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M J Elliott

Publications and source records attributed to M J Elliott.

At least 127 records · Page 7Linked to original sources
PubMed1991

Inhibition of human monocyte adhesion by interleukin-4.

The adhesion of monocytes to vascular surfaces is central to inflammation and atherogenesis; however, very little is known about regulatory factors that can prevent these processes. Here we report the inhibition of human monocyte adhesion to human endothelial layers and plastic by interleukin-4 (IL-4), a T-cell-derived glycoprotein with pleiotropic activities. The inhibitory effects of IL-4 were seen with basal and cytokine-stimulated monocyte adhesion, were apparent at low concentration, and were abolished by inactivating IL-4. No direct toxic effect of IL-4 on monocytes was detected. Inhibition of adhesion was accompanied by small increases in monocyte surface expression of the leukocyte-functional antigen group of adhesion structures, suggesting that absolute levels of expression may be less important than the functional status of such molecules in the regulation of monocyte adhesion. In addition, inhibition by IL-4 of cytokine-stimulated monocyte adhesion was not associated with changes in the surface expression of cytokine receptors. These results suggest a role for IL-4 in the regulation of monocyte adhesion, and may provide for a common mechanism for the inhibitory effects of IL-4 on monocyte function.

Antigens, CD↗
PubMed1991

Fibrous skeleton and ventricular outflow tracts in double-outlet right ventricle.

Twenty-four hearts in which both great arteries arose from the right ventricle were studied to establish variations present within the fibrous skeleton and infundibular morphologies. Variations were also noted in the location of the ventricular septal defect and measurements were obtained of the outlet septum and the circumferences of the arterial valves. Completely muscular subarterial infundibulums were present in only 9 (37.5%) of the hearts, with varying degrees of fibrous continuity between the leaflets of the arterial and atrioventricular valves in the remainder. The aorta was rightward and posterior in 12 (50%) of the hearts, and subaortic and subpulmonary ventricular septal defects were present in equal numbers in this group. No subaortic defects were present when the aorta was side-by-side and right-sided. No subpulmonary defects were present in hearts with a posterior aorta. The mean ratio of 0.91 +/- 0.36 for the subpulmonary to subaortic length of the outlet septum was significantly less than the value of 1.54 +/- 0.41 noted previously in hearts with tetralogy of Fallot (p less than 0.001).

Aortic Valve↗
PubMed1991

Current surgical technique to repair Fallot's tetralogy with absent pulmonary valve syndrome.

The experience with surgical repair of Fallot's tetralogy and absent pulmonary valve syndrome is reviewed. Twenty-two patients aged 1 day to 8 years were treated between 1982 and 1989 using one surgical technique. This consisted of resection of the main pulmonary artery and large parts of the anterior wall of the right and left pulmonary artery. The ventricular septal defect was closed with a patch, and an aortic or pulmonary homograft (size, 8 to 24 mm) was interposed between the right ventricle and the pulmonary artery. Two of the 8 infants operated on died; there was one late death. All 14 older children survived the operation. All survivors are well up to 7 years follow-up (mean follow-up, 3.6 years). We recommend early treatment of infants; older children can be treated electively. The technique used in our series gives excellent results.

Child↗
PubMed1991

A successful modification of ultrafiltration for cardiopulmonary bypass in children.

Total body water (TBW) is increased after cardiopulmonary bypass (CPB) resulting in tissue oedema and organ dysfunction. Ultrafiltration has been used to reduce this accumulation of water, although conventional ultrafiltration seemed ineffective in reducing the rise in TBW after CPB in our clinical experience. We describe a modified technique in which ultrafiltration is performed in the first 10 minutes after the patient is weaned from bypass, returning nearly all the blood in the circuit to the patient and elevating the haematocrit (Hct) to any predetermined level. We carried out a pilot study on 21 children aged 4-144 months undergoing open-heart surgery and CPB for congenital heart defects. They were divided into three comparable groups: (1) controls (n = 6); (2) conventional ultrafiltration (n = 7); and (3) modified ultrafiltration (n = 8). TBW (bio-impedance), Hct, osmolality, mean corpuscular volume and mean corpuscular haemoglobin concentration were recorded at frequent intervals. Control patients showed elevation of TBW by 18.2% median (range 14.5-20.3), conventional ultrafiltration by 12.4% (7.9-15.0), modified ultrafiltration by 5.7% (4.5-7.1) (p less than 0.0001 compared to controls, p. less than 0.005 compared to conventional ultrafiltration, Mann-Whitney U test). Hct could be elevated to preoperative levels only by the modified method. Mean corpuscular volume, and mean corpuscular haemoglobin concentration osmolality were unaltered. Ultrafiltration by the modified method was more effective than conventional ultrafiltration in reducing the rise in TBW and elevating Hct after CPB.

