1 United States Department of Agriculture/Agricultural Research Service, Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030; and 2 Tropical Metabolism Research Unit, University of the West Indies, Mona, Kingston 7, Jamaica
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
It is not known whether malnourished infants can
mount a comprehensive acute-phase protein (APP) response and, if so,
whether this is achieved by increasing APP synthesis rates. To address these issues, we measured 1) the
plasma concentrations of five APPs (C-reactive protein,
1-acid glycoprotein,
1-antitrypsin, haptoglobin, and
fibrinogen) and 2) the synthesis
rates of three APPs
(
1-antitrypsin, haptoglobin,
and fibrinogen) using a constant intragastric infusion of
[2H3]leucine
in nine infected marasmic children at ~2 days postadmission (study 1), ~9 days postadmission
when infections had cleared (study 2), and ~59 days postadmission at recovery
(study 3). Except for fibrinogen,
the plasma concentrations of all APPs were higher in
study 1 than in
studies 2 and
3. Although the rate of synthesis of
haptoglobin was significantly greater in study
1 than study 2, the
rates of fibrinogen and
1-antitrypsin synthesis were
similar in all three studies. These results show that
1) severely malnourished children
can mount an APP response to infection which does not include
fibrinogen and 2) the APP response
is accomplished through different mechanisms.
1-antitrypsin; C-reactive
protein; haptoglobin; marasmus
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
THE ACUTE-PHASE RESPONSE to the stress of injury or infection is characterized by higher plasma concentrations of the positive acute-phase proteins (APPs) (5, 6). These plasma proteins are of clinical relevance because they have important roles in combating infections, including modulating T-lymphocyte function and the complement system, scavenging hemoglobin, and protecting the integrity of healthy tissues against the effects of proteases produced by the pathogen or released from damaged cells (5, 15). Although the physicochemical properties of APPs have been studied in great detail, there is very little information on the in vivo metabolism of these proteins, particularly in pathological states such as severe protein-energy malnutrition.
Although it is well established that nearly every aspect of the body's
defense system is damaged by severe malnutrition (2), it is not clear
whether the capacity to mount an APP response is severely impaired. The
finding that infected malnourished children have higher plasma
concentrations of one family of APPs, the antiproteases (23, 24),
suggests that these patients retain the capacity to mount an APP
response involving that family of proteins. These findings do not
necessarily prove, however, that the severely malnourished can elicit a
comprehensive APP response to the stress of infection or injury. To
find out whether the limited capacity of the severely malnourished to
mount an APP response to infection includes a full spectrum of APPs,
the present study aimed to determine the changes in plasma
concentrations of a roster of five different APPs in infected
malnourished children before and after treatment. The five APPs
selected, C-reactive protein,
1-acid glycoprotein,
1-antitrypsin, haptoglobin, and
fibrinogen, were chosen because they are representative of APPs with
widely different functions (4, 5, 15, 20).
Another question concerns the mechanism by which malnourished individuals mount an APP response. Although there are few in vivo studies of the kinetic mechanisms responsible for the increased availability of APP in injured or infected well-nourished humans (19, 25), the evidence from these studies and from in vivo studies in infected animals (13, 14) suggests that a marked stimulation of the APP synthesis rate leads to increased availability of these proteins. In the malnourished state, however, the capacity to synthesize more protein may not be achievable because of a chronically poor dietary protein intake (29). It is therefore possible that, when stressed by infections, the severely malnourished may increase the availability of APPs through kinetic mechanisms other than stimulated synthesis rates.
The present study was therefore performed in marasmic children with
infections to determine 1) the
ability of malnourished children to mount a general APP response and
2) the kinetic mechanisms responsible for the increased plasma pool sizes of three APPs with
widely different functions, i.e.,
1-antitrypsin, haptoglobin, and
fibrinogen. A newly developed stable isotope tracer technique (10) was
used to directly measure the rates of synthesis of the three APPs in
infected protein-energy malnourished children at three time points
during hospitalization: when the children were both malnourished and
infected (~2 days postadmission); after infections were under
control, but the patients were still severely malnourished (~9 days
postadmission); and after the patients were fully recovered and had
achieved at least 90% of expected weight for height (~59 days
postadmission).
