scholarly journals The transition from HK to LK phenotype in the red cells of newborn genetically LK lambs.

1982 ◽  
Vol 79 (5) ◽  
pp. 893-915 ◽  
Author(s):  
E M Tucker ◽  
C E Smalley ◽  
J C Ellory ◽  
P B Dunham
Keyword(s):  
Transport Properties ◽  
Developmental Process ◽  
Fetal Hemoglobin ◽  
Kinetic Studies ◽  
Red Cells ◽  
Small Cells ◽  
Adult Hemoglobin ◽  
K Concentration ◽  
Cell Volumes ◽  
K Transport

Red cells from newborn lambs were separated into different age populations by centrifugation, and cells with fetal hemoglobin (Hb) were distinguished from those with adult Hb by an acid elution technique. Changes were followed during development in rates of K+ transport (active and passive), numbers of Na+/K+ pump sites per cell, cell volumes, and numbers of Lp and L1 antigen sites per cell. These changes were correlated with the percentage of cells with adult hemoglobin. (The Lp and L1 antigens are associated with K+ transport in that specific alloantibody against Lp, anti-Lp, stimulates active transport, and anti-L1 inhibits passive transport.) Active K+ transport decreased during development because of a decline in number of Na+/K+ pumps (from measurements of ouabain binding) and because of an alteration in the affinity of the pumps for intracellular K+ (from kinetic studies in which the intracellular K+ concentration was varied). Cells with fetal Hb had fewer Lp sites and were larger than cells with adult Hb. As transport properties changed, the number of Lp sites increased and continued to increase after all the cells had adult Hb Cells with fetal Hb had as many L1 sites as lamb cells with adult Hb, but the number of L1 sites was less than those found previously for adult sheep. A population of small cells with intermediate K+ concentration and intermediate numbers of Lp sites appeared soon after birth. The various points of evidence suggested that the developmental process leading to cells with adult transport properties was a gradual one and did not coincide precisely with the switch from fetal to adult Hb.

scholarly journals Passive potassium transport in LK sheep red cells. Effects of anti-L antibody and intracellular potassium.

1976 ◽  
Vol 68 (6) ◽  
pp. 567-581 ◽  
Author(s):  
P B Dunham
Keyword(s):  
Maximum Velocity ◽  
Red Cells ◽  
Na Transport ◽  
Sheep Red Cells ◽  
The Common ◽  
K Concentration ◽  
Mode Of Transport ◽  
Low K ◽  
K Transport ◽  
External K

The passive K influx in low K(LK) red blood cells of sheep saturates with increasing external K concentration, indicating that this mode of transport is mediated by membrane-associated sites. The passive K influx, iMLK, is inhibited by external Na. Isoimmune anti-L serum, known to stimulate active K transport in LK sheep red cells, inhibits iMLK about twofold. iMLK is affected by changes in intracellular K concentration, [K]i, in a complex fashion: increasing [K]i from near zero stimulates iMLK, while further increases in [K]i, above 3 mmol/liter cells, inhibit iMLK. The passive K influx is not mediated by K-K exchange diffusion. The effects of anti-L antibody and [K]i on passive cation transport are specific for K: neither factor affects passive Na transport. The common characteristics of passive and active K influx suggest that iMLK is mediated by inactive Na-K pump sites, and that the inability to translocate Na characterizes the inactive pumps. Anti-L antibody stimulates the K pump in reticulocytes of LK sheep. However, anti-L has no effect on iMLK in these cells, apparently because reticulocytes do not have the inactive pump sites which, in mature LK cells, are a consequence of the process of maturation of circulating LK cells. The results also indicate that anti-L alters the maximum velocity of both active and passive K fluxes by converting pumps sites from a form mediating passive K influx to an actively transporting form.

scholarly journals Cytodifferentiation and Membrane Transport Properties in LK Sheep Red Cells

1966 ◽  
Vol 50 (2) ◽  
pp. 379-390 ◽  
Author(s):  
Ping Lee ◽  
Anna Woo ◽  
D. C. Tosteson
Keyword(s):  
Transport Properties ◽  
Membrane Transport ◽  
Gradient Centrifugation ◽  
Massive Bleeding ◽  
Massive Hemorrhage ◽  
Red Cells ◽  
Density Fractions ◽  
Before And After ◽  
Genetically Determined ◽  
K Transport

