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Biomedical subjects

E M Spencer

Publications and source records attributed to E M Spencer.

At least 19 recordsLinked to original sources
PubMed1994

The relation between human fetal growth and fetal blood levels of insulin-like growth factors I and II, their binding proteins, and receptors.

OBJECTIVE: To determine the relation between normal human fetal growth and the levels of insulin-like growth factors (IGF-I, IGF-II), their receptors, and IGF binding protein-3 (IGFBP-3) in both the maternal and fetal compartments. METHODS: Serum samples were obtained from normal pregnant women (n = 52) and their fetuses (n = 32) via funipuncture at 21-34 weeks' gestation (mean 29 +/- 4.3) and from term neonates (n = 20) between 38-41 weeks (mean 39 +/- 0.9). Neonates were divided into two groups: the "large" group, whose weights were above the mean for gestational age, and the "small" group, whose weights were below the mean. Aliquots of amniotic fluid (AF) and serum samples were analyzed for levels of IGF-I, IGF-II, and IGFBP-3. Type 1 IGF receptors were assayed from placental extracts of first-trimester elective abortions and from term deliveries. RESULTS: Fetal IGF-I serum levels remained stable throughout most of pregnancy until 34 weeks' gestation (56 +/- 30 ng/mL). Thereafter, IGF-I increased significantly until term (79 +/- 8 ng/mL) (P < .05). Fetal IGF-II levels were relatively unchanged from 23 weeks to term except for a significant increase at 34 weeks. Fetal serum levels of IGFBP-3 averaged 0.8 +/- 0.05 microgram/mL up to 30 weeks' gestation and then increased slightly toward term, at 0.96 +/- 0.05 micrograms/mL. At term, the levels of IGF-I and IGF-II in the AF were not different from the levels in the neonatal serum, but were lower (P < .005) than those in maternal blood. All placental tissue obtained from first-trimester terminations of pregnancy assayed positive for IGF type 1 receptors. There was a direct correlation between neonatal weight and the levels of IGF-I (P < .02), but not with the levels of IGF-II. There were no significant correlations between newborn weights and IGFBP-3, or maternal serum levels of IGF-I and IGF-II. Amniotic fluid IGF-I and IGF-II levels were almost similar to fetal serum levels. CONCLUSION: These data demonstrate the presence of type 1 receptors and the bioavailability of IGF-I, IGF-II, and IGFBP-3 throughout pregnancy. Insulin-like growth factor-I is shown to be adjunctively and directly associated with fetal size in normal pregnancies. The precise role that IGFs play in deviant fetal growth or whether IGFs can be used to treat reduced fetal growth remains unknown and awaits further investigation.

Amniotic Fluid↗
PubMed1992

Isoflurane for prolonged sedation in the intensive care unit; efficacy and safety.

OBJECTIVE: To compare isoflurane with midazolam for prolonged sedation in ventilated patients. DESIGN: Randomised controlled study. SETTING: General intensive care unit in university teaching hospital. PATIENTS: Sixty patients aged 17-80 years who required mechanical ventilation for more than 24 h. INTERVENTIONS: Sedation with either 0.1-0.6% isoflurane in an air-oxygen mixture (30 patients) or a continuous infusion of midazolam 0.02-0.20 mg/kg/h (30 patients). Sedation was assessed initially and hourly thereafter on a six point scale. The trial sedative was stopped when the patient was ready for weaning from ventilatory support. MEASUREMENTS AND RESULTS: Measurements were made of haemodynamic, respiratory and biochemical variables regularly during the period of sedation and for a week after stopping the sedative agent. There was no difference in any of the physiological or biochemical variables recorded between the two groups. Patients sedated with isoflurane recovered more rapidly and were weaned from mechanical ventilation sooner than those sedated with midazolam. CONCLUSIONS: Isoflurane is a useful agent for prolonged sedation of ventilated patients and does not have any adverse effect on the cardiorespiratory system or on hepatic, renal or adrenal function.

