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Biomedical subjects

E Murphy

Publications and source records attributed to E Murphy.

At least 235 records · Page 13Linked to original sources
PubMed1987

Cord transferrin and ferritin values in newborn infants at risk for prenatal uteroplacental insufficiency and chronic hypoxia.

We measured cord transferrin and ferritin levels in 50 newborn infants with fetal conditions associated with either uteroplacental vascular insufficiency or chronic hypoxia. Sixteen small for gestational age infants, 21 infants of mothers with preeclampsia, and 13 symptomatic infants of diabetic mothers had significantly higher transferrin levels and lower ferritin levels and calculated iron stores than did asymptomatic gestational age-matched control infants without these conditions. Cord ferritin levels and calculated iron stores were significantly lower in the infants of diabetic mothers than in any other group of infants. Cord transferrin levels were inversely correlated with ferritin levels (r = -0.59, P less than 0.001) and were unrelated to transthyretin levels and birth weight in the high-risk infants, but were positively correlated with ferritin levels (r = 0.50, P less than 0.001), transthyretin levels (r = 0.65, P less than 0.001), and birth weight (r = 0.75, P less than 0.001) in the control infants. We conclude that cord transferrin levels do not reflect protein-energy status in newborn infants with prenatal histories suggesting uteroplacental insufficiency or chronic hypoxia, and that when associated with decreased cord ferritin levels, indicate possible impaired iron stores in these infants.

Chronic Disease↗
PubMed1987

Mood and behaviour problems following the relocation of elderly patients with mental illness.

A prospective case-controlled study was carried out to evaluate the effect of an enforced move of elderly dementia sufferers from a large psychiatric hospital to smaller units in two general district hospitals. Changes in behaviour and nursing dependency, and mortality rate were used as outcome variables. The main finding was that a large proportion of the sample showed significant depressive behaviour following transfer. A significant degree of disturbed behaviour and disorientation remained 3 months after the move. There was some increase in the mortality rate of the group transferred relative to a comparison group but this did not reach statistical significance.

Affect↗
PubMed1987

Effects of sodium-potassium pump inhibition and low sodium on membrane potential in cultured embryonic chick heart cells.

1. When the Na+-K+ pump of cultured embryonic chick heart cells was inhibited by addition of ouabain with or without removal of external K+, the membrane potential rapidly depolarized to -40 mV and the Na+ content approximately doubled within 3 min. 2. After this, exposure to an [Na+]o of 27 mM caused a fall in Na+ content, a gain in Ca2+ content and a hyperpolarization. The hyperpolarization was approximately 25 mV in a [K+]o of 0 or 5.4 mM after 3 min of pump inhibition. After approximately 10 min of pump inhibition, the same hyperpolarization was observed in a [K+]o of 5.4 mM but in K+-free solution the hyperpolarization increased to approximately 44 mV. 3. Varying [K+]o during the 10 min period of Na+-K+ pump inhibition showed that the increase in hyperpolarization was associated with the period of exposure to K+-free solution rather than the [K+]o at the time of lowering [Na+]o. 4. Changes in Na+ and Ca2+ content induced by exposure to an [Na+]o of 27 mM in K+-free solution were similar at 3 and 10 min. This and the above observations suggest that the increased hyperpolarization was due to an increased membrane resistance. 5. 10 mM-Cs+ reduced the low-[Na+]o hyperpolarization by 26% but did not significantly affect the movements of Na+ and Ca2+. 1 mM-La3+ reduced the low-[Na+]o hyperpolarization by 15%: it also totally blocked the rise in Ca2+ content and partially blocked the fall in Na+ content. 1 mM-Ba2+ reduced the low-[Na+]o hyperpolarization by 20%. 6. Raising [Ca2+]o from 2.7 to 13.5 mM produced similar but smaller hyperpolarizations (approximately 6 mV after 3 min pump inhibition). High [Ca2+]o caused a rise in Ca2+ content but no significant drop in Na+ content. The hyperpolarization in high [Ca2+]o was insensitive to verapamil (20 microM) and 10 mM-Cs+. 7. We conclude from the disparities between the magnitudes of the hyperpolarizations and the changes in ion contents that Na+-Ca2+ exchange cannot be unequivocally identified as electrogenic solely from the low-[Na+]o hyperpolarizations.

Animals↗
PubMed1987

Synthesis and characterization of 19F NMR chelators for measurement of cytosolic free Ca.

