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)

To analyse the relationship between the presence of liver cirrhosis and hepatic inflammation and the serum concentrations of the aminoterminal propeptide of procollagen type III (P-III-NP) and of hyaluronic acid (HA) in chronic liver disease, we measured P-III-NP and HA concentrations in paired serum samples from 133 patients with various chronic liver diseases, from 22 patients with acute hepatitis and from 50 healthy age-matched controls. In 24 (of the 133) patients with autoimmune chronic liver disease, follow-up determination was performed during therapeutic treatment with immunosuppressive drugs. Compared with controls P-III-NP concentrations (medians) were significantly elevated in 65% of patients with chronic active hepatitis (P = 0.00097) and in 79% of patients with active liver cirrhosis (P = 0.0126) but not in patients with chronic persistent hepatitis (P = 0.06). Serum concentrations (medians) of HA were increased (P = 0.0058) in 32% of patients with chronic active hepatitis and in 91% of patients with active cirrhosis (P less than 6 x 10(-7)). The difference of HA serum concentrations but not that of P-III-NP serum concentrations in patients with chronic active hepatitis and in patients with active cirrhosis was statistically significant. HA and P-III-NP serum concentrations were significantly elevated in 22 patients with acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum hyaluronate and type III procollagen aminoterminal propeptide concentration in chronic liver disease. Relationship to cirrhosis and disease activity. 190 36

It is suggested that during active phases of acute and chronic pancreatitis (aP and cP) a major breakdown of extracellular matrix occurs. Since our group previously established that serum levels of the precollagen-III-peptide (P-III-P) are good markers for changes in the extracellular matrix in liver disease (e.g. fibrosis and cirrhosis), we investigated whether this would also serve as a possible marker for pancreatitis. A total of 52 patients with pancreatitis were studied (aP = 17; cP = 35) and compared to 194 controls. Diagnosis of pancreatitis was done on the basis of established classifications. Concomitant diseases, e.g. of the liver, were excluded. Serum levels of P-III-P (three assays with polyclonal and monoclonal antibodies and Fab-Fragments), hyaluronic acid (HA) and laminin (LAM) were measured by RIA or IRMA. Patients with pancreatitis displayed elevated levels in all groups, when compared with the controls. Since the P-III-P-Fab RIA measures the Col1-fragment by 50%, which is considered to be a degradation product of P-III-P, this could mean that neogenesis of collagen is paralleled by degradation during the initial course of an acute episode of pancreatitis. The ratio (quotient) of P-III-P-Fab and P-III-PMoAb (nl = 127.3 +/- 27) is changed in patients with pancreatitis towards P-III-P-Fab (aP: 115.4 +/- 84.7*, cP: 94.9 +/- 21.8*, cP-I: 89.3 +/- 9.2*; * = p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Parameters of connective tissue metabolism as markers in acute and chronic pancreatitis. A retrospective study with a cohort of normal subjects]. 195 31

Hyaluronic acid (HA), an unbranched high molecular weight polysaccharide can now be measured by several immunometric assays. The connective tissues are the main source of HA and it is destroyed mainly in the liver. Very high levels of HA occur in mesothelioma. Wilms' tumour and acute liver failure, and moderate increases in rheumatoid diseases, renal failure and cirrhosis. Local increased production of HA is a feature of several forms of lung disease. HA is an indicator of connective tissue turnover, of the function of the receptor mechanisms for its capture and destruction by the liver, and of the removal of low molecular weight fragments by the kidney.
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PMID:Clinical significance of the immunometric measurements of hyaluronic acid. 228 24

There is increasing interest in the changes of the endothelial lining of the hepatic sinusoids during the development of chronic liver disease. In this study we looked for evidence of hepatic sinusoidal endothelial cell transformation and basement membrane production in patients with primary biliary cirrhosis. Morphological transformation to vascular-type endothelial cells, as evidenced by the development VIII-related antigen, was seen at the interface between portal tracts or fibrous septae and hepatic parenchyma; the most marked changes were observed in patients with established cirrhosis. Increased immunohistochemical staining for the basement membrane components type IV collagen and laminin was also found in a similar distribution. Raised serum levels of hyaluronic acid, a glycosaminoglycan metabolized by normal hepatic endothelial cells, were found in most patients and correlated strongly with advancing histological stage. Furthermore, significant positive correlations were found between serum hyaluronic acid and serum levels of laminin and type IV collagen. The unique structure of the normal endothelial lining of the hepatic sinusoids is important in the maintenance of hepatic function. Our data show that significant changes in endothelial cell structure and function occur in primary biliary cirrhosis and appear to be a contributing factor to the progression of the disease. Further studies are needed to determine the extent and importance of these changes in other forms of chronic liver disease.
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PMID:Endothelial cell transformation in primary biliary cirrhosis: a morphological and biochemical study. 234 45

