The 1994 G. Malcolm Brown Lecture. Biological barriers and medicine. 1995

C A Goresky
McGill University Medical Clinic, Montreal General Hospital, Quebec.

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.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D010599 Pharmacokinetics Dynamic and kinetic mechanisms of exogenous chemical DRUG LIBERATION; ABSORPTION; BIOLOGICAL TRANSPORT; TISSUE DISTRIBUTION; BIOTRANSFORMATION; elimination; and DRUG TOXICITY as a function of dosage, and rate of METABOLISM. LADMER, ADME and ADMET are abbreviations for liberation, absorption, distribution, metabolism, elimination, and toxicology. ADME,ADME-Tox,ADMET,Absorption, Distribution, Metabolism, Elimination, and Toxicology,Absorption, Distribution, Metabolism, and Elimination,Drug Kinetics,Kinetics, Drug,LADMER,Liberation, Absorption, Distribution, Metabolism, Elimination, and Response
D012109 Research Support as Topic Work about financial support of research activities. Grants and Subsidies, Research,Subsidies, Research,Research Subsidies,Research Subsidy
D002322 Career Mobility The upward or downward mobility in an occupation or the change from one occupation to another. Career Ladders,Clinical Ladders,Job Ladders,Clinical Ladder,Ladder, Clinical,Ladders, Clinical,Career Ladder,Career Mobilities,Job Ladder,Ladder, Career,Ladder, Job,Ladders, Career,Ladders, Job,Mobilities, Career,Mobility, Career
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic

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