Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many tests for hepatitis C virus (HCV) infection have been developed and have proved useful for prevention of post-blood transfusion hepatitis C. However, there are at least 4 genotypes of HCV and the predominant type is different among countries. None of the tests using antigens from one genotype are sensitive in detecting the antibodies against another genotype. More sensitive tests using a more stable part of the HCV RNA sequences such as 5'-noncoding region must be developed for clinical use. Automated PCR methods and DNA sandwich hybridization methods using branched DNA amplification multimers may be candidates. Recently a hepatocyte growth factor test has been developed in Japan. Multicenter trials of this test reveal that it is useful for assessment of acute severe hepatitis. Tests for collagen type IV, fibronectin receptor, and prolyl hydroxylase have been reported useful for assessment of liver fibrosis. However, serum prolyl hydroxylase is prone to increase in response to hepatocellular damage as well as fibrotic processes. Enzymatic methods for determination of branched amino acids and tyrosine have been developed. The molar ratio of branched amino acids to tyrosine seems to have same pathophysiological meaning as the ratio of branched amino acids to aromatic amino acids (Fischer ratio) in assessment of liver cirrhosis. Lidocaine test is reported to be useful for predicting survival of transplanted liver and also assessing the function of the cirrhotic liver. Profiles of alpha-fetoprotein subfractions based on lectin-reactivity and galactosyl transferase II isoenzyme have been reported to be useful for detecting hepatocellular carcinoma but this remains to be proved.
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PMID:[Recent advances in laboratory tests for liver diseases]. 130 30

Hepatocyte growth factor (HGF) is the most potent mitogen for mature hepatocytes and seems to act as a hepatotropic factor that has not been purified over the past 30 years. HGF was first purified from rat platelets in 1986. HGF is a hetrodimer molecule composed of 69-kDa alpha-subunit and 34-beta-subunit. In 1989, cDNAs of both human and rat HGF were cloned and primary structure of HGF was determined. HGF is derived from preproprecursor of of 728 amino acids, which is proteolytically processed to form mature HGF. The alpha-chain contains four kringle domains and it has 38% homology with plasmin. HGF mRNA and HGF activity increase markedly in the liver of rats after various liver injuries such as hepatitis, ischemia, physical crush, and partial hepatectomy. Production of HGF in the liver occurs in Kupffer cells and sinusoidal endothelial cells, but not in parenchymal hepatocytes. HGF mRNA is also markedly increased even in the intact lung, kidney, and spleen after injuries of the liver. Therefore, HGF may act as a trigger for liver regeneration through two mechanisms: a paracrine mechanism and an endocrine mechanism. Moreover, HGF mRNA increases markedly in the kidney after various renal injuries, thus it suggests that HGF may act not only as a hepatotropic factor but also as a renotropic factor. HGF receptor with a Kd of 20 to 30 pM is widely distributed in various epithelial cells including hepatocytes. HGF receptor was recently identified as the product of c-met protooncogene, which encodes a 190-kDa transmembrane protein possessing tyrosine kinase domain. HGF has recently been shown to be a pleiotropic factor. HGF stimulates growth of various epithelial cells, including renal tubular cells (Mitogen). It is worth noting that HGF strongly enhances motility of epithelial cells (Motogen) and induces epithelial tubule formation (Morphogen), while it strongly inhibits growth of several tumor cells. All these findings indicate that HGF may have important roles in organogenesis, morphogenesis, carcinogenesis, as well as in organ regeneration.
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PMID:Hepatocyte growth factor: molecular structure, roles in liver regeneration, and other biological functions. 131 69

Hepatocyte growth factor, a potent mitogen for mature hepatocytes in vitro, seems to function as a hepatotrophic factor for liver regeneration. We examined the mitogenic effect of hepatocyte growth factor on mouse liver in vivo. The labeling index of hepatocytes was markedly increased when recombinant human hepatocyte growth factor was injected intravenously into mice subjected to 30% hepatectomy (control, 1.7% +/- 0.1%; 1 microgram hepatocyte growth factor, 6.4% +/- 1.3%; 5 micrograms hepatocyte growth factor, 18.3% +/- 0.2%) and into mice administered carbon tetrachloride (control, 12.7% +/- 1.0%; 1 microgram hepatocyte growth factor, 26.3% +/- 2.8%) or alpha-naphthylisothiocyanate (control, 0.4% +/- 0.1%; 1 microgram hepatocyte growth factor, 3.8% +/- 1.1%; 5 micrograms hepatocyte growth factor, 14.2% +/- 2.0%). In addition, weights of the remnant livers in mice given hepatocyte growth factor 60 hr after 30% hepatectomy were significantly greater than those of untreated control mice (control, 0.93 +/- 0.04 gm; 5 micrograms hepatocyte growth factor, 1.06 +/- 0.04 gm). Hepatocyte growth factor prevented any marked increase in the serum levels of liver enzymes and bilirubin when it was administered to mice also treated with alpha-naphthylisothiocyanate (control: ALT, 394 +/- 278 IU/L; lactate dehydrogenase, 2,644 +/- 1,109 IU/L; bilirubin, 9.6 +/- 2.6 mg/dl; and 5 micrograms hepatocyte growth factor: ALT, 135 +/- 7.9 IU/L; lactate dehydrogenase, 1,672 +/- 626 IU/L; bilirubin, 1.0 +/- 0.8 mg/dl). Our findings show that intravenously injected hepatocyte growth factor stimulates the growth of hepatocytes in mouse liver and protects the integrity of hepatocytes in vivo against hepatitis caused by hepatotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Direct evidence that hepatocyte growth factor is a hepatotrophic factor for liver regeneration and has a potent antihepatitis effect in vivo. 142 61