Young cells produced in LK sheep during rapid hematopoiesis after massive hemorrhage contain more K than the cells which are normally released into the circulation. The K content in these new cells falls to that characteristic of mature LK cells after a few days in the circulation. K transport properties in young and old cells before and after massive bleeding were studied. Young and old cells were separated by means of a density gradient centrifugation technique. Evidence showing that younger cells are found in the lower density fractions is presented. Active transport of K in the lightest fraction as measured by strophanthidin-sensitive influx was four to five times greater in red cells drawn 6 days after massive bleeding while the K leak as measured by strophanthidin-insensitive influx was only slightly larger. No change after bleeding was observed in older cells which had been present in the circulation prior to the hemorrhage. It is concluded that the high K content of young cells produced in LK sheep after bleeding is due to temporary retention of membrane K transport properties characteristic of HK cells. Thus, genetically determined modification of membrane transport properties has been shown to occur in nondividing circulating red cells.

scholarly journals Determinants of Erythrocyte Size in Chronic Liver Disease

Blood ◽  
1969 ◽  
Vol 34 (6) ◽  
pp. 739-746 ◽  
Author(s):  
THOMAS M. KILBRIDGE ◽  
PAUL HELLER
Keyword(s):  
Bone Marrow ◽  
Liver Disease ◽  
Chronic Liver Disease ◽  
Peripheral Blood ◽  
Hepatic Cirrhosis ◽  
Alcoholic Cirrhosis ◽  
Clinical Findings ◽  
Red Cells ◽  
Red Cell ◽  
Cell Volumes

Abstract Serial determinations of red cell volumes were made with an electronic sizing device in 30 patients with hepatic cirrhosis. Variations in red cell volumes were correlated with other hematologic and clinical findings. The results of these studies suggest that volume macrocytosis in patients with alcoholic cirrhosis is either due to megaloblastosis of the bone marrow or to an accelerated influx of young red cells into the peripheral blood.

scholarly journals Understanding heterogeneity of fetal hemoglobin induction through comparative analysis of F and A erythroblasts

Blood ◽  
2020 ◽  
Vol 135 (22) ◽  
pp. 1957-1968 ◽  
Author(s):  
Eugene Khandros ◽  
Peng Huang ◽  
Scott A. Peslak ◽  
Malini Sharma ◽  
Osheiza Abdulmalik ◽  
...  
Keyword(s):  
Fetal Hemoglobin ◽  
Erythroid Cell ◽  
Transcriptional Level ◽  
Globin Genes ◽  
Proteomic Profiling ◽  
A Cells ◽  
F Cells ◽  
Adult Hemoglobin ◽  
Differentiation Stage ◽  
Developmental Switch

Abstract Reversing the developmental switch from fetal hemoglobin (HbF, α2γ2) to adult hemoglobin (HbA, α2β2) is an important therapeutic approach in sickle cell disease (SCD) and β-thalassemia. In healthy individuals, SCD patients, and patients treated with pharmacologic HbF inducers, HbF is present only in a subset of red blood cells known as F cells. Despite more than 50 years of observations, the cause for this heterocellular HbF expression pattern, even among genetically identical cells, remains unknown. Adult F cells might represent a reversion of a given cell to a fetal-like epigenetic and transcriptional state. Alternatively, isolated transcriptional or posttranscriptional events at the γ-globin genes might underlie heterocellularity. Here, we set out to understand the heterogeneity of HbF activation by developing techniques to purify and profile differentiation stage-matched late erythroblast F cells and non–F cells (A cells) from the human HUDEP2 erythroid cell line and primary human erythroid cultures. Transcriptional and proteomic profiling of these cells demonstrated very few differences between F and A cells at the RNA level either under baseline conditions or after treatment with HbF inducers hydroxyurea or pomalidomide. Surprisingly, we did not find differences in expression of any known HbF regulators, including BCL11A or LRF, that would account for HbF activation. Our analysis shows that F erythroblasts are not significantly different from non-HbF–expressing cells and that the primary differences likely occur at the transcriptional level at the β-globin locus.

scholarly journals Increased nitrite reductase activity of fetal versus adult ovine hemoglobin

2009 ◽  
Vol 296 (2) ◽  
pp. H237-H246 ◽  
Author(s):  
Arlin B. Blood ◽  
Mauro Tiso ◽  
Shilpa T. Verma ◽  
Jennifer Lo ◽  
Mahesh S. Joshi ◽  
...  
Keyword(s):  
Nitrite Reductase ◽  
Chronic Hypoxia ◽  
Reductase Activity ◽  
Fetal Hemoglobin ◽  
Nitrite Reduction ◽  
No Production ◽  
Low Oxygen ◽  
Nitrite Reductase Activity ◽  
Adult Hemoglobin ◽  
Severe Ischemia

