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W C Mentzer

Publications and source records attributed to W C Mentzer.

At least 55 records · Page 3Linked to original sources
PubMed1987

Unique alpha-spectrin mutant in a kindred with common hereditary elliptocytosis.

We report here a unique variant of alpha spectrin in a kindred with hereditary elliptocytosis. This novel red blood cell-membrane protein migrated to a position between the normal alpha- and beta-spectrin subunits in SDS polyacrylamide gel electrophoresis. It was identified as an alpha spectrin by its binding to anti-alpha spectrin antibodies, by the absence of a phosphorylation site, and by the normal 1:1 stoichiometry between total alpha- and beta-spectrin molecules. The quantity of the alpha-spectrin mutant, expressed as a percentage of the total alpha spectrin, varied from 9.9-45.2% among six affected individuals. Two-dimensional electrophoretic analysis of spectrin tryptic digests was qualitatively normal but showed a decreased quantity of a normal alpha IV fragment. The variable quantity of alpha-spectrin mutant among family members correlated directly with the increased percentage of spectrin dimers in cold low ionic strength spectrin extracts (r = 0.92) and inversely with red blood cell ghost mechanical stability (r = -0.98). The data suggest that this new alpha-spectrin mutant is responsible for decreased spectrin dimer-dimer association and for red cell instability in affected individuals.

Electrophoresis, Polyacrylamide Gel↗
PubMed1986

The aging process of human neonatal erythrocytes.

The red blood cell population of the human newborn is more heterogeneous than that of adults. To characterize this heterogeneity, red cells were separated on Stractan gradients into populations according to their density and, therefore, generally according to their age. Lipid content, phospholipid asymmetry, osmotic fragility, and deformability were measured. With increasing density, osmotic resistance and deformability decreased to a greater extent in the neonatal than the adult red cell. There was a marked loss of surface area throughout the life span of the neonatal red cell which was not accompanied by a parallel loss of membrane lipid. This apparent discrepancy could be explained at least in part by internalization of membrane lipid as a result of endocytosis, a process shown to be present in even the densest neonatal red cells.

Adult↗
PubMed1985

AUR memorial Award. Induced alignment of flowing sickle erythrocytes in a magnetic field. A preliminary report.

Deoxygenated sickle erythrocytes in static suspension align perpendicular to a magnetic field. To assess the importance of this observation to MRI of sickle-cell disease, an in vitro flow apparatus was devised and the orientation of sickle erythrocytes flowing through a 0.38 T magnetic field was investigated. We showed a significant perpendicular alignment of fully deoxygenated sickle erythrocytes flowing at 3 to 4 mm/minute (P less than .001). These results suggest that deoxygenated erythrocytes in a sickle-cell patient could orient perpendicular to a magnetic field, and therefore that MRI of such patients could possibly result in worsening of vaso-occlusive complications. Further studies are needed to assess the possible hazards of MRI of sickle-cell disease, especially at high field strengths.

Anemia, Sickle Cell↗
PubMed1985

Haemolytic anaemia associated with increased cation permeability.

Volume regulation in the red cell depends on the balance between the osmotic swelling pressure contributed by the polyvalent anions 2,3-DPG and haemoglobin, and the counterbalancing osmotic pressure provided by extracellular Na+. Although changes in 2,3-DPG have been identified in some cases, increases in the electrodiffusional leak of Na+ and K+ are most likely responsible for the disorders of volume regulation leading to haemolytic anaemia. The current challenge is to identify the membrane proteins and/or lipids which play a key role in passive transport of the monovalent cations.

Anemia, Hemolytic↗
PubMed1984

Two-dimensional electrophoretic analysis of human erythrocyte cylindrin.

Cylindrin, a macromolecule isolated from the human erythrocyte, and the band 7 proteins of the erythrocyte membrane were analyzed by one- and two-dimensional electrophoresis. Cylindrin was recovered from both the cytosol and cell membranes of hypotonically lysed erythrocytes, and its identity was confirmed by electrophoresis and transmission electron microscopy. Cylindrin from either source produced eight bands on one-dimensional SDS gels, and seventeen spots on two-dimensional gels, revealing a more complex composition than previously reported. It is unlikely that this complexity was due to proteolysis, since preparations of cylindrin with various protease inhibitors gave the same electrophoretic patterns. Mixing experiments showed that the polypeptide subunits of the cylindrin complex are distinct from the band 7 proteins of the erythrocyte membrane. This finding failed to support a role for the cylindrin macromolecule in the permeability disorders of the erythrocyte membrane associated with a missing band 7 protein.

Blood Proteins↗
PubMed1984

Prenatal diagnosis of chronic granulomatous disease.

