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Sample records for fetal hemoglobin

  1. Fetal hemoglobin in sickle cell anemia.

    PubMed

    Akinsheye, Idowu; Alsultan, Abdulrahman; Solovieff, Nadia; Ngo, Duyen; Baldwin, Clinton T; Sebastiani, Paola; Chui, David H K; Steinberg, Martin H

    2011-07-01

    Fetal hemoglobin (HbF) is the major genetic modulator of the hematologic and clinical features of sickle cell disease, an effect mediated by its exclusion from the sickle hemoglobin polymer. Fetal hemoglobin genes are genetically regulated, and the level of HbF and its distribution among sickle erythrocytes is highly variable. Some patients with sickle cell disease have exceptionally high levels of HbF that are associated with the Senegal and Saudi-Indian haplotype of the HBB-like gene cluster; some patients with different haplotypes can have similarly high HbF. In these patients, high HbF is associated with generally milder but not asymptomatic disease. Studying these persons might provide additional insights into HbF gene regulation. HbF appears to benefit some complications of disease more than others. This might be related to the premature destruction of erythrocytes that do not contain HbF, even though the total HbF concentration is high. Recent insights into HbF regulation have spurred new efforts to induce high HbF levels in sickle cell disease beyond those achievable with the current limited repertory of HbF inducers. PMID:21490337

  2. 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) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal...

  3. 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) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal...

  4. 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) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal...

  5. 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) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7455 Fetal...

  6. 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...

  7. Fetal hemoglobin reactivation in baboon and man: a short perspective.

    PubMed

    Lavelle, D; DeSimone, J; Heller, P

    1993-01-01

    Present concepts of the mechanism of reactivation of synthesis of fetal hemoglobin (HbF) in the adult under conditions of erythropoietic stress are briefly reviewed. Since HbF can be considered an effective natural antisickling agent, the reactivation of its synthesis in patients with sickle cell anemia as a desirable therapeutic goal has been extensively explored since the discovery in 1982 that 5-azacytidine increases HbF levels in the baboon. Hydroxyurea (HU) has become the most widely used agent, although its effectiveness in increasing HbF levels and the number of F cells is highly variable. Recent investigations are cited showing that other agents such as butyrate, and the addition of recombinant hemopoietic growth factors, such as erythropoietin and stem cell factor, especially in combination with HU, offer important therapeutic possibilities. Transacting nuclear proteins are briefly discussed as possibly having a future role in the efforts of stimulating gamma-chain synthesis. PMID:7677951

  8. Fetal hemoglobin in sickle cell anemia: a glass half full?

    PubMed

    Steinberg, Martin H; Chui, David H K; Dover, George J; Sebastiani, Paola; Alsultan, Abdulrahman

    2014-01-23

    Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia by inhibiting deoxy sickle hemoglobin (HbS) polymerization. The blood concentration of HbF, or the number of cells with detectable HbF (F-cells), does not measure the amount of HbF/F-cell. Even patients with high HbF can have severe disease because HbF is unevenly distributed among F-cells, and some cells might have insufficient concentrations to inhibit HbS polymerization. With mean HbF levels of 5%, 10%, 20%, and 30%, the distribution of HbF/F-cell can greatly vary, even if the mean is constant. For example, with 20% HbF, as few as 1% and as many as 24% of cells can have polymer-inhibiting, or protective, levels of HbF of ∼10 pg; with lower HbF, few or no protected cells can be present. Only when the total HbF concentration is near 30% is it possible for the number of protected cells to approach 70%. Rather than the total number of F-cells or the concentration of HbF in the hemolysate, HbF/F-cell and the proportion of F-cells that have enough HbF to thwart HbS polymerization is the most critical predictor of the likelihood of severe sickle cell disease. PMID:24222332

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2016-07-01

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

  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. The LSD1 inhibitor RN-1 recapitulates the fetal pattern of hemoglobin synthesis in baboons (P. anubis).

    PubMed

    Rivers, Angela; Vaitkus, Kestis; Ibanez, Vinzon; Ruiz, Maria Armila; Jagadeeswaran, Ramasamy; Saunthararajah, Yogen; Cui, Shuaiying; Engel, James D; DeSimone, Joseph; Lavelle, Donald

    2016-06-01

    Increased fetal hemoglobin levels lessen the severity of symptoms and increase the lifespan of patients with sickle cell disease. Hydroxyurea, the only drug currently approved for the treatment of sickle cell disease, is not effective in a large proportion of patients and therefore new pharmacological agents that increase fetal hemoglobin levels have long been sought. Recent studies identifying LSD-1 as a repressor of γ-globin expression led to experiments demonstrating that the LSD-1 inhibitor RN-1 increased γ-globin expression in the sickle cell mouse model. Because the arrangement and developmental stage-specific expression pattern of the β-like globin genes is highly conserved between man and baboon, the baboon model remains the best predictor of activity of fetal hemoglobin-inducing agents in man. In this report, we demonstrate that RN-1 increases γ-globin synthesis, fetal hemoglobin, and F cells to high levels in both anemic and non-anemic baboons with activity comparable to decitabine, the most potent fetal hemoglobin-inducing agent known. RN-1 not only restores high levels of fetal hemoglobin but causes the individual 5' Iγ- and 3' Vγ-globin chains to be synthesized in the ratio characteristic of fetal development. Increased fetal hemoglobin was associated with increased levels of acetylated Histone H3, H3K4Me2, H3K4Me3, and RNA polymerase II at the γ-globin gene, and diminished γ-globin promoter DNA methylation. RN-1 is likely to induce clinically relevant levels of fetal hemoglobin in patients with sickle cell disease, although careful titration of the dose may be required to minimize myelotoxicity. PMID:26858356

  13. The LSD1 inhibitor RN-1 recapitulates the fetal pattern of hemoglobin synthesis in baboons (P. anubis)

    PubMed Central

    Rivers, Angela; Vaitkus, Kestis; Ibanez, Vinzon; Ruiz, Maria Armila; Jagadeeswaran, Ramasamy; Saunthararajah, Yogen; Cui, Shuaiying; Engel, James D.; DeSimone, Joseph; Lavelle, Donald

    2016-01-01

    Increased fetal hemoglobin levels lessen the severity of symptoms and increase the lifespan of patients with sickle cell disease. Hydroxyurea, the only drug currently approved for the treatment of sickle cell disease, is not effective in a large proportion of patients and therefore new pharmacological agents that increase fetal hemoglobin levels have long been sought. Recent studies identifying LSD-1 as a repressor of γ-globin expression led to experiments demonstrating that the LSD-1 inhibitor RN-1 increased γ-globin expression in the sickle cell mouse model. Because the arrangement and developmental stage-specific expression pattern of the β-like globin genes is highly conserved between man and baboon, the baboon model remains the best predictor of activity of fetal hemoglobin-inducing agents in man. In this report, we demonstrate that RN-1 increases γ-globin synthesis, fetal hemoglobin, and F cells to high levels in both anemic and non-anemic baboons with activity comparable to decitabine, the most potent fetal hemoglobin-inducing agent known. RN-1 not only restores high levels of fetal hemoglobin but causes the individual 5′ Iγ- and 3′ Vγ-globin chains to be synthesized in the ratio characteristic of fetal development. Increased fetal hemoglobin was associated with increased levels of acetylated Histone H3, H3K4Me2, H3K4Me3, and RNA polymerase II at the γ-globin gene, and diminished γ-globin promoter DNA methylation. RN-1 is likely to induce clinically relevant levels of fetal hemoglobin in patients with sickle cell disease, although careful titration of the dose may be required to minimize myelotoxicity. PMID:26858356

  14. Pomalidomide and lenalidomide regulate erythropoiesis and fetal hemoglobin production in human CD34+ cells

    PubMed Central

    Moutouh-de Parseval, Laure A.; Verhelle, Dominique; Glezer, Emilia; Jensen-Pergakes, Kristen; Ferguson, Gregory D.; Corral, Laura G.; Morris, Christopher L.; Muller, George; Brady, Helen; Chan, Kyle

    2007-01-01

    Sickle-cell disease (SCD) and β thalassemia constitute worldwide public health problems. New therapies, including hydroxyurea, have attempted to augment the synthesis of fetal hemoglobin (HbF) and improve current treatment. Lenalidomide and pomalidomide are members of a class of immunomodulators used as anticancer agents. Because clinical trials have demonstrated that lenalidomide reduces or eliminates the need for transfusions in some patients with disrupted blood cell production, we investigated the effects of lenalidomide and pomalidomide on erythropoiesis and hemoglobin synthesis. We used an in vitro erythropoiesis model derived from human CD34+ progenitor cells from normal and SCD donors. We found that both compounds slowed erythroid maturation, increased proliferation of immature erythroid cells, and regulated hemoglobin transcription, resulting in potent induction of HbF without the cytotoxicity associated with other HbF inducers. When combined with hydroxyurea, pomalidomide and, to a lesser extent, lenalidomide were found to have synergistic effects on HbF upregulation. Our results elucidate what we believe to be a new mechanism of action of pomalidomide and lenalidomide and support the hypothesis that pomalidomide, used alone or in combination with hydroxyurea, may improve erythropoiesis and increase the ratio of fetal to adult hemoglobin. These findings support the evaluation of pomalidomide as an innovative new therapy for β-hemoglobinopathies. PMID:18064299

  15. Hereditary persistence of fetal hemoglobin, beta thalassemia, and the hemoglobin delta-beta locus: further family data and genetic interpretations.

    PubMed Central

    Bethlenfalvay, N C; Motulsky, A G; Ringelhann, B; Lehmann, H; Humbert, J R; Konotey-Ahulu, F I

    1975-01-01

    Three Negro kindreds with hereditary persistence of fetal hemoglobin (HPFH) alone and in combination with various other hemoglobin abnormalities including beta thalassemia are presented. Among 11 offspring of two women heterozygous for both HPFH and the delta chain mutation Hb B2, five inherited the HPFH gene and six inherited the Hb B2 gene. In another kindred, a man inferred to be heterozygous for both HPFH and Hb C had six children; three offsprivg obtained the Hb C gene and three the HPFH gene. Similarly, a woman heterozygous for both Hb S and HPFH transmitted the Hb S gene to one of her two children and the HPFH gene to the other. Thus among 19 offspring, no crossovers between the HPFH locus or the Hb delta-beta locus were observed. These and earlier data are compatible with deletion of the Hb beta and delta loci as the primary event to explain the genetic origin of HPFH. Genetic considerations indicate that the finding of a single person with a hematologically normal phenotype among offspring of heterozygotes for both the African type of HPFH and a Hb beta or Hb delta structural abnormality would invalidate the deletion model. Images Fig. 2 PMID:1124762

  16. Forced chromatin looping raises fetal hemoglobin in adult sickle cells to higher levels than pharmacologic inducers.

    PubMed

    Breda, Laura; Motta, Irene; Lourenco, Silvia; Gemmo, Chiara; Deng, Wulan; Rupon, Jeremy W; Abdulmalik, Osheiza Y; Manwani, Deepa; Blobel, Gerd A; Rivella, Stefano

    2016-08-25

    Overcoming the silencing of the fetal γ-globin gene has been a long-standing goal in the treatment of sickle cell disease (SCD). The major transcriptional enhancer of the β-globin locus, called the locus control region (LCR), dynamically interacts with the developmental stage-appropriate β-type globin genes via chromatin looping, a process requiring the protein Ldb1. In adult erythroid cells, the LCR can be redirected from the adult β- to the fetal γ-globin promoter by tethering Ldb1 to the human γ-globin promoter with custom-designed zinc finger (ZF) proteins (ZF-Ldb1), leading to reactivation of γ-globin gene expression. To compare this approach to pharmacologic reactivation of fetal hemoglobin (HbF), hematopoietic cells from patients with SCD were treated with a lentivirus expressing the ZF-Ldb1 or with chemical HbF inducers. The HbF increase in cells treated with ZF-Ldb1 was more than double that observed with decitabine and pomalidomide; butyrate had an intermediate effect whereas tranylcypromine and hydroxyurea showed relatively low HbF reactivation. ZF-Ldb1 showed comparatively little toxicity, and reduced sickle hemoglobin (HbS) synthesis as well as sickling of SCD erythroid cells under hypoxic conditions. The efficacy and low cytotoxicity of lentiviral-mediated ZF-Ldb1 gene transfer compared with the drug regimens support its therapeutic potential for the treatment of SCD. PMID:27405777

  17. Compound heterozygote state for GgammaAgamma(deltabeta) degrees -thalassemia and hereditary persistence of fetal hemoglobin.

    PubMed

    Fucharoen, Supan; Panyasai, Sitthichai; Surapot, Satja; Fucharoen, Goonnapa; Sanchaisuriya, Kanokwan

    2005-10-01

    We report a hitherto undescribed interaction of a deletional (deltabeta) degrees -thalassemia and a deletional hereditary persistence of fetal hemoglobin (HPFH) in an adult Thai individual. He was a 40-year-old Thai male who had the following hematologic data: Hb 13.9 g/dL, Hct 43.8%, MCV 78.0 fL, MCH 24.7 pg, MCHC 31.6 g/dL, and RDW 17.1%. Hemoglobin analysis revealed 97% Hb F with Ggamma-globin chain predominant. Globin gene analyses demonstrated that he carried the GgammaAgamma(deltabeta) degrees -thalassemia deletion in trans to the HPFH-6. Hematologic data of the patient were compared to those of the heterozygotes for these high-Hb F determinants found in his parents and an unrelated Thai patient with a compound HPFH-6/deletion-inversion Ggamma(Agammadeltabeta) degrees -thalassemia previously described. PMID:16184575

  18. Disruption of the Hbs1l-Myb locus causes hereditary persistence of fetal hemoglobin in a mouse model.

    PubMed

    Suzuki, Mikiko; Yamazaki, Hiromi; Mukai, Harumi Y; Motohashi, Hozumi; Shi, Lihong; Tanabe, Osamu; Engel, James Douglas; Yamamoto, Masayuki

    2013-04-01

    The human β-globin locus is comprised of embryonic, fetal, and adult globin genes, each of which is expressed at distinct stages of pre- and postnatal development. Functional defects in globin proteins or expression results in mild to severe anemia, such as in sickle-cell disease or β-thalassemia, but the clinical symptoms of both disorders are ameliorated by persistent expression of the fetal globin genes. Recent genome-wide association studies (GWAS) identified the intergenic region between the HBS1L and MYB loci as a candidate modifier of fetal hemoglobin expression in adults. However, it remains to be clarified whether the enhancer activity within the HBS1L-MYB regulatory domain contributes to the production of fetal hemoglobin in adults. Here we report a new mouse model of hereditary persistence of fetal hemoglobin (HPFH) in which a transgene was randomly inserted into the orthologous murine Hbs1l-Myb locus. This mutant mouse exhibited typically elevated expression of embryonic globins and hematopoietic parameters similar to those observed in human HPFH. These results support the contention that mutation of the HBS1L-MYB genomic domain is responsible for elevated expression of the fetal globin genes, and this model serves as an important means for the analysis of networks that regulate fetal globin gene expression. PMID:23428869

  19. The investigation of resveratrol and analogs as potential inducers of fetal hemoglobin.

    PubMed

    Theodorou, Andria; Phylactides, Marios; Forti, Luca; Cramarossa, Maria Rita; Spyrou, Pantelis; Gambari, Roberto; Thein, Swee Lay; Kleanthous, Marina

    2016-05-01

    Βeta-thalassemia, is a hemoglobinopathy characterized by reduced beta-globin chain synthesis, leading to imbalanced globin chain production, ineffective erythropoiesis and anemia. Increasing gamma-globin gene expression is a promising therapeutic approach as it reduces this imbalance by combining with the excess alpha globin chains and producing fetal hemoglobin (HbF). Furthermore, increased iron absorption and repeated blood transfusions lead to iron overload and tissue damage secondary to reactive oxygen species. Compounds exhibiting both antioxidant and HbF inducing activities are, therefore, highly desirable therapeutic agents. Resveratrol, a natural phytoalexin, combines these two activities but is also cytotoxic. Nine hydroxystilbenic resveratrol derivatives were synthesized in an attempt to identify compounds that retain the HbF-inducing and antioxidant activities of resveratrol but exhibit reduced cytotoxicity. Three derivatives (P1, P4 and P11) exhibited similar hemoglobin-inducing properties to resveratrol in K562 cells, however, only P11 showed reduced cytotoxicity. All three derivatives demonstrated variable HbF-inducing activity in primary erythroid progenitor cells from healthy donors. Resveratrol and P11 increased HbF induction significantly, with P11 having the highest activity. Additionally, P4 significantly increased progenitor numbers. A combinatorial treatment in K562 cells using resveratrol and decitabine resulted in a statistically significant increase in hemoglobin-inducing activity only above the level shown by resveratrol alone. PMID:27067481

  20. Original Research: Stable expression of miR-34a mediates fetal hemoglobin induction in K562 cells.

    PubMed

    Ward, Christina M; Li, Biaoru; Pace, Betty S

    2016-04-01

    Sickle cell anemia is a common genetic disorder caused by a point mutation in the sixth codon of the β-globin gene affecting people of African descent worldwide. A wide variety of clinical phenotypes ranging from mild to severe symptoms and complications occur due to hemoglobin S polymerization, red blood cell sickling, and vaso-occlusion. Research efforts are ongoing to develop strategies of fetal hemoglobin (HbF; α2γ2) induction to inhibit sickle hemoglobin polymerization and improve clinical outcomes. Insights have been gained from investigating mutations in the β-globin locus or transcription factors involved in the mechanisms of hemoglobin switching. Recent efforts to expand molecular targets that modulate γ-globin expression involve microRNAs that work through posttranscriptional gene regulation. Therefore, the goal of our study was to identify novel microRNA genes involved in fetal hemoglobin expression. Using in silico analysis, we identified a miR-34a binding site in the γ-globin mRNA which was tested for functional relevance. Stable expression of the shMIMIC miR-34a lentivirus vector increased fetal hemoglobin levels in single cell K562 clones consistent with silencing of a γ-globin gene repressor. Furthermore, miR-34a promoted cell differentiation supported by increased expression of KLF1, glycophorin A, and the erythropoietin receptor. Western blot analysis of known negative regulators of γ-globin including YY1, histone deacetylase 1, and STAT3, which are regulated by miR-34a showed no change in YY1 and histone deacetylase 1 levels; however, total- and phosphorylated-STAT3 levels were decreased in single cell miR-34a K562 clones. These data support a mechanism of fetal hemoglobin activation by miR-34a involving STAT3 gene silencing. PMID:26940952

  1. The X-linked F cell production locus: Genetic mapping and role in fetal hemoglobin production

    SciTech Connect

    Chang, Y.C.; Smith, K.D.; Moore, R.D.

    1994-09-01

    Postnatal fetal hemoglobin (Hb F) production is confined to a subset of erythocytes termed F-cells. There is a 10-20 fold variation in F-cell production in sickle cell disease (SCD) and normal individuals. Most of the variation in F-cell production has been attributed to a diallelic (High, Low) X-linked gene, the F-cell production (FCP) locus that we recently mapped to Xp22.2-22.3 (LOD=4.56, theta=0.04). Using multiple regression analysis in 262 Jamaican SCD patients we determined the relative contribution of the FCP locus and other variables previously associated with variation in Hb F level (gender, age, beta-globin haplotypes, number of alpha-globin genes and the FCP locus phenotypes). When the FCP locus is in the regression model, the FCP locus alone accounts for approximately 40% of the variation in Hb F level while the contribution of age, alpha-globin gene number, and beta-globin haplotypes was insignificant. When individuals with High FCP allele are removed from the analysis, the beta globin haplotype now contribute to >10% of the Hb F variation. We conclude that the X-linked FCP locus is the major determinant of all known variables in Hb F production. Using 4 highly polymorphic dinucleotide repeat markers that we identified from cosmids in Xp22.2-22.3, have localized the FCP locus to a 1 Mb minimal candidate region between DXS143 and DXS410.

  2. Genetics of fetal hemoglobin in Tanzanian and British patients with sickle cell anemia.

    PubMed

    Makani, Julie; Menzel, Stephan; Nkya, Siana; Cox, Sharon E; Drasar, Emma; Soka, Deogratius; Komba, Albert N; Mgaya, Josephine; Rooks, Helen; Vasavda, Nisha; Fegan, Gregory; Newton, Charles R; Farrall, Martin; Thein, Swee Lay

    2011-01-27

    Fetal hemoglobin (HbF, α(2)γ(2)) is a major contributor to the remarkable phenotypic heterogeneity of sickle cell anemia (SCA). Genetic variation at 3 principal loci (HBB cluster on chromosome 11p, HBS1L-MYB region on chromosome 6q, and BCL11A on chromosome 2p) have been shown to influence HbF levels and disease severity in β-thalassemia and SCA. Previous studies in SCA, however, have been restricted to populations from the African diaspora, which include multiple genealogies. We have investigated the influence of these 3 loci on HbF levels in sickle cell patients from Tanzania and in a small group of African British sickle patients. All 3 loci have a significant impact on the trait in both patient groups. The results suggest the presence of HBS1L-MYB variants affecting HbF in patients who are not tracked well by European-derived markers, such as rs9399137. Additional loci may be identified through independent genome-wide association studies in African populations. PMID:21068433

  3. Decitabine Increases Fetal Hemoglobin in P. Anubis by Increasing γ-globin Gene Transcription

    PubMed Central

    Akpan, Imo; Banzon, Virryan; Ibanez, Vinzon; Vaitkus, Kestis; DeSimone, Joseph; Lavelle, Donald

    2014-01-01

    1) Objective The mechanism responsible for increased fetal hemoglobin (HbF) levels following decitabine treatment remains controversial. These experiments were performed to evaluate the role of transcriptional versus translational mechanisms in the ability of decitabine to increase HbF levels in vivo. 2) Methods Three normal, nonanemic baboons were treated with decitabine subcutaneously (0.5mg/kg/d) for 10 days. The effect of decitabine on globin chain synthesis and globin mRNA levels was measured in pre- and post-treatment bone marrow (BM) aspirates by biosynthetic radiolabelling with [3H] leucine followed by separation of globin chains by HPLC, and real time PCR, respectively. The effect on DNA methylation of the ε- and γ-globin gene promoters was determined by bisulfite sequence analysis. 3) Results Decitabine treatment of normal, nonanemic baboons induced similar increases in the γ/γ+β chain synthetic ratio and the γ/total β-like globin RNA ratio and also increased expression of ε-globin transcripts. Increased expression of ε- and γ-globin was associated with decreased DNA methylation of the ε- and γ-globin gene promoters. 4) Conclusion Decitabine increases HbF in vivo by transcriptional activation of the γ-globin gene. PMID:20713129

  4. S110, a novel decitabine dinucleotide, increases fetal hemoglobin levels in baboons (P. anubis)

    PubMed Central

    2010-01-01

    Background S110 is a novel dinucleoside analog that could have advantages over existing DNA methyltransferase (DNMT) inhibitors such as decitabine. A potential therapeutic role for S110 is to increase fetal hemoglobin (HbF) levels to treat β-hemoglobinopathies. In these experiments the effect of S110 on HbF levels in baboons and its ability to reduce DNA methylation of the γ-globin gene promoter in vivo were evaluated. Methods The effect of S110 on HbF and γ-globin promoter DNA methylation was examined in cultured human erythroid progenitors and in vivo in the baboon pre-clinical model. S110 pharmacokinetics was also examined in the baboon model. Results S110 increased HbF and reduced DNA methylation of the γ-globin promoter in human erythroid progenitors and in baboons when administered subcutaneously. Pharmacokinetic analysis was consistent with rapid conversion of S110 into the deoxycytosine analog decitabine that binds and depletes DNA. Conclusion S110 is rapidly converted into decitabine, hypomethylates DNA, and induces HbF in cultured human erythroid progenitors and the baboon pre-clinical model. PMID:20932295

  5. Screening of Transcription Factors Involved in Fetal Hemoglobin Regulation Using Phylogenetic Footprinting

    PubMed Central

    de Souza Carrocini, Gisele Cristine; Venancio, Larissa Paola Rodrigues; Bonini-Domingos, Claudia Regina

    2015-01-01

    Fetal hemoglobin (Hb F) is an important genetic modulator of the beta-hemoglobinopathies. The regulation of Hb F levels is influenced by transcription factors. We used phylogenetic footprinting to screen transcription factors that have binding sites in HBG1 and HBG2 genes’ noncoding regions in order to know the genetic determinants of the Hb F expression. Our analysis showed 354 conserved motifs in the noncoding regions of HBG1 gene and 231 motifs in the HBG2 gene between the analyzed species. Of these motifs, 13 showed relation to Hb F regulation: cell division cycle-5 (CDC5), myelo-blastosis viral oncogene homolog (c-MYB), transcription factor CP2 (TFCP2), GATA binding protein 1 (GATA-1), GATA binding protein 2 (GATA-2), nuclear factor erythroid 2 (NF-E2), nuclear transcription factor Y (NF-Y), runt-related transcription factor 1 (RUNX-1), T-cell acute lymphocytic leukemia 1 (TAL-1), YY1 transcription factor (YY1), beta protein 1 (BP1), chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII), and paired box 1 (PAX-1). The last three motifs were conserved only in the noncoding regions of the HBG1 gene. The understanding of genetic elements involved in the maintenance of high Hb F levels may provide new efficient therapeutic strategies in the beta-hemoglobinopathies treatment, promoting reduction in clinical complications of these genetic disorders. PMID:26543346

  6. Compound heterozygosity for KLF1 mutations associated with remarkable increase of fetal hemoglobin and red cell protoporphyrin

    PubMed Central

    Satta, Stefania; Perseu, Lucia; Moi, Paolo; Asunis, Isadora; Cabriolu, Annalisa; Maccioni, Liliana; Demartis, Franca Rosa; Manunza, Laura; Cao, Antonio; Galanello, Renzo

    2011-01-01

    The persistence of high fetal hemoglobin level in adults may ameliorate the clinical phenotype of beta-thalassemia and sickle cell anemia. Several genetic variants responsible for hereditary persistence of fetal hemoglobin, linked and not linked to the beta globin gene cluster, have been identified in patients and in normal individuals. Monoallelic loss of KLF1, a gene with a key role in erythropoiesis, has been recently reported to be responsible for persistence of high levels of fetal hemoglobin. In a Sardinian family, high levels of HbF (22.1–30.9%) were present only in compound heterozygotes for the S270X nonsense and K332Q missense mutations, while the isolated S270X nonsense (haploinsufficiency) or K332Q missense mutation were associated with normal HbF levels (<1.5%). Functionally, the K332Q Klf1 mutation impairs binding to the BCl11A gene and activation of the γ- and β-globin promoters. Moreover, we report for the first time the association of KLF1 mutations with very high levels of zinc protoporphyrin. PMID:21273267

  7. Fetal hemoglobin in sickle cell anemia: genetic studies of the Arab-Indian haplotype.

    PubMed

    Ngo, Duyen; Bae, Harold; Steinberg, Martin H; Sebastiani, Paola; Solovieff, Nadia; Baldwin, Clinton T; Melista, Efthymia; Safaya, Surinder; Farrer, Lindsay A; Al-Suliman, Ahmed M; Albuali, Waleed H; Al Bagshi, Muneer H; Naserullah, Zaki; Akinsheye, Idowu; Gallagher, Patrick; Luo, Hong-yuan; Chui, David H K; Farrell, John J; Al-Ali, Amein K; Alsultan, Abdulrahman

    2013-06-01

    Sickle cell anemia is common in the Middle East and India where the HbS gene is sometimes associated with the Arab-Indian (AI) β-globin gene (HBB) cluster haplotype. In this haplotype of sickle cell anemia, fetal hemoglobin (HbF) levels are 3-4 fold higher than those found in patients with HbS haplotypes of African origin. Little is known about the genetic elements that modulate HbF in AI haplotype patients. We therefore studied Saudi HbS homozygotes with the AI haplotype (mean HbF 19.2±7.0%, range 3.6 to 39.6%) and employed targeted genotyping of polymorphic sites to explore cis- and trans- acting elements associated with high HbF expression. We also described sequences which appear to be unique to the AI haplotype for which future functional studies are needed to further define their role in HbF modulation. All cases, regardless of HbF concentration, were homozygous for AI haplotype-specific elements cis to HBB. SNPs in BCL11A and HBS1L-MYB that were associated with HbF in other populations explained only 8.8% of the variation in HbF. KLF1 polymorphisms associated previously with high HbF were not present in the 44 patients tested. More than 90% of the HbF variance in sickle cell patients with the AI haplotype remains unexplained by the genetic loci that we studied. The dispersion of HbF levels among AI haplotype patients suggests that other genetic elements modulate the effects of the known cis- and trans-acting regulators. These regulatory elements, which remain to be discovered, might be specific in the Saudi and some other populations where HbF levels are especially high. PMID:23465615

  8. Chemical Inhibition of Histone Deacetylases 1 and 2 Induces Fetal Hemoglobin through Activation of GATA2

    PubMed Central

    Golonzhka, Olga; Chonkar, Apurva; Tamang, David; van Duzer, John H.; Jones, Simon S.; Jarpe, Matthew B.

    2016-01-01

    Therapeutic intervention aimed at reactivation of fetal hemoglobin protein (HbF) is a promising approach for ameliorating sickle cell disease (SCD) and β-thalassemia. Previous studies showed genetic knockdown of histone deacetylase (HDAC) 1 or 2 is sufficient to induce HbF. Here we show that ACY-957, a selective chemical inhibitor of HDAC1 and 2 (HDAC1/2), elicits a dose and time dependent induction of γ-globin mRNA (HBG) and HbF in cultured primary cells derived from healthy individuals and sickle cell patients. Gene expression profiling of erythroid progenitors treated with ACY-957 identified global changes in gene expression that were significantly enriched in genes previously shown to be affected by HDAC1 or 2 knockdown. These genes included GATA2, which was induced greater than 3-fold. Lentiviral overexpression of GATA2 in primary erythroid progenitors increased HBG, and reduced adult β-globin mRNA (HBB). Furthermore, knockdown of GATA2 attenuated HBG induction by ACY-957. Chromatin immunoprecipitation and sequencing (ChIP-Seq) of primary erythroid progenitors demonstrated that HDAC1 and 2 occupancy was highly correlated throughout the GATA2 locus and that HDAC1/2 inhibition led to elevated histone acetylation at well-known GATA2 autoregulatory regions. The GATA2 protein itself also showed increased binding at these regions in response to ACY-957 treatment. These data show that chemical inhibition of HDAC1/2 induces HBG and suggest that this effect is mediated, at least in part, by histone acetylation-induced activation of the GATA2 gene. PMID:27073918

  9. 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

  10. 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

  11. Inhibition of G9a methyltransferase stimulates fetal hemoglobin production by facilitating LCR/γ-globin looping.

    PubMed

    Krivega, Ivan; Byrnes, Colleen; de Vasconcellos, Jaira F; Lee, Y Terry; Kaushal, Megha; Dean, Ann; Miller, Jeffery L

    2015-07-30

    Induction of fetal hemoglobin (HbF) production in adult erythrocytes can reduce the severity of sickle cell disease and β-thalassemia. Transcription of β-globin genes is regulated by the distant locus control region (LCR), which is brought into direct gene contact by the LDB1/GATA-1/TAL1/LMO2-containing complex. Inhibition of G9a H3K9 methyltransferase by the chemical compound UNC0638 activates fetal and represses adult β-globin gene expression in adult human hematopoietic precursor cells, but the underlying mechanisms are unclear. Here we studied UNC0638 effects on β-globin gene expression using ex vivo differentiation of CD34(+) erythroid progenitor cells from peripheral blood of healthy adult donors. UNC0638 inhibition of G9a caused dosed accumulation of HbF up to 30% of total hemoglobin in differentiated cells. Elevation of HbF was associated with significant activation of fetal γ-globin and repression of adult β-globin transcription. Changes in gene expression were associated with widespread loss of H3K9me2 in the locus and gain of LDB1 complex occupancy at the γ-globin promoters as well as de novo formation of LCR/γ-globin contacts. Our findings demonstrate that G9a establishes epigenetic conditions preventing activation of γ-globin genes during differentiation of adult erythroid progenitor cells. In this view, manipulation of G9a represents a promising epigenetic approach for treatment of β-hemoglobinopathies. PMID:25979948

  12. SENP1, but not fetal hemoglobin, differentiates Andean highlanders with chronic mountain sickness from healthy individuals among Andean highlanders.

    PubMed

    Hsieh, Matthew M; Callacondo, David; Rojas-Camayo, Jose; Quesada-Olarte, Jose; Wang, Xunde; Uchida, Naoya; Maric, Irina; Remaley, Alan T; Leon-Velarde, Fabiola; Villafuerte, Francisco C; Tisdale, John F

    2016-06-01

    Chronic mountain sickness (CMS) results from chronic hypoxia. It is unclear why certain highlanders develop CMS. We hypothesized that modest increases in fetal hemoglobin (HbF) are associated with lower CMS severity. In this cross-sectional study, we found that HbF levels were normal (median = 0.4%) in all 153 adult Andean natives in Cerro de Pasco, Peru. Compared with healthy adults, the borderline elevated hemoglobin group frequently had symptoms (headaches, tinnitus, cyanosis, dilatation of veins) of CMS. Although the mean hemoglobin level differed between the healthy (17.1 g/dL) and CMS (22.3 g/dL) groups, mean plasma erythropoietin (EPO) levels were similar (healthy, 17.7 mIU/mL; CMS, 12.02 mIU/mL). Sanger sequencing determined that single-nucleotide polymorphisms in endothelial PAS domain 1 (EPAS1) and egl nine homolog 1 (EGLN1), associated with lower hemoglobin in Tibetans, were not identified in Andeans. Sanger sequencing of sentrin-specific protease 1 (SENP1) and acidic nuclear phosphoprotein 32 family, member D (ANP32D), in healthy and CMS individuals revealed that non-G/G genotypes were associated with higher CMS scores. No JAK2 V617F mutation was detected in CMS individuals. Thus, HbF and other classic erythropoietic parameters did not differ between healthy and CMS individuals. However, the non-G/G genotypes of SENP1 appeared to differentiate individuals with CMS from healthy Andean highlanders. PMID:26952840

  13. Detection of a major gene for heterocellular hereditary persistence of fetal hemoglobin after accounting for genetic modifiers.

    PubMed

    Thein, S L; Sampietro, M; Rohde, K; Rochette, J; Weatherall, D J; Lathrop, G M; Demenais, F

    1994-02-01

    "Heterocellular hereditary persistence of fetal hemoglobin" (HPFH) is the term used to describe the genetically determined persistence of fetal hemoglobin (Hb F) production into adult life, in the absence of any related hematological disorder. Whereas some forms are caused by mutations in the beta-globin gene cluster on chromosome 11, others segregate independently. While the latter are of particular interest with respect to the regulation of globin gene switching, it has not been possible to determine their chromosomal location, mainly because their mode of inheritance is not clear, but also because several other factors are known to modify Hb F production. We have examined a large Asian Indian pedigree which includes individuals with heterocellular HPFH associated with beta-thalassemia and/or alpha-thalassemia. Segregation analysis was conducted on the HPFH trait FC, defined to be the percentage of Hb F-containing cells (F-cells), using the class D regressive model. Our results provide evidence for the presence of a major gene, dominant or codominant, which controls the FC values with residual familial correlations. The major gene was detected when the effects of genetic modifiers, notably beta-thalassemia and the XmnI-G gamma polymorphism, are accounted for in the analysis. Linkage with the beta-globin gene cluster is excluded. The transmission of the FC values in this pedigree is informative enough to allow detection of linkage with an appropriate marker(s). The analytical approach outlined in this study, using simple regression to allow for genetic modifiers and thus allowing the mode of inheritance of a trait to be dissected out, may be useful as a model for segregation and linkage analyses of other complex phenotypes. PMID:7508182

  14. Absolute Reticulocyte Count Acts as a Surrogate for Fetal Hemoglobin in Infants and Children with Sickle Cell Anemia

    PubMed Central

    Meier, Emily Riehm; Byrnes, Colleen; Weissman, Maxine; Lee, Y. Terry; Miller, Jeffery L.

    2015-01-01

    Hemoglobin switching is largely complete in humans by six months of age. Among infants with sickle cell anemia (HbSS, SCA), reticulocytosis begins early in life as fetal hemoglobin (HbF) is replaced by sickle hemoglobin (HbS). The objective of this study was to determine if absolute reticulocyte count (ARC) is related to HbF levels in a cohort of pediatric SCA patients. A convenience sample of 106 children with SCA between the ages of 1 month and 20 years who were not receiving hydroxyurea or monthly blood transfusions were enrolled in this observational study. Hematologic data, including ARC and HbF levels, were measured at steady state. F-cells were enumerated by flow cytometry. Initial studies compared infants with ARC greater than or equal to 200 K/μL (ARC ≥ 200) based upon the previously reported utility of this threshold as a predictive marker for SCA severity. Mean HbF and F-cell levels were significantly lower in the ARC ≥ 200 group when compared to the ARC < 200 group. Both HbF and F-cell percentages were negatively correlated to ARC in infants and in children between the ages of 1 and 9 years. However, the inverse relationship was lost after the age of 10 years. Overall, decreased expression and distribution of HbF during childhood SCA is well-correlated with increased reticulocyte production and release into the peripheral blood. As such, these data further support the clinical use of reticulocyte enumeration as a disease severity biomarker for childhood sickle cell anemia. PMID:26366562

  15. Fetal Hemoglobin in Tunisian Sickle Cell Disease Patient: Relationship with Polymorphic Sequences Cis to the β-Globin Gene.

    PubMed

    Moumni, Imen; Ben Mustapha, Maha; Ben Mansour, Ikbel; Zoraï, Amine; Douzi, Kaïs; Sassi, Sarah; Chaouachi, Dorra; Mellouli, Fethi; Bejaoui, Mohamed; Abbes, Salem

    2016-03-01

    Fetal hemoglobin (HbF) plays a dominant role in ameliorating morbidity and mortality of hemoglobinopathies. We evaluated the effects of polymorphic markers within the β-globin gene cluster to identify the genetic mechanics that influence HbF on Tunisian sickling patients (n = 242). Haplotype analysis was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and the framework polymorphism was established by PCR-sequencing, four independent regions of interest were identified: the 5' region of β-LCR-HS2 site, the intervening sequence II (IVSII) region of two fetal (Gγ and Aγ) genes and the 5' region of β-globin gene. The correlation of these various Haplotypes and SNPs with HbF expression and clinical data was studied. Our data showed that among the various polymorphic markers analyzed, only the sequence (AT)xN12(AT)y in LCR HS2 region was significantly associated (p < 0.05) with increased HbF levels, suggesting that the β-globin gene cluster exerts a significant effect on HbF in sickle cell patients. This study can improve understanding of the physiopathology of the disease and aid to increase our ability to predict clinical severity. PMID:26855518

  16. Original Research: Generation of non-deletional hereditary persistence of fetal hemoglobin β-globin locus yeast artificial chromosome transgenic mouse models: -175 Black HPFH and -195 Brazilian HPFH.

    PubMed

    Braghini, Carolina A; Costa, Flavia C; Fedosyuk, Halyna; Neades, Renee Y; Novikova, Lesya V; Parker, Matthew P; Winefield, Robert D; Peterson, Kenneth R

    2016-04-01

    Fetal hemoglobin is a major genetic modifier of the phenotypic heterogeneity in patients with sickle cell disease and certain β-thalassemias. Normal levels of fetal hemoglobin postnatally are approximately 1% of total hemoglobin. Patients who have hereditary persistence of fetal hemoglobin, characterized by elevated synthesis of γ-globin in adulthood, show reduced disease pathophysiology. Hereditary persistence of fetal hemoglobin is caused by β-globin locus deletions (deletional hereditary persistence of fetal hemoglobin) or γ-globin gene promoter point mutations (non-deletional hereditary persistence of fetal hemoglobin). Current research has focused on elucidating the pathways involved in the maintenance/reactivation of γ-globin in adult life. To better understand these pathways, we generated new β-globin locus yeast artificial chromosome transgenic mice bearing the (A)γ-globin -175 T > C or -195 C > G hereditary persistence of fetal hemoglobin mutations to model naturally occurring hereditary persistence of fetal hemoglobin. Adult -175 and -195 mutant β-YAC mice displayed a hereditary persistence of fetal hemoglobin phenotype, as measured at the mRNA and protein levels. The molecular basis for these phenotypes was examined by chromatin immunoprecipitation of transcription factor/co-factor binding, including YY1, PAX1, TAL1, LMO2, and LDB1. In -175 HPFH versus wild-type samples, the occupancy of LMO2, TAL1 and LDB1 proteins was enriched in HPFH mice (5.8-fold, 5.2-fold and 2.7-fold, respectively), a result that concurs with a recent study in cell lines showing that these proteins form a complex with GATA-1 to mediate long-range interactions between the locus control region and the (A)γ-globin gene. Both hereditary persistence of fetal hemoglobin mutations result in a gain of (A)γ-globin activation, in contrast to other hereditary persistence of fetal hemoglobin mutations that result in a loss of repression. The mice provide additional tools to

  17. Generation of non-deletional hereditary persistence of fetal hemoglobin β-globin locus yeast artificial chromosome transgenic mouse models: −175 Black HPFH and −195 Brazilian HPFH

    PubMed Central

    Braghini, Carolina A; Costa, Flavia C; Fedosyuk, Halyna; Neades, Renee Y; Novikova, Lesya V; Parker, Matthew P; Winefield, Robert D; Peterson, Kenneth R

    2016-01-01

    Fetal hemoglobin is a major genetic modifier of the phenotypic heterogeneity in patients with sickle cell disease and certain β-thalassemias. Normal levels of fetal hemoglobin postnatally are approximately 1% of total hemoglobin. Patients who have hereditary persistence of fetal hemoglobin, characterized by elevated synthesis of γ-globin in adulthood, show reduced disease pathophysiology. Hereditary persistence of fetal hemoglobin is caused by β-globin locus deletions (deletional hereditary persistence of fetal hemoglobin) or γ-globin gene promoter point mutations (non-deletional hereditary persistence of fetal hemoglobin). Current research has focused on elucidating the pathways involved in the maintenance/reactivation of γ-globin in adult life. To better understand these pathways, we generated new β-globin locus yeast artificial chromosome transgenic mice bearing the Aγ-globin −175 T >C or −195 C >G hereditary persistence of fetal hemoglobin mutations to model naturally occurring hereditary persistence of fetal hemoglobin. Adult −175 and −195 mutant β-YAC mice displayed a hereditary persistence of fetal hemoglobin phenotype, as measured at the mRNA and protein levels. The molecular basis for these phenotypes was examined by chromatin immunoprecipitation of transcription factor/co-factor binding, including YY1, PAX1, TAL1, LMO2, and LDB1. In −175 HPFH versus wild-type samples, the occupancy of LMO2, TAL1 and LDB1 proteins was enriched in HPFH mice (5.8-fold, 5.2-fold and 2.7-fold, respectively), a result that concurs with a recent study in cell lines showing that these proteins form a complex with GATA-1 to mediate long-range interactions between the locus control region and the Aγ-globin gene. Both hereditary persistence of fetal hemoglobin mutations result in a gain of Aγ-globin activation, in contrast to other hereditary persistence of fetal hemoglobin mutations that result in a loss of repression. The mice provide additional tools to study

  18. A physiological delay in human fetal hemoglobin switching is associated with specific globin DNA hypomethylation.

    PubMed

    Perrine, S P; Greene, M F; Cohen, R A; Faller, D V

    1988-02-01

    The human fetal-to-adult globin switch normally occurs on a fixed schedule, beginning at 32-34 weeks gestation, and recent studies have suggested an association between this developmental inactivation of the fetal (gamma) globin genes and the appearance of methylation within and around these genes. We have studied a population of infants in whom this switch does not occur before birth (infants of diabetic mothers, IDM) and examined the patterns of methylation surrounding their active gamma-globin genes, in comparison to the gamma-globin genes of age-matched controls who have switched their pattern of globin gene expression on schedule. All genomic DNA samples from infants with delays in the globin switch demonstrated extensive hypomethylation in the region of the gamma-globin genes, comparable to that found in the genomes of fetuses of less than 21 weeks gestation. DNA from the erythroid cells of infants of 32-40 weeks gestation had no detectable hypomethylation in the gamma-globin region. These findings support the concept that hypomethylation is an accurate developmental marker of globin gene switching, and suggest that globin gene expression in IDM may be arrested at an early preswitch stage. PMID:2449361

  19. The LSD1 inhibitor RN-1 induces fetal hemoglobin synthesis and reduces disease pathology in sickle cell mice.

    PubMed

    Cui, Shuaiying; Lim, Kim-Chew; Shi, Lihong; Lee, Mary; Jearawiriyapaisarn, Natee; Myers, Greggory; Campbell, Andrew; Harro, David; Iwase, Shigeki; Trievel, Raymond C; Rivers, Angela; DeSimone, Joseph; Lavelle, Donald; Saunthararajah, Yogen; Engel, James Douglas

    2015-07-16

    Inhibition of lysine-specific demethylase 1 (LSD1) has been shown to induce fetal hemoglobin (HbF) levels in cultured human erythroid cells in vitro. Here we report the in vivo effects of LSD1 inactivation by a selective and more potent inhibitor, RN-1, in a sickle cell disease (SCD) mouse model. Compared with untreated animals, RN-1 administration leads to induced HbF synthesis and to increased frequencies of HbF-positive cells and mature erythrocytes, as well as fewer reticulocytes and sickle cells, in the peripheral blood of treated SCD mice. In keeping with these observations, histologic analyses of the liver and spleen of treated SCD mice verified that they do not exhibit the necrotic lesions that are usually associated with SCD. These data indicate that RN-1 can effectively induce HbF levels in red blood cells and reduce disease pathology in SCD mice, and may therefore offer new therapeutic possibilities for treating SCD. PMID:26031919

  20. Intermediaries of branched chain amino acid metabolism induce fetal hemoglobin, and repress SOX6 and BCL11A, in definitive erythroid cells.

