Biomedical subjects

D R Powell

Publications and source records attributed to D R Powell.

At least 37 records · Page 2Linked to original sources

PubMed1999

Activation of the insulin-like growth factor binding protein-1 promoter by progesterone receptor in decidualized human endometrial stromal cells.

Insulin-like growth factor binding protein-1 (IGFBP-1) is induced extensively when human endometrial stromal cells are decidualized by progestin and relaxin in a long-term primary culture system. The purpose of this study is to investigate whether progesterone receptor (PR) directly activates the IGFBP-1 gene promoter. In decidualized stromal cells, activity of the IGFBP-1 promoter (from -1.2 kb to +68 bp) containing putative progesterone-response elements (PREs) was increased 80-fold. Mutation of either 5' or 3' half-site of the putative PRE1 site (from -193 to -179 bp) reduced the promoter activity. Mutations that converted PRE1 closer to consensus PRE increased the promoter activity. In undifferentiated stromal cells, mutations of PRE sites had no effect on the promoter activity. When a PR expression vector (hPR1) was cotransfected, progestin increased promoter activity derived from p275CAT but not from p1.2CAT, suggesting that the function of PRE1 was repressed by the region from -1.2 kb to -275 bp in the promoter. Progestin did not increase promoter activity derived from p275CAT without cotransfection of hPR1, suggesting that endogenous PR alone is insufficient to activate PRE1. In summary, results indicate that the PRE1 site of the IGFBP-1 promoter mediates a direct activation of PR on transcription specifically in decidualized stromal cells.

Adult↗

PubMed1999

Direct control of the Forkhead transcription factor AFX by protein kinase B.

The phosphatidylinositol-3-OH-kinase (PI(3)K) effector protein kinase B regulates certain insulin-responsive genes, but the transcription factors regulated by protein kinase B have yet to be identified. Genetic analysis in Caenorhabditis elegans has shown that the Forkhead transcription factor daf-16 is regulated by a pathway consisting of insulin-receptor-like daf-2 and PI(3)K-like age-1. Here we show that protein kinase B phosphorylates AFX, a human orthologue of daf-16, both in vitro and in vivo. Inhibition of endogenous PI(3)K and protein kinase B activity prevents protein kinase B-dependent phosphorylation of AFX and reveals residual protein kinase B-independent phosphorylation that requires Ras signalling towards the Ral GTPase. In addition, phosphorylation of AFX by protein kinase B inhibits its transcriptional activity. Together, these results delineate a pathway for PI(3)K-dependent signalling to the nucleus.

3T3 Cells↗

PubMed1999

NF-ATc isoforms are differentially expressed and regulated in murine T and mast cells.

NF of activated T cells (NF-AT) denotes a family of transcription factors that regulate the activation-dependent expression of many immunologically important proteins. At least four distinct genes encode the various family members, and several isoforms of these have been identified as well. The overlapping expression patterns and similar in vitro binding and trans-activation activities on various promoter elements of NF-AT-regulated genes suggest some redundancy in the function of these proteins. However, the phenotypic analysis of NF-AT-deficient mice supports the idea that there are tissue- and gene-specific functions as well. In this study we have characterized the expression of NF-AT cDNAs in murine mast cells. The majority of clones identified correspond to two NF-ATc isoforms that differ only in their amino-terminal sequence. Despite minimal discrepancies in the coding region, there are striking tissue- and cell type-specific differences in isoform expression patterns. Detection of NF-ATc.alpha mRNA is strictly dependent on cell activation signals in both T and mast cell lines. In contrast, the beta isoform is expressed at very low constitutive levels in both cell types but is only up-regulated in response to mast cell activation signals delivered through the FcepsilonRI or via calcium ionophores. These results demonstrate another level of regulation within the NF-AT family that can contribute to cell type-specific gene expression.

Amino Acid Sequence↗

PubMed1999

FKHR binds the insulin response element in the insulin-like growth factor binding protein-1 promoter.