A luminol enhanced chemiluminescence micromethod has been adapted for use in prenatal diagnosis of chronic granulomatous disease (CGD). After validation of the assay in normal adults, newborns, fetuses, CGD carriers, and CGD patients, the fetuses of two pregnant CGD carriers were tested after fetoscopic aspiration of fetal blood. Normal neutrophil chemiluminescence and nitroblue tetrazolium slide tests were followed by delivery of two healthy infants whose normality was confirmed. Amniocytes proved useless for the prenatal diagnosis of CGD. They were found to have negligible nitroblue tetrazolium reduction, oxygen metabolism, and oxygen dependence.

Adult↗
PubMed1984

Influence of pH on the rheologic and antisickling effects of dimethyl adipimidate.

Dimethyl adipimidate, a bifunctional imidoester, is an effective inhibitor of sickling in vitro. We determined the reaction conditions necessary to inhibit sickling without impairing cell deformability. Although imidoesters are routinely used at alkaline pH, we found that reaction of red blood cells with dimethyl adipimidate at pH 8.4 shortened the survival of rat red blood cells and impaired the deformability of human red blood cells. These adverse effects were eliminated by changing the pH of the reaction from 8.4 to 7.4. Furthermore, treatment of sickle cells with dimethyl adipimidate at pH 7.4 inhibited sickling, as demonstrated by dose-dependent reductions in the percentage of sickle forms, viscosity, and potassium efflux. Dimethyl adipimidate appeared to inhibit sickling by several mechanisms: namely, it increased deoxygenated sickle hemoglobin solubility, oxygen affinity, and cell hydration. We conclude that dimethyl adipimidate at pH 7.4 can inhibit sickling without impairing the rheologic properties of the red blood cell.

Anemia, Sickle Cell↗
PubMed1984

Identification of the hereditary pyropoikilocytosis carrier state.

We evaluated the hematologic, rheologic, and biochemical features of erythrocytes obtained from 10 relatives of a 5-yr-old black female with hereditary pyropoikilocytosis (HPP) and severe hemolytic anemia. Erythrocyte morphology was normal in the father and five other relatives, but ghost mechanical fragility and drug-induced red cell endocytosis were increased, as was the percentage of spectrin dimers noted on 3.2% nondenaturing PAGE of spectrin extracts. Identical changes were also noted in the mother and her sister, whose erythrocytes were elliptocytic and exhibited morphological changes upon heating to 45 degrees-48 degrees C (normal 49 degrees). The two other family members were normal in every respect. SDS-PAGE analysis of membrane proteins demonstrated diminished amounts of spectrin in HPP erythrocytes, but was normal in other family members. A diffuse band (mol wt 575,000-665,000), composed entirely of spectrin, was apparent adjacent to the dimer region on nondenaturing PAGE of spectrin extracts from the propositus, mother, and aunt. In this family, HPP appears to have resulted from compound heterozygosity for two distinct genetic abnormalities (reflected by the differences between elliptocytic and nonelliptocytic carriers). Although the membrane abnormalities in carriers did not result in hemolytic anemia, they were of sufficient magnitude to allow the detection of the carrier state.

Adult↗
PubMed1984

Prolongation of sickle cell survival by dimethyl adipimidate is compromised by immune sensitization.

The effect of dimethyl adipimidate (DMA), an amino-reactive crosslinking reagent with demonstrated antisickling properties in vitro, on the survival of 51Cr-labeled autologous sickle cells was evaluated in five adult males with sickle cell anemia. The survival of cells pretreated with 5 mmol/L DMA (pH 7.4), normal (t1/2 28-33 days) in four subjects and near-normal (t1/2 20 days) in the fifth, was considerably longer than that usually observed in sickle cell disease. In fact, the effect of DMA on the survival of sickle cells in vivo equals or exceeds that of any other agent tested to date. In three subjects, the survival of a second infusion of DMA-treated red cells was much shorter (t1/2 1.8, 3, 4.5 days) than in the initial study. An antibody was detected in the serum of these subjects that was directed to DMA-treated red cells. Modification of the immunogenicity of treated cells will be required before further consideration of DMA for use in the therapy of sickle cell anemia.

Adult↗
PubMed1983

Increased serum opsonic activity and antibody concentration in patients with sickle cell disease after pneumococcal polysaccharide immunization.

Opsonic defects have been reported in unimmunized patients with sickle cell disease. We found significant increases (P less than 0.001) in serum opsonic activity, measured by a radiolabeled bacterial uptake assay, and in type 7 pneumococcal polysaccharide antibody concentration in 17 such patients 2 years of age or older after pneumococcal polysaccharide immunization. All 17 patients and six healthy controls achieved a type 7 antibody concentration of more than 300 ng antibody nitrogen per milliliter, believed to be the protective level of antibody in vivo. Six patients with sickle cell disease less than 2 years of age did not have a significant increase in type 7 antibody concentration after immunization. Only three of these six patients achieved a postimmunization type 7 antibody concentration exceeding 300 ng Ab N/ml. Overall, 16 of 23 patients with sickle cell disease (70%) had a twofold or greater increase in type 7 antibody concentration, and 13 of these (81%) had a corresponding increase in opsonic activity (P less than 0.001). Thus most patients who responded to pneumococcal polysaccharide immunization had a concurrent increase in opsonic activity in vitro.

