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Salivary glands
Contemporary salivary gland research Arnold Tam arin, * D .D .S., M .S.D., Seattle
Research pertaining to saliva and the salivary glands is multifaceted and covers a spectrum of inquiry as broad as biology itself. Primary to any discussion of the investigative work being done in this area is an understanding that the salivary glands and their secretions do not consti tute biologically unique systems. Rather, they are particular examples of organs and organ products which, although spe cialized, are analogous to other organ systems which are associated with protein synthesis, ion transfer and water trans port. In view of this, it is not surprising that many of the questions concerning the salivary glands are similar to basic ques tions in other areas of research. Q U E S T IO N S
M any questions about salivary glands are not new ones but are presented in the light of new research approaches made possible by recent advances in technology. Some questions, on the other hand, could not have even been asked a decade ago, for they are the result of new concepts in biology, chemistry and physics. In general terms, research on salivary glands is being pursued to answer the fol lowing questions: 1. What is the nature of the various cells which constitute the salivary glands and how does their form reflect their function? 2. What are the various products of cellular synthesis in salivary glands and what is their role?
3. What are the constituents of se creted saliva; how do they vary in kind and in amount under different condi tions? 4. How do constituents of saliva affect maintenance of homeostasis in the oral cavity? 5. How do the salivary glands interact with other organs and body systems; that is, what is their place in the economy of the entire organism? Specific problems contained within these questions are attacked from various points of view depending on the primary interests of the investigator. Methods of collecting data involve light and electron microscopy, histochemistry, fluorescent antibody technic, cell fractionation and ultracentrifugation, biochemical identifi cation of cell constituents and assay of enzyme activity, radioautography, elec trophoresis, chromatography, immunochemistry and the application of elec tronic sensor devices. C U R R E N T R E SE A R C H
Different parenchymal cell types within a gland demonstrate great specialization. The electron microscope has enabled us to visualize some aspects of secretion at the fine structure level. Acinar cells are characterized by large quantities of ergastoplasm, which is a cell organelle sys tem associated with ribonucleic acid ( R N A ). This system is responsible for the organization of amino acids of the proper variety into the correct number and se-
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quence for the formation of specific pro teins.1 An important phase of cellular secretion is the “packaging” of products into membrane-bound granules. M aterial within these granules is expelled into the conduit system of the gland by a phenom enon whereby their surrounding mem branes become confluent with the plasma membrane which surrounds the cell. The granules thus ruptured release their mate rials into the ductal system. Apparently, some water may be secreted in a similar manner, and evidence exists that minute quantities of cytoplasm also may be dis charged by the cells.2-4 Cells comprising the different tubular portions of various salivary glands have specific functions. In some animals, a prominent tubular segment is associated with enzyme synthesis. All animals ap parently have a tubular segment special izing in water and electrolyte metabolism. Structurally this segment is akin, al though not identical, to the convoluted tubules of the kidney.5 Characteristically, the tubular cells have prominent plasma membrane infoldings at their base (asso ciated with water and ion transport), great numbers of mitochondria (associ ated with oxidative phosphorylation and energy transduction in cell respiration), many intracytoplasmic vesicles (associ ated with water metabolism and trans port) and microvilli at the luminal sur face (associated with the passage of diluted substances into and out of cells). Ergastoplasm, which is so prominent in cells actively engaged in protein synthe sis, is sparse in these cells.4,6'10 By histochemical methods the various cells of different salivary glands are char acterized according to the nature and lo cation of their organic products. These fall into two broad divisions: carbohydrate-protein complexes and enzymes.11"15 All of the glands produce neutral glyco proteins and sialopolysaccharides (mucin) in varying amounts. Acid mucopolysac charides, however, have not been demon strated in these tissues.14
T he chemical composition, the physical properties and the biological distribution of mucus is receiving a great amount of attention.16,17 T he localization and iden tification of mucus in the salivary glands of different species reveals a great di versity, the significance of which is not completely understood. The relationship of mucus production to the formation of other materials has been studied under such conditions as starvation.18 It has been shown that orders of priority exist in the synthesis of different moieties by different glands.19 A diverse variety of enzymes has been demonstrated in salivary glands.11 Some of these are intrinsic to the sustenance of normal cell metabolism and some are as sociated with cell degeneration and dis solution. These, however, constitute a relatively small portion of the total en zyme content of the glands. T he m ajor portion of enzyme production is associ ated with the secretions which are syn thesized for export.5,20 By ligating the m ajor excretory duct of the submaxillary gland, a readjustment of cellular organization takes place wherein no exocrine secretory activity occurs; that is, the gland is in a “ resting” state. Under these conditions, the gland tissue demon strates a decrease in oxygen consumption and high energy phosphate content; how ever, anaerobic glycolysis appears not to change. Starvation and x-irradiation also result in changes of cellular aerobic car bohydrate metabolism which in turn a f fect other enzyme systems such as iodide peroxidase associated with iodothyrine synthesis. Estimation of oxidative en zymes in different cells of the gland shows that ducts have a higher oxidase capacity than acini.21,22 Amylase, an enzyme which hydrolyzes some carbohydrate compounds, has been identified in salivary glands. Curiously, there seems to be a difference in the regu lative mechanisms controlling the pro duction of this enzyme in the m ajor glands. In the parotid gland (and the
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pan creas), interference with parasym pa thetic stimulation has no effect on the accumulation of amylase whereas, in the submandibular glands, parasympathomi metic activity results in an increase of this enzyme.23 In a routine analysis of desoxyribonu cleic acid (D N A ) concentration in the parotid glands of rats, it was discovered that a great disparity exists between the actual and expected amounts. By con trolling some of the variables in D N A determination, it was postulated that the low D N A content in gland homogenates was the result of a high concentration of desoxyribonuclease. This was verified by comparing the activity of this enzyme in various organs.24 Some of the proteolytic enzyme activity of salivary glands demonstrates a compli cated interdependency not only with stimulatory or inhibitory factors which directly control secretion but with hor mone systems of other organs. This is demonstrated by the changing status of the gland during the maturation of the organism.20 (This, incidentally, is re flected by the micromorphologic meta morphosis of the submaxillary gland during prepubertal development.25) Pro teolytic activity is higher in male than in female rats. Experiments involving cas tration or administration of gonadotropic hormones give us some insight as to the mechanisms responsible for this. T he ex treme complexity of hormonal regulation of salivary gland activity is demonstrated further by investigation of their relation ship to the hypophysis. Hypophysectomy results in a decrease in gland weight, atrophy of the intralobular duct segment, and decline of proteolytic activity which cannot be attributed solely to the decline of gonadotropic hormones.26 Changes in the activity of the thyroid gland also have been shown to affect the salivary glands. Increasing the amount of thyroxin increases the amount of salivary flow but decreases arginase activity in saliva, whereas inhibition of thyroid ac
tivity decreases salivary flow and increases the viscosity of saliva. T he salivary glands also possess a powerful mechanism for concentrating iodide which is independ ent of thyrotrophic hormone. This ap parently takes place in the secretory ducts and involves an active transport mecha nism.27 A dietary factor contained in dried and defatted preparations of pig pancreas (pancreatin) causes an overall enlarge ment of the salivary glands. This hyper trophic effect is not permanent but is reversed when the administration of the pancreatic extract is stopped. This phe nomenon is apparently dependent on an intact sympathetic nervous system and certain intraoral factors which mediate a reflex mechanism causing gland growth.28 Extremely intriguing studies are con cerned with the problem of endocrine secretion by the salivary glands. A potent nerve-growth factor has been isolated from mouse submaxillary salivary glands. Chemically this factor is a protein which, when injected into newborn mice, causes a sixfold increase in the volume of the sympathetic ganglia and an increased number of neurons of the viscera and blood vessels. Other effects which are similar to those induced by cortisone also are elicited. Curiously, snake venom glands, which are specialized salivary glands, also contain this factor.29 Other workers have isolated a substance from salivary glands reputedly capable of low ering serum calcium levels, of decreasing and subsequently increasing the number of circulating leukocytes and of promot ing the calcification of incisor dentin in rabbits.30 Simple inanition also depresses the serum calcium level in rabbits, whereas extirpation of the m ajor salivary glands exerts no influence.31 A great deal of interest concerns the relationship between the constituents of saliva and the constituents of blood. The presence of blood group substances (that is, A, B or O antigen) in saliva is under
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genetic control as a Mendelian dominant characteristic. Recent work indicates that there is a difference between the three m ajor salivary glands as to the degree of concentration of these antigens. Ap parently sublingual glands have the high est concentration and the parotid gland the least.32 The presence or absence of plasma clotting factors in saliva has been studied in normal patients and those with various bleeding disorders. It was found that clotting factors V I II , I X and X I are present in normal saliva as well as in the saliva of patients with various hemophiloid diseases, whereas factor V II is present in normal saliva but not in pa tients with proconvertin deficiency. F ac tors V and X are not detected in saliva.33 Analysis of electrophoretic patterns de rived from the saliva of various primates reveals some similarities and dissimilari ties which may be of value in the study of comparative anthropology. There is an indication that, as we ascend the phylo genetic ladder, there is an increase in the amount of positively charged salivary proteins.34 T he inorganic components of saliva have special pertinence to the under standing of acid-base balance, the mecha nisms of ion transfer and osmolarity. The hydrogen ion concentration of saliva is related to the amount of dissolved carbon dioxide which in turn relates directly to the concentration of bicarbonate. Studies concerning these relationships reveal that the saliva-plasma ratio of bicarbonate is directly dependent on the concentration of carbon dioxide in the arterial blood. When arterial carbon dioxide pressure is reduced, the saliva-plasma ratio of bicar bonate decreases; however, when the plasm a bicarbonate level is increased, there is no effect on the saliva-plasma ratio of bicarbonate. It becomes apparent that bicarbonate concentration in saliva is dependent on a metabolic alkalosis or acidosis.35 T he secretion and concentration of cal
cium and inorganic phosphate by salivary glands can be modified by the retrograde perfusion of cytoplasmic poisons, such as mercuric chloride into the ductal tree. The result of such an experiment indi cates that, although the acini actually secrete these substances, the ducts supple ment their secretion.36 Another area of research concerns the nature of the mechanisms which initiate and mediate salivary flow. Stimulation of the sympathetic as well as the parasym pathetic nerves which innervate the sali vary glands will evoke secretion. T he ac tual mechanism of reactance to nerve stimulation is mediated by specific chemi cal “ transmitters” produced by the nerve cells, which must reach the gland cell in order to be effective. These “ transmit ters” not only induce immediate secretory activity but also exert a long-term effect on the responsiveness of gland cells to secretory stimuli. If afferent fibers of the secretory reflex arc are sectioned, or if drugs which interfere with “ transmitter” substance are administered, the salivary glands acquire a supersensitivity. This state of supersensitivity is greater when transmitter substance is interfered with directly than when the nerves are cut. One concludes from these experiments that transmitter agents are released from postganglionic fibers even in the absence of nerve stimulation and thus are in volved with the regulation of gland sensi tivity.37 T he interactions of saliva with the oral flora or with dental caries involve prob lems relating to microbiology and epi demiology which are not within the scope of this review. T he material presented here is, at best, a brief, incomplete survey of some of the things which are receiving attention in the sphere of research on salivary glands and their secretions. C O N C L U S IO N
Increasing emphasis is being placed on defining the intrinsic mechanisms of cel
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lular activity and how they relate to spe cific functions. The total activity of sali vary glands is shown to be extremely complex not only in respect to specialized cellular function but also as related to their interdependence with other organs and homeostatic systems. Salivary secre tions vary from gland to gland and under different conditions, not to mention inter species differences. It also is demonstrated that the production of saliva is not the only function of salivary glands. The study of salivary glands has a prom inent place in the history of biology. In recent years an even greater interest has been demonstrated in the nature of these organs. T he information gathered in this area has been a significant contribution to the general pool of knowledge con cerning living systems. In 1962 the first international conference relating specifi cally to the salivary glands and their se cretions was held in Seattle. T he pub lished proceedings38 of this conference form a valuable compendium of funda mental information. A number of other excellent books concerned with various aspects of this subject also have been pub lished within the past few years.35,39-43 T he bibliography itself is far from com plete, but hopefully can be the source of further reference material for the inter ested reader.
