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Biomedical subjects

J Stocks

Publications and source records attributed to J Stocks.

At least 163 records · Page 9Linked to original sources

DNA polymorphism adjacent to human apoprotein A-1 gene: relation to hypertriglyceridaemia.

Polymorphism in a DNA sequence has been observed on the 3'-flanking region of the human apoprotein-A-1 gene. The frequency of the heterozygous state in a healthy control population (n = 73) is around 0.05. However, 12 (frequency 0.34) out of 35 subjects with hypertriglyceridaemia were found to have the polymorphic site, and 2 were homozygous for this variant. The mutant allele may constitute a linkage marker for some abnormality within the apoprotein-A-1 gene, affecting either expression of or some minor structural modification of the A-1 apoprotein, that may predispose to hypertriglyceridaemia.

Apolipoprotein A-I↗

Esophageal pressure in infants at elevated lung volumes and positive airway pressure.

The measurement of esophageal pressure changes (delta Pes) under conditions of elevated lung volume or continuous positive airway pressure (CPAP) was investigated in a group of 17 infants by use of an esophageal balloon. Eleven of the infants were studied in a whole-body plethysmograph, and lung volume was increased by a volume injection technique. Reproducible measurements of lung volume in the plethysmograph showed that changes in mask pressure (delta Pm) were accurate during airway occlusion in 10 of the 11 infants. A progressive elevation of the ratio delta Pes/delta Pm during respiratory efforts against occlusion at lung volumes above the tidal range was observed in 8 of the 11 infants. In only one of these infants could the error have been in delta Pm measurement. Of seven infants (including one common to both studies) studied under CPAP, six also showed this effect, which occurred predominantly in very young or preterm infants. Changes in esophageal pressure in infancy, measured at high lung volumes or pressures, may not be representative of mean pleural pressure changes.

Esophagus↗

Studies of anti-Xa activity in human plasma. II: The role of lipoproteins.

The major plasma inhibitor of factor Xa is thought to be anti-thrombin III (At III). However, adsorption of plasma by aluminium hydroxide (A1(OH)3) increases its rate of neutralisation 7-8 fold, and this 'fast-acting' anti-Xa activity has been shown to be independent of At III. Gel filtration of plasma indicated that the anti-Xa activity after A1(OH)3 adsorption was located largely in the high molecular weight (greater than 200,000) fractions, which contain most of the plasma lipoproteins. Purified lipoproteins of very low-density (VLDL), low-density (LDL) and high density (HDL) were prepared by ultracentrifugation and their anti-Xa activities measured before and after adsorption by A1(OH)3. Both LDL and HDL had significant anti-Xa activities by clotting and amidolytic assays. A1(OH)3 adsorption of LDL and HDL gave a marked increase in anti-Xa clotting activity and a decrease in amidolytic activity. Incubation of the adsorbed lipoproteins with phospholipase enzymes destroyed the anti-Xa activity, and prior incubation of Factor Xa with Ca++ and phospholipid protected it against inactivation, indicating that the anti-Xa activity of the adsorbed lipoproteins is mediated via binding of Xa to phospholipid in the lipoproteins. These results indicate that lipoproteins, especially LDL and HDL, are responsible for the increased anti-Xa activity of plasma after A1(OH)3 adsorption. These lipoproteins appear to contain high affinity phospholipid binding sites for Xa which are revealed by A1(OH)3 adsorption.

Adsorption↗

Lung function in infants with congenital pulmonary hypoplasia.

