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J Stuart

Publications and source records attributed to J Stuart.

At least 109 records · Page 6Linked to original sources
PubMed1988

Polymerization of sickle cell hemoglobin at arterial oxygen saturation impairs erythrocyte deformability.

We have examined the filterability of sickle erythrocytes, using an initial-flow-rate method, to determine whether sufficient hemoglobin S polymer forms at arterial oxygen saturation to adversely affect erythrocyte deformability. The amount of intracellular polymer was calculated as a function of oxygen saturation to estimate the polymerization tendency for each of eight patients with sickle cell anemia (SCA). Progressive reduction of oxygen tension within the arterial range caused a sudden loss of filterability of SCA erythrocytes through 5-micron-diam pores at a critical PO2 between 110 and 190 mmHg. This loss of filterability occurred at a higher PO2 than did morphological sickling, and the critical PO2 correlated significantly (r = 0.844-0.881, P less than 0.01) with the polymerization tendency for each patient. Study of density-gradient fractionated cells from four SCA patients indicated that the critical PO2 of dense cells was reached when only a small amount of polymer had formed, indicating the influence of this subpopulation on the results obtained for unfractionated cells. Impairment of erythrocyte filterability at high oxygen saturation (greater than 90%) suggests that small changes in oxygen saturation within the arterial circulation cause rheological impairment of sickle cells.

Anemia, Sickle Cell↗
PubMed1987

Unfolding of iron and copper complexes of human lactoferrin and transferrin.

1. Human lactoferrin and transferrin are capable of binding two iron or copper ions into specific binding sites in the presence of bicarbonate. 2. Urea and several alkyl ureas have been effective in unfolding these metal-protein complexes. 3. Biphasic transitions are observed for the unfolding of each of the metal complexes of these proteins as determined by direct visible spectroscopy suggesting the release of iron(III) and Cu(II) ions from both of these metal-binding proteins during the unfolding process. 4. Greater stabilization and increased resistance to protein unfolding is observed for all iron(III) complexes compared to Cu(II) complexes of lactoferrin and transferrin as determined by isothermal unfolding and thermal denaturation. 5. Relative stabilization of the different metal-protein complexes investigated within this study were determined to be as follows: Lf-Fe(III) greater than Lf-Cu(II); Tf-Fe(III) greater than Tf-Cu(II), and Lf-Fe(III) greater than Tf-Fe(III); Lf-Cu(II) greater than Tf-Cu(II).

Circular Dichroism↗
PubMed1987

Rheology of the sickle cell disorders.

The sickling process causes secondary changes in cell shape, size, cation and water content, and membrane structure that contribute to the impairment of intrinsic cell deformability (Figure 2). This rheological defect is partially compensated by a low haematocrit, which moderates the rise in whole-blood viscosity, and by a rise in cardiac output which increases capillary flow velocity (Berger and King, 1982). A delicate balance exists between these mechanisms and any local disturbance of this balance by pathological changes in factors extrinsic to the sickle cell (Figure 2) can precipitate vaso-occlusion. There is still considerable controversy over the site (arteriolar, capillary, or venular) of vaso-occlusion, the type of sickle cell (reversibly sickled or irreversibly sickled) that is primarily involved, and the relative importance of extra-erythrocytic precipitating factors such as stasis, hypoxia, hyperosmolality, acidosis, alteration in temperature, acute-phase rise in plasma proteins and leukocytes, prothrombotic changes in coagulation factors and platelets, and adhesion of blood cells to vascular endothelium (Figure 2). A low-grade hypercoagulable state has been described in patients with SS (Leichtman and Brewer, 1978; Richardson et al, 1979) which may be related to the procoagulant effect of the shift of phosphatidyl serine to the outer lipid bilayer of the sickle cell (Chiu et al, 1981; Franck et al, 1985). Platelets appear to accumulate at sites of vaso-occlusion (Siegel et al, 1985) and their migration to the vessel wall may be enhanced by the presence of poorly deformable erythrocytes (Aarts et al, 1984). Endothelial cell damage in the arterial or venous circulation may also contribute (Klug et al, 1982). Thus vaso-occlusion appears to result from a complex interaction between blood cells, plasma proteins and endothelium and any one of several precipitating factors may disturb the fragile steady state and cause a painful crisis. The study of sickle cells by rheological methods has considerable potential for investigating the pathophysiology of vaso-occlusive episodes in the SCD and for monitoring, both in vitro and ex vivo, the efficacy of antisickling compounds. Because of the multiple intrinsic and extrinsic factors that contribute to the rheological defect, it is not yet known which of these should be the primary target for an antisickling agent. In-vitro rheological studies in which different metabolic stresses can be applied to intact sickle cells in the presence of a putative antisickling drug should help to answer this question.(ABSTRACT TRUNCATED AT 400 WORDS)

Anemia, Sickle Cell↗
PubMed1987

Acute abdominal distension following Cryptosporidium infection.