*Assistant professor, department of oral pathology, School of Dentistry, University of Washington, Seattle. 1. Loftfield, R. B. The biosynthesis of protein. Prog ress Biophysics & Biophysical Chem. 8:348, 1958. 2. Parks, H. F. Morphological study of the extrusion of secretory materials by the parotid glands of mouse and rat. J. Ultrastructure Res. 6:449 June 1962. 3. Parks, H. F. On the fine structure of the parotid gland of mouse and rat. Am. J . Anat. 108:303 May 1961. 4. Scott, B. L., and Pease, D. C. Electron microscopy of the salivary and lacrimal glands of the rat. Ann. J. Anat. 104:115 1959. 5. Junqueira, L. C. U. Studies on the physiology of rat and mouse salivary glands. III. On the function of the striated ducts of the mammalian salivary glands. In Sreebny, L. M., and Meyer, J. (ed.). Salivary glands and their secretions. In press. 6. Jacoby, F., and Leeson, C. R. The post natal de velopment of the submaxillary gland. J. Anat. 93:201 April 1959. 7. Rutberg, U. Ultrastructure and secretory mecha nism of the parotid gland. Acta Odont. Scand. 19:30 suppl., 1961.
8. Sreebny, L. M., and Meyer, J . Hormones, inanition and salivary glands. II. On protease and convoluted tubules of the rat submaxillary gland. In Sreebny, L. M., and Meyer, J . (ed.). Salivary glands and their secretions. In press. 9. Tandler, B. Ultrastructure of the human submaxil lary gland. I. Architecture and histological relationships of the secretory cells. Am. J. Anat. 3:287, 1962. 10. Tandler, B. Ultrastructure of the human submaxil lary gland. II. The base of the striated duct cells. J. Ultrastructure Res. 9:65, 1963. 11. Arvy, L. Comparative histoenzymology of the salivary glands. Ann. New York Acad. Sci. 106:472 March 30, 1963. 12. Ellison, S. A. Chemical and immunological stud* ies of proteins and glycoproteins of human parotid saliva. In Sreebny, L. M., and Meyer, J. (ed.). Salivary glands and their secretions. In press. 13. Kent, S. P. A study of mucins in tissue sections by the fluorescent antibody technique. III. The specific ity of antibody to salivary gland mucins and the effect of chemical alterations of mucins on the specificity of the antibody. Ann. New York Acad. Sci. 106:389 March 30, 1963. 14. Quentarelli, G. Histological identification of sali vary mucins. Ann. New York Acad. Sci. 106:339 March 30, 1963. 15. Spicer, S. S. A correlative study of the histochemical properties of rodent acid mucopolysaccharides. J. Histochem. & Cytochem. 8:18 Jan. I960. 16. Chernick, W. S., and Barbero, G. J. Studies on human tracheobronchial and submaxillary secretions in normal and pathophysiological conditions. Ann. New York Acad. Sci. 106:698 March 30, 1963. 17. Shackleford, J. M. Histochemical comparison of mucous secretions in rodent, carnivore, ungulate, and primate major salivary glands. Ann. New York Acad. Sci. 106:572 March 30, 1963. 18. Tamarin, A., and Sreebny, L. M. Effects of total inanition on the submaxillary gland of the rat. Arch. Oral Biol. 7;469 July*Aug. 1962. 19. Tamarin, A.; Wanamaker, B., and Sreebny, L. M. The effect of inanition on the submandibular salivary glands and exocrine pancreas of the rat. Ann. New York Acad. Sci. 106:609 March 30, 1963. 20. Sreebny, L M. Studies of salivary gland proteases. Ann. New York Acad. Sci. 85:182 March 29, I960. 21. English, J . A. Effects of radiation upon the sali vary glands. Ann. New York Acad. Sci. 85:342 March 29, I960. 22. Schneider, R. M., and Person, P. Aerobic oxida tive metabolism of salivary glands. Ann. New York Acad. Sci. 85:201 March 29, I960. 23. Schneyer, L. H., and Schneyer, C. A. Regulation of salivary gland amylase activity. Ann. New York Acad. Sci. 85:189 March 29, I960. 24. Wanamaker, Barbara, and Sreebny, Leo M. DNA determinations in the parotid gland of the rat. Ab stract, I.A.D.R. March 1963, p. 81. 25. Jacoby, F., and Leeson, C. R. The postnatal de velopment of the rat submaxillary gland. J . Anat. 93:201 April 1959. 26. Shafer, W . G., and Muhler, J. C. Endocrine influences upon the salivary glands. Ann. New York Acad. Sci. 85:215 March 29, I960. 27. Myant, N. B. Iodine metabolism of salivary glands. Ann. New York Acad. Sci. 85:208 March 29, I960. 28. Wells, H., and Voelkel, E. F. Partial purification and mode of action of a pancreatic substance that enhances salivary gland growth. Abstract, I.A.D.R., March 1963, p. 123. 29. Levi-Montalcini, R., and Cohen, S. Effects of the extract of the mouse submaxillary salivary glands on the sympathetic system of mammals. Ann. New York Acad. Sci. 85:324 March 29, I960. 30. Ito, Yosop. Parotin: a salivary gland hormone. Ann. New York Acad. Sci. 85:228 March 29, I960.
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31. Saxe, Stanley R., and Sreebny, Leo M. Salivary glands and serum calcium. Abstract, J . D. Res. 40:719 July-Aug. 1961. 32. Wolf, Robert O., and Taylor, Leonard L. Concen tration of blood group substances in the parotid, sub lingual and submaxillary salivas. Abstract, I.A.D.R. March 1963, p. 51. 33. Taylor, R. G., and Doku, H. C. Salivary thromboplastic activity in hemophilia and hemophiloid diseases. Abstract, I.A.D.R. March 1963, p. 52. 34. Sweeney, Edward A., and Shaw, James H. The protein composition of pilocarpine induced saliva from four primates. Abstract, I.A.D.R. March 1963, p. 121. 35. Burqen, A. S. V., and Emmelin, N. G. Physiology of the salivary glands. Baltimore, Williams & Wilkins Co., 1961. 36. Henriques, B. L. Salivary gland secretion of cal cium and inorganic phosphate. Abstract, I.A.D.R. March 1963, p. 121. 37. Emmelin, N. Secretory nerves of the salivary glands. In Sreebny, L. M., and Meyer, J. (ed.). Salivary glands and their secretions. In press. 38. Sreebny, L. M., and Meyer, J. (ed.). Salivary glands and their secretions. Norwich, Pergamon Press, in press. 39. Afonsky, D. A. (ed.). Saliva and its relation to oral health. University, Ala., University of Alabama Press, 1961. 40. Kerr, Alexander C. The physiological regulation of salivary secretions in man. New York, Pergamon Press, 1961. 41. Office ^ of Naval Research, Department of the Navy, Washington, D.C. Bibliography on saliva com piled by Bibliography Section, Science and Technology Division, Library of Congress. March I960. 42. Parhon, C. !.; Babes, A., and Petrea, I. En docrinología glandelor salivare. Edltura Academlei Republicii Populare Romine, 1957. 43. Rauch, S. Die speicheldrüsen desmenschen. Stutt gart, Georg Thieme Verlag, 1959. A D D IT IO N A L B IB L IO G R A P H Y Abrams, E. Tongue nerves in vitamin Bi deficient rats with ligated salivary glands. Abstract, I.A.D.R. March 1963, p. 88. Andlaw, Reginald J. Paper chromatography of acids produced during salivary fermentation of foodstuffs in vitro. Abstract, J . D. Res. 41:1251 Nov.-Dee. 1962. Apostolopoulos, A. X. On the isolation and identifica tion of human salivary mucins. Abstract, I.A.D.R. March 1963, p. 122, Bates, J. F. Influence of plasma phosphate on the phosphate concentration of human parotid saliva. Arch. Oral Biol. 3:1 Dec. I960. Beck, Donald J., and Gil lings, Barrie R. D. Investiga tion of the usefulness of neutron activation analysis for studying trace elements in sajiva. J. D. Res. 40:383 March-April 1961. Betz, P. K.; Wanamaker, Barbara B., and Sreebny, L. M. Induction of exocrine pancreatic atrophy and its effects on the submaxillary salivary gland in the rat. Abstract, J . D. Res. 41:1274 Nov.-Dee. 1962. Beutnert>E. H.; Genco, R., and Djanian, A. Studies of immunization routes and dose response relationships in the production of autoantibodies to salivary glands in rabbits. Abstract, I.A.D.R. March 1963, p. 51. Blechrnan, Harry, and Bartels, Henry A. Food and water intake and body weight in the sialoadenecto mized animal. Abstract, I.A.D.R. March 1963. Boucher, N. E., Jr., and Wanek, R. M. Study of the antigenic components of saliva. Abstract, I.A.D.R. March 1963, page 51. Bulman, J . S., and Ten Cate, A. R. Experimental in vestigation of zinc in saliva. Abstract, J . D. Res. 41:1259 Nov.-Dee. 1962. Buttner, W ., and Muhler, J. C. Effects of salivary fluoride on enamel solubility. J. D. Res. 41:617 MayJune 1962.
