Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentration of the N-terminal peptide of procollagen III and the activity of collagen peptidase (PZ-peptidase) were measured in sera from 92 patients with chronic liver disease. In patients with liver cirrhosis and chronic hepatitis with transformation of liver structure, high values were found for both variables compared with hepatoses and chronic hepatitis without transformation. The concentration of procollagen III peptide and the activity of collagen peptidase in serum increased with increasing degrees of fibrosis and, even more markedly, with increasing degrees of mesenchymal activity in the liver.
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PMID:Collagen peptidase and type III procollagen peptide serum levels in chronic liver diseases. 164 85

9-beta-D-Arabinofuranosyladenine 5'-monophosphate (ara-AMP) coupled to lactosaminated human albumin (L-HSA), injected i.v. into rats, selectively enters the liver. The conjugate concentration in parenchymal and sinusoidal hepatic cells, isolated by collagenase perfusion, was found to be practically equal in both cell types. This indicates that the high uptake of L-HSA-ara-AMP complex by the whole liver also corresponds to a high conjugate concentration in hepatocytes where ara-AMP should be targeted in order to increase its chemotherapeutic index in chronic hepatitis B treatment.
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PMID:Distribution of a conjugate of 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) with lactosaminated albumin in parenchymal and sinusoidal cells of rat liver. 244 May 49

Since there is a remarkable increase in connective tissue around the proliferating bile ductules in chronic hepatitis and liver cirrhosis, the participation of proliferating bile ductules in hepatic fibrosis has been discussed by many during the past. With the use of immunofluorescent method, the present authors have recently succeeded in detecting alpha1-antitrypsin, a protease inhibitor, in the epithelial cells of proliferating bile ductules and a portion of the hepatocytes connected with these epithelial cells. When considering the posibility of alpha1-antitrypsin being secreted into the interstitial tissue, it is conceivable that this glycoprotein plays an important role in restraining collagenase activity, which takes part in the degradation of collagen, and leads to abnormal proliferation of collagen.
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PMID:Hepatic fibrosis. The relation between proliferating bile ductules and alpha1-antitrypsin. 696 23

To investigate the viral replication cycle and genomic heterogeneity of hepatitis C virus (HCV), we established an HCV cultivation system by using a primary hepatocyte culture from patients with chronic hepatitis C. Liver tissue was obtained by needle biopsy or surgery, then hepatocytes were isolated by collagenase digestion. After several weeks, we determined the HCV RNA titre of the cultured cells and supernatant by a competitive polymerase chain reaction (PCR) method. A significant amount of HCV RNA was observed in the cells and supernatant during cultivation. Negative-strand RNA, regarded as a marker of viral replication, could be detected by a strand-specific reverse transcription PCR method and the HCV core protein could be detected by immunofluorescence microscopy. Many HCV particles released into the supernatant were infectious. In addition, we compared the nucleotide sequences in the E2/NS1 region of pre- and post-cultivation hepatocytes for 8 weeks. At the beginning of the culture period, three major HCV types containing two subtypes were isolated. Following cultivation, the same types were isolated from the cultured hepatocytes in the same ratio as prior to cultivation. We could detect the same clones in this patient's serum, but in vivo we observed genetic variability over a 6 month interval. One clone detected throughout the 6 month period mutated extensively in the hypervariable region. These results indicated that HCV can replicate in cultured hepatocytes, and that infectious virions are released into the supernatant. This cultivation system should facilitate the study of HCV genomic heterogeneity, infection and replication.
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PMID:Cultivation of hepatitis C virus in primary hepatocyte culture from patients with chronic hepatitis C results in release of high titre infectious virus. 860 70

Disruption or absence of hepatocyte keratins 8 and 18 is associated with chronic hepatitis, marked hepatocyte fragility, and a significant predisposition to stress-induced liver injury. In contrast, pancreatic keratin disruption in transgenic mice that express keratin 18 Arg89 --> Cys (K18C) is not associated with an obvious pancreatic pathology. We compared the effects of keratin filament disruption on pancreatic acini or acinar cell viability, and on cholecystokinin (CCK)-stimulated secretion, in transgenic mice that overexpress wild-type keratin 18 and harbor normal extended keratin filaments (TG2) and K18C mice. We also compared the response of these mice to pancreatitis induced by a choline-deficient ethionine-supplemented diet or by caerulein. Despite extensive cytoplasmic keratin filament disruption, the apicolateral keratin filament bundles appear intact in the acinar pancreas of K18C mice, as determined ultrastructurally and by light microscopy. No significant pancreatitis-associated histologic, serologic, or F-actin/keratin apicolateral redistribution differences were noted between TG2 and K18C mice. Acinar cell viability and yield after collagenase digestion were lower in K18C than in TG2 mice, but the yields of intact acini and their (125)I-CCK uptake and responses to CCK-stimulated secretion were similar. Our results indicate that keratin filament reorganization is a normal physiologic response to pancreatic cell injury, but an intact keratin cytoplasmic filament network is not as essential in protection from cell injury as in the liver. These findings raise the possibility that the abundant apicolateral acinar keratin filaments, which are not as evident in hepatocytes, may play the cytoprotective role that is seen in liver and other tissues. Alternatively, identical keratins may function differently in different tissues.
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PMID:Effects of keratin filament disruption on exocrine pancreas-stimulated secretion and susceptibility to injury. 1069 32

