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)

Serum levels of soluble forms of intracellular adhesion molecule-1 (sICAM-1) and lymphocyte function-associated antigen-3 (sLFA-3) in 122 patients with chronic liver disease including hepatocellular carcinoma (HCC) were measured by enzyme-linked immunosorbent assays. Serum levels of sICAM-1 in patients with HCC were significantly higher than those of chronic hepatitis (CH) and cirrhosis. On the other hand, serum levels of sLFA-3 in patients with HCC were almost the same as those of cirrhosis. Western blot analyses showed that molecular sizes of sICAM-1 and sLFA-3 detected in the sera were 90 kd and 50 kd, respectively, indicating that both molecules include whole extracellular domains. In patients with HCC, circulating sICAM-1 levels were significantly (P < .001) correlated with tumor volume (r = .50), total bilirubin (r = .38), serum aspartate aminotransferase levels (r = .51), and gamma-globulin (r = .63). Furthermore, serum sICAM-1 levels were significantly elevated in patients with multiple HCC (tumor number > 3) or HCC with tumor embolus in the first branch or trunk of portal vein. Survival periods were analyzed in relation to serum sICAM-1 levels in patients with HCC who had been treated by transcatheter arterial chemoembolization. The HCC patients with < 1,000 ng/mL of serum ICAM-1 showed significantly (P = .0005) longer survival than those with higher levels of the molecule. The same results were obtained when only patients with moderately differentiated HCC were analyzed (P = .02). Analyses by Cox's proportional hazard model showed that sICAM-1 is a significant (P = .032) prognostic factor for patients with HCC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum concentration of intercellular adhesion molecule-1 in patients with hepatocellular carcinoma is a marker of the disease progression and prognosis. 754 36

Hepatic innervation participates in the control of sinusoidal blood flow and in the regulation of certain metabolic functions of the liver. The study of the distribution of hepatic nerves has been hampered by the lack of adequate markers. We therefore tested the value of the neural cell-adhesion molecule (NCAM) as a probe for the study of parenchymal nerves in the normal and cirrhotic human liver. Four antibodies against various epitopes of NCAM were tested by light and electron microscopic immunohistochemistry: Leu19, ERIC-1, VC1.1, and HNK-1. Their reactivity was compared with that of antibodies against the following neural cell markers: S100 protein, neurofilaments, and neuron-specific enolase (NSE). The tissue reactivity of anti-NCAM antibodies was variable, suggesting a microheterogeneity of the NCAM molecule in the normal liver. Clones Leu19 and ERIC-1 proved to be the most sensitive of the anti-NCAM antibodies. Their sensitivity was superior to that of the antibodies directed against the other neural cell markers tested. In the normal liver, both Leu19 and ERIC-1 demonstrated a heterogeneous distribution of nerve fibers inside the hepatic lobule. Intralobular nerve fibers predominated in Zone 1. This might contribute to the constitution of distinct zonal microenvironments inside the hepatic lobule. In cirrhosis, no nerve fiber was detected inside parenchymal nodules; no nerve plexus was visible at the contact of proliferating neoductules. These alterations might contribute to the pathogenesis of the hemodynamic and metabolic disorders observed in cirrhosis.
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PMID:Parenchymal innervation of normal and cirrhotic human liver: a light and electron microscopic study using monoclonal antibodies against the neural cell-adhesion molecule. 831 80

