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)

We report a case of severe hypoglycemia and hepatic masses suspected to be an insulin-like growth factor-II (IGF-II)-producing hepatocellular carcinoma. A 62-year-old man presented with mental disorder in the night and early morning associated with extremely low blood sugar levels (less than 21 mg/dl). Computerized axial tomography and ultrasonography revealed a massive tumor in the right lobe of the liver with multiple secondary nodules, and a tumor thrombus in the portal vein. At autopsy 107 days after admission, the liver weighed 3070 g, histologically showing an Edmondson type II tumor with liver cirrhosis. IGF-II in plasma (899 ng/ml) and tumor tissue (2.4 micrograms/g) was higher than that in normal plasma (374-804 ng/ml) and non-tumor liver tissue (0.2 micrograms/ml), while IGF-I (14 ng/ml) was significantly reduced. IGF-II, probably produced by the liver tumor, appeared to be involved in the mechanism of hypoglycemia.
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PMID:Primary hepatocellular carcinoma with severe hypoglycemia: involvement of insulin-like growth factors. 132 Jan 77

Insulin-like growth factor II (IGF-II) levels in human plasma were measured in physiological and pathological conditions by radioimmunoassay (RIA) with biosynthetic IGF-II. This RIA was specific for IGF-II and cross-reactivity with IGF-I was 1%. The sensitivity was 15 pg/tube with 50% displacement at 50 pg/tube. The intra- and inter-assay coefficients of variation for IGF-II were 6.3 and 9.3%, respectively. The plasma IGF-II levels in normal adults, patients with hypopituitarism and patients with active acromegaly were 589.6 +/- 15.8, 800.9 +/- 45.6 and 330.3 +/- 24.3 ng/ml, respectively. After human growth hormone (hGH) treatment in hypopituitarism, IGF-II slightly increased, but not significantly. After adenomectomy in patients with acromegaly, IGF-II significantly decreased. These data indicate that IGF-II concentrations in plasma were partially GH dependent. This GH dependency was less than that of IGF-I. IGF-II was low in patients with anorexia nervosa and with liver cirrhosis and high in patients with renal failure. In two cases with extrapancreatic tumor-associated hypoglycemia, plasma IGF-II was increased to 1123.8 and 843.5 ng/ml, and returned to normal after tumor resection. These data showed that IGF-II was partly dependent on GH and nutritional conditions and that IGF-II was the most likely cause of some cases of hypoglycemia with extrapancreatic tumor. This specific and sensitive RIA of IGF-II would be useful in evaluating its physiological and pathological role in plasma and tissue.
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PMID:Radioimmunoassay for insulin-like growth factor II (IGF-II). 208 2

Insulin-like growth factor (IGF) I and IGF-II were measured by radioimmunoassay in the sera of seven patients with acromegaly, 36 normal control subjects, 15 patients with chronic hepatitis, 15 patients with cirrhosis, 25 patients with hepatocellular carcinomas (HCCs) who did not have hypoglycemia, 20 patients with HCCs who did have hypoglycemia, and 10 patients with metastatic liver tumors. Both IGF-I and IGF-II levels decreased as liver disease progressed from the normal control stage to chronic hepatitis and cirrhosis, and both levels reflected the severity of liver disease. Patients with HCCs who had hypoglycemia had relatively higher IGF-II levels in their sera in comparison with those who did not have hypoglycemia (272 +/- 167.5 ng/ml vs 110.4 +/- 85.9 ng/ml [mean +/- SD], p less than 0.0005), despite the fact that those with hypoglycemia had more advanced liver cancer and had lower IGF-I levels in sera (16.7 +/- 14.1 ng/ml vs 46.8 +/- 47.9 ng/ml, p less than 0.002). It is possible that a labile IGF-II material is produced by the cancer cells of patients with hypoglycemia. This factor is reactive to the IGF-II receptor and partially cross-reacts with an antibody to IGF-II; it accounted for the mildly elevated levels of serum IGF-II. Hypoglycemia may be an integral effect of relatively elevated IGF-II like material and an advanced liver cancer. Also, higher serum alpha-fetoprotein (AFP) levels were more frequently found in patients with hypoglycemia who had relatively elevated IGF-II levels and short survivals.
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PMID:Radioimmunoassay of serum IGF-I and IGF-II in patients with chronic liver diseases and hepatocellular carcinoma with or without hypoglycemia. 246 May 70