Decorin is a small extracellular matrix proteoglycan. It binds and modulates transforming growth factor (TGF)-beta 1 action, the major stimulator of fibrogenesis. Its role in the pathogenesis of human liver cirrhosis is unknown. Therefore, we studied the relationship of the 2 proteins in normal human liver and in 43 chronic hepatitis and liver cirrhosis specimens. To understand the mechanism that maintains matrix deposition in stage IV hepatitis, we studied expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2, as well as the activities of type IV collagenases. Gene expression was analyzed on messenger RNA and protein level by morphologic and biochemical approaches. Decorin proved to be an early marker of fibrogenesis, and its deposition increased parallel to that of TGF-beta 1 and to inflammatory activity. Liver fibrosis progressed despite high temporospatial expression of decorin with TGF-beta 1. Neither decorin nor TGF-beta 1 protein deposition increased further in cirrhosis with low inflammatory activity, suggesting that impaired extracellular matrix catabolism rather than active production plays a role in this stage. This possibility was supported by high message levels of metalloproteinase inhibitors, no 72-kd collagenase activities, and low 92-kd collagenase activities.
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PMID:Expression of decorin, transforming growth factor-beta 1, tissue inhibitor metalloproteinase 1 and 2, and type IV collagenases in chronic hepatitis. 1134 37

Matrix metalloproteinases (MMPs) are central to tissue remodelling; however, little is known about the temporal pattern and differential regulation of hepatic MMP expression in the course of chronic human liver disease. Using quantitative reverse transcription-PCR ELISA assays, we studied hepatic mRNA expression of MMP-1, -2, -3, -7, -9, -10, -11, -13 and -14 in patients with chronic hepatitis C and hepatitis C virus-induced end-stage liver cirrhosis and controls. Results were compared with histology, hepatic expression of tissue inhibitor of metalloproteinases (TIMP)-1, -2 and -3, procollagen types I and IV, laminin, and with circulating protein levels of hyaluronate, TIMP-1 and -2 and MMP proenzymes, as measured by ELISA. The impact of the MMP-3(-1171) promoter polymorphism on hepatic MMP-3 expression was analysed. Hepatic mRNA expression data identified differentially regulated groups of MMPs during the course of chronic hepatitis C, showing either steadily increasing mRNA expression with disease progression (MMP-1, -2, -7 and -14) or transiently elevated expression (MMP-9, -11 and -13). The first group closely correlated to the parameters of fibrogenesis. Hepatic MMP-3 expression was unrelated to disease stage, but was determined by the MMP-3(-1171) promoter polymorphism. In conclusion, MMP expression during the course of chronic hepatitis C appears to be a closely regulated process, with different clusters of coordinately regulated MMP genes being identified.
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PMID:Expression and coordinated regulation of matrix metalloproteinases in chronic hepatitis C and hepatitis C virus-induced liver cirrhosis. 1276 Jul 42

Recently a new field of immunological research and clinical application of vaccines for therapeutic purposes (vaccine therapy) has been developed for treating several chronic viral infections including chronic hepatitis B virus (HBV) infection. Administration of vaccine containing hepatitis B surface antigen (HBsAg) for 1 year has resulted in negative HBsAg and development of antibody to HBsAg (anti-HBs) in some, but not in all, HBV transgenic mouse (HBV-Tg). In order to develop more potent regimen of vaccine therapy for chronic HBV carrier, we prepared a dendritic cell (DC)-based therapeutic vaccine and evaluated their therapeutic potential in HBV-Tg. DCs were isolated from single cell suspensions of murine spleen cells by collagenase digestion, density centrifugation and depletion of lymphocytes. Spleen DCs were cultured with HBsAg (100 microg) for 24 h to produce HBsAg-pulsed DCs. HBV-Tg expressing HBsAg and HBV DNA in the sera were randomly assigned to receive either HBsAg-pulsed DCs (n = 20) or unpulsed DC (n = 20) or vaccine containing HBsAg (n = 39) or complete Freund's adjuvant (n = 20) or left untreated (n = 20). Only two intraperitoneal injections of HBsAg-pulsed DCs resulted in negative HBsAg and production of anti-HBs in the sera in all HBV-Tg (n = 20). However, administration of un-pulsed DCs (n = 20) or vaccine containing HBsAg (n = 39) or only complete Freund's adjuvant did not induce negative HBsAg or production of anti-HBs in any HBV-Tg within 6 months of therapy commencement. Taken together, this study showed that HBsAg-pulsed DCs represent a highly potent therapeutic vaccine for chronic HBV infection and inspire optimism of using this vaccine in clinical conditions. A clinical trial of HBsAg-pulsed DC in patients with chronic hepatitis B is warranted.
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PMID:Production and efficacy of a dendritic cell-based therapeutic vaccine for murine chronic hepatitis B virus carrierer. 1525 81

