Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Difficulty in obtaining human liver specimens has made a delay in the development of methodology for isolation and primary culture of human hepatocytes compared to animal hepatocyte cultures. Recently the collagenase-liver-perfusion technique, which was developed for rat hepatocyte isolation, has been applied to prepare isolated human hepatocytes. This method greatly improved the yield and viability of hepatocytes of human liver tissues. Since then, the isolated human hepatocytes and their primary culture have been widely used for studies of hepatic metabolism, regeneration, transplantation, hepatitis B virus infection, hepatotoxins, detection of human carcinogens, hepatocarcinogenesis and so forth. These current studies were reviewed.
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PMID:[Cell culture and its application primary culture of human hepatocytes and its application]. 150 93

In July 1986, a 46-year old male patient was admitted for a bullous skin disease of 4 years' duration. The disease fulfilled all the criteria of epidermolysis bullosa acquisita (EBA), as laid down by Roenigk and Pearson. Despite a guided investigation, none of the diseases classically associated with EBA could be found, but it must be noted that immunological stigmata of an old hepatitis B were present. After failures or partial results with prednisone alone (1 mg/kg/day from August to October 1986), then methotrexate (30 mg/week) combined with prednisone (20 mg/day), the patient was treated with colchicine in doses of 2 mg per day, and within a fortnight a dramatic improvement of buccal mucosal lesions and cutaneous fragility was observed. Colchicine was withdrawn, but 5 days later bullae and erosions of the mucosa reappeared. The reintroduction of colchicine in the same doses (2 mg/day) resulted in remission of the lesions. The disease has now remained stable for one year under colchicine 1 mg/day. Four attempts at reducing this dosage to 1 mg every other day brought about the recurrence of a few bullae and of cutaneous fragility. To our knowledge, colchicine has not yet been reported to be effective in the treatment of EBA. Its effectiveness may be due, to a great extent, to its immunomodulating properties, notably on some functions of neutrophils the role of which in the pathogenesis of bullous lesions seems to have been established. By modulating collagen synthesis and collagenase activity colchicine might induce structural modifications of the EBA antigen, identified as the carboxyterminal group of type VII collagen, and inhibit its recognition by autoantibodies.
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PMID:[Value of colchicine in treating acquired epidermolysis bullosa]. 267 32

An attempt was made to infect primary duck hepatocyte cultures with duck hepatitis B virus in vitro in order to clarify the biology of hepatitis B virus. Livers of ducklings, 0 to 17 days posthatch, without viremia were digested ex situ by perfusion of collagenase solution through the portal or hepatic vein. Homogeneous hepatocyte suspensions were seeded into plastic dishes in L-15 medium containing 10(-8) M insulin, 2 X 10(-8) M glucagon and 10(-8) M dexamethasone and were subsequently inoculated with sufficient numbers of duck hepatitis B virus. As a result, duck hepatitis B virus multiplication started weakly on Day 2, gradually increased and reached the maximum level approximately on Day 10 postinoculation. Viral replication was revealed by duck hepatitis B virus DNA in the cell pellet and in the culture medium and duck hepatitis B virus DNA-specific transcripts in the cell pellet. Immunostaining demonstrated duck hepatitis B virus core antigen in approximately 10% of cultured hepatocytes, and an increase in numbers of positive cells was not observed with time for up to 18 days of culture. Viral particles were found within the endoplasmic reticulum, and the inoculation of culture medium provoked viremia in the ducklings. The age of ducklings did not influence the numbers of cells infected. The in vitro infection system was similar to the in vivo one; however, the former seemed to be age-independent and to allow replication of duck hepatitis B virus in the limited number of hepatocytes.
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PMID:In vitro transmission of duck hepatitis B virus to primary duck hepatocyte cultures. 329 62

