Whey components: Millennia of evolution create functionalities for mammalian nutrition: What we know and what we may be overlooking

Critical Reviews in Food Science and Nutrition

Volumn 42, Issue 4, 2002, Pages 353-375

  Walzem, R L ^a   Dillard, C J ^b   German, J B ^b  

^a TEXAS A AND M UNIVERSITY   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Bioactive molecules; Functional properties; Lipids; Proteins

Indexed keywords

BIOACTIVE MOLECULES; FUNCTIONAL PROPERTIES; NEONATAL SURVIVAL; PREBIOTICS;

AMINO ACIDS; FOOD ADDITIVES; HEALTH CARE; IMMUNOLOGY; LIPIDS; PROTEINS;

NUTRITION;

BOVINAE; DARWINIA; MAMMALIA;

BRANCHED CHAIN AMINO ACID; LACTOFERRIN; MILK PROTEIN; SULFUR AMINO ACID; WHEY PROTEIN;

ANIMAL; BABY FOOD; CATTLE; CHEMISTRY; ENZYMOLOGY; HUMAN; INFANT; MILK; NEWBORN; NUTRITIONAL VALUE; PHYSIOLOGY; REVIEW; STANDARD;

AMINO ACIDS, BRANCHED-CHAIN; AMINO ACIDS, SULFUR; ANIMALS; CATTLE; HUMANS; INFANT; INFANT FOOD; INFANT, NEWBORN; LACTOFERRIN; MILK; MILK PROTEINS; NUTRITIVE VALUE;

EID: 0036653591     PISSN: 10408398     EISSN: None     Source Type: Journal    
DOI: 10.1080/10408690290825574     Document Type: Article

References (138)