Adolescent↗
PubMed1983

Molecular and functional changes in spectrin from patients with hereditary pyropoikilocytosis.

The structural and functional properties of spectrin from normal and hereditary pyropoikilocytosis (HPP) donors from the two unrelated families were studied. The structural domains of the spectrin molecule were generated by mild tryptic digestion and analyzed by two-dimensional electrophoresis (isoelectric focusing; sodium dodecyl sulfate-polyacrylamide gel electrophoresis). The alpha I-T80 peptide (Mr 80,000) is not detectable in two related HPP donors; instead, two new peptides (Mr 50,000 and 21,000) are generated and have been identified as fragments of the normal alpha I-T80. A third sibling has reduced levels of both the normal alpha I-T80 and the two new peptides. A similar analysis of spectrin from another HPP family indicates that their spectrins contain reduced amounts of the alpha I-T80 and the 50,000 and 21,000 fragments of the alpha I domain. The HPP donor also has other structural variations in the alpha I, alpha II, and alpha III domains. The alpha I-T80 domain of normal spectrin has been shown to be an important site for spectrin oligomerization (J. Morrow and V.T. Marchesi. 1981. J. Cell Biol. 88: 463-468), and in vitro assays indicate that HPP spectrin has an impaired ability to oligomerize. Ghost membranes from HPP donors are also more fragile than membranes from normal erythrocytes when measured by ektacytometry. In both the oligomerization and fragility assays, the degree of impairment is correlated with the amount of normal alpha I-T80 present in the spectrin molecule. We believe that a structural alteration in the alpha I-T80 domain perturbs normal in vivo oligomerization of spectrin, producing a marked decrease in erythrocyte stability.

Adult↗
PubMed1982

Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia.

We studied 47 patients with sickle-cell anemia to determine the effect of alpha-thalassemia on the severity of their hemolytic anemia. We diagnosed alpha-thalassemia objectively by using alpha-globin-gene mapping to detect alpha-globin-gene deletions, studying 25 subjects with the normal four alpha-globin-genes, 18 with three, and four with two. The mean hemoglobin, hematocrit, and absolute reticulocyte levels (+/- S.D.) were 7.9 +/- 0.9 g per deciliter (4.9 +/- 0.6 mmol per liter), 22.9 +/- 2.9 per cent, and 501,000 +/- 126,000 per cubic millimeter, respectively, in the non-thalassemic group; 9.8 +/- 1.6 g per deciliter (6.1 +/- 1.0 mmol per liter), 29.0 +/- 5.0 per cent, and 361,000 +/- 51,000 per cubic millimeter in the group with three alpha-globin genes; and 9.2 +/- 1.0 g per deciliter (5.7 +/- 0.6 mmol per liter), 27.5 +/- 3.0 per cent, and 100,000 +/- 15,000 per cubic millimeter in the group with two alpha-globin genes. Deletion of alpha-globin genes was also accompanied by a decreased mean corpuscular hemoglobin concentration (MCHC) in post-reticulocyte erythrocytes and by increased hemoglobin F levels. The decreased intraerythrocytic hemoglobin S concentration and elevated hemoglobin F levels associated with alpha-thalassemia appear to diminish the degree of hemolytic anemia found in sickle-cell disease.

Adolescent↗
PubMed1982

Missing band 7 membrane protein in two patients with high Na, low K erythrocytes.

We investigated the erythrocyte membrane proteins of two patients with congenital hemolytic anemia due to increased permeability of the erythrocyte membrane to Na and K (hereditary stomatocytosis and cryohydrocytosis). One-dimensional sodium dodecyl sulfate (SDS) gel electrophoresis resolved the band 7 erythrocyte membrane proteins into three components with approximate molecular weights of 30,000, 28,000, and 26,000. The 28,000-dalton component was decreased in both patients with permeability disorders. Two-dimensional electrophoresis (nonequilibrium pH gradient electrophoresis in the first dimension combined with SDS gel electrophoresis in the first dimension combined with SDS gel electrophoresis in the second dimension) resolved the 28,000-dalton component from normal erythrocyte membranes into two proteins with different isoelectric points, designated 22 x 8 and 60 x 8. In the patients with hereditary stomatocytosis and cryohydrocytosis, 22 x 8 was completely absent, whereas 60 x 8 was detected as usual. In contrast, all the band 7 proteins (including 22 x 8) were invariably present in a survey of normal subjects and reticulocytosis controls. The unique finding of a missing band 7 protein in the patients with hereditary stomatocytosis and cryohydrocytosis raises the possibility that the absence of this protein is responsible for the increased Na and K permeability in these disorders.

Anemia, Hemolytic↗