Vitamins/Nutritional Supplements

» optimal58 - Glyconutritionals and Implications on Fibromyalgia

Stephen Boyd, PhD, MD
Kathryn Dykman, MD
John Hall, DDS
Bill McAnalley, PhD
H. Reginald McDaniel, MD
Bob Ward, PED
Kia Gary, RN
Eric Moore, DChem
Jane Ramberg, MS
EXTERNAL EDITORIAL BOARD MANNATECH INCORPORATED
INTERNAL EDITORIAL BOARD
TECHNICAL STAFF
GRAPHIC ARTIST
Tom Gardiner, PhD
Global Health Safety Environment and
Regulatory Affairs Coordinator
Shell Chemical Company (Retired)
Houston, Texas
James C. Garriott, PhD, D-ABFT
Professor (Clinical Adjunct Faculty)
University of Texas Health Science Center
Consulting Toxicologist
San Antonio, Texas
Alice Johnson-Zeiger, PhD
Professor of Biochemistry (Retired)
University of Texas Health Center
Tyler, Texas
Doris Lefkowitz, PhD
Associate Clinical Professor of Microbiology
University of South Florida
College of Medicine
Tampa, Florida
Stanley S. Lefkowitz, PhD
Professor of Microbiology and Immunology
Texas Tech School of Medicine
Lubbock, Texas
Robert K. Murray, MD, PhD
Professor (Emeritus), Biochemistry
University of Toronto
Toronto, Ontario, Canada
Glyconutritional Implications in Fibromyalgia and
Chronic Fatigue Syndrome
Tom Gardiner, PhD
Bruce Peschel
EDITOR IN CHIEF
Eileen Vennum, RAC
ABSTRACT
In order to understand how the biological activities of
specific nutritional elements, such as glycoconjugate sugars,
relate to fibromyalgia/chronic fatigue syndrome (FM/CFS),
this review will first discuss what is known regarding the
possible causes and mechanisms of FM and CFS, and then
review which of those mechanisms involve glycoconjugate
sugars and complex carbohydrates. Although they are considered
by some clinicians as separate disorders with overlapping
symptoms, FM/CFS will be discussed together,
whenever possible, since affected systems are similar.
Scientific studies of the effects of specific glyconutritional
elements on FM/CFS are reviewed. Conclusions are then
summarized regarding nutritional implications in FM/CFS
patients. Most of the journal articles referenced in this
review were published in the last 3-5 years and represent the
most current information available on this topic.
INTRODUCTION
Fibromyalgia (FM) and chronic fatigue syndrome (CFS)
are two similar disorders with overlapping symptoms, such
as chronic fatigue, sleep disturbances, immune system dysfunction,
and psychological depression. FM is further characterized
by muscle and fibrous tissue pain, and its prevalence
has been estimated at greater than 7% in women aged
60-79 years and 3.4% for women vs. 0.5% for men in the
general population.1 Although accurate numbers are not
available for the prevalence of CFS, since definitive diagnosis
is more difficult, CFS mainly affects middle-aged females,
with a peak age of onset of 20-40 years.2 Even though
FM/CFS disorders affect several millions of people each year,
medical management and treatment consist mainly of education,
relief of discomfort, and improvement of quality of
sleep, exercise, and emotional balance.3
Since the cause(s) of FM/CFS and mechanism(s) for the
disorders are still unclear, it has not been possible for specific
drugs to be developed which would target a discreet,
causative, malfunction; only symptomatic drug therapy is
available. In fact, it appears that there are subpopulations
within these disorders that may have more or less involvement
of certain biologic systems (eg. immune, nervous,
muscular), which further complicates diagnosis and treatment
with conventional drugs.4 Some clinicians actually
prefer to think of FM/CFS as syndromes rather than discrete
diseases.5
With all these complexities, it is understandable that the
role of nutrition in FM/CFS has largely been overlooked.
However, since we now understand the importance of
dietary ingredients, such as the necessary glycoconjugate
sugars (mannose, galactose, fucose, glucose, N-acetylgalactosamine,
N-acetylglucosamine, sialic acid, xylose) and
complex carbohydrates in regulating the immune, nervous,
The Official Publication of
www.usa.GlycoScience.com: The Nutrition Science Site
Published by the Research and Development Department of Mannatech Incorporated, Coppell, Texas, USA. © 2000 All rights reserved.