Cataldo, Edmond; Shklar, Gerald, and Chauncey, Howard. Enzyme histochemistry of salivary gland tumors induced in rats by a chemical carcinogen. Abstract, I.A.D.R. March 1963, p. 110. Charlton, G. Oxygen tension of saliva within the parotid duct and on the floor of the mouth of humans. Abstract, J . D. Res. 41:512 May-June 1962. Chaudhry, A. P., and others. Experimental carcino genesis in submandibular glands of hamsters. J. D. Res. 40:426 May-June 1961. Chaudhry, A. P., and others. Effects of vitamin A deficiency on experimental carcinogenesis in subman dibular glands of hamsters. J . D. Res. 40:327 MarchApril 1961. Chauncey, H. H., and others. Effect of partial desallvation and parotin administration on hamster epiphyseal plate. J . D. Res. 42:894 May-June 1963. Chauncey, H. H.; Winer, R. A., and Barber, T. X. Influence of verbal suggestion on parotid gland secre tion rate. Abstract, I.A.D.R. March 1963, p. 50. Claycomb, C. K., and others. Presence of Se75 in rat saliva after intracardiac infection of radioactive sodium selenite. J. D. Res. 39:1264 Nov.-Dec. I960. Claycomb, C. K., and others. Further studies on the presence of Se7S in rat saliva and teeth after intracardiac injection of radioactive sodium selenite. J. D. Res. 40:504 May-June 1961. Coykendahl, A., and Henriques, Basil L. Time-course study of Na, K, and flow rate for the parotid secretion in man. Abstract, J. D. Res. 40:719 July-Aug. 1961. Dain, Joel A., and Manly, R. S. Identity of the poly saccharide produced by oral samples from sucrose solu tions. Abstract, J. D. Res. 40:720 July-Aug. 1961. Dawes, C., and Jenkins, G. N. Studies In man on the composition of duct saliva secreted in response to a variety of stimuli. Abstract, J. D. Res. 41:1260 Nov.Dec. 1962. Dirksen, T. R. Lipid constituents of whole and parotid saliva. J . D. Res. 42:920 July-Aug. 1963. Doku, Hrlsto Chris. Thromboplastic activity of human saliva. J . D. Res. 39:1210 Nov.-Dee. I960. Doku, Hristo Chris, and Taylor, Richard G. Thrombo plastin generation by saliva. Abstract, J . D. Res. 40:688 July-Aug. 1961. Draus, F. J., and Leung, S. W. Quantitative amino acid analysis of a bovine submaxillary mucoid. J. D. Res. 41:491 March-April 1962. Draus, F. J.; MIklos, F. L., and Leung, S. W. Carbonic anhydrase in a bovine submaxillary gland extract. J. D. Res. 41:497 March-April 1962. Dreisbach, Robert H. Calcium binding by normal human saliva. J. D. Res. 39:1133 Nov.-Dec. I960. Drum, D. E. Simple technique for direct cannulatlon of rat salivary ducts. J. D. Res. 42:892 May-June 1963. D’Silva, J. L., and Ferguson, D. B. Zone electrophore sis of human parotid saliva in various media. Arch. Oral Biol. 7:563 Sept.-Oct. 1962. Ellison, Solon A.; Mashimo, Paul A., and Mandel, Irwin D. Immunochemical studies of human saliva. I. The demonstration of serum proteins in whole and paro tid saliva. J . D. Res. 39:892 Sept.-Oct. I960. Emmelin, N. On "antllytic" secretion of saliva. J. Physiol. 157:410 July 1961. Feller, R. P.; Chauncey, H. H., and Shannon, I. L. Partial kinetic characterization of acid action on gusta tory chemoreceptors using the gustato-salivary reflex. Abstract, I.A.D.R. March 1963, p. 123. Ferguson, D. B. Media for zone electrophoresis of parotid saliva. Abstract, J. D.Res. 41:1261 Nov.-Dec. 1962. Fischer, Clary J.; Wyshak, George H., and Weisberger, David. Effect of inorganic ions on the electro phoretic pattern of whole saliva. Abstract, J . D. Res. 40:722 July-Aug. 1961. Fleming, H. S. The effect of parotin in mice. Ann. New York Acad. Sci. 85:313 March 29, I960. Fleming, H. S. Transplants of salivary glands and parotin. Abstract, J. D. Res. 40:690 July-Aug. 1961. Fleming, H. S. Parotid gland extracts and mice sub maxillary glands. J. D. Res. 41:939 Sept.-Oct. 1962.
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Fritz, M.; Cohen, D. W., and Rabinowitz, J. L. Rela tionship between uptake Ca45 and cholesterogenesis and lipogenesis in the rat parotid gland. Abstract, I.A.D.R. March 1963, p. 69. Geever, E. F.; McClure, F. J., and Zipkin, I. Salivary glands in lysine-deficient young rats. J. D. Res. 39:129 Jan.-Feb. I960. Goaz, Paul W., and Biswell, Helen A. Nitrate reduc tion in whole saliva. J. D. Res. 40:355 March-April 1961. Gow, B., and Newbrun, E. Application of atomic absorption spectroscopy to the determination of cal cium and magnesium in saliva. Abst'ract, J. D. Res. 41:512 May-June 1962. Hall, Walter B.; Betz, Peter K., and Sreebny, Leo M. Induced pancreatic atrophy and digestive glands. III. Effects on the parotid glands and gastric mucosa. Abstract, I.A.D.R. March 1963, p. 114. Harnach, Frances A. Analysis of calcium in unashed saliva. J. D. Res. 39:1069 Sept.-Oct. I960. Harris, N. O., and others. Infrared spectral charac teristics of pilocarpine-stimulated saliva of normally caries-resistant animals compared with caries-resistant and susceptible humans. J. D. Res. 39:810 July-Aug. I960. Hartles, R. L. Metabolic factors in saliva. J . D. Res. 42:553 suppl. Jan.-Feb. 1963. Hawkins, G. R., and Zipkin, I. Spectrophotometric determination of tryosine, tryptophan, protein, and uric acid in human parotid saliva. Abstract, J. D. Res. 40:721 July-Aug. 1961. Hawkins, G. R.; Zipkin, I., and Marshall, L. M. Deter mination of uric acid, tyrosine, tryptophan, and protein in whole human parotid saliva by ultraviolet absorption spectrophotometry. J. D. Res. 42:1015 July-Aug. 1963. Henriques, B. L.. Acinar duct transport in the dog's submaxillary saliva gland. Abstract, J. D. Res. 40:719 July-Aug. 1961. Henriques, B. L. Stop-flow analysis of salivary gland duct transport localization. J. D. Res. 39:859 July-Aug. 1960. Hoerman, K. C.; Mancewicz, S. A., and Forziati, A. F. Improved starch-gel electrophoretic resolution of paro tid-fluid protein. J. D. Res. 40:1293 Nov.-Dec. 1961. Holen, Sheldon; Haber, Norman, and Tuck-Weiss, Irma. Standardized paper electrophoresis of parotid saliva. A study of variables in technique and flow rate as factors in resolution. J. D. Res. 40:470 May-June 1961. Isbell, Gerald M.; Shannon, Ira L., and Prigmore, John R. Water content of oral fluids. Abstract, J. D. Res. 40:720 July-Aug. 1961. Jenkins, G. N. Pyrophosphateas a factor influencing the solubility of enamel in saliva. Abstract, J. D. Res. 41:1267 Nov.-Dee. 1962. Kawakatsu, K., and others. Histochemical study of protein-bound sulfhydry! and disulfide groups In normal salivary glands. J . D. Res. 41:104 Jan.-Feb. 1962. Keene, H. J. Parotid fluid collection system with vacuum-trap modification. J. D. Res. 42:1041 July-Auq. 1963. Kimmelman, Benedict B. Modified method of in vitro production of salivary deposits. J. D. Res. 39:1076 Sept.Oct. I960. Klein, H. Cellular elements in the saliva of infants before and after eruption of teeth. J. D. Res. 41:1017 Sept.-Oct. 1962. Krasse, Bo. Amount, pH, buffer effect and amylolytic activity of parotid saliva between and immediately fol lowing meals. J. D. Res. 40:433 May-June 1961. Kraus, Frederick W. Salivary gamma globulin in oral health and disease. Abstract, J. D. Res. 40:689 JulyAug. 1961. Kraus, F. W., and Konno, J. Hemagglutinins and bac terial agglutinins in parotid secretion. Abstract, I.A.D.R. March 1963, p. 35. Krikszens, Arthur E.; Wilson, Robert M., and Green, Gordon E. Some studies on salivary proteins. Abstract, I.A.D.R. March 1963, p. 122. Kronman, J. H. Hamster salivary gland sexual dimor phism. I. Protein histochemical study. J. D. Res. 42:123 Jan.-Feb. 1963.