Two children, aged 15 months and 3 years, developed abdominal distension following proven Cryptosporidium enteritis. Both required readmission to hospital and both improved rapidly, one spontaneously and one with the help of an enema. The association of abdominal distension and Cryptosporidium infection has not been described previously.

Abdomen↗
PubMed1987

Induction of siderophore activity in Anabaena spp. and its moderation of copper toxicity.

Growth of Anabaena sp. strain 7120 (in the absence of chelators or added iron) was inhibited by the addition of 2.1 to 6.5 microM copper and was abolished by copper concentration of 10 microM or higher. When the copper was chelated to schizokinen (the siderophore produced by this organism in response to iron starvation), the toxic effects were eliminated. Analysis of culture filtrates showed that the cupric schizokinen remains in the medium, thereby lowering the amount of copper taken up by the cells. Although this organism actively transports ferric schizokinen, it apparently does not recognize the cupric complex. Thus, Anabaena sp. is protected from copper toxicity under conditions in which siderophore is being produced. For cells grown in low iron, the accumulation of extracellular schizokinen was observed to parallel cell growth and continue well into stationary phase. The actual iron status of the organism was monitored by using iron uptake velocity as an assay. Cultures grown on 0.1 microM added iron were found to be severely iron limited upon reaching stationary phase, thus explaining the continued production of schizokinen. These data show that the siderophore system in Anabaena spp. has developed primarily as a response to iron starvation and that additional functions such as alleviation of copper toxicity or allelopathic inhibition of other algal species are merely secondary benefits.

Copper↗
PubMed1987

Oxpentifylline and cetiedil citrate improve deformability of dehydrated sickle cells.

Erythrocytes from 14 patients with homozygous sickle cell anaemia were treated with the calcium ionophore A23187 to induce loss of cellular potassium and water. The dehydrated cells showed a decrease in filterability (loss of deformability) through pores of 5 micron diameter. Oxpentifylline and cetiedil citrate, which preserve erythrocyte cation and water content, had a significant (p less than 0.01) protective effect against loss of deformability at a concentration of 1 mumol/l. Oxpentifylline showed no adverse effect on the rheology, morphology, or haemolysis of sickle cells at concentrations up to 500 mumol/l. Drugs that act on the erythrocyte membrane to maintain cell hydration are of potential rheological benefit in sickle cell anaemia.

Anemia, Sickle Cell↗
PubMed1987

Rheological effects of bed rest in sickle cell disease.

A serial rheological study in two patients with homozygous sickle cell disease whose leg ulcers healed as a consequence of bed rest showed an improvement in erythrocyte deformability (filterability) associated with evidence of decreased haemolysis and a fall in the number of irreversibly sickled cells. This rheological improvement may aid the healing of leg ulcers by increasing blood flow in the ulcer base. The effects of bed rest on the rheology of sickle cell disease should be taken into account in future studies of vaso-occlusive crisis.

Adult↗
PubMed1987

Painful sickle cell crises precipitated by stopping prophylactic exchange transfusions.

A patient with homozygous sickle cell disease showed a reduced incidence of painful crises as a result of regular exchange transfusion, but on three occasions when transfusion treatment was interrupted, a painful crisis occurred. Onset of painful crisis was associated with raised packed cell volume (PCV) or percentage of haemoglobin S (HbS%), or both. Measurement of whole blood viscosity using in vitro mixtures of blood group compatible normal (AA) and sickle (SS) cells showed that above an HbS of 25% any increase in PCV caused a disproportionate increase in whole blood viscosity. These clinical observations and laboratory data suggest that when regular exchange transfusions are terminated both HbS% and PCV should be carefully monitored. Prophylactic venesection should be considered for patients who maintain their PCV after transfusion as HbS% rises.

Adult↗
PubMed1986

Intrinsic factors that influence measurement of erythrocyte deformability.

The efficiency of rheological tests for measuring erythrocyte deformability is a function of test specificity and test sensitivity. Recent improvements in both specificity and sensitivity have revealed that rheological measurements of erythrocyte deformability are affected by the volume, haemoglobin concentration, and shape of the test erythrocytes. This applies both to filtration methods, using pores of 3-5 micron diameter, and to the measurement of erythrocyte elongation by laser diffractometry. Erythrocyte indices and morphology should therefore be measured routinely in both patients and controls so that the values for these intrinsic factors can be correlated with the results of rheological measurements in all published studies.