The insulin response element (IRE) in the IGFBP-1 promoter, and in other gene promoters, contains a T(A/G)TTT motif essential for insulin inhibition of transcription. Studies presented here test whether FKHR may be the transcription factor that confers insulin inhibition through this IRE motif. Immunoblots using antiserum to the synthetic peptide FKHR413-430, RNase protection, and Northerns blots show that FKHR is expressed in HEP G2 human hepatoma cells. Southwestern blots, electromobility shift assays, and DNase I protection assays show that Escherichia coli-expressed GST-FKHR binds specifically to IREs from the IGFBP-1, PEPCK and TAT genes; however, unlike HNF3beta, another protein proposed to be the insulin regulated factor, GST-FKHR does not bind the insulin unresponsive G/C-A/C mutation of the IGFBP-1 IRE. When HEP G2 cells were cotransfected with FKHR expression vectors and with IGFBP-1 promoter plasmids containing either native or mutant IREs, FKHR expression induced a 5-fold increase in activity of the native IGFBP-1 promoter but no increase in activity of promoter constructs containing insulin unresponsive IRE mutants. These data suggest that FKHR, and/or a related family member, is the important T(G/A)TTT binding protein that confers the inhibitory effect of insulin on gene transcription.

DNA-Binding Proteins↗

PubMed1999

Effects of chronic renal failure and growth hormone on serum levels of insulin-like growth factor-binding protein-4 (IGFBP-4) and IGFBP-5 in children: a report of the Southwest Pediatric Nephrology Study Group.

Children with chronic renal failure (CRF) have high serum levels of insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1), -2, and -6. The excess IGFBP-2 and -1 may play a role in the growth failure of CRF children by sequestering IGF peptides. In contrast, IGFBP-3 levels rise with GH treatment of CRF children, suggesting a role for IGFBP-3 in their accelerated growth. The present studies used sensitive and specific antisera to characterize levels and forms of IGFBP-4 and -5 in serum from CRF children. By RIA, the mean baseline serum level of IGFBP-4 was high in CRF children compared to that in normal children, but the IGFBP-4 level in CRF serum did not correlate with height SD score; by immunoblot, high CRF levels were associated with increases in both intact and fragmented IGFBP-4. Mean RIA levels of IGFBP-5 were comparable in sera from CRF and normal children. Treating CRF children with GH for 12 months increased serum IGFBP-4 levels by 26% and IGFBP-5 levels by 49%, as determined by RIA; levels of IGFBP-5, but not IGFBP-4, correlated significantly with serum levels of IGF-I, IGF-II, IGFBP-3, and acid-labile subunit and with growth rate in these GH-treated children. In summary, IGFBP-4 levels are high in serum of CRF children, and GH increases serum levels of IGFBP-4 and IGFBP-5 in these children. The data suggest a role for IGFBP-5 in the accelerated growth of GH-treated CRF children, perhaps as part of a ternary complex with acid-labile subunit and IGFs. Additional studies on the relationship between intact IGFBP-4 levels and growth are needed to determine what role IGFBP-4 plays in the linear growth process in vivo.

Body Height↗

PubMed1999

Conservation of an insulin response unit between mouse and human glucose-6-phosphatase catalytic subunit gene promoters: transcription factor FKHR binds the insulin response sequence.

Because overexpression of the glucose-6-phosphatase catalytic subunit (G-6-Pase) in both type 1 and type 2 diabetes may contribute to the characteristic increased rate of hepatic glucose production, we have investigated whether the insulin response unit (IRU) identified in the mouse G-6-Pase promoter is conserved in the human promoter. A series of human G-6-Pase-chloramphenicol acetyltransferase (CAT) fusion genes was transiently transfected into human HepG2 hepatoma cells, and the effect of insulin on basal CAT expression was analyzed. The results suggest that the IRU identified in the mouse promoter is conserved in the human promoter, but that an upstream multimerized insulin response sequence (IRS) motif that is only found in the human promoter appears to be functionally inactive. The G-6-Pase IRU comprises two distinct promoter regions, designated A and B. Region B contains an IRS, whereas region A acts as an accessory element to enhance the effect of insulin, mediated through region B, on basal G-6-Pase gene transcription. We have previously shown that the accessory factor binding region A is hepatocyte nuclear factor-1, and we show here that the forkhead protein FKHR is a candidate for the insulin-responsive transcription factor binding region B.

Animals↗

PubMed1999

Characteristics of successful wellness programs.

Wellness programs have proved to be an effective tool to use in reining in health care costs. This author describes successful wellness programs and shows that these programs not only improve the bottom line for employers or Taft-Hartley funds, but they also help employees feel better about themselves and more positive about the organization they work for.

