1 United States Department of
Agriculture/Agricultural Research Service, Children's Nutrition
Research Center, Department of Pediatrics, Baylor College of Medicine,
Houston, Texas 77030-2600;
2 Chelsea and Westminster
Hospital, Although several studies have shown that
asymptomatic human immunodeficiency virus infection elicits an increase
in whole body protein turnover, it is not known whether this increased protein turnover includes changes in the kinetics of acute-phase proteins (APPs). To answer this question, we measured
1) the plasma concentrations of four
positive (C-reactive protein,
acute-phase protein synthesis; symptom-free acquired
immunodeficiency syndrome; stable isotope
THE ACUTE-PHASE RESPONSE to the stress of injury or
infection is characterized by an increase in whole body protein
turnover plus an increased net loss of protein (2, 17). A fraction of
the increase in protein turnover is contributed by components of the
body's defense system. These include increased leukocyte proliferation
and synthesis of cytokines, immunoglobulins, and positive acute-phase
proteins (APPs; see Ref. 7). Reports of increased protein turnover in
humans with symptom-free acquired immunodeficiency syndrome (AIDS,
e.g., see Refs. 19 and 26) suggest that infection by the virus, in the
absence of clinical signs and symptoms, can elicit changes in protein
metabolism. It is not known, however, whether the increased
protein turnover in these individuals involves changes in the kinetics
of the APPs.
First, it is important to know whether infection by the virus alone
elicits an increase in the rate of synthesis of positive APPs, because
these proteins serve a variety of important functions related to
restoration of homeostasis when the integrity of the animal organism is
perturbed by injury or infection (18). These functions include the
containment and destruction of infectious agents by modulating T
lymphocyte function and the complement system, the repair of damaged
tissues, the protection of healthy tissues, the salvaging of useful
components released from damaged tissues, and the indirect alteration
of substrate metabolism via the induction of cytokine production (7,
18, 25).
Second, whereas the plasma concentrations of the positive APPs increase
in the acute-phase response to the stress of infection or injury, there
is a concomitant decrease in the concentrations of several
transport proteins, the so-called negative APPs (3, 6, 7, 18, 25). The
negative APPs are a diverse group that includes albumin, the
lipoproteins, transferrin, retinol-binding protein (RBP), and
transthyretin, just to name a few (3, 6,7,18,25). Adequate quantities
of these proteins are necessary for survival because they serve a
variety of functions that contribute to physiological and metabolic
homeostasis through the mechanisms of hemodynamics, transport, and
nutrition (7, 25). A reduction in transport proteins and the secondary
pathological and physiological effects of this reduction, such as
decreased transport of absorbed nutrients, hormones, and drugs to
sites of utilization, are closely associated with higher morbidity and
mortality (21). Hence, the ability to respond with an increase in
positive APPs, while maintaining adequate negative APPs, is
intrinsically linked to survival of the individual subjected to chronic
infection or inflammation.
To determine the effect of human immunodeficiency virus (HIV) infection
on the APP response of symptom-free patients, we measured the plasma
concentration of four positive and four negative APPs and the rates of
synthesis of three positive and three negative APPs in five
symptom-free AIDS and five noninfected healthy adult subjects. The
plasma flux of phenylalanine was also measured and used as an index of
whole body protein breakdown rate. The glutathione kinetics of these
subjects were also measured; these data have been reported previously
(14).
Subjects. Five male subjects were
recruited from HIV-infected patients attending the St. Stephen's
Clinic at Chelsea and Westminster Hospital, London. HIV infection
was confirmed by enzyme-linked immunosorbent assay. At the time of the
study, the subjects had been diagnosed with HIV for 4 ± 1.0 yr.
None of the subjects had any signs or symptoms of secondary infections
at the time of the study. None had a low-grade fever, and during
routine follow-up none developed any specific symptoms. They remained
symptom free during the study and for 6 mo after the study. All
symptom-free AIDS subjects were on treatment with a combination of
zidovudine, zalcitabine, and lamivudine. Five normal healthy subjects
(3 males, 2 females) were recruited from the staff of the Clinical
Nutrition and Metabolism Unit, University of Southampton, Southampton.
