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Biomedical subjects

R D Milner

Publications and source records attributed to R D Milner.

At least 55 records · Page 3Linked to original sources
PubMed1987

Growth hormone regulation of somatomedin C/insulin-like growth factor I production and DNA replication in fetal rat islets in tissue culture.

The regulation of DNA replication by growth hormone and the production of somatomedin C/insulin-like growth factor I (SM-C/IGF-I) and insulin by fetal rat islets in culture has been studied. Islets were cultured for 3 days in medium containing 2.7 or 16.7 mM glucose, various concentrations of fetal calf serum (FCS), and 100-1000 ng/ml human growth hormone (GH). DNA replication was determined by incorporation of [3H]thymidine into islet DNA; SM-C/IGF-I and insulin secreted into the medium were measured by specific radioimmunoassays. Glucose caused a twofold stimulation of islet DNA replication in medium containing greater than or equal to 1% FCS but failed to stimulate DNA replication at lower serum concentrations. In the presence of 16.7 mM glucose, GH (100-1000 ng/ml) stimulated DNA replication at all serum concentrations. In medium containing 2.7 mM glucose, GH was stimulatory only in the presence of 1% FCS. Somatomedin C/IGF-I release into the culture medium could be detected in all experimental groups. Glucose alone did not affect SM-C/IGF-I release, and in serum concentrations less than 0.1% FCS, GH also failed to increase the release of the peptide. In medium containing 1% FCS and 16.7 mM glucose, 100-1000 ng/ml GH caused a 50-100% increase in SM-C/IGF-I release into the medium. Addition of 100 ng/ml exogenous SM-C/IGF-I to medium containing 16.7 mM glucose and 0.1-1.0% FCS caused a twofold stimulation of the islet DNA replication. This effect could be abolished by the addition of an antibody to SM-C/IGF-I.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Reduced vital capacity in insulin-dependent diabetes.

Spirometry was performed on 88 children with insulin-dependent diabetes mellitus (IDDM) and 216 healthy controls living in Sheffield. Children with IDDM had significantly lower percentage predicted forced vital capacity (FVC) than did control children or reference norms. There was no evidence that the reduced FVC was confined to a subgroup of children, and there was no correlation with duration of IDDM or glycemic control. A longitudinal study of 27 children with IDDM did not show progressive deterioration in percentage predicted FVC with age. These findings suggest that a tendency toward reduced lung volumes exists in IDDM and may not be a direct result of the metabolic disturbances in the disease.

Adolescent↗
PubMed1987

Persistent impairment of insulin secretory response to glucose in adult rats after limited period of protein-calorie malnutrition early in life.

The effect of a limited period of protein-calorie malnutrition in young rats on glucose tolerance, insulin secretory response to glucose, and tissue composition in the adult was studied. Three-week-old rats were weaned onto semisynthetic diets containing either 5% protein (low protein; LP) or 15% protein (control; C) and maintained for 3 wk on their respective diets. At 6 wk of age all rats were returned to a commercial rat chow diet (18% protein). Glucose tolerance, insulin secretory response to glucose, and the protein/DNA ratio in liver, skeletal muscle, heart, kidney, small intestine, and lung were investigated at 3, 6, and 12 wk of age. Rats receiving LP diet failed to gain weight, but growth resumed immediately when they were transferred to commercial rat chow. They did not, however, catch up with C rats. Glucose tolerance and insulin secretory response to glucose remained similar between 3 and 12 wk in C rats. In 6-wk-old LP rats, glucose tolerance was impaired, and the insulin secretory response to glucose was absent. At 12 wk of age the glucose tolerance of the LP rats had normalized, but the insulin secretory response was still blunted. In 6-wk-old LP rats there was an inhibition of the age-dependent increase in cell size, shown by lowered protein/DNA ratios in all tissues studied. This decrease in cell size persisted at 12 wk in liver, skeletal muscle, heart, and lung. We conclude that protein-calorie malnutrition early in life persistently impairs the insulin secretion. The persistently lowered protein/DNA ratios in many tissues may be related to this lowered capacity for insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Somatomedin-C in human fetal pancreas. Cellular localization and release during organ culture.

