Table Of ContentBIOACTIVE COMPONENTS
OF HUMAN MILK
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
EditorialBoard:
NATHAN BACK,State UniversityofNew YorkatBuffalo
IRUN R. COHEN, The WeivnannInstituteofScience
DAVIDKRITCHEVSKY, WistarInstitute
ABELLAJTHA,N. S. Kline Institutefor PsychiatricResearch
RODOLFOPAOLETTI, UniversityofMilan
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BIOACTIVE COMPONENTS
OF HUMAN MILK
Edited by
David S. Newburg
Shriver Center
Waltham, Massachusetts
andHarvardMedical School
Boston, Massachusetts
Kluwer Academic/Plenum Publishers
New York, Boston, Dordrecht, London, Moscow
LibraryofCongress Cataloging-in-PublicationData
Bioactivecomponentsofhumanmilk/editedby DavidS. Newburg.
p. em.- (Advances inexperimental medicineand biology; v. 501)
Includes bibliographicalreferences and index.
ISBN0-306-46653-8
1. Breastmilk-Composition. 2. Breastmilk-Physiologicaleffect. L Newburg, David
S. II. Series.
QP246 .B625 2001
612.6'64-dc21
2001038550
Proceedingsofthe8thInternational ConferenceofTheInternational Society for Research on Human Milk
and Lactation,heldOctober25-29, 1997,in Plymouth,Massachusetts
ISBN0-306-46653-8
©2001 KluwerAcademic/PlenumPublishers, New York
233 Spring Street,New York, N.Y. 10013
http://www.wkap.nl/
1098765432
AC.LP. record for this bookis availablefrom the LibraryofCongress
All rights reserved
Nopartofthis bookmay bereproduced, storedinaretrievalsystem, ortransmittedinany form orbyany
means,electronic,mechanical, photocopying, microfilming, recording, orotherwise,without written
permissionfrom the Publisher
Dedicated to
Richard Kuhn
Icie Macy
Paul Gy6rgy
... we walk in thefootsteps ofgiants
PREFACE
Although breast-feedinghas long been associated with lowered infant morbid
ity and mortality from infectious disease, until relatively recently little was known
regarding the individual components of human milk aside from their nutritive func
tions and the presence of secretory antibodies. Over the last40 years, and especially
over the last decade, evidence has been growing that human milk contains a large
number of materials that are bioactive and that are not found in artificially formu
latedinfantdiets. Disparatelinesofresearcharecurrentlyproducingsurprisinglylong
listsofnewlyrecognizedhumanmilkcomponents-antimicrobialsandimmunomod
ulators,includinganti-inflammatoryagents,antioxidants,cytokines,andhormones
with biological activities that relate to pathogenesis, inflammation, development,
metabolic regulation, and otherfunctions. The sumof all of these biologicallyactive
milk components may account for the strong protection that human milk affords
nursing infants.
Strictlyspeaking, mostcomponents of human milkcould beconsideredbioac
tive, sincenutrientsare bioactivebydefinition. A majoremphasis ofthis book, how
ever, is on defining what is known about components of human milk that inhibit
commonpathogensofthe infant, those that have hormonal and/orcytokineactivity,
those that have immunomodulatory and/or anti-inflammatory activity, xenobiotics,
and nutrients that are uniquely essential to early development.
The topic of bioactive substances in human milk was explored in depth at the
8th International Conference of the International Society for Research on Human
Milk and Lactation (ISRHML) held at Plymouth, Massachusetts, October 25-29,
1997. This bookcontains the proceedings of thatconference.
ThefriendsoftheISRHMLaregratefullyacknowledgedfortheirgenerousspon
sorshipofourmeetingandcontinuedsupportoftheISRHMLmissionofpromoting
excellence in research and disseminatingcurrent, accurate information on human milk
andlactation:
The Public Health Service participated in the support of this meeting under
grant #IR13 HD35622, from the National Institute of Child Health and Human
vii
viii Preface
Development and the National Institute of Diabetes and Digestive and Kidney Dis
eases. Private help came from the H.J. Heinz Company Foundation, Wyeth-Ayerst
Research, the National Institute of Child Health and Human Development, the
National Institute of Diabetes and Digestive and Kidney Diseases, Ross Products
Division of Abbott Laboratories, Mead-Johnson Nutritional Group, Neose Tech
nologies, Inc., Milupa, Nestle USA, The Gerber Foundation, and Genzyme Trans
genies Corporation. Their support made this book possible.
Assistance in editing this book was graciously provided by Kathryn Newburg,
Louise Kittredge, and Drs. Richard Schanler, Katherine Dewey, Armond Goldman,
Larry K Pickering, Ardythe L Morrow, Thomas G Cleary, and Mary Jacewicz.
I hope that this book will help to define important research agendas in the
emerging area of bioactive substances in human milk and contribute to ourappreci
ation and understanding of unique human milk components.