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Kronman, J. H. Hamster salivary gland sexual dimor phism. 2. A histochemical study of acid phosphatase. J. D. Res. 42:825 May-June 1963. Kronman, J. H. Salivary gland histochemistry In hypophysectomized rats. Abstract, I.A.D.R. March 1963, p. III. Lamberts, B. L.* Meyer, T. S., and Mazzarella, M. A. Studies of pH changes and infra-red absorbance of parotid secretions. Abstract, J. D. Res. 40:687 July-Aug. 1961. Laudig, L. W., and others. Use of pentamethylentetrazol to decrease mortality during collection of saliva from rats. J. D. Res. 39:862 July-Aug. I960. Leach, L. B.; Wyshak, G. H., and Weisberger, D. Human saliva: its antigenic composition. J. D. Res. 42:568 March-April 1963. Leach, L. B.; Wyshak, G. H., and Weisberger, D. Human saliva: its antigenic composition. Abstract, J. D. Res. 40:723 July-Aug. 1961. Lightfoot, Lois, and Coolidge, T. B. Ionized calcium in saliva. J. D. Res. 40:282 March-April 1961. Loftfield, R. B. The biosynthesis of protein. Progress in Biophys. & Biophysical Chem. 8:348, 1958. Losee, F. L. Use of the thermobalance in the analysis of lyophilized human parotid saliva. Abstract, I.A.D.R. March 1963, p. 121. McAnear, James F.; Shannon, Ira L., and Isbell, Gerald M. Specific gravity of parotid fluid. Abstract, J. D. Res. 40:720 July-Aug. 1961. Mandel, I. D.; Thompson, R. H., Jr., and Ellison, S. A. Carbohydrate components of submaxillary saliva. Abstract, I.A.D.R. March 1963, p. 122. Manhold, John H., Jr., and Bolder, Theodore E. Com parative study of submaxillary and lacrimal glands of the rat. Abstract J. D. Res. 40:690 July-Aug. 1961. Manly, R. S. Retention ofcarbohydrate from sugar solutions by salivary sediment. J. D. Res. 40:379 MarchApril 1961. Mazzarella, M. A.; Lamberts, B. L., and Meyer, T. S. Physical variations and pH values of saliva and parotid fluid. Abstract, J. D. Res. 40:687 July-Aug. 1961. Meyer, T. S.; Lamberts, B. L., and Mazzarella, M. A. Spectroscopic studies on human saliva. J. D. Res. 41:446 March-April 1962. Meyer, T. S.; Wolcott, R. B., and Shklair, I. L. Spec troscopic studies on human saliva. Abstract, J. D. Res. 40:687 July-Aug. 1961. Miller, John L. Method of pure parotid saliva collec tion with cannulization. J. D. Res. 39:1075 Sept.-Oct. I960. Miller, M. D., Ill; Biswell, H. A., and Goaz, P. W. Application of the method of steepest ascent to the response surface of the nitrate-nitrite reductase activity in salivary sediment. J. D. Res. 41:549 May-June 1962. Nagai, ^ Iwao; Yoshioka, Wataru, and Kumegawa, Masayoshi, influence of polyoma virus on tooth germs and salivary gland in fetal mice. Abstract, J . D. Res. 42:753 May-June 1963. Newbrun, E. Observations on the amylase content and flow rate of human saliva following gustatory stim ulation. J. D. Res. 41:459 March-April 1962. Onisi, M., and Kondo, V/. Ecological aspects of hu man parotid saliva. 1. The existence of constant rH values. J. D. Res. 39:433 May-June I960. Osorio, Joaquim A. Relation of the adrenal cortex to the salivary secretion mechanism of the dog. J . D. Res. 39:997 Sept.-Oct. I960. Prader, F. Inhibitory effect of copper arginine on glycolysis in human saliva. J. D. Res. 39:525 May-June 1960. Rapp, G. W. Synthesis and secretion of amylase by rat parotid gland slices. J. D. Res. 40:1225 Nov.-Dec. 1961. Rosen, S.; Hoppert, C. A,, and Hunt, H. R. Effect of diet and parotid gland secretions on dental caries in rats. J. D. Res. 39:415 March-April I960. Rovelstad, Gordon H. Histochemical characteristics of salivary corpuscles. Abstract, J. D. Res. 40:722 JulyAug. 1961.
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Ruben, Morris P., and Goldman, Henry M. The effect of partial desalivation on the gingiva. Abstract, I.A.D.R. March 1963, p. 128. Shafer, W. G. Experimental salivary gland tumorigenesis. J. D. Res. 41:117 Jan.-Feb. 1962. Shafer, W. G. Tissue culture characteristics of the BWI08I mouse salivary gland tumor. I. Preliminary in vestigation of nutrient medium components. J. D. Res. 41:125 Jan.-Feb. 1962. Shannon, I. L. Corticosteroids in human parotid fluid following oral hydrocortisone dosage. Abstract, I.A.D.R. March 1963, p. 64. Shannon, I. L.; Isbell, G. M., and Chauncey, H. H. Chloride concentration in parotid fluid at low rates of flow. J. D. Res. 41:661 May-June 1962. Shannon, I. L., and Prigmore, J. R. Human whole stimulated saliva sodium and potassium concentrations during 16 hours of the day. J . D. Res. 41:23 Jan.-Feb. 1962. Shannon, I. L.; Prigmore, J. R., and Chauncey, H. H. Modified Carlson-Crittenden device for the collection of parotid fluid. J. D. Res. 41:778 July-Aug. 1962. Shaw, R. W.; Bozek, R. G., and Connell, G. E. Elec trophoresis of saliva in starch gel. J. D. Res. 41:1322 Nov.-Dee. 1962. Shklar, G., and Chauncey, H. H. Effects of hypophysectomy on the enzyme histochemistry of the rat sub maxillary gland. J. D. Res. 42:71 Jan.-Feb. 1963. Suddick, R. P. Effect of salivariadenectomy and ad ministration of salivary gland homogenates upon the reproductive organs of the female rat. J. D. Res. 39:554 I960. Sweeney, E. A., and others. Studies on the protein composition of rodent saliva, f. Application of methods of paper electrophoresis to two strains of laboratory rat. Arch. Oral Biol. 7:621 Sept.-Oct. 1962. Tamarin, Arnold, and Sreebny, Leo M. Histometric, densltometric and electron microscopic analysis of tubular cell desmosomes in the rat submaxillary gland. Abstract, I.A.D.R. March 1963, p. 53. Tanzer, J., and Henriques, B. L. A time course study of alphaamylase secretion. Abstract, I.A.D.R. March 1963, p. 123.
Tomasi, Thomas B., Jr., and Zigelbaum, Sheldon D. Excretion of immunoglobulin in human saliva, colostrum, and urine. Abstract, I.A.D.R. March 1963, p. 52. Vogel, J. J., and others. Studies on the activities of calcium and dibasic phosphate in salivary secretions. Abstract, I.A.D.R. March 1963, p. 121. Wade, George W., and Fleming, Harold S. Salivary gland ligation extraction wound healing. Abstract, J . D. Res. 40:690 July-Aug. 1961. Wade, George W., and Jeter, Vera H. Salivary gland ligation: food, water, and weight. Abstract, J. D. Res. 40:720 July-Aug. 1961; Quart. N. D. A. 20:13 Oct. 1961. Waterhouse, J. P. Focal inflammation in salivary and lacrimal glands. Incidence and hlstopathology in human post mortem glands and experiments to sensitize the rat and guinea pig with homologous salivary and lacri mal gland extracts. Abstract, J. D. Res. 41:1253 Nov.Dec. 1962. Williams, N. B., and Powlen, D. O. Human parotid saliva as a sole source of nutrient for micro-organisms. Arch. Oral Biol. 1:48 Aug. 1959. Wilson, Robert M.t and Green, Gordon E. Study of salivary secretions related to blood type. Abstract, I.A.D.R. March 1963, p. 51. Winer, R. A.; Cohen, M. M., and Chauncey, H. H. Parotid secretion rate, pH, sodium and potassium val ues in mentally subnormal persons. Abstract, I.A.D.R. March 1963, p. 50. Wright, D. E. Microchamber of defined depth for the observation of salivary cells. Abstract, J. D. Res. 41:1260 Nov.-Dec. 1962. Wynn, Winfrey; Haldi, John, and Law, M. L. Effect of sialoadenectomy on growth of body composition of rats. Abstract, J. D. Res. 40:688 July-Aug. 1961. Zipkin, I., and Hawkins, G. R. Tyrosine and tryptophan content of human parotid saliva by ultraviolet spectro photometry. Abstract, J. D. Res. 40:721 July-Aug. 1961. Zwemer, Jack D., and Steinman, Ralph R. Endotoxic activity of human saliva. J. D. Res. 39:1074 Sept.-Oct. I960.