Adolescent↗
PubMed1992

Insulin-like growth factor-I reverses the impairment of wound healing induced by corticosteroids in rats.

Corticosteroids are widely used therapeutic agents that have as a major side-effect the impairment of wound healing. Two hypotheses were tested: 1) that antiinflammatory corticosteroids decrease the local insulin-like growth factor-I (IGF-I) response to injury; and 2) that locally administered IGF-I would overcome methylprednisolone-mediated suppression of healing. The IGF-I concentration was measured in fluid from wire mesh cylinder wounds in rats given saline or methylprednisolone im. Rats receiving 8 and 16 mg had decreased wound IGF-I levels of 32% and 56%, respectively, compared to the saline-injected controls. IGF-I was infused (15 micrograms/day) by osmotic minipumps into wire mesh cylinder wound chambers of methylprednisolone (8 mg)-treated rats for 7 and 14 days. Methylprednisolone decreased wound DNA to 21%, hydroxyproline to 30%, and total protein to 5% of the values found in saline-infused controls. A 14-day treatment with IGF-I completely reversed the effect of methylprednisolone and increased DNA, hydroxyproline, and total protein to 216%, 109%, and 96% of saline control values, respectively. In conclusion, corticosteroids depressed wound IGF-I concentrations in rats, and an infusion of IGF-I into wound chambers reversed the corticosteroid-induced impairment of wound healing, as determined by the DNA, hydroxyproline, and total protein contents in wound chambers.

Adrenal Cortex Hormones↗
PubMed1992

Basal and regulated secretion of insulin-like growth factor binding proteins in osteoblast-like cells is cell line specific.

Local secretion of insulin-like growth factor binding proteins (IGFBPs) may modulate the effects of IGF-I and IGF-II on bone cell metabolism and proliferation. Several osteoblast-derived cell lines are currently used as interchangeable models to study IGFBP production, although it is unknown whether findings in one cell line can be extrapolated to another cell line or to normal human osteoblasts. In this study, we examined by Western ligand blotting both basal and regulated secretion of IGFBPs in vitro in 1) normal human osteoblast-like (hOB) cells cultured from explants of human trabecular bone; 2) an SV40-transformed hOB (HOBIT) cell line; and 3) several human (U-2, MG-63, TE-85) and rat (ROS 17/2.8 and UMR-106-01) osteosarcoma cell lines. Constitutively, hOB and HOBIT cells produced a similar pattern of IGFBPs, while all other cell lines produced their own unique pattern of IGFBPs. The two rat cell lines differed from the human cell lines as well as from each other. The response to hormonal stimulation also varied among the cell lines. Treatment of hOB and HOBIT cells with IGF-I resulted in a 2-fold increase in medium levels of IGFBP-3; IGF-I decreased levels of 24-kilodalton (kDa) IGFBP in hOB cell-conditioned medium. In addition, IGF-I markedly increased levels of the 29/32/34 kDa IGFBP triplet in U-2 cells, but had little or no effect in the other human and rat osteosarcoma cell lines. PTH increased a 29-kDa IGFBP apparent only in UMR 106-01 cell-conditioned medium, whereas GH had no direct effect on IGFBP secretion in any of the osteoblast-like cells tested. We conclude that basal and regulated secretion of IGFBPs from osteoblast-like cells is cell-line specific. Spontaneously transformed human or rat osteoblast-like cells provide unique model systems to study features of distinct IGFBPs and their regulation; however, hOB cells and their derivatives may be more appropriate models for understanding the regulation of IGFs in human bone.

Animals↗
PubMed1991

Basic fibroblast growth factor and somatomedin C in human medulloepithelioma.

