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Biomedical subjects

D Hull

Publications and source records attributed to D Hull.

At least 163 records · Page 9Linked to original sources

Rabbit placental clearing-factor lipase and transfer to the foetus of fatty acids derived from triglycerides injected into the mother.

1. Lipase activity was measured in rabbit placental tissue fragments in late pregnancy. The activity in incubated tissue was greater with heparin (69%), reduced by NaCl (90%), but not affected by acetone or ether. 2. Pregnant rabbits (28-days gestation) were given triglyceride emulsions intravenously and the change in profile of fatty acids in the maternal and umbilical artery and vein plasma free fatty acid (FFA) measured. 3. Those fatty acids predominant in the emulsion were higher in concentration in the umbilical vein FFA than in the maternal plasma FFA and the venous-arterial difference was altered such that the placental transfer of FFA was enriched in a pattern corresponding to the profile of the fatty acids in the emulsion. 4. It is concluded that (i) the rabbit placenta shows considerable lipase activity and the lipase has the same characteristics as clearing-factor (lipoprotein) lipase, (ii) triglyceride infused into the mother is taken up by the placenta and hydrolysed, and (iii) the fatty acids so released pass through the placenta and are taken up by the foetus.

Animals↗

Fibrosing alveolitis in infancy and childhood.

Fibrosing alveolitis is a rare, diffuse lung disease characterized by varying combinations of two histological features: thickening of alveolar walls and the presence of large mononuclear cells in the alveolar spaces. Clinical details of 10 children with fibrosing alveolitis are reported. The main symptoms in children are tachypnoea or dyspnoea, cough, poor weight gain, and cyanosis. The condition is similar to that in adults, but it is usually a more acute illness, and if untreated, more predictably fatal. Respiratory failure, pulmonary hypertension, and cardiac failure are the major complications. Less commonly, superimposed bacterial infection and pneumothorax occur. Chest x-rays often show a sequence of changes with a ground-glass appearance and fine mottling in the early stage of the disease, progressing to a picture of mainly hilar linear markings in those children who recover. The histological features at lung biopsy or necropsy are described; these correlated poorly with the radiological features, steroid responsiveness, and clinical course. Lung function tests in 3 older children showed evidence of markedly reduced lung volumes in 2. Static lung compliance in 4 children in the acute stage of the illness was normal in 3 and diminished in one. The response to steroid therapy was analysed in cases from the literature and the 10 reported cases. No spontaneous remissions occurred, all the survivors having been treated with corticosteroids. In children fibrosing alveolitis is almost always a corticosteroid-responsive disease. An appropriate course of prednisolone would be of at least 4 week's, but preferably of 8 weeks' duration, at a minimum daily dose of 2 mg/kg. After improvement the steroid withdrawal should be cautious and protracted, comprising at least a year's continuous treatment.

Adrenal Cortex Hormones↗

Uptake and metabolism of 14C-palmitate by fetal rabbit tissues.

The uptake and esterification of 14C-palmitate into lipid classes in placenta, fetal brown adipose tissue (BAT) and liver of rabbits were investigated in vitro. Fetal BAT showed a high rate of fatty acid uptake, 8.5 mumol-a-1 tissue-h-1. From 5 min onwards, the majority of incorporated label was in the triglyceride fraction. The placenta and fetal liver also incorporated I-[14C]-palmitate into both FFA and esterified lipid fractions, although at much lower rates than observed for BAT. In the liver, triglycerides, but in the placenta phospholipids, contained the majority of the label after 1 h incubation. BAT from both fetal and newborn rabbits released 14CO2 and the production of 14 CO2 was greater in the presence of noradrenaline. The specific activity of the CO2 was the same in stimulated and unstimulated tissue. It is concluded that BAT as well as the liver are important sites of free fatty acid removal from the fetal circulation. The potential for fatty acid oxidation is present in BAT of the 28-day rabbit fetus.

Adipose Tissue, Brown↗

Incorporation in vivo of 1-14C-palmitic acid into placental and fetal liver lipids of the rabbit.

