Search PubMed⌕ Search

Biomedical subjects

R D Milner

Publications and source records attributed to R D Milner.

At least 109 records · Page 6Linked to original sources
PubMed1983

Metabolic and hormonal response to endotoxin fever in fed and starved one-week rabbits.

The metabolic and hormonal effect of Escherichia coli endotoxin injected intraperitoneally was studied in fed and starved rabbits aged 6-9 days. Fed rabbits responded to endotoxin with fever, starved animals became hypothermic. Endotoxin caused a transient rise in blood glucose in both groups which was associated with a rise in plasma insulin concentration. Blood glycerol levels fell only in starved rabbits, and hydroxybutyrate concentration in both groups following endotoxin treatment. No change in blood pyruvate, lactate, alanine, or acetoacetate level was observed in either group.

Adipose Tissue↗
PubMed1983

Increased thymidine incorporation into fetal rat cartilage in vitro in the presence of human somatomedin, epidermal growth factor and other growth factors.

The incorporation of [3H]thymidine by rat costal cartilage in vitro was studied at different fetal and postnatal ages and the effect of partially purified human somatomedin, mouse epidermal growth factor, platelet secretion products, insulin and growth hormone on thymidine uptake by fetal cartilage was examined. Thymidine uptake in plasma-free medium was many times greater in late fetal life than after birth. The incorporation of [3H]thymidine into costal cartilage from 21-day fetuses was significantly (P less than 0.05) increased above control values in the presence of 10 micrograms somatomedin/1, and when cartilage was incubated in medium containing somatomedin and diluted human plasma there was a synergistic action. Epidermal growth factor at a concentration of 1 ng/l was a potent stimulator of thymidine uptake. Secretion products from human platelets after their aggregation by thrombin stimulated [3H]thymidine uptake at a concentration of 2% (v/v), but were inhibitory at high concentrations. High concentrations of platelet secretion products stimulated the incorporation of [35S]sulphate by cartilage. A pharmacological concentration of 10 mu. insulin/ml stimulated [3H]thymidine uptake, but not concentrations of 1 or 100 mu./ml. Growth hormone had no effect. The results showed that fetal cartilage had a greater endogenous mitogenic activity than postnatal cartilage. While somatomedins may be important in the regulation of fetal body growth, other protein growth factors also stimulate fetal skeletal tissues.

Aging↗
PubMed1983

Pancreatic endocrine cell fractions in erythroblastosis fetalis.

Pancreatic sections from 21 cases of rhesus disease and 20 control newborn infants of 30--40-wk gestational age were stained by the immunoperoxidase method for insulin, glucagon, somatostatin, and pancreatic polypeptide (PP). The fractional area occupied by each cell type was estimated, taking note of whether the gland contained PP-rich (ventral lobe) or PP-poor islets (dorsal lobe). In the PP-rich part of the pancreas, the volume fraction of all four endocrine cell types was significantly greater in the rhesus cases than in the controls. No difference was found between the two groups in the PP-poor part of the gland. The results show that abnormal development of the PP-rich part of the pancreas occurs in erythroblastosis fetalis. The localization of the changes to one part of the pancreas may explain some of the earlier conflicting reports on this topic.

Erythroblastosis, Fetal↗
PubMed1982

Raised plasma somatomedin activity and cartilage metabolic activity (35S sulphate uptake in vitro) in the fetus of the mildly diabetic pregnant rat.

A mildly diabetic state was induced in pregnant rats following treatment with streptozotocin the day after mating. On day 21 of gestation, these rats had a lower plasma insulin (55 +/- 9 versus 107 +/- 23 mU/l for control rats; p less than 0.05, mean +/- SEM) and a reduced pancreatic area occupied by insulin-containing cells compared with control animals (0.40 +/- 0.04 versus 1.03 +/- 0.08%; p less than 0.001), but hyperglycaemia was not apparent. Fetuses from mildly diabetic animals were longer but not heavier than those from control rats. Plasma somatomedin activity measured by fetal rat cartilage bioassay was higher in fetuses from mildly diabetic rats (1.12 +/- 0.07 versus: 0.74 +/- 0.05 U/ml for control fetuses; p less than 0.001) as was cartilage metabolic activity in basal culture medium (35S sulphate uptake) (1883 +/- 141 versus 1473 +/- 104 c.p.m./mg for control rats; p less than 0.05), but plasma insulin levels and the pancreatic area occupied by insulin-containing cells did not differ between the two groups of fetuses. Fetal plasma somatomedin activity, measured by fetal cartilage assay, showed a significant positive correlation with both body weight and length. It is concluded that by day 21 of gestation a small body overgrowth had occurred in the fetus of the mildly diabetic rat and this was associated with an increase in plasma somatomedin activity, but not with any abnormality of circulating insulin levels or volume density of B cells in the pancreatic islets.