    PubMed

    Karkashon, Shay; Raghupathy, Radha; Bhatia, Himanshu; Dutta, Amrita; Hess, Sonja; Higgs, Jaimie; Tifft, Cynthia J; Little, Jane A

    2015-08-01

    High levels of fetal hemoglobin (HbF) can ameliorate human β-globin gene disorders. The short chain fatty acid butyrate is the paradigmatic metabolic intermediary that induces HbF. Inherited disorders of branched-chain amino acid (BCAA) metabolism have been associated with supranormal HbF levels beyond infancy, e.g., propionic acidemia (PA) and methylmalonic acidemia (MMA). We tested intermediaries of BCAA metabolism for their effects on definitive erythropoiesis. Like butyrate, the elevated BCAA intermediaries isovalerate, isobutyrate, and propionate, induce fetal globin gene expression in murine EryD in vitro, are associated with bulk histone H3 hyperacylation, and repress the transcription of key gamma globin regulatory factors, notably BCL11A and SOX6. Metabolic intermediaries that are elevated in Maple Syrup Urine Disease (MSUD) affect none of these processes. Percent HbF and gamma (γ) chain isoforms were also measured in non-anemic, therapeutically optimized subjects with MSUD (Group I, n=6) or with Isovaleric Acidemia (IVA), MMA, or PA (Group II, n=5). Mean HbF was 0.24 ± 0.15% in Group I and 0.87 ± 0.13% in Group II (p=.01); only the Gγ isoform was detected. We conclude that a family of biochemically related intermediaries of branched chain amino acid metabolism induces fetal hemoglobin during definitive erythropoiesis, with mechanisms that mirror those so far identified for butyrate. PMID:26142333

  1. Locus control region HS2 point mutations are generally not responsible for elevated fetal hemoglobin expression of sickle cell patients

    SciTech Connect

    Gilman, J.G.

    1994-09-01

    The locus control region (LCR), composed of four hypersensitive sites (HS1-4) 5{prime} of the {epsilon} globin gene, confers strong, copy-number dependent expression on globin genes in transgenic mice. Several {beta}-globin gene cluster haplotypes carry the sickle cell gene, and show variable levels of fetal hemoglobin (Hb F) expression in association with DNA sequence differences in HS2, {gamma} and {beta} globin promoters, and {gamma}IVSII: The Senegal (SEN or No. 3) haplotype generally has high (>10%) Hb F, Benin (BEN or No. 19) has intermediate Hb F (but some low and some high), and Banu (BAN or No. 20) generally has low Hb F. Huisman and colleagues have proposed that `factors produced under conditions of hematopoietic stress, together with genetic determinants on the haplotype-3 like LCR sequences, allow for high level expression of {gamma} globin genes`. We have now used slot blot to screen high Hb F (>9.5%) and low Hb F cases for two of the three HS2 point mutations described by Oener et al. Comparing eight high Hb F BEN/BEN with two low Hb F BEN/BEN, all ten had the BEN mutations considered by Oener et al. to be associated with low Hb F. Comparing three high Hb F BEN/BAN with two low Hb F BEN/BAN, all five were heterozygous at three positions; this is consistent with BEN having G and T and BAN having A at both positions. DNA sequencing of HS2 for BAN, which is generally associated with low HB F, showed that the point mutations at all three positions were those seen in SEN (generally high Hb F); only the AT repeat region showed major differences, confirming results of Huisman and colleagues. Hence, if there is any effect of HS2 of the Senegal sickle cell haplotype in causing elevated Hb F under hematopoietic stress, it must be due to specific variation in the AT repeat region, which Oener et al. have suggested may bind a silencer.

  2. Natural Remedies for the Treatment of Beta-Thalassemia and Sickle Cell Anemia—Current Status and Perspectives in Fetal Hemoglobin Reactivation

    PubMed Central

    Ng, Noel Yat Hey

    2014-01-01

    For the treatment of β-thalassemia and sickle cell disease (SCD), pharmacological induction of fetal hemoglobin (HbF) production may be a promising approach. To date, numerous studies have been done on identifying the novel HbF-inducing agents and understanding the underlying mechanism for stimulating the HbF production. In this review, we have summarized the identified HbF-inducing agents by far. By examining the action mechanisms of the HbF-inducing agents, various studies have suggested that despite the ability of stimulating HbF production, the chemotherapeutic agents could not be practically applied for treating β-hemoglobinopathies, especially β-thalassemia, due to the their cytotoxicity and growth-inhibitory effect. Owing to this therapeutic obstacle, much effort has been put on identifying new HbF-inducing agents from the natural world with the combination of efficacy, safety, and ease of use. Therefore, this review aims to (i) reveal the novel screening platforms for identifying potential inducers with high efficiency and accuracy and to (ii) summarize the new identified natural remedies for stimulating HbF production. Hopefully, this review can provide a new insight into the current status and future perspectives in fetal hemoglobin reactivation for treating β-thalassaemia and SCD. PMID:27350962

  3. Fetal Hemoglobin Inducers from the Natural World: A Novel Approach for Identification of Drugs for the Treatment of {beta}-Thalassemia and Sickle-Cell Anemia.

    PubMed

    Bianchi, Nicoletta; Zuccato, Cristina; Lampronti, Ilaria; Borgatti, Monica; Gambari, Roberto

    2009-06-01

    The objective of this review is to present examples of lead compounds identified from biological material (fungi, plant extracts and agro-industry material) and of possible interest in the field of a pharmacological approach to the therapy of beta-thalassemia using molecules able to stimulate production of fetal hemoglobin (HbF) in adults. Concerning the employment of HbF inducers as potential drugs for pharmacological treatment of beta-thalassemia, the following conclusions can be reached: (i) this therapeutic approach is reasonable, on the basis of the clinical parameters exhibited by hereditary persistence of fetal hemoglobin patients, (ii) clinical trials (even if still limited) employing HbF inducers were effective in ameliorating the symptoms of beta-thalassemia patients, (iii) good correlation of in vivo and in vitro results of HbF synthesis and gamma-globin mRNA accumulation indicates that in vitro testing might be predictive of in vivo responses and (iv) combined use of different inducers might be useful to maximize HbF, both in vitro and in vivo. In this review, we present three examples of HbF inducers from the natural world: (i) angelicin and linear psoralens, contained in plant extracts from Angelica arcangelica and Aegle marmelos, (ii) resveratrol, a polyphenol found in grapes and several plant extracts and (iii) rapamycin, isolated from Streptomyces hygroscopicus. PMID:18955291

  4. Nine known and five novel mutations in the erythroid transcription factor KLF1 gene and phenotypic expression of fetal hemoglobin in hemoglobin E disorder.

    PubMed

    Tepakhan, Wanicha; Yamsri, Supawadee; Sanchaisuriya, Kanokwan; Fucharoen, Goonnapa; Xu, Xiangmin; Fucharoen, Supan

    2016-07-01

    Hemoglobin E is the most common Hb variant found in South East Asia. Variation of Hb F expression in Hb E syndrome is associated with several genetic modifiers. We report several single nucleotide polymorphisms (SNPs), including nine known and five novel mutations of the Krüppel-like factor 1 (KLF1; an erythroid specific transcription factor) gene and determine their associations with phenotypic expression of Hb F in Hb E disorders. KLF1 mutations were examined using high resolution melting (HRM) assay and DNA sequencing in 575 homozygous Hb E, 278 heterozygous Hb E and 100 normal subjects. Fourteen mutations were mostly observed in subjects with elevated Hb F, including nine known mutations (G176AfsX179, T334R, R238H, -154 (C>T), A298P, S270W, R301H, -148 (G>A) and G335R and five novel mutations (Q217X, Q223X, Y290_S293del, K307N, and M358I). None of them, but the -148 (G>A), were observed in normal controls to have Hb F <1%. Combined KLF1 mutations with other SNPs including (G)γ-XmnI, BCL11A and HBS1L-MYB were associated with higher Hb F levels. KLF1 is therefore an important genetic factor associated with increased Hb F and in combination with other modifying factors could explain the phenotypic variation of Hb F expression in this common hemoglobinopathy. PMID:27282573

  5. 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

  6. The intrauterine diagnosis of hemoglobin disorders.

    PubMed

    Wong, S C; Ali, M A; Benzie, R

    1984-06-01

    This article presents an overview of the use of fetal blood and DNA for prenatal testing. The molecular organization of the human hemoglobin genes, the structure of human hemoglobins, and the molecular defects of hemoglobinopathies are also discussed. PMID:6086205

  7. The Natural History of Hb S/Hereditary Persistence of Fetal Hemoglobin in 13 Children from the State of Minas Gerais, Brazil.

    PubMed

    Belisário, André R; Sales, Rahyssa R; Silva, Célia M; Velloso-Rodrigues, Cibele; Viana, Marcos Borato

    2016-06-01

    Children with Hb S (HBB: c.20A > T)/hereditary persistence of fetal hemoglobin (Hb S/HPFH) have a mild clinical phenotype, but some complications have been reported. The natural history of Hb S/HPFH in children from the State of Minas Gerais, Brazil newborn cohort is described. Clinical and hematological data regarding participants' phenotypes were retrieved from medical records. The HPFH-1, HPFH-2, and HPFH-3 and α-thalassemia (α-thal) deletions were detected by gap-polymerase chain reaction (gap-PCR). Thirteen children were included, nine (69.2%) had the Hb S/HPFH-2 deletion, and four (30.8%) had Hb S/HPFH-1 deletion; 11 children (84.6%) had αα/αα, and two (15.4%) carried the αα/-α(3.7) (rightward) deletion. The mean concentration of total hemoglobin (Hb) and Hb F was 12.52 ± 0.56 g/dL and 42.31% ± 1.97%, respectively. Mild microcytosis and hypochromia were observed. We found acute clinical manifestations of sickle cell disease, such as acute chest syndrome (ACS) and acute pain crisis in four children; nine (69.2%) children were completely asymptomatic during the follow-up period. All children were classified as having low-risk transcranial Doppler (TDC). In conclusion, children with Hb S/HPFH have a mild clinical phenotype of sickle cell disease, although acute clinical manifestations may occur. High Hb F levels and absence of anemia are common hematological characteristics. PMID:27117574

  8. Association between Variants at BCL11A Erythroid-Specific Enhancer and Fetal Hemoglobin Levels among Sickle Cell Disease Patients in Cameroon: Implications for Future Therapeutic Interventions.

    PubMed

    Pule, Gift Dineo; Ngo Bitoungui, Valentina Josiane; Chetcha Chemegni, Bernard; Kengne, Andre Pascal; Antonarakis, Stylianos; Wonkam, Ambroise

    2015-10-01

    Variants in BCL11A were previously associated with fetal hemoglobin (HbF) levels among Cameroonian sickle cell disease (SCD) patients, however explaining only ∼2% of the variance. In the same patients, we have investigated the relationship between HbF and two SNPs in a BCL11A erythroid-specific enhancer (N=626). Minor allele frequencies in rs7606173 and rs1427407 were 0.42 and 0.24, respectively. Both variants were significantly associated with HbF levels (p=3.11e-08 and p=6.04e-06, respectively) and explained 8% and 6.2% variations, respectively. These data have confirmed a stronger effect on HbF of genomic variations at the BCL11A erythroid-specific enhancer among patients with SCD in Cameroon, the first report on a West African population. The relevance of these findings is of prime importance because the disruption of this enhancer would alter BCL11A expression in erythroid precursors and thus HbF expression, while sparing the induced functional challenges of any alterations on the expression of this transcription factor in non-erythroid lineages, thus providing an attractive approach for new treatment strategies of SCD. PMID:26393293

  9. Annotated definition of BCL11A and HMIP-2 haplotypes through the analysis of sicilian β-thalassemia patients with high levels of fetal hemoglobin.

    PubMed

    Buccheri, Maria A; Spina, Sonia; Ruberto, Concetta; Lombardo, Turi; Labie, Dominique; Ragusa, And Angela

    2013-01-01

    Fetal hemoglobin (Hb F) is the principal ameliorating factor of β-thalassemia (β-thal) and sickle cell disease. Persistent production in adult life is a quantitative trait regulated by loci inside or outside the β-globin gene cluster. From genome-wide association studies, principal quantitative trait loci (QTL) (accounting for 50.0% of Hb F variability in different populations) have been identified in the BCL11A gene, HBS1L-MYB intergenic polymorphism and the β-globin gene cluster itself. In this study, we analyzed quantitative trait haplotypes in two Sicilian families with extremely mild β-thal and unusually high Hb F expression, in order to examine possible genetic background variations in a similar β-thalassemic phenotype. This study redefines the linkage disequilibrium blocks at these loci, but also shows slight differences between probands in haplotype combinations which could reflect different mechanisms of high Hb F production in patients with β-thal. We proposed a haplotype-based approach as a useful tool for the understanding of β-thal phenotype variation in patients with similar β-thalassemic backgrounds in an attempt to answer the recurring question of why patients with the same β-thalassemic genotype show different phenotypes. PMID:23777413

  10. Simvastatin and t-butylhydroquinone suppress KLF1 and BCL11A gene expression and additively increase fetal hemoglobin in primary human erythroid cells

    PubMed Central

    Macari, Elizabeth R.; Schaeffer, Emily K.; West, Rachel J.

    2013-01-01

    Although increased fetal hemoglobin (HbF) levels have proven benefit for people with β-hemoglobinopathies, all current HbF-inducing agents have limitations. We previously reported that drugs that activate the NRF2 antioxidant response signaling pathway increase HbF in primary human erythroid cells. In an attempt to increase HbF levels achieved with NRF2 activators, in the present study, we investigated potential complementary activity between these agents and HMG-CoA reductase inhibitors (statins) based on their ability to induce KLF2 protein levels. Experiments in K562 cells showed that simvastatin increased KLF2 mRNA and protein and KLF2 binding to HS2 of the β-globin locus control region and enhanced γ-globin mRNA production by the NRF2 activator Tert-butylhydroquinone (tBHQ). When tested in differentiating primary human erythroid cells, simvastatin induced HbF alone and additively with tBHQ, but it did not increase KLF2 mRNA or locus control region binding above levels seen with normal differentiation. Investigating alternative mechanisms of action, we found that both simvastatin and tBHQ suppress β-globin mRNA and KLF1 and BCL11A mRNA and protein, similar to what is seen in people with an HPFH phenotype because of KLF1 haploinsufficiency. These findings identify statins as a potential class of HbF-inducing agents and suggest a novel mechanism of action based on pharmacologic suppression of KLF1 and BCL11A gene expression. PMID:23223429

  11. Original Research: A case-control genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease.

    PubMed

    Liu, Li; Pertsemlidis, Alexander; Ding, Liang-Hao; Story, Michael D; Steinberg, Martin H; Sebastiani, Paola; Hoppe, Carolyn; Ballas, Samir K; Pace, Betty S

    2016-04-01

    Sickle cell disease (SCD) is a group of inherited blood disorders that have in common a mutation in the sixth codon of the β-globin (HBB) gene on chromosome 11. However, people with the same genetic mutation display a wide range of clinical phenotypes. Fetal hemoglobin (HbF) expression is an important genetic modifier of SCD complications leading to milder symptoms and improved long-term survival. Therefore, we performed a genome-wide association study (GWAS) using a case-control experimental design in 244 African Americans with SCD to discover genetic factors associated with HbF expression. The case group consisted of subjects with HbF≥8.6% (133 samples) and control group subjects with HbF≤£3.1% (111 samples). Our GWAS results replicated SNPs previously identified in an erythroid-specific enhancer region located in the second intron of the BCL11A gene associated with HbF expression. In addition, we identified SNPs in the SPARC, GJC1, EFTUD2 and JAZF1 genes as novel candidates associated with HbF levels. To gain insights into mechanisms of globin gene regulation in the HBB locus, linkage disequilibrium (LD) and haplotype analyses were conducted. We observed strong LD in the low HbF group in contrast to a loss of LD and greater number of haplotypes in the high HbF group. A search of known HBB locus regulatory elements identified SNPs 5' of δ-globin located in an HbF silencing region. In particular, SNP rs4910736 created a binding site for a known transcription repressor GFi1 which is a candidate protein for further investigation. Another HbF-associated SNP, rs2855122 in the cAMP response element upstream of Gγ-globin, was analyzed for functional relevance. Studies performed with siRNA-mediated CREB binding protein (CBP) knockdown in primary erythroid cells demonstrated γ-globin activation and HbF induction, supporting a repressor role for CBP. This study identifies possible molecular determinants of HbF production. PMID:27022141

  12. 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 ...

  13. Noninvasive cerebral hemoglobin oxygenation quantification of fetal sheep under hypoxic stress in utero using frequency-domain diffuse optical two-layer model

    NASA Astrophysics Data System (ADS)

    Choe, Regine; Durduran, Turgut; Yu, Guoqiang; Nijland, Mark J. M.; Nathanielsz, Peter W.; Chance, Britton; Yodh, Arjun G.; Ramanujam, Nirmala

    2003-07-01

    A study using pregnant sheep was designed to simulate fetal hypoxia in order to investigate the ability of near-infrared spectroscopy (NIRS) to detect and quantify fetal hypoxia in utero. The near-infrared spectroscopic probe consisted of two detectors and six source positions. It was placed on the maternal ewe abdomen above the fetal head. The light sources were modulated at 70 MHz and frequency-encoded so that simultaneous measurements at 675, 786, 830 nm for each source position were possible. After the baseline measurements, fetal hypoxia was induced by blocking the aorta of pregnant ewe and thus compromising the blood supply to the uterus. Blood gas samples were concurrently drawn from the fetal brachial artery and jugular veins. Analysis of the diffuse optical data used a two-layer model to separate the maternal layer from the fetal head. The analysis also employed a priori spectral information about tissue chromophores. This approach provided good quantification of blood oxygenation changes, which correlated well with the blood gas analyses. By contrast the homogeneous model underestimated oxygenation changes during hypoxia.

  14. Treatment of sickle cell anemia with 5-azacytidine results in increased fetal hemoglobin production and is associated with nonrandom hypomethylation of DNA around the gamma-delta-beta-globin gene complex.

    PubMed Central

    Charache, S; Dover, G; Smith, K; Talbot, C C; Moyer, M; Boyer, S

    1983-01-01

    Increased production of fetal hemoglobin (HbF) was observed in a patient with sickle cell anemia treated with 5-azacytidine. Each of four courses of therapy resulted in a rapid and prolonged increase in the percentage of HbF containing reticulocytes (F reticulocytes) and HbF containing erythrocytes (F cells). The percentage of HbF in peripheral blood rose from 1.8 to 8.9%. The rise in HbF production was accompanied by an increase in peripheral blood hemoglobin concentration from 8 to 12 g/dl and an increase in mean erythrocyte volume. Treatment with 5-azacytidine resulted in hypomethylation of total genomic and a Y-chromosome-specific DNA fragment isolated from both peripheral blood and bone marrow. Of 15 restriction enzyme sites around the gamma-delta-beta-globin gene complex, only 2 became hypomethylated: one 107 bases 5' to the gamma G and the other 107 bases 5' to the gamma A globin genes. Images PMID:6192443

  15. 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

  16. Hemoglobin electrophoresis

    MedlinePlus

    ... is an abnormal form of hemoglobin associated with sickle cell anemia . In people with this condition, the red blood ... symptoms are much milder than they are in sickle cell anemia. Other, less common, abnormal Hb molecules cause anemias . ...

  17. Hemoglobin electrophoresis

    MedlinePlus

    ... is an abnormal form of hemoglobin associated with sickle cell anemia . In people with this condition, the red blood ... symptoms are much milder than they are in sickle cell anemia. Other, less common, abnormal Hb molecules cause anemias .

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. 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 a type of hemoglobinopathy. The disease is caused by a problem with ...

  2. Serum free hemoglobin test

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/003677.htm Serum free hemoglobin test To use the sharing features on this page, please enable JavaScript. Serum free hemoglobin is a blood test that measures the ...

  3. Fetal Research

    NASA Astrophysics Data System (ADS)

    Hansen, John T.; Sladek, John R.

    1989-11-01

    This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.

  4. Fetal development

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/002398.htm Fetal development To use the sharing features on this page, ... Cunningham FG, Leveno KJ, Bloom SL, et al. Fetal growth and development. In: Cunningham FG, Leveno KL, Bloom SL, et ...

  5. 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

  6. Hemoglobin patterns in American Indians.

    PubMed

    POLLITZER, W S; CHERNOFF, A I; HORTON, L L; FROEHLICH, M

    1959-01-23

    Two populations of North Carolina have been analyzed for hemoglobin patterns by paper electrophoresis. Of 534 Cherokee Indians, both mixed and full bloods, all showed normal hemoglobin. Lumbee Indians of less certain ethnic status had 1.7 percent of hemoglobin S, an equal amount of hemoglobin C, and one possible hemoglobin D trait among 1332 bloods studied. PMID:13624709

  7. High altitude genetic adaptation in Tibetans: no role of increased hemoglobin-oxygen affinity.

    PubMed

    Tashi, Tsewang; Feng, Tang; Koul, Parvaiz; Amaru, Ricardo; Hussey, Dottie; Lorenzo, Felipe R; RiLi, Ge; Prchal, Josef T

    2014-01-01

    High altitude exerts selective evolutionary pressure primarily due to its hypoxic environment, resulting in multiple adaptive responses. High hemoglobin-oxygen affinity is postulated to be one such adaptive change, which has been reported in Sherpas of the Himalayas. Tibetans have lived on the Qinghai-Tibetan plateau for thousands of years and have developed unique phenotypes, such as protection from polycythemia which has been linked to PDH2 mutation, resulting in the downregulation of the HIF pathway. In order to see if Tibetans also developed high hemoglobin-oxygen affinity as a part of their genetic adaptation, we conducted this study assessing hemoglobin-oxygen affinity and their fetal hemoglobin levels in Tibetan subjects from 3 different altitudes. We found normal hemoglobin-oxygen affinity in all subjects, fetal hemoglobin levels were normal in all except one and no hemoglobin variants in any of the subjects. We conclude that increased hemoglobin-oxygen affinity or increased fetal hemoglobin are not adaptive phenotypes of the Tibetan highlanders. PMID:24618341

  8. Fetal endocrinology

    PubMed Central

    Kota, Sunil Kumar; Gayatri, Kotni; Jammula, Sruti; Meher, Lalit Kumar; Kota, Siva Krishna; Krishna, S. V. S.; Modi, Kirtikumar D.

    2013-01-01

    Successful outcome of pregnancy depends upon genetic, cellular, and hormonal interactions, which lead to implantation, placentation, embryonic, and fetal development, parturition and fetal adaptation to extrauterine life. The fetal endocrine system commences development early in gestation and plays a modulating role on the various physiological organ systems and prepares the fetus for life after birth. Our current article provides an overview of the current knowledge of several aspects of this vast field of fetal endocrinology and the role of endocrine system on transition to extrauterine life. We also provide an insight into fetal endocrine adaptations pertinent to various clinically important situations like placental insufficiency and maternal malnutrition. PMID:23961471

  9. Fetal Diagnostics and Fetal Intervention.

    PubMed

    McLaughlin, Ericka S; Schlosser, Brian A; Border, William L

    2016-03-01

    Advances in ultrasound technology and specialized training have allowed clinicians to diagnose congenital heart disease in utero and counsel families on perinatal outcomes and management strategies, including fetal cardiac interventions and fetal surgery. This article gives a detailed approach to fetal cardiac assessment and provides the reader with accompanying figures and video clips to illustrate unique views and sweeps invaluable to diagnosing congenital heart disease. We demonstrate that using a sequential segmental approach to evaluate cardiac anatomy enables one to decipher the most complex forms of congenital heart disease. Also provided is a review of fetal cardiac intervention and surgery from the fetal cardiologist's perspective. PMID:26876119

  10. Examiner's finger-mounted fetal tissue oximetry

    NASA Astrophysics Data System (ADS)

    Kanayama, Naohiro; Niwayama, Masatsugu

    2014-06-01

    The best way to assess fetal condition is to observe the oxygen status of the fetus (as well as to assess the condition of infants, children, and adults). Previously, several fetal oximeters have been developed; however, no instrument has been utilized in clinical practice because of the low-capturing rate of the fetal oxygen saturation. To overcome the problem, we developed a doctor's finger-mounted fetal tissue oximeter, whose sensor volume is one hundredth of the conventional one. Additionally, we prepared transparent gloves. The calculation algorithm of the hemoglobin concentration was derived from the light propagation analysis based on the transport theory. We measured neonatal and fetal oxygen saturation (StO2) with the new tissue oximeter. Neonatal StO was measured at any position of the head regardless of amount of hair. Neonatal StO was found to be around 77%. Fetal StO was detected in every position of the fetal head during labor regardless of the presence of labor pain. Fetal StO without labor pain was around 70% in the first stage of labor and around 60% in the second stage of labor. We concluded that our new concept of fetal tissue oximetry would be useful for detecting fetal StO in any condition of the fetus.

  11. 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

  12. Fetal ultrasonography.

    PubMed Central

    Garmel, S H; D'Alton, M E

    1993-01-01

    Since its introduction in the 1950s, ultrasonography in pregnancy has been helpful in determining gestational age, detecting multiple pregnancies, locating placentas, diagnosing fetal anomalies, evaluating fetal well-being, and guiding obstetricians with in utero treatment. We review current standards and controversies regarding the indications, safety, accuracy, and limitations of ultrasonography in pregnancy. Images PMID:8236969

  13. Fetal Abuse.

    ERIC Educational Resources Information Center

    Kent, Lindsey; And Others

    1997-01-01

    Five cases of fetal abuse by mothers suffering from depression are discussed. Four of the women had unplanned pregnancies and had considered termination of the pregnancy. Other factors associated with fetal abuse include pregnancy denial, pregnancy ambivalence, previous postpartum depression, and difficulties in relationships. Vigilance for…

  14. [Fetal programming].

    PubMed

    Lang, U; Fink, D; Kimmig, R

    2008-01-01

    The intrauterine environment not only influences fetal well-being and behaviour during pregnancy, but also predisposes the fetus in many health aspects of later life. The terms 'fetal programming' and 'developmental origins of health and disease' reflect the enormous impact of pregnancy-related factors on the individual and the health. PMID:19096216

  15. Fetal development

    MedlinePlus

    Cunningham FG, Leveno KJ, Bloom SL, et al. Fetal growth and development. In: Cunningham FG, Leveno KL, Bloom SL, et al, eds. Williams Obstetrics . 23rd ed. New York, NY: McGraw-Hill; ... and fetal physiology. In: Gabbe SG, Niebyl JR, Simpson JL, ...

  16. Fetal echocardiography

    MedlinePlus

    ... Fetal echocardiography is a test that uses sound waves ( ultrasound ) to evaluate the baby's heart for problems ... over the area. The probe sends out sound waves, which bounce off the baby's heart and create ...

  17. 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...

  18. Hemoglobin oxidative stress

    NASA Astrophysics Data System (ADS)

    Croci, S.; Ortalli, I.; Pedrazzi, G.; Passeri, G.; Piccolo, P.

    2000-07-01

    Venous blood obtained from healthy donors and from patients suffering from breast cancer have been treated with acetylphenylhydrazine (APH) for different time. Mössbauer spectra of the packed red cells have been recorded and compared. The largest difference occurs after 50 min of treatment with APH where the patient samples show a broad spectral pattern indicating an advanced hemoglobin oxidation. These results may have some relevance in early cancer diagnosis.

  19. Hemoglobin research and the origins of molecular medicine

    PubMed Central

    2008-01-01

    Much of our understanding of human physiology, and of many aspects of pathology, has its antecedents in laboratory and clinical studies of hemoglobin. Over the last century, knowledge of the genetics, functions, and diseases of the hemoglobin proteins has been refined to the molecular level by analyses of their crystallographic structures and by cloning and sequencing of their genes and surrounding DNA. In the last few decades, research has opened up new paradigms for hemoglobin related to processes such as its role in the transport of nitric oxide and the complex developmental control of the α-like and β-like globin gene clusters. It is noteworthy that this recent work has had implications for understanding and treating the prevalent diseases of hemoglobin, especially the use of hydroxyurea to elevate fetal hemoglobin in sickle cell disease. It is likely that current research will also have significant clinical implications, as well as lessons for other aspects of molecular medicine, the origin of which can be largely traced to this research tradition. PMID:18988877

  20. FLOW CYTOMETRIC DETECTION OF ABNORMAL FETAL ERYTHROPOIESIS: APPLICATION TO 5-FLUOROURACIL-INDUCED ANEMIA

    EPA Science Inventory

    Previously, we observed that administration of 20-40 mg/kg 5-fluorouracil (5-FU) to pregnant rats on gestational day (GD) 14 produced fetal anemia on GD 16-17, as evidenced by dose-dependent decreases in the cell counts, hematocrit, and hemoglobin content of fetal blood obtained ...

  1. Hemoglobin binding to deglycosylated haptoglobin.

    PubMed

    Kaartinen, V; Mononen, I

    1988-04-14

    The carbohydrate portion of polymeric haptoglobin was gradually removed by exoglycosidases in order to investigate its role in complex formation between haptoglobin and hemoglobin. Total removal of sialic acid diminished the haptoglobin-hemoglobin complex formation 15%. Removal of about 25% of the galactose residues from asialohaptoglobin, i.e., about 40% of the total weight of the carbohydrate moiety, totally inhibited the ability of haptoglobin to form complex with hemoglobin and react with haptoglobin-specific antibodies. Liberation of further galactose residues resulted in slow precipitation of the protein. Removal of a similar part of the carbohydrate moiety from haptoglobin-hemoglobin complex did not liberate hemoglobin from it, and the complex reacted with haptoglobin antibodies. The combined data indicate that the carbohydrate portion is essential for the functionally active form of polymeric haptoglobin to complex with hemoglobin, but it hardly has any direct role in the binding event, and other factors are responsible for the stability of the complex. PMID:3128331

  2. 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.

  3. Fetal electrocardiograph

    NASA Astrophysics Data System (ADS)

    Rios, Heriberto; Andrade, Armando; Puente, Ernestina; Lizana, Pablo R.; Mendoza, Diego

    2002-11-01

    The high intra-uterine death rate is due to failure in appropriately diagnosing some problems in the cardiobreathing system of the fetus during pregnancy. The electrocardiograph is one apparatus which might detect problems at an early stage. With electrodes located near the womb and uterus, in a way similar to the normal technique, the detection of so-called biopotential differences, caused by concentrations of ions, can be achieved. The fetal electrocardiograph is based on an ultrasound technique aimed at detecting intrauterine problems in pregnant women, because it is a noninvasive technique due to the very low level of ultrasound power used. With this system, the following tests can be done: Heart movements from the ninth week onwards; Rapid and safe diagnosis of intrauterine fetal death; Location and size of the placenta. The construction of the fetal electrocardiograph requires instrument level components directly mounted on the printed circuit board, in order to avoid stray capacitance in the cabling which prevents the detection of the E.C.G. activity. The low cost of the system makes it affordable to low budget institutions; in contrast, available commercial systems are priced in U.S. Dollars. (To be presented in Spanish.)

  4. Fetal Alcohol Syndrome

    MedlinePlus

    ... Conditions Frequently Asked Questions Español Condiciones Chinese Conditions Fetal Alcohol Syndrome Read in Chinese What is Fetal Alcohol Syndrome (FAS)? Fetal Alcohol Syndrome (FAS) describes changes in ...

  5. Intrapartum fetal resuscitation.

    PubMed

    Cowan, D B

    1980-08-30

    Fetal distress is defined. The pathophysiology of fetal distress is discussed and tretment is recommended. The principles of intrapartum fetal resuscitation are proposed, with particular reference to the inhibition of uterine activity. PMID:7404260

  6. Fetal syringomyelia.

    PubMed

    Guo, Anne; Chitayat, David; Blaser, Susan; Keating, Sarah; Shannon, Patrick

    2014-01-01

    We explored the prevalence of syringomyelia in a series of 113 cases of fetal dysraphism and hindbrain crowding, of gestational age ranging from 17.5 to 34 weeks with the vast majority less than 26 weeks gestational age. We found syringomyelia in 13 cases of Chiari II malformations, 5 cases of Omphalocele/Exostrophy/Imperforate anus/Spinal abnormality (OEIS), 2 cases of Meckel Gruber syndrome and in a single pair of pyopagus conjoined twins. Secondary injury was not uncommon, with vernicomyelia in Chiari malformations, infarct like histology, or old hemorrhage in 8 cases of syringomyelia. Vernicomyelia did not occur in the absence of syrinx formation. The syringes extended from the sites of dysraphism, in ascending or descending patterns. The syringes were usually in a major proportion anatomically distinct from a dilated or denuded central canal and tended to be dorsal and paramedian or median. We suggest that fetal syringomyelia in Chiari II malformation and other dysraphic states is often established prior to midgestation, has contributions from the primary malformation as well as from secondary in utero injury and is anatomically and pathophysiologically distinct from post natal syringomyelia secondary to hindbrain crowding. PMID:25092126

  7. Fetal nutrition

    PubMed Central

    Rosa, Franz W.; Turshen, Meredeth

    1970-01-01

    The extensive literature on nutrition in pregnancy is reviewed with special reference to international experience, including observations on nutritional trials in pregnancy, pregnancy during famines caused by war, and studies of birth-weight in relation to pregnancy interval, parity and multiple pregnancies. Recent research on the significance of fetal nutrition suggests that ”small-for-dates” infants, i.e., those that are developmentally retarded in utero, suffer long-term developmental sequelae. A high world-wide incidence of small-for-dates births was reported by the World Health Organization in 1960. Although a definite correlation has been found between socio-economic status and birth-weight, it is not known to what extent the smaller birth-weights observed in the lower socio-economic groups can be improved by specific nutritional measures. In addition to the general advice given on maternal nutrition and family-planning, further studies are needed to determine the precise means of achieving improvement in fetal nutrition and a better outcome of pregnancy. PMID:5314013

  8. 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)

  9. 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.

  10. Nonlinear photoacoustic spectroscopy of hemoglobin

    PubMed Central

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

    2015-01-01

    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. PMID:26045627

  11. Nonlinear photoacoustic spectroscopy of hemoglobin

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

    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.

  12. GENOME-WIDE ASSOCIATION ANALYSES BASED ON WHOLE-GENOME SEQUENCING IN SARDINIA PROVIDE INSIGHTS INTO REGULATION OF HEMOGLOBIN LEVELS

    PubMed Central

    Danjou, Fabrice; Zoledziewska, Magdalena; Sidore, Carlo; Steri, Maristella; Busonero, Fabio; Maschio, Andrea; Mulas, Antonella; Perseu, Lucia; Barella, Susanna; Porcu, Eleonora; Pistis, Giorgio; Pitzalis, Maristella; Pala, Mauro; Menzel, Stephan; Metrustry, Sarah; Spector, Timothy D.; Leoni, Lidia; Angius, Andrea; Uda, Manuela; Moi, Paolo; Thein, Swee Lay; Galanello, Renzo; Abecasis, Gonçalo R.; Schlessinger, David; Sanna, Serena; Cucca, Francesco

    2015-01-01

    We report GWAS results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, FOG1, NFIX, and CCND3. Among those at known loci, 10 are new lead variants and 4 are novel independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and revealed features of coordinated hemoglobin species production. PMID:26366553

  13. 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

  14. Anesthesia for fetal surgery.

    PubMed

    Cauldwell, Charles B

    2002-03-01

    Fetal surgery is the antenatal treatment of fetal malformations that cannot be adequately corrected after birth. Anesthesia for fetal surgery involves two patients, and issues of maternal safety, avoidance of fetal asphyxia, adequate fetal anesthesia and monitoring, and uterine relaxation are important. Communication with the surgeon to determine the surgical approach and need for uterine relaxation allows the anesthesiologist the ability to vary the anesthetic technique. Lessons learned from fetal surgery may help other neonates with life-threatening anomalies and may help understand the complex issues related to preterm labor. PMID:11892506

  15. 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.

  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. Challenge of Fetal Mortality

    MedlinePlus

    ... Death Data File and Linked Birth/Infant Death Data Set, National Vital Statistics System The magnitude of fetal ... Death Data File and Linked Birth/Infant Death Data Set, NVSS. The vital statistics Fetal Death Data File ...

  18. Fetal Alcohol Spectrum Disorders

    MedlinePlus

    ... alcohol can cause a group of conditions called fetal alcohol spectrum disorders (FASDs). Effects can include physical and behavioral problems such ... alcohol syndrome is the most serious type of FASD. People with fetal alcohol syndrome have facial abnormalities, ...

  19. Fetal Alcohol Spectrum Disorders

    MedlinePlus

    ... Daily life skills, such as feeding and bathing Fetal alcohol syndrome is the most serious type of FASD. People with fetal alcohol syndrome have facial abnormalities, including wide-set and narrow ...

  20. Effects of Vivax Malaria Acquired Before 20 Weeks of Pregnancy on Subsequent Changes in Fetal Growth

    PubMed Central

    Machado Filho, Amantino C.; da Costa, Elenice P.; da Costa, Emely P.; Reis, Iracema S.; Fernandes, Emanoela A. C.; Paim, Bernardo V.; Martinez-Espinosa, Flor E.

    2014-01-01

    The resistance index (RI), pulsatility index (PI), fetal biometry, fetal heart rate (FHR), placental thickness, and hemoglobin levels were compared in 30 Plasmodium vivax-infected women between 14 and 20 weeks of pregnancy and a control group. Evaluations were performed at the moment of the malaria diagnosis and 26 weeks of pregnancy. The malaria group had lower levels of hemoglobin and greater placental thickness in both assessments, higher FHR in the first evaluation, and lower values on fetal biometry in the second assessment. There were no differences when comparing RI and PI on umbilical arteries between the two groups. Birth weight and height were lower in newborns in the malaria group than the control group. The results suggest that P. vivax infections at an earlier gestational age do not affect umbilical arteries blood flow but do affect fetal biometry in the second trimester of pregnancy and at birth. PMID:24420773

  1. Advances in fetal surgery

    PubMed Central

    Pedreira, Denise Araujo Lapa

    2016-01-01

    ABSTRACT This paper discusses the main advances in fetal surgical therapy aiming to inform health care professionals about the state-of-the-art techniques and future challenges in this field. We discuss the necessary steps of technical evolution from the initial open fetal surgery approach until the development of minimally invasive techniques of fetal endoscopic surgery (fetoscopy). PMID:27074241

  2. Hemodynamics in fetal arrhythmia.

    PubMed

    Sonesson, Sven-Erik; Acharya, Ganesh

    2016-06-01

    Fetal arrhythmias are among the few conditions that can be managed in utero. However, accurate diagnosis is essential for appropriate management. Ultrasound-based imaging methods can be used to study fetal heart structure and function noninvasively and help to understand fetal cardiovascular pathophysiology, and they remain the mainstay of evaluating fetuses with arrhythmias in clinical settings. Hemodynamic evaluation using Doppler echocardiography allows the elucidation of the electrophysiological mechanism and helps to make an accurate diagnosis. It can also be used as a tool to understand fetal cardiac pathophysiology, for assessing fetal condition and monitoring the effect of antiarrhythmic treatment. This narrative review describes Doppler techniques that are useful for evaluating fetal cardiac rhythms to refine diagnosis and provides an overview of hemodynamic changes observed in different types of fetal arrhythmia. PMID:26660845

  3. Effects of prenatal nicotine on expression of nicotine receptor subunits in the fetal brain

    PubMed Central

    Lv, Juanxiu; Mao, Caiping; Zhu, Liyan; Zhang, Hong; Pengpeng, Hui; Xu, Feichao; Liu, Yujuan; Zhang, Lubo; Xu, Zhice

    2008-01-01

    Previous studies have suggested that prenatal exposure to nicotine is associated with abnormal development in fetuses, including fetal brain damage. The present study determined the effect of maternal administration of nicotine during different gestational periods on brain nicotine receptor subunits in fetal rats. Subcutaneous injections of nicotine in maternal rats from the early and middle gestation decreased fetal blood PO2, increased fetal blood PCO2 and hemoglobin, and decreased fetal brain weight. The nicotinic acetylcholine receptor (nAChRs) mRNA abundance in the fetal brain was significantly changed by prenatal treatment with nicotine during pregnancy. Fetal α2, α4, α7, and β2 units were significantly increased in the brain by prenatal exposure to nicotine in rat fetuses. However, the expression of mRNA of fetal brain α3, α5, β3, and β4 units were not changed. The results showed that prenatal nicotine can change the development of both α and β subunits of nAChRs in the fetal brain at gene level in association with restriction of fetal brain growth and in utero hypoxia. PMID:18541304

  4. Fetal Health and Development

    MedlinePlus

    ... specific prenatal tests to monitor both the mother's health and fetal health during each trimester. With modern technology, health professionals can Detect birth defects Identify problems that ...

  5. 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 ...

  6. Hemoglobin

    MedlinePlus

    ... and after major surgery During pregnancy Presence of chronic kidney disease or many other chronic medical problems Monitoring of ... from digestive tract or bladder, heavy menstrual periods Chronic kidney disease Bone marrow being unable to produce new blood ...

  7. 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.

  8. Effects of hydroxyurea treatment for patients with hemoglobin SC disease.

    PubMed

    Luchtman-Jones, Lori; Pressel, Sara; Hilliard, Lee; Brown, R Clark; Smith, Mary G; Thompson, Alexis A; Lee, Margaret T; Rothman, Jennifer; Rogers, Zora R; Owen, William; Imran, Hamayun; Thornburg, Courtney; Kwiatkowski, Janet L; Aygun, Banu; Nelson, Stephen; Roberts, Carla; Gauger, Cynthia; Piccone, Connie; Kalfa, Theodosia; Alvarez, Ofelia; Hassell, Kathryn; Davis, Barry R; Ware, Russell E

    2016-02-01

    Although hemoglobin SC (HbSC) disease is usually considered less severe than sickle cell anemia (SCA), which includes HbSS and HbS/β(0) -thalassemia genotypes, many patients with HbSC experience severe disease complications, including vaso-occlusive pain, acute chest syndrome, avascular necrosis, retinopathy, and poor quality of life. Fully 20 years after the clinical and laboratory efficacy of hydroxyurea was proven in adult SCA patients, the safety and utility of hydroxyurea treatment for HbSC patients remain unclear. Recent NHLBI evidence-based guidelines highlight this as a critical knowledge gap, noting HbSC accounts for ∼30% of sickle cell patients within the United States. To date, only 5 publications have reported short-term, incomplete, or conflicting laboratory and clinical outcomes of hydroxyurea treatment in a total of 71 adults and children with HbSC. We now report on a cohort of 133 adult and pediatric HbSC patients who received hydroxyurea, typically for recurrent vaso-occlusive pain. Hydroxyurea treatment was associated with a stable hemoglobin concentration; increased fetal hemoglobin (HbF) and mean corpuscular volume (MCV); and reduced white blood cell count (WBC), absolute neutrophil count (ANC), and absolute reticulocyte count (ARC). Reversible cytopenias occurred in 22% of patients, primarily neutropenia and thrombocytopenia. Painful events were reduced with hydroxyurea, more in patients >15 years old. These multicenter data support the safety and potentially salutary effects of hydroxyurea treatment for HbSC disease; however, a multicenter, placebo-controlled, Phase 3 clinical trial is needed to determine if hydroxyurea therapy has efficacy for patients with HbSC disease. PMID:26615793

  9. 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.

  10. Fetal Neurobehavioral Development.

    ERIC Educational Resources Information Center

    DiPietro, Janet A.; And Others

    1996-01-01

    Investigated the ontogeny of fetal autonomic, motoric, state, and interactive functioning in 31 healthy fetuses from 20 weeks through term. Found that male fetuses were more active than female fetuses, and that greater maternal stress appraisal was associated with reduced fetal heart rate variability. Found that an apparent period of…

  11. Fetal alcohol syndrome

    MedlinePlus

    Fetal alcohol syndrome is growth, mental, and physical problems that may occur in a baby when a mother drinks ... A baby with fetal alcohol syndrome may have the following symptoms: Poor growth while the baby is in the womb and after birth Decreased muscle ...

  12. Fetal Alcohol Spectrum Disorder

    ERIC Educational Resources Information Center

    Caley, Linda M.; Kramer, Charlotte; Robinson, Luther K.

    2005-01-01

    Fetal alcohol spectrum disorder (FASD) is a serious and widespread problem in this country. Positioned within the community with links to children, families, and healthcare systems, school nurses are a critical element in the prevention and treatment of those affected by fetal alcohol spectrum disorder. Although most school nurses are familiar…

  13. Led Astray by Hemoglobin A1c

    PubMed Central

    Chen, Jean; Diesburg-Stanwood, Amy; Bodor, Geza; Rasouli, Neda

    2016-01-01

    Hemoglobin A1c (A1c) is used frequently to diagnose and treat diabetes mellitus. Therefore, it is important be aware of factors that may interfere with the accuracy of A1c measurements. This is a case of a rare hemoglobin variant that falsely elevated a nondiabetic patient’s A1c level and led to a misdiagnosis of diabetes. A 67-year-old male presented to endocrine clinic for further management after he was diagnosed with diabetes based on an elevated A1c of 10.7%, which is approximately equivalent to an average blood glucose of 260 mg/dL. Multiple repeat A1c levels remained >10%, but his home fasting and random glucose monitoring ranged from 92 to 130 mg/dL. Hemoglobin electrophoresis and subsequent genetic analysis diagnosed the patient with hemoglobin Wayne, a rare hemoglobin variant. This variant falsely elevates A1c levels when A1c is measured using cation-exchange high-performance liquid chromatography. When the boronate affinity method was applied instead, the patient’s A1c level was actually 4.7%. Though hemoglobin Wayne is clinically silent, this patient was erroneously diagnosed with diabetes and started on an antiglycemic medication. Due to this misdiagnosis, the patient was at risk of escalation in his “diabetes management” and hypoglycemia. Therefore, it is important that providers are aware of factors that may result in hemoglobin A1c inaccuracy including hemoglobin variants. PMID:26848480

  14. 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.…

  15. The fetal urinoma revisited.

    PubMed

    Yitta, Silaja; Saadai, Payam; Filly, Roy A

    2014-01-01

    The fetal urinoma is a rare but important diagnosis, as it indicates substantial underlying obstruction with implications for the functionality of the affected kidney. This case series describes a single center's experience with the diagnosis and management of fetal urinomas. All 25 cases were diagnosed or referred to our medical center over an 11-year period. Most cases were secondary to either posterior urethral valves or ureteropelvic junction obstruction. Fetal interventions, including percutaneous drainage of the urinoma and cystoscopic alleviation of bladder outlet obstruction, were performed in 4 cases. PMID:24371112

  16. 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.