They were in good health based on a complete medical history and
physical examination. The physical characteristics of all subjects,
which have been reported (14), are shown in Table
1. They were within the normal range of
ideal body weight, and there were no differences between the body mass
indexes and plasma volumes of the two groups. The symptom-free AIDS
subjects were all weight stable at the time of study, and as a group
their weights had increased by an average of 1.9 kg during the 4 ± 1.0-yr interval from diagnosis to the time of this study. The two
groups had similar habitual energy and protein intakes as assessed by
the 3-day weighed record method (Table 1). The female subjects were
studied during the preluteal phase (days
10-12) of their menstrual cycle.
ABSTRACT
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
1-antitrypsin, haptoglobin, and
fibrinogen) and four negative APPs [albumin, high-density
lipoprotein (HDL)-apolipoprotein (apo) A1, transthyretin, and
retinol-binding protein] and
2) the fractional (FSR) and absolute (ASRs) synthesis rates of three positive and three negative APPs using
a constant intravenous infusion of
[2H5]phenylalanine
in five subjects with symptom-free acquired immunodeficiency syndrome
(AIDS) and five noninfected control subjects. Compared with the values
of the controls, the plasma concentrations, FSRs, and ASRs of most
positive APPs were higher in the AIDS group. The negative APPs had
faster FSRs in the AIDS group, there was no difference between the ASRs
of the two groups, and only HDL-apoA1 had a lower plasma concentration.
These results suggest that symptom-free AIDS elicits an APP response
that is different from bacterial infections, as the higher
concentrations and faster rates of synthesis of the positive APPs are
not accompanied by lower concentrations and slower rates of synthesis
of most of the negative APPs.
INTRODUCTION
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
METHODS
TOP
ABSTRACT
INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES
Table 1.
Physical characteristics and habitual intakes of energy and protein of
all subjects
Hematology, Centers for Disease Control classification
of HIV-infected subjects. The total white blood cell
(WBC) count, lymphocyte profile, and Centers for Disease Control (CDC)
classification of the HIV-infected subjects, also reported earlier
(14), are shown in Table 2. All of the
HIV-infected subjects had previous clinical conditions attributed to
HIV infection that met the CDC criteria for AIDS (5). As shown in Table
2, only one HIV-infected subject had a WBC count below the normal
range. One subject had a CD4+ T
cell count >500 cells/µl (CD4+
T cell category 1), three had CD4+
T cell counts >200 cells/µl
(CD4+ T cell category 2), and one
had a CD4+ T cell count <200
cells/µl (CD4+ T cell category
3; see Ref. 5).
|
The protocol was approved by the ethical committees of all participating institutions. Signed informed consents of all subjects were obtained after the nature of the study had been explained to them. The symptom-free AIDS subjects were studied at the Chelsea and Westminster Hospital, and the healthy subjects were studied in the metabolic ward of the Clinical Nutrition and Metabolism Unit at the University of Southampton.
Isotope infusion protocol. The rates
of synthesis of the APPs were measured from the rates of incorporation
of
[2H5]phenylalanine
into the proteins, using plasma very low density lipoprotein
(VLDL)-apolipoprotein (apo) B-100 isotopic enrichment at plateau to
represent the isotopic enrichment of the phenylalanine precursor pool
from which the liver synthesized the other plasma proteins. A sterile
solution of
[2H5]phenylalanine
(Cambridge Isotope Laboratories, Woburn, MA) prepared in 4.5 g/l NaCl
was infused to measure the rates of synthesis of the positive APPs,
fibrinogen, haptoglobin, and
1-antitrypsin, and the negative
APPs, albumin, transthyretin, and high-density lipoprotein (HDL)-apoA1.