1. Anon. Reference Manual for U.S. Whey Products, Arlington, VA,: U.S. Dairy Export Council, 1997.
2. Mawson, A. J. Bioconversions for whey utilization and waste abatement, Bioresource Tech. 47: 195-203, 1994.
3. Boyd, L. C., Drye, N. C., and Hansen, A. P. Isolation and characterization of whey phospholipids, J. Dairy Sci. 82: 2550-2557, 1999.
4. Smithers, G. W., Ballard, F. J., Copeland, A. D., De Silva, K. J., Dionysius, D. A., Francis, G. L., Goddard, C., Grieve, P. A., McIntosh, G. H., Mitchell, I. R., Pearce, R. J. and Regester, G. O. New opportunities from the isolation and utilization of whey proteins, J. Dairy Sci. 79: 1454-1459, 1996.
5. Cuthbertson, W. F. J. Evolution of infant nutrition, Br. J. Nutr. 81: 359-371, 1999.
6. Goldman, A. S. Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspective, J. Nutr. 130: 426S-431S, 2000.
7. Perlman, D. and Hayes, K. C. Hyper-Absorption of Vitamin E Dispersed in Milks, US Patent 6,156,354, 2000.
8. Hurley, L. S., Developmental Nutrition, Englewood Cliffs, NJ, Prentice-Hall, Inc., 1980.
9. Johnson, T. R., Moore, W., and Jeffries, J. E., Eds. Children Are Different: Developmental Physiology, 2nd. ed., Columbus, OH, Ross Laboratories, Columbus, OH, 1978.
10. Gibson, G. R. Dietary modulation of the human gut microflora using prebiotics, Br. J. Nutr, 80: S209-S212, 1998.
11. Defilippi, C., Gomez, E., Charlin, V., and Silva. C., Inhibition of small intestinal motility by casein: a role of beta casomorphins? Nutrition 11: 751-755, 1995.
12. Khun, T. S. The structure of scientific revolutions. In: Foundations of the Unity of Science, Vol. II, No 2., Neurath, O., Ed. Chicago, IL, International Encyclopedia of Unified Science, The University of Chicago Press, 1962, pp. 52-91.
13. Farrell, H. M., Jr., Wickham, E. D., Dower, H. J., Piotrowski E G., Hoagland P. D., Cooke, P. H., and Groves, M. L. Characterization of the particles of purified kappa-casein: trypsin as a probe of surface-accessible residues, Protein Chem. 18:637-635, 1999.
14. Yvon, M., Beucher, S., Guilloteau, P., Le Huerou-Luron, I., and Corring, T. Effects of caseinomacropeptide (CMP) on digestion regulation, Reprod. Nutr. Dev. 34: 527-537, 1994.
15. Bal dit Sollier, C., Drouet, L., Pignaud, G., Chevallier, C., Caen, J., Fiat, A. M., Izquierdo, C., and Jolles, P. Effect of kappa-casein split peptides on platelet aggregation and on thrombus formation in the guineapig, Thromb. Res. 81: 427-137, 1996.
16. Meisel, H. and Bockelmann, W. Bioactive peptides encrypted in milk proteins: proteolytic activation and thropho-functional properties, Antonie Van Leeuwenhoek 76: 207-215, 1999.
17. Kinsella, J. E. and Whitehead, D. Proteins in whey: chemical physical and functional properties, Adv. Food Nutr. Res. 33: 343-438, 1989.
18. Korhonen, H., Pihlanto-Leppälä, A., Rantamäki, P., and Tupasela Tuomo. The functional and biological properties of whey proteins: prospects for the development of functional foods, Agric. Food Sci. Finland 7: 283-296, 1998.
19. de Wit, J. N., Marschall Rhone-Poulenc Award Lecture. Nutritional and functional characteristics of whey proteins in food products, J. Dairy Sci. 81: 597-608, 1998.
20. Mahé, S., Huneau, J.-F, Marteau, Ph., Thuillier, F. and Tome, D. Gastro-ileal nitrogen and electrolyte movements after bovine milk ingestion in humans, Am. J. Clin. Nutr. 56: 410-416, 1991.
21. Mahé, S., Benamouzig, R., Gaudicho, C., Huneau, J.-F., De Cruz, I., and Tomé, D. Nitrogen movements in the upper jejunum lumen in humans fed low amounts of caseins of β-lactoglobulin, Gastroentérol. Clin. Biol. 19: 20-26, 1995.
22. Boirie, Y., Dangin, M., Gachon, P., Vasson, M.-P., Maubois, J.-L., and Beaufrere, B., Slow and fast dietary proteins differently modulate postprandial protein accretion, Proc. Natl. Acad. Sci. USA 94: 14930-14935, 1997.