  17. 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

  18. Lipopolysaccharides of Actinobacillus pleuropneumoniae bind pig hemoglobin.

    PubMed Central

    Bélanger, M; Bégin, C; Jacques, M

    1995-01-01

    A previous study indicated that lipopolysaccharides (LPS) extracted from Actinobacillus pleuropneumoniae bind two low-molecular-mass proteins, of approximately 10 and 11 kDa, present in porcine respiratory tract secretions (M. Bélanger, D. Dubreuil, and M. Jacques, Infect. Immun. 62:868-873, 1994). In the present study, we determined the N-terminal amino acid sequences of these two proteins, which revealed high homology with the alpha and beta chains of pig hemoglobin. Some isolates of A. pleuropneumoniae were able to use hemoglobin from various animal species as well as other heme compounds as sole sources of iron for growth, while other isolates were unable to use them. Immunoelectron microscopy showed binding of pig hemoglobin at the surface of all A. pleuropneumoniae isolates as well as labeling of outer membrane blebs. We observed, using Western blotting (immunoblotting), that the lipid A-core region of LPS of all isolates was binding pig hemoglobin. Furthermore, lipid A obtained after acid hydrolysis of LPS extracted from A. pleuropneumoniae was able to bind pig hemoglobin and this binding was completely abolished by preincubation of lipid A with polymyxin B but was not inhibited by preincubation with glucosamines. Fatty acids constituting the lipid A of A. pleuropneumoniae, namely, dodecanoic acid, tetradecanoic acid, 3-hydroxytetradecanoic acid, hexadecanoic acid, and octadecanoic acid, were also binding pig hemoglobin. Our results indicate that LPS of all A. pleuropneumoniae isolates tested bind pig hemoglobin and that lipid A is involved in this binding. Our results also indicate that some A. pleuropneumoniae isolates are, in addition, able to use hemoglobin for growth. Binding of hemoglobin to LPS might represent an important means by which A. pleuropneumoniae acquires iron in vivo from hemoglobin released from erythrocytes lysed by the action of its hemolysins. PMID:7822035

  19. Fetal Alcohol Syndrome

    MedlinePlus

    ... drink other beverages instead, such as water, fruit juices or milk. Questions to Ask Your Doctor If your baby was born with fetal alcohol syndrome: What health problems does my baby have? Does my baby ...

  20. Fetal alcohol syndrome

    MedlinePlus

    Alcohol in pregnancy; Alcohol-related birth defects; Fetal alcohol effects; FAS ... the baby is in the womb and after birth Decreased muscle tone and ... Heart defects such as ventricular septal defect (VSD) or atrial ...

  1. Fetal Health and Development

    MedlinePlus

    ... fetus grows and develops. There are specific prenatal tests to monitor both the mother's health and fetal health during each trimester. With modern technology, health professionals can Detect birth defects Identify problems ...

  2. Fetal medicine and treatment.

    PubMed

    Westgren, Magnus

    2011-01-01

    Fetal medicine covers a broad spectrum of conditions that can be diagnosed before birth. Different disorders will require different treatment strategies and there is often an important ontogenetic aspect on how and when treatment can be implemented. Due to the limited availability there is a general lack of knowledge on how pharmacotherapy can be provided in the most efficient way. Until recently most knowledge about how different drugs are transferred and metabolized in the human fetus is based on very limited observational studies on concentrations of drugs in fetal blood and other fetal compartments. It might be that the rapid development of other non-invasive methods for fetal diagnostics such as isolation of fetal DNA and RNA in maternal serum, NMR imaging and other techniques could in the future be explored in fetal pharmacotherapy. Introduction of new treatment strategies are often based on extrapolation from experience in neonates and adults. However some fetal conditions are very specific for this time period in life. This especially entails disturbances in development as malformations, early growth restriction and several congenital disorders. Here it might be required to introduce new treatment strategies without any previous experience in humans. Example of this ethical dilemma is gene therapy for lung growth in severe cases of diaphragmatic hernia and early growth restriction. The risk-benefit issues need to be discussed in all these alternatives. However, it is likely that the concept of the human fetus as a potential patient is still in its infancy and with an improved understanding about fetal patho-physiology there will be a continued need for better knowledge of pharmacotherapy during this crucial time period in life. PMID:21882116

  3. Management of fetal malpresentation.

    PubMed

    Sharshiner, Rita; Silver, Robert M

    2015-06-01

    Fetal malpresentation is an important cause of the high cesarean delivery rate in the United States and around the world. This includes breech, face, brow, and compound presentations as well as transverse lie. Risk factors include multiparity, previously affected pregnancy, polyhydramnios, and fetal and uterine anomalies. Appropriate management can reduce the need for cesarean delivery in some cases. This review discusses management options and focuses specifically on external cephalic version and vaginal breech delivery. PMID:25811125

  4. Genome-wide association analyses based on whole-genome sequencing in Sardinia provide insights into regulation of hemoglobin levels.

    PubMed

    Danjou, Fabrice; Zoledziewska, Magdalena; Sidore, Carlo; Steri, Maristella; Busonero, Fabio; Maschio, Andrea; Mulas, Antonella; Perseu, Lucia; Barella, Susanna; Porcu, Eleonora; Pistis, Giorgio; Pitzalis, Maristella; Pala, Mauro; Menzel, Stephan; Metrustry, Sarah; Spector, Timothy D; Leoni, Lidia; Angius, Andrea; Uda, Manuela; Moi, Paolo; Thein, Swee Lay; Galanello, Renzo; Abecasis, Gonçalo R; Schlessinger, David; Sanna, Serena; Cucca, Francesco

    2015-11-01

    We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production. PMID:26366553

  5. Interaction of Human Hemoglobin with Methotrexate

    NASA Astrophysics Data System (ADS)

    Zaharia, M.; Gradinaru, R.

    2015-05-01

    This study focuses on the interaction between methotrexate and human hemoglobin using steady-state ultraviolet-visible and fluorescence quenching methods. Fluorescence quenching was found to be valuable in assessing drug binding to hemoglobin. The quenching of methotrexate is slightly smaller than the quenching observed with related analogs (dihydrofolate and tetrahydrofolate). The quenching studies were performed at four different temperatures and various pH values. The number of binding sites for tryptophan is ~1. Parameter-dependent assays revealed that electrostatic forces play an essential role in the methotrexate-hemoglobin interaction. Furthermore, the complex was easily eluted using gel filtration chromatography.

  6. ALTERATIONS IN MATERNAL-FETAL CELLULAR TRAFFICKING AFTER FETAL SURGERY

    PubMed Central

    Saadai, Payam; Lee, Tzong-Hae; Bautista, Geoanna; Gonzales, Kelly D.; Nijagal, Amar; Busch, Michael P.; Kim, CJ; Romero, Roberto; Lee, Hanmin; Hirose, Shinjiro; Rand, Larry; Miniati, Douglas; Farmer, Diana L.; MacKenzie, Tippi C.

    2012-01-01

    Background/Purpose Bi-directional trafficking of cells between the mother and the fetus is routine in pregnancy and a component of maternal-fetal tolerance. Changes in fetal-to-maternal cellular trafficking have been reported in prenatal complications, but maternal-to-fetal trafficking has never been studied in the context of fetal intervention. We hypothesized that patients undergoing open fetal surgery would have altered maternal-fetal cellular trafficking. Methods Cellular trafficking was analyzed in patients with myelomeningocele (MMC) who underwent open fetal surgical repair (n=5), MMC patients who had routine postnatal repair (n=6), and normal term patients (n=9). As a control for the fetal operation, trafficking was also analyzed in patients who were delivered by an ex utero intrapartum treatment (EXIT) procedure (n=6). Microchimerism in maternal and cord blood was determined using quantitative real-time PCR for non-shared alleles. Results Maternal-to-fetal trafficking was significantly increased in patients who underwent open fetal surgery for MMC compared to normal controls, postnatal MMC repair, and EXIT patients. There were no differences in fetal-to-maternal cell trafficking between groups. Conclusion Patients undergoing open fetal surgery for MMC have elevated levels of maternal microchimerism. These results suggest altered trafficking and/or increased proliferation of maternal cells in fetal blood and may have important implications for preterm labor. PMID:22703775

  7. 21 CFR 884.2900 - Fetal stethoscope.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by...

  8. 21 CFR 884.2900 - Fetal stethoscope.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by...

  9. 21 CFR 884.2900 - Fetal stethoscope.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by...

  10. 21 CFR 884.2900 - Fetal stethoscope.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by...

  11. 21 CFR 884.2900 - Fetal stethoscope.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Fetal stethoscope. (a) Identification. A fetal stethoscope is a device used for listening to fetal heart sounds. It is designed to transmit the fetal heart sounds not only through sound channels by...

  12. Sulfate in fetal development.

    PubMed

    Dawson, Paul A

    2011-08-01

    Sulfate (SO(4)(2-)) is an important nutrient for human growth and development, and is obtained from the diet and the intra-cellular metabolism of sulfur-containing amino acids, including methionine and cysteine. During pregnancy, fetal tissues have a limited capacity to produce sulfate, and rely on sulfate obtained from the maternal circulation. Sulfate enters and exits placental and fetal cells via transporters on the plasma membrane, which maintain a sufficient intracellular supply of sulfate and its universal sulfonate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) for sulfate conjugation (sulfonation) reactions to function effectively. Sulfotransferases mediate sulfonation of numerous endogenous compounds, including proteins and steroids, which biotransforms their biological activities. In addition, sulfonation of proteoglycans is important for maintaining normal structure and development of tissues, as shown for reduced sulfonation of cartilage proteoglycans that leads to developmental dwarfism disorders and four different osteochondrodysplasias (diastrophic dysplasia, atelosteogenesis type II, achondrogenesis type IB and multiple epiphyseal dysplasia). The removal of sulfate via sulfatases is an important step in proteoglycan degradation, and defects in several sulfatases are linked to perturbed fetal bone development, including mesomelia-synostoses syndrome and chondrodysplasia punctata 1. In recent years, interest in sulfate and its role in developmental biology has expanded following the characterisation of sulfate transporters, sulfotransferases and sulfatases and their involvement in fetal growth. This review will focus on the physiological roles of sulfate in fetal development, with links to human and animal pathophysiologies. PMID:21419855

  13. Magnesium and fetal growth

    SciTech Connect

    Weaver, K.

    1988-01-01

    Fetal growth retardation and premature labor are major problems in perinatal medicine today and account for a great deal of the observed fetal morbidity. While the neonatal death rate has steadily declined over the past decade, there has been a lack of concommitant decrease in these two leading problems. Magnesium (Mg/sup ++/) plays a major role in both of these areas of concern. The fact that it is used as a treatment for premature labor has led investigators to look at low Mg/sup ++/ as a possible cause of this poorly understood phenomenon. The second major cause of small for gestational age infants is intrauterine growth retardation, a condition which may be of either fetal or maternal origin. In either case, Mg/sup ++/ may be implicated since it exerts a strong influence on the underlying pathophysiology of placental failure and maternal hypertension. Both of these conditions are mediated by vascular and platelet hyperactivity as well as by and increase in the ration of thromboxane to prostacyclin. Studies in both the human and animal species are beginning to show how Mg/sup ++/ interacts in these conditions to produce such a damaging fetal outcome. The recent use of Doppler velocimetry of the developing fetus has shown reduced fetal vascular and maternal uterine vascular compliance as early as 14 weeks of gestation in those who would be so affected.

  14. Stabilized hemoglobins as acellular resuscitative fluids.

    PubMed

    Cerny, L C; Green, A; Noga, B; Cerny, E R

    1992-01-01

    This study reports some recent work dealing with the stabilization of the tetramers of hemoglobin. It is shown that by using a variety of diacids, it is possible to increase the P50 above that of stroma free hemoglobin. In order to lengthen the retention times in the circulatory system, the stabilized hemoglobins were complexed with both hydroxyethyl starch polymers and polyol tetronic polymers. The resulting hemoglobin-polymer compounds were then freeze-dried. It was possible to reconstitute the powder by the addition of physiological saline when needed. The methods presented here appear to be appear to be as effective as using pyridoxal phosphate but at a fraction of the cost. PMID:1391448

  15. 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 ...

  16. Artificial oxygen carriers rescue placental hypoxia and improve fetal development in the rat pre-eclampsia model

    PubMed Central

    Li, Heng; Ohta, Hidenobu; Tahara, Yu; Nakamura, Sakiko; Taguchi, Kazuaki; Nakagawa, Machiko; Oishi, Yoshihisa; Goto, Yu-ichi; Wada, Keiji; Kaga, Makiko; Inagaki, Masumi; Otagiri, Masaki; Yokota, Hideo; Shibata, Shigenobu; Sakai, Hiromi; Okamura, Kunihiro; Yaegashi, Nobuo

    2015-01-01

    Pre-eclampsia affects approximately 5% of all pregnant women and remains a major cause of maternal and fetal morbidity and mortality. The hypertension associated with pre-eclampsia develops during pregnancy and remits after delivery, suggesting that the placenta is the most likely origin of this disease. The pathophysiology involves insufficient trophoblast invasion, resulting in incomplete narrow placental spiral artery remodeling. Placental insufficiency, which limits the maternal-fetal exchange of gas and nutrients, leads to fetal intrauterine growth restriction. In this study, in our attempt to develop a new therapy for pre-eclampsia, we directly rescued placental and fetal hypoxia with nano-scale size artificial oxygen carriers (hemoglobin vesicles). The present study is the first to demonstrate that artificial oxygen carriers successfully treat placental hypoxia, decrease maternal plasma levels of anti-angiogenic proteins and ameliorate fetal growth restriction in the pre-eclampsia rat model. PMID:26471339

  17. 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.

  18. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 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...

  19. Maternal-fetal thyroid hormone relationships and the fetal brain.

    PubMed

    Morreale de Escobar, G; Obregon, M J; Escobar del Rey, F

    1988-01-01

    Thyroid hormones are transferred from the mother to the fetus. Thus, despite the deiodinating enzymes of the placenta (26), some T4 and T3 is transferred, both before and after onset of fetal thyroid function, at least in those cases where fetal thyroid function is impaired. It is also possible that transfer occurs under normal conditions. Maternal to fetal transfer of T3 and T4 is partially limited. But it might be enough to mitigate severe fetal T4 and T3 deficiencies. However, the mitigating effects of both hormones are not equivalent for all fetal tissues. 1) Maternal T4 mitigates T4 and T3 deficiency of most fetal tissues, the brain included. 2) Maternal T3 mitigates T3 deficiency only in some fetal tissues, the brain being excluded. It does not mitigate cerebral T3 deficiency even at doses which are toxic for the mother, and it does not depress fetal plasma TSH. 3) Normal maternal thyroid function is important for fetal development. Maternal hypothyroxinemia is damaging to the developing fetal brain early in gestation. It might also later have adverse effects in gestation, if the fetal thyroid is impaired. Normal maternal T3 levels might avoid overt hypothyroidism of some fetal tissues, but is of no benefit to the brain. PMID:3176827

  20. Fetal Alcohol Spectrum Disorders (FASDs)

    MedlinePlus

    ... FASD Cancel Submit Search The CDC Fetal Alcohol Spectrum Disorders (FASDs) Note: Javascript is disabled or is ... Recommend on Facebook Tweet Share Compartir Fetal alcohol spectrum disorders (FASDs) are a group of conditions that ...

  1. Metal complexes as allosteric effectors of human hemoglobin: an NMR study of the interaction of the gadolinium(III) bis(m-boroxyphenylamide)diethylenetriaminepentaacetic acid complex with human oxygenated and deoxygenated hemoglobin.

    PubMed

    Aime, S; Digilio, G; Fasano, M; Paoletti, S; Arnelli, A; Ascenzi, P

    1999-05-01

    The boronic functionalities on the outer surface of the Gd(III) bis(m-boroxyphenylamide)DTPA complex (Gd(III)L) enable it to bind to fructosamine residues of oxygenated glycated human adult hemoglobin. The formation of the macromolecular adduct can be assessed by NMR spectroscopy via observation of the enhancement of the solvent water proton relaxation rate. Unexpectedly, a strong binding interaction was also observed for the oxygenated unglycated human adult hemoglobin, eventually displaying a much higher relaxation enhancement. From relaxation rate measurements it was found that two Gd(III)L complexes interact with one hemoglobin tetramer (KD = 1.0 x 10(-5) M and 4.6 x 10(-4) M, respectively), whereas no interaction has been observed with monomeric hemoproteins. A markedly higher affinity of the Gd(III)L complex has been observed for oxygenated and aquo-met human adult hemoglobin derivatives with respect to the corresponding deoxy derivative. Upon binding, a net change in the quaternary structure of hemoglobin has been assessed by monitoring the changes in the high-resolution 1H-NMR spectrum of the protein as well as in the Soret absorption band. On the basis of these observations and the 11B NMR results obtained with the diamagnetic La(III)L complex, we suggest that the interaction between the lanthanide complex and deoxygenated, oxygenated, and aquo-met derivatives of human adult hemoglobin takes place at the 2, 3-diphosphoglycerate (DPG) binding site, through the formation of N-->B coordinative bonds at His143beta and His2beta residues of different beta-chains. The stronger binding to the oxygenated form is then responsible for a shift of the allosteric equilibrium toward the high-affinity R-state. Accordingly, Gd(III)L affinity for oxygenated human fetal hemoglobin (lacking His143beta) is significantly lower than that observed for the unglycated human adult tetramer. PMID:10233088

  2. Structural investigations into the interaction of hemoglobin and part structures with bacterial endotoxins.

    PubMed

    Howe, Jörg; Garidel, Patrick; Roessle, Manfred; Richter, Walter; Alexander, Christian; Fournier, Karin; Mach, Jean Pierre; Waelli, Thierry; Gorczynski, Reginald M; Ulmer, Artur J; Zähringer, Ulrich; Hartmann, Alfred; Rietschel, Ernst Th; Brandenburg, Klaus

    2008-02-01

    An understanding of details of the interaction mechanisms of bacterial endotoxins (lipopolysaccharide, LPS) with the oxygen transport protein hemoglobin is still lacking, despite its high biological relevance. Here, a biophysical investigation into the endotoxin:hemoglobin interaction is presented which comprises the use of various rough mutant LPS as well as free lipid A; in addition to the complete hemoglobin molecule from fetal sheep extract, also the partial structure alpha-chain and the heme-free sample are studied. The investigations comprise the determination of the gel-to-liquid crystalline phase behaviour of the acyl chains of LPS, the ultrastructure (type of aggregate structure and morphology) of the endotoxins, and the incorporation of the hemoglobins into artificial immune cell membranes and into LPS. Our data suggest a model for the interaction between Hb and LPS in which hemoglobins do not react strongly with the hydrophilic or with the hydrophobic moiety of LPS, but with the complete endotoxin aggregate. Hb is able to incorporate into LPS with the longitudinal direction parallel to the lipid A double-layer. Although this does not lead to a strong disturbance of the LPS acyl chain packing, the change of the curvature leads to a slightly conical molecular shape with a change of the three-dimensional arrangement from unilamellar into cubic LPS aggregates. Our previous results show that cubic LPS structures exhibit strong endotoxic activity. The property of Hb on the physical state of LPS described here may explain the observation of an increase in LPS-mediating endotoxicity due to the action of Hb. PMID:18387918

  3. Fetal blood testing (image)

    MedlinePlus

    ... testing is performed during labor to test the blood pH of the baby which can determine its well- ... puncture is made in the scalp and fetal blood droplets are collected in a thin glass tube. Testing the scalp pH can help your doctor decide if your fetus ...

  4. The Fetal Alcohol Syndrome.

    ERIC Educational Resources Information Center

    Umbreit, John; Ostrow, Lisa S.

    1980-01-01

    Fetal alcohol syndrome is a pattern of altered growth and morphogenesis found in about half the offspring of severely and chronically alcoholic women who continue drinking throughout their pregnancy. Of children studied, mild to moderate mental retardation was the most common disorder, occurring in 44 percent of the cases. (PHR)

  5. Fetal Alcohol Syndrome.

    ERIC Educational Resources Information Center

    Zerrer, Peggy

    The paper reviews Fetal Alcohol Syndrome (FAS), a series of effects seen in children whose mothers drink alcohol to excess during pregnancy. The identification of FAS and its recognition as a major health problem in need of prevention are traced. Characteristics of children with FAS are described and resultant growth retardation, abnormal physical…

  6. Screening of umbilical cord blood hemoglobins by isoelectric focusing in capillaries.

    PubMed

    Conti, M; Gelfi, C; Righetti, P G

    1995-08-01

    Separation and quantitation of the three main hemoglobin components of umbilical cord blood (fetal, acetylated fetal and adult hemoglobins; Hb F, Fac, A) by capillary isoelectric focusing (IEF) in a pH 6-8 gradient is reported. Even in coated capillaries (with covalently bound chains of linear acrylamido derivatives, notably N-acryloylaminoethoxyethanol), no base line separation is obtained between Hb F and A, although this is routinely achieved in gel slab IEF. However, when the carrier ampholyte buffers were added to 3% short-chain liquid linear polyacrylamide, base line resolution and stabilization of peak transit times were obtained. This suggests that even in the best coating procedures, patches of the inner capillary surface could still be naked, so that the static coating is complemented by a dynamic coating on the unoccupied sites. An additional improvement in separation occurs if the above mixture, comprising 5% carrier ampholytes in the pH 6-8 range and 3% soluble polyacrylamide, is made to contain 50 mM beta-alanine, a "separator" known to flatten the pH gradient around pH 7. In the normal newborns analyzed (n = 30), the following average values were obtained: Hb F, 70.1% (range 65-75%); Hb A, 20.2% (range 15-25%); and HbFac, 9.5% (range 7-11%). PMID:8529619

  7. Effect of nitric oxide on the transport and release of oxygen in fetal blood.

    PubMed

    Clementi, Maria Elisabetta; Orsini, Federica; Schininà, Maria Eugenia; Noia, Giuseppe; Giardina, Bruno

    2003-03-14

    It is well known that nitric oxide (NO), the most important vasodilator agent, plays an important role in lowering vascular resistance in the human umbilical-placental circulation and that its deficiency is related to the pathogenesis of pre-eclamptic disorder. Besides it has recently been demonstrated that human hemoglobin (HbA) is able to transport nitric oxide, as S-nitrosohemoglobin (SNO-Hb), from the arterial to the venous blood. In the present study we examine the functional properties of the adult and fetal nitrosated hemoglobins to see if the double transport of oxygen and NO may influence the fetal oxygenation and the relation between maternal and fetal blood. Our results show that S-nitrosation significantly increases the oxygen affinity of the adult Hb (HbA) with respect to native protein (no-nitrosated) while the functional properties of HbF are less influenced. The oxygen affinity modification, found for SNO-HbA, was ascribed to the nitrosation of cysteine beta 93: really, the same residue is also present in the gamma chains of fetal hemoglobin, while the increase of affinity is less evidenced; hence, it is probable that the 39 aminoacidic substitutions between beta and gamma chains allay the effects of S-nitrosation. As regards the physiological modulators (protons, chloride ions, 2,3-diphosphoglyceric acid, and temperature), they influence the oxygen affinity of the two hemoglobins S-nitrosated, in equal mode with respect to the native forms determining the same variation on the oxygen affinity. Hence, our results evidence the fact that the NO release by SNO-HbA "in vivo" would be limited to regions of extremely low oxygen tension (such as hypoxic regions), while in fetus, SNO-HbF would unload nitric oxide and oxygen at pressure values close to normal. PMID:12615064

  8. Association between diabetic retinopathy and hemoglobin level

    PubMed Central

    Bahar, Adele; Kashi, Zahra; Ahmadzadeh Amiri, Ahmad; Nabipour, Majid

    2013-01-01

    Background: Anemia may be considered to be an independent risk factor for the development of diabetic retinopathy (DR) in patients with renal failure. The purpose of this study was to investigate the association between blood hemoglobin level and retinopathy in diabetic patients with normal renal function tests. Methods: From 2009 to 2011, 1100 diabetic patients underwent retinal examination. Among them, 159 subjects were diagnosed to have DR and were compared with 318 diabetic subjects with normal retinal examination as the control group. The level of hemoglobin (Hb), Hb A1C, serum iron, ferritin, and total iron binding capacity were compared between these two groups. Results: Among the 159 patients with DR, 112 (70.4%) had mild to moderate no proliferative retinopathy (NPDR) and 47 (29.6%) had advanced retinopathy (severe NPDR or proliferative). The mean hemoglobin level in case and control group was 12.15±1.50 and 12.73±1.38 g/dl, respectively (p<0.001). Anemia was seen in 45.9% and 26.1% in the case and the control groups, respectively (p<0.001). Ferritin <15ng/ml was seen in 7.4% and 6.1% of patients with and without DR, respectively (p=0.8). Conclusion: The results show that diabetic patients with retinopathy have lower level of hemoglobin and higher frequency of anemia. It is suggested that the level of hemoglobin should be evaluated periodically in diabetic patients. PMID:24294469

  9. Ligand binding and hexacoordination in synechocystis hemoglobin.

    PubMed

    Hvitved, A N; Trent, J T; Premer, S A; Hargrove, M S

    2001-09-14

    A large and phylogenetically diverse group of organisms contain truncated hemoglobins, including the unicellular cyanobacterium Synechocystis (Pesce, A., Couture, M., Dewilde, S., Guertin, M., Yamauchi, K., Ascenzi, P., Moens, L., and Bolognesi, M. (2000) EMBO J. 19, 2424-2434). Synechocystis hemoglobin is also hexacoordinate, with a heme pocket histidine that reversibly coordinates the ligand binding site. Hexacoordinate hemoglobins are ubiquitous in plants and are now being identified in a diverse array of organisms including humans (Arredondo-Peter, R., Hargrove, M. S., Moran, J. F., Sarath, G., and Klucas, R. V. (1998) Plant Physiol. 118, 1121-1125; Trent, J. T., III, Watts, R. A., and Hargrove, M. S. (2001) J. Biol. Chem. 276, 30106-30110). Rate constants for association and dissociation of the hexacoordinating amino acid side chain in Synechocystis hemoglobin have been measured along with bimolecular rate constants for association of oxygen and carbon monoxide following laser flash photolysis. These values were compared with ligand binding initiated by rapid mixing. Site-directed mutagenesis was used to determine the roles of several heme pocket amino acids in facilitating hexacoordination and stabilizing bound oxygen. It is demonstrated that Synechocystis hemoglobin contains a very reactive binding site and that ligand migration through the protein is rapid. Rate constants for hexacoordination by His(46) are also large and facilitated by other heme pocket amino acids including Gln(43). PMID:11438545

  10. Classification of the disorders of hemoglobin.

    PubMed

    Forget, Bernard G; Bunn, H Franklin

    2013-02-01

    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

  11. The Genetics of Hemoglobin A2 Regulation in Sickle Cell Anemia

    PubMed Central

    Griffin, Paula J.; Sebastiani, Paola; Edward, Heather; Baldwin, Clinton T.; Gladwin, Mark; Gordeuk, Victor; Chui, David H.K.; Steinberg, Martin H.

    2014-01-01

    Hemoglobin A2, a tetramer of α- and δ-globin chains, comprises less than 3% of total hemoglobin in normal adults. In northern Europeans, single nucleotide polymorphisms (SNPs) in the HBS1L-MYB locus on chromosome 6q and the HBB cluster on chromosome 11p were associated with HbA2 levels. We examined the genetic basis of HbA2 variability in sickle cell anemia using genome-wide association studies (GWAS). HbA2 levels were associated with SNPs in the HBS1L-MYB interval that affect erythropoiesis and HbF expression and SNPs in BCL11A that regulate the γ-globin genes. These effects are mediated by the association of these loci with γ-globin gene expression and fetal hemoglobin (HbF) levels. The association of polymorphisms downstream of the β-globin gene (HBB) cluster on chromosome 11 with HbA2 was not mediated by HbF. In sickle cell anemia, levels of HbA2 appear to be modulated by trans-acting genes that affect HBG expression and perhaps also elements within the β-globin gene cluster. HbA2 is expressed pancellularly and can inhibit HbS polymerization. It remains to be seen if genetic regulators of HbA2 can be exploited for therapeutic purposes. PMID:25042611

  12. 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.

  13. Persistent fetal circulation.

    PubMed

    Saucier, P H

    1980-01-01

    A review of persistent fetal circulation, which involves the presence of a right to left extrapulmonary shunt that is sustained into neonatal life, is presented. Clinical signs exhibited by the infant often resemble those of respiratory distress. Treatment is accomplished with hyperventilation and/or pharmacologically with tolazoline which, in addition to the usual attention to the overall condition of the infant, requires intensive monitoring by the nurse. PMID:6898712

  14. Passive fetal monitoring sensor

    NASA Astrophysics Data System (ADS)

    Zuckerwar, Allan J.; Hall, Earl T.; Baker, Donald A.; Bryant, Timothy D.

    1992-08-01

    An ambulatory, passive sensor for use in a fetal monitoring system is discussed. The invention is comprised of a piezoelectric polymer film, combined with a metallic mounting plate fastened to a belt, and electrically connected to a signal processing unit by means of a shielded cable. The purpose of the sensor is to receive pressure pulses emitted by a fetus inside an expectant mother. Additionally, the monitor will filter out pressure pulses arising from other sources, such as the maternal heart.

  15. Passive fetal monitoring sensor

    NASA Technical Reports Server (NTRS)

    Zuckerwar, Allan J. (Inventor); Hall, Earl T. (Inventor); Baker, Donald A. (Inventor); Bryant, Timothy D. (Inventor)

    1992-01-01

    An ambulatory, passive sensor for use in a fetal monitoring system is discussed. The invention is comprised of a piezoelectric polymer film, combined with a metallic mounting plate fastened to a belt, and electrically connected to a signal processing unit by means of a shielded cable. The purpose of the sensor is to receive pressure pulses emitted by a fetus inside an expectant mother. Additionally, the monitor will filter out pressure pulses arising from other sources, such as the maternal heart.

  16. Hemoglobin D-Punjab: origin, distribution and laboratory diagnosis

    PubMed Central

    Torres, Lidiane de Souza; Okumura, Jéssika Viviani; Silva, Danilo Grünig Humberto da; Bonini-Domingos, Claudia Regina

    2015-01-01

    This review discusses hemoglobin D-Punjab, also known as hemoglobin D-Los Angeles, one of the most common hemoglobin variants worldwide. It is derived from a point mutation in the beta-globin gene (HBB: c.364G>C; rs33946267) prevalent in the Punjab region, Northwestern Indian. Hemoglobin D-Punjab can be inherited in heterozygosis with hemoglobin A causing no clinical or hematological alterations, or in homozygosis, the rarest form of inheritance, a condition that is commonly not related to clinical symptomatology. Moreover, this variant can exist in association with other hemoglobinopathies, such as thalassemias; the most noticeable clinical alterations occur when hemoglobin D-Punjab is associated to hemoglobin S. The clinical manifestations of this association can be similar to homozygosis for hemoglobin S. Although hemoglobin D-Punjab is a common variant globally with clinical importance especially in cases of double heterozygosis, hemoglobin S/D-Punjab is still understudied. In Brazil, for example, hemoglobin D-Punjab is the third most common hemoglobin variant. Thus, this paper summarizes information about the origin, geographic distribution, characterization and occurrence of hemoglobin D-Punjab haplotypes to try to improve our knowledge of this variant. Moreover, a list of the main techniques used in its identification is provided emphasizing the importance of complementary molecular analysis for accurate diagnosis. PMID:25818823

  17. Maternal-fetal conflict.

    PubMed

    Fasouliotis, S J; Schenker, J G

    2000-03-01

    Advances in prenatal care have brought about a greater understanding as to the special status of the fetus to the point that it is considered a patient in its own regard. Pregnant women generally follow the medical recommendations of their physicians that are intended for the benefit of their baby. Any situation where maternal well-being or wishes contradict fetal benefit constitutes a maternal-fetal conflict. Such situations include a broad range of possible interventions, non-interventions, and coercive influences. In such cases, the attending physician is expected to attain an attitude that involves either the respect of the woman's autonomy and right to privacy, which precludes any approach other than to accept her decision, or to modify this absolute for the beneficence of the fetus. Current ethical viewpoints range from absolute respect for maternal autonomy with no persuasion allowed, to gentle persuasion and to others which permit intervention and overriding of the woman's autonomy. Court-ordered decisions enforcing the pregnant woman to undergo a procedure in order to improve fetal outcome have been criticized as an invasion of a woman's privacy, limitation of her autonomy, and taking away of her right to informed consent. PMID:10733034

  18. Fetal Alcohol Spectrum Disorders.

    PubMed

    Williams, Janet F; Smith, Vincent C

    2015-11-01

    Prenatal exposure to alcohol can damage the developing fetus and is the leading preventable cause of birth defects and intellectual and neurodevelopmental disabilities. In 1973, fetal alcohol syndrome was first described as a specific cluster of birth defects resulting from alcohol exposure in utero. Subsequently, research unequivocally revealed that prenatal alcohol exposure causes a broad range of adverse developmental effects. Fetal alcohol spectrum disorder (FASD) is the general term that encompasses the range of adverse effects associated with prenatal alcohol exposure. The diagnostic criteria for fetal alcohol syndrome are specific, and comprehensive efforts are ongoing to establish definitive criteria for diagnosing the other FASDs. A large and growing body of research has led to evidence-based FASD education of professionals and the public, broader prevention initiatives, and recommended treatment approaches based on the following premises:▪ Alcohol-related birth defects and developmental disabilities are completely preventable when pregnant women abstain from alcohol use.▪ Neurocognitive and behavioral problems resulting from prenatal alcohol exposure are lifelong.▪ Early recognition, diagnosis, and therapy for any condition along the FASD continuum can result in improved outcomes.▪ During pregnancy:◦no amount of alcohol intake should be considered safe;◦there is no safe trimester to drink alcohol;◦all forms of alcohol, such as beer, wine, and liquor, pose similar risk; and◦binge drinking poses dose-related risk to the developing fetus. PMID:26482673

  19. Intrapartum fetal monitoring.

    PubMed

    Cahill, Alison G; Spain, Janine

    2015-06-01

    Intrapartum fetal monitoring to assess fetal well-being during the labor and delivery process has been a central component of intrapartum care for decades. Today, electronic fetal monitoring (EFM) is the most common method used to assess the fetus during labor without substantial evidence to suggest a benefit. A Cochrane review of 13 trials, which included over 37,000 women, found that continuous EFM provided no significant improvement in perinatal death rate [risk ratio (RR) 0.86; 95% confidence interval (CI), 0.59-1.23] or cerebral palsy rate (RR 1.75; 95% CI, 0.84-3.63) as compared with intermittent auscultation; however, there was a significant decrease in neonatal seizures (RR 0.50; 95% CI, 0.31-0.80). In addition, there was a significant increase in cesarean delivery (RR 1.63; 95% CI, 1.29-2.07) and operative vaginal delivery (RR 1.15; 95% CI, 1.01-1.33). Despite the lack of scientific support to suggest that EFM reduces adverse neonatal outcomes, its use is almost universal in the hospital setting and very likely has contributed to the rise in cesarean rate. PMID:25811127

  20. MOESSBAUER EFFECT IN HEMOGLOBIN WITH DIFFERENT LIGANDS.

    PubMed

    GONSER, U; GRANT, R W; KREGZDE, J

    1964-02-14

    Recoil-free nuclear gamma-ray resonance adsorption was observed in the iron-57 of blood. The spectral parameters are dependent on the ligand bound to the iron atoms in hemoglobin. The results are interpreted in terms of isomeric shifts and quad rupole splittings. PMID:14081237

  1. 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

  2. Hemoglobin: A Nitric-Oxide Dioxygenase

    PubMed Central

    Gardner, Paul R.

    2012-01-01

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

  3. BINDING OF CHEMICAL CARCINOGENS AND MUTAGENS TO RAT HEMOGLOBIN

    EPA Science Inventory

    The alkylation of hemoglobin is a proposed dose monitor for chemical carcinogens and mutagens. The binding of fifteen chemical carcinogens and mutagens to rat hemoglobin was determined. Direct acting carcinogens and indirect acting carcinogens including aromatic amines, halogenat...

  4. Alpha chain hemoglobins with electrophoretic mobility similar to that of hemoglobin S in a newborn screening program

    PubMed Central

    Silva, Marcilene Rezende; Sendin, Shimene Mascarenhas; Araujo, Isabela Couto de Oliveira; Pimentel, Fernanda Silva; Viana, Marcos Borato

    2013-01-01

    Objective To characterize alpha-chain variant hemoglobins with electric mobility similar to that of hemoglobin S in a newborn screening program. Methods βS allele and alpha-thalassemia deletions were investigated in 14 children who had undefined hemoglobin at birth and an electrophoretic profile similar to that of hemoglobin S when they were six months old. Gene sequencing and restriction enzymes (DdeI, BsaJI, NlaIV, Bsu36I and TaqI) were used to identify hemoglobins. Clinical and hematological data were obtained from children who attended scheduled medical visits. Results The following alpha chain variants were found: seven children with hemoglobin Hasharon [alpha2 47(CE5) Asp>His, HbA2:c.142G>C], all associated with alpha-thalassemia, five with hemoglobin Ottawa [alpha1 15(A13) Gly>Arg, HBA1:c.46G>C], one with hemoglobin St Luke's [alpha1 95(G2) Pro>Arg, HBA1:c.287C>G] and another one with hemoglobin Etobicoke [alpha212 84(F5) Ser>Arg, HBA212:c.255C>G]. Two associations with hemoglobin S were found: one with hemoglobin Ottawa and one with hemoglobin St Luke's. The mutation underlying hemoglobin Etobicoke was located in a hybrid α212 allele in one child. There was no evidence of clinically relevant hemoglobins detected in this study. Conclusion Apparently these are the first cases of hemoglobin Ottawa, St Luke's, Etobicoke and the α212 gene described in Brazil. The hemoglobins detected in this study may lead to false diagnosis of sickle cell trait or sickle cell disease when only isoelectric focusing is used in neonatal screening. Additional tests are necessary for the correct identification of hemoglobin variants. PMID:23741188

  5. 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 Electrophoretic hemoglobin analysis system. (a) Identification. An electrophoretic hemoglobin analysis system is a device that electrophoretically separates and identifies normal and...

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  7. 21 CFR 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...

  8. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 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...

  9. 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...

  10. Self-Assembly of a Functional Triple Protein: Hemoglobin-Avidin-Hemoglobin via Biotin-Avidin Interactions.

    PubMed

    Singh, Serena; Kluger, Ronald

    2016-05-24

    Hypertension resulting from vasoconstriction in clinical trials of cross-linked tetrameric (α2β2) human hemoglobins implicates the extravasation of the hemoglobins into endothelia where they scavenge nitric oxide (NO), which is the signal for relaxation of the surrounding smooth muscle. Thus, we sought an efficient route to create a larger species that avoids extravasation while maintaining the oxygenation function of hemoglobin. Selectively formed cysteine-linked biotin conjugates of hemoglobin undergo self-assembly with avidin into a stable triple protein, hemoglobin-avidin-hemoglobin (HbAvHb), which binds and releases oxygen with moderate affinity and cooperativity. The triple protein is likely to be stabilized by interactions of each constituent hemoglobin (pI 6.9) with the oppositely charged avidin (pI 10.5) as well as the strong association of the biotin moieties on hemoglobin with avidin. PMID:27126305

  11. Assessment of fetal heart disorder by means of fetal magnetocardiography

    NASA Astrophysics Data System (ADS)

    Łozińska, Maria; Dunajski, Zbigniew

    2006-10-01

    Fetal magnetocardiography is new method for investigations of electrical activity of the fetal heart. The idea and build of system for magnetic signal registration is described. Two cases of premature atrial contraction and complete AV block diagnosis by means of magnetic field recording system are described.

  12. Fetal Alcohol Syndrome and Fetal Alcohol Effects in Child Development.

    ERIC Educational Resources Information Center

    Pancratz, Diane R.

    This literature review defines Fetal Alcohol Syndrome (FAS) and Fetal Alcohol Effects (FAE) and considers their causes, diagnoses, prevalence, and educational ramifications. Effects of alcohol during each of the trimesters of pregnancy are summarized. Specific diagnostic characteristics of FAS are listed: (1) growth deficiency, (2) a…

  13. Combined FISH, anti-γ-Hb and DAPI for detection of fetal nucleated RBCs in maternal blood

    NASA Astrophysics Data System (ADS)

    Farhad, Mona; Price, Jeffrey H.

    2002-05-01

    Since the 1970s, extensive research has been devoted to the development of a standard procedure for the isolation of fetal nucleated red cells (fnRBCs) from maternal blood. Since these cells are sources of fetal DNA, cytogenetic analysis would lead to a minimally-invasive method for the prenatal diagnosis of chromosomal and genetic disorders early in gestation. FnRBCs constitute a significant portion of the fetal blood, have a short and finite life span, and are rare in peripheral adult blood. They have been reported to exist in the maternal circulation at frequencies as low as 1:105 - 1:109 maternal nucleated cells. Due to these ultra-rare frequencies, isolation with minimal loss has been a time and labor-intensive process. To overcome this problem, a fully automated scanning cytometer that incorporates high-performance autofocus and image segmentation has been built and shown higher rate, quantity, sensitivity (true positive rate) and specificity (true negative rate) in a model cell preparation. For detecting fnRBCs, two discriminating characteristics may suffice: (1) the presence of fetal hemoglobin, which is the major intracytoplasmic protein found in fetal red cells from 5 to 35 weeks gestation, and (2) the presence of a nucleus. In clinical trials, the fetal origin of the isolated cells will be confirmed by fluorescence in situ hybridization (FISH) on the X and Y chromosomes in male pregnancies. The aim of the present study was to develop a reliable and reproducible staining method for combined immunofluorescence and FISH analysis for these clinical trials. This staining technique was developed using fnRBCs extracted from fetal liver blood and a human erythroleukemia cell line (HEL) that expresses fetal hemoglobin. The resulting method for four-color X- and Y-FISH , anti-(gamma) -Hb fluorescence and DAPI staining was consistent and bright.

  14. Fetal and Neonatal Arrhythmias.

    PubMed

    Jaeggi, Edgar; Öhman, Annika

    2016-03-01

    Cardiac arrhythmias are an important aspect of fetal and neonatal medicine. Premature complexes of atrial or ventricular origin are the main cause of an irregular heart rhythm. The finding is typically unrelated to an identifiable cause and no treatment is required. Tachyarrhythmia most commonly relates to supraventricular reentrant tachycardia, atrial flutter, and sinus tachycardia. Several antiarrhythmic agents are available for the perinatal treatment of tachyarrhythmias. Enduring bradycardia may result from sinus node dysfunction, complete heart block and nonconducted atrial bigeminy as the main arrhythmia mechanisms. The management and outcome of bradycardia depend on the underlying mechanism. PMID:26876124

  15. Prenatal Depression Restricts Fetal Growth

    PubMed Central

    Diego, Miguel A.; Field, Tiffany; Hernandez-Reif, Maria; Schanberg, Saul; Kuhn, Cynthia; Gonzalez-Quintero, Victor Hugo

    2009-01-01

    Objective To identify whether prenatal depression is a risk factor for fetal growth restriction. Methods Midgestation (18-20 weeks GA) estimated fetal weight and urine cortisol and birth weight and gestational age at birth data were collected on a sample of 40 depressed and 40 non-depressed women. Estimated fetal weight and birthweight data were then used to compute fetal growth rates. Results Depressed women had a 13% greater incidence of premature delivery (Odds Ratio (OR) = 2.61) and 15% greater incidence of low birthweight (OR = 4.75) than non-depressed women. Depressed women also had elevated prenatal cortisol levels (p = .006) and fetuses who were smaller (p = .001) and who showed slower fetal growth rates (p = .011) and lower birthweights (p = .008). Mediation analyses further revealed that prenatal maternal cortisol levels were a potential mediator for the relationship between maternal symptoms of depression and both gestational age at birth and the rate of fetal growth. After controlling for maternal demographic variables, prenatal maternal cortisol levels were associated with 30% of the variance in gestational age at birth and 14% of the variance in the rate of fetal growth. Conclusion Prenatal depression was associated with adverse perinatal outcomes, including premature delivery and slower fetal growth rates. Prenatal maternal cortisol levels appear to play a role in mediating these outcomes. PMID:18723301

  16. Hormonal Control of Fetal Growth.

    ERIC Educational Resources Information Center

    Cooke, Paul S.; Nicoll, Charles S.

