help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McNurlan, M. A.
Right arrow Articles by Gelato, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McNurlan, M. A.
Right arrow Articles by Gelato, M.
The Journal of Clinical Endocrinology & Metabolism Vol. 83, No. 9 3050-3055
Copyright © 1998 by The Endocrine Society

Original Studies

Albumin Synthesis and Bone Collagen Formation in Human Immunodeficiency Virus-Positive Subjects: Differential Effects of Growth Hormone Administration1

Margaret A. McNurlan, Peter J. Garlick, Robert A. Frost, Kim A. DeCristofaro, Charles H. Lang, Roy T. Steigbigel, Jack Fuhrer and Marie Gelato

Departments of Surgery (M.A.M., P.J.G., C.H.L.) and Medicine (R.A.F., K.A.D., R.T.S., J.F., M.G.) at the State University of New York at Stony Brook, Stony Brook, New York 11794

Address all correspondence and requests for reprints to: Margaret McNurlan, Department of Surgery, Health Science Center T19, State University of New York at Stony Brook, Stony Brook, New York 11794-8191. E-mail: mcnurlan{at}surg.som.sunysb.edu


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Loss of lean tissue often accompanies human immunodeficiency virus (HIV) infection. Exogenous human recombinant GH (hrGH) has been shown to be beneficial in reversing this wasting. However, catabolic effects of hrGH on muscle protein metabolism have also been reported. Therefore, the responsiveness of other GH-sensitive tissues, including bone formation and albumin synthesis, has been examined.

Anabolic activity in bone, from serum levels of carboxy-terminal propeptide of type I collagen, was stimulated by 2 weeks of hrGH in controls (56 ± 15%, P = 0.002), patients with asymptomatic HIV (24 ± 10%, not significant), patients with AIDS (47 ± 7%, P < 0.001), and patients with AIDS and >10% weight loss (21 ± 12%, P = 0.02). Albumin synthesis, determined from the incorporation of L-[2H5]phenylalanine, was increased in response to hrGH in controls (23 ± 7%, P < 0.05), HIV+ subjects (39 ± 16%, P < 0.05), and patients with AIDS (25 ± 7%, P < 0.01). Patients with AIDS and weight loss, however, did not increase albumin synthesis (-0.6 ± 12%) in response to hrGH.

The results indicate variable anabolic responses to hrGH. Bone collagen synthesis remained sensitive to hrGH, whereas, the anabolic action of hrGH on the synthesis of albumin diminished with severity of disease. However unlike muscle protein synthesis, albumin synthesis was not depressed below basal levels by hrGH.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
INFECTION with human immunodeficiency virus (HIV) results in significant loss of body protein, and this wasting impacts on both morbidity and mortality (1, 2, 3, 4). The loss of body protein in HIV infection would appear to be a metabolic abnormality characteristic of the disease, even when patients are clinically stable (1). This loss of body protein is accompanied by an accelerated rate of muscle protein degradation and normal rates of protein synthesis (5). Although GH levels were not depressed in patients with AIDS and weight loss (6), human recombinant GH (hrGH), given in pharmacological doses of 6 mg/day, has been shown to retard the loss of body protein, with an increase in lean body mass reported in wasted AIDS patients treated with hrGH (7, 8, 9).

An improvement in the loss of body protein with GH treatment at pharmacological levels has also been demonstrated in other catabolic conditions, including under-feeding (10, 11, 12), cancer cachexia (13), surgical trauma (14, 15), and glucocorticoid administration (16). In weight-losing cancer patients (13), burned patients (17), and healthy subjects consuming a hyponitrogenous diet (12), the improvement in the loss of body protein with GH treatment was associated with a stimulation in the rate of protein synthesis in skeletal muscle. In contrast, in patients with AIDS and weight loss, treatment with hrGH has been shown to decrease the rate of muscle protein synthesis (5). Moreover, the negative response of muscle protein synthesis to hrGH was inversely related to the progression of the disease (5). Although a catabolic response to circulating GH is unlikely to be the cause of the muscle loss in AIDS, the response to pharmacologocal doses of hrGH does indicate that patients with AIDS and weight loss do not mount the anabolic response observed in healthy individuals (5) and other individuals with loss of body protein from other conditions (10, 11, 12, 13, 14, 15, 16, 17).

