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)

Hepatitis C virus (HCV) is the aetiological agent responsible for most cases of non-A non-B hepatitis. Hepatitis C is a disease of clinical importance because of its high infection rate in blood donors and its persistence as chronic infections which may lead to cirrhosis and hepatocellular carcinoma in the long term. The variability of the HCV genome has posed difficulties in serological detection and vaccine design. The recent advance in phage technology offers a means of cloning human anti-HCV antibodies of a defined specificity that may have potential therapeutic use. We now report the generation of a phage display library using the V(H) genes of a HCV-infected patient and the V(L) genes of two non-immune individuals. From this library we were able to obtain specific IgG single-chain Fvs (scFvs) that recognize viral core and envelope proteins by selection on synthetic peptides derived from the core sequence PKARRPEGRTWAQPG and the envelope E2 sequence RPIDDFDQGWGPITY. The specificity of the scFvs was demonstrated by their specific reactions with homologous peptides in ELISA and the specific blocking of scFv binding by homologous peptides, in a dose-dependent manner, in inhibition ELISA. The binding of the anticore 4c2 to homologous peptide was blocked by HCV-positive human sera in an antibody-concentration-dependent manner, suggesting that the scFv recognizes a similar if not identical epitope to those of one or more of the polyclonal antibodies present in the sera.
J Gen Virol 1996 Oct
PMID:Human recombinant antibodies specific for hepatitis C virus core and envelope E2 peptides from an immune phage display library. 888 87

1. Pentoxifylline (PTX), a derivative of the methylxanthine theobromine, has been used for many years in the treatment of peripheral vascular diseases. Increased red blood cell flexibility, reduction of blood viscosity, and decreased potential of platelet aggregation are the basic actions of PTX, resulting in therapeutic benefits due to improved microcirculation and tissue oxygenation. 2. PTX's generally accepted mechanism of action is the inhibition of phosphodiesterases, leading to increased intracellular levels of cyclic adenosine monophosphate (cAMP). 3. A number of studies have shown PTX's effects on the cytokine network. The most relevant clinical results are the therapeutic benefits of PTX in attenuating the effects of tumor necrosis factor-alpha (TNF-alpha) in conditions such as septic shock. 4. PTX also has been found to exert antifibrogenic actions, using cultured fibroblasts or animal models of fibrosis, including liver fibrosis. 5. In hepatic stellate cell culture PTX has been shown to inhibit the basic reactions of liver fibrogenesis, being effective on cytokines and growth factors relevant in fibrogenesis of the liver, too. 6. Therefore, PTX might be an effective drug with few side effects in the treatment of liver fibrosis. Further clinical studies have to be done to establish the real therapeutic benefits of PTX in liver fibrosis and cirrhosis.
Gen Pharmacol 1997 Aug
PMID:Pharmacological aspects of pentoxifylline with emphasis on its inhibitory actions on hepatic fibrogenesis. 925 97

Hepatitis B virus (HBV) infection is the leading cause of chronic hepatitis and cirrhosis in Turkey. The prevalence of hepatitis B surface antigen (HBsAg) positivity in Turkey is 5 to 10%. HBV is almost completely preventable with the use of hepatitis B vaccines. The most commonly used vaccine is that which contains the predominant viral surface (S) polypeptide. It elicits protective antibodies in greater than 90% of healthy subjects. A vaccine containing the PreS1 and PreS2 antigenic domains has recently been reported as being more efficient in achieving successful immunization in individuals who have not previously responded to the isolated S-antigen vaccine. In this study, the efficacy of a S and PreS-containing vaccine was compared with that of two different standard isolated S-antigen-containing vaccines in terms of the immunization protection produced against HBV in normal healthy adults who had not previously been immunized. Seventy-six young adults (aged 17-22) were randomly assigned to receive 1 ml (20 micrograms) of either one of two standard S-subunit recombinant hepatitis B vaccines (Engerix B. or Hepavax) or the combined S and PreS subunit vaccine (Gen Hevac B) intramuscularly in the deltoid muscle at 0, 1 and 2 months. Hepatitis B surface antigen antibody titres were measured at 1, 2 and 12 months. A titre > or = 10 IU ml-1 was considered to be protective. All subjects receiving the two standard isolated S-antigen-containing vaccines responded to the vaccination with reasonable antibody titres. One-half to two-thirds of those vaccinated developed high antibody titres (> 100 IU ml-1). In contrast, 9% of those receiving the combined PreS1 and PreS2 plus S antigens failed to respond, as demonstrated by antibody titres below the level considered to be protective. The mean titres at 12 months were 107 +/- 12 IU ml-1 (Engerix B), 102 +/- 12 IU ml-1 (Gen Hevac B) and 117 +/- 12 IU ml-1 (Hepavax Gene). Hence, no important difference in term of response to vaccination was found between the two different types of vaccines. As recombinant S-subunit vaccines are less expensive than those that combine S and PreS antigens, it is suggested that, when immunizing normal healthy adults, a standard isolated S-antigen-containing vaccine should be used.
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PMID:A comparative trial of two surface subunit recombinant hepatitis B vaccines vs a surface and PreS subunit vaccine for immunization of healthy adults. 975 Oct 13

