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Biomedical subjects

E A Carter

Publications and source records attributed to E A Carter.

At least 73 records · Page 4Linked to original sources
PubMed1988

Pure-tone sensitivity of human infants.

Pure-tone thresholds at frequencies ranging from 250 to 8000 Hz were estimated for 3-, 6-, and 12-month-old infants and for adults, using the Observer-based Psychoacoustic Procedure (OPP). Sounds were presented monaurally using an earphone. Psychometric functions of infants were similar to those of adults, although 3-month-olds had shallower functions at higher frequencies. The thresholds of 6- and 12-month-old infants were 10-15 dB higher than those of the adults, with the difference being greater at lower frequencies. This result is in general agreement with results from other laboratories. The thresholds of 3-month-olds were 15-30 dB higher than those of adults. The greatest difference between 3-month-olds and adults was at 8000 Hz. This threshold difference is smaller than that reported in earlier behavioral studies; higher thresholds at high frequencies have been previously reported for newborn and 3-month-old infants. The relative contributions of sensory and nonsensory variables to these age differences are discussed.

Arousal↗
PubMed1988

Redistribution of blood flow after thermal injury and hemorrhagic shock.

Diminished mucosal mass and a diminished rate of DNA synthesis by the intestinal mucosa have been identified in the rat after thermal injury. Because these changes may be associated with ischemia, the distribution of intestinal blood flow was studied after a thermal injury and compared with the blood flow distribution after hemorrhagic shock. For the thermal injury, anesthetized animals received a standardized 20% body surface area, full-thickness injury and were given intraperitoneal saline resuscitation. By the use of 46Sc- or 141Ce-labeled microspheres, no changes in intestinal and hepatic blood flow occurred after thermal injury. In contrast, a marked redistribution of blood flow was identified after hemorrhagic shock in which a decrease in arterial blood flow was identified to the stomach and to the small and large intestine. Although clinical shock was not present, the cardiac output decreased to a comparable degree in the hemorrhagic shock and the thermal injury. These studies indicate that although physiological changes in intestinal mucosa can be demonstrated after burn injury, these changes are not due to decreases in mesenteric arterial blood flow.

Animals↗
PubMed1986

Agonist interactions at hepatic alpha 1- and beta-adrenergic receptors: affinity-state regulation by guanine nucleotides and temperature.

We investigated the binding characteristics of agonists to alpha 1- and beta-adrenergic receptors of intact liver cells, broken rat liver cell membranes, and detergent-solubilized preparations under varying experimental conditions, focusing on the different "states" of the receptor for agonists and the regulation of these states by temperature and guanine nucleotides. While only low-affinity binding of agonists to both receptor subtypes was evident in studies performed at 37 degrees C with solubilized preparations, biphasic competition curves for agonists were observed in both intact cells and membrane preparations; the majority of sites were of low affinity. In membrane preparations, the nonhydrolyzable GTP analogue Gpp(NH)p caused a rightward shift of agonist competition curves and a loss of high-affinity binding. These results are consistent with the involvement of guanine nucleotide binding proteins in both alpha 1- and beta-adrenergic transduction pathways. When competition studies were performed at 4 degrees C, receptor sites existed predominantly in the high-affinity configuration, in intact cells and membranes, as well as in soluble preparations. In contrast to the studies conducted at 37 degrees C, no Gpp(NH)p-induced conversion to the lower affinity state could be demonstrated in studies performed with membrane preparations at 4 degrees C. Thus, the high-affinity state of alpha 1- and beta-adrenergic receptors is stabilized at 4 degrees C in intact cells, membranes, and soluble preparations. After incubations had been performed at 37 degrees C, high-affinity binding of agonists could not be restored by subsequent incubation at 4 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1986

Agonist-induced isomerization of the alpha 1-adrenergic receptor: kinetic analysis using broken-cell and solubilized preparations.

