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Biomedical subjects

A McLaughlin

Publications and source records attributed to A McLaughlin.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Exercise-induced ST-segment elevation in leads V1 or aVL. A predictor of anterior myocardial ischemia and left anterior descending coronary artery disease.

Exercise-induced ST-segment elevation in leads V1 and/or aVL in the absence of anterior Q waves occurred in 46 of 190 patients (24%) who underwent 12-lead exercise electrocardiography with thallium-201 myocardial perfusion imaging and coronary arteriography. Significant left anterior descending coronary artery (LAD) disease was present in 38 of 46 patients (83%) with V1/aVL ST evaluation and in 72 of 144 patients (50%) without V1/aVL ST elevation (p less than 0.0005). Anterior myocardial ischemia, indicated by reversible anterior perfusion defects on thallium scanning, was present in 40 of 46 patients (87%) with V1/aVL ST elevation and in 25 of 144 patients (17%) without V1/aVL ST elevation (p less than 0.0005). Exercise ST elevation in V1/aVL was detected in 38 of 110 of the patients (35%) with LAD disease, for a specificity of 90%, and in 40 of 65 of the patients (62%) with anterior myocardial ischemia, for a specificity of 95%. We conclude that during 12-lead exercise electrocardiography, ST-segment elevation in V1 and/or a VL in the absence of anterior Q waves predicts anterior myocardial ischemia and LAD disease.

Arterial Occlusive Diseases↗

Serial exercise thallium myocardial perfusion scanning and exercise electrocardiography in the diagnosis of coronary artery disease.

Serial exercise thallium-201 myocardial perfusion scanning (exercise and 4-hour redistribution) was compared to rest and exercise electrocardiography (ECG) for the detection of coronary artery disease in 125 patients with known or suspected coronary artery disease. All patients underwent coronary arteriography and 108 were found to have significant coronary artery lesions. The serial exercise thallium scan was significantly more sensitive than rest and exercise ECG in detecting coronary artery disease (94% v. 83% P less than 0.01). The sensitivity of a reversible thallium perfusion scan abnormality and a positive exercise ECG for detecting exercise induced myocardial ischaemia in coronary artery disease was similar (69% v. 63%). The exercise thallium scan complemented the exercise ECG, and the sensitivity of the combined test was significantly greater than the exercise ECG alone (84% v. 63% P less than 0.001). The specificity for coronary artery disease of the exercise ECG was 65% and that of the exercise thallium-201 myocardial perfusion scan was 82% (P = NS). Thallium-201 myocardial perfusion scanning complements the rest and exercise ECG in the non-invasive detection of coronary artery disease.

Adult↗

The adsorption of divalent cations to phosphatidylcholine bilayer membranes.

Electrophoretic mobility and 31P NMR measurements were combined to test whether the combination of the Henry, Boltzmann and Grahame equations is capable of describing the adsorption of divalent cations of phosphatidylcholine membranes. Cobalt was chosen for this study because, of all the common divalent cations, its effects on the 31P NMR spectrum of phosphatidylcholine membranes are easiest to interpret. Both the 31P NMR data on the adsorption of cobalt and the zeta potential data calculated from the electrophoretic mobility in the presence of cobalt are well described by the combination of these three equations. Electrophoretic mobility measurements were also performed with a number of other divalent cations and the zeta potentials were, in all cases, well described by the combination of these three equations. The binding deduced from such measurements decreases in the sequence: Mn2+, Mg2+, Ca2+, Co2+, Ni2+, Sr2+, Ba2+. If we assume that a lipid molecule occupies an area of 60 A2 and that there is a 1 : 1 stoichiometry for the binding of the divalent ions to phosphatidylcholine, the dissociation constants are, respectively: 0.3, 1.0, 1.0, 1.2, 1.2, 2.8, 3.6 M.

Adsorption↗

Myocardial perfusion scanning with thallium--201 for the non-invasive diagnosis of coronary artery disease.

Thallium--201 myocardial perfusion scanning has been evaluated in Australia in patients with coronary artery disease. Myocardial scans reliably detect both acute myocardial infarction and the transient myocardial ischaemia of angina pectoris. The non-invasive nature, ease of study, and the ability to scan patients with conventional cameras makes thallium--201 an attractive additional diagnostic agent for patients with suspected coronary artery disease. Although thallium--201 reliably indicates perfusion defects in the myocardium, its diagnostic use at the moment should be reserved to clarify such diagnostic problems in patients with coronary artery disease which cannot be satisfactorily explained by conventional investigation.

Angina Pectoris↗

Radionuclide imaging to assess myocardial damage during open heart surgery.

Technetium 99m Pyrophosphate imaging before and after open heart surgery was performed in 38 patients to estimate the incidence of peri-operative infarction. Positive images were present pre-operatively in 11 of 30 patients with coronary artery disease. In three patients the images changed from negative to positive and in two this was thought to be due to infarction produced at operation. The high incidence of positive pre-operative images emphasises that many patients with evolving myocardial infarction, unstable angina or severe heart failure are now operated upon without delay. Because many patients have positive images before surgery pre-operative and post-operative images must be compared to assess myocardial damage due to surgery.

Adult↗

"Hot spot" myocardial scanning: experiences with a mobile nuclear camera in a coronary care unit.

Twenty-nine patients with suspected or actual myocardial infarction have had myocardial "hot spot" scans with technietium 99m pyrophosphate, using a mobile nuclear camera in a coronary care unit. Nine patients with transmural infarcts had positive scans. Nine out of 12 patients thought to have had endocardial infarction had positive scans. Two patients who had had intramuscular injections presented with chest pain and abnormally high serum enzyme levels, but had negative scans. Myocardial radionuclide scanning with a mobile nuclear camera is a rapid, easy, repeatable, non-invasive method of helping to confirm or exclude the diagnosis of myocardial infarction and, used together with other available tests, is a valuable additional diagnostic aid.

Adult↗

The value of the brain scan and cerebral arteriogram in the Sturge-Weber syndrome.

In a series of eight patients with the Sturge-Weber syndrome, the brain scan was shown to be the most accurate, non-invasive, diagnostic test, being abnormal in all eight patients. In four cases examined by cerebral arteriography, this study was also conspicuously abnormal. Some of the neurological disturbances occurring in these patients are more likely to be due to transient ischaemic attacks and cerebral infarctions than to epilepsy.

Adolescent↗