Publications by authors named "Milner R"

In the absence of added calcium, inhibition of NAD-specific isocitrate dehydrogenase by ATP occurred without ADP (I0.5 = 1.8 mM) and with 0.

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The growth of all children from one referral centre alive and well more than three years following the diagnosis of malignancy was analysed. Those treated with chemotherapy alone showed significant catch up growth. Children treated with chemotherapy and spinal irradiation showed no overall height loss, but manifested significant reduction in sitting height.

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The mechanism of pantothenate transport across the plasma membrane was investigated with initial velocity studies of [14C]pantothenate uptake and efflux in rat liver parenchymal cells maintained in primary culture. At 116 mM sodium, double-reciprocal plots of the initial velocity of uptake versus [pantothenate] were linear from 0.3 to 36.

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The COOH-terminal amino acid sequence of the rat brain-specific polypeptide 1B236 was previously deduced from molecular cloning and nucleotide sequence determination of its mRNA and the 1B236 protein shown to exist in the rat brain. The amino acid sequence of 1B236 contained at least three peptide sequences demarcated by pairs of basic amino acids--a structure similar to known neuropeptide and hormone precursors--which suggested that the protein might be processed in vivo to generate peptides. We have developed radioimmunoassays specific for 1B236 with antibodies against three synthetic peptides corresponding to putative cleavage products of this protein and have used these assays to define the molecular forms of 1B236 in rat brain extracts.

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The final growth pattern of 27 children who developed growth hormone deficiency after treatment of an intracranial tumour other than craniopharyngioma was assessed retrospectively. No patient achieved his or her genetic potential, though 12 attained an adult height above the the third centile for the population. All patients showed a tendency to a eunuchoid body build irrespective of whether puberty was spontaneous or not.

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Rat Tamm-Horsfall glycoprotein (THG) was isolated from urine and disaggregated by gel filtration. Purity was confirmed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and autoradiography. Antibodies were raised and used in the development of a specific radioimmunoassay for rat THG.

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Insulin has been implicated in the regulation of fetal growth. The aim of these studies was to determine if insulin has a direct mitogenic effect on fetal and neonatal rat cells in vitro. Myoblasts and fibroblasts were isolated from skeletal muscle and grown until myotube formation began or until fibroblasts were confluent.

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The actions of partially purified porcine platelet-derived growth factor (PDGF) and highly purified multiplication-stimulating activity (MSA) II and MSA III-2, which are somatomedins, were investigated on the incorporation of [3H]thymidine and [35S]sulphate by fetal rat costal cartilage in vitro. This was compared with their effects in the presence of 1% fetal calf serum (FCS) on the uptake of thymidine by growth-arrested fetal rat fibroblasts. Platelet-derived growth factor at concentrations of 0.

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Rat kidney cortex slices were incubated for 30 min at 37 degrees C in unmodified Krebs-Henseleit buffer containing aldosterone, vasopressin, theophylline, ethacrynic acid, frusemide, spironolactone or ouabain. Tamm-Horsfall glycoprotein (THG) released into the media was measured by radioimmunoassay and at the end of each experiment the slices were homogenized and assayed for THG content. Incubation of kidney cortex slices in unmodified buffer resulted in a significant increase in the slice THG content when compared with pre-incubation levels.

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In this study, the experimental model of Wigglesworth was used to limit the maternal blood supply to the rat fetus and induce intrauterine growth retardation. The associated changes in plasma somatomedin activity, insulin, glucose, and cartilage metabolic activity are reported. The mean body weight (+/- SEM) of 108 fetuses in ligated uterine horns was significantly lower than that of 146 control fetuses (ligated, 2820 +/- 50 mg; control, 3180 +/- 50 mg; p less than 0.

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Both insulin and the related peptides, the insulin-like growth factors/somatomedins, may function as anabolic factors in the regulation of fetal body size. Infants born to women suffering from diabetes mellitus may show increased deposition of subcutaneous fat and enhanced lean body mass, findings reproduced in experimental animal fetuses with induced hyperinsulinaemia. Fetal adiposity may be associated with a life-time tendency to obesity and its associated diseases.

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Some 30,000 genes are expressed exclusively in the rat brain, many of which contain a genetic element called an identifier sequence located in at least one of their introns. The identifier sequences are transcribed by RNA polymerase III exclusively in neurons to produce two RNA species, BC1 and BC2, of 160 and 100 to 110 nucleotides. This transcriptional event may define regions of chromatin that contain neuronal-specific genes and may poise these genes for transcription by polymerase II by rendering the gene promoters accessible to soluble trans-acting molecules.

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Somatomedin activity was determined by porcine cartilage bioassay and somatomedin-C RIA in matched samples of tracheal fluid (TF), amniotic fluid (AF), and cord (CP) and maternal plasma collected during the delivery of normal infants of 36-40 weeks gestation. Somatomedin levels determined by both assay systems were significantly greater in TF than in AF [TF, 0.40 +/- 0.

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The mode of delivery and one minute Apgar score were taken from the neonatal records of 2086 full term infants born at one obstetric unit over 12 months. There were 1554 spontaneous vaginal vertex deliveries, 26 vaginal breech deliveries, and 506 operative or instrumental deliveries. The obstetric records of the operative deliveries were reviewed to determine whether fetal distress had been an indication for intervention, and the obstetric records of the spontaneous vaginal vertex deliveries were also reviewed for fetal distress detected antenatally.

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The messenger RNA (mRNA) coding for the adrenal precursor of enkephalins (preproenkephalin-A) has been detected in bovine adrenal medulla cells using in situ hybridization with 32P-labelled preproenkephalin A (PPA) complementary DNA. In formaldehyde- and Carnoy-fixed tissue sections, an intense elective labelling restricted to the cells located at the periphery of the adrenal medulla can be detected after hybridization procedure, using X-ray film and classical autoradiographic procedure. Adequate controls show that this labelling is obtained only using PPA complementary DNA, inserted or not in its vector.

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Twenty nine (1.8%) of a national cohort of 1600 patients with growth hormone deficiency presented before the age of 2 years. Sixteen of the 29 presented before 6 months of age--11 with symptomatic hypoglycaemia, four with failure to thrive, and one with obesity.

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The production of immunologically and biologically active somatomedin activity from isolated myoblasts and fibroblasts from fetal rats of 21 days gestational age was investigated. Myoblast-rich cell populations were derived from primary cultures of dispersed muscle cells by the tendency of myoblasts to become detached from the culture dish in the presence of cytochalasin B. Fibroblasts were obtained from fetal muscle.

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