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Subjects. This study was approved by the Medical Ethics Committee of the University Hospital of the West Indies and the Baylor Affiliates Review Board for Human Subject Research of Baylor College of Medicine. Nine Jamaican children (6 males, 3 females) were diagnosed as marasmic using the Wellcome Classification (28). They were recruited into the study after written informed consent was received from their parents. The main criteria for selection into the study were a deficit in body weight for age of >40% and clinical evidence of infection. The weight of the children was measured using an electronic balance (Sartorius model F150S, Göttingen, Germany), and length was measured on a horizontally mounted stadiometer (Holtain, Crymych, UK). The children were deemed to have concurrent infection(s) if one or more of the following parameters were present at admission: leukocyte count >11 × 109 cells/l, temperature at admission >37 or <35.5°C, abnormal shadowing on chest X-ray, and positive blood, urine, or stool culture (Table 1).
|
Treatment.
The children were admitted to the metabolic ward of the Tropical
Metabolism Research Unit, University Hospital of the West Indies, and
managed according to a standard treatment protocol (9). This involved
correction of fluid and electrolyte imbalances and administration of
broad-spectrum antibiotics. The course of antibiotics consisted of
parenteral penicillin and gentamicin and oral metronidazole. After
admission, they were started immediately on a maintenance milk-based
diet that provided 417 kJ of energy and 1.2 g · kg1 · day
1
of protein with additional supplements of vitamins and trace elements
(18) until appetite was restored (~9 days postadmission). During the
catch-up growth phase, the patients were fed an energy-dense, milk-based formula that provided 625-750 kJ of energy and ~3 g protein · kg
1 · day
1.
Study design.
The patients were studied at three different times: first, when they
were both infected and malnourished; second, when they were still
malnourished but their infections were under control; and third, when
they were fully recovered. They were fed the maintenance diet of 417 kJ
of energy and 1.2 g
protein · kg1 · day
1
during each study. The first isotope infusion (study
1) was performed at 2 days postadmission, immediately
after fluid resuscitation when the children were clinically stable as
indicated by blood pressure and heart and respiratory rates.
Study 2 was undertaken 9 days
postadmission when the children were still severely malnourished, they
were still on the maintenance diet, their appetite had recovered, and
their infections had cleared. The latter was determined by normalization of temperature, respiratory and pulse rates, and resolution of clinical features of the infective episode (e.g., cessation of diarrhea and absence of chest crepitations).
Study 3 was performed at ~59 days
postadmission when the child had fully recovered from malnutrition,
i.e., after the catch-up growth rate had started to plateau and weight
for height was
90%. At this point, the child was restarted on the
maintenance diet for 3 days before the isotope infusion.
Experimental protocol.
The isotope infusion protocol has been described in detail previously
(17). Briefly, a sterile solution of
[2H3]leucine
(Cambridge Isotope Laboratories, Woburn, MA) was prepared in 9 g/l
saline and infused for 8 h to measure the rate of synthesis of
haptoglobin, 1-antitrypsin, and
fibrinogen. About 40% of the subject's daily food intake was given by
constant intragastric infusion starting 2 h before the
isotope infusion commenced. After a 2-ml venous blood sample was drawn,
the
[2H3]leucine
solution was infused nasogastrically at a rate of 26 µmol · kg
1 · h
1
for 8 h. Additional 2-ml blood samples were drawn at 2-h intervals throughout the infusion. The same infusion and blood sampling protocol
were repeated in studies 2 and
3.
Sample analysis.
Blood was drawn in prechilled tubes (containing
Na2EDTA and a cocktail of sodium
azide, thimerosal, and soybean trypsin inhibitor) and immediately
centrifuged at 1,000 g for 15 min at
5°C. The plasma was removed and stored at 70°C for later
analysis.