The current study was undertaken to determine whether the responses of other tissues were similarly affected by AIDS. Bone metabolism is sensitive to GH, possibly through elevations in the levels of insulin growth factor I (IGF-I) (18, 19), and increased turnover of bone has been reported in response to exogenously administered GH in both GH-deficient (20) and normal individuals (21). Therefore, the effect of GH on bone metabolism was assessed in HIV+ individuals to determine whether the observed defect in muscle protein synthesis was specific to muscle or represented a more generalized catabolic response to hrGH and/or IGF-I. In addition, the impact of exogenous GH on protein synthesis in the liver, reflected in the synthesis of albumin, was also assessed.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Written consent was obtained from each subject, and both studies were approved by the Committee on Research Involving Human Subjects at Stony Brook.

GH protocol

Twenty-nine HIV+ individuals (24 males, 5 females) and 10 control subjects (8 males, 2 females) participated in this study. Data on muscle protein metabolism and function of these subjects (26 HIV+, 9 controls) has been previously reported (5). All subjects were screened and excluded for metabolic or hormonal abnormalities, and all were euthyroid and eugonadal. HIV+ individuals with acute illness, diarrhea, malignancy, or recent surgery were also excluded. All HIV+ subjects were studied on their normal drug regimen, which included, in some cases, antiretrovirals, prophylactic antibiotics, and/or antimycotics.

HIV+ patients were stratified into three groups based on severity of disease. The group denoted as HIV+ were asymptomatic. The group denoted AIDS had CD4+ counts below 200 cells/mm3 with less than 10% loss of body weight. Some of these individuals had been previously treated for characteristic opportunistic infections. The group denoted AIDS-weight loss had CD4+ counts less than 200 cells/mm3 and had lost greater than 10% of their preillness weight. Some of these individuals had also been previously treated for opportunistic infections, although none had active infection or rapid weight loss at the time of study.

Subjects were studied in the Clinical Research Center at Stony Brook after an overnight stay, which included a brief physical examination. At 0700 h two angiocaths were inserted in contralateral, forearm veins, and blood samples were taken for baseline measurements. L-[2H5, ring]phenylalanine (Mass Trace, Woburn, MA) was injected over 10 min at 45 mg/kg body weight, 10% enrichment (20% for the second measurement), as a 2% solution. Blood samples for the determination of plasma phenylalanine enrichment and for the enrichment of phenylalanine in albumin were taken at intervals after the injection, centrifuged, and plasma stored at -20 C. At 20 min into the protocol, 5 µCi 125I-labeled albumin (Mallinckrodt, Hicksville, NY) was injected for the determination of plasma volume. Measurements of albumin synthesis were made on two occasions: before hrGH treatment and after 14 days of daily sc injections of 6 mg hrGH (Serostim, generously provided by Serono Laboratories, Norwell, MA).

In addition to hrGH injections, subjects were also provided with dietary advice and sample menus to achieve an energy intake of 1.5x basal energy expenditure (from Harris-Benedict predictive equations) with 20% of calories from protein, 25% from fat, and 55% from carbohydrate. During the 2-week treatment period, subjects were monitored for blood pressure and blood glucose and were also monitored by telephone for compliance with the protocol.

Diet-only protocol

Nine subjects (7 males, 2 females) were recruited into a study to follow the above protocol, with two measurements of albumin synthesis and the same dietary instruction, but without the treatment with hrGH. Four of these subjects were controls (3 males, 1 female), and five were HIV+ (4 males, 1 female). The HIV+ subjects were divided between the HIV+ group (1) and the AIDS group (4).

Plasma volume

The measurement of plasma volume was made from the injection of 5 µCi 125I-albumin (Mallinckrodt). The radioactivity in five plasma samples, taken over 70 min following injection, was used to construct a semi-log graph for the determination of plasma volume.

Albumin concentration

The concentration of albumin in plasma was determined with bromocresol purple (Sigma, St. Louis, MO) with the addition of hexadimethrine bromide (Aldrich Chemical Corp, Milwaukee, WI) as recommended by Duggan and Duggan (22).

Albumin synthesis

Albumin synthesis was determined from the rate of transfer of L-[2H5]phenylalanine from the plasma into plasma albumin. We previously demonstrated that plasma phenylalanine enrichment closely approximates the enrichment within the liver when a flooding amount of L-[2H5]phenylalanine is given (23). Albumin was isolated from plasma by ethanol extraction of trichloracetic acid-precipitated plasma protein as described previously (24). Following hydrolysis in 6 M HCl, phenylalanine from albumin was enzymatically converted to ß-phenylethylamine (tyrosine decarboxylase (Sigma), solvent extracted, and converted to the n-heptafluorobutyryl derivative. The enrichment was determined following electron ionization by monitoring the ions at m/z 106 and 109 with a VG 800 quadrupole gas chromatography mass spectrometry (Fisons Instruments, Beverly, MA) as described previously (5, 25). The enrichment of phenylalanine in plasma was assessed after acid precipitation and cation-exchange chromatography by monitoring m/z 336 and 341 of the tertiary butyldimethylsilyl derivative.

