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Biomedical subjects

C Feo

Publications and source records attributed to C Feo.

At least 37 records · Page 2Linked to original sources
PubMed1984

Molecular defect of spectrin in the family of a child with congenital hemolytic poikilocytic anemia.

We present the study of a black family in which the proband suffered from a severe neonatal hemolytic anemia with poikilocytosis. Both the parents, sister's, and brother's proband were clinically normal. The presence of poikilocytes in proband led to a search for a red cell membrane skeleton defect. Owing to recent improvements in the erythrocyte membrane knowledge, it is now possible to approach the diagnosis by means of biochemical evaluation of both parents, even if they are asymptomatic. So, the first time discovery of a spectrin self-association defect in both parents allowed us to suspect double inheritance of this abnormality in the proband. A complete morphological and biochemical evaluation of the family allowed us to propound the diagnosis of heterozygous type I hereditary elliptocytosis (HE) for both parents and the sister and the diagnosis of homozygous type I HE for the proband owing to the following reasons: slight ovalocytosis was present in both parents and the sister; cell deformability ektacytometric studies gave the same profiles of curve as those observed in patients with HE. Defective spectrin dimer self-association found in both parents was also observed in the sister and proband, associated with the same abnormal spectrin digest pattern, namely a decrease in the amount of a 80,000-dalton peptide and a corresponding increase in a 74,000-dalton peptide. However, clinical presentation of the proband was consistent either with hereditary pyropoikilocytosis or homozygous hereditary elliptocytosis; erythrocyte thermal sensitivity studies in the proband could not be conclusive because of the presence of transfused cells. Both these diagnoses are discussed in detail.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Hemolytic, Congenital↗
PubMed1983

[Neonatal hemolysis secondary to congenital poikilocytosis].

Hereditary pyropoikilocytosis is a congenital haemolytic anaemia recently described. A new case is reported in which the condition was diagnosed by a study of erythrocyte membrane proteins in the parents. The unusual clinical features of this case lead to a discussion of the relationship between hereditary pyropoikilocytosis and other rare forms of elliptocytosis in children.

Anemia, Hemolytic, Congenital↗
PubMed1982

The effect of cell hydration on the deformability of normal and sickle erythrocytes.

The deformability of the erythrocyte (RBC) is greatly influenced by its state of hydration. The purpose of this investigation is to quantitate this relationship by measuring the deformability of an RBC population over a broad range of cell water content. By manipulation of the ion content of the RBC, we performed all of the experiments in media which were isotonic with plasma. To raise ion and water content, RBC were incubated in a Li2CO3 medium. To lower cell ion and water content, RBC were exposed to the K ionophore, valinomycin. The range of cell water content achieved during the entire experiment was 900-3200 g/kg cell solid (normal in vivo cell water content being 1800-1950 g/kg cell solid). By using the Ektacytometer, an automated cylindrical viscometer, we were able to measure deformability of the RBC sampled at various points along this range of cell water content. We found that optimal rheologic behavior was exhibited by normal RBC when their water content was in the normal range. A rise or a fall in cell hydration resulted in a decrease in cell deformability. By contrast, the deformability of freshly drawn, well-oxygenated sickle RBC was well below that found for normal RBC. Upon volume expansion, however, the deformability of these sickle RBC improved markedly. This observation suggests that sickle RBC are suboptimally hydrated and that their abnormal rheology is at least in part a consequence of cell dehydration.

Anemia, Sickle Cell↗
PubMed1982

Echinocytic sensitivity and deformability of human newborn red cells.

Echinocytic red cells are present in the peripheral blood of normal human newborns in small but significant numbers. This is in contrast to normal adults in whom no echinocytes are found in peripheral blood. In addition, red cells from newborns have increased susceptibility to echinocyte transformation induced by naturally occurring phospholipid lysolecithin. The mechanism for this increased susceptibility does not appear to be related to the lipid composition of these cells. Cellular deformability of red cells from newborns, as determined by a newly developed viscodiffractometric technique, is similar to that of adult red cells. This finding differs from an earlier report of reduced deformability of fetal red cells.

Erythrocytes↗
PubMed1982

Spectrin beta-chain variant associated with hereditary elliptocytosis.