Research pertaining to saliva and the salivary glands is multifaceted and covers a spectrum of inquiry as broad as biology itself. Primary to any discussion of the investigative work being done in this area is an understanding that the salivary glands and their secretions do not consti tute biologically unique systems. Rather, they are particular examples of organs and organ products which, although spe cialized, are analogous to other organ systems which are associated with protein synthesis, ion transfer and water trans port. In view of this, it is not surprising that many of the questions concerning the salivary glands are similar to basic ques tions in other areas of research. Q U E S T IO N S
M any questions about salivary glands are not new ones but are presented in the light of new research approaches made possible by recent advances in technology. Some questions, on the other hand, could not have even been asked a decade ago, for they are the result of new concepts in biology, chemistry and physics. In general terms, research on salivary glands is being pursued to answer the fol lowing questions: 1. What is the nature of the various cells which constitute the salivary glands and how does their form reflect their function? 2. What are the various products of cellular synthesis in salivary glands and what is their role?
3. What are the constituents of se creted saliva; how do they vary in kind and in amount under different condi tions? 4. How do constituents of saliva affect maintenance of homeostasis in the oral cavity? 5. How do the salivary glands interact with other organs and body systems; that is, what is their place in the economy of the entire organism? Specific problems contained within these questions are attacked from various points of view depending on the primary interests of the investigator. Methods of collecting data involve light and electron microscopy, histochemistry, fluorescent antibody technic, cell fractionation and ultracentrifugation, biochemical identifi cation of cell constituents and assay of enzyme activity, radioautography, elec trophoresis, chromatography, immunochemistry and the application of elec tronic sensor devices. C U R R E N T R E SE A R C H
Different parenchymal cell types within a gland demonstrate great specialization. The electron microscope has enabled us to visualize some aspects of secretion at the fine structure level. Acinar cells are characterized by large quantities of ergastoplasm, which is a cell organelle sys tem associated with ribonucleic acid ( R N A ). This system is responsible for the organization of amino acids of the proper variety into the correct number and se-
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quence for the formation of specific pro teins.1 An important phase of cellular secretion is the “packaging” of products into membrane-bound granules. M aterial within these granules is expelled into the conduit system of the gland by a phenom enon whereby their surrounding mem branes become confluent with the plasma membrane which surrounds the cell. The granules thus ruptured release their mate rials into the ductal system. Apparently, some water may be secreted in a similar manner, and evidence exists that minute quantities of cytoplasm also may be dis charged by the cells.2-4 Cells comprising the different tubular portions of various salivary glands have specific functions. In some animals, a prominent tubular segment is associated with enzyme synthesis. All animals ap parently have a tubular segment special izing in water and electrolyte metabolism. Structurally this segment is akin, al though not identical, to the convoluted tubules of the kidney.5 Characteristically, the tubular cells have prominent plasma membrane infoldings at their base (asso ciated with water and ion transport), great numbers of mitochondria (associ ated with oxidative phosphorylation and energy transduction in cell respiration), many intracytoplasmic vesicles (associ ated with water metabolism and trans port) and microvilli at the luminal sur face (associated with the passage of diluted substances into and out of cells). Ergastoplasm, which is so prominent in cells actively engaged in protein synthe sis, is sparse in these cells.4,6'10 By histochemical methods the various cells of different salivary glands are char acterized according to the nature and lo cation of their organic products. These fall into two broad divisions: carbohydrate-protein complexes and enzymes.11"15 All of the glands produce neutral glyco proteins and sialopolysaccharides (mucin) in varying amounts. Acid mucopolysac charides, however, have not been demon strated in these tissues.14
T he chemical composition, the physical properties and the biological distribution of mucus is receiving a great amount of attention.16,17 T he localization and iden tification of mucus in the salivary glands of different species reveals a great di versity, the significance of which is not completely understood. The relationship of mucus production to the formation of other materials has been studied under such conditions as starvation.18 It has been shown that orders of priority exist in the synthesis of different moieties by different glands.19 A diverse variety of enzymes has been demonstrated in salivary glands.11 Some of these are intrinsic to the sustenance of normal cell metabolism and some are as sociated with cell degeneration and dis solution. These, however, constitute a relatively small portion of the total en zyme content of the glands. T he m ajor portion of enzyme production is associ ated with the secretions which are syn thesized for export.5,20 By ligating the m ajor excretory duct of the submaxillary gland, a readjustment of cellular organization takes place wherein no exocrine secretory activity occurs; that is, the gland is in a “ resting” state. Under these conditions, the gland tissue demon strates a decrease in oxygen consumption and high energy phosphate content; how ever, anaerobic glycolysis appears not to change. Starvation and x-irradiation also result in changes of cellular aerobic car bohydrate metabolism which in turn a f fect other enzyme systems such as iodide peroxidase associated with iodothyrine synthesis. Estimation of oxidative en zymes in different cells of the gland shows that ducts have a higher oxidase capacity than acini.21,22 Amylase, an enzyme which hydrolyzes some carbohydrate compounds, has been identified in salivary glands. Curiously, there seems to be a difference in the regu lative mechanisms controlling the pro duction of this enzyme in the m ajor glands. In the parotid gland (and the
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pan creas), interference with parasym pa thetic stimulation has no effect on the accumulation of amylase whereas, in the submandibular glands, parasympathomi metic activity results in an increase of this enzyme.23 In a routine analysis of desoxyribonu cleic acid (D N A ) concentration in the parotid glands of rats, it was discovered that a great disparity exists between the actual and expected amounts. By con trolling some of the variables in D N A determination, it was postulated that the low D N A content in gland homogenates was the result of a high concentration of desoxyribonuclease. This was verified by comparing the activity of this enzyme in various organs.24 Some of the proteolytic enzyme activity of salivary glands demonstrates a compli cated interdependency not only with stimulatory or inhibitory factors which directly control secretion but with hor mone systems of other organs. This is demonstrated by the changing status of the gland during the maturation of the organism.20 (This, incidentally, is re flected by the micromorphologic meta morphosis of the submaxillary gland during prepubertal development.25) Pro teolytic activity is higher in male than in female rats. Experiments involving cas tration or administration of gonadotropic hormones give us some insight as to the mechanisms responsible for this. T he ex treme complexity of hormonal regulation of salivary gland activity is demonstrated further by investigation of their relation ship to the hypophysis. Hypophysectomy results in a decrease in gland weight, atrophy of the intralobular duct segment, and decline of proteolytic activity which cannot be attributed solely to the decline of gonadotropic hormones.26 Changes in the activity of the thyroid gland also have been shown to affect the salivary glands. Increasing the amount of thyroxin increases the amount of salivary flow but decreases arginase activity in saliva, whereas inhibition of thyroid ac
tivity decreases salivary flow and increases the viscosity of saliva. T he salivary glands also possess a powerful mechanism for concentrating iodide which is independ ent of thyrotrophic hormone. This ap parently takes place in the secretory ducts and involves an active transport mecha nism.27 A dietary factor contained in dried and defatted preparations of pig pancreas (pancreatin) causes an overall enlarge ment of the salivary glands. This hyper trophic effect is not permanent but is reversed when the administration of the pancreatic extract is stopped. This phe nomenon is apparently dependent on an intact sympathetic nervous system and certain intraoral factors which mediate a reflex mechanism causing gland growth.28 Extremely intriguing studies are con cerned with the problem of endocrine secretion by the salivary glands. A potent nerve-growth factor has been isolated from mouse submaxillary salivary glands. Chemically this factor is a protein which, when injected into newborn mice, causes a sixfold increase in the volume of the sympathetic ganglia and an increased number of neurons of the viscera and blood vessels. Other effects which are similar to those induced by cortisone also are elicited. Curiously, snake venom glands, which are specialized salivary glands, also contain this factor.29 Other workers have isolated a substance from salivary glands reputedly capable of low ering serum calcium levels, of decreasing and subsequently increasing the number of circulating leukocytes and of promot ing the calcification of incisor dentin in rabbits.30 Simple inanition also depresses the serum calcium level in rabbits, whereas extirpation of the m ajor salivary glands exerts no influence.31 A great deal of interest concerns the relationship between the constituents of saliva and the constituents of blood. The presence of blood group substances (that is, A, B or O antigen) in saliva is under
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genetic control as a Mendelian dominant characteristic. Recent work indicates that there is a difference between the three m ajor salivary glands as to the degree of concentration of these antigens. Ap parently sublingual glands have the high est concentration and the parotid gland the least.32 The presence or absence of plasma clotting factors in saliva has been studied in normal patients and those with various bleeding disorders. It was found that clotting factors V I II , I X and X I are present in normal saliva as well as in the saliva of patients with various hemophiloid diseases, whereas factor V II is present in normal saliva but not in pa tients with proconvertin deficiency. F ac tors V and X are not detected in saliva.33 Analysis of electrophoretic patterns de rived from the saliva of various primates reveals some similarities and dissimilari ties which may be of value in the study of comparative anthropology. There is an indication that, as we ascend the phylo genetic ladder, there is an increase in the amount of positively charged salivary proteins.34 T he inorganic components of saliva have special pertinence to the under standing of acid-base balance, the mecha nisms of ion transfer and osmolarity. The hydrogen ion concentration of saliva is related to the amount of dissolved carbon dioxide which in turn relates directly to the concentration of bicarbonate. Studies concerning these relationships reveal that the saliva-plasma ratio of bicarbonate is directly dependent on the concentration of carbon dioxide in the arterial blood. When arterial carbon dioxide pressure is reduced, the saliva-plasma ratio of bicar bonate decreases; however, when the plasm a bicarbonate level is increased, there is no effect on the saliva-plasma ratio of bicarbonate. It becomes apparent that bicarbonate concentration in saliva is dependent on a metabolic alkalosis or acidosis.35 T he secretion and concentration of cal
cium and inorganic phosphate by salivary glands can be modified by the retrograde perfusion of cytoplasmic poisons, such as mercuric chloride into the ductal tree. The result of such an experiment indi cates that, although the acini actually secrete these substances, the ducts supple ment their secretion.36 Another area of research concerns the nature of the mechanisms which initiate and mediate salivary flow. Stimulation of the sympathetic as well as the parasym pathetic nerves which innervate the sali vary glands will evoke secretion. T he ac tual mechanism of reactance to nerve stimulation is mediated by specific chemi cal “ transmitters” produced by the nerve cells, which must reach the gland cell in order to be effective. These “ transmit ters” not only induce immediate secretory activity but also exert a long-term effect on the responsiveness of gland cells to secretory stimuli. If afferent fibers of the secretory reflex arc are sectioned, or if drugs which interfere with “ transmitter” substance are administered, the salivary glands acquire a supersensitivity. This state of supersensitivity is greater when transmitter substance is interfered with directly than when the nerves are cut. One concludes from these experiments that transmitter agents are released from postganglionic fibers even in the absence of nerve stimulation and thus are in volved with the regulation of gland sensi tivity.37 T he interactions of saliva with the oral flora or with dental caries involve prob lems relating to microbiology and epi demiology which are not within the scope of this review. T he material presented here is, at best, a brief, incomplete survey of some of the things which are receiving attention in the sphere of research on salivary glands and their secretions. C O N C L U S IO N
Increasing emphasis is being placed on defining the intrinsic mechanisms of cel
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lular activity and how they relate to spe cific functions. The total activity of sali vary glands is shown to be extremely complex not only in respect to specialized cellular function but also as related to their interdependence with other organs and homeostatic systems. Salivary secre tions vary from gland to gland and under different conditions, not to mention inter species differences. It also is demonstrated that the production of saliva is not the only function of salivary glands. The study of salivary glands has a prom inent place in the history of biology. In recent years an even greater interest has been demonstrated in the nature of these organs. T he information gathered in this area has been a significant contribution to the general pool of knowledge con cerning living systems. In 1962 the first international conference relating specifi cally to the salivary glands and their se cretions was held in Seattle. T he pub lished proceedings38 of this conference form a valuable compendium of funda mental information. A number of other excellent books concerned with various aspects of this subject also have been pub lished within the past few years.35,39-43 T he bibliography itself is far from com plete, but hopefully can be the source of further reference material for the inter ested reader.
