Physiologic differences in hemoglobin variants

1965 ◽  
Vol 208 (1) ◽  
pp. 198-202 ◽  
Author(s):  
Robert B. Thompson ◽  
Richard L. Warrington ◽  
Warren N. Bell
Keyword(s):  
Cord Blood ◽  
Whole Blood ◽  
Fold Increase ◽  
Twofold Increase ◽  
Hemoglobin A ◽  
Hb E ◽  
Hb S ◽  
Hemoglobin Variants

Studies were carried out on whole blood, concentrated hemoglobin solutions, and isolated hemoglobin fractions as related to oxygen association. In hemoglobins Ao, A1, Dalpha, GPhiladelphia, and C, no difference was found in the oxygen association curve. Hemoglobins A1, B2, and Lepore showed a 2½ fold increased oxygen association over normal Hb-A. Hemoglobin solutions from cord blood showed no difference from Hb-A, whereas cord blood showed a twofold increase. Hb-H and Hb-Barts showed identical oxygen association curves with a 10- to 12-fold increase over Hb-A; no heme-heme interaction and no Bohr was found with Hb-H or Barts. Hb-E and Hb-S showed a slight decrease in oxygen equilibria over hemoglobin A.

scholarly journals Hemoglobin variants and activity of the (K+Cl-) cotransport system in human erythrocytes

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 793-797 ◽  
Author(s):  
O Olivieri ◽  
D Vitoux ◽  
F Galacteros ◽  
D Bachir ◽  
Y Blouquit ◽  
...  
Keyword(s):  
Los Angeles ◽  
Beta Chain ◽  
San Jose ◽  
Hb E ◽  
Hb S ◽  
Cotransport System ◽  
Hemoglobin Variants ◽  
Residue Substitution ◽  
K Transport ◽  
Positively Charged

Abstract To determine if the activation of the (K+Cl-) cotransport system observed in hemoglobin (Hb) S- or C-containing erythrocytes is related either to a global change of isoelectric point of the Hb molecule or to the specific location of these mutations on the position 6 of the beta chain of Hb, we studied the (K+Cl-) cotransport system in erythrocytes containing beta chain variants exhibiting either the Glu----Lys substitution observed in position beta 6 in Hb C (Hb E: beta 26 Glu---- Lys; Hb O-Arab: beta 121 Glu----Lys; Hb Siriraj:beta 7 Glu----Lys) or the Glu----neutral residue substitution observed in position beta 6 in Hb S (Hb G-San Jose: beta 7 Glu----Gly; Hb D Punjab or D-Los Angeles: beta 121 Glu----Gln). The K transport mediated by the (K+Cl-) cotransport was increased in AC, AS and A-Siriraj and A-San Jose red blood cells and was similar to AA control in the other variants. These results indicate that an enhanced (K+Cl-) cotransport is not a property of all positively charged Hb variants, but it is mainly associated with mutations occurring at the beta 6 or beta 7 residues. An interaction of Hb with the cell membrane mediated by the disappearance of one of the negative charged residues (Glu) at this site of the A helix of the beta chain is the most likely candidate for the persistent activation of the (K+Cl-) cotransport system in these Hb variants.

scholarly journals Hemoglobin variants and activity of the (K+Cl-) cotransport system in human erythrocytes

Blood ◽  
1992 ◽  
Vol 79 (3) ◽  
pp. 793-797 ◽  
Author(s):  
O Olivieri ◽  
D Vitoux ◽  
F Galacteros ◽  
D Bachir ◽  
Y Blouquit ◽  
...  
Keyword(s):  
Los Angeles ◽  
Beta Chain ◽  
San Jose ◽  
Hb E ◽  
Hb S ◽  
Cotransport System ◽  
Hemoglobin Variants ◽  
Residue Substitution ◽  
K Transport ◽  
Positively Charged

To determine if the activation of the (K+Cl-) cotransport system observed in hemoglobin (Hb) S- or C-containing erythrocytes is related either to a global change of isoelectric point of the Hb molecule or to the specific location of these mutations on the position 6 of the beta chain of Hb, we studied the (K+Cl-) cotransport system in erythrocytes containing beta chain variants exhibiting either the Glu----Lys substitution observed in position beta 6 in Hb C (Hb E: beta 26 Glu---- Lys; Hb O-Arab: beta 121 Glu----Lys; Hb Siriraj:beta 7 Glu----Lys) or the Glu----neutral residue substitution observed in position beta 6 in Hb S (Hb G-San Jose: beta 7 Glu----Gly; Hb D Punjab or D-Los Angeles: beta 121 Glu----Gln). The K transport mediated by the (K+Cl-) cotransport was increased in AC, AS and A-Siriraj and A-San Jose red blood cells and was similar to AA control in the other variants. These results indicate that an enhanced (K+Cl-) cotransport is not a property of all positively charged Hb variants, but it is mainly associated with mutations occurring at the beta 6 or beta 7 residues. An interaction of Hb with the cell membrane mediated by the disappearance of one of the negative charged residues (Glu) at this site of the A helix of the beta chain is the most likely candidate for the persistent activation of the (K+Cl-) cotransport system in these Hb variants.