Fluorine 19 nuclear magnetic resonance (NMR) studies of intracellular fluorinated calcium chelators provide a useful strategy for the determination of cytosolic free calcium levels in cells and perfused organs. However, the fluorinated chelator with the highest affinity for calcium ions which has been described to date. 1,2-bis-(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBAPTA), exhibits a dissociation constant (Kd) value 5- to 10-fold greater than the intracellular calcium concentration levels in most cell types, thus limiting the ability of fluorine NMR to report these concentrations reliably. We have consequently designed and synthesized several fluorinated calcium chelators with higher affinity for calcium. The best of these, 2-(2-amino-4-methyl-5-fluorophenoxy)-methyl-8 aminoquinidine-N,N,N',N'-tetraacetic acid (quinMF), has a Kd value approximately 10 times lower than that of 5FBAPTA. Several of the newly synthesized indicators have different chemical shifts for the calcium complexed and uncomplexed chelators to allow the simultaneous use of two indicators. In addition to providing information about the level of cytosolic free calcium, chelators containing a quinoline ring exhibit considerable sensitivity to magnesium levels and hence have potential application for the determination of cytosolic-magnesium concentrations. Application of these chelators is illustrated by determination of the cytosolic-free calcium level in erythrocytes. Use of quinMF, the chelator with the lowest Kd value, gives a calcium value of 25-30 nM.

Calcium↗
PubMed1987

Free calcium in isolated chick embryo heart cells measured using quin2 and fura-2.

Cytosolic free calcium (Cai) was measured using quin2 and fura-2 in isolated chick embryo heart cells. Account was taken of extracellular quin2 and fura-2 (which could not be entirely washed away) by adding Mn. Shortly after loading with quin2, Cai was 49 nM (n = 7) but then rose continuously at a rate varying between 13 and 88%/h. By varying the time between cell isolation and quin2 loading, it was ascertained that the loading was causing the rise in Cai. In one set of experiments, Cai was stable in time and the apparent Cai increased steadily from 55 to 179 nM as dye loading (quin2 or fura-2) was decreased from 1 mM to 5 microM. We conclude that although quin2 and fura-2 are useful for comparing Cai levels and determining whether Cai changes as a result of certain maneuvers, they do not provide an absolute measure of Cai in isolated embryonic heart cells.

Aminoquinolines↗
PubMed1987

Biochemical and structural changes in cultured heart cells induced by metabolic inhibition.

We examined the relationship between ionic homeostasis, ATP, and irreversible cell injury in cultured embryonic chick heart cells treated with rotenone (10(-4) M) alone or in combination with iodoacetate (IAA) (10(-3) M), in the presence of extracellular calcium (Ca0) (2.7 mM) and its nominal absence. Changes in Na, K, and total cell Ca content did not correlate with parameters indicative of irreversible injury, i.e., ultrastructural damage or lactate dehydrogenase (LDH) release. Because structural defects in the plasma membrane occurred without a significant release of LDH after exposure to rotenone plus IAA for 1 h, LDH release appears to be a relatively late event in cell injury. In addition, cells exposed to rotenone in the presence of Ca0 for 2.5 h showed a significant fall in ATP and a rise in LDH release. This response was attenuated in the nominal absence of Ca0, and the addition of rotenone caused an eightfold increase in intracellular sodium (Nai), whereas in the presence of Ca0, Nai increased only threefold in 2.5 h. Thus Ca0 appears to promote Nai-Ca0 exchange and lead to an increase in cell Ca that can then stimulate ATP breakdown by Ca-activated ATPases. Of the measured variables associated with myocardial cell injury, a decline in ATP correlates best with changes in either LDH or morphology. The apparent lack of correlation between changes in intracellular ion content, LDH release, and morphology supports the conclusion that myocardial cell injury is a multifactorial process.

Adenosine Triphosphate↗
PubMed1987

Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart.

Changes in cytosolic free calcium concentration during myocardial ischemia were measured by 19F NMR in 5FBAPTA-loaded perfused rat hearts. The hearts were perfused with Krebs-Henseleit buffer containing 5 microM of the acetoxymethyl ester of 5FBAPTA, which was hydrolyzed by cytosolic esterases to achieve cytosolic concentrations of 5FBAPTA of 0.12 to 0.65 mM. Cytosolic free calcium concentrations were calculated as the product of the ratio of peak areas for bound and free 5FBAPTA in the NMR spectra and the dissociation constant (708 nM). The basal cytosolic calcium concentration, measured in potassium or magnesium arrested hearts, was 252 nM, and the time-average calcium concentration in beating hearts was 630 nM. Following the onset of total ischemia, there was no immediate substantial change in cytosolic calcium despite a rapid decline in creatine phosphate and ATP and a marked increase in inorganic phosphate as monitored by 31P NMR, but by 10 minutes, there was a substantial increase in free calcium concentration. The ratio of peak areas of bound and free 5FBAPTA returned to the preischemic value during reperfusion, and there was no detectable loss of 5FBAPTA from the heart. Creatine phosphate was also restored to its preischemic level during reperfusion. These results indicate that cytosolic free calcium increases during ischemia and is not immediately associated with lethal injury. This increase in cytosolic calcium may activate degradative enzymes that eventually could compromise myocyte viability.

