scholarly journals Metabolic effects of antisickling amounts of nitrogen and nor-nitrogen mustard on rabbit and human erythrocytes

Blood ◽  
1975 ◽  
Vol 45 (6) ◽  
pp. 779-788 ◽  
Author(s):  
EF Jr Roth ◽  
RL Nagel ◽  
G Neuman ◽  
G Vanderhoff ◽  
BH Kaplan ◽  
...  
Keyword(s):  
Cell Survival ◽  
Glutathione Reductase ◽  
Nitrogen Mustard ◽  
Sulfhydryl Group ◽  
Red Cells ◽  
Metabolic Effects ◽  
Red Cell ◽  
Metabolic Studies ◽  
Heinz Body ◽  
Red Cell Survival

Abstract Nitrogen mustard (NH2) and Nor-nitrogen mustard (Nor-HN2) both inhibit the polymerization of deoxyhemoglobin S in solution and in intact erythrocytes. Metabolic studies were undertaken to determine the feasability of an extracorporeal treatment with these or related agents. Glucose utilization, hexose monophosphate shunt activity, methemoglobin reduction, and incubation with acetylphenylhydrazine for Heinz body formation were performed, as well as specific assays for hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glutathione reductase, ATP, reduced glutathione (GSH), and survival of autologous mustard-treated cells in rabbits. HN2 was found to enter red cells rapidly and bind to intracellular contents. Metabolic studies revealed no significant inhibition or alteration of function by Nor-HN2 at 10 mg/ml of whole blood. Rabbit red cell survival was also normal. HN2, however, inhibited glutathione reductase and blocked the free sulfhydryl group of GSH by forming serveral addition products of alkylated GSH. Heinz body test with acetylphenylhydrazine became positive in HN2-treated cells, and rabbit red cell survival was shortened considerably in the concentration range used to inhibit sickling. Ascorbic acid stimulation of the hexose shunt pathway was inhibited by HN2, but methylene blue stimulation remained unaffected. 14-C-HN2 remains bound to red cells in vivo, and the disappearance of radioactivity is similar to that found with 14-C-DFP (disopropylfluorophosphate). Oxygen affinity of both HN2 and Nor-HN2 treated human red cells remains virtually the same as that found in control samples. It is concluded that Nor-HN2 may be a suitable agent for an extracorporeal therapy, and that each mustard needs to be evaluated individually for its antisickling effects and its suitability for extracorporeal use.

scholarly journals Metabolic effects of antisickling amounts of nitrogen and nor-nitrogen mustard on rabbit and human erythrocytes

Blood ◽  
1975 ◽  
Vol 45 (6) ◽  
pp. 779-788
Author(s):  
EF Jr Roth ◽  
RL Nagel ◽  
G Neuman ◽  
G Vanderhoff ◽  
BH Kaplan ◽  
...  
Keyword(s):  
Cell Survival ◽  
Glutathione Reductase ◽  
Nitrogen Mustard ◽  
Sulfhydryl Group ◽  
Red Cells ◽  
Metabolic Effects ◽  
Red Cell ◽  
Metabolic Studies ◽  
Heinz Body ◽  
Red Cell Survival

Nitrogen mustard (NH2) and Nor-nitrogen mustard (Nor-HN2) both inhibit the polymerization of deoxyhemoglobin S in solution and in intact erythrocytes. Metabolic studies were undertaken to determine the feasability of an extracorporeal treatment with these or related agents. Glucose utilization, hexose monophosphate shunt activity, methemoglobin reduction, and incubation with acetylphenylhydrazine for Heinz body formation were performed, as well as specific assays for hexokinase, pyruvate kinase, glucose-6-phosphate dehydrogenase, glutathione reductase, ATP, reduced glutathione (GSH), and survival of autologous mustard-treated cells in rabbits. HN2 was found to enter red cells rapidly and bind to intracellular contents. Metabolic studies revealed no significant inhibition or alteration of function by Nor-HN2 at 10 mg/ml of whole blood. Rabbit red cell survival was also normal. HN2, however, inhibited glutathione reductase and blocked the free sulfhydryl group of GSH by forming serveral addition products of alkylated GSH. Heinz body test with acetylphenylhydrazine became positive in HN2-treated cells, and rabbit red cell survival was shortened considerably in the concentration range used to inhibit sickling. Ascorbic acid stimulation of the hexose shunt pathway was inhibited by HN2, but methylene blue stimulation remained unaffected. 14-C-HN2 remains bound to red cells in vivo, and the disappearance of radioactivity is similar to that found with 14-C-DFP (disopropylfluorophosphate). Oxygen affinity of both HN2 and Nor-HN2 treated human red cells remains virtually the same as that found in control samples. It is concluded that Nor-HN2 may be a suitable agent for an extracorporeal therapy, and that each mustard needs to be evaluated individually for its antisickling effects and its suitability for extracorporeal use.

scholarly journals Evaluation of extracorporeal alkylation of red cells as a potential treatment for sickle cell anemia