After a 10-h overnight fast, the subject's weights and heights were
measured, and venous catheters were inserted under local anesthesia in
each arm. One catheter was used for infusion of isotope, and the other
was used for blood sampling. The hand and forearm with the sampling
catheter was wrapped in a heating pad to arterialize venous blood. A
sterile solution of
[2H5]phenylalanine
was infused continuously for 6 h at 4 µmol · kg1 · h
1
through the catheter in one forearm after a priming dose of 4 µmol/kg
was injected. A 6-ml blood sample was drawn before the start of the
infusion and at hourly intervals throughout the infusion.
To estimate plasma volume, each subject was administered a dose of 5 mg/kg of Evans Blue dye by intravenous injection, and a blood sample was withdrawn before and 10 min later.
Sample analyses. Blood was drawn in
prechilled tubes (containing
Na2EDTA and a cocktail of sodium
azide, merthiolate, and soybean trypsin inhibitor) and immediately
centrifuged at 1,000 g for 15 min at
4°C. The plasma was removed and stored at 70°C for later analysis.
Plasma concentrations of eight proteins [RBP, albumin, HDL-apoA1,
transthyretin, C-reactive protein (CRP),
1-antitrypsin, haptoglobin, and
fibrinogen] were measured by radial immunodiffusion using NL RID
kits (The Binding Site, San Diego, CA).
Albumin was extracted from plasma with acidified ethanol, fibrinogen
was extracted as fibrin by thrombin precipitation, and VLDL-apoB-100
was separated by ultracentrifugation and isopropanol precipitation. The
HDL fraction was separated on a 1.21 g/ml NaBr-EDTA gradient by
ultracentrifugation at 450,000 g and
22°C for 16 h (13). Transthyretin, haptoglobin, and
1-antitrypsin were isolated from plasma by sequential immunoprecipitation with anti-human transthyretin, haptoglobin, and
1-antitrypsin (Behring,
Somerville, NJ) as previously described (15). The immunoprecipitates
and protein precipitates were subjected to SDS-gel electrophoresis to
separate the particular protein from its specific antibody and to
separate apoA1 from HDL. A pure standard of the protein (Sigma, St.
Louis, MO) and low-molecular-weight standards (Bio-Rad Laboratories,
Richmond, CA) were also included in the gel (15). After staining with
Coomassie brilliant blue dye, the bands corresponding to the protein
standard were cut out and washed several times. The dried protein
precipitates and gel bands were hydrolyzed in 6 mol/l HCl at 110°C
for 12 h. Amino acids released from hydrolysis of the proteins and
plasma amino acids were extracted by cation exchange chromatography,
and the tracer-to-tracee ratio of the phenylalanine was determined by
negative chemical ionization gas chromatography-mass spectrometry on a
Hewlett-Packard 5988A GC-MS (Palo Alto, CA). The amino acid was
converted to the n-propyl ester
heptafluorobutyramide derivative, and the phenylalanine isotope ratio
was determined by monitoring ions at mass-to-charge ratio 383 to 388.
Calculations and statistics. The fractional synthesis rates (FSR) of all proteins were calculated with the precursor-product equation
![]() |
The absolute intravascular synthesis rate (iv ASR) of albumin (or
transthyretin, HDL-apoA1, fibrinogen, haptoglobin,
1-antitrypsin) was estimated as
the product of FSR and the intravascular mass of the protein
![]() |
The plasma volume of each subject was calculated by the dye dilution technique as described by Gibson and Evans (9).