Hepatocyte growth factor (HGF) is a potent growth factor for various epithelial cells including mature hepatocytes and renal tubular cells. When 70% of the rat liver was excised, HGF mRNA in the intact lung markedly increased at 6 h later, then decrease to normal levels at 24 h. A similar marked increase of HGF mRNA was found in the lung of rats with hepatitis induced by CCl4. Moreover HGF mRNA in the intact lung also increased to about a 5 times higher level than the normal, within 12 h after unilateral nephrectomy. Isolated alveolar macrophages significantly expressed HGF mRNA, yet the amount remained unchanged after injury of the liver. The marked increase of HGF mRNA in lungs of partially hepatectomized rats remained even after removal of alveolar macrophages. In situ hybridization showed a marked increase of HGF mRNA signal found in endothelial cells in the lung after partial hepatectomy. We postulate that endothelial cells in the lung recognize damage of distal organs through a mediator and that lung-derived HGF may contribute to tissue repair or regeneration of injured organs, through endocrine-related mechanisms.
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PMID:Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs. 153 Nov 75

The levels of human hepatocyte growth factor (hHGF) in sera obtained from patients with various liver diseases were determined using adult rat hepatocytes maintained in primary culture. The mean hHGF activity for 22 patients with fulminant hepatic failure was about nine times greater than that found in normal human serum. The increase in serum hHGF activity seen in two patients with "acute-on-chronic" hepatitis was similar to that found in patients with fulminant hepatic failure. The serum level of hHGF from patients with acute hepatitis is related to the stage of their illness. The average value for 31 patients was about three times that of normal human serum. In some patients, the time course for the increase in serum hHGF activity was similar to that demonstrated for alpha-fetoprotein. The mean hHGF activity in serum for the 33 patients with chronic hepatitis and from 25 patients with liver cirrhosis was increased also compared with that of normal human serum. In addition, serum hHGF activity in three of seven patients studied after partial hepatectomy for a space-occupying lesion of the liver was increased. These data suggest that the increase in serum hHGF activity present in patients with various liver diseases reflects a self-defense mechanism that is involved in the process of liver cell regeneration.
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PMID:Human hepatocyte growth factor in blood of patients with fulminant hepatic failure. I. Clinical aspects. 182 61

Human hepatocyte growth factor (hHGF) was purified from the plasma of six patients with fulminant hepatic failure due to hepatitis B in two and non-A, non-B hepatitis in four. The purified hHGF from each patient contained two major protein bands having molecular weights of 79,000 and 86,000 and several minor bands having molecular weights between 76,000 and 92,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis performed under nonreduced conditions. After reduction with 2-mercaptoethanol, three major bands having molecular weights of 58,000, 34,500, and 31,500 were evident. In addition, a band having a molecular weight of 21,000 was detected. hHGF activity was destroyed by its reduction. The hHGF purified from patients demonstrated a dose response in terms of an increase in DNA synthesis using cultured hepatocytes. The hHGF concentration in the plasma of the patients with grade III-IV hepatic coma was calculated to be in the range of 1.8-3.0 nM. Finally the heavy chain of hHGF was not recognized by an anti-human albumin antibody, indicating that hHGF is not biliprotein, an albumin-bilirubin complex, that has been reported to be a putative liver growth factor.
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PMID:Human hepatocyte growth factor in blood of patients with fulminant hepatic failure. Basic aspects. 182 62