Blood ◽  
1976 ◽  
Vol 47 (3) ◽  
pp. 481-488 ◽  
Author(s):  
S Charache ◽  
R Dreyer ◽  
I Zimmerman ◽  
CK Hsu
Keyword(s):  
Cell Survival ◽  
Alkylating Agent ◽  
Nitrogen Mustard ◽  
Alkylating Agents ◽  
Red Cells ◽  
Red Cell ◽  
Cell Life ◽  
Red Cell Survival ◽  
Toxic Reactions ◽  
Unacceptable Toxicity

Abstract Nitrogen mustard and nor-nitrogen mustard inhibit sickling, but the concentrations required would be associated with unacceptable toxicity if these agents were administered to patients. Red cells could be treated extracorporeally and infused back into donors, if the alkylating agent could be removed or inactivated, if the treatment per se did not significantly shorten red cell survival, and if viable alkylated lymphocytes could be eliminated from the treated blood. To estimate whether these conditions could be met in a clinical trial, red cells from four dogs were alkylated at 6-wk intervals. No toxic reactions were observed, although not all nor-nitrogen mustard was removed by the washing procedure. Red cell survival was shortened to about half that of control cells, using concentrations of alkylating agent which reduce sickling by 50%. Lymphocytes from treated blood could still exclude trypan blue, but could not be shown to circulate after reinfusion into donor dogs. If alkylating agents are used to treat patients' cells, inhibition of sickling may outweigh the shortening of red cell life span induced by the treatment; blood should probably be irradiated before infusion to avoid administration of alkylated and potentially mutated, but viable, lymphocytes.

scholarly journals Evaluation of extracorporeal alkylation of red cells as a potential treatment for sickle cell anemia

Blood ◽  
1976 ◽  
Vol 47 (3) ◽  
pp. 481-488
Author(s):  
S Charache ◽  
R Dreyer ◽  
I Zimmerman ◽  
CK Hsu
Keyword(s):  
Cell Survival ◽  
Alkylating Agent ◽  
Nitrogen Mustard ◽  
Alkylating Agents ◽  
Red Cells ◽  
Red Cell ◽  
Cell Life ◽  
Red Cell Survival ◽  
Toxic Reactions ◽  
Unacceptable Toxicity

Nitrogen mustard and nor-nitrogen mustard inhibit sickling, but the concentrations required would be associated with unacceptable toxicity if these agents were administered to patients. Red cells could be treated extracorporeally and infused back into donors, if the alkylating agent could be removed or inactivated, if the treatment per se did not significantly shorten red cell survival, and if viable alkylated lymphocytes could be eliminated from the treated blood. To estimate whether these conditions could be met in a clinical trial, red cells from four dogs were alkylated at 6-wk intervals. No toxic reactions were observed, although not all nor-nitrogen mustard was removed by the washing procedure. Red cell survival was shortened to about half that of control cells, using concentrations of alkylating agent which reduce sickling by 50%. Lymphocytes from treated blood could still exclude trypan blue, but could not be shown to circulate after reinfusion into donor dogs. If alkylating agents are used to treat patients' cells, inhibition of sickling may outweigh the shortening of red cell life span induced by the treatment; blood should probably be irradiated before infusion to avoid administration of alkylated and potentially mutated, but viable, lymphocytes.

scholarly journals Excess Hemolysis in Subjects with Severe Iron Deficiency Anemia Associated and Nonassociated with Hookworm Infection

Blood ◽  
1965 ◽  
Vol 25 (1) ◽  
pp. 73-91 ◽  
Author(s):  
MIGUEL LAYRISSE ◽  
JESÚS LINARES ◽  
MARCEL ROCHE ◽  
Adelina Ojeda ◽  
Alvaro Carstens ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Cell Survival ◽  
Iron Deficiency Anemia ◽  
Red Cells ◽  
Deficiency Anemia ◽  
Intrinsic Defect ◽  
Red Cell ◽  
Hookworm Infection ◽  
Iron Treatment ◽  
Red Cell Survival

Abstract An excess hemolysis was found in subjects with iron deficiency anemia associated with hookworm infection. Red cell survival, measured with Cr51 and DFP32 in the subjects before deworming, showed a marked disproportion between the decrease of the survival and the amount of daily intestinal blood loss in most cases. Excess of hemolysis was still present after more than 90 per cent of the parasites were removed. Red cell survival became normal after correction of anemia through iron treatment. Excess of hemolysis was also present in noninfected subjects with iron deficiency anemia due to other causes. The reduction in the survival of the erythrocytes from infected subjects transfused into normal recipients shows that the hemolytic process is due to an intrinsic defect of the red cells. The low values of hemoglobinemia and the presence of haptoglobins in the plasma indicate that hemoglobin has not been liberated in excess intravascularly. Finally, the fact that the red cells from an infected patient taken after deworming survived normally in splenectomized recipients indicates that the spleen is probably the principal site of the red cell destruction. The clinical and autopsy findings suggest that splenic function is not pathologically increased, but rather that this organ is acting physiologically at a more rapid rate, "culling" the abnormal circulating red cells and thus leading to a decrease in red cell survival. The studies presented here also indicate that the hookworm infection per se does not induce hemolysis.

