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Prospects for microscopical cytochemistry

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Synopsis

This review is devoted mainly to an evaluation of the status of microscopical cytochemistry seen as a discipline aiming at both the localization and the quantification of molecular processes in cells. Its relationships to ultramicrochemistry, as well as, in a broader sense, to biochemistry and cell biology, are discussed from both the historical and the methodological points of view. Recent developments in quantitative cytophysical techniques, such as automated cytophotometry using microscopes fitted with flying spot systems, TV cameras, or scanning stages, and the development of rapid flow cytometers are discussed. Analytical electron microscopy is touched upon too.

The main part of the review is devoted to recent trends that strengthen the analytical basis of cytochemical staining methods. The special character of staining procedures as a kind of matrix chemistry is discussed and the potentialities of the use of matrixincorporated compounds for the fundamental study and calibration of microscopical staining procedures are elaborated. Parallel developments in the theory and practice of matrix chemistry in biochemistry are stressed. Growing interrelations between microscopical cytochemistry and related fields of investigation, such as the controlled fragmentation of cells, and methods like ultramicroanalysis of individual cells are indicated.

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References

  • Ackerknecht, E. M. (1953)Rudolf Virchow, doctor statesman anthropologist. Wisconsin: The University of Wisconsin Press.

    Google Scholar 

  • Altman, F. P. (1975). Quantitation in histochemistry: a review of some commercially available microdensitometers.Histochem. J. 7, 375–95.

    Google Scholar 

  • Anderson, W. L. (1972). Quantitative microscopic holography (ed. R. E. Herron) Quantitative imagery in the biomedical sciences.Proceedings Society of Photo-optical Instrumentation Engineers, Vol.26, 177–86.

    Google Scholar 

  • Axén, R. &Ernback, S. (1971). Chemical fixation of enzymes to cyanogen halide activated polysaccharide carriers.Eur. J. Biochem. 18, 351–60.

    Google Scholar 

  • Barbotin, J. N. &Thomas, D. (1974). Electron microscopic and kinetic studies dealing with an artificial enzyme membrane. Application to a cytochemical model with the horseradish peroxidase-3,3′-diaminobenzidine system.J. Histochem. Cytochem. 22, 1048–59.

    Google Scholar 

  • Beeuwkes, R. &Rosen, S. (1975). Renal sodium-potassium adenosine triphosphatase optical localization and X-ray microanalysis.J. Histochem. Cytochem. 23, 828–39.

    Google Scholar 

  • Bensley, R. R. &Hoerr, N. L. (1934). Studies on cell structure by the freezing-drying method. VI. The preparation and properties of mitochondria.Anat. Rec. 60, 449–55.

    Google Scholar 

  • Bergquist, N. R. (1973). The pulsed dye laser as a light source for the fluorescent antibody technique.Scand. J. Immunol. 2, 37–44.

    Google Scholar 

  • Caspersson, T. (1932). Die quantitative Bestimmung von Thymonucleinsaüre mittels fuchsinschwefliger Saüre.Biochem. Z. 253, 97–111.

    Google Scholar 

  • Caspersson, T. (1936). Uber die chemische Aufbau der Strukturen des Zellkernes.Scand. Arch. Physiol. 73, suppl.8, 1.

    Google Scholar 

  • Caspersson, T. (1940). Scharlach-R dye dissolved in hexane suspended in water sucrose solution.J. R. microsc. Soc. 60, 8.

    Google Scholar 

  • Caspersson, T. (1957). A project for the development of quantitative methods for the endocellular range. Symposium Cytochemical methods with quantitative aims, Biophysical and Biochemical approaches.Expl. Cell Res. 4, 3–8.

    Google Scholar 

  • Chandler, J. A. (1975). Electron probe X-ray microanalysis in cytochemistry. In:Techniques of Biochemical and Biophysical Morphology, Vol. 2 (eds. D. Glick & R. M. Rosenbaum), pp. 307–437. New York, London, Sidney, Toronto: Wiley Interscience.

    Google Scholar 

  • Christie, K. N. &Stoward, P. J. (1974). A quantitative study of the fixation of acid phosphatase by formaldehyde and its relevance to histochemistry.Proc. R. Soc. Lond. B. 186, 137–64.