Animals↗
PubMed1987

Effects of E. coli endotoxin on rat plasma angiotensin converting enzyme activity in vitro and in vivo.

Angiotensin converting enzyme (ACE), a glycoprotein, is found in high concentration in pulmonary capillary endothelial cells. Several investigators have studied the relationship between various direct and indirect pulmonary insults and ACE activity and in some cases have found conflict. In an attempt to clarify this relationship we have examined the effect of endotoxin on rat plasma ACE activity in vitro and in vivo. We used the synthetic ACE substrate 3H-BPAP and the assay described by Catravas and Gillis [J Pharmacol Exp Ther 217:263-270, 1981]. In vitro, a statistically significant concentration-dependent reduction in ACE activity was demonstrated (p less than .005). In vivo an intravenous dose of endotoxin (20 mg/kg) alone resulted in no significant change in plasma ACE activity. However, the combination of intravenous endotoxin (20mg/kg) and mild hemorrhage (5-10% of blood volume) caused a statistically significant reduction in plasma ACE activity by 15 min as compared to control rats with hemorrhage only (39% vs. 66%, p less than .005). This reduction persisted at 30 and 60 min. However, by 180 min ACE activity was no longer statistically different from control values. We have demonstrated an acute reduction of plasma ACE activity in the endotoxemic rat that appears to be dependent on the amount of circulating endotoxin and the presence of mild blood loss.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1987

Cytosolic free calcium levels in sickle red blood cells.

In this study, we used a recently developed nuclear magnetic resonance (NMR) technique to measure ionized calcium in sickle erythrocytes. The NMR technique, which involves 19F NMR studies of a fluorinated calcium chelator quinMF, [2-(2-amino-4-methyl-5-fluorophenoxy)methyl-8-aminoquinoline-N,N,N',N'- tetraacetic acid] provides a novel approach to the study of ionized calcium in erythrocytes since the presence of hemoglobin precludes the use of fluorescent calcium indicators. The mean value for ionized calcium in oxygenated sickle erythrocytes was 18 +/- 2 nmol/L (SE). Experiments with normal RBCs gave a mean value of 21 +/- 2 nmol/L (SE). After 1 hour of deoxygenation, mean values for ionized calcium in sickle erythrocytes did not increase as compared with values obtained under oxygen. To investigate whether deoxygenation stimulated endocytosis, sickle erythrocytes were deoxygenated for 1 hour in the presence of impermeant FBAPTA (1,2 bis-(2-amino-5-fluorophenoxy) ethane N,N,N',N'-tetraacetic acid). Cells were then separated from the extracellular medium and assayed for the presence of FBAPTA; they had incorporated significant quantities of the extracellular FBAPTA. This incorporation was not observed with normal erythrocytes. These data are consistent with at least a portion of the elevation in total cell calcium in sickle erythrocytes arising as a consequence of an endocytotic process in which extracellular calcium ions are incorporated into vesicles. Additional experiments show that these intracellular vesicles accumulate Ca2+ on further deoxygenation, consistent with a transient increase in ionized cell calcium. These studies represent the first use of NMR spectroscopy to evaluate endocytotic processes.

Aminoquinolines↗
PubMed1986

c-K-ras codon 12 GGT-CGT point mutation. An infrequent event in human lung cancer.

Hu-c-ras represent a family of oncogenes which are capable of inducing malignant transformation in the NIH/3T3 mouse cell line. Associated with this transformation are specific point mutations observed in the 12th and 61st codon of c-K-ras and N-ras and c-Ha-ras, respectively. These base changes generate, in some instances, a new restriction enzyme cleavage site and a restriction fragment length polymorphism (RFLP). One such RFLP has recently been reported for the mutation GGT-CGT at codon 12 of c-K-ras. Our data suggest that this point mutation is rarely present in human lung cancer and therefore is not likely to play a major role in cancer development.

Cell Transformation, Neoplastic↗
PubMed1986

Arachidonic acid stimulates 45calcium efflux and hPL release in isolated trophoblast cells.