The standard steady-state equation was used to calculate the flux of phenylalanine in the circulation
![]() |
Data are expressed as means ± SE for each group. Differences between groups were detected by the nonpaired t-test. A probability of 5% (P > 0.05) was assumed to represent statistical significance.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The net tracer-to-tracee molar ratio (mol% above baseline) of free
plasma phenylalanine reached a steady state after 2 h of the isotope
infusion in all four studies; hence, the flux of phenylalanine was
calculated using the average tracer-to-tracee ratio during the last 4 h
of the tracer infusion (Fig. 1). The
tracer-to-tracee ratio of VLDL-apoB-100-bound phenylalanine reached a
steady state after 3 h of the isotope infusion in all four studies
(Fig. 1). Hence, the FSRs and APPs were calculated from the rate of
incorporation of labeled phenylalanine in each protein during the last
2 h of the tracer infusion.
|
The positive APPs. The symptom-free
AIDS group had significantly higher plasma CRP
(P < 0.01), fibrinogen
(P < 0.05), and haptoglobin
(P < 0.01) concentrations than the
control group (Tables 3 and
4). There was no difference, however, in
the plasma concentration of
1-antitrypsin between the two
groups. The larger plasma pools of fibrinogen and haptoglobin in the
symptom-free AIDS group were associated with faster FSRs
(P < 0.05;
P < 0.01) of the proteins in this
group than in the control group (Table 4). Similarly, the ASRs of
fibrinogen and haptoglobin were significantly greater (P < 0.01) in the symptom-free AIDS
group than in the control group. There was no difference,
however, between the groups in either FSR or ASR of
1-antitrypsin.
|
|
The negative APPs. There was no
difference in the plasma concentration of RBP, albumin, or
transthyretin between the two groups (Tables 3 and
5). The plasma concentration of HDL-apoA1
was, however, lower in the symptom-free AIDS group than in the control group (P < 0.05). The FSRs of
albumin, transthyretin, and HDL-apoA1 were significantly faster
(P < 0.05) in the HIV-infected group than in the control group (Table 5). Despite the faster FSRs of the
symptom-free AIDS group, there was no difference in the ASRs of
albumin, transthyretin, and HDL-apoA1 compared with the rates of the
control group. There was, however, a trend toward a faster ASR in
albumin and transthyretin in the symptom-free AIDS group.
|
The plasma flux of phenylalanine was significantly faster
(P < 0.05) in the symptom-free AIDS
group (64 ± 6 µmol · kg1 · h
1)
compared with the control group (48 ± 2 µmol · kg
1 · h
1).
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Although there have been reports of increased whole body protein turnover rates in asymptomatic HIV-infected and AIDS patients (e.g., see Refs. 19 and 26), it is not known whether this increased protein turnover rate includes changes in the rates of synthesis of the APPs. This study aimed to determine the effect of infection by the HIV alone on the APP response in AIDS patients who were free of signs and symptoms of secondary infections or any other AIDS-related complications. The findings show that the plasma concentrations and both the FSRs and ASRs of most of the positive APPs are considerably higher in symptom-free AIDS individuals than in noninfected healthy controls. Although the negative APPs had faster FSRs in the symptom-free AIDS group, there was no difference in the ASRs of these proteins between the two groups. In the symptom-free AIDS group, one of the negative APPs, HDL-apoA1, had a lower plasma concentration despite a faster FSR. These results suggest that HIV infection does elicit an APP response. However, the response is atypical, as the higher concentrations and faster rates of synthesis of the positive APPs are not accompanied by lower concentrations and slower rates of synthesis of most of the negative APPs.
Although the APP response to bacterial infections has been well
established in the literature (e.g., see Refs. 3 and 6), very few
studies have investigated the response to viral infections. In the
typical APP response to the stress of a bacterial infection, the plasma
concentrations of the positive APPs increase, whereas the
concentrations of the negative APPs decrease (2, 4, 14, 20). On
average, there is a two- to fourfold increase in the plasma
concentration of most positive APPs in response to injury or infection
(3, 6, 7, 18, 25). Concomitantly, the plasma concentrations of the
negative APPs decrease by as much as 25-75% (3, 6, 7, 18, 25). It
is not known, however, whether this APP response can be elicited by
viral infections, especially chronic subclinical viral infections such
as HIV infection. The limited data available in the literature suggest
that, whereas acute viral infections can elicit an APP response,
chronic subclinical viral infections cannot. For example, Miwata et al.
