbaum

    ERIC Educational Resources Information Center

    Plumb, Donovan

    2014-01-01

    This article argues that philosopher Martha Nussbaum's reflections on the role of the emotions in human flourishing can contribute in important ways to our understanding of the emotions in adult education contexts. The article summarises Nussbaum's exploration of the contributions of classical philosophers like Socrates, Aristotle, and…

  6. Evaluation of Serum Creatinine Changes With Integrase Inhibitor Use in Human Immunodeficiency Virus-1 Infected Adults

    PubMed Central

    Lindeman, Tara A.; Duggan, Joan M.; Sahloff, Eric G.

    2016-01-01

    This retrospective chart review evaluated changes in serum creatinine and creatinine clearance (CrCl) after initiation of an integrase inhibitor (INSTI)-based regimen as initial treatment in human immunodeficiency virus-infected adults. Serum creatinine and CrCl changes were similar to those seen in clinical trials for INSTIs. No renal-related serious adverse events or discontinuations occurred. PMID:27092314

  7. NIRS Measurement of Venous Oxygen Saturation in the Adult Human Head

    NASA Astrophysics Data System (ADS)

    Brown, Derek W.; Haensse, Daniel; Bauschatz, Andrea; Wolf, Martin

    Provided that both the breathing frequency remains constant and that the temporal resolution of the instrument is sufficiently high, NIRS spiroximetry enables measurement of cerebral SvO2 in healthy human adults. Furthermore, simultaneous measurements of StO2, SaO2, and SvO2 enable calculation of both OEF and the compartmental distribution of cerebral blood volume.

  8. Equality and Human Capital: Conflicting Concepts within State-Funded Adult Education in Ireland

    ERIC Educational Resources Information Center

    Hurley, Kevin

    2015-01-01

    This article offers a critique of the concept of equality as it informs the White Paper on Adult Education: Learning for Life (2000). It also outlines the extent to which human capital theory can be seen to have effectively colonised lifelong learning from the outset of its adoption by the European Union with highly constraining implications for…

  9. Severe Infections with Human Adenovirus 7d in 2 Adults in Family, Illinois, USA, 2014

    PubMed Central

    Ison, Michael G.

    2016-01-01

    Human adenovirus 7d, a genomic variant with no reported circulation in the United States, was isolated from 2 adults with severe respiratory infections in Illinois. Molecular typing identified a close relationship with strains of the same genome type isolated from cases of respiratory disease in several provinces of China since 2009. PMID:26982199

  10. Bridging the Gap between Human Resource Development and Adult Education: Part One, Assumptions, Definitions, and Critiques

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2006-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995).…

  11. Bridging the Gap between Human Resource Development and Adult Education: Part Two, the Critical Turn

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2006-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995). The…

  12. An Assessemnt of Graduate Adult Education and Human Resource Development Programs: A U.S. Perspective

    ERIC Educational Resources Information Center

    Akdere, Mesut; Conceicao, Simone C. O.

    2009-01-01

    Due to recent changes in the workplace, the workforce and higher education have driven academic programs of adult education (AE) and human resource development (HRD) in the U.S. to become more integrated as part of the mission of institutions of higher education. In this exploratory study, existing graduate programs in AE and HRD in the U.S. were…

  13. Bridging the Gap between Human Resource Development and Adult Education: Part Two, the Critical Turn

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2014-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995). The…

  14. Bridging the Gap between Human Resource Development and Adult Education: Part One, Assumptions, Definitions, and Critiques

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2013-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995).…

  15. A Brief Review on the Use of Functional Near-Infrared Spectroscopy (fNIRS) for Language Imaging Studies in Human Newborns and Adults

    ERIC Educational Resources Information Center

    Quaresima, Valentina; Bisconti, Silvia; Ferrari, Marco

    2012-01-01

    Upon stimulation, real time maps of cortical hemodynamic responses can be obtained by non-invasive functional near-infrared spectroscopy (fNIRS) which measures changes in oxygenated and deoxygenated hemoglobin after positioning multiple sources and detectors over the human scalp. The current commercially available transportable fNIRS systems have…

  16. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  17. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  18. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated...

  19. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated...

  20. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  1. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  2. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  3. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  4. Self-Control and Impulsiveness in Nondieting Adult Human Females: Effects of Visual Food Cues and Food Deprivation

    ERIC Educational Resources Information Center

    Forzano, Lori-Ann B.; Chelonis, John J.; Casey, Caitlin; Forward, Marion; Stachowiak, Jacqueline A.; Wood, Jennifer

    2010-01-01

    Self-control can be defined as the choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer, and impulsiveness as the opposite. Previous research suggests that exposure to visual food cues affects adult humans' self-control. Previous research also suggests that food deprivation decreases adult humans' self-control. The…

  5. Predictions of ozone absorption in human lungs from newborn to adult

    SciTech Connect

    Overton, J.H.; Graham, R.C.

    1989-01-01

    Dosimetry models for gases mainly have been used to predict absorption in adult humans and laboratory animals. The lack of lower respiratory tract (LRT) lung models for children has discouraged the application of theoretical gaseous dosimetry to this important sub-population. To fill this gap the authors have used several sources of data on age dependent LRT volumes, age dependent airway dimensions, a model of an adult tracheobronchial region, and a model of the adult acinus to construct theoretical LRT lung models for humans from birth to adult. An ozone (O{sub 3}) dosimetry model was then used to estimate the regional and local uptake of O{sub 3} in the (theoretical) LRTs of children and adults. For sedentary breathing, the LRT distribution of absorbed O{sub 3}, the percent uptake (76 to 85%), and the centriacinar O{sub 3} tissue dose are not very sensitive to age. For maximal work during exercise, predicted uptakes range from 83 to 91%, and the regional percent uptakes are more dependent on age than during quiet breathing. In general, total O{sub 3} absorption per minute increases with age. Regardless of age and state of breathing, the largest tissue dose of O{sub 3} is predicted to occur in the centriacinar region, where many animal studies show the maximal morphological damage due to O{sub 3}.

  6. Larval food quantity affects the capacity of adult mosquitoes to transmit human malaria

    PubMed Central

    Shapiro, Lillian L. M.; Murdock, Courtney C.; Jacobs, Gregory R.; Thomas, Rachel J.; Thomas, Matthew B.

    2016-01-01

    Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites. However, the ecology of larval insects that vector disease remains poorly understood. Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria. We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet. Emerging adult females were then provided an infectious blood meal. We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time. Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious. Together, these effects increased transmission potential of mosquitoes in the high food regime by 260–330%. Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics. PMID:27412284

  7. The mechanical properties of human ribs in young adult.

    PubMed

    Pezowicz, Celina; Głowacki, Maciej

    2012-01-01

    A good understanding of thoracic biomechanics is important for complete examination and control of chest behaviour under conditions of physiological and pathological work, and under the impact of external forces leading to traumatic loading of the chest. The purpose of the study was to analyse the mechanical properties of human ribs obtained from individuals under the age of 25 with scoliosis deformation and to correlate them with geometric properties of ribs. Thirty three fragments of ribs (9th to 12th) were tested in three-point bending. Rib fragments were collected intraoperatively from female patients treated for scoliosis in the thoracic, thoracolumbar, and lumbar spine. The results were used to determine the maximum failure force, stiffness, and Young's modulus. A significant relationship was found between the age and elastic modulus of the ribs. The analysis was carried out for two age groups, i.e., between the ages of 10 and 15 and between the ages of 16 and 22, and statistically significant differences were obtained for Young's modulus (p = 0.0001) amounting to, respectively, 2.79 ± 1.34 GPa for the first group and 7.44 ± 2.85 GPa for the second group. The results show a significant impact of age on the mechanical properties of ribs.

  8. A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice.

    PubMed

    Hammerschmidt, K; Schreiweis, C; Minge, C; Pääbo, S; Fischer, J; Enard, W

    2015-11-01

    The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico-striatal-dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the 'humanized' Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2(hum/hum) allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms.

  9. 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.

  10. 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 ...

  11. 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.

  12. Predictions of ozone absorption in human lungs from newborn to adult

    SciTech Connect

    Overton, J.H.; Graham, R.C. )

    1989-01-01

    Although children are an important human population, dosimetry models for gases have been used to predict absorption mainly in laboratory animals and adult humans. To correct this omission, we have used several sources of data on age-dependent lower respiratory tract (LRT) volumes, age-dependent airway dimensions, a model of the adult tracheobronchial region, and a model of the adult acinus to construct theoretical LRT lung models for humans from birth to adulthood. An ozone (O3) dosimetry model was then used to estimate the regional and local uptake of O3 in the (theoretical) LRT of children and adults. For sedentary or quiet breathing, the LRT distribution of absorbed O3, the percent uptake (84 to 88%) and the centriacinar O3 tissue dose are not very sensitive to age. For maximal work during exercise, predicted LRT uptakes range from 87 to 93%, and the regional percent uptakes are more dependent on age than during quiet breathing. In general, the total quantity of O3 absorbed per minute increases with age. Regardless of age and state of breathing, the largest tissue dose of O3 is predicted to occur in the centriacinar region, where many animal studies show the maximal morphological damage from O3.

  13. Localization of PPAR isotypes in the adult mouse and human brain

    PubMed Central

    Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B.; Mayfield, R. Dayne; Harris, R. Adron

    2016-01-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain. PMID:27283430

  14. The response of the anterior striatum during adult human vocal learning

    PubMed Central

    Leech, Robert; Iverson, Paul; Wise, Richard J. S.

    2014-01-01

    Research on mammals predicts that the anterior striatum is a central component of human motor learning. However, because vocalizations in most mammals are innate, much of the neurobiology of human vocal learning has been inferred from studies on songbirds. Essential for song learning is a pathway, the homolog of mammalian cortical-basal ganglia “loops,” which includes the avian striatum. The present functional magnetic resonance imaging (fMRI) study investigated adult human vocal learning, a skill that persists throughout life, albeit imperfectly given that late-acquired languages are spoken with an accent. Monolingual adult participants were scanned while repeating novel non-native words. After training on the pronunciation of half the words for 1 wk, participants underwent a second scan. During scanning there was no external feedback on performance. Activity declined sharply in left and right anterior striatum, both within and between scanning sessions, and this change was independent of training and performance. This indicates that adult speakers rapidly adapt to the novel articulatory movements, possibly by using motor sequences from their native speech to approximate those required for the novel speech sounds. Improved accuracy correlated only with activity in motor-sensory perisylvian cortex. We propose that future studies on vocal learning, using different behavioral and pharmacological manipulations, will provide insights into adult striatal plasticity and its potential for modification in both educational and clinical contexts. PMID:24805076

  15. Neuroscience of human social interactions and adult attachment style

    PubMed Central

    Vrtička, Pascal; Vuilleumier, Patrik

    2012-01-01

    attachment insecurity and particularly anxiety. Emotion regulation strategies such as reappraisal or suppression of social emotions are also differentially modulated by attachment style. This research does not only help better understand the neural underpinnings of human social behavior, but also provides important insights on psychopathological conditions where attachment dysregulation is likely to play an important (causal) role. PMID:22822396

  16. 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

  17. Human Centred Design Considerations for Connected Health Devices for the Older Adult

    PubMed Central

    Harte, Richard P.; Glynn, Liam G.; Broderick, Barry J.; Rodriguez-Molinero, Alejandro; Baker, Paul M. A.; McGuiness, Bernadette; O’Sullivan, Leonard; Diaz, Marta; Quinlan, Leo R.; ÓLaighin, Gearóid

    2014-01-01

    Connected health devices are generally designed for unsupervised use, by non-healthcare professionals, facilitating independent control of the individuals own healthcare. Older adults are major users of such devices and are a population significantly increasing in size. This group presents challenges due to the wide spectrum of capabilities and attitudes towards technology. The fit between capabilities of the user and demands of the device can be optimised in a process called Human Centred Design. Here we review examples of some connected health devices chosen by random selection, assess older adult known capabilities and attitudes and finally make analytical recommendations for design approaches and design specifications. PMID:25563225

  18. Acceptability, Safety, and Efficacy of Oral Administration of Extracts of Black or Red Maca (Lepidium meyenii) in Adult Human Subjects: A Randomized, Double-Blind, Placebo-Controlled Study

    PubMed Central

    Gonzales-Arimborgo, Carla; Yupanqui, Irma; Montero, Elsa; Alarcón-Yaquetto, Dulce E.; Zevallos-Concha, Alisson; Caballero, Lidia; Gasco, Manuel; Zhao, Jianping; Khan, Ikhlas A.; Gonzales, Gustavo F.

    2016-01-01

    The plant maca, grown at 4000 m altitude in the Peruvian Central Andes, contains hypocotyls that have been used as food and in traditional medicine for centuries. The aim of this research was to provide results on some health effects of oral administration of spray-dried extracts of black or red maca (Lepidium meyenii) in adult human subjects living at low (LA) and high altitude (HA). A total of 175 participants were given 3 g of either placebo, black, or red maca extract daily for 12 weeks. Primary outcomes were changes in sexual desire, mood, energy, health-related quality of life score (HRQL), and chronic mountain sickness (CMS) score, or in glycaemia, blood pressure, and hemoglobin levels. Secondary outcomes were acceptability and safety, assessed using the Likert test and side effect self-recording, respectively, and the effect of altitude. At low altitude, 32, 30, and 32 participants started the study receiving placebo, red maca, or black maca, respectively. At high altitudes, 33, 35, and 31 participants started the study receiving placebo, red maca, and black maca, respectively. Consumption of spray-dried extracts of red and black maca resulted in improvement in mood, energy, and health status, and reduced CMS score. Fatty acids and macamides were higher in spray-dried extracts of black maca than in red maca. GABA predominated in spray-dried extracts of red maca. Effects on mood, energy, and CMS score were better with red maca. Black maca and, in smaller proportions, red maca reduced hemoglobin levels only in highlanders with abnormally high hemoglobin levels; neither variety of maca reduced hemoglobin levels in lowlanders. Black maca reduced blood glucose levels. Both varieties produced similar responses in mood, and HRQL score. Maca extracts consumed at LA or HA had good acceptability and did not show serious adverse effects. In conclusion, maca extract consumption relative to the placebo improved quality of life parameters. Differences in the level of

  19. Acceptability, Safety, and Efficacy of Oral Administration of Extracts of Black or Red Maca (Lepidium meyenii) in Adult Human Subjects: A Randomized, Double-Blind, Placebo-Controlled Study.