Blood Volume↗
PubMed1991

Alternative method of gestational age assessment by the measurement of human erythrocyte differentiation antigen expression.

Standard estimates of gestational age are dependent on such subjective data as maternal recollection of last menstrual period, ultrasound examination of the fetus, and the postnatal physical and neurological examination (Ballard score). We hypothesized that a quantitative, objective laboratory test using flow cytometric analysis of erythroid differentiation antigens could be useful to predict gestational age. For this study erythrocyte samples were obtained within 24 hours of birth from 25 infants (gestational ages 20 to 41 weeks) who met the criteria that traditional estimates of gestational age, such as the Ballard score, fetal ultrasound, and maternal estimate of last menstrual period all agreed within 1 week for the assessed infant's gestational age. Study measurements included reticulocyte count and determination of the percentage of erythrocytes that expressed the 5F1 and 20.3 erythropoietic differentiation antigens. Linear regression analysis indicated that the best correlations with gestational age were reticulocyte count (R2 = .354) and the reciprocal of the percentage of erythrocytes expressing the 5F1 antigen (R2 = .470). When both variables were incorporated into a linear regression model, the predictability of gestational age achieved an R2 = .608. Through this study we have established the feasibility and methodology of using fetal and newborn erythrocytes to provide an objective assessment of gestational age by flow cytometric analysis of erythroid differentiation antigen expression. This methodology will allow for an independent assessment of gestational age when fetal blood sampling is performed for other prenatal diagnostic studies. Further investigation is needed to identify other erythroid differentiation markers that would improve the accuracy of our model to predict gestational age.

Antigens, Differentiation↗
PubMed1991

Heart and lung transplantation for terminal cystic fibrosis. A 4 1/2-year experience.

From among 112 patients with cystic fibrosis who were assessed for heart-lung transplantation, 83 were accepted. Twenty-six died while awaiting heart-lung transplantation and 32 had the operation. The management and the outcome of these 32 patients is reported. Survival, infection, and rejection rates among these patients were compared with those of 61 patients without cystic fibrosis who underwent heart-lung transplantation between 1984 and 1990. The cumulative survival rate was 72.29% +/- 94.91% at 1 year and 55.59% +/- 7.50% at 3 years. The mortality rate was slightly higher in the group with cystic fibrosis during the first year after the operation but it was lower at 3 years. The difference, however, could have been due to chance alone (p = 0.308). The same was true for the prevalence of rejection (up to 6 months: chi 2 = 1.8141, p = 0.17), and infection (up to 6 months: chi 2 = 2.20, p = 0.14), between the two groups. It is concluded that cystic fibrosis does not constitute an additional risk in terms of survival and morbidity after heart-lung transplantation.

Adolescent↗
PubMed1990

IL-3 and granulocyte-macrophage colony-stimulating factor stimulate two distinct phases of adhesion in human monocytes.

IL-3 and granulocyte-macrophage CSF are hemopoietic growth factors involved in monocytopoiesis and functional stimulation of circulating blood monocytes. We demonstrate that both cytokines enhance the adhesion of purified human monocytes to cultured human umbilical vein endothelial cells and to plastic surfaces. The stimulation seen was biphasic: an early phase detectable by 10 min, and a late phase seen after 9 h of in vitro culture. IL-3- and granulocyte-macrophage-CSF-stimulated adhesion was seen at concentrations as low as 6 pM, with maximal monocyte adhesion of up to 60% seen at concentrations of 60 pM and above. Both phases of stimulated adhesion were partially inhibited by a monoclonal antibody to CD18, the common beta-chain of the leukocyte functional Ag family of adhesion molecules, but not by an antibody to CD11b, the alpha-chain of MAC-1. However, a difference in the mechanism by which the early and late phases of stimulated adhesion arise could be shown by the use of cycloheximide as an inhibitor of protein synthesis. Although the late phase was totally dependent on de novo protein synthesis, early phase adhesion was not inhibited by cycloheximide, suggesting receptor redistribution or conformational change as the mechanism mediating enhanced adhesion at this time. These findings may be relevant to the pathogenesis of inflammatory disease and may have implications for the clinical use of these cytokines.