An electrophoretically fast-moving variant of the spectrin beta-chain was discovered in the erythrocyte membranes of a woman and her father who both exhibited elliptocytosis and mild hemolytic anemia. This abnormal beta'-subunit (Mr = 214,000) co-existed with a decreased normal beta-chain and represented about half of the total beta-chains in the membrane. In contrast to the spectrin beta-chain, the beta'-chain was phosphorylated neither in the membrane by endogenous protein kinases nor in solution by pure membrane casein kinase whether or not the spectrin was dephosphorylated by erythrocyte cytosolic spectrin phosphatase. The presence of the beta'-chain was associated with a defective self-association of spectrin dimer to form tetramer as manifested by: (a) an excess of spectrin dimer in the 4 degrees C spectrin crude extract, (b) a defective self-association of the spectrin dimer in the 37 degrees C crude spectrin extracts. Gel electrophoretic analysis of the tetramer and dimer species isolated from the proband's 4 degrees C extract showed that the tetramer contained trace amounts of the beta'-chain, whereas in contrast, a large proportion of beta'-chain was present in the dimer. These results demonstrated the responsibility of the beta'-chain for the defective reassociation of spectrin dimer into tetramer. The study of this abnormal spectrin confirms the participation of spectrin beta-chain in dimer-dimer association and strongly suggests that the phosphorylation sites of the normal beta-chain are located at the end of the molecule involved in the dimer-dimer interactions.

Adult↗
PubMed1982

The influence of suspension osmolarity and erythrocyte volume on cell deformability.

Erythrocytes were suspended in dextran solutions of phosphate buffered saline with solution osmolarities from 400 to 20 mosM/kg. The dilute suspensions were subjected to linear shear and their deformation determined by laser diffractometry (Ektacytometer). Cell volumes were measured using a Coulter counter following fixation in glutaraldehyde to eliminate the influence of deformability on the volume measurement. Minimum deformability generally agreed with the maximum cellular volume produced by hypotonic solutions. However, reduced deformability was observed for both hyperosmotic and hypoosmotic conditions. The oncotic effect of the dextran delayed hemolysis to surprisingly low values of solution osmolarity. In contrast with the usual osmotic fragility results, in the hypotonic dextran solutions there was no evidence of hemoglobin release. At low shear stresses, deformability was found to be enhanced by reducing intracellular viscosity (via osmotic water transport into the cell). However, the maximum cellular deformation obtained at high shear stress was always less than that for the normal discocyte at normal osmolarities.

Blood Viscosity↗
PubMed1982

Quantitation of red cell deformability during progressive deoxygenation and oxygenation in sickling disorders (the use of an automated Ektacytometer).

1. The Ektacytometer, which allows quantitation of cell fluidity under known environmental conditions, has been recently modified so that cells can be exposed to any desired O2 tension during shear stress. 2. Heterozygotes (HbAS)show a pO2 vs deformability curve which varies from patient to patient in relation to the quantity of HbS. In the high viscosity medium used for this measurement, erythrocytes are normally deformable at any pO2 from 5 mmHg to normoxic conditions, at physiologic pH [7.3] and osmolarity (290 mOsm Kg-1). Modulation of the pH and osmolarity induces cell rigidity at different pO2 below 40 mmHg. 3. Homozygotes (HbSS) blood contains heterogeneous erythrocyte populations from the reticulocytes to abnormally dense cells (heterogeneity in cell volume, Hb concentration, shape, etc.). After separation by differential centrifugation, the various fractions each show a characteristic response to pO2 changes, pH, osmolarity and other parameters, which are specific to each patient and his pathological status at a given time. 4. This method was used to evaluate the activity of anti-sickling drugs. In addition, the action of such compounds on normal cells gives information on the mechanism of activity (changes in volume, in oxygen affinity, membrane properties or other--yet poorly explored--parameters). 5. This new application of the Ektacytometer may be of value for a) evaluating anti-sickling drugs and designing new therapeutic modalities, b) monitoring therapy of sickle cell patients, and c) research into the phenomenon of sickling.

Anemia, Sickle Cell↗
PubMed1981

Evidence for imbalanced furosemide-sensitive Na+, K+ cotransport in hereditary stomatocytosis.

The red cells from 5 related patients with hereditary stomatocytosis were investigated. Maximal rate constant of Na+ passive permeability was increased while that of K+ passive permeability was nearly normal. Ouabain-sensitive Na+ efflux was elevated. The Na+ component of furosemide-sensitive Na+, K+ cotransport was also increased. However, its K+ component, determined in 2 patients, remained within normal limits, thus departing from the strict 1:1 stoichiometry of the Na+, K+ cotransport system. Yet, intracellular Na+ and K+ concentrations displayed limited and inconstant changes. A variety of abnormally-shaped cells, including stomatocytes, were observed in scanning electron micrographs. Upon differential centrifugation, reticulocytes usually concentrated in the most dense region of the gradient. Red cell deformability, as studied by ektacytometry, was reduced. Membrane phosphatidylcholines and sphingomyelins were increased and decreased, respectively, where-as fatty acid distribution was unchanged. Membrane microviscosity was normal.