(22) reported higher plasma concentrations of the positive APPs CRP and
serum amyloid A in children infected with measles, varicella, rubella, and echo-30 meningitis but not in children with chronic hepatitis B and
C. In the present study, however, the higher plasma concentrations of
the positive APPs, CRP, fibrinogen, and haptoglobin, and the faster
FSRs and ASRs of fibrinogen and haptoglobin suggest that presence of
the virus does elicit an APP response in symptom-free AIDS subjects.
However, the failure to elicit any change in
1-antitrypsin concentration and
rate of synthesis suggests that the HIV-induced APP response does not
include all of the positive APPs. Similarly, Miwata et al. reported no
changes in the plasma concentrations of two,
1-acid glycoprotein and
2-microglobulin, out of four positive APPs in response to measles, varicella, rubella, and echo-30
meningitis infections. Together, the findings of Miwata et al. and our
present data suggest that HIV infection elicits an APP response that is
similar to that elicited by symptomatic viral infections.
The increased FSRs and ASRs of fibrinogen and haptoglobin suggest that
the larger plasma pools of the positive APPs were due to stimulated
rates of synthesis. At present, we are not aware of any other kinetic
study of the APPs in symptom-free AIDS patients, and there are only a
few studies in the literature that have looked at changes in the plasma
concentrations of the APPs (11, 12, 23). In agreement with our present
findings, Grunfeld et al. (11) reported higher plasma concentrations of
CRP in a similar group of symptom-free AIDS patients compared with the
plasma concentrations of a group of healthy controls. There was,
however, no difference in the plasma concentration of haptoglobin
between the two groups. In another study, Monnet et al. (23) reported
that one (2-microglobulin) of
three positive APPs
(
2-microglobulin, CRP, and
1-antitrypsin) had a higher
plasma concentration in a group of symptom-free AIDS patients. The
findings of these two studies, together with our present data,
demonstrate that infection by the HIV elicits an APP response even in
the absence of secondary infections. However, the response does not
include all of the positive APPs and is of a lesser magnitude than that
observed in response to severe injury or bacterial infection (3, 6, 7,
18, 25).
Our data show that there were no differences in the plasma concentrations of the negative APPs, albumin, RBP, and transthyretin between the symptom-free AIDS group and the noninfected control group. The exception was HDL-apoA1, which had a lower plasma concentration in the symptom-free AIDS group. These findings are in agreement with those of Hommes et al. (12), who reported no difference in the plasma concentrations of albumin, RBP, or transferrin between a group of asymptomatic HIV-infected patients and a group of control subjects. Our data do not agree, however, with the findings of Monnet et al. (23) that plasma RBP and transthyretin concentrations were significantly lower in a group of symptom-free AIDS patients than in a group of noninfected control subjects. The negative APPs albumin, transthyretin, and HDL-apoA1 had faster FSRs in the symptom-free AIDS group than in the control group, and, although the differences between the ASRs of the two groups were not statistically significant, there was a trend toward faster ASRs for albumin and transthyretin in the symptom-free AIDS subjects. These findings suggest that the symptom-free AIDS group was turning over these proteins at a faster rate to maintain the plasma pool and hence the availability of the proteins.
The symptom-free AIDS group had a significantly lower plasma HDL-apoA1 concentration despite a faster FSR and an ASR that was almost identical to that of the control group. This finding is in agreement with that of Grunfeld et al. (11), who reported lower plasma concentrations of HDL-apoA1 in a similar group of symptom-free AIDS patients than in healthy controls. Because the pool size of a plasma protein is determined by the balance between its rates of synthesis and catabolism or loss, our present findings suggest that the lower HDL-apoA1 concentrations of the symptom-free AIDS subjects result from faster rates of catabolism, or loss from the intravascular space, relative to the rates of synthesis of the protein. The lower plasma HDL-apoA1 concentrations suggest that cholesterol transport, hence its metabolism, is impaired in symptom-free AIDS patients even in the absence of secondary infections. This suggestion is supported by the findings of Grunfeld et al. who reported that both total plasma and HDL cholesterol and plasma HDL-apoA1 were lower in symptom-free AIDS patients even before the onset of hypertriglyceridemia. Based on these findings, they concluded that disturbances in cholesterol metabolism precede frank elevations in serum triglyceride concentrations during asymptomatic HIV infection (11). Our present findings further support this proposal by Grunfeld et al.