Antibodies, Monoclonal↗
PubMed1990

Identification of a novel integrin beta subunit expressed on cultured monocytes (macrophages). Evidence that one alpha subunit can associate with multiple beta subunits.

The vitronectin receptor (VnR) is one member of a subset of cell adhesion receptors within the integrin supergene family which shares the beta 3 subunit (IIIa). We show here that the VnR is absent from the surface of monocytes freshly isolated from blood but is expressed on these cells after a period of in vitro culture. Such cultured monocytes (macrophages) from a patient with type I Glanzmann's thrombasthenia, however, failed to express the VnR. Instead, immunoprecipitation with a monoclonal antibody directed to the VnR alpha chain (alpha v) revealed a novel integrin comprising alpha v associated noncovalently with a 100-kDa beta subunit (beta 3b), immunologically unrelated to the VnR beta subunit (beta 3a). This same novel integrin complex was also identified on 10-day-old macrophages from healthy donors, but on these cells, the beta 3b subunit was co-expressed with the classical VnR complex of alpha v beta 3a. The novel beta 3b subunit was not identified by monoclonal or polyclonal antibodies to IIIa (beta 3a) nor by a monoclonal antibody to the classical VnR complex. The beta 3b subunit could be distinguished from beta 3a by its relatively greater migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction, by its distinct isoelectric point upon two-dimensional gel electrophoresis, and by one-dimensional peptide mapping. Neither platelets nor B lymphoblasts from this patient with Glanzmann's thrombasthenia expressed any VnR on their surface, whereas control cells from a normal donor expressed the classical VnR but not the beta 3b subunit. The two beta chains, and hence also the combined receptor complexes, appeared to be differentially regulated. These findings provide the first example of an integrin alpha chain complexed with more than a single beta chain in the same cell. Furthermore, the differential regulation of expression of the different beta subunits that associate with the VnR alpha chain on cultured monocytes suggests a role for the novel receptor complex during monocyte/macrophage differentiation.

Adult↗
PubMed1990

Variations within the fibrous skeleton and ventricular outflow tracts in tetralogy of Fallot.

We studied 20 hearts with tetralogy of Fallot with particular reference to the morphology of the fibrous continuity between the aortic and atrioventricular valves and of the ventricular outflow tracts. The extent of valvar fibrous continuity varied with the degree of aortic override, with the extent of the perimembranous ventricular septal defect opening between the ventricular inlets, and with the development of the ventriculoinfundibular fold. This, when fused with the septomarginal trabeculation, produced discontinuity between the leaflets of the tricuspid valve and the continuous leaflets of the aortic and mitral valves, as well as a muscular posteroinferior rim to the defect. Rotation of the aortic root ranged through 119 degrees. Aortic override varied from 33% to 94%, with 35% of these hearts having more than half of the aortic circumference connected to the right ventricle. The pulmonary valves had three leaflets in 50%, two leaflets in 45%, and four leaflets in one (5%). All hearts had two main coronary arterial orifices, 45% of which were atypical in location. One heart displayed a transmural course of the left coronary artery arising from the nonfacing sinus. By measurement, the subpulmonary length was, on average, roughly 50% greater than the subaortic length, and, when the selected hearts were sectioned, much of the subpulmonary infundibulum was found to be composed of free-standing musculature rather than true outlet septum. The proportion of total right ventricular length represented by the infundibulum was 0.31 +/- 0.07, confirming that, compared with that of normal hearts, the narrowed infundibulum in tetralogy is longer rather than shorter.

Aortic Valve↗
PubMed1990

Paralysed diaphragm after cardiac surgery in children: value of plication.

Over a 2-year period (1987-1988), 31 children (3% of 960 operations) were found to have a paralysed diaphragm following cardiac surgery. The median age was 5 months with 65% less than 1 year of age. In the 31 patients, 38 paralysed diaphragms were identified. The phrenic nerve injury was on the right in 8 cases, the left in 16, bilateral in 7 and 40% were related to modified Blalock Taussig shunts. The time to extubation was analysed for each patient in two separate groups: Group A: (greater than 1 year): 11 children of whom 5 were extubated without difficulty, 4 had non-respiratory reasons for prolonged ventilation and only 2 were plicated--both were extubated within 4 days. Group B: (less than 1 year): 20 infants of whom 16 were plicated and 4 were not. Three of the children who were plicated died from cardiac causes. Of the 13 survivors, there were 3 who had other reasons for prolonged ventilation. Thus 10 infants required prolonged ventilation (mean 11 days) because of respiratory difficulties. All underwent plication and were extubated at a mean of 2.4 days postoperatively. The 4 who were not plicated were extubated at a mean of 11 days postoperatively. In infants in whom there is no cardiac cause for failure to wean from ventilation, diaphragmatic paralysis should be suspected and plication performed if not extubated 2 weeks after operation.