23. Cumberbatch, M., Dearman, R. J., Uribe-Luna, S., Headon, D. R., Ward, P. P., Conneely, O. M., and Kimber, I. Regulation of epidermal Langerhans cell migration by lactoferrin, Immunology 100: 21-28, 2000.
24. Kawasaki, Y., Isoda, H., Tanimoto, M., Dosako, S., Idota, T., and Ahiko, K. Inhibition by lactoferrin and kappa-casein glycomacropeptide of binding of Cholera toxin to its receptor, Biosci. Biotechnol. Biochem. 56: 195-198, 1992.
25. Bounous, G., Batist, G., and Gold, P. Immunoenhancing property of dietary whey protein in mice: role of glutathione, Clin Invest Med. 12: 154-161, 1989.
26. Grimble, R. F. and Grimble, G. K. Immunonutrition: role of sulfur amino acids, related amino acids, and polyamines, Nutrition 14: 605-610, 1998.
27. Bounous, G. and Gold, P. The biological activity of undenatured dietary whey proteins: role of glutathione, Clin. Invest. Med. 14: 296-309, 1991.
28. Glass, L. and Hedrick, T. I. Nutritional composition of sweet and acid type dry wheys. I. Major factors including amino acids, J. Dairy Sci. 60: 185-189, 1976.
29. Mourier, A., Bigard, A. X., de Kerviler, E., Roger, B., Legrand, H., and Guezennec, C. Y. Combined effects of caloric restriction and branched-chain amino acid supplementation on body composition and exercise performance in elite wrestlers, Int. J. Sports Med. 18: 47-55, 1997.
30. Blomstrand, E. and Newsholme, E. A. Effect of branched-chain amino acid supplementation on the exercise-induced change in aromatic amino acid concentration in human muscle, Acta Physiol. Scand. 146: 293-298, 1992.
31. Schena, F., Guerrini, F., Tregnaghi, P., and Kayser, B. Branched-chain amino acid supplementation during trekking at high altitude. The effects on loss of body mass, body composition, and muscle power, Eur. J. Appl. Physiol. 65: 394-398, 1992.
32. Kuwata, H., Yip, T.-T., Tomita, M., and Hutchens, T. W. Direct evidence of the generation in human stomach of an antimicrobial peptide domain (lactoferricin) from ingested lactoferrin, Biochim. Biophys. Acta 1429: 129-141, 1998.
33. Kuwata, H., Yip, T.-T., Yamauchi, K., Teraguchi, S., Hayasawa, H., Tomita, M., and Hutchens, T. W. The survival of ingested lactoferrin in the gastrointestinal tract of adult mice, Biochem. J. 334: 321-323, 1998.
34. Kuwata, H., Yip, T.-T., Yip, C. L., Tomita, M., and Hutchens, T. W. Bactericidal domain of lactoferrin: detection, quantitation, and characterization of lactoferricin in serum by SELDI affinity mass spectrometry, Biochem. Biophys. Res. Commun. 245: 764-773 1998.
35. Bahna, S. L. Pathogenesis of milk hypersensitivity, Immunol. Today 6: 153-154, 1985.
36. Bland, P. W. and Kambaragne, D. M. Antigen processing by isolated rat intestinal villus enterocytes, Gastroenterol. Clin. North Am. 20: 577-596, 1991.
37. Corkins, M. R., Park, J. H., Davis, D. V., Slentz, D. H., and MacDonald R. G. Regulation of the insulin-like growth factor axis by increasing cell number in intestinal epithelial (IEC-6) cells, Growth Horm. IGF Res. 9: 414-424, 1999.
38. Donnet-Hughes, A., Duc, N., Serrant, P., Vidal, K., and Schiffrin, E. J. Bioactive molecules in milk and their role in health and disease: the role of transforming growth factor-beta, Immunol. Cell Biol. 78: 74-79, 2000.
39. Yamauchi, K., Tomita, M., Giehl, T. J., and Ellison, R. T., III. Antibacterial activity of lactoferrin and a pepsin-derived lactoferrin peptide fragment, Infect. Immun. 61: 719-728, 1993.
40. Petschow, B. W., Talbott, R. D., and Batema, R. P. Ability of lactoferrin to promote the growth of Bifidobacterium spp. in vitro is independent of receptor binding capacity and iron saturation level, J. Med. Microbiol. 48: 541-549, 1999.
