Factors affecting vitamin A transport in animals and man.
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Biomedical subjects
Publications and source records attributed to J Glover.
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This work was prompted by the observation that corneal ulceration was apparently more common in young children in the guinea savannah area of northern Nigeria than in children in the tropical rainforest areas of southern Nigeria, where the intake of vitamin A, as the provitamin in red palm oil, is higher. Since corneal ulceration was usually seen in association with measles, a study was carried out to clarify the relationship between nutritional status, measles infection and vitamin A status in young children. The concentration of total retinol was measured in the plasma of well-nourished and malnourished children under three years of age, with or without a clinical record of recent measles. One hundred and twenty children were studied of whom 17 had corneal lesions. Malnutrition and measles were both found to depress the plasma concentrations of retinol and albumin. Measles depressed retinol levels (-20 to -30%) more than did malnutrition (-4 to -12%) while malnutrition had a greater depressing effect on albumin concentration (-23 to -30%) than did measles (-11 to -23%). The results support the hypothesis that corneal ulceration found in association with measles in northern Nigeria, although clinically similar to xerophthalmia, is not simply mediated through an effect of measles on the concentrations of vitamin A in plasma.
Altogether 54 children exposed prenatally to maternal cytomegalovirus (CMV) infection were followed up in a prospective study. Nine had congenital infection with CMV and 37 escaped congenital infection; in 8 congenital CMV could not be confirmed. The birthweight of children with congenital CMV was significantly lower than that of both controls and those who escaped congenital infection. Intrauterine infection was not clinically suspected in any of the children with congenital CMV, although two had head circumferences less than the third centile. Subsequently one child with congenital CMV developed marked psychomotor retardation, and one, in whom congenital CMV was not confirmed, showed mild developmental delay. Speech and language ability was significantly impaired in children with congenital CMV compared with controls and those who escaped congenital infection, suggesting that subtle damage may have occurred. The incidence of intrauterine transmission of CMV after exposure to infection in the first trimester was 20% and in the third trimester 40%, but no congenital infections resulted from exposure in the second trimester. The severity of congenital infection was not related to the time of exposure in utero. Our findings suggest that the risk to an individual fetus from maternal infection in early gestation is so low that termination of pregnancy cannot be recommended; screening of women for primary CMV infection in pregnancy seems therefore to have limited value.
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In a controlled trial 69 children with corneal xerophthalmia were given 200 000 IU oil-miscible vitamin A by mouth and a matched group of 45 children were given 100 000 IU water-miscible vitamin A intramuscularly. Both groups received an additional oral dose the next day. There was no detectable difference in the clinical response to the two regimes, even when analysis was limited to patients with concomitant diarrhoea or protein-energy malnutrition. Although serum-vitamin-A levels were significantly higher after parenteral than oral therapy, holoretinol-binding-protein levels were not. Oral administration of vitamin A is not only more practical but appears to be just as effective as parenteral administration in the treatment of severe xerophthalmia.
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1. Male and female Japanese quail (Coturnix coturnix japonica) were reared under short daily photo-periods (8 h light-16 h dark) to inhibit sexual development with free access to food and water. Blood was sampled at frequent intervals for 13 weeks from hatching in order to monitor the developmental changes in plasma concentrations of the two proteins which are important in the transport of retinol, retinol-binding protein (RBP) and thyroxine-binding prealbumin (TBPA). 2. Measurements of body-weight, blood packed cell volume and plasma total protein concentration showed that the birds had a normal pattern of growth and haematological development. Plasma concentrations of TBPA, total immunoreactive RBP (IRBP) and holoRBP were 220, 60 and 45 micrograms/ml respectively in 1-d-old quail and rose to 430, 165 and 140 micrograms/ml at 14 d of age, which was 10 d after the corresponding change in total protein. Neither RBP nor TBPA concentrations were significantly different between the sexes during the 13 weeks, but there were minor fluctuations in concentration within relatively narrow limits.