    PubMed

    Gonzales-Arimborgo, Carla; Yupanqui, Irma; Montero, Elsa; Alarcón-Yaquetto, Dulce E; Zevallos-Concha, Alisson; Caballero, Lidia; Gasco, Manuel; Zhao, Jianping; Khan, Ikhlas A; Gonzales, Gustavo F

    2016-01-01

    The plant maca, grown at 4000 m altitude in the Peruvian Central Andes, contains hypocotyls that have been used as food and in traditional medicine for centuries. The aim of this research was to provide results on some health effects of oral administration of spray-dried extracts of black or red maca (Lepidium meyenii) in adult human subjects living at low (LA) and high altitude (HA). A total of 175 participants were given 3 g of either placebo, black, or red maca extract daily for 12 weeks. Primary outcomes were changes in sexual desire, mood, energy, health-related quality of life score (HRQL), and chronic mountain sickness (CMS) score, or in glycaemia, blood pressure, and hemoglobin levels. Secondary outcomes were acceptability and safety, assessed using the Likert test and side effect self-recording, respectively, and the effect of altitude. At low altitude, 32, 30, and 32 participants started the study receiving placebo, red maca, or black maca, respectively. At high altitudes, 33, 35, and 31 participants started the study receiving placebo, red maca, and black maca, respectively. Consumption of spray-dried extracts of red and black maca resulted in improvement in mood, energy, and health status, and reduced CMS score. Fatty acids and macamides were higher in spray-dried extracts of black maca than in red maca. GABA predominated in spray-dried extracts of red maca. Effects on mood, energy, and CMS score were better with red maca. Black maca and, in smaller proportions, red maca reduced hemoglobin levels only in highlanders with abnormally high hemoglobin levels; neither variety of maca reduced hemoglobin levels in lowlanders. Black maca reduced blood glucose levels. Both varieties produced similar responses in mood, and HRQL score. Maca extracts consumed at LA or HA had good acceptability and did not show serious adverse effects. In conclusion, maca extract consumption relative to the placebo improved quality of life parameters. Differences in the level of

  20. Acceptability, Safety, and Efficacy of Oral Administration of Extracts of Black or Red Maca (Lepidium meyenii) in Adult Human Subjects: A Randomized, Double-Blind, Placebo-Controlled Study.

    PubMed

    Gonzales-Arimborgo, Carla; Yupanqui, Irma; Montero, Elsa; Alarcón-Yaquetto, Dulce E; Zevallos-Concha, Alisson; Caballero, Lidia; Gasco, Manuel; Zhao, Jianping; Khan, Ikhlas A; Gonzales, Gustavo F

    2016-08-18

    The plant maca, grown at 4000 m altitude in the Peruvian Central Andes, contains hypocotyls that have been used as food and in traditional medicine for centuries. The aim of this research was to provide results on some health effects of oral administration of spray-dried extracts of black or red maca (Lepidium meyenii) in adult human subjects living at low (LA) and high altitude (HA). A total of 175 participants were given 3 g of either placebo, black, or red maca extract daily for 12 weeks. Primary outcomes were changes in sexual desire, mood, energy, health-related quality of life score (HRQL), and chronic mountain sickness (CMS) score, or in glycaemia, blood pressure, and hemoglobin levels. Secondary outcomes were acceptability and safety, assessed using the Likert test and side effect self-recording, respectively, and the effect of altitude. At low altitude, 32, 30, and 32 participants started the study receiving placebo, red maca, or black maca, respectively. At high altitudes, 33, 35, and 31 participants started the study receiving placebo, red maca, and black maca, respectively. Consumption of spray-dried extracts of red and black maca resulted in improvement in mood, energy, and health status, and reduced CMS score. Fatty acids and macamides were higher in spray-dried extracts of black maca than in red maca. GABA predominated in spray-dried extracts of red maca. Effects on mood, energy, and CMS score were better with red maca. Black maca and, in smaller proportions, red maca reduced hemoglobin levels only in highlanders with abnormally high hemoglobin levels; neither variety of maca reduced hemoglobin levels in lowlanders. Black maca reduced blood glucose levels. Both varieties produced similar responses in mood, and HRQL score. Maca extracts consumed at LA or HA had good acceptability and did not show serious adverse effects. In conclusion, maca extract consumption relative to the placebo improved quality of life parameters. Differences in the level of

  1. 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.

  2. 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.

  3. Osmotic and diffusive properties of intracellular water in camel erythrocytes: effect of hemoglobin crowdedness.

    PubMed

    Bogner, Peter; Miseta, Attila; Berente, Zoltan; Schwarcz, Attila; Kotek, Gyula; Repa, Imre

    2005-09-01

    Camel erythrocytes have exceptional osmotic resistance and is believed to be due to augmented water-binding associated with the high hydrophilicity of camel hemoglobin. In practical terms this means that the proportion of osmotically non-removable water in camel erythrocytes is nearly 3-fold greater than that in human erythrocytes (approximately 65 vs approximately 20%). The relationship between water diffusion and the osmotic characteristics of intracellular water is the subject of this report. The amount of osmotically inactive water is 2-fold greater in camel hemoglobin solution in vitro compared to that of human, but water diffusion does not differ in camel and human hemoglobin solutions. However, the evaluation of water diffusion by magnetic resonance measurements in camel erythrocytes revealed approximately 15% lower apparent diffusion coefficient (ADC) compared with human erythrocytes. When human erythrocytes were dehydrated to the level of camel erythrocytes, their osmotic and water diffusion properties were similar. These results show that a lower ADC is associated with a more pronounced increase in osmotically inactive water fraction. It is proposed that increased hemoglobin hydrophilicity allows not only augmented water-binding, but also a closer hemoglobin packaging in vivo, which in turn is associated with slower ADC and increased osmotic resistance. PMID:15951204

  4. Short-Term Monocular Deprivation Alters GABA in the Adult Human Visual Cortex

    PubMed Central

    Lunghi, Claudia; Emir, Uzay E.; Morrone, Maria Concetta; Bridge, Holly

    2016-01-01

    Summary Neuroplasticity is a fundamental property of the nervous system that is maximal early in life, within the critical period [1–3]. Resting GABAergic inhibition is necessary to trigger ocular dominance plasticity and to modulate the onset and offset of the critical period [4, 5]. GABAergic inhibition also plays a crucial role in neuroplasticity of adult animals: the balance between excitation and inhibition in the primary visual cortex (V1), measured at rest, modulates the susceptibility of ocular dominance to deprivation [6–10]. In adult humans, short-term monocular deprivation strongly modifies ocular balance, unexpectedly boosting the deprived eye, reflecting homeostatic plasticity [11, 12]. There is no direct evidence, however, to support resting GABAergic inhibition in homeostatic plasticity induced by visual deprivation. Here, we tested the hypothesis that GABAergic inhibition, measured at rest, is reduced by deprivation, as demonstrated by animal studies. GABA concentration in V1 of adult humans was measured using ultra-high-field 7T magnetic resonance spectroscopy before and after short-term monocular deprivation. After monocular deprivation, resting GABA concentration decreased in V1 but was unaltered in a control parietal area. Importantly, across participants, the decrease in GABA strongly correlated with the deprived eye perceptual boost measured by binocular rivalry. Furthermore, after deprivation, GABA concentration measured during monocular stimulation correlated with the deprived eye dominance. We suggest that reduction in resting GABAergic inhibition triggers homeostatic plasticity in adult human V1 after a brief period of abnormal visual experience. These results are potentially useful for developing new therapeutic strategies that could exploit the intrinsic residual plasticity of the adult human visual cortex. PMID:26004760

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. Combined reflectance spectroscopy and stochastic modeling approach for noninvasive hemoglobin determination via palpebral conjunctiva

    PubMed Central

    Kim, Oleg; McMurdy, John; Jay, Gregory; Lines, Collin; Crawford, Gregory; Alber, Mark

    2014-01-01

    Abstract A combination of stochastic photon propagation model in a multilayered human eyelid tissue and reflectance spectroscopy was used to study palpebral conjunctiva spectral reflectance for hemoglobin (Hgb) determination. The developed model is the first biologically relevant model of eyelid tissue, which was shown to provide very good approximation to the measured spectra. Tissue optical parameters were defined using previous histological and microscopy studies of a human eyelid. After calibration of the model parameters the responses of reflectance spectra to Hgb level and blood oxygenation variations were calculated. The stimulated reflectance spectra in adults with normal and low Hgb levels agreed well with experimental data for Hgb concentrations from 8.1 to 16.7 g/dL. The extracted Hgb levels were compared with in vitro Hgb measurements. The root mean square error of cross‐validation was 1.64 g/dL. The method was shown to provide 86% sensitivity estimates for clinically diagnosed anemia cases. A combination of the model with spectroscopy measurements provides a new tool for noninvasive study of human conjunctiva to aid in diagnosing blood disorders such as anemia. PMID:24744871

  17. Hemoglobin binding to A beta and HBG2 SNP association suggest a role in Alzheimer's disease.

    PubMed

    Perry, Rodney T; Gearhart, Debra A; Wiener, Howard W; Harrell, Lindy E; Barton, James C; Kutlar, Abdullah; Kutlar, Ferdane; Ozcan, Ozan; Go, Rodney C P; Hill, William D

    2008-02-01

    From a normal human brain phage display library screen we identified the gamma (A)-globin chain of fetal hemoglobin (Hb F) as a protein that bound strongly to A beta1-42. We showed the oxidized form of adult Hb (metHb A) binds with greater affinity to A beta1-42 than metHb F. MetHb is more toxic than oxyhemoglobin because it loses its heme group more readily. Free Hb and heme readily damage vascular endothelial cells similar to Alzheimer's disease (AD) vascular pathology. The XmnI polymorphism (C-->T) at -158 of the gamma (G)-globin promoter region can contribute to increased Hb F expression. Using family-based association testing, we found a significant protective association of this polymorphism in the NIMH sibling dataset (n=489) in families, with at least two affected and one unaffected sibling (p=0.006), with an age of onset >50 years (p=0.010) and >65 years (p=0.013), and families not homozygous for the APOE4 allele (p=0.041). We hypothesize that Hb F may be less toxic than adult Hb in its interaction with A beta and may protect against the development of AD.

  18. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord.

    PubMed

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-12-04

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1(HIGH) cell subpopulation described in rodents. Our results support the existence of ependymal CB1(HIGH) cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.

  19. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord

    PubMed Central

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-01-01

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1HIGH cell subpopulation described in rodents. Our results support the existence of ependymal CB1HIGH cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions. PMID:26634814

  20. Immunohistochemical Study of Expression of Sohlh1 and Sohlh2 in Normal Adult Human Tissues

    PubMed Central

    Zhang, Xiaoli; Liu, Ruihua; Su, Zhongxue; Zhang, Yuecun; Zhang, Wenfang; Liu, Xinyu; Wang, Fuwu; Guo, Yuji; Li, Chuangang; Hao, Jing

    2015-01-01

    The expression pattern of Sohlh1 (spermatogenesis and oogenesis specific basic helix-loop-helix 1) and Sohlh2 in mice has been reported in previous studies. Sohlh1 and Sohlh2 are specifically expressed in spermatogonia, prespermatogonia in male mice and oocytes of primordial and primary follicles in female mice. In this report, we studied the expression pattern of Sohlh1 and Sohlh2 in human adult tissues. Immunohistochemical staining of Sohlh1 and Sohlh2 was performed in 5 samples of normal ovaries and testes, respectively. The results revealed that Sohlh genes are not only expressed in oocytes and spermatogonia, but also in granular cells, theca cells, Sertoli cells and Leydig cells, and in smooth muscles of blood vessel walls. To further investigate the expression of Sohlh genes in other adult human tissues, we collected representative normal adult tissues developed from three embryonic germ layers. Compared with the expression in mice, Sohlhs exhibited a much more extensive expression pattern in human tissues. Sohlhs were detected in testis, ovary and epithelia developed from embryonic endoderm, ectoderm and tissues developed from embryonic mesoderm. Sohlh signals were found in spermatogonia, Sertoli cells and also Leydig cells in testis, while in ovary, the expression was mainly in oocytes of primordial and primary follicles, granular cells and theca cells of secondary follicles. Compared with Sohlh2, the expression of Sohlh1 was stronger and more extensive. Our study explored the expression of Sohlh genes in human tissues and might provide insights for functional studies of Sohlh genes. PMID:26375665

  1. 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.

  2. Evaluating the capacity to generate and preserve nitric oxide bioactivity in highly purified earthworm erythrocruorin: a giant polymeric hemoglobin with potential blood substitute properties.