    Google Scholar 

  • Cohn, N. S. (1973). A model system analysis of the parameters in histone staining. I. Alkaline Fast Green.Histochem. J. 5, 529–45.

    Google Scholar 

  • Cornelisse, C. J. (1974). The localization problem in enzyme cytochemistry.Thesis, Leiden.

  • Cornelisse, C. J., Hermens, W. Th., Tjok Joe, M., Duijndam, W. A. L. &Van Duijn, P. (1976). A theoretical study of concentration of profiles of primary cytochemical-enzyme reaction products in membrane-bound cell organelles and its application to lysosomal acid phosphatase.Histochem. J. 8, 609–24.

    Google Scholar 

  • Coujard, R. (1943). Essais sur la signification chimique de quelques methodes histologiques.Bull. Histol. Techn. Micr. 20, 161–73.

    Google Scholar 

  • Cox, M. E., (1971). Holographic microscopy—a review.Microscope 19, 137–49.

    Google Scholar 

  • Crissman, H., Mullaney, P. &Steinkamp, J. (1974). Methods and applications of flow systems for analysis and sorting of mammalian cells. In:Methods for Cell Biology, Vol. 9 (ed. D. M. Prescott), pp. 179–246. New York, London: Academic Press.

    Google Scholar 

  • Daems, W. Th., Cornelisse, C. J. &Poelman, R. E. (1972). Interpretation of the results of metal salt methods for electronmicroscopical enzyme cytochemistry. In:Electron Microscopy 1972.Proc. 5th European Congress, Manchester 1972, pp. 264–69. Institute of Physics, London, Bristol 1972.

    Google Scholar 

  • David, A., Metayer, M., Thomas, D. &Brown, G. (1974). Enzyme activity and membrane potential interaction in an artificial enzyme membrane.J. Membrane Biol. 18, 113–24.

    Google Scholar 

  • Davis, G. A. &Bloom, F. E. (1973). Subcellular particles separated through a histochemical reaction.Analyt. Biochem. 51, 429–35.

    Google Scholar 

  • Deelder, A. M., Snoijink, J. J. &Ploem, J. S. (1975). Experimental optimization of the DASS system for immuno-diagnosis of some helminth infections.Ann. N.Y. Acad. Sci. 177, 119–36.

    Google Scholar 

  • Deeley, E. M., Richards, B. M., Walker, P. M. B. &Davis, H. G. (1954). Measurements of Feulgen stain during the cell cycle with a new photo-electric scanning device.Expl. Cell Res. 6, 569–72.

    Google Scholar 

  • Deitch, A. D. (1964). A method for the cytophotometric estimation of nucleic acids using methylene blue.J. Histochem. Cytochem. 12, 451–61.

    Google Scholar 

  • De Jong, A. S. H., Van Duijn, P. &Daems, W. Th. (1976). A cytochemical model system for microsomal rat liver glucose-6-phosphatase.J. Histochem. Cytochem. 24, 643–51.

    Google Scholar 

  • De Jong,A.S.H.& Van Der Ploeg, M. (1976). Personal communication.

  • Den Tonkelaar, E.M. &Van Duijn, P. (1964). Photographic colorimetry as a quantitative cytochemical method. III. Determination of the absolute amount of DNA in cell nuclei.Histochemie 4, 16–19.

    Google Scholar 

  • Duijndam, W.A.L., Hermans, J. &Van Duijn, P. (1973a). A new method to distinguish separate components in cytochemically stained macromolecules by analysis of the kinetics of the staining and destaining processes.J. Histochem. Cytochem. 21, 723–8.

    Google Scholar 

  • Duijndam, W.A.L., Hermans, J. &Van Duijn, P. (1973b). Application of the method of kinetic analysis of staining and destaining processes to the complex formed between hydrolyzed deoxyribonucleoprotein and Schiff's reagent in model films.J. Histochem. Cytochem. 21, 729–36.