David SNewburg
Program in Glycobiology
Eunice Kennedy Shriver Center
Waltham, Massachusetts
andHarvard Medical School
Boston, Massachusetts
CONTENTS
SECTION I. INTRODUCTION
1. Bioactive components of human milk: Evolution, efficiency,
and protection 3
David SNewburg
2. Human milk and the response of intestinal epithelium to infection 11
Kathrin Bernt and W Allan Walker
Introduction to the Macy-Gyorgy award lecture 31
David SNewburg
3. MUCI and MUC-X, epithelial mucins of breast and milk. . . . . . . . . . . 35
Stuart Patton
4. Drug transport into milk 47
Patrick J McNamara
SECTION II. HORMONES AND GROWTH FACTORS IN
MAMMARY DEVELOPMENTAND IN MILK
Overview: Hormones and growth factors . . .. . . . . . .. . .. . . . . . . . . . . . . . 59
David SNewburg
5. The transforming growth factors beta in development and functional
differentiation of the mouse mammary gland 61
Charles W Daniel, Stephen Robinson, and Gary BSilberstein
6. Is milk a conduit for developmental signals? 71
Kevin D Nusser and L Stephen Frawley
7. Regulation of cell apoptosis by insulin-like growth factor I 79
Darryl L Hadsell and Ghada Abdel-Fattah
ix
x Contents
8. Human milk contains detectable levels of immunoreactive leptin . . . ... 87
Robert E Lyle, Stephen C Kincaid, Janet C Bryant, Audra M Prince,
and Robert E McGehee Jr
9. Induction ofexpression of branched-chain aminotransferase and alpha-
keto acid dehydrogenase in rat tissues during lactation . . . . . .. . . . . .. . 93
Soledad DeSantiago, NimbeTorres, Susan Hutson,
and Armando R Tovar
10. A low-fat diet but not food restriction improves lactational performance
in obese rats . . . . . . . . . . . .. . . . . . . . . .. . .. .. . . . . . .. . . . . . .. ... 101
KatWeen M Rasmussen, Mary H Wallace, and Effie Gournis
11. Human1actoferrin in the milk of transgenic mice increases intestinal
growth in ten-day-old suckling neonates 107
P Zhang, VSawicki, A Lewis, L Hanson, JH Nuijens, and MC Neville
12. Growth rates of a human colon adenocarcinoma cell line are regulated by
the milk protein alpha-lactalbumin 115
Lisa G Sternhagen and Jonathan CAllen
SECTION III. MILK LIPIDS AND THE MILK FAT GLOBULE
Overview: Milk lipids 123
David SNewburg
13. Assembly and secretion of the lipid globules of milk 125
Thomas W Keenan
14. Prolonged breast-feeding (six months or more) and milk fat content at
sixmonths are associated with higher developmental scores at
one year of age within a breast-fed population 137
C Agostoni, F Marangoni, M Giovannini, C Galli,and E Riva
15. Presence ofcarotenoid, an anticarcinogenicmarker, in nipple aspirates
postlactation 143
Chandice Covington, Anne Mitchell-Gieleghem, David Lawson,
Isao Eto, and Clinton Grubbs
16. The anticarcinogenicconjugated fatty acid c9, t11-C18:2, or rumenic acid,
in human milk: Amounts and effects . . . .. . .. . . . .. . . . . .. . . . . . .. . 153
Robert G Jensen and Carol Lammi-Keefe
17. Long-chain polyunsaturated fatty acid concentrations in human hindmi1k
are constant throughout twelve months of lactation 157
C Agostoni, F Marangoni, AM Lammardo, C Galli, M Giovannini,
and E Riva
Contents xi
18. Parenteral infusion of a lactatingwoman with intralipid: Changes in milk
and plasma fatty acids 163
Robert G Jensen, Carol J Lammi-Keefe, Maureen MacBurney,
and Vasuki Wijendran
19. Investigation of long-chain polyunsaturated fatty acid metabolism in
lactating women by means of stable isotope techniques . . . . . . . . . . . . . 169
H Demmelmair, M Baumheuer, BKoletzko, K Dokoupil, and G Kratl
20. Structural and functional aspects of three major glycoproteins of the
human milk fat globule membrane 179
Jerry A Peterson, Ciaran D Scallan, Roberto L Ceriani,
and Margit Hamosh
21. Anti-infectious properties of the human milk fat globule membrane 189
H Schroten, M Bosch, R Nobis-Bosch, H Koehler, F-G Hanisch,
and R Plogmann
SECTION IV IMMUNOMODULATORYAND
ANTI-INFLAMMATORY AGENTS IN MILK
Overview: Immunomodulatory and anti-inflammatory agents 195
David SNewburg
22. Homeostasis of the mucosal immune system: Human milk and lactation 197
Jiri Mestecky
23. Anti-inflammatory characteristics of human milk: How, where, why 207
E Stephen Buescher
24. Development of a topical vaginal microbicide: Lessons learned from
human milk 223
Charles E Isaacs,Raju Pullarkat, and Richard Kascsak
25. Does human lactoferrin in the milk of transgenic mice deliver iron to
suckling neonates? 233
Linda H Hanson, Valerie Sawicki, Andrew Lewis, Jan H Nuijens,
Margaret C Neville, and Peifang Zhang
26. Changes in lactoferrin and lysozyme levels in human milk during thefirst
twelve weeks of lactation 241
P Montagne, ML Cuilliere, C Mole, MC Bene, and G Faure
27. The association of allergic sensitization in mother and child in breast-fed
and formula-fed infants 249
Anne L Wright, Debra A Stern, and Marilyn Halonen