The recent cloning and genomic identification of hepatitis C virus (HCV) by sensitive and specific immune techniques has allowed a better definition of both histopathological and clinical features of the previously not well defined non-A, non-B hepatitis. In this regard, antibodies to different HCV antigens are usually found during infection, even if some of them such as anti-E1 and anti-E2/NS1 have been shown to be associated with significant viraemic levels. Acute hepatitis C is self-limiting in a minority of cases only. Over 60% of acute hepatitis becomes in fact chronic and may progress towards cirrhosis. In about 10% of cases, hepatocellular carcinoma may develop in cirrhotic livers. The occurrence of a strict relationship between immunoresponsiveness and disease activity is suggested by the observation that peripheral blood mononuclear cell (PBMC) proliferation induced by NS3 structure is associated with self-limiting acute hepatitis, while PBMC stimulation by core antigen characterizes chronic C hepatitis. The demonstration of lymphoid aggregates, bile duct lesions, intraportal lymphocyte infiltration, increased adhesion molecule expression and augmented cytokine release clearly emphasizes the involvement of immune-mediated reactions in the development of liver damage, even if a direct cytopathic effect cannot be excluded. Finally, it is likely that HCV may favour, through immune-mediated mechanisms, autoantibody generation and/or the appearance of some extrahepatic autoimmune manifestations during the course of HCV chronic infection.
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PMID:Hepatitis C virus infection. Biological and immunological features. 876 58

Adhesion molecules are cell surface glycoproteins that are critical for the localization of leukocytes at sites of inflammation. This review discusses the current knowledges of adhesion molecule expression in normal liver and its upregulation on individual liver cell types during liver inflammation. Cytokines, chemokines, complement factors, and lipid-derived mediators are critical for increased gene transcription and activation of constitutively expressed adhesion molecules. The specific role of selectins, integrins, and members of the immunoglobulin gene superfamily in sinusoidal and venular leukocyte sequestration, transendothelial migration, and adherence to target cells in the liver is described. Increased understanding of these basic mechanisms of communication between resident liver cells and infiltrating leukocytes (neutrophils, lymphocytes, macrophages) not only advances our insight into the pathophysiology of hepatic inflammation but also identifies promising new targets for therapeutic interventions and expands the spectrum of diagnosis and treatment of liver diseases, including alcoholic hepatitis and cirrhosis, viral hepatitis, ischemia-reperfusion injury (transplantation, tumor resection, shock), sepsis- or endotoxin-induced liver injury, acute and chronic rejection, primary biliary cirrhosis, and primary sclerosing cholangitis.
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PMID:Cellular adhesion molecules: regulation and functional significance in the pathogenesis of liver diseases. 934 Oct 49

Hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) gene was identified because of its increased expression in 25% of human hepatocellular carcinoma. HIP/PAP protein, a C-type lectin, binds laminin, acts as an adhesion molecule for hepatocytes, and has also been described as an acute phase secretory protein during acute pancreatitis in humans and rats. We investigated HIP/PAP protein expression in patients with various liver diseases associated with ductular reaction. At the same time, we analyzed patients with hepatocellular carcinoma and cholangiocarcinoma, and tested HIP/PAP protein levels in sera to establish the pattern of secretion. Our data show that HIP/PAP expression was not restricted to hepatocellular carcinoma, but was also detected in cholangiocarcinoma cells as well as in reactive non-malignant bile ductules. In contrast, HIP/PAP protein expression was undetectable in normal mature hepatocytes, but some ductular cells localized at the interface of portal tracts with parenchyma were HIP/PAP immunoreactive in normal liver. Finally, we present evidence that HIP/PAP serum levels were increased in 21/28 (75%) patients with hepatocellular carcinoma, and in 25/51 (49%) patients with nonmalignant cirrhosis. Altogether, these results suggest that HIP/PAP protein may be implicated in hepatocytic and cholangiolar differentiation and proliferation.
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PMID:Hepatocarcinoma-intestine-pancreas/pancreatic associated protein (HIP/PAP) is expressed and secreted by proliferating ductules as well as by hepatocarcinoma and cholangiocarcinoma cells. 1055 Mar 9