Calculations. The fractional synthesis rate (FSR) of each APP was calculated with the precursor-product equation
![]() |
![]() |
![]() |
Statistical analysis. The data were analyzed by ANOVA with repeated measures by using the StatView II statistical package (Abacus Concepts, Berkeley, CA). When there were significant differences over time, individual time points were compared with univariate post-ANOVA contrasts. Significance of difference was assumed at P < 0.05, and numerical data are expressed as means ± SE.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
All nine subjects had evidence of infection at admission (Table 1). The mean age of the subjects was 10.1 ± 1.4 mo. They were all severely malnourished at admission with a mean body weight of 5.0 ± 0.2 kg and mean weight for age and height of only 55 ± 2.1 and 75 ± 2.6% of expected, respectively (Table 2). At study 2, after 9 days of antibiotic therapy, the patients' infections had cleared as determined by normalization of temperature, respiratory and pulse rates, and resolution of clinical features of the infective episode (e.g., cessation of diarrhea and absence of chest crepitations). At study 2, there were no significant differences between the mean body weight, weight for age, and height compared with the study 1 values (Table 2). At study 3, when the subjects had fully recovered, the mean weight for age and height were 73 ± 2.5 and 92 ± 2.3%, respectively (Table 2).
|
Plasma APP concentrations.
With the exception of fibrinogen, the plasma concentrations of all five
APPs in study 1 were significantly
higher (P < 0.05) compared with the
concentrations in study 2, when the
infections had cleared, and with the concentrations in
study 3, when the subjects were fully
recovered (Tables 3 and 4).
In study 2, the plasma concentrations
of 1-antitrypsin and
1-acid glycoprotein were still
significantly greater than the recovered values
(P < 0.05); however, the
concentrations of C-reactive protein, haptoglobin, and fibrinogen were
not different from the values at recovery (P < 0.05; Tables 3 and 4). Unlike
the other four APPs, the plasma concentration of fibrinogen was within
the normal range in all three studies and did not differ in any of the
studies (Table 4).
|
|
1-Antitrypsin,
haptoglobin, and fibrinogen synthesis rates.
The tracer-to-tracee ratio of VLDL apoB-100-bound leucine reached a
steady state after 4 h of the isotope infusion in all three studies
(Fig. 1), and there was a linear increase
in the amount of labeled leucine incorporated into plasma
1-antitrypsin, haptoglobin, and
fibrinogen during this period of time (Fig. 1). Hence the FSRs of
1-antitrypsin, haptoglobin, and
fibrinogen were calculated from the rate of incorporation of labeled
leucine into each protein during the last 4 h of the isotope infusion.
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The aims of this study were to determine whether severely malnourished
children can mount a general APP response to infection that includes
different types of APPs and whether changes in the pool size of these
proteins were achieved solely through changes in synthesis rates. The
higher plasma concentrations of four of five APPs in the infected
malnourished state confirm that severely malnourished children are
capable of mounting an APP response, but the response does not include
all of the APPs. The kinetic data demonstrate that the APP response in
these children is accomplished through different mechanisms. Although
the larger haptoglobin pool of the infected malnourished state was
associated with an increased rate of synthesis of the protein, the
larger 1-antitrypsin pool was
not associated with an increased rate of synthesis. Hence expansion of
the
1-antitrypsin pool may have
occurred through a decrease in the rate of catabolism of this protein.
These findings suggest that, in the severely malnourished, the APP
response is not achieved solely through an increased rate of APP
synthesis.
