PubMed · 5722307
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M E Wise. 1968. The changing pattern after a few days.. https://pubmed.ncbi.nlm.nih.gov/5722307/
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Fluid and macromolecule secretion by submucosal glands in mammalian airways is believed to be important in normal airway physiology and in the pathophysiology of cystic fibrosis (CF). An in situ fluorescence method was applied to measure the ionic composition and viscosity of freshly secreted fluid from airway glands. Fragments of human large airways obtained at the time of lung transplantation were mounted in a humidified perfusion chamber and the mucosal surface was covered by a thin layer of oil. Individual droplets of secreted fluid were microinjected with fluorescent indicators for measurement of [Na(+)], [Cl(-)], and pH by ratio imaging fluorescence microscopy and viscosity by fluorescence recovery after photobleaching. After carbachol stimulation, 0.1--0.5 microl of fluid accumulated in spherical droplets at gland orifices in approximately 3--5 min. In gland fluid from normal human airways, [Na(+)] was 94 +/- 8 mM, [Cl(-)] was 92 +/- 12 mM, and pH was 6.97 +/- 0.06 (SE, n = 7 humans, more than five glands studied per sample). Apparent fluid viscosity was 2.7 +/- 0.3-fold greater than that of saline. Neither [Na(+)] nor pH differed in gland fluid from CF airways, but viscosity was significantly elevated by approximately 2-fold compared to normal airways. These results represent the first direct measurements of ionic composition and viscosity in uncontaminated human gland secretions and indicate similar [Na(+)], [Cl(-)], and pH to that in the airway surface liquid. The elevated gland fluid viscosity in CF may be an important factor promoting bacterial colonization and airway disease.
Proteomics is one of the technologies rapidly changing our approach to drug development. The applications of proteomics, particularly with reference to analysis of body fluid samples, will be described. Proteomic analysis involves the systematic separation, identification and characterisation of proteins present in a biological sample. By comparing the proteins present in diseased samples with those present in normal samples, it is possible to identify changes in expression of proteins that potentially may be related to organ toxicity. Proteomics is regarded as a sister technology to genomics. Although the pattern of gene activity will be abnormal in a tissue with a pathological lesion, there can be a poor correlation between the level of activity of different genes and the relative abundance within the tissue of the corresponding proteins. This is especially true where the mode of action of the test material interferes with protein synthesis and/or post translational modification. Consequently, the information about a pathological process that can be derived at the level of gene activity is incomplete. Proteomics has now made it possible to analyse proteins using high throughput, automated techniques. Although both mRNA and proteomic profiling can be applied to tissue samples, analysis of body fluids (e.g. serum, urine, CSF, synovial fluid) is restricted to proteomics. In these cases the protein composition is derived from many tissues and processes. Proteomic analysis can yield information on disease processes and potential response to treatment. Examples will be presented of the identification of surrogate markers for hepatocellular carcinoma, breast cancer, from cerebrospinal fluid in humans and gentamicin toxicity in the rat.
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