scholarly journals Study of a kindred with hereditary spherocytosis and glyceraldehyde-3- phosphate dehydrogenase deficiency

Blood ◽  
1976 ◽  
Vol 47 (2) ◽  
pp. 171-181
Author(s):  
SR McCann ◽  
B Finkel ◽  
S Cadman ◽  
DW Allen
Keyword(s):  
Hereditary Spherocytosis ◽  
Sodium Dodecyl ◽  
Metabolic Stress ◽  
Protein Band ◽  
Red Cells ◽  
Clinical Severity ◽  
Red Cell ◽  
Cell Enzyme ◽  
Severity Of The Disease ◽  
Red Cell Membranes

A patient with hereditary spherocytosis (HS) was found to have glyceraldehyde-3-phosphate dehydrogenase (G3PD) deficiency by electrophoresis of the isolated red cell membranes on polyacrylamide gels with sodium dodecyl sulfate (PAGE SDS) as demonstrated by a diminished band 6 (G3PD) and confirmed by specific enzyme assay. Thirteen members of his family were studied: four were normal, two had HS alone, three had G3PD deficiency alone, and four had both HS and G3PD deficiency. G3PD deficient kindred members were probably heterozygous, since their red cell enzyme, while qualitatively normal, was present in half normal amounts. The G3PD deficiency alone was asymptomatic, and there was no evidence that the combination of HS with G3PD deficiency increased the clinical severity of the disease. However, G3PD deficiency, when combined with HS, was associated with an increase in protein band 4.5 on PAGE SDS. This band was also increased by incubation of normal red cells without glucose, and appeared to be a protein absorbed to the membrane as a consequence of metabolic stress. Hence, red cells with the combined abnormalities of both HS and G3PD deficiency showed signs of the exceptional metabolic stress to which they were exposed.

scholarly journals Study of a kindred with hereditary spherocytosis and glyceraldehyde-3- phosphate dehydrogenase deficiency

Blood ◽  
1976 ◽  
Vol 47 (2) ◽  
pp. 171-181 ◽  
Author(s):  
SR McCann ◽  
B Finkel ◽  
S Cadman ◽  
DW Allen
Keyword(s):  
Hereditary Spherocytosis ◽  
Sodium Dodecyl ◽  
Metabolic Stress ◽  
Protein Band ◽  
Red Cells ◽  
Clinical Severity ◽  
Red Cell ◽  
Cell Enzyme ◽  
Severity Of The Disease ◽  
Red Cell Membranes

Abstract A patient with hereditary spherocytosis (HS) was found to have glyceraldehyde-3-phosphate dehydrogenase (G3PD) deficiency by electrophoresis of the isolated red cell membranes on polyacrylamide gels with sodium dodecyl sulfate (PAGE SDS) as demonstrated by a diminished band 6 (G3PD) and confirmed by specific enzyme assay. Thirteen members of his family were studied: four were normal, two had HS alone, three had G3PD deficiency alone, and four had both HS and G3PD deficiency. G3PD deficient kindred members were probably heterozygous, since their red cell enzyme, while qualitatively normal, was present in half normal amounts. The G3PD deficiency alone was asymptomatic, and there was no evidence that the combination of HS with G3PD deficiency increased the clinical severity of the disease. However, G3PD deficiency, when combined with HS, was associated with an increase in protein band 4.5 on PAGE SDS. This band was also increased by incubation of normal red cells without glucose, and appeared to be a protein absorbed to the membrane as a consequence of metabolic stress. Hence, red cells with the combined abnormalities of both HS and G3PD deficiency showed signs of the exceptional metabolic stress to which they were exposed.

Cytoadherence-related neoantigens on Plasmodium falciparum (human malaria)-infected human erythrocytes result from the exposure of normally cryptic regions of the band 3 protein

Parasitology ◽  
1994 ◽  
Vol 108 (3) ◽  
pp. 257-267 ◽  
Author(s):  
I. Crandall ◽  
I. W. Sherman
Keyword(s):  
Plasmodium Falciparum ◽  
Protein Band ◽  
Band 3 ◽  
Amelanotic Melanoma ◽  
Red Cells ◽  
Sequence Motif ◽  
Red Cell ◽  
Band 3 Protein ◽  
Red Cell Membranes

SUMMARYMurine monoclonal antibodies (Mabs) were produced by vaccination of Balb/c mice with live Plasmodium falciparum infected red cells (iRBC). The iRBC Mabs recognized altered forms of the human erythrocyte membrane protein band 3; however, these Mabs did not recognize the band 3 molecule in uninfected or ring-infected red cells. The location of epitopes was determined by studying the binding of the iRBC Mabs after selective proteolysis of band 3 as well as by the reactivity of these Mabs to synthetic peptides that corresponded to putative exofacial regions of band 3. Treatment of uninfected red cell membranes with trypsin under low ionic strength conditions resulted in exposure of cryptic epitopes of band 3 which were recognized by the iRBC Mabs. Several of the anti-iRBC Mabs (two of which were described previously) inhibited the in vitro adherence of infected erythrocytes to C32 amelanotic melanoma cells. A mouse polyclonal serum against a synthetic peptide based on an amino acid sequence motif of band 3 reacted (by immunostaining) only with the surface of iRBC and blocked adhesion. Thus, it appears that cryptic residues of the band 3 protein become exposed upon parasitization, and their presence contributes to the increased adhesiveness of the P. falciparum-infected red cell.