41. Boes, M., Prodeus, A. P., Schmidt, T., Carroll, M. C., and Chen, J. A critical role of natural immunoglobulin in immediate defense against systemic bacterial infection, J. Exp. Med. 188: 2381-2386, 1998.
42. Tsuda, H., Sekine, K., Ushida, Y., Kuhara, T., Takasuka, N., Iigo, M., Han, B. S., and Moor, M. A. Milk and dairy products in cancer prevention: focus on bovine lactoferrin, Mutat. Res. 462: 227-233, 2000.
43. Iigo, M., Kuhara, T., Ushida, Y., Sekine, K., Moore, M. A., and Tsuda, H. Inhibitory effects of bovine lactoferrin on colon carcinoma 26 lung metastasis in mice. Clin. Exp. Metastasis 17: 35-40, 1999.
44. Ushida, Y., Sekine, K., Kuhara, T., Takasuka, N., Iigo, M., and Tsuda, H. Inhibitory effects of bovine lactoferrin on intestinal polyposis in the Apc(Min) mouse, Cancer Lett. 134: 141-145, 1998.
45. Ushida, Y., Sekine, K., Kuhara, T., Takasuka, N., Iigo, M., Maeda, M., and Tsuda, H. Possible chemopreventive effects of bovine lactoferrin on esophagus and lung carcinogenesis in the rat, J. Cancer Res. 90: 262-267, 1999.
46. Zhang, X. and Beynen, A. C. Lowering effect of dietary milk-whey protein v. casein on plasma and liver cholesterol concentrations in rats, Br. J. Nutr. 70: 139-146, 1993.
47. Beena, A. and Prasad, V. Effect of yogurt and bifidus yogurt fortified with skim milk powder, condensed whey and lactose-hydrolysed condensed whey on serum cholesterol and triacylglycerol levels in rats, J. Dairy Res. 64: 453-457, 1997.
48. Bounous, G., Gervais, F., Amer, V., Batist, G., and Gold, P. The influence of dietary whey protein on tissue glutathione and the diseases of aging, Clin. Invest. Med. 12: 343-349, 1989.
49. Guimont, C., Marchall, E., Girardet, J. M., and Linden, G. Biologically active factors in bovine milk and dairy byproducts: influence on cell culture, Cril. Rev. Food Sci. Nutr. 37: 393-410, 1997.
50. Tomé, D. Bioactive proteins and peptides from milk: potential health benefits in milk and health. In: Salminen, K., Ed. Proceedings of the 25th International Dairy Congress. Aarhus, Denmark: Silkeborg Bogtryk, 163-181, 1999.
51. Koldovsky O. and Goldman A. S. Growth factors and cytokines in milk. In: Ogra, P. L., Mestecky, J., Lamm, M. E., Strober, W., Bienenstock, J., and McGhee, J. R., Eds., Mucosal Immunology, 2nd ed., San Diego, CA. Academic Press, 1999, 1523-1530.
52. McCuskey, R. S., Nishida, J., McDonnell, D., Williams, C., and Koldovsky, O. Effect of milk-borne epidermal growth factor upon the hepatic microcirculation and Kupffer cell function in suckling rats, Biol. Neonate 71: 202-206, 1997.
53. Ma, L. and Xu, R. J. Oral insulinlike growth factor-I stimulates intestinal enzyme maturation in newborn rats, Life Sci. 61: 51-58, 1997.
54. Krishnaraj, R., Zaks, A., and Unterman, T. Relationship between plasma IGF-I levels, in vitro correlates of immunity, and human senescence, Clin. Immunol. Immunopathol. 88: 264-270, 1998.
55. Hashimoto K. and Shimizu M. Epithelial properties of human intestinal Caco-2 cells cultured in a serum-free medium, Cytotechnology 13: 175-184, 1993.
56. Playford, R. J., MacDonald, C. E., and Johnson, W.S. Colostrum and milk-derived peptide growth factors for the treatment of gastrointestinal disorders, Am J. Clin. Nutr. 72: 5-14, 2000.
57. Coe, C. L., Lubach, G. R., and Karaszewski, J. W. Prenatal stress and immune recognition of self and nonself in the primate neonate and tolerance to various antigens, Biol. Neonate 76: 301-310, 1999.
58. Labeta, M. O., Vidal, K., Mores, J. E. R., Arias, M., Vita, N., Morgan, B. P., Guillemot, J. C., Loyaux, D., Ferrara, P., Schmid, D., et al. Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14, J. Exp. Med. 191: 1807-1812, 2000.
59. Thoreux, K. and Schmucker, D. L. Kefir milk enhances intestinal immunity in young but not old rats, J. Nutr. 2001 (in press).