Anastomosis, Surgical↗
PubMed1990

Blood leukocytes bind platelet glycoprotein (IIb-IIIa)' but do not express the vitronectin receptor.

Within the integrin family of Arg-Gly-Asp(RGD)-binding adhesion receptors, the subfamily defined by the beta chain known as beta-3 or glycoprotein (GP)IIIa is known to contain two individual receptors. These are the GPIIb-IIIa complex of platelets, where the alpha chain of the heterodimer is GPIIb, and the vitronectin receptor (VnR) containing the alpha V subunit. The presence of either GPIIb-IIIa and/or the VnR on blood leukocytes has been controversial. We have investigated this problem by performing immunoprecipitation and immunoblotting studies with rabbit and monoclonal antibodies (mAb) to each of the subunits of GPIIb-IIIa and the VnR. On cultured cells of different origin, it was established that almost all expressed the VnR but none had GPIIb-IIIa, and the only polypeptide associated with beta 3 was alpha V. Platelets expressed predominantly GPIIb-IIIa, and weakly, the VnR. Monocytes and neutrophils freshly isolated from blood did not express the VnR but bore on their surface a modified form of GPIIb-IIIa. This molecule appeared identical to GPIIb-IIIa but an epitope on GPIIb was masked on the intact cell and was only revealed after immunoblotting. We have termed this modified form of GPIIb-IIIa, GP(IIb-IIIa)'. With differentiation in culture, monocytes rapidly lost surface GP(IIb-IIIa)' and concurrently began to express the VnR. Evidence is presented that GP(IIb-IIIa)' is derived from particles released by activated platelets and is bound firmly to the leukocyte membrane. Its primary function does not seem to be to mediate attachment to matrix proteins; thus, although U937 cells bearing platelet-derived GP(IIb-IIIa)' bound fibrinogen in an RGD-dependent manner, isolated blood monocytes did not. It is suggested that this transfer of membrane proteins from platelets to monocytes and neutrophils may regulate the expression of the leukocyte VnR and also serve as a means of facilitating leukocyte procoagulant activity.

Amino Acid Sequence↗
PubMed1990

The metabolic consequences of a "washed" cardiopulmonary bypass pump-priming fluid in children undergoing cardiac operations.

The substrate load of the pump-priming fluid, especially glucose and lactate, has a major influence on the metabolic response of children during cardiac operations and may be detrimental neurologically. It is possible to cleanse the priming fluid of these excess substrates by ultrafiltration followed by the addition of a balanced electrolyte solution. We have used this technique in the bypass management of nine children over 1 year of age and weighing less than 18 kg who were studied from induction of anesthesia to 6 hours postoperatively. Frequent blood samples were taken for measurement of electrolytes, intermediary metabolites, and stress-related hormones. Throughout the study period electrolyte concentrations were maintained within the physiologic range and changes in blood glucose and lactate were minimized compared with those of matched historical controls from previous studies. During the period of cardiopulmonary bypass mean serum glucose concentrations varied between 4.4 and 7.7 mmol/L and peaked at 10.7 mmol/L just before skin closure. The mean serum lactate concentration did not exceed 2.3 mmol/L during the period studied. Thus ultrafiltration of the priming fluid and replacement with a balanced electrolyte solution results in the delivery to the patient of a reasonably physiologic substrate load, which is reflected in improved control of mean plasma intermediary metabolite concentrations. The method may form the basis of further clinical studies to determine specific aspects of the metabolic stress response in children.

Blood Glucose↗
PubMed1989

Recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor show common biological effects and binding characteristics on human monocytes.