JUNE 3, 2000 VOL 1, NO 21
PROVIDING SCIENTIFIC INFORMATION RELATED TO NUTRITIONAL SACCHARIDES AND OTHER DIETARY INGREDIENTS.
TM
The scientific information in this journal is educational and is not to be used as a substitute for a doctor's care or for proven therapy.
and muscular systems, as well as
cell-to-cell communications in general,
6, 7, 8, 9, 10, 11, 12, 13, 14, 15 it is not surprising
that the biological activities of
such nutritional elements play a significant
role in maintaining the
health of these systems. More specifically,
glycoproteins and glycolipids, containing one or
more of eight necessary sugars, function as receptors on the
surface of mammalian cells and invading pathogens. These
glycoconjugate sugar residues on the surface of one cell bind
to glycoconjugate receptors on another cell, which allows the
cells to communicate with one another.16 These communications
then result in other cellular events, such as secretion of
bioactive substances like interferon, interleukin-1 and complement,
17 phagocytosis of bacteria and cell debris18 and
inhibition of adherence necessary for bacterial infection.19
The principal symptoms of FM/CFS include muscle and
joint pain, chronic (> 6 months) fatigability, non-restorative
sleep, chronic tension and migraine headaches, and bowel
and bladder irritability.20, 21, 22 Due to the fatigue and pain
associated with movement, muscular systems are also significantly
affected in FM/CFS patients. For example, physical
and cardiovascular deconditioning is clearly evident in
some CFS patients. Findings include smaller left heart ventricles
and smaller diameter carotid arteries and changes in
serum cholesterol, triglycerides, and thyroid hormone levels,
consistent with physical deconditioning.23 Cardiovascular
deconditioning also explains changes in the autonomic
nervous system control of orthostatic blood pressure
in CFS patients.24
Several possible causes of FM/CFS have been proposed.
For example, it has been hypothesized that there is a relationship
between sleep disturbance and the pathogenesis of
FM/CFS, and that correction of the disturbed sleep pattern
can effect improvement in symptoms.2, 3 A strong association
with sleep disturbance is suggested by a) increased frequency
of non-restorative sleep, b) electroencephalographic
evidence of reduced deep non-REM sleep, and c) reproduction
of FM symptoms and painfully tender sites in normal
subjects by selective deprivation of non-REM sleep.20 It has
also been suggested that FM pain might be caused by muscle
microtrauma associated with sleep interference, and that
lower serum levels of the growth hormone, somatomedin C,
seen in FM patients, may affect their ability to heal from the
microtrauma.3 Somatomedin C is necessary for proper muscle
tissue repair and homeostasis and is produced during
non-REM (stage IV) sleep, which is decreased in FM/CFS.
Growth hormone response to hypoglycemia was reduced in
CFS patients, further suggesting a pathogenic role for the
hormone.25
With regard to a role for proper nutrition in this mechanism,
the necessary conjugate sugar, mannose, functions to
promote wound healing and tissue repair.26 Also, glycoconjugate
sugar residues form an essential part of the cellular
receptors to which many hormones bind in order to produce
their biological effects.17
Another possible cause of FM/CFS
is an imbalance of neurotransmitters.
27 For example, the amino acid
tryptophan is metabolized to serotonin,
an important neurotransmitter
in sleep and pain nerve pathways.
FM/CFS patients have reduced
plasma levels of both tryptophan
and serotonin and a higher density
of serotonin receptors on their circulating
blood platelets. These findings,
plus lower levels of serotonin-related amino acids and
lower cerebrospinal fluid levels of biogenic amines in FM
patients, suggest a possible deficit of serotonin metabolism
in FM/CFS patients. In fact, when serotonin is depleted,
there is a decrease in restorative non-REM sleep and an
increase in somatic complaints, depression, and perceived
pain.21, 28 Substance P, another neurotransmitter involved in
pain transmission, is believed to be inhibited by endorphins
(neuropeptides), which increase with exercise; this would
modulate pain and further indicate the importance of balance
of neurotransmitters in FM/CFS.21 In this regard, cerebrospinal
fluid levels of substance P were found to be threefold
higher in blood mononuclear cells of CFS patients,1
and endorphin concentrations were fivefold lower in CFS
patients.29 In addition, serotonin is known to influence pain
thresholds by interacting with substance P and potentiating
the effect of endorphins. It is possible that the tender points
in FM patients may be nothing more than normally tender
anatomic structures that become more tender when levels
of substance P fall.30 Interestingly, CFS is not characterized
by tender points, and differs from FM, in that substance P
levels are not elevated in cerebrospinal fluid from CFS
patients.31
The necessary conjugate sugars appear to be important in
modulating the activity of neurotransmitters. For example,
neurotransmitter transporters are cell membrane glycoproteins
that are responsible for termination of neurotransmission
impulses. It has been shown that N-glycosylation
(attachment of sugars to the nitrogen atom in the side chain
of asparagine) of these transporters is important for the stability
of the proteins that transport norepinephrine32 and
serotonin33 to appropriate membrane compartments.