60. Newburg, D. S. Do the binding properties of oligosaccharides in milk protect human infants from gastrointestinal bacteria? J. Nutr. 127(5 Suppl.): 980S-984S, 1997.
61. Newburg, D. S. Human milk glycoconjugates that inhibit pathogens, Curr. Med. Chem. 6: 117-127, 1999.
62. Wu, X., Tolvanen, J. P., Hutri-Kahonen, N., Kahonen, M., Makynen, H., Korpela, R., Ruskoaho, H., Karjala, K., and Porsti, I. Comparison of the effects of supplementation with whey mineral and potassium on arterial tone in experimental hypertension, Cardiovasc. Res. 40: 364-374, 1998.
63. Sandstrom, O., Mahdavi, J., and El-Salhy, M. Effect of ageing on colonic endocrine cell population in mouse, Gerontology 44: 324-330, 1998.
64. Baruchel, S. and Viau, G. In vitro selective modulation of cellular glutathione by a humanized native milk protein isolate in normal cells and rat mammary carcinoma model, Anticancer Res. 16(3A): 1095-1099, 1996.
65. National Cholesterol Education Program, Report of the national cholesterol education program expert panel on detection, evaluation and treatment of high blood cholesterol in adults, Arch. Intern. Med. 148: 36-69, 1988.
66. Huff, M.W., Hamilton, R. M. G., and Carroll, K. K. Plasma cholesterol levels in rabbits fed low fat, cholesterol-free semipurified diets: effects of dietary proteins, protein hydrolysates and amino acid mixtures, Atherosclerosis 28: 187-195, 1979.
67. Richardson, M., Kurowska, E. M., and Carroll, K. K. Early lesion development in the aortas of rabbits fed low-fat, cholesterol-free, semipurified casein diet, Atherosclerosis 107: 165-178, 1994.
68. Ritzel, G., Stahelin, H. B., Schneeberger, H., Wanne, R. M., and Jost, M. Serum lipids in swine fed large quantities of whey, Int. J. Vitam. Nutr. Res. 49: 4419-4427, 1979.
69. Said, H. M., Ong, D. E., and Shingleton, J. L., Intestinal uptake of retinol: enhancement by bovine milk beta-lactoglobulin, Am. J. Clin. Nutr. 49: 690-694, 1989.
70. Ali, S. and Clark, A. J. Characterization of the gene encoding ovine beta-lactoglobulin, J. Mol. Biol. 199: 415-426, 1988.
71. Perez, M. D. and Calvo, M. Interaction of beta-lactoglobulin with retinol and fatty acids and its role as a possible biological function for this protein: a review, J. Dairy Sci. 78: 978-988, 1995.
72. Narayan, M. and Berliner, L. J. Fatty acids and retinoids bind independently and simultaneously to beta-lactoglobulin, Biochemistry 36: 1906-1911, 1997.
73. Wu, S. Y., Perez, M. D., Puyol, P., and Sawyer, L. β-Lactoglobulin binds palmitate within its central cavity, J. Biol. Chem. 274: 170-174, 1999.
74. Tawa, N. E., Jr. and Goldberg, A. L. Suppression of muscle protein turnover and amino acid degradation by dietary protein deficiency, Am. J. Physiol. 263 (2 Pt. 1): E317-325, 1992.
75. Michael, J. G., Ringenback, R., and Honenstein, S. The antimicrobial activity of human colostral antibody in the newborn, J. Infect. Dis. 124: 445-448, 1971.
76. Seyfert, H. M., Tuckoricz, A., Interthal, H., Koczan, D., and Hobom, G. Structure of the bovine lactoferrin-encoding gene and its promoter, Gene 143: 265-269, 1994.
77. Goodman, R. E. and Schanbacher, F. L. Bovine lactoferrin mRNA: sequence, analysis, and expression in the mammary gland, Biochem. Biophys. Res. Commun. 180: 75-84, 1991.
78. Al-Mashikhi, S. A. and Nakai, S. Isolation of bovine immunoglobulins and lactoferrin from whey proteins by gel filtration techniques, J. Dairy Sci. 70: 2486-2492, 1987.
79. Kirstila, V., Lenander-Lumikari, M., Soderling, E., and Tenovuo, J. Effects of oral hygiene products containing lactoperoxidase, lysozyme, and lactoferrin on the composition of whole saliva and on subjective oral symptoms in patients with xerostomia, Acta Odontol. Scand. 54: 391-397, 1996.
80. Ward, P. P., Piddington, C. S, Cunningham, G. A., Zhou, X., Wyatt, R. D., and Conneely, O. M. A system for production of commercial quantities of human lactoferrin: A broad spectrum natural antibiotic, BioTechnology 13: 498-503, 1995.