Animals↗
PubMed1982

The pancreatic beta cell fraction in children with errors of amino acid metabolism.

Blocks of pancreas were obtained from the following cases of errors of amino acid metabolism: eight cystinosis, eight tyrosinosis, five phenylketonuria, three hypermethioninemia, two hyperprolinemia and two maple syrup urine disease. Blocks were also obtained from four cases of homocystinuria and 72 control patients of the same age range who had died from a variety of conditions believed not to affect the pancreas. Sections were cut from each pancreatic block and stained with haematoxylin or for insulin and pancreatic polypeptide (PP) by the immunoperoxidase method. Measurements were performed separately in the PP rich and the PP poor regions of all sections. The fractional surface area of section occupied by insulin stained cells (%) and the cellular density (nuclei/100 microgram2) of each specimen were estimated. The beta cell fractional area in the PP poor region of the experimental cases was plotted against the logarithm of gestational age and compared to a reference grid of the 10th, 50th and 90th centile estimates of the control cases (Fig. 1). The distribution of results from the cases of tyrosinosis, phenylketonuria and cystinosis were skewed positively; four of eight tyrosinosis and three of five phenylketonuria cases lying above the 90th centile (P less than 0.001). The beta cell fractional area of the cystinosis cases was also significantly increased (Table 1, P less than 0.05). The results from the cases dying from maple syrup urine disease, hyperprolinemia, hypermethioninemia or homocystinuria were distributed as might be expected to occur by chance.

Amino Acid Metabolism, Inborn Errors↗
PubMed1982

The sustained release of antimicrobial drugs from bone cement. An appraisal of laboratory investigations and their significance.

The release of gentamicin sulphate, sodium fusidate and diethanolamine fusidate from Palacos and CMW cements was studied using elution and serial plate transfer tests. Further tests were made to assay the drug remaining in the cement after antibacterial activity could no longer be detected by the above methods, to detect the sustained slow release of the residual drug, and to ascertain the mechanism of release. The results confirmed that the release of gentamicin sulphate could be detected for longer from Palacos cement than from CMW cement, but the opposite was true for sodium fusidate. Little difference was found in the case of diethanolamine fusidate. Comparison of elution and serial plate transfer tests, and of results of elution in buffers of different pH, demonstrated that the test method employed had a significant effect on the results, and the omission of details of methodology from some publications made comparison and evaluation of results difficult. Varying quantities of residual drug were found in cement from which antibacterial activity could no longer be demonstrated; further tests for sustained, slow release showed that the antibiotic did not remain fixed in the cement but was released at a rate too slow to be detected in the elution and serial plate transfer tests. It is concluded that antibiotics are released from the cement by a process of diffusion, but tests to determine the mechanism of diffusion were unhelpful. The theory of diffusion of drugs through solid matrices, and the clinical implications of the experimental findings, are discussed.

Acrylic Resins↗
PubMed1981

The autonomic nervous system and perinatal metabolism.

The development of the autonomic nervous system in relation to perinatal metabolism is reviewed with particular attention given to the adipocyte, hepatocyte and the A and B cells of the islets of Langerhans. Adrenergic receptors develop in the B cell independently of normal innervation and by the time of birth, in most species studied, the pancreas, liver and adipose tissue respond appropriately to autonomic signals. Birth is associated with a huge surge in circulating catecholamines which is probably responsible for the early postnatal rise in free fatty acids and glucagon concentrations in plasma. beta-Blocking drugs such as propranolol have an adverse effect on fetal growth and neonatal metabolism, being responsible for hypoglycemia and for impairing the thermogenic response to cold exposure. beta-Mimetic drugs are commonly used to prevent premature labour and may help the fetus in other ways, for example, by improving the placental blood supply and the delivery of nutrients by increasing maternal fat and carbohydrate mobilization.

