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Biomedical subjects

A McLaughlin

Publications and source records attributed to A McLaughlin.

At least 19 recordsLinked to original sources
PubMed1996

A technique for single-channel MR brain tissue segmentation: application to a pediatric sample.

A segmentation method is presented for gray matter, white matter, and cerebrospinal fluid (CSF) in thin-sliced single-channel brain magnetic resonance (MR) scans. The method is based on probabilistic modeling of intensity distributions and on a region growing technique. Interrater and intrarater reliabilities for the method were high, and comparison with phantom studies and hand-traced results from an experienced rater indicated good validity. The method was designed to account for spatially dependent image intensity inhomogeneities. Segmentation of MR brain scans of 105 (56 male and 49 female) healthy children and adolescents showed that although the total brain volume was stable over age 4-18, white matter increased and gray matter decreased significantly. There were no sex differences in total gray and white matter growth after correction for total brain volume. White matter volume increased the most in superior and posterior regions and laterality effects were seen in hemisphere tissue volumes. These findings are consistent with other reports, and further validate the segmentation technique.

Adolescent↗
PubMed1996

Noise levels in a cardiac surgical intensive care unit: a preliminary study conducted in secret.

Noise in hospitals frequently exceeds recommended levels and has detrimental psychological and physiological effects on patients and staff. The aim of this study was to record the noise levels within the cardiac surgical intensive care unit (CSICU) environment in secret. The device used was a CEL Instruments environmental noise meter concealed in a dummy box featuring temperature and humidity digital displays. It allowed greater than 16 hours recording time at a 1-minute resolution. The 24-hour period was covered by overlapping recordings. The data collected were downloaded onto a personal computer for analysis. The maximum sound level recorded was 100.9 decibel level (dBA), 1 min Lmax (the maximum sound level occurring in a 1-min period). The minimum sound level was 61.3 dBA 1 min Lmax. The continuous background noise was at its lowest at 57.5 dBA 1 min equivalent continuous sound pressure levels (Leq) and at its peak 77.3 dBA 1 min Leq. Noise in the CSICU was above the recommended levels for patients and staff well-being. Future studies will be designed to establish a correlation between sound levels and events.

Cardiac Surgical Procedures↗
PubMed1995

The antiinflammatory activity of topically applied novel calcium-channel antagonists.

The antiinflammatory activities of two novel calcium-channel antagonists, AGN 190742 and AGN 190744, were evaluated in murine models of cutaneous inflammation. These 2(5H)-furanone ring compounds block both depolarization-dependent Ca2+ entry and receptor-mediated responses in GH3 cells. Topical application of AGN 190742 or AGN 190744 inhibits neutrophil infiltration and epidermal hyperplasia induced by repeated treatment of mouse skin with phorbol ester. AGN 190744 also is active in an arachidonic acid model of acute inflammation. These data suggest that topical application of calcium-channel antagonists can inhibit cutaneous inflammatory responses and that AGN 190742 and/or AGN 190744 may serve as useful pharmacological probes for examining these responses in vivo.

Administration, Cutaneous↗
PubMed1995

An EP receptor with a novel pharmacological profile in the T-cell line Jurkat.

1. Comparison of the rank order of potency of the natural prostanoids prostaglandin E2 (PGE2), PGD2, PGF2 alpha and carbaprostacyclin in stimulating cyclic AMP in Jurkat cells is consistent with the presence of an EP receptor. 2. Lack of responsiveness to the EP1/EP3 selective agonist, sulprostone, and the EP2 agonists, butaprost and AH 13205, indicates that this receptor is not of the EP1, EP2 or EP3 subtypes. 3. Inhibition of PGE2-stimulated cyclic AMP by the EP4 antagonist, AH 23848 is non-competitive, unlike the competitive antagonism reported in the pig saphenous vein EP4 preparation. Furthermore, 16,16-dimethyl PGE2 is 100 fold less potent than PGE2 in Jurkat cells, while these agonists are equipotent in the rabbit jugular vein purported EP4 preparation. In addition, 1-OH PGE1, which also is active in the rabbit jugular vein preparation, is inactive in Jurkat cells at concentrations up to 1 x 10(-4) M. These data are not wholly consistent with any adenylate cyclase coupled EP receptor described to date. 4. It is postulated that an EP receptor, positively coupled to adenylate cyclase, with a unique pharmacological profile is present in Jurkat cells.