    Google Scholar 

  • Duijndam, W.A.L. &Van Duijn, P. (1975a). The influence of chromatin compactness on the stoichiometry of the Feulgen-Schiff procedure studied in model films. I. Theoretical kinetics and experiments with films containing isolated deoxyribonucleic acid.J. Histochem. Cytochem. 23, 882–90.

    Google Scholar 

  • Duijndam, W.A.L. &Van Duijn, P. (1975b). The influence of chromatin compactness on the stoichiometry of the Feulgen-Schiff procedure studied in model films. II. Investigations on films containing condensed or swollen chicken erythrocyte nuclei.J. Histochem. Cytochem. 23, 891–900.

    Google Scholar 

  • Gahrton, G. (1964). Microspectrophotometric quantitation of the periodic acid-Schiff (PAS) reaction in human neutrophil leukocytes based on a model system of glycogen microdroplets.Expl. Cell Res. 34, 488–506.

    Google Scholar 

  • Gahrton, G., Olsson, I. &Dahlqvist, A. (1975). Determination of the glycogen content in single neutrophil leukocytes using a micromodel of leukocyte glycogen.J. Histochem. Cytochem. 23, 59–64.

    Google Scholar 

  • Gaillard, J.L.J., Van Duijn, P. &Schaberg, A. (1968). Photometric determination of DNA in human chromosomes.Expl. Cell Res. 53, 417–31.

    Google Scholar 

  • Gray, J.W., Van Carrano, A., Steinmetz, L.L., Van Dilla, M.A., Moore III, D.H., Mayall, B.H. &Mendelsohn, M.L. (1975). Chromosome measurement and sorting by flow systems.Proc. natn. Acad. sci. 72, 1231–4.

    Google Scholar 

  • Greenstein, J.P. (1943). Friedrich Miescher founder of nuclear chemistry.Scientific Monthly 57, 523–32.

    Google Scholar 

  • Haanen, C. A. M., Hillen, H. F. P. &Wessels, J. M. C. (eds.) (1974). First International Symposium on Pulse-Cytophotometry. Medikon, Ghent: European Press.

    Google Scholar 

  • Haaijman, J.J. &Van Dalen, J.P.R. (1974). Quantification in immunofluorescence microscopy. A new standard for fluorescein and rhodamine emission measurement.J. Immun. Meth. 5, 359–74.

    Google Scholar 

  • Hayes, T.L. (1973). Trends and prospects in scanning electron microscopy.J. Microsc. 100, 133–42.

    Google Scholar 

  • Jakoby, W. B. &Wilchek, M. (1974). Affinity techniques (Enzyme Purification: Part B). In:Methods in Enzymology, Vol. XXXIV (eds. S. P. Colowick & N. O. Kaplan). New York, San Francisco, London: Academic Press.

    Google Scholar 

  • Jongkind, J.F., Ploem, J.S., Reuser, A.J.J. &Galjaard, H. (1974). Enzyme assays at the single cell level using a new type of microfluorimeter.Histochemistry 40, 221–9.

    Google Scholar 

  • Jonsson, G. (1971). Quantitation of fluorescence of biogenic monoamines.Progr. Histochem. Cytochem. 2, 299–333.

    Google Scholar 

  • Kamentsky, L.A. (1973). Cytology-automation. In:Advances in biological and medical physics, Vol. 14 (eds. J. H. Lawrence & J. W. Gofman), p. 93. New York, London: Academic Press.

    Google Scholar 

  • Kelly, J.Z. &Carlson, L. (1963). Protein droplets, especially gelatin, hemoglobin and histone, as microscopic standards for quantitation of cytochemical reactions.Expl. Cell Res. 30, 106–24.

    Google Scholar 

  • Krishan, A. (1975). Cytofluorograf in Biophysics. Rapid flow cytofluorimetric analysis of mammalian cell cycle by propidium iode staining.J. Cell Biol. 66, 188–93.

    Google Scholar 

  • Leeman, U. &Ruch, F. (1972). Cytofluorometric determination of basic and total proteins with sulfaflavine.J. Histochem. Cytochem. 20, 659–71.

    Google Scholar 

  • Lemons, R.A. &Quate, C.F. (1975). Acoustic Microscopy: Biomedical applications.Science 188, 905–11.