The incorporation of free fatty acid into the placental and fetal liver lipids of rabbits was studied after fetal injections of albumin-bound 1-14C-palmitic acid. The fetuses were killed either 5--10 or 10--20 min after the injection. The placentas and livers were extracted for lipids and the specific activities of triglycerides (TG), phospholipids (PL), free fatty acids (FFA), monoglycerides (MG) and diglycerides (DG) measured. The lipids of the liver and placenta took up 17.0 and 3.6% of the dose, respectively, and of that liver TG accounted for 74% and the placental TG 34% of the label in each tissue. Most of the remaining counts were in the PL fraction with the rest more or less evely distributed between the FFA, DG and MG fractions. No activity was recorded in the cholesterol esters. The placental TG, PL, DG and MG specific activities reached the same level as that of the placental FFA, while in the liver these esters had higher specific activities (than the liver FFA). The liver TG, DG and PL had higher specific activities when compared with those of the placenta. The specific activity of the placental FFA was lower at 10--20 min than at 5--10 min; the opposite was seen for the placental TG. No time-related changes were seen in the liver lipids. It is concluded that (i) both placenta and fetal liver incorporate FFA into glycerides and PL; (ii) the liver incorporates FFA more rapidly and to a greater extent than the placenta; (iii) most of the FFA is incorporated into TG and to a lesser extent (PL; (iv) in both organs hydrolysis of PL or TG occurs. These results are discussed with reference to placental transport of FFA and fetal fat metabolism.

Animals↗

Distribution of label in maternal plasma, placenta, fetal plasma and tissues after injection of 14C-palmitate into the circulation of 21- and 28-day-pregnant rabbits.

Tissue and plasma samples were obtained from fetuses removed 1--20 min after injection of 14C-palmitate into the doe at day 21 or day 28 of gestation. Specific activity of maternal plasma free fatty acids (FFA) was higher, but that of fetal plasma FFA lower in 21- than 28-day-pregnant rabbits. In 21-day fetuses, total radioactivity in the liver never exceeded that in the placenta; in 28-day fetuses, the liver radioactivity exceeded that in the placenta after 3 min. Total radioactivity in the fetal brown adipose tissue (BAT) never exceeded that in the placental. Most of the placental radioactivity was initially in the FFA, but at later time intervals the majority of the label was in the phospholipids. The fetal liver and BAT rapidly esterified label into triglycerides. It is concluded that transport of FFA across the placenta is greater at 28 days than at 21 days gestation. The evidence suggests that a pool of placental FFA, which equilibrates rapidly with the maternal plasma FFA, is a possible source of fetal plasma FFA. The rapidity and quantity of label appearing in the fetal liver suggest that fatty acids may first be processed by the liver before transport to extrahepatic tissues.

Adipose Tissue↗

The effect of maternal starvation on the metabolic response to cold of the newborn rabbit.

Acute starvation of the pregnant rabbit before delivery leads to lipid mobilization, the circulating concentrations of free fatty acids (FFA) increase, and more fatty acids cross the placenta and are stored as triglyceride in fetal tissues, particularly the liver and adipose tissue. Thus the newborns from these unfed does are born with larger fat stores than normal. In this investigation the responses of newborns of unfed and fed does were compared with respect to aspects of the metabolic responses to birth and subsequent cold exposure. It was found that at 2 hr of age the newborns of unfed does had higher circulating concentrations of FFA and triglycerides. The glucose and glycerol concentrations were similar in the two groups, but after 2 hr of cold exposure the newborns of fed does had much higher blood concentrations of both glucose and glycerol. In both, a large increase in FFA concentration was seen. The newborns of unfed and fed does had similar minimal metabolic rates, but the maximal rate of heat production was greater on average by 15% in the newborns of unfed does over the first 3 days of life. Maternal nutrition immediately before delivery has considerable effect on the circulating concentrations of metabolites and the responses to cold of the newborn.

Acute Disease↗

Propionyl-CoA carboxylase deficiency in a patient with biotin-responsive 3-methylcrotonylglycinuria.

The abnormal metabolites 3-hydroxypropionic acid (1.6-4.0 mg/day) and methylcitric acid (3.7-5.8 mg/day) were identified and quantitated in the urine of a patient in whom biotin-responsive 3-methylcrotonylglycinuria and deficiency of 3-methylcrotonyl-CoA carboxylase had previously been documented. The level of excretion of these metabolites was in the lower range of those found in patients with propionic acidemia in whom there is a deficiency of propionyl-CoA carboxylase. The activity of this enzyme in fibroblasts derived from the patient and grown in media low in biotin was 4% of normal. This is the range of patients with propionyl-CoA carboxylase deficiency. Documented deficiency in this patient of two carboxylase, both of which contain biotin, suggests that the primary defect is in the metabolism of biotin.

Biotin↗

Concentrations of free fatty acids in maternal and umbilical cord blood during elective Caesarean section.

The concentration of free fatty acids was measured in blood taken from the umbilical artery and vein of 29 infants during elective Caesarean section and compared with levels in maternal venous blood. The mean venous-arterial (v-a) difference was 0.07 mEq/l. There was a direct and significant correlation between the umbilical v-a difference and maternal venous concentrations.

Adolescent↗

Lung function in childhood. I. The forced expiratory volumes in healthy children using a spirometer and reverse plethysmograph.