Adenylyl Cyclases↗
PubMed1988

Adsorption of cations to phosphatidylinositol 4,5-bisphosphate.

We investigated the binding of physiologically and pharmacologically relevant ions to the phosphoinositides by making 31P NMR, electrophoretic mobility, surface potential, and calcium activity measurements. We studied the binding of protons to phosphatidylinositol 4,5-bisphosphate (PIP2) by measuring the effect of pH on the chemical shifts of the 31P NMR signals from the two monoester phosphate groups of PIP2. We studied the binding of potassium, calcium, magnesium, spermine, and gentamicin ions to the phosphoinositides by measuring the effect of these cations on the electrophoretic mobility of multilamellar vesicles formed from mixtures of phosphatidylcholine (PC) and either phosphatidylinositol, phosphatidylinositol 4-phosphate, or PIP2; the adsorption of these cations depends on the surface potential of the membrane and can be described qualitatively by combining the Gouy-Chapman theory with Langmuir adsorption isotherms. Monovalent anionic phospholipids, such as phosphatidylserine and phosphatidylinositol, produce a negative electrostatic potential at the cytoplasmic surface of plasma membranes of erythrocytes, platelets, and other cells. When the electrostatic potential at the surface of a PC/PIP2 bilayer membrane is -30 mV and the aqueous phase contains 0.1 M KCl at pH 7.0, PIP2 binds about one hydrogen and one potassium ion and has a net charge of about -3. Our mobility, surface potential, and electrode measurements suggest that a negligible fraction of the PIP2 molecules in a cell bind calcium ions, but a significant fraction may bind magnesium and spermine ions.

Adsorption↗
PubMed1988

An in vivo phosphorus nuclear magnetic resonance study of the variations with age in the phosphodiester content of human muscle.

Human gastrocnemius and slow twitch muscles contain phosphodiesters that may be detected in vivo by phosphorus nuclear magnetic resonance (NMR). This work represents a study of 354 spectra obtained from healthy subjects of various ages and from patients with peripheral vascular disease. The analysis of the data indicate a correlation between the concentration of phosphodiesters and age. By comparing the data obtained with healthy subjects and patients it is concluded that the increase in phosphodiesters is not due to disease, but to ageing itself. The significance of this increase is discussed.

Adenosine Triphosphate↗
PubMed1985

Interaction of gentamicin and spermine with bilayer membranes containing negatively charged phospholipids.

We measured the electrophoretic mobility of multilamellar phospholipid vesicles, the 31P NMR spectra of both sonicated and multilamellar vesicles, and the conductance of planar bilayer membranes to study the binding of spermine and gentamicin to membranes. Spermine and gentamicin do not bind significantly to the zwitterionic lipid phosphatidylcholine. We measured the concentrations of gentamicin and spermine that reverse the charge on vesicles formed from a mixture of phosphatidylcholine and either phosphatidylserine or phosphatidylinositol. From these measurements, we determined that the intrinsic association constants of the cations with these negative lipids are all about 10 M-1. This value is orders of magnitude lower than the apparent binding constants reported in the literature by other groups because the negative electrostatic surface potential of the membranes and the resultant accumulation of these cations in the aqueous diffuse double layer adjacent to the membranes have not been explicitly considered in previous studies. Our main conclusion is that the Gouy-Chapman-Stern theory of the aqueous diffuse double layer can describe surprisingly well the interaction of gentamicin and spermine with bilayer membranes formed in a 0.1 M NaCl solution if the negative phospholipids constitute less than 50% of the membrane. Thus, the theory should be useful for describing the interactions of these cations with the bilayer component of biological membranes, which typically contain less than 50% negative lipids. For example, our results support the suggestion of Sastrasinh et al. [Sastrasinh, M., Krauss, T. C., Weinberg, J. M., & Humes, H. D. (1982) J. Pharmacol. Exp. Ther. 222, 350-358] that phosphatidylinositol is the major binding site for gentamicin in renal brush border membranes.

Electric Conductivity↗
PubMed1984

Bilayer membranes containing the ganglioside GM1: models for electrostatic potentials adjacent to biological membranes.