Lung volume and lung mechanics were measured in 19 infants, aged 2 to 8 weeks, with congenital pulmonary hypoplasia of various causes. These included nine infants with congenital diaphragmatic hernia, five infants with Werdnig-Hoffman disease of intrauterine onset, and five infants with isolated pulmonary hypoplasia or associated anomalies such as thoracic dystrophy and spina bifida. Infants were studied within the first two months of life in order to exclude the effects of natural adaptation and adverse influences such as lower respiratory tract infection. Lung volume and airway resistance were estimated by whole body plethysmography, total pulmonary resistance, and dynamic lung compliance with esophageal balloons and pneumotachography. Reductions in dynamic lung compliance were found in seven of the nine infants with congenital diaphragmatic hernia, probably reflecting lung overdistention after operative repair. Low airflow resistance was found in 12 infants, representing subjects from each category. The low airflow resistance may be related to reductions in airway generation number found when the disturbance of lung development occurs before 16 weeks of gestational age. This finding suggests a role for measurements of airflow resistance in characterizing the type of pulmonary hypoplasia.

Airway Resistance↗

Studies of a variant very-low-density lipoprotein with an acquired deficiency of apolipoprotein C-II.

1. A variant very-low-density lipoprotein was associated with severe hypertriglyceridaemia. Urea-polyacrylamide gel electrophoresis of the tetramethylurea-soluble apolipoproteins of these very-low-density lipoproteins (VLDL) showed that the apolipoprotein C-II content was less than 10% of that in VLDL from hypertriglyceridaemic (3-120 mmol/l) controls. 2. VLDL were incubated with bovine milk lipoprotein lipase (LPL) and a 9,10-3H-labelled triglyceride emulsion. The VLDL deficient in apolipoprotein C-II were a poor activator of LPL, compared with the effect of VLDL with normal content of apolipoprotein C-II obtained from either normal or hypertriglyceridaemic sera. 3. The efficacies of various VLDL as substrates fo activated LPL were examined. Apolipoprotein C-II-deficient VLDL were a poor substrate for the activated enzyme compared with normal or hypertriglyceridaemic VLDL, and compared wtih an artificial triglyceride emulsion. 4. The abnormal VLDL were obtained from a subject with an IgG3 lambda myeloma protein. Intravenous infusion of normal plasma containing apolipoprotein C-II was followed by rapid, complete, but short-lived (5-10 days) clearance of serum triglyceride. The effect was observed on three occasions until treatment of the myeloma was effective. 5. The monoclonal protein behaved as a cryoglobulin, and formed large particle complexes with triglyceride-rich lipoproteins, especially at temperatures below 37 degrees C. The apolipoprotein C-II deficiency, and consequent hypertriglyceridaemia, may be secondary to an autoantibody directed against apolipoprotein C-II. VLDL from relatives with hypertriglyceridaemia, but without myeloma, had normal apolipoprotein content, activated LPL, and were efficient substrates for the enzyme.

Adult↗

Bronchial hypersecretion in preterm neonates.

During an 18-month period, 11 preterm infants with birthweights between 700 and 1560 g (mean 1.2 kg) developed excessive tracheobronchial secretions during intensive care. No single obstetric factor was incriminated. Copious, viscous, tracheobronchial secretions were noted at about 5 days during mechanical ventilation via endotracheal tube causing recurrent segmental collapse, hypoxia, and hypercapnia (median peak PCO2 13.5 kPa). All infants were treated with frequent bronchial lavages and continued intermittent positive pressure ventilation, together with high concentrations of oxygen. No infant died, but morbidity was high. Tracheostomy was performed on 2 infants (one at age 3 months, because of severe croup) and 2 others had clinical or physiological evidence of upper airways narrowing. Follow-up studies showed that this group had more problems of airways obstruction throughout the first year of life as well as increased lung stiffness. The hypersecretion group showed a higher incidence of chronic lung disease. Likely aetiological factors were sought. Contamination of the mechanical ventilation equipment by detergent and activated glutaraldehyde was found; this could have been a contributory factor.

Airway Obstruction↗

Problems in measurement of thoracic gas volume in infancy.