Two published cases of medulloepithelioma, a rare malignant pediatric brain tumor composed of a mixture of primitive neuroepithelium and its differentiated neuronal and glial descendants, were examined by immunohistochemical staining for the presence of growth factors. From a panel of antibodies, those identifying basic fibroblast growth factor and insulin-like growth factor I, formerly known as somatomedin C, were strongly immunoreactive within the neuroepithelial cell population of the tumors. Immunoblots of purified recombinant basic fibroblast growth factor and insulin-like growth factor I showed antibody specificity without cross-reactivity. In controls, immunostaining of tissue sections was abolished by preabsorption of primary antibodies with the appropriate growth factor polypeptide antigen. Preabsorption with inappropriate growth factor did not reduce the intensity or alter the distribution of staining. The congruent histologic patterns of immunoreactivities suggest that more than one type of growth factor may be produced by the neuroepithelial component of medulloepithelioma. These growth factors may stimulate proliferation and differentiation of tumor cells by autocrine molecular mechanisms.

Animals↗
PubMed1991

In vivo actions of insulin-like growth factor-I (IGF-I) on bone formation and resorption in rats.

The in vivo action of insulin-like growth factor-I on bone metabolism has been studied using a new model. Insulin-like growth factor-I (IGF-I) was continuously infused into the arterial supply of the right hindlimb of ambulatory rats for up to 14 days and the effects on cortical and trabecular bone formation and the number of osteoclasts were determined by histomorphometric techniques. The contralateral limb acted as an internal control. IGF-I infusion significantly increased cortical bone formation (p less than 0.01). Trabecular bone was increased 22% (p = 0.07), but the infusion was only for seven days. These effects of IGF-I were age dependent, being absent in young, rapidly growing animals, but present at least until one year of age. IGF-I appears to be a purely anabolic hormone for bone formation, since it significantly stimulates osteoblasts and decreases the number of osteoclasts. Thus, although IGF-I mediates the growth-promoting effect of growth hormone, it does not mediate growth hormone's action on bone resorption.

Animals↗
PubMed1991

Plasma inorganic fluoride concentrations during and after prolonged (greater than 24 h) isoflurane sedation: effect on renal function.

We studied the effect of prolonged sedation (greater than 24 h) with isoflurane on plasma inorganic fluoride concentrations and renal function in 60 critically ill patients allocated randomly to receive either isoflurane or midazolam for sedation. In the isoflurane group, plasma fluoride increased from a mean concentration of 3.1 mumol/L to 20.0 mumol/L at the end of sedation, continued to increase to a peak of 25.3 mumol/L 16 h later, and then decreased exponentially (t1/2 = 111 h) to reach normal levels by the fifth day. In the midazolam group, the plasma fluoride increased from a mean concentration of 4.2 mumol/L to a peak of 6.8 mumol/L 12 h after starting the sedation and then decreased toward normal. Serum and urinary electrolytes, urine osmolality, and creatinine clearance during and after sedation were similar in the two groups. Isoflurane sedation was associated with an increase in plasma fluoride concentration without any clinical deterioration of renal function.

Adolescent↗
PubMed1990

Lack of effect of exogenous insulin-like growth factor-I (IGF-I) on chick embryo growth rate.

Direct evidence that IGF-I has any significant effect on embryo growth is lacking. We therefore studied the effect of administration of IGF-I on the chick embryo in ovo. Five hundred ng pure IGF-I (purified from human plasma) were given to chick embryos on 2 occasions (7 and 14 d) by injection directly into the allantoic sac. Treated and control (saline injected) chicks hatched on the same day and were killed. IGF-I appeared to reach the tissues as the [35S]-sulphate uptake of treated sternal cartilage was significantly greater than that of control (P less than 0.02). However, there were no significant effects of treatment on total body weight, bone length measurements, organ (lung, liver, heart) weights, muscle DNA, RNA or protein levels. From these results we conclude that administration of exogenous IGF-I to the chick embryo at 7 and 14 d does not stimulate further growth of the chick embryo.

Animals↗
PubMed1990

Cloning and expression of human insulin-like growth factor binding protein 3.