    1983-01-01

    Summarizes recent research on hormonal control of fetal growth, presenting data obtained using a new method for studying the area. Effects of endocrine ablations and congenital deficiencies, studies of hormone/receptor levels, in-vitro techniques, hormones implicated in promoting fetal growth, problems with existing methodologies, and growth of…

  17. Fetal nuchal translucency thickness.

    PubMed

    Witters, I; Fryns, J R

    2007-01-01

    In the early 1990s Nicolaides introduced screening for trisomy 21 by fetal nuchal translucency thickness measurement with ultrasound between 11-13(+6) weeks. Already in 1866 L. Down noted that common features of patients with trisomy 21 are a skin being too large for the body and a flat face with a small nose. While detection rates for trisomy 21, given an invasive testing rate of 5%, were only 30% for screening by maternal age and 65% for screening by maternal serum triple test, the detection rate for screening by nuchal translucency combined with maternal age was 75% and this could be increased to 90% in combination with maternal serum screening (serum B-human chorionic gonadotropin and pregnancy-associated plasma protein-A) at 11-13(+6) weeks. The additional soft markers in the first trimester are the fetal nasal bone, the Doppler velocity waveform in the ductus venosus and tricuspid regurgitation and these markers can be used to further increase the detection rate of trisomy 21. In addition increased nuchal translucency thickness can also identify other chromosomal defects (mainly trisomy 13 and 18 and monosomy X) and major congenital malformations (mainly cardiac defects) and genetic syndromes. PMID:17515296

  18. Fetal alcohol spectrum disorders.

    PubMed

    Dörrie, Nora; Föcker, Manuel; Freunscht, Inga; Hebebrand, Johannes

    2014-10-01

    Prenatal alcohol exposure (PAE) is one of the most prevalent and modifiable risk factors for somatic, behavioral, and neurological abnormalities. Affected individuals exhibit a wide range of such features referred to as fetal alcohol spectrum disorders (FASD). These are characterized by a more or less specific pattern of minor facial dysmorphic features, growth deficiency and central nervous system symptoms. Nevertheless, whereas the diagnosis of the full-blown fetal alcohol syndrome does not pose a major challenge, only a tentative diagnosis of FASD can be reached if only mild features are present and/or maternal alcohol consumption during pregnancy cannot be verified. The respective disorders have lifelong implications. The teratogenic mechanisms induced by PAE can lead to various additional somatic findings and structural abnormalities of cerebrum and cerebellum. At the functional level, cognition, motor coordination, attention, language development, executive functions, memory, social perception and emotion processing are impaired to a variable extent. The long-term development is characterized by disruption and failure in many domains; an age-adequate independency is frequently not achieved. In addition to primary prevention, individual therapeutic interventions and tertiary prevention are warranted; provision of extensive education to affected subjects and their caregivers is crucial. Protective environments are often required to prevent negative consequences such as delinquency, indebtedness or experience of physical/sexual abuse. PMID:24965796

  19. [Fetal microchimerism in rheumatic diseases].

    PubMed

    Huerta Sil, Gabriela; Medrano Ramírez, Gabriel

    2006-07-01

    Fetal microchimerism is the presence of fetal cells inmaternal tissues and vice versa, i.e., the coexistence of2 different cellular populations from genetically differentindividuals within a single person. The most frequentcause of microchimerism is pregnancy, in which there is abi-directional fetal-maternal interchange of cells duringpregnancy and delivery. Fetal cells have been demonstrated in the tissues ofpatients with rheumatic, endocrine or infectious diseases,as well as in those of healthy individuals. Microchimerism has been most extensively studied insystemic sclerosis. It seems that during pregnancyallogenic fetal or maternal cells cross the placenta bidirectionallyand persist in the systemic circulation andtissues of both mother and child. Subsequently, they areactivated, resulting in is a graft-against-host reactionassociated with the onset of clinical manifestations.Microchimerism has been also studied in otherconnective tissue diseases. PMID:21794328

  20. Best practice guidelines: fetal surgery.

    PubMed

    Sudhakaran, Nada; Sothinathan, Uma; Patel, Shailesh

    2012-01-01

    Fetal intervention encompasses a range of procedures on the fetus with congenital structural anomalies, whilst still on the placental circulation. The concept of fetal surgery was conceived in order to prevent fetal or early postnatal death, or to prevent permanent irreversible organ damage. The benefit of these procedures has to be balanced with risks to both the mother and the fetus. Open fetal surgery, more commonly conducted in North American centres, involves open surgery to the uterus in order to operate on the fetus. Fetal intervention centres in Europe more commonly use minimally invasive fetoscopic surgery. This paper elaborates on the various strategies used in dealing with anomalies of different organ systems of the fetus. PMID:22196142

  1. 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.

  2. New antibacterial peptide derived from bovine hemoglobin.

    PubMed

    Daoud, Rachid; Dubois, Veronique; Bors-Dodita, Loredana; Nedjar-Arroume, Naima; Krier, Francois; Chihib, Nour-Eddine; Mary, Patrice; Kouach, Mostafa; Briand, Gilbert; Guillochon, Didier

    2005-05-01

    Peptic digestion of bovine hemoglobin at low degree of hydrolysis yields an intermediate peptide fraction exhibiting antibacterial activity against Micrococcus luteus A270, Listeria innocua, Escherichia coli and Salmonella enteritidis after separation by reversed-phase HPLC. From this fraction a pure peptide was isolated and analyzed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and electrospray ionization tandem mass spectrometry (ESI-MS/MS). This peptide correspond to the 107-136 fragment of the alpha chain of bovine hemoglobin. The minimum inhibitory concentrations (MIC) towards the four strains and its hemolytic activity towards bovine erythrocytes were determined. A MIC of 38 microM was reported against L. innocua and 76 microM for other various bacterial species. This peptide had no hemolytic activity up to 380 microM concentration. PMID:15808900

  3. Measurement of phenol concentrations using hemoglobin

    SciTech Connect

    Woodward, J.; Allen, B.F.; Scott, M.A.

    1984-01-01

    A major pollutant found in coal conversion wastewaters is phenol. Its removal by methods such as gravity separation, steam stripping, solvent extraction, biotreatment, and carbon adsorption must be monitored in order to determine that the water has been made safe for release back into the environment. Monitoring phenol concentrations in aqueous waste solutions is usually by the aminoantipyrine method. Other methods described for phenol determination include the use of enzyme electrodes based on immobilized tyrosinase and immobilized phenol hydroxylase. The authors present preliminary data upon which a new assay for phenols could be based. It concerns the peroxidatic activity of hemoglobin. When phenol, hemoglobin, and hydrogen peroxide are incubated together, there is an increase in absorbance at 260 nm which is proportional to the concentration of phenol. 5 references, 2 figures.

  4. Free heme and sickle hemoglobin polymerization

    NASA Astrophysics Data System (ADS)

    Uzunova, Veselina V.

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

  5. Successful intrauterine treatment and good long-term outcome in an extremely severe case of fetal hemolytic disease

    PubMed Central

    Kretowicz, Piotr; Tarasiuk, Anna; Dangel, Joanna; Dębski, Romuald

    2014-01-01

    A 34-year-old multiparous woman presented with anti-Rh-D antibodies (1: 512) and fetal hydrops at the 21st week of gestation. Ultrasound revealed massive fetal skin edema, ascites, hepatomegaly, placentomegaly, and anhydramnios. No fetal movements were observed. Fetal heart was enlarged, with reportedly decreased contractibility. The Doppler parameters were abnormal: the peak systolic velocity in median cerebral artery (MCA PSV) was increased (84 cm/s, 3 MoM), and absent end diastolic flow (AEDF) was reported in the umbilical artery. Ultrasound examination indicated severe fetal anemia and heart failure. Umbilical vein puncture was performed and the fetal blood count was determined (RBC 0.01 × 106/µl, Ht 0.1%, PLT 67 × 103/µl, WBC 2.1 × 103/µl, indeterminable hemoglobin level). Packed red blood cells (0 Rh-, 30 ml) were immediately transfused to the fetus. Altogether, seven intrauterine transfusions were performed. Fetal hydrops disappeared gradually during the next few weeks. The male neonate (1860 g, 45 cm, Apgar score 3–4) was delivered after the last transfusion at 34th week of gestation due of intrauterine asphyxia. The infant was discharged after 21 days, in good condition, on breastfeeding. There was one 10 mm focus of periventricular leukomalacia in the brain, diagnosed based on trans-fontanel ultrasound, without any signs of damage to other organs. At the age of 5 years, the child is healthy, with no abnormalities in his neurodevelopmental parameters. PMID:26673879

  6. Successful intrauterine treatment and good long-term outcome in an extremely severe case of fetal hemolytic disease.

    PubMed

    Dębska, Marzena; Kretowicz, Piotr; Tarasiuk, Anna; Dangel, Joanna; Dębski, Romuald

    2014-06-01

    A 34-year-old multiparous woman presented with anti-Rh-D antibodies (1: 512) and fetal hydrops at the 21(st) week of gestation. Ultrasound revealed massive fetal skin edema, ascites, hepatomegaly, placentomegaly, and anhydramnios. No fetal movements were observed. Fetal heart was enlarged, with reportedly decreased contractibility. The Doppler parameters were abnormal: the peak systolic velocity in median cerebral artery (MCA PSV) was increased (84 cm/s, 3 MoM), and absent end diastolic flow (AEDF) was reported in the umbilical artery. Ultrasound examination indicated severe fetal anemia and heart failure. Umbilical vein puncture was performed and the fetal blood count was determined (RBC 0.01 × 10(6)/µl, Ht 0.1%, PLT 67 × 10(3)/µl, WBC 2.1 × 10(3)/µl, indeterminable hemoglobin level). Packed red blood cells (0 Rh-, 30 ml) were immediately transfused to the fetus. Altogether, seven intrauterine transfusions were performed. Fetal hydrops disappeared gradually during the next few weeks. The male neonate (1860 g, 45 cm, Apgar score 3-4) was delivered after the last transfusion at 34(th) week of gestation due of intrauterine asphyxia. The infant was discharged after 21 days, in good condition, on breastfeeding. There was one 10 mm focus of periventricular leukomalacia in the brain, diagnosed based on trans-fontanel ultrasound, without any signs of damage to other organs. At the age of 5 years, the child is healthy, with no abnormalities in his neurodevelopmental parameters. PMID:26673879

  7. Interference with hemoglobin A(1C) determination by the hemoglobin variant Shelby.

    PubMed

    Scuderi, Richard T; Griffin, Terrance L; Mehta, Shruti P; Herold, David A; Fitzgerald, Robert L

    2007-09-01

    Hemoglobin variant carrier status was found in a 46-year-old African American man following detection of a falsely elevated hemoglobin A1c (HbA1c) by ionexchange high-performance liquid chromatography (HPLC, VARIANT A1c, Bio-Rad Laboratories, Hercules, CA). Additional analysis of the hemoglobin variant using the Beta Thal Short program (Bio-Rad) revealed an unknown peak with a retention time of 4.84 minutes and a proportion of 26.3%. No mass shift in alpha-globin or beta-globin proteins was observed by mass spectrometry. DNA sequencing revealed a missense mutation in 1 beta-globin allele corresponding to the hemoglobin Shelby trait. The patient was asymptomatic with a normal hemoglobin value of 13.6 g/dL (136 g/L) but had increased target cells on a peripheral blood smear. An alternative method for HbA1c determination using boronate-affinity HPLC provided a value of 3.9% (0.04; reference range, 4.0%-6.9% [0.04-0.07]), more consistent with the patient's recent blood glucose values in the normal range. PMID:17709318

  8. Studies on hemoglobin tryptophanyl contact residues in the haptoglobin-hemoglobin complex.

    PubMed

    Rogard, M; Waks, M

    1977-07-15

    Hemoglobin and apohemoglobin bind heptoglobin in the same molar ratio. Structural studies on haptoglobin-hemoglobin complex do not suggest any important structural changes in either protein upon binding. However, when apohemoglobin is bound to haptoglobin, a marked reduction in secondary structure, attributed to unfolding of globin chains, has been observed. Here we describe some properties of the haptoglobin-apohemoglobin (Hp-apoHb) complex, prepared by isoelectric focusing in the presence of an excess of haptoglobin. This complex does not exhibit the irreversibility of complexes obtained with hemoglobin in identical experimental conditions. The 'freezing' of the conformation of apohemoglobin upon binding to haptoglobin has been studied by fluorescence quenching experiments carried out in the presence of 8 M acrylamide. Changes in conformation of haptoglobin upon binding to apohemoglobin have been detected by titration of the exposed tryptophans using N-bromosuccinimide. Comparison of the additivity of exposed tryptophans in the complexes reveal that two tryptophans become inaccessible in the complex formation of haptoglobin with hemoglobin but not with apohemoglobin. These tryptophans, probably located on the alpha1beta2 contact interface of hemoglobin, have been tentatively identified as Trp-C3(37)beta. PMID:891540

  9. Fetal MRI: A pictorial essay

    PubMed Central

    Rathee, Sapna; Joshi, Priscilla; Kelkar, Abhimanyu; Seth, Nagesh

    2016-01-01

    Ultrasonography (USG) is the primary method for antenatal fetal evaluation. However, fetal magnetic resonance imaging (MRI) has now become a valuable adjunct to USG in confirming/excluding suspected abnormalities and in the detection of additional abnormalities, thus changing the outcome of pregnancy and optimizing perinatal management. With the development of ultrafast sequences, fetal MRI has made remarkable progress in recent times. In this pictorial essay, we illustrate a spectrum of structural abnormalities affecting the central nervous system, thorax, genitourinary and gastrointestinal tract, as well as miscellaneous anomalies. Anomalies in twin gestations and placental abnormalities have also been included. PMID:27081224

  10. Fetal malposition: impact and management.

    PubMed

    Caughey, Aaron B; Sharshiner, Rita; Cheng, Yvonne W

    2015-06-01

    Fetal malposition, either occiput posterior or transverse (OT), leads to greater risk of cesarean delivery, prolonged labor, and increased perinatal morbidity. Historically, there is a known association between epidural use and malposition that was assumed to be due to the increased discomfort of laboring with a fetus in the occiput posterior position. However, evidence now suggests that the epidural itself may contribute to fetal malposition by impacting the probability of internal rotation. Fetal malposition may be impacted by manual rotation. Manual rotation has been associated with greater rates of delivering in the occiput anterior position and lower rates of cesarean delivery. PMID:25851845

  11. Acute and Chronic Fetal Anemia as a Result of Fetomaternal Hemorrhage

    PubMed Central

    Swanson, Tara

    2014-01-01

    Introduction. Fetomaternal hemorrhage represents a transfer of fetal blood to the maternal circulation. Although many etiologies have been described, most causes of fetomaternal hemorrhage remain unidentified. The differentiation between acute and chronic fetomaternal hemorrhage may be accomplished antenatally and may influence perinatal management. Case. A 36-year-old gravida 6 para 3 presented at 37 and 5/7 completed gestational weeks with ultrasound findings suggestive of chronic fetal anemia such as right ventricular enlargement, diminished cerebral vascular resistance, and elevated middle cerebral artery end-diastolic velocity. On the other hand, signs of acute fetal decompensation such as deterioration of the fetal heart tracing, diminished biophysical score, decreased cord pH, and increased cord base deficit were noted. Following delivery, the neonate's initial hemoglobin was 4.0 g/dL and the maternal KB ratio was 0.015 indicative of a significant fetomaternal hemorrhage. Discussion. One should consider FMH as part of the differential diagnosis for fetal or immediate neonatal anemia. We describe a unique case of FMH that demonstrated both acute and chronic clinical features. It is our hope that this case will assist practitioners in differentiating acute FMH that may require emergent delivery from chronic FMH which may be able to be expectantly managed. PMID:24804127

  12. Relationship of Baseline Hemoglobin Level with Serum Ferritin, Postphlebotomy Hemoglobin Changes, and Phlebotomy Requirements among HFE C282Y Homozygotes.

    PubMed

    Mousavi, Seyed Ali; Mahmood, Faiza; Aandahl, Astrid; Knutsen, Teresa Risopatron; Llohn, Abid Hussain

    2015-01-01

    Objectives. We aimed to examine whether baseline hemoglobin levels in C282Y-homozygous patients are related to the degree of serum ferritin (SF) elevation and whether patients with different baseline hemoglobin have different phlebotomy requirements. Methods. A total of 196 patients (124 males and 72 females) who had undergone therapeutic phlebotomy and had SF and both pre- and posttreatment hemoglobin values were included in the study. Results. Bivariate correlation analysis suggested that baseline SF explains approximately 6 to 7% of the variation in baseline hemoglobin. The results also showed that males who had higher (≥150 g/L) baseline hemoglobin levels had a significantly greater reduction in their posttreatment hemoglobin despite requiring fewer phlebotomies to achieve iron depletion than those who had lower (<150 g/L) baseline hemoglobin, regardless of whether baseline SF was below or above 1000 µg/L. There were no significant differences between hemoglobin subgroups regarding baseline and treatment characteristics, except for transferrin saturation between male subgroups with SF above 1000 µg/L. Similar differences were observed when females with higher (≥138 g/L) baseline hemoglobin were compared with those with lower (<138 g/L) baseline hemoglobin. Conclusion. Dividing C282Y-homozygous patients into just two subgroups according to the degree of baseline SF elevation may obscure important subgroup variations. PMID:26380265

  13. Diffuse optical tomography and spectroscopy of breast cancer and fetal brain

    NASA Astrophysics Data System (ADS)

    Choe, Regine

    Diffuse optical techniques utilize light in the near infrared spectral range to measure tissue physiology non-invasively. Based on these measurements, either on average or a three-dimensional spatial map of tissue properties such as total hemoglobin concentration, blood oxygen saturation and scattering can be obtained using model-based reconstruction algorithms. In this thesis, diffuse optical techniques were applied for in vivo breast cancer imaging and trans-abdominal fetal brain oxygenation monitoring. For in vivo breast cancer imaging, clinical diffuse optical tomography and related instrumentation was developed and used in several contexts. Bulk physiological properties were quantified for fifty-two healthy subjects in the parallel-plate transmission geometry. Three-dimensional images of breast were reconstructed for subjects with breast tumors and, tumor contrast with respect to normal tissue was found in total hemoglobin concentration and scattering and was quantified for twenty-two breast carcinomas. Tumor contrast and tumor volume changes during neoadjuvant chemotherapy were tracked for one subject and compared to the dynamic contrast-enhanced MRI. Finally, the feasibility for measuring blood flow of breast tumors using optical methods was demonstrated for seven subjects. In a qualitatively different set of experiments, the feasibility for trans-abdominal fetal brain oxygenation monitoring was demonstrated on pregnant ewes with induced fetal hypoxia. Preliminary clinical experiences were discussed to identify future directions. In total, this research has translated diffuse optical tomography techniques into clinical research environment.

  14. Passive Fetal Heart Monitoring System

    NASA Technical Reports Server (NTRS)

    Zuckerwar, Allan J. (Inventor); Mowrey, Dennis L. (Inventor)

    2003-01-01

    A fetal heart monitoring system and method for detecting and processing acoustic fetal heart signals transmitted by different signal transmission modes. One signal transmission mode, the direct contact mode, occurs in a first frequency band when the fetus is in direct contact with the maternal abdominal wall. Another signal transmission mode, the fluid propagation mode, occurs in a second frequency band when the fetus is in a recessed position with no direct contact with the maternal abdominal wall. The second frequency band is relatively higher than the first frequency band. The fetal heart monitoring system and method detect and process acoustic fetal heart signals that are in the first frequency band and in the second frequency band.

  15. Universal Metastability of Sickle Hemoglobin Polymerization

    PubMed Central

    Weng, Weijun; Aprelev, Alexey; Briehl, Robin W.; Ferrone, Frank A.

    2008-01-01

    Summary Sickle hemoglobin (HbS) polymerization occurs when deoxy HbS concentration exceeds a well-defined solubility. In experiments using sickle hemoglobin droplets suspended in oil, it has been shown that when polymerization ceases the monomer concentration is above equilibrium solubility. We find that the final concentration in uniform bulk solutions (i.e. with negligible boundaries) agrees with the droplet measurements, and both exceed the expected solubility. To measure hemoglobin in uniform solutions we used modulated excitation of trace amounts of CO in gels of HbS. In this method, a small amount of CO is introduced to a spatially uniform deoxyHb sample, so that less than 2% of the sample is liganded. The liganded fraction is repeatedly photolyzed and the rate of recombination allows the concentration of deoxyHbS in the solution phase to be determined, even if polymers have formed. Both uniform and droplet samples exhibit the same quantitative behavior, exceeding solubility by an amount that depends on the initial concentration of the sample, as well as conditions under which the gel was formed. We hypothesize that the early termination of polymerization is due to the obstruction in polymer growth, which is consistent with the observation that pressing on slides lowers the final monomer concentration, making it closer to solubility. The thermodynamic solubility in free solution is thus only achieved in conditions with low polymer density or under external forces (such as found in sedimentation) that disrupt polymers. Since we find that only about 67% of the expected polymer mass forms, this result will impact any analysis predicated on predicting the polymer fraction in a given experiment. PMID:18308336

  16. Oxygen binding by single crystals of hemoglobin.

    PubMed

    Rivetti, C; Mozzarelli, A; Rossi, G L; Henry, E R; Eaton, W A

    1993-03-23

    Reversible oxygen binding curves for single crystals of hemoglobin in the T quaternary structure have been measured using microspectrophotometry. Saturations were determined from complete visible spectra measured with light linearly polarized parallel to the a and c crystal axes. Striking differences were observed between the binding properties of hemoglobin in the crystal and those of hemoglobin in solution. Oxygen binding to the crystal is effectively noncooperative, the Bohr effect is absent, and there is no effect of chloride ion. Also, the oxygen affinity is lower than that of the T quaternary structure in solution. The absence of the Bohr effect supports Perutz's hypothesis on the key role of the salt bridges, which are known from X-ray crystallography to remain intact upon oxygenation. The low affinity and absence of the Bohr effect can be explained by a generalization of the MWC-PSK model (Monod, Wyman, & Changeux, 1965; Perutz, 1970; Szabo & Karplus, 1972) in which both high- and low-affinity tertiary conformations, with broken and unbroken salt bridges, respectively, are populated in the T quaternary structure. Because the alpha and beta hemes make different projections onto the two crystal axes, separate binding curves for the alpha and beta subunits could be calculated from the two measured binding curves. The approximately 5-fold difference between the oxygen affinities of the alpha and beta subunits is much smaller than that predicted from the crystallographic study of Dodson, Liddington, and co-workers, which suggested that oxygen binds only to the alpha hemes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8457555

  17. 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.

  18. Mini-hemoglobins from nemertean worms.

    PubMed

    Vandergon, Thomas L; Riggs, Austen F

    2008-01-01

    Hemoglobins (Hbs) found in members of the phylum Nemertea are smaller than any other known Hb molecules. These mini-Hbs have been of great interest because of their unique three-dimensional structure and their stable ligand-binding properties. Also of interest is the expression of mini-Hb in neural tissue, body wall muscle tissue, and red blood cells. This chapter outlines methods that may be used to isolate and purify functional mini-Hbs from all three tissue types in nemertean worms. PMID:18237651

  19. [Structural anomalies of dog hemoglobin after ionizing irradiation].

    PubMed

    Sukhomlinov, B F; Savich, A V; Shal'no, M I; Starikovich, L S; Dudok, E P

    1981-01-01

    Heterogeneity of dog hemoglobin is established with application of chromatographic analysis. Ionizing radiation (4 Grey) induces no changes in the ratio of hemoglobin components. The comparative dactylographical analysis of the hemoglobin components in norm and in different periods after irradiation revealed differences in responses to tryptophan in peptide T-25. The changes found are connected with disturbances in the structure of the DNA molecule as well as with modification of the protein molecule under conditions of radiation injury. PMID:7324186

  20. The Role of Alpha-Hemoglobin Stabilizing Protein in Redox Chemistry, Denaturation, and Hemoglobin Assembly

    PubMed Central

    Mollan, Todd L.; Yu, Xiang; Weiss, Mitchell J.

    2010-01-01

    Abstract Hemoglobin biosynthesis in erythrocyte precursors involves several steps. The correct ratios and concentrations of normal alpha (α) and beta (β) globin proteins must be expressed; apoproteins must be folded correctly; heme must be synthesized and incorporated into these globins rapidly; and the individual α and β subunits must be rapidly and correctly assembled into heterotetramers. These events occur on a large scale in vivo, and dysregulation causes serious clinical disorders such as thalassemia syndromes. Recent work has implicated a conserved erythroid protein known as Alpha-Hemoglobin Stabilizing Protein (AHSP) as a participant in these events. Current evidence suggests that AHSP enhances α subunit stability and diminishes its participation in harmful redox chemistry. There is also evidence that AHSP facilitates one or more early-stage post-translational hemoglobin biosynthetic events. In this review, recent experimental results are discussed in light of several current models describing globin subunit folding, heme uptake, assembly, and denaturation during hemoglobin synthesis. Particular attention is devoted to molecular interactions with AHSP that relate to α chain oxidation and the ability of α chains to associate with partner β chains. Antioxid. Redox Signal. 12, 219–232. PMID:19659437

  1. Ultrasonic findings of fetal axillary lymphangioma with intralesional hemorrhage.

    PubMed

    Furue, Akiko; Mochizuki, Junko; Onishi, Yoko; Kawano, Shoko; Kanai, Yuji; Kemmochi, Manabu; Tanaka, Kiyoshi; Unno, Nobuya

    2016-04-01

    We report a case of an axillary lymphangioma in a fetus delivered at 30 weeks' gestation with suspected intralesional hemorrhage based on the ultrasonic findings. In the ultrasonic examination at 15 weeks' gestation, the fetus was found to have a multilocular mass spreading from the axilla to the chest wall, which was diagnosed as an axillary lymphangioma. Chromosome analysis by amniocentesis showed a normal karyotype, and no other malformations were observed. At 29 weeks, the mass had increased in size, and color Doppler ultrasound examination revealed that the middle cerebral artery peak systolic velocity (MCA-PSV) reached 80.2 cm/s [1.86 MoM (multiples of the median)]. Intralesional bleeding was suspected because of the multiple images of hemorrhage in which sites of blood spouting in a pulsatile fashion were detected within the mass. Cordocentesis at 30 weeks revealed that fetal hemoglobin concentration was 5.1 g/dL. An emergency Cesarean section was performed. A female weighing 2810 g, including the mass, was delivered, and the blood hemoglobin level was 5.9 g/dL at birth. Blood transfusion, fine-needle aspiration of the fluid in the mass, intralesional injection of OK-432, and partial excision of the lymphangioma were performed after birth. Ultrasonic examination proved useful in the diagnosis of intralesional bleeding in this lymphangioma. PMID:26707998

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

    PubMed

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

    2012-09-01

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

  3. 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.

  4. Sex differences and hemoglobin levels in relation to stroke outcomes

    PubMed Central

    Lima, Fabricio O.; O’Connor, Sydney; Furie, Karen L.

    2013-01-01

    Objective: Women have worse outcomes after stroke compared to men. Since women have lower hemoglobin values, we examined whether hemoglobin levels may associate with worse stroke outcomes in women. Methods: We retrospectively studied 274 patients enrolled in a prospective multicenter study. We explored the relationship of hemoglobin with clinical outcome at 6 months, as measured by the modified Rankin Scale (mRS). Ordinal logistic regression was used to evaluate the independent effect of hemoglobin on clinical outcome, and to explore the influence of sex on that association. Results: Women had a lower mean hemoglobin level (11.7 ± 1.8 g/dL) compared to men (13.3 ± 1.7 g/dL). Low hemoglobin was associated with worse 6-month mRS outcomes in univariate analysis (p < 0.001). Lower hemoglobin remained independently associated with poor outcome after adjustment for comorbid disease, stroke severity, age, and sex. The inclusion of hemoglobin in the model attenuated the independent effect of sex on outcome. Conclusions: Sex differences in stroke outcome are linked to lower hemoglobin level, which is more prevalent in women. Further examination of this potentially modifiable predictor is warranted. PMID:23365064

  5. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  6. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  7. Uterine artery blood flow, fetal hypoxia and fetal growth

    PubMed Central

    Browne, Vaughn A.; Julian, Colleen G.; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G.

    2015-01-01

    Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100–4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

  8. Uterine artery blood flow, fetal hypoxia and fetal growth.

    PubMed

    Browne, Vaughn A; Julian, Colleen G; Toledo-Jaldin, Lillian; Cioffi-Ragan, Darleen; Vargas, Enrique; Moore, Lorna G

    2015-03-01

    Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100-4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success. PMID:25602072

  9. Average fetal depth in utero: data for estimation of fetal absorbed radiation dose

    SciTech Connect

    Ragozzino, M.W.; Breckle, R.; Hill, L.M.; Gray, J.E.

    1986-02-01

    To estimate fetal absorbed dose from radiographic examinations, the depth from the anterior maternal surface to the midline of the fetal skull and abdomen was measured by ultrasound in 97 pregnant women. The relationships between fetal depth, fetal presentation, and maternal parameters of height, weight, anteroposterior (AP) thickness, gestational age, placental location, and bladder volume were analyzed. Maternal AP thickness (MAP) can be estimated from gestational age, maternal height, and maternal weight. Fetal midskull and abdominal depths were nearly equal. Fetal depth normalized to MAP was independent or nearly independent of maternal parameters and fetal presentation. These data enable a reasonable estimation of absorbed dose to fetal brain, abdomen, and whole body.

  10. Hemoglobin alpha in the blood vessel wall

    PubMed Central

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

    2014-01-01

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

  11. Modeling and measuring extravascular hemoglobin: aging contusions

    NASA Astrophysics Data System (ADS)

    Lines, Collin; Kim, Oleg; Duffy, Susan; Alber, Mark; Crawford, Gregory P.

    2011-07-01

    Medical expertise is frequently elicited to aid in determining the age and the cause of the trauma or injury. Child protection and law enforcement frequently rely on the physical assessment of the trauma which involves delineating intentional from unintentional types of trauma. Recent studies have shown that current methods to assess the age of traumatic injuries are highly inaccurate and do not give reasonable predictions. Hemoglobin is one of the strongest chromophores in human tissues. Transport of hemoglobin and its breakdown products in tissue determines the spectrophotometric characteristics of the skin and its variations in time. Therefore, measurements of diffuse reflective spectra of the skin allow noninvasive screening. This paper reviews potential transmission and diffusive reflection spectroscopy based techniques and predictive and quantitative modeling methods assisting in efficient retrieval of the age of extravascular contusions. This paper then presents a novel Monte Carlo technique for 3D photon tracking and blood transport model. In future studies, clinically obtained spectra will be used to validate the model as well as fine-tune coefficients for absorption. It is the goal of this study to develop a model that would allow a non-invasive, accurate determination of the age of a bruise.

  12. Screening for fetal aneuploidy.

    PubMed

    Rink, Britton D; Norton, Mary E

    2016-02-01

    Screening is currently recommended in pregnancy for a number of genetic disorders, chromosomal aneuploidy, and structural birth defects in the fetus regardless of maternal age or family history. There is an overwhelming array of sonographic and maternal serum-based options available for carrying out aneuploidy risk assessment in the first and/or second trimester. As with any screening test, the patient should be made aware that a "negative" test or "normal" ultrasound does not guarantee a healthy baby and a "positive" test does not mean the fetus has the condition. The woman should have both pre- and post-test counseling to discuss the benefits, limitations, and options for additional testing. Rapid advancements of genetic technologies have made it possible to screen for the common aneuploidies traditionally associated with advanced maternal age with improved levels of accuracy beyond serum and ultrasound based testing. Prenatal screening for fetal genetic disorders with cell-free DNA has transformed prenatal care with yet unanswered questions related to the financial, ethical, and appropriate application in the provision of prenatal risk assessment. PMID:26725144

  13. Persistent fetal circulation

    PubMed Central

    D’cunha, Chrysal; Sankaran, Koravangattu

    2001-01-01

    Persistent fetal circulation (PFC), also known as persistent pulmonary hypertension of the newborn, is defined as postnatal persistence of right-to-left ductal or atrial shunting, or both in the presence of elevated right ventricular pressure. It is a relatively rare condition that is usually seen in newborns with respiratory distress syndrome, overwhelming sepsis, meconium and other aspiration syndromes, intrauterine hypoxia and ischemia, and/or neonatal hypoxia and ischemia. This condition causes severe hypoxemia, and, as a result, has significant morbidity and mortality. Improved antenatal and neonatal care; the use of surfactant; continuous monitoring of oxygenation, blood pressure and other vital functions; and early recognition and intervention have made this condition even more rare. In modern neonatal intensive care units, anticipation and early treatment of PFC and its complications in sick newborns are commonplace. Thus, severe forms of PFC are only seen on isolated occasions. Consequently, it is even more imperative to revisit PFC compared with the time when there were occasional cases of PFC seen in neonatal intensive care units, and to discuss evolving treatment and management issues that pertain to this syndrome. PMID:20084150

  14. Fetal sex and race modify the predictors of fetal growth.

    PubMed

    Reynolds, Simone A; Roberts, James M; Bodnar, Lisa M; Haggerty, Catherine L; Youk, Ada O; Catov, Janet M

    2015-04-01

    The objective of this study is unknown if fetal sex and race modify the impact of maternal pre-pregnancy body mass index (BMI), and smoking on fetal growth. The authors studied markers of fetal growth in singleton offspring of 8,801 primiparous, normotensive women, enrolled in the Collaborative Perinatal Project. The authors tested for departures from additivity between sex/race and each predictor. The head-to-chest circumference ratio (HCC) decreased more, while birthweight and ponderal index (PI) increased more for each 1 kg/m(2) increase in pre-pregnancy BMI among term females versus males (P = 0.07, P < 0.01 and P = 0.08, interaction respectively). For term offspring of White compared with Black women, smoking independent of "dose" was associated with larger reductions in growth (165 g vs. 68 g reduction in birthweight, P < 0.01, interaction), greater reduction in fetal placental ratio (P < 0.01, interaction), PI (P < 0.01, interaction), and greater increase in HCC (P = 0.02), respectively. The association of BMI and smoking with fetal size appeared to be reversed in term versus preterm infants. Our study provides evidence that the associations of pre-pregnancy BMI and smoking are not constant across sex and race. This finding may be relevant to sex and race differences in neonatal and long term health outcomes. PMID:25030701

  15. Fetal Globin Gene Inducers: Novel Agents & New Potential

    PubMed Central

    Perrine, Susan P.; Castaneda, Serguei A.; Chui, David H.; Faller, Douglas V.; Berenson, Ronald J.; Fucharoen, Suthat

    2013-01-01

    Inducing expression of endogenous fetal globin (γ-globin) gene expression to 60-70% of alpha globin synthesis produces β-thalassemia trait globin synthetic ratios and can reduce anemia to a mild level. Several classes of therapeutics have induced γ-globin expression in beta thalassemia patients and subsequently raised total hemoglobin levels, demonstrating proof-of-concept of the approach. Butyrate treatment eliminated transfusion requirements in formerly transfusion-dependent patients with treatment for as long as 7 years. However, prior generations were not readily applicable for widespread use. Currently, a novel oral dual-action therapeutic sodium 2,2-dimethylbutyrate is in clinical trials, an oral decitabine formulation is under development, and agents with complementary mechanisms of action can be applied in combined regimens. Identification of 3 major genetic trait loci which modulate clinical severity provides avenues for developing tailored regimens. These refinements offer renewed potential to apply fetal globin induction as a treatment approach in patient-friendly regimens that can be used world-wide. PMID:20712788

  16. Rate of Nitric Oxide Scavenging by hemoglobin bound to haptoglobin

    PubMed Central

    Azarov, Ivan; He, Xiaojun; Jeffers, Anne; Basu, Swati; Ucer, Burak; Hantgan, Roy R.; Levy, Andrew; Kim-Shapiro, Daniel B.

    2008-01-01

    Cell-free hemoglobin, released from the red cell, may play a major role in regulating the bioavailability of nitric oxide. The abundant serum protein haptoglobin, rapidly binds to free hemoglobin forming a stable complex accelerating its clearance. The haptoglobin gene is polymorphic with two classes of alleles denoted 1 and 2. We have previously demonstrated that the haptoglobin 1 protein-hemoglobin complex is cleared twice as fast as the haptoglobin 2 protein-hemoglobin complex. In this report we explored whether haptoglobin binding to hemoglobin reduces the rate of nitric oxide scavenging using time-resolved absorption spectroscopy. We found that both the haptoglobin 1 and haptoglobin 2 protein complexes react with nitric oxide at the same rate as unbound cell-free hemoglobin. To confirm these results we developed a novel assay where free hemoglobin and hemoglobin bound to haptoglobin competed in the reaction with NO. The relative rate of the NO reaction was then determined by examining the amount of reacted species using analytical ultracentrifugation. Since complexation of hemoglobin with haptoglobin does not reduce NO scavenging, we propose that the haptoglobin genotype may influence nitric oxide bioavailability by determining the clearance rate of the haptoglobin-hemoglobin complex. We provide computer simulations showing that a two-fold difference in the rate of uptake of the haptoglobin hemoglobin complex by macrophages significantly affects nitric oxide bioavailability thereby providing a plausible explanation for why there is more vasospasm after subarachnoid hemorrhage in individuals and transgenic mice homozygous for the Hp 2 allele. PMID:18364244

  17. Computation Of Facilitated Transport of O2 In Hemoglobin

    NASA Technical Reports Server (NTRS)

    Davis, Sanford

    1991-01-01

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

  18. Hemoglobin Screening Independently Predicts All-Cause Mortality.

    PubMed

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

    2015-01-01

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

  19. 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) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7400 Hemoglobin A...

  20. 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) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7400 Hemoglobin...

  1. 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) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7400 Hemoglobin...

  2. 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) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7400 Hemoglobin...

  3. 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) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7400 Hemoglobin A...

  4. 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. PMID:19337276

  5. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hemoglobin immunological test system. 866.5470 Section 866.5470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  6. 21 CFR 866.5470 - Hemoglobin immunological test system.

    Code of Federal Regulations, 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... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  7. 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... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  8. 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 Section 866.5470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...

  9. HEMOGLOBIN BINDING AS A DOSE MONITOR FOR CHEMICAL CARCINOGENS

    EPA Science Inventory

    The covalent binding of chemical carcinogens and mutagens to hemoglobin has been proposed as a dose monitor for environmental exposure. The binding of chloroform and bromoform to hemoglobin in rats was demonstrated to result from the formation of adducts to amino acids in the glo...

  10. Fetal Programming and Cardiovascular Pathology

    PubMed Central

    Alexander, Barbara T.; Dasinger, John Henry; Intapad, Suttira

    2016-01-01

    Low birth weight serves as a crude proxy for impaired growth during fetal life and indicates a failure for the fetus to achieve its full growth potential. Low birth weight can occur in response to numerous etiologies that include complications during pregnancy, poor prenatal care, parental smoking, maternal alcohol consumption or stress. Numerous epidemiological and experimental studies demonstrate that birth weight is inversely associated with blood pressure and coronary heart disease. Sex and age impact the developmental programming of hypertension. In addition, impaired growth during fetal life also programs enhanced vulnerability to a secondary insult. Macrosomia, which occurs in response to maternal obesity, diabetes and excessive weight gain during gestation, is also associated with increased cardiovascular risk. Yet, the exact mechanisms that permanently change the structure, physiology and endocrine health of an individual across their lifespan following altered growth during fetal life are not entirely clear. Transmission of increased risk from one generation to the next in the absence of an additional prenatal insult indicates an important role for epigenetic processes. Experimental studies also indicate that the sympathetic nervous system, the renin angiotensin system, increased production of oxidative stress and increased endothelin play an important role in the developmental programming of blood pressure in later life. Thus, this review will highlight how adverse influences during fetal life and early development program an increased risk for cardiovascular disease including high blood pressure and provide an overview of the underlying mechanisms that contribute to the fetal origins of cardiovascular pathology. PMID:25880521

  11. Mechanism of two-photon excited hemoglobin fluorescence emission

    NASA Astrophysics Data System (ADS)

    Sun, Qiqi; Zheng, Wei; Wang, Jiannong; Luo, Yi; Qu, Jianan Y.

    2015-10-01

    Hemoglobin, one of the most important proteins in the human body, is composed of "heme" groups (iron-containing rings) and "globins" (proteins). We investigate the two-photon excited fluorescence of hemoglobin and its subunit components (heme and globin). We measure the hemoglobin fluorescence lifetime by using a streak camera of ps resolution and confirm that its lifetime is in femtosecond scale. In the study of the fluorescence properties of heme and globin, the experimental results reveal that heme is the sole fluorophore of hemoglobin. Hemoglobin fluorescence can be effectively excited only via two-photon process, because heme has a centrosymmetric molecular structure and two-photon allowed transition is forbidden for single-photon process and vice versa due to the Laporte parity selection rule.

  12. Hemoglobin-Based Nanoarchitectonic Assemblies as Oxygen Carriers.

    PubMed

    Jia, Yi; Duan, Li; Li, Junbai

    2016-02-10

    Safe and effective artificial oxygen carriers are the subject of great interest due to the problems of traditional blood transfusion and enormous demand in clinical use. In view of its unique oxygen-transport ability and normal metabolic pathways, hemoglobin is regarded as an ideal oxygen-carrying unit. With advances in nano-biotechnology, hemoglobin assemblies as artificial oxygen carriers achieve great development. Here, recent progress on hemoglobin-based oxygen carriers is highlighted in view of two aspects: acellular hemoglobin-based oxygen carriers and cellular hemoglobin-based oxygen carriers. These novel oxygen carriers exhibit advantages over traditional carriers and will greatly promote research on reliable and feasible oxygen carriers. PMID:26479864

  13. Mechanism of two-photon excited hemoglobin fluorescence emission.

    PubMed

    Sun, Qiqi; Zheng, Wei; Wang, Jiannong; Luo, Yi; Qu, Jianan Y

    2015-10-01

    Hemoglobin, one of the most important proteins in the human body, is composed of “heme” groups (iron-containing rings) and “globins” (proteins). We investigate the two-photon excited fluorescence of hemoglobin and its subunit components (heme and globin). We measure the hemoglobin fluorescence lifetime by using a streak camera of ps resolution and confirm that its lifetime is in femtosecond scale. In the study of the fluorescence properties of heme and globin, the experimental results reveal that heme is the sole fluorophore of hemoglobin. Hemoglobin fluorescence can be effectively excited only via two-photon process, because heme has a centrosymmetric molecular structure and two-photon allowed transition is forbidden for single-photon process and vice versa due to the Laporte parity selection rule. PMID:26506468

  14. Computational Study on Hemoglobin Protein Family

    NASA Astrophysics Data System (ADS)

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

    2009-05-01

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

  15. Mycobacterial truncated hemoglobins: from genes to functions.

    PubMed

    Ascenzi, Paolo; Bolognesi, Martino; Milani, Mario; Guertin, Michel; Visca, Paolo

    2007-08-15

    Infections caused by bacteria belonging to genus Mycobacterium are among the most challenging threats for human health. The ability of mycobacteria to persist in vivo in the presence of reactive nitrogen and oxygen species implies the presence in these bacteria of effective detoxification mechanisms. Mycobacterial truncated hemoglobins (trHbs) have recently been implicated in scavenging of reactive nitrogen species. Individual members from each trHb family (N, O, and P) can be present in the same mycobacterial species. The distinct features of the heme active site structure combined with different ligand binding properties and in vivo expression patterns of mycobacterial trHbs suggest that these globins may accomplish diverse functions. Here, recent genomic, structural and biochemical information on mycobacterial trHbs is reviewed, with the aim of providing further insights into the role of these globins in mycobacterial physiology. PMID:17532149

  16. [The glycated hemoglobin: indication, interpretation and limitations].

    PubMed

    Zendjabil, M

    2015-09-01

    HbA1c is defined by the slow and irreversible binding of glucose to the N-terminal valine of one or both of the beta chains of hemoglobin A (HbA). It is a marker that is becoming increasingly important because of its role in both the diagnosis and monitoring of diabetic patients with type 1 and type 2. It reflects glycemic control of two or three months. Learned societies such as the IFCC and NGSP contributed to its standardization, which allows inter-laboratory comparison of results. Its assay uses chromatographic, electrophoretic or immunochemical methods. The HbA1c concentration is expressed in percent and in mmol/mol, and a number that is between 4 and 6% (20 and 42mmol/mol) is desirable. However, HbA1c cannot be used in some cases and fructosamine assay must be considered. PMID:25857744

  17. Haptoglobin: the hemoglobin detoxifier in plasma.

    PubMed

    Alayash, Abdu I; Andersen, Christian Brix Folsted; Moestrup, Søren Kragh; Bülow, Leif

    2013-01-01

    Hemoglobin (Hb) is one of the most studied proteins. However, oxidative toxicity associated with free Hb in circulation and its contribution to inflammation and complications of transfusion have only recently become active areas of research. New insights into the protective mechanisms of haptoglobin (Hp), a plasma protein, and a timely resolution of the crystal structure of the Hb-Hp complex made it possible to definitively link the functional and structural interplay between the two proteins. Here, we summarize current knowledge of the interactions between Hb and Hp under oxidative stress conditions, and how Hb's own damaging radicals are harnessed by complex formation. Potential therapeutic benefits of using Hp for inactivation and clearance of free Hb under a number of clinical settings are considered. PMID:23140673

  18. Hemoglobin loaded polymeric nanoparticles: preparation and characterizations.

    PubMed

    Dessy, Alberto; Piras, Anna M; Schirò, Giorgio; Levantino, Matteo; Cupane, Antonio; Chiellini, Federica

    2011-05-18

    In the present work polymeric nanoparticles based on Poly (maleic anhydride-alt-butyl vinyl ether) 5% grafted with m-PEG (2000) and 95% grafted with 2-methoxyethanol (VAM41-PEG) were loaded with human hemoglobin (Hb) and characterized from a physicochemical point of view. The assessment of structural and functional features of the loaded Hb was performed and the effect of the introduction of different reducing agents as aimed at minimizing Hb oxidation during the nanoparticles formulation process, was also investigated. Nanoparticles possessing an average diameter of 138±10 nm and physicochemical features suitable for this kind of application were successfully obtained. Although the oxidation of the protein was not avoided during its loading into nanoparticles, the presence of acidic moieties in the polymeric structure is proposed to be directly involved in the protein inactivation mechanism. PMID:21443949

  19. [Evaluation of D10 hemoglobin testing system for hemoglobin A1C assay].