Although the Gouy-Chapman-Stern theory of the aqueous diffuse double layer describes well the electrostatic potential adjacent to negatively charged phospholipid bilayer membranes, it does not describe adequately the zeta potential of biological membranes: the zeta potential of an erythrocyte is about half the value predicted from the theory by using the known density of negatively charged sialic acid residues. To investigate the factors responsible for this low electrophoretic mobility, we formed membranes from mixtures of the zwitterionic lipid phosphatidylcholine, PC, and the glycolipid galactosyl-N-acetylgalactosaminyl(N-acetylneuraminyl) -galactosylglucosylceramide, GM1. This glycolipid differs from phospholipids in two respects. First, the negative charge on GM1 is located about 1 nm from the surface, which tends to increase the electrophoretic mobility of vesicles. Second, the head group of GM1 contains five sugar groups that exert a hydrodynamic drag, which tends to decrease the mobility of the vesicles. In a decimolar monovalent salt solution, where the Debye length is about 1 nm, the electrophoretic mobility of the PC-GM1 vesicles is about half the mobility of PC-phosphatidylserine or PC-phosphatidylglycerol vesicles of equivalent composition. In addition, conductance measurements with planar bilayer membranes as well as 31P nuclear magnetic resonance and fluorescence measurements with sonicated vesicles indicate that the potential at the surface of PC-GM1 membranes is about half the value measured for PC-phosphatidylserine membranes in a 0.1 M monovalent salt solution.

G(M1) Ganglioside↗
PubMed1984

A radionuclide method of evaluating shunt function and CSF circulation in hydrocephalus. Technical note.

A simple technique for the evaluation of shunt function and cerebrospinal fluid (CSF) circulation in hydrocephalic patients is described. The method utilizes clearance rates of a radionuclide tracer injected into the lateral ventricle via an indwelling frontal catheter which is separate from the shunt apparatus. This permits an accurate assessment of drainage of ventricular CSF via the shunt, or the patency of normal or alternative CSF pathways where the shunt is malfunctioning.

Cerebrospinal Fluid↗
PubMed1983

Dimethonium, a divalent cation that exerts only a screening effect on the electrostatic potential adjacent to negatively charged phospholipid bilayer membranes.

Calcium and other alkaline earth cations change the electrostatic potential adjacent to negatively charged bilayer membranes both by accumulating in the aqueous diffuse double layer adjacent to the membrane and by adsorbing to the phospholipids. The effects of these cations on the electrostatic potential are described adequately by the Gouy-Chapman-Stern theory. We report the results of experiments with ethane-bis-trimethylammonium, a cation that has been termed "dimethonium" or "ethamethonium" in analogy with hexamethonium (hexane-1,6-bis-trimethylammonium) and decamethonium (decane-1,10-bis-trimethylammonium). We examined the effect of dimethonium on the zeta potential of multilamellar vesicles formed from the negative lipid phosphatidylserine (PS) and from 5:1 phosphatidylcholine/phosphatidylserine mixtures in solutions containing 0.1, 0.01 and 0.001 M sodium, cesium, or tetramethylammonium chloride. We also examined the effect of dimethonium on the conductance of planar PS bilayer membranes and the 31P NMR signal from sonicated PS vesicles formed in 0.1 M NaCl. We found no evidence that dimethonium adsorbs specifically to bilayer membranes. All the results, except for those obtained with vesicles of low charge density formed in a solution with a high salt concentration, are consistent with the predictions of the Gouy-Chapman theory. We conclude that dimethonium, which does not have the pharmacological effects of hexamethonium and decamethonium, is a useful divalent cation for physiologists interested in investigating electrostatic potentials adjacent to biological membranes.

Bis-Trimethylammonium Compounds↗
PubMed1983

Large divalent cations and electrostatic potentials adjacent to membranes. Experimental results with hexamethonium.

A simple extension of the Gouy-Chapman theory predicts that the ability of a divalent cation to screen charges at a membrane-solution interface decreases significantly if the distance between the charges on the cation is comparable with the Debye length. We tested this prediction by investigating the effect of hexamethonium on the electrostatic potential adjacent to negatively charged phospholipid bilayer membranes. The distance between the two charges of an extended hexamethonium molecule is approximately 1 nm, which is the Debye length in the 0.1 M monovalent salt solutions used in these experiments. Six different experimental approaches were utilized. We measured the electrophoretic mobility of multilamellar vesicles to determine the zeta potential, the line width of the 31P nuclear magnetic resonance (NMR) signal from sonicated vesicles to calculate the change in potential at the phosphodiester moiety of the lipid, and the conductance of planar bilayer membranes exposed to either carriers (nonactin) or pore formers (gramicidin) to estimate the change in potential within the membrane. We also measured directly the effect of hexamethonium on the potential above a monolayer formed from negative lipids, and attempted to calculate the change in the surface potential of a bilayer membrane from capacitance measurements. With the exception of the capacitance calculations, each of the techniques gave comparable results: hexamethonium exerts a smaller effect on the potential than that predicted by the classic screening theory. The results are consistent with the predictions of the extended Gouy-Chapman theory and are relevant to the interpretation of physiological and pharmacological experiments that utilize hexamethonium and other large divalent cations.