scholarly journals Hemoglobin Variants Influence Plasmodium Falciparum Sexual Differentiation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 965-965
Author(s):  
Bethany Flage ◽  
Matthew Dent ◽  
Jesús Tejero ◽  
Solomon Fiifi Ofori-Acquah
Keyword(s):  
Plasmodium Falciparum ◽  
Sexual Differentiation ◽  
Conflicts Of Interest ◽  
Causative Factor ◽  
Hemoglobin A ◽  
Conversion Rates ◽  
Significant Difference ◽  
Hb S ◽  
Hemoglobin Variants ◽  
Digestion Efficiency

Abstract It has long been recognized that individuals who express variations of the hemoglobin-A (HbA) protein experience less severe malaria disease. As malaria remains to be one of the most significant infectious diseases in history, this human adaptation has led to the persistence of HbA variants (HbVARs) in the population. The intricate lifecycle of the parasite which causes the most cases of clinical malaria, Plasmodium falciparum, relies on both asexual and sexual reproductive cycles, with host to vector transmission reliant on sexual stage gametocyte formation. Multiple epidemiological studies have shown that HbVARs may influence gametocyte production during P. falciparum infection, with greater gametocyte numbers reported in individuals with hemoglobin variant containing erythrocytes (Hb VAR-Ery) when compared to hemoglobin A containing erythrocytes (Hb A-Ery). Here we provide experimental support for these studies by showing significantly higher sexual differentiation rates among parasites grown in Hb S containing erythrocytes (Hb S-Ery) obtained from sickle cell patients than those differentiated in Hb A-Ery (p=0.038). Because the digestion of hemoglobin is such an integral part of the intraerythrocytic cycle, we then sought to determine whether there was a difference between the hydrolysis efficiencies of HbA and other hemoglobin variants (HbVAR). By using a prominent recombinant P. falciparum hemoglobinase we found the hydrolysis efficiency of HbA to be significantly (p=0.0058) more efficient after 24 hours compared to a HbVAR sample containing mixed amounts of HbA, HbF, and HbS. To further determine whether there is a link between hemoglobin digestion efficiency and sexual differentiation, we therapeutically inhibited the hemoglobin digestion and hemozoin formation process in a culture of P. falciparum using sub-optimal doses of chloroquine diphosphate. We found a significant difference (p<0.001) among gametocyte conversion rates between treated and non-treated cultures, as well as a moderate negative correlation between hemozoin formation and gametocyte conversion rate (Pearson r=0.72, p=0.008). Gene expression analysis also revealed patterns of expression that were consistent with increased gametocytogenesis. We conclude that hemoglobin type plays a significant role in the process of sexual conversion in P. falciparum. Though further studies should be completed in order to confirm these results, these findings may suggest hemoglobin digestion efficiency as a causative factor for sexual differentiation. As individuals with hemoglobinopathies make up approximately 7% of the global population, and malaria infection rates have been shown to differ depending on these genetic dynamics, these findings may support the creation of targeted initiatives to reduce transmission specifically in areas where there is a high percentage of hemoglobinopathy carriage. Disclosures No relevant conflicts of interest to declare.

Monitoring Anticoagulant Therapy by Activated Partial Thromboplastin Time: Hirudin Assessment

1994 ◽  
Vol 72 (05) ◽  
pp. 685-692 ◽  
Author(s):  
Michael T Nurmohamed ◽  
René J Berckmans ◽  
Willy M Morriën-Salomons ◽  
Fenny Berends ◽  
Daan W Hommes ◽  
...  
Keyword(s):  
Whole Blood ◽  
Partial Thromboplastin Time ◽  
Ex Vivo ◽  
Fold Increase ◽  
Heparin Therapy ◽  
Activated Partial Thromboplastin Time ◽  
Recombinant Hirudin ◽  
Interindividual Differences ◽  
The Relationship