Hepatocyte growth factor (HGF) is a most potent factor for mature parenchymal hepatocytes in primary culture and may act as a trigger for liver regeneration. We purified HGF from rat platelets to homogeneity and cloned both human and rat HGF cDNA. HGF is a heterodimer molecule composed of the 69 kDa alpha-subunit and the 34 kDa beta-subunit. HGF has no amino acid sequence homology with other known peptide growth factors and possesses the highest potential among known growth factors to stimulate proliferation of hepatocytes in primary culture. HGF is derived from a single chain precursor of 728 amino acid residues and the precursor is proteolytically processed to form a two-chain mature HGF. The alpha-subunit of HGF contains 4 kringle structures and HGF has a homology (38%) with plasmin. Biologically active recombinant human HGF could be expressed from COS-1 cells and CHO cells transfected with cloned cDNA. HGF activity and the HGF mRNA level are markedly increased in the liver following insult such as hepatitis, by the administration of hepatotoxins, ischaemia, physical damage and partial hepatectomy. Moreover, HGF mRNA is induced in the lung and kidney, in the presence of liver injury. In situ hybridization revealed that HGF-producing cells in liver are non-parenchymal liver cells, presumably Kupffer and sinusoidal endothelial cells. Therefore, HGF from neighbouring cells (Kupffer and sinsuoidal endothelial cells) and distal organs (lung and kidney) may function as a trigger for liver regeneration by both a paracrine mechanism and an endocrine mechanism. HGF has mitogenic activity for renal tubular epithelial cells, epidermal melanocytes and keratinocytes as well as mature hepatocytes, and has the potential to promote cell migration for some epithelial cells, including normal human keratinocytes. Since cell growth and cell motility are relevant to tissue repair and embryogenesis, HGF may well have important roles in tissue repair and embryogenesis as well as in liver regeneration.
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PMID:Hepatocyte growth factor: molecular structure and implications for a central role in liver regeneration. 183 43

Hepatocyte growth factor (HGF) has been demonstrated to be synthesized and secreted by non-parenchymal liver cells for liver regeneration after hepatic injury. We performed in situ hybridization to identify HGF-producing cell types in rat liver hepatitis induced by administrating carbon tetrachloride as a hepatotoxin. We found that transcripts of the HGF gene are localized in the Kupffer and endothelial cells in normal livers and increased remarkably in the Kupffer cells of the damaged livers. Thus, HGF is concluded to be synthesized in the Kupffer and endothelial cells to repair the liver tissue in paracrine fashion. No significant increase in the transcripts of the HGF gene was observed in livers after partial hepatectomy, indicating that a mechanism on liver regeneration after the hepatectomy differs from that on liver repairs. Since the HGF gene expression was also found in lung and kidney, HGF may be a ubiquitous factor for tissue repairs.
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PMID:Expression of hepatocyte growth factor gene in endothelial and Kupffer cells of damaged rat livers, as revealed by in situ hybridization. 214 53

The role of hepatocyte growth factor (HGF) in LEC rats were investigated at various phases of liver diseases by the detection of HGF expression, using ELISA assay, mRNA analysis and immunohistochemistry. Levels of plasma HGF increase in the fulminant hepatitis phase, decreased during chronic/cholangiofibrosis phase, and in some LEC rats, high levels of HGF were observed in hepatoma phase. HGF mRNA level in the liver was very high in fulminant hepatitis phase and low in chronic hepatitis phase. In hepatoma phase, HGF mRNA level was intermediate or high in the liver. In fulminant hepatitis phase, HGF mRNA level in the lung was slightly increased, while it was almost stable in the kidney in all the conditions studied. Immunohistochemical studies revealed that the frequency of HGF positive cells increased remarkably in fulminant hepatitis phase, and that many of them were located at the portal triads. Fewer HGF-positive cells were found in chronic hepatitis phase and were not found in the tissue of cholangiofibrosis. HGF was found in the surface of hepatocellular carcinoma cells and in the cytoplasm of the non-epithelial cells in cancerous liver tissues. HGF-positive cells appeared 24h after partial hepatectomy, diffusely, and HGF mRNA increased earlier in the kidney and lung than in the liver. Moreover, HGF mRNA level was higher in the lung than in the liver. These results suggest that in the natural course of spontaneous hepatitis and hepatoma in LEC rats, HGF is expressed mainly in the liver and that HGF may play an important role in the regeneration of hepatocytes in a paracrine manner. In contrast, after partial hepatectomy, HGF produced in the lung may be effective for liver regeneration in an endocrine manner.
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PMID:[Expression of hepatocyte growth factor (HGF) in LEC rats at various phases of hepatitis and hepatoma]. 759 Jun 6

Serum levels of human hepatocyte growth factor (hHGF) in patients with various liver diseases were determined using an ELISA kit to explore its clinical significance. Significantly high levels of serum hHGF were found in patients with acute hepatitis, fulminant hepatitis, liver cirrhosis, and hepatocellular carcinoma. Increased levels of hHGF were observed during severe liver injury in patients who died of fulminant hepatitis. However, the levels returned to normal during the repair process of liver injury in the surviving cases. In patients with liver cirrhosis, serum hHGF levels were negatively correlated with serum albumin (Alb) levels. These results indicate that serum hHGF levels are not useful for detecting repair processes of the injured liver, but serve as an index of the severity of liver dysfunction in various liver diseases.
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PMID:Clinical significance of serum hepatocyte growth factor levels in liver diseases. 768 68


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