Cost-Benefit Analysis↗

PubMed1998

Hypoxia stimulates insulin-like growth factor binding protein 1 (IGFBP-1) gene expression in HepG2 cells: a possible model for IGFBP-1 expression in fetal hypoxia.

IGFBP-1 is elevated in fetuses with long-term, chronic hypoxia and intrauterine growth restriction. We investigated the hypothesis that hypoxia regulates IGFBP-1 in the human fetus in vivo and IGFBP-1 gene expression and protein in vitro. Umbilical artery IGFBP-1 levels (mean +/- SEM) from term babies with respiratory acidosis (acute hypoxia), normal babies, and those with mixed respiratory/metabolic acidosis (more profound and prolonged hypoxia) were measured using an immunoradiometric assay. IGFBP-1 levels were similar in normal (n = 12) and acutely hypoxic (n = 6) babies (189.1 +/- 71.8 vs. 175.8 +/- 45.9 ng /ml, respectively, P = 0.789). However, with more profound and prolonged hypoxia (n = 19), IGFBP-1 levels were markedly elevated (470.6 +/- 80.0 ng /ml, P = 0.044). To investigate IGFBP-1 regulation by hypoxia in vitro, HepG2 cells were incubated under hypoxia (pO2 = 2%) and normoxia (pO2 = 20%). IGFBP-1 protein and mRNA increased 8- and 12-fold, respectively, under hypoxic conditions. Hypoxia did not affect protein or mRNA levels of IGFBP-2 or -4. IGFBP-5 and -6 mRNAs, undetectable in control cells, were not induced by hypoxia, whereas minimally expressed IGFBP-3 mRNA increased twofold. Investigation into IGFBP-1 gene structure revealed three potential consensus sequences for the hypoxia response element (HRE) in the first intron. To investigate functionality, a 372-bp fragment of IGFBP-1 intron 1, containing putative HREs, was placed 5' to a heterologous hsp70 promoter in a plasmid using luciferase as a reporter gene. Under hypoxia, reporter gene activity increased up to 30-fold. Mutations in the middle HRE abolished reporter activity in response to hypoxia, suggesting that this HRE is functional in the IGFBP-1 hypoxia response. Cotransfection of HRE reporter genes with a constitutively expressing hypoxia-inducible factor 1 plasmid in HepG2 cells resulted in a fourfold induction of reporter activity, suggesting a role for hypoxia-inducible factor 1 in hypoxia induction of IGFBP-1 gene expression. These data support the hypothesis that hypoxia regulation of IGFBP-1 may be a mechanism operating in the human fetus to restrict insulin-like growth factor-mediated growth in utero under conditions of chronic hypoxia and limited substrate availability.

Animals↗

PubMed1998

Age and ethnicity affect the risk and outcome of focal segmental glomerulosclerosis.

In patients with proteinuria, African-American (AA) ethnicity is reported to be a risk factor for focal segmental glomerulosclereosis (FSGS) and its progression to end-stage renal disease (ESRD). We reviewed our single-center experience to determine the probability of FSGS and its progression to ESRD based on ethnicity and age at presentation in children with proteinuria with or without nephrotic syndrome. Proteinuria without systemic disease or acute glomerulonephritis was the presenting feature in 17% (236/1,403) of children in the renal patient database of Texas Children's Hospital, Baylor College of Medicine. Histopathological diagnoses were established in 107 of 236 patients (45%). FSGS was identified in 65 patients, accounting for 28% of all patients with proteinuria and 61% of patients who underwent renal biopsy. FSGS was more prevalent in AA (45%) than in non-AA patients (22%) (P=0.001), and AA patients with FSGS were older at presentation (12.7+/-4.4 years) than non-AA patients (5.6+/-4.6 years) (P<0.001). Among patients who underwent renal biopsy, increasing age at presentation increased the probability of having FSGS in AA but not non-AA patients (P=0.04). Five-year actuarial renal survival of FSGS was worse in AA (8%) than in non-AA patients (31%) (P=0.01). These data suggest an increased risk and worse outcome of FSGS in AA compared with non-AA children.

Adolescent↗

PubMed1998

Ergosteroids III. Syntheses and biological activity of seco-steroids related to dehydroepiandrosterone.