SummaryBackground. Recombinant hirudin (RH) is a new anticoagulant for prophylaxis and treatment of venous and arterial thrombosis. To which extent the activated partial thromboplastin time (APTT) is suitable for monitoring of RH has not been properly evaluated. Recently, a capillary whole blood device was developed for bed-side monitoring of the APTT and it was demonstrated that this device was suitable to monitor heparin therapy. However, monitoring of RH was not evaluated.Study Objectives. To evaluate in vitro and ex vivo the responsiveness and reproducibility for hirudin monitoring of the whole blood monitor and of plasma APTT assays, which were performed with several reagents and two conventional coagulometers.Results. Large interindividual differences in hirudin responsiveness were noted in both the in vitro and the ex vivo experiments. The relationship between the APTT, expressed as clotting time or ratio of initial and prolonged APTT, and the hirudin concentration was nonlinear. A 1.5-fold increase of the clotting times was obtained at 150-200 ng/ml plasma. However, only a 2-fold increase was obtained at hirudin levels varying from 300 ng to more than 750 ng RH/ml plasma regardless of the assays. The relationship linearized upon logarithmic conversion of the ratio and the hirudin concentration. Disregarding the interindividual differences, and presuming full linearity of the relationship, all combinations were equally responsive to hirudin.Conclusions. All assays were equally responsive to hirudin. Levels up to 300 ng/ml plasma can be reliably estimated with each assay. The manual device may be preferable in situations where rapid availability of test results is necessary.

Abstract 3259: Leukocyte Subset Specific Gene Expression In Acute Stroke Patients

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Mateusz G Adamski ◽  
Yan Li ◽  
Hua Yu ◽  
Erin Wagner ◽  
Sareen Amarjeet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Stroke ◽  
Whole Blood ◽  
Peripheral Blood ◽  
Fold Increase ◽  
Specific Gene ◽  
Related Gene ◽  
Stroke Patients ◽  
Leukocyte Subset ◽  
Control Subjects

Background: Alterations in gene expression in the peripheral blood of patients with acute stroke have been demonstrated using microarray technology. Whole blood and peripheral blood mononuclear cells (PBMCs) were used in prior studies in which panels of genes diagnostic for stroke were developed. We aimed to determine the cellular sources of alterations in gene expression by studying individual leukocyte subsets. Methods: The expression of four genes previously found to be upregulated in ischemic and hemorrhagic stroke (IL1R2, S100A9, ETS2 and F5) was measured in four leukocyte subsets: CD14+ monocytes, CD4+ T cell lymphocytes, CD20+ B cell lymphocytes and PBMCs. These four genes had been reported in at least two of the previously published stroke-related gene panels. Peripheral blood was obtained from six acute stroke patients (all <48 hours from symptom onset) and 6 age, race and sex matched control subjects. Leukocytes were separated from whole blood using density gradient centrifugation and column magnetic bead cell sorting. The purity of separated leukocyte subsets exceeded 90% and was verified with flow cytometry. Messenger RNA was isolated from each leukocyte subset and analyzed by two step RT PCR and qPCR. The expression of the four stroke-related genes was compared to the expression of a housekeeping gene (GAPDH). The relative expression of individual genes and of the 4 gene panel within cellular subsets was compared between stroke patients and control subjects. Results: Individually, IL1R2 and S100A9 were significantly over-expressed in stroke patients with a 10 fold increase for IL1R2 in PBMCs (p<0.05) and a 3 fold increase for S100A9 in the CD4+ T and CD20+ B lymphocyte subsets (p<0.05). When analyzed as a panel of four genes the expression of IL1R2, S100A9, ETS2 and F5 was significantly higher in both the CD4+ T lymphocytes (p<0.05) and CD20+ B lymphocytes (p<0.05) of stroke patients but not in the monocytes or the PBMCs. Conclusion: These results show the potential diagnostic value of selected genes from panels previously found in microarray studies in stroke patients. They also emphasize the value of panel analysis over that of single gene expression and the potential cellular specificity of alterations in gene expression. Analysis of whole blood and PBMCs alone may not reflect important dynamic changes in stroke-related gene expression.

scholarly journals Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation

2017 ◽  
Author(s):  
John Dou ◽  
Rebecca J. Schmidt ◽  
Kelly S. Benke ◽  
Craig Newschaffer ◽  
Irva Hertz-Picciotto ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Blood Cell ◽  
Cord Blood ◽  
Whole Blood ◽  
Cell Types ◽  
Buffy Coat ◽  
Sample Type ◽  
Blood Samples ◽  
Cell Composition ◽  
Cell Counts

AbstractBackgroundCord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells by generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability.ObjectivesTo evaluate differences in cell composition and DNA methylation between buffy coat and whole cord blood samples.MethodsCord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in 8 individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition.ResultsDNA methylation PCs were associated with individual (PPC1=1.4x10-9; PPC2=2.9x10-5; PPC3=3.8x10-5; PPC4=4.2x10-6; PPC5=9.9x10-13), and not with sample type (PPC1-5>0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired individual samples ranged from r=0.66 to r=0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (5 sites had unadjusted P<10-5). Estimated cell type proportions did not differ by sample type (P=0.86), and estimated cell counts were highly correlated between paired samples (r=0.99).ConclusionsDifferences in methylation and cell composition between buffy coat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.