Removal of essential sugar residues from the dopamine
(another neurotransmitter) transporter also results in
decreased dopamine uptake.34
Several virus groups, including herpes viruses, retroviruses,
and enteroviruses, and other pathogens have been implicated
in FM/CFS, because symptoms of these disorders are
often found associated with an active virus infection,35
although none is considered a uniquely causative agent of
the disorders.35, 36, 37 For example, Coxsackie B virus and herpes
virus6 have been identified in CFS patients by antibody
or actual virus presence. In fact, it has been postulated that
CFS patients may have a genetic predisposition to viral
infection.37 Enteroviral infection is a common feature of
some groups of CFS patients, and there is evidence for
enteroviral persistence in CFS patients.38 Chronic parvovirus
B19 infection has been observed in a CFS patient,39 and a
cytopathic stealth virus was cultured from the cerebrospinal
fluid of another CFS patient.40 CFS patients have also had
antibody titers to Epstein-Barr virus,
cytomegalovirus, herpes simplex
virus, and measles virus.35 Evidence
of lentivirus infection was also seen
GlycoScience Vol. 1, No. 21 June 3, 2000 2
...glycoproteins and glycolipids,
containing one or more of eight
necessary sugars, function as receptors
on the surface of mammalian cells and
invading pathogens.
The necessary conjugate sugars appear
to be important in modulating the
activity of neurotransmitters.
in CFS patients but not in controls.41
Other non-viral pathogens, such as
Mycoplasma, have been found with
some frequency in CFS patients.42
The frequency of Mycoplasma infection was found to be
52% in CFS patients and only 15% in healthy individuals.
Although Yersinia enterocolitica is unlikely to cause CFS, it
can persist in gut-associated lymphatic tissue and cause a
variety of CFS symptoms.
Glycoconjugate sugars have biological activities that can
prevent viral or bacterial infection in mammalian hosts. For
example, bacteria have sugar binding proteins (lectins) on
their surface, which bind glycoconjugate receptors on the
surface of mammalian host cells, resulting in attachment
and infection. Dietary galactose and glucose are also important
in maintaining normal colonic bacteria.43 In animals,
mannose blocks Salmonella typhimurium adherence to chicken
intestine in vitro44 and markedly reduces (50-100%) the
incidence of Salmonella infection in vivo when given to
chickens in their drinking water.45 Mannose reduces
Escherichia coli infection in newborn mice (from 77% normally
to 25% post-treatment) when a solution is applied
topically to maternal vaginas prior to delivery.46 Sialic acid
inhibited bacterial adhesion, due to its ability to modulate
cellular aggregation and attachment.47, 48 Glycoconjugate
sugars display anti-viral activity because of their ability to
stimulate macrophages to release interferon, and they also
inhibit glycosylation of the viral envelope and thereby
interfere with normal viral function (discussion of immune
system activities follow).
