Biomedical subjects

F Liu

Publications and source records attributed to F Liu.

At least 433 records · Page 24Linked to original sources

PubMed1997

Characterization of cationic liposome-mediated gene transfer in vivo by intravenous administration.

Physicochemical properties of the cationic liposomes, including structure of the cationic lipid-to-DNA ratio, liposome particle size, and inclusion of the helper lipids, were studied for their effect on the level, site, and duration time of gene expression in vivo by intravenous administration. Using a cytomegalovirus (CMV)-driven gene expression system containing either the luciferase or green fluorescence protein gene as a reporter and two cationic lipids [N-(2,3-dioleoyloxy)propyl-N,N,N-trimethylammonium chloride (DOTMA) and 1,2-dioleoyloxy-3-trimethylammonium propane (DOTAP)], we demonstrated in vivo by a single intravenous injection of DNA/liposome complexes into mice, that cationic liposomes are capable of transfecting cells in organs such as the lung, heart, liver, spleen, and kidney. Transfection efficiency is determined mainly by the structure of the cationic lipid and the ratio of cationic lipid to DNA. Although the presence of cholesterol in DOTAP liposomes did not affect transfection activity, inclusion of dioleoylphosphatidylethanolamine (DOPE) into either DOTAP or DOTMA liposomes significantly decreases liposome transfection activity in vivo. Results form time course show that gene expression in different organs is transient, with a peak level between 4 and 24 hr, dropping to less than 1% of the peak level by day 4. Experiments with repeated injections showed that the peak level of gene expression could be regained by subsequent injection.

Animals↗

PubMed1997

Permeability and metabolic properties of a trophoblast cell line (HRP-1) derived from normal rat placenta.

The HRP-1 cell line is derived from normal rat placenta and appears morphologically similar to and retains characteristic expression of cellular markers of labyrinthine trophoblast cells. In this study, monolayers of HRP-1 cells grown on permeable supports were evaluated as a potential in vitro system to study trophoblast transport and metabolism. The cell line was shown to express and retain functional activity of the predominant placental cytochrome P450 isozyme, CYP1A1. Additionally, the HRP-1 cells retain functional activity of angiotensin I converting enzyme and carboxypeptidase N-like enzyme, peptidases characteristic of the trophoblast. The permeation of several hydrophilic, inert markers across the HRP-1 monolayers was observed to be dependent on effective molecular size and to be passive in nature. Functional asymmetry of the HRP-1 cells was illustrated by the predominant permeation of linoleic acid in the apical-to-basolateral direction across the monolayers. Transferrin passage across HRP-1 monolayers was concentration-dependent, was bidirectional, and could be inhibited by unlabeled transferrin, features typical of the trophoblast transport system for transferrin. Collectively, these properties suggest that the HRP-1 cell line may provide a useful tool for evaluating some of the permeability and metabolic properties of the trophoblast.

Animals↗

PubMed1997

Mechanism of TGFbeta receptor inhibition by FKBP12.

Transforming growth factor-beta (TGFbeta) signaling requires phosphorylation of the type I receptor TbetaR-I by TbetaR-II. Although TGFbeta promotes the association of TbetaR-I with TbetaR-II, these receptor components have affinity for each other which can lead to their ligand-independent activation. The immunophilin FKBP12 binds to TbetaR-I and inhibits its signaling function. We investigated the mechanism and functional significance of this effect. FKBP12 binding to TbetaR-I involves the rapamycin/Leu-Pro binding pocket of FKBP12 and a Leu-Pro sequence located next to the activating phosphorylation sites in TbetaR-I. Mutations in the binding sites of FKBP12 or TbetaR-I abolish the interaction between these proteins, leading to receptor activation in the absence of added ligand. FKBP12 does not inhibit TbetaR-I association with TbetaR-II, but inhibits TbetaR-I phosphorylation by TbetaR-II. Rapamycin, which blocks FKBP12 binding to TbetaR-I, reverses the inhibitory effect of FKBP12 on TbetaR-I phosphorylation. By impeding the activation of TGFbeta receptor complexes formed in the absence of ligand, FKBP12 may provide a safeguard against leaky signaling resulting from the innate tendency of TbetaR-I and TbetaR-II to interact with each other.