81. Yoo, Y.C., Watanabe, R., Koike, Y., Mitobe, M., Shimazaki, K., Watanabe, S., and Azuma, I. Apoptosis in human leukemic cells induced by lactoferricin, a bovine milk protein-derived peptide: involvement of reactive oxygen species, Biochem. Biophys. Res. Commun. 237: 624-628, 1997.
82. Howard, J. B. and Rees, D. C. Perspectives on nonheme iron protein chemistry. Adv. Protein Chem. 42: 199-280, 1991.
83. Moore, S. A., Anderson, B. F., Groom, C. R., Haridas, M., and Baker, E. N. Three dimensional structure of diferric bovine lactoferrin at 2.8 Å resolution, J. Mol. Biol. 274: 222-236, 1997.
84. Karthikeyan, S., Sharma, S., Sharma, A. K., Paramasivam, M., Yadav, S., Srinivasan, A., and Singh, T. P. Structural variability and functional convergence in lactoferrins, Curr. Sci. (Bangalore) 77: 241-255, 1999.
85. Brock, J. H. Lactoferrin in human milk: Its role in iron absorption and protection against enteric infection in the newborn infant, Arch. Dis. Childhood 55: 417-42, 1980.
86. Moreau, M. C., Duval-Iflah, Y., Muller, M. C., Raibaud, P., Vial, M., Gabilan, J. C., and Daniel, N. Effect of orally administered bovine lactoferrin and bovine IgG on the establishment of Eacherichia coli in the digestive tract of gnotobiotic mice and human newborn infants, French. Annal. Microbiol. 134B: 429-441, 1983.
87. Kruzel, M. L., Harari, Y., Chen, C. Y., and Castro, G. A. Lactoferrin protects gut mucosal integrity during endotoxemia induced by lipopolysaccharide in mice, Inflammation 24: 33-44, 2000.
88. Ellison, R. T., III, Giehl, T. J., and LaForce, F. M. Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin. Infect. Immun. 56: 2774-2781, 1988.
89. Bellamy, W., Takase, M., Wakabayashi, H., Kawase, K., and Tomita, M. Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin, J. Appl. Bacteriol. 73: 472-479, 1992.
90. Tomita, M., Takase, M., Bellamy, W., and Shimamura, S. A review: the active peptide of lactoferrin, Acta Paediatr. Jpn. 36: 585-591, 1994.
91. Tomita, M., Bellamy, W., Takase, M., Yamauchi, K., Wakabayashi, H., and Kawase, K. Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin, J. Dairy Sci. 74: 4137-4142, 1991.
92. Erdei, J., Forsgren, A., and Satyanarayan-Naidu, A. Lactoferrin binds to porins OmpF and OmpC in Escherichia coli, Infect. Immun. 62: 1336-1340, 1993.
93. Kishore, A. R., Erdei, J., Naidu, S. S., Falsen, E., Forsgren, A., and Naidu, A. S. Specific binding of lactoferrin to Aeromonas hydrophila, FEMS-Microbiol. Lett. 83: 115-120, 1991.
94. Siemion, I. Z., Slon, J., and Wieczorek, Z. The immunosuppressive mini-domain of human lactoferrin, J. Peptide Sci. 1: 295-302, 1995.
95. Zimecki, M., Wlaszczyk, A., Cheneau, P., Brunel, A.S., Mazurier, J., Spik, G., and Kubler, A. Immunoregulatory effects of a nutritional preparation containing lactoferrin taken orally by healthy individuals, Arch. Immunol. Therap. Exp. (Warsz) 46: 231-240, 1998.
96. Adamik, B., Zimecki, M., Wlaszczyk, A., Berezowicz, P., and Kubler, A. Lactoferrin effects on the in vitro immune response in critically ill patients, Arch. Immunol. Ther. Exp. 46: 169-176, 1998.
97. Wong, C. W., Liu, A. H., Regester, G. O., Francis, G. L., and Watson, D. L. Influence of whey and purified whey proteins on neutrophil functions in sheep, J. Dairy Res. 64: 281-288, 1997.
98. Wong, C. W., Seow, H. F., Husband, A. J., Regester, G. O., and Watson, D. L. Effects of purified bovine whey factors on cellular immune functions in ruminants, Vet. Immunol. Immunopathol. 56: 85-96, 1997.
99. Fleet, J. C. A new role for lactoferrin: DNA binding and transcription activation, Nutr. Rev. 53: 226-227, 1995.