The fractional rate of albumin synthesis (FSR) (expressed as a fraction of the intravascular albumin mass) was calculated from the increase in enrichment of albumin between 50–90 min of incorporation divided by the area inscribed by the enrichment of the plasma phenylalanine vs. time curve. The area used in the calculation corresponded to the time of synthesis, with correction for the time of secretion of albumin from the liver as described by Ballmer et al. (24).

The absolute rate of albumin synthesis (ASR) (expressed as the total amount synthesized per day) was calculated from the fractional rate of synthesis, the albumin concentration in plasma, and the plasma volume in each subject (24). The measurements of ASR were normalized for body weight.

IGF-I

As previously described, the concentration of IGF-I in serum was determined by RIA following removal of IGF-binding activity with acid-ethanol extraction and cryoprecipitation (26). The IGF-I antibody was from the National Pituitary Program, and standards of IGF-1 were supplied by Upstate Biotechnology Inc (Lake Placid, NY).

PICP

The concentration of the carboxy-terminal propeptide of type 1 procollagen (PICP) in serum was measured by RIA with a kit supplied by Incstar (Stillwater, MN).

Statistical analysis

Comparisons among the groups of individuals were made by an ANOVA with the Student-Newman-Keuls test for multiple comparisons. Within groups, the differences between pre- and post-GH values were assessed by paired t tests. Among-group comparisons of the proportional increases after hrGH treatment were assessed as the log post-GH log of the pre-GH value with ANOVA and Student-Newman-Keuls. All data are presented as means ± SEM, and P < 0.05 was taken as significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
GH study

Individuals with HIV+ infection vary considerably in the severity of disease, from HIV+ asymptomatic individuals to those with severe wasting. In this study patients with diarrhea, acute secondary illness, or cancer were excluded. Individuals who were studied were stratified into four groups depending on the severity of disease. The clinical and anthropometric measurements of the subjects are shown in Table 1Go. The control group had a significantly higher body mass index than the other three groups. In the HIV group, the difference from control may be because of the higher proportion of females in this group. The number of CD4+ cells of individuals in the HIV+ group were significantly higher than either of the AIDS groups, which were not different from each other.


View this table:
[in this window]
[in a new window]
  		Table 1. Clinical and anthropometric parameters of subjects

 
Following 2 weeks of hrGH treatment (6 mg/day), all of the individuals, including those with weight loss, increased significantly in body weight, with the largest increase occurring in the HIV+ group (Table 2Go). There were no significant differences in the basal levels of IGF-I among the groups (Table 2Go), and all of the groups showed a substantial 4- to 5-fold increase in IGF-I levels following hrGH administration. The degree of stimulation of IGF-I with hrGH treatment was not different among the groups. Despite the increased IGF-I levels, plasma glucose concentrations following hrGH treatment were not significantly different from basal levels: control 71 ± 4 mg/dL, HIV 75 ± 2 mg/dL, AIDS 77 ± 2 mg/dL, and AIDS weight loss 85 ± 4 mg/dL.


View this table:
[in this window]
[in a new window]
  		Table 2. Body weight and serum IGF-1 changes with hrGH treatment

 
The plasma levels of the carboxy-terminal PICP are shown in Fig. 1Go. The pre-GH levels were not different among the groups of patients. Even patients with AIDS and weight loss had levels of PICP that were comparable with the levels in healthy subjects. In response to hrGH treatment for 2 weeks, there were increased levels of PICP in controls (56 ± 15%, P = 0.002), HIV+ (24 ± 9%, not significant), AIDS (51 ± 7%, P < 0.001), and AIDS with weight loss (21 ± 12%,P = 0.02), with no significant difference in the degree of stimulation among the groups. In the HIV+ group, the increase in PICP did not reach statistical significance by paired t analysis, because one individual decreased PICP levels following 2 weeks of hrGH treatment. Despite the disparity in age among the groups, there was no correlation of the elevation of plasma PICP levels with age following hrGH.



View larger version (38K):
[in this window]
[in a new window]
  		Figure 1. Bone collagen formation (PICP levels in nanograms per milliliter) before and after hrGH. Data are expressed as means ± SEM. hrGH treatment was 6 mg/day for 14 days. *, Difference between before and after treatment, P < 0.02 (paired t test). There is no significant difference in the degree of stimulation among the groups.