    PubMed

    Roche, Camille J; Talwar, Abhinav; Palmer, Andre F; Cabrales, Pedro; Gerfen, Gary; Friedman, Joel M

    2015-01-01

    The giant extracellular hemoglobin (erythrocruorin) from the earth worm (Lumbricus terrestris) has shown promise as a potential hemoglobin-based oxygen carrier (HBOC) in in vivo animal studies. An important beneficial characteristic of this hemoglobin (LtHb) is the large number of heme-based oxygen transport sites that helps overcome issues of osmotic stress when attempting to provide enough material for efficient oxygen delivery. A potentially important additional property is the capacity of the HBOC either to generate nitric oxide (NO) or to preserve NO bioactivity to compensate for decreased levels of NO in the circulation. The present study compares the NO-generating and NO bioactivity-preserving capability of LtHb with that of human adult hemoglobin (HbA) through several reactions including the nitrite reductase, reductive nitrosylation, and still controversial nitrite anhydrase reactions. An assignment of a heme-bound dinitrogen trioxide as the stable intermediate associated with the nitrite anhydrase reaction in both LtHb and HbA is supported based on functional and EPR spectroscopic studies. The role of the redox potential as a factor contributing to the NO-generating activity of these two proteins is evaluated. The results show that LtHb undergoes the same reactions as HbA and that the reduced efficacy for these reactions for LtHb relative to HbA is consistent with the much higher redox potential of LtHb. Evidence of functional heterogeneity in LtHb is explained in terms of the large difference in the redox potential of the isolated subunits. PMID:25371199

  3. Origin of germ cells and formation of new primary follicles in adult human ovaries

    PubMed Central

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Upadhyaya, Nirmala B

    2004-01-01

    Recent reports indicate that functional mouse oocytes and sperm can be derived in vitro from somatic cell lines. We hypothesize that in adult human ovaries, mesenchymal cells in the tunica albuginea (TA) are bipotent progenitors with a commitment for both primitive granulosa and germ cells. We investigated ovaries of twelve adult women (mean age 32.8 ± 4.1 SD, range 27–38 years) by single, double, and triple color immunohistochemistry. We show that cytokeratin (CK)+ mesenchymal cells in ovarian TA differentiate into surface epithelium (SE) cells by a mesenchymal-epithelial transition. Segments of SE directly associated with ovarian cortex are overgrown by TA, forming solid epithelial cords, which fragment into small (20 micron) epithelial nests descending into the lower ovarian cortex, before assembling with zona pellucida (ZP)+ oocytes. Germ cells can originate from SE cells which cover the TA. Small (10 micron) germ-like cells showing PS1 meiotically expressed oocyte carbohydrate protein are derived from SE cells via asymmetric division. They show nuclear MAPK immunoexpression, subsequently divide symmetrically, and enter adjacent cortical vessels. During vascular transport, the putative germ cells increase to oocyte size, and are picked-up by epithelial nests associated with the vessels. During follicle formation, extensions of granulosa cells enter the oocyte cytoplasm, forming a single paranuclear CK+ Balbiani body supplying all the mitochondria of the oocyte. In the ovarian medulla, occasional vessels show an accumulation of ZP+ oocytes (25–30 microns) or their remnants, suggesting that some oocytes degenerate. In contrast to males, adult human female gonads do not preserve germline type stem cells. This study expands our previous observations on the formation of germ cells in adult human ovaries. Differentiation of primitive granulosa and germ cells from the bipotent mesenchymal cell precursors of TA in adult human ovaries represents a most

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. Self-control in adult humans: variation in positive reinforcer amount and delay.

    PubMed Central

    Logue, A W; Peña-Correal, T E; Rodriguez, M L; Kabela, E

    1986-01-01

    In five experiments, choice responding of female human adults was examined, as a function of variations in reinforcer amount and reinforcer delay. Experiment 1 used a discrete-trials procedure, and Experiments 2, 3, 4, and 5 used a concurrent variable-interval variable-interval schedule. Reinforcer amount and reinforcer delay were varied both separately and together. In contrast to results previously reported with pigeons, the subjects in the present experiments usually chose the larger reinforcers even when those reinforcers were delayed. Together, the results from all the experiments suggest that the subjects followed a maximization strategy in choosing reinforcers. Such behavior makes it easy to observe self-control and difficult to observe impulsiveness in traditional laboratory experiments that use adult human subjects. PMID:3760749

  10. 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.

  11. Monocular advantage for face perception implicates subcortical mechanisms in adult humans.

    PubMed

    Gabay, Shai; Nestor, Adrian; Dundas, Eva; Behrmann, Marlene

    2014-05-01

    The ability to recognize faces accurately and rapidly is an evolutionarily adaptive process. Most studies examining the neural correlates of face perception in adult humans have focused on a distributed cortical network of face-selective regions. There is, however, robust evidence from phylogenetic and ontogenetic studies that implicates subcortical structures, and recently, some investigations in adult humans indicate subcortical correlates of face perception as well. The questions addressed here are whether low-level subcortical mechanisms for face perception (in the absence of changes in expression) are conserved in human adults, and if so, what is the nature of these subcortical representations. In a series of four experiments, we presented pairs of images to the same or different eyes. Participants' performance demonstrated that subcortical mechanisms, indexed by monocular portions of the visual system, play a functional role in face perception. These mechanisms are sensitive to face-like configurations and afford a coarse representation of a face, comprised of primarily low spatial frequency information, which suffices for matching faces but not for more complex aspects of face perception such as sex differentiation. Importantly, these subcortical mechanisms are not implicated in the perception of other visual stimuli, such as cars or letter strings. These findings suggest a conservation of phylogenetically and ontogenetically lower-order systems in adult human face perception. The involvement of subcortical structures in face recognition provokes a reconsideration of current theories of face perception, which are reliant on cortical level processing, inasmuch as it bolsters the cross-species continuity of the biological system for face recognition.

  12. Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

    PubMed Central

    Santana, Magda M.; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Karl; Bastos, Carlos A.; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R.; Cavadas, Cláudia

    2012-01-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10–12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)+/β-3-tubulin+ cells and TH−/β-3-tubulin+ cells, and into chromaffin cells (TH+/PNMT+). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  13. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    PubMed

    Santana, Magda M; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Klaus; Bastos, Carlos A; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R; Cavadas, Cláudia; Ehrhart-Bornstein, Monika

    2012-11-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10-12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)(+)/β-3-tubulin(+) cells and TH(-)/β-3-tubulin(+) cells, and into chromaffin cells (TH(+)/PNMT(+)). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  14. Normalizing the environment recapitulates adult human immune traits in laboratory mice.

    PubMed

    Beura, Lalit K; Hamilton, Sara E; Bi, Kevin; Schenkel, Jason M; Odumade, Oludare A; Casey, Kerry A; Thompson, Emily A; Fraser, Kathryn A; Rosato, Pamela C; Filali-Mouhim, Ali; Sekaly, Rafick P; Jenkins, Marc K; Vezys, Vaiva; Haining, W Nicholas; Jameson, Stephen C; Masopust, David

    2016-04-28

    Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans. PMID:27096360

  15. Normalizing the environment recapitulates adult human immune traits in laboratory mice.

    PubMed

    Beura, Lalit K; Hamilton, Sara E; Bi, Kevin; Schenkel, Jason M; Odumade, Oludare A; Casey, Kerry A; Thompson, Emily A; Fraser, Kathryn A; Rosato, Pamela C; Filali-Mouhim, Ali; Sekaly, Rafick P; Jenkins, Marc K; Vezys, Vaiva; Haining, W Nicholas; Jameson, Stephen C; Masopust, David

    2016-04-28

    Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.

  16. 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

  17. Human induced pluripotent stem cells can reach complete terminal maturation: in vivo and in vitro evidence in the erythropoietic differentiation model

    PubMed Central

    Kobari, Ladan; Yates, Frank; Oudrhiri, Noufissa; Francina, Alain; Kiger, Laurent; Mazurier, Christelle; Rouzbeh, Shaghayegh; El-Nemer, Wassim; Hebert, Nicolas; Giarratana, Marie-Catherine; François, Sabine; Chapel, Alain; Lapillonne, Hélène; Luton, Dominique; Bennaceur-Griscelli, Annelise; Douay, Luc

    2012-01-01

    Background Human induced pluripotent stem cells offer perspectives for cell therapy and research models for diseases. We applied this approach to the normal and pathological erythroid differentiation model by establishing induced pluripotent stem cells from normal and homozygous sickle cell disease donors. Design and Methods We addressed the question as to whether these cells can reach complete erythroid terminal maturation notably with a complete switch from fetal to adult hemoglobin. Sickle cell disease induced pluripotent stem cells were differentiated in vitro into red blood cells and characterized for their terminal maturation in terms of hemoglobin content, oxygen transport capacity, deformability, sickling and adherence. Nucleated erythroblast populations generated from normal and pathological induced pluripotent stem cells were then injected into non-obese diabetic severe combined immunodeficiency mice to follow the in vivo hemoglobin maturation. Results We observed that in vitro erythroid differentiation results in predominance of fetal hemoglobin which rescues the functionality of red blood cells in the pathological model of sickle cell disease. We observed, in vivo, the switch from fetal to adult hemoglobin after infusion of nucleated erythroid precursors derived from either normal or pathological induced pluripotent stem cells into mice. Conclusions These results demonstrate that human induced pluripotent stem cells: i) can achieve complete terminal erythroid maturation, in vitro in terms of nucleus expulsion and in vivo in terms of hemoglobin maturation; and ii) open the way to generation of functionally corrected red blood cells from sickle cell disease induced pluripotent stem cells, without any genetic modification or drug treatment. PMID:22733021

  18. Seasonal influence on hematologic values and hemoglobin electrophoresis in Brazilian boa constrictor amarali.

    PubMed

    Machado, Carla C; Silva, Luis F N; Ramos, Paulo R R; Takahira, Regina K

    2006-12-01

    As ectothermic animals, snakes depend exclusively on the environment for proper temperature maintenance, which may greatly influence their activity. Twenty-five adult Boa constrictor amarali snakes maintained in captivity were used to determine the influence of seasons on their hematologic values and electrophoretic profile of hemoglobin. A complete blood cell count (CBC) and examination for hemoparasites were performed in the summer and winter of 2004. Hemoglobin was stored for later electrophoresis. Significant differences (P < 0.05) were obtained in RBC, WBC, lymphocyte, thrombocyte, and monocyte counts, demonstrating the importance of the period of the year in the interpretation of reference values in these animals. Two snakes were detected with blood parasites (Hepatozoon sp.) in the winter and four in the summer, although it appears that their presence did not cause any significant alterations in the CBC. The electrophoretic analysis of the samples demonstrated two-four hemoglobin bands in this species.

  19. The effect of gamma-rays on the hemoglobin of whole-body irradiated mice

    NASA Astrophysics Data System (ADS)

    Ashry, H. A.; Selim, N. S.; El-Behay, A. Z.

    1994-07-01

    Changes in the UV-visible absorption spectrum of mouse hemoglobin as a result of whole body irradiation were studied. White albino adult mice were exposed to a Cs-137 γ-source at a dose rate of 47.5 Gy/h to different absorbed dose values ranging from 1 to 8 Gy. Blood specimens were taken 24 h after irradiation. The UV-visible absorption spectra of hemoglobin of irradiated and control mice were measured in the wavelength range from 200 to 700 nm. The obtained results showed significant changes in the bands measured at 340 nm, in the Soret band measured at 410 nm, also, the α- and β-bands measured at 537 and 572 nm showed significant decrease in intensity with the absorbed dose increase. The absorbance measured at 630 nm showed no significant changes. The radiation effect on the animal hemoglobin was discussed on the basis of the obtained results.

  20. Designing Instruction for Adult Learners. Second Edition. Professional Practices in Adult Education and Human Resource Development Series.

    ERIC Educational Resources Information Center

    Dean, Gary J.

    This book focuses on applying instructional design to development of classroom learning for adults. Chapter 1 presents an overview of the model and addresses concerns about use of instructional design in adult education. Chapter 2 deals with assessing and developing skills as an adult educator; a literature review on behavior, beliefs, knowledge,…

  1. Cell signaling pathways involved in drug-mediated fetal hemoglobin induction: Strategies to treat sickle cell disease

    PubMed Central

    Liu, Li; Li, Biaoru; Makala, Levi H

    2015-01-01

    The developmental regulation of globin gene expression has shaped research efforts to establish therapeutic modalities for individuals affected with sickle cell disease and β-thalassemia. Fetal hemoglobin has been shown to block sickle hemoglobin S polymerization to improve symptoms of sickle cell disease; moreover, fetal hemoglobin functions to replace inadequate hemoglobin A synthesis in β-thalassemia thus serving as an effective therapeutic target. In the perinatal period, fetal hemoglobin is synthesized at high levels followed by a decline to adult levels by one year of age. It is known that naturally occurring mutations in the γ-globin gene promoters and distant cis-acting transcription factors produce persistent fetal hemoglobin synthesis after birth to ameliorate clinical symptoms. Major repressor proteins that silence γ-globin during development have been targeted for gene therapy in β-hemoglobinopathies patients. In parallel effort, several classes of pharmacological agents that induce fetal hemoglobin expression through molecular and cell signaling mechanisms have been identified. Herein, we reviewed the progress made in the discovery of signaling molecules targeted by pharmacologic agents that enhance γ-globin expression and have the potential for future drug development to treat the β-hemoglobinopathies. PMID:26283707

  2. Moxidectin causes adult worm mortality of human lymphatic filarial parasite Brugia malayi in rodent models.

    PubMed

    Verma, Meenakshi; Pathak, Manisha; Shahab, Mohd; Singh, Kavita; Mitra, Kalyan; Misra-Bhattacharya, Shailja

    2014-12-01

    Moxidectin is a macrocyclic lactone belonging to milbemycin family closely related to ivermectin and is currently progressing towards Phase III clinical trial against human infection with the filaria Onchocerca volvulus (Leuckart, 1894). There is a single report on the microfilaricidal and embryostatic activity of moxidectin in case of the human lymphatic filarial parasite Brugia malayi (Brug, 1927) in Mastomys coucha (Smith) but without any adulticidal action. In the present study, the in vitro and in vivo antifilarial efficacy of moxidectin was evaluated on, B. malayi. In vitro moxidectin showed 100% reduction in adult female worm motility at 0.6 μM concentration within 7 days with 68% inhibition in the reduction of MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye) (which is used to detect viability of worms). A 50% inhibitory concentration (IC50) of moxidectin for adult female parasite was 0.242 μM, for male worm 0.186 μM and for microfilaria IC50 was 0.813 μM. In adult B. malayi-transplanted primary screening model (Meriones unguiculatus Milne-Edwards), moxidectin at a single optimal dose of 20 mg/kg by oral and subcutaneous route was found effective on both adult parasites and microfilariae. In secondary screening (M coucha, subcutaneously inoculated with infective larvae), moxidectin at the same dose by subcutaneous route brought about death of 49% of adult worms besides causing sterilisation in 54% of the recovered live female worms. The treated animals exhibited a continuous and sustained reduction in peripheral blood microfilaraemia throughout the observation period of 90 days. The mechanism of action of moxidectin is suggested to be similar to avermectins. The in silico studies were also designed to explore the interaction of moxidectin with glutamate-gated chloride channels of B. malayi. The docking results revealed a close interaction of moxidectin with various GluCl ligand sites of B. malayi. PMID:25651699