Primary cultures of non-proliferating hepatocytes isolated by the two-step collagenase perfusion method from woodchuck naturally infected with hepatitis virus (WHV) were used to study WHV propagation in vitro. Hepatocytes carrying WHV DNA exhibited a very high level of survival and retained their morphological characteristics for 2 to 3 months. Over this time, they were found to produce virus-specific proteins and release viral particles with DNA polymerase activity into the medium. Using Southern blot analysis and a recombinant hepatitis B virus DNA plasmid probe, intracellular and extracellular viral DNA was consistently detected. Only extrachromosomal forms of WHV DNA were observed and no integration could be demonstrated in the DNA of the cells. The WHV DNA patterns were repeatedly identical with a characteristic smear starting from 3.3 kb associated with other smaller DNA fragments which presumably represented intermediate replicative forms of viral DNA. Furthermore, dot blot hybridization of the total RNA revealed the presence of WHV-specific transcripts in cells after 3 weeks of culture. All these results are compatible with the maintenance of active WHV replication in vitro although it was somewhat reduced after the first day of culture. This provides a mammalian model for hepadnavirus replication studies in stable primary hepatocyte cultures.
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PMID:Maintenance of woodchuck hepatitis virus activity in woodchuck hepatocyte primary culture. 357 56

The DNA fragment coding for the hepatitis B virus surface antigen (HBsAg) was placed under the control of a human 70 kDa heat-shock protein (hsp70) promotor sequence. This plasmid construct has been used in transfection experiments to establish a stable amnion cell line of human origin (Wish), expressing an HBsAg in a heat-regulated fashion. Post-translational modifications, such as assembly, glycosylation, secretion and production of both major and middle S proteins appear to function normally. In addition, production of HBsAg under various protocols of heat induction is described. After inoculation into nude mice, development of tumours has been observed at the site of injection. Tumour cells, dispersed by means of collagenase or trypsin treatment from excised tumours, and subsequently seeded into Petri dishes, were able to secrete the same quantities of HBsAg after heat induction as were cells of the original cell line.
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PMID:Heat-regulated expression of the hepatitis B virus surface antigen in the human Wish cell line. 366 Sep 44

Recent studies of hepatitis B virus suggest that polymeric human serum albumin may facilitate the attachment of the virus via albumin receptors to hepatocytes during the infectious process. If this hypothesis is correct, hepatocytes should express binding sites for polymeric albumin. We employed the red blood cell adherence test using albumin-coated red blood cells as indicator cells on frozen sections of normal human livers to demonstrate these binding sites. Hepatocytes showed binding activity for both polymeric and monomeric albumin from different species. The receptor-ligand interaction was temperature and pH dependent, Ca++ independent and not altered by mercaptoethanol treatment. The binding activity was sensitive to neuraminidase and pronase, but resistant to trypsin, lipase and collagenase digestion. These findings suggest that human hepatocytes display species-non-specific albumin binding sites, which are glycoproteins.
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PMID:Albumin binding sites of human hepatocytes. 631 67

This work was designed to assess the reflection of early treatment by praziquantel (CAS 55268-74-1, EMBAY 8440, Biltricide) on serum connective tissue metabolite markers (hyaluronic acid and procollagen III peptide) in patients with active intestinal schistosomiasis. Children and adolescent subjects from primary and secondary schools in an endemic area of schistosomiasis mansoni were included. Age-matched subjects from an urban area served as normal controls. All subjects were examined clinically and parasitologically. Detection of hepatitis B seromarkers was also done. The infected subjects were treated with praziquantel at a dose of 60 mg/kg of body weight which was repeated after 4 weeks. Serum hyaluronic acid and procollagen III peptide were measured by radioimmunoassay. High hyaluronic acid was encountered in infected subjects when compared to their respective age-matched controls. Significant decrease of 4 and 8 weeks post-treatment was noted when compared to ist level before treatment. There was no significant change in serum procollagen III peptide on comparing infected subjects to their controls, whereas a significant increase was observed in its level after 4 and 8 weeks post-treatment compared to that before treatment. This work suggests that early treatment of intestinal schistosomiasis with specific chemotherapy (praziquantel) decreases serum hyaluronic acid and increases procollagen III peptide probably via downregulation of granulomatous inflammatory cell reaction and activation of collagenase enzymes, respectively.
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PMID:Effect of early treatment with praziquantel on serum connective tissue metabolite markers in children and adolescents with intestinal schistosomiasis mansoni. 903 50

