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Biomedical subjects

R D Milner

Publications and source records attributed to R D Milner.

At least 19 recordsLinked to original sources
PubMed1992

Genetic linkage studies of X-linked hypophosphataemic rickets in a Saudi Arabian family.

UNLABELLED: OBJECTIVE, PATIENTS AND DESIGN: X-linked hypophosphataemic rickets (HYP) is the most common inherited form of rickets and the gene causing this disorder has been localized to Xp22.3-p21.3 by linkage studies of affected families of Northern European origin. In addition, the locus order Xpter-(DXS207-DXS43,DXS197)-HYP-DXS41-X cen has been established and the flanking markers are useful for the presymptomatic diagnosis of HYP. However, a recent study indicates locus heterogeneity and this may hinder the use of the flanking markers for presymptomatic diagnosis in additional families and in particular those from different populations. We have therefore investigated one Saudi-Arabian family (13 affected and six unaffected members) with hypophosphataemic rickets for linkage to these and other X-linked markers. A total of 17 cloned human X chromosome sequences identifying restriction fragment length polymorphisms were used to localize the mutant gene causing this disorder in the Saudi Arabian family. RESULTS: Nine (four from Xp and five from Xq) of the 17 X-linked DNA probes proved informative and linkage was established between HYP and the DSX41 locus, peak LOD score = 4.22 (recombination fraction, theta = 0.00). A positive peak LOD score of 2.32 (theta = 0.05) was also obtained between HYP and the DXS207 locus. Thus, the HYP gene in this Saudi Arabian family is linked to two of the four flanking markers which demonstrated linkage in families of Northern European origin. CONCLUSION: We conclude that the X-linked hypophosphataemic rickets gene in a Saudi Arabian family is located in the Xp22.3-p21.3, a region where this gene has previously been mapped by linkage studies of families of Northern European origin. Our studies have not demonstrated locus heterogeneity, so the flanking markers for HYP previously established in the families of Northern-European origin will be useful in the genetic counselling and presymptomatic diagnosis of this disorder in the Saudi Arabian family.

Adolescent↗
PubMed1991

Tissue and serum insulin-like growth factor I (IGF I) concentrations in rats subjected to temporary protein-energy malnutrition early in life.

Rats subjected to temporary protein-energy malnutrition and subsequent nutritional rehabilitation remain smaller than adequately fed animals, have a subnormal insulin secretion and persisting cellular hypoplasia in several tissues. This investigation studies whether impaired production of insulin-like growth factor I (IGF I) is another persisting consequence of malnutrition. Rats were subjected to severe protein-energy malnutrition between 3 and 6 weeks of age and subsequently fed adequate diet up to 12 weeks of age. Serum and tissue samples for analysis of IGF I were obtained at 12 weeks of age. IGF I concentrations were similar in serum, heart, liver and lung of previously malnourished and control rats. In the kidneys of previously-malnourished rats the IGF I concentration was twice that of control rats. Results suggest that during protein-energy malnutrition and subsequent nutritional rehabilitation IGF I tissue concentrations are primarily regulated by the prevailing plane of nutrition. It is speculated that the temporary protein-energy malnutrition blunts the cellular capacity for IGF I production and, except in the kidney, prevents increased IGF I tissue concentrations and associated compensatory growth.

Aging↗
PubMed1991

Long-term effects on glucose tolerance and insulin secretory response to glucose following a limited period of severe protein or energy malnutrition in young rats.

The long-term effects on growth, glucose tolerance and insulin secretory response to glucose of temporary malnutrition early in life have been investigated. Rats were weaned onto either normal diet (18% protein), a protein-restricted diet (5% protein) or a diet adequate in protein but restricted in amount to equal the energy intake of protein-restricted rats ("energy restriction"). From 6 weeks of age and onwards all rats were fed normal diet. Body weight gain was inhibited by both protein and energy restriction but growth was resumed when rats were transferred to normal diet. Protein restriction impaired glucose tolerance and blunted insulin secretory response to glucose. Following refeeding glucose tolerance was normalized but insulin secretory response remained impaired at 12 weeks of age. Energy restriction did not initially affect glucose tolerance and insulin secretion. However, after refeeding male energy restricted rats developed a delayed and exaggerated insulin secretory response to glucose without concomitant deterioration of glucose tolerance. It is suggested that temporary protein restriction at a young age impairs pancreatic B-cell function and decreases peripheral sensitivity to insulin. By contrast, temporary energy restriction does not directly affect B-cell function but confers insulin resistance and compensatory increases of the insulin secretory response to glucose later in life. These models of malnutrition offer possibilities to further study long-term effects of early nutritional insults.

Animals↗
PubMed1979

Experience with human growth hormone in Great Britain: the report of the MRC Working Party.

The Working Party on human growth hormone (hGH) has during the past decade developed a system for the evaluation and treatment of patients suffering from hGH lack. Today there are nineteen measurement centres in the United Kingdom at which patients are assessed and where the effects of therapy are monitored. The current supply of hGH, which is prepared from pituitary glands collected by pathologists in the National Health Service, is just enough to meet demand, but research conducted on behalf of the Working Party suggests that hGH deficiency is more common than has been thought and that the prevalence may be as high as one in 10 000. If, as is hoped, patients are diagnosed younger and more patients with partial deficiency are recognized, demand may soon outstrip supply. Work is in progress to define better methods of hGH production and optimal dose regimens, both of which will help to minimize the problem of supply and demand. A few children have anti-hGH antibodies, which block growth as a result of treatment. Improved hGH production techniques may result in a less antigenic product and the resolution of this problem. Many of the Working Party's activities began as research and have evolved into service. Because of this shift in emphasis, and although much research is still to be done, responsibility for provision of treatment with hGH transferred from the Medical Research Council to the Department of Health and Social Security in July 1977.