Activin Receptors, Type I↗

PubMed1997

[Treatment of a large intracoronary thrombus with urokinase and a chimeric monoclonal platelet aggregation inhibitor].

HISTORY AND CLINICAL FINDINGS: 7 days after an operation for intervertebral disc prolapse a 43-year-old man was referred with the clinical and ECG signs of an acute posterior wall myocardial infarction. INVESTIGATIONS: Creatine kinase (CK) activity was raised to 204 U/I (myocardial-specific isoenzyme CKMB of 23.6 U/I, 11.6% of total) and glutamic-oxalate transferase (GOT) activity to 37 U/I. Emergency cardiac catheterisation, performed 4 hours after renewed onset of precordial pain showed no abnormal findings in the right coronary artery, despite the ECG signs, but a definite filling defect in the anterior interventricular branch, which on intravascular ultrasound was an echo-dense noncalcified structure. TREATMENT AND COURSE: After percutaneous transluminal coronary angioplasty in the area of the obstructing structure a free-floating mass was identified in the proximal part of the anterior interventricular branch, most likely a thrombus. Intercoronary thrombolysis was therefore undertaken with urokinase (bolus of 1 mill. IU) together with the chimeric monoclonal antibody c7E3, which inhibits platelet aggregation by blocking the platelet glycoprotein surface receptor IIb/IIIa. Coronary angiography 12 hours later revealed almost complete dissolution of the previously obstructing mass. CONCLUSION: Combining the platelet aggregation inhibitor c7E3 with a thrombolytic agent is an alternative treatment to the current management of intracoronary thrombi. Intravascular ultrasound is a suitable method for demonstrating angiographically inconspicuous or unclear but pathogenetically significant vessel changes.

Abciximab↗

PubMed1997

The TGF-beta family mediator Smad1 is phosphorylated directly and activated functionally by the BMP receptor kinase.

Bone morphogenetic proteins (BMPs) are members of the TGF-beta family that regulate cell proliferation, apoptosis, and differentiation, and participate in the development of most tissues and organs in vertebrates. Smad proteins function downstream of TGF-beta receptor serine/threonine kinases and undergo serine phosphorylation in response to receptor activation. Smad1 is regulated in this fashion by BMP receptors, and Smad2 and Smad3 by TGF-beta and activin receptors. Here, we report that BMP receptors phosphorylate and activate Smad1 directly. Phosphorylation of Smad1 in vivo involves serines in the carboxy-terminal motif SSXS. These residues are phosphorylated directly by a BMP type I receptor in vitro. Mutation of these carboxy-terminal serines prevents several Smad1 activation events, namely, Smad1 association with the related protein DPC4, accumulation in the nucleus, and gain of transcriptional activity. Similar carboxy-terminal serines in Smad2 are required for its phosphorylation and association with DPC4 in response to TGF-beta, indicating the generality of this process of Smad activation. As a direct physiological substrate of BMP receptors, Smad1 provides a link between receptor serine/threonine kinases and the nucleus.

Activin Receptors↗

PubMed1997

The mature osteoblast phenotype is characterized by extensive plasticity.

While both morphological and biochemical-molecular attributes demarcate differentiation stages in specific cell and tissue types, what constitutes necessary and sufficient expression to define particular cell types is not always known. For example, mature osteoblasts (OBs) are defined morphologically as the cuboidal, biosynthetically active, basophilic cells residing on bone surfaces and responsible for the deposition of osteoid matrix. However, several recent observations suggest that not all mature OBs are identical. To explore further the validity of the hypothesis that heterogeneity of phenotype exists among mature OBs, we grew fetal rat calvaria cells in vitro at low density under conditions in which bone nodules form and mineralize in isolation of other contaminating cell and colony types. Cells resident in mature OB colonies, i.e., those comprising mainly cuboidal cells associated with an osteoid matrix that had begun to mineralize, were analyzed in situ for protein expression by immunocytochemistry with antibodies against collagen type I, alkaline phosphatase, osteopontin, bone sialoprotein, and osteocalcin. Consistent with the expected phenotype of mature OBs, many OBs expressed high levels of all of these markers, but strikingly even adjacent morphologically indistinguishable cuboidal OBs had differences in protein expression, especially in relation to osteopontin, bone sialoprotein, and osteocalcin expression. Double-labeling with Hoechst 33258 and osteocalcin indicated that the variation in antibody labeling intensity/protein expression appeared independent of a variation in cell cycle. To further ascertain the extent of this heterogeneity, 20 single cells were micromanipulated from colonies and subjected to poly(A)-PCR to analyze the simultaneous coexpression profiles of the same five markers analyzed by immunocytochemistry and two other markers, the OB-osteocyte transition marker E11 and the parathyroid hormone/parathyroid hormone-related protein receptor. Notably, the repertoire of genes expressed and their levels of expression varied markedly in individual OBs. The observed heterogeneity suggests that the mature OB phenotype is not a single unique phenotype but rather encompasses a flexible pattern of expression from the repertoire of OB-associated markers.