The affinity of agonists but not antagonists at hepatic membrane alpha 1-adrenergic receptors is temperature dependent; a 100-fold higher affinity is observed at 4 degrees C than at 37 degrees C. The relationship between these two agonist affinity states was investigated by using a strategy that allows the kinetics of this transition to be examined under equilibrium conditions. When competition assays are performed at 37 degrees C for varying intervals and the reaction mixture is then rapidly cooled by freezing, allowed to thaw, and further equilibrated at 4 degrees C, a rapid and progressive decrease (t1/2 of 1-2 min) in agonist affinity occurs, the extent of which is directly related to the incubation time at 37 degrees C. This decrease in agonist affinity is sustained as long as agonist is present but can be reversed by its subsequent removal. In contrast, no change in affinity is seen in identical experiments when antagonists are employed as the competing ligand. High-affinity binding of agonists is also demonstrated in short-term nonequilibrium experiments, indicating that the low-temperature incubations do not induce, but rather stabilize, a receptor conformation of high affinity for agonists. These findings suggest that the predominantly low-affinity binding of agonists to alpha 1-adrenergic receptors demonstrated in equilibrium studies at physiological temperatures may be the result of a ligand-driven decrease in affinity. Since the transition in receptor affinity for agonists occurs not only in broken-cell preparations but also after detergent solubilization of the membrane receptor, it most likely is due to an agonist-induced change in the conformation of the receptor protein per se.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Food proteins and gut mucosal barrier. IV. Effects of acute and chronic ethanol administration on handling and uptake of bovine serum albumin by rat small intestine.

The effects of ethanol exposure on small intestinal handling and uptake of radiolabeled bovine serum albumin were investigated using everted gut sacs. There was less breakdown of BSA after acute ethanol administration in vitro and after acute and chronic in vivo exposure. Thus, the vascular compartment of the small intestine was confronted with more complete and potentially more antigenic material after ethanol. Changes in BSA binding and uptake after acute exposure were shown to be reversible after 4-6 hr. In all groups, there was more BSA binding when the small intestine was exposed to ethanol. This difference was most pronounced after chronic exposure. In the same group, uptake of BSA was correlated with binding and significantly increased. Combined effects of ethanol on the gut mucosal barrier may account for changes in food antigen handling and uptake.

Alcoholism↗
PubMed1986

Nuclear magnetic resonance spectroscopy and imaging in the study of experimental liver diseases.

We are investigating potential noninvasive new strategies for the assessment of liver injury, steatosis, and hepatic tumor development. These techniques employ nuclear magnetic resonance (NMR) imaging and spectroscopy. Accordingly, several experimental animal models of liver injury and steatosis produced in rats by ethanol, azaserine, L-ethionine, carbon tetrachloride, and D-galactosamine. Ethanol and L-ethionine induce acute steatosis without necrosis, whereas azaserine, carbon tetrachloride, and D-galactosamine are known to produce steatosis with varying degrees of hepatic necrosis. Triglyceride content and protein spin relaxation times were measured. T1 values were analyzed by using an inversion recovery technique at eight different tau values (20 msec to 2.50 sec) and T2 by Carr-Purcell-Meibloom-Gill pulse sequences with 10 spin echoes (4-40 msec). We also performed NMR imaging studies on controls and ethanol-induced steatosis using a 60-MHz Technicare 8-cm bore superconducting system. Results of these experiments indicate that varying degrees of steatosis produce striking changes in T2 without inducing changes in T1, whereas necrosis superimposed on steatosis produces T1 changes as well. Thus, these NMR spectroscopy and imaging studies demonstrated that steatosis may be clearly defined in vitro and in vivo.

Animals↗
PubMed1986

Secretion of hydrogen peroxide by phagocytic cells from bovine non-lactating mammary glands.

Phagocytic cells from non-lactating bovine mammary glands have the capacity to secrete hydrogen peroxide when exposed to the soluble membrane stimulant phorbol myristate acetate (PMA). Unfractionated cell suspensions, containing mainly neutrophils and macrophages, and cell monolayers enriched for macrophages secreted hydrogen peroxide. A correlation was observed between the amount of hydrogen peroxide secreted, the antibacterial activity of the cells and the number of neutrophils present in the cell suspensions. Pre-exposure of cells to PMA significantly impaired their antibacterial activity against Staphylococcus aureus suggesting the importance of oxygen metabolism in the bactericidal capacity of these cells.