Adipose Tissue↗
PubMed1981

Quantitation of the B and A cell fractions in human pancreas from early fetal life to puberty.

The morphological development of B and A cells in human pancreas was studied with immunoperoxidase strains in 172 cases ranging in age from 12 weeks of fetal life to puberty. Tissue was defined as polypeptide rich or poor to take account of the known islet heterogeneity in the gland. Pancreatic cell density was measured and B and A cell development was calculated in terms of (a) volume fraction and (b) density (micron2/100 nuclei). B cell density increased throughout fetal life to reach a peak at the postnatal age of 2 months, whereas A cell density was greatest in the 6 month fetus. The ratio of B to A cell volume fractions is approximately 1.5 throughout most of fetal life and rises postnatally to a stable value of 5 by the age of 2.5 years.

Adolescent↗
PubMed1981

Growth and metabolic and hormonal profiles during transpyloric and nasogastric feeding in preterm infants.

The effect of transpyloric and nasogastric feeding on the blood concentration of glucose, lactate, pyruvate, glycerol, hydroxybutyrate, acetoacetate, alanine, insulin, pancreatic and total glucagon was determined in 20 preterm infants. The babies were studied on the last day of transpyloric feeding and the first and fifth days of ensuing nasogastric feeding. In 9 infants hourly measurements of hormones and metabolites were made at 1000, 1100, 1200, 1300 and 1400 hours. The blood concentrations of glucose, alanine, pancreatic and total glucagon were stable, the concentration of the other metabolites and insulin, less so. No significant difference in mean metabolite or hormone concentration was noted by time of day or type of feeding. Measurements made on the fifth day of nasogastric feeding showed no significant differences from those at the time of changeover. The infants were clinically well and growing normally at the time of study, but had low plasma insulin and high plasma glucagon concentrations. We conclude (i) the site of presentation of milk in the gastrointestinal tract has no effect on the circulating concentration of selected metabolites and hormones in the preterm infants, (ii) the preterm infant grows at a normal rate with a plasma insulin/glucagon ratio that in the adult would be expected to favour catabolism.

Alanine↗
PubMed1981

Antimicrobial activity of silicone rubber used in hydrocephalus shunts, after impregnation with antimicrobial substances.

Colonisation of cerebrospinal fluid shunts by coagulate-negative staphylococci (Staphylococcus albus) is a serious problem. Because of its possible role in prevention of the condition, the antimicrobial activity of silicone rubber after impregnation with antimicrobial drugs was studied. The method of impregnation used and test methods were found to be important. Formaldehyde-urea condensates gave no activity. Gentamicin sulphate gave activity which was short-lived. Sodium and diethanolamine fusidates and clindamycin hydrochloride gave prolonged activity. A method of impregnation was developed which could be applied to commercially available shunts before use.

Anti-Bacterial Agents↗
PubMed1981

Hepatic cellular development in the rabbit.

Cellular development of rabbit liver from late fetal life to adulthood was analysed by quantitative histology and chemical techniques. Hepatocytes and non-hepatocytes were described in number and size. Two thirds of the cells in fetal liver are non-hepatocytes but the volume fraction occupied by them is only 18%. Both number and volume fraction fall with advancing development. Hepatocyte cytoplasm doubles in late fetal life, falls in the 1st postnatal week and then increases to a maximum size in the adult. Perinatal changes in hepatocyte size are related to the accumulation and discharge of glycogen and lipid but also include changes in the protein concentration of the cell.

Aging↗
PubMed1981

Rapid changes in somatomedin activity during insulin-induced hypoglycemia: possible release of an inhibitory factor.

Somatomedin activity was determined by bioassay during insulin-induced hypoglycemia in 24 patients with a variety of pituitary disorders. Initial somatomedin levels appeared to depend primarily on the state of GH secretion and were unaffected by abnormal PRL secretion. During the test, somatomedin activity fell to a minimum after 45 to 60 min and subsequently returned to initial values in those patients whose GH levels rose in response to insulin hypoglycemia, but not in patients lacking a GH response. Heat treatment of the plasma abolished the change in somatomedin activity in the majority of patients, and it is likely that the apparent fall in somatomedin was due to the presence of a heat-labile inhibitor of somatomedin action on cartilage.

