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)

Four markers for hepatic fibrosis--N-terminal peptide of Type III procollagen (PIIIP), Laminin P1 (laminin), Type IV collagen (Type IV-C), and 7S domain (7S)--were measured in the sera of 90 patients with various chronic liver diseases diagnosed by liver biopsy--fatty liver (FL), chronic inactive hepatitis (CIH), chronic active hepatitis (CAH), and liver cirrhosis (LC)--and in the sera of 20 healthy controls. The values of markers were compared with the grade of histologic findings of the liver. Four markers were significantly raised in the CAH group and the LC group, and they were considered to be indicators of hepatic fibrosis. PIIIP reflected necrosis and inflammation as well as fibrosis of the liver. Laminin, Type IV-C, and 7S reflected severe fibrosis. 7S was considered to be useful marker for liver cirrhosis.
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PMID:[Clinical significance of measurement of PIIIP, laminin P1, type IV-C and 7S in patients with chronic liver diseases--with special reference to histological findings]. 140 88

Liver biopsy specimens with or without liver diseases were examined immunohistochemically to determine the distribution of endothelial cell markers, factor VIII-related antigen (FVIII-RAg). Ulex europaeus agglutinin I (UEA-I) lectin and PAL-E. We also investigated the localization of laminin, a component of the basement membrane. In normal livers, FVIII-RAg, UEA-I and laminin were negative in sinusoidal endothelial cells, but positive in blood vascular endothelia of the portal area. The antigen detected by PAL-E was distributed in venous endothelial cells. PAL-E did not label endothelial cells of the artery. In the lobule, immunoreactivity with PAL-E was weakly detected only in some sinusoids of the periportal area. In chronic active hepatitis and liver cirrhosis, FVIII-RAg and UEA-I stained endothelial cells of neovasculatures in the enlarged portal areas of the fibrous septum surrounding pseudolobules. Some sinusoidal endothelial cells in cirrhotic livers were reactive to UEA-I and FVIII-RAg, whereas PAL-E-positive cells were found rarely in the pseudolobules. In carcinomatous sinusoidal endothelial cells, FVIII-RAg, UEA-I and PAL-E were strongly stained. Laminin underlay these carcinomatous sinusoids. These suggest capillarization of sinusoids in hepatocellular carcinoma. The histochemical approach using endothelial cell markers could be a practical tool in the diagnosis of hepatocellular carcinoma.
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PMID:Histochemical properties of vascular and sinusoidal endothelial cells in liver diseases. 165 46

In vitro models have shown that metabolites of ethanol (acetaldehyde and lactate) stimulate collagen synthesis, thereby, suggesting that they may be important as fibrogenic mediators. The relevance of these findings for fibrogenesis in the human liver in vivo, however, has not as yet been demonstrated. Serum markers for collagen (PIIINP, using radioimmunoassays employing polyclonal antibodies and Fab-fragments (PIIINP-Fab), respectively) and basement membrane (laminin) metabolism were therefore investigated in 25 alcoholic cirrhotics (Pugh-Score: 6.7 +/- 1.9 S.D.) and in 19 comparable nonalcoholic cirrhotics (Pugh-Score: 6.3 +/- 1.5, n.s.) with only slight evidence for inflammation: GOT 28 +/- 22 vs. 24 +/- 21 U/l; GPT 24 +/- 23 vs. 31 +/- 28 U/l; gamma-globulins 24 +/- 8 vs. 22 +/- 5%, respectively (all n.s.). Severity of the disease was assessed by quantitative liver function tests. Levels of PIIINP, PIIINP-Fab and laminin measured by RIA were 21 +/- 19 micrograms/l, 90 +/- 42 micrograms/l and 2.5 +/- 0.8 U/ml in alcoholic cirrhosis and 10 +/- 6 micrograms/l, 61 +/- 10 micrograms/l and 1.9 +/- 0.4 U/ml in nonalcoholic cirrhosis, respectively (all p less than 0.01). Differences on PIIINP and PIIINP-Fab remained significant even after accurate matching for galactose elimination capacity, aminopyrine breath test and hepatic sorbitol clearance. Laminin levels were higher in alcoholic cirrhosis only after matching for the hepatic sorbitol clearance (p less than 0.01). The higher levels of serum markers for collagen and basement membrane metabolism in alcoholic vs. nonalcoholic patients with cirrhosis at equal severity of the disease and with only minimal signs of inflammation may be the clinical reflection of a specific fibrogenic effect of ethanol metabolites.
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PMID:Higher levels of serum aminoterminal type III procollagen peptide, and laminin in alcoholic than in nonalcoholic cirrhosis of equal severity. 173 19