Alkaline Phosphatase↗

PubMed1997

Novel repeat elements direct rat proenkephalin transcription during spermatogenesis.

The developmental program controlling sperm formation occurs in multiple stages that sequentially involve mitosis, meiosis, and spermiogenesis. The transcriptional mechanisms regulating these distinct phases are poorly understood. In particular, while a required role for the germ cell transcription factor cyclic AMP response element modulator-tau during spermiogenesis has recently been demonstrated, the transcriptional mechanisms leading to early haploid cell formation are unknown. The rat and mouse proenkephalin genes are selectively expressed from an alternate, germ cell-specific promoter in meiotic and early haploid cells. In this study, the minimal rat proenkephalin germ line promoter was localized to a 116-bp region encompassing the transcriptional start site region. Further, a proximal 51-bp sequence located in the 5'-flanking region is absolutely required for germ line promoter activity. This 51 bp sequence corresponds to a previously characterized binding element (GCP1) that forms cell-specific complexes with rat spermatogenic cell nuclear factors distinct from cyclic AMP response element binding proteins. Further, GCP1 contains novel direct repeat sequences required for factor binding and transgene expression in spermatogenic cells. These repeat elements are highly similar to sequences within the active regions of other male germ line promoters expressed during meiosis. GCP1 may therefore contain transcriptional elements that participate more generally during meiosis in the differentiation of spermatocytes and early haploid spermatids.

Animals↗

PubMed1997

Protein-tyrosine phosphatase 1B complexes with the insulin receptor in vivo and is tyrosine-phosphorylated in the presence of insulin.

In response to insulin, protein-tyrosine phosphatase 1B (PTPase 1B) dephosphorylates 95- and 160-180-kDa tyrosine phosphorylated (PY) proteins (Kenner, K. A., Anyanwu, E., Olefsky, J. M., and Kusari, J. (1996) J. Biol. Chem. 271, 19810-19816). To characterize these proteins, lysates from control and insulin-treated cells expressing catalytically inactive PTPase 1B (CS) were immunoadsorbed and subsequently immunoblotted using various combinations of phosphotyrosine, PTPase 1B, and insulin receptor (IR) antibodies. Anti-PTPase 1B antibodies coprecipitated a 95-kDa PY protein from insulin-stimulated cells, subsequently identified as the IR beta-subunit. Similarly, anti-IR antibodies coprecipitated the 50-kDa PY-PTPase 1B protein from insulin-treated cells. To identify PTPase 1B tyrosine (Tyr) residues that are phosphorylated in response to insulin, three candidate sites (Tyr66, Tyr152, and Tyr153) were replaced with phenylalanine. Replacing Tyr66 or Tyr152 and Tyr153 significantly reduced insulin-stimulated PTPase 1B phosphotyrosine content, as well as its association with the IR. Studies using mutant IRs demonstrated that IR autophosphorylation is necessary for the PTPase 1B-IR interaction. These results suggest that PTPase 1B complexes with the autophosphorylated insulin receptor in intact cells, either directly or within a complex involving additional proteins. The interaction requires multiple tyrosine phosphorylation sites within both the receptor and PTPase 1B.

Insulin↗

PubMed1997

Induction of glyoxylate cycle expression in Caenorhabditis elegans: a fasting response throughout larval development.