Considerable scientific evidence also suggests that
FM/CFS is related to immune system dysfunction, based on
measurements of various immune markers in patients with
the disorders. Although this does not imply causality, it supports
the hypothesis that the immune system is a pathogenetic
mechanism for FM/CFS.49 For example, the activity/
activation of natural killer lymphocytes (NK), which participate
in the immune defense system against a wide range
of pathogens, especially viral infections, is decreased in CFS
patients.50, 51, 52 Cytokines, which are believed to play a role in
the fatigue and depression of CFS via their effects on the
central nervous system, pituitary, and gonadal hormones,
are increased in CFS. For example, production of interleukin-
6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)
increased and IL-10 decreased in CFS.53, 54 There was also
increased IL-1 activity by cells from CFS patients, that were
sensitive to the female hormones, estradiol and progesterone,
55 coincident with a greater frequency of FM/CFS in
females. Interestingly, the symptoms of CFS are similar to
the reactions observed in humans following infusion of
TNF-alpha and IL-1.56 A high frequency of autoantibodies
have also been reported in CFS
patients, suggesting that the disorder
may have an autoimmune
basis.57 However, other investigators
have been unable to detect consistent
or predictive changes in antimuscle
or anti-CNS circulating antibodies
in CFS.58, 59
Unfortunately, serum markers of
immune activation are of limited
diagnostic use in the evaluation of
FM/CFS patients,60 and some clinicians
have been unable to find any
important associations between
clinical status, treatment response, and immunological status.
61 The reasons for these discrepancies may be that there
are subsets of patients with different types of immune dysfunction.
For example, when patients were subgrouped by
type of disease onset (gradual or sudden) or by how well
they were feeling on the day of testing, more pronounced
differences were seen in various measures of immune function.
4
Since one of the most important biological activities of
the necessary glycoconjugate sugars and complex carbohydrates
is immune system modulation,14 any role that the
immune system might play in FM/CFS would logically be
influenced by these particular nutritional elements. In this
regard, mannose stimulates the migration of macrophages,
immune system cells that orchestrate the release of various
bioactive substances that modulate the immune response
and tissue inflammation and phagocytize bacteria and cell
debris.62 Acemannan, an acetylated mannose polysaccharide,
also enhances killing of Candida albicans by
macrophages.18 In one of the few studies in which possible
effects have actually been measured, FM/CFS patients who
consumed a nutritional supplement containing freeze-dried
aloe vera extract, which is rich in acetylated mannans,
reported significant improvement in their symptoms.63
A host of other immune-modulating effects are part of
the activities of glycoconjugate sugars. Mannose-containing
glycopeptides can also directly inhibit antigen-driven T-cell
responses.64 Galactose-containing glycoproteins induce
prostaglandin synthesis and directly stimulate IL-1, which
are involved in regulating mammalian inflammatory
responses.65 A galactose-containing polymer stimulates
macrophages and other immune system activities important
in resolving inflammation and in wound healing.62, 66 In
experimental animal studies, galactose conjugated to protein
decreases experimentally induced necrotizing gastritis
to a greater extent than antacids.67 Fucose stimulates rabbit
macrophages62 and inhibits neutrophil and macrophage
chemotactive factors, which are also important
immunomodulatory activities. If sialic acid residues are
removed from peripheral blood mononuclear cells, the multiplication
of HIV-1 is increased in vitro, possibly due to
decreased interferon secretion.68
Secondary FM has also been documented in patients with
rheumatoid arthritis, osteoarthritis, sleep apnea, irritable
bowel syndrome, and menstrual dysfunction.3 With regard
to rheumatoid arthritis, immunoglobulin-G in some
patients has fewer galactosyl residues; the reduction of
residues worsens with disease severity69
and reverses during symptomatic
remission.70
Since FM/CFS is considered to
have a strong psychological component,
it is important to consider
how the CNS can also modulate the
immune response and influence the
expression of latent viruses, and
how cytokine synthesis, NK cell
Glycoconjugate sugars have biological
activities that can prevent viral or
bacterial infection in mammalian hosts.
Since one of the most important
biological activities of the necessary
glycoconjugate sugars and complex
carbohydrates is immune system
modulation, any role that the immune
system might play in FM/CFS would
logically be influenced by these
particular nutritional elements.