BRIEF REPORT: Freeze-Cleaving of Red Cell Membranes in Paroxysmal Nocturnal Hemoglobinuria

Blood ◽  
1967 ◽  
Vol 30 (6) ◽  
pp. 785-791 ◽  
Author(s):  
RONALD S. WEINSTEIN ◽  
ROGER A. WILLIAMS
Keyword(s):  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Cell Membranes ◽  
Red Cells ◽  
Red Cell ◽  
Electron Microscopic ◽  
Structural Differences ◽  
Microscopic Studies ◽  
Red Cell Membranes

Abstract Electron microscopic studies on dried isolated red cell ghosts have been reported to show lesions associated with cell membranes in paroxysmal nocturnal hemoglobinuria (PNH). In this study, carbon-platinum replicas of membranes of freeze-cleaved, partially hydrated PNH red cells and isolated PNH cell ghosts failed to confirm the existence of these abnormalities. This suggests that the previously described lesions are the products of drying artifacts, although they may reflect hidden structural differences between PNH and normal red cell membranes.

PAROXYSMAL NOCTURNAL HEMOGLOBINURIA IN CHILDHOOD AND ADOLESCENCE

PEDIATRICS ◽  
1967 ◽  
Vol 39 (5) ◽  
pp. 675-688
Author(s):  
Denis R. Miller ◽  
Robert L. Baehner ◽  
Louis K. Diamond
Keyword(s):  
Fetal Hemoglobin ◽  
Normal Activity ◽  
Glycolytic Enzyme ◽  
Clinical Severity ◽  
Childhood And Adolescence ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Severity Of The Disease ◽  
Increased Activity ◽  
Aldolase A

Two cases of PNH in adolescence and childhood are reported. The first presented at age 7½ years with aplastic anemia and improved after splenectomy performed at age 14. The second, a 15-year-old girl, presented with a Coombs-positive hemolytic anemia and has had a course complicated by multiple peripheral thromboses. The clinical and laboratory manifestations, complications, and certain therapeutic aspects of PNH are discussed. Anticoagulant therapy appears indicated in the presence of multiple thrombotic episodes. Erythrocyte metabolic studies revealed normal glycolysis, ATP stability, and GSH content in the cells of a child with a normal reticulocyte count. Mild elevations of glycolysis, noted in the child with a reticulocytosis, was ascribed to a younger mean red cell population since further elevations found in the "top" reticulocyte-rich layer after centrifugation. Heparin, the anticoagulant used in these studies, had no adverse effect on glycolysis but did inhibit hemolysis and minimize ATP instability when compared to cells suspended in defibrinated serum. Erythrocytes fractionated by centrifugation revealed increased glycolytic enzyme activities of hexokinase, G3PD, PGK, TPI, PK, LDH, G6PD, and 6PGD in the reticulocyte-rich layer. Normal, rather than increased activity of aldolase, a membrane enzyme, may reflect damage to the red cell membrane. PFK, known to be decreased in the erythrocyte of neonates, showed normal activity, but it was lowest in the reticulocyte-rich layer. Fetal hemoglobin was elevated in this layer. AChE deficiency and increased suceptibility to hydrogen perioxide and acid hemolysis confirmed previous reports and were most marked in the young cell layer. The level of increased glycolytic rates and enzyme activity, AChE deficiency, acid hemolysis and peroxide hemolysis were related to the clinical severity of the disease.

scholarly journals Erythrocyte cellular and membrane deformability in hereditary spherocytosis

Blood ◽  
1979 ◽  
Vol 53 (3) ◽  
pp. 481-485 ◽  
Author(s):  
K Nakashima ◽  
E Beutler
Keyword(s):  
Cell Membrane ◽  
Hereditary Spherocytosis ◽  
Volume Ratio ◽  
Osmotic Fragility ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Relative Rigidity ◽  
Altered Surface ◽  
Red Cell Membranes ◽  
Expected Increase

In order to determine whether the relative rigidity of the hereditary spherocytosis (HS) red cell is due to membrane rididity or merely to an altered surface/volume ratio, we investigated the deformability of resealed red cell membranes from patients with HS. Whereas the osmotic fragility of intact red cells of HS patients showed the expected increase, the osmotic fragility of resealed HS membranes was normal, thus indicating that their surface/volume ratio was normal. Measurements with an ektacytometer showed that deformability of intact HS cells was markedly diminished, whereas deformability of resealed HS membranes was normal. These findings indicate that the HS red cell membrane is not intrinsically abnormally rigid, as has been suggested, but that the lack of deformability of the erythrocyte is primarily a function of the altered surface/volume ratio.