The advantage of any study of APP kinetics that uses an isotopic amino acid tracer and precursor-product analysis (as in present study) is that it permits the measurement of the rate of incorporation of the labeled amino acid precursor into the protein, hence a direct measurement of the fractional synthesis rate of the protein. A disadvantage of this method is that the kinetic information obtained is pertinent to APP within the intravascular pool only. Because the extravascular APP pool cannot be sampled, the isotopic enrichment and concentration cannot be measured in this pool. This precludes any calculation of rate of transfer of newly synthesized APP to the extravascular pool, hence calculation of the total ASR for an APP. As a consequence, studies of APP kinetics that use an isotopic amino acid tracer and precursor-product analysis are limited to calculations of intravascular APP synthesis rate as an index of the ASR.
In agreement with the earlier findings of others (3, 24), in the
present study, the plasma concentrations of C-reactive protein,
1-acid glycoprotein,
haptoglobin, and
1-antitrypsin in the infected marasmic children were markedly higher than the uninfected-malnourished and recovered values. The plasma fibrinogen concentration, however, was unaffected by the presence of infection, suggesting that marasmic children can mount an APP response to infection for most but not all APPs. At study
2, the plasma concentration of C-reactive protein had
fallen to an almost undetectable level, suggesting that the concurrent
infections had been cleared.
In the past, investigations of the kinetic mechanisms responsible for the APP response to injury or infection were limited to the study of fibrinogen synthesis because convenient tracer methods were not available to study the other APPs. The proposal that the increased availability of APPs was due to an increased rate of APP synthesis (5, 15) is primarily based on in vitro evidence of increased APP mRNA concentrations in rat hepatocytes after burn injury (21) or endotoxin administration (22), increased C-reactive protein production in perfused rabbit livers after injury (16), and in vivo measurements of fibrinogen synthesis rate in injured humans (25) and laboratory animals (14). In the malnourished state, however, there is no information to support the assertion that increased plasma APP concentrations in response to injury or infection are achieved through a stimulation of synthesis rate. Furthermore, whole body protein synthesis is reduced in the infected malnourished child compared with both infected and uninfected well-nourished children (7, 26), suggesting that the malnourished child may be mounting an APP response through a mechanism other than a stimulation of synthesis rate. Our present results suggest that, in severe malnutrition, the increased plasma pool sizes of the APPs are achieved through mechanisms that involve changes in both the rate of synthesis and catabolism of these proteins.
For example, the higher plasma concentration of
1-antitrypsin in the infected
malnourished state was not associated with an increased intravascular
absolute synthesis rate of the protein. In fact, the amounts of
1-antitrypsin synthesized per
unit of time in the infected malnourished state, the uninfected
malnourished state, and the recovered state were almost identical
(Table 4). This finding indicates that expansion and contraction of the
1-antitrypsin pool in response
to the presence and absence of infection are achieved by a mechanism
other than an increased synthesis rate. The pool size of a plasma
protein is determined by the balance between its rates of synthesis and
catabolism or its loss from the intravascular compartment. Hence an
increase in the pool size of an APP can be achieved by one of two
kinetic mechanisms: an increased rate of synthesis relative to
catabolism-intravascular loss or a decreased rate of catabolism-loss
relative to synthesis rate. Therefore, the most likely mechanism by
which the
1-antitrypsin pool
size is expanded in response to infection in the malnourished individual is through a reduction in the rate of catabolism relative to
a normal rate of synthesis. Similarly, it can be argued that contraction of the pool size as the infection is cleared is due to
normalization of rate of catabolism. In previous studies in infected
malnourished children, we reported that the same mechanism, a decreased
rate of catabolism, may be responsible for the initial expansion of the
plasma pools of the negative APPs, albumin and transferrin, as the
infection is cleared but the child is still malnourished (17, 18). It
is possible that the ability of the severely malnourished individual to
increase the availability of an APP by reducing its rate of catabolism
may represent an adaptive mechanism which has the advantage of
conserving the limited supply of amino acids.