GlycoScience Vol. 1, No. 21 June 3, 2000 3
activity, and T-lymphocyte function
relate to FM/CFS. These relationships
have been aptly described by
Drs. R. Glaser and J.K. Kiecolt-
Glaser35 as follows: Psychological
stress can stimulate release of corticotropin-
releasing hormone (CRH)
from the hypothalamus, which
leads to production of adrenocorticotropic hormone
(ACTH). ACTH stimulates the adrenal cortex to increase levels
of glucocorticoid hormones, which suppress the immune
response and can reactivate latent viruses. Glucocorticoid
hormones, ACTH and CRH have also been shown to
enhance viral replication in vitro. Other "stress" hormones,
such as prolactin and growth hormone, can act as immune
enhancers. Communication between the CNS and immune
system is bidirectional. For example, IL-1 can influence the
hypothalamus to modulate CRH production, and lymphocytes
can synthesize hormones such as ACTH, prolactin,
and growth hormone. The release of ACTH and cortisol
(glucocorticoid) was also found to be decreased in a group of
CFS patients, suggesting that other factors may also be
important in the pathogenesis of the disorder.71
CONCLUSION
Regardless of the precise mechanism(s) of pathogenesis
for FM/CFS, it should be clear from this review of the most
recent scientific and medical literature that the immune (eg.
cytokines, lymphocytes, virus infection),
endocrine (eg. hormones),
nervous (eg. neurotransmitters,
sleep pathways, psychological stress)
and muscular (eg. tender points, cardiovascular
deconditioning) systems
of the body are all intimately
involved in the FM/CFS syndrome.
It should also be apparent that the necessary glycoconjugate
sugars and complex carbohydrates all play important roles
in maintaining the health and normal functioning of these
systems. Moreover, dietary mannose (and, perhaps, other
necessary glycoconjugate sugars) has been shown to be well
absorbed and preferentially utilized for biosynthesis of glycoproteins
in humans.72 Maintenance of body health also
seems particularly important, considering the major medical
and pharmaceutical challenges of diagnosis and therapy
of FM/CFS and the long-term difficulties facing FM/CFS
patients. Certainly, the complex pathogenesis of FM/CFS
and variations in symptoms among individual patients
combine to challenge the medical understanding of these
debilitating syndromes.
GlycoScience Vol. 1, No. 21 June 3, 2000 4
...dietary mannose (and, perhaps, other
necessary glycoconjugate sugars) has
been shown to be well absorbed and
preferentially utilized for biosynthesis of
glycoproteins in humans.
REFERENCE LIST
1. Goldenberg DL. Fibromyalgia, chronic fatigue syndrome, and myofascial pain.
Curr Opin Rheumatol. 1996;8113-123.
2. McCluskey DR. Chronic fatigue syndrome: its cause and a strategy for management.
Comp Ther. 1998;24(8):357-363.
3. Cunningham ME. Becoming familiar with fibromyalgia.
Orthop.Nurs. 1996;15(2):33-36.
4. Mawle AC, Nisenbaum R, Dobbins JG. Immune responses associated with chronic fatigue syndrome: a case-control
study. J Infect Dis. 1997;175(1):136-141.
5. Goldenberg DL. What is the future of fibromyalgia? Rheum Dis Clin North Am. 1996;22(2):393-406.
6. Gardiner T. Dietary xylose: absorption, distribution, metabolism, excretion (ADME) and biological activity.
GlycoScience & Nutrition (Official Publication of GlycoScience.com: The Nutrition Science Site). 2000;1(5):1-2.
7. Gardiner T. Dietary fucose: absorption, distribution, metabolism, excretion (ADME) and biological activity.
GlycoScience & Nutrition (Official Publication of GlycoScience.com: The Nutrition Science Site). 2000;1(6):1-4.
8. Gardiner T. Dietary galactose: absorption, distribution, metabolism, excretion (ADME) and biological activity.
GlycoScience & Nutrition (Official Publication of GlycoScience.com: The Nutrition Science Site). 2000;1(7):1-4.
9. Gardiner T. Dietary N-acetylgalactosamine (GalNAc): absorption, distribution, metabolism, excretion (ADME) and
biological activity. GlycoScience & Nutrition (Official Publication of GlycoScience.com: The Nutrition Science Site).
2000;1(8):1-3.
10. Gardiner T. Dietary N-acetylglucomsamine (GlcNAc): absorption, distribution, metabolism, excretion (ADME) and
biological activity. GlycoScience & Nutrition (Official Publication of GlycoScience.com: The Nutrition Science Site).
2000;1(9):1-3.
11. Gardiner T. Dietary N-acetylneuraminic acid (NANA): absorption, distribution, metabolism, excretion (ADME) and
biological activity. GlycoScience & Nutrition (Official Publication of GlycoScience.com: The Nutrition Science Site).
2000;1(10):1-3.