The mRNA and the bifunctional protein for the two glyoxylate cycle (GC) enzymes, isocitrate lyase and malate synthase, are expressed in a tissue- and stage-specific pattern in Caenorhabditis elegans. Since expression of the two enzymes for the carbon-conserving glyoxylate cycle is regulated by the availability of carbon sources in microorganisms, we have studied the bifunctional GCP gene expression under fasting conditions and in certain mutants of C. elegans in order to understand possible mechanisms regulating its expression during nematode development. The GCP mRNA and protein levels were elevated in early larvae which were never fed, a result consistent with previous enzyme activity measurements (Khan, F.R., & McFadden, B.A. (1982) Exp. Parasitol. 54, 48-54]. However, larvae of later stages also expressed higher levels of GCP mRNA and protein when they were shifted from normal to fasting growing conditions. The GCP expression appeared to be regulated primarily at the transcriptional level throughout development. Although the expression of both the GCP gene and lin-14 peaks at about the same time during development and are induced by fasting, the regulation of the GCP gene is independent of the heterochronic lin-14 control mechanism of postembryonic lineages, as demonstrated by the fact that there was no significant change of the GCP at both mRNA and protein levels in the heterochronic lin-4 (lf) and lin-14 (gf) mutants compared to the wild type.

Animals↗

PubMed1997

High-volume nonionic dimeric contrast medium: first experiences during complex coronary interventions.

Interventional cardiology is a rapidly developing field of medicine with annually increasing numbers of coronary interventions. Especially through the development of alternative techniques for coronary angioplasty, new indications have been found and more difficult lesions are tackled. Inevitably, such complex interventions are time-consuming and require high amounts of contrast medium. Newer, mostly nonionic agents have been developed with improved tolerability as well as fewer cardiac and renal side effects due to their nonionic, hydrophilic structure, and their osmolality isotonic to plasma. This study sought to investigate the effects of high-volume nonionic, dimeric contrast medium during coronary interventions with special emphasis on renal and hemodynamic side effects during routine hospital stays. Retrospectively, 25 consecutive patients (age 56 +/- 10 yr) with normal renal and cardiac function receiving > 500 ml of the nonionic dimeric contrast medium iodixanol during complex coronary interventions were analyzed. The analysis was based on serum creatinine levels 1 day before and 2 days after contrast medium administration for the monitoring of renal function. Additionally, heart rate and left ventricular pressures were evaluated before and after left ventricular angiography. Mean serum creatinine rose from 0.9 +/- 0.2 mg/dl to 1.1 +/- 0.2 mg/dl (P < 0.05) after 2 days of coronary intervention. Heart rate, left ventricular systolic pressure, and left ventricular end-diastolic pressure did not change significantly. No major side effects were encountered in the short follow-up period of 2 days. Based on this retrospective analysis, high-volume nonionic, dimeric contrast medium administration in patients without preexisting renal insufficiency is associated with little impairment of renal function, and has only minor hemodynamic and general side effects. Iodixanol 320 mg I/ml is well-tolerated and effective for the use of cardioangiography. Given the limitations of this retrospective analysis, future prospective studies should systematically address the effects of high-volume contrast medium administration in otherwise healthy patients as well as in high-risk patients undergoing coronary interventions.

Aged↗

PubMed1997

Neuronal responses to vestibular stimulation in the guinea pig hypothalamic paraventricular nucleus.

We investigated the effects of caloric stimulation on neuronal activity in the hypothalamic paraventricular nucleus (PVN) in anesthetized guinea pigs. Hot water stimulation of the contralateral labyrinth produced excitation in 29.4% of the PVN neurons tested, while cold water produced excitation in 22.2% of the neurons. Hot water resulted in inhibition of 22.4% of the neurons and cold water inhibition of 24.7% of the neurons. Intracranial vestibular nerve section greatly reduced responsiveness of the PVN neurons to caloric stimulation, indicating that the majority of the responses observed were vestibular in origin. The response pattern of the individual PVN neurons was similar following hot and cold water stimulation and after stimulation of the contralateral and ipsilateral labyrinths. These results suggest that the PVN neurons receive vestibular afferents bilaterally according to the intensity of vestibular stimulation, with the information received probably integrated in the hypothalamus to participate in vestibulo-autonomic reflexes.