    PubMed

    Marzullo, C; Minery, M

    2008-01-01

    Bio-Rad D10 hemoglobin testing system with rack loader for hemoglobinA1C assay was evaluated. Analytical qualities were satisfactory. Imprecision was good (within-run cv was 0,5% for 4,5% of HBA(1C), 0,63% for 7,4% of HBA1C, 0,46% for 11,1% of HBA1C, between-run cv was 1,16% for 4,7% of HBA1C, 1,01% for 7,6% of HBA1C, 1,04% for 11,2% of HBA1C). Results were very well correlated with those obtained on Bio-Rad Variant II (r = 0,998). Bland and Altman graph showed good agreement between the two methods for HbA1C under 15%. The measuring range was up to 18,3% of HBA1C. There was no specimen related carry over. Triglycerides under 5,5 mmol/L and bilirubin under 734 mumol/L did not interfere. Carbamylation of HBA1C did not interfere for urea concentration under 14 mmol/L. Practicability was very good. Detection of common hemoglobin variants (HbS, C, D, E, O) is available. Fast and easy switching between short and long program allows to perform HBA1C determination for patients with hemoglobin variants. So, D10 is an interesting and easy to use small HPLC automate witch offers accurate HBA1C quantification certified by NGSP. PMID:18227011

  20. Fetal Programming and Metabolic Syndrome

    PubMed Central

    Rinaudo, Paolo; Wang, Erica

    2014-01-01

    Metabolic syndrome is reaching epidemic proportions, particularly in developing countries. In this review, we explore the concept—based on the developmental-origin-of-health-and-disease hypothesis—that reprogramming during critical times of fetal life can lead to metabolic syndrome in adulthood. Specifically, we summarize the epidemiological evidence linking prenatal stress, manifested by low birth weight, to metabolic syndrome and its individual components. We also review animal studies that suggest potential mechanisms for the long-term effects of fetal reprogramming, including the cellular response to stress and both organ- and hormone-specific alterations induced by stress. Although metabolic syndrome in adulthood is undoubtedly caused by multiple factors, including modifiable behavior, fetal life may provide a critical window in which individuals are predisposed to metabolic syndrome later in life. PMID:21910625

  1. Passive Fetal Heart Monitoring System

    NASA Technical Reports Server (NTRS)

    Bryant, Timothy D. (Inventor); Wynkoop, Mark W. (Inventor); Holloway, Nancy M. H. (Inventor); Zuckerwar, Allan J. (Inventor)

    2004-01-01

    A fetal heart monitoring system preferably comprising a backing plate having a generally concave front surface and a generally convex back surface, and at least one sensor element attached to the concave front surface for acquiring acoustic fetal heart signals produced by a fetus within a body. The sensor element has a shape that conforms to the generally concave back surface of the backing plate. In one embodiment, the at least one sensor element comprises an inner sensor, and a plurality of outer sensors surrounding the inner sensor. The fetal heart monitoring system can further comprise a web belt, and a web belt guide movably attached to the web belt. The web belt guide being is to the convex back surface of the backing plate.

  2. [Fetal macrosomia: mode of delivery].

    PubMed

    Tatarova, S; Popov, I; Khristova, P

    2004-01-01

    This study was provided among 1847 deliveries from January, 1 to December, 31, 2003. The aim of the study was to examine the correlation between antenatal diagnosis "fetal macrosomia" and the mode of delivery. We found that among the cases with birth weight > or = 4000 g and antenatal diagnosis "fetal macrosomia" the rate of cesarean section was fourfold higher than among the cases without such a diagnosis. There weren't statistically significant correlation between the cases with antenatal diagnosis "fetal macrosomia " and the cases with estimated birth weight < or = 3999g in reference to the mother's age and weight, parity, fundal height and abdominal circumference. There are insignificant differences between both of groups in reference to gestacional age and birth. PMID:15669645

  3. Fetal Heart Rate Monitoring during Labor

    MedlinePlus

    ... fetal heart rate. The other belt measures the length of contractions and the time between them. How ... uterus. Doppler Transducer: A device that uses sound waves to reflect motion—such as the fetal heartbeat— ...

  4. Interference of the Hope Hemoglobin With Hemoglobin A1c Results.

    PubMed

    Chakraborty, Sutirtha; Chanda, Dalia; Gain, Mithun; Krishnan, Prasad

    2015-01-01

    Hemoglobin A1c (HbA1c) is now considered to be the marker of choice in diagnosis and management of diabetes mellitus, based on the results of certain landmark clinical trials. Herein, we report the case of a 52-year-old ethnic Southeast Asian Indian man with impaired glucose tolerance whose glycated hemoglobin (ie, HbA1c) levels, as measured via Bio-Rad D10 high-performance liquid chromatography (HPLC) and Roche Tina-quant immunoassay were 47.8% and 44.0%, respectively. No variant hemoglobin (Hb) peak was observed via the D10 chromatogram. We assayed the patient specimen on the Sebia MINICAP capillary electrophoresis platform; the HbA1c level was 6.8%, with a large variant Hb peak of 42.0%. This finding suggested the possible presence of the heterozygous Hb Hope, which can result in spuriously elevated HbA1c results on HPLC and turbidimetric immunoassays. Although the capillary electrophoresis system was able to identify the variant, the A1c results should not be considered accurate due to overlapping of the variant and adult Hb peaks on the electrophoretogram reading. Hb Hope is usually clinically silent but can present such analytical challenges. Through this case study, we critically discuss the limitations of various HbA1c assay methods, highlighting the fact that laboratory professionals need to be aware of occurrences of Hb Hope, to help ensure patient safety. PMID:26199262

  5. Hemoglobin-oxygen equilibrium at different hemoglobin and 2,3-diphosphoglycerate concentrations.

    PubMed

    Torelli, G; Celantano, F; Cortili, G; D'Angelo, E; Cazzaniga, A; Radford, E P

    1977-01-01

    Hemoglobin-oxygen equilibrium curves at constant pH, ionic strength, and temperature were determined (a) on 2,3-DPG-free solutions at various hemoglobin (Hb) concentrations, (b) on solutions at various Hb concentrations but constant 2,3-DPG/Hb molar ratio, (c) on solutions at constant hemoglobin concentration but various 2,3-DPG/Hb molar ratios, and (d) on hemolysates at various Hb concentrations. Under all conditions the shape of the equilibrium curve was the same (n = 2.62 +/- 0.04, 33 experiments). Half-saturation pressure (P 1/2) did not change with increasing Hb concentration in case (a), whereas P 1/2 was linearly related to Hb concentration in case (b). In case (c) at 200 g/l Hb, P 1/2 increased sharply as 2,3-DPG/Hb molar ratio increased up to 0.4 but changed little as the ratio was further increased up to 1.5. This behavior is very different from that observed in diluted (5 g/l) solutions. P 1/2 of the hemolysates was also linearly related to Hb concentration but the slope was about twice that for case (b). These results cannot be explained by linked function theory or by a dimer-tetramer equilibrium. It is suggested that intermolecular interactions in the presence of organic phosphates may be responsible for the observed changes in Hb affinity for oxygen. PMID:909950

  6. Increasing fetal ovine number per gestation alters fetal plasma clinical chemistry values.

    PubMed

    Zywicki, Micaela; Blohowiak, Sharon E; Magness, Ronald R; Segar, Jeffrey L; Kling, Pamela J

    2016-08-01

    Intrauterine growth restriction (IUGR) is interconnected with developmental programming of lifelong pathophysiology. IUGR is seen in human multifetal pregnancies, with stepwise rises in fetal numbers interfering with placental nutrient delivery. It remains unknown whether fetal blood analyses would reflect fetal nutrition, liver, and excretory function in the last trimester of human or ovine IUGR In an ovine model, we hypothesized that fetal plasma biochemical values would reflect progressive placental, fetal liver, and fetal kidney dysfunction as the number of fetuses per gestation rose. To determine fetal plasma biochemical values in singleton, twin, triplet, and quadruplet/quintuplet ovine gestation, we investigated morphometric measures and comprehensive metabolic panels with nutritional measures, liver enzymes, and placental and fetal kidney excretory measures at gestational day (GD) 130 (90% gestation). As anticipated, placental dysfunction was supported by a stepwise fall in fetal weight, fetal plasma glucose, and triglyceride levels as fetal number per ewe rose. Fetal glucose and triglycerides were directly related to fetal weight. Plasma creatinine, reflecting fetal renal excretory function, and plasma cholesterol, reflecting placental excretory function, were inversely correlated with fetal weight. Progressive biochemical disturbances and growth restriction accompanied the rise in fetal number. Understanding the compensatory and adaptive responses of growth-restricted fetuses at the biochemical level may help explain how metabolic pathways in growth restriction can be predetermined at birth. This physiological understanding is important for clinical care and generating interventional strategies to prevent altered developmental programming in multifetal gestation. PMID:27565903

  7. Verification of fetal brain responses by coregistration of fetal ultrasound and fetal magnetoencephalography data

    PubMed Central

    Micheli, C.; McCubbin, J.; Murphy, P.; Eswaran, H.; Lowery, C. L.; Ortiz, E.; Preissl, H.

    2009-01-01

    Fetal magnetoencephalography (fMEG) is used to study neurological functions of the developing fetus by measuring magnetic signals generated by electrical sources within the fetal brain. For this aim either auditory or visual stimuli are presented and evoked brain activity or spontaneous activity is measured at the sensor level. However a limiting factor of this approach is the low signal to noise ratio (SNR) of recorded signals. To overcome this limitation, advanced signal processing techniques such as spatial filters (e.g. beamformer) can be used to increase SNR. One crucial aspect of this technique is the forward model and, in general, a simple spherical head model is used. This head model is an integral part of a model search approach to analyze the data due to the lack of exact knowledge about the location of the fetal head. In the present report we overcome this limitation by a coregistration of volumetric ultrasound images with fMEG data. In a first step we validated the ultrasound to fMEG coregistration with a phantom and were able to show that the coregistration error is below 2 cm. In the second step we compared the results gained by the model search approach to the exact location of the fetal head determined on pregnant mothers by ultrasound. The results of this study clearly show that the results of the model search approach are in accordance with the location of the fetal head. PMID:19778620

  8. Fetal assessment in postterm pregnancy.

    PubMed

    Boylan, P; McParland, P

    1991-02-01

    There is considerable disagreement over the management of postterm pregnancies. The main controversy is whether to adopt a policy of routine induction or one of selective induction allied to frequent fetal surveillance. Current evidence suggests that routine induction at 42 weeks' gestation does not increase the risk of instrumental delivery or cesarean section. To adopt the former approach, it is important that gestation is confirmed by early ultrasound examination, which has reduced the true incidence of postterm pregnancy to less than 6%. There have been no recent significant advances regarding methods of fetal surveillance in the postterm pregnancy. PMID:1878496

  9. Fetal Alcohol Syndrome and Fetal Alcohol Effects: Principles for Educators.

    ERIC Educational Resources Information Center

    Burgess,Donna M.; Streissguth, Ann P.

    1992-01-01

    Fetal alcohol syndrome (FAS), the leading cause of mental retardation, often goes unrecognized because of social and emotional taboos about alcohol and alcoholism. This article describes medical and behavioral characteristics of FAS children and describes guiding principles for educators, based on early intervention, teaching communication and…

  10. Human Fetal Behavior: 100 Years of Study.

    ERIC Educational Resources Information Center

    Kisilevsky, B. S.; Low, J. A.

    1998-01-01

    Reviews literature on human fetal behavior. Includes descriptions of coupling of body movements and fetal heart rate and behavior maturation from conception to term. Discusses use of stimulus-induced behavior to examine sensory and cognitive development, and spontaneous and stimulus-induced behavior to assess fetal well-being. Notes research focus…

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

    PubMed Central

    Jacob, Harry S.; Winterhalter, Kaspar H.

    1970-01-01

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

  12. Relationship between hemoglobin and cardiovascular risk factors in young adults.

    PubMed

    Shimakawa, T; Bild, D E

    1993-11-01

    To understand mechanisms of association between hemoglobin and cardiovascular disease (CVD), the relationships between hemoglobin and CVD risk factors were examined in 5115 black and white men and women who participated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Hemoglobin was higher in men than women, whites than blacks, and smokers than non-smokers (p < 0.001). After adjusting for age, body mass index, current smoking status, and clinical center, hemoglobin correlated with diastolic blood pressure (0.11 < or = r < or = 0.22, p < 0.001) and plasma total cholesterol (0.08 < or = r < or = 0.11, p < 0.01) in all four race-sex groups and with systolic blood pressure in all but black women (0.07 < or = r < or = 0.13, p < 0.05). Among other factors possibly related to CVD risk, only serum albumin and white blood cell count showed significant correlations with hemoglobin in all groups (0.19 < or = r < or = 0.27, 0.07 < or = r < or = 0.18, respectively). These findings suggest that an association of hemoglobin with CVD risk factors may explain the association of hemoglobin with CVD. PMID:8229103

  13. Molecular characterization of hemoglobin from the honeybee Apis mellifera.

    PubMed

    Hankeln, Thomas; Klawitter, Sabine; Krämer, Melanie; Burmester, Thorsten

    2006-07-01

    Due to the prevailing importance of the tracheal system for insect respiration, hemoglobins had been considered rare exceptions in this arthropod subphylum. Here we report the identification, cloning and expression analysis of a true hemoglobin gene in the honeybee Apis mellifera (Hymenoptera). The deduced amino acid sequence covers 171 residues (19.5kDa) and harbors all globin-typical features, including the proximal and the distal histidines. The protein has no signal peptide for transmembrane transport and was predicted to localize in the cytoplasm. The honeybee hemoglobin gene shows an ancient structure, with introns in positions B12.2 and G7.0, while most other insect globins have divergent intron positions. In situ hybridization studies showed that hemoglobin expression in the honeybee is mainly associated with the tracheal system. We also observe hemoglobin expression in the Malpighi tubes and testis. We further demonstrated that hemoglobins occur in other insect orders (Hemiptera, Coleoptera, Lepidoptera), suggesting that such genes belong to the standard repertoire of an insect genome. Phylogenetic analyses show that globins evolved along with the accepted insect systematics, with a remarkable diversification within the Diptera. Although insect hemoglobins may be in fact involved in oxygen metabolism, it remains uncertain whether they carry out a myoglobin-like function in oxygen storage and delivery. PMID:16698031

  14. Two-photon excited fluorescence emission from hemoglobin

    NASA Astrophysics Data System (ADS)

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

    2015-03-01

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

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

    SciTech Connect

    Grassman, J.A.

    1993-01-01

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

  16. Hemoglobin concentration of high-altitude Tibetans and Bolivian Aymara.

    PubMed

    Beall, C M; Brittenham, G M; Strohl, K P; Blangero, J; Williams-Blangero, S; Goldstein, M C; Decker, M J; Vargas, E; Villena, M; Soria, R; Alarcon, A M; Gonzales, C

    1998-07-01

    Elevated hemoglobin concentrations have been reported for high-altitude sojourners and Andean high-altitude natives since early in the 20th century. Thus, reports that have appeared since the 1970s describing relatively low hemoglobin concentration among Tibetan high-altitude natives were unexpected. These suggested a hypothesis of population differences in hematological response to high-altitude hypoxia. A case of quantitatively different responses to one environmental stress would offer an opportunity to study the broad evolutionary question of the origin of adaptations. However, many factors may confound population comparisons. The present study was designed to test the null hypothesis of no difference in mean hemoglobin concentration of Tibetan and Aymara native residents at 3,800-4,065 meters by using healthy samples that were screened for iron deficiency, abnormal hemoglobins, and thalassemias, recruited and assessed using the same techniques. The hypothesis was rejected, because Tibetan males had a significantly lower mean hemoglobin concentration of 15.6 gm/dl compared with 19.2 gm/dl for Aymara males, and Tibetan females had a mean hemoglobin concentration of 14.2 gm/dl compared with 17.8 gm/dl for Aymara females. The Tibetan hemoglobin distribution closely resembled that from a comparable, sea-level sample from the United States, whereas the Aymara distribution was shifted toward 3-4 gm/dl higher values. Genetic factors accounted for a very high proportion of the phenotypic variance in hemoglobin concentration in both samples (0.86 in the Tibetan sample and 0.87 in the Aymara sample). The presence of significant genetic variance means that there is the potential for natural selection and genetic adaptation of hemoglobin concentration in Tibetan and Aymara high-altitude populations. PMID:9696153

  17. Fetal MR Imaging of Gastrointestinal Abnormalities.

    PubMed

    Furey, Elizabeth A; Bailey, April A; Twickler, Diane M

    2016-01-01

    Fetal magnetic resonance (MR) imaging plays an increasing and valuable role in antenatal diagnosis and perinatal management of fetal gastrointestinal (GI) abnormalities. Advances in MR imaging data acquisition and use of motion-insensitive techniques have established MR imaging as an important adjunct to obstetric ultrasonography (US) for fetal diagnosis. In this regard, MR imaging provides high diagnostic accuracy for antenatal diagnosis of common and uncommon GI pathologic conditions. In the setting of fetal GI disease, T1-weighted images demonstrate the amount and distribution of meconium, which is crucial to the diagnostic capability of fetal MR imaging. Specifically, knowledge of the T1 signal intensity characteristics of fetal meconium, the normal pattern of meconium with advancing gestational age, and the expected caliber of small and large bowel in the fetus is key to diagnosis of abnormalities of the GI tract. Use of ultrafast T2-weighted sequences for evaluation of the expected location and morphology of fluid-containing structures, including the stomach and small bowel, in the fetal abdomen further aids in diagnostic confidence. Uncommonly encountered fetal GI pathologic conditions, especially cloacal dysmorphology, may demonstrate characteristic MR imaging patterns, which may add additional information to that from fetal US, allowing improved fetal and neonatal management. This article discusses common indications for fetal MR imaging of the GI tract, imaging protocols for fetal GI MR imaging, the normal appearance of the fetal GI tract with advancing gestational age, and the imaging appearances of common fetal GI abnormalities, as well as uncommon fetal GI conditions with characteristic appearances. (©)RSNA, 2016. PMID:27163598

  18. Tissue engineering a fetal membrane.

    PubMed

    Mi, Shengli; David, Anna L; Chowdhury, Bipasha; Jones, Roanne Razalia; Hamley, Ian William; Squires, Adam M; Connon, Che John

    2012-02-01

    The aim of this study was to construct an artificial fetal membrane (FM) by combination of human amniotic epithelial stem cells (hAESCs) and a mechanically enhanced collagen scaffold containing encapsulated human amniotic stromal fibroblasts (hASFs). Such a tissue-engineered FM may have the potential to plug structural defects in the amniotic sac after antenatal interventions, or to prevent preterm premature rupture of the FM. The hAESCs and hASFs were isolated from human fetal amniotic membrane (AM). Magnetic cell sorting was used to enrich the hAESCs by positive ATP-binding cassette G2 selection. We investigated the use of a laminin/fibronectin (1:1)-coated compressed collagen gel as a novel scaffold to support the growth of hAESCs. A type I collagen gel was dehydrated to form a material mimicking the mechanical properties and ultra-structure of human AM. hAESCs successfully adhered to and formed a monolayer upon the biomimetic collagen scaffold. The resulting artificial membrane shared a high degree of similarity in cell morphology, protein expression profiles, and structure to normal fetal AM. This study provides the first line of evidence that a compacted collagen gel containing hASFs could adequately support hAESCs adhesion and differentiation to a degree that is comparable to the normal human fetal AM in terms of structure and maintenance of cell phenotype. PMID:21919796

  19. Hypoxia and fetal heart development.

    PubMed

    Patterson, A J; Zhang, L

    2010-10-01

    Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart formation, further abnormal hypoxia in utero adversely affects cardiogenesis. Prenatal hypoxia alters myocardial structure and causes a decline in cardiac performance. Not only are the effects of hypoxia apparent during the perinatal period, but prolonged hypoxia in utero also causes fetal programming of abnormality in the heart's development. The altered expression pattern of cardioprotective genes such as protein kinase c epsilon, heat shock protein 70, and endothelial nitric oxide synthase, likely predispose the developing heart to increased vulnerability to ischemia and reperfusion injury later in life. The events underlying the long-term changes in gene expression are not clear, but likely involve variation in epigenetic regulation. PMID:20712587

  20. Fetal Alcohol Syndrome Resource Guide.

    ERIC Educational Resources Information Center

    Snyder, Lisa

    This resource guide provides information on programs, publications, organizations, and other resources related to prevention of fetal alcohol syndrome (FAS). The purpose of this guide is to assist health care providers to comply with Indian Health Service (IHS) FAS goals and objectives. It gives examples of community approaches to FAS prevention,…

  1. Fetal Alcohol Syndrome Resource Guide.

    ERIC Educational Resources Information Center

    All Indian Pueblo Council, Albuquerque, NM.

    The guide was developed to assist professionals working with American Indian people as a resource in obtaining printed and non-printed materials on Fetal Alcohol Syndrome. The resource guide is divided into the following sections: films (4), books (5), bibliographies (2), pamphlets (16), posters (5), slides (2), training curriculum (3), and…

  2. Fetal Alcohol Syndrome "Chemical Genocide."

    ERIC Educational Resources Information Center

    Asetoyer, Charon

    In the Northern Plains of the United States, 100% of Indian reservations are affected by alcohol related problems. Approximately 90% of Native American adults are currently alcohol users or abusers or are recovering from alcohol abuse. Alcohol consumption has a devastating effect on the unborn. Fetal Alcohol Syndrome (FAS) is an irreversible birth…

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

    SciTech Connect

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

    1986-08-01

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

  4. Development of the human fetal testis.

    PubMed

    O'Shaughnessy, Peter J; Fowler, Paul A

    2014-05-01

    Masculinisation and adult fertility in the male are dependent on appropriate fetal endocrine programming. There is also now increasing evidence to indicate that the same mechanisms which regulate masculinisation also affect the general wellbeing of males throughout their life and, particularly, during ageing. Testosterone, secreted by the fetal testes, is the main factor regulating these processes and an understanding of fetal testis development in the human male is essential if we are to prevent adult reproductive disorders. This review focuses on what is known about human testis development and describes the effects of maternal smoking, a surrogate of possible xenotoxicant exposure on fetal testis and fetal liver function. PMID:24746112

  5. Unsupervised fetal cortical surface parcellation

    NASA Astrophysics Data System (ADS)

    Dahdouh, Sonia; Limperopoulos, Catherine

    2016-03-01

    At the core of many neuro-imaging studies, atlas-based brain parcellations are used for example to study normal brain evolution across the lifespan. These atlases rely on the assumption that the same anatomical features are present on all subjects to be studied and that these features are stable enough to allow meaningful comparisons between different brain surfaces and structures These methods, however, often fail when applied to fetal MRI data, due to the lack of consistent anatomical features present across gestation. This paper presents a novel surface-based fetal cortical parcellation framework which attempts to circumvent the lack of consistent anatomical features by proposing a brain parcellation scheme that is based solely on learned geometrical features. A mesh signature incorporating both extrinsic and intrinsic geometrical features is proposed and used in a clustering scheme to define a parcellation of the fetal brain. This parcellation is then learned using a Random Forest (RF) based learning approach and then further refined in an alpha-expansion graph-cut scheme. Based on the votes obtained by the RF inference procedure, a probability map is computed and used as a data term in the graph-cut procedure. The smoothness term is defined by learning a transition matrix based on the dihedral angles of the faces. Qualitative and quantitative results on a cohort of both healthy and high-risk fetuses are presented. Both visual and quantitative assessments show good results demonstrating a reliable method for fetal brain data and the possibility of obtaining a parcellation of the fetal cortical surfaces using only geometrical features.

  6. Diagnosis and Treatment of Fetal Arrhythmia

    PubMed Central

    Wacker-Gussmann, Annette; Strasburger, Janette F.; Cuneo, Bettina F.; Wakai, Ronald T.

    2014-01-01

    Detection and careful stratification of fetal heart rate (FHR) is extremely important in all pregnancies. The most lethal cardiac rhythm disturbances occur during apparently normal pregnancies where FHR and rhythmare regular and within normal or low-normal ranges. These hidden depolarization and repolarization abnormalities, associated with genetic ion channelopathies cannot be detected by echocardiography, and may be responsible for up to 10% of unexplained fetal demise, prompting a need for newer and better fetal diagnostic techniques. Other manifest fetal arrhythmias such as premature beats, tachycardia, and bradycardia are commonly recognized. Heart rhythm diagnosis in obstetrical practice is usually made by M-mode and pulsed Doppler fetal echocardiography, but not all fetal cardiac time intervals are captured by echocardiographic methods. This article reviews different types of fetal arrhythmias, their presentation and treatment strategies, and gives an overview of the present and future diagnostic techniques. PMID:24858320

  7. Functional behavior of tortoise hemoglobin Geochelone denticulata.

    PubMed

    Torsoni, M A; Stoppa, G R; Turra, A; Ogo, S H

    2002-11-01

    The hemolysate from Geochelone denticulata contains two main hemoglobin components, as shown by ion exchange chromatography and polyacrylamide gel electrophoresis (PAGE). Electrophoresis under dissociating conditions showed three types of globin chains. The apparent molecular mass, as determined by gel filtration on Sephadex G-200, was compatible with tetrameric Hb, which was unable to polymerize. The G. denticulata Hb has a P50 value of 9.56 mm Hg at pH 7.4. The Hb oxygenation appears to be under the control of organic phosphates and hydrogen ion since it is strongly affected by those species. In the presence ATP or IHP the P50 values increased to 29.51 mm Hg and 54.95 mm Hg, respectively, at pH 7.4. The n50 was generally lower than 1.5 in stripped Hb, suggesting a dissociation of tetramers. In the presence of organic phosphates n50 values increased to approximately 2.5. The Bohr effect was evident in oxygen equilibrium experiments. The hematocrit (32%) and Hb concentration (5.7 mM as heme) of G. denticulata blood were substantially larger than those of G. carbonaria, but the methemoglobin levels were similar in both species, approximately 1%. Thus, the oxygen capacity of blood appears to be higher in G. denticulata than in G. carbonaria, particularly considering the functional properties of their Hbs, which would guarantee the survival of animals. PMID:12659022

  8. MP4, a vasodilatory PEGylated hemoglobin.

    PubMed

    Cole, Russell H; Vandegriff, Kim D

    2011-01-01

    A vasodilatory hemoglobin (Hb)-based O(2) carrier (HBOC) has been developed by surface conjugation polyethylene glycol to tetrameric human Hb (MP4, Sangart, San Diego). Because the NO-binding kinetics of MP4 are similar to vasoconstrictive HBOCs, we propose that the decoupling of NO scavenging from vascular response is a consequence of MP4's high O(2) affinity (p50 = 5 mmHg) and unique surface chemistry. The release of ATP from erythrocytes is vasodilatory and the application of a high O(2) affinity HBOC minimizes ATP interference with intravascular ATP signaling. A second potential mechanism of action for MP4 involves the surface conjugation of polyethylene glycol (PEG) to tetrameric human Hb. It has been shown that the addition of unconjugated high molecular weight (Mw) PEG to cultured lung endothelial cells causes an immediate and significant reduction in endothelial permeability; an effect opposite to that of endothelial agonists such as cell-free Hb. It appears that some of the benefits of the PEG-endothelium interaction are carried onto molecules such as PEGylated Hb and PEGylated albumin, as demonstrated by favorable hemodynamic responses in vivo. PEGylation of ß93 cysteine residues, as in MP4, has also been reported to increase the nitrite reductase activity of Hb and enhance conversion of endogenous nitrite to bioactive NO. PMID:21445773

  9. PARALLEL ASSAY OF OXYGEN EQUILIBRIA OF HEMOGLOBIN

    PubMed Central

    Lilly, Laura E.; Blinebry, Sara K.; Viscardi, Chelsea M.; Perez, Luis; Bonaventura, Joe; McMahon, Tim J.

    2013-01-01

    Methods to systematically analyze in parallel the function of multiple protein or cell samples in vivo or ex vivo (i.e. functional proteomics) in a controlled gaseous environment have thus far been limited. Here we describe an apparatus and procedure that enables, for the first time, parallel assay of oxygen equilibria in multiple samples. Using this apparatus, numerous simultaneous oxygen equilibrium curves (OECs) can be obtained under truly identical conditions from blood cell samples or purified hemoglobins (Hbs). We suggest that the ability to obtain these parallel datasets under identical conditions can be of immense value, both to biomedical researchers and clinicians who wish to monitor blood health, and to physiologists studying non-human organisms and the effects of climate change on these organisms. Parallel monitoring techniques are essential in order to better understand the functions of critical cellular proteins. The procedure can be applied to human studies, wherein an OEC can be analyzed in light of an individual’s entire genome. Here, we analyzed intraerythrocytic Hb, a protein that operates at the organism’s environmental interface and then comes into close contact with virtually all of the organism’s cells. The apparatus is theoretically scalable, and establishes a functional proteomic screen that can be correlated with genomic information on the same individuals. This new method is expected to accelerate our general understanding of protein function, an increasingly challenging objective as advances in proteomic and genomic throughput outpace the ability to study proteins’ functional properties. PMID:23827235

  10. Effects of cerebral ischemia on neuronal hemoglobin

    PubMed Central

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

    2009-01-01

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

  11. Geminate recombination of O2 and hemoglobin.

    PubMed Central

    Chernoff, D A; Hochstrasser, R M; Steele, A W

    1980-01-01

    The photolysis of HbO2 and HbCO has been studied by measuring transient absorption spectra in the Soret region after excitation with picosecond pulses at 530 nm. Dissociation occurred promptly in both cases, followed (for HbO2) by geminate recombination of ca. 40% of the photodissociated O2 with a lifetime of 200 +/- 70 psec (25 degrees C). No recombination of Hb + CO was observed up to 1200 psec after photolysis. The HbO2 and HbCO photoproduct spectra were broader, weaker, and red-shifted in comparison to the spectrum of stable Hb and Gibson's fast-reacting form, Hb. For HbO2 the spectrum was initially much broader to longer wavelengths but relaxed to a constant shape within 90 psec, whereas for HbCO there was no spectral evolution. The photophysics is analyzed by considering the effect of spin constraints as well as spin--orbit coupling and orbital correlation among the various electronic states of liganded and deoxy hemoglobins. The small quantum yield of HbO2 dissociation is not primarily due to rebinding but rather to electronic relaxation to nonreactive states. PMID:6932659

  12. Increased Fetal Plasma Erythropoietin in Monochorionic Twin Pregnancies With Selective Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler.

    PubMed

    Chang, Yao-Lung; Chao, An-Shine; Peng, Hsiu-Huei; Chang, Shuenn-Dyh; Su, Sheng-Yuan; Chen, Kuan-Ju; Cheng, Po-Jen; Wang, Tzu-Hao

    2016-08-01

    Hypoxia is the primary stimulus for the production of erythropoietin (EPO) in both fetal and adult life. Here, we investigated fetal plasma EPO concentrations in monochorionic (MC) twin pregnancies with selective intrauterine growth restriction (sIUGR) and abnormal umbilical artery (UA) Doppler. We diagnosed sIUGR in presence of (1) birth-weight discordance >20% and (2) either twin with a birth weight <10th percentile. An abnormal UA Doppler was defined as a persistent absent-reverse end diastolic flow (AREDF). The intertwin EPO ratio was calculated as the plasma EPO level of the smaller (or small-for-gestational-age) twin divided by the EPO concentration of the larger (or appropriate-for-gestational-age (AGA)) twin. Thirty-two MC twin pairs were included. Of these, 17 pairs were normal twins (Group 1), seven pairs were twins with sIUGR without UA Doppler abnormalities (Group 2), and eight pairs were twins with sIUGR and UA Doppler abnormalities (Group 3). The highest EPO ratio was identified in Group 3 (p < .001) but no significant differences were observed between Groups 1 and 2. Fetal hemoglobin levels did not differ significantly in the three groups, and fetal EPO concentration did not correlate with gestational age at birth. We conclude that fetal plasma EPO concentrations are selectively increased in MC twin pregnancies with sIUGR and abnormal UA Doppler, possibly as a result of uncompensated hypoxia. PMID:27161360

  13. Identification of hemoglobin AC heterozygote status in a Malay family: a decision between hemoglobin electrophoresis and high performance liquid chromotography.

    PubMed

    Rosline, H; Roshan, T M; Ahmed, S A; Ilunihayati, I

    2007-05-01

    Thalassemia is a common public health problem among Malays. Hemoglobin C (Hb C) is a hemoglobin beta variant resulting from a single base mutation at the 6th position of the beta-globin gene leading to the substitution of glycine for glutamic acid. Hb C is commonly detected in West Africans and in African American but has not been reported in Malaysia. It can be falsely diagnosed as HbE trait in the Malaysian Thalassemia Screening Program which utilizes cellulose acetate hemoglobin electrophoresis. This is the first reported case of Hb AC heterozygote status in a Malay family, with unusual splenomegaly in one of the family members. PMID:17877232

  14. Passive fetal heart rate monitoring apparatus and method with enhanced fetal heart beat discrimination

    NASA Technical Reports Server (NTRS)

    Zahorian, Stephen A. (Inventor); Livingston, David L. (Inventor); Pretlow, III, Robert A. (Inventor)

    1996-01-01

    An apparatus for acquiring signals emitted by a fetus, identifying fetal heart beats and determining a fetal heart rate. Multiple sensor signals are outputted by a passive fetal heart rate monitoring sensor. Multiple parallel nonlinear filters filter these multiple sensor signals to identify fetal heart beats in the signal data. A processor determines a fetal heart rate based on these identified fetal heart beats. The processor includes the use of a figure of merit weighting of heart rate estimates based on the identified heart beats from each filter for each signal. The fetal heart rate thus determined is outputted to a display, storage, or communications channel. A method for enhanced fetal heart beat discrimination includes acquiring signals from a fetus, identifying fetal heart beats from the signals by multiple parallel nonlinear filtering, and determining a fetal heart rate based on the identified fetal heart beats. A figure of merit operation in this method provides for weighting a plurality of fetal heart rate estimates based on the identified fetal heart beats and selecting the highest ranking fetal heart rate estimate.

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

    PubMed

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

    2015-09-15

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

  16. On the tryptic peptides from hemoglobin chains of six carnivores.

    PubMed

    Brimhall, B; Stenzel, P; Dresler, S L; Hermodson, M; Stangland, K; Joyce, J; Jones, R T

    1977-05-13

    The amino acid compositions of the tryptic peptides of the following carnivore hemoglobin chains have been determined: gray fox (Urocyon cineroargenteus); raccoon (Procyon lotor); polar bear (Thalarctos maritimus); coati mundi (Nasua nasua) beta chain; coati mundi (Nasua narica) two beta chains; cat (Felis catus) alpha chain; and lion (Pantbera leo) beta chain. These provide a basis for future sequencing of these hemoglobins and construction of an evolutionary tree. The specific results are summarized in the following article (Stenzel and Brimhall, 1977). PMID:864727

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

    PubMed Central

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

    2014-01-01

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

  18. Erythrocytosis associated with hemoglobin Rainier: oxygen equilibria and marrow regulation

    PubMed Central

    Adamson, John W.; Parer, Julian T.; Stamatoyannopoulos, George; Heinenberg, S.

    1969-01-01

    Hemoglobin Rainier (β145 tyrosine→histidine) is an abnormal hemoglobin associated with increased oxygen affinity, decreased heme-heme interaction, presence of a Bohr effect, and erythrocytosis, but without obvious clinical sequelae. Regulation of erythropoiesis was studied in affected members of families having either hemoglobin Rainier or Yakima, abnormal hemoglobins associated with erythrocytosis. Apart from the elevated but stable hemoglobin concentration and red cell mass, parameters of red cell production in the subjects were normal. Initially normal values of erythropoietin excretion were increased by phlebotomy indicating a significant hypoxic stress at an otherwise normal hematocrit. This stress led to increased reticulocyte production and an eventual return to the prephlebotomy hematocrit. The erythrocytosis in carriers of hemoglobins Rainer and Yakima appears to be secondary to the increased oxygen affinity and this, with the response to phlebotomy, is consistent with the postulate that the renal sensor tissue regulating erythropoietin production is primarily influenced by the oxygen tensions of venous rather than arterial blood. Images PMID:5796352

  19. Reaction of tobacco smoke aldehydes with human hemoglobin.

    PubMed

    Hoberman, H D; San George, R C

    1988-01-01

    Formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde, and acrolein, all of which are constituents of tobacco smoke, were reacted in 5 mM concentration with the purified major fraction of normal adult human hemoglobin (hemoglobin Ao) in 1 mM concentration. A cigarette smoke condensate, diluted to contain 5 mM total aldehydes, was also reacted with 1 mM hemoglobin Ao. Cationic exchange high-performance liquid chromatography (HPLC) showed that the products formed from simple aliphatic aldehydes, with the exception of formaldehyde, were analogues of those formed from acetaldehyde, earlier shown by us to be imidazolidinone derivatives, that is, cyclic addition products of the N-terminal aminoamide function of alpha and beta chains. Formaldehyde and acrolein produced a heterogeneous mixture of derivatives including cross-linked hemoglobin dimers. The greater proportion of modified hemoglobins produced by condensate aldehydes resembled those formed from acetaldehyde, the most abundant aldehyde in the condensate. A smaller fraction consisted of cross-linked hemoglobin dimers, presumably due to the action of formaldehyde. Mass spectrometric and HPLC analyses of the 2,4-dinitrophenylhydrazones precipitated from the condensate documented the presence of formaldehyde, acetaldehyde, propionaldehyde, butyraldehyde, furfural, and methylfurfural. The toxicity of aldehydes is briefly discussed in the context of the findings of this study. PMID:3236330

  20. Novel hemoglobin particles--promising new-generation hemoglobin-based oxygen carriers.

    PubMed

    Bäumler, Hans; Xiong, Yu; Liu, Zhi Zhao; Patzak, Andreas; Georgieva, Radostina

    2014-08-01

    During the last 30 years, artificial oxygen carriers have been investigated intensively with the aim to develop universal blood substitutes. Favorably, hemoglobin-based oxygen carriers (HBOCs) are expected to meet the sophisticated requirements. However, the HBOCs tested until now show serious side effects, which resulted in failure of clinical trials and Food and Drug Administration disapproval. The main problem consists in vasoconstriction triggered by nitric oxide (NO) scavenging or/and oxygen oversupply in the pre-capillary arterioles. HBOCs with a size between 100 nm and 1 µm and high oxygen affinity are needed. Here we present a highly effective and simple fabrication procedure, which can provide hemoglobin particles (HbPs) with a narrow size distribution of around 700 nm, nearly uniform morphology, high oxygen affinity, and low immunogenicity. Isolated mouse glomeruli are successfully perfused with concentrated HbP suspensions without any observable vasoconstriction of the afferent arterioles. The results suggest no oxygen oversupply and limited NO scavenging by these particles, featuring them as a highly promising blood substitute. PMID:24962099

  1. The primary structure of the hemoglobin of Malayan sun bear (Helarctos malayanus, Carnivora) and structural comparison to other hemoglobin sequences.

    PubMed

    Hofmann, O; Braunitzer, G; Göltenboth, R

    1987-05-01

    The complete primary structure of the alpha- and beta-chains of the hemoglobin of Malayan Sun Bear (Helarctos malayanus) is presented. After cleavage of the heme-protein link and chain separation by RP-HPLC, amino-acid sequences were determined by Edman degradation in liquid- and gas-phase sequenators. An interesting result of this work is the demonstration that the hemoglobin of Malayan Sun Bear is identical to the hemoglobins of Polar Bear (Ursus maritimus) and Asiatic Black Bear (Ursus tibetanus). The paper gives an updated table of identical hemoglobin chains from different species. This paper may be considered as a compilation of work on the genetic relationship of Pandas. PMID:3620104

  2. Fetal cardiac interventions: clinical and experimental research

    PubMed Central

    Humuruola, Gulimila

    2016-01-01

    Fetal cardiac interventions for congenital heart diseases may alleviate heart dysfunction, prevent them evolving into hypoplastic left heart syndrome, achieve biventricular outcome and improve fetal survival. Candidates for clinical fetal cardiac interventions are now restricted to cases of critical aortic valve stenosis with evolving hypoplastic left heart syndrome, pulmonary atresia with an intact ventricular septum and evolving hypoplastic right heart syndrome, and hypoplastic left heart syndrome with an intact or highly restrictive atrial septum as well as fetal heart block. The therapeutic options are advocated as prenatal aortic valvuloplasty, pulmonary valvuloplasty, creation of interatrial communication and fetal cardiac pacing. Experimental research on fetal cardiac intervention involves technical modifications of catheter-based cardiac clinical interventions and open fetal cardiac bypass that cannot be applied in human fetuses for the time being. Clinical fetal cardiac interventions are plausible for midgestation fetuses with the above-mentioned congenital heart defects. The technical success, biventricular outcome and fetal survival are continuously being improved in the conditions of the sophisticated multidisciplinary team, equipment, techniques and postnatal care. Experimental research is laying the foundations and may open new fields for catheter-based clinical techniques. In the present article, the clinical therapeutic options and experimental fetal cardiac interventions are described. PMID:27279868

  3. Fetal cardiac interventions: clinical and experimental research.

    PubMed

    Yuan, Shi-Min; Humuruola, Gulimila

    2016-01-01

    Fetal cardiac interventions for congenital heart diseases may alleviate heart dysfunction, prevent them evolving into hypoplastic left heart syndrome, achieve biventricular outcome and improve fetal survival. Candidates for clinical fetal cardiac interventions are now restricted to cases of critical aortic valve stenosis with evolving hypoplastic left heart syndrome, pulmonary atresia with an intact ventricular septum and evolving hypoplastic right heart syndrome, and hypoplastic left heart syndrome with an intact or highly restrictive atrial septum as well as fetal heart block. The therapeutic options are advocated as prenatal aortic valvuloplasty, pulmonary valvuloplasty, creation of interatrial communication and fetal cardiac pacing. Experimental research on fetal cardiac intervention involves technical modifications of catheter-based cardiac clinical interventions and open fetal cardiac bypass that cannot be applied in human fetuses for the time being. Clinical fetal cardiac interventions are plausible for midgestation fetuses with the above-mentioned congenital heart defects. The technical success, biventricular outcome and fetal survival are continuously being improved in the conditions of the sophisticated multidisciplinary team, equipment, techniques and postnatal care. Experimental research is laying the foundations and may open new fields for catheter-based clinical techniques. In the present article, the clinical therapeutic options and experimental fetal cardiac interventions are described. PMID:27279868

  4. Glycosylated hemoglobin and hyperbaric oxygen coverage denials.

    PubMed

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

    2015-01-01

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

  5. Fetal origin of vascular aging

    PubMed Central

    Pitale, Shailesh; Sahasrabuddhe, Anagha

    2011-01-01

    Aging is increasingly regarded as an independent risk factor for development of cardiovascular diseases such as atherosclerosis and hypertension and their complications (e.g. MI and Stroke). It is well known that vascular disease evolve over decades with progressive accumulation of cellular and extracellular materials and many inflammatory processes. Metabolic syndrome, obesity and diabetes are conventionally recognized as risk factors for development of coronary vascular disease (CVD). These conditions are known to accelerate ageing process in general and vascular ageing in particular. Adverse events during intrauterine life may programme organ growth and favour disease later in life, popularly known as, ‘Barker's Hypothesis’. The notion of fetal programming implies that during critical periods of prenatal growth, changes in the hormonal and nutritional milieu of the conceptus may alter the full expression of the fetal genome, leading to permanent effects on a range of physiological. PMID:22145131

  6. Fetal epigenetic programming of adipokines.

    PubMed

    Houde, Andrée-Anne; Hivert, Marie-France; Bouchard, Luigi

    2013-01-01

    Epigenetics generates a considerable interest in the field of research on complex traits, including obesity and diabetes. Recently, we reported a number of epipolymorphisms in the placental leptin and adiponectin genes associated with maternal hyperglycemia during pregnancy. Our results suggest that DNA methylation could partly explain the link between early exposure to a detrimental fetal environment and an increased risk to develop obesity and diabetes later in life. This brief report discusses the potential importance of adipokine epigenetic changes in fetal metabolic programming. Additionally, preliminary data showing similarities between methylation variations of different tissues and cell types will be presented along with the challenges and future perspectives of this emerging field of research. PMID:23700551

  7. Fetal status: sources and implications.

    PubMed

    Shannon, T A

    1997-10-01

    This essay considers the ways in which the various contexts--abortion, prenatal diagnosis, fetal research, and the use of fetuses in transplantation--shape the American debate on the moral standing of the fetus. This discussion gives rise to several philosophical debates on the status of the preimplantation embryo, particularly the debate over when the preimplantation embryo becomes individuated. How that question is resolved has critical ethical and policy implications. PMID:9360195

  8. Fetal and Neonatal Alloimmune Thrombocytopenia

    PubMed Central

    CONSTANTINESCU, Simona; ZAMFIRESCU, Vlad; VLADAREANU, Prof. Radu

    2012-01-01

    ABSTRACT Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is the commonest cause of severe neonatal thrombocytopenia. FNAIT is usually suspected in neonates with bleeding or severe, unexplained, and/or isolated postnatal thrombocytopenia. Affected fetuses should be managed in referral centers with experience in the ante-natal management of FNAIT. Close collaboration is required between specialists in fetal medicine, obstetrics, hematology/transfusion medicine, and pediatrics. The mother and her partner should be provided with detailed information about FNAIT and its potential clinical consequences, and the benefits and risks of different approaches to ante-natal management. There has been huge progress in the ante-natal management of FNAIT over the last 20 years. However, the ideal effective treatment without significant side effects to the mother or fetus has yet to be determined. Key issues: Fetal and neonatal alloimmune thrombocytopenia is a condition that is underdiagnosed. Immunization seldom occurs in the first pregnancy. Immunization takes place in association with delivery in most cases. Anti-HPA-1a level is a predictor for the severity of thrombocytopenia. PMID:23482913

  9. [Fetal-neonatal alloimmune thrombocytopenia].