  3. Urinary concentrations of parabens in Chinese young adults: implications for human exposure.

    PubMed

    Ma, Wan-Li; Wang, Lei; Guo, Ying; Liu, Li-Yan; Qi, Hong; Zhu, Ning-Zheng; Gao, Chong-Jing; Li, Yi-Fan; Kannan, Kurunthachalam

    2013-10-01

    Parabens are widely used as preservatives in foods, cosmetics, and pharmaceuticals. However, recent studies have indicated that high and systemic exposure to parabens can be harmful to human health. Although a few studies have reported urinary paraben levels in western countries, studies on paraben exposure in the Chinese population are limited. China is currently a major producer of parabens in the world. In this study, 109 urine samples collected from Chinese young adults (approximately 20 years old) were analyzed for five parabens (methyl-, ethyl-, propyl-, butyl-, and benzyl-parabens) by high-performance liquid chromatography-tandem mass spectrometry. Methyl-, propyl-, and ethyl-parabens were the three major paraben analogues found in all (100%) samples. The concentration of the sum of the five parabens ranged from 0.82 to 728 ng/mL with a geometric mean value of 17.4 ng/mL. Urinary concentration of parabens was 2-fold greater in females than in males. Based on the measured urinary concentrations, daily intake of parabens by the Chinese young adults was estimated and compared with those reported for United States adults. The estimated daily intakes (EDIurine) of parabens were 18.4 and 40.8 μg/kg bw/day for Chinese males and females, respectively, values that were lower than those reported for United States adults (74.7 μg/kg bw/day). Based on the reported concentrations of parabens in foods from China and the United States, the contribution of dietary intake to EDIurine was estimated to be 5.5, 2.6, and 0.42% for Chinese males, Chinese females, and United States adults, respectively, which indicates the significance of nondietary sources of parabens to human exposures.

  4. Populations of subplate and interstitial neurons in fetal and adult human telencephalon

    PubMed Central

    Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

    2010-01-01

    In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the ‘waiting’ compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input–output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

  5. Drosophila as a model for the identification of genes causing adult human heart disease

    PubMed Central

    Wolf, Matthew J.; Amrein, Hubert; Izatt, Joseph A.; Choma, Michael A.; Reedy, Mary C.; Rockman, Howard A.

    2006-01-01

    Drosophila melanogaster genetics provides the advantage of molecularly defined P-element insertions and deletions that span the entire genome. Although Drosophila has been extensively used as a model system to study heart development, it has not been used to dissect the genetics of adult human heart disease because of an inability to phenotype the adult fly heart in vivo. Here we report the development of a strategy to measure cardiac function in awake adult Drosophila that opens the field of Drosophila genetics to the study of human dilated cardiomyopathies. Through the application of optical coherence tomography, we accurately distinguish between normal and abnormal cardiac function based on measurements of internal cardiac chamber dimensions in vivo. Normal Drosophila have a fractional shortening of 87 ± 4%, whereas cardiomyopathic flies that contain a mutation in troponin I or tropomyosin show severe impairment of systolic function. To determine whether the fly can be used as a model system to recapitulate human dilated cardiomyopathy, we generated transgenic Drosophila with inducible cardiac expression of a mutant of human δ-sarcoglycan (δsgS151A), which has previously been associated with familial dilated cardiomyopathy. Compared to transgenic flies overexpressing wild-type δsg, or the standard laboratory strain w1118, Drosophila expressing δsgS151A developed marked impairment of systolic function and significantly enlarged cardiac chambers. These data illustrate the utility of Drosophila as a model system to study dilated cardiomyopathy and the applicability of the vast genetic resources available in Drosophila to systematically study the genetic mechanisms responsible for human cardiac disease. PMID:16432241

  6. Rabbit Neonates and Human Adults Perceive a Blending 6-Component Odor Mixture in a Comparable Manner

    PubMed Central

    Sinding, Charlotte; Thomas-Danguin, Thierry; Chambault, Adeline; Béno, Noelle; Dosne, Thibaut; Chabanet, Claire; Schaal, Benoist; Coureaud, Gérard

    2013-01-01

    Young and adult mammals are constantly exposed to chemically complex stimuli. The olfactory system allows for a dual processing of relevant information from the environment either as single odorants in mixtures (elemental perception) or as mixtures of odorants as a whole (configural perception). However, it seems that human adults have certain limits in elemental perception of odor mixtures, as suggested by their inability to identify each odorant in mixtures of more than 4 components. Here, we explored some of these limits by evaluating the perception of three 6-odorant mixtures in human adults and newborn rabbits. Using free-sorting tasks in humans, we investigated the configural or elemental perception of these mixtures, or of 5-component sub-mixtures, or of the 6-odorant mixtures with modified odorants' proportion. In rabbit pups, the perception of the same mixtures was evaluated by measuring the orocephalic sucking response to the mixtures or their components after conditioning to one of these stimuli. The results revealed that one mixture, previously shown to carry the specific odor of red cordial in humans, was indeed configurally processed in humans and in rabbits while the two other 6-component mixtures were not. Moreover, in both species, such configural perception was specific not only to the 6 odorants included in the mixture but also to their respective proportion. Interestingly, rabbit neonates also responded to each odorant after conditioning to the red cordial mixture, which demonstrates their ability to perceive elements in addition to configuration in this complex mixture. Taken together, the results provide new insights related to the processing of relatively complex odor mixtures in mammals and the inter-species conservation of certain perceptual mechanisms; the results also revealed some differences in the expression of these capacities between species putatively linked to developmental and ecological constraints. PMID:23341948

  7. Comparison of human growth hormone products' cost in pediatric and adult patients. A budgetary impact model.

    PubMed

    Bazalo, Gary R; Joshi, Ashish V; Germak, John

    2007-09-01

    We assessed the economic impact to the United States payer of recombinant human growth hormone (rhGH) utilization, comparing the relative dosage efficiency of marketed pen-based and vial-based products in a pediatric and in an adult population. A budgetary impact model calculated drug costs based on product waste and cost. Waste was the difference between prescribed dose, based on patient weight, and actual delivered dose, based on dosing increments and maximum deliverable dose for pens and a fixed-percent waste as derived from the literature for vials. Annual wholesale acquisition costs were calculated based upon total milligrams delivered, using a daily dose of 0.03 mg/kg for pediatric patients and 0.016 mg/kg for adults. Total annual drug costs were compared for two scenarios: 1) a product mix based on national market share and 2) restricting use to the product with lowest waste. Based on the literature, waste for each vial product was 23 percent. Among individual pens, waste was highest for Humatrope 24 mg (19.5 percent pediatric, 14.3 percent adult) and lowest for Norditropin Nordi-Flex 5 mg (1.1 percent pediatric, 1 percent adult). Restricting use to the brand with least waste (Norditropin), compared to national product share mix, resulted in a 10.2 percent reduction in annual pediatric patient cost from $19,026 to $17,089 and an 8 percent reduction in annual adult patient cost from $24,099 to $22,161. We concluded that pen delivery systems result in less waste than vial and syringe. Considering all approved delivery systems, Norditropin resulted in the least product waste and lower annual patient cost for both pediatric and adult populations.

  8. The mental representation of the human gait in young and older adults

    PubMed Central

    Stöckel, Tino; Jacksteit, Robert; Behrens, Martin; Skripitz, Ralf; Bader, Rainer; Mau-Moeller, Anett

    2015-01-01

    The link between mental representation (MREP) structures and motor performance has been evidenced for a great variety of movement skills, but not for the human gait. Therefore the present study sought to investigate the cognitive memory structures underlying the human gait in young and older adults. In a first experiment, gait parameters at comfortable gait speed (OptoGait) were compared with gait-specific MREPs (structural dimensional analysis of MREP; SDA-M) in 36 young adults. Participants were divided into a slow- and fast-walking group. The proven relationship between gait speed and executive functions such as working memory led to the hypothesis that gait pattern and MREP differ between slow- and fast-walking adults. In a second experiment, gait performance and MREPs were compared between 24 young (27.9 years) and 24 elderly (60.1 years) participants. As age-related declines in gait performance occur from the seventh decade of life onward, we hypothesized that gait parameters would not be affected until the age of 60 years accompanied by unchanged MREP. Data of experiment one revealed that gait parameters and MREPs differed significantly between slow and fast walkers. Notably, eleven previously incurred musculoskeletal injuries were documented for the slow walkers but only two injuries and one disorder for fast walkers. Experiment two revealed no age-related differences in gait parameters or MREPs between healthy young and older adults. In conclusion, the differences in gait parameters associated with lower comfortable gait speeds are reflected by differences in MREPs, whereby SDA-M data indicate that the single limb support phase may serve as a critical functional period. These differences probably resulted from previously incurred musculoskeletal injuries. Our data further indicate that the human gait and its MREP are stable until the age of 60. SDA-M may be considered as a valuable clinical tool for diagnosis of gait abnormalities and monitoring of

  9. The Ecology of Human Performance Framework: A Model for Identifying and Designing Appropriate Accommodations for Adult Learners.

    ERIC Educational Resources Information Center

    Dunn, Winnie; Gilbert, Mary Pat; Parker, Kathy

    This paper proposes a model framework, The Ecology of Human Performance (EHP) framework, for organizing adult basic education to utilize the skills of occupational therapists. The paper also includes two responses to the proposed framework by Janet S. Stotts and Cheryl Keenan. Reasons for the inclusion of occupational therapy in adult education…

  10. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults. 26.1704 Section 26.1704 Protection of Environment... research with non-pregnant, non-nursing adults. (a) This section applies to research subject to...

  11. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults. 26.1704 Section 26.1704 Protection of Environment... research with non-pregnant, non-nursing adults. (a) This section applies to research subject to...

  12. 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

  13. Maternal and child undernutrition: consequences for adult health and human capital.

    PubMed

    Victora, Cesar G; Adair, Linda; Fall, Caroline; Hallal, Pedro C; Martorell, Reynaldo; Richter, Linda; Sachdev, Harshpal Singh

    2008-01-26

    In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and

  14. Isoforms of Hsp70-binding human LDL in adult Schistosoma mansoni worms.

    PubMed

    Pereira, Adriana S A; Cavalcanti, Marília G S; Zingali, Russolina B; Lima-Filho, José L; Chaves, Maria E C

    2015-03-01

    Schistosoma mansoni is one of the most common parasites infecting humans. They are well adapted to the host, and this parasite's longevity is a consequence of effective escape from the host immune system. In the blood circulation, lipoproteins not only help to conceal the worm from attack by host antibodies but also act as a source of lipids for S. mansoni. Previous SEM studies showed that the low-density lipoprotein (LDL) particles present on the surface of adult S. mansoni worms decreased in size when the incubation time increased. In this study, immunocytochemical and proteomic analyses were used to locate and identify S. mansoni binding proteins to human plasma LDL. Ultrathin sections of adult worms were cut transversely from the anterior, medial and posterior regions of the parasite. Immunocytochemical experiments revealed particles of gold in the tegument, muscle region and spine in male worms and around vitelline cells in females. Immunoblotting and 2D-electrophoresis using incubations with human serum, anti-LDL antibodies and anti-chicken IgG peroxidase conjugate were performed to identify LDL-binding proteins in S. mansoni. Analysis of the binding proteins using LC-MS identified two isoforms of the Hsp70 chaperone in S. mansoni. Hsp70 is involved in the interaction with apoB in the cytoplasm and its transport to the endoplasmic reticulum. However, further studies are needed to clarify the functional role of Hsp70 in S. mansoni, mainly related to the interaction with human LDL.

  15. Uptake of dietary milk miRNAs by adult humans: a validation study

    PubMed Central

    Auerbach, Amanda; Vyas, Gopi; Li, Anne; Halushka, Marc; Witwer, Kenneth

    2016-01-01

    Breast milk is replete with nutritional content as well as nucleic acids including microRNAs (miRNAs). In a recent report, adult humans who drank bovine milk appeared to have increased circulating levels of miRNAs miR-29b-3p and miR-200c-3p. Since these miRNAs are homologous between human and cow, these results could be explained by xeno-miRNA influx, endogenous miRNA regulation, or both. More data were needed to validate the results and explore for additional milk-related alterations in circulating miRNAs. Samples from the published study were obtained, and 223 small RNA features were profiled with a custom OpenArray, followed by individual quantitative PCR assays for selected miRNAs. Additionally, small RNA sequencing (RNA-seq) data obtained from plasma samples of the same project were analyzed to find human and uniquely bovine miRNAs. OpenArray revealed no significantly altered miRNA signals after milk ingestion, and this was confirmed by qPCR. Plasma sequencing data contained no miR-29b or miR-200c reads and no intake-consistent mapping of uniquely bovine miRNAs. In conclusion, the results do not support transfer of dietary xenomiRs into the circulation of adult humans. PMID:27158459

  16. Identification of novel molecular markers through transcriptomic analysis in human fetal and adult corneal endothelial cells.