Insulin-like growth factors (IGFs) found in plasma and other body fluids circulate in association with specific binding proteins. We report here the cloning and the nucleotide sequence of cDNAs for the growth-hormone-dependent acid-stable IGF binding protein, hIGF-BP3. The derived protein begins with a putative 27-amino acid signal peptide followed by 264 residues of the mature polypeptide. The predicted sequence contains three potential N-linked glycosylation sites and shares two region of homology with the low-molecular-weight non-growth-hormone-dependent binding proteins BP-1 and BP-2. The protein contains 18 cysteine residues clustered in the amino and carboxy termini. Chinese Hamster ovary cells transfected with this cDNA secrete a 43-45 kD protein doublet, which bound IGF. The expressed IGF-binding protein is indistinguishable from the native BP-3 found in human plasma.

Amino Acid Sequence↗
PubMed1989

Insulin-like growth factors in fetal macrosomia with and without maternal diabetes.

Insulin-like growth factors (IGFs/somatomedins) have been implicated as regulators of fetal growth. This study investigates whether IGFs are related to macrosomia in infants of normal or insulin-dependent diabetic mothers. Cord concentrations of IGF-I (radioimmunoassay), total IGF (radioreceptor assay) and IGF binding protein (radiobinding assay) were measured in 15 term infants of diabetic mothers (IDM) and 29 term infants of nondiabetic mothers. In infants of control mothers cord IGF and total IGF levels were significantly higher in large-for-gestational-age than appropriate-for-gestational-age infants; but this relationship was lost in IDM, in whom IGF-I concentrations were similar to control infants. IGF binding protein levels were not significantly different in any of these groups. The absence of elevated IGF levels in macrosomic IDM indicates that the pathologic process does not involve a simple increase in these growth factors.

Adult↗
PubMed1989

Parathyroid hormone potentiates the effect of insulin-like growth factor-I on bone formation.

Insulin-like growth factor-I and parathyroid hormone are both known regulators of bone formation. In this study, human recombinant IGF-I and bovine PTH (1-34) and their combination were studied for their effects in vitro on the proliferation of embryonic chick osteoblast-like cells (osteoblasts) and in vivo on bone formation in normal rats. Osteoblasts from 17-day-old chick embryos were cultured in serum-free BGJb medium containing 0.1% bovine albumin. After 2 days, IGF-I and/or PTH were added. Twenty-four hours later [3H]thymidine incorporation into trichloroacetic acid precipitable material was quantified as an index of cell proliferation. This has previously been shown to reflect actual cell division. IGF-I at doses ranging from 0.85 to 13.6 nmol/l caused a dose-dependent increase in [3H]thymidine incorporation into osteoblasts. PTH alone (10 to 1000 pmol/l) had no significant effect. However, when combined with IGF-I, PTH potentiated the mitogenic effect of IGF-I and achieved statistical significance at 30 and 100 pmol/l (p less than 0.05). This potentiation was also studied in vivo. The right hind-limbs of rats weighing 150 g were infused intra-arterially by an osmotic minipump with graded doses of IGF-I (0.1 to 0.4 nmol/day) and/or PTH (0.27 nmol/day) for 7 days. The rate of trabecular bone apposition (formation) was measured by double tetracycline labelling and compared with the contralateral uninfused limb which acted as the control. Histomorphometric data revealed that neither IGF-I nor PTH alone had a significant effect on trabecular bone apposition rate compared with control limbs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Criteria for the cure of acromegaly: comparison between basal growth hormone and somatomedin C plasma concentrations in active and non-active acromegalic patients.

Fasting plasma growth hormone (GH) and somatomedin C (SmC) levels were compared as criteria for the cure of acromegaly in 7 untreated and 16 treated acromegalic patients studied 1 to 16 yr after pituitary surgery and/or radiotherapy. The patients without active disease presented a significant correlation between GH and SmC. Only when basal GH was lower than 2.5 ng/ml were SmC values within the normal range. The subjects with active acromegaly (both treated and untreated) presenting GH higher than 5 ng/ml did not show any correlation between GH and SmC levels.

Acromegaly↗