    PubMed

    Muñiz-Díaz, E; Ginovart Galiana, G

    2003-06-01

    Fetal-neonatal alloimmune thrombocytopenia is the commonest cause of severe thrombocytopenia in the newborn. This disorder is due to the destruction of fetal platelets by a maternal platelet-specific antibody caused by fetal-maternal incompatibility. The most serious complication is intracranial hemorrhage (10-30 % of newborns), which may cause death (10 % of the reported cases) or irreversible neurological sequelae (20 %). The diagnosis is usually made after birth when most affected neonates have petechiae, purpura or overt bleeding. The degree of severity varies according to platelet count. Current methods allow detection of maternal platelet alloantibodies (usually HPA-1a). Clinical grounds and the exclusion of other causes of neonatal thrombocytopenia are required to establish an accurate diagnosis. Recurrence of this disease is very high and has prompted clinicians to develop antenatal prophylactic programs in subsequent pregnancies. However, the optimal treatment of at-risk pregnancies remains controversial. The early diagnosis of this process allows effective therapy based on the infusion of compatible platelets and IgG immunoglobulins when hemorrhage is not obvious. Antenatal management of subsequent pregnancies can prevent recurrence of thrombocytopenia and intracranial hemorrhage. The aim of this review is to draw pediatricians' attention to the importance of this probably under-diagnosed disease in which early diagnosis can prevent potentially severe complications. PMID:12781112

  10. Fetal programming in meat production.

    PubMed

    Du, Min; Wang, Bo; Fu, Xing; Yang, Qiyuan; Zhu, Mei-Jun

    2015-11-01

    Nutrient fluctuations during the fetal stage affects fetal development, which has long-term impacts on the production efficiency and quality of meat. During the early development, a pool of mesenchymal progenitor cells proliferate and then diverge into either myogenic or adipogenic/fibrogenic lineages. Myogenic progenitor cells further develop into muscle fibers and satellite cells, while adipogenic/fibrogenic lineage cells develop into adipocytes, fibroblasts and resident fibro-adipogenic progenitor cells. Enhancing the proliferation and myogenic commitment of progenitor cells during fetal development enhances muscle growth and lean production in offspring. On the other hand, promoting the adipogenic differentiation of adipogenic/fibrogenic progenitor cells inside the muscle increases intramuscular adipocytes and reduces connective tissue, which improves meat marbling and tenderness. Available studies in mammalian livestock, including cattle, sheep and pigs, clearly show the link between maternal nutrition and the quantity and quality of meat production. Similarly, chicken muscle fibers develop before hatching and, thus, egg and yolk sizes and hatching temperature affect long-term growth performance and meat production of chicken. On the contrary, because fishes are able to generate new muscle fibers lifelong, the impact of early nutrition on fish growth performance is expected to be minor, which requires further studies. PMID:25953215

  11. 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. PMID:26391926

  12. 21 CFR 884.1560 - Fetal blood sampler.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade...

  13. 21 CFR 884.1560 - Fetal blood sampler.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade...

  14. 21 CFR 884.1560 - Fetal blood sampler.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade...

  15. 21 CFR 884.1560 - Fetal blood sampler.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade...

  16. 21 CFR 884.1560 - Fetal blood sampler.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal blood sampler. 884.1560 Section 884.1560... § 884.1560 Fetal blood sampler. (a) Identification. A fetal blood sampler is a device used to obtain fetal blood transcervically through an endoscope by puncturing the fetal skin with a short blade...

  17. Fetal microchimeric cells in autoimmune thyroid diseases

    PubMed Central

    Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter

    2013-01-01

    Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD. PMID:23723083

  18. 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

  19. Ligand-dependent Bohr effect of Chrionomus hemoglobins.

    PubMed

    Steffens, G; Buse, G; Wollmer, A

    1977-01-01

    The O2 and CO Bohr effects of monomeric and dimeric hemoglobins of the insect Chironomus thummi thummi were determined as proton releases upon ligation. For the O2 Bohr effect of the monomeric hemoglobin III a maximum value of 0.20 H+/heme was obtained at pH 7.5. Upon ligation with CO, however, only 0.04 H+/heme were released at the same pH. In agreement with this finding isoelectric focusing experiments revealed different isoelectric points for O2-liganded and CO-liganded states of hemoglobin III. Analogous results were obtained in the cases of the monomeric hemoglobin IV and the dimeric hemoglobins of Chironomus thummi thummi; here O2 Bohr effects of 0.43 and 0.86 H+/heme were observed. For the corresponding CO Bohr effects values of 0.08 and 0.31 H+/heme were obtained respectively. On the basis of the available structural data the reduced CO Bohr effect in hemoglobin III is discussed as arising from a steric hindrance of the CO ligand by the side chain of isoleucine-E11, obstructing the movement of the heme-iron upon reaction with carbon monoxide. It should, however, be noted that ligands, according to their different electron donor and acceptor properties, may generally induce different conformational changes and thus different Bohr effects, in those hemoglobins in which distinct tertiary and/or quaternary constraints have not evolved. The general utilization of CO instead of O2 as allosteric effector is ruled out by the results reported here. PMID:12977

  20. Fetal outcome in murine Lyme disease.

    PubMed

    Silver, R M; Yang, L; Daynes, R A; Branch, D W; Salafia, C M; Weis, J J

    1995-01-01

    Lyme disease is an inflammatory syndrome caused by infection with Borrelia burgdorferi. Although this syndrome has important implications for human pregnancy, little is known about gestational infection with B. burgdorferi. Fetal death occurred in 33 of 280 gestational sacs (12%) in 39 C3H/HeN female mice infected by intradermal injection of B. burgdorferi 4 days after mating (acute infection), compared with 0 of 191 sacs in 25 control mice (P = 0.0001). Forty-six percent of acutely infected mice suffered at least one fetal death, compared with none of the control animals (P = 0.0002). There were no fetal deaths in 18 C3H/HeN mice infected 3 weeks prior to mating (chronic infection). A sensitive PCR technique detected B. burgdorferi DNA in the uteri of acutely infected mice but did not detect DNA in the uteri of controls or chronically infected mice. Spirochete DNA was only rarely detected in fetal tissues, and its presence was not required for fetal death. The inclusion of an internal competitive PCR target indicated that the lack of B. burgdorferi sequences in fetal DNA was not due to the presence of a PCR inhibitor. Histologic analysis of gestational tissues from infected animals demonstrated nonspecific pathology consistent with fetal death. These findings indicate an association between murine fetal death and acute infection with B. burgdorferi early in gestation but not with chronic infection. Our data suggest that fetal death is due to a maternal response to infection rather than fetal infection. These findings could provide an explanation for observations in humans in which sporadic cases of fetal death in women infected with B. burgdorferi during pregnancy have been reported, while previous infection has not been associated with fetal death. PMID:7806385

  1. Fetal serine fluxes across fetal liver, hindlimb, and placenta in late gestation.

    PubMed

    Cetin, I; Fennessey, P V; Sparks, J W; Meschia, G; Battaglia, F C

    1992-10-01

    Eleven studies of fetal serine fluxes were performed in chronically catheterized fetal lambs by continuous infusion of [1-13C]- and [U-14C]serine into a fetal brachial vein. At tracer serine steady state, samples were collected from the fetal abdominal aorta, umbilical vein, fetal hepatic vein, and fetal femoral vein and from the maternal femoral artery and uterine vein. Analyses were performed for plasma serine and glycine concentration, for serine and glycine 13C mole percent enrichment, and for whole blood 14CO2 and O2 concentrations. Uterine and umbilical blood flows were also measured. The placenta had a significant net uptake of fetal serine (2.1 +/- 0.5 mumol.min-1.kg-1, P < 0.01). Fetal plasma serine disposal rate (DR) was 42.5 +/- 3.9 mumol.min-1.kg-1.CO2 production from decarboxylation of fetal plasma serine represented 7.9 +/- 0.5% of DR, or 10.1 +/- 1.2 mumol CO2.min-1.kg-1. Fetal plasma glycine enrichment was 59.7 +/- 4.9% of fetal plasma serine enrichment. There was a significant loss of tracer serine from the fetal circulation into the placenta accounting for approximately 45% of infused tracer. Fifteen percent of this was converted to glycine and released into the umbilical circulation. There was a significant uptake of tracer serine by both fetal liver and fetal hindlimb with a significant CO2 production by both sites with serine oxidation predominantly in the carcass. These results indicate a high fetal serine disposal rate in the lamb, with rapid fetoplacental serine exchange, resulting in a net uptake of fetal serine by the placenta.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1415701

  2. Fetal movements as a predictor of health.

    PubMed

    Lai, Jonathan; Nowlan, Niamh C; Vaidyanathan, Ravi; Shaw, Caroline J; Lees, Christoph C

    2016-09-01

    The key determinant to a fetus maintaining its health is through adequate perfusion and oxygen transfer mediated by the functioning placenta. When this equilibrium is distorted, a number of physiological changes, including reduced fetal growth, occur to favor survival. Technologies have been developed to monitor these changes with a view to prolong intrauterine maturity while reducing the risks of stillbirth. Many of these strategies involve complex interpretation, for example Doppler ultrasound for fetal blood flow and computerized analysis of fetal heart rate changes. However, even with these modalities of fetal assessment to determine the optimal timing of delivery, fetal movements remain integral to clinical decision-making. In high-risk cohorts with fetal growth restriction, the manifestation of a reduction in perceived movements may warrant an expedited delivery. Despite this, there has been little evolution in the development of technologies to objectively evaluate fetal movement behavior for clinical application. This review explores the available literature on the value of fetal movement analysis as a method of assessing fetal wellbeing, and demonstrates how interdisciplinary developments in this area may aid in the improvement of clinical outcomes. PMID:27374723

  3. Fetal Alcohol Syndrome: Facts and Prevention.

    ERIC Educational Resources Information Center

    Shelton, Maria; Cook, Martha

    1993-01-01

    This article provides a brief introduction to fetal alcohol syndrome (FAS) including characteristics, incidence, current government programs, successful local programs, and implications for school administrators. (DB)

  4. Drug Resistant Fetal Arrhythmia in Obstetric Cholestasis

    PubMed Central

    Altug, Nahide; Kirbas, Ayse; Daglar, Korkut; Biberoglu, Ebru; Uygur, Dilek; Danisman, Nuri

    2015-01-01

    Obstetric cholestasis (OC) is a pregnancy specific liver disease characterized by increased levels of bile acid (BA) and pruritus. Raised maternal BA levels could be associated with intrauterine death, fetal distress, and preterm labor and also alter the rate and rhythm of cardiomyocyte contraction and may cause fetal arrhythmic events. We report a case of drug resistant fetal supraventricular tachycardia and concomitant OC. Conclusion. If there are maternal OC and concomitant fetal arrhythmia, possibility of the resistance to antiarrhythmic treatment should be kept in mind. PMID:25821617

  5. Fetal Sex Differences in Intrapartum Electronic Fetal Monitoring.

    PubMed

    Porter, Anne C; Triebwasser, Jourdan E; Tuuli, Methodius; Caughey, Aaron B; Macones, George A; Cahill, Alison G

    2016-07-01

    Objective The article aimed to estimate differences in electronic fetal monitoring (EFM) patterns in term gestations attributable to fetal sex. Study Design We conducted a prospective cohort study of consecutive, singleton, nonanomalous, term gestations that labored during admission. EFM characteristics in the 30 minutes prior to delivery were evaluated. Logistic regression models estimated adjusted risks for EFM features by sex. To further estimate the impact of sex, we limited the analysis to gestations without composite morbidity (morbidity defined as arterial cord pH <7.20, 5-minute Apgar <7, or neonatal intensive care unit admission). Results Of 2,639 deliveries, 1,400 (53%) were male. Male fetuses had a higher number of decelerations (median [interquartile range]: 8 [5, 11] vs. 7 [4, 10], p < 0.003) and increased total deceleration area (adjusted odds ratio [aOR]: 1.11, 95% confidence interval [CI] :1.04, 1.18). Male fetuses were at increased risk for prolonged decelerations (aOR: 1.21, 95% CI: 1.03, 1.42) and repetitive variable decelerations (aOR: 1.24, 95% CI: 1.05, 1.47). Among neonates without composite morbidity (n = 2,446, 92.7%), male sex conferred an increased risk of late decelerations (aOR: 1.21, 95% CI: 1.02, 1.43) and increased total deceleration area (aOR: 1.12, 95% CI: 1.05, 1.20). Conclusion There are significant sex differences in EFM patterns at term among pregnancies without evidence of acidemia. This suggests that interpretation of EFM patterns may need to take into account factors such as fetal sex. PMID:26906183

  6. Neutrophil recruitment by fetal procine endothelial cells: Implications in scarless fetal wound healing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fetal dermal wounds heal scarlessly and with a minimal inflammatory response. When a robust inflammatory response is induced at the site of fetal dermal wounds by the application of cytokines, healing results in fibrosis. To test the hypothesis that the reduced inflammatory response in fetal wounds ...

  7. Reference values of fetal erythrocytes in maternal blood during pregnancy established using flow cytometry.

    PubMed

    de Wit, Harry; Nabbe, Karin C A M; Kooren, Jurgen A; Adriaansen, Henk J; Roelandse-Koop, Elianne A; Schuitemaker, Joost H N; Hoffmann, Johannes J M L

    2011-10-01

    The aim of our study was to assess the fetal RBC count in maternal blood during uncomplicated pregnancies from 26 weeks onward. We used a flow cytometric method specifically designed for use in a routine hematology analyzer. Pregnant women were recruited through midwives. The participating laboratories used the FMH QuikQuant method (Trillium Diagnostics, Brewer, ME) in a CELL-DYN Sapphire hematology analyzer (Abbott Diagnostics, Santa Clara, CA). The method is based on a monoclonal antibody to hemoglobin F. Flow cytometric data were analyzed by 2 independent observers. The 95th percentile reference range was estimated according to Clinical and Laboratory Standards Institute guidelines. A total of 236 samples were statistically analyzed. Gestational ages ranged from 21.6 to 41 weeks (mean, 32.0 weeks), and the fetal RBC count in maternal blood ranged from 0.00% to 0.50% (median, 0.025%). The fetal RBC count in maternal blood shows no correlation with gestational age. The established reference range during normal pregnancy is less than 0.125%. PMID:21917687

  8. Automated microscopy system for detection and genetic characterization of fetal nucleated red blood cells on slides

    NASA Astrophysics Data System (ADS)

    Ravkin, Ilya; Temov, Vladimir

    1998-04-01

    The detection and genetic analysis of fetal cells in maternal blood will permit noninvasive prenatal screening for genetic defects. Applied Imaging has developed and is currently evaluating a system for semiautomatic detection of fetal nucleated red blood cells on slides and acquisition of their DNA probe FISH images. The specimens are blood smears from pregnant women (9 - 16 weeks gestation) enriched for nucleated red blood cells (NRBC). The cells are identified by using labeled monoclonal antibodies directed to different types of hemoglobin chains (gamma, epsilon); the nuclei are stained with DAPI. The Applied Imaging system has been implemented with both Olympus BX and Nikon Eclipse series microscopes which were equipped with transmission and fluorescence optics. The system includes the following motorized components: stage, focus, transmission, and fluorescence filter wheels. A video camera with light integration (COHU 4910) permits low light imaging. The software capabilities include scanning, relocation, autofocusing, feature extraction, facilities for operator review, and data analysis. Detection of fetal NRBCs is achieved by employing a combination of brightfield and fluorescence images of nuclear and cytoplasmic markers. The brightfield and fluorescence images are all obtained with a single multi-bandpass dichroic mirror. A Z-stack of DNA probe FISH images is acquired by moving focus and switching excitation filters. This stack is combined to produce an enhanced image for presentation and spot counting.

  9. Obtaining antimicrobial peptides by controlled peptic hydrolysis of bovine hemoglobin.

    PubMed

    Adje, Estelle Yaba; Balti, Rafik; Kouach, Mostafa; Dhulster, Pascal; Guillochon, Didier; Nedjar-Arroume, Naïma

    2011-08-01

    Under standard conditions, the peptides and specially the active peptides were obtained from either the denatured hemoglobin that all structures are completely modified or either the native hemoglobin where all structures are intact. In these conditions, antibacterial peptides were isolated from a very complex peptidic hydrolysate which contains more than one hundred peptides having various sizes and characteristics, involving a complex purification process. The new hydrolysis conditions were obtained by using 40% methanol, 30% ethanol, 20% propanol or 10% butanol. These conditions, where only the secondary structure of hemoglobin retains intact, were followed in order to enrich the hydrolyzed hemoglobin by active peptides or obtain new antibacterial peptides. In these controlled peptic hydrolysis of hemoglobin, a selective and restrictive hydrolysate contained only 29 peptides was obtained. 26 peptides have an antibacterial activity against Micrococcus luteus, Listeria innocua, and Escherichia coli with MIC from 187.1 to 1 μM. Among these peptides, 13 new antibacterial peptides are obtained only in these new hydrolysis conditions. PMID:21510973

  10. Interpretation of the electronic fetal heart rate during labor.

    PubMed

    Sweha, A; Hacker, T W; Nuovo, J

    1999-05-01

    Electronic fetal heart rate monitoring is commonly used to assess fetal well-being during labor. Although detection of fetal compromise is one benefit of fetal monitoring, there are also risks, including false-positive tests that may result in unnecessary surgical intervention. Since variable and inconsistent interpretation of fetal heart rate tracings may affect management, a systematic approach to interpreting the patterns is important. The fetal heart rate undergoes constant and minute adjustments in response to the fetal environment and stimuli. Fetal heart rate patterns are classified as reassuring, nonreassuring or ominous. Nonreassuring patterns such as fetal tachycardia, bradycardia and late decelerations with good short-term variability require intervention to rule out fetal acidosis. Ominous patterns require emergency intrauterine fetal resuscitation and immediate delivery. Differentiating between a reassuring and nonreassuring fetal heart rate pattern is the essence of accurate interpretation, which is essential to guide appropriate triage decisions. PMID:10323356

  11. [Prevalence of hemoglobin S in the State of Paraná, Brazil, based on neonatal screening].

    PubMed

    Watanabe, Alexandra M; Pianovski, Mara Albonei D; Zanis Neto, José; Lichtvan, Leniza C L; Chautard-Freire-Maia, Eleidi A; Domingos, Mouseline T; Wittig, Ehrenfried O

    2008-05-01

    The Brazilian Ministry of Health created the National Neonatal Screening Program under ruling no. 822/2001, including neonatal screening for hemoglobinopathies. In the State of Paraná, neonatal screening is conducted by the Ecumenical Foundation for the Protection of the Handicapped. The prevalence rates were determined for homozygous and heterozygous hemoglobin S and Sbeta-thalassemia. Blood samples drawn on filter paper were examined by isoelectric focusing (IEF) and high-performance liquid chromatography (HPLC). From January 2002 to December 2004, 548,810 newborns were screened, with the detection of 21 with FS, two FSA/FS, and four FSA. After confirmatory tests at six months of age, 12 were defined as sickle-cell anemia, or a prevalence of 2.2:100,000 newborns; Sbeta-thalassemia was confirmed in 15 (2.7:100,000 newborns); and 8,321 newborns were diagnosed as heterozygous HbS (1,500:100,000 newborns). HbS prevalence in Paraná (in southern Brazil) is lower than in the Central-West, North, and Northeast of the country. Ethnic origin of the population, fetal deaths, and non-random procreation may contribute to the relatively low number of homozygous individuals in the State. Sbeta-thalassemia interaction suggests the presence of Euro-Mediterranean peoples in this population's miscegenation. PMID:18461228

  12. Changes in fetal ovine metabolism and oxygen delivery with fetal bypass.

    PubMed

    Lam, Christopher T; Baker, R Scott; Clark, Kenneth E; Eghtesady, Pirooz

    2011-07-01

    Since the 1980s, attempts at experimental fetal cardiac bypass for the purpose of correcting severe congenital heart defects in the womb have been hampered by deterioration of placental function. This placental pathophysiology in turn affects transplacental transport of nutrients and gas exchange. To date, the effects of bypass on fetal metabolism and oxygen delivery have not been studied. Nine Suffolk sheep fetuses from 109-121 days gestation were instrumented and placed on fetal bypass for 30 min and followed postbypass for 2 h. Blood gases, glucose, and lactate were serially measured in the fetal arterial and umbilical venous circulations throughout the procedure. Insulin and glucagon levels were serially measured by immunoassay in fetal plasma. Fetal-placental hemodynamics were measured continuously. The expression of glycogen content was examined in fetal liver. Oxygen delivery to the fetus and fetal oxygen consumption were significantly deranged after the conduct of bypass (in-group ANOVA (P = 0.001) and overall contrast (P = 0.072) with planned contrast (P < 0.05) for delivery and consumption, respectively). There were significant alterations in fetal glucose metabolism in the postbypass period; however, insulin and glucagon levels did not change. Fetal liver glycogen content appeared lower after bypass. This is the first report documenting fetal metabolic dysregulation that occurs in response to the conduct of fetal bypass. The significant alterations in fetal oxygen and glucose delivery coupled with hepatic glycogen depletion complicate and impede fetal recovery. These initial findings warrant further investigation of interventions to restore metabolic and hemodynamic homeostasis after fetal bypass. PMID:21508289

  13. Atomic Gradiometers for Fetal Magnetocardiography

    NASA Astrophysics Data System (ADS)

    Sulai, Ibrahim; Deland, Zack; Wahl, Colin; Bulatowicz, Michael; Wakai, Ron; Walker, Thad

    2015-05-01

    We present results on development of 87 Rb atomic magnetometers configured as magnetic field gradiometers for fetal Magnetocardiography (fMCG). Operating in the Spin Exchange Relaxation Free (SERF) regime, the magnetometers have a sensitivity 1 fT /√{ Hz} . Magnetic field gradient measurements significantly reduce the interference of uniform background fields. In fMCG applications, the field from the mother's heart is one such background and cannot be passively shielded. We report schemes for implementing such gradiometers along with recent fMCG measurements. This work is supported by the National Institutes of Health.

  14. An Atomistic View on Human Hemoglobin Carbon Monoxide Migration Processes

    PubMed Central

    Lucas, M. Fátima; Guallar, Víctor

    2012-01-01

    A significant amount of work has been devoted to obtaining a detailed atomistic knowledge of the human hemoglobin mechanism. Despite this impressive research, to date, the ligand diffusion processes remain unclear and controversial. Using recently developed computational techniques, PELE, we are capable of addressing the ligand migration processes. First, the methodology was tested on myoglobin's CO migration, and the results were compared with the wealth of theoretical and experimental studies. Then, we explored both hemoglobin tense and relaxed states and identified the differences between the α-and β-subunits. Our results indicate that the proximal site, equivalent to the Xe1 cavity in myoglobin, is never visited. Furthermore, strategically positioned residues alter the diffusion processes within hemoglobin's subunits and suggest that multiple pathways exist, especially diversified in the α-globins. A significant dependency of the ligand dynamics on the tertiary structure is also observed. PMID:22385860

  15. Electro-enzymatic degradation of chlorpyrifos by immobilized hemoglobin.

    PubMed

    Tang, Tiantian; Dong, Jing; Ai, Shiyun; Qiu, Yanyan; Han, Ruixia

    2011-04-15

    Electro-enzymatic processes, which are enzyme catalysis combined with electrochemical reactions, have been used in the degradation of many environment pollutants. For some pollutants, the catalytic mechanisms of the electrochemical-enzyme reaction are still poorly understood. In this paper, the degradation of chlorpyrifos by a combination of immobilized hemoglobin and in situ generated hydrogen peroxide is reported for the first time. Hemoglobin was immobilized on graphite felts to catalyze the removal of chlorpyrifos in an electrochemical-enzyme system. Under the optimal conditions, more than 98% of the chlorpyrifos was degraded. Furthermore, the degradation products of chlorpyrifos were also studied and identified using liquid chromatography-mass spectrometry analysis. The results suggest a possible degradation mechanism for chlorpyrifos with low power and high efficiency, reveal the feasibility of hemoglobin as a substitute for some expensive natural enzymes, and demonstrate the application of an electro-enzymatic process in the treatment of organophosphorus compounds in wastewater. PMID:21316849

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

    PubMed Central

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

    2011-01-01

    Researchers tested male and female infants from rural Ethiopia to investigate relations among hemoglobin, anthropometry, and attention. They utilized a longitudinal design to examine differences in attention performance from 6 (M = 24.9 weeks, n = 89) to 9 months of age (M = 40.6 weeks, n = 85), differences hypothesized to be related to changes in iron status and growth delays. Stunting (length-for-age z-scores < −2.0) and attention performance [t(30) = −2.42, p = .022] worsened over time. Growth and hemoglobin predicted attention at 9 months [R2 = .15, p < .05], but not at 6. The use of the attention task at 9 months was supported. The study contributes to the knowledge base of hemoglobin, growth, and attention. PMID:21545582

  17. Development of fetal brain renin–angiotensin system and hypertension programmed in fetal origins

    PubMed Central

    Mao, Caiping; Shi, Lijun; Xu, Feichao; Zhang, Lubo; Xu, Zhice

    2010-01-01

    Since the concept of fetal origins of adult diseases was introduced in 1980s, the development of the renin–angiotensin system (RAS) in normal and abnormal patterns has attracted attention. Recent studies have shown the importance of the fetal RAS in both prenatal and postnatal development. This review focuses on the functional development of the fetal brain RAS, and ontogeny of local brain RAS components in utero. The central RAS plays an important role in the control of fetal cardiovascular responses, body fluid balance, and neuroendocrine regulation. Recent progress has been made in demonstrating that altered fetal RAS development as a consequence of environmental insults may impact on “programming” of hypertension later in life. Given that the central RAS is of equal importance to the peripheral RAS in cardiovascular regulation, studies on the fetal brain RAS development in normal and abnormal patterns could shed light on “programming” mechanisms of adult cardiovascular diseases in fetal origins. PMID:19428956

  18. Aspects of Fetal Learning and Memory

    ERIC Educational Resources Information Center

    Dirix, Chantal E. H.; Nijhuis, Jan G.; Jongsma, Henk W.; Hornstra, Gerard

    2009-01-01

    Ninety-three pregnant women were recruited to assess fetal learning and memory, based on habituation to repeated vibroacoustic stimulation of fetuses of 30-38 weeks gestational age (GA). Each habituation test was repeated 10 min later to estimate the fetal short-term memory. For Groups 30-36, both measurements were replicated in a second session…

  19. Sonography in Fetal Birth Weight Estimation

    ERIC Educational Resources Information Center

    Akinola, R. A.; Akinola, O. I.; Oyekan, O. O.

    2009-01-01

    The estimation of fetal birth weight is an important factor in the management of high risk pregnancies. The information and knowledge gained through this study, comparing a combination of various fetal parameters using computer assisted analysis, will help the obstetrician to screen the high risk pregnancies, monitor the growth and development,…

  20. Fetal Brain Behavior and Cognitive Development.

    ERIC Educational Resources Information Center

    Joseph, R.

    2000-01-01

    Presents information on prenatal brain development, detailing the functions controlled by the medulla, pons, and midbrain, and the implications for cognitive development. Concludes that fetal cognitive motor activity, including auditory discrimination, orienting, the wake-sleep cycle, fetal heart rate accelerations, and defensive reactions,…

  1. Fetal Pain: Life in Troubled Waters

    PubMed Central

    Johnson, Johnnye S.

    2007-01-01

    Maternal well-being is the key to fetal well-being. A fetus is highly vulnerable and sensitive to pain and stress, and exposure has the potential for negative developmental consequences. Childbirth educators can help raise parental awareness about the importance of the maternal environment for best outcomes in fetal development. PMID:18311338

  2. Advances in evaluating the fetal skeleton

    PubMed Central

    Noel, Ann-Edwidge; Brown, Richard N

    2014-01-01

    In this review, we discuss aspects of the prenatal diagnosis of fetal skeletal malformations, concentrating on the advantages offered by different imaging techniques and the approaches that are of value in evaluating a suspected skeletal dysplasia. We also briefly address the findings in some of the commoner malformations of the fetal skeleton that may be encountered. PMID:24868173

  3. Fetal deaths in Brazil: a systematic review

    PubMed Central

    Barbeiro, Fernanda Morena dos Santos; Fonseca, Sandra Costa; Tauffer, Mariana Girão; Ferreira, Mariana de Souza Santos; da Silva, Fagner Paulo; Ventura, Patrícia Mendonça; Quadros, Jesirée Iglesias

    2015-01-01

    OBJECTIVE To review the frequency of and factors associated with fetal death in the Brazilian scientific literature. METHODS A systematic review of Brazilian studies on fetal deaths published between 2003 and 2013 was conducted. In total, 27 studies were analyzed; of these, 4 studies addressed the quality of data, 12 were descriptive studies, and 11 studies evaluated the factors associated with fetal death. The databases searched were PubMed and Lilacs, and data extraction and synthesis were independently performed by two or more examiners. RESULTS The level of completeness of fetal death certificates was deficient, both in the completion of variables, particularly sociodemographic variables, and in defining the underlying causes of death. Fetal deaths have decreased in Brazil; however, inequalities persist. Analysis of the causes of death indicated maternal morbidities that could be prevented and treated. The main factors associated with fetal deaths were absent or inadequate prenatal care, low education level, maternal morbidity, and adverse reproductive history. CONCLUSIONS Prenatal care should prioritize women that are most vulnerable (considering their social environment or their reproductive history and morbidities) with the aim of decreasing the fetal mortality rate in Brazil. Adequate completion of death certificates and investment in the committees that investigate fetal and infant deaths are necessary. PMID:25902565

  4. Fetal trauma from motor vehicle collisions.

    PubMed

    Friese, Greg; Wojciehoski, Randal F

    2005-07-01

    To summarize: The best fetal protection is proper maternal use of seat belt restraints. All pregnant occupants in a motor vehicle crash require physician evaluation. Focus on maternal assessment. Maternal stability is the best indicator of fetal stability. Key treatments are high-flow oxygen, i.v. fluid loading and immobilizing in left lateral position. Evaluate the fetus after maternal stabilization. PMID:16116864

  5. FETAL ALCOHOL SYNDROME SURVEILLANCE NETWORK (FASSNET)

    EPA Science Inventory

    CDC, in collaboration with four states, has developed the first state-based program specifically designed to monitor trends in the occurrence of fetal alcohol syndrome (FAS). The program, Fetal Alcohol Syndrome Surveillance Network (FASSNet), reports that many children continue t...

  6. [Hypoxaemia, peripheral chemoreceptors and fetal heart rate].

    PubMed

    Secourgeon, J-F

    2012-02-01

    The perinatal results of the widespread adoption of the continuous electronic fetal heart rate monitoring during labor remain rather disappointing. This is due in part to a lack of consistent interpretation of the fetal heart tracings. Despite efforts by referral agencies over the past decade the situation has not improved. In defense of practitioners the heterogeneity and complexity of definitions and classifications patterns especially morphological currently proposed should be noted. Whereas with the recent advances in the field of neuroscience, it is now possible to visualize the chain of pathophysiological events that lead from the hypoxemic stimulus of the glomus cell to changes in the morphology of the fetal heart rate tracing. Thus by taking some examples of real situations, we propose a method of analysis that dissects the fetal heart tracing and take into account the functional specifications of the chemoreceptor when exposed to a hypoxic environment. Furthermore we can identify tracings with a "threshold effect" and also "sensitization and desensitization effects" according to the intensity, duration and recurrence of hypoxaemic episodes. This new approach based upon specific research into the mechanism behind the fetal heart rate abnormalities may be useful to complement the morphological study of the fetal heart tracing, to provide a better idea of the fetal status and to better define the indications of fetal blood sampling procedures. PMID:21798673

  7. Fetal Alcohol Syndrome: An International Concern.

    ERIC Educational Resources Information Center

    Asetoyer, Charon

    1987-01-01

    Describes Fetal Alcohol Effects (FAE) and Fetal Alcohol Syndrome (FAS) in infants, caused by mothers' consumption of alcohol during pregnancy. Both disabilities found in relatively high proportions of American Indian children. Discusses impact of disabilities on education. Discusses parent education programs in United States and abroad. (TES)

  8. 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.

  9. Fetal Origins of Adult Disease

    PubMed Central

    Calkins, Kara; Devaskar, Sherin U.

    2015-01-01

    Dr. David Barker first popularized the concept of fetal origins of adult disease (FOAD). Since its inception, FOAD has received considerable attention. The FOAD hypothesis holds that events during early development have a profound impact on one’s risk for development of future adult disease. Low birth weight, a surrogate marker of poor fetal growth and nutrition, is linked to coronary artery disease, hypertension, obesity, and insulin resistance. Clues originally arose from large 20th century, European birth registries. Today, large, diverse human cohorts and various animal models have extensively replicated these original observations. This review will focus on the pathogenesis related to FOAD and examines Dr. David Barker’s landmark studies, along with additional human and animal model data. Implications of the FOAD extend beyond the low birth weight population and include babies exposed to stress, both nutritional and non-nutritional, during different critical periods of development, which ultimately result in a disease state. By understanding FOAD, health care professionals and policy makers will make this issue a high healthcare priority and implement preventative measures and treatment for those at higher risk for chronic diseases. PMID:21684471

  10. Fetal origins of adult disease.

    PubMed

    Calkins, Kara; Devaskar, Sherin U

    2011-07-01

    Dr. David Barker first popularized the concept of fetal origins of adult disease (FOAD). Since its inception, FOAD has received considerable attention. The FOAD hypothesis holds that events during early development have a profound impact on one's risk for development of future adult disease. Low birth weight, a surrogate marker of poor fetal growth and nutrition, is linked to coronary artery disease, hypertension, obesity, and insulin resistance. Clues originally arose from large 20th century, European birth registries. Today, large, diverse human cohorts and various animal models have extensively replicated these original observations. This review focuses on the pathogenesis related to FOAD and examines Dr. David Barker's landmark studies, along with additional human and animal model data. Implications of the FOAD extend beyond the low birth weight population and include babies exposed to stress, both nutritional and nonnutritional, during different critical periods of development, which ultimately result in a disease state. By understanding FOAD, health care professionals and policy makers will make this issue a high health care priority and implement preventive measures and treatment for those at higher risk for chronic diseases. PMID:21684471

  11. Routine fetal genitourinary tract screening.

    PubMed

    Arger, P H; Coleman, B G; Mintz, M C; Snyder, H P; Camardese, T; Arenson, R L; Gabbe, S G; Aquino, L

    1985-08-01

    To evaluate routine fetal genitourinary tract obstetrical ultrasound screening, and to determine what size renal pelvis is indicative of significant renal disease, we reviewed 4,832 examinations, which had been performed over 2 years, of 3,530 consecutive obstetrical patients. Any fetus that had a renal pelvis greater than 5 mm or a definable cystic area was identified for follow-up. The fetuses of 39 patients (1.1%) who underwent 112 examinations fulfilled these criteria and constitute the basis of this report. A variety of examination criteria were recorded and analyzed in relationship to the follow-up, which ranged from 2-3 days to 21 months. The fetuses of the 39 patients were grouped into three categories: those with renal pelves between 5 and 9 mm in size; those with renal pelves larger than 10 mm; and those with cystic abnormalities. Those with renal pelves larger than 10 mm had either an obstructing lesion or exceptional extrarenal pelves. The clinical and pathologic aspects of these three groups are detailed, discussed, and analyzed. Criteria for significant fetal renal hydronephrosis and aspects of a loculated appearance are given. PMID:3892578

  12. HTS magnetometers for fetal magnetocardiography.

    PubMed

    Li, Z; Wakai, R T; Paulson, D N; Schwartz, B

    2004-01-01

    High temperature superconducting (HTS) SQUID sensors have adequate magnetic field sensitivity for adult magnetocardiography (MCG) measurements, but it remains to be seen how well they perform for fetal MCG (fMCG), where the heart signals are typically ten times smaller than the adult signals. In this study, we assess the performance of a prototype HTS SQUID system; namely, a three-SQUID gradiometer formed from three vertically-aligned HTS dc-SQUID magnetometers integrated into a fiberglass liquid nitrogen dewar of diameter 12.5 cm and height 30 cm. Axial gradiometers with short or long baseline, as well as a second order gradiometer, can be formed out of these magnetometers via electronic subtraction. The calibrated magnetometer sensitivities at 1 kHz are 109 fT/square root of Hz, 155 fT/square root of Hz and 51 fT/square root of Hz. Direct comparison is made between the HTS SQUID system and a LTS SQUID system by making recordings with both systems during the same session on adult and fetal subjects. Although the fMCG could be resolved with the HTS SQUID system in most near-term subjects, the signal-to-noise ratio was relatively low and the system could not be operated outside of a shielded room. PMID:16012655

  13. System for objective assessment of fetal activity.

    PubMed

    Kaluzynski, K J; Kret, T; Czajkowski, K; Sieńko, J; Zmigrodzki, J

    2011-07-01

    Fetal activity is an important indicator of fetal well-being. It is proposed to assess this activity using the pulsed wave Doppler method to collect fetal activity data and dedicated software for on-line processing. The system, addressed to 3rd trimester pregnancies, provides information on presence of pseudobreathing, the heart rate trace, the fetal movement trace, the movement velocity spectrogram, histograms of the velocity and acceleration of both the body movements and pseudobreathing, parameters of these histograms (mean values, standard deviations, shape descriptors), and cumulative counts of the velocity histograms. These parameters form the feature vector of the fetal activity. The system was validated by simultaneous echographic and cardiotocographic recordings and during oxytocin challenge tests. Feature vectors obtained from 1h recordings in 61 pregnancies were submitted to multivariate analysis of variance. Activity patterns of physiological cases and "borderline pathologies" were discriminated using reduced feature vectors, containing cumulative counts of velocity histograms. PMID:21277248

  14. Propofol Pharmacokinetics and Estimation of Fetal Propofol Exposure during Mid-Gestational Fetal Surgery: A Maternal-Fetal Sheep Model

    PubMed Central

    Niu, Jing; Venkatasubramanian, Raja; Vinks, Alexander A.; Sadhasivam, Senthilkumar

    2016-01-01

    Background Measuring fetal drug concentrations is extremely difficult in humans. We conducted a study in pregnant sheep to simultaneously describe maternal and fetal concentrations of propofol, a common intravenous anesthetic agent used in humans. Compared to inhalational anesthesia, propofol supplemented anesthesia lowered the dose of desflurane required to provide adequate uterine relaxation during open fetal surgery. This resulted in better intraoperative fetal cardiac outcome. This study describes maternal and fetal propofol pharmacokinetics (PK) using a chronically instrumented maternal-fetal sheep model. Methods Fetal and maternal blood samples were simultaneously collected from eight mid-gestational pregnant ewes during general anesthesia with propofol, remifentanil and desflurane. Nonlinear mixed-effects modeling was performed by using NONMEM software. Total body weight, gestational age and hemodynamic parameters were tested in the covariate analysis. The final model was validated by bootstrapping and visual predictive check. Results A total of 160 propofol samples were collected. A 2-compartment maternal PK model with a third fetal compartment appropriately described the data. Mean population parameter estimates for maternal propofol clearance and central volume of distribution were 4.17 L/min and 37.7 L, respectively, in a typical ewe with a median heart rate of 135 beats/min. Increase in maternal heart rate significantly correlated with increase in propofol clearance. The estimated population maternal-fetal inter-compartment clearance was 0.0138 L/min and the volume of distribution of propofol in the fetus was 0.144 L. Fetal propofol clearance was found to be almost negligible compared to maternal clearance and could not be robustly estimated. Conclusions For the first time, a maternal-fetal PK model of propofol in pregnant ewes was successfully developed. This study narrows the gap in our knowledge in maternal-fetal PK model in human. Our study confirms

  15. Noninvasive Fetal Sex Determination Using Cell-Free Fetal DNA

    PubMed Central

    Devaney, Stephanie A.; Palomaki, Glenn E.; Scott, Joan A.; Bianchi, Diana W.

    2015-01-01

    Context Noninvasive prenatal determination of fetal sex using cell-free fetal DNA provides an alternative to invasive techniques for some heritable disorders. In some countries this testing has transitioned to clinical care, despite the absence of a formal assessment of performance. Objective To document overall test performance of noninvasive fetal sex determination using cell-free fetal DNA and to identify variables that affect performance. Data Sources Systematic review and meta-analysis with search of PubMed (January 1, 1997–April 17, 2011) to identify English-language human studies reporting primary data. References from review articles were also searched. Study Selection and Data Extraction Abstracts were read independently to identify studies reporting primary data suitable for analysis. Covariates included publication year, sample type, DNA amplification methodology, Y chromosome sequence, and gestational age. Data were independently extracted by 2 reviewers. Results From 57 selected studies, 80 data sets (representing 3524 male-bearing pregnancies and 3017 female-bearing pregnancies) were analyzed. Overall performance of the test to detect Y chromosome sequences had the following characteristics: sensitivity, 95.4% (95% confidence interval [CI], 94.7%–96.1%) and specificity, 98.6% (95% CI, 98.1%–99.0%); diagnostic odds ratio (OR), 885; positive predictive value, 98.8%; negative predictive value, 94.8%; area under curve (AUC), 0.993 (95% CI, 0.989–0.995), with significant interstudy heterogeneity. DNA methodology and gestational age had the largest effects on test performance. Methodology test characteristics were AUC, 0.988 (95% CI, 0.979–0.993) for polymerase chain reaction (PCR) and AUC, 0.996 (95% CI, 0.993–0.998) for real-time quantitative PCR (RTQ-PCR) (P=.02). Gestational age test characteristics were AUC, 0.989 (95% CI, 0.965–0.998) (<7 weeks); AUC, 0.994 (95% CI, 0.987–0.997) (7–12 weeks); AUC, 0.992 (95% CI, 0.983–0.996) (13

  16. DETERMINATION OF HEMOGLOBIN ADDUCTS IN HUMANS OCCUPATIONALLY EXPOSED TO ACRYLAMIDE

    EPA Science Inventory

    Hemoglobin (Hb) adduct determinations were used to monitor occupational exposure to acrylamide (AA) and acrylonitrile (AN). orth-one workers in a factory in the People's Republic of China who were involved in the synthesis of a AA by catalytic hydration of AN and the manufacturin...

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

    PubMed

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

    2016-01-01

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

  18. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. Effect of Some High Consumption Spices on Hemoglobin Glycation

    PubMed Central

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

    2014-01-01

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

  1. The Relationship Between Hemoglobin Level and Intellectual Function.

    ERIC Educational Resources Information Center

    Munro, Nancy

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

  2. Ultrasonic processing for recovery of chicken erythrocyte hemoglobin

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  3. 21 CFR 522.1125 - Hemoglobin glutamer-200 (bovine).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  4. 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.

  5. A new colorimetric method for the estimation of glycosylated hemoglobin.

    PubMed

    Nayak, S S; Pattabiraman, T N

    1981-02-01

    A new colorimetric method, based on the phenol sulphuric acid reaction of carbohydrates, is described for the determination of glycosylated hemoglobin. Hemolyzates were treated with 1 mol/l oxalic acid in 2 mol/l Hcl for 4 h at 100 degrees C, the protein was precipitated with trichloroacetic acid, and the free sugars and hydroxymethyl furfural in the protein free supernatant were treated with phenol and sulphuric acid to form the color. The new method is compared to the thiobarbituric acid method and the ion-exchange chromatographic method for the estimation of glycosylated hemoglobin in normals and diabetics. The increase in glycosylated hemoglobin in diabetic patients as estimated by the phenol-sulphuric acid method was more significant (P less than 0.001) than the increase observed by the thiobarbituric acid method (P less than 0.01). The correlation between the phenol-sulphuric acid method and the column method was better (r = 0.91) than the correlation between the thiobarbituric acid method and the column method (r = 0.84). No significant correlation between fasting and postprandial blood sugar level and glycosylated hemoglobin level as determined by the two colorimetric methods was observed in diabetic patients. PMID:7226519

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

    ERIC Educational Resources Information Center

    Herrick, Richard S.; Cording, Robert K.

    2013-01-01

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

  7. Therapeutic Strategies to Alter Oxygen Affinity of Sickle Hemoglobin

    PubMed Central

    Safo, Martin K.; Kato, Gregory J.

    2014-01-01

    The fundamental pathophysiology of sickle cell disease involves the polymerization of sickle hemoglobin in its T-state which develops under low oxygen saturation. One therapeutic strategy is to develop pharmacologic agents to stabilize the R-state of hemoglobin, which has higher oxygen affinity and would be expected to have slower kinetics of polymerization, potentially delaying the sickling of red cells during circulation. This therapeutic strategy has stimulated the laboratory investigation of aromatic aldehydes, aspirin derivatives, thiols and isothiocyanates that can stabilize the R-state of hemoglobin in vitro. One representative aromatic aldehyde agent, 5-hydoxymethyl-2-furfural (5-HMF, also known as Aes-103) increases oxygen affinity of sickle hemoglobin and reduces hypoxia-induced sickling in vitro and protects sickle cell mice from effects of hypoxia. It has completed pre-clinical testing and has entered clinical trials. The development of Hb allosteric modifiers as direct anti-sickling agents is an attractive investigational goal for the treatment of sickle cell disease. PMID:24589263

  8. 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 864.7500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7500...

  9. 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...

  10. 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 §...

  11. 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 864.7500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7500...

  12. 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 864.7500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7500...

  13. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Glycosylated hemoglobin assay. 864.7470 Section 864.7470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  14. 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...

  15. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Glycosylated hemoglobin assay. 864.7470 Section 864.7470 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages §...

  16. 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 §...

  17. 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...

  18. 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 §...

  19. 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 §...

  20. 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 864.7500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7500...

  1. 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...

  2. 21 CFR 864.7470 - Glycosylated hemoglobin assay.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Glycosylated hemoglobin assay. 864.7470 Section 864.7470 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 864.7500 - 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 864.7500 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7500...

  5. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  6. 21 CFR 864.5620 - 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 §...

  7. 21 CFR 864.5620 - Automated hemoglobin system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  8. 21 CFR 864.5620 - 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 §...

  9. 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 §...

  10. BINDING OF CHLOROFORM TO THE CYSTEINE OF HEMOGLOBIN

    EPA Science Inventory

    The products of the covalent binding of chloroform to rat hemoglobin during microsomal metabolism were isolated and identified by gas chromatography (GC) and mass spectroscopy (MS). After isolation by Proteinase K hydrolysis, amino acid analysis and cellulose thin-layer chromatog...

