Effect of Androgens on the Red Cell 2, 3 Diphosphoglycerate Hemoglobin Oxygen Affinity and Red Cell Mass in Mammals

1974 ◽  
Vol 147 (3) ◽  
pp. 616-618 ◽  
Author(s):  
D. Gorshein ◽  
F. A. Oski ◽  
M. Delivoria-Papadopoulos
Blood ◽  
1972 ◽  
Vol 39 (3) ◽  
pp. 398-406 ◽  
Author(s):  
Frank G. de Furia ◽  
Denis R. Miller

Abstract Oxygen affinity studies in a splenectomized patient with sporadically occurring Hb Köln disease revealed high whole blood oxygen affinity (P50 O2 17.6 mm Hg) with increased 2, 3-diphosphoglycerate (DPG), low ATP, and normal RBC ΔpH. Isolated electrophoretically slow migrating Hb Köln had a high oxygen affinity, decreased Hill’s number, and normal DPG reactivity. Functional evidence for hybrid tetramers with normal mobility is presented. Partial deoxygenation may play a role in the denaturation of the Hb Köln molecule and thus account for a higher oxygen affinity (low P50 O2), measured by the mixing technique, than the actual values for P50 that exist in vivo. Increased oxygen affinity and decreased P50 O2 would result in increased erythropoiesis and account for a well-compensated hemolytic process in this patient with a normal red cell mass and normal values of hemoglobin.


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3730-3730
Author(s):  
Ghislain Cournoyer ◽  
Harry Bard ◽  
Xiaoduan Weng ◽  
Louise Robin ◽  
Carmen Gagnon ◽  
...  

Abstract Introduction: A 38-year-old causasian male with hepatomegaly, splenomegaly and erythrocytosis (Ht 69.2%, Hb 217 g/L, MCV 76fl, normal WBC and platelets counts) presented with flank pain found to be a renal artery thrombosis. He had a history of increased Ht since birth without bone marrow (BM), cardiac, pulmonary, renal or cerebral anomalies and for which a diagnosis of a high oxygen affinity hemoglobinopathy was made. The disease had previously been uncomplicated without therapy. Initial evaluation in our center revealed a normal BM morphology, a normal karyotype and an abnormal Hb HPLC (elevated HbF (4.9%) and an abnormal Hb eluting after normal HbA1). The red cell mass was increased at 74.9 ml/kg (normal = 26.5 ml/kg). The oxygen (O2) P50 saturation determined from the Hb-O2 dissociation curve using an Hemox-Analyser was markedly decreased at 6 mmHg (normal = 27 mmHg). α and β globins (gb) HPLC demonstrated normal α, but 100% abnormal β-gb. A diagnosis of a double heterozygote for β-gb gene was established: an allele with mutation causing high affinity for O2 and an allele causing β-thalassemia (thal) minor. Anticoagulation and serial phlebotomies did not improve the erythrocytosis. Therapy with hydroxyurea (HU) was therefore proposed to the patient. Objectives: To determine the β-gb genotype and to evaluate the effect of HU therapy at maximally tolerated dose (MTD) on induction of HbF and its effect on Ht, P50, red cell mass, 2,3-DPG and total HbNO concentrations. Methods and results: Sequencing of the β-gb locus was done by RT-PCR amplified mRNA and by PCR amplified DNA, using primers spanning almost the entire gene (−450 to 601 bp, excluding a small portion of IVS2). Two mutations were identified: Leu96→Val (339C→G) in exon 2, producing Hb Regina, a high O2 affinity hemoglobin variant, and IVS1-110 G/A, a frequent mutation causing β-thal minor. Therapy with HU was initiated at 7 mg/kg/day. Dose was increased to MTD resulting in a dose of 25 mg/kg/day. Table 1 summarizes variations in relevant parameters while on HU therapy. Conclusion: HU rapidly induced HgF and improved measured parameters in this patient with a high O2 affinity Hb/β-thal minor. HU’s effect in this case did not seem to be strictly related to its anti-proliferation properties. Induction of HbF and subsequent increase in P50 probably reduced Epo production (data pending) and erythropoiesis. Modifications in other mediators of O2 release were also modified by HU. The changes in HbNO are not totally consistant with the rest of the data, being increased at 3 months but decreased at 6 months. While on HU therapy, the patient did not present any new complications (thrombotic or other) and clinically reported an improved exercise tolerance. Further evaluation will focus on epigenetic factors affecting HbF expression and correlation of NO level with plasma L-arginine concentration. Time HU dose (mg/kg) Ht (%) HbF (%) P50 (mm/Hg) 2,3-DPG (umol/g Hb) Total HbNO (nM) Red cell mass (ml/kg) NA: not available, TBD: to be determined Baseline 0 61.1 3.6 6 21.3 242.7 74.9 3 months 21 69.4 9.1 6 19.0 694.3 NA 6 months 25 56.9 15.1 9 21.4 105.8 NA 8 months 25 46.7 25.4 TBD TBD TBD 51.7


1979 ◽  
Vol 237 (1) ◽  
pp. H71-H75 ◽  
Author(s):  
P. A. Mueggler ◽  
J. S. Peterson ◽  
R. D. Koler ◽  
J. Metcalfe ◽  
J. A. Black

Hematologic parameters influencing tissue oxygen delivery in dogs during the first 4 mo of life have been investigated. The rapid growth and increase in body temperature during this period imply an increased metabolic rate and increased tissue oxygen demand. Hemoglobin concentration and hematocrit decrease during the 1st mo following birth. The total red cell mass does not decrease during this period. The observed hemodilution can be attributed to an increasing plasma volume in the growing animal. The blood oxygen affinity decreases during this same period, resulting in a more effective tissue oxygen delivery. Erythropoiesis, as estimated from the percent circulating reticulocytes, decreases following birth and does not increase until 1 mo of postnatal life. The increase of erythropoietic activity during the 2nd mo of postnatal life coincides with an increase in red cell mass, hematocrit, and hemoglobin concentration.


