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M Metcalfe

Publications and source records attributed to M Metcalfe.

At least 37 records · Page 2Linked to original sources

Free energy potential for aggregation of giant, neutral lipid bilayer vesicles by Van der Waals attraction.

Here, we report the first direct observation of Van der Waals' attraction between biomembrane capsules using measurements of the free energy reduction per unit area of membrane-membrane contact formation. In these studies, the membrane capsules were reconstituted neutral (egg phosphatidylcholine) lipid bilayers of giant (greater than 10(-3) cm diam) vesicles. Micromanipulation methods were used to select and maneuver two vesicles into proximity for contact; after adhesion was allowed to occur, the extent of contact formation was regulated through the vesicle membrane tensions that were controlled by micropipette suction. The free energy reduction per unit area of contact formation was proportional to the membrane tension multiplied by a simple function of the pipette and vesicle dimensions. The free energy potential for Van der Waals attraction between the neutral bilayers in 120 mM NaCl solutions was 1.5 X 10(-2) ergs/cm2. Also, when human serum albumin was added to the medium in the range of 0-1 mg/ml, the free energy potential for bilayer-bilayer adhesion was not affected. Using published values for equilibrium spacing between lipid bilayers in multilamellar lipid-water dispersions and the theoretical equation for van der Waals attraction between continuous dielectric layers, we calculated the value for the Hamaker coefficient of the Van der Waals attraction to be 5.8 X 10(-14) ergs.

Cell Aggregation↗

Free energy potential for aggregation of mixed phosphatidylcholine/phosphatidylserine lipid vesicles in glucose polymer (dextran) solutions.

The energetics of lipid vesicle-vesicle aggregation in dextran (36,000 mol wt) solutions have been studied with the use of micromechanical experiments. The affinities (free energy reduction per unit area of contact) for vesicle-vesicle aggregation were determined from measurements of the tension induced in an initially flaccid vesicle membrane as it adhered to another vesicle. The experiments involved controlled aggregation of single vesicles by the following procedure: two giant (approximately 20 micron diam) vesicles were selected from a chamber on the microscope stage that contained the vesicle suspension and transferred to a second chamber that contained a dextran (36,000 mol wt) salt solution (120 mM); the vesicles were then maneuvered into position for contact. One vesicle was aspirated with sufficient suction pressure to create a rigid sphere outside the pipette; the other vesicle was allowed to spread over the rigid vesicle surface. The aggregation potential (affinity) was derived from the membrane tension vs. contact area. Vesicles were formed from mixture of egg lecithin (PC) and phosphatidylserine (PS). For vesicles with a PC/PS ratio of 10:1, the affinity showed a linear increase with concentration of dextran; the values were on the order of 10(-1) ergs/cm2 at 10% by weight in grams. Similarly, pure PC vesicle aggregation was characterized by an affinity value of 1.5 X 10(-1) ergs/cm2 in 10% dextran by weight in grams. In 10% by weight in grams solutions of dextran, the free energy potential for vesicle aggregation decreased as the surface charge (PS) was increased; the affinity extrapolated to zero at a PC/PS ratio of 2:1. When adherent vesicle pairs were transferred into a dextran-free buffer, the vesicles did not spontaneously separate. They maintained adhesive contact until forceably separated, after which they would not read here. Thus, it appears that dextran forms a "cross-bridge" between the vesicle surfaces.

Animals↗

Dexamethasone suppression test in depression and other psychiatric illness.

The prevalence of an abnormal response to the dexamethasone suppression test (DST) was examined in 119 in-patients suffering from a major depressive disorder and in 79 normal controls. Only 11 per cent of controls showed an abnormal DST as against 70 per cent of depressed patients. The specificity of the DST was examined by testing patients with other psychiatric disorders. Abnormal responses were found in one-fifth of a sample of schizophrenics, over one-quarter of abstinent alcoholics, two-fifths of neurotics (including neurotic depressives) and almost half of senile dements. Abnormal DST was also found in 33 per cent of patients receiving prophylactic lithium for recurrent affective disorders.

Adult↗

Lithium continuation therapy following electroconvulsive therapy.

Thirty-eight depressed patients who were treated with ECT were randomly assigned to receive lithium therapy or identical-looking placebo tablets for one year after clinical recovery in a double-blind trial. The patients who received placebo tablets spent an average of 7.8 weeks with an episode of depression (either as in-patients or day-patients) during the year. In comparison, patients who received lithium spent on average 1.7 weeks with an episode (P less than 0.02). The trial confirms the high rate of relapses after ECT and suggests that lithium considerably reduces this morbidity. It is suggested that ECT without continuation therapy is not a satisfactory treatment of depressive illness.

Adult↗

Informed consent: how much does the patient understand?

Comprehension and recall of the information contained in the informed consent statement was tested in clinically hypertensive patients entering a controlled trial comparing hydrochlorothiazide and propranolol. The consent statement was the primary vehicle for conveying the information to the patient. The average of correct answers to a multiple-choice quiz was 71.6% at 2 hr and 61.2% at 3 mo after the consent procedure. The effectiveness of recall did not correlate with level of education. Patients exhibited greater comprehension of the action of the drugs than of their side effects. Nearly all patients indicated their belief that they would receive the best possible care. While 95% wanted to be informed about the trial, 75% stated they would have given their consent even without this information.

Adult↗

Beta blockade in lithium tremor.

Practolol, propranolol, and placebo have been tested on an objective test of lithium induced tremor. Both beta-blocking agents produced significantly more tremor than the placebo. It is argued that lithium induced tremor is closer to essential than to physiological tremor.

Affective Symptoms↗

Seasonal variations in the dexamethasone suppression test.

One hundred and fifty-six patients from Epsom (U.K.) and Brussels, all suffering from major depressive disorder, were tested on the dexamethasone suppression test. Post-dexamethasone cortisol concentration in the plasma was found to be much lower in the winter months (November to February) than in the rest of the year.

Adult↗