Growing evidence indicates that nitrite, NO2−, serves as a circulating reservoir of nitric oxide (NO) bioactivity that is activated during physiological and pathological hypoxia. One of the intravascular mechanisms for nitrite conversion to NO is a chemical nitrite reductase activity of deoxyhemoglobin. The rate of NO production from this reaction is increased when hemoglobin is in the R conformation. Because the mammalian fetus exists in a low-oxygen environment compared with the adult and is exposed to episodes of severe ischemia during the normal birthing process, and because fetal hemoglobin assumes the R conformation more readily than adult hemoglobin, we hypothesized that nitrite reduction to NO may be enhanced in the fetal circulation. We found that the reaction was faster for fetal than maternal hemoglobin or blood and that the reactions were fastest at 50–80% oxygen saturation, consistent with an R-state catalysis that is predominant for fetal hemoglobin. Nitrite concentrations were similar in blood taken from chronically instrumented normoxic ewes and their fetuses but were elevated in response to chronic hypoxia. The findings suggest an augmented nitrite reductase activity of fetal hemoglobin and that the production of nitrite may participate in the regulation of vascular NO homeostasis in the fetus.

K+ transport across the lamprey erythrocyte membrane: characteristics of a Ba(2+)- and amiloride-sensitive pathway

1991 ◽  
Vol 159 (1) ◽  
pp. 303-324 ◽  
Author(s):  
K. Kirk
Keyword(s):  
Membrane Potential ◽  
Erythrocyte Membrane ◽  
Inhibitory Effect ◽  
Extracellular Ph ◽  
Transport Pathway ◽  
Full Effect ◽  
River Lamprey ◽  
K Concentration ◽  
86Rb Influx ◽  
K Transport

The characteristics of K+ transport in erythrocytes from the river lamprey (Lampetra fluviatilis) were investigated using standard radioisotope flux techniques. The cells were shown to have a ouabain-sensitive transport pathway that carried 43K+ and 86Rb+ into the cell at similar rates. Most of the ouabain-resistant 43K+ and 86Rb+ influx was via a pathway that was insensitive to cotransport inhibitors and to the replacement of extracellular Cl- or Na+. This pathway showed a strong selectivity for 43K+ over 86Rb+. It was inhibited fully by Ba2+ (I50 approximately 2.8 mumol l-1), amiloride (I50 approximately 150 mumol l-1) and ethylisopropylamiloride (I50 approximately 3.3 mumol l-1) and less effectively by quinine and by the tetraethylammonium ion. Inhibition by Ba2+ took full effect within a few minutes whereas the full inhibitory effect of amiloride took more than 1 h to develop. Experiments with the membrane potential probe [14C]tetraphenylphosphonium ion gave results consistent with the lamprey erythrocyte membrane having a Ba(2+)-sensitive K+ conductance that was significantly greater than the membrane Na+ conductance and which gave rise to a marked dependence of the membrane potential on the extracellular K+ concentration. The rate constants for Ba(2+)-sensitive 43K+ and 86Rb+ influx decreased (proportionally) with increasing extracellular K+ concentration in a manner that was consistent with the transport being via a conductive pathway. The decrease was attributed to a depolarisation of the membrane (in response to the increasing extracellular K+ concentration) and a consequent decrease in the driving force for the conductive movement of 43K+ and 86Rb+ into the cells. Ba(2+)-sensitive 86Rb+ influx increased significantly with decreasing cell volume and with increasing intracellular pH (at a constant extracellular pH) but increased only slightly with increasing extracellular pH. The pathway operated normally in the complete absence of extracellular Ca2+ but its activity decreased in cells pretreated with ionomycin and EGTA; this suggests a role for intracellular Ca2+ in the operation of the pathway.

scholarly journals Glycerol-3-phosphate dehydrogenase activity in the red cells of patients with thalassemia

Blood ◽  
1980 ◽  
Vol 55 (4) ◽  
pp. 564-569
Author(s):  
P Fessas ◽  
NP Anagnou ◽  
D Loukopoulos
Keyword(s):  
Cord Blood ◽  
Fetal Hemoglobin ◽  
Thalassemia Major ◽  
Red Cells ◽  
Beta Thalassemia ◽  
Gamma Chain ◽  
Cord Blood Cells ◽  
Chain Synthesis ◽  
Glycerol 3 Phosphate Dehydrogenase ◽  
Normal Adults

L-alpha-Glycerol-3-phosphate dehydrogenase (EC 1.1.1.8) has been reported to be absent in the erythrocytes of normal adults, but can be found in those of cord blood and of thalassemia major. The aid of this study was to investigate whether there is any relation between GDH and gamma-chain synthesis. Erythrocyte GDH activity was determined on 118 different blood samples. It was undetectable in normal adult erythrocytes and definitely high in cord blood cells (23.6 UI/10(11) RBC). Considerable GDH activity was also noted in patients with thalassemia major (11.0 IU10(11) RBC) as well as in cases with pronounced reticulocytosis (11.4 IU/10(11) RBC). Red cells from beta- thalassemia heterozygotes exhibited moderate but distinct GDH activity (5.2 IU/10(11) RBC). After fractionation into young and old erythrocyte populations, clearly higher GDH activity was found in the younger cells; however, there was no significant correlation with the reticulocyte count. Presence of reticulocytes alone appears insufficient to explain the values obtained in cord blood and the thalassemias, especially heterozygous. Furthermore, no direct correlation between GDH and fetal hemoglobin (HbF) was obtained in cord and thalassemic erythrocytes.