1999 ◽  
Vol 55 (2) ◽  
pp. 101-104 ◽  
Author(s):  
M. M. R. Young ◽  
L. Squassante ◽  
J. Wemer ◽  
S. P. van Marle ◽  
P. Dogterom ◽  
...  
Keyword(s):  
Red Cell ◽  

2000 ◽  
Vol 26 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Ingrid Balga ◽  
Max Solenthaler ◽  
Miha Furlan
Keyword(s):  
Red Cell ◽  

2005 ◽  
Vol 129 (1) ◽  
pp. 89-91 ◽  
Author(s):  
Mordechai Lorberboym ◽  
Naomi Rahimi-Levene ◽  
Helena Lipszyc ◽  
Chun K. Kim

Abstract Context.—Polycythemia describes an increased proportion of red blood cells in the peripheral blood. In absolute polycythemia, there is increased red cell mass (RCM) with normal plasma volume, in contrast with apparent polycythemia, in which there is increased or normal RCM and decreased plasma volume. In order to deliver the appropriate treatment it is necessary to differentiate between the two. Objective.—A retrospective analysis of RCM and plasma volume data are presented, with special attention to different methods of RCM interpretation. Design.—The measurements of RCM and plasma volume in 64 patients were compared with the venous and whole-body packed cell volume, and the incidence of absolute and apparent polycythemia was determined for increasing hematocrit levels. Measurements of RCM and plasma volume were performed using chromium 51–labeled red cells and iodine 125–labeled albumin, respectively. The measured RCM of each patient was expressed as a percentage of the mean expected RCM and was also defined as being within or outside the range of 2 SD of the mean. The results were also expressed in the traditional manner of mL/kg body weight. Results.—Twenty-one patients (13 women and 8 men) had absolute polycythemia. None of them had an increased plasma volume beyond 2 SD of the mean. When expressed according to the criteria of mL/kg body weight, 17 of the 21 patients had abnormally increased RCM, but 4 patients (19%) had a normal RCM value. Twenty-eight patients had apparent polycythemia. The remaining 15 patients had normal RCM and plasma volume. Conclusions.—The measurement of RCM and plasma volume is a simple and necessary procedure in the evaluation of polycythemia. In obese patients, the expression of RCM in mL/kg body weight lacks precision, considering that adipose tissue is hypovascular. The results of RCM are best described as being within or beyond 2 SD of the mean value.


1996 ◽  
Vol 270 (1) ◽  
pp. H121-H126 ◽  
Author(s):  
J. K. Shoemaker ◽  
H. J. Green ◽  
J. Coates ◽  
M. Ali ◽  
S. Grant

The purpose of this study was to investigate the time-dependent effects of long-term prolonged exercise training on vascular volumes and hematological status. Training using seven untrained males [age 21.1 +/- 1.4 (SE) yr] initially consisted of cycling at 68% of peak aerobic power (VO2peak) for 2 h/day, 4-5 days/wk, for 11 wk. Absolute training intensity was increased every 3 wk. Red cell mass (RCM), obtained using 51Cr, was unchanged (P > 0.05) with training (2,142 +/- 95, 2,168 +/- 86, 2,003 +/- 112, and 2,080 +/- 116 ml at 0, 3, 6, and 11 wk, respectively) as were serum erythropoietin levels (17.1 +/- 4.3, 13.9 +/- 3.5, and 17.0 +/- 2.0 U/l at 0, 6, and 11 wk, respectively). Plasma volume measured with 125I-labeled albumin and total blood volume (TBV) were also not significantly altered. The increase in mean cell volume that occurred with training (89.7 +/- 0.95 vs. 91.0 +/- 1.0 fl, 0 vs. 6 wk, P < 0.05) was not accompanied by changes in either mean cell hemoglobin or mean cell hemoglobin concentration. Serum ferritin was reduced 73% with training (67.4 +/- 13 to 17.9 +/- 1 microgram/l, 0 vs. 11 wk, P < 0.05). Total hemoglobin (HbTot) calculated as the product of hemoglobin concentration and TBV was unaltered (P > 0.05) at both 6 and 11 wk of training. The 15% increase in VO2peak (3.39 +/- 0.16 to 3.87 +/- 0.14 l/min, 0 vs. 11 wk, P < 0.05) with training occurred despite a failure of training to change TBV, RCM, or HbTot.


1972 ◽  
Vol 54 (5) ◽  
pp. 1001-1014 ◽  
Author(s):  
P. E. BIRON ◽  
J. HOWARD ◽  
M. D. ALTSCHULE ◽  
C. R. VALERI

Blood ◽  
1964 ◽  
Vol 24 (6) ◽  
pp. 726-738 ◽  
Author(s):  
J. H. JEPSON ◽  
L. LOWENSTEIN

Abstract The effect of prolactin, growth hormone, progesterone, testosterone, lactating mouse plasma (fifth postpartum day), pregnant mouse plasma (sixteenth to nineteenth day of pregnancy) on erythropoiesis in the polycythemic mouse has been studied and compared. Prolactin was found to stimulate erythropoiesis in the intact mouse. Also, pregnant mouse plasma and lactating mouse plasma had an erythropoietic stimulating effect. Prolactin produced an increase in the red cell mass when administered over a prolonged period to normal and orchidectomized mice. This suggests that the testes are not necessary for the action of prolactin. It is suggested that prolactin could function as an erythropoietic stimulatory component in pregnant and lactating mouse plasma.


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