Blood Viscosity↗
PubMed1986

Ranking of laboratory tests by consensus analysis.

A new analytical technique (consensus analysis) was devised to assess the performance of laboratory tests that are commonly used to monitor the acute and chronic phases of inflammatory disease. On thirty-one tests carried out monthly for 7 months in seventeen patients with rheumatoid arthritis, the consensus analysis procedure ranked plasma viscosity and erythrocyte sedimentation rate in a tie for first place. Measurement of the acute-phase serum protein orosomucoid ranked third. Consensus analysis has the potential to reduce laboratory costs by identifying the most useful tests; it also promises to be helpful in the design of new laboratory tests that are more sensitive and specific.

Adult↗
PubMed1986

Effect of BW12C on oxygen affinity of haemoglobin in sickle-cell disease.

Eight subjects with sickle-cell disease in the symptom-free steady-state received a single one-hour infusion of the new anti-sickling agent BW12C on a total of eleven occasions. A dose-dependent increase in wholeblood oxygen affinity was observed, resulting from the action of BW12C in stabilising the oxy-conformation of haemoglobin and causing a left shift of the oxygen saturation curve. At the highest dose given (20 mg/kg bodyweight), up to 23% of haemoglobin was modified to a BW12C-reacted high-affinity form without evidence of tissue hypoxia. There was biochemical and rheological evidence for a transient decrease in haemolytic rate.

Adult↗
PubMed1986

Blood rheology and proliferative retinopathy in homozygous sickle cell disease.

Some haematological and rheological features were compared in 27 age and sex matched pairs of patients (15 male, 12 female) with homozygous sickle cell (SS) disease with and without proliferative sickle retinopathy (PSR). Significant haematological differences between the groups were a higher haemoglobin and a lower fetal haemoglobin in PSR positive males and a higher MCHC in PSR positive females. The plasma viscosity and characteristics of erythrocyte filterability did not differ between those with and those without PSR, although PSR positive males had a significantly higher whole blood viscosity when measured at high shear and at the patient's own packed cell volume.

Adult↗
PubMed1986

Effects of hyperglycaemia and sorbitol accumulation on erythrocyte deformability in diabetes mellitus.

Erythrocyte deformability was studied in a total of 83 poorly controlled diabetics (mean blood glucose 12.2 mmol/l) who were divided into three groups, each with matched healthy controls. There was no appreciable difference between diabetics and matched controls regarding the filtration of erythrocytes through 3 micron diameter straight channel pores (25 diabetics) or tortuous channel pores (28 diabetics), or for the measurement of erythrocyte elongation over a range of osmolalities in the Ektacytometer (30 diabetics). When erythrocytes from 17 additional diabetics and 17 healthy controls were incubated for two hours at 37 degrees C in hyperglycaemic (50 mmol glucose/l) buffer, however, there was a considerable reduction in erythrocyte filterability for both diabetics and controls in parallel with an increase in erythrocyte sorbitol concentration. This loss of filterability was prevented by the addition of an aldose reductase inhibitor (Sorbinil). High glucose concentrations (congruent to 50 mmol/l) impair the filterability of erythrocytes through 3 micron pores, and the intracellular accumulation of sorbitol in poorly controlled outpatients is therefore unlikely to have a major adverse effect on erythrocyte rheology in diabetes mellitus.

Adult↗
PubMed1986

Rheological importance of acute-phase reactants.

Acute vascular events, and also chronic atherosclerotic vascular disease, are associated with a rise in blood level of several acute-phase reactants. Of these, fibrinogen is of particular rheological importance since hyperfibrinogenaemia causes hyperviscosity of plasma and whole blood and is an adverse prognostic factor in intermittent claudication, coronary artery disease, and stroke. Activation of the monocyte-macrophage system by fibrinogen degradation products, with release of interleukin-1 and secondary stimulation of liver and bone marrow, may be of pathogenic importance in the stress responses of acute and chronic vascular disease.

Acute-Phase Proteins↗
PubMed1985

Fluctuating deformability of oxygenated sickle erythrocytes in the asymptomatic state and in painful crisis.

A new gravity filtration technique for the study of sickle cell deformability has shown a significant loss of filterability of oxygenated erythrocytes on day 2 of painful crisis in eight patients with homozygous sickle cell anaemia; there was no increase in irreversibly sickled cell (ISC) count. Serial study (mean of 5.2 occasions) in six out-patients when asymptomatic also showed considerable fluctuation in sickle cell filterability with time; this was again independent of ISC count. Erythrocyte filtration methods demonstrate fluctuations in the rheology of sickle cells that are not detected by ISC counts and which are probably secondary to clinically occult, as well as overt, vaso-occlusive events in the microcirculation.

Adult↗