On the other hand, in the infected malnourished state, when the plasma concentration of haptoglobin was higher, the rate of synthesis of haptoglobin was greater than in the uninfected malnourished state. In study 2, as the malnourished child's infection cleared, both the plasma concentration and rate of synthesis of haptoglobin decreased by ~60%, suggesting that the haptoglobin pool of the malnourished child expanded (in response to infection) and contracted (as infection was cured) through changes in the rate of synthesis of the protein. A closer examination of the results, however, reveals that a concomitant reduction in the rate of catabolism of haptoglobin was also involved in mediating the expansion of the plasma pool. When the results of the infected malnourished state are compared with those of the recovered state, it can be seen that, despite the more than twofold expansion of the plasma haptoglobin pool in the infected malnourished state, the amount of haptoglobin synthesized is not different from the amount synthesized in the recovered state, suggesting that there had to be a concurrent reduction in the rate of catabolism of haptoglobin for its pool to expand.
Another interesting finding is that although the pools of haptoglobin are almost the same in the uninfected malnourished and recovered states, only half as much of the protein is synthesized by the malnourished child, and the pool turns over half as fast (indicated by 50% slower FSR). This finding suggests that, in the absence of infection, the severely malnourished child synthesizes far less haptoglobin but maintains a normal pool of protein by simultaneously suppressing the rate of catabolism. This is further evidence to support the argument that the malnourished are capable of increasing or maintaining normal or larger pools of APPs without stimulating the rate of synthesis.
Both the rate of synthesis and plasma concentration of fibrinogen were unaffected by the presence of an infection in the malnourished child. Typically, in response to an inflammatory episode, plasma fibrinogen concentration is markedly increased and remains elevated for several days (5). Furthermore, the rate of fibrinogen synthesis is increased 400% in rabbits inoculated with endotoxin (14), suggesting that infection does elicit a fibrinogen response. Hence the failure to find significantly higher plasma fibrinogen concentrations and rates of synthesis in the infected malnourished children was surprising and suggests that fibrinogen is not responding like a classical APP in severe malnutrition. The lack of a fibrinogen response to infection by the severely malnourished child may be related to the unique function of fibrinogen or to its relatively large pool size and fast synthesis rate. Although the lack of an increase in fibrinogen availability may not adversely affect the capacity to fight an infection, it will certainly have a detrimental effect on the ability of a malnourished individual to recover from surgery or injury because of the critical role of fibrinogen in wound healing (8). On the other hand, our finding does not rule out the possibility that malnourished patients may be able to mount a fibrinogen response to surgery.
Finally, it should be pointed out that the magnitude of the increase in
plasma concentrations of the four APPs that had elevated concentrations
when the malnourished children were infected was actually greater than
that reported in the literature for healthy adults subjected to an
infection (1) and similar to the response in infected well-nourished
children (30). For example, Bostian et al. (1) reported that
1-acid glycoprotein,
1-antitrypsin, and haptoglobin
increased by 150, 72, and 86%, respectively, in healthy men exposed to
Salmonella typhi, and Wiedermann et
al. (30) reported a 78% increase in the plasma
1-antitrypsin concentration in
well-nourished children infected with Salmonella
enteritidis. In comparison, in the present study,
1-acid glycoprotein,
1-antitrypsin, and haptoglobin
increased by >600, 66, and 200%, respectively, in the infected
malnourished children, suggesting that severely malnourished
individuals can mount an adequate response to infection for most APPs.
In conclusion, the findings of this study showed that marasmic children can mount an APP response to combat infection. The APP response in severely malnourished children is achieved by different mechanisms, either through a decrease in the rate of catabolism or a combination of increased APP synthesis and decreased catabolism.
![]() |
ACKNOWLEDGEMENTS |
---|
We are grateful to the nursing staff of the Tropical Metabolism Research Unit, Kingston, Jamaica, for care of the children, Melanie Del Rosario and Margaret Frazer for technical support, and Leslie Loddeke for editorial assistance.