In order to identify the most useful marker to diagnose hepatic fibrosis, type III procollagen peptide (P-III-P), laminin P1, and prolyl-hydroxylase (PH) in sera obtained from patients with liver diseases were simultaneously measured and compared with histological features of chronic hepatitis and with tumor size estimated on abdominal CT scan. Further more, the diagnostic accuracy of these markers was evaluated by using discriminant analysis. P-III-P and laminin P1 were closely correlated with the activity of chronic hepatitis. These two markers most accurately discriminated between the compensated stage of liver cirrhosis and the decompensated stage, and between liver cirrhosis and hepatocellular carcinoma. Laminin P1 was found to most clearly distinguish chronic hepatitis from liver cirrhosis. P-III-P was significantly correlated with the size of hepatocellular carcinoma. However, PH failed to discriminate among liver diseases, and showed no significant correlation with a liver tumor size. And none of the markers examined were correlated with a degree of hepatic fibrosis. From these results, the analysis of both serum P-III-P and laminin P1 is a useful approach to evaluate hepatic collagen metabolism.
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PMID:[Assay of serum collagen markers in chronic liver diseases and liver cancer]. 217 Jul 16

Chronic liver diseases are characterized by an increase in connective tissue components in liver tissue. The determination of Col 1-3 peptide of type III procollagen (P-III-P) in serum of patients seems to be a useful parameter of hepatic fibroplasia. Specific radioimmunoassays are available for Col 1-3 (P-III-P) and the Col 1 and Col 1-3 (P-III-P-Fab) peptides of type III procollagen and for laminin P1 fragment. These proteins and the activity of N-acetyl-beta-glucosaminidase (beta-NAG) were measured in 94 patients with chronic liver diseases, and in 74 healthy controls. In addition, direct immunofluorescence studies were done for laminin P1 in normal and fibrotic liver tissues. In normal human liver, laminin was found in the basement membrane of bile ducts and in blood vessel walls. In fibrotic liver tissue, laminin additionally occurred in periportal areas and in sinusoids co-distributed with other connective tissue components. In serum concentrations of P-III-P, P-III-P-Fab and laminin were higher in patients than in healthy subjects. Laminin concentration was increased in early stages of chronic liver disease, possibly as a marker of regeneration; the highest concentrations were in active cirrhosis and chronic active hepatitis. The determination of P-III-P and P-III-P-Fab provided information on synthesis and degradation of type III collagen: In inactive cirrhosis, Col 1 peptide was increased in relation to Col 1-3 peptide.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evaluation of serum laminin P1, procollagen-III peptides, and N-acetyl-beta-glucosaminidase for monitoring the activity of liver fibrosis. 269 3

In sera of patients with fibrotic liver diseases (n = 33) classified histologically into various degrees of liver fibrosis (n = 21) and cirrhosis (n = 12) the concentrations of the basement membrane protein laminin and of its pepsinresistant fragment P1 and of the N-terminal propeptide of type III procollagen were determined. The concentrations of both proteins were related to the portal venous pressure measured in these patients. Compared with the reference population (n = 146) the concentration of laminin increases from 1.04 U/ml (normal persons) to 1.69 +/- 0.46 U/ml in liver fibrotic and 2.58 +/- 0.87 U/ml in liver cirrhotic patients. Although the concentrations of the propeptide of type III procollagen increase also there exist only weak correlations between both connective tissue proteins in serum. Laminin is correlated highly positive with the portal venous pressure in cirrhotic subjects (r = 0.9206), the extent of laminin elevation reflects closely the degree of portal hypertension. Virtually all of the fibrotic patients having a laminin concentration within the reference range had a normal portal venous pressure. The data suggest laminin as a potentially useful parameter for monitoring the portal venous pressure in cirrhotic and severe fibrotic patients.
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PMID:Serum concentrations of laminin and aminoterminal propeptide of type III procollagen in relation to the portal venous pressure of fibrotic liver diseases. 380 32

The concentrations in serum of the high molecular weight glycoprotein laminin and of the N-terminal propeptide of type III procollagen were determined in various histologically proven fibrotic liver diseases (n = 33), of which the portal venous pressure has been measured indirectly. The concentrations of both biomatrix proteins were related to the portal venous pressure. Laminin in serum of normal persons (n = 146) ranged from 0.81 to 1.43 U/ml. Compared with the mean normal concentration (1.04 U/ml) the glycoprotein is increased in fibrotic liver lesions in parallel with the severity of the fibrotic organ transformation reaching the highest values (2.58 +/- 0.87 U/ml, P less than 0.001) in liver cirrhosis (n = 12). The level of N-terminal propeptide of type III procollagen increased similarly, but the concentrations of both matrix proteins exhibit only weak statistical correlations (r = 0.6680). The level of laminin is correlated strongly with the elevation of the portal venous pressure in cirrhotic (r = 0.9206) and fibrotic (r = 0.7157) subjects. For the propeptide of procollagen the respective correlation is r = 0.4808. Molecular sieve chromatography reveals a heterogeneous composition of laminin-related antigens in serum with two main molecular weight fractions of 700 and 300 kD, respectively.
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PMID:Serum laminin--its concentration increases with portal hypertension in cirrhotic liver disease. 380 71