Previous investigations from this laboratory have indicated that arachidonic acid stimulates a rapid, dose-dependent and reversible increase in hPL release which is not dependent on cyclooxygenase or lipoxygenase metabolism. To investigate further the mechanism by which arachidonic acid stimulates the release of hPL, the effect of arachidonic acid on the release of 45Ca from perifused cells prelabelled with 45CaCl was examined in an enriched cell culture population of term human syncytiotrophoblast. Arachidonic acid (10-100 microM) stimulated a dose-dependent, rapid, and reversible increase in the release of both 45Ca and hPL from the perifused placental cells. On the other hand, palmitic acid had little effect on either hPL release or 45Ca release even at concentrations as high as 100 microM. Ionophore A23187 (1-10 microM) also stimulated a dose-dependent and reversible increase in hPL release. Since arachidonic acid increases the mobilization of cellular calcium, as reflected by the increased 45calcium efflux, and since an increase in the intracellular calcium concentration appears to stimulate an increase in hPL release, these results suggest that the stimulation of hPL release by arachidonic acid may be due, at lease in part, to the effects of the fatty acid on cellular calcium mobilization.

Arachidonic Acid↗
PubMed1986

60 years of suicide in England and Wales. A cohort study.

In a cohort analysis of suicides recorded in England and Wales from 1921 to 1980, there was no discernible trend across the younger cohorts, but there was a fall in the suicide rates of successive older cohorts over this period. The impact of period events (eg, World War II and the detoxification of domestic gas) is demonstrated in these cohorts. In addition to the period effects, there was evidence of a more prolonged cohort effect on suicide rates of the middle-aged and elderly associated with these events. Little relationship was found between early and later suicide rates within cohorts, casting doubt on the usefulness of predicting the future rates of cohorts from their early behavior.

Adolescent↗
PubMed1986

Prognostic value of programmed electrical stimulation in patients with a recent episode of unstable angina.

Patients with a recent episode of unstable angina have a 10% 1-year risk of sudden cardiac death. To determine prospectively whether electrophysiologic testing might be useful in predicting sudden death, 20 patients admitted to our hospital underwent programmed electrical stimulation as part of their evaluation. None had persistent angina, severe congestive heart failure, or sustained arrhythmias at the time of testing. Because of their long-term benefits, beta-blocking agents were continued whenever possible (18 of 20 patients). Ten of 20 patients (50%) had inducible ventricular tachycardia. In 19.5 months' mean follow-up, three patients (15%) either died suddenly or survived an episode of ventricular fibrillation. Programmed electrical stimulation was an insensitive (33%) and nonspecific (47%) predictor of sudden death in these patients. Programmed ventricular stimulation soon after admission for unstable angina is not a useful prognostic indicator for sudden death. Such patients do have a frequent induction of ventricular arrhythmias which appears to be a nonspecific marker of underlying coronary disease.

Actuarial Analysis↗
PubMed1986

Volume regulation by Amphiuma red blood cells: cytosolic free Ca and alkali metal-H exchange.

Osmotic swelling of Amphiuma red blood cells results in activation of electroneutral K-H exchange, whereas cell shrinkage activates an electroneutral Na-H exchange. These K-H and Na-H exchangers function to restore cell volume to normal after cell swelling and shrinkage, respectively. Our previous studies have suggested that Ca plays a role in volume-dependent activation of K-H exchange. In the present studies, intracellular free Ca levels were measured employing the Ca-sensitive extracellular dye arsenazo III and a previously described null-point method. Control values for intracellular free Ca averaged 0.46 +/- 0.15 microM. Cell shrinkage caused this value to decrease to 0.16 +/- 0.11 microM, whereas either cell swelling or addition of 5 microM A23187 resulted in saturation of intracellular Ca buffers, suggesting that both treatments caused an increase in intracellular free Ca. In the presence of 7 microM A23187, the rate of K-H exchange displayed a hyperbolic relationship as a function of extracellular Ca (Cao). The apparent half-maximal concentration for Cao (in the presence of 7 microM A23187) was 0.27 mM for osmotically swollen cells and 1.9 mM for cells in isotonic medium, suggesting that the Ca affinity of a modulating site is increased in swollen cells. Inhibitors of Ca-mediated processes, such as quinidine and the phenothiazines, inhibited K-H exchange. In contrast, the phenothiazines chlorpromazine and trifluoperazine stimulated Na-H exchange by osmotically shrunken cells. These results suggest that increases in intracellular free Ca are involved in stimulating K-H exchange while repressing Na-H exchange in Amphiuma red blood cells.

Acid-Base Equilibrium↗