![]() |
FOOTNOTES |
---|
This work was supported by National Institute of Child Health and Human Development Grant RO1-HD-34224-01A1, grants from the International Atomic Energy Agency and The Wellcome Trust, and federal funds from the US Dept. of Agriculture (USDA)/Agricultural Research Service under Cooperative Agreement 58-6250-1-003.
This work was presented in part at the Experimental Biology 1997 Meeting, New Orleans, LA, 6-9 April 1997, and was published in abstract form (Jahoor et al. Magnitude of the acute-phase protein response to infection in protein-energy malnourished children. FASEB J. 11: 2105, 1997).
This is a publication of the USDA/Agricultural Research Service and Children's Nutrition Research Center, Dept. 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 USDA nor does mention of tradenames, commercial products, or organizations imply endorsement by the US Government.
Address for reprint requests: F. Jahoor, Children's Nutrition Research Center, Dept. of Pediatrics, Baylor College of Medicine, 1100 Bates St., Houston, TX 77030-2600.
Received 5 December 1997; accepted in final form 10 March 1998.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
1.
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].
2.
Chandra, R. K.
1991 McCollum Award Lecture. Nutrition and immunity: lessons from the past and new insights into the future.
Am. J. Clin. Nutr.
53:
1087-1101,
1990[Medline].
3.
Doherty, J. F.,
M. H. N. Golden,
J. G. Raynes,
G. E. Griffin,
and
K. P. W. J. McAdam.
Acute-phase protein response is impaired in severely malnourished children.
Clin. Sci. (Lond.)
84:
169-175,
1993[Medline].
4.
Dominini, L.,
and
R. Dionigi.
Immunological function and nutritional assessment.
JPEN J. Parenter. Enteral Nutr.
11:
70S-72S,
1987[Medline].
5.
Dowton, S. B.,
and
H. R. Colton.
Acute phase reactants in inflammation and infection.
Sem. Hematol.
25:
84-90,
1988[Medline].
6.
Fleck, A.
Clinical and nutritional aspects of changes in acute-phase proteins during inflammation.
Proc. Nutr. Soc.
48:
347-354,
1989[Medline].
7.
Golden, M.,
J. C. Waterlow,
and
D. Picou.
Protein turnover, synthesis and breakdown before and after recovery from protein-energy malnutrition.
Clin. Sci. (Lond.)
53:
473-477,
1977.
8.
Gordon, A. H.
Acute phase proteins in wound healing.
In: Protein Turnover. Ciba Foundation Symposium 9 (New Ser.),, edited by A. S. McFarlane. Amsterdam, Netherlands: Assoc. Sci., 1972, p. 73-90.
9.
Jackson, A. A.,
and
M. H. N. Golden.
Severe malnutrition.
In: The Oxford Textbook of Medicine, edited by D. J. Weatherall,
J. G. Ledingham,
and D. A. Warrell. Oxford, UK: Oxford Univ. Press, 1988, p. 8.12-8.23.
10.
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
11.
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].
12.
James, W. P. T.,
and
A. M. Hay.
Albumin metabolism: effect of the nutritional state and the dietary protein intake.
Clin. Invest.
47:
1958-1972,
1968[Medline].
13.
Jennings, G.,
C. Bourgeois,
and
M. Elia.
The magnitude of the acute phase protein response is attenuated by protein deficiency in rats.
J. Nutr.
122:
1325-1331,
1992[Medline].
14.
Koj, A.,
and
A. S. McFarlane.
Effect of endotoxin on plasma albumin and fibrinogen synthesis rates in rabbits as measured by the [14C]carbonate method.
Biochem. J.
108:
137-146,
1967.
15.
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].
16.
Kushner, I.,
W. N. Ribich,
and
J. B. Blair.
Control of the acute phase response. C-reactive protein synthesis by isolated perfused rabbit livers.
J. Lab. Clin. Med.
96:
1037-1045,
1980[Medline].
17.
Morlese, J. F.,
T. Forrester,
A. Badaloo,
M. Del Rosario,
M. Frazer,
and
F. Jahoor.
Albumin kinetics in edematous and non-edematous protein-energy malnourished children.