    PubMed

    Chen, Yinyin; Huang, Kevin; Nakatsu, Martin N; Xue, Zhigang; Deng, Sophie X; Fan, Guoping

    2013-04-01

    The corneal endothelium is composed of a monolayer of corneal endothelial cells (CECs), which is essential for maintaining corneal transparency. To better characterize CECs in different developmental stages, we profiled mRNA transcriptomes in human fetal and adult corneal endothelium with the goal to identify novel molecular markers in these cells. By comparing CECs with 12 other tissue types, we identified 245 and 284 signature genes that are highly expressed in fetal and adult CECs, respectively. Functionally, these genes are enriched in pathways characteristic of CECs, including inorganic anion transmembrane transporter, extracellular matrix structural constituent and cyclin-dependent protein kinase inhibitor activity. Importantly, several of these genes are disease target genes in hereditary corneal dystrophies, consistent with their functional significance in CEC physiology. We also identified stage-specific markers associated with CEC development, such as specific members in the transforming growth factor beta and Wnt signaling pathways only expressed in fetal, but not in adult CECs. Lastly, by the immunohistochemistry of ocular tissues, we demonstrated the unique protein localization for Wnt5a, S100A4, S100A6 and IER3, the four novel markers for fetal and adult CECs. The identification of a new panel of stage-specific markers for CECs would be very useful for characterizing CECs derived from stem cells or ex vivo expansion for cell replacement therapy. PMID:23257286

  17. Adult education as a human right: The Latin American context and the ecopedagogic perspective

    NASA Astrophysics Data System (ADS)

    Gadotti, Moacir

    2011-08-01

    This article presents the concept and practice of adult education as a key issue for Brazil and other Latin American countries, both for formal and non-formal education in the public and private sectors. It includes citizen education focused on democratisation of society and sustainable development. The concept is pluralist and ideological as well as technical. All along the history of contemporary education it is essential to highlight the importance of the CONFINTEA conferences for the construction of an expanded vision of this concept. Adult education is understood as a human right. The right to education does not end when a person has reached the so-called "proper" age; it continues to be a right for the duration of everyone's entire life. This article explores Paulo Freire's contribution, particularly the methodology of MOVA (Youth and Adult Literacy Movement). It also presents the ecopedagogic perspective, which was inspired by Paulo Freire's legacy. Finally, this article stresses the need to support a long-term policy for adult education, following the recommendations of the Civil Society International Forum (FISC) and CONFINTEA VI, both held in Belém, Brazil, in 2009.

  18. Oral Human Papillomavirus Detection in Older Adults Who Have Human Immunodeficiency Virus Infection

    PubMed Central

    Fatahzadeh, Mahnaz; Schlecht, Nicolas F.; Chen, Zigui; Bottalico, Danielle; McKinney, Sharod; Ostoloza, Janae; Dunne, Anne; Burk, Robert D.

    2014-01-01

    Objective To evaluate reproducibility of oral rinse self-collection for HPV detection and investigate associations between oral HPV, oral lesions, immune and sociodemographic factors, we performed a cross-sectional study of older adults with HIV infection. Study Design We collected oral rinse samples from 52 subjects at two different times of day followed by an oral examination and interview. We identified HPV using PCR platforms optimized for detection of mucosal and cutaneous types. Results Eighty seven percent of individuals had oral HPV, of which 23% had oncogenic alpha, 40% had non-oncogenic alpha, and 46% had beta or gamma HPV. Paired oral specimens were concordant in all parameters tested. Significant associations observed for oral HPV with increased HIV viral load, hepatitis-C seropositivity, history of sexually transmitted diseases and lifetime number of sexual partners. Conclusions Oral cavity may be a reservoir of subclinical HPV in older adults who have HIV infection. Understanding natural history, transmission and potential implications of oral HPV warrants further investigations. PMID:23375488

  19. Adoptive transfer of macrophages from adult mice reduces mortality in mice infected with human enterovirus 71.

    PubMed

    Liu, Jiangning; Li, Xiaoying; Fan, Xiaoxu; Ma, Chunmei; Qin, Chuan; Zhang, Lianfeng

    2013-02-01

    Human enterovirus 71 (EV71) causes hand, foot and mouth disease in children under 6 years of age, and the neurological complications of this virus can lead to death. Until now, no vaccines or drugs have been available for the clinical control of this epidemic. Macrophages can engulf pathogens and mediate a series of host immune responses that play a role in the defence against infectious diseases. Using immunohistochemistry, we observed the localizations of virus in muscle tissues of EV71-infected mice. The macrophages isolated from the adult mice could kill the virus gradually in vitro, as shown using quantitative real-time PCR (qRT-PCR) and virus titration. Co-localisation of lysosomes and virus within macrophages suggested that the lysosomes were possibly responsible for the phagocytosis of EV71. Activation of the macrophages in the peritoneal cavity of mice four days pre-infection reduced the mortality of mice upon lethal EV71 infection. The adoptive transfer of macrophages from adult mice inhibited virus replication in the muscle tissues of infected mice, and this was followed by a relief of symptoms and a significant reduction of mortality, which suggested that the adoptive transfer of macrophages from adult humans represents a potential strategy to treat EV71-infected patients.

  20. Acceptance and Attitudes Toward a Human-like Socially Assistive Robot by Older Adults.

    PubMed

    Louie, Wing-Yue Geoffrey; McColl, Derek; Nejat, Goldie

    2014-01-01

    Recent studies have shown that cognitive and social interventions are crucial to the overall health of older adults including their psychological, cognitive, and physical well-being. However, due to the rapidly growing elderly population of the world, the resources and people to provide these interventions is lacking. Our work focuses on the use of social robotic technologies to provide person-centered cognitive interventions. In this article, we investigate the acceptance and attitudes of older adults toward the human-like expressive socially assistive robot Brian 2.1 in order to determine if the robot's human-like assistive and social characteristics would promote the use of the robot as a cognitive and social interaction tool to aid with activities of daily living. The results of a robot acceptance questionnaire administered during a robot demonstration session with a group of 46 elderly adults showed that the majority of the individuals had positive attitudes toward the socially assistive robot and its intended applications.

  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. 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.

  3. 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

  4. Physical Exercise Habits Correlate with Gray Matter Volume of the Hippocampus in Healthy Adult Humans

    NASA Astrophysics Data System (ADS)

    Killgore, William D. S.; Olson, Elizabeth A.; Weber, Mareen

    2013-12-01

    Physical activity facilitates neurogenesis of dentate cells in the rodent hippocampus, a brain region critical for memory formation and spatial representation. Recent findings in humans also suggest that aerobic exercise can lead to increased hippocampal volume and enhanced cognitive functioning in children and elderly adults. However, the association between physical activity and hippocampal volume during the period from early adulthood through middle age has not been effectively explored. Here, we correlated the number of minutes of self-reported exercise per week with gray matter volume of the hippocampus using voxel-based morphometry (VBM) in 61 healthy adults ranging from 18 to 45 years of age. After controlling for age, gender, and total brain volume, total minutes of weekly exercise correlated significantly with volume of the right hippocampus. Findings highlight the relationship between regular physical exercise and brain structure during early to middle adulthood.

  5. Health and population effects of rare gene knockouts in adult humans with related parents

    PubMed Central

    Narasimhan, Vagheesh M.; Hunt, Karen A.; Mason, Dan; Baker, Christopher L.; Karczewski, Konrad J.; Barnes, Michael R.; Barnett, Anthony H.; Bates, Chris; Bellary, Srikanth; Bockett, Nicholas A.; Giorda, Kristina; Griffiths, Christopher J.; Hemingway, Harry; Jia, Zhilong; Kelly, M. Ann; Khawaja, Hajrah A.; Lek, Monkol; McCarthy, Shane; McEachan, Rosie; O’Donnell-Luria, Anne; Paigen, Kenneth; Parisinos, Constantinos A.; Sheridan, Eamonn; Southgate, Laura; Tee, Louise; Thomas, Mark; Xue, Yali; Schnall-Levin, Michael; Petkov, Petko M.; Tyler-Smith, Chris; Maher, Eamonn R.; Trembath, Richard C.; MacArthur, Daniel G.; Wright, John; Durbin, Richard; van Heel, David A.

    2016-01-01

    Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3,222 British Pakistani-heritage adults with high parental relatedness, discovering 1,111 rare-variant homozygous genotypes with predicted loss of gene function (knockouts) in 781 genes. We observed 13.7% fewer than expected homozygous knockout genotypes, implying an average load of 1.6 recessive-lethal-equivalent LOF variants per adult. Linking genetic data to lifelong health records, knockouts were not associated with clinical consultation or prescription rate. In this dataset we identified a healthy PRDM9 knockout mother, and performed phased genome sequencing on her, her child and controls, which showed meiotic recombination sites localised away from PRDM9-dependent hotspots. Thus, natural LOF variants inform upon essential genetic loci, and demonstrate PRDM9 redundancy in humans. PMID:26940866

  6. Adult stem cells: simply a tool for regenerative medicine or an additional piece in the puzzle of human aging?

    PubMed

    Tollervey, James R; Lunyak, Victoria V

    2011-12-15

    Adult stem cells have taken center stage in current research related to regenerative medicine and pharmacogenomic studies seeking new therapeutic interventions. As we learn more about these cells, it is becoming apparent that the next big leap in our understanding of adult stem cell biology and adult stem cell aging will depend on the integration of approaches from various disciplines. Major advances and technological breakthroughs at the crossroad of fields such as biomaterials, genomics, epigenomics, and proteomics will enable the design of better tools to model human diseases, and warrant safe usage of adult stem cells in the clinic.

  7. Human tau expression reduces adult neurogenesis in a mouse model of tauopathy.

    PubMed

    Komuro, Yutaro; Xu, Guixiang; Bhaskar, Kiran; Lamb, Bruce T

    2015-06-01

    Accumulation of hyperphosphorylated and aggregated microtubule-associated protein tau (MAPT) is a central feature of a class of neurodegenerative diseases termed tauopathies. Notably, there is increasing evidence that tauopathies, including Alzheimer's disease, are also characterized by a reduction in neurogenesis, the birth of adult neurons. However, the exact relationship between hyperphosphorylation and aggregation of MAPT and neurogenic deficits remains unclear, including whether this is an early- or late-stage disease marker. In the present study, we used the genomic-based hTau mouse model of tauopathy to examine the temporal and spatial regulation of adult neurogenesis during the course of the disease. Surprisingly, hTau mice exhibited reductions in adult neurogenesis in 2 different brain regions by as early as 2 months of age, before the development of robust MAPT pathology in this model. This reduction was found to be due to reduced proliferation and not because of enhanced apoptosis in the hippocampus. At these same time points, hTau mice also exhibited altered MAPT phosphorylation with neurogenic precursors. To examine whether the effects of MAPT on neurogenesis were cell autonomous, neurospheres prepared from hTau animals were examined in vitro, revealing a growth deficit when compared with non-transgenic neurosphere cultures. Taken together, these studies provide evidence that altered adult neurogenesis is a robust and early marker of altered, cell-autonomous function of MAPT in the hTau mouse mode of tauopathy and that altered adult neurogenesis should be examined as a potential marker and therapeutic target for human tauopathies.

  8. Three-dimensional dental arch curvature in human adolescents and adults.

    PubMed

    Ferrario, V F; Sforza, C; Poggio, C E; Serrao, G; Colombo, A

    1999-04-01

    The three-dimensional arrangement of dental cusps and incisal edges in human dentitions has been reported to fit the surface of a sphere (the curve of Monson), with a radius of about 4 inches in adults. The objective of the current study was to compare the three-dimensional curvature of the mandibular dental arch in healthy permanent dentitions of young adults and adolescents. The mandibular casts of 50 adults (aged 19 to 22 years) and 20 adolescents (aged 12 to 14 years) with highly selected sound dentitions that were free from temporomandibular joint problems were obtained. The three coordinates of cusp tips excluding the third molars were digitized with a three-dimensional digitizer, and used to derive a spherical model of the curvature of the occlusal surfaces. From the best interpolating sphere, the radii of the left and right curves of Spee (quasi-sagittal plane) and of molar curve of Wilson (frontal plane) were computed. Mandibular arch size (interdental distances) was also calculated. The occlusal curvature of the mandibular arch was not significantly influenced by sex, although a significant effect of age was found (Student t, P <.005). The radii of the overall sphere, right and left curves of Spee, and curve of Wilson in the molar area were about 101 mm in adults, and about 80 mm in adolescents. Arch size was not influenced by either sex or age. The different curvatures of the occlusal plane in adolescents and adults may be explained by a progressive rotation of the major axis of the teeth moving the occlusal plane toward a more buccal position. These dental movements should be performed in a frontal plane on an anteroposterior axis located next to the dental crown.

  9. 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.

  10. Characterization of diverse forms of myosin heavy chain expressed in adult human skeletal muscle.

    PubMed Central

    Saez, L; Leinwand, L A

    1986-01-01

    In an attempt to define myosin heavy chain (MHC) gene organization and expression in adult human skeletal muscle, we have isolated and characterized genomic sequences corresponding to different human sarcomeric MHC genes (1). In this report, we present the complete DNA sequence of two different adult human skeletal muscle MHC cDNA clones, one of which encodes the entire light meromyosin (LMM) segment of MHC and represents the longest described MHC cDNA sequence. Additionally, both clones provide new sequence data from a 228 amino acid segment of the MHC tail for which no protein or DNA sequence has been previously available. One clone encodes a "fast" form of skeletal muscle MHC while the other clone most closely resembles a MHC form described in rat cardiac ventricles. We show that the 3' untranslated region of skeletal MHC cDNAs are homologous from widely separated species as are cardiac MHC cDNAs. However, there is no homology between the 3' untranslated region of cardiac and skeletal muscle MHCs. Isotype-specific preservation of MHC 3' untranslated sequences during evolution suggests a functional role for these regions. Images PMID:2421254

  11. 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

  12. 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

  13. 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

  14. Cortical surface area and cortical thickness in the precuneus of adult humans.

    PubMed

    Bruner, E; Román, F J; de la Cuétara, J M; Martin-Loeches, M; Colom, R

    2015-02-12

    The precuneus has received considerable attention in the last decade, because of its cognitive functions, its role as a central node of the brain networks, and its involvement in neurodegenerative processes. Paleoneurological studies suggested that form changes in the deep parietal areas represent a major character associated with the origin of the modern human brain morphology. A recent neuroanatomical survey based on shape analysis suggests that the proportions of the precuneus are also a determinant source of overall brain geometrical differences among adult individuals, influencing the brain spatial organization. Here, we evaluate the variation of cortical thickness and cortical surface area of the precuneus in a sample of adult humans, and their relation with geometry and cognition. Precuneal thickness and surface area are not correlated. There is a marked individual variation. The right precuneus is thinner and larger than the left one, but there are relevant fluctuating asymmetries, with only a modest correlation between the hemispheres. Males have a thicker cortex but differences in cortical area are not significant between sexes. The surface area of the precuneus shows a positive allometry with the brain surface area, although the correlation is modest. The dilation/contraction of the precuneus, described as a major factor of variability within adult humans, is associated with absolute increase/decrease of its surface, but not with variation in thickness. Precuneal thickness, precuneal surface area and precuneal morphology are not correlated with psychological factors such as intelligence, working memory, attention control, and processing speed, stressing further possible roles of this area in supporting default mode functions. Beyond gross morphology, the processes underlying the large phenotypic variation of the precuneus must be further investigated through specific cellular analyses, aimed at considering differences in cellular size, density

  15. Understanding and Managing Learning Disabilities in Adults. Professional Practices in Adult Education and Human Resource Development Series.