 
The concentration of plasma albumin before GH treatment was not different among the groups: 38.55 ± 1.23 mg/mL in the control subjects, 31.33 ± 2.41 mg/mL in HIV subjects, 35.02 ± 1.89 mg/mL in AIDS, and 31.93 ± 1.52 mg/mL in AIDS subjects with weight loss. The rates of albumin synthesis are shown in Table 3Go. Albumin synthesis is expressed as a FSR, which is the fraction of the intravascular albumin mass synthesized each day, and as an ASR, which is the amount of albumin synthesized per kg body weight per day. In the basal state there were no differences among the groups in the rate of albumin synthesis, expressed either as a fractional rate or as an absolute rate. Thus, despite the increasing severity of disease from control and HIV+ to AIDS with weight loss, the basal synthesis of albumin was similar for all groups.


View this table:
[in this window]
[in a new window]
  		Table 3. Albumin synthesis, as a FSR and as amount of ASR, in controls and HIV+ individuals in response to hrGH treatment

 
In response to hrGH treatment, there were no significant changes in the concentration of plasma albumin or the plasma volume (Table 3Go). However, the FSR (Table 3Go) was increased significantly in control subjects (35 ± 5%, P < 0.001), in patients with HIV+ (37 ± 12.5%, P < 0.01) and AIDS (22.5 ± 5.5%, P < 0.001). The patients with AIDS and weight loss did not increase albumin FSR in response to hrGH treatment (-2.6 ± 5%). Although the AIDS weight loss group was, on average, older than the other groups, there was no correlation of the proportional change in albumin FSR with age. When albumin synthesis was assessed as an absolute rate (Table 3Go) there was also a significant increase in control subjects (23 ± 7%, P < 0.05), in HIV+ patients (39 ± 16%, P < 0.05), and in patients with AIDS (25 ± 7%, P < 0.01). However ASR, like FSR, was not increased by hrGH treatment in patients with AIDS and weight loss (-0.6 ± 12%).

Diet-only study

The subjects of the diet-only study were similar to those in the GH study with respect to age (38 ± 3 yr), height (1.75 ± 0.03 m), weight (75 ± 3 kg), and CD4+ cell number (352 ± 65 cells/mm3). These subjects, who were given the same dietary advice as the subjects in the GH study but no GH, did not increase weight significantly during the 2 weeks of the study. The values for the synthesis of albumin during the two measurements with the diet-only protocol are shown in Table 4Go. Despite the observations that albumin synthesis has been shown to be responsive to the intake of food (27, 28) and also to the presence of protein in the diet (29, 30, 31), the more modest increase in intake of 20% in this experiment did not alter albumin synthesis expressed as FSR or ASR (Table 4Go).


View this table:
[in this window]
[in a new window]
  		Table 4. Albumin synthesis rates, expressed as FSR and ASR, in healthy and HIV+ subjects measured before (basal) and 2 weeks after dietary advice to increase protein and energy (diet)

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
In this study an anabolic response to GH administration was observed for the formation of bone collagen in healthy subjects and in HIV+ patients, including asymptomatic patients and those with AIDS. Even patients with AIDS and weight loss of >10% of body weight increased bone formation in response to GH treatment. Albumin synthesis responded anabolically to GH treatment in the controls, HIV+, and AIDS patients, but did not respond anabolically in patients with AIDS and >10% loss of body weight. Both the response of bone collagen and of albumin synthesis are unlike the catabolic response of muscle protein synthesis previously reported (5).

Bone metabolism

The basal, pretreatment levels of PICP, formed from the cleavage of newly synthesized type 1 collagen, were similar in all groups (Fig. 1Go). Serum levels of this cleavage product, which is not incorporated into the collagen, are correlated with bone formation (32, 33, 34). Bone formation was stimulated by 2 weeks of hrGH (Fig. 1Go) in all patient groups. Mauras and colleagues (21) reported an increase in serum PICP levels of 24% in a group of healthy subjects treated with hrGH (0.025 mg/kg per day). In addition, serum PICP levels in those healthy subjects were increased further when IGF-I (10 µg/kg per h) was added to the hrGH protocol. In the present study, IGF-I levels were 4- to 5-fold higher than in the basal state, and there was no correlation between the serum concentrations of PICP and IGF-I. However, this lack of correlation may be because of the very high levels of IGF-I producing a maximal response rather than a graded one.