Hepadnaviruses are known to be sensitive to various extracellular mediators. Therefore, bacterial endotoxin, which induces the secretion of proinflammatory mediators in the liver, was studied for its effect on hepadnavirus infection in vitro using the duck hepatitis B virus (DHBV) model. In initial experiments, endotoxin was shown to inhibit DHBV replication in primary duck hepatocyte cultures prepared by standard collagenase perfusion. As a primary endotoxin target, hepatic nonparenchymal cells (NPC) contaminating primary hepatocyte cultures, and among these probably macrophages (Kupffer cells), were identified to secrete polypeptide mediators into the cell culture medium. When added during DHBV infection, these mediators elicited the principal antiviral effect in a dose-dependent fashion. On the molecular level, they inhibited accumulation of viral proteins as well as amplification of the nuclear extrachromosomal DHBV DNA templates. In hepatocytes with an established DHBV infection, DHBV protein and progeny virus production was inhibited while the levels of established nuclear DHBV DNA templates and viral transcripts remained unaffected. Finally, in hepatocytes infected with a replication-deficient recombinant DHBV-green fluorescent protein (GFP) virus, the endotoxin-induced mediators markedly reduced GFP expression from chimeric DHBV-GFP transcripts, indicating that the major effect is at a level of translation of viral RNAs. Taken together, the data obtained demonstrate that antiviral mediators, and among these the cytokines alpha interferon (IFN-alpha) and IFN-gamma, are released from hepatic NPC, most probably liver macrophages, upon endotoxin stimulation; furthermore, these mediators act at a posttranscriptional step of hepadnavirus replication.
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PMID:Endotoxin stimulates liver macrophages to release mediators that inhibit an early step in hepadnavirus replication. 1082 58

Liver cirrhosis represents a worldwide health problem and is a major cause of mortality. Cirrhosis is the result of extensive hepatocyte death and fibrosis induced by chronic alcohol abuse and hepatitis B and C viruses. Successful gene therapy approaches to this disease may require both reversal of fibrosis and stimulation of hepatocyte growth. Urokinase-type plasminogen activator (uPA) may serve this function, as it is an initiator of the matrix proteolysis cascade and induces hepatocyte growth factor expression. In a rat cirrhosis model, a single iv administration of a replication-deficient adenoviral vector encoding a nonsecreted form of human uPA resulted in high production of functional uPA protein in the liver. This led to induction of collagenase expression and reversal of fibrosis with concomitant hepatocyte and improved liver function. Thus, uPA gene therapy may be an effective strategy for treating cirrhosis in humans.
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PMID:Liver cirrhosis is reverted by urokinase-type plasminogen activator gene therapy. 1112 55

Matrix metalloproteases (MMPs) and their inhibitors are effector molecules involved in extracellular matrix remodelling. The serum profile for these proteolytic enzymes and their inhibitors during acute self-limiting viral hepatitis has not been studied. We therefore determined serum concentrations of MMP-1, MMP-3, MMP-2, MMP-9 and their inhibitors (tissue inhibitors of metalloproteinase) TIMP-1, TIMP-2 and alpha2 macroglobulin (AMG) in the serum of patients during the icteric stage of self-limiting acute viral hepatitis. Transforming growth factor-beta (TGF-beta) and interleukin (IL)-10, two cytokines involved in the regulation of MMPs and TIMPs were also assessed. Nineteen patients (12 men, seven women) with a mean age of 29.9 years (range 16-65 years) participated in the study. Fifteen had hepatitis B virus (HBV, two HCV and two HAV infection. The values of patients were compared with those obtained from 15 blood donor controls (eight men, seven women), mean age 36.2 years (range 18-55 years). Serum levels of TGF-beta, IL-10, MMP-1, MMP-3, MMP-2, MMP-9, TIMP-1 and TIMP-2 were assessed by ELISA. MMP-2 and MMP-9 were also measured by a zymogram protease assay. alpha2 macroglobulin (AMG) was measured by nephelometry. Compared with the healthy controls the mean serum concentrations of all MMPs were significantly decreased in the acute hepatitis patients. There was no difference in the serum concentration of TIMP-1 between patients and the controls. Serum levels of TIMP-2 (P < 0001), TGF-beta (P < 0.05), IL-10 (P < 0.001) and AMG (P < 0001) were increased in patients compared to healthy controls. A statistically significant negative correlation by linear regression analysis was found between AMG and MMP-1 (P=0003). The decreased levels of MMPs observed, together with normal and increased levels of TIMP-1 and TIMP-2, may indicate an attempt to limit matrix degradation at this stage of disease resolution. The increased levels of the anti-inflammatory cytokines IL-10 and TGF-beta might be the underlying mechanism responsible for the above effect. AMG inhibition especially for MMP-1 may play an additional important role.
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PMID:Matrix metalloproteinases and their inhibitors in acute viral hepatitis. 1201 May 6


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