Animals↗

PubMed1997

FORUM: Dynamics and Causation of Environmental Equity, Locally Unwanted Land Uses, and Neighborhood Changes

/ Why are some environmental risks distributed disproportionately in the neighborhoods of the minorities and the poor? A hypothesis was proposed in a recent study that market dynamics contributed to the current environmental inequity. That is, locally unwanted land uses (LULUs) make the host communities home to more poor people and people of color. This hypothesis was allegedly supported by a Houston case study, whereby its author analyzed the postsiting changes of the socioeconomic characteristics of the neighborhoods surrounding solid waste facilities. I argue that such an analysis of postsiting changes alone is insufficient to test the causation hypothesis. Instead, I propose a conceptual framework for analysis of environmental equity dynamics and causation. I suggest that the presiting neighborhood dynamics and the characteristics of control neighborhoods be analyzed as the first test for the causation hypothesis. Furthermore, I present theories of neighborhood change and then examine alternative hypotheses that these theories offer for explaining neighborhood changes and for the roles of LULUs in neighborhood changes. These alternative hypotheses should be examined when analyzing the relationship between LULUs and neighborhood changes in a metropolitan area. Using this framework of analysis, I revisited the Houston case. First, I found no evidence that provided support for the hypothesis that the presence of LULUs made the neighborhoods home to more blacks and poor people, contrary to the conclusion made by the previous study. Second, I examined alternative hypotheses for explaining neighborhood changes-invasion-succession, other push forces, and neighborhood life-cycle; the former two might offer better explanation.KEY WORDS: Environmental equity and justice; Locally unwanted lane uses; Siting; Market dynamics; Invasion-succession; Neighborhood changes

Journal Article↗

PubMed1997

[Emergency stent implantation in the area of extensive muscle bridging of the anterior interventricular ramus after post-interventional dissection].

In a 64-year-old male patient with severe angina pectoris (CCS III) a systolic compression caused by a coronary muscle bridging in the left anterior descending artery could be detected by coronary angiography. Intravascular ultrasound (IVUS) as well as intracoronary Doppler examination showed a significant systolic reduction of the cross-sectional luminal area of 35.9% and a reduced coronary flow velocity ratio (CFVR) of 2.6. Two highly significant stenosis were detected proximal and distal of the muscle bridge. Percutaneous transluminal coronary angioplasty was performed at the distal lesion, resulting in a flow reducing dissection, and therefore subsequently a stent implantation was performed. Since the transition between the stent and the muscle bridge showed a severe flexion with continued systolic compression of the vessel, two further stents were employed to reinforce the entire area of the muscle bridging. A fourth stent was implanted in the proximal lesion. In the following angiographic and IVUS examinations a systolic compression was not detectable and the CFVR increased to 3.3. In the 6 months follow-up coronary angiography a restenosis in the stented area by intimal hyperplasia could be observed. However, IVUS showed all stents to be circular and fully expanded without signs of compression by the muscle bridge.

Aortic Dissection↗

PubMed1997

Cholesterol and ergosterol superlattices in three-component liquid crystalline lipid bilayers as revealed by dehydroergosterol fluorescence.

We have examined the fractional sterol concentration dependence of dehydroergosterol (DHE) fluorescence in DHE/cholesterol/dimyristoyl-L-alpha-phosphatidylcholine (DMPC), DHE/ergosterol/DMPC and DHE/cholesterol/dipalmitoyl-L-alpha-phosphatidylcholine (DPPC) liquid-crystalline bilayers. Fluorescence intensity and lifetime exhibit local minima (dips) whenever the total sterol mole fraction, irrespective of the DHE content, is near the critical mole fractions predicted for sterols being regularly distributed in hexagonal superlattices. This result provides evidence that all three of these naturally occurring sterols (e.g., cholesterol, ergosterol, and DHE) can be regularly distributed in the membrane and that the bulky tetracyclic ring of the sterols is the cause of regular distribution. Moreover, at the critical sterol mole fractions, the steady-state anisotropy of DHE fluorescence and the calculated rotational relaxation times exhibit distinct peaks, suggesting that membrane free volume reaches a local minimum at critical sterol mole fractions. This, combined with the well-known sterol condensing effect on lipid acyl chains, provides a new understanding of how variations in membrane sterol content change membrane free volume. In addition to the fluorescence dips/peaks corresponding to hexagonal superlattices, we have observed intermediate fluorescence dips/peaks at concentrations predicted by the centered rectangular superlattice model. However, the 22.2 mol% dip for centered rectangular superlattices in DHE/ergosterol/DMPC mixtures becomes diminished after long incubation (4 weeks), whereas on the same time frame the 22.2 mol% dip in DHE/cholesterol/DMPC mixtures remains discernible, suggesting that although all three of these sterols can be regularly distributed, subtle differences in sterol structure cause changes in lateral sterol organization in the membrane.