Cations↗
PubMed1981

Separate mechanisms of deformability loss in ATP-depleted and Ca-loaded erythrocytes.

Membrane rigidity has been widely accepted as the dominant cause of reduced deformability both of ATP-depleted erythrocytes and erythrocytes containing excess calcium (Ca). However, recent studies have shown normal membrane deformability in ATP-depleted erythrocytes. In addition, Ca accumulation causes massive ion and water loss, and it has been shown that extensive dehydration causes an increase in intracellular viscosity with attendant loss of whole cell deformability. To obtain a detailed understanding of the processes accompanying ATP depletion and/or Ca accumulation that limit cell deformability, we have used a viscodiffractometric method to identify the cellular factors contributing to reduced whole cell deformability. Analysis of the influence of the suspending medium osmolality on deformability showed the presence of two independent processes. One was a Ca-independent reduction in cell surface area/volume ratio, resulting from the spheroechinocyte formation that follows total ATP consumption. The other was a Ca-dependent increase in intracellular viscosity resulting from a Ca-induced loss of intracellular potassium and water. This deformability loss due to increased intracellular viscosity was found for cells depleted of ATP in the presence of Ca and in cells treated with Ca and A23187 without prior depletion. Ionophore-treated cells at high Ca concentration (>500 muM) formed spheroechinocytes with reduced surface area and a further loss of whole cell deformability. The rate of deformability loss associated with Ca-induced spheroechinocytosis was much more rapid than that associated with ATP-depletion-induced spheroechinocytosis, suggesting different mechanisms for the morphologic changes. No major effects of altered membrane elasticity on the reduced deformability of either ATP-depleted or Ca-loaded cells were observed.

Adenosine Triphosphate↗
PubMed1981

Factors that limit whole cell deformability in erythrocytes after calcium loading and ATP depletion.

Whole cell deformability of ATP-depleted and Ca-loaded red cells has been measured at various osmolalities to determine those cellular factors responsible for the reduce deformability of these cells. For cells depleted of ATP in Ca-free medium, a progressive loss of hypotonic deformability identified membrane loss with reduced surface area-to-volume ratio as the dominant mechanism of deformability loss. For cells treated with Ca and the ionophore A23187 without prior depletion, a rapid loss of isotonic deformability, reversible in hypotonic medium, identified dehydration with increased internal viscosity as the dominant mechanism of deformability loss. In contrast to previously held concepts, increased membrane rigidity was not found to have a major influence.

Adenosine Triphosphate↗
PubMed1980

Automated ektacytometry: a new method of measuring red cell deformability and red cell indices.

The automated ektacytometer enables rapid measurement of red cell deformability by using small aliquots of blood (25 microliter). By subjecting red cells to varying shear stress in suspending media of different osmolalities, one can identify separate contributions of membrane viscoelastic properties, internal viscosity, and surface area-to-volume ratio to overall cellular deformability. The influence of drugs on red cell deformability can also be investigated. Analysis of the diffraction pattern of red cells that are aligned in the ektacytometer at minimal shear stress enables improved measurement of red cell diameter. Modern computerized image analysis can further improve the reliability of this measurement. Volume measurement of red cells of unusual shape is possible. since, under certain conditions, they transform into uniform ellipsoids in the ektacytometer. Aided again by improved image analysis, simple accurate computation of red cell volume becomes possible Ektacytometric measurement may provide a sensitive assessment of the overall functional integrity of living red cells or subpopulations of red cells. As such, these measurements are of research interest and may have major clinical utility.

Computers↗
PubMed1979

[Homogeneity of the erythrocyte volume distribution during chronic alcoholism macrocytosis (author's transl)].

The increase in volume of human erythrocytes during chronic alcoholic intoxication and its decrease after alcoholic deprivation was studied with a multichannel analyzer. When fractions of the population of red cells were separated by differential centrifugation the macrocytosis was found to be uniformly distributed. The presence of macrocytes was not related to changes of plasma osmolality or hyperhydration of red cells. A central origin was evoked, however, the role of the folic acid deficiency could not explain the macrocytosis, the mechanism of which remains to be elucidated.

Adult↗