1. To investigate the effectiveness of recombinant human serum albumin (rHSA) in the treatment of ascites in liver cirrhosis, we examined its effect on rats with carbon tetrachloride-induced liver cirrhosis. 2. Twenty-five percent rHSA was administered intravenously at a dose of 0.25 to 1.0 g/kg for 2 days to rats with liver cirrhosis accompanied by ascites retention and hypoalbuminemia. 3. rHSA dose dependently decreased abdominal circumference, a clinical index of ascites, with significant difference at a dose of 1.0 g/kg. 4. Although there was no significant difference, rHSA increased blood colloid osmotic pressure (b-COP) and urine volume (UV) in a nearly dose-dependent manner, with significant negative correlation between changes from baseline value in these parameters and in abdominal circumference. 5. These findings suggest that rHSA has abdominal circumference-decreasing action associated with b-COP improvement and UV increase and that it could be effective as a therapeutic drug for ascites in patients with liver cirrhosis accompanied by hypoalbuminemia.
Gen Pharmacol 1998 Nov
PMID:Effectiveness of recombinant human serum albumin in the treatment of ascites in liver cirrhosis: evidence from animal model. 980 84

Recently a novel DNA virus, designated TT virus (TTV), that possibly accounts for some of the cases of liver disease of unknown aetiology, was identified in Japanese patients. Using specific primer pairs for conserved regions, we detected TTV DNA by PCR in 16/84 (19%) German patients awaiting orthotopic liver transplantation because of decompensated liver cirrhosis (of diverse causes); in 4/25 (16%) patients with non-A-G hepatitis; in 1/7 patients with autoimmune hepatitis; and in one intravenous drug user. Sequence analysis showed that in contrast to the findings in Japanese patients only about 37% of our TTV sequences belonged to genomic group 1 but about 58% belonged to group 2, including several sequences belonging to a further subgroup tentatively designated group 2c. Further studies to clarify whether the novel virus has hepatitis-inducing capacity or other clinical significance are needed.
J Gen Virol 1998 Nov
PMID:Detection of sequences of TT virus, a novel DNA virus, in German patients. 982 Jan 52

The immunogenicity of hepatitis B vaccine is unknown for patients with chronic hepatitis C, although hepatitis B vaccination is highly recommended in these patients. We therefore studied in a prospective open trial of 59 patients with chronic hepatitis C (mean age 42 years, hepatitis C for >10 years, Child-Pugh score < or = 5) and 58 healthy hospital staff persons the rate of nonresponse (anti-HBs <10 mIU/mL at 9 months) to recombinant hepatitis B vaccine (Gen H-B-Vax(R),10 microg intradeltoidal at month 0, 1, and 6). Nonresponse was observed in 18/59 (31%) patients with chronic hepatitis C and 5/58 (9%) healthy staff persons (P <.005) (vs. 7% in historical controls; P <.005), low response (anti-HBs 10-99 mIU/mL) in 19% of patients with chronic hepatitis C and 17% of staff persons. High-dose booster vaccination led to seroconversion in 12/15 (80%) of primary nonresponders. Primary nonresponse to HB vaccine was related neither to presence of early-stage liver cirrhosis nor magnitude of serum hepatitis C virus (HCV) RNA concentration, nor explained by the presence of human leukocyte antigen (HLA) types (B8 DR3, B44, DR7, DQ2) predisposing to low antibody response to hepatitis B surface antigen. The rate of primary nonresponse to the standard regimen of recombinant hepatitis B vaccine is surprisingly high in patients with longstanding chronic hepatitis C. Therefore, the antibody to HBV surface antigen (anti-HBs) titer response should be determined in these patients. Depending on the response titer, higher booster doses may be required to achieve and maintain seroprotection in these patients.
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PMID:Decreased immunogenicity of recombinant hepatitis B vaccine in chronic hepatitis C. 1096 Feb 83

Hepatitis C virus (HCV) persists in the majority of infected individuals and is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis C is currently treated with interferon (IFN)-alpha or with a combination of IFN-alpha and ribavirin. The availability of an HCV replicon system (Lohmann et al., SCIENCE: 285, 110-113, 1999) allowed the investigation of the effects of IFN on genuine HCV replication in cultured cells. It is shown here that IFN-alpha inhibits subgenomic HCV RNA replication in HuH-7 human hepatoma cells. Immunofluorescence, Western blot and Northern blot analysis revealed that levels of both HCV protein and replicon RNA were reduced after treatment with IFN-alpha in a dose-dependent manner. In further experiments, it was investigated whether MxA plays a role in the inhibition of HCV. The human MxA protein is an IFN-induced GTPase that has antiviral activity against various RNA viruses. However, HCV RNA replication was not affected in transfected HuH-7 cells that transiently overexpressed MxA. Moreover, a dominant-negative mutant of MxA did not interfere with the antiviral activity of IFN-alpha against HCV RNA replication. Taken together, these results demonstrate that IFN-alpha inhibits HCV replicons via an MxA-independent pathway.
J Gen Virol 2001 Apr
PMID:Interferon-alpha inhibits hepatitis C virus subgenomic RNA replication by an MxA-independent pathway. 1125 76