Anisotropy↗

PubMed1997

Free radical scavenging activities of mushroom polysaccharide extracts.

The superoxide and hydroxyl radical scavenging activities of eight mushroom antitumor polysaccharide extracts were investigated using phenazin methosulphate-NADH-nitroblue tetrazolium system and ascorbic acid-Cu(2+)-cytochrome C system respectively. The results showed that six of eight mushroom polysaccharide extracts had superoxide and hydroxyl radical scavenging activities. The protein content of the polysaccharide extracts appeared to contribute a direct effect on free radical scavenging activity. However, none of the mushroom polysaccharide extracts had antioxidative activity as measured by detecting malondialdehyde (MDA) contents of liver microsomes.

Antineoplastic Agents↗

PubMed1997

TxA2-induced pulmonary artery contraction requires extracellular calcium.

In order to examine the role of extracellular calcium in the pulmonary arterial vasoconstriction that is elicited by thromboxane A2 (TxA2), rabbits were sacrificed and the main trunk of the pulmonary artery removed. Contractile responses of the isolated vessel to the TxA2 mimetic, U46 619, were measured in a temperature controlled (37 degrees C) organ bath. Compared with control responses, U46 619 microM) contractions were nearly eliminated when 1 mM EGTA was added to the buffer. In the presence of normal extracellular calcium concentrations, antagonists of voltage sensitive calcium channels (e.g. verapamil and nifedipine) attenuated the U46 619-induced contractions. These voltage sensitive calcium channel blockers were more effective in eliminating contractile responses to high KCl concentrations (6) or 120 mM KCl). The inability of these calcium channel antagonists to completely eliminate U46 619 responses was confirmed in the anesthetized rabbit where both nifedipine and verapamil failed to block the increase in pulmonary arterial blood pressure resulting from intravenous U46 619 infusion. These results indicate that extracellular calcium is essential for U46 619-induced pulmonary vascular contraction, and that mechanisms in addition to voltage operated calcium channels participate in the movement of extracellular calcium through the plasma membrane.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1997

Early experience with extended use of insulin-like growth factor-1 in advanced chronic renal failure.

Short-term high-dose insulin-like growth factor-1 (IGF-1) therapy has been shown to enhance glomerular filtration rate (GFR) in end-stage chronic renal failure (CRF), but the efficacy and safety of prolonged therapy is unproven. To determine if prolonged therapy with IGF-1 can enhance renal function in advanced CRF, eight patients were entered into a study to receive one month of IGF-1 treatment, 60 micrograms/kg subcutaneously b.i.d. Six patients completed the study and two dropped out for reasons considered to be unrelated to the IGF-I treatment. Baseline inulin and PAH clearances averaged 17 +/- 3 and 66 +/- 14 ml/min/1.73 m2, respectively, in the subjects who completed the study. With treatment there was a modest 14% increase in the average GFR which approached statistical significance (P = 0.051). After stopping treatment the clearance values returned to basal values. The PAH clearance showed a similar trend. There were no significant changes in BUN, serum creatinine or electrolyte levels. On the other hand there were marked changes in the serum IGF binding protein (IGFBP) profile. Serum IGFBP-3 levels fell while IGFBP-1 and -2 levels rose during treatment, changes that likely affect the bioavailability of IGF-I. Thus, in this small series of patients IGF-1 treatment produced significant changes in the serum IGFBP profile and a modest upward trend in the GFR.

Adult↗

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↗