It is generally accepted that, in the presence of injury and infection, protein metabolism accommodates the demands related to increased lymphocyte proliferation and synthesis of cytokines, immunoglobulins, and positive APPs by redistribution of amino acid precursors, hence protein synthetic activity, away from the synthesis of muscle and the negative APPs (7). Although the increased synthesis of positive APPs necessary to mount a successful response to stress obviously is beneficial, the decreased syntheses of the negative APPs, most of which play major roles in the transport of nutrients, hormones, metabolites, and drugs, are equally important. For example, a reduction in negative APPs, which are responsible for the transport of absorbed nutrients to sites of utilization, will further impede nutrient utilization. Our present data demonstrate that symptom-free AIDS subjects are capable of maintaining a higher plasma concentration and rate of synthesis of most positive APPs without a corresponding decrease in the plasma concentration of most negative APPs. Because HIV-infected individuals are prone to malnutrition, it is imperative that they maintain adequate quantities of transport proteins. Hence, the ability to mount a positive APP response and also to maintain higher rates of synthesis of negative APPs may represent a beneficial adaptation by the individual subjected to infection by the virus.
On the other hand, it is possible that subclinical infections, such as the HIV infection, are incapable of eliciting a full-blown APP response. For example, whereas plasma concentration of interleukin (IL)-6, the primary mediator of the APP response, is 16 times higher in HIV-infected subjects with secondary infections (4), Hommes et al. (12) reported only a doubling of IL-6 in asymptomatic HIV-infected subjects, to a value that was still within the normal range. Secondly, in severe injury and acute infections, plasma CRP concentration can increase up to 100-fold or more (7, 18). In the present study, however, whereas CRP concentration was significantly higher in the symptom-free AIDS subjects, it was only nine times the control value. Together these findings (4, 12) plus our present data suggest that the atypical APP response observed in the present study may be due to the inability of HIV infection to stimulate IL-6 production, or the production of other cytokines and factors necessary to elicit an intense APP response.
Finally, although in the past it was believed that the lower concentration of the negative APPs induced by stressed states was due to a reduced rate of synthesis of these proteins (1), the faster FSRs of the three negative APPs in the present study were not surprising. This finding is in agreement with our previous finding that the lower albumin concentration of marasmic children was accompanied by a faster albumin FSR when the children were also stressed by infections compared with when their infections were cleared (24). Similarly, Mansoor et al. (20) reported that the hypoalbuminemia of head trauma subjects was accompanied by a 60% increase in the rate of albumin synthesis during the acute response to head trauma. Together, these findings suggest that the stress of infection, inflammation, and injury stimulates and does not suppress the rate of synthesis of albumin. In all likelihood, the concentrations of albumin and other negative APPs decrease precipitously in response to infections, severe trauma, and inflammation because of an increased transcapillary escape rate and an increased catabolic rate (8, 10). More recently, we have reported that turpentine inflammmation induced marked increases in albumin FSR in both protein-malnourished and healthy pigs (16). Whereas the stimulation of albumin FSR was associated with an increase in albumin concentration in the healthy pigs, there was, however, a precipitous fall in plasma albumin concentration in the protein-malnourished pigs, suggesting that the turpentine inflammation was sufficient to elicit an increase in albumin catabolism or intravascular loss in the protein-malnourished pigs but not in the healthy pigs (16). It is therefore possible that symptom-free AIDS subjects are capable of maintaining normal plasma concentrations of negative APPs because the stress of the infection is not of sufficient magnitude to elicit an increase in albumin catabolism or intravascular loss.