Monospecific antibodies against collagen types I, IV, fibronectin, and laminin were used to characterize the hepatic extracellular matrix in CCl4-induced cirrhosis. Of the four antigens studied, fibronectin was the first (2 weeks) to be deposited in Disse's space. Synthesis of fibronectin by hepatocytes was demonstrable by 3 weeks. This increased synthesis and deposition of fibronectin continued throughout the cirrhotic process. Type I collagen was deposited in the same areas as fibronectin, but there was a delay of 2 weeks between fibronectin deposition and the subsequent type I collagen deposition. Like fibronectin, type I collagen was localized in the rough endoplasmic reticulum of hepatocytes, but unlike fibronectin type I collagen synthesis was restricted to hepatocytes near zones of necrosis. Type I collagen and fibronectin synthesis were demonstrable only in hepatocytes. Type IV collagen deposition was noticeable after 3 to 4 weeks of CCl4 administration and continued throughout the cirrhotic process. Laminin deposition was delayed, with regard to type IV collagen, by 1 to 2 weeks. Except for this time lag, both basement membrane components codistributed in the space of Disse and were synthesized by the same cells: endothelial, smooth muscle, and Ito cells. The deposition of these two basement membrane components culminated with the formation of continuous endothelial basement membranes. The four extracellular matrix components studied were synthesized and secreted by resident cells of the normal liver. It is proposed that fibronectin deposition in the space of Disse, modulating collagen deposition, may be the crucial event in the cirrhotic process. The interposition of basement membranes between plasma and hepatocytes may have profound effects on hepatic systemic functions.
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PMID:The hepatic extracellular matrix. II. Electron immunohistochemical studies in rats with CCl4-induced cirrhosis. 389 94

We have measured serum laminin, a marker of portal hypertension, in 151 patients with nonmalignant liver diseases, to evaluate its utility in cirrhosis and portal hypertension. There were abnormal serum levels in 43.1% of the patients as a whole and in 62.7% of the cirrhotics. Laminin showed a correlation with many laboratory tests, especially those that reflect liver insufficiency and alcohol intake. Cirrhotics had higher laminin levels than noncirrhotics (p < 0.0001); an association was also found with portal hypertension (p < 0.0001), but laminin was also increased in patients without portal hypertension. Our results suggest that liver dysfunction can also lead to abnormal laminin concentrations, probably through slower metabolization rate. Laminin serum concentrations reflect the severity of the liver disease, and are also a marker of alcohol consumption. Determination of laminin serum levels could play an adjunctive role with respect to other liver tests in the evaluation of these patients although the measure does not really provide more useful information.
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PMID:Serum laminin levels offer only a little additional information in liver disease. 818 3

Laminin, a glycoprotein synthesised by Ito cells, has been considered a marker of fibrogenesis. The behaviour of laminin and clinical and laboratory data in 83 patients with cirrhosis were studied to find the factors associated with increases in this glycoprotein. There were increased concentrations of laminin in 62.7% of the patients (40% of the Child's A, 64.5% of the Child's B, and 75% of the Child's C categories). Significant differences in laminin concentrations were found between the Child's grades (p = 0.009) and between patients and controls (p < 0.0001). Correlations were found between laminin concentrations and mean corpuscular volume, aspartate aminotransferase, aspartate aminotransferase: alanine aminotransferase ratio, alkaline phosphatase activity, bilirubin and glycocholic acid concentrations, and hypoalbuminaemia--that is, variables related to liver insufficiency and alcohol intake. Moreover, patients with an alcohol intake higher than 100 g/day had higher laminin concentrations than those with a lower intake (p = 0.03). Conversely, there was no significant association with portal hypertension. Multivariate analysis showed that mean corpuscular volume, bilirubin concentrations, and hypoalbuminaemia were independently associated with laminin concentrations. Poor degradation associated with liver insufficiency seems to play an important part in the increase in serum laminin concentrations in these patients.
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PMID:Serum concentrations of laminin in cirrhosis of the liver. 834 86


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