Lead Levels in Cord Blood

PEDIATRICS ◽  
1972 ◽  
Vol 49 (4) ◽  
pp. 606-608
Author(s):  
Paul Harris ◽  
Marshall R. Holley
Keyword(s):  
Cord Blood ◽  
Lead Poisoning ◽  
Whole Blood ◽  
Blood Lead ◽  
Mean Value ◽  
Diagnosis And Treatment ◽  
Normal Blood ◽  
Blood Lead Levels ◽  
Lead Levels ◽  
The Mean

Blood lead levels were determined on 24 mothers during labor and on the blood of their newborn offspring. The mean value for the mother's blood lead was 13.2 µg/100 gm (range 10 to 20) and for the cord blood 12.3 (range 10 to 20) µg/100 gm whole blood. These levels are lower than "normal" blood lead standards usually accepted in the diagnosis and treatment of childhood lead poisoning.

Carboxyhemoglobin Concentration in Fetal Cord Blood

PEDIATRICS ◽  
1983 ◽  
Vol 71 (3) ◽  
pp. 461-462
Author(s):  
R. HUCH ◽  
A. HUCH ◽  
P. TUCHSCHMID ◽  
W. G. ZIJLSTRA ◽  
A. ZWART
Keyword(s):  
Cord Blood ◽  
Whole Blood ◽  
Venous Blood ◽  
Fetal Blood ◽  
Multicomponent Analysis ◽  
Fetal Cord Blood ◽  
Blood Data

To the Editor.— Bureau et al1 reported that the concentration of carboxyhemoglobin (HbCO) is increased more than twofold in cord blood of newborns of smoking mothers as compared to corresponding values in maternal venous blood. Data were obtained from an IL 282 (Instrumentation Laboratory, Lexington) Co-oximeter, an instrument using spectroscopic multicomponent analysis of HbO2, Hb, MetHb, and HbCO in whole blood. We are concerned that the data presented are due to an artifact of HbCO measurement as the instrument used is not suitable for the correct measurement of HbCO concentrations in fetal blood.

Quantification of Drug-Induced mRNA in Human Whole Blood ex vivo

2008 ◽  
Vol 1 ◽  
pp. CMBD.S507 ◽  
Author(s):  
Masato Mitsuhashi ◽  
Katsuya Endo ◽  
Kazuhiko Obara ◽  
Hiroshi Izutsu ◽  
Taishi Ishida ◽  
...  
Keyword(s):  
Whole Blood ◽  
Kinase Inhibitor ◽  
Ex Vivo ◽  
Fold Increase ◽  
Drug Induced ◽  
Human Whole Blood ◽  
Cyclin Dependent Kinase Inhibitor ◽  
Sensitivity Tests ◽  
Data Points ◽  
Mrna Markers

Apoptosis was induced in heparinized human whole blood by 3 different ways (radiation, bleomycin, or etoposide), and various mRNA were quantified using the method we reported (Clin. Chem. 2006; 52:634-642). We found that cyclin-dependent kinase inhibitor 1A (p21) and p53 upregulated modulator of apoptosis (PUMA) were the most sensitive and universal mRNA markers of apoptosis in leukocytes. In order to define positive and negative responses, a synthetic RNA was spiked into the lysis buffer and the fold increase was calculated. As a result, 837/880 (95.1%) of data points stayed between 0.75 and 1.5 fold increase, and 874/880 (99.3%) were within 0.5-2.0 fold increase. When blood samples from 40 healthy adults were stimulated with 22 different drugs, more than 75% of the samples responded to bleomycin (1 μM), idarubicin (2 μM), vincristine (1 μM), daunorubicin (2 μM), cytarabine (10 μM), to induce p21 and/or PUMA mRNA, and approximately 25% showed no induction. Significant correlation was found between p21 and PUMA mRNA responses, and between daunorubicin and cytarabine, idarubicin, and vincristine for both p21 and PUMA. The quantification of drug-induced mRNA in whole blood will be considered as ex vivo, and is a suitable platform for biomarker screening as well as a model system for drug sensitivity tests in future.

Sign in / Sign up

Export Citation Format

Share Document