The purpose of this investigation was to explore the psychiatric complications of liver cirrhosis in a Nigerian general hospital setting. The mental state of 31 consecutive patients with liver cirrhosis seen in a gastroenterology unit, from July 1996 to August 1998, was assessed using the 30-item General Health Questionnaire (GHQ-30) and Present State Examination (PSE) and compared with those of 20 hypertensive patients and 20 apparently healthy controls. The socio-demographic characteristics of patients with liver cirrhosis who developed psychiatric complications were compared with those without such complications. The mental status of the cirrhosis patients in the present study was also compared with those of Chronic Obstructive Pulmonary Disease (COPD) and hemodialysis patients in earlier studies. About fifty-five percent of all the liver cirrhosis patients developed diagnosable psychiatric morbidity. This was significantly higher than that of the hypertensive patients (15%) or healthy controls (5%) (P=0.0001). The psychiatric conditions were depressive episode, generalized anxiety disorder, delirium and adjustment disorder. No socio-demographic parameter had a significant effect on the mental state of the patients with liver cirrhosis. The same proportion (55%) of hemodialysis and a lower proportion (30%) of COPD patients compared with cirrhosis patients had psychiatric morbidity. We found a high rate of psychiatric morbidity in the patients with liver cirrhosis compared with those of hypertension and normal subjects. None of the socio-demographic variables considered was found to be associated with psychiatric complications in the liver cirrhosis patients. Poor medical conditions seem to be associated with high levels of psychiatric morbidity.
Gen Hosp Psychiatry
PMID:Specific psychiatric morbidity in liver cirrhosis in a Nigerian general hospital setting. 1249 Mar 47

We determined the sequence of the hepatitis delta virus (HDV) genome in 40 Japanese patients, most of whom were from the Miyako Islands, Okinawa, Japan. Consensus sequences from 33 HDV full genomes out of a total of 40 patients were determined by directly sequencing four partially overlapping PCR products. Phylogenetic tree analysis classified these 33 complete HDV genomes as HDV genotype I (two patients), genotype IIa (one patient) and genotype IIb (30 patients). Among the 30 genotype IIb patients, there were two clusters of genetic variants. One group consisted of six isolates showing significant homology with genotype IIb, previously reported from Taiwan. The other group consisted of 24 isolates, whose sequences formed a new genetic subgroup (genotype IIb-Miyako; IIb-M). When the genetic structures were compared in detail between IIb and IIb-M, characteristic variations were found in the C-terminal sequence of the large delta antigen-conferring packaging signal as well as the RNA editing site. Determination of subclasses of genotype IIb in a total of 37 patients, including seven HDV patients whose partial HDV sequence was determined, revealed eight patients with IIb and 29 patients with IIb-M. Although there was no significant difference in the clinical background or virological state of hepatitis B virus between these two groups, patients with genotype IIb-M showed greater progression of chronic hepatitis and cirrhosis than those with genotype IIb (P=0.0009). These data indicate the existence of a genetic subgroup of HDV genotype IIb, which is associated with different clinical characteristics and which could be related to genetic variations in functionally important parts of the HDV genome.
J Gen Virol 2003 Dec
PMID:Chronic hepatitis delta virus infection with genotype IIb variant is correlated with progressive liver disease. 1464 9

The majority of hepatitis C virus (HCV)-infected individuals become chronically infected, which can result in liver cirrhosis and hepatocellular carcinoma. Patients with chronic HCV are unable to prime and maintain vigorous T-cell responses, which are required to rid the body of the viral infection. Dendritic cells (DCs) are the professional antigen-presenting cells that probably play a dominant role in priming and maintaining vigorous T-cell responses in HCV infection. Furthermore, inefficient DC function may play an important role in HCV chronicity. In order to determine the effect of HCV NS3 and core proteins on phenotype and function of human DCs, recombinant adenoviral vectors containing NS3 or core genes were used to infect human DCs. HCV NS3- or core-protein expression in DCs was confirmed by Western blotting and immunofluorescence staining. The DCs expressing HCV NS3 or core proteins expressed several inflammatory cytokine mRNAs, had a normal phenotype and effectively stimulated allogeneic T cells, as well as T cells specific for another foreign antigen (tetanus toxoid). These findings are important for rational design of cellular-vaccine approaches for the immunotherapy of chronic HCV.
J Gen Virol 2006 Jan
PMID:Expression of hepatitis C virus-derived core or NS3 antigens in human dendritic cells leads to induction of pro-inflammatory cytokines and normal T-cell stimulation capabilities. 1636 18


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