Drug Stability↗
PubMed1981

Cartilage response to plasma and plasma somatomedin activity in rats related to growth before and after birth.

Cartilage response to plasma, plasma somatomedin activity, body weight and length were measured in rats from 15 days of fetal age to 37 days postnatally. The metabolic activity of costal cartilage was assessed by the incorporation of [35S]sulphate in basal medium and after stimulation by plasma. It was found that (a) A significant stimulation of isotope uptake above basal levels occurred in the presence of 15% standard adult rat plasma at every age studied. (b) The degree of stimulation, a measure of cartilage sensitivity to plasma growth factors, increased through the latter part of fetal life but fell after birth. A high degree of cartilage stimulation was seen on day 6 of postnatal life. (c) The changes in cartilage sensitivity and in the stimulated isotope uptake, resembled the changes observed in growth rate for body weight, nose-rump length and tail length. (d) Plasma somatomedin activity measured by the pig costal cartilage assay was low in the fetus and neonate but rose to adult values 9 days after birth. However, plasma from fetal or neonatal rats tested on cartilage from rats of the same age was equipotent to adult rat plasma. (e) Plasma from hypophysectomized adult rats had a low potency in stimulating isotope uptake by neonatal rat cartilage but was equipotent to normal adult rat plasma in its action on fetal cartilage. (f) The action of plasma from hypophysectomized rats on fetal cartilage was unaffected by dialysis but was destroyed by incubation with trypsin.

Animals↗
PubMed1981

Effect of non-essential amino acids on fetal rat pancreatic growth and insulin secretion in vitro.

Fetal rat pancreatic rudiments explanted on day 14 of gestation were grown for 6 days in organ culture in medium containing glucose (5.5 or 16.5 mmol/l) and essential amino acids (3.5 or 13.1 mmol/l). Non-essential amino acids (alanine, aspartic acid, asparagine, glycine, proline and serine) were added to the culture medium in a number of combinations and at a maximum total concentration of 4.0 mmol/l. At the end of the period of culture rudiments were compared for DNA content, insulin concentration and quantitative morphology. The release of insulin from the rudiments was tested during 6-h incubations on day 6 of culture. Enrichment of the culture medium with any combination of non-essential amino acids had a slight or no effect on the growth or cellular composition of the rudiment of insulin release from it. Addition of all the non-essential amino acids to medium containing 16.5 mmol glucose and 13.1 mmol essential amino acids/l caused a dramatic reduction in the net insulin accumulation by the cultured rudiment. Combinations of non-essential amino acids in which one or more were omitted did not have the same effect. These findings suggest that fetal rat pancreas grown in vitro may require both essential and non-essential amino acids for the full expression of insulin biosynthesis and secretion.

Alanine↗
PubMed1981

Quantitative morphology of B, A, D, and PP cells in infants of diabetic mothers.

Pancreatic specimens from 34 infants of diabetic mothers (IDM) and 32 control infants of gestational ages 26-44 wk were examined histologically using immunocytochemical stains for insulin, glucagon, somatostatin, and pancreatic polypeptide (PP). Each section was divided into PP-rich and PP-poor regions that are thought to be derived from the ventral and dorsal lobes of the gland, respectively. In some of these, the fractional area (%) occupied by positively stained B, A, and PP cells was determined by automatic image analysis, and the area occupied by D cells was determined by conventional point counting. The B cell fractional area was significantly higher in the IDM in both PP-poor and PP-rich areas (P less than 0.02). the fractional area of A cells in PP-poor areas and of PP cells in PP-rich areas was also significantly greater in IDM (P less than 0.02). The total endocrine cell fractional area was significantly greater in IDM in PP-poor but not in PP-rich regions of the pancreas. These results are not compatible with the hypothesis that maternal hyperglycemia results in specific fetal B cell hyperplasia and raise the possibility that hyperplasia of B, A, and PP cells in IDM may result from a variety of stimuli or that one stimulus acts on a pluripotential stem cell.

Female↗