During human and experimental liver fibrogenesis, the pattern of glycosaminoglycans in fibrotic liver matrix is greatly changed by severalfold increases of hyaluronic acid, chondroitin sulfate, and dermatan sulfate, respectively. The present study aimed to determine whether hepatocytes take part during fibrogenesis in the alteration of the glycosaminoglycan profile in liver matrix. Rats received thioacetamide orally for 2 and 10 weeks, respectively. After 10 weeks a typical micronodular cirrhosis had developed. Hepatocytes isolated at these time points were characterized by light and electron microscopy and incubated for up to 4 h in suspension cultures in [35S]-sulfate and [3H]-glucosamine containing medium to study the synthesis and intra-/extracellular distribution of total and specific types of glycosaminoglycans. A biphasic change of glycosaminoglycan synthesis in hepatocytes was found. After 2 weeks of TAA-treatment parenchymal cells synthesized about 25% more labeled glycosaminoglycans than control liver cells, but at 10 weeks the synthesis was reduced by more than 40%. Thus, between 2 and 10 weeks of TAA-treatment hepatocellular glycosaminoglycan synthesis decreased by more than 50%. The major portion of newly synthesized glycosaminoglycans was nitrous acid labile and, hence, identified as heparan sulfate. Its fractional synthesis decreased from 0.90 in control cells to 0.84 (2 weeks TAA) and 0.76 (10 weeks TAA), respectively. Thus, the absolute synthesis of heparan sulfate was reduced by 50% in hepatocytes from cirrhosis liver. Eighty to 90% of labeled glycosaminoglycans remained cell-associated. Hyaluronic acid was detected neither in normal hepatocytes nor in hepatocytes from injured liver. We conclude from these data that parenchymal liver cells will not contribute actively to the accumulation of galactosaminoglycans (chondroitin sulfate, dermatan sulfate) and hyaluronic acid in the extracellular matrix during fibrogenesis. The diminished rate of synthesis of heparan sulfate in hepatocytes from cirrhotic liver might explain its fractional decrease in cirrhotic liver matrix.
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PMID:The synthesis of glycosaminoglycans in isolated hepatocytes during experimental liver fibrogenesis. 235 59

Part of the hyaluronic acid (HA) synthesized in peripheral tissues enters the blood circulation through the lymph. It is rapidly taken up by the endothelial cells in the liver (half-life in blood is 2.5-5.5 minutes) and degraded. Pure primary cultures of liver endothelial cells were obtained by a newly developed technique and used to follow the metabolism of the polysaccharide on the cell surface. At 37 degrees C the HA is effectively endocytosed and degraded to acetate and lactate. A radioassay specific for HA and sensitive in the nanogram range has been developed to follow the concentration of HA in serum. The normal level in man is 10 to 100 micrograms/l. Elevated serum levels of HA are seen in liver cirrhosis, rheumatoid arthritis and scleroderma indicating that both an impaired catabolism in the liver and an increased synthesis in the peripheral tissues can modify the HA level.
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PMID:The catabolic fate of hyaluronic acid. 294

Hyaluronan (hyaluronic acid) is a linear polysaccharide formed from disaccharide units containing N-acetylglucosamine and glucuronic acid. It is ubiquitously distributed in the organism but is found in the highest concentrations in soft connective tissues. The molecular weight of hyaluronan is usually in the order of 10(6) to 10(7). Due to hydrogen bonding, the chain is rather stiff and the molecule behaves in solution as an extended, randomly kinked coil. Molecules of hyaluronan start to entangle already at concentrations of less than 1 g/l and form a continuous polymer network. Some of the functions of the polysaccharide have been connected with the unique physical chemical characteristics of the network such as its rheological properties, flow resistance, osmotic pressure, exclusion properties and filter effect. Hyaluronan is synthesized in the cell membrane by adding monosaccharides to the reducing end of the chain. The precursors are UDP-glucuronic acid and UDP-N-acetylglucosamine. The polysaccharide grows out from the cell surface and it can be shown that fibroblasts, for example, surround themselves with a coat of hyaluronan. The rate of biosynthesis is regulated by various factors, such as growth factors, hormones, inflammatory mediators, etc. The responsible enzyme, hyaluronan synthase, is a phosphoprotein and the regulation of the synthetic rate is apparently via phosphorylation. The hyaluronan is at least partly carried by lymph flow from the tissues. Part of the material is taken up and degraded in the lymph nodes. Another part is carried to the general circulation and taken up in the endothelial cells in the liver sinusoids. These cells have specific receptors for hyaluronan, which also recognize chondroitin sulphate. The uptake in the liver of high-molecular weight hyaluronan is very efficient and its normal half-life in serum is only in the order of 2 to 5 min. The polysaccharide is rapidly degraded in the lysosomes to low-molecular weight products, lactate and acetate. The total turnover of hyaluronan in serum is in the order of 10-100 mg/24 h. The normal concentration of hyaluronan in serum is less than 100 micrograms/l with a mean of 30-40 micrograms/l. High serum levels have been noted in liver cirrhosis (impaired uptake in the liver) and rheumatoid arthritis (increased synthesis in the tissues). Hyaluronan has been shown to interact specifically with certain proteins and cell surfaces. It binds to proteoglycans in cartilage and other tissues and fills an important structural role in the organization of the extra-cellular matrix.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Biochemistry of hyaluronan. 312 95