    ERIC Educational Resources Information Center

    Jordan, Dale R.

    This book reviews learning disabilities (LD) in adults and makes suggestions for helping adults cope with these disabilities. Each chapter covers a type of learning disability or related syndrome or explains characteristics of the brain. Chapter 1 explains several types of specific learning disabilities that make classroom performance difficult…

  16. Development of a Physiologically Based Model to Describe the Pharmacokinetics of Methylphenidate in Juvenile and Adult Humans and Nonhuman Primates

    PubMed Central

    Yang, Xiaoxia; Morris, Suzanne M.; Gearhart, Jeffery M.; Ruark, Christopher D.; Paule, Merle G.; Slikker, William; Mattison, Donald R.; Vitiello, Benedetto; Twaddle, Nathan C.; Doerge, Daniel R.; Young, John F.; Fisher, Jeffrey W.

    2014-01-01

    The widespread usage of methylphenidate (MPH) in the pediatric population has received considerable attention due to its potential effect on child development. For the first time a physiologically based pharmacokinetic (PBPK) model has been developed in juvenile and adult humans and nonhuman primates to quantitatively evaluate species- and age-dependent enantiomer specific pharmacokinetics of MPH and its primary metabolite ritalinic acid. The PBPK model was first calibrated in adult humans using in vitro enzyme kinetic data of MPH enantiomers, together with plasma and urine pharmacokinetic data with MPH in adult humans. Metabolism of MPH in the small intestine was assumed to account for the low oral bioavailability of MPH. Due to lack of information, model development for children and juvenile and adult nonhuman primates primarily relied on intra- and interspecies extrapolation using allometric scaling. The juvenile monkeys appear to metabolize MPH more rapidly than adult monkeys and humans, both adults and children. Model prediction performance is comparable between juvenile monkeys and children, with average root mean squared error values of 4.1 and 2.1, providing scientific basis for interspecies extrapolation of toxicity findings. Model estimated human equivalent doses in children that achieve similar internal dose metrics to those associated with pubertal delays in juvenile monkeys were found to be close to the therapeutic doses of MPH used in pediatric patients. This computational analysis suggests that continued pharmacovigilance assessment is prudent for the safe use of MPH. PMID:25184666

  17. Gastrointestinal absorption of plutonium, uranium and neptunium in fed and fasted adult baboons: Application to humans

    SciTech Connect

    Bhattacharyya, M.H.; Larsen, R.P.; Oldham, R.D.; Moretti, E.S. ); Cohen, N.; Ralston, L.G.; Ayres, L. )

    1992-03-01

    Gastrointestinal (GI) absorption values of plutonium, uranium, and neptunium were determined in fed and fasted adult baboons. A dual isotope method of determining GI absorption, which does not require animal sacrifice, was validated and shown to compare well with the sacrifice method (summation of oral isotope in urine with that in tissues at sacrifice). For all three elements, mean GI absorption values were significantly high (5- to 50-fold) in 24-hour (h)-fasted animals than in fed animals, and GI absorption values for baboons agreed well with those for humans.

  18. 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...

  19. 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...

  20. 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...

  1. 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.

  2. Cloning of a DNA fragment encoding a heme-repressible hemoglobin-binding outer membrane protein from Haemophilus influenzae.

    PubMed Central

    Jin, H; Ren, Z; Pozsgay, J M; Elkins, C; Whitby, P W; Morton, D J; Stull, T L

    1996-01-01

    Haemophilus influenzae is able to use hemoglobin as a sole source of heme, and heme-repressible hemoglobin binding to the cell surface has been demonstrated. Using an affinity purification methodology, a hemoglobin-binding protein of approximately 120 kDa was isolated from H. influenzae type b strain HI689 grown in heme-restricted but not in heme-replete conditions. The isolated protein was subjected to N-terminal amino acid sequencing, and the derived amino acid sequence was used to design corresponding oligonucleotides. The oligonucleotides were used to probe a Southern blot of EcoRI-digested HI689 genomic DNA. A hybridizing band of approximately 4.2 kb was successfully cloned into pUC19. Using a 1.9-kb internal BglII fragment of the 4.2-kb clone as a probe, hybridization was seen in both typeable and nontypeable H. influenzae but not in other bacterial species tested. Following partial nucleotide sequencing of the 4.2-kb insert, a putative open reading frame was subcloned into an expression vector. The host Escherichia coli strain in which the cloned fragment was expressed bound biotinylated human hemoglobin, whereas binding of hemoglobin was not detected in E. coli with the vector alone. In conclusion, we hypothesize that the DNA fragment encoding an approximately 120-kDa heme-repressible hemoglobin-binding protein mediates one step in the acquisition of hemoglobin by H. influenzae in vivo. PMID:8757844

  3. Oxygen-organophosphate linkage in hemoglobin A. The double hump effect.

    PubMed Central

    Kister, J; Poyart, C; Edelstein, S J

    1987-01-01

    At low concentrations of chloride ions, and in the presence of nonsaturating concentrations of organophosphates, the oxygen equilibrium curves (OEC) for solutions of human adult hemoglobin exhibit a biphasic shape conveniently revealed by graphical analysis of the first derivative of the Hill equation with a characteristic form that we call "the double hump effect." This shape, observed for sub-saturating concentrations of organophosphates, stands in marked contrast to the simple lateral shifts of the OEC represented largely by scaling factors when pH or chloride are varied. In the case of protons or chloride, there is a self-buffering effect due to the presence of a large reservoir of proton or chloride binding sites not necessarily linked to oxygen, whereas such sites do not exist in the case of organophosphates. In addition, in the former case, we are dealing with curves measured at constant activity of the effector, while in the latter, at constant concentration. In the presence of saturating concentrations of inositol hexaphosphate (IHP), at low chloride concentration, the entire OEC is shifted to the right, including both its upper and lower asymptotes, indicating a decrease in the intrinsic oxygen affinities of both the T and R states. Theoretical considerations leading to a successful modeling of OEC obtained under nonsaturating and saturating concentrations of IHP required an expanded two-state allosteric model in which IHP-dependent variations in oxygen association constants for both the T and R conformations are taken into account. PMID:3676434

  4. Genetic Diversity of Coastal Bottlenose Dolphins Revealed by Structurally and Functionally Diverse Hemoglobins

    PubMed Central

    Remington, Nicole; Stevens, Robert D.; Wells, Randall S.; Hohn, Aleta; Dhungana, Suraj; Taboy, Celine H.; Crumbliss, Alvin L.; Henkens, Robert; Bonaventura, Celia

    2007-01-01

    Studies of structure-function relationships in the respiratory proteins of marine mammals revealed unexpected variations in the number and types of hemoglobins (Hbs) present in coastal bottlenose dolphins, Tursiops truncatus. We obtained blood samples from free-ranging coastal bottlenose dolphins as a component of capture-release studies. We found that the oxygen-binding functions of bottlenose dolphin blood are poised between effector-saturated and unsaturated levels, enabling exercise-dependent shifts in oxygen transfer functions. Isolated bottlenose dolphin Hbs showed elevated pH sensitivities (Bohr effects) and appreciably lower oxygen affinities than adult human Hb in the absence of allosteric effectors. These properties may be an adaptive modification that enhance oxygen delivery during diving episodes when oxygen tensions and effector levels are low. The Hbs of individual dolphins showed similar oxygen affinities, responses to effectors, and expression of heme-heme interaction in oxygen binding, but differed in their redox potentials and rates of autoxidation. The heterogeneity suggested by these functional variations in Hbs of individual dolphins was born out by variations in the molecular weights and numbers of their α and β globin chains. Although coastal bottlenose dolphins were expected to have a single type of Hb, the mass differences observed revealed considerable genetic diversity. There were multiple Hb forms in some individuals and differences in Hb patterns among individuals within the same community. PMID:17604574

  5. A comparative study of the temperature dependence of the oxygen-binding properties of mammalian hemoglobins.

    PubMed

    Coletta, M; Clementi, M E; Ascenzi, P; Petruzzelli, R; Condò, S G; Giardina, B

    1992-03-15

    The effect of temperature on the oxygen-binding properties of hemoglobin (Hb) from ruminants, such as ox, reindeer, musk ox, mouflon and egyptian water buffalo is compared to that of human adult Hb (HbA). A striking difference emerges where in the presence of chloride ions and in the absence of 2,3-diphosphoglycerate [Gri(2,3)P2] a strongly reduced exothermic oxygenation process is observed for all ruminant Hb investigated with respect to HbA. Next, in the presence of physiological concentrations of Gri(2,3)P2, HbA displays a less exothermic oxygenation process, with values tending toward those observed in ruminant Hb [where Gri(2,3)P2 is not a physiological effector and for which the addition of Gri(2,3)P2 has essentially no effect on the oxygenation enthalpy]. Different from HbA, the intrinsically less exothermic oxygen binding seems to be independent of the experimental conditions for ruminant Hb, underlying specific structural characteristics which might be responsible for this feature.

  6. 21 CFR 864.8165 - Calibrator for hemoglobin or hematocrit measurement.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Calibrator for hemoglobin or hematocrit measurement. 864.8165 Section 864.8165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents §...

  7. 21 CFR 864.8165 - Calibrator for hemoglobin or hematocrit measurement.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Calibrator for hemoglobin or hematocrit measurement. 864.8165 Section 864.8165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents §...

  8. 21 CFR 864.8165 - Calibrator for hemoglobin or hematocrit measurement.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Calibrator for hemoglobin or hematocrit measurement. 864.8165 Section 864.8165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents §...

  9. 21 CFR 864.8165 - Calibrator for hemoglobin or hematocrit measurement.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Calibrator for hemoglobin or hematocrit measurement. 864.8165 Section 864.8165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents §...

  10. 21 CFR 864.8165 - Calibrator for hemoglobin or hematocrit measurement.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Calibrator for hemoglobin or hematocrit measurement. 864.8165 Section 864.8165 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents §...

  11. Simultaneous imaging of blood flow and hemoglobin concentration change in skin tissue using NIR speckle patterns

    NASA Astrophysics Data System (ADS)

    Aizu, Yoshihisa; Hirata, Tatsuya; Maeda, Takaaki; Nishidate, Izumi; Yokoi, Naomichi

    2009-07-01

    We propose a method for imaging simultaneously blood flow and hemoglobin concentration change in skin tissue using speckle patterns acquired at two wavelengths of 780 and 830 nm. Experimental results demonstrate that the method is useful for time-varying analysis of blood circulation in human forearm skin tissue from one set of sequential speckle images.

  12. 76 FR 51041 - Hemoglobin Standards and Maintaining Adequate Iron Stores in Blood Donors; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... HUMAN SERVICES Food and Drug Administration Hemoglobin Standards and Maintaining Adequate Iron Stores in... Standards and Maintaining Adequate Iron Stores in Blood Donors.'' The purpose of this public workshop is to... donor safety and blood availability, and potential measures to maintain adequate iron stores in...

  13. Spin state transition in the active center of the hemoglobin molecule: DFT + DMFT study

    NASA Astrophysics Data System (ADS)

    Novoselov, D.; Korotin, Dm. M.; Anisimov, V. I.

    2016-05-01

    An ab initio study of electronic and spin configurations of the iron ion in the active center of the human hemoglobin molecule is presented. With a combination of the Density Functional Theory (DFT) method and the Dynamical Mean Field Theory (DMFT) approach, the spin state transition description in the iron ion during the oxidation process is significantly improved in comparison with previous attempts. It was found that the origin of the iron ion local moment behavior both for the high-spin and for the low-spin states in the hemoglobin molecule is caused by the presence of a mixture of several atomic states with comparable statistical probability.

  14. Detecting free hemoglobin in blood plasma and serum with luminescent terbium complexes.

    PubMed

    Morgner, Frank; Lecointre, Alexandre; Charbonnière, Loïc J; Löhmannsröben, Hans-Gerd

    2015-01-21

    Hemolysis, the rupturing of red blood cells, can result from numerous medical conditions (in vivo) or occur after collecting blood specimen or extracting plasma and serum out of whole blood (in vitro). In clinical laboratory practice, hemolysis can be a serious problem due to its potential to bias detection of various analytes or biomarkers. Here we present the first "mix-and-measure" method to assess the degree of hemolysis in biosamples using luminescence spectroscopy. Luminescent terbium complexes (LTC) were studied in the presence of free hemoglobin (Hb) as indicators for hemolysis in TRIS-buffer, and in fresh human plasma with absorption, excitation and emission measurements. Our findings indicate dynamic as well as resonance energy transfer (FRET) between the LTC and the porphyrin ligand of hemoglobin. This transfer leads to a decrease in luminescence intensity and decay time even at nanomolar hemoglobin concentrations either in buffer or plasma. Luminescent terbium complexes are very sensitive to free hemoglobin in buffer and blood plasma. Due to the instant change in luminescence properties of the LTC in presence of Hb it is possible to access the concentration of hemoglobin via spectroscopic methods without incubation time or further treatment of the sample thus enabling a rapid and sensitive detection of hemolysis in clinical diagnostics.