Thoracic gas volume (TGV) was measured with a whole-body plethysmograph in 20 infants at functional residual capacity (FRC) and at a series of higher lung volumes achieved by artificial inflation of the lungs with known volumes of air after airway occlusion. There was a discrepancy between the corrected values of TGV measured at high and low lung volumes in nine infants; in six cases TGV measured at high lung volumes exceeded that measured at FRC, and in three cases it was reduced when compared with the measurement made at FRC. These changes were not related to age, size, or clinical status and could be explained by airway closure at FRC, combined with an uneven distribution of pleural pressure.

Gases↗

An abnormal triglyceride-rich lipoprotein containing excess sialylated apolipoprotein C-III.

An abnormal triglyceride-rich lipoprotein has been isolated from some patients with chronic renal failure or severe hypertriglyceridemia. The abnormal lipoprotein was characterized by an increased content of apolipoprotein (apo) C-III-2 (57.5% of total apo C-III peptides compared with 35.5% for controls, P less than 0.001) as characterized by isoelectric focusing and scanning densitometry. As determined by a substrate competition assay, the abnormal lipoprotein was a less efficient substrate for purified bovine milk lipoprotein lipase than control lipoproteins. Neuraminidase digestion of abnormal or control lipoprotein resulted in a reduction of the apo C-III-2 band with a corresponding increase in the region of apo C-III-0, which suggests that the increased content of apo C-III-2 in the abnormal is due to excessive sialylation of the C-III peptide. Limited incubation of the abnormal lipoproteins with neuraminidase caused a partial loss of sialic acid and resulted in a triglyceride-rich lipoprotein with a normal C-III-2:C-III-1 ratio. This preparation displayed normal substrate interaction with lipoprotein lipase. Three severely hypertriglyceridemic patients with the abnormal lipoprotein showed a marked reduction in serum triglyceride concentration, which is associated with a reversion to a normal C-peptide profile after dietary therapy. The results suggest that the extent of sialylation of the apo C-III peptide carried on triglyceride-rich lipoproteins may be critical for their interaction with lipoprotein lipase.

Apolipoproteins↗

High-fibre and low-fat diets in diabetes mellitus.

1. Eight insulin-dependent and eight insulin-independent diabetic patients and twenty-eight non-diabetic essential hypertensive patients were given a high-fibre, high-unrefined carbohydrate and low-fat diet for 3 months duration. 2. The effects of this dietary regimen on the patients' fasting blood glucose, hypoglycaemic therapy and weight was observed. 3. Fasting lipid profiles were obtained before and after 3 months on the dietary regimen, and total serum lipids and lipoprotein fractions were analysed. 4. The insulin-dependent and insulin-independent diabetic patients showed a reduction in hypoglycaemic therapy, with no significant change in fasting blood glucose. The insulin-independent and non-diabetic groups both showed significant weight loss. 5. The three groups of patients showed a significant reduction in cardiovascular risk factors with either an elevation of high-density lipoprotein (HDL)-cholesterol or a fall in low-density lipoprotein (LDL)-cholesterol and a reduction in the total cholesterol: HDL-cholesterol value.

Adult↗

Absolute intraesophageal pressure at functional residual capacity in frequency.

Absolute intraesophageal pressure at functional residual capacity (FRC) has been estimated in 15 infants (age 1-30 wk) by the extrapolation of the esophageal pressure-volume relationships to zero balloon volume by use of air-filled balloons in their ranges of infinite compliance. The pressure-volume relationships of the esophageal balloons (length 3.5-5.0 cm, perimeter 1.7-2.5 cm, wall thickness 0.045-0.075 mm) were determined in air and in erect and horizontal positions under water, the behavior of the balloons placed horizontally under water closely approximated that of the balloons in vivo. The mean absolute intraesophageal pressure at FRC was -1.44 cmH2O in eight normal infants and -1.56 cmH2O in seven convalescent infants with a variety of cardiorespiratory disorders. The less negative absolute end-expiratory esophageal pressure in infants when compared with that in adults can be explained by changes in lung elastic recoil, chest wall recoil, or a combination of these factors during the development and growth of the respiratory system from birth to adulthood.

Esophagus↗