The unusual activity of some D-ring-seco estrogens led us to prepare several seco steroids related to dehydroepiandrosterone (DHEA) and to test for their ability to mimic thyroid hormone and 7-oxo-DHEA (1) as inducers of thermogenic enzymes in rats' livers. Only one, 3 beta-acetoxy-17a-oxa-androst-5-ene-7,17-dione (17), was capable of inducing both mitochondrial glycerophosphate dehydrogenase and malic enzyme. The closely related 3 beta-hydroxy-17a-oxa-androsta-5,15-diene-7,17-diones (both 14 alpha and 14 beta, 14 and 15) induce the formation of malic enzyme but not of glycerophosphate dehydrogenase. The 3 beta-propionyl ester of the above 14 alpha steroid was not active, presumably because it was not deacylated in vivo. The 16,17 dicarboxylic acid (9) produced by opening the D-ring also induced the formation of malic enzyme but not of glycerophosphate dehydrogenase. 3 beta-Acetoxyandrost-5-ene-7,16,17-trione, an intermediate in the synthesis of D-ring seco compounds enhanced the formation of both enzymes. Twelve other D-ring seco compounds were not active. Seco androstanes oxygenated at position 7 and with expanded A or B rings were not active.

Animals↗

PubMed1998

Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3.

Limited proteolysis lowers affinity of insulin-like growth factor (IGF)-binding protein (IGFBP)-3 for bound IGFs, resulting in greater IGF bioavailability. Plasmin is one of many proteases that cleave IGFBP-3, and the plasmin system may regulate IGFBP-3 proteolysis and IGF bioavailability in cultured cells in vitro. A role for the plasmin system in IGFBP-3 proteolysis in vivo is suggested by data presented here showing that IGFBP-3 binds plasminogen (Pg; Glu-Pg) with a dissociation constant (Kd) ranging from 1.43 to 3.12 nM. IGF-I and Glu-Pg do not compete for IGFBP-3 binding; instead, the binary IGFBP-3/Glu-Pg complex binds IGF-I with high affinity (Kd = 0. 47 nM) to form a ternary complex. Competitive binding studies suggest that the kringle 1, 4, and 5 domains of Glu-Pg and the heparin-binding domain of IGFBP-3 participate in forming the IGFBP-3/Glu-Pg complex, and other studies show that Glu-Pg in this complex is activated at a normal rate by tissue Pg activator. Importantly, IGFBP-3/Glu-Pg complexes were detected in both human citrate plasma and serum, indicating that these complexes exist in vivo. Binding of IGFBP-3 to Glu-Pg in vivo suggests how Glu-Pg activation can specifically lead to IGFBP-3 proteolysis with subsequent release of IGFs to local target tissues.

Amino Acid Sequence↗

PubMed1998

The insulin-like growth factor axis and growth in children with chronic renal failure: a report of the Southwest Pediatric Nephrology Study Group.

Children with chronic renal failure (CRF) are often growth recarded despite normal serum levels of GH and insulin-like growth factors (IGFs). Recent studies suggest that excess IGF-binding proteins (IGFBPs) in the 35-kDa fractions of CRF serum contribute to CRF growth failure. This report characterizes the relationship between IGFBP-3 and IGF peptides in the serum of growth-retarded CRF children. Size-exclusion chromatography at pH 7.4 found IGFBP-3 and IGFs almost exclusively in the 150-kDa fractions of normal serum, where their molar stoichiometry was approximately 1:1. However, similar chromatography of CRF serum found a molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions and large amounts of IGFs in the 35-kDa fractions. In the 150-kDa fractions of CRF serum, IGFBP-3 was present in normal amounts, but a greater than normal amount was in the form of a 29-kDa IGFBP-3 fragment. Treatment of these CRF children with recombinant human GH increased the molar excess of IGFBP-3 over total IGFs in the 150-kDa fractions, the amount of IGFBP-3 and total IGFs in the 150-kDa fractions, and the amount of IGFs, but not IGFBPs, in the 35-kDa fractions. These data suggest that in untreated CRF children, proteolysis of IGFBP-3 in the 150-kDa fractions releases IGFs to the excess IGFBPs in the 35-kDa fractions, but insufficient IGF is released to overcome the growth-inhibiting effects of these excess IGFBPs. Treatment with recombinant human GH increases levels of IGFs and IGFBP-3 in the 150-kDa fractions, and subsequent IGFBP-3 proteolysis releases sufficient IGF to overcome the growth inhibitory effects of excess IGFBPs in the 35-kDa fractions of CRF serum.

