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R H Notter

Publications and source records attributed to R H Notter.

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Path dependence of adsorption behavior of mixtures containing dipalmitoyl phosphatidylcholine.

The adsorption of aqueous phospholipid dispersions containing dipalmitoyl phosphatidylcholine (DPPC) is investigated at 35-37 degrees C as a function of dispersion preparation technique. Systems studied in terms of surface pressure-time (pi-t) adsorption behavior were pure DPPC, 9:1 DPPC:dipalmitoyl phosphatidylethanolamine, 7:3 DPPC:egg phosphatidylglycerol (PG), and lipids extracted from cow lung lavage. The results show that pi-t characteristics can differ significantly depending on the technique by which the DPPC-containing mixtures are initially dispersed in 0.15 M NaCl solution. Examples of path dependence include the fact that DPPC, which will not adsorb at T = 35 degrees C when placed in powdered crystals on the subphase surface, exhibits measurable pi-t changes after subphase dispersion by sonication or by mechanical vortexing. For 7:3 DPPC:PG, dispersion by sonication on ice or by mechanical vortexing gives faster adsorption than dispersion by sonication without temperature control. The effect of heating to T = 45 degrees C, which is greater than the gel to liquid crystal transition temperature of DPPC (Tc = 41 degrees C), is found to be particularly detrimental to the adsorption of 7:3 DPPC:PG. Of the phospholipid mixtures studied, extracted cow lung lipids exhibited by far the greatest adsorption capability and also showed less path dependence than 7:3 DPPC:PG. Similarly, in terms of dispersion techniques investigated, sonication on ice tended to give the most rapid adsorption for a given phospholipid mixture.

Adsorption↗

Hysteresis in saturated phospholipid films and its potential relevance for lung surfactant function in vivo.

The surface pressure-area (pi-A) hysteresis in films of dipalmitoyl phosphatidylcholine (DPPC) is investigated under dynamic cycling at 22 degrees C. The dynamic pi-a hysteresis of such films increases with extent of film compression, becoming maximal when compression is carried out past the point of generalized monolayer collapse based on fatty acid chain limiting areas. Several characteristics of the pi-A hysteresis found in the dynamic cycling of pure DPPC films are shown to be present in mixed surface films containing this saturated phospholipid, including binary DPPC:dioleoyl phosphatidylcholine (DOPC) films and multicomponent lung extract films at body temperature. Specific hysteresis characteristics, particularly a rapid surface pressure fall over a small area change at the beginning of film expansion, may have direct importance for lung surfactant function in vivo, and a possible model for this is presented. A major consequence stressed in terms of pulmonary mechanics concerns the role of lung surfactant pi-A hysteresis characteristics upon alveolar recruitment and increased inflation uniformity during inspiration. An attempt is made to reconcile lung surfactant surface behavior with recent concepts of alveolar area and shape changes during breathing, as well as with known clinical findings in states of lung surfactant deficiency. Some possible numerical parameters that may be useful in evaluating surfactant "activity" are presented.

Humans↗

Lung surfactant in an era of replacement therapy.

In this paper current knowledge of the pulmonary surfactant system with particular emphasis on aspects that relate to exogenous surfactant replacement therapy for the neonatal respiratory distress syndrome (RDS) is considered. The work provides an overview, but concentrates on several facets of lung surfactant research that help to elucidate and evaluate past and present attempts toward such therapy. Subjects addressed include the functional need for specific lung surfactant components to obtain optimal surface activity and some of the required surface property measurements to characterize such activity. Also discussed is current knowledge of lung surfactant synthesis and secretion and the potential effect of exogenous surfactant on the endogenous pulmonary surfactant system. A primary theme throughout is that an analysis of previous clinical trials involving surfactant replacement shows the necessity for strong interactions with related basic science investigations. It is suggested that future human infant surfactant replacement trials proceed deliberately, and include maximal correlations with basic in vitro research on lung surfactant biophysics and biochemistry and with experiments in animal models.

Humans↗

Surface properties of binary mixtures of some pulmonary surfactant components.

