The 1994 G. Malcolm Brown Lecture. Biological barriers and medicine.

Career support provides the essential element needed for the detailed development of thematic areas of inquiry. Dr Goresky outlines how career support provided for him the substratum for the investigation and definition of tracer exchange processes in the liver. Classical interstitial substances (labeled albumin, inulin, sucrose, and sodium) and labeled water were found to undergo flow limited distribution in the liver. An excluded volume phenomenon created systematic variation in accessible interstitial space (that is, Disse space) values, smaller for larger molecular weight substances. Labeled rubidium entered liver cells in a concentrative fashion (return from cells was very small, early in time). Labeled glucose liver cell entry was found to exhibit the characteristics of a carrier-mediated membrane transport process. Labeled galactose showed saturation of intracellular sequestration, as well as of the cell entry process, the former at much lower galactose concentrations. Straight-chain labeled monohydric alcohols were found to enter liver cells in a flow-limited fashion. Labeled ethanol consumption, when related to underlying steady ethanol values, exhibited Michaelis-Menten kinetics. A substantial extra intracellular enzymic space of distribution was found for the C3- and C4- straight-chain alcohols, predicted by the kinetics. Development of the tracer approach allowed the differentiation and characterization of the processes by which substances penetrate the cell membrane barrier and those resulting in intracellular sequestration.