![]() |
ACKNOWLEDGEMENTS |
---|
We thank Leslie Loddeke for editorial assistance.
![]() |
FOOTNOTES |
---|
This research was supported with funds from the United States Department of Agriculture/Agricultural Research Service, the Wessex Medical Trust, and the Charing Cross and Westminster Research Fund.
This is a publication of the U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX. The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: F. Jahoor, USDA/ARS Children's Nutrition Research Center, Dept. of Pediatrics, Baylor College of Medicine, 1100 Bates St., Houston, TX 77030-2600 (E-mail: fjahoor{at}bcm.tmc.edu).
Received 28 September 1998; accepted in final form 3 March 1999.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
Aldred, A. R.,
and
G. Schreiber.
The negative acute phase proteins.
In: Acute Phase Proteins, Molecular Biology, Biochemistry and Clinical Applications, edited by A. Mackiewicz,
I. Kushner,
and H. Baumann. Boca Raton, FL: CRC, 1993, p. 21-38.
2.
Biesel, W. R.
Magnitude of the host nutritional responses to infection.
Am. J. Clin. Nutr.
8:
1236-1247,
1977.
3.
Bostian, K. A.,
B. S. Blackburn,
R. W. Wannemacher,
V. G. McGann,
W. R. Beisel,
and
H. L. Dupont.
Sequential changes in the concentrations of specific serum proteins during typhoid fever infection in man.
J. Lab. Clin. Med.
87:
577-585,
1976[Medline].
4.
Breen, E. C.,
A. R. Reza,
K. Nakajima,
G. N. Beall,
R. T. Hirano,
T. Kishimoto,
and
O. Martinez-Maza.
Infection with HIV is associated with elevated IL-6 levels and production.
J. Immunol.
144:
480-484,
1990
5.
Centers for Disease Control.
1993 Revised classification system for HIV infection, and expanded surveillance case definition for AIDS among adolescents and adults.
Morbidity and Mortality Weekly Report
14:
1-18,
1992.
6.
Dowton, S. B.,
and
H. R. Colton.
Acute phase reactants in inflammation and infection.
Semin. Haematol.
25:
84-90,
1988[Medline].
7.
Fleck, A.
Clinical and nutritional aspects of changes in acute-phase proteins during inflammation.
Proc. Nutr. Soc.
48:
347-354,
1989[Medline].
8.
Fleck, A.,
F. Hawker,
P. I. Wallace,
G. Raines,
J. Trotters,
I. M. Ledingham,
and
K. C. Calma.
Increased vascular permeability: a major cause of hypoalbuminemia in disease and injury.
Lancet
1:
781-784,
1985[Medline].
9.
Gibson, J. G.,
and
W. A. Evans.
Clinical studies of the blood volume. I. Clinical application of a method employing the azo dye "Evans Blue" and the spectrophotometer.
J. Clin. Invest.
16:
301-316,
1937.
10.
Grossman, J.,
A. A. Yalow,
and
R. E. Weston.
Albumin degradation and synthesis as influenced by hydrocortisone, corticotrophin and infection.
Metabolism
9:
528-550,
1960.
11.
Grunfeld, C.,
M. Pang,
W. Doerrler,
J. K. Shigenaga,
P. Jensen,
and
K. R. Feingold.
Lipids, lipoproteins, triglyceride clearance and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome.
J. Clin. Endocrinol. Metab.
74:
1045-1052,
1992[Abstract].
12.
Hommes, M. J. T.,
J. A. Romijn,
E. Endert,
and
H. P. Sauerwein.
Resting energy expenditure and substrate oxidation in human immunodeficiency virus (HIV)-infected asymptomatic men: HIV affects host metabolism in the early asymptomatic stage.
Am. J. Clin. Nutr.
54:
311-315,
1991[Abstract].
13.