Two human hemopoietic growth factors involved in monocytopoiesis, interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were studied for their ability to stimulate blood monocytes and to bind to the monocyte membrane. Both cytokines maintained monocyte/macrophage numbers during long-term culture and increased cell size as compared with controls. Effects on cell numbers were present at low cytokine concentrations (6 to 20 pmol/L), whereas enhanced 3H-thymidine incorporation was observed only at higher concentrations (greater than or equal to 60 pmol/L). Autoradiographic studies showed only 1% to 3% of stimulated monocytes with nuclear grains. These results suggest that the primary mechanism for IL-3 and GM-CSF-induced maintenance of monocyte/macrophage numbers in humans is through an effect on cell survival. Surface receptors for both IL-3 and GM-CSF were studied by using 125I-labeled recombinant human (rh) cytokines and performing Scatchard analyses. Both cytokines showed curvilinear Scatchard plots, and computer analyses favored a two-site binding model. High-affinity binding data for 125I rhIL-3 (Kd 7.7 to 38.2 pmol/L; receptor number/cell 95 to 580) and for 125I rhGM-CSF (Kd 4.7 to 38.9 pmol/L; receptor number/cell 8 to 67) show similar binding affinities for the two cytokines but a lower receptor number/cell for 125I rhGM-CSF. Low-affinity binding characteristics for 125I rhIL-3 (Kd 513 to 939 pmol/L; receptor number/cell 179 to 5,274) and for 125I rhGM-CSF (Kd 576 to 1,120 pmol/L; receptor number/cell 130 to 657) show a similar pattern for the two cytokines. Specificity of 125I rhIL-3 and 125I rhGM-CSF binding to monocytes was established by the ability of the homologous cytokine to inhibit binding and the inability of a range of other cytokines to compete at 100-fold excess molar concentration. It is important, however, that binding of 125I rhIL-3 was partially inhibited by rhGM-CSF and that rhIL-3 partially inhibited binding of 125I rhGM-CSF to the monocyte membrane under conditions shown to prevent receptor internalization. The degree of inhibition varied between 25% and 80% in different experiments, and quantitative inhibition experiments showed that 1,000-fold excess concentrations of competitor failed to inhibit binding of the heterologous ligand completely. These results demonstrate that human IL-3 and GM-CSF have similar effects on growth and survival of human monocytes in vitro and suggest that these and other common biological effects may be mediated either through a common receptor or through distinct receptors associated on the monocyte membrane.

Binding, Competitive↗
PubMed1989

Long-term results of homograft valves in extracardiac conduits.

Between 1971 and 1986, 335 patients received various extracardiac valved conduits between one of the heart chambers and the pulmonary arteries. The group of patients who received aortic homograft conduits and survived the operation were analysed in detail. The age varied between 9 days and 18 years (mean 7.1 +/- 0.7 years), weight 2.4 kg-63.5 kg (mean 17.8 +/- 10.8 kg). The diameter of the conduit used was 10-30 mm (mean 20.8 mm). Multivariate analysis revealed a highly significant model (P less than 0.005) which showed that the time interval between harvesting and use of the homograft (P less than 0.02) and the earlier date of operation (P less than 0.05) were the major risk factors for obstruction. Homografts used within 3 weeks of harvesting had freedom from obstruction of 79% at 8 years; homografts used between 3-6 weeks had freedom from obstruction of only 55% at 8 years. Homografts used alone performed significantly better than those extended with woven Dacron tubes. At 10 years, 93% of homografts used alone were free of obstruction compared to 52% of homografts extended with a Dacron tube. We conclude that aortic homografts used within 3 weeks of harvesting provide a reasonably durable conduit for a period of 12 years. Longer storage, and extension of the homograft with a woven Dacron tube should be avoided.

Adolescent↗
PubMed1989

Factors associated with age of onset of necrotizing enterocolitis.

To investigate factors associated with risk and age of onset for necrotizing enterocolitis (NEC), a retrospective case-control review was performed of patients with NEC and control infants matched for birthweight and date of admission. NEC cases were defined by Bell staging criteria and were included if pneumatosis intestinalis, histologic confirmation, or a recognized complication of NEC was identified in association with clinical signs and symptoms. NEC was significantly related to birthweight and premature post-conceptional age. In contrast to control infants, patients with NEC had higher 5 minute Apgar scores, less significant respiratory disease, and more rapid feeding practices. Two distinct subgroups of patients with NEC based on postnatal age of onset were apparent. Patients with early onset NEC (21 days or less postnatal age) had less significant respiratory disease and were fed more rapidly than late onset patients. Late onset NEC (more than 21 days postnatal age) occurred frequently in convalescing, relatively well premature infants who were still, however, of preterm postconceptional age. Relatively well premature infants with minimal respiratory disease are still at risk for NEC. Advances in neonatal care and survival of very low birthweight infants may account for a shift in prevalence to older infants who are yet of preterm postconceptional age.

Age Factors↗