Albumin synthesis

Circulating levels of albumin tend to decrease either from depressed synthesis, such as occurs with malnutrition and cancer cachexia, or through enhanced permeability of capillaries to albumin, such as with acute infection (35). Reduced levels of albumin have also been reported in patients with AIDS (36). In animal studies, experimental conditions in which the albumin levels are reduced have been associated with reduced levels of albumin messenger RNA (mRNA) in liver (37), reduced albumin synthesis (38, 39), and enhanced albumin degradation (38). However, the latter study in cachexic mice suggested that the depression in albumin synthesis results from a reduction in dietary intake associated with the increase in tumor burden, since dietary-restricted, healthy animals showed a similar depression of albumin synthesis (38).

In the present study, patients with HIV infection and even the patients who had progressed to AIDS with weight loss had levels of plasma albumin that were not different from those in control subjects. The rates of albumin synthesis before hrGH treatment were also not depressed in any of the patient groups (Table 3Go), confirming that at the time of study these patients were neither acutely ill nor sufficiently malnourished to depress the rate of albumin synthesis. Synthesis of albumin has been expressed as both a fraction of the intravascular albumin mass that is synthesized (FSR), and as the amount of albumin synthesized over 24 h (ASR), derived from the intravascular albumin mass and the FSR. HIV+ infection, even with progression to AIDS with weight loss, did not depress the synthesis of albumin expressed either as FSR or ASR.

In healthy subjects, 2 weeks of hrGH treatment (6 mg/day), increased albumin synthesis (FSR, Table 3Go) substantially (35%). This increase in the synthesis of albumin was not associated with an increase in intravascular albumin mass, suggesting either that the degradation rate of albumin was also increased, or that the distribution of albumin into the extravascular space was increased in response to GH treatment.

In AIDS patients with >10% weight loss, albumin synthesis was not increased by hrGH treatment (-3%, difference from other groups, P < 0.05). An inability to stimulate protein synthesis at the tissue level after 2 weeks of hrGH is in contrast to the accumulation of lean body mass observed with longer treatment regimens in patients with weight loss (7, 8, 9). It may be that longer treatment regimens are necessary to facilitate anabolic responsiveness in patients with AIDS and weight loss.

The inability of large amounts of hrGH to stimulate albumin synthesis in patients with AIDS wasting contrasts with the demonstration that treatment of isolated hepatocytes with 500 ng GH/mL is associated with increased transcription of both IGF-I and albumin (40). This study also reported decreased mRNA stability, so that the levels of mRNA for IGF-I and albumin were not altered (40). The inability of patients with AIDS wasting to increase albumin synthesis despite the observed increase in IGF-I, suggests a modification of the response in the liver to IGF-I.

A failure to increase albumin synthesis with hrGH treatment (2.8 mg/day for 2 weeks or 0.7 mg/day for 4 weeks) has also been observed in elderly subjects, despite an improvement in nitrogen retention in these individuals (41). There was no correlation of the response of ASR with age in this study. Thus, it would seem that resistance to the stimulatory effect of hrGH on albumin synthesis occurs in both the elderly and in patients with AIDS that have progressed to weight loss. This resistance to the action of hrGH occurs despite uniformly high levels of IGF-I.

The activity of IGF-I is influenced by the concentration of binding proteins (reviewed in Ref. 42). The pattern of circulating binding proteins is altered in both AIDS patients with weight loss (6) and the elderly (42, 43). In both groups there was an elevation in IGF-I binding protein 1 (IGFBP-1). It is possible that the elevation of IGFBP-1 reduced the availa-bility of IGF-I to the tissues. However, the 4-fold elevation in concentration of IGF-I following GH administration makes this somewhat unlikely. Previously reported data on elevations of IGFBP-1 following fasting indicated that the changes in IGFBP-1 were not associated with decreased availability of metabolically active free IGF-I (44). In response to hrGH treatment, the circulating level of IGFBP-1 was decreased, but IGFBP-3 concentrations were increased in control subjects and all the patient groups (6). Therefore, it seems unlikely that the diminished response of albumin in the AIDS with weight loss group was mediated by an alteration in IGF-I bioavailability brought about by changes in IGF binding proteins.

Both the elderly and the AIDS patients with weight loss have a resistance to IGF-I-mediated stimulation of albumin synthesis though elevated levels of IGF binding proteins is unlikely to explain this resistance. However, both elderly subjects (45, 46) and patients with AIDS wasting (47) have elevated levels of cytokines, including tumor necrosis factor-{alpha} and interferon-{alpha}, and it may be that the elevated cytokines mediate the observed resistance to IGF-I.

In conclusion, GH stimulated the formation of bone and the synthesis of albumin in healthy controls and in individuals with HIV infection at early stages of disease. When the disease had progressed to AIDS with >10% weight loss, there was a decrease in the sensitivity of albumin synthesis to hrGH. However even in patients with AIDS and wasting, the sensitivity to hrGH was retained by collagen and IGF-I formation.