    Google Scholar 

  • Lesker, A., Siekevitz, P. &Palade, G.E. (1971). Differentiation of endoplasmic reticulum in hepatocytes.J. Cell Biol. 49, 288–302.

    Google Scholar 

  • Lessler, M.A. (1951). The nature and specificity of the Feulgen reaction.Arch. Biochem. Biophys. 32, 42–54.

    Google Scholar 

  • Lessler, M.A. (1953). The nature and specificity of the Feulgen nucleal reaction.Int. Rev. Cytol. 2, 231–47.

    Google Scholar 

  • Lichtensteiger, W. (1970). Katecholaminhaltige Neuronen in den neuroendokrinen Steuerung, Prinzip und Anwendung der Mikrofluorimetrie.Progr. Histochem. Cytochem. 1, 185–276.

    Google Scholar 

  • Lima de Faria, A. (1969).Handbook of Molecular Cytology. Amsterdam: North Holland.

    Google Scholar 

  • Lison, L. (1936).Histochimie Animale. Paris: Gauthier-Villars.

    Google Scholar 

  • Loken, M.R. &Herzenberg, L.A. (1975). Analysis of cell populations with a fluorescence-activated cell sorter.Ann. N.Y. Acad. Sci. 254, 163–71.

    Google Scholar 

  • Mahon, D.C. &Nair, K.K. (1975). Stoichiometry of the aldehyde fuchsin staining reaction for proteins.J. Histochem. Cytochem. 23, 652–9.

    Google Scholar 

  • Mansberg, H.P., Saunders, A.M. &Groner, W. (1974). The Hemalog D white cell differential system.J. Histochem. Cytochem. 23, 711–24.

    Google Scholar 

  • Melamed, M.R. &Kamentsky, L.A. (1975). Automated cytology.Int. Rev. Exp. Path. 14, 205–95.

    Google Scholar 

  • Mendelsohn, M.L. (1974). The third Engineering Foundation Conference on Automated Cytology.J. Histochem. Cytochem. 22, 452.

    Google Scholar 

  • Mitchell, J.P. (1975). Combined staining of protein-bound sulphydryl groups and DNA in polyacrylamide model systems.Histochem. J. 7, 283–90.

    Google Scholar 

  • Mullaney, P.F., Steinkamp, J.A., Crissman, H.A., Cram, L.S. &Holm, D.M. (1974). Laser flow microphotometers for rapid analysis and sorting of individual mammalian cells. In:Laser applications in medicine and biology, Vol. 2 (ed. M. L. Wolbarscht), pp. 151–204. New York, London: Plenum Press.

    Google Scholar 

  • Ornstein, L. &Ainsley, H.R. (1974). Spectral matching of classical cytochemistry to automated cytology.J. Histochem. Cytochem. 22, 453–69.

    Google Scholar 

  • Papadimitriou, J.M. &Van Duijn, P. (1970). Effects of fixation and substrate protection on the isoenzymes of aspartate aminotransferase studied in a quantitative cytochemical model system.J. Cell Biol. 47, 71–83.

    Google Scholar 

  • Pearse, A.G.E. (1953).Histochemistry, Theoretical and Applied. London: Churchill.

    Google Scholar 

  • Pearse, A.G.E. (1968).Histochemistry, Theoretical and Applied, Vols. 1 and 2, 3rd Edn. London: Churchill.

    Google Scholar 

  • Ploem, J.S. (1970). Standards for fluorescence microscopy. In:Standardization in Immunofluorescence (ed. E. J. Holborow), pp. 137–53. Oxford, Edinburgh: Blackwell.

    Google Scholar 

  • Ploem, J.S. (1975). General introduction. In:Fifth International Conference on Immunofluorescence and related staining techniques (eds. W. Hijmans & M. Schaeffer).Ann N.Y. Acad. Sci. 254, 4–20.

  • Pollister, A.W. &Ris, H. (1948). Nucleoprotein determinations in cytological preparations.Cold Spring Harb. Symp. quant. Biol. 12, 147–54.

    Google Scholar 

  • Pollister, A.W. &Ornstein, L. (1959).Analytical Cytology (ed., Mellows), 2nd Edn, pp. 431–518. New York: McGraw-Hill.