*Assistant professor, department of oral pathology, School of Dentistry, University of Washington, Seattle. 1. Loftfield, R. B. The biosynthesis of protein. Prog ress Biophysics & Biophysical Chem. 8:348, 1958. 2. Parks, H. F. Morphological study of the extrusion of secretory materials by the parotid glands of mouse and rat. J. Ultrastructure Res. 6:449 June 1962. 3. Parks, H. F. On the fine structure of the parotid gland of mouse and rat. Am. J . Anat. 108:303 May 1961. 4. Scott, B. L., and Pease, D. C. Electron microscopy of the salivary and lacrimal glands of the rat. Ann. J. Anat. 104:115 1959. 5. Junqueira, L. C. U. Studies on the physiology of rat and mouse salivary glands. III. On the function of the striated ducts of the mammalian salivary glands. In Sreebny, L. M., and Meyer, J. (ed.). Salivary glands and their secretions. In press. 6. Jacoby, F., and Leeson, C. R. The post natal de velopment of the submaxillary gland. J. Anat. 93:201 April 1959. 7. Rutberg, U. Ultrastructure and secretory mecha nism of the parotid gland. Acta Odont. Scand. 19:30 suppl., 1961.
8. Sreebny, L. M., and Meyer, J . Hormones, inanition and salivary glands. II. On protease and convoluted tubules of the rat submaxillary gland. In Sreebny, L. M., and Meyer, J . (ed.). Salivary glands and their secretions. In press. 9. Tandler, B. Ultrastructure of the human submaxil lary gland. I. Architecture and histological relationships of the secretory cells. Am. J. Anat. 3:287, 1962. 10. Tandler, B. Ultrastructure of the human submaxil lary gland. II. The base of the striated duct cells. J. Ultrastructure Res. 9:65, 1963. 11. Arvy, L. Comparative histoenzymology of the salivary glands. Ann. New York Acad. Sci. 106:472 March 30, 1963. 12. Ellison, S. A. Chemical and immunological stud* ies of proteins and glycoproteins of human parotid saliva. In Sreebny, L. M., and Meyer, J. (ed.). Salivary glands and their secretions. In press. 13. Kent, S. P. A study of mucins in tissue sections by the fluorescent antibody technique. III. The specific ity of antibody to salivary gland mucins and the effect of chemical alterations of mucins on the specificity of the antibody. Ann. New York Acad. Sci. 106:389 March 30, 1963. 14. Quentarelli, G. Histological identification of sali vary mucins. Ann. New York Acad. Sci. 106:339 March 30, 1963. 15. Spicer, S. S. A correlative study of the histochemical properties of rodent acid mucopolysaccharides. J. Histochem. & Cytochem. 8:18 Jan. I960. 16. Chernick, W. S., and Barbero, G. J. Studies on human tracheobronchial and submaxillary secretions in normal and pathophysiological conditions. Ann. New York Acad. Sci. 106:698 March 30, 1963. 17. Shackleford, J. M. Histochemical comparison of mucous secretions in rodent, carnivore, ungulate, and primate major salivary glands. Ann. New York Acad. Sci. 106:572 March 30, 1963. 18. Tamarin, A., and Sreebny, L. M. Effects of total inanition on the submaxillary gland of the rat. Arch. Oral Biol. 7;469 July*Aug. 1962. 19. Tamarin, A.; Wanamaker, B., and Sreebny, L. M. The effect of inanition on the submandibular salivary glands and exocrine pancreas of the rat. Ann. New York Acad. Sci. 106:609 March 30, 1963. 20. Sreebny, L M. Studies of salivary gland proteases. Ann. New York Acad. Sci. 85:182 March 29, I960. 21. English, J . A. Effects of radiation upon the sali vary glands. Ann. New York Acad. Sci. 85:342 March 29, I960. 22. Schneider, R. M., and Person, P. Aerobic oxida tive metabolism of salivary glands. Ann. New York Acad. Sci. 85:201 March 29, I960. 23. Schneyer, L. H., and Schneyer, C. A. Regulation of salivary gland amylase activity. Ann. New York Acad. Sci. 85:189 March 29, I960. 24. Wanamaker, Barbara, and Sreebny, Leo M. DNA determinations in the parotid gland of the rat. Ab stract, I.A.D.R. March 1963, p. 81. 25. Jacoby, F., and Leeson, C. R. The postnatal de velopment of the rat submaxillary gland. J . Anat. 93:201 April 1959. 26. Shafer, W . G., and Muhler, J. C. Endocrine influences upon the salivary glands. Ann. New York Acad. Sci. 85:215 March 29, I960. 27. Myant, N. B. Iodine metabolism of salivary glands. Ann. New York Acad. Sci. 85:208 March 29, I960. 28. Wells, H., and Voelkel, E. F. Partial purification and mode of action of a pancreatic substance that enhances salivary gland growth. Abstract, I.A.D.R., March 1963, p. 123. 29. Levi-Montalcini, R., and Cohen, S. Effects of the extract of the mouse submaxillary salivary glands on the sympathetic system of mammals. Ann. New York Acad. Sci. 85:324 March 29, I960. 30. Ito, Yosop. Parotin: a salivary gland hormone. Ann. New York Acad. Sci. 85:228 March 29, I960.
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31. Saxe, Stanley R., and Sreebny, Leo M. Salivary glands and serum calcium. Abstract, J . D. Res. 40:719 July-Aug. 1961. 32. Wolf, Robert O., and Taylor, Leonard L. Concen tration of blood group substances in the parotid, sub lingual and submaxillary salivas. Abstract, I.A.D.R. March 1963, p. 51. 33. Taylor, R. G., and Doku, H. C. Salivary thromboplastic activity in hemophilia and hemophiloid diseases. Abstract, I.A.D.R. March 1963, p. 52. 34. Sweeney, Edward A., and Shaw, James H. The protein composition of pilocarpine induced saliva from four primates. Abstract, I.A.D.R. March 1963, p. 121. 35. Burqen, A. S. V., and Emmelin, N. G. Physiology of the salivary glands. Baltimore, Williams & Wilkins Co., 1961. 36. Henriques, B. L. Salivary gland secretion of cal cium and inorganic phosphate. Abstract, I.A.D.R. March 1963, p. 121. 37. Emmelin, N. Secretory nerves of the salivary glands. In Sreebny, L. M., and Meyer, J. (ed.). Salivary glands and their secretions. In press. 38. Sreebny, L. M., and Meyer, J. (ed.). Salivary glands and their secretions. Norwich, Pergamon Press, in press. 39. Afonsky, D. A. (ed.). Saliva and its relation to oral health. University, Ala., University of Alabama Press, 1961. 40. Kerr, Alexander C. The physiological regulation of salivary secretions in man. New York, Pergamon Press, 1961. 41. Office ^ of Naval Research, Department of the Navy, Washington, D.C. Bibliography on saliva com piled by Bibliography Section, Science and Technology Division, Library of Congress. March I960. 42. Parhon, C. !.; Babes, A., and Petrea, I. En docrinología glandelor salivare. Edltura Academlei Republicii Populare Romine, 1957. 43. Rauch, S. Die speicheldrüsen desmenschen. Stutt gart, Georg Thieme Verlag, 1959. A D D IT IO N A L B IB L IO G R A P H Y Abrams, E. Tongue nerves in vitamin Bi deficient rats with ligated salivary glands. Abstract, I.A.D.R. March 1963, p. 88. Andlaw, Reginald J. Paper chromatography of acids produced during salivary fermentation of foodstuffs in vitro. Abstract, J . D. Res. 41:1251 Nov.-Dee. 1962. Apostolopoulos, A. X. On the isolation and identifica tion of human salivary mucins. Abstract, I.A.D.R. March 1963, p. 122, Bates, J. F. Influence of plasma phosphate on the phosphate concentration of human parotid saliva. Arch. Oral Biol. 3:1 Dec. I960. Beck, Donald J., and Gil lings, Barrie R. D. Investiga tion of the usefulness of neutron activation analysis for studying trace elements in sajiva. J. D. Res. 40:383 March-April 1961. Betz, P. K.; Wanamaker, Barbara B., and Sreebny, L. M. Induction of exocrine pancreatic atrophy and its effects on the submaxillary salivary gland in the rat. Abstract, J . D. Res. 41:1274 Nov.-Dee. 1962. Beutnert>E. H.; Genco, R., and Djanian, A. Studies of immunization routes and dose response relationships in the production of autoantibodies to salivary glands in rabbits. Abstract, I.A.D.R. March 1963, p. 51. Blechrnan, Harry, and Bartels, Henry A. Food and water intake and body weight in the sialoadenecto mized animal. Abstract, I.A.D.R. March 1963. Boucher, N. E., Jr., and Wanek, R. M. Study of the antigenic components of saliva. Abstract, I.A.D.R. March 1963, page 51. Bulman, J . S., and Ten Cate, A. R. Experimental in vestigation of zinc in saliva. Abstract, J . D. Res. 41:1259 Nov.-Dee. 1962. Buttner, W ., and Muhler, J. C. Effects of salivary fluoride on enamel solubility. J. D. Res. 41:617 MayJune 1962.