   Acknowledgments
 
We thank Dr. Monica Scantlebury and the nursing staff of the CRC for their assistance in carrying out these studies. Skillful technical assistance was provided by Dawn Sasvary for the isolation of albumin and by George Casella for mass spectrometry. We also thank Joshua Rosenthal for his help in expanding our data handling capabilities.


   Footnotes
 
1 This work was supported by the National Institutes of Health Grant DK 49316–01 (to M.C. Gelato) and a National Institutes of Health-sponsored Institutional Research Service Award T32DK07521 to the Diabetes and Metabolic Diseases Research Program at Stony Brook (to R.A. Frost). Both the Serostim and a small travel grant were generously provided by Serono Laboratories (Norwell, Massachusetts). Back

Received February 2, 1998.

Revised May 7, 1998.

Accepted May 28, 1998.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Kotler DP, Tierney J, Wang J, Pierson RN, Jr. 1989 Magnitude of body-cell-mass depletion, and the timing of death from wasting in AIDS. Am J Clin Nutr. 50:444–447.[Abstract/Free Full Text]
  2. Palenicek JP, Graham NMH, He YD, et al. 1995 Weight loss prior to clinical AIDS as a predictor of survival. J AIDS. 10:366–373.
  3. Suttman U, Ockenga J, Selberg O, Hoogestraat L, Deicher H, Muller MJ. 1995 Incidence and prognostic value of malnutrition and wasting in HIV-infected outpatients. J AIDS. 8:239–246.
  4. Ott M, Fischer H, Polat H, et al. 1995 Bioelectrical impedance analysis as a predictor of survival in patients with human immunodeficiency virus infection. J AIDS. 9:20–25.
  5. McNurlan MA, Garlick PJ, Steigbigel RT, et al. 1997 Responsiveness of muscle protein synthesis to growth hormone administration in HIV-infected individuals declines with severity of disease. J Clin Invest. 100:2125–2132.[Medline]
  6. Gelato MC, Frost RA, DeCristofaro K, et al. 1996 Growth hormone (GH) deficiency and diminished anabolic response in muscle of HIV-infected adults. Prog 10th International Congress of Endocrinology. 253 (Abstr P1–476).
  7. Krentz AJ, Koster FT, Crist DM, et al. 1993 Anthropometric, metabolic, and immunological effects of recombinant human growth hormone in AIDS and AIDS-related complex. J AIDS. 6:245–251.
  8. Mulligan K, Grunfeld C, Hellerstein MK, Neese RA, Schambelan M. 1993 Anabolic effects of recombinant human growth hormone in patients with wasting associated with human immunodeficiency virus infection. J Clin Endocrinol Metab. 77:956–962.[Abstract]
  9. Schambelan M, Mulligan K, Grunfeld C, et al. 1996 Recombinant human growth hormone in patients with HIV-associated wasting: a randomized, placebo-controlled trial. Ann Intern Med. 125:873–882.[Abstract/Free Full Text]
  10. Clemmons DR, Snyder DK, Williams R, Underwood LE. 1987 Growth hormone administration conserves lean body mass during dietary restriction in obese subjects. J Clin Endocrinol Metab. 64:878–883.[Abstract]
  11. Fong Y, Rosenbaum M, Tracey KJ, et al. 1989 Recombinant growth hormone enhances muscle myosin heavy-chain mRNA accumulation and amino acid accrual in humans. Proc Natl Acad Sci USA. 86:3371–3374.[Abstract/Free Full Text]
  12. Lundeberg S, Belfrage M, Wernerman J, von der Decken A, Thunell S, Vinnars E. 1991 Growth hormone improves muscle protein metabolism and whole body nitrogen economy in man during a hyponitrogenous diet. Metabolism. 40:315–322.[CrossRef][Medline]
  13. Wolf RF, Pearlstone DB, Newman E, et al. 1992 Growth hormone and insulin reverse net whole body and skeletal muscle protein catabolism in cancer patients. Ann Surg. 216:280–312.[Medline]
  14. Ward HC, Halliday D, Sim AJW. 1987 Protein and energy metabolism with biosynthetic human growth hormone after gastrointestinal surgery. Ann Surg. 206:56–61.[Medline]
  15. Mjaaland M, Unneberg K, Larsson J, Nilsson L, Revhaug A. 1993 Growth hormone after abdominal surgery attenuated forearm glutamine, alanine, 3-methylhistidine, and total amino acid efflux in patients receiving total parenteral nutrition. Ann Surg. 217:413–422.[CrossRef][Medline]
  16. Horber FF, Haymond MW. 1990 Human growth hormone prevents the protein catabolic side effects of prednisone in humans. J Clin Invest. 86:265–272.
  17. Gore DC, Honeycutt D, Jahoor F, Wolfe RR, Herndon DN. 1991 Effect of exogenous growth hormone on whole-body and isolated-limb protein kinetics in burned patients. Arch Surg. 126:38–43.[Abstract]
  18. Canalis E, McCarthy T, Centrella M. 1988 Growth factors and the regulation of bone remodeling. J Clin Invest. 81:277–281.
  19. McCarthy TL, Centrella M, Canalis E. 1989 Insulin-like growth factor (IGF) and bone. Connect Tissue Res. 20:277–282.[Medline]
  20. Bollerslev J, Moller J, Thomas S, Djoseland O, Christiansen JS. 1996 Dose-dependent effects of recombinant human growth hormone on biochemical markers of bone and collagen metabolism in adult growth hormone deficiency. Eur J Endocrinol. 135:666–671.[Abstract/Free Full Text]
  21. Mauras N, Doi SQ, Shapiro JR. 1996 Recombinant human insulin-like growth factor I, recombinant human growth hormone, and sex steroids: effects on markers of bone turnover in humans. J Clin Endocrinol Metab. 81:2222–2226.[Abstract]
  22. Duggan J, Duggan PF. 1982 Albumin by bromcresol green–a case of laboratory conservatism. Clin Chem. 28:1408–1407.[Free Full Text]