12. Gardiner T. Dietary mannose: absorption, distribution, metabolism, excretion (ADME) of eight known dietary
monosaccharides required for glycoprotein synthesis and cellular recognition processes. GlycoScience & Nutrition
(Official Publication of GlycoScience.com: The Nutrition Science Site). 2000;1(11):1-5.
REFERENCE LIST (continued next page)
GlycoScience Vol. 1, No. 21 June 3, 2000 5
REFERENCE LIST (continued)
13. Gardiner T. Absorption, distribution, metabolism, and excretion (ADME) of eight known dietary monosaccharides
required for glycoprotein synthesis and cellular recognition processes: summary. GlycoScience & Nutrition (Official
Publication of GlycoScience.com: The Nutrition Science Site). 2000;1(12):1-7.
14. Gardiner T. Biological activity of eight known dietary monosaccharides required for glycoprotein synthesis and
cellular recognition processes: summary. GlycoScience & Nutrition (Official Publication of GlycoScience.com: The
Nutrition Science Site). 2000;1(13):1-4.
15. Gardiner T. Dietary glucose: absorption, distribution, metabolism, excretion (ADME) and biological activity.
GlycoScience & Nutrition (Official Publication of GlycoScience.com: The Nutrition Science Site). 2000;1(18):1-4.
16. Axford J. Glycobiology and medicine: an introduction. J R Soc Med. 1997;90(5):260-264.
17. Rademacher TW, Parekh RB, Dwek RA. Glycobiology. Ann Rev Biochem. 1988;57785-838.
18. Stuart RW, Lefkowitz DL, Lincoln JA, et al. Upregulation of phagocytosis and candidicidal activity of macrophages
exposed to the immunostimulant acemannan. Int J Immunopharmacol. 1997;19(2):75-82.
19. Adam EC, Mitchell BS, Schumacher DU, et al. Pseudomonas aeruginosa II lectin stops human ciliary beating:
therapeutic implications of fucose. Am J Respir Crit Care Med. 1997;155(6):2102-2104.
20. Doherty M, Jones A. Fibromyalgia syndrome. BMJ. 1995;310386-389.
21. Krsnich-Shriwise S. Fibromyalgia syndrome: an overview. Physical Therapy. 1997;77(1):68-75.
22. Reiffenberger DH, Amundson LH. Fibromyalgia syndrome: a review. Am Fam Physician. 1996;53(5):1698-1712.
23. De Lorenzo F, Xiao H, Mukherje M, et al. Chronic fatigue syndrome: physical and cardiovascular deconditioning.
Q J Med. 1998;91475-481.
24. Freeman R, Komaroff AL. Does the chronic fatigue syndrome involve the autonomic nervous system?
Am J Med. 1997;102357-364.
25. Allain TJ, Bearn JA, Coskeran P, et al. Changes in growth hormone, insulin, insulinlike growth factors (IGFs), and IGFbinding
protein-1 in chronic fatigue syndrome. Biol.Psychiatry. 1997;41567-573.
26. Kossi J, Peltonen J, Ekfors T, et al. Effects of hexose sugars: glucose, fructose, galactose and mannose on wound healing
in the rat. Eur Surg Res. 1999;31(1):74-82.
27. Parziale JR, Chen JJ. Fibromyalgia. Med.Health. 1996;79(5):188-192.
28. Simms RW. Fibromyalgia syndrome: current concepts in pathophysiology, clinical features, and management.
Arthritis Care Res. 1996;9(4):315-328.
29. Conti F, Pittoni V, Sacerdote P, et al. Decreased immunoreactive beta-endorphin in mononuclear leucocytes from
patients with chronic fatique syndrome. Clin.Exper.Rheumatol. 1998;16729-732.
30. Wilke WS. Fibromyalgia. Recognizing and addressing the multiple interrelated factors.
Postgrad.Med. 1996;100(1):153-156.
31. Evengard B, Nilsson CG, Lindh G, et al. Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated
substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome. Pain. 1998;78153-155.
32. Melikian HE, Ramamoorthy S, Tate CG, Blakely RD. Inability to N-glycosylate the human norepinephrine transporter
reduces protein stability, surface trafficking, and transport activity but not ligand recognition.
Mol.Pharmacol. 1996;50(2):266-276.