The presence of somatomedin-C/insulin-like growth factor I (SM-C/IGF-I) was investigated in human fetal pancreatic glands obtained after prostaglandin-induced abortion at 14-17 wk of gestation. Pancreatic explants were cultured in medium containing 11.1 or 22.2 mM glucose and 20% fetal calf serum for 8-10 days. During this period they were exposed, on two separate occasions, to serum-free culture medium for 24 h. SM-C/IGF-I and insulin were measured radioimmunologically in the serum-free media and in acid-ethanol-extracted homogenates of the cultured explants. SM-C/IGF-I was measurable in the conditioned media only after extraction by reverse-phase chromatography to remove somatomedin-binding proteins. On gel filtration at neutral pH of extracted medium samples, the immunoreactive SM-C/IGF-I was recovered in the region of the homogeneous peptide with an apparent molecular weight of 7000-8000. Explants cultured in 22.2 mM glucose contained more SM-C/IGF-I and had a tendency to release more of the peptide into the culture medium than explants cultured in 11.1 mM. There was no difference in insulin content or release between the two groups. By immunocytochemistry, SM-C/IGF-I was localized to the beta-cells of the endocrine pancreas in both freshly fixed tissue and cultured explants. We conclude that the human fetal pancreas contains SM-C/IGF-I and secretes the peptide during tissue culture. The presence of SM-C/IGF-I in the islets of Langerhans may contribute to the growth and development of the insulin-producing beta-cell.

Adult↗
PubMed1986

Which children should have growth hormone therapy?

Existing criteria for the diagnosis of growth hormone (GH) deficiency do not identify all children who can be made to grow faster with GH. There is a spectrum of GH secretion in short slowly growing normal children and in some cases the secretion may be inadequate to promote optimum growth in height. A diagnostic/therapeutic trial of GH therapy, with auxological monitoring, may be the only means of identifying some patients who will benefit. Assessment of the place for GH therapy in the treatment of short stature requires special knowledge of childhood diseases, growth, and endocrinology.

Anthropometry↗
PubMed1986

Bi-functional action of transforming growth factor-beta on DNA synthesis in early passage human fetal fibroblasts.

We investigated the influence of transforming growth factor-beta (TGF-beta) on DNA synthesis in human fetal fibroblasts, as measured by the incorporation of [3H]thymidine and cell replication. In serum-free medium, without additional peptide growth factors, TGF-beta had no action on thymidine incorporation. However, in the presence of 0.1% v/v fetal calf serum, TGF-beta exhibited a bi-functional action on the cells. A dose-dependent stimulation of [3H]thymidine incorporation, and an increase in cell number, occurred with fibroblasts established from fetuses under 50 g body weight, with a maximum stimulation seen at 1.25 ng/ml. For fibroblasts from fetuses of 100 g or greater body weight, TGF-beta caused a dose-related decrease in thymidine uptake with a maximal inhibition at 2.5 ng/ml, and a small decrease in cell number. When DNA synthesis was stimulated by the addition of somatomedin-C/insulin-like growth factor I, epidermal growth factor, or platelet-derived growth factor, their actions were potentiated by the presence of TGF-beta on cells derived from fetuses under 50 g body weight, but inhibited on cells obtained from the larger fetuses weighing more than 100 g. Similar results were found for changes in cell number in response to TGF-beta when stimulated by SM-C/IGF I. The ability of TGF-beta to modulate [3H] thymidine incorporation did not involve a change in the time required for growth-restricted cells to enter the S phase of the replication cycle. These data suggest that TGF-beta may exert either a growth-promoting or growth-inhibiting action on human fetal connective tissues in the presence of other peptide growth factors, which is dependent on fetal age and development.

Body Weight↗
PubMed1986

Divergent action of transforming growth factor beta on DNA synthesis in human foetal liver cells.

Purified human transforming growth factor beta (TGF beta) was found to be a potent inhibitor of DNA synthesis in human foetal hepatocytes. Half-maximal inhibition occurred at 0.5-1 pM and was reversible, with an increase in DNA synthesis within 24 h following removal of TGF beta. By contrast, in the same cultures, 'fibroblast-like' non-hepatocytes retained the ability to synthesize DNA in the presence of up to 200 fold higher doses of TGF beta. This differential response to TGF beta suggests that it may act as an important cell growth regulator in the human foetal liver.