Adolescent↗
PubMed1979

Reactogenicity and immunogenicity of a surface-antigen-adsorbed influenza virus vaccine in children.

An influenza virus vaccine containing the purified surface haemagglutinin and neuraminidase antigens of A/Victoria/75 and B/Hong Kong/73 viruses adsorbed to an aluminium hydroxide gel was assessed for reactogenicity and immunogenicity in children aged 4 to 11 years, since there is no influenza virus vaccine available for this age group. Significant serum haemagglutination-inhibiting antibody responses to the A/Victoria/75 and B/Hong Kong/73 haemagglutinin antigens present in the vaccine were observed in 47% and 35%, respectively, of the children vaccinated, with a single dose. The vaccine induced no significant local or systemic reactions.

Antibodies, Viral↗
PubMed1979

Retention of plasma somatomedin activity in the foetal rabbit following decapitation in utero.

One rabbit foetus within each litter was decapitated in utero on day 24 of gestation. Plasma somatomedin activity and costal cartilage metabolism were studied 5 days later in the experimental foetuses and control litter-mates. Somatomedin was assayed by the uptake of [35S]sulphate in vitro into costal cartilage from intact foetuses. Uptake was proportional to logarithmic increases in the concentration of both foetal and maternal rabbit plasma. The mean (+/- 1 S.D.) somatomedin activity of four plasma pools, each pool being derived from the intact foetuses within each of four litters, was 1.3 +/- 0.3 compared with a potency of unity for the reference pool of maternal plasma. The plasma somatomedin activity of decapitated foetuses did not differ significantly from that of control litter-mates when analysed by rank test, but the costal cartilage of decapitated foetuses took up less [35S]-sulphate in basal medium when compared with that of intact litter-mates. The headless body weight of the decapitated foetueses did not rank in a position significantly different from the one expected. The concentration of plasma growth hormone in the decapitated foetuses was less than 5 ng/ml and that of the intact foetuses was more than 157 ng/ml. It is concluded that plasma somatomedin in the rabbit foetus is not dependent on foetal growth hormone.

Animals↗
PubMed1979

Effects of glucose and amino acids on insulin, glucagon and zymogen granule size of foetal rat pancreas grown in organ culture.

Foetal rat pancreatic rudiments explanted on day 14 of gestation were grown for 6 days in organ culture in medium containing glucose (5.5(1G) or 16.5(3G)mmol/l) and amino acids at the 'physiological' (1AA) or seven times the 'physiological' (7AA) concentration. Cultures were also performed in medium to which zinc sulphate had been added at 10(-7) to 10(-5) mol/l concentration. At the end of the period of culture the diameters of insulin, glucagon and zymogen granule profiles in the rudiments were compared with those in normal 20-day foetal pancreas by quantitative morphology. The beta cell volume, the number of granules per beta cell, the insulin granular volume fraction and the area of insulin granule core and halo were also measured under selected experimental conditions. Zymogen granule profiles were largest in vivo, intermediate in diameter when grown in 1G x 7AA medium and smallest in 1G x 1AA medium. The mean diameter of glucagon granule profiles remained constant for growth in vivo, in 1G x 7AA medium. Insulin granule profiles were largest in 1G x 1AA medium or in 1G x 7AA medium, smallest in 3G x 1AA mdeium and of intermediate diameter in vivo. Amino-acid enrichment increased the diameter of insulin granules and glucose enrichment decreased it. The addition of zinc to the culture medium had no effect on insulin granule diameter. In 1G x 7AA cultures the beta cells were of similar size to those in vivo, but there were 29% fewer insulin granules per cell. The increased size of the insulin granules in 1G x 7AA cultures resulted in the insulin granule volume fraction in 1G x 7AA being 17.6 compared with 10.8% in vivo. Insulin granule cores were made larger by amino-acid enrichment of the culture medium but they were unaffected by glucose. The haloes were larger in 7AA medium and smaller in 3G medium. Glucose and amino-acid enrichment had a significant interaction on halo area, the mean area in 3G x 7AA medium being less than would have been expected from the summation of the effects of the two conditions.

Amino Acids↗
PubMed1978

Renin and aldosterone response in human newborns to acute change in blood volume.

Increased activity of the renin/aldosterone system in the neonatal period is now well established in both animals and man but the control mechanisms are poorly understood. We have monitored the plasma renin activity (PRA) and plasma aldosterone concentration (PAldo) in 14 infants undergoing 21 exchange transfusions. PRA and PAldo were measured before and at 5, 10, 15, 30, 45, and 60 minutes after the injection, and 5, 10, 15, and 30 minutes after the withdrawal of 7 ml blood/kg birthweight immediately before exchange transfusions. PRA increased to a maximum of 53% and decreased to a maximum of 39% of the resting values after withdrawal or injection of blood respectively. PAldo values did not change significantly during the same period. Thus the renin-angiotensin system in the newborn infant is responsive to changes in blood volume.

Aldosterone↗
PubMed1977

Hypoglycin stimulates insulin secretion.

Hypoglycin A(0.01--1.0 mmol/l) stimulated insulin release from pieces of rabbit pancreas in vitro in the presence or absence of extracellular glucose. The relevance of this finding to the hypoglycaemia of Jamaican vomiting sickness is discussed.

Animals↗