Measurements of FEV0-5, FEV0-75 and FEV1 and FVG have been made on 241 healthy schoolchildren using a spirometer and a reverse plethysmorgraph system. The results obtained by the two systems were very similar. The FEV0-75 was selected as the most appropriate forced expiratory volume for routine clinical use. Normal data charts for FEV0-75 and FVG are presented.

Adolescent↗

Lung function in childhood. III. Measurement of airflow resistance in healthy children.

Indices of airflow resistance have been obtained in a group of 248 healthy London schoolchildren from recordings of peak expiratory flow rate (PEFR), forced expiratory volume in 0-75 seconds (FEV 0-75) and maximum mid-expiratory flow (MMEF) and two more direct methods, airways resistance (Raw) measured plethysmographyically and total respiratory resistance (PT) by the forced oscillation technique. The normal data are presented.

Adolescent↗

Transfer of fatty acids across the rabbit placenta.

1. Transfer of fatty acids across the placenta was studied in anaesthetized rabbits at 28-days gestation by measuring umbilical venous-arterial differences, by injection of labelled palmitate into the mother and observing its appearance in the foetus, by injection of labelled palmitate into the foetus and measuring its appearance in the mother and the foetal clearance rate. 2. The release of fatty acids and glycerol by foetal adipose tissues was investigated in vitro by measuring the effect of addition of noradrenaline to the incubation medium and in vivo by measuring the effect of noradrenaline infusion into the foetus on circulating glycerol and free fatty acid concentrations. 3. In anaesthetized rabbits at 28-days gestation the maternal circulating free fatty acid concentrations were high and there was a positive umbilical venous-arterial difference. High maternal free fatty acid concentrations were associated with high umbilical venous-arterial differences. 4. Label was present in the foetus in 2 min and reached a peak in 3 min after injection of labelled palmitate into the mother. Label appeared in the maternal circulation in 1 min after injection into the foetus. The half-life of labelled palmitate was of the order of 30-60 sec in both mother in foetus. 5. Foetal white adipose tissue released both free fatty acids and glycerol into the medium and the rate of release increased four to five fold after addition of noradrenaline. Infusion of noradrenaline in the foetus led to a rise in glucose and glycerol concentrations, but the change in free fatty acid concentrations was not significant. 6. It was concluded that (i) free fatty acids can cross the rabbit placenta in amounts sufficient to provide the fatty acid components of stored triglyceride and structural lipids; (ii) placental transport of free fatty acids depends in part on maternal blood concentration and on foetal uptake; (iii) foetal circulating free fatty acids are continually exchanging with fatty acid pools in the placenta and with the maternal circulating free fatty acids.

Adipose Tissue↗

Evidence of increased fatty acid transfer across the placenta during a maternal fast in rabbits.

Fetal rabbits were obtained by Caesarian section from 28-day pregnant does which had been fasted for 48 h (days 26-28). Organ weights, fat contents and blood metabolite levels were compared with a group obtained in a similar manner from non-fasted does. Similar data were obtained for term fetuses (31 days) born by natural delivery. In 28-day pregnant, fasted does, blood levels of free fatty acids (FFA) and glycerol were doubled compared with non-fasted controls. Fetal levels showed a similar increase. Both groups of fetuses from fasted does had increased fat stores both in the liver and adipose tissue. The overall increase in fat stores was 80-100%. It is suggested that during maternal fasting increased amounts of maternal FFA cross the placenta into the fetal circulation and are incorporated into the fetal fat stores.

Animals↗

Growth of adipose tissue in the fetal rabbit.

(1) Fetal rabbits of different gestational ages (20-29 days) were obtained by Caesarian section and term rabbits (31 days) by natural delivery. After dissection, organ weights were obtained and growth curves drawn. Brown adipose tissue was first visible at 22 days gestation and increased relatively more quickly than the body weight till day 26 after which it formed a constant percentage of the body weight. Growth of white adipose tissue followed a similar pattern, except that it was not visible until day 24. (2) The percentage triglyceride content of both types of adipose tissue increased throughout the latter part of gestation. (3) Fetuses of low birth weight had depressed fat stores in brown adipose tissue. (4) Some, but not all, of the high birth weight fetuses had relatively enlarged fat stores. (5) It is suggested that the conditions which produce fetuses of unusually low or high birth weight tend to have a greater corresponding effect on the fetal fat stores.

Adipose Tissue↗

Lung function in childhood. 2. Thoracic gas volumes and helium functional residual capacity measurements in healthy children.

The helium dilution functional residual capacity (FRC) and the total gas volume by plethysmograph (TGV) were measured on 236 healthy London schoolchildren. There was no difference between the results obtained by the boys and girls. The results of the TGV were higher than the FRC values. From the results, normal data charts have been devised for clincial use.

Adolescent↗