The effect of replacing fetal hemoglobin with adult hemoglobin on blood gas and acid-base parameters in human fetuses

1988 ◽  
Vol 158 (1) ◽  
pp. 66-69 ◽  
Author(s):  
Peter W. Soothill ◽  
Kypros H. Nicolaides ◽  
Charles H. Rodeck ◽  
Authony J. Bellingham
Keyword(s):  
Fetal Hemoglobin ◽  
Human Fetuses ◽  
Blood Gas ◽  
Acid Base ◽  
Base Parameters ◽  
Adult Hemoglobin

Relative Rates of Fetal Hemoglobin and Adult Hemoglobin Synthesis in Cord Blood of Infants of Insulin-Dependent Diabetic Mothers

PEDIATRICS ◽  
1985 ◽  
Vol 75 (6) ◽  
pp. 1143-1147 ◽  
Author(s):  
Harry Bard ◽  
Janie Prosmanne
Keyword(s):  
Newborn Infants ◽  
Methyl Cellulose ◽  
Fetal Hemoglobin ◽  
Acid Mixture ◽  
Hemoglobin Synthesis ◽  
Infants Of Diabetic Mothers ◽  
Insulin Dependent ◽  
Adult Hemoglobin ◽  
Insulin Dependent Diabetic ◽  
Diabetic Mothers

Erythrocytosis, extramedullary erythropoiesis, and increased levels of plasma erythropoietin have been observed in newborn infants of diabetic mothers. Because there is evidence that there is a relationship between increased fetal hemoglobin production and acute erythropoietic expansion, it was considered important to study the proportion of fetal hemoglobin and adult hemoglobin synthesis in newborn infants of insulin-dependent diabetic mothers. Samples from nine newborn infants of diabetic mothers as well as nine control infants, ranging from 36 to 38 weeks of gestation, were incubated in an amino acid mixture containing [14C]leucine. The adult hemoglobin and fetal hemoglobin were then separated by column chromatography on DEAE [O-(diethylaminoethyl)] Sephadex. To confirm that the fetal hemoglobin obtained after Sephadex chromatography was not contaminated with other hemoglobins, several of the DEAE separations from each group were reconstituted and subjected to polypeptide chain elution using carboxyl-methyl cellulose chromatography. The data demonstrated that the newborn infants of diabetic mothers are synthesizing significantly more fetal hemoglobin than is expected for their period of development (82.2 ± 3.6 v 72.8 ± 4.2; P < .005). It is suggested that the in utero environment of the fetus of the diabetic mother causes an increase in fetal hemoglobin synthesis.

scholarly journals The effect of alpha-thalassemia on the expression of the beta- thalassemia/HPFH heterozygote in a black family

Blood ◽  
1981 ◽  
Vol 57 (6) ◽  
pp. 1132-1134 ◽  
Author(s):  
E Beutler ◽  
E Turner ◽  
W Kuhl
Keyword(s):  
Black Family ◽  
Clinical Manifestations ◽  
Fetal Hemoglobin ◽  
Pedigree Analysis ◽  
Red Cells ◽  
Beta Thalassemia ◽  
Hemoglobin Gene ◽  
Alpha Thalassemia ◽  
Alpha Globin ◽  
Hereditary Persistence

Abstract A 2-yr-old black girl presented with a thalassemic clinical picture and was found to have nearly 100% fetal hemoglobin in her red cells. Pedigree analysis indicated that she was a heterozygote for the hereditary persistence of fetal hemoglobin gene and for a beta O- thalassemia gene. A brother, who also had nearly 100% fetal hemoglobin in his red cells, manifested, in contrast to his sister, no anemia and only minimal splenomegaly. Examination of the family's alpha-globin loci using the restriction endonuclease Eco Rl demonstrated that the brother had a single alpha-locus deletion that he had inherited from his mother. The mild clinical manifestations of this boy are consistent with the often expressed view that excess alpha chains may contribute significantly to the hematologic manifestation of beta-thalassemia.

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