The dynamic surface pressure-area properties of pure and binary mixed films of rac-1,2-dipalmitoyl-glycero-3-phosphocholine, 1,2-diocoyl-sn-glycero-3-phosphocholine and cholesterol were investigated at 23 degrees C and 37 degrees C. The pure films and binary mixtures of rac-1,2-dipalmitoyl-glycero-3-phosphocholine: 1,2-dioeoyl-sn-glycero-3-phosphocholine and rac-1,2-dipalmitoyl-glycero-3-phosphocholine:cholesterol were characterized both for dilute surface initial concentrations of 150 Angstrom 2/molecule and for surface excess initial values of 15-50 Angstrom 2/molecule. The results show that the addition of 1,2-dioeoyl-sn-glycero-3-phosphocholine or cholesterol in a binary film with rac-1,2 dipalmitoyl-glycero-3-phosphocholine acts to improve the surface reentry and respreading properties over those of pure rac-1,2-dipalmitoyl-glycero-3-phosphocholine films upon dynamic compression past collapse. This effect is even more pronounced at 37 degrees C than at 23 degrees C, as demonstrated by the application of a collapse plateau ratio criterion. The enhanced dynamic respreading correlates with the effect of 1,2-dioleoyl-sn-glycero-3-phosphocholine and cholesterol in decreasing the gel to liquid crystal transition temperature of rac-1,2-dipalmitoyl-glycero-3-phosphocholine water dispersons, as well as with their facilitation of post-collapse dynamic surface pressure relaxation in binary films with rac-1,2-dipalmitoyl-glycero-3-phosphocholine.

Cholesterol↗

Biophysical inhibition of synthetic phospholipid-lung surfactant apoprotein admixtures by plasma proteins.

Biophysical activity and inhibition characteristics were studied for a series of synthetic surfactants composed of purified bovine lung surfactant proteins (SP)-B or -C combined with dipalmitoyl phosphatidylcholine (DPPC) and egg-phosphatidylglycerol (PG) in a weight ratio of 80:20:1 DPPC/PG/protein. Surfactant protein preparations included two isolates of SP-B, confirmed by amino terminal sequence analysis, three isolates of SP-C which were free of SP-B by ELISA and Western blot analysis, and two isolates containing both SP-B and -C. In oscillating bubble studies, mixtures of phospholipids with isolates containing pure SP-B or both SP-B and -C lowered surface tension to less than 1 mN/m within 2 min of pulsation at both 1.25 mg/ml and 2.5 mg/ml. Phospholipids combined with isolates of pure SP-C also had substantial activity, lowering surface tension to between 1 mN/m and 3 mN/m depending on the SP-C preparation used. The surface activity of synthetic phospholipid-apoprotein admixtures was decreased significantly by the plasma proteins albumin and fibrinogen, but with varying characteristics depending on the apoprotein preparation involved. At 1.25 mg/ml phospholipid, admixtures containing either isolate of SP-B were inhibited by 10 mg/ml of plasma proteins, as were those with one of the SP-C preparations. However, admixtures containing the two other pure SP-C preparations were not inhibited until 20-50 mg/ml of albumin or fibrinogen were present. The highest resistance to inhibition was shown by admixtures containing one of the apoprotein isolates having both SP-B and -C.(ABSTRACT TRUNCATED AT 250 WORDS)

1,2-Dipalmitoylphosphatidylcholine↗

Chemical synthesis and surface activity of lung surfactant phospholipid analogs. III. Chiral N-substituted ether-amide phosphonolipids.

A homologous series of chiral (R) ether-amide phosphonolipid analogs of naturally occurring (R) glycerophospholipids were synthesized and characterized for their interfacial behaviors. The phosphonolipids possess isoteric ether, amide, and phosphonate functions at positions corresponding to the sn-1, sn-2, and sn-3 ester functions, respectively, of naturally occurring glycerophospholipids. All compounds were synthesized with disaturated C16:0 alkyl/acyl moieties to give structural analogy with dipalmitoyl phosphatidylcholine (DPPC), the major glycerophospholipid component of lung surfactant. Further substitutions at the headgroup nitrogen were also used to generate differences in headgroup size and polarity in the synthetic compounds. The surface activity of the ether-amide phospholipids was investigated in terms of adsorption to the air-water interface, together with studies of dynamic respreading after monolayer collapse and surface tension lowering in dynamically compressed spread films and dispersions. Results showed that several ether-amide phosphonolipids had more rapid adsorption and improved dynamic respreading behavior compared to DPPC, plus the ability to lower surface tension into the range of less than 1 to 4 mN/m in spread films and in dispersions under dynamic conditions. In combination with a series of diether phosphonolipids synthetized in a companion study [1], these ether-amide compounds are useful in the development of molecular structure-surface activity correlates for lung surfactant-related materials, and should assist in investigating the specificity of interactions between phospholipids and other pulmonary biological molecules.

Amides↗