We evaluated levels of insulin-like growth factor-I and interleukin-1 alpha and beta in patients with pancreatic cancer; the role of these substances in tumor spread and in hyperglycemia was also investigated. Thirty pancreatic cancer patients (21 with hyperglycemia) were compared with others with diseases causing hyperglycemia [liver cirrhosis (14 cases, 12 with hyperglycemia), chronic pancreatitis (20 cases, 12 with hyperglycemia), type I diabetes mellitus (13 cases, all hyperglycemic)]. Insulin-like growth factor-I was significantly reduced in patients with liver cirrhosis, probably due to a reduced hepatic capacity for synthesis. It was increased in 6 of 30 pancreatic cancer patients; in these subjects it was correlated with alanine aminotransferase and C-peptide, but not with tumor diameter or the presence of metastases. Interleukin-1 alpha and beta were both elevated in pancreatic cancer patients. The former was high, while the latter was low when liver metastases were present. Neither was related to glucose or C-peptide levels. In summary, insulin-like growth factor-I levels are increased in some pancreatic cancer patients but this does not seem to favor tumor spread; however IGF-I could be involved influencing glucose homeostasis. Interleukin-1 alpha increased, while interleukin-1 beta decreased in pancreatic cancer patients with metastases, suggesting a different involvement of these two substances in pancreatic cancer spread.
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PMID:Insulin-like growth factor-I, interleukin-1 alpha and beta in pancreatic cancer: role in tumor invasiveness and associated diabetes. 778 9

A competitive enzyme immunoassay for the determination of human insulin-like growth factor I in microtiter plates was established. Using a polyclonal antiserum raised in rabbits against hIGF-I ovalbumin conjugate the assay system was able to detect IGF-I at a range of 12-800 pg/well with a sensitivity of 10 pg/well. It showed a low (< 0.5%) cross reactivity with hIGF-II. The serum concentrations of IGF-I found by EIA agreed well with those found in a conventional RIA (r = 0.965, p < 0.001). Effects of age and sex on IGF-I levels were studied in 260 normal adults. There was no evidence for sex differences but a steep decline of values from the third to the fourth and from the eight to the ninth decade, respectively. To asses the diagnostic capability of the IGF-I determination in liver cirrhosis, 71 sera of patients classified according to Child classes (A-C) were measured. Although significantly diminished concentrations were found in class B vs A and in class C vs B, the diagnostic sensitivity in cross-sectional examinations proved to be low (class A: 0.33, class B: 0.67). Only in the case of extensively destroyed liver parenchyma (Child C: 0.94) IGF-I was a good indicator of impaired hepatocellular capacity. In 29 patients with acromegaly serum IGF-I levels were investigated. All patients with active acromegaly showed increased IGF-I levels. In contrast, in inactive or weakly active acromegaly values were considerably lower.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Measurement of insulin-like growth factor I (IGF-I) in normal adults, patients with liver cirrhosis and acromegaly: experience with a new competitive enzyme immunoassay. 822 82

Decreased serum insulin-like growth factor (IGF-I) levels have been shown in malnutrition and liver diseases. To analyse which of them is the main cause of GH-IGF-I axis alterations, serum levels of growth hormone (GH), growth-hormone releasing factor (GHRH), IGF-I and its binding protein IGFBP-3 were measured in 85 hospitalized alcoholics (51 without cirrhosis, 15 with compensated cirrhosis and 19 with cirrhosis with ascites) and in 25 healthy controls. Liver function tests and objective nutritional assessment were also performed. Serum IGF-I and IGFBP-3 levels were lower in alcoholics, particularly in those with liver cirrhosis. Serum GH was raised in cirrhotics with ascites but GHRH levels were not significantly altered. Although these patients were frequently malnourished there was no relationship between data derived from GH-IGF-I axis and nutritional parameters. However, there was a significant positive correlation between serum GH concentrations and impaired liver function and a significant negative correlation between serum IGF-I and IGFBP-3 and impaired liver function. This suggests that, in this population, serum IGF-I and IGFBP-3 levels reflect liver dysfunction rather than malnutrition.
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PMID:Effects of alcohol and liver cirrhosis on the GH-IGF-I axis. 867 9

The liver plays a central role in the IGF-I axis producing the majority of circulating hormone and some of its binding proteins (IGFBPs). Cirrhosis of the liver is characterised by changes in IGF-I and IGFBPs associated with liver fibrosis and regeneration. We have studied steady state levels of mRNA for the genes in the IGF-I axis in normal and cirrhotic human liver, localised the most highly expressed gene, IGFBP-1, and measured circulating IGFBP-3 by radioimmunoassay (RIA), IGFBP-2 and IGFBP-3 by Western ligand blot (WLB), and protease activity for IGFBP-3 in cirrhotic patients. Messenger RNA for IGF-I, IGFBP-1, IGFBP-2, and IGFBP-3 was detectable by Northern blotting in normal and cirrhotic liver although there was considerable variation in expression. IGFBP-2 and IGFBP-3 tended to be more highly expressed in cirrhotic liver and IGFBP-1 was more highly expressed in normal liver, although there were no significant differences. In normal liver, in situ hybridisation localised IGFBP-1 to hepatocytes. In cirrhotic liver the regenerating nodules showed expression of IGFBP-1 while there was none in fibrotic tissue. Circulating IGFBP-3 levels were low as measured by RIA and WLB but protease activity was only found in one patient. IGFBP-2 levels, assessed by WLB, were similar to the normal serum pool. Our data show that key mRNAs involved in the IGF-I axis continue to be expressed in cirrhotic liver despite end stage liver disease. The low levels of IGFBP-3 do not appear to be due to reduced gene transcription or increased protease activity.
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PMID:Expression of IGF-I and IGF-binding protein genes in cirrhotic liver. 870 31