100. Nichols, B. L., McKee, K. S., Henry, F. F., Heubers, H. A., and Putman, M. Human lactoferrin stimulates thymidine incorporation into the DNA of rat crypt cells, Pediat. Res. 21: 563-567, 1987.
101. Azuma, N., Mori, H., Kaminogawa, S., and Yamauchi, K. Stimulatory effect of human lactoferrin on DNA synthesis in BALB/c 3T3 cells, Agric. Biol. Chem. 53: 31-35, 1989.
102. Kohno, Y., Shiraki, K., Mura, T., and Ikawa, S. Iron-saturated lactoferrin as a comitogenic substance for neonatal rat hepatocytes in primary cultures, Acta Paediatr. 82: 650-655, 1993.
103. Hagiwara, T., Shinoda, I., Fukuwatari, Y., and Shimamura, S. Effects of lactoferrin and its peptides on proliferation of rat intestinal epithelial cell line. IEC-18, in the presence of epidermal growth factor, Biosci. Biotech. Biochem. 59: 1875-1881, 1995.
104. Oguchi, S., Walker, W. A., and Sanderson, I. R. Iron saturation alters the effect of lactoferrin on the proliferation and differentiation of human enterocytes (Caco-2 cells), Biol. Neonate 67: 330-339, 1995.
105. Hashizume, S., Kuroda, K., and Murakami, K. Identification of lactoferrin as an essential growth factor for human lymphocytic cell lines in serum-free medium, Biochim. Biophys. Acta 763: 377-382, 1983.
106. Mazurier, J., Legrand, D., Hu, W. L., Montreuil, J., and Spik. Expression of human lactoferrin receptors in phytohemagglutimn-stimulated human peripheral blood lymphocytes, Eur. J. Biochem. 179: 481-497, 1989.
107. Bennett, R. M. and Davis, J. Lactoferrin binding to human peripheral blood cells: an interaction with a B-enriched population of lymphocytes and a subpopulation of adherent mononuclear cells, J. Immunol. 127: 1211-1216, 1981.
108. Sato, K., Shinmoto, H., Tanimoto, M., Dosako, S., and Nakajima, I. Uptake and secretion of human lactoferrin by B lymphocytes, Agric. Biol. Chem. 54: 1275-1279, 1990.
109. Hu, W. L., Mazurier, J., Sawatzki, G., Montreuil, J., and Spik, G. Lactoferrin receptor of mouse small intestinal brush border, Biochem. J. 248: 435-441, 1988.
110. Eda, S., Kikugawa, K., and Beppu, M. Characterization of lactoferrin binding proteins of human macrophages membrane: multiple species of lactoferrin-binding proteins with polylactosamine-binding activity, Biol. Pharmaceut. Bull. 20: 127-133, 1997.
111. McAbee, D. D. and Ling, Y. Y. Iron-loading of cultured adult rat hepatocytes reversibly enhances lactoferrin binding and endocytosis, J. Cell. Physiol. 171: 75-86, 1997.
112. Zimecki, M., Mazurier, J., Machnicki, M., Wieczorek, Z., Montreuil, J., and Spik, G. Immunostimulatory activity of lactotransferrin and maturation of CD4-CD*-murine thymycytes, Immunol. Lett. 30: 119-124, 1991.
113. Debbabi, H., Dubarry, M., Rautureau, M., and Tomé, D. Bovine lactoferrin induces both mucosal and systemic immune responses in mice, J. Dairy Res. 65: 283-293, 1998.
114. Crouch, S. P., Slater, K. J., and Fletcher, J. Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin, Blood 80: 235-240, 1992.
115. Machnicki, M., Zimecki, M., and Zagulski, T. Lactoferrin regulates the release of tumor necrosis factor alpha and interleukin 6 in vivo, Int. J. Exp. Pathol. 74: 433-439, 1993.
116. Paul-Eugéne, N., Dugas, B., Kolb, J.-P., Damais, C., Braquet, P., Paubert-Braquet, M., and Rialland, J.-P. Effets immunomodulateurs et anti-oxydants de la lactoferrine bovine chez l'homme. Comptes Rendus de l'Academie des Sciences Serie III-Sciences de la Vie 316: 113-119, 1993.
117. Zimecki, M., Mazurier, J., Spik, G., and Kapp, J. A. Human lactoferrin induces phenotypic and functional changes in murine splenic cells, Immunology 86: 122-127, 1995.
118. Zimeki, M., Mazurier, J., Spik, G., and Kapp, J. A. Lactoferrin inhibits proliferative responses and cytokine production of Th1 but not Th2 cell lines, Arch. Immunol., Therap. Exp. (Warsz) 44: 51-56, 1996.