1. Seasonal changes in retinol-binding holoprotein (holoRBP) concentration in plasma of groups of male and female Japanese quail (Coturnix coturnix japonica) were examined over 18 months. 2. In Expts 1 and 2 the birds were maintained under natural lighting conditions and in Expt 3 under artificial-light photoperiods corresponding to the changing daylength at 56 degrees N latitude. All groups were at 18-20 degrees and received Superlayers' (Rank Hovis McDougall) pellet diet. 3. The mean plasma holoRBP concentration in all groups changed in an annual cycle with minimal values in September-October and maximal values in February-April, when daylength or light photoperiod increased to more than 10 h. 4. The group mean values in the female cycle change 2-3-fold from 50-100 microgram/ml in late summer to 220-280 microgram/ml in the spring, whereas in the male the range is only 1.3-1.5 times, from 140-170 to 180-250 microgram/ml. 5. In the female the rate of egg laying was maximal in April-May and lowest in November-December. 6. The spring increase in plasma holoRBP reflects the increased vitamin A requirement of birds for reproduction and it is presumably under hormonal control. The wider amplitude in the female cycle compared with the male probably arises from the additional demand for the transfer of vitamin A into the eggs and hence the need for a higher initial secretion rate from the female liver to meet it.
1. Changes in total retinol-binding protein (RBP), the holoprotein (holoRBP) and prealbumin (PA) concentrations have been monitored in plasma of thirty protein- and vitamin A-deficient preschool children from within a few hours up to 7 weeks after treatment with retinol and a good-quality protein diet. 2. The children were classified into groups according to nutritional status as having either kwashiorkor, marasmus-kwashiorkor or marasmus, and given formula diets whose protein and energy contents increased stepwise from 1 g and 105 kJ/kg body-weight respectively up to 4 g and 733 kJ/kg body-weight after 4 weeks. Retinol was administered in the forms of retinyl palmitate either orally or intramuscularly. 3. PA and total RBP were determined by electroimmunoassay procedures and the holoRBP by its fluorescence after separation from other plasma proteins. 4. RBP in plasma of the vitamin A-deficient child is largely denatured and incapable of binding administered retinol, which must first be taken up by the liver before native holoRBP is released. An increased pool of native apoprotein accumulates in the liver during vitamin A deficiency which is released into plasma quickly after retinol uptake to form peak concentrations of total and holoRBP approximately 3 h after dosing intramuscularly and 6 h orally. 5. The accumulated pool of RBP was highest in livers from the marasmus group and lowest in those from the kwashiorkor group, reflecting their relative capacities to synthesize plasma proteins. 6. The mean plasma concentrations of total and holoRBP for the various groups were minimal 24-48 h after dosing with retinol and then improved almost linearly over the following week. 7. Mean plasma PA concentrations of the various groups on admission were also in order of the severity of their malnutrition. There was little or no change in this protein concentration over the first 24 h after dosing with retinol, but thereafter the mean values rose almost linearly over 2 weeks. Albumin on the other hand changed little during the first week. The results show that PA is the more sensitive measurement of protein nutritional status.
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To identify prosthetic characteristics that support the proliferation of an endothelial lining, 14 different graft designs were studied in dogs. The grafts were prepared by the use of a technique of endothelial seeding that we described previously. They were studied two and four weeks after their implantation. Weft-knit Dacron grafts (water porosity from 1,400 to 1,650 mL/min/sq cm) were the most successful. A velour index (velour stitch frequency times velour loop height) was computed. When the internal velour index (IVI) was greater than 60,000 loop-mu/sq cm, the percentage of clot-free surface was 17.2 +/- 14.5%, compared with 62.0 +/- 26.9% when the IVI less than 60,000 loop-mu/sq cm. Endothelium could be detected on 61.5% of the grafts when the IVI less than 60,00 loop-mu/sq cm, compared with 0% when the IVI greater than 60,000 loop-mu/sq cm. The cells that formed the outer capsule were better organized and more adherent to the graft when an external velour was present, but external velour did not affect the inner lining. We conclude that weft-knit Dacron grafts with water porosities from 1,400 to 1,650 mL/min/sq cm and with limited internal velour (IVI less than 60,000 loop-mu/sq cm) are suitable substrates for single-staged endothelial-cell seeding.