Autoradiography↗
PubMed1986

Presence of transforming growth factor-beta-like activity in multiple fetal rat tissues.

The presence and ontogeny of transforming growth factor-beta (TGF-beta)-like bioactivity in rat tissues was studied. Eight separate tissues were extracted in acetic acid and assayed for TGF-beta-like activity by NRK-49F cell colony formation in soft agar. Bioactivity was present in each tissue during late fetal life, being most abundant in skeletal muscle, liver and lung (7.6-87.3 ng equivalents TGF-beta/g tissue), but fell to barely detectable levels from 12 days after birth. Gel filtration (pH 2.5) on Sephadex G75 of extracted fetal skeletal muscle, or culture medium conditioned by isolated fetal myoblasts demonstrated bioactivity in the molecular weight range 25-40 Kd. The results show that TGF-beta-like activity is selectively present in multiple fetal and neonatal, but not adult, rat tissues. Expression may therefore be developmentally regulated.

Aging↗
PubMed1986

Amino acid profiles in early diabetic and non-diabetic pregnancy.

Plasma amino acid concentrations were measured in six insulin-dependent diabetic women and seven non-diabetic women in early pregnancy while fasting and one hour after a standard meal. Fasting plasma levels of total amino acids and individual amino acids were similar in the two groups, excepting isoleucine, which was raised in the diabetics. One hour post-prandially total amino acid concentrations were similar in the two groups; however, mean concentrations of total branched chain amino acids and mean concentration of the individual amino acids, serine, valine, isoleucine, leucine and tyrosine were elevated in the diabetics. Amino acids are important in early islet development and in insulin secretion from fetal pancreas in vitro. The elevated post-prandial amino acid levels found in pregnant diabetics in early pregnancy may contribute to fetal islet hypertrophy and hyperinsulinaemia.

Adult↗
PubMed1986

Energy metabolism in healthy black Kenyan children.

1. Twenty-four healthy black Kenyan children, mean age 29 (SD 19) months, were studied over a 24 h period. Energy expenditure (EE) was determined using a ventilated-hood indirect calorimeter; measuring oxygen consumption and carbon dioxide production. Metabolizable energy intake was measured in twenty children. Anthropometric measurements were used to estimate surface area and lean body-weight. 2. The mean daily intake of metabolizable energy was 338.4 (SE 28.4) kJ/kg; 70% of gross dietary energy being provided by carbohydrate. The level of postprandial EE was significantly (P less than 0.05) higher than the resting level (12.6 (SE 0.47) and 11.38 (SE 0.37) kJ/kg per h respectively) while the level of the postprandial respiratory quotient (RQ) was similar to the resting level (0.94 (SE 0.02) and 0.98 (SE 0.03 respectively). In 33% of total observations of the resting RQ the value was more than 1.0. These findings suggest that short-term fat storage may be a normal feature of metabolism in children, and also that the energy cost of (postprandial) fat synthesis is increased by a high-carbohydrate diet. 3. Values for the resting metabolic rate and various estimators of body size were compared using regression analysis. It was evident that, in these young children with considerable variation in body composition, body-weight remained a satisfactory metabolic-size estimator.

Black People↗
PubMed1986

The maintenance energy requirement for children: an estimate based on a study of children with infection associated underfeeding.

An estimate of the maintenance energy requirement (MER) has been based on energy balance data from children fed at different levels of intake during and after acute measles. The relationship between apparent energy balance (B) and the metabolizable energy intake (ME) was investigated by regression analysis. The relationship between B and ME in 34 balance studies is given by B = 0.79 ME -211.9 (r = 0.91). The ME at zero B [268.3 kJ (64.1 kcal)/kg X 24 h] is equivalent to the maintenance energy requirement (MER). Paired data on 16 children were used to study the relationship between MER and the resting metabolic rate (RMR). The relationship between MER and RMR during measles, ie at low levels of energy intake, is given by MER = 1.52 RMR -140.9 kJ/kg X 24 h (r = 0.79). The factorial relationship between MER and mean RMR was estimated, and also the safe level of intake to supply the MER when ME represents between 76% and 84% of gross energy (GE). The safe level of GE intake, between 381 and 416 kJ/kg X 24 h (ie between 91.1 and 99.4 kcal/kg X 24 h), is very close to the WHO/FAO (1973) recommendations for growing children.