Child↗

PubMed1998

Discovering simple DNA sequences by compression.

An information-theoretic DNA compression scheme devised by Milosavljevic and Jurka (1993) has been used in many places in the literature for both the discovery of new genes and the compression of DNA. Their compression method applies an encoding of previously occurring runs. They use 5 different code-words: four being the DNA bases, A, C, G and T, and the other being a pointer to a previously occurring run. They advocate a code-word of length log2 5 for each of these and then encoding a run by a code-word of length 2 x log2 n, where n is the length of the sequence. This scheme encodes the start of the sequence with a code-word of length log2 n and likewise encodes the end of the sequence with a code-word of length log2 n. In this paper, we show the above coding scheme to be inefficient in various ways and improve upon it so that it can compress DNA. We discuss our implementation of various schemes some of which run in linear time.

Algorithms↗

PubMed1997

Residue-based control of helix shape in beta-peptide oligomers.

Proteins and RNA are unique among known polymers in their ability to adopt compact and well-defined folding patterns. These two biopolymers can perform complex chemical operations such as catalysis and highly selective recognition, and these functions are linked to folding in that the creation of an active site requires proper juxtaposition of reactive groups. So the development of new types of polymeric backbones with well-defined and predictable folding propensities ('foldamers') might lead to molecules with useful functions. The first step in foldamer development is to identify synthetic oligomers with specific secondary structural preferences. Whereas alpha-amino acids can adopt the well-known alpha-helical motif of proteins, it was shown recently that beta-peptides constructed from carefully chosen beta-amino acids can adopt a different, stable helical conformation defined by interwoven 14-membered-ring hydrogen bonds (a 14-helix; Fig. 1a). Here we report that beta-amino acids can also be used to design beta-peptides with a very different secondary structure, a 12-helix (Fig. 1a). This demonstrates that by altering the nature of beta-peptide residues, one can exert rational control over the secondary structure.

Amino Acids↗

PubMed1997

Effects of renal failure on the growth hormone-insulin-like growth factor axis.

Children with chronic renal failure (CRF) often have retarded growth, and abnormalities of the growth hormone-insulin-like growth factor (GH-IGF) axis in CRF may contribute to this growth failure. The serum GH and IGF levels are normal in these children, but IGF bioactivity is low as a result of excess IGF binding proteins (IGFBPs) in the 35 kd serum fractions. The levels of intact IGFBP-1, -2, and -6 and of a 29 kd IGFBP-3 fragment are all high, and the IGFBP-1 and -2 levels correlate negatively with height. Children with CRF who are treated with GH show catch-up growth that correlates positively with the increase in each component of the 150 kd serum ternary complex (acid-labile subunit, IGFBP-3, IGF-I, and IGF-II). Consistent with this observation, the increase in IGFBP-3 levels is confined to the 150 kd serum fractions. Serum levels of IGFBP-1, -2, and -6 do not rise, but serum IGF bioactivity does. Thus GH appears to induce an increase in the ternary complex in the serum of children with CRF. It is possible that IGFs released by the 150 kd serum complex promote growth by overcoming the inhibitory effects of excess IGFBPs in the 35 kd serum fractions.

Body Height↗

PubMed1997

Chicken insulin-like growth factor binding protein (IGFBP)-5: conservation of IGFBP-5 structure and expression during evolution.

A complementary DNA (cDNA) clone encoding chicken insulin-like growth factor binding protein-5 (cIGFBP-5) was isolated. The nucleotide sequence of the 1236-bp clone encodes a mature polypeptide of 251 amino acids with a calculated molecular weight of approximately 28.2 kDa. The deduced amino acid sequence is 83% identical to human IGFBP-5. Labeled cIGFBP-5 cDNA detected a single mRNA transcript of approximately 6 kb by Northern blot analysis of various tissues obtained from embryonic and 6 weeks post-hatch chickens; interestingly, adult heart showed an approximately 10-fold increase in cIGFBP-5 mRNA relative to embryonic heart. The pattern of IGFBP-5 mRNA expression in chicken tissues was similar to that found in mammals during fetal and extrauterine life. In addition, IGFBP-5 mRNA was abundant in primary cultures of chicken myoblasts throughout in vitro differentiation and fusion. The conservation of IGFBP-5 primary structure and expression pattern across vertebrate species suggests conservation of important functions during evolution, particularly in muscle differentiation.