119. Renner, E., Ed., Micronutrients in Milk and Milk-based Food Products. New York, Elsevier Science, 1989.
120. Bjorck, L. Antibacterial activity of the lactoperoxidase system in milk against pseudomonads and other Gram-negative bacteria, Appl. Microbiol. 30: 199-204, 1975.
121. Bjorck, L. Antibacterial effect of the lactoperoxidase system on psychotrophic bacteria in milk, J. Dairy Res. 45: 109-118, 1978.
122. Hirano, R., Hirano, M., Oooka, M., Dosako, S., Nakajima, I., and Igoshia, K. Lactoperoxidae effects on rheological properties of yogurt, J. Food Sci. 63: 35-38, 1998.
123. Barrett, N. E., Grandison, A. S., and Lewis, M. J. Contribution of the lactoperoxidase system to the keeping quality of pasteurized milk, J. Dairy Res. 66: 73-80, 1999.
124. Champagne, C. P., Laing, R. R., Roy, D., Mafu, A. A., and Griffiths, M. W. Psychrotrophs in dairy products: their effects and their control, Crit. Rev. Food Sci. Nutr. 34: 1-30, 1994.
125. Hoogendoorn, H. and Moorer, W. R. Lactoperoxidase in the prevention of plaque accumulation, gingivitis and dental caries. I. Effect on oral streptococci and lactobacilli, Odontologisk Revy 24: 355-366, 1973.
126. Yang, S. T. and Silva, E. M. Novel products and new technologies for use of a familiar carbohydrate, milk lactose, Dairy Sci. 78: 2541-2562, 1995.
127. Ito, M., Kimura, M., Deguchi, Y., Miyamori-Watabe, A., Yajima, T., and Kan, T. Effects of transgalactosylated disaccharides on the human intestinal microflora and their metabolism, J. Nutr. Sci. Vitaminol. (Tokyo) 39: 279-288, 1993.
128. Young, J. European market developments in prebiotic- and probiotic-containing foodstuffs, Br. J. Nutr. 80: S231-233, 1998.
129. Vaghela, M. and Kilara, A. Lipid composition of whey protein concentrates manufactured commercially and in the laboratory, J. Dairy Sci. 79: 1172-1183, 1996.
130. Vesper, H., Schmelz, E.-M., Nikolova-Karakashian, M. N., Dillehay, D. L., Lynch, D. V., and Merrill, A. H., Jr. Sphingolipids in food and the emerging importance of sphingolipids to nutrition, J. Nutr. 129: 1239-1250, 1999.
131. Parodi, P. W. A role for milk proteins in cancer prevention, Aust. J. Dairy Technol. 53: 37-47, 1998.
132. Nyberg, L., Farooqi, A., Blackberg, L., Duan, R.-D., Nilsson, A., and Hernell, O. Digestion of ceramide by human milk bile salt-stimulated lipase, J. Pediatr. Gastroenterol. Nutr. 27: 560-567, 1998.
133. Dillehay, D. L., Webb, S. K., Schmelz, E. M., and Merrill, A. H., Jr. Dietary sphingomyelin inhibits 1,2-dimethylhydrazine-induced colon cancer in CF1 mice, J. Nutr. 124: 615-620, 1994.
134. Schmelz, E. M., Dillehay, D. L., Webb, S. K., Reiter, A., Adams J., and Merrill, A. H., Jr. Sphingomyelin consumption suppresses aberrant colonie crypt foci and increases the proportion of adenomas versus adenocarcinomas in CF1 mice treated with 1,2-dimethylhydrazine: implications for dietary sphingolipids and colon carcinogenesis, Cancer Res. 56: 4936-4941, 1996.
135. Schmelz, E. M., Bushnev, A. S., Dillehay, D. L., Liotta, D. C., and Merrill, A. H., Jr. Suppression of aberrant colonie crypt foci by synthetic sphinogmyelins with saturated or unsaturated sphingoid base backbones, Nutr. Cancer 28: 81-85, 1997.
136. Hiraiwa, M., O'Brien, J. S., Kishimoto, Y., Galdzicka, M., Fluharty, A. L., Ginns, E. I., and Martin, B. M. Isolation characterization, and proteolysis of human prosaposin, the precursor of saposins (sphingolipid activator proteins), Arch. Biochem. Biophys. 304: 116-116, 1993.
137. Pattern, S., Carson, G. S., Hiraiwa, M., O'Brien, J. S., and Sano, A. Prosaposin, a neurotrophic factor: presence and properties in milk, J. Dairy Sci. 80: 264-272, 1997.
138. O'Brien, J. S., Carson, G. S., Seo, H. C., Hiraiwa, M., and Kishimoto, Y. Identification of prosaposin as a neurotrophic factor, Proc. Natl. Acad. Sci. USA 91: 9593-9596, 1994.