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

    PubMed

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

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

    SciTech Connect

    Not Available

    1980-01-01

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

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

    PubMed

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

    2007-08-01

    The evolution of oxygen transport hemoglobins occurred on at least two independent occasions. The earliest event led to myoglobin and red blood cell hemoglobin in animals. In plants, oxygen transport "leghemoglobins" evolved much more recently. In both events, pentacoordinate heme sites capable of inert oxygen transfer evolved from hexacoordinate hemoglobins that have unrelated functions. High sequence homology between hexacoordinate and pentacoordinate hemoglobins in plants has poised them for potential structural analysis leading to a molecular understanding of this important evolutionary event. However, the lack of a plant hexacoordinate hemoglobin structure in the exogenously ligand-bound form has prevented such comparison. Here we report the crystal structure of the cyanide-bound hexacoordinate hemoglobin from barley. This presents the first opportunity to examine conformational changes in plant hexacoordinate hemoglobins upon exogenous ligand binding, and reveals structural mechanisms for stabilizing the high-energy pentacoordinate heme conformation critical to the evolution of reversible oxygen binding hemoglobins. PMID:17560601

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

    SciTech Connect

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

    2007-01-01

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

  16. 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

  17. Fetal magnetic resonance imaging and ultrasound.

    PubMed

    Wataganara, Tuangsit; Ebrashy, Alaa; Aliyu, Labaran Dayyabu; Moreira de Sa, Renato Augusto; Pooh, Ritsuko; Kurjak, Asim; Sen, Cihat; Adra, Abdallah; Stanojevic, Milan

    2016-07-01

    Magnetic resonance imaging (MRI) has been increasingly adopted in obstetrics practice in the past three decades. MRI aids prenatal ultrasound and improves diagnostic accuracy for selected maternal and fetal conditions. However, it should be considered only when high-quality ultrasound cannot provide certain information that affects the counseling, prenatal intervention, pregnancy course, and delivery plan. Major indications of fetal MRI include, but are not restricted to, morbidly adherent placenta, selected cases of fetal brain anomalies, thoracic lesions (especially in severe congenital diaphragmatic hernia), and soft tissue tumors at head and neck regions of the fetus. For fetal anatomy assessment, a 1.5-Tesla machine with a fast T2-weighted single-shot technique is recommended for image requisition of common fetal abnormalities. Individual judgment needs to be applied when considering usage of a 3-Tesla machine. Gadolinium MRI contrast is not recommended during pregnancy. MRI should be avoided in the first half of pregnancy due to small fetal structures and motion artifacts. Assessment of fetal cerebral cortex can be achieved with MRI in the third trimester. MRI is a viable research tool for noninvasive interrogation of the fetus and the placenta. PMID:27092644

  18. Prediction of fetal acidemia in placental abruption

    PubMed Central

    2013-01-01

    Background To determine the major predictive factors for fetal acidemia in placental abruption. Methods A retrospective review of pregnancies with placental abruption was performed using a logistic regression model. Fetal acidemia was defined as a pH of less than 7.0 in umbilical artery. The severe abruption score, which was derived from a linear discriminant function, was calculated to determine the probability of fetal acidemia. Results Fetal acidemia was seen in 43 survivors (43/222, 19%). A logistic regression model showed bradycardia (OR (odds ratio) 50.34, 95% CI 11.07 – 228.93), and late decelerations (OR 15.13, 3.05 – 74.97), but not abnormal ultrasonographic findings were to be associated with the occurrence of fetal acidemia. The severe abruption score was calculated for the occurrence of fetal acidemia, using 6 items including vaginal bleeding, gestational age, abdominal pain, abnormal ultrasonographic finding, late decelerations, and bradycardia. Conclusions An abnormal FHR pattern, especially bradycardia is the most significant risk factor in placental abruption predicting fetal acidemia, regardless of the presence of abnormal ultrasonographic findings or gestational age. PMID:23915223

  19. Modeling photon transport in transabdominal fetal oximetry

    NASA Astrophysics Data System (ADS)

    Jacques, Steven L.; Ramanujam, Nirmala; Vishnoi, Gargi; Choe, Regine; Chance, Britton

    2000-07-01

    The possibility of optical oximetry of the blood in the fetal brain measured across the maternal abdomen just prior to birth is under investigated. Such measurements could detect fetal distress prior to birth and aid in the clinical decision regarding Cesarean section. This paper uses a perturbation method to model photon transport through a 8- cm-diam fetal brain located at a constant 2.5 cm below a curved maternal abdominal surface with an air/tissue boundary. In the simulation, a near-infrared light source delivers light to the abdomen and a detector is positioned up to 10 cm from the source along the arc of the abdominal surface. The light transport [W/cm2 fluence rate per W incident power] collected at the 10 cm position is Tm equals 2.2 X 10-6 cm-2 if the fetal brain has the same optical properties as the mother and Tf equals 1.0 X 10MIN6 cm-2 for an optically perturbing fetal brain with typical brain optical properties. The perturbation P equals (Tf - Tm)/Tm is -53% due to the fetal brain. The model illustrates the challenge and feasibility of transabdominal oximetry of the fetal brain.

  20. Manipulation of hemoglobin expression affects Arabidopsis shoot organogenesis.

    PubMed

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

    2011-10-01

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

  1. 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

  2. Atomic Magnetometry for fetal Magnetocardiography

    NASA Astrophysics Data System (ADS)

    Sulai, Ibrahim; Walker, Thad; Wakai, Ronald

    2013-05-01

    We present results of using an array of atomic magnetometers in detecting fetal Magnetocardiograms(fMCG). The array consists of four 87-Rb atomic magnetometers operating in the spin exchange relaxation free (SERF) regime. They have a demonstrated sensitivity of 5 - 10 fT /√{ Hz } -limited by the Johnson noise of the magnetic shielding. We report measurements of fMCG on gestational ages as small as 21 weeks and describe the technical challenges and design features that make the measurements possible. We present a method for minimizing the impact of AC Stark Shifts on the magnetometer array performance by relying on diffusion to transport polarized atoms from a pumping region to an AC Stark shift free active region. This work was supported by the NIH.

  3. The influence of experimental conditions on the spectrin-hemoglobin interaction.

    PubMed

    Vincentelli, J; Fraboni, A; Paul, C; Schnek, A G

    1989-01-01

    Human spectrin, when isolated, purified and stored in such conditions that preserve its tetrameric form, is able to associate with human hemoglobin as it is clearly shown by gel filtration. However, this hemoglobin-spectrin association does not seem to have a significant effect on hemoglobin oxygenation as indicated by equilibrium and rapid kinetics measurements. PMID:2713099

  4. Fetal Heart Rate Response to Maternal Exercise.

    PubMed

    Monga, Manju

    2016-09-01

    Current guidelines regarding recommended exercise in pregnancy appear consistent with reported research regarding fetal heart changes in response to maternal exercise. Fetal heart rate increases during pregnancy, but maternal exercise appears well tolerated if performed in uncomplicated pregnancies and not in the supine position. Maximal levels of exercise that are well tolerated by the fetus have not yet been well defined; however, recent literature suggests that sustained exercise during pregnancy may have beneficial effects on autonomic control of fetal heart rate and variability that may lead to long-term health benefits. PMID:27388963

  5. Fetal Surgery for Myelomeningocele: Trials and Tribulations

    PubMed Central

    Adzick, N.Scott

    2011-01-01

    The rationale for in utero repair of myelomeningocele (MMC) in the context of pathologic observations, animal models, and outcomes from the initial experience with human fetal myelomeningocele repair is presented. This has now culminated in a randomized trial, Management of Myelomeningocele Study (the MOMS Trial), the findings of which are listed. The story is focused on the milestone contributions of members of the Center for Fetal Diagnosis and Treatment at the Children's Hospital of Philadelphia (CHOP) on the road to successful fetal surgery for spina bifida. This is now performed in selected patients and presents an additional therapeutic alternative for expectant mothers carrying a fetus with MMC. PMID:22325376

  6. A novel hemoglobin-binding peptide reduces cell-free hemoglobin in murine hemolytic anemia.

    PubMed

    Hanson, Madelyn S; Xu, Hao; Flewelen, Timothy C; Holzhauer, Sandra L; Retherford, Dawn; Jones, Deron W; Frei, Anne C; Pritchard, Kirkwood A; Hillery, Cheryl A; Hogg, Neil; Wandersee, Nancy J

    2013-01-15

    Hemolysis can saturate the hemoglobin (Hb)/heme scavenging system, resulting in increased circulating cell-free Hb (CF-Hb) in hereditary and acquired hemolytic disease. While recent studies have suggested a central role for intravascular hemolysis and CF-Hb in the development of vascular dysfunction, this concept has stimulated considerable debate. This highlights the importance of determining the contribution of CF-Hb to vascular complications associated with hemolysis. Therefore, a novel Hb-binding peptide was synthesized and linked to a small fragment of apolipoprotein E (amino acids 141-150) to facilitate endocytic clearance. Plasma clearance of hE-Hb-b10 displayed a rapid phase t(1/2) of 16 min and slow phase t(1/2) of 10 h, trafficking primarily through the liver. Peptide hE-Hb-B10 decreased CF-Hb in mice treated with phenylhydrazine, a model of acute hemolysis. Administration of hE-Hb-B10 also attenuated CF-Hb in two models of chronic hemolysis: Berkeley sickle cell disease (SS) mice and mice with severe hereditary spherocytosis (HS). The hemolytic rate was unaltered in either chronic hemolysis model, supporting the conclusion that hE-Hb-B10 promotes CF-Hb clearance without affecting erythrocyte lysis. Interestingly, hE-Hb-B10 also decreased plasma ALT activity in SS and HS mice. Although acetylcholine-mediated facialis artery vasodilation was not improved by hE-Hb-B10 treatment, the peptide shifted vascular response in favor of NO-dependent vasodilation in SS mice. Taken together, these data demonstrate that hE-Hb-B10 decreases CF-Hb with a concomitant reduction in liver injury and changes in vascular response. Therefore, hE-Hb-B10 can be used to investigate the different roles of CF-Hb in hemolytic pathology and may have therapeutic benefit in the treatment of CF-Hb-mediated tissue damage. PMID:23125208

  7. Fetal cell-free DNA fraction in maternal plasma is affected by fetal trisomy.

    PubMed

    Suzumori, Nobuhiro; Ebara, Takeshi; Yamada, Takahiro; Samura, Osamu; Yotsumoto, Junko; Nishiyama, Miyuki; Miura, Kiyonori; Sawai, Hideaki; Murotsuki, Jun; Kitagawa, Michihiro; Kamei, Yoshimasa; Masuzaki, Hideaki; Hirahara, Fumiki; Saldivar, Juan-Sebastian; Dharajiya, Nilesh; Sago, Haruhiko; Sekizawa, Akihiko

    2016-07-01

    The purpose of this noninvasive prenatal testing (NIPT) study was to compare the fetal fraction of singleton gestations by gestational age, maternal characteristics and chromosome-specific aneuploidies as indicated by z-scores. This study was a multicenter prospective cohort study. Test data were collected from women who underwent NIPT by the massively parallel sequencing method. We used sequencing-based fetal fraction calculations in which we estimated fetal DNA fraction by simply counting the number of reads aligned within specific autosomal regions and applying a weighting scheme derived from a multivariate model. Relationships between fetal fractions and gestational age, maternal weight and height, and z-scores for chromosomes 21, 18 and 13 were assessed. A total of 7740 pregnant women enrolled in the study, of which 6993 met the study criteria. As expected, fetal fraction was inversely correlated with maternal weight (P<0.001). The median fetal fraction of samples with euploid result (n=6850) and trisomy 21 (n=70) were 13.7% and 13.6%, respectively. In contrast, the median fetal fraction values for samples with trisomies 18 (n=35) and 13 (n=9) were 11.0% and 8.0%, respectively. The fetal fraction of samples with trisomy 21 NIPT result is comparable to that of samples with euploid result. However, the fetal fractions of samples with trisomies 13 and 18 are significantly lower compared with that of euploid result. We conclude that it may make detecting these two trisomies more challenging. PMID:26984559

  8. Fetal and maternal manifestations of tuberous sclerosis complex: Value of fetal MRI.

    PubMed

    Goel, Reema; Aggarwal, Nishant; Lemmon, Monica E; Bosemani, Thangamadhan

    2016-02-01

    Tuberous sclerosis complex (TSC) is a genetic disorder characterized by benign hamartomas in various organ systems of the body. Prenatal screening of fetuses of mothers affected with TSC using ultrasonography (US) may detect cardiac lesions. Fetal US is not sensitive for evaluation of the brain. We describe brain MRI findings in a fetus with cardiac rhabdomyomas identified on prenatal screening US. Postnatal brain MRI at 5 days of age demonstrated fetal MRI findings without significant added information. Fetal MRI is the imaging modality of choice for evaluation of cerebral manifestations of TSC. Maternal manifestations of TSC in the abdomen or pelvis may also be demonstrated on fetal MRI. PMID:26838171

  9. Fetal research: the question in the states.

    PubMed

    Baron, C H

    1985-04-01

    Baron, a law professor, traces the history of state and federal regulation of fetal research from 1973 to 1983. He explores the dilemmas raised by research on fetuses, particularly aborted fetuses, and the aspects of fetal research that the federal regulations and state laws were enacted to control. While criticizing many of the states' actions for lack of uniformity and blanket prohibitions based on the status of the fetus or abortus, Baron acknowledges that less-than-perfect legislation is the price of rule making in a pluralistic society that is still working toward a consensus on controversial issues such as abortion and fetal research. Using as an example the 1973-1974 debate between researchers and law makers in Massachusetts, he discusses how advocates on both sides of the fetal research question might educate and persuade each other to reach an acceptable regulatory compromise. PMID:4008234

  10. Fetal therapy, ethics and public policies.

    PubMed

    Fletcher, J C

    1992-01-01

    This article reviews the evolution of ethical problems in the first generation of experimental fetal therapy and the prevailing approaches to them. The problems include: review of risks/benefits, case selection, informed consent, twin pregnancies, and refusal of proven fetal therapy. The article further discusses ethical and public policy issues in the lack of U.S. federal support for fetal diagnosis, fetal therapy, and human embryo research. An argument is made for such support, beginning with experimental gene therapy in the fetus. Ethical principles are identified that support an obligation to learn to relieve and treat such human suffering at the earliest time. Contradictions of these principles are also identified in terms of research not now supported. PMID:1503651

  11. Fetal alloimmune thrombocytopenia and maternal intravenous immunoglobulin infusion

    PubMed Central

    Giers, Günther; Wenzel, Folker; Stockschläder, Markus; Riethmacher, Regina; Lorenz, Horst; Tutschek, Boris

    2010-01-01

    Background Different therapeutic approaches have been used in fetal-neonatal alloimmune thrombocytopenia, but many centers administer immunoglobulin G infusions to the pregnant woman. We studied the effect of maternal antenatal immunoglobulin infusions on fetal platelet counts in pregnancies with fetal alloimmune thrombocytopenia. Design and Methods We retrospectively analyzed the clinical courses of fetuses with fetal alloimmune thrombocytopenia whose mothers were treated with immunoglobulin G infusions in a single center between 1999 and 2005. In a center-specific protocol, weekly maternal immunoglobulin G infusions were given to 25 pregnant women with previously affected neonates and four women with strong platelet antibodies, but no previous history of fetal alloimmune thrombocytopenia; before each infusion diagnostic fetal blood sampling was performed to determine fetal platelet counts and immunoglobulin G levels. Results There were 30 fetuses with fetal alloimmune thrombocytopenia, confirmed by initial fetal blood sampling showing fetal platelet counts between 4×109/L and 130×109/L and antibody-coated fetal platelets using a glycoprotein specific assay. Despite weekly antenatal maternal immunoglobulin G infusions fetal platelet counts did not change significantly. Maternal and fetal immunoglobulin G levels, measured before every infusion, increased significantly with the number of maternal immunoglobulin G infusions. Conclusions In this group of fetuses with fetal alloimmune thrombocytopenia no consistent increase of fetal platelets was achieved as a result of regular maternal immunoglobulin G infusions. PMID:20534698

  12. 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. PMID:26212998

  13. Methylomic trajectories across human fetal brain development.

    PubMed

    Spiers, Helen; Hannon, Eilis; Schalkwyk, Leonard C; Smith, Rebecca; Wong, Chloe C Y; O'Donovan, Michael C; Bray, Nicholas J; Mill, Jonathan

    2015-03-01

    Epigenetic processes play a key role in orchestrating transcriptional regulation during development. The importance of DNA methylation in fetal brain development is highlighted by the dynamic expression of de novo DNA methyltransferases during the perinatal period and neurodevelopmental deficits associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. However, our knowledge about the temporal changes to the epigenome during fetal brain development has, to date, been limited. We quantified genome-wide patterns of DNA methylation at ∼ 400,000 sites in 179 human fetal brain samples (100 male, 79 female) spanning 23 to 184 d post-conception. We identified highly significant changes in DNA methylation across fetal brain development at >7% of sites, with an enrichment of loci becoming hypomethylated with fetal age. Sites associated with developmental changes in DNA methylation during fetal brain development were significantly underrepresented in promoter regulatory regions but significantly overrepresented in regions flanking CpG islands (shores and shelves) and gene bodies. Highly significant differences in DNA methylation were observed between males and females at a number of autosomal sites, with a small number of regions showing sex-specific DNA methylation trajectories across brain development. Weighted gene comethylation network analysis (WGCNA) revealed discrete modules of comethylated loci associated with fetal age that are significantly enriched for genes involved in neurodevelopmental processes. This is, to our knowledge, the most extensive study of DNA methylation across human fetal brain development to date, confirming the prenatal period as a time of considerable epigenomic plasticity. PMID:25650246

  14. [Disputes and history of fetal heart monitoring].

    PubMed

    Dueñas-García, Omar Felipe; Díaz-Sotomayor, Maricela

    2011-01-01

    The concept of fetal heart monitoring to determine the fetal wellbeing state has been employed for almost 300 years, but in the last 50 years it has observed drastic changes due to the incorporation of the electronic devices that has started controversy since the moment of its description and point of start. The purpose of this article is to mention the key points and controversial moments in the history of the cardiotocography PMID:23650679

  15. Biomedical Instruments for Fetal and Neonatal Surveillance

    NASA Astrophysics Data System (ADS)

    Rolfe, P.; Scopesi, F.; Serra, G.

    2006-10-01

    Specialised instruments have been developed to aid the care of the fetus and the newborn baby. Miniature sensors using optical, electrical, chemical, mechanical and magnetic principles have been produced for capturing key measurands. These include temperature, pressure, flow and dimension, as well as several specific molecules such as glucose, oxygen and carbon dioxide. During pregnancy ultrasound imaging and blood flow techniques provide valuable information concerning fetal abnormalities, fetal growth, fetal breathing and fetal heart rate. Signal processing and pattern recognition can be useful for deriving indicators of fetal distress and clinical status, based on biopotentials as well as ultrasound signals. Fetal pH measurement is a critical requirement during labour and delivery. The intensive care of ill preterm babies involves provision of an optimal thermal environment and respiratory support. Monitoring of blood gas and acid-base status is essential, and this involves both blood sampling for in vitro analysis as well as the use of invasive or non-invasive sensors. For the future it will be vital that the technologies used are subjected to controlled trials to establish benefit or otherwise.

  16. The Use of Fetal Noninvasive Electrocardiography

    PubMed Central

    2016-01-01

    Preeclampsia (PE) is one of the severe complications of pregnancy that leads to fetal deterioration. The aim was to survey the validity of fetal distress diagnostics in case of Doppler ultrasonic umbilical vein and arteries blood flow velocity investigation and ECG parameters analysis obtained from maternal abdominal signal before labor in preeclamptic patients. Fetal noninvasive ECG and umbilical arterial and venous Doppler investigation were performed in 120 patients at 34–40 weeks of gestation. And 30 of them had physiological gestation and were involved in Group I. In Group II 52 pregnant women with mild-moderate PE were observed. 38 patients with severe PE were monitored in Group III. The most considerable negative correlation was determined in pair Apgar score 1 versus T/QRS (R = −0.50; p < 0.05). So the increased T/QRS ratio was the most evident marker of fetal distress. Fetal noninvasive ECG showed sensitivity of 96.6% and specificity of 98.4% and, therefore, was determined as more accurate method for fetal monitoring. PMID:27006859

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

    PubMed Central

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

    2014-01-01

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

  18. [Studies on features of fetal movement and development of human fetus with use of fetal actogram].

    PubMed

    Tatsumura, M

    1991-08-01

    In 167 normal fetuses at 26 to 41 weeks of gestation, features of fetal movement and fetal development were investigated with use of actocardiograph in connection with a microcomputer system. The signals of fetal movement obtained by actocardiograph were stored in a floppy disc every 250 ms for 5 minutes through an AD-converter, and were analyzed every 5 minutes with the computer to reveal 3-dimensional (3-D) histograms. The 3-D histogram of fetal movement was composed of number, amplitude and interval of the signals in 11 voltage steps between 0.05 and 0.55V. The histogram clearly indicated state of fetal behavior, being either resting or active state. Fetal movement such as rolling movement, breathing movement and hiccup could be also identified with the computer analysis. In 68 normal fetuses at 14 to 41 weeks of gestation, the cross-correlation between fetal movement and fetal heart rate (FHR) were examined with the computer analysis. Finally fetal responses to acoustic and light stimulation were evaluated with use of pure-tone generator and flashlight. Acoustic stimulation was carried out in 53 normal fetuses at 28 to 41 weeks and light stimulation was performed in 116 normal fetuses at 18 to 41 weeks of gestation. The fetal responses were evaluated with actocardiogram. As a result, 1) Frequency in active state decreased and resting state increased as gestational weeks advanced, and then the frequencies of both state remained constant after 37 weeks of gestation. Duration of resting state also increased from 26 weeks to 37 weeks. These observations may suggest that fetal behavior can be established by 37 weeks of gestation. 2) Frequency in rolling movement decreased until 37 weeks of gestation, and then the movement increased during 38-41 weeks. Frequency in breathing movement increased to 33 weeks of gestation, then it remained constant. Hiccup occurred most frequently at 30-33 weeks, and it decreased thereafter. The function in fetal respiratory movement may

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

    PubMed Central

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

    2014-01-01

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

  20. Vitreoscilla hemoglobin promotes Salecan production by Agrobacterium sp. ZX09.

    PubMed

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

    2014-11-01

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

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

    SciTech Connect

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

    1980-10-01

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

  2. Immobilization and characterization of hemoglobin on modified sporopollenin surfaces.

    PubMed

    Gubbuk, Ilkay Hilal; Ozmen, Mustafa; Maltas, Esra

    2012-06-01

    Hemoglobin was covalently immobilized onto modified sporopollenin surface with different functional groups by chemical reactions to enhance binding ability of protein. In this study, the influence of various silane linker molecules on the capacity of protein binding was studied. For this purpose, activated sporopollenin was modified by 3-aminopropyltriethoxysilane (APTS), 3-chloropropyltrimethoxysilane (CPTS) and (3-glycidyloxypropyl)trimethoxysilane (GPTS). Hemoglobin (Hb) was immobilized on modified sporopollenin surfaces in phosphate buffer saline solution (PBS, pH 7.4) at 4°C. Results showed that GPTS modified sporopollenin surfaces resulted in the highest binding capacity for Hb. Micro porosity of samples was observed through scanning electron microscopy (SEM) and thermal behavior of the samples were studied with thermogravimetric analysis (TGA) within a temperature range: 25-900°C. TGA studies demonstrated the advantages of silane modification for high temperature applications and illustrated differences of the structures due to the different tail groups. PMID:22537474

  3. Oxygenation properties of hemoglobin from the turtle Geochelone carbonaria.

    PubMed

    Torsoni, M A; Ogo, S H

    1995-01-01

    The oxygen-binding properties of hemoglobin (Hb) from the adult terrestrial turtle Geochelone carbonaria are described. Turtle hemoglobins have a low intrinsic oxygen affinity and a low sensitivity to an endogenous cofactor (ATP) usually present at high concentrations in the reptile erythrocytes. The amplitude of the Bohr effect for O2 binding was virtually the same in the absence and presence of saturating ATP concentrations (delta logP50/delta pH, about -0.60) and increased in the total hemolysate (-0.83). The large Bohr effect found in G. carbonaria Hb may be important for O2 delivery to the tissue. The degree of cooperativity displayed by Hb for O2 binding ranged between 1.5 and 2.0 in stripped solution and total hemolysate. These observations suggest that stability of the low affinity conformation, which needs to be confirmed by additional experiments. PMID:8728839

  4. Isolation and characterization of four antibacterial peptides from bovine hemoglobin.

    PubMed

    Nedjar-Arroume, Naima; Dubois-Delval, Véronique; Miloudi, Khalil; Daoud, Rachid; Krier, François; Kouach, Mostafa; Briand, Gilbert; Guillochon, Didier

    2006-09-01

    Peptic digestion of bovine hemoglobin at low degree of hydrolysis yields several intermediate peptide fractions after separation by reversed phase HPLC exhibiting antibacterial activity against Micrococcus luteus A270, Listeria innocua, Escherichia coli, and Salmonella enteritidis. From these fractions, four new antibacterial peptides were isolated and analyzed by ESI-MS/MS. Three of these peptides correspond to fragments of the alpha-chain of bovine hemoglobin: alpha107-141, alpha137-141, and alpha133-141, and one peptide to the beta-chain: beta126-145. The minimum inhibitory concentrations (MIC) of these peptides towards the four strains and their hemolytic activity towards bovine erythrocytes were determined. PMID:16730859

  5. Hemoglobin-oxygen-carbon monoxide equilibria with the MWC model.

    PubMed

    Senozan, N M; DeVore, J A; Lesniewski, E K

    1998-11-16

    Fractional saturation equations for the Monod, Wyman and Changeux model are derived for the case of two distinct ligands bonding to a host molecule with four ligand sites and two conformational states. A variety of useful graphical studies can be derived from these equations when applied to normal human hemoglobin with O2 and CO as ligands. For example, the oxygen transport capability of hemoglobin can be assessed at different environmental CO levels and the concentrations of various liganded species can be displayed as a function of fractional saturation with oxygen. In addition, the CO pressure in the tissue, PCOtissue, can be calculated as a function of the tissue oxygen pressure, PO2tissue, at different environmental levels of CO. In an environment of a given CO concentration, PCOtissue decreases with PO2tissue until a minimum is reached. Further decrease in PO2tissue results in a fairly steep rise in PCOtissue. PMID:9857482

  6. Virucidal levels of ozone induce hemolysis and hemoglobin degradation

    SciTech Connect

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

    1991-10-01

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

  7. Multimeric hemoglobin of the Australian brine shrimp Parartemia.

    PubMed

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

    2001-04-01

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

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

    SciTech Connect

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

    1984-03-01

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

  9. Hemoglobin Status and Externalizing Behavioral Problems in Children

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2015-04-01

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

  11. Hydrogen-tritium exchange survey of allosteric effects in hemoglobin

    SciTech Connect

    Englander, J.J.; Englander, S.W.

    1987-04-07

    The oxy and deoxy forms of hemoglobin display major differences in H-exchange behavior. Hydrogen-tritium exchange experiments on hemoglobin were performed in the low-resolution mode to observe the dependence of these differences on pH (Bohr effect), organic phosphates, and salt. Unlike a prior report, increasing pH was found to decrease the oxy-deoxy difference monotonically, in general accordance with the alkaline Bohr effect. A prior report that the H-exchange difference between oxy- and deoxyhemoglobin vanishes at pH 9, and thus appears to reflect the Bohr effect alone, was found to be due to the borate buffer used, which at high pH tends to abolish the oxy-deoxy difference in a limited region of the H-exchange curve. Effects on hemoglobin H exchange due to organic phosphates parallel the differential binding of these agents (inositol hexaphosphate more than diphosphoglycerate, deoxy more than oxy, at low pH more than at high pH). Added salt slows H exchange of deoxyhemoglobin and has no effect on the oxy form. These results display the sensitivity of simple H-exchange measurements for finding and characterizing effects on structure and dynamics that may occur anywhere in the protein and help to define conditions for higher resolution approaches that can localize the changes observed.

  12. Validation of the WHO Hemoglobin Color Scale Method

    PubMed Central

    Darshana, Leeniyagala Gamaralalage Thamal; Uluwaduge, Deepthi Inoka

    2014-01-01

    This study was carried out to evaluate the diagnostic accuracy of WHO color scale in screening anemia during blood donor selection in Sri Lanka. A comparative cross-sectional study was conducted by the Medical Laboratory Sciences Unit of University of Sri Jayewardenepura in collaboration with National Blood Transfusion Centre, Sri Lanka. A total of 100 subjects participated in this study. Hemoglobin value of each participant was analyzed by both WHO color scale method and cyanmethemoglobin method. Bland-Altman plot was used to determine the agreement between the two methods. Sensitivity, specificity, predictive values, false positive, and negative rates were calculated. The sensitivity of the WHO color scale was very low. The highest sensitivity observed was 55.55% in hemoglobin concentrations >13.1 g/dL and the lowest was 28.57% in hemoglobin concentrations between 7.1 and 9.0 g/dL. The mean difference between the WHO color scale and the cyanmethemoglobin method was 0.2 g/dL (95% confidence interval; 3.2 g/dL above and 2.8 g/dL below). Even though the WHO color scale is an inexpensive and portable method for field studies, from the overall results in this study it is concluded that WHO color scale is an inaccurate method to screen anemia during blood donations. PMID:24839555

  13. Pitfalls in the biological diagnosis of common hemoglobin disorders.

    PubMed

    Wajcman, Henri; Moradkhani, Kamran

    2015-01-01

    In West-European countries, hemoglobin disorders are no more rare diseases. Programs for diagnosis of heterozygous carriers have been established to prevent cases with major sickle cell disease or thalassemias. These studies have been done essentially by high performance liquid chromatography on cation-exchange columns and electrophoresis (mostly capillary electrophoresis). They have been done through systematic population studies or premarital diagnosis. We describe in this work the frequent or rare pitfalls encountered, which led to false negative or positive diagnosis both in the field of sickle cell disease and thalassemias. In the absence of a well identified hemoglobin disorder in the proband's family, it is a rule that the use of a single test is insufficient to identify formally HbS. The presence of HbS could also be masked by another hemoglobin abnormality. The sole measurement of HbA2 level is insufficient to characterize a thalassemic trait: this level needs always to be interpreted considering RBC parameters and iron metabolic status. In difficult cases, the definitive answer may require a family study and/or a molecular genetic characterization. PMID:26489811

  14. Bovine hemoglobin: an attractive source of antibacterial peptides.

    PubMed

    Nedjar-Arroume, Naïma; Dubois-Delval, Véronique; Adje, Estelle Yaba; Traisnel, Jonathan; Krier, François; Mary, Patrice; Kouach, Mostafa; Briand, Gilbert; Guillochon, Didier

    2008-06-01

    A peptic hemoglobin hydrolysate was fractioned by a semi-preparative reversed-phase HPLC and some fractions have an antibacterial activity against four bacteria strains: Micrococcus luteus A270, Listeria innocua, Escherichia coli and Salmonella enteritidis. These fractions were analyzed by ESI/MS and ESI/MS/MS, in order to characterize the peptides in these fractions. Each fraction contains at least three peptides and some fractions contain five peptides. All these fractions were purified several times by HPLC to obtain pure peptides. Thirty antibacterial peptides were identified. From the isolated antibacterial peptides, 24 peptides were derived from the alpha chains of hemoglobin and 6 peptides were derived from the beta chains of hemoglobin. The lowest concentration of these peptides (minimum inhibitory concentration (MIC)) necessary to completely inhibit the growth of four bacteria strain was determined. The cell population of all of the tested bacteria species decreased by at least 97% after a 24-h incubation with any of the peptides at the minimum inhibitory concentration. PMID:18342399

  15. Evolutionary and Functional Relationships in the Truncated Hemoglobin Family

    PubMed Central

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

    2016-01-01

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

  16. Fluorescence and reflectance properties of hemoglobin-pigmented skin disorders

    NASA Astrophysics Data System (ADS)

    Troyanova, P.; Borisova, E.; Avramov, L.

    2007-06-01

    There has been growing interest in clinical application of laser-induced autofluorescence (LIAF) and reflectance spectroscopy (RS) to differentiate disease from normal surrounding tissue, including skin pathologies. Pigmented cutaneous lesions diagnosis plays important role in clinical practice, as malignant melanoma, which is characterized with greatest mortality from all skin cancer types, must be carefully discriminated form other colorized pathologies. The goals of this work were investigation of cutaneous hemoglobin-pigmented lesions (heamangioma, angiokeratoma, and fibroma) by the methods of LIAFS and RS. Spectra from healthy skin areas near to the lesion were detected to be used posteriori in analysis. Fluorescence and reflectance of cutaneous hemoglobin-pigmented lesions are used to develop criterion for differentiation from other pigmented pathologies. Origins of the spectral features obtained are discussed and determination of lesion types is achieved using selected spectral features. The spectral results, obtained were used to develop multispectral diagnostic algorithms based on the most prominent spectral features from the fluorescence and reflectance spectra of the lesions investigated. In comparison between normal skin and different cutaneous lesion types and between lesion types themselves sensitivities and specificities higher than 90 % were achieved. These results show a perspective possibility to differentiate hemoglobin-pigmented lesions from other pigmented pathologies using non-invasive and real time discrimination procedure.

  17. Vibrational modes of hemoglobin in red blood cells.

    PubMed Central

    Martel, P; Calmettes, P; Hennion, B

    1991-01-01

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

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

    PubMed

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

    2016-01-01

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

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

    PubMed Central

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

    2009-01-01

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

  20. Fetal tissue sampling. The San Francisco experience with 190 pregnancies.

    PubMed Central

    Golbus, M S; McGonigle, K F; Goldberg, J D; Filly, R A; Callen, P W; Anderson, R L

    1989-01-01

    Prenatal diagnosis of genetic defects was done using fetal blood sampling in 167 at-risk pregnancies, by fetal skin biopsy in 15 pregnancies, and by fetal liver biopsy in 8 pregnancies. Fetal blood sampling was done by fetoscopy through January 1985 and by sonographically directed percutaneous umbilical blood sampling since then. In our series, cytogenetics has become the major indication for fetal blood sampling, increasing from 6% of the cases with fetoscopy to 48% with umbilical blood sampling. Fetoscopy provided pure fetal blood in 61% of cases while umbilical blood sampling provided pure fetal blood 97% of the time. The corrected risk of fetal demise after percutaneous umbilical fetal blood sampling was 2% and after fetoscopy was 4%. Images PMID:2735048

  1. Preschool Teacher Attitude and Knowledge Regarding Fetal Alcohol Syndrome and Fetal Alcohol Effects.

    ERIC Educational Resources Information Center

    Mack, Faite R-P.

    The Centers for Disease Control estimate that each year more than 8,000 Fetal Alcohol Syndrome (FAS) babies are born, and that many more babies go undiagnosed with Fetal Alcohol Effects (FAE), a less severe condition. FAS and FAE have been identified as major contributors to poor memory, shorter attention spans, lower IQs, diminished achievement…

  2. Evaluation of the fetal QT interval using non-invasive fetal ECG technology.

    PubMed

    Behar, Joachim; Zhu, Tingting; Oster, Julien; Niksch, Alisa; Mah, Douglas Y; Chun, Terrence; Greenberg, James; Tanner, Cassandre; Harrop, Jessica; Sameni, Reza; Ward, Jay; Wolfberg, Adam J; Clifford, Gari D

    2016-09-01

    Non-invasive fetal electrocardiography (NI-FECG) is a promising alternative continuous fetal monitoring method that has the potential to allow morphological analysis of the FECG. However, there are a number of challenges associated with the evaluation of morphological parameters from the NI-FECG, including low signal to noise ratio of the NI-FECG and methodological challenges for getting reference annotations and evaluating the accuracy of segmentation algorithms. This work aims to validate the measurement of the fetal QT interval in term laboring women using a NI-FECG electrocardiogram monitor. Fetal electrocardiogram data were recorded from 22 laboring women at term using the NI-FECG and an invasive fetal scalp electrode simultaneously. A total of 105 one-minute epochs were selected for analysis. Three pediatric electrophysiologists independently annotated individual waveforms and averaged waveforms from each epoch. The intervals measured on the averaged cycles taken from the NI-FECG and the fetal scalp electrode showed a close agreement; the root mean square error between all corresponding averaged NI-FECG and fetal scalp electrode beats was 13.6 ms, which is lower than the lowest adult root mean square error of 16.1 ms observed in related adult QT studies. These results provide evidence that NI-FECG technology enables accurate extraction of the fetal QT interval. PMID:27480078

  3. Fetal Alcohol Syndrome and Fetal Alcohol Effects-- Support for Teachers and Families.

    ERIC Educational Resources Information Center

    Duckworth, Susanna V.; Norton, Terry L.

    2000-01-01

    Reviews genesis of fetal alcohol syndrome and fetal alcohol effects in children. Identifies physical characteristics and behavioral indicators found and provides three checklists of observable signs for both disorders. Recommends seven steps for educators to follow in seeking assistance with these conditions. (DLH)

  4. Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy

    PubMed Central

    Nishio, Hisanori; Takada, Hidetoshi; Sakai, Yasunari; Nanishi, Etsuro; Ochiai, Masayuki; Onimaru, Mitsuho; Chen, Si Jing; Matsui, Toshiro; Hara, Toshiro

    2016-01-01

    Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL-6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface. PMID:26880761

  5. Fetal magnetic resonance imaging in obstetric practice

    PubMed Central

    Köşüş, Aydın; Köşüş, Nermin; Usluoğulları, Betül; Duran, Müzeyyen; Turhan, Nilgün Öztürk; Tekşam, Mehmet

    2011-01-01

    Ultrasonography (USG) is the primary imaging method for prenatal diagnosis of fetal abnormalities since its discovery. Although it is the primary method of fetal imaging, it cannot provide sufficient information about the fetus in some conditions such as maternal obesity, oligohydramnios and engagement of the fetal head. At this stage, magnetic resonance imaging (MRI) facilitates examination by providing more specific information. The need and importance of fetal MRI applications further increased by the intrauterine surgery which is currently gaining popularity. Some advantages of fetal MRI over USG are the good texture of contrast, a greater study area and visualization of the lesion and neighbourhood relations, independence of the operators. Also it is not affected by maternal obesity and severe oligohydramnios. However, MRI is inadequate in detecting fetal limb and cardiac abnormalities when compared to USG. MRI is not used routinely in pregnancy. It is used in situations where nonionizing imaging methods are inadequate or ionizing radiation is required in pregnant women. It is not recommended during the first trimester. Contrast agent (Godalinium) is not used during pregnancy. It is believed that MRI is not harmful to the fetus, although the biological risk of MRI application is not known. MRI technique is superior to USG in the detection of corpus callosum dysgenesis, third-trimester evaluation of posterior fossa malformations, bilateral renal agenesis, diaphragmatic hernia and assessment of lung maturation. Especially, it is the method of choice for evaluation of central nervous system (CNS) abnormalities. Fetal MRI has a complementary role with USG. It provides important information for prenatal diagnosis, increases diagnostic accuracy, and in turn affects the prenatal treatment, prenatal interventions and birth plan. PMID:24591956

  6. Lactate metabolism in the fetal rabbit lung

    SciTech Connect

    Engle, M.J.; Brown, D.J.; Dooley, M.

    1986-05-01

    Lactate is frequently overlooked as a potential substrate for the fetal lung, even though it is present in the fetal circulation in concentrations as high as 8 mM. These high concentrations, coupled with the relatively low levels of glucose in the fetal blood, may indicate that lactate can substitute for glucose in pulmonary energy generation and phospholipid synthesis. A series of experiments was therefore undertaken in order to investigate the role of lactate in perinatal pulmonary development. Explants from 30 day gestation fetal rabbit lungs were incubated in Krebs-Ringer bicarbonate buffer supplemented with 3 mM (U-/sup 14/C)-glucose and varying levels of lactate. In the absence of medium lactate, fetal rabbit lung explants were capable of producing lactate at a rate of approximately 200 etamoles/mg protein/hour. The addition of lactate to the bathing medium immediately reduced net lactate production and above 4 mM, fetal rabbit lung explants became net utilizers of lactate. Media lactate concentrations of 2.5 mM, 5 mM and 10 mM also decreased glucose incorporation into total tissue disaturated phosphatidylcholine by approximately 20%, 35%, and 45%, respectively. Glucose incorporation into surfactant phosphatidylcholine was also reduced by approximately 50%, when lactate was present in the incubation medium at a concentration of 5 mM. Additional experiments also revealed that fetal lung lactate dehydrogenase activity was almost twice that found in the adult rabbit lung. These data indicate that lactate may be an important carbon source for the developing lung and could be a significant component in the manufacture of surfactant phosphatidylcholine during late gestation.

  7. Fetal magnetic resonance imaging in obstetric practice.

    PubMed

    Köşüş, Aydın; Köşüş, Nermin; Usluoğulları, Betül; Duran, Müzeyyen; Turhan, Nilgün Öztürk; Tekşam, Mehmet

    2011-01-01

    Ultrasonography (USG) is the primary imaging method for prenatal diagnosis of fetal abnormalities since its discovery. Although it is the primary method of fetal imaging, it cannot provide sufficient information about the fetus in some conditions such as maternal obesity, oligohydramnios and engagement of the fetal head. At this stage, magnetic resonance imaging (MRI) facilitates examination by providing more specific information. The need and importance of fetal MRI applications further increased by the intrauterine surgery which is currently gaining popularity. Some advantages of fetal MRI over USG are the good texture of contrast, a greater study area and visualization of the lesion and neighbourhood relations, independence of the operators. Also it is not affected by maternal obesity and severe oligohydramnios. However, MRI is inadequate in detecting fetal limb and cardiac abnormalities when compared to USG. MRI is not used routinely in pregnancy. It is used in situations where nonionizing imaging methods are inadequate or ionizing radiation is required in pregnant women. It is not recommended during the first trimester. Contrast agent (Godalinium) is not used during pregnancy. It is believed that MRI is not harmful to the fetus, although the biological risk of MRI application is not known. MRI technique is superior to USG in the detection of corpus callosum dysgenesis, third-trimester evaluation of posterior fossa malformations, bilateral renal agenesis, diaphragmatic hernia and assessment of lung maturation. Especially, it is the method of choice for evaluation of central nervous system (CNS) abnormalities. Fetal MRI has a complementary role with USG. It provides important information for prenatal diagnosis, increases diagnostic accuracy, and in turn affects the prenatal treatment, prenatal interventions and birth plan. PMID:24591956

  8. Oligomerization and ligand binding in a homotetrameric hemoglobin: two high-resolution crystal structures of hemoglobin Bart's (gamma(4)), a marker for alpha-thalassemia.

    PubMed

    Kidd, R D; Baker, H M; Mathews, A J; Brittain, T; Baker, E N

    2001-09-01

    Hemoglobin (Hb) Bart's is present in the red blood cells of millions of people worldwide who suffer from alpha-thalassemia. alpha-Thalassemia is a disease in which there is a deletion of one or more of the four alpha-chain genes, and excess gamma and beta chains spontaneously form homotetramers. The gamma(4) homotetrameric protein known as Hb Bart's is a stable species that exhibits neither a Bohr effect nor heme-heme cooperativity. Although Hb Bart's has a higher O(2) affinity than either adult (alpha(2)beta(2)) or fetal (alpha(2)gamma(2)) Hbs, it has a lower affinity for O(2) than HbH (beta(4)). To better understand the association and ligand binding properties of the gamma(4) tetramer, we have solved the structure of Hb Bart's in two different oxidation and ligation states. The crystal structure of ferrous carbonmonoxy (CO) Hb Bart's was determined by molecular replacement and refined at 1.7 A resolution (R = 21.1%, R(free) = 24.4%), and that of ferric azide (N(3)(-)) Hb Bart's was similarly determined at 1.86 A resolution (R = 18.4%, R(free) = 22.0%). In the carbonmonoxy-Hb structure, the CO ligand is bound at an angle of 140 degrees, and with an unusually long Fe-C bond of 2.25 A. This geometry is attributed to repulsion from the distal His63 at the low pH of crystallization (4.5). In contrast, azide is bound to the oxidized heme iron in the methemoglobin crystals at an angle of 112 degrees, in a perfect orientation to accept a hydrogen bond from His63. Compared to the three known quaternary structures of human Hb (T, R, and R2), both structures most closely resemble the R state. Comparisons with the structures of adult Hb and HbH explain the association and dissociation behaviour of Hb homotetramers relative to the heterotetrameric Hbs. PMID:11514664

  9. 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.

  10. 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

  11. 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. PMID:21041946

  12. Role of fetal breathing movements in control of fetal lung distension.

    PubMed

    Miller, A A; Hooper, S B; Harding, R

    1993-12-01

    Our aim was to determine the role of fetal breathing movements (FBM) in the maintenance of fetal lung liquid volume. Experiments were performed in 14 chronically catheterized fetal sheep. FBM were selectively abolished for 48 h by the infusion of tetrodotoxin (TTX) onto the phrenic nerves of five fetuses. Lung liquid volumes and secretion rates were measured before each treatment, 46-48 h after the start of the TTX infusion, and 22-24 h after the end of the infusion. Blockade of the phrenic nerves reduced fetal lung liquid volumes from 27.6 +/- 1.9 to 21.8 +/- 2.6 ml/kg and increased lung liquid secretion rates from 3.8 +/- 0.6 to 6.2 +/- 1.1 ml.h-1.kg-1. Control experiments confirmed the lack of effect of TTX infused intravenously and saline infused intrapleurally on changes in fetal lung liquid volume and secretion rate. To measure the static relaxation volume of the fetal lung, in six fetuses we combined skeletal muscle paralysis with bypass of the upper airway for 48 h. This reduced fetal lung liquid volume from 39.1 +/- 3.1 to 23.0 +/- 2.5 ml/kg and increased lung liquid secretion rates from 4.1 +/- 0.7 to 5.8 +/- 0.9 ml.h-1.kg-1. This experiment demonstrates that the fetal lung is normally maintained at a level of expansion that is much greater than its static relaxation volume. We conclude that the volume of luminal liquid in the fetal lungs is dependent on the diaphragmatic contractions associated with FBM. Their effect is to resist the elastic recoil of the fetal lungs, thereby reducing the loss of liquid from the lungs via the trachea. PMID:8125894

  13. Boy or Girl? Maternal Psychological Correlates of Knowing Fetal Sex

    PubMed Central

    Kotila, Letitia E.; Schoppe-Sullivan, Sarah J.; Kamp Dush, Claire M.