  15. Quantitative Absorption Cytometry for Measuring Red Blood Cell Hemoglobin Mass and Volume

    PubMed Central

    Schonbrun, Ethan; Malka, Roy; Di Caprio, Giuseppe; Schaak, Diane; Higgins, John M.

    2015-01-01

    We present an optical system, called the quantitative absorption cytometer (QAC), to measure the volume and hemoglobin mass of red blood cells flowing through a microfluidic channel. In contrast to clinical hematology analyzers, where cells are sphered in order for both volume and hemoglobin to be measured accurately, the QAC measures cells in their normal physiological shape. Human red blood cells are suspended in a refractive index-matching absorbing buffer, driven through a microfluidic channel, and imaged using a transmission light microscope onto a color camera. A red and a blue LED illuminate cells and images at each color are used to independently retrieve cell volume and hemoglobin mass. This system shows good agreement with red blood cell indices retrieved by a clinical hematology analyzer and in fact measures a smaller coefficient of variation of hemoglobin concentration. In addition to cell indices, the QAC returns height and mass maps of each measured cell. These quantitative images are valuable for analyzing the detailed morphology of individual cells as well as statistical outliers found in the data. We also measured red blood cells in hypertonic and hypotonic buffers to quantify the correlation between volume and hemoglobin mass under osmotic stress. Because this method is invariant to cell shape, even extremely nonspherical cells in hypertonic buffers can be measured accurately. PMID:24677669

  16. Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin.

    PubMed

    Feng, Liang; Gell, David A; Zhou, Suiping; Gu, Lichuan; Kong, Yi; Li, Jianqing; Hu, Min; Yan, Nieng; Lee, Christopher; Rich, Anne M; Armstrong, Robert S; Lay, Peter A; Gow, Andrew J; Weiss, Mitchell J; Mackay, Joel P; Shi, Yigong

    2004-11-24

    Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.

  17. Hemoglobin adducts of N-substituted aryl compounds in exposure control and risk assessment.

    PubMed

    Neumann, H G; Birner, G; Kowallik, P; Schütze, D; Zwirner-Baier, I

    1993-03-01

    Arylamines, nitroarenes, and azo dyes yield a common type of metabolite, the nitroarene, which produces a hydrolyzable adduct with protein and is closely related to the critical, ultimate toxic and genotoxic metabolite. The target dose as measured by hemoglobin adducts in erythrocytes reflects not only the actual uptake from the environment but also an individual's capacity for metabolic activation and is therefore an improved dosimeter for human exposure. The usefulness of hemoglobin adducts in molecular epidemiology is now widely recognized. With regard to risk assessment, many questions need to be answered. The described experiments in rats address some of these questions. The relationship between binding to hemoglobin in erythrocytes and to proteins in plasma has been found to vary considerably for a number of diamines. The fraction of hydrolyzable adducts out of the total protein adducts formed also varies in both compartments. This indicates that the kind of circulating metabolites and their availability in different compartments is compound specific. This has to do with the complex pattern of competing metabolic pathways, and the role of N-acetylation and deacetylation is emphasized. An example of nonlinear dose dependence adds to the complexity. Analysis of hemoglobin adducts reveals interesting insights into prevailing pathways, which not only apply to the chemical, but may also be useful to assess an individual's metabolic properties. In addition, it is demonstrated that the greater part of erythrocytes and benzidine-hemoglobin adducts are eliminated randomly in rats, i.e., following first-order kinetics.

  18. Molecular Mechanism of AHSP-Mediated Stabilization of Alpha-Hemoglobin

    SciTech Connect

    Feng,L.; Gell, D.; Zhou, S.; Gu, L.; Kong, Y.; Li, J.; Hu, M.; Yan, N.; Lee, C.; et al.

    2005-01-01

    Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.

  19. Red blood with blue-blood ancestry: Intriguing structure of a snail hemoglobin

    PubMed Central

    Lieb, Bernhard; Dimitrova, Konstantina; Kang, Hio-Sun; Braun, Sabrina; Gebauer, Wolfgang; Martin, Andreas; Hanelt, Ben; Saenz, Steven A.; Adema, Coen M.; Markl, Jürgen

    2006-01-01

    The phylogenetic enigma of snail hemoglobin, its isolated occurrence in a single gastropod family, the Planorbidae, and the lack of sequence data, stimulated the present study. We present here the complete cDNA and predicted amino acid sequence of two hemoglobin polypeptides from the planorbid Biomphalaria glabrata (intermediate host snail for the human parasite Schistosoma mansoni). Both isoforms contain 13 different, cysteine-free globin domains, plus a small N-terminal nonglobin “plug” domain with three cysteines for subunit dimerization (total Mr ≈ 238 kDa). We also identified the native hemoglobin molecule and present here a preliminary 3D reconstruction from electron microscopical images (3 nm resolution); it suggests a 3 × 2-mer quaternary structure (Mr ≈ 1.43 MDa). Moreover, we identified a previously undescribed rosette-like hemolymph protein that has been mistaken for hemoglobin. We also detected expression of an incomplete hemocyanin as trace component. The combined data show that B. glabrata hemoglobin evolved from pulmonate myoglobin, possibly to replace a less-efficient hemocyanin, and reveals a surprisingly simple evolutionary mechanism to create a high molecular mass respiratory protein from 78 similar globin domains. PMID:16877545

  20. Long-term culture of genome-stable bipotent stem cells from adult human liver.

    PubMed

    Huch, Meritxell; Gehart, Helmuth; van Boxtel, Ruben; Hamer, Karien; Blokzijl, Francis; Verstegen, Monique M A; Ellis, Ewa; van Wenum, Martien; Fuchs, Sabine A; de Ligt, Joep; van de Wetering, Marc; Sasaki, Nobuo; Boers, Susanne J; Kemperman, Hans; de Jonge, Jeroen; Ijzermans, Jan N M; Nieuwenhuis, Edward E S; Hoekstra, Ruurdtje; Strom, Stephen; Vries, Robert R G; van der Laan, Luc J W; Cuppen, Edwin; Clevers, Hans

    2015-01-15

    Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy. PMID:25533785

  1. Learning new color names produces rapid increase in gray matter in the intact adult human cortex

    PubMed Central

    Kwok, Veronica; Niu, Zhendong; Kay, Paul; Zhou, Ke; Mo, Lei; Jin, Zhen; So, Kwok-Fai; Tan, Li Hai

    2011-01-01

    The human brain has been shown to exhibit changes in the volume and density of gray matter as a result of training over periods of several weeks or longer. We show that these changes can be induced much faster by using a training method that is claimed to simulate the rapid learning of word meanings by children. Using whole-brain magnetic resonance imaging (MRI) we show that learning newly defined and named subcategories of the universal categories green and blue in a period of 2 h increases the volume of gray matter in V2/3 of the left visual cortex, a region known to mediate color vision. This pattern of findings demonstrates that the anatomical structure of the adult human brain can change very quickly, specifically during the acquisition of new, named categories. Also, prior behavioral and neuroimaging research has shown that differences between languages in the boundaries of named color categories influence the categorical perception of color, as assessed by judgments of relative similarity, by response time in alternative forced-choice tasks, and by visual search. Moreover, further behavioral studies (visual search) and brain imaging studies have suggested strongly that the categorical effect of language on color processing is left-lateralized, i.e., mediated by activity in the left cerebral hemisphere in adults (hence “lateralized Whorfian” effects). The present results appear to provide a structural basis in the brain for the behavioral and neurophysiologically observed indices of these Whorfian effects on color processing. PMID:21464316

  2. Adult Human Nasal Mesenchymal-Like Stem Cells Restore Cochlear Spiral Ganglion Neurons After Experimental Lesion

    PubMed Central

    Bas, Esperanza; Van De Water, Thomas R.; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M.

    2014-01-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

  3. Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver

    PubMed Central

    Huch, Meritxell; Gehart, Helmuth; van Boxtel, Ruben; Hamer, Karien; Blokzijl, Francis; Verstegen, Monique M.A.; Ellis, Ewa; van Wenum, Martien; Fuchs, Sabine A.; de Ligt, Joep; van de Wetering, Marc; Sasaki, Nobuo; Boers, Susanne J.; Kemperman, Hans; de Jonge, Jeroen; Ijzermans, Jan N.M.; Nieuwenhuis, Edward E.S.; Hoekstra, Ruurdtje; Strom, Stephen; Vries, Robert R.G.; van der Laan, Luc J.W.; Cuppen, Edwin; Clevers, Hans

    2015-01-01

    Summary Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy. PMID:25533785

  4. Morphologic characteristics of processes of nucleus pulposus cells in adult human intervertebral disc

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoyun; Wu, Xinghuo; Hui, Liu; Xu, Weihua; Liu, Xianze; Yang, Shuhua

    2008-12-01

    To explore morphologic characterizatics of cellular processes from adult human nucleus pulposus cells, the nucleus pulposus of adult human intervertebral disc were obtained from 8 patients (Thompson's grade I~II) and then the tissues specimens were carried out by frozen section and electron microscopic section as well as cell isolation and cultured, processes of nucleus pulposus cells were examined using light microscopy, laser scanning confocal microscopy and transmission electron microscopy. When examined at both the confocal and electron microscope level, all the cells possessed the processes and adjacent nucleus pulposus cells processes possessed a gap junction. But elongated and round cells can be examined when NP cells were monolayer cultured. The rate of elongated cells to round cells is 2.3 to 1. The elongated cells protrude along with the long axis of cell body without second processes. Dendritic processes of round cells protrude to all directions from the cell body with multiple-level processes. Processes are one of the morphologic characteristics of intervertebral disc cells which are different from articular cartilage chondrocytes. The research on processes functions will be helpful to understand pathomechanism of intervertebral disc degradation and open a new approach for cytobiology treatment of the intervertebral disc diseases.

  5. Human amniotic epithelial cells are reprogrammed more efficiently by induced pluripotency than adult fibroblasts.

    PubMed

    Easley, Charles A; Miki, Toshio; Castro, Carlos A; Ozolek, John A; Minervini, Crescenzio F; Ben-Yehudah, Ahmi; Schatten, Gerald P

    2012-06-01

    Cellular reprogramming from adult somatic cells into an embryonic cell-like state, termed induced pluripotency, has been achieved in several cell types. However, the ability to reprogram human amniotic epithelial cells (hAECs), an abundant cell source derived from discarded placental tissue, has only recently been investigated. Here we show that not only are hAECs easily reprogrammed into induced pluripotent stem cells (AE-iPSCs), but hAECs reprogram faster and more efficiently than adult and neonatal somatic dermal fibroblasts. Furthermore, AE-iPSCs express higher levels of NANOG and OCT4 compared to human foreskin fibroblast iPSCs (HFF1-iPSCs) and express decreased levels of genes associated with differentiation, including NEUROD1 and SOX17, markers of neuronal differentiation. To elucidate the mechanism behind the higher reprogramming efficiency of hAECs, we analyzed global DNA methylation, global histone acetylation, and the mitochondrial DNA A3243G point mutation. Whereas hAECs show no differences in global histone acetylation or mitochondrial point mutation accumulation compared to adult and neonatal dermal fibroblasts, hAECs demonstrate a decreased global DNA methylation compared to dermal fibroblasts. Likewise, quantitative gene expression analyses show that hAECs endogenously express OCT4, SOX2, KLF4, and c-MYC, all four factors used in cellular reprogramming. Thus, hAECs represent an ideal cell type for testing novel approaches for generating clinically viable iPSCs and offer significant advantages over postnatal cells that more likely may be contaminated by environmental exposures and infectious agents. PMID:22686477

  6. Carnivora: the primary structure of the Pacific Walrus (Odobenus rosmarus divergens, Pinnipedia) hemoglobin.

    PubMed

    Lin, H X; Kleinschmidt, T; Johnson, M L; Braunitzer, G

    1989-02-01

    The primary structure of the alpha- and beta-chains of the hemoglobin from the Pacific Walrus (Odobenus rosmarus divergens, Pinnipedia) is presented. Sequence analysis revealed only one hemoglobin component whereas two bands were found in polyacrylamide gel electrophoresis. The globin chains were separated by high-performance liquid chromatography and the sequences determined by automatic liquid- and gas-phase sequencing of the chains and their tryptic peptides. The alpha-chains show 20 and the beta-chains 12 exchanges compared to the corresponding human chains. In the alpha-chains one heme- and two alpha 1/beta 1-contacts were exchanged whereas in the beta-chains one alpha 1/beta 1-, one alpha 1/beta 2-and one heme-contact are substituted. Compared to Harbour Seal (Phoca vitulina) the Walrus hemoglobin shows 9 amino-acid replacements in the alpha-chains and 5 in the beta-chains. The relation between Pinnipedia and Arctoidea is discussed.

  7. Characteristics of High-Resolution Hemoglobin Measurement Microchip Integrated with Signal Processing Circuit

    NASA Astrophysics Data System (ADS)

    Noda, Toshihiko; Takao, Hidekuni; Ashiki, Mitsuaki; Ebi, Hiroyuki; Sawada, Kazuaki; Ishida, Makoto

    2004-04-01

    In this study, a microchip for measurement of hemoglobin in human blood has been proposed, fabricated and evaluated. The measurement principle of hemoglobin is based on the “cyanmethemoglobin method” that calculates the cyanmethemoglobin concentration by absorption photometry. A glass/silicon/silicon structure was used for the microchip. The middle silicon layer includes flow channels, and 45° mirrors formed at each end of the flow channels. Photodiodes and metal oxide semiconductor (MOS) integrated circuits were fabricated on the bottom silicon layer. The performance of the microchip for hemoglobin measurement was evaluated using a solution of red food color instead of a real blood sample. The fabricated microchip exhibited a similar performance to a nonminiaturized absorption cell which has the same optical path length. Signal processing output varied with solution concentration from 5.32 V to 5.55 V with very high stability due to differential signal processing.