The aim of this study was to characterize acidic glycosaminoglycan components in normal human liver and in alcoholic cirrhosis, and to determine whether the proportions of individual glycosaminoglycans change with advancing cirrhosis. Acidic glycosaminoglycans are components of extracellular matrices and consist of repeating disaccharides of hexosamine and hexuronic acid with molecular weights ranging from 5 X 10(3) to 5 X 10(4), except for hyaluronic acid, whose molecular weight ranges from 3 X 10(4) to 1.6 X 10(6). The acidic glycosaminoglycan components in normal liver and at different stages of liver cirrhosis were found to be polydisperse as to the molecular weight and the degree of sulfation. The increased content of glycosaminoglycans with advancing liver cirrhosis was related to those of heparan sulfate and dermatan sulfate components. Heparan sulfates were the most prominent components of smaller molecular weight fractions. In the normal state, moderate amounts of dermatan sulfate and the oversulfated isomer were present in intermediate molecular weight fractions, but increasing amounts of the components shifted to higher molecular weight fractions with advancing cirrhosis. A small amount of hyaluronic acid was found in higher molecular weight fractions and the amount increased at the initial stage as a reversible phenomenon. The possible roles of hepatic glycosaminoglycan components in the process of fibrosis are discussed.
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PMID:Polydispersity of acidic glycosaminoglycan components in human liver and the changes at different stages in liver cirrhosis. 405 17

The extractable and nonextractable collagen and glycosaminoglycuronans (GAG) were estimated and characterized in 32 dried, defatted human livers obtained at necropsy. 10 had normal livers. 22 of the 32 livers were from patients who drank in excess: 5 had fatty livers, 7 had alcholic hepatitis, and 10 had cirrhosis. Livers with alcoholic hepatitis or cirrhosis had significantly increased total and 1 N NaCl-extractable collagen. Only alcoholic hepatitis livers had significantly increased Tris-buffer-extractable GAG, but the amino acid composition of these GAG (proteoglycans) was no different from that of normal livers. The major fraction of these GAG had isoelectric pH (pI) </= 3.1 in all livers. Livers with alcoholic hepatitis or cirrhosis had significantly increased nonextractable GAG. The major GAG fraction of all livers was chondroitin-4 or -6-SO(4). Alcoholic hepatitis livers had a significant increase of hyaluronic acid and an unidentified hyaluronidase-resistant GAG. Fatty livers showed no differences from normal ones. The data indicates that alcoholic hepatitis is associated with a significantly increased fibroblast activity, but fatty livers of alcoholics are not. The changes in histologically "inactive" micronodular cirrhosis of alcoholic patients indicate continued activity of fibroblasts in the connective tissue of these cirrhotic livers.
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PMID:Natural history of alcoholic hepatitis. IV. Glycosaminoglycuronans and collagen in the hepatic connective tissue. 427 Jun 46

Acidic glycosaminoglycan (AGAG) components in normal human liver and at different stages of liver cirrhosis were studied at the constitutional disaccharide level by enzymatic assay methods. The AGAG content in human cirrhotic liver was 5-6 times that in the normal state. The most predominant AGAG components in normal human liver tissue were heparan sulfates (HS) which accounting for 63% of the total AGAG, followed by a moderate amount of dermatan sulfate (DS) and small amounts of chondroitin sulfate isomers and hyaluronic acid (HA). In addition, the oversulfated DS detected in human liver. The increase in both HS and DS content reflects an increase in total AGAG with advancing liver cirrhosis. The ratio of non-sulfated AGAG, HA plus chondroitin, to DS plus its oversulfated isomer was 0.24 in the normal state but it increased to 0.80 at the early stage of liver cirrhosis. However, the ratio decreased to 0.36 and 0.21 at the typical and advanced stages of liver cirrhosis, respectively, with progress in the fibrotic process.
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PMID:Changes in acidic glycosaminoglycan components at different stages of human liver cirrhosis. 644 Aug 47


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