    Google Scholar 

  • Porath, J., Axén, R. &Ernback, S. (1967). Chemical coupling of proteins to agarose.Nature 215, 1491–2.

    Google Scholar 

  • Rigler, R. JR. (1966). Microfluorometric characterization of intracellular nucleic acids and nucleoproteins by acridine orange.Acta physiol. scand. 27, suppl. 267.

    Google Scholar 

  • Ritzén, M. (1966). Quantitative fluorescence microspectrophotometry of catecholamineformaldehyde products.Expl. Cell Res. 44, 405–20.

    Google Scholar 

  • Saccho, C.A., Svelto, O. &Prenna, G. (1974). Pulsed turnable lasers in cytofluorometry.Histochem. J. 6, 251–8.

    Google Scholar 

  • Sandritter, W. &Kasten, F.H. (1964). IooYears of histochemistry in Germany. Stuttgart: Schattauer Verlag.

    Google Scholar 

  • Schuman, J., Göhde, W. &Buchner, Th. (1976). Second International Symposium on Pulse-Cytophotometry. Medikon, Ghent: European Press.

    Google Scholar 

  • Silverman, L. &Glick, D. (1969). Measurement of protein concentration by quantitative electron microscopy.J. Cell Biol. 40, 773–7.

    Google Scholar 

  • Simmons, A. &Elbert, G. (1975). Hemalog-D and manual differential leukocyte counts a laboratory comparison of results obtained with blood of hospitalized patients.Am. J. Clin. Path. 64, 512–17.

    Google Scholar 

  • Singer, M. (1952). Factors which control the staining of tissue sections with acid and basic dyes.Int. Rev. Cytol. 1, 211–55.

    Google Scholar 

  • Streefkerk, J.G., Van Der Ploeg, M. &Van Duijn, P. (1975). Agarose beads as matrices for proteins in cytophotometric investigations of immunoperoxidase procedures.J. Histochem. Cytochem. 23, 243–50.

    Google Scholar 

  • Swift, H. (1953). Quantitative aspects of nuclear nucleoproteins.Int. Rev. Cytol. 2, 1–76.

    Google Scholar 

  • Tas, J. &Roozemond, R.C. (1973). Direct recording of metachromatic spectra in a model system of polyacrylamide films.Histochem. J. 5, 425–36.

    Google Scholar 

  • Tas, J., Oud, P. &James, J. (1974). The naphtol yellow S stain for proteins tested in a model system of polyacrylamide films and evaluated for practical use in histochemistry.Histochemistry 40, 231–40.

    Google Scholar 

  • Tas, J. (1975a). Histochemical conditions influencing metachromatic staining. A comparative study by means of a model system of polyacrylamide films.Histochem. J. 7, 1–19.

    Google Scholar 

  • Tas, J. (1975b). Histochemical aspects of metachromasy investigated with a model system andin situ. Thesis, Amsterdam.

  • Thaer, A. A. &Sernetz, M. (eds.) (1973).Fluorescence Techniques in Cell Biology. Berlin, Heidelberg, New York: Springer-Verlag.

    Google Scholar 

  • Thomas, D. &Caplan, S.R. (1976). Artificial enzyme membranes. In:Membrane Separation Processes (ed. P. Meares). pp. 351–97. Amsterdam: Elsevier.

    Google Scholar 

  • Thomas, D., Bourdillon, C., Brown, G. &Kernevez, J.P. (1974). Kinetic behavior of enzymes in artificial membranes inhibition and reversibility effects.Biochemistry 13, 2995–3000.

    Google Scholar 

  • Tilders, F.J.H., Ploem, J.S. &Smelik, P.G. (1974). Quantitative microfluorimetric studies on formaldehyde-induced fluorescence of 5-hydroxy-tryptamine in the pineal gland of the rat.J. Histochem. Cytochem. 22, 967–75.

    Google Scholar 

  • Toepfer, K. (1975). Quantitative Untersuchungen der metachromatischen Reaktion von Mucopolysacchariden in Polyacrylamid-Membranen nach der van Duijn-Methode. Symposion XVI der Gesellschaft für Histochemie, Leiden-Noordwijk, October 1973, “Aussagewert und Fehlermöglichkeiten histochemischer Enzymraktionen’.Acta histochem. (Suppl.) XIV.