As chronic liver disease progresses, an imbalance occurs between synthesis and breakdown of extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are involved in degrading ECM while tissue inhibitors of metalloproteinases (TIMPs) prevent their fibrolytic action. In the present study, serum levels of matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were investigated as non-invasive parameters for the diagnosis of hepatic fibrosis in patients with HCV related chronic liver disease. Their diagnostic potential was evaluated in comparison to hepatic histology and standard liver function tests. A sandwich enzyme immunoassay technique was used to study circulating values of MMP-2 and TIMP-1 in forty-one patients with HCV antibodies in their sera (27 patients with biopsy ascertained chronic hepatitis C and 14 patients with histologically proven liver cirrhosis. Hepatic histology was evaluated using the hepatitis-activity-index according to Ishak et al. (1995), quantifying separately inflammatory activity and fibrosis. Ten healthy individuals were also included in the study as controls. Serum levels of MMP-2 were similar in controls and in chronic hepatitis C patients with (n = 15) and without (n = 12) fibrosis, but increased significantly in cirrhosis. TIMP-1 serum values showed a steady increase from normal controls to chronic hepatitis C without fibrosis, hepatitis C with fibrosis, and cirrhosis. The diagnostic potential of MMP-2 to detect fibrosis was low with a sensitivity of 7% and a diagnostic efficiency of 56%. The diagnostic potential of circulating MMP-2 to detect cirrhosis was higher with a sensitivity of 83% and a specificity of 96% resulting in a diagnostic efficiency of 92%. Serum TIMP-1 values detected fibrosis with a sensitivity of 67% and a specificity of 69% resulting in an efficiency rate of 70%. TIMP-1 values detected cirrhosis with 100% sensitivity but only 75% specificity. The diagnostic potential of circulating TIMP-1 was higher than that of serum ALT, AST or albumin values. In conclusion, serum values of MMP-2 and TIMP-1 are able to detect cirrhosis with a high sensitivity. Moreover, TIMP-1 values can detect fibrosis with comparable efficiency. Regular determinations of both TIMP-1 and MMP-2 in patients with chronic hepatitis C may be used as indicators of increasing fibrosis and the development of cirrhosis.
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PMID:Diagnostic potential of serum matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as non-invasive markers of hepatic fibrosis in patients with HCV related chronic liver disease. 1571 20

Several beneficial effects of splenectomy on the liver integrity have been recently reported by both experimental and clinical studies. However, the effects of splenectomy on hepatic functional reserve and structural damage in patients with chronic hepatitis C (CHC) were not studied by objective evidence. The aim of this study was to assess the effect of splenectomy on hepatic functional reserve and structural damage in patients with CHC by non-invasive serum markers. The study involved 22 patients with histopathological diagnosis of CHC undergoing splenectomy for treatment of associated hypersplenism. The hepatic functional reserve and structural damage markers were assessed before and after splenectomy surgery on the 2nd and 60th postoperative days by aspartate aminotransferase to alanine aminotransferase (AST/ALT ratio), AST to platelet ratio index (APRI) and serum levels of gamma-glutamyl transferase (GGT), hyaluronic acid (HA), type IV collagen (CIV) and tissue inhibitor of metalloproteinase-1 (TIMP-1). After splenectomy, the levels of serum HA showed a significant decrease in relation to the preoperative values both in PO-1 (mean pre-splenectomy: 272+/-88.6 versus 185+/-77.4 ng/ml; P=0.01) and PO-2 (169+/-58.1 ng/ml; 0.017). The levels of type IV collagen showed a significant decrease in relation to the preoperative values both in PO-1 (mean pre-splenectomy: 208+/-134 versus 125+/-100 ng/ml; P=0.01) and PO-2 (121+/-74.7 ng/ml; P=0.02). Serum levels of TIMP-1 also showed a significant decrease in relation to the preoperative values both in PO-1 (mean pre-splenectomy: 764+/-571 versus 261+/-195 ng/ml; P=0.006) and PO-2 (149+/-110.1 ng/ml; P=0.004). There was no significant difference between PO-1 and PO-2 mean values for each of those serum markers. This study found that splenectomy induced a reduction of biochemical markers of liver functional reserve and fibrosis in patients with chronic hepatitis C which reflect a change in the processes involved in of liver fibrosis. However, it cannot be concluded whether this reflects a change in the rate of its progression or a prevention of further fibrosis.
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PMID:A study of the effect of splenectomy on hepatic functional reserve and structural damage in patients with chronic hepatitis C virus infection by non-invasive serum markers. A prospective study. 1866 98


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