Amino Acid Sequence↗

PubMed1997

Modulation of growth factors by growth hormone in children with chronic renal failure. The Southwest Pediatric Nephrology Study Group.

Anthropometric measurements and circulating growth factors were studied serially in 44 prepubertal children with growth failure and chronic renal failure (GFR = 10 to 40 ml/min/1.73 m2) who were randomized to receive either recombinant human growth hormone (rhGH; N = 30) or no treatment (N = 14). RhGH was given as Nutropin, 0.05 mg/kg/day, and the studies were carried out at baseline and after 3 and 12 months. At baseline, serum insulin-like growth factor binding protein (IGFBP)-1 and -2 levels were, while IGFBP-3 levels were not, higher than those of children with normal renal function. In addition, height SDS at baseline correlated inversely with serum IGFBP-2 levels (r = -0.461, P = 0.0016), but did not correlate significantly with any other factor. After 12 months of study, the 30 children receiving rhGH showed: (i) greater increase in height (9.1 +/- 2.8 vs. 5.5 +/- 1.9 cm, P < 0.0001); (ii) increases in serum levels of IGF-I, IGF-II, free IGF-I, IGFBP-3 and acid labile subunit (ALS); (iii) a greater decrease in serum IGFBP-1 levels; and (iv) no significant difference in serum IGFBP-2 levels, when compared to the 14 control patients. The change in height SDS after 12 months of rhGH (+0.8) in the 30 treated children correlated significantly and positively with serum ALS, IGFBP-3, total IGF, IGF-I, IGF-II and free IGF-I levels measured during treatment. These observations suggest that, in children with growth failure associated with chronic renal failure: (i) IGFBP-2, and not IGFBP-3, is likely to be a growth inhibitor; (ii) rhGH stimulates catch-up growth in part by increasing serum levels of IGF peptides; and (iii) linear growth is influenced by the balance between growth stimulating IGFs and growth inhibitory IGFBPs.

Age Determination by Skeleton↗

PubMed1997

Bioactivity of a 29-kilodalton insulin-like growth factor binding protein-3 fragment present in excess in chronic renal failure serum.

Children with chronic renal failure (CRF) have normal or high serum levels of GH, IGF-I, and IGF-II. Despite this, the serum of CRF patients has low IGF bioactivity, which may contribute to CRF growth failure. Recent studies suggest that excess IGF binding proteins (IGFBPs) in the approximately 35-kD fractions of CRF serum contribute to this low IGF bioactivity. This report characterizes a 29-kD form of IGFBP-3, IGFBP-3(29), which accumulates in the approximately 35-kD fractions of CRF serum and peritoneal dialysate. Deglycosylation and [125I]IGF ligand blot studies show that IGFBP-3(29) is a glycosylated IGFBP-3 fragment with low affinity for IGF peptides. Using an IGFBP-3 antibody column, IGFBP-3(29) was purified to homogeneity from the approximately 35-kD fractions of peritoneal dialysate from children with CRF. Compared with native IGFBP-3, pure IGFBP-3(29) has a 4-10-fold lower affinity for IGF-II and a 200-fold lower affinity for IGF-I. Consistent with the binding data, IGFBP-3(29) inhibited IGF-II-stimulated thymidine incorporation in chondrosarcoma cells, but was a less potent inhibitor than native IGFBP-3; also, native IGFBP-3 clearly inhibited IGF-I-stimulated thymidine incorporation in chondrosarcoma cells and potentiated IGF-I-stimulated aminoisobutyric acid uptake in bovine fibroblasts, but higher concentrations of IGFBP-3(29) had no effect on these IGF-I actions. Thus, the 29-kD IGFBP-3 form that accumulates in CRF serum and extravascular spaces is an IGFBP-3 fragment that may modulate IGF-II, but not IGF-I, effects on target tissues. Whether IGFBP-3(29) plays any role in the growth failure of children with CRF remains to be determined.

Animals↗