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Biomedical subjects

M A Singer

Publications and source records attributed to M A Singer.

69 records · Page 4Linked to original sources
PubMed1978

Effect of different drugs on a cytochrome c--phospholipid bilayer membrane.

Liposomes were prepared from dipalmitoyl phosphatidylcholine and dicetylphosphate and their interaction with the extrinsic membrane protein cytochrome c examined in terms of changes in 22Na permeability, electrophoretic mobility, protein binding, and motion of an incorporated spin label. The amount of cytochrome c bound displays no significant temperature dependence over the temperature range studied (from 30 to 55 degrees C) whereas cytochrome c causes an increase in 22Na efflux only above the phospholipid phase transition temperature. Interaction of the protein with the lipid vesicles causes no significant disturbance in the bilayer interior as monitored by the motion of the incorporated spin probe. The drugs 2,4-dinitrophenol and ethacrynic acid, both of which increase the magnitude of the vesicle negative charge, enhance both cytochrome c binding and its effect on 22Na permeability. In contrast, the local anesthetic dibucaine, which induces a positive surface charge on these liposomes, reduces both protein binding and the protein-induced increase in 22Na efflux. Finally, the chemicals butylated hydroxytoluene, 2-tert-butylphenol, and tert-butylbenzene, all of which cause early 'melting' of the phospholipid fatty acyl chains, block the capacity of cytochrome c to enhance 22Na permeability while having no effect on its binding to the vesicles.

Cytochrome c Group↗
PubMed1975

Effect of various sterols on the 22Na permeability and fluidity of phospholipid bilayer membranes.

Sodium-22 efflux was measured in multilamellar liposomes composed of egg lecithin, dicetylphosphate, and various sterols. In a parallel series of experiments a spin labelled fatty acid ester was incorporated into similar vesicles and the molecular motion of the spin label monitored by electron spin resonance spectroscopy. Spin lable mobility was used as a measure of phospholipid hydrocarbon chain motion. There was a poor correlation between the effects of these sterols on sodium permeability and their effects on the motion of the lipid chains. It is postulated that sterols alter sodium transport not only through a reduction in the motional freedom of membrane lipids, but also through changes in the partitioning of sodium between membrane and aqueous phases.

Chemical Phenomena↗
PubMed1975

Interaction of amphotericin B and nystatin with phospholipid bilayer membranes:effect of cholesterol.

Sodium-22 efflux was measured in multilamellar liposomes, exposed to one of the two polyene antibiotics amphotericin B or nystatin. Polyene mediated 22Na transport progressively rises with membrane sterol concentrations up to about 20 mol %, but falls with higher cholesterol concentrations. The polyene induced 22Na movement in cholesterol rich liposomes could be 'restored' by the addition of either dibucaine or propranolol (two local anesthetics) to the aqueous solution. These observations are interpreted in terms of the model of De Kruijff and Demel (Biochim. Biophys. Acta, 339, 57-70, 1974). In this model, nystatin and amphotericin B first complex with cholesterol and then these complexes aggregate to form transmembrane channels. It is here proposed that the aggregation of these complexes is inhibited by a high cholesterol content (decreased membrane fluidity) but that the two local anesthetics, by disrupting phospholipid-sterol interactions (increased membrane fluidity), can 'restore' this process of aggregation.

Amphotericin B↗
PubMedDate not supplied

The thermal properties of dilauryl phosphatidylethanolamine liposomes are affected by lipid source and preparation.

Dilauryl phosphatidylethanolamine (DLPE) dispersions in water ('liposomes') display phase metastability. We find, by differential scanning calorimetry (d.s.c.), that the new phases are dependent upon lipid source and temperature of initial hydration. These observations may explain inconsistencies in the reported metastability behaviour of saturated PEs.

Calorimetry, Differential Scanning↗
PubMedDate not supplied

Cholesterol-multilipid interactions in bilayers.

To extend our knowledge of model membrane systems based upon one lipid component, multi-lamellar bilayers were made of cholesterol with two phospholipids in equimolar ratio, and the enthalpy change delta H of the main phase transition of the temary mixture was measured by differential scanning calorimetry (DSC) as a function of increasing cholesterol concentration c. The lipids were saturated phosphatidylcholines CnPC of acyl chain length n, and as the n of the two lipids became more different (from C13PC/C14PC to C14PC/C15PC to C14PC/C18PC to C14PC/C19PC) distinct breaks in the delta H versus c plots were observed. These mixtures displayed only one broad DSC endotherm. Mixtures of an unsaturated lipid C18: 1PC (dioleoyl) with C16PC or with C18PC showed two peaks, with each peak being associated with its parent lipid. However, the delta H versus c plots for each of these peaks showed an initial independence of cholesterol concentration followed by a dependence on cholesterol concentration. These results indicate that, in lipid mixtures, the type of interaction of cholesterol with each lipid component depends on the concentration of cholesterol present.

Calorimetry, Differential Scanning↗
PubMedDate not supplied

Quantity of dialysis: quality of life--what is the relationship?

Health related quality of life (HRQOL) is increasingly being used to evaluate physical and psychosocial parameters in patients receiving dialysis. In patients with chronic illness, these indices are important adjuncts to biochemical measurements. Inadequate dialysis with low urea clearance (Kt/Vurea) has been linked to adverse outcomes in dialysis patients. Little is known about the relationship between dialysis adequacy and patient reported HRQOL. We evaluated HRQOL in 55 hemodialysis and 60 peritoneal dialysis patients using the RAND 36 Item Health Survey 1.0, measuring the following: physical functioning; role limitations (physical); role limitations (emotional); social functioning; emotional well being; pain; energy; and general health perceptions. Kt/V was also calculated for each patient. Mean HD Kt/V was 1.44 +/- 0.31 (range, 0.5-2.0); mean weekly PD Kt/V was 2.28 +/- 0.90 (range, 1.13-6.02). The relationship between Kt/V and HRQOL was tested using Pearson's correlation. No significant association was found for either treatment group between Kt/V and any of the domains of HRQOL. Thus, HRQOL seems to be influenced by factors other than dialysis adequacy, enhancing its role as an independent measure of patient problems otherwise undetected by traditional objective parameters.

Adult↗