Am. J. Clin. Nutr.
64:
952-959,
1996[Abstract].
18.
Morlese, J. F.,
T. Forrester,
M. Del Rosario,
M. Frazer,
and
F. Jahoor.
Transferrin kinetics are altered in children with severe protein-energy malnutrition.
J. Nutr.
127:
1469-1474,
1997
19.
Rock, C. S.,
S. M. Coyle,
C. V. Keogh,
D. D. Lazarus,
A. S. Hawes,
M. Leskiw,
L. L. Moldawer,
T. P. Stein,
and
S. F. Lowry.
Influence of hypercortisolemia on the acute-phase response to endotoxin in humans.
Surgery
112:
467-474,
1992[Medline].
20.
Schreiber, G.
Synthesis, processing, and secretion of plasma proteins by the liver and other organs and their regulation.
In: The Plasma Proteins, edited by F. W. Putnam. New York: Academic, 1988, p. 361-399.
21.
evaljevic, L.,
M. Gilbetic,
G. Poznanovic,
J. Savic,
and
M. Petrovic.
Effect of lethal scald on the mechanisms of acute phase protein synthesis in rat liver.
Circ. Shock
33:
98-107,
1991[Medline].
22.
Sharma, R. J.,
D. C. Macallan,
P. Sedgwick,
D. G. Remick,
and
G. E. Griffin.
Kinetics of endotoxin-induced acute-phase protein gene expression and its modulation by TNF- monoclonal antibody.
Am. J. Physiol.
262 (Regulatory Integrative Comp. Physiol. 31):
R786-R793,
1992
23.
Shelp, F. P.,
P. Migasena,
P. Pongpaew,
W. H. P. Schreurs,
and
V. Supawan.
Serum proteinase inhibitors and other serum proteins in protein-energy malnutrition.
Br. J. Nutr.
38:
31-38,
1977[Medline].
24.
Shelp, F. P.,
O. Thanangkul,
V. Supawan,
M. Suttajit,
C. Meyers,
R. Pimpantha,
P. Pongpaew,
and
P. Migasena.
Serum proteinase inhibitors and acute phase reactants from protein-energy malnutrition children during treatment.
Am. J. Clin. Nutr.
32:
1415-1422,
1979[Medline].
25.
Thompson, C.,
F. A. Blumenstock,
T. M. Saba,
P. J. Feustel,
J. E. Kaplan,
J. B. Fortune,
L. Hough,
and
V. Gray.
Plasma fibronectin synthesis in normal and injured humans as determined by stable isotope incorporation.
J. Clin. Invest.
84:
1226-1235,
1989[Medline].
26.
Tomkins, A. M.,
P. J. Garlick,
W. N. Schofield,
and
J. C. Waterlow.
The combined effects of infection and malnutrition on protein metabolism in children.
Clin. Sci. (Lond.)
65:
313-324,
1983[Medline].
27.
Viart, P.
Blood volume (51C) in severe protein-calorie malnutrition.
Am. J. Clin. Nutr.
29:
25-37,
1976[Abstract].
28.
Wellcome Working Party.
Classification of infantile malnutrition.
Lancet
2:
302,
1970.
29.
Whitehead, R. G.,
W. A. Coward,
P. G. Lunn,
and
I. Rutishauser.
A comparison of the pathogenesis of protein-energy malnutrition in Uganda and the Gambia.
Trans. R. Soc. Trop. Med. Hyg.
71:
189-195,
1977[Medline].
30.
Wiedermann, D.,
D. Wiedermannová,
J. P. Vaerman,
and
J. F. Heremans.
A longitudinal study of serum 1-antitrypsin,
2-macroglobulin, transferrin, immunoglobulins IgG, IgA and IgM, and H- and O-agglutinin titers in children following infection with Salmonella enteritidis.
J. Infect. Dis.
121:
74-77,
1970[Medline].