33. Tate CG, Blakely RD. The effect of N-linked glycosylation on activity of the Na(+)- and Cl(-)-dependent serotonin
transporter expressed using recombinant baculovirus in insect cells. J.Biol.Chem. 1994;269(42):26303-26310.
34. Zaleska MM, Erecinska M. Involvement of sialic acid in high-affinity uptake of dopamine by synaptosomes from rat
brain. Neurosci.Lett. 1987;82(1):107-112.
35. Glaser R, Kiecolt-Glaser JK. Stress-associated immune modulation: relevance to viral infections and chronic fatigue
syndrome. Am.J.Med. 1998;105(3A):35S-42S.
36. Vedhara K, Llewelyn MB, Fox JD, et al. Consequences of live poliovirus vaccine administration in chronic fatigue
syndrome. J.Neuroimmunol. 1997;75183-195.
37. Dickinson CJ. Chronic fatigue syndrome-aetiological aspects. Euro.J.Clin.Invest. 1997;27257-267.
38. Galbraith DN, Nairn C, Clements GB. Evidence for enteroviral persistence in humans. J.Gen.Virol. 1997;78307-312.
39. Jacobson SK, Daly JS, Thorne GM, McIntosh K. Chronic parvovirus B19 infection resulting in chronic fatigue
syndrome: Case history and review. Clin.Infect.Dis. 1997;241048-1051.
40. Martin WJ. Detection of RNA sequences in cultures of a stealth virus isolated from the cerebrospinal fluid of a health
care worker with chronic fatigue syndrome. Pathobiol. 1997;6557-60.
41. Holmes MJ, Diack DS, Easingwood RA, et al. Electron microscopic immunocytological profiles in chronic fatigue
syndrome. J.Psychiat.Res. 1997;31(1):115-122.
42. Choppa PC, Vojdani A, Tagle C, et al. Multiplex PCR for the detection of Mycoplasma fermentans, M. hominis and M.
penetrans in cell cultures and blood samples of patients with chronic fatigue syndrome.
Molec.Cell.Probes. 1998;12301-308.
43. Bouhnik Y, Flourie B, D'Agay-Abensour L, et al. Administration of transgalacto-oligosaccharides increases fecal
bifidobacteria and modifies colonic fermentation metabolism in healthy humans. J.Nutr. 1997;127(3):444-448.
REFERENCE LIST (continued next page)
GlycoScience Vol. 1, No. 21 June 3, 2000 6
REFERENCE LIST (continued)
44. Oyofo BA, DeLoach JR, Corrier DE, et al. Prevention of Salmonella typhimurium colonization of broilers with
D-mannose. Poult.Sci. 1989;68(10):1357-1360.
45. Oyofo BA, DeLoach JR, Corrier DE, et al. Effect of carbohydrates on Salmonella typhimurium colonization in broiler
chickens. Avian Dis. 1989;33(3):531-534.
46. Cox F, Taylor L. Prevention of Escherichia coli K1 bacteremia in newborn mice by using topical vaginal carbohydrates.
J.Infect.Dis. 1990;162(4):978-981.
47. Schauer R. Chemistry, metabolism, and biological functions of sialic acids.
Adv.Carbohydr.Chem.Biochem. 1982;40131-234.
48. Weinmeister KD, Dal Nogare AR. Buccal cell carbohydrates are altered during critical illness.
Am.J.Respir.Crit.Care Med. 1994;150(1):131-134.
49. Hassan IS, Bannister BA, Akbar A, et al. A study of the immunology of the chronic fatigue syndrome: correlation of
immunologic parameters to health dysfunction. Clin.Immunol.Immunopathol. 1998;87(1):60-67.
50. Levine PH, Whiteside TL, Friberg D, et al. Dysfunction of natural killer activity in a family with chronic fatigue
syndrome. Clin.Immunol.Immunopathol. 1998;88(1):96-104.
51. Whiteside TL, Friberg D. Natural killer cells and natural killer cell activity in chronic fatigue syndrome.
Am.J.Med. 1998;105(3A):27S-34S.
52. Ogawa M, Nishiura T, Yoshimura M, et al. Decreased nitric oxide-mediated natural killer cell activation in chronic
fatigue syndrome. Euro.J.Clin.Invest. 1998;28937-943.