Animals↗
PubMed1985

Transient high-affinity binding of agonists to alpha 1-adrenergic receptors of intact liver cells.

At alpha 1-adrenergic receptors in isolated rat liver parenchymal cells, (-)-epinephrine is potent in eliciting a maximal increase in glycogenolysis (Kact = 24 nM). This contrasts with a 100-fold lower affinity for the agonist at alpha 1-adrenergic receptors of intact hepatocytes determined from equilibrium competition assays with the alpha 1-adrenergic antagonist [3H]prazosin. We demonstrate here that agonists bind to alpha 1-adrenergic receptors of intact liver cells initially with a markedly higher affinity than under equilibrium conditions. When incubations are performed for 15 s at 37 degrees C, the affinity is more than 100-fold higher than that obtained in equilibrium (45 min) assays (IC50 = 28 +/- 3 vs 5300 +/- 400 nM for (-)-epinephrine and 32 +/- 3 vs 6100 +/- 500 nM for (-)-norepinephrine). When incubations are performed at 4 degrees C (150 min), high-affinity binding similar to that obtained in short-term incubations can also be demonstrated. In contrast, antagonist compete with similar affinities in 15 s and 45 min assays, and their dissociation constants are not affected by changes in the incubation temperature. These results indicate that agonists bind to native alpha 1-adrenergic receptors transiently with high affinity. The conversion of receptors to a state of predominantly low affinity for agonists, which occurs rapidly and irreversibly with increasing incubation at 37 degrees C, is inhibited at low incubation temperatures. It is suggested that the high-affinity configuration of the alpha 1-adrenergic receptor for agonists observed in nonequilibrium experiments or at reduced incubation temperatures represents the physiologically relevant state of the alpha 1-adrenergic receptor.

Adrenergic alpha-Agonists↗
PubMed1985

Ethanol inhibits hormone stimulated hepatocyte DNA synthesis.

Insulin, glucagon, and epidermal growth factor (EGF) addition stimulated DNA synthesis in primary hepatocyte cell cultures prepared from adult rat liver. The addition of ethanol (20-200mM) to the culture medium resulted in a substantial reduction in DNA synthesis as measured by 3H-thymidine incorporation and autoradiography. This effect was specific for differentiated hepatocytes compared to fibroblasts and two other human hepatoma cell lines. These studies demonstrate in a cell culture system that one of the major properties of ethanol is the inhibition of hepatocyte DNA synthesis.

Animals↗
PubMed1985

Proton chemical shift imaging: an evaluation of its clinical potential using an in vivo fatty liver model.

The potential laboratory and clinical utility of proton chemical shift imaging (PCSI) was evaluated by studying fatty liver change in rats, which offered a simple animal model for tissue lipid buildup. There was excellent correlation between lipid group signal intensities from in vivo PCSI studies and liver triglyceride levels obtained from in vitro measurements (R = 0.97). The in vivo T1 relaxation time measurements in fatty liver tissue demonstrated two distinct populations of nonexchanging protons. We explain the reason for the lack of sensitivity in conventional magnetic resonance (MR) imaging studies of fatty liver change and discuss the implications of our findings for MR imaging studies of other tissues. PCSI promises improved diagnostic sensitivity and specificity in studying a wide range of human pathologic conditions.

Animals↗
PubMed1985

Rapid reciprocal changes in adrenergic receptors in intact isolated hepatocytes during primary cell culture.