  23. Barle H, Nyberg B, Andersson K, et al. 1997 The effects of short-term parenteral nutrition on human liver protein and amino acid metabolism during laproscopic surgery. JPEN J Parenteral Enteral Nutr. 21:330–335.[Abstract]
  24. Ballmer PE, McNurlan MA, Milne E, et al. 1990 Measurement of albumin synthesis in humans: a new approach employing stable isotopes. Am J Physiol. 259:E797–E803.
  25. McNurlan MA, Essen P, Thorell A, et al. 1994 Response of protein synthesis in human skeletal muscle to insulin: an investigation with L-[2H5]-phenylalanine. Am J Physiol 267:E102–E108.
  26. Frost RA, Fuhrer J, Steigbigel R, Mariuz P, Lang CH, Gelato MC. 1996 Wasting in the acquired immune deficiency syndrome is associated with multiple defects in the serum insulin-like growth factor system. Clin Endocrinol (Oxf). 44:501–514.[CrossRef][Medline]
  27. De Feo P, Horber FF, Haymond MW. 1992 Meal stimulation of albumin synthesis: a significant contributor to whole body protein synthesis in humans. Am J Physiol. 263:E794–E799.
  28. Hunter KA, Ballmer PE, Anderson SE, Broom J, Garlick PJ, McNurlan MA. 1995 Acute stimulation of albumin synthesis rate with oral meal feeding in healthy subjects measured with [2H5-ring]phenylalanine. Clin Sci. 88:235–242.[Medline]
  29. Gersovitz M, Munro HN, Udall J, Young VR. 1980 Albumin synthesis in young and elderly subjects using a new stable isotope methodology: response to level of protein intake. Metabolism. 29:1075–1085.[CrossRef][Medline]
  30. Kelman L, Saunders SJ, Frith L, Wicht S, Corrigal A. 1972 Effects of dietary protein restriction on albumin synthesis, albumin catabolism, and the plasma aminogram. Am J Clin Nutr. 25:1174–1178.[Abstract]
  31. Cayol M, Boirie Y, Prugnaud J, Gachon P, Beaufrere B, Obled C. 1996 Precursor pool for hepatic protein synthesis in humans: effects of tracer route infusion and dietary proteins. Am J Physiol. 270:E980–E987.
  32. Parfitt AM, Simon LS, Villanueva AR, Krane SM. 1987 Procollagen type I carboxy-terminal extension peptide in serum as a marker of collagen biosynthesis in bone. Correlation with iliac bone formation rates and comparison with total alkaline phosphatase. J Bone Miner Res. 2:427–436.[Medline]
  33. Hassager C, Jensen LT, Johansen JS, et al. 1991 The carboxy-terminal propeptide of type I procollagen in serum as a marker of bone formation: the effect of nandrolone decanoate and female sex hormones. Metabolism. 40:205–208.[CrossRef][Medline]
  34. Eriksen EF, Charles P, Melsen F, Mosekilde L, Risteli L, Risteli J. 1993 Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry. J Bone Miner Res. 8:127–132.[Medline]
  35. Rothschild MA, Oratz M, Schreiber SS. 1988 Serum albumin. [Review]. Hepatology. 8:385–401.[Medline]
  36. Chlebowski RT, Grosvenor MB, Bernhard NH, Morales LS, Bulcavage LM. 1989 Nutritional status, gastrointestinal dysfunction, and survival in patients with AIDS. Am J Gastroenterol. 84:1288–1293.[Medline]
  37. Brenner DA, Buck M, Feitelberg SP, Chojkier M. 1990 Tumor necrosis factor-{alpha} inhibits albumin gene expression in a murine model of cachexia. J Clin Invest. 85:248–255.
  38. Andersson CE, Lonnroth IC, Gelin LJ, Moldawer LL, Lundholm KG. 1991 Pretranslational regulation of albumin synthesis in tumor-bearing mice. The role of anorexia and undernutrition. Gastroenterology. 100:938–945.[Medline]
  39. Ballmer PE, McNurlan MA, Grant L, Garlick PJ. 1995 Down-regulation of albumin synthesis in the rat by human recombinant interleukin-1ß or turpentine and the response to nutrients. JPEN J Parenter Enteral Nutr. 19:266–271.[Abstract]
  40. Johnson RR, Rudin SD, Blossey BK, Ilan J, Ilan J. 1991 Newly sunthesized RNA: simultaneous measurement in intact cells of transcription rates and RNA stability of insulin-like growth factor I, actin, and albumin in growth hormone-stimulated hepatocytes. Proc Natl Acad Sci USA. 88:5287–5291.[Abstract/Free Full Text]
  41. Zachwieja JJ, Bier DM, Yarasheski KE. 1994 Growth hormone administration in older adults: effects on albumin synthesis. Am J Physiol. 266:E840–E844.
  42. Gelato MC, Frost RA. 1997 IGFBP-3. Functional and structural implications in aging and wasting syndromes. Endocrine. 7:81–85.[Medline]
  43. Rutanen EM, Kärkkäinen T, Stenman UH, Yki-Jävinen H. 1993 Aging is associated with decreased suppression of insulin-like growth factor binding protein-1 by insulin. J Clin Endocrinol Metab. 77:1152–1155.[Abstract]
  44. Bereket A, Lang CH, Blethen SL, Gelato, MC, Fan J, Frost RA, Wilson TA. 1995 Effect of insulin on the insulin-like growth factor system in children with new-onset insulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 80:1312–1317.[Abstract]
  45. Cannon JG. 1995 Cytokines in aging and muscle homeostasis. J Gerontol. 50A:120–123.
  46. Rall LC, Rosen CJ, Dolnikowski G, et al. 1996 Protein metabolism in rheumatoid arthritis and aging: effects of strength training and tumor necrosis factor {alpha}. Arthritis Rheum. 39:1115–1124.[Medline]
  47. Grunfeld C, Feingold KR. 1992 Seminars in medicine of the Beth Israel Hospital, Boston. Metabolic disturbances and wasting in the acquired immunodeficiency syndrome. N Engl J Med. 327:329–337.[Medline]