  8. The primary structure of pale-throated three-toed sloth (Bradypus tridactylus, Xenarthra) hemoglobin.

    PubMed

    Kleinschmidt, T; März, J; Braunitzer, G

    1989-04-01

    The hemoglobin of the Pale-Throated Three-Toed Sloth (Bradypus tridactylus, Xenarthra) was separated into two components (ratio 4:1) with identical amino-acid analyses for the alpha- and beta-chains. The primary structures of both chains from the major component are given. They could be isolated by chromatography on carboxymethyl cellulose CM-52. The sequences have been determined by automatic Edman degradation of the native chains and their tryptic peptides. The comparison with human hemoglobin showed 27 substitutions in the alpha-chains and 33 in the beta-chains. In the alpha-chains one amino-acid exchange involves an alpha 1/beta 1-contact. In the beta-chains two heme- and four alpha 1/beta 1-contacts are substituted. The hemoglobin of the Sloth is compared to that of the Nine-Banded Armadillo (Dasypus novemcinctus), another representative of the order Xenerthra.

  9. High individual consistency in fear of humans throughout the adult lifespan of rural and urban burrowing owls

    NASA Astrophysics Data System (ADS)

    Carrete, Martina; Tella, José L.

    2013-12-01

    Human-induced rapid environmental changes challenge individuals by creating evolutionarily novel scenarios, where species encounter novel enemies, the new species sometimes being humans themselves. However, little is known about how individuals react to human presence, specifically whether they are able to habituate to human presence, as frequently assumed, or are selected based on their fear of humans. We tested whether fear of humans (measured as flight initiation distance in a diurnal owl) is reduced through habituation to human presence (plasticity) or whether it remains unchanged throughout the individuals' life. Results show an unusually high level of individual consistency in fear of humans throughout the adult lifespan of both rural (r = 0.96) and urban (r = 0.90) birds, lending no support to habituation. Further research should assess the role of inter-individual variability in fear of humans in shaping the distribution of individuals and species in an increasingly humanized world.

  10. High individual consistency in fear of humans throughout the adult lifespan of rural and urban burrowing owls.

    PubMed

    Carrete, Martina; Tella, José L

    2013-01-01

    Human-induced rapid environmental changes challenge individuals by creating evolutionarily novel scenarios, where species encounter novel enemies, the new species sometimes being humans themselves. However, little is known about how individuals react to human presence, specifically whether they are able to habituate to human presence, as frequently assumed, or are selected based on their fear of humans. We tested whether fear of humans (measured as flight initiation distance in a diurnal owl) is reduced through habituation to human presence (plasticity) or whether it remains unchanged throughout the individuals' life. Results show an unusually high level of individual consistency in fear of humans throughout the adult lifespan of both rural (r = 0.96) and urban (r = 0.90) birds, lending no support to habituation. Further research should assess the role of inter-individual variability in fear of humans in shaping the distribution of individuals and species in an increasingly humanized world. PMID:24343659

  11. Naturally crystalline hemoglobin of the nematode Mermis nigrescens. An in situ microspectrophotometric study of chemical properties and dichroism.

    PubMed Central

    Burr, A H; Harosi, F I

    1985-01-01

    A dichroic microspectrophotometer was used to measure isotropic and dichroic absorbance spectra of this unique cytoplasmic hemoglobin and its derivatives. A perfusion slide enabled changing the media bathing the Mermis head. The native spectrum, which has an exceptionally low alpha-band extinction, was shown to be entirely due to oxyhemoglobin. The CO-hemoglobin spectrum is more typical, however, the alpha- and beta-bands are unusually closely spaced. A ferric hemochrome was formed on oxidation with ferricyanide or hydroxylamine and was readily converted to ferric hemoglobin cyanide on adding cyanide. Aquoferric hemoglobin and ferric hemoglobin fluoride were not easily formed. Deoxyhemoglobin, identified by its typical absorption spectrum, was formed only under the extremely low O2 pressures attainable in the presence of dithionite. A glucose oxidase, catalase solution deoxygenated hemoglobin in human erythrocytes but not in adjacent Mermis preparations. The affinity for O2 is much greater than for CO. Also, spectral evidence points to an oxyheme environment that is different than in vertebrate hemoglobin and myoglobin. The polarization ratio (PR) magnitude and the PR spectrum were unaffected by perfusion with high refractive index solvents; therefore, form dichroism due to the rodlike crystals is negligible. Maximum extinction is approximately perpendicular to the long axis of the microscopic crystals, which are oriented parallel to the body axis within the hypodermal cells. The PR spectra of the hemoglobin derivatives strongly resemble the corresponding spectra previously reported of single crystals made of horse hemoglobin, whale myoglobin, or Aplysia myoglobin and change appropriately when the ligand is changed. This confirms that the intracellular crystals of Mermis are of oxyhemoglobin. PMID:3986282

  12. Primary structure of the hemoglobins from Sphenodon (Sphenodon punctatus, Tuatara, Rynchocephalia). Evidence for the expression of alpha D-gene.

    PubMed

    Abbasi, A; Wells, R M; Brittain, T; Braunitzer, G

    1988-08-01

    Sphenodon is the sole representative of the "beakhead" reptiles which were widely distributed during the Triassic period before the spectacular rise of dinosaurs. Sphenodon punctatus is the only survivor ("living fossil") of this period. The morphological features of Sphenodon are remarkably conservative and differ little from reptiles living 200 million years ago. In the present paper the determination of the primary structure of the tetrameric hemoglobins is described: three components are identified: hemoglobin A' (alpha A2 beta II2), hemoglobin A (alpha A2 beta I2) and hemoglobin D (alpha D2 beta II2). The components were characterized electrophoretically, the four different peptide chains were characterized by Triton electrophoresis as well as by high-performance liquid chromatography. The hemoglobins and--under dissociating conditions--also the chains, were isolated on columns of cellulose ion exchangers. Sequence determination was carried out after cleavage of the individual chains with trypsin and after a specific chemical cleavage of the Asp-Pro bond. For sequence determination the film technique and gas-phase method were employed. The data are compared with the sequence of the human hemoglobin, and interpretations of the amino-acid sequences are given. Particularly notable is the evidence of hemoglobin D: this hemoglobin (alpha D2 beta II2) is found only in birds, and in two cases in turtles. However, this component is not found in other reptiles. The results make possible an interpretation of the relatively high oxygen affinity and explain the lack of cooperativity (myoglobin properties) of these tetrameric hemoglobins. PMID:3214555

  13. Primary structure of the hemoglobins from Sphenodon (Sphenodon punctatus, Tuatara, Rynchocephalia). Evidence for the expression of alpha D-gene.

    PubMed

    Abbasi, A; Wells, R M; Brittain, T; Braunitzer, G

    1988-08-01

    Sphenodon is the sole representative of the "beakhead" reptiles which were widely distributed during the Triassic period before the spectacular rise of dinosaurs. Sphenodon punctatus is the only survivor ("living fossil") of this period. The morphological features of Sphenodon are remarkably conservative and differ little from reptiles living 200 million years ago. In the present paper the determination of the primary structure of the tetrameric hemoglobins is described: three components are identified: hemoglobin A' (alpha A2 beta II2), hemoglobin A (alpha A2 beta I2) and hemoglobin D (alpha D2 beta II2). The components were characterized electrophoretically, the four different peptide chains were characterized by Triton electrophoresis as well as by high-performance liquid chromatography. The hemoglobins and--under dissociating conditions--also the chains, were isolated on columns of cellulose ion exchangers. Sequence determination was carried out after cleavage of the individual chains with trypsin and after a specific chemical cleavage of the Asp-Pro bond. For sequence determination the film technique and gas-phase method were employed. The data are compared with the sequence of the human hemoglobin, and interpretations of the amino-acid sequences are given. Particularly notable is the evidence of hemoglobin D: this hemoglobin (alpha D2 beta II2) is found only in birds, and in two cases in turtles. However, this component is not found in other reptiles. The results make possible an interpretation of the relatively high oxygen affinity and explain the lack of cooperativity (myoglobin properties) of these tetrameric hemoglobins.

  14. Sustained Engraftment of Cryopreserved Human Bone Marrow CD34(+) Cells in Young Adult NSG Mice.

    PubMed

    Wiekmeijer, Anna-Sophia; Pike-Overzet, Karin; Brugman, Martijn H; Salvatori, Daniela C F; Egeler, R Maarten; Bredius, Robbert G M; Fibbe, Willem E; Staal, Frank J T

    2014-06-01

    Hematopoietic stem cells (HSCs) are defined by their ability to repopulate the bone marrow of myeloablative conditioned and/or (lethally) irradiated recipients. To study the repopulating potential of human HSCs, murine models have been developed that rely on the use of immunodeficient mice that allow engraftment of human cells. The NSG xenograft model has emerged as the current standard for this purpose allowing for engraftment and study of human T cells. Here, we describe adaptations to the original NSG xenograft model that can be readily implemented. These adaptations encompass use of adult mice instead of newborns and a short ex vivo culture. This protocol results in robust and reproducible high levels of lympho-myeloid engraftment. Immunization of recipient mice with relevant antigen resulted in specific antibody formation, showing that both T cells and B cells were functional. In addition, bone marrow cells from primary recipients exhibited repopulating ability following transplantation into secondary recipients. Similar results were obtained with cryopreserved human bone marrow samples, thus circumventing the need for fresh cells and allowing the use of patient derived bio-bank samples. Our findings have implications for use of this model in fundamental stem cell research, immunological studies in vivo and preclinical evaluations for HSC transplantation, expansion, and genetic modification.

  15. Isolation and Characterization of Human Adult Epithelial Stem Cells from the Periodontal Ligament.

    PubMed

    Athanassiou-Papaefthymiou, M; Papagerakis, P; Papagerakis, S

    2015-11-01

    We report a novel method for the isolation of adult human epithelial stem cells (hEpiSCs) from the epithelial component of the periodontal ligament-the human epithelial cell rests of Malassez (hERM). hEpiSC-rich integrin-α6(+ve) hERM cells derived by fluorometry can be clonally expanded, can grow organoids, and express the markers of pluripotency (OCT4, NANOG, SOX2), polycomb protein RING1B, and the hEpiSC supermarker LGR5. They maintain the growth profile of their originating hERM in vitro. Subcutaneous cotransplantation with mesenchymal stem cells from the dental pulp on poly-l-lactic acid scaffolds in nude mice gave rise to perfect heterotopic ossicles in vivo with ultrastructure of dentin, enamel, cementum, and bone. These remarkable fully mineralized ossicles underscore the importance of epithelial-mesenchymal crosstalk in tissue regeneration using human progenitor stem cells, which may have already committed to lineage despite maintaining hallmarks of pluripotency. In addition, we report the clonal expansion and isolation of human LGR5(+ve) cells from the hERM in xeno-free culture conditions. The genetic profile of LGR5(+ve) cells includes both markers of pluripotency and genes important for secretory epithelial and dental epithelial cell differentiation, giving us a first insight into periodontal ligament-derived hEpiSCs. PMID:26392003

  16. In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells

    PubMed Central

    Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P.; Walles, Heike

    2015-01-01

    In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions. PMID:26488607

  17. Examining the relationship between childhood animal cruelty motives and recurrent adult violent crimes toward humans.

    PubMed

    Overton, Joshua C; Hensley, Christopher; Tallichet, Suzanne E

    2012-03-01

    Few researchers have studied the predictive ability of childhood animal cruelty motives as they are associated with later recurrent violence toward humans. Based on a sample of 180 inmates at one medium- and one maximum-security prison in a Southern state, the present study examines the relationship among several retrospectively identified motives (fun, out of anger, hate for the animal, and imitation) for childhood animal cruelty and the later commission of violent crimes (murder, rape, assault, and robbery) against humans. Almost two thirds of the inmates reported engaging in childhood animal cruelty for fun, whereas almost one fourth reported being motivated either out of anger or imitation. Only one fifth of the respondents reported they had committed acts of animal cruelty because they hated the animal. Regression analyses revealed that recurrent animal cruelty was the only statistically significant variable in the model. Respondents who had committed recurrent childhood animal cruelty were more likely to have had committed recurrent adult violence toward humans. None of the motives for committing childhood animal cruelty had any effect on later violence against humans.

  18. In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

    PubMed

    Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P; Walles, Heike; Braspenning, Joris; Breitkopf-Heinlein, Katja

    2015-01-01

    In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.

  19. Non-Viral Generation of Neural Precursor-like Cells from Adult Human Fibroblasts

    PubMed Central

    Maucksch, C; Firmin, E; Butler-Munro, C; Montgomery, JM; Dottori, M; Connor, B

    2012-01-01

    Recent studies have reported direct reprogramming of human fibroblasts to mature neurons by the introduction of defined neural genes. This technology has potential use in the areas of neurological disease modeling and drug development. However, use of induced neurons for large-scale drug screening and cell-based replacement strategies is limited due to their inability to expand once reprogrammed. We propose it would be more desirable to induce expandable neural precursor cells directly from human fibroblasts. To date several pluripotent and neural transcription factors have been shown to be capable of converting mouse fibroblasts to neural stem/precursor-like cells when delivered by viral vectors. Here we extend these findings and demonstrate that transient ectopic insertion of the transcription factors SOX2 and PAX6 to adult human fibroblasts through use of non-viral plasmid transfection or protein transduction allows the generation of induced neural precursor (iNP) colonies expressing a range of neural stem and pro-neural genes. Upon differentiation, iNP cells give rise to neurons exhibiting typical neuronal morphologies and expressing multiple neuronal markers including tyrosine hydroxylase and GAD65/67. Importantly, iNP-derived neurons demonstrate electrophysiological properties of functionally mature neurons with the capacity to generate action potentials. In addition, iNP cells are capable of differentiating into glial fibrillary acidic protein (GFAP)-expressing astrocytes. This study represents a novel virusfree approach for direct reprogramming of human fibroblasts to a neural precursor fate. PMID:24693194

  20. 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.