    2015-01-01

    Ultrasound provides a reliable, convenient way to determine fetal sex, but not all expectant mothers pursue this knowledge. We used logistic regression to investigate whether maternal personality, parenting perfectionism, and gender role beliefs were associated with knowing fetal sex in a recent sample of first-time expectant mothers. We also tested whether conscientiousness and extraversion moderated the association between gender role beliefs and knowing fetal sex. Mothers who were more open to experience were less likely to know fetal sex, whereas mothers high in parenting perfectionism were more likely to know fetal sex. Conscientious mothers who espoused more egalitarian gender role beliefs were less likely to know fetal sex. PMID:26279598

  14. Mössbauer Effect in Hemoglobin and Some Iron-Containing Biological Compounds

    PubMed Central

    Gonser, U.; Grant, R. W.

    1965-01-01

    The Mössbauer effect in Fe57 has been used to study the molecules, hemoglobin, O2-hemoglobin, CO2-hemoglobin, and CO-hemoglobin (within red cells) and the molecules, hemin and hematin (in the crystalline state). Quadrupole splittings and isomeric shifts observed in the Mössbauer spectra of these molecules are tabulated. The temperature dependence of the quadrupole splitting and relative recoil-free fraction for hemoglobin with different ligands has been investigated. An estimate of the Debye-Waller factor in O2-hemoglobin at 5°K is 0.83. An asymmetry in the quadrupole splitting observed in hemoglobin is attributed to a directional dependence of the recoil-free fraction which establishes the sign of the electric field gradient in the molecule and indicates that the lowest lying d orbital of the Fe atoms is |xy>. This asymmetry indicates that the iron atoms in hemoglobin are vibrating farther perpendicular to the heme planes than parallel to them, and, in fact, the ratio of the mean square displacements perpendicular and parallel to the heme planes in hemoglobin is ≈5.5 at 5°K. The temperature dependence of the quadrupole splitting in hemoglobin has been used to estimate a splitting between the lowest lying iron atom d orbitals of ≈420 cm-1. PMID:5884013

  15. Hemoglobin C Trait Provides Protection From Clinical Falciparum Malaria in Malian Children

    PubMed Central

    Travassos, Mark A.; Coulibaly, Drissa; Laurens, Matthew B.; Dembélé, Ahmadou; Tolo, Youssouf; Koné, Abdoulaye K.; Traoré, Karim; Niangaly, Amadou; Guindo, Aldiouma; Wu, Yukun; Berry, Andrea A.; Jacob, Christopher G.; Takala-Harrison, Shannon; Adams, Matthew; Shrestha, Biraj; Mu, Amy Z.; Kouriba, Bourema; Lyke, Kirsten E.; Diallo, Dapa A.; Doumbo, Ogobara K.; Plowe, Christopher V.; Thera, Mahamadou A.

    2015-01-01

    Background. Hemoglobin C trait, like hemoglobin S trait, protects against severe malaria in children, but it is unclear whether hemoglobin C trait also protects against uncomplicated malaria. We hypothesized that Malian children with hemoglobin C trait would have a lower risk of clinical malaria than children with hemoglobin AA. Methods. Three hundred children aged 0–6 years were enrolled in a cohort study of malaria incidence in Bandiagara, Mali, with continuous passive and monthly active follow-up from June 2009 to June 2010. Results. Compared to hemoglobin AA children (n = 242), hemoglobin AC children (n = 39) had a longer time to first clinical malaria episode (hazard ratio [HR], 0.19; P = .001; 364 median malaria-free days vs 181 days), fewer episodes of clinical malaria, and a lower cumulative parasite burden. Similarly, hemoglobin AS children (n = 14) had a longer time to first clinical malaria episode than hemoglobin AA children (HR, 0.15; P = .015; 364 median malaria-free days vs 181 days), but experienced the most asymptomatic malaria infections of any group. Conclusions. Both hemoglobin C and S traits exerted a protective effect against clinical malaria episodes, but appeared to do so by mechanisms that differentially affect the response to infecting malaria parasites. PMID:26019283

  16. Indicated preterm birth for fetal anomalies.

    PubMed

    Craigo, Sabrina D

    2011-10-01

    Between 2% and 3% of pregnancies are complicated by fetal anomalies. For most anomalies, there is no advantage to late preterm or early-term delivery. The risks of maternal or fetal complication are specific for each anomaly. Very few anomalies pose potential maternal risk. Some anomalies carry ongoing risks to the fetus, such as an increased risk of fetal death, hemorrhage, or organ damage. In a limited number of select cases, the advantages of late preterm or early-term birth may include avoiding an ongoing risk of fetal death related to the anomaly, allowing delivery in a controlled setting with availability of subspecialists and allowing direct care for the neonate with organ injury. The optimal gestational age for delivery cannot be determined for all pregnancies complicated by fetal anomalies. For most pregnancies complicated by anomalies, there is no change to obstetrical management regarding timing of delivery. For those that may benefit from late preterm or early-term delivery, variability exists such that each management plan should be individualized. PMID:21962626

  17. Fetal and infant origins of asthma.

    PubMed

    Duijts, Liesbeth

    2012-01-01

    Previous studies have suggested that asthma, like other common diseases, has at least part of its origin early in life. Low birth weight has been shown to be associated with increased risks of asthma, chronic obstructive airway disease, and impaired lung function in adults, and increased risks of respiratory symptoms in early childhood. The developmental plasticity hypothesis suggests that the associations between low birth weight and diseases in later life are explained by adaptation mechanisms in fetal life and infancy in response to various adverse exposures. Various pathways leading from adverse fetal and infant exposures to growth adaptations and respiratory health outcomes have been studied, including fetal and early infant growth patterns, maternal smoking and diet, children's diet, respiratory tract infections and acetaminophen use, and genetic susceptibility. Still, the specific adverse exposures in fetal and early postnatal life leading to respiratory disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life, and their epigenetic mechanisms may underlie the complex associations of low birth weight with respiratory disease in later life. New well-designed epidemiological studies are needed to identify the specific underlying mechanisms. This review is focused on specific adverse fetal and infant growth patterns and exposures, genetic susceptibility, possible respiratory adaptations and perspectives for new studies. PMID:22350146

  18. Intrauterine resuscitation: active management of fetal distress.

    PubMed

    Thurlow, J A; Kinsella, S M

    2002-04-01

    Acute fetal distress in labour is a condition of progressive fetal asphyxia with hypoxia and acidosis. It is usually diagnosed by finding characteristic features in the fetal heart rate pattern, wherever possible supported by fetal scalp pH measurement. Intrauterine resuscitation consists of applying specific measures with the aim of increasing oxygen delivery to the placenta and umbilical blood flow, in order to reverse hypoxia and acidosis. These measures include initial left lateral recumbent positioning followed by right lateral or knee-elbow if necessary, rapid intravenous infusion of a litre of non-glucose crystalloid, maternal oxygen administration at the highest practical inspired percentage, inhibition of uterine contractions usually with subcutaneous or intravenous terbutaline 250 microg, and intra-amniotic infusion of warmed crystalloid solution. Specific manoeuvres for umbilical cord prolapse are also described. Intrauterine resuscitation may be used as part of the obstetric management of labour, while preparing for caesarean delivery for fetal distress, or at the time of establishment of regional analgesia during labour in the compromised fetus. The principles may also be applied during inter-hospital transfers of sick or labouring parturients. PMID:15321562

  19. Adjustable fetal phantom for pulse oximetry

    NASA Astrophysics Data System (ADS)

    Stubán, Norbert; Niwayama, Masatsugu

    2009-05-01

    As the measuring head of a fetal pulse oximeter must be attached to the head of the fetus inside the mother's uterus during labor, testing, and developing of fetal pulse oximeters in real environment have several difficulties. A fetal phantom could enable evaluation of pulse oximeters in a simulated environment without the restrictions and difficultness of medical experiments in the labor room. Based on anatomic data we developed an adjustable fetal head phantom with three different tissue layers and artificial arteries. The phantom consisted of two arteries with an inner diameter of 0.2 and 0.4 mm. An electronically controlled pump produced pulse waves in the arteries. With the phantom we investigated the sensitivity of a custom-designed wireless pulse oximeter at different pulsation intensity and artery diameters. The results showed that the oximeter was capable of identifying 4% and 2% changes in diameter between the diastolic and systolic point in arteries of over 0.2 and 0.4 mm inner diameter, respectively. As the structure of the phantom is based on reported anatomic values, the results predict that the investigated custom-designed wireless pulse oximeter has sufficient sensitivity to detect the pulse waves and to calculate the R rate on the fetal head.

  20. Noninvasive fetal RhD genotyping.

    PubMed

    Clausen, Frederik Banch; Damkjær, Merete Berthu; Dziegiel, Morten Hanefeld

    2014-04-01

    Immunization against RhD is the major cause of hemolytic disease of the fetus and newborn (HDFN), which causes fetal or neonatal death. The introduction of postnatal immune prophylaxis in the 1960s drastically reduced immunization incidents in pregnant, D-negative women. In several countries, antenatal prophylaxis is combined with postnatal prophylaxis to further minimize the immunization risk. Due to lack of knowledge of the fetal RhD type, antenatal prophylaxis is given to all D-negative women. In the European population, approximately 40% of pregnant women carry a D-negative fetus and are thus at no risk of immunization. Noninvasive fetal RhD genotyping enables antenatal prophylaxis to be targeted to only those women carrying a D-positive fetus to avoid unnecessary treatment. Based on an analysis of cell-free fetal DNA from the plasma of pregnant women, this approach has recently undergone technical improvements and rapid clinical implementation. As a screening assay, the sensitivity is >99.3% from a gestational age of approximately 10-11 weeks. In addition, fetal RhD genotyping is widely used to assess the risk of HDFN in anti-D immunized women. PMID:24642067

  1. Automatic real-time tracking of fetal mouth in fetoscopic video sequence for supporting fetal surgeries

    NASA Astrophysics Data System (ADS)

    Xu, Rong; Xie, Tianliang; Ohya, Jun; Zhang, Bo; Sato, Yoshinobu; Fujie, Masakatsu G.

    2013-03-01

    Recently, a minimally invasive surgery (MIS) called fetoscopic tracheal occlusion (FETO) was developed to treat severe congenital diaphragmatic hernia (CDH) via fetoscopy, by which a detachable balloon is placed into the fetal trachea for preventing pulmonary hypoplasia through increasing the pressure of the chest cavity. This surgery is so dangerous that a supporting system for navigating surgeries is deemed necessary. In this paper, to guide a surgical tool to be inserted into the fetal trachea, an automatic approach is proposed to detect and track the fetal face and mouth via fetoscopic video sequencing. More specifically, the AdaBoost algorithm is utilized as a classifier to detect the fetal face based on Haarlike features, which calculate the difference between the sums of the pixel intensities in each adjacent region at a specific location in a detection window. Then, the CamShift algorithm based on an iterative search in a color histogram is applied to track the fetal face, and the fetal mouth is fitted by an ellipse detected via an improved iterative randomized Hough transform approach. The experimental results demonstrate that the proposed automatic approach can accurately detect and track the fetal face and mouth in real-time in a fetoscopic video sequence, as well as provide an effective and timely feedback to the robot control system of the surgical tool for FETO surgeries.

  2. Killing Me Softly: The Fetal Origins Hypothesis.

    PubMed

    Almond, Douglas; Currie, Janet

    2011-01-01

    In the epidemiological literature, the fetal origins hypothesis associated with David J. Barker posits that chronic, degenerative conditions of adult health, including heart disease and type 2 diabetes, may be triggered by circumstance decades earlier, in utero nutrition in particular. Economists have expanded on this hypothesis, investigating a broader range of fetal shocks and circumstances and have found a wealth of later-life impacts on outcomes including test scores, educational attainment, and income, along with health. In the process, they have provided some of the most credible observational evidence in support of the hypothesis. The magnitude of the impacts is generally large. Thus, the fetal origins hypothesis has not only survived contact with economics, but has flourished. PMID:25152565

  3. Intrapartum sonographic imaging of fetal head asynclitism.

    PubMed

    Ghi, T; Youssef, A; Pilu, G; Malvasi, A; Ragusa, A

    2012-02-01

    Anterior asynclitism was suspected on digital examination of a laboring woman with late arrest of dilatation and no evidence of fetal head progression. Clinical examination revealed a fixed non-engaged fetal head (station −1), with a transverse posterior sagittal suture. A static three-dimensional volume was obtained by translabial ultrasound, offline analysis of which confirmed the clinical diagnosis of anterior asynclitism. Owing to the posterior twisting of the head towards the sacrum, the midline echo could only be obtained by cutting the volume with an oblique line, the direction of which was not perpendicular to the pubis as expected in cases of synclitic head. The sonographic appearance of the midline echo approaching the sacrum in a non-engaged transverse fetal head strongly supports the clinical suspicion of anterior asynclitism. PMID:21523842

  4. Surgery during pregnancy and fetal outcome

    SciTech Connect

    Brodsky, J.B.; Cohen, E.N.; Brown, B.W.; Wu, M.L.; Whitcher, C.

    1988-01-01

    Information was sought on wives of dentists or female dental assistants who underwent surgery during their pregnancies to determine the effects of anesthesia and surgery on fetal outcome. Occupational exposure to inhalation anesthetics either directly (dental assistants) or indirectly (wives of exposed male dentists) was associated with a significant increase in spontaneous abortion rate over a comparison group during both trimesters. Anesthesia for surgery was also associated with increased fetal loss when administered during the first or second trimesters. The number of congenital abormalities in children born to women who had surgery during pregnancy was not increased. For women surgically exposed to anesthetics and occupationally exposed as well, either directly or indirectly, the risk of spontaneous abortion increased almost threefold above control lvels. The authors conclude that elective surgery should be deferred during early pregnanacy to minimize potential fetal loss.

  5. Adrenergic receptors in human fetal liver membranes

    SciTech Connect

    Falkay, G.; Kovacs, L. )

    1990-01-01

    The adrenergic receptor binding capacities in human fetal and adult livers were measured to investigate the mechanism of the reduced alpha-1 adrenoreceptor response of the liver associated with a reciprocal increase in beta-adrenoreceptor activity in a number of conditions. Alpha-1 and beta-adrenoreceptor density were determined using {sup 3}H-prazosin and {sup 3}H-dihydroalprenolol, respectively, as radioligand. Heterogeneous populations of beta-adrenoreceptors were found in fetal liver contrast to adult. Decreased alpha-1 and increased beta-receptor density were found which may relate to a decreased level in cellular differentiation. These findings may be important for the investigation of perinatal hypoglycemia of newborns after treatment of premature labor with beta-mimetics. This is the first demonstration of differences in the ratio of alpha-1 and beta-adrenoceptors in human fetal liver.

  6. Imaging the fetal central nervous system

    PubMed Central

    De Keersmaecker, B.; Claus, F.; De Catte, L.

    2011-01-01

    The low prevalence of fetal central nervous system anomalies results in a restricted level of exposure and limited experience for most of the obstetricians involved in prenatal ultrasound. Sonographic guidelines for screening the fetal brain in a systematic way will probably increase the detection rate and enhance a correct referral to a tertiary care center, offering the patient a multidisciplinary approach of the condition. This paper aims to elaborate on prenatal sonographic and magnetic resonance imaging (MRI) diagnosis and outcome of various central nervous system malformations. Detailed neurosonographic investigation has become available through high resolution vaginal ultrasound probes and the development of a variety of 3D ultrasound modalities e.g. ultrasound tomographic imaging. In addition, fetal MRI is particularly helpful in the detection of gyration and neurulation anomalies and disorders of the gray and white matter. PMID:24753859

  7. Biomarker tests for fetal lung maturity.

    PubMed

    Leung-Pineda, Van; Gronowski, Ann M

    2010-12-01

    The production of surfactant is a key step in fetal lung development. Surfactant decreases alveolar surface tension, thereby preventing alveolar collapse and allowing efficient gas exchange. The lack of adequate amounts of lung surfactant results in respiratory distress syndrome. Tests that assess surfactant concentrations in amniotic fluid are good predictors of infants that will not develop respiratory distress syndrome. The most frequently used test to assess fetal lung maturity (TDx FLM II) will not be available after December 2011. Therefore, we review the currently available tests for fetal lung maturity including lecithin:sphingomyelin ratio, phosphatidyl glycerol, surfactant:albumin ratio and lamellar body counts. Herein, we discuss their clinical utility and consider a suitable replacement for the future. PMID:21133706

  8. Killing Me Softly: The Fetal Origins Hypothesis*

    PubMed Central

    Almond, Douglas

    2013-01-01

    In the epidemiological literature, the fetal origins hypothesis associated with David J. Barker posits that chronic, degenerative conditions of adult health, including heart disease and type 2 diabetes, may be triggered by circumstance decades earlier, in utero nutrition in particular. Economists have expanded on this hypothesis, investigating a broader range of fetal shocks and circumstances and have found a wealth of later-life impacts on outcomes including test scores, educational attainment, and income, along with health. In the process, they have provided some of the most credible observational evidence in support of the hypothesis. The magnitude of the impacts is generally large. Thus, the fetal origins hypothesis has not only survived contact with economics, but has flourished. PMID:25152565

  9. 21 CFR 884.2600 - Fetal cardiac monitor.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen...

  10. 21 CFR 884.2600 - Fetal cardiac monitor.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen...

  11. 21 CFR 884.2600 - Fetal cardiac monitor.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen...

  12. 21 CFR 884.2600 - Fetal cardiac monitor.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen...

  13. 21 CFR 884.2600 - Fetal cardiac monitor.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... ascertain fetal heart activity during pregnancy and labor. The device is designed to separate fetal heart signals from maternal heart signals by analyzing electrocardiographic signals (electrical potentials generated during contraction and relaxation of heart muscle) obtained from the maternal abdomen...

  14. Andreas Vesalius (1514-1564), Padua, and the fetal "shunts".

    PubMed

    Dunn, P M

    2003-03-01

    Three remarkable medical anatomists working in Padua during the 16th century described the anatomy of the fetal cardiovascular system, thus laying the foundation for William Harvey's discovery and description of the fetal circulation in the following century. PMID:12598509

  15. Prostaglandin E2 decreases fetal breathing movements, but not pulmonary blood flow, in fetal sheep.

    PubMed

    Savich, R D; Guerra, F A; Lee, C C; Kitterman, J A

    1995-04-01

    Fetal breathing movements are vital for normal fetal lung growth. Inhibition of these fetal breathing movements is associated with pulmonary hypoplasia. Pulmonary hypoplasia also occurs subsequent to alterations in other factors, such as a significant decrease in pulmonary blood flow. The prostaglandin system is known to have profound effects on both fetal breathing movements and on the pulmonary vascular system. We studied six late-gestation chronically instrumented fetal sheep by using an electromagnetic flow transducer around the left pulmonary artery to determine whether a decrease in fetal breathing movements, subsequent to a continuous infusion of prostaglandin E2 (PGE2), is associated with a decrease in pulmonary blood flow. A continuous PGE2 infusion of 0.88 +/- 0.11 microgram.kg-1.min-1 over 120 min led to a significant decrease in fetal breathing movements (control 40.5 +/- 3.6%, infusion 3.3 +/- 1.6%; P < 0.001). In contrast, the PGE2 infusion had no effect on mean left pulmonary artery blood flow (control 27.7 +/- 9.3 ml.min-1.kg-1, infusion 23.8 +/- 7.0 ml.min-1.kg-1. The PGE2 infusion demonstrated central effects in the percentage of time the fetus was in high-voltage electrocortical activity (control 41.9 +/- 2.5%, infusion 56.5 +/- 5.4%; P < 0.05) and in the amount of time spent in low-voltage electrocortical activity without fetal breathing movements (control 17.5 +/- 2.7%, infusion 40.2 +/- 4.8%; P < 0.05). A significant decrease in the fetal heart rate during the infusion was seen with no effect on either the systemic or pulmonary blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7615458

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

    PubMed

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

    2015-07-01

    Several studies have previously proposed that blood hemoglobin concentration in nestling passerines is a reliable index of individual condition and nutritional state. In this paper we present results concerning variation in hemoglobin concentration in the blood of ca. 14-day-old nestling great tits Parus major in central Poland in an 11-year-long period, 2003-2013, in two distinct habitat types: urban park and deciduous forest. The most important findings of the study were: (i) variation in hemoglobin concentration was consistent within broods, (ii) hemoglobin concentration of nestlings varied markedly across years, (iii) hemoglobin concentration was significantly higher in the forest study site which is richer in terms of food abundance during the short period of tits breeding season and (iv) high hemoglobin level was a predictor of nestling survival from hatching to fledging. PMID:25770667

  17. 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.

  18. 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.

  19. Molecular imaging of hemoglobin using ground state recovery pump-probe optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Applegate, Brian E.; Izatt, Joseph A.

    2007-02-01

    We have undertaken an effort to further develop ground state recovery Pump-Probe Optical Coherence Tomograpy (gsrPPOCT) to specifically target and measure 3-D images of hemoglobin concentration with the goals of mapping tissue vasculature, total hemoglobin, and hemoglobin oxygen saturation. As a first step toward those goals we have measured the gsrPPOCT signal from the hemoglobin in the filament arteries of a zebra danio fish. We have further processed the resulting signal to extract a qualitative map of the hemoglobin concentration. We have also demonstrated the potential to use ground state recovery times to differentiate between two chromophores which may prove to be an effective tool for differentiating between oxy and deoxy hemoglobin.

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

    PubMed Central

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

    2013-01-01

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

  1. 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.

  2. Automatic identification of fetal breathing movements in fetal RR interval time series.

    PubMed

    Van Leeuwen, Peter; Voss, Anna; Cysarz, Dirk; Edelhäuser, Friedrich; Grönemeyer, Dietrich

    2012-03-01

    Fetal breathing movements are associated with respiratory sinus arrhythmia (RSA). We present an algorithm which processes RR interval time series in the time and frequency domain, identifying spectral peaks with characteristics consistent with fetal RSA. Tested on 50 data sets from the second and third trimester, the algorithm had a sensitivity of 96.1%, false positive rate 35.7%, false negative rate 3.9%. The characteristics of automatically and visually identified episodes were very similar and corresponded the expected changes over gestation. The method is suited for easy and reliable identification of fetal breathing movements. PMID:21621759

  3. Acoustically based fetal heart rate monitor

    NASA Technical Reports Server (NTRS)

    Baker, Donald A.; Zuckerwar, Allan J.

    1991-01-01

    The acoustically based fetal heart rate monitor permits an expectant mother to perform the fetal Non-Stress Test in her home. The potential market would include the one million U.S. pregnancies per year requiring this type of prenatal surveillance. The monitor uses polyvinylidene fluoride (PVF2) piezoelectric polymer film for the acoustic sensors, which are mounted in a seven-element array on a cummerbund. Evaluation of the sensor ouput signals utilizes a digital signal processor, which performs a linear prediction routine in real time. Clinical tests reveal that the acoustically based monitor provides Non-Stress Test records which are comparable to those obtained with a commercial ultrasonic transducer.

  4. The measurement of hemoglobin oxygen saturation using multiwavelength photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Deng, Zilin; Yang, Xiaoquan; Yu, Lejun; Gong, Hui

    2009-10-01

    Hemoglobin oxygen saturation (SO2) is one of the most critical functional parameters to the metabolism. In this paper, we mainly introduced some initial results of measuring blood oxygen using multi-wavelength photoacoustic microscopy (PAM). In phantom study, we demonstrate the photoacoustic signal amplitude increases linearly with the concentration of red or blue ink. Then the calculated concentration of red ink in double-ink mixtures with PAM has a 5% difference with the result measured with spectrophotometric analysis. In ex vivo experiment, the measured result exhibt 15% difference between the PAM and spectrophotometric analysis. Experiment results suggest that PAM could be used to determine the SO2 quantitatively.

  5. The measurement of hemoglobin oxygen saturation using multiwavelength photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Deng, Zilin; Yang, Xiaoquan; Yu, Lejun; Gong, Hui

    2010-02-01

    Hemoglobin oxygen saturation (SO2) is one of the most critical functional parameters to the metabolism. In this paper, we mainly introduced some initial results of measuring blood oxygen using multi-wavelength photoacoustic microscopy (PAM). In phantom study, we demonstrate the photoacoustic signal amplitude increases linearly with the concentration of red or blue ink. Then the calculated concentration of red ink in double-ink mixtures with PAM has a 5% difference with the result measured with spectrophotometric analysis. In ex vivo experiment, the measured result exhibt 15% difference between the PAM and spectrophotometric analysis. Experiment results suggest that PAM could be used to determine the SO2 quantitatively.

  6. Ligand migration in nonsymbiotic hemoglobin AHb1 from Arabidopsis thaliana.

    PubMed

    Abbruzzetti, Stefania; Grandi, Elena; Bruno, Stefano; Faggiano, Serena; Spyrakis, Francesca; Mozzarelli, Andrea; Cacciatori, Elena; Dominici, Paola; Viappiani, Cristiano

    2007-11-01

    AHb1 is a hexacoordinated type 1 nonsymbiotic hemoglobin recently discovered in Arabidopsis thaliana. To gain insight into the ligand migration inside the protein, we studied the CO rebinding kinetics of AHb1 encapsulated in silica gels, in the presence of glycerol. The CO rebinding kinetics after nanosecond laser flash photolysis exhibits complex ligand migration patterns, consistent with the existence of discrete docking sites in which ligands can temporarily be stored before rebinding to the heme at different times. This finding may be of relevance to the physiological NO dioxygenase activity of this protein, which requires sequential binding of two substrates, NO and O2, to the heme. PMID:17924689

  7. Mössbauer studies of hemoglobin in high altitude polycythemia

    NASA Astrophysics Data System (ADS)

    Xiufang, Zhang; Linming, Shen; Songsen, Chen; Yuanyuan, Liu; Naifei, Gao; Yuanming, Zheng; Zhaohui, Ao; Liangquan, Shong

    1990-07-01

    The Mössbauer spectra have been measured in erythrocytes from normal adults and the patients with high altitude polycythemia (HAPC). The results indicated that two subspectra “a” and “b”, corresponding to oxy- and deoxyhemoglobin respectively, were present in all blood samples, and a third subspectrum “c” was found to exist in almost all samples from the patients. The parameters of the third subspectra “cl” in most samples from the patients were similar to those of carbon monoxyhemoglobin. The components were considered to be the denatured hemoglobin in RBCs (red blood cells). Together with clinical analysis, a possible mechanism of HAPC has been discussed.

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

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

    NASA Technical Reports Server (NTRS)

    Davis, Sanford

    1990-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-07-01

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

  11. Carbon Monoxide Poisoning: Some Surprising Aspects of the Equilibrium between Hemoglobin, Carbon Monoxide, and Oxygen

    NASA Astrophysics Data System (ADS)

    Senozan, N. M.; Devore, J. A.

    1996-08-01

    Carbon monoxide poisoning and some aspects of the equilibrium between carbon monoxide, oxygen, and hemoglobin are discussed within the framework of Haldane's laws. The effect of CO on respiration is analyzed quantitatively using oxygen dissociation curves of hemoglobin in presence of carboxyhemoglobin. The analysis shows that the adverse cardiovascular consequences of chronic CO exposure are unlikely to be due to reduced O2 transport capability of hemoglobin.

  12. Fetal Pulmonary Arterial Vascular Impedance Reflects Changes in Fetal Oxygenation at Near-Term Gestation in a Nonhuman Primate Model

    PubMed Central

    Arraut, Amaryllis Maria Elpida; Frias, Antonio E.; Hobbs, Theodore R.; McEvoy, Cindy; Spindel, Eliot R.; Rasanen, Juha

    2013-01-01

    Objective: We tested the hypothesis that fetal pulmonary arterial circulation reacts to changes in fetal oxygenation status at near-term gestation. Study Design: A total of 20 rhesus macaques underwent fetal Doppler ultrasonography at near-term gestation. Right pulmonary artery (RPA), umbilical artery (UA), ductus arteriosus (DA), and ductus venosus (DV) blood velocity waveforms were obtained, and pulsatility index (PI) values were calculated. Fetal right and left ventricular cardiac outputs were determined. Ultrasonographic data were collected during 3 maternal oxygenation states: room air (baseline), hyperoxemia, and hypoxemia. Results: Fetal RPA PI values increased (P < .05) during maternal hypoxemia and decreased (P < .05) during maternal hyperoxemia, compared with baseline. Maternal hyperoxemia increased (P < .05) DA PI values from baseline. Fetal cardiac outputs, UA, and DV PI values were not affected. Conclusions: Our results demonstrate that at near-term gestation, fetal pulmonary arterial circulation is a dynamic vascular bed that reflects acute and short-term changes in fetal oxygenation. PMID:22991382

  13. Agonist mediated fetal muscle-type nicotinic acetylcholine receptor desensitization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The exposure of a developing embryo or fetus to teratogenic alkaloids from plants has the potential to cause developmental defects in livestock due to the inhibition of fetal movement by alkaloids. The mechanism behind the inhibition of fetal movement is the desensitization of fetal muscle-type nico...

  14. Fetal Bowel Dilatation: A Sonographic Sign of Uncertain Prognosis

    PubMed Central

    Silva, Patrícia; Reis, Filipa; Alves, Paulo; Farinha, Luís; Gomes, Manuel Sousa; Câmara, Pilar

    2015-01-01

    Fetal bowel dilatation is an indirect sonographic sign of mechanical or functional bowel obstruction. The etiology of fetal bowel dilatation is a difficult prenatal diagnosis since ultrasound has limited accuracy for bowel evaluation. The authors describe a case of fetal bowel dilatation diagnosed in the third trimester. PMID:26819789

  15. [The value of current echographic parameters in fetal biometry].

    PubMed

    Sussmann, M; Curie, P; Dreyfus, M; Renaud, R

    1985-05-01

    A review of current literature concerning developments of new parameters in fetal biometry is presented. To be sure, these parameters are very useful for detection of fetal malformations but outside of femoral length they do not contribute more valuable information than the already accepted parameters for determination of gestational age or detection of disorders of fetal growth. PMID:3895364

  16. 21 CFR 884.2660 - Fetal ultrasonic monitor and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal ultrasonic monitor and accessories. 884.2660... Devices § 884.2660 Fetal ultrasonic monitor and accessories. (a) Identification. A fetal ultrasonic monitor is a device designed to transmit and receive ultrasonic energy into and from the pregnant...

  17. 21 CFR 884.2660 - Fetal ultrasonic monitor and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal ultrasonic monitor and accessories. 884.2660... Devices § 884.2660 Fetal ultrasonic monitor and accessories. (a) Identification. A fetal ultrasonic monitor is a device designed to transmit and receive ultrasonic energy into and from the pregnant...

  18. 21 CFR 884.4340 - Fetal vacuum extractor.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Fetal vacuum extractor. 884.4340 Section 884.4340....4340 Fetal vacuum extractor. (a) Identification. A fetal vacuum extractor is a device used to... means of a suction cup attached to the scalp and is powered by an external vacuum source. This...

  19. 21 CFR 884.4340 - Fetal vacuum extractor.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Fetal vacuum extractor. 884.4340 Section 884.4340....4340 Fetal vacuum extractor. (a) Identification. A fetal vacuum extractor is a device used to... means of a suction cup attached to the scalp and is powered by an external vacuum source. This...

  20. 21 CFR 884.4340 - Fetal vacuum extractor.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fetal vacuum extractor. 884.4340 Section 884.4340....4340 Fetal vacuum extractor. (a) Identification. A fetal vacuum extractor is a device used to... means of a suction cup attached to the scalp and is powered by an external vacuum source. This...

  1. 21 CFR 884.4340 - Fetal vacuum extractor.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Fetal vacuum extractor. 884.4340 Section 884.4340....4340 Fetal vacuum extractor. (a) Identification. A fetal vacuum extractor is a device used to... means of a suction cup attached to the scalp and is powered by an external vacuum source. This...

  2. 21 CFR 884.4340 - Fetal vacuum extractor.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fetal vacuum extractor. 884.4340 Section 884.4340....4340 Fetal vacuum extractor. (a) Identification. A fetal vacuum extractor is a device used to... means of a suction cup attached to the scalp and is powered by an external vacuum source. This...

  3. Fetal Alcohol Syndrome: A Guide for Families and Communities.

    ERIC Educational Resources Information Center

    Streissguth, Ann

    The 14 chapters of this book review the research and offer guidelines for intervention with infants and children having fetal alcohol syndrome or fetal alcohol effects (FAS/FAE). Chapters are grouped into five sections on the diseases of fetal alcohol, the science of FAS, a life-span approach to FAS, preparing people with FAS for life in the…

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

    PubMed

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

    2014-01-01

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

  5. Immunocytochemical mapping of the hemoglobin biosynthesis site in amphibian erythroid cells.

    PubMed

    Cianciarullo, A M; Beçak, W; Soares, M J

    1999-06-01

    During the past 25 years, several studies have attempted to determine the site of integration of the heme and the four globin chains in vertebrate erythroid cells that is important in the formation of the hemoglobin molecule. Mitochondrion-like organelles or hemosomes were pointed out as responsible for this task. We performed several experiments to investigate this hypothesis. The intracellular distribution of hemoglobin in amphibian erythroid cells was detected by post-embedding immuno-electron microscopy, using a polyclonal anti-human hemoglobin-proteinA-gold complex. Hemoglobin mapping showed an intense labeling in the cell cytoplasm, but none in cytoplasmic structures such as endoplasmic reticulum, mitochondria, mitochondrion-like organelles, Golgi complex, ribosomes or ferruginous inclusions. The mitochondrial fraction obtained according to the protocol described for some authors, showed by ultrastructural examination that this fraction has a heterogeneous content, also composed by microvesicles rich in cytoplasmic hemoglobin, an artifact generated by mechanical action during cell fractionation. Thus, when this fraction is lysed and its content submitted to electrophoresis, hemoglobin bands would be found inevitably, causing false-positive results, erroneously attributed to hemoglobin content of mitochondrion-like organelles. Our data do not confirm the hypothesis that the final hemoglobin biosynthesis occurs inside mitochondrion-like organelles. They suggest that the hemoglobin molecule be assembled in the erythrocyte cytoplasm outside of mitochondria or hemosomes. PMID:10481306

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

    NASA Astrophysics Data System (ADS)

    Lazareva, Ekaterina N.; Tuchin, Valery V.

    2016-04-01

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

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

    PubMed Central

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

    2008-01-01

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

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

    PubMed

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

    2012-06-01

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

  9. Prenatal diagnosis of a placental infarction hematoma associated with fetal growth restriction, preeclampsia and fetal death: clinicopathological correlation

    PubMed Central

    Aurioles-Garibay, Alma; Hernandez-Andrade, Edgar; Romero, Roberto; Qureshi, Faisal; Ahn, Hyunyoung; Jacques, Suzanne M.; Garcia, Maynor; Yeo, Lami; Hassan, Sonia S.

    2014-01-01

    The lesion termed “placental infarction hematoma” is associated with fetal death and adverse perinatal outcome. Such lesion has been associated with a high risk of fetal death and abruption placentae. The fetal and placental hemodynamic changes associated with placental infarction hematoma have not been reported. This communication describes a case of early and severe growth restriction with preeclampsia, and progressive deterioration of the fetal and placental Doppler parameters in the presence of a placental infarction hematoma. PMID:24852332

  10. Adaptation of an articulated fetal skeleton model to three-dimensional fetal image data

    NASA Astrophysics Data System (ADS)

    Klinder, Tobias; Wendland, Hannes; Wachter-Stehle, Irina; Roundhill, David; Lorenz, Cristian

    2015-03-01

    The automatic interpretation of three-dimensional fetal images poses specific challenges compared to other three-dimensional diagnostic data, especially since the orientation of the fetus in the uterus and the position of the extremities is highly variable. In this paper, we present a comprehensive articulated model of the fetal skeleton and the adaptation of the articulation for pose estimation in three-dimensional fetal images. The model is composed out of rigid bodies where the articulations are represented as rigid body transformations. Given a set of target landmarks, the model constellation can be estimated by optimization of the pose parameters. Experiments are carried out on 3D fetal MRI data yielding an average error per case of 12.03+/-3.36 mm between target and estimated landmark positions.

  11. Comparative Plasma Protein Profiling of Hemoglobin H Disease

    PubMed Central

    Khungwanmaythawee, Kornpat; Paemanee, Atchara; Chaichana, Chartchai; Roytrakul, Sittiruk; Fucharoen, Suthat; Svasti, Saovaros; Smith, Duncan R.

    2014-01-01

    HbH and HbH-constant spring (HbH-CS) are the most common forms of α-thalassemia detected in the Thai population. The accumulation of excess β globin chains in these diseases results in increased red cell hemolysis, and patients with HbH-CS normally have a more severe clinical presentation than patients with HbH disease. This study aimed to detect alterations in the expression of plasma proteins of HbH and HbH-CS patients as compared to normal plasma. Platelet poor plasma was separated from HbH and HbH-CS and normal subjects and differential plasma proteins were detected using two-dimensional gel electrophoresis and identified using LC/MS/MS. A total of 14 differentially expressed proteins were detected of which 5 proteins were upregulated and 9 were downregulated. Most of the differentially expressed proteins are liver secreted proteins involved in hemolysis, oxidative stress response, and hemoglobin degradation. Seven proteins were found to be differentially expressed between HbH and HbH-CS. Levels of haptoglobin, a hemoglobin scavenging protein, were significantly increased in HbH patients as compared to HbH-CS patients. The identification of differentially expressed proteins may lead to a better understanding of the biological events underlying the clinical presentation of HbH and HbH-CS patients and can have application as hemolytic markers or severity predictors. PMID:25024506

  12. A cooperative oxygen-binding hemoglobin from Mycobacterium tuberculosis

    PubMed Central

    Couture, Manon; Yeh, Syun-Ru; Wittenberg, Beatrice A.; Wittenberg, Jonathan B.; Ouellet, Yannick; Rousseau, Denis L.; Guertin, Michel

    1999-01-01

    Two putative hemoglobin genes, glbN and glbO, were recently discovered in the complete genome sequence of Mycobacterium tuberculosis H37Rv. Here, we show that the glbN gene encodes a dimeric hemoglobin (HbN) that binds oxygen cooperatively with very high affinity (P50 = 0.013 mmHg at 20°C) because of a fast combination (25 μM−1⋅s−1) and a slow dissociation (0.2 s−1) rate. Resonance Raman spectroscopy and ligand association/dissociation kinetic measurements, along with mutagenesis studies, reveal that the stabilization of the bound oxygen is achieved through a tyrosine at the B10 position in the distal pocket of the heme with a conformation that is unique among the globins. Physiological studies performed with Mycobacterium bovis bacillus Calmette–Guérin demonstrate that the expression of HbN is greatly enhanced during the stationary phase in aerobic cultures but not under conditions of limited oxygen availability. The results suggest that, physiologically, the primary role of HbN may be to protect the bacilli against reactive nitrogen species produced by the host macrophage. PMID:10500158

  13. Structure of Greyhound hemoglobin: origin of high oxygen affinity.

    PubMed

    Bhatt, Veer S; Zaldívar-López, Sara; Harris, David R; Couto, C Guillermo; Wang, Peng G; Palmer, Andre F

    2011-05-01

    This study presents the crystal structure of Greyhound hemoglobin (GrHb) determined to 1.9 Å resolution. GrHb was found to crystallize with an α₁β₁ dimer in the asymmetric unit and belongs to the R2 state. Oxygen-affinity measurements combined with the fact that GrHb crystallizes in the R2 state despite the high-salt conditions used for crystallization strongly indicate that GrHb can serve as a model high-oxygen-affinity hemoglobin (Hb) for higher mammals, especially humans. Structural analysis of GrHb and its comparison with the R2-state of human Hb revealed several regions that can potentially contribute to the high oxygen affinity of GrHb and serve to rationalize the additional stability of the R2-state of GrHb. A previously well studied hydrophobic cluster of bar-headed goose Hb near α119 was also incorporated in the comparison between GrHb and human Hb. Finally, a structural comparison with generic dog Hb and maned wolf Hb was conducted, revealing that in contrast to GrHb these structures belong to the R state of Hb and raising the intriguing possibility of an additional allosteric factor co-purifying with GrHb that can modulate its quaternary structure. PMID:21543841

  14. Screening for Structural Hemoglobin Variants in Bahia, Brazil.

    PubMed

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

    2016-02-01

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

  15. Thalassemia and Hemoglobin E in Southern Thai Blood Donors

    PubMed Central

    Kruachan, Kwanta; Sengking, Warachaya; Horpet, Dararat; Sungyuan, Ubol

    2014-01-01

    Thalassemia and hemoglobin E (Hb E) are common in Thailand. Individuals with thalassemia trait usually have a normal hemoglobin concentration or mild anemia. Therefore, thalassemic individuals who have minimum acceptable Hb level may be accepted as blood donors. This study was aimed at determining the frequency of α-thalassemia 1 trait, β-thalassemia trait, and Hb E-related syndromes in Southern Thai blood donors. One hundred and sixteen voluntary blood donors, Southern Thailand origin, were recruited for thalassemia and Hb E screening by red blood cell indices/dichlorophenolindophenol precipitation test. β-Thalassemia and Hb E were then identified by high performance liquid chromatography and 4 common α-thalassemia deletions were characterized by a single tube-multiplex gap-polymerase chain reaction. Overall frequency of hemoglobinopathies was 12.9%, classified as follows: homozygous α-thalassemia 2 (1.7%), heterozygous α-thalassemia 1 (1.7%), heterozygous β-thalassemia without α-thalassemia (0.9%), heterozygous Hb E without α-thalassemia (5.2%), double heterozygotes for Hb E/α-thalassemia 1 (1.7%), homozygous Hb E without α-thalassemia (0.9%), and homozygous Hb E with heterozygous α-thalassemia 2 (0.9%). The usefulness of thalassemia screening is not only for receiving highly effective red blood cells in the recipients but also for encouraging the control and prevention program of thalassemia in blood donors. PMID:25050123

  16. Screening for Structural Hemoglobin Variants in Bahia, Brazil

    PubMed Central

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

    2016-01-01

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

  17. Optical mammography: bilateral breast symmetry in hemoglobin saturation maps.

    PubMed

    Anderson, Pamela G; Sassaroli, Angelo; Kainerstorfer, Jana M; Krishnamurthy, Nishanth; Kalli, Sirishma; Makim, Shital S; Graham, Roger A; Fantini, Sergio

    2016-10-01

    We present a study of the bilateral symmetry of human breast hemoglobin saturation maps measured with a broadband optical mammography instrument. We have imaged 21 patients with unilateral breast cancer, 32 patients with unilateral benign lesions, and 27 healthy patients. An image registration process was applied to the bilateral hemoglobin saturation (SO 2 SO2 ) images by assigning each pixel to the low, middle, or high range of SO 2 SO2 values, where the thresholds for the categories were the 15th and 85th percentiles of the individual saturation range. The Dice coefficient, which is a measure of similarity, was calculated for each patient’s pair of right and left breast SO 2 SO2 images. The invasive cancer patients were found to have an average Dice coefficient value of 0.55±0.07 0.55±0.07 , which was significantly lower than the benign and healthy groups (0.61±0.11 0.61±0.11 and 0.62±0.12 0.62±0.12 , respectively). Although differences were seen in a group analysis, the healthy patient Dice coefficients spanned a wide range, limiting the diagnostic capabilities of this SO 2 SO2 symmetry analysis on an individual basis. Our results suggest that for assessing the SO 2 SO2 contrast of breast lesions, it may be better to select a reference tissue in the ipsilateral rather than the contralateral breast. PMID:26849841

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

    PubMed

    Mollan, Todd L; Alayash, Abdu I

    2013-06-10

    In the last several years, significant work has been done studying hemoglobin (Hb) oxidative reactions and clearance mechanisms using both in vitro and in vivo model systems. One active research area involves the study of molecular chaperones and other proteins that are thought to mitigate the toxicity of acellular Hb. For example, the plasma protein haptoglobin (Hp) and the pre-erythroid protein alpha-hemoglobin-stabilizing protein (AHSP) bind to acellular Hb and alpha-subunits of Hb, respectively, to reduce these adverse effects. Moreover, there has been significant work studying hemopexin and alpha-1 microglobulin, both of which are thought to be involved with hemin degradation. These studies have coincided with the timely publication of the first crystal structure of the Hb-Hp complex. In constructing this Forum, we have invited a number of researchers in the area of Hb and myoglobin (Mb) redox biochemistry, as well as those who have contributed fundamentally to our knowledge of Hp function. Our goal has been to update this critically important research area, because we believe that it will ultimately impact the practice of transfusion medicine in a number of important ways. PMID:23330885

  19. Autofluorescence characterization of advanced glycation end products of hemoglobin

    NASA Astrophysics Data System (ADS)

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

    2005-01-01

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

  20. Interaction of recombinant octameric hemoglobin with endothelial cells.

    PubMed

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

    2015-02-01

    Hemoglobin-based oxygen carriers (HBOCs) may generate oxidative stress, vasoconstriction and inflammation. To reduce these undesirable vasoactive properties, we increased hemoglobin (Hb) molecular size by genetic engineering with octameric Hb, recombinant (r) HbβG83C. We investigate the potential side effects of rHbβG83C on endothelial cells. The rHbβG83C has no impact on cell viability, and induces a huge repression of endothelial nitric oxide synthase gene transcription, a marker of vasomotion. No induction of Intermolecular-Adhesion Molecule 1 and E-selectin (inflammatory markers) transcription was seen. In the presence of rHbβG83C, the transcription of heme oxygenase-1 (oxidative stress marker) is weakly increased compared to the two other HBOCs (references) or Voluven (control). This genetically engineered octameric Hb, based on a human Hb βG83C mutant, leads to little impact at the level of endothelial cell inflammatory response and thus appears as an interesting molecule for HBOC development. PMID:25543885