Animals↗
PubMed1982

Comparison of thallium-201 scanning in idiopathic dilated cardiomyopathy and severe coronary artery disease.

To determine whether cardiomyopathy could be distinguished from coronary artery disease, we used thallium scanning to study 25 patients with severe left ventricular dysfunction and chronic heart failure. Ten patients had normal coronary arteries and idiopathic cardiomyopathy (ejection fraction 20 +/- 5%), and 15 patients had multivessel coronary disease and left ventricular dysfunction (ejection fraction 25 +/- 6%). The exercise time and maximal heart rate were similar in the two groups. Two patients with cardiomyopathy and 11 with coronary artery disease had a positive exercise ECG (p less than 0.05). Thallium scans showed perfusion defects in all 25 patients. The perfusion defects were complete in nine coronary artery disease patients (60%) and in one patient (10%) with cardiomyopathy (p less than 0.05). Extensive defects involving more than 40% of the left ventricular circumference, the number of segments involved, redistribution on the 4-hour scan, lung uptake and ventricular size were similar in the two groups. Perfusion defects on thallium scanning can occur in patients with idiopathic dilated cardiomyopathy and chronic heart failure. Thallium scanning cannot be reliably used in patients with chronic heart failure to distinguish coronary artery disease from cardiomyopathy unless complete defects are present.

Adult↗
PubMed1981

The adsorption of divalent cations to phosphatidylglycerol bilayer membranes.

The ability of Stern equation to describe the adsorption of divalent cations to phosphatidylglycerol membranes was tested by combining 31P-NMR and electrophoretic mobility measurements. In 0.1 M sodium chloride both the 31P-NMR and the zeta potential data are well described by the Stern equation. 31P-NMR and 13C-NMR results indicate that cobalt forms inner-sphere complexes only with the phosphate group of phosphatidylglycerol molecules and that a substantial fraction of the adsorbed cobalt ions form outer-sphere complexes. Evidence is presented that suggests the alkaline earth cations also bind to phospholipids mainly by forming outer sphere complexes. Electrophoretic mobility measurements were performed with several different divalent cations. In all cases the zeta potentials in 0.1 M sodium chloride were well described by the Stern equation. The intrinsic 1:1 association constants (M-1) for the phosphatidylglycerol complexes decreased in the sequence: Mn2+, 11.5; Ca2+, 8.5; Ni2+, 7.5; Co2+, 6.5; Mg2+, 6.0; Ba2+, 5.5 and Sr2+, 5.0.

Adsorption↗
PubMed1981

Adsorption of divalent cations to bilayer membranes containing phosphatidylserine.

The Stern equation, a combination of the Langmuir adsorption isotherm, the Boltzmann relation, and the Grahame equation from the theory of the diffuse double layer, provides a simple theoretical framework for describing the adsorption of charged molecules to surfaces. The ability of this equation to describe the adsorption of divalent cations to membranes containing brain phosphatidylserine (PS) was tested in the following manner. Charge reversal measurements were first made to determine the intrinsic 1:1 association constants of the divalent cations with the anionic PS molecules: when the net charge of a PS vesicle is zero one-half of the available sites are occupied by divalent cations. The intrinsic association constant, therefore, is equal to the reciprocal of the divalent cation concentration at which the mobility of a PS vesicle reverses sign. The Stern equation with this association constant is capable of accurately describing both the zeta potential data obtained with PS vesicles at other concentrations of the divalent cations and the data obtained with with vesicles formed from mixtures of PS and zwitterionic phospholipids. Independent measurements of the number of ions adsorbed to sonicated PS vesicles were made with a calcium-sensitive electrode. The results agreed with the zeta potential results obtained with multilamellar vesicles. When membranes are formed at 20 degrees C in 0.1 M NaCl, the intrinsic 1:1 association constants of Ni, Co, Mn, Ba, Sr, Ca, and Mg with PS are 40, 28, 25, 20, 14, 12, and 8 M-1, respectively.

Cations, Divalent↗