In hepatocytes freshly isolated from adult female rat livers, catecholamine-stimulated glycogenolysis is mediated predominantly by alpha 1-adrenergic receptors, and to only a minimal extent by beta 2 receptors. Primary cell culture of these hepatocytes results in a switch in the adrenergic control of glycogenolysis from an alpha 1 to a predominant beta 2 type of response. To investigate whether this switch is due to an alteration in the plasma membrane receptor composition, we characterized alpha 1 and beta 2-adrenergic receptors in both freshly isolated and cultured hepatocytes, using radioligand-binding techniques. Binding of the selective alpha 1-adrenergic antagonist [3H]prazosin and the beta-adrenergic antagonist [125I]pindolol to intact freshly isolated hepatocytes was of high affinity, saturable, and of appropriate specificity for an alpha 1- and beta 2-adrenergic receptor, respectively. Equilibrium binding studies evaluated by a computer-assisted curve-fitting procedure indicated interaction with a single class of high affinity sites for radiolabeled prazosin (KD = 126 +/- 10 pM; Bmax = 93,000 +/- 5,500 sites/cell) and pindolol (KD = 66 +/- 6 pM; Bmax = 2,000 +/- 700 sites/cell). In intact hepatocytes and in membranes prepared from these hepatocytes, competitive inhibition curves revealed the coexistence of two different sites with high and low affinities for agonists at both alpha 1- and beta 2-adrenergic receptors. When isolated hepatocytes were kept in monolayer cell culture for up to 72 hr, the switch in adrenergic control of glycogenolysis (phosphorylase a activation) from an alpha to a beta pathway was confirmed and was associated with a progressive decrease in the number of alpha 1 receptors and an increase in beta 2-adrenergic receptor density, without marked change in the affinity of agonists or antagonists. To investigate the mechanism(s) of this reciprocal change, a number of perturbations were examined including alterations in the composition of the culture medium and the influence of various hormones and inhibitors of cellular function. De novo protein synthesis is implicated in both receptor alterations as the inhibitors cycloheximide and actinomycin D prevented the increase in beta- and attenuated the decrease in alpha-adrenergic sites. The other perturbations were without effect. Thus, these studies provide evidence for a coupling of the functional alteration in glycogenolysis to changes at the receptor level per se. The mechanism underlying the reciprocal changes in hepatocyte adrenergic receptors during culture remains undefined.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Phagocytic and bactericidal properties of bovine macrophages from non-lactating mammary glands.

Macrophages were isolated from the mammary glands of non-lactating (dry) cows and their ability to phagocytose and kill staphylococci in vitro assessed. Normal bovine serum enhanced the uptake of staphylococci and was required for optimal killing in the bactericidal test. Dry gland secretion interfered with uptake. Secretions taken progressively into the dry period became more inhibitory. The phagocytic ability of macrophages was significantly less than that of neutrophils present in the same gland preparation when tested in the presence of dry gland secretion. A marked variation in the antibacterial activity of macrophages from different cows was noted.

Animals↗
PubMed1984

Effects of propylthiouracil on D-galactosamine hepatotoxicity in the rat. Evidence for a non-thyroidal effect.

The cytoprotective effects of propylthiouracil (PTU) were studied in rats treated with the hepatotoxin D-galactosamine (D-GNH2). Five days of PTU pretreatment prior to D-GNH2 caused hypothyroidism and a significant reduction in liver injury as assessed by serum transaminase levels. When PTU was administered as a single dose with D-GNH2, significant decreases in transaminase also occurred at times when thyroid function was unchanged. Furthermore, aminopyrine oxidation showed significant impairment after D-GNH2 and was normalized by one dose of PTU. Further studies were carried out in thyroidectomized rats. PTU caused significant reductions in transaminase levels when given for 5 days pretreatment or as a single dose. Animals receiving pretreatment with PTU plus thyroxine (T4) also had significant decreases in serum transaminase. The antithyroid drug methimazole also had a hepatoprotective effect, while two other potent antithyroid compounds (2-thiouracil and 2-thiobarbituric acid) did not. These data suggest that PTU can protect against liver injury induced by D-GNH2, that the effect is independent of thyroid function, and that this effect is not common to all thiol-containing antithyroid drugs.

Aminopyridines↗
PubMed1983

Inhibition of primary and metastatic tumor growth in mice by cancer-associated galactosyltransferase acceptor.