NORMAL FLUIDITY OF RED CELL MEMBRANES IN HEREDITARY SPHEROCYTOSIS

1980 ◽  
Vol 46 (2) ◽  
pp. 299-301 ◽  
Author(s):  
Richard A. Cooper ◽  
William H. Sawyer ◽  
Mary H. Leslie ◽  
John S. Hill ◽  
Frances M. Gill ◽  
...  
Keyword(s):  
Cell Membranes ◽  
Hereditary Spherocytosis ◽  
Red Cell ◽  
Red Cell Membranes

scholarly journals The relationship between in vivo generated hemoglobin skeletal protein complex and increased red cell membrane rigidity

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1427-1431 ◽  
Author(s):  
N Fortier ◽  
LM Snyder ◽  
F Garver ◽  
C Kiefer ◽  
J McKenney ◽  
...  
Keyword(s):  
Protein Complex ◽  
Sodium Dodecyl ◽  
Red Cells ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Cellular Dehydration ◽  
Thalassemia Minor ◽  
Membrane Rigidity

Abstract In vitro induced oxidative damage to normal human RBCs has previously been shown to result in increased membrane rigidity as a consequence of the generation of a protein complex between hemoglobin and spectrin. In order to determine if in vivo generated hemoglobin-spectrin complexes may play a role in increased membrane rigidity of certain pathologic red cells, we measured both these parameters in membranes prepared from hereditary xerocytosis (Hx), sickle cell disease (Sc), and red cells from thalassemia minor (beta thal). Membranes were prepared from density-fractionated red cells, and membrane deformability was measured using an ektacytometer. Hemoglobin-spectrin complex was determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel analysis, as well as by Western blot analysis using a monoclonal antibody against the beta- subunit of hemoglobin. For these three types of pathologic red cells, progressive cellular dehydration was associated with increased membrane rigidity and increased content of hemoglobin-spectrin complex. Moreover, the increase in membrane rigidity appeared to be directly related to the quantity of hemoglobin-spectrin complex associated with the membrane. Our findings imply that hemoglobin-spectrin complex is generated in vivo, and this in turn results in increased membrane rigidity of certain pathologic red cells. The data further suggest that oxidative crosslinking may play an important role in the pathophysiology of certain red cell disorders.

scholarly journals Spinal cord disease in hereditary spherocytosis: report of two cases with a hypothesized common mechanism for neurologic and red cell abnormalities

Blood ◽  
1976 ◽  
Vol 48 (2) ◽  
pp. 259-263 ◽  
Author(s):  
SR McCann ◽  
HS Jacob
Keyword(s):  
Spinal Cord ◽  
Hereditary Spherocytosis ◽  
Case Reports ◽  
Individual Case ◽  
Nerve Tissue ◽  
Common Mechanism ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Red Cell Membranes ◽  
Spinal Cord Dysfunction

Abstract Two unrelated patients with hereditary spherocytosis developed idiopathic spinal cord dysfunction. This coincidence, combined with similar individual case reports in the older European literature, suggests that abnormalities may exist in constituents common to red cell membranes and nerve tissue. A similar conclusion has been proposed to explain red cell membrane abnormalities in some of the muscular dystrophies.

scholarly journals A Red Cell Enzyme Method for the Diagnosis of Acute Intermittent Porphyria

Blood ◽  
1974 ◽  
Vol 44 (6) ◽  
pp. 857-868 ◽  
Author(s):  
C. Richard Magnussen ◽  
Joel B. Levine ◽  
Joyce M. Doherty ◽  
Judy O. Cheesman ◽  
Donald P. Tschudy
Keyword(s):  
Aminolevulinic Acid ◽  
Acute Intermittent Porphyria ◽  
Mean Value ◽  
Red Cells ◽  
Red Cell ◽  
Enzyme Preparations ◽  
Cell Enzyme ◽  
Enzyme Method ◽  
Latent Disease ◽  
The Mean

Abstract A method has been devised for the measurement of uroporphyrinogen I synthetase ih red cells. By using trichloroacetic acid as a protein precipitant, heme is removed from the final solution, allowing accurate measurement of porphyrins. The method is highly reproducible and adaptable to varying incubation volumes and enzyme preparations. It is of great value as an enzyme diagnostic method for acute intermittent porphyria and appears capable of detecting patients with the latent disease who have normal urinary δ-aminolevulinic acid and porphobilinogen excretion. It also appears to distinguish other types of porphyria from acute intermittent porphyria. The mean value of the enzyme in red cells of patients with acute intermittent porphyria was approximately 50% that of normals, indicating that the mutation causes complete lack of catalytic activity in the mutant enzyme.

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