Females have a greater susceptibility to ethanol-induced liver injury than males. Females who drink ethanol regularly and have been overweight for 10 years or more are at greater risk for both hepatitis and cirrhosis than males, and females develop ethanol-induced liver injury more rapidly and with less ethanol than males. Female rats on an enteral ethanol protocol exhibit injury more quickly than males and have widespread fatty changes over a larger portion of the liver lobule. Moreover, levels of plasma endotoxin, intracellular adhesion molecule-1, free radical adducts, infiltrating neutrophils and nuclear factor kappa B are doubled in female rat livers compared with male rat livers after enteral ethanol treatment. Additionally, estrogen treatment in vivo increases the sensitivity of hepatic macrophages or Kupffer cells to endotoxin. Evidence has been presented that Kupffer cells are pivotal in the development of ethanol-induced liver injury. Destroying Kupffer cells with gadolinium chloride or decreasing bacterial endotoxin by sterilizing the gut with antibiotics inhibits early inflammation due to ethanol. Similar results have been obtained with anti-tumour necrosis factor-alpha antibody. These data pointed to the hypothesis that ethanol-induced liver injury involves elevations in circulating endotoxin concentrations leading to activation of Kupffer cells, which causes a hypoxia-reoxygenation injury. This theory has been tested using pimonidazole, a 2-nitroimidazole marker, to quantify hypoxia in downstream, pericentral regions of the hepatic lobule. After chronic enteral ethanol treatment, pimonidazole binding doubles. Enteral ethanol also increases free radicals detected with electron spin resonance. Radical adducts, with coupling constants such as alpha-hydroxyethyl radical, have been shown to arise from ethanol. Importantly, hypoxia and radical production detected in bile are also decreased by the destruction of Kupffer cells with gadolinium chloride. These data support the hypothesis that Kupffer cells contribute to the vital sex differences in liver injury caused by ethanol.
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PMID:Sex-related liver injury due to alcohol involves activation of Kupffer cells by endotoxin. 1111 Jun 25

Intercellular adhesion molecule-I (ICAM-I) is a member of the immunoglobulin supergene family. It is expressed on the surface membrane of cells of multiple lineages at sites of inflammation. A soluble form of ICAM (sICAM-I) comprising the five extracellular Ig-like domains of ICAM-I has been detected in human serum and has been found to be increased in a variety of acute and chronic liver disorders. However, little is known about sICAM-I levels in children with chronic liver disease. Therefore, we measured sICAM-I in 23 children with chronic hepatitis, 14 children with cirrhosis, and 10 age- and sex-matched normal children by commercially available ELISA. We also correlated the sICAM-I levels with the histological activity index (HAI) score as determined from liver biopsies. Patients with chronic hepatitis had higher sICAM-I levels compared to controls (723 +/- 272 ng/ml vs 282 +/- 43 ng/ml, mean +/- SD; P < 0.05). sICAM-I levels were also higher in patients with cirrhosis compared to controls (630 +/- 218 ng, mean +/- SD; P < 0.05). However, there was no significant difference between sICAM levels in patients with chronic hepatitis and cirrhosis. A significant correlation was found between the ICAM-I level and the histological activity index score in patients with chronic hepatitis (r = 0.58; P < 0.001) and in patients with cirrhosis (r = 0.7; P < 0.001). We also found that by using the cutoff level of 346 ng/ml, sICAM-I can be used as a screening test with high specificity (100%) and sensitivity (94%) to differentiate children with chronic liver disease from normal children. We conclude that sICAM is increased in children with chronic hepatitis and cirrhosis compared to controls. The degree of elevation correlates with the HAI score. sICAM may be used as a marker of the disease activity and may provide diagnostic and prognostic information in children with chronic liver disease. However, this needs to be further studied.
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PMID:Serum intercellular adhesion molecule-I in children with chronic liver disease: relationship to disease activity. 1206 92