Measurement of red cell survival using biotin-labeled red cells: validation against 51Cr-labeled red cells

Transfusion ◽  
1999 ◽  
Vol 39 (2) ◽  
pp. 156-162 ◽  
Author(s):  
Donald M. Mock ◽  
Gary L. Lankford ◽  
John A. Widness ◽  
Leon F. Burmeister ◽  
Daniel Kahn ◽  
...  
Keyword(s):  
Cell Survival ◽  
Red Cells ◽  
Red Cell ◽  
Red Cell Survival

scholarly journals Reticulocyte Survival in Sickle Cell Anemia: Effect of Cyanate

Blood ◽  
1972 ◽  
Vol 40 (5) ◽  
pp. 733-739 ◽  
Author(s):  
Blanche P. Alter ◽  
Yuet Wai Kan ◽  
David G. Nathan
Keyword(s):  
Cell Survival ◽  
Sickle Cell ◽  
Fetal Hemoglobin ◽  
Red Cells ◽  
Red Cell ◽  
Hemoglobin Molecule ◽  
Red Cell Survival ◽  
And Control

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.

THE EFFECT OF SULPHAEMOGLOBIN ON RED CELL VIABILITY

1957 ◽  
Vol 35 (1) ◽  
pp. 1171-1181
Author(s):  
L. G. Israels ◽  
A. Chutorian ◽  
G. E. Delory ◽  
Esther Israels
Keyword(s):  
Cell Viability ◽  
Life Span ◽  
Cell Survival ◽  
Red Cells ◽  
Red Cell ◽  
Disappearance Rate ◽  
Cell Life ◽  
Red Cell Survival ◽  
Calcium Sulphide ◽  
True Measure

Sulphaemoglobinaemia was produced in rabbits by the injection of para-aminopropriophenone and calcium sulphide. The disappearance of this pigment from the blood was used as an index of red cell survival. Sulphaemoglobin disappeared in an exponential fashion, indicating a mean red cell life span of 36 days. The red cells were also tagged with Cr51, and this method of measuring erythrocyte life span yielded values strongly suggesting that sulphaemoglobin in the red cell impairs its viability and leads to random cell destruction. Under these conditions it would seem that the disappearance rate of sulphaemoglobin is not a true measure of red cell survival.

Quantitative measurement of erythropoiesis in the dog

1960 ◽  
Vol 198 (1) ◽  
pp. 183-186 ◽  
Author(s):  
S. M. Weissman ◽  
T. A. Waldmann ◽  
N. I. Berlin
Keyword(s):  
Life Span ◽  
Cell Survival ◽  
Cell Volume ◽  
Quantitative Measurement ◽  
Red Cells ◽  
Red Cell ◽  
Red Cell Volume ◽  
Cell Life ◽  
Red Cell Survival

The quantitative measurement of erythropoiesis requires the simultaneous determination of total red cell volume, rate of production of red cells and the red cell life span. The total red cell volume was measured with autologous Cr51-labeled red cells, the rate of production of red cells from the rate of disappearance of radioiron from the plasma and uptake by red cells, the red cell life span with C14-labeled glycine and the apparent red cell survival T1/2 with Cr51. The average total red cell volume of the dogs studied was 38.6 cc/kg; the plasma radioiron T1/2 was 66 minutes; the red cell radio-iron uptake was 80%; the serum iron was 102 µg/100 cc, and the plasma volume calculated from the peripheral hematocrit and total red cell volume was 46 cc/kg, and from the extrapolation to t0 of the radioiron disappearance was 48 cc/kg. From these figures the plasma iron turnover was calculated to be 0.63 mg/kg/day and the red cell iron renewal rate 1.26%/day. The average red cell life span was 108 days; the average apparent T1/2 of Cr51 red cell survival was 24.3 days; the average elution rate of Cr51 was 1.77%/day.

scholarly journals Satisfactory Red Cell Viability with Slight Excess of Acid Citrate Dextrose

Blood ◽  
1968 ◽  
Vol 32 (3) ◽  
pp. 469-472 ◽  
Author(s):  
KLAUS MAYER ◽  
JOSEPH D'AMARO
Keyword(s):  
Cell Viability ◽  
Cell Survival ◽  
Blood Donors ◽  
Red Cells ◽  
Red Cell ◽  
Slight Excess ◽  
Great Excess ◽  
Red Cell Survival ◽  
Acid Citrate Dextrose ◽  
Citrate Dextrose

Abstract Platelet suspensions obtained from blood donors are improved by increased acidification. The simplest way to accomplish this is to collect less blood into the standard quantity of ACD. Since we have previously reported an impairment in red cell viability when blood is collected in a great excess of ACD, it became pertinent to test the survival of stored red cells collected in a "slight" excess of ACD. The volume of the blood collected was lowered to 375 ml. in 75 ml. ACD (N. I. H. formula A). At this ratio the pH. was 6.5 which is sufficiently low to minimize platelet clumping. The red cells were separated, stored for 21 days at 4 C., and viability was tested by the 51Chromate method. The results showed adequate red cell survival for blood collected and stored in this manner.

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