The antitumor activity of a glycopeptide purified from human malignant effusion, termed cancer-associated galactosyltransferase acceptor (CAGA), was assessed in BALB/c mice bearing primary and metastatic tumors. Initial studies with the fast-growing KA31 and slow-growing KB521 Kirsten sarcoma-transformed mouse fibroblast cell lines confirmed their tumorigenicity and metastatic potential. Inoculation of 1 X 10(5) KA31 cells s.c. resulted in palpable tumor formation in recipient animals within 14 days and death within 42 days from primary tumor growth (mean survival, 26 days; total survival, 0%). Inoculation of the slower-growing KB521 resulted in tumor formation in 85% of recipients, and tumor-bearing animals succumbed within 56 days after primary inoculation (mean survival, 48 days; total survival, 15%). Administration of CAGA by i.p. injection as a single dose or series of five daily doses (each 50 micrograms) inhibited primary tumor growth by 35 to 68% in animals receiving KA31 cells and by 25 to 70% in animals receiving KB521 cells. CAGA increased mean survival 50% from 26 to 38 days and total survival from 0 to 27% in animals bearing KA31-derived primary tumors. In animals bearing KB521-derived tumors, CAGA increased mean survival from 48 to 90 days and total survival from 15 to 50%. Similarly, CAGA was also found to significantly inhibit formation of pulmonary metastases in animals after excision of primary tumors. CAGA administration reduced death from metastatic deposits by 55 to 66% in animals initially inoculated with the KA31 cell line and by 58 to 90% in animals initially bearing primary tumors derived from the KB521 line. There was a corresponding decrease in the number of metastatic deposits per lung after administration of CAGA. Thus, CAGA appears to have potential antitumor activity against tumors with a range of growth rates and appears to inhibit both primary and metastatic tumor growth.

Animals↗
PubMed1982

Lysyl oxidase and collagenase in experimental acute and chronic liver injury.

Lysyl oxidase and collagenase activities were measured in experimental acute and chronic liver injury in mice and rats, and correlated with collagen synthesis and accumulation. Acute liver injury was induced in mice and rats by a single dose of carbon tetrachloride given by gavage, and also in mice by a single injection of murine hepatitis virus. Chronic liver injury was induced in rats by repeated injections of carbon tetrachloride. Elevated plasma glutamic oxaloacetic transaminase levels, increased hepatic prolyl hydroxylase activity, and increased synthesis of collagen-bound hepatic hydroxyproline occurred in animals with acute as well as with chronic liver injury. However, only chronic liver injury appeared to be associated with fibrosis, increased collagen-bound hydroxyproline content, increased hepatic lysyl oxidase and collagenase activities, as well as with increased serum lysyl oxidase activity. These data suggest that lysyl oxidase and collagenase may play an important role in the collagen accumulation associated with hepatic fibrosis.

Amino Acid Oxidoreductases↗
PubMed1982

Breath tests: principles, problems, and promise.

Breath tests rely on the measurement of gases produced in the intestine, absorbed, and expired in the breath. Carbohydrates, such as lactose and sucrose, can be administered in physiologic doses; if malabsorbed, they will be metabolized to hydrogen by colonic bacteria. Since hydrogen is not produced by human metabolic reactions, a rise in breath hydrogen, as measured by gas chromatography, is evidence of carbohydrate malabsorption. Likewise, a rise in breath hydrogen marks the transit time of nonabsorbable carbohydrates such as lactulose through the small intestine into the colon. Simple end-expiratory interval collection into nonsiliconized vacutainer tubes has made these noninvasive tests quite convenient to perform, but various problems, including changes in stool pH, intestinal motility, or metabolic rate, may influence results. Another group of breath tests uses substrates labeled with radioactive or stable isotopes of carbon. Labeled fat substrates such as trioctanoin, tripalmitin, and triolein do not produce the expected rise in labeled breath CO2 if there is fat malabsorption. Bile acid malabsorption and small intestinal bacterial overgrowth can be measured with labeled cholylglycine or cholyltaurine. Labeled drugs such as aminopyrine, methacetin, and phenacetin can be used as an indication of drug metabolism and liver function. Radioactive substrates have been used to trace metabolic pathways and can be measured by scintillation counters. The availability of nonradioactive stable isotopes has made these ideal for use in children and pregnant women, but the cost of substrates and the mass spectrometers to measure them has so far limited their use to research centers. It is hoped that new techniques of processing and measurement will allow further realization of the exciting potential breath analysis has in a growing list of clinical applications.

Bile Acids and Salts↗