53. Gupta S, Aggarwal S, See DL, Starr A. Cytokine production by adherent and non-adherent mononuclear cells in
chronic fatigue syndrome. J.Psychiat.Res. 1997;31(1):149-156.
54. Borish L, Schmaling K, DiClementi JD, et al. Chronic fatigue syndrome: identification of distinct subgroups on the
basis of allergy and psychologic variables. J.Allergy Clin.Immunol. 1998;102(2):222-230.
55. Cannon JG, St Pierre BA. Gender differences in host defense mechanisms. J.Psychiat.Res. 1997;31(1):99-113.
56. Cannon JG, Angel JB, Abad LW, et al. Interleukin-1B, interleukin-1 receptor antagonist, and soluble interleukin-1
receptor type II secretion in chronic fatigue syndrome. J.Clin.Immunol. 1997;17(3):253-261.
57. von Mikecz A, Konstantinov K, Buchwald DS, et al. High frequency of autoantibodies to insoluble cellular antigens in
patients with chronic fatigue syndrome. Arthritis Rheum. 1997;40(2):295-305.
58. Plioplys AV. Antimuscle and anti-CNS circulating antibodies in chronic fatigue syndrome. Neurol. 1997;481717-1719.
59. Natelson BH, LaManca JJ, Denny TN, et al. Immunologic parameters in chronic fatigue syndrome, major depression,
and multiple sclerosis. Am.J.Med. 1998;105(3A):43S-49S.
60. Buchwald D, Wener MH, Pearlman T, Kith P. Markers of inflammation and immune activation in chronic fatigue and
chronic fatigue syndrome. J.Rheumatol. 1997;24(2):372-376.
61. Peakman M, Deale A, Field R, et al. Clinical improvement in chronic fatigue syndrome is not associated with l
ymphocyte subsets of function or activation. Clin.Immunol.Immunopath. 1997;82(1):83-91.
62. Takata I, Chida K, Gordon MR, et al. L-fucose, D-mannose, L-galactose, and their BSA conjugates stimulate
macrophage migration. J.Leukoc.Biol. 1987;41(3):248-256.
63. Dykman KD, Ford CR: A longitudinal study of the effects of dietary supplements on the symptoms of fibromyalgia
and chronic fatigue syndrome. Proc.Annual Meet.Pavlovian Soc. 1998;(Abstract)
64. Muchmore AV, Sathyamoorthy N, Decker J, Sherblom AP. Evidence that specific high-mannose oligosaccharides can
directly inhibit antigen-driven T-cell responses. J.Leukoc.Biol. 1990;48(5):457-464.
65. Sathyamoorthy N, Decker JM, Sherblom AP, Muchmore A. Evidence that specific high mannose structures directly
regulate multiple cellular activities. Mol.Cell.Biochem. 1991;102(2):139-147.
66. Kelly GS. Larch arabinogalactan: clinical relevance of a novel immune-enhancing polysaccharide.
Altern.Med.Rev. 1999;4(2):96-103.
67. Lambelin G, Roba J. Curative activity of a sulphated polygalactoside (CP 1200) on experimental gastric ulcers in the
rat. Arch.Int.Pharmacodyn.Ther. 1974;211(1):18-23.
68. Stamatos NM, Gomatos PJ, Cox J, et al. Desialylation of peripheral blood mononuclear cells promotes growth of
HIV-1. Virol. 1997;228(2):123-131.
69. Malhotra R, Wormald MR, Rudd PM, et al. Glycosylation changes of IgG associated with rheumatoid arthritis can
activate complement via the mannose-binding protein. Nat.Med. 1995;1(3):237-243.
70. Flogel M, Lauc G, Gornik I, Macek B. Fucosylation and galactosylation of IgG heavy chains differ between acute and
remission phases of juvenile chronic arthritis. Clin.Chem.Lab.Med. 1998;36(2):99-102.
71. Scott LV, Medbak S, Dinan TG. Blunted adrenocorticotropin and cortisol responses to corticotropin-releasing hormone
stimulation in chronic fatigue syndrome. Acta.Psychiatr.Scand. 1998;97450-457.
72. Alton G, Hasilik M, Niehues R, et al. Direct utilization of mannose for mammalian glycoprotein biosynthesis.
Glycobiology. 1998;8(3):285-295.

-- posted by optimal58

Permalink Print Discussion Email Discussion Join the latest discussions