This article has been cited by other articles:


Home page
 Am. J. Clin. Nutr.Home page
G. Caso, J. Feiner, I. Mileva, L. J Bryan, P. Kelly, K. Autio, M. C Gelato, and M. A McNurlan
Response of albumin synthesis to oral nutrients in young and elderly subjects
Am. J. Clinical Nutrition, February 1, 2007; 85(2): 446 - 451.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. A. Frost, G. J. Nystrom, and C. H. Lang
Regulation of IGF-I mRNA and Signal Transducers and Activators of Transcription-3 and -5 (Stat-3 and -5) by GH in C2C12 Myoblasts
Endocrinology, February 1, 2002; 143(2): 492 - 503.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. C. Person, L. L. Waite, R. N. Taylor, and T. S. Scanlan
Albumin Regulates Induction of Peroxisome Proliferator-Activated Receptor-{{gamma}} (PPAR{{gamma}}) by 15-Deoxy-{{Delta}}12-14-Prostaglandin J2 in Vitro and May Be an Important Regulator of PPAR{{gamma}} Function in Vivo
Endocrinology, February 1, 2001; 142(2): 551 - 556.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
R. A. Frost and C. H. Lang
Differential Effects of Insulin-Like Growth Factor I (IGF-I) and IGF-Binding Protein-1 on Protein Metabolism in Human Skeletal Muscle Cells
Endocrinology, September 1, 1999; 140(9): 3962 - 3970.
[Abstract] [Full Text]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McNurlan, M. A.
Right arrow Articles by Gelato, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McNurlan, M. A.
Right arrow Articles by Gelato, M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals