Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The recently characterized GH-binding protein (GH-BP) has an amino acid sequence identical to the extracellular domain of the GH receptor. Serum GH-BP reflects the amount of GH receptors, and the liver seems to be their main source. To evaluate the effect of liver disease on GH-BP, 52 patients with liver cirrhosis were studied. Serum GH-BP was measured by a binding assay with dextran-coated charcoal separation. Levels of GH-BP were correlated against the clinical state, assessed by Pugh's score. The GH-BP of 31 Pugh's class A patients was 9.7 +/- 0.5%/50 microL serum, and that of 21 Pugh's class B and C patients was 7.2 +/- 0.5%/50 microL serum compared to 11.3 +/- 0.5%/50 microL serum in age-matched controls. GH-BP correlated negatively with Pugh's score and serum bilirubin, and positively with serum albumin. It did not correlate with serum liver enzymes or serum insulin-like growth factor-I. Scatchard analysis of GH binding to the GH-BP revealed similar binding affinities in Pugh's A, B, and C patients and controls. The binding capacity in cirrhosis was significantly lower than that in controls. We conclude that serum GH-BP is controlled mainly by the liver and can provide an additional measure of disease severity in liver cirrhosis.
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PMID:Decreased serum growth hormone-binding protein in patients with liver cirrhosis. 189 Jan 52

The recent discovery of a GH-binding protein (GH-BP) in human serum has important implications for the distribution, metabolism, and physiological activity of human GH (hGH). In this report we describe an accurate, simple, and rapid assay for measuring GH-BP in human serum, based on the dextran-coated charcoal technique for separating bound from free hGH. The present method reduces the degree of dissociation of the GH-BP complex during the separation procedure, thus increasing accuracy, allows routine use of small working volumes of sera, and can be practically used for running large scale assays. Binding of [125I]hGH to human serum GH-BP, identified and characterized by this procedure, was time, temperature, and dose dependent; the binding was highly specific for hGH and with a high affinity (Ka, 1.08 +/- 0.19 x 10(9) L/mol). Preliminary results, expressed as percent specifically bound [125I]hGH corrected for endogenous hGH, indicate that the mean GH-BP activity in 50 microL sera from normal adult men and women was 11.32 +/- 0.45%. Significantly lower values were obtained in sera of infants, 3 days after birth (1.65 +/- 0.15%), and in short-statured children with normal GH secretion (7.38 +/- 0.22%). In patients with liver cirrhosis GH-BP levels decreased to 5.93 +/- 1.14%. The availability of a simple and convenient procedure for large scale determination of GH-BP coupled with the suggestion that this protein can reflect the GH receptor provides us with an indirect means for assessing changes in GH receptor activity in various physiological and pathological conditions.
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PMID:A new and convenient assay of growth hormone-binding protein activity in human serum. 238 Mar 42

Binding proteins (BP) for growth hormone (GH) have recently been discovered in human plasma. The main BP is related to the GH receptor and probably corresponds to the extracellular portion of the receptor. The BP influence several aspects of GH homeostasis and action. Their level and activity in blood, therefore, become important variables in overall GH physiology. However, to date little is known about the regulation of GH-BP in health and disease. To gain initial information about this point, GH-BP activity was examined in the plasma of 124 subjects with various physiologic and pathologic conditions. The conditions were selected to provide basic physiologic data (men, women, children, age, pregnancy and to investigate key disease states attended by abnormal GH physiology (liver cirrhosis, uremia, infection, acromegaly). A standardized GH binding assay was used to measure BP activity as an index of BP levels. Both the principal, high affinity BP (peak II) and the minor, low affinity BP (peak I) showed considerable individual variation in all groups. Neonates had the lowest levels of both BPs, but by the age of 1 year the levels had increased and remained fairly stable through the seventh decade. In males but not females between the ages of 1 and 20 years, the main (peak II) BP showed a slight upward trend, whereas the minor (peak I) BP declined moderately. Patients with cirrhosis showed the most variation in both BP, and uremic patients demonstrated decreased peak II, but not peak I, binding. Neither BP was affected in acromegaly. We conclude that BP activity in plasma is well conserved in most conditions, but substantial individual variability exists. BP activity increases dramatically during the first year of life.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of plasma growth hormone-binding proteins in health and disease. 273 78

The newly discovered circulating growth hormone binding proteins dictate a re-evaluation of the state of GH in plasma in health and disease as the binding proteins are known to affect GH metabolism and action. We describe a rapid and simple GH-binding assay that allows determination of free and complexed plasma GH, as well as GH-binding protein activity as an index of GH-binding protein levels, with relative ease. The method is based on incubation of plasma with 125I-GH and separation of bound from free GH on small DEAE-cellulose columns; it can be used on a large scale for routine determinations. The results obtained by this method are comparable to those obtained with the previously used slow and more cumbersome gel filtration technique. Initial data obtained in normal subjects and certain disease states show that the bound fraction of plasma GH is similar in men, women and children, is unaffected by pregnancy or acute infection, but is marginally decreased in liver cirrhosis. In acromegaly, binding protein activity also appears normal when allowance is made for partial saturation of the binding proteins by the high prevailing GH levels. The technique we describe should facilitate investigations of normal and abnormal regulation of the GH binding proteins.
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PMID:A rapid and simple assay for growth hormone-binding protein activity in human plasma. 320 82

Two growth hormone-binding proteins (GHBPs), one with high and the other with low affinity, have recently been described in the blood of humans and several other species. The high-affinity GHBP represents a circulating fragment of the GH receptor, encompassing its extracellular domain. The molecular nature of the low-affinity GHBP is not known in detail. GHBPs form complexes with circulating GH, prolong its biological half-life, restrict its distribution in the body, and modulate the binding of GH to receptors in tissues. Their net effect in vivo is to enhance GH action. The level of high-affinity GHBP in plasma probably reflects receptor concentrations in tissues. The level/activity of GHBP is linked to GH action, and several congenital or acquired conditions with altered GHBP levels are characterized by parallel changes in GH action (Laron-type dwarfism, pygmy dwarfism, malnutrition, obesity, insulin-dependent diabetes mellitus, liver cirrhosis, renal insufficiency). The GHBP/receptor level is nutritionally regulated, with levels low in undernutrition and high in overnutrition. Regulation of lean body mass anabolism/catabolism at the level of the GHBP/receptor provides a rational explanation for the derangements in the GH axis and their biological consequences (retarded or accelerated somatic growth) observed in nutrition disorders.
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PMID:Growth hormone-binding proteins in plasma. 750 16

The purpose of this study was to assess GH sensitivity in children with Alagille syndrome (syndromic intrahepatic bile duct paucity) by examining their response to short term administration of recombinant human GH (rhGH). Serum levels of insulin-like growth factor-I (IGF-I) were low despite elevated overnight integrated serum GH concentrations. Administration of rhGH (0.05 mg/kg.day for 3 days) to four growth-retarded children with Alagille syndrome did not significantly alter the serum concentrations of IGF-I and insulin, blood urea nitrogen, or urinary calcium excretion. In contrast, circulating IGF-I increased 2-fold in two children with Alagille syndrome and normal stature. In the control group, consisting of seven prepubertal children with GH deficiency, the predicted changes in response to rhGH in serum concentrations of IGF-I and insulin, urea nitrogen, and urinary calcium excretion were observed. Serum GH-binding protein levels, measured by a ligand-mediated immunofunctional assay, were significantly higher in children with Alagille syndrome than in children with cirrhosis or GH deficiency. We conclude that growth-retarded children with Alagille syndrome are insensitive to GH. The growth disturbances and metabolic defects may be due in part to failure to increase IGF-I concentrations in response to GH, implying that growth-retarded children with Alagille syndrome may benefit from IGF-I treatment.
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PMID:Growth hormone insensitivity associated with elevated circulating growth hormone-binding protein in children with Alagille syndrome and short stature. 850 Nov 53

The aim of this study was to investigate the regulation of various proteins of the GHIGF axis during progression of liver failure and to search for potential prognostic markers of functional hepatic reserve. Serum levels of growth hormone (GH) and high affinity growth hormone binding protein (GHBP), insulin-like growth factor I (IGF-I) and IGF binding proteins (IGFBP) -1, -2 and -3 were determined in patients with liver cirrhosis. A continuous decline in the concentrations of IGF-I, IGFBP-3 and serum GH-binding activity (GHBP) was observed during progression of cirrhosis and the data correlated significantly with choline esterase, total serum protein and the Child score. In addition, GHBP showed a significant correlation with the enzymatic activity of glutamate dehydrogenase or transaminases and seems so to be influenced by the degree of liver cell damage. In contrast, IGFBP-1 and IGFBP-2 levels were significantly elevated in preterminal disease suggesting an upregulatory mechanism is still effective in this situation. Only when liver function had markedly deteriorated, the serum levels of these two parameters decreased again, possibly due to an impaired synthesis. The excellent correlation between the serum levels of IGF-I (r = -0.64, p < 0.001) or IGFBP-3 (r = -0.67, p < 0.001) and the Child score index suggests that they reflect the hepatic functions just as conventional indicators. For an appropriate interpretation of the liver function the measurement of the growth related peptides can be a valuable tool to estimate pathological alteration in the functional hepatic reserve or in the glucose homeostasis.
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PMID:Regulation of growth hormone (GH), insulin-like growth factor (IGF)I, IGF binding proteins -1, -2, -3 and GH binding protein during progression of liver cirrhosis. 853 56

Our aim was to study the prognostic value of growth hormone (GH) -stimulated insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3) generation in patients with compensated [group 1 (N = 8) with a Child-Pugh (CP) score of 5-8] and decompensated postnecrotic liver cirrhosis [group 2 (N = 7) with a CP score of 9-12]. Serum levels of IGF-I, GH-binding protein (GHBP), and IGFBP-3 were measured before and 24 hr after a single subcutaneous injection of recombinant human GH (rhGH, 0.14 units/kg). Patients (mean age 56 years) were followed prospectively for three years. Six patients (40%) died during the follow-up period, of whom half had a CP score <9. Mean serum IGF-I levels 24 hr after rhGH injection (group 1 vs group 2, 17.4 +/- 6.8 vs 7.4 +/- 0.7 nmol/liter) predicted survival with 93% accuracy. Levels <10 nmol/liter portended a poor prognosis, with 15% survival at one year, whereas levels >10 nmol/liter had a 100% survival rate at one and two years, respectively. Baseline IGF-I (9.98 +/- 2.0 vs 6.38 +/- 0.8 nmol/liter), GHBP (9.2 +/- 3 vs 5.7 +/- 0.8%/50 microl), and IGFBP-3 serum levels at baseline (1.7 +/- 0.3 vs 0.86 +/- 0.2 mg/liter) and at 24 hr (2.04 +/- 0.38 vs 0.99 +/- 0.3 mg/liter) did not add to the predictive value of stimulated IGF-I levels at 24 hr and were less accurate in predicting the outcome in comparison to CP score (80%). We conclude that stimulated IGF-1 <10 nmol/liter may be a true predictor of a negative prognosis in patients with liver cirrhosis.
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PMID:Prognostic value of generation of growth hormone-stimulated insulin-like growth factor-I (IGF-I) and its binding protein-3 in patients with compensated and decompensated liver cirrhosis. 963 25

In cirrhosis, as in other conditions of protein catabolism, there is a state of acquired GH resistance, as defined by high circulating GH levels with low insulin-like growth factor I levels. However, patients with end-stage liver failure respond to supraphysiological doses of GH with an increase in circulating insulin-like growth factor I levels. The present study represents a detailed analysis of GH receptor (GHR) expression in cirrhotic liver from 17 patients with end-stage liver disease. Specific binding of labeled GH was identified in all cirrhotic livers studied. The binding affinity for the GHR was similar in cirrhotic and normal livers, but the number of binding sites per mg protein of liver membrane was variable in both normal and cirrhotic liver, although it were generally lower in cirrhotic liver. GHR expression was identified in cirrhotic liver by Northern blotting, RT-PCR, and ribonuclease protection assay. On Northern blotting, a single transcript of 4.8 kb was identified in normal and cirrhotic tissues. RT-PCR identified expression of both full-length GHR and a truncated form of the GHR; this was confirmed by ribonuclease protection assay. In situ hybridization and immunohistochemistry confirmed the expression of GHR in regenerating hepatocytes and isolated cells in fibrous tissue. In conclusion, 1) the low level of GHR in cirrhotic liver may contribute to the acquired GH resistance found in cirrhotic patients; 2) the reduced expression of both full-length and truncated GHR is compatible with the low level of GH-binding protein found in cirrhosis, as this truncated receptor has previously been reported to generate large amounts of GH-binding protein; and 3) the demonstration of GH binding to cirrhotic liver explains why these patients with GH resistance may still respond to supraphysiological doses of GH.
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PMID:Cirrhotic liver expresses low levels of the full-length and truncated growth hormone receptors. 966 39

Malnutrition adversely affects mortality and morbidity before and after liver transplantation. Outcome might be improved if liver transplant recipients were in a better nutritional state at the time of transplantation. In this review, we will examine the potential use of GH and IGF-I to improve nutritional status in patients with cirrhosis. Patients with cirrhosis have low circulating IGF-I levels in the face of elevated serum GH concentrations. IGFBP-3 levels are low while IGFBP-1 levels are high. In patients with cirrhosis, IGF-I levels do not increase in response to treatment with GH. Patients with cirrhosis are insensitive to GH, and rhGH treatment is not likely to reverse malnutrition. The pathobiology of GH insentivity may reflect decreased nutritional intake, low GH receptor density, decreased IGF-I half-life and hepatic insensitivity to insulin.
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PMID:Resistance to growth hormone in children with chronic liver disease. 1008 90


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