scholarly journals The Dpg gene: an intracorpuscular modifier of red cell metabolism

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1210-1214
Author(s):  
NA Noble ◽  
G Rothstein

The genetic locus designated Dpg has two alleles in outbred Long-Evans rats. Genotype at this locus affects quantities of red cell 2,3- diphosphoglycerate (DPG) and adenosine triphosphate, as well as activities of two important glycolytic enzymes: phosphofructokinase and pyruvate kinase. Intravascular red cell survival is shortened in low- DPG animals. In order to get closer to the specific action of this locus, we addressed the question of whether the Dpg gene acts through intracorpuscular or extracorpuscular factors. Bone marrow transplantation after total body irradiation and 51Cr red cell survival after cross transfusion were the methods used. Because the animals that were used differed in hemoglobin phenotype, donor and recipient cells could be quantified in cross-transplanted animals. Phenotypic markers of Dpg genotype were measured in animals 40 to 50 days after transplantation. Values for these markers correlated highly with the percentage of donor and recipient cells present. In vivo survival of low-DPG red cells was significantly shorter than that of high-DPG cells (P less than .05), regardless of the genotype of the recipient. From the present studies, we conclude that the action of the Dpg gene is exerted by an intracorpuscular factor.

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1210-1214 ◽  
Author(s):  
NA Noble ◽  
G Rothstein

Abstract The genetic locus designated Dpg has two alleles in outbred Long-Evans rats. Genotype at this locus affects quantities of red cell 2,3- diphosphoglycerate (DPG) and adenosine triphosphate, as well as activities of two important glycolytic enzymes: phosphofructokinase and pyruvate kinase. Intravascular red cell survival is shortened in low- DPG animals. In order to get closer to the specific action of this locus, we addressed the question of whether the Dpg gene acts through intracorpuscular or extracorpuscular factors. Bone marrow transplantation after total body irradiation and 51Cr red cell survival after cross transfusion were the methods used. Because the animals that were used differed in hemoglobin phenotype, donor and recipient cells could be quantified in cross-transplanted animals. Phenotypic markers of Dpg genotype were measured in animals 40 to 50 days after transplantation. Values for these markers correlated highly with the percentage of donor and recipient cells present. In vivo survival of low-DPG red cells was significantly shorter than that of high-DPG cells (P less than .05), regardless of the genotype of the recipient. From the present studies, we conclude that the action of the Dpg gene is exerted by an intracorpuscular factor.


Blood ◽  
1972 ◽  
Vol 40 (5) ◽  
pp. 733-739 ◽  
Author(s):  
Blanche P. Alter ◽  
Yuet Wai Kan ◽  
David G. Nathan

Abstract Cyanate prevents sickling in vitro and apparently prolongs the survival of 51Cr-tagged sickle erythrocytes in vivo. Cautious interpretation is required because the effects of cyanate on 51Cr binding to sickle and fetal hemoglobin-containing red cells are unknown, and comparison of the effect of cyanate on sickle red cell survival to control red cell survival must be performed sequentially. We have studied the survival of sickle reticulocytes utilizing radioactive amino acids that are incorporated into hemoglobin. Two informed adult patients with sickle cell disease were studied. In each study, two 50-ml samples of blood were incubated separately with 14C- and 3H-leucine for 2 hr, after which 50 mM cyanate was added to one aliquot for 1 hr. The cells were then washed and reinfused. Frequent venous samples were obtained, and the specific activities of 14C and 3H in the hemoglobin were followed. The t ½ of the carbamylated cells was tripled, but remained below normal. This method provides a generally useful measurement of the influence of drugs bound to red cells on reticulocyte lifespan. The labels are incorporated into the hemoglobin molecule of the reticulocyte, and simultaneous comparison of the survivals of the same cohort of drug-treated and control cells is achieved.


1997 ◽  
Vol 7 (1) ◽  
pp. 25-28 ◽  
Author(s):  
F. Regan ◽  
P. Teesdale ◽  
S. Garner ◽  
T. Callaghan ◽  
M. Brennan ◽  
...  

Transfusion ◽  
1985 ◽  
Vol 25 (1) ◽  
pp. 34-38 ◽  
Author(s):  
ML Baldwin ◽  
PM Ness ◽  
C Barrasso ◽  
TS Kickler ◽  
H Drew ◽  
...  

Blood ◽  
1980 ◽  
Vol 55 (1) ◽  
pp. 55-60 ◽  
Author(s):  
RD Propper ◽  
LN Button ◽  
DG Nathan

Recent advances in the treatment of patients with thalassemia major have centered around the removal of iron from individuals already overloaded due to repeated transfusions. In this report we present therapeutic maneuvers designed to decrease the rate of iron accumulation. We demonstrate that the persistent maintenance of hematocrits above 35% (“supertransfusion”) is not associated with an increased transfusion requirement because it produces a decrease in whole blood volume (21% +/- 2%). Supertransfusion is also associated with normalization or even prolongation of plasma iron turnover. In addition, we describe a method for obtaining units of blood from normal donors that contain primarily young red cells (“neocytes”). These cells have prolonged in vivo survival as measured by the interval between transfusions (30 +/- 2.5 days to 43 +/- 4.5 days) and 51Cr red cell survival (43.8 days versus 27.8 days). Supertransfusion with neocytes is effective in decreasing the rate of iron accumulation in thalassemia.


Blood ◽  
1975 ◽  
Vol 46 (2) ◽  
pp. 253-259 ◽  
Author(s):  
E Beutler

Abstract Carbon monoxide at a concentration of 1000–2000 ppm was administered to sickle cell disease patients. In each of two patients, one 51Cr red cell survival study was carried out before CO administration, and a second study was initiated a few days before CO administration was started. In both, significant prolongation of red cell survival was observed, suggesting that the rheologic properties of sickle cells were favorably influenced in vivo. The administration of carbon monoxide is not recommended as a treatment for sickle cell disease. However, further trials would seem to be justified if conducted under carefully controlled conditions.


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