Cataldo, Edmond; Shklar, Gerald, and Chauncey, Howard. Enzyme histochemistry of salivary gland tumors induced in rats by a chemical carcinogen. Abstract, I.A.D.R. March 1963, p. 110. Charlton, G. Oxygen tension of saliva within the parotid duct and on the floor of the mouth of humans. Abstract, J . D. Res. 41:512 May-June 1962. Chaudhry, A. P., and others. Experimental carcino genesis in submandibular glands of hamsters. J. D. Res. 40:426 May-June 1961. Chaudhry, A. P., and others. Effects of vitamin A deficiency on experimental carcinogenesis in subman dibular glands of hamsters. J . D. Res. 40:327 MarchApril 1961. Chauncey, H. H., and others. Effect of partial desallvation and parotin administration on hamster epiphyseal plate. J . D. Res. 42:894 May-June 1963. Chauncey, H. H.; Winer, R. A., and Barber, T. X. Influence of verbal suggestion on parotid gland secre tion rate. Abstract, I.A.D.R. March 1963, p. 50. Claycomb, C. K., and others. Presence of Se75 in rat saliva after intracardiac infection of radioactive sodium selenite. J. D. Res. 39:1264 Nov.-Dec. I960. Claycomb, C. K., and others. Further studies on the presence of Se7S in rat saliva and teeth after intracardiac injection of radioactive sodium selenite. J. D. Res. 40:504 May-June 1961. Coykendahl, A., and Henriques, Basil L. Time-course study of Na, K, and flow rate for the parotid secretion in man. Abstract, J. D. Res. 40:719 July-Aug. 1961. Dain, Joel A., and Manly, R. S. Identity of the poly saccharide produced by oral samples from sucrose solu tions. Abstract, J. D. Res. 40:720 July-Aug. 1961. Dawes, C., and Jenkins, G. N. Studies In man on the composition of duct saliva secreted in response to a variety of stimuli. Abstract, J. D. Res. 41:1260 Nov.Dec. 1962. Dirksen, T. R. Lipid constituents of whole and parotid saliva. J . D. Res. 42:920 July-Aug. 1963. Doku, Hrlsto Chris. Thromboplastic activity of human saliva. J . D. Res. 39:1210 Nov.-Dee. I960. Doku, Hristo Chris, and Taylor, Richard G. Thrombo plastin generation by saliva. Abstract, J . D. Res. 40:688 July-Aug. 1961. Draus, F. J., and Leung, S. W. Quantitative amino acid analysis of a bovine submaxillary mucoid. J. D. Res. 41:491 March-April 1962. Draus, F. J.; MIklos, F. L., and Leung, S. W. Carbonic anhydrase in a bovine submaxillary gland extract. J. D. Res. 41:497 March-April 1962. Dreisbach, Robert H. Calcium binding by normal human saliva. J. D. Res. 39:1133 Nov.-Dec. I960. Drum, D. E. Simple technique for direct cannulatlon of rat salivary ducts. J. D. Res. 42:892 May-June 1963. D’Silva, J. L., and Ferguson, D. B. Zone electrophore sis of human parotid saliva in various media. Arch. Oral Biol. 7:563 Sept.-Oct. 1962. Ellison, Solon A.; Mashimo, Paul A., and Mandel, Irwin D. Immunochemical studies of human saliva. I. The demonstration of serum proteins in whole and paro tid saliva. J . D. Res. 39:892 Sept.-Oct. I960. Emmelin, N. On "antllytic" secretion of saliva. J. Physiol. 157:410 July 1961. Feller, R. P.; Chauncey, H. H., and Shannon, I. L. Partial kinetic characterization of acid action on gusta tory chemoreceptors using the gustato-salivary reflex. Abstract, I.A.D.R. March 1963, p. 123. Ferguson, D. B. Media for zone electrophoresis of parotid saliva. Abstract, J. D.Res. 41:1261 Nov.-Dec. 1962. Fischer, Clary J.; Wyshak, George H., and Weisberger, David. Effect of inorganic ions on the electro phoretic pattern of whole saliva. Abstract, J . D. Res. 40:722 July-Aug. 1961. Fleming, H. S. The effect of parotin in mice. Ann. New York Acad. Sci. 85:313 March 29, I960. Fleming, H. S. Transplants of salivary glands and parotin. Abstract, J. D. Res. 40:690 July-Aug. 1961. Fleming, H. S. Parotid gland extracts and mice sub maxillary glands. J. D. Res. 41:939 Sept.-Oct. 1962.
REVIEW OF DENTAL RESEARCH
Fritz, M.; Cohen, D. W., and Rabinowitz, J. L. Rela tionship between uptake Ca45 and cholesterogenesis and lipogenesis in the rat parotid gland. Abstract, I.A.D.R. March 1963, p. 69. Geever, E. F.; McClure, F. J., and Zipkin, I. Salivary glands in lysine-deficient young rats. J. D. Res. 39:129 Jan.-Feb. I960. Goaz, Paul W., and Biswell, Helen A. Nitrate reduc tion in whole saliva. J. D. Res. 40:355 March-April 1961. Gow, B., and Newbrun, E. Application of atomic absorption spectroscopy to the determination of cal cium and magnesium in saliva. Abst'ract, J. D. Res. 41:512 May-June 1962. Hall, Walter B.; Betz, Peter K., and Sreebny, Leo M. Induced pancreatic atrophy and digestive glands. III. Effects on the parotid glands and gastric mucosa. Abstract, I.A.D.R. March 1963, p. 114. Harnach, Frances A. Analysis of calcium in unashed saliva. J. D. Res. 39:1069 Sept.-Oct. I960. Harris, N. O., and others. Infrared spectral charac teristics of pilocarpine-stimulated saliva of normally caries-resistant animals compared with caries-resistant and susceptible humans. J. D. Res. 39:810 July-Aug. I960. Hartles, R. L. Metabolic factors in saliva. J . D. Res. 42:553 suppl. Jan.-Feb. 1963. Hawkins, G. R., and Zipkin, I. Spectrophotometric determination of tryosine, tryptophan, protein, and uric acid in human parotid saliva. Abstract, J. D. Res. 40:721 July-Aug. 1961. Hawkins, G. R.; Zipkin, I., and Marshall, L. M. Deter mination of uric acid, tyrosine, tryptophan, and protein in whole human parotid saliva by ultraviolet absorption spectrophotometry. J. D. Res. 42:1015 July-Aug. 1963. Henriques, B. L.. Acinar duct transport in the dog's submaxillary saliva gland. Abstract, J. D. Res. 40:719 July-Aug. 1961. Henriques, B. L. Stop-flow analysis of salivary gland duct transport localization. J. D. Res. 39:859 July-Aug. 1960. Hoerman, K. C.; Mancewicz, S. A., and Forziati, A. F. Improved starch-gel electrophoretic resolution of paro tid-fluid protein. J. D. Res. 40:1293 Nov.-Dec. 1961. Holen, Sheldon; Haber, Norman, and Tuck-Weiss, Irma. Standardized paper electrophoresis of parotid saliva. A study of variables in technique and flow rate as factors in resolution. J. D. Res. 40:470 May-June 1961. Isbell, Gerald M.; Shannon, Ira L., and Prigmore, John R. Water content of oral fluids. Abstract, J. D. Res. 40:720 July-Aug. 1961. Jenkins, G. N. Pyrophosphateas a factor influencing the solubility of enamel in saliva. Abstract, J. D. Res. 41:1267 Nov.-Dee. 1962. Kawakatsu, K., and others. Histochemical study of protein-bound sulfhydry! and disulfide groups In normal salivary glands. J . D. Res. 41:104 Jan.-Feb. 1962. Keene, H. J. Parotid fluid collection system with vacuum-trap modification. J. D. Res. 42:1041 July-Auq. 1963. Kimmelman, Benedict B. Modified method of in vitro production of salivary deposits. J. D. Res. 39:1076 Sept.Oct. I960. Klein, H. Cellular elements in the saliva of infants before and after eruption of teeth. J. D. Res. 41:1017 Sept.-Oct. 1962. Krasse, Bo. Amount, pH, buffer effect and amylolytic activity of parotid saliva between and immediately fol lowing meals. J. D. Res. 40:433 May-June 1961. Kraus, Frederick W. Salivary gamma globulin in oral health and disease. Abstract, J. D. Res. 40:689 JulyAug. 1961. Kraus, F. W., and Konno, J. Hemagglutinins and bac terial agglutinins in parotid secretion. Abstract, I.A.D.R. March 1963, p. 35. Krikszens, Arthur E.; Wilson, Robert M., and Green, Gordon E. Some studies on salivary proteins. Abstract, I.A.D.R. March 1963, p. 122. Kronman, J. H. Hamster salivary gland sexual dimor phism. I. Protein histochemical study. J. D. Res. 42:123 Jan.-Feb. 1963.
