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Biomedical subjects

A L MacDonald

Publications and source records attributed to A L MacDonald.

11 recordsLinked to original sources

The lateral distribution of cholesterol in the plane of lipid multibilayers.

We consider three models of cholesterol distribution in the plane of a bilayer of DMPC. We analyse recent 2H-NMR data obtained from deuterated fluorescent probes and show that, on the characteristic time-scale of 2H-NMR, it is in accord with a random distribution of cholesterol in a fluid-like DMPC bilayer in a single phase at least for T greater than or approximately equal to 35 degrees C and for 0 less than or equal to c less than or equal to 0.42.

Cholesterol↗

Thermodynamics of glycophorin in phospholipid bilayer membranes.

We have developed a model of glycophorin in a phospholipid bilayer membrane in order to study the thermodynamics of this system and to understand the detailed behavior of recent calorimetric data. We assume that the larger glycophorin polar group can be considered as either adopting a pancakelike conformation at the bilayer interface (D state) or be directed generally away from the interface (U state) [Ruppel, D., Kapitza, H.G., Galla, H.J., Sixl, F., & Sackmann, E. (1982) Biochim. Biophys. Acta 692, 1-17]. Lipid hydrocarbon chains are described either as excited (e state) with high energy and relatively many gauche conformers or as generally extended (g state) with low energy. We performed a Monte-Carlo simulation using the Glauber and Kawasaki procedures on a triangular lattice which represents the plane of half of the bilayer. Lattice sites can be occupied either by lipid hydrocarbon chains or by model glycophorin alpha-helical hydrophobic cores. The states D and U are represented by hexagons of different sizes in the plane of the lattice, and the hard core repulsion between two such polar groups is accounted for by forbidding hexagon-hexagon overlap. We have studied the effect of having the glycophorin polar group interact in various ways with the lipid bilayer. We find that the protein polar group in its D state interacts, either directly or indirectly, with the lipid bilayer so as to reduce the effective lateral pressure acting on the lipid hydrocarbon chains by about 3 dyn/cm. Polar groups in their U states do not reduce this lateral pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Computer Simulation↗

Lateral diffusion of gramicidin S, M-13 coat protein and glycophorin in bilayers of saturated phospholipids. Mean field and Monte Carlo studies.

We have developed a general model that relates the lateral diffusion coefficient of one isolated large intrinsic molecule (mol. wt. greater than or approximately 1000) in a phosphatidylcholine bilayer to the static lipid hydrocarbon chain order. We have studied how protein lateral diffusion can depend upon protein-lipid interactions but have not investigated possible non-specific contributions from gel-state lattice defects. The model has been used in Monte Carlo simulations or in mean-field approximations to study the lateral diffusion coefficients of Gramicidin S, the M-13 coat protein and glycophorin in dimyristoyl- and dipalmitoylphosphatidylcholine (DMPC and DPPC) bilayers as functions of temperature. Our calculated lateral diffusion coefficients for Gramicidin S and the M-13 coat protein are in good agreement with what has been observed and suggest that Gramicidin S is in a dimeric form in DMPC bilayers. In the case of glycophorin we find that the 'ice breaker' effect can be understood as a consequence of perturbation of the lipid polar region around the protein. In order to understand this effect is necessary that the protein hydrophilic section perturb the polar regions of at least approx. 24 lipid molecules, in good agreement with the numbers of 29-30 measured using 31P-NMR. Because of lipid-lipid interactions this effect extends itself out to four or five lipid layers away from the protein so that the hydrocarbon chains of between approx. 74 and approx. 108 lipid molecules are more disordered in the gel phase, so contributing less to the transition enthalpy, in agreement with the numbers of 80-100 deduced from differential scanning calorimetry (DSC). An understanding of the abrupt change in the diffusion coefficient at a temperature below the main bilayer transition temperature requires an additional mechanism. We propose that this change may be a consequence of a 'coupling-uncoupling' transition involving the protein hydrophilic section and the lipid polar regions, which may be triggered by the lipid bilayer pretransition. Our calculation of the average number of gauche bonds per lipid chain as a function of temperature and distance away from an isolated polypeptide or integral protein shows the extent of statically disordered lipid around such molecules. The range of this disorder depends upon temperature, particularly near the main transition.

Capsid↗

Are serum antibody, complement or K-cell dependent cellular cytotoxicity involved in corneal graft rejection?

Having shown that complement independent cellular cytotoxicity (CICC) plays a part in destroying the donor cell we wished to see if serum antibody cytotoxicity (SAC), complement dependent cellular cytotoxicity (CDCC) or K-cell mediated cellular cytotoxicity (KCC) might not also be involved in the rejection of corneal grafts. Rabbits were grafted with allo- and xenogreneic corneas. At various times, lymphoid cells and sera were collected from a recipient and a control animal. The donor's corneal cells and those of the control animal were cultivated in vitro, and then labelled with 51chromium. The recipient and control lymphoid cells and sera and/or complement were mixed with the labelled cells. A 51chromium release assay was done after incubation. The test was negative for SAC, CDCC, and KCC and we feel that they have no major part in the rejection of corneal grafts.

Animals↗

The systemic production of cytotoxic lymphoid cells in corneal allograft reaction. 1. A quantitantitative study utilizing 51chromium release assay.

The purpose of the study was to determine whether the mechanism of corneal allograft rejection is systemic in nature. Utilizing a 51Cr release assay in which labelled donor and recipient corneal cells were used as targets, it was demonstrated that cytotoxic cells specific for antigens located in donor corneal cells were present in spleen and lymph nodes.

Animals↗

Systemic sensitization of corneal allograft recipients before the clinical onset of graft reaction.

We wished to know if full-thickness corneal allografts placed centrally in clear host corneas would cause systemic sensitization. Keratoplasty was done in 13 rabbits and a leucocyte migration inhibition test was done on their systemic blood five to seven days operation using donor specific corneal antigen. All but two animals had positive results (mean inhibition 27% "/- 2.2) showing that, following keratoplasty, systemic sensitization does occur. Absence of blood vessels and lymphatics thus does not constitute an absolute barrier to sensitization of the recipient.

Animals↗

Binocular visual field in strabismus.

The binocular visual field of 100 patients with a variety of manifest strabismus was analysed using a complex visual environment and polaroid dissociation. A significant area of the picture, both nasal and temporal to fixation, was suppressed by all patients. Eighty-nine per cent showed correct localisation and identification in an area which was not suppressed and was approximately 45 prism dioptres peripheral to fixation.

Humans↗

Sodium cromoglycate (intal) in the treatment of vernal keratoconjunctivitis and allergic conjunctivitis.

Intal drops (sodium cromoglycate) relieved symptoms of vernal conjunctivitis in all the 19 patients we studied, reducing the need for steroids although the response varied. Intal was also effective in all 11 patients with acute or subacute seasonal allergic conjunctivitis, but in only 4 of 11 patients with mild chronic conjunctivitis associated with atopy. No side-effects were noted other than mild irritation in some cases.

Adolescent↗