Metastases rarely occur in human livers with cirrhosis in clinical studies. We postulated that this phenomenon would also occur in experimental cirrhosis. Cirrhosis was established in C57BL/6 mice by carbon tetrachloride (CCl(4)) gastrogavage. B16F1 melanoma cells were injected into the mesenteric vein to induce hepatic metastases. Contrary to our postulate, there was greater than 4-fold increase in metastasis in animals with cirrhosis compared to controls. Intravital videomicroscopy showed that the hepatic sinusoids were narrower and more tumor cells were retained in the terminal portal vein (TPV) in cirrhotic livers. Immunohistochemistry demonstrated that the expression of vascular adhesion molecules was significantly increased in cirrhosis. Using confocal microscopy and the fluorescent nitric oxide (NO) probe 4,5-diaminofluorescein diacetate, a significantly lower level of NO release was detected in livers with cirrhosis both in basal conditions and after tumor cell arrest. Eight hours after mesenteric vein tumor cell injection, the percentage of apoptotic tumor cells in the sinusoids was 17% +/- 2% in livers with cirrhosis and 30% +/- 5% in normal livers. More mitotic and Ki-67 labeled tumor cells were seen in livers with cirrhosis. In conclusion, the changes in architecture and adhesion molecule expression in livers with cirrhosis may cause more tumor cells to arrest in the TPV. Lower levels of NO production may reduce apoptosis of B16F1 cells in livers with cirrhosis. As a result, these changes may promote the growth of metastasis in this cirrhotic model.
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PMID:Impact of cirrhosis on the development of experimental hepatic metastases by B16F1 melanoma cells in C57BL/6 mice. 1538 52

Chronic ethanol-induced liver injury follows a typical progression from its earliest stage of steatosis to more advanced injury, characterized by the development of inflammation, hepatocyte necrosis/apoptosis, fibrosis and finally cirrhosis. Kupffer cells, the resident macrophage in the liver, play a critical role in the progression of liver injury. Increased exposure of Kupffer cells to lipopolysaccharide (LPS) during chronic ethanol exposure leads to the production of a number of inflammatory mediators, including tumor necrosis factor alpha (TNF-alpha). Recent evidence indicates that in addition to increased exposure to LPS, Kupffer cells also develop an enhanced sensitivity to LPS after chronic ethanol feeding. We have recently identified early growth response-1 (Egr-1), an immediate-early gene transcription factor, as an important contributor to increased LPS-stimulated TNF-alpha secretion by Kupffer cells after chronic ethanol exposure. In other models of tissue injury, such as ischemia-reperfusion in the lung, Egr-1 acts as a coordinator of the complex response to stress. Here we review the literature regarding the role of EGR-1 in regulation of a number of genes implicated in each of the stages of chronic ethanol-induced liver injury. In addition to the critical role of Egr-1 in generating maximal LPS-stimulated TNF-alpha expression, Egr-1 also controls the expression of a number of inflammatory mediators, including intercellular adhesion molecule (ICAM)-1, monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-2, as well as genes contributing to fibrosis, such as transforming growth factor (TFG)-beta1, platelet-derived growth factor PDGF-A chain and fibroblast growth factor (FGF). Understanding the contribution of Egr-1 to the expression of genes involved in the development of chronic ethanol-induced liver injury may lead to the development of improved therapies designed to prevent and/or reverse alcohol-induced liver injury.
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PMID:Ethanol-induced liver injury: potential roles for egr-1. 1634

SSAO/VAP-1 is not only involved in the metabolism of biogenic and xenobiotic primary amines and in the production of metabolites with cytotoxic effects or certain physiological actions, but also plays a role, for example, as an adhesion molecule, in leukocyte trafficking, in regulating glucose uptake and in adipocyte homeostasis. Interest in the enzyme has been stimulated by the findings that the activities of the SSAOs are altered (mostly increased) in various human disorders, including diabetes, congestive heart failure, liver cirrhosis, Alzheimer's disease and several inflammatory diseases, although the underlying causes are often unknown. On the basis of their insulin-mimicking effect, SSAO substrates are possibly capable of ameliorating metabolic changes in diabetes, while SSAO inhibitors (somewhat of a contradiction) are of potential benefit in preventing diabetes complications, atherosclerosis and oxidative stress contributing to several disorders or modulating inflammation, and hence may be of substantial therapeutic value. Great efforts have been made to develop novel compounds which may lead to future drugs useful in therapy, based on their effects on SSAO/VAP-1, and some of the results relating to novel substrates and inhibitors are surveyed in the present review.
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PMID:Semicarbazide-sensitive amine oxidase/vascular adhesion protein 1: recent developments concerning substrates and inhibitors of a promising therapeutic target. 1869 Oct 41


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