Jahoor, F.,
D. Burrin,
P. J. Reeds,
and
M. E. Frazer.
Measurement of plasma protein synthesis rate in the infant pig: an investigation of alternative tracer approaches.
Am. J. Physiol.
267 (Regulatory Integrative Comp. Physiol. 36):
R221-R227,
1994
14.
Jahoor, F.,
A. Jackson,
B. Gazzard,
G. Philips,
D. Sharpstone,
M. Frazer,
and
W. Heird.
Erythrocyte glutathione deficiency in symptom-free HIV infection is associated with decreased synthesis rate.
Am. J. Physiol.
276 (Endocrinol. Metab. 39):
E205-E211,
1999
15.
Jahoor, F.,
B. Sivakumar,
M. Del Rosario,
and
M. E. Frazer.
Isolation of acute-phase proteins from plasma for determination of fractional synthesis rates by a stable isotope tracer technique.
Anal. Biochem.
236:
95-100,
1996[Medline].
16.
Jahoor, F.,
L. Wykes,
M. Del Rosario,
M. E. Frazer,
and
P. J. Reeds.
Chronic protein undernutrition and an acute inflammatory stimulus elicit different protein kinetic responses in plasma but not in muscle of piglets.
J. Nutr.
129:
693-699,
1999
17.
Kinney, J. M.
Surgical hypermetabolism and nitrogen metabolism.
In: Metabolism and the Response to Injury. Chicago, IL: Pitman Med. Publ., 1972, p. 237-252.
18.
Kushner, I.
The phenomenon of the acute phase response. C-reactive protein and the plasma protein response to tissue injury.
Ann. NY Acad. Sci.
389:
39-48,
1982[Medline].
19.
Macallan, D. C.,
M. A. McNurlan,
E. Milne,
A. G. Calder,
P. J. Garlick,
and
G. E. Griffin.
Whole-body protein turnover from leucine kinetics and the response to nutrition in human immunodeficiency virus infection.
Am. J. Clin. Nutr.
61:
818-826,
1995[Abstract].
20.
Mansoor, O.,
M. Cayol,
P. Gachon,
Y. Boirie,
P. Schoeffler,
C. Obled,
and
B. Beaufrere.
Albumin and fibrinogen syntheses increase while muscle protein synthesis decreases in head-injured patients.
Am. J. Physiol.
273 (Endocrinol. Metab. 36):
E898-E902,
1997
21.
McLaren, D. S.,
E. Shirajian,
and
S. Shadarevian.
Short-term prognosis in protein-calorie malnutrition.
Am. J. Clin. Nutr.
22:
863-870,
1969[Medline].
22.
Miwata, H.,
T. Yamada,
M. Okada,
T. Kudo,
H. Kimura,
and
T. Morishima.
Serum amyloid A protein in acute viral infections.
Arch. Dis. Child.
68:
210-214,
1993[Abstract].
23.
Monnet, D.,
E. Kacou,
G. M. Gershy Damet,
A. Lonsdorfer,
K. Odehouri,
and
A. E. Yapo.
Inflammatory reaction markers and nutritional markers in HIV infection.
Ann. Biol. Clin. (Paris)
49:
428-432,
1991[Medline].
24.
Morlese, J. F.,
T. Forrester,
A. Badaloo,
M. Del Rosario,
M. E. Frazer,
and
F. Jahoor.
Albumin kinetics in edematous and non-edematous protein-energy malnourished children.
Am. J. Clin. Nutr.
64:
952-959,
1996[Abstract].
25.
Schreiber, G.
Synthesis, processing, and secretion of plasma proteins by the liver and other organs and their regulation.
In: The Plasma Proteins. New York: Academic, 1988, p. 361-399.
26.
Selberg, O.,
U. Suttman,
A. Melzer,
H. Deicher,
M. J. Muller,
E. Henkel,
and
D. C. McMillan.
Effect of increased protein intake and nutritional status on whole-body protein metabolism of AIDS patients with weight loss.
Metabolism
44:
1159-1165,
1995[Medline].