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Biomedical subjects

D M Small

Publications and source records attributed to D M Small.

210 records · Page 12Linked to original sources
PubMed1968

The physicochemical basis of cholesterol gallstone formation in man.

The concentrations of bile salt, lecithin, and cholesterol were determined on each of 66 samples of gall bladder bile from patients with cholesterol gallstones and 25 samples of normal gall bladder bile. When these three constituents were plotted simultaneously on triangular coordinates, a complete separation of the normal and "abnormal" bile was achieved. This separation was the result of an increase in the quantity of cholesterol relative to the amounts of bile salts and lecithin contained in the bile from patients with cholesterol gallstones. An in vitro model system was constructed (on triangular coordinates) that allows prediction of the maximum amount of cholesterol that can be solubilized in solutions containing varying proportions of bile salt and lecithin. When the bile data were compared with the solubility of cholesterol derived from the model system, normal biles were found to be less than saturated with cholesterol, whereas biles from patients with cholesterol gallstones were saturated and in some cases contained insoluble cholesterol in the form of microcrystals. It is suggested that the physical state of bile (i.e., the presence or absence of insoluble cholesterol) is determined by the relative concentrations of bile salt, lecithin, and cholesterol, and the other biliary constituents do not appear to significantly effect the solubility of cholesterol in bile.

Bile↗
PubMed1967

Phase equilibria and structure of dry and hydrated egg lecithin.

The behavior of purified egg lecithin in water has been investigated in relation to the quantity of water present and the temperature. The complete binary phase diagram of egg lecithin-water is presented as well as X-ray diffraction data on selected mixtures. Dry egg lecithin is present in at least partially crystalline form until about 40 degrees C. Above this temperature it forms a "wax-like" phase up to about 88 degrees C. From 88 to 109 degrees C it forms a viscous isotropic phase which gives face-centered cubic spacings by X-ray analysis. Above 110 degrees C its texture is "neat" and the structure is assumed to be lamellar until its final melting point at 231 degrees C. Hydrated lecithin forms (except for a small zone of cubic phase at low water concentrations and high temperature) a lamellar liquid crystalline phase. This phase contains up to 45% water at 20 degrees C. Mixtures containing more water separate into two phases, the lamellar liquid crystalline phase and water. In the melting curve of hydrated lecithin a eutectic is noted at about 16% water and the cubic phase seen when less water is present disappears at this composition of the mixture. These facts, along with previous vapor pressure measurements, suggest that there is a structural change at about 16% water. X-ray diffraction studies of lecithin at 24 degrees C and calculations from these data suggest that the reason for this may be the presence of a "free water layer" when more than 16% water is present.

Eggs↗
PubMedDate not supplied

The ionization behavior of fatty acids and bile acids in micelles and membranes.

The ionization behavior of carboxylic acids including aliphatic chain fatty acids and bile acids in solutions, micelles, membranes and proteins is of considerable biological interest. The 13C nuclear magnetic resonance chemical shift of carboxyl carbon of a variety of acids has been shown to be a linear function of the state of ionization of the carboxyl group. Thus, by measuring the chemical shift as a function of the amount of acid or base added to a solution, the state of ionization and the apparent pKa of the carboxyl group may be determined. The method is illustrated in this paper using butyric acid, and results (given as apparent pKa values) are tabulated for a variety of fatty acids and cholic acid in different environments such as monomeric solutions, micelles, membranes and bound to albumin. The apparent pKa varies greatly depending upon the environment. For instance, the apparent pKa of oleic acid is about 4.2 when bound to albumin whereas it is about 7.5 when incorporated in the bilayer of a phospholipid vesicle. Cholic acid shows similar changes in the apparent pKa, being approximately 5.2 in sodium taurocholate micelles and at least 6.8 in phospholipid vesicles. The use of 13C nuclear magnetic resonance (NMR) and, in particular, 13C NMR of 13C-enriched carboxyl groups provides a method for direct observation of the state of ionization of the carboxyl group in biologically interesting acids. Such techniques may be adapted for use in biological systems, such as cells or tissues.

Albumins↗
PubMedDate not supplied

George Lyman Duff memorial lecture. Progression and regression of atherosclerotic lesions. Insights from lipid physical biochemistry.

This review summarizes the evidence that the physical properties of lipids which accumulate in the intima play major roles in the progression and regression of lesions of atherosclerosis. All of the three major classes of lipids that accumulate in lesions (phospholipids, cholesterol, and cholesterol esters) are water insoluble. Phospholipids and cholesterol esters are almost mutually insoluble, but cholesterol, a crystalline solid at 37 degrees C, has considerable solubility in phospholipid bilayers and cholesterol esters. In normal infant intima, cholesterol is solubilized by phospholipid membranes. During fatty streak development, groups of cells are stimulated to take up more cholesterol than they excrete. The excess cholesterol is biochemically converted to cholesterol ester, which separates as droplets to form foam cells. Some fatty streaks then undergo a transition to an intermediate lesion containing excess cholesterol which is carried in cholesterol-supersaturated membranes and droplets. When nucleation of this excess cholesterol occurs, it precipitates as crystals; their formation coincides with the onset of necrosis and plaque formation. The hallmark of plaque is the presence of inert cholesterol crystals. They appear to form from hydrolysis of the older deposits of cholesterol esters in the base of intermediate lesions. Thus, the lipids in plaques are stratified, with recently deposited cholesterol esters present in the luminal part of the intima and older deposits in the deeper regions. When plasma cholesterol is lowered below about 150 mg/dl, lipids are mobilized from lesions and regression gradually occurs. Early in the regression process, cholesterol esters are reduced at least partly by hydrolysis to yield cholesterol, some of which may crystallize and inhibit rapid regression. After prolonged periods of low plasma cholesterol, cholesterol esters and foam cells disappear and crystalline cholesterol gradually dissolves, leading to true regression.

Aging↗
PubMedDate not supplied

Intravenous cholangiography in the rhesus monkey. part I: Determination of optimal iodipamide dose during a one-hour infusion.

One-hour infusion intravenous cholangiography with iodipamide was performed in 3 rhesus monkeys with intact enterohepatic circulations. A series of four different doses including standard (0.3 ml/kg) and "double dose" (0.6 ml/kg) levels were compared. The 0.6 ml/kg dose resulted in significantly higher biliary iodine excretion and concentration than the lower two doses. A 1.2 ml/kg dose probably increased biliary iodine concentration a small amount when compared to the 0.6 ml/kg dose but did not increase iodine excretion. Peak iodine excretion and concentration occurred, on the average, at one hour. The excretion of iodine in the bile demonstrated no inhibitory effect on the concomitant excretion of bile salts.

Animals↗