  • Van Dalen, J.P.R., Ashmann, W.B.A. &Van Duijn, P. (1970). A method for the determination of the molar extinction coefficient of structure-linked chromophores.Histochem. J. 2, 329–42.

    Google Scholar 

  • Van Dalen, J.P.R., Knapp, W. &Ploem, J.S. (1973). Microfluorometry on antigen-antibody interaction in immunofluorescence using antigens covalently bound to agarose beads.J. Immunol. Meth. 2, 383–92.

    Google Scholar 

  • Van Dalen, J.P.R. &Haaijman, J.J. (1974). Determination of the molar absorbance coefficient of bound tetramethyl rhodamine isothiocyanate relative to fluorescein isothiocyanate.J. Immunol. Meth. 5, 103–6.

    Google Scholar 

  • Van Duijn, P. (1956). Histo- en cytochemie, een nieuwe ontwikkeling in een grensgebied (a review).Chem. Weekbbl. 52, 17–32.

    Google Scholar 

  • Van Duijn, P. &Persijn, J.-P. (1960). A new technique for studying the quantitative aspects of cytochemical reactions and its application to the Feulgen reaction.Nature 186, 805–6.

    Google Scholar 

  • Van Duijn, P., Pascoe, E., &Van Der Ploeg, M. (1967). Theoretical and experimental aspects of enzyme determination in a cytochemical model system of polyacrylamide films containing alkaline phosphatase.J. Histochem. Cytochem. 15, 631–45.

    Google Scholar 

  • Van Duijn, P. &Van Der Ploeg, M. (1970). Potentialities of cellulose and polyacrylamide films as vehicles in quantitative cytochemical investigations on model substances. In:Introduction to Quantitative Cytochemistry, Vol. 2 (eds. G. L. Wied & G. F. Bahr), pp. 223–62. New York, London: Academic Press.

    Google Scholar 

  • Van Duijn, P. (1974). Fundamental aspects of enzyme cytochemistry. In:Electron microscopy and cytochemistry. Proc. 2nd Internat. Symp. Drienerloo, The Netherlands, 25–29 June (1973) (eds. E. Wisse, W. Th. Daems, I. Molenaar and P. van Duijn), pp. 3–23. Amsterdam: North-Holland.

    Google Scholar 

  • Van Duijn, P. (1975). Carrier-bound model substances: a bridge between quantitative microscopical histochemistry and biochemistry.Acta histochem. (Suppl.) XV, 103–17.

    Google Scholar 

  • Van Der Ploeg, M. &Van Duijn, P. (1968). Cytophotometric determination of alkaline phosphatase activity of individual neutrophilic leukocytes with a biochemically calibrated model system.J. Histochem. Cytochem. 16, 693–706.

    Google Scholar 

  • Van Der Ploeg, M. (1975). Quantitative model film studies: a link between enzyme cytochemistry and biochemistry.Acta histochem. (Suppl.) XIV, 69–77.

    Google Scholar 

  • Wenk, H., Krug, H. &Fletcher, A.M. (1973). Eine mikrospectrophotometrische Methode zur quantitativen Aktivitätsbestimmung von Acetyl-Cholinesterase an Gewebeschnitten.Acta histochem. 45, 37–60.

    Google Scholar 

  • Wied, G.L. & Bartels, G.F. (eds.) (1971). Automated cytology, a symposium by correspondence.Acta cytol. 15, 1, 87, 216.

    Google Scholar 

  • Wolbarscht, M. L. (ed.) (1974).Laser Applications in Medicine and Biology, Vol. 2. New York, London: Plenum Press.

    Google Scholar 

  • Yokota, S. (1973). Assay of antihorseradish peroxidase antibody in an immunocytochemical model system of polyacrylamide gel films.J. Histochem. Cytochem. 21, 779–87.

    Google Scholar 

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Van Duijn, P. Prospects for microscopical cytochemistry. Histochem J 8, 653–676 (1976). https://doi.org/10.1007/BF01003967

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