Basal Metabolism↗
PubMed1986

Clinical experience of somatrem: UK preliminary report.

A total of 63 patients with hGH deficiency were recruited, of whom 59 are evaluable. Somatrem (Somatonorm), 4 IU three times/week, was given either subcutaneously or intramuscularly. Height velocity increased from a mean of 4.7 +/- 2.1 cm/year before therapy to 8.2 +/- 2.6 cm/year in the 15 patients who have been followed for 1 year. In patients with isolated hGH deficiency height velocity increased similarly to the whole group, but in those with multiple pituitary hormone deficiencies the pretreatment and on-treatment growth velocities were lower. Of four children who had previously received spinal irradiation, three experienced only a small increase in height velocity on Somatonorm treatment; the fourth showed a considerable increase in height velocity. Anti-hGH antibodies were present in about 80% of the children tested after 12 months of treatment, but the titres and binding capacities were low. Anti-ECP antibodies were also detected, but again the titres were low, and 39% of the children tested had anti-ECP antibodies before treatment commenced.

Antibody Formation↗
PubMed1986

The nutritional cost of measles in Africa.

A 24 hour energy balance study was carried out on 20 black Kenyan children with acute measles and repeated after recovery. The energy content of a weighed 24 hour food intake and of a simultaneous collection of faeces and urine was determined by bomb calorimetry. Energy expenditure was measured by indirect calorimetry using a purpose built flow over calorimeter. The nutritional state of the children was assessed by anthropometry at the time of each study and during convalescence. The results showed a fall of roughly 75% in the intake of gross and metabolisable energy during measles, while the resting energy expenditure was little affected. Thus the severe degree of negative apparent energy balance observed during measles is the combined effect of underfeeding in ill children, and failure, during starvation related to infection, of the early fall in metabolic rate that characterises simple underfeeding.

Acute Disease↗
PubMed1986

When are we diagnosing growth hormone deficiency?

The height and age at presentation of 458 children beginning treatment with growth hormone between January 1980 and June 1984 were retrospectively analysed. Three hundred and nine children with isolated growth hormone deficiency had a mean (SD) age of 10 (4.1) years on beginning treatment and a mean (SD) height standard deviation score (SDS) of -3.73 (0.93). One hundred and nine patients with hypothalamopituitary tumours began treatment with growth hormone on average 3.3 years after diagnosis of the tumour and at a mean (SD) height SDS of -2.42 (1.49). In both of these categories the height SDS showed a considerable improvement compared with previous reports. Forty two patients with growth hormone deficiency secondary to cranial irradiation started treatment with growth hormone on average 6.1 years after treatment for their tumours and had a height SDS of -2.45 (1.02) compared with that of -2.45 (0.98) seen in nine similar patients from the United Kingdom starting treatment with growth hormone between 1975 and 1978. Although closer surveillance of short children in the community is leading to earlier diagnosis of growth hormone deficiency, this could possibly be diagnosed earlier if routine screening of height was to be carried out at school entry. In addition, patients who have received cranial irradiation should be regularly measured and investigated when their height velocity becomes subnormal.

Adolescent↗
PubMed1986

Energy cost of measles infection.

A model predicting the nutritional cost of measles has been based on data from a study of energy balance in Kenyan children during and after measles. The energy shortfall, consequent upon a reduction in energy intake and a sustained level of energy expenditure, is met by tissue catabolism. The magnitude of resulting weight loss will be greater in lean than in plump children. During recovery, the intake of gross dietary energy to regain lost weight must take account of obligatory energy losses in stool and urine and also of the energy cost of biosynthesis. The speed of recovery is influenced both by the energy density of the available food and its palatability. The nutritional cost of infection and other illnesses causing negative energy balance will be greater to lean people whose diet is of low energy density.

Body Weight↗