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Kronman, J. H. Hamster salivary gland sexual dimor phism. 2. A histochemical study of acid phosphatase. J. D. Res. 42:825 May-June 1963. Kronman, J. H. Salivary gland histochemistry In hypophysectomized rats. Abstract, I.A.D.R. March 1963, p. III. Lamberts, B. L.* Meyer, T. S., and Mazzarella, M. A. Studies of pH changes and infra-red absorbance of parotid secretions. Abstract, J. D. Res. 40:687 July-Aug. 1961. Laudig, L. W., and others. Use of pentamethylentetrazol to decrease mortality during collection of saliva from rats. J. D. Res. 39:862 July-Aug. I960. Leach, L. B.; Wyshak, G. H., and Weisberger, D. Human saliva: its antigenic composition. J. D. Res. 42:568 March-April 1963. Leach, L. B.; Wyshak, G. H., and Weisberger, D. Human saliva: its antigenic composition. Abstract, J. D. Res. 40:723 July-Aug. 1961. Lightfoot, Lois, and Coolidge, T. B. Ionized calcium in saliva. J. D. Res. 40:282 March-April 1961. Loftfield, R. B. The biosynthesis of protein. Progress in Biophys. & Biophysical Chem. 8:348, 1958. Losee, F. L. Use of the thermobalance in the analysis of lyophilized human parotid saliva. Abstract, I.A.D.R. March 1963, p. 121. McAnear, James F.; Shannon, Ira L., and Isbell, Gerald M. Specific gravity of parotid fluid. Abstract, J. D. Res. 40:720 July-Aug. 1961. Mandel, I. D.; Thompson, R. H., Jr., and Ellison, S. A. Carbohydrate components of submaxillary saliva. Abstract, I.A.D.R. March 1963, p. 122. Manhold, John H., Jr., and Bolder, Theodore E. Com parative study of submaxillary and lacrimal glands of the rat. Abstract J. D. Res. 40:690 July-Aug. 1961. Manly, R. S. Retention ofcarbohydrate from sugar solutions by salivary sediment. J. D. Res. 40:379 MarchApril 1961. Mazzarella, M. A.; Lamberts, B. L., and Meyer, T. S. Physical variations and pH values of saliva and parotid fluid. Abstract, J. D. Res. 40:687 July-Aug. 1961. Meyer, T. S.; Lamberts, B. L., and Mazzarella, M. A. Spectroscopic studies on human saliva. J. D. Res. 41:446 March-April 1962. Meyer, T. S.; Wolcott, R. B., and Shklair, I. L. Spec troscopic studies on human saliva. Abstract, J. D. Res. 40:687 July-Aug. 1961. Miller, John L. Method of pure parotid saliva collec tion with cannulization. J. D. Res. 39:1075 Sept.-Oct. I960. Miller, M. D., Ill; Biswell, H. A., and Goaz, P. W. Application of the method of steepest ascent to the response surface of the nitrate-nitrite reductase activity in salivary sediment. J. D. Res. 41:549 May-June 1962. Nagai, ^ Iwao; Yoshioka, Wataru, and Kumegawa, Masayoshi, influence of polyoma virus on tooth germs and salivary gland in fetal mice. Abstract, J . D. Res. 42:753 May-June 1963. Newbrun, E. Observations on the amylase content and flow rate of human saliva following gustatory stim ulation. J. D. Res. 41:459 March-April 1962. Onisi, M., and Kondo, V/. Ecological aspects of hu man parotid saliva. 1. The existence of constant rH values. J. D. Res. 39:433 May-June I960. Osorio, Joaquim A. Relation of the adrenal cortex to the salivary secretion mechanism of the dog. J . D. Res. 39:997 Sept.-Oct. I960. Prader, F. Inhibitory effect of copper arginine on glycolysis in human saliva. J. D. Res. 39:525 May-June 1960. Rapp, G. W. Synthesis and secretion of amylase by rat parotid gland slices. J. D. Res. 40:1225 Nov.-Dec. 1961. Rosen, S.; Hoppert, C. A,, and Hunt, H. R. Effect of diet and parotid gland secretions on dental caries in rats. J. D. Res. 39:415 March-April I960. Rovelstad, Gordon H. Histochemical characteristics of salivary corpuscles. Abstract, J. D. Res. 40:722 JulyAug. 1961.
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Ruben, Morris P., and Goldman, Henry M. The effect of partial desalivation on the gingiva. Abstract, I.A.D.R. March 1963, p. 128. Shafer, W. G. Experimental salivary gland tumorigenesis. J. D. Res. 41:117 Jan.-Feb. 1962. Shafer, W. G. Tissue culture characteristics of the BWI08I mouse salivary gland tumor. I. Preliminary in vestigation of nutrient medium components. J. D. Res. 41:125 Jan.-Feb. 1962. Shannon, I. L. Corticosteroids in human parotid fluid following oral hydrocortisone dosage. Abstract, I.A.D.R. March 1963, p. 64. Shannon, I. L.; Isbell, G. M., and Chauncey, H. H. Chloride concentration in parotid fluid at low rates of flow. J. D. Res. 41:661 May-June 1962. Shannon, I. L., and Prigmore, J. R. Human whole stimulated saliva sodium and potassium concentrations during 16 hours of the day. J . D. Res. 41:23 Jan.-Feb. 1962. Shannon, I. L.; Prigmore, J. R., and Chauncey, H. H. Modified Carlson-Crittenden device for the collection of parotid fluid. J. D. Res. 41:778 July-Aug. 1962. Shaw, R. W.; Bozek, R. G., and Connell, G. E. Elec trophoresis of saliva in starch gel. J. D. Res. 41:1322 Nov.-Dee. 1962. Shklar, G., and Chauncey, H. H. Effects of hypophysectomy on the enzyme histochemistry of the rat sub maxillary gland. J. D. Res. 42:71 Jan.-Feb. 1963. Suddick, R. P. Effect of salivariadenectomy and ad ministration of salivary gland homogenates upon the reproductive organs of the female rat. J. D. Res. 39:554 I960. Sweeney, E. A., and others. Studies on the protein composition of rodent saliva, f. Application of methods of paper electrophoresis to two strains of laboratory rat. Arch. Oral Biol. 7:621 Sept.-Oct. 1962. Tamarin, Arnold, and Sreebny, Leo M. Histometric, densltometric and electron microscopic analysis of tubular cell desmosomes in the rat submaxillary gland. Abstract, I.A.D.R. March 1963, p. 53. Tanzer, J., and Henriques, B. L. A time course study of alphaamylase secretion. Abstract, I.A.D.R. March 1963, p. 123.
Tomasi, Thomas B., Jr., and Zigelbaum, Sheldon D. Excretion of immunoglobulin in human saliva, colostrum, and urine. Abstract, I.A.D.R. March 1963, p. 52. Vogel, J. J., and others. Studies on the activities of calcium and dibasic phosphate in salivary secretions. Abstract, I.A.D.R. March 1963, p. 121. Wade, George W., and Fleming, Harold S. Salivary gland ligation extraction wound healing. Abstract, J . D. Res. 40:690 July-Aug. 1961. Wade, George W., and Jeter, Vera H. Salivary gland ligation: food, water, and weight. Abstract, J. D. Res. 40:720 July-Aug. 1961; Quart. N. D. A. 20:13 Oct. 1961. Waterhouse, J. P. Focal inflammation in salivary and lacrimal glands. Incidence and hlstopathology in human post mortem glands and experiments to sensitize the rat and guinea pig with homologous salivary and lacri mal gland extracts. Abstract, J. D. Res. 41:1253 Nov.Dec. 1962. Williams, N. B., and Powlen, D. O. Human parotid saliva as a sole source of nutrient for micro-organisms. Arch. Oral Biol. 1:48 Aug. 1959. Wilson, Robert M.t and Green, Gordon E. Study of salivary secretions related to blood type. Abstract, I.A.D.R. March 1963, p. 51. Winer, R. A.; Cohen, M. M., and Chauncey, H. H. Parotid secretion rate, pH, sodium and potassium val ues in mentally subnormal persons. Abstract, I.A.D.R. March 1963, p. 50. Wright, D. E. Microchamber of defined depth for the observation of salivary cells. Abstract, J. D. Res. 41:1260 Nov.-Dec. 1962. Wynn, Winfrey; Haldi, John, and Law, M. L. Effect of sialoadenectomy on growth of body composition of rats. Abstract, J. D. Res. 40:688 July-Aug. 1961. Zipkin, I., and Hawkins, G. R. Tyrosine and tryptophan content of human parotid saliva by ultraviolet spectro photometry. Abstract, J. D. Res. 40:721 July-Aug. 1961. Zwemer, Jack D., and Steinman, Ralph R. Endotoxic activity of human saliva. J. D. Res. 39:1074 Sept.-Oct. I960.