Search PubMed⌕ Search

Biomedical subjects

R D Milner

Publications and source records attributed to R D Milner.

At least 127 records · Page 7Linked to original sources

The timing of fetal B cell hyperplasia in diabetic rat pregnancy.

Fetal pancreatic development was measured in terms of total organ DNA and insulin concentration (ng/migrogram DNA) in the offspring of rats made mildly diabetic by intraperitoneal streptozotocin injection (60 mg/kg) on the first and second day of life. On day 20 the mean pancreatic insulin concentration of fetuses of diabetic mothers was significantly higher than that of controls (27.8 versus 20.8 ng/microgram DNA) but no significant difference was observed on day 18 (4.47 versus 4.68 ng/microgram DNA), day 16 (0.64 versus 0.77 ng/microgram DNA) or day 14 (0.04 versus 0.03 ng/microgram DNA). No significant difference in total pancreatic DNA was observed between test and control animals on day 14, 16, 18 or 20 of gestation. It is concluded that maternal streptozotocin diabetes alters the development of the differentiated fetal B cell (20 days) but has no effect on the protodifferentiated B cell (14 days), or during the period of secondary transition (16-18 days).

Animals↗

Increased somatomedin and cartilage metabolic activity in rabbit fetuses injected with insulin in utero.

The effect of insulin injection in fetal rabbits on plasma somatomedin activity and cartilage metabolism was investigated. One fetus in each of 12 litters was injected with 1 unit of insulin zinc suspension subcutaneously on day 27 of gestation and a control fetus was injected with the same volume of 0.154 mol/l saline. The litter was delivered by caesarean section on day 29 and each fetus identified. Plasma somatomedin activity was determined by fetal rabbit cartilage bioassay. Costal cartilage from individual fetuses was incubated in medium containing [3H]thymidine or [35S]sulphate as indicators of cell replication and matrix synthesis respectively. Individual values for somatomedin activity or cartilage isotope uptake were ranked within a litter. In each case the rank in the litter of the insulin-injected fetus, but not the saline-injected fetus, was significantly higher than the mean rank of the litter. Insulin did not stimulate cartilage metabolism in vitro.

Animals↗

Growth in height compared with advancement in skeletal maturity in patients treated with human growth hormone.

Height growth and skeletal maturation were compared in 201 patients treated for between 1 and 15 years with growth hormone (GH) supplied by the Medical Research Council. 107 patients had isolated GH-deficiency, 30 had panhypopituitarism, and 64 craniopharyngiomata. The mean rate of skeletal maturation did not differ between the first year and the total period of treatment, averaging 1 'year'/year in the patients with isolated GH-deficiency or panhypopituitarism, and 0.6 'years'/year in those with craniopharyngioma. No association was observed between the rate of skeletal maturation and the bone age or the bone age deficit (chronological minus bone age) at the start of treatment. Mean height standard deviation score for bone age was negative in all three diagnostic groups at the start of treatment, but became less negative as treatment progressed in patients with isolated GH-deficiency or craniopharyngioma. In patients with panhypopituitarism there was no significant change in height standard deviation score for bone age as a result of treatment. The findings do not support the suggestion that treatment with GH(UK) causes ultimate stunting due to greater osseous maturation than growth in height.

Adolescent↗

Location of the gene for 21-hydroxylase deficiency.

HLA typing of 33 families with one or more children suffering from congenital adrenal hyperplasia confirmed that the gene for 21-hydroxylase deficiency is closely associated with the HLA region. Analysis of two families in which recombination of chromosome 6 had occurred indicated that the gene locus is between the A and D loci of the HLA region. The rare allele Bw47 was observed in 18 parents and was always associated with the carrier state for 21-hydroxylase deficiency.

Adrenal Hyperplasia, Congenital↗

Age-related changes in the degradation of thyrotrophin releasing hormone by human and rat serum.

Changes in the rate of in-vitro degradation of thyrotrophin releasing hormone (TRH) in serum as related to age have been investigated in the rat and man. In rats, no inactivation was found up to the age of 15 days but therafter an age-related increase in inactivation was detected with approximately 75% inactivation in 60 min at 40 days and reaching a maximum of 88-93% inactivation in adult male and female animals. The human serum samples studied (both male and female) showed a similar but less clear-cut pattern of inactivation of TRH compared with that found in the rat. A physiological role for these age-related changes in the degradation of TRH remains to be established but it has been concluded that the changes observed in both rat and man may be associated with growth and development, possibly by facilitating feedback control of thyrotrophin secretion through the degradation of TRH.

Adolescent↗

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↗

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↗

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↗

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↗

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↗