Patients with cirrhosis of the liver require an increased amount of protein to achieve N balance. However, the utilization of protein with increased protein intake, i.e. the slope from regression analysis of N balance v. intake, is highly efficient (Nielsen et al. 1995). In the present study, protein requirement and protein utilization were investigated further by measuring protein synthesis and degradation. In two separate studies, five or six patients with cirrhosis of the liver were refed on a balanced diet for an average of 2 or 4 weeks. Protein and energy intakes were doubled in both studies. Initial and final whole-body protein metabolism was measured in the fed state by primed continuous [15N]glycine infusion. Refeeding caused a statistically significant increase of about 30% in protein synthesis in both studies while protein degradation was only slightly affected. The increase in protein synthesis was associated with significant increases in plasma concentrations of total amino acids (25%), leucine (58%), isoleucine (82%), valine (72%), proline (48%) and triiodothyronine (27%) while insulin, growth hormone, insulin-like growth factor (IGF)-I and IGF-binding protein-3 were not changed significantly. The results indicate that the efficient protein utilization is due to increased protein synthesis, rather than decreased protein degradation, and suggest that increases in plasma amino acids may be responsible for the increased protein synthesis. A comparison of the patients who had a normal protein requirement with the patients who had an increased protein requirement suggests that the increased protein requirement is due to a primary increase in protein degradation. It is speculated that this is due to low levels of IGF-I secondary to impaired liver function, since initial plasma concentration of IGF-I was about 25% of control values and remained low during refeeding.
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PMID:Effect of long-term refeeding on protein metabolism in patients with cirrhosis of the liver. 913 67

Increased GH together with decreased IGF-I levels pointing to peripheral GH insensitivity in critically ill patients have been reported by some but not by other authors. To clarify whether elevated GH levels are coupled with low IGF-I levels in all catabolic conditions, basal GH and IGF-I levels were evaluated in patients with sepsis (SEP, no.=13; age [mean+/-SE]=59.2+/-1.2 yr), trauma (TRA, no.=16; age=42.3+/-3.4 yr), major burn (BUR, no.=26; age=52.8+/-4.2 yr) and post-surgical patients (SUR, no.=11; age=55.0+/-4.7 yr) 72 hours after ICU admission or after cardiac surgery. GH and IGF-I levels were also evaluated in normal subjects (NS, no.=75; age=44.0+/-1.5 yr), in adult hypopituitaric patients with severe GH deficiency (GHD, no.=54; age=44.8+/-2.3 yr), in patients with liver cirrhosis (LC, no.=12; age=50.4+/-2.8 yr) and in patients with anorexia nervosa (AN, no.=19; age=18.7+/-0.8 yr). Basal IGF-I and GH levels in GHD were lower than in NS (68.6+/-6.4 vs 200.9+/-8.7 microg/l and 0.3+/-0.1 vs 1.4+/-0.2 microg/l; p<0.01). On the other hand, AN and LC showed IGF-I levels (70.4+/-9.1 and 52.4+/-10.5 microg/l) similar to those in GHD while GH levels (10.0+/-2.8 and 7.9+/-2.1 microg/l) were higher than those in NS (p<0.01). IGF-I levels in SEP (84.5+/-8.8 microg/l) were similar to those in GHD, AN and LC and lower than those in NS (p<0.01). IGF-I levels in BUR (105.2+/-10.9 microg/l) were lower than in NS (p<0.01) but higher than those in GHD, AN, LC and SEP (p<0.01). On the other hand, in TRA (162.8+/-17.4 microg/l) and SUR (135.0+/-20.7 microg/l) IGF-I levels were lower but not significantly different from those in NS and clearly higher than those in GHD, AN, LC, SEP and BUR. Basal GH levels in SEP (0.6+/-0.2 microg/l), TRA (1.8+/-0.5 microg/l), SUR (2.2+/-0.5 microg/l) and BUR (2.2+/-0.5 microg/l) were similar to those in NS, higher (p<0.05) than those in GHD and lower (p<0.01) than those in AN and LC. In conclusion, our data demonstrate that low IGF-I levels are not always coupled with elevated GH levels in all catabolic conditions. Differently from cirrhotic and anorectic patients, in burned and septic patients GH levels are not elevated in spite of very low IGF-I levels similar to those in panhypopituitaric GHD patients. These findings suggest that in some catabolic conditions peripheral GH insensitivity and somatotrope insufficiency could be concomitantly present.
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PMID:Low IGF-I levels are often uncoupled with elevated GH levels in catabolic conditions. 958 86

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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