Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute hepatitis models are widely used for the evaluation of drugs for liver disease or for basic research on hepatitis. However, it is difficult to produce similar liver conditions to human chronic hepatitis with an acute hepatitis model. The interferon-gamma (IFN-gamma) transgenic mouse, which carries the mouse IFN-gamma gene, strongly expresses the IFN-gamma gene in the liver and develops chronic hepatitis from the age of 6-10 weeks. We found that the hepatitis in this mouse reflects human chronic hepatitis at least in the following points, i) infiltration by lymphoid cells into the portal areas and necroinflammation in the lobules, and ii) expression of Fas antigen and Fas ligand mRNAs in the liver. Furthermore, the induction of CPP32-like protease activity in the transgenic mouse liver suggests the involvement of this protease activity in the development of chronic hepatitis.
Int J Mol Med 1999 May
PMID:The mouse interferon-gamma transgene chronic hepatitis model (Review). 1020 84

Background: Detection of hepatitis C virus (HCV) RNA in serum or plasma is currently the best means of identifying active HCV infection. In this study, we assessed the clinical utility of the HCV Amplicor Monitor (Roche Molecular Diagnostics, Branchburg, NJ) quantitative assay for monitoring viral burden and its implications for identifying responders among alpha-interferon-treated patients with chronic hepatitis C. Methods and Results: Precision and linearity were determined on aliquots of a pooled control serum. Error of the mean was normally distributed. The coefficient of variation of log10-transformed titers was 2%-6% over a range of 1.5 x 10(4)-1.5 x 10(5) copies/mL. Linearity over this range was high (R=.98-.99). Accuracy, as evaluated by comparison of split samples, showed that the Amplicor assay provided an unbiased estimate of the values from a reference laboratory. In a sample of 36 patients treated with alpha-interferon for chronic hepatitis C disease, mean viral titer declined with improvement of disease. The assay demonstrated heterogeneity among clinical responders with regard to their ability to actually clear their viral burden. Conclusions: Decreased viral burden as measured by the HCV Amplicor assay is potentially useful for monitoring individuals with HCV infection.
Mol Diagn 1996 Jun
PMID:Assessing Clinical Utility of Hepatitis C Virus Quantitative RT-PCR Data: Implications for Identification of Responders Among alpha-Interferon-treated Patients. 1033 Feb 6

The interferon-gamma (IFN-gamma) transgenic mouse expresses the IFN-gamma gene strongly in the liver and develops chronic hepatitis from 6-10 weeks of age. Previously we reported the detection of hepatocyte apoptosis and the expression of the Fas system in the transgenic mouse liver. The objective of the present study was to examine the possible development of favorable conditions for predisposing cells to malignancy. The connection between the cell cycle and cancer has become evident, and the relation of cyclin D1 (CD1) with hepatocellular carcinomas has been strengthened. In the liver of transgenic mice of 48 weeks of age, c-myc and CD1 gene expression was induced, indicating progression of the cell cycles. p21 gene expression in the transgenic mouse liver might counteract cell-cycle progression promoted by c-myc and CD1. In the liver of 8-week-old transgenic mice, expression of c-myc mRNA was correlated with the levels of plasma transaminase activities. In these 8-week-old transgenic mice, however, CD1 mRNA was not induced, regardless of the progression of hepatitis. Based on these results, we conclude that long lasting hepatitis may lead to favorable conditions for predisposing cells to malignancy.
Int J Mol Med 1999 Sep
PMID:Long lasting chronic hepatitis is accompanied by cyclin D1 gene expression in the mouse. 1042 76

Background: Accurate quantitation of hepatitis C virus (HCV) RNA in serum may provide a means to predict disease course and response to interferon-alpha therapy. Several quantitative assays are commercially available, but none have been accepted as the gold standard. Methods and Results: The branched DNA quantitative hybridization assay (Quantiplex HCV 1.0, Chiron, Emeryville, CA) and a quantitative reverse transcription polymerase chain reaction (Amplicor HCV MONITOR, Roche Diagnostic Systems, Branchburg, NJ) were compared using a panel of 53 sera from patients with chronic hepatitis C. All sera contained HCV RNA of known genotype. Overall, there was a positive correlation between the results for the 41 sera that gave discrete values in both tests (r =.81, linear regression; P <.01, Kendall's rank test); however, the mean number of HCV copies per milliliter was 13.5-fold higher with Quantiplex (P <.01). A plot of the difference between methods against their means showed poor agreement between the methods. No correlation between the results of the two tests was observed for sera with MONITOR values greater than 5.0 x 10(5) copies/mL. Discrete MONITOR values were obtained for all 12 sera that were below the lower limit of quantitation of Quantiplex (mean, 1.78 x 10(5)). Parallel testing of serial dilutions of two sera showed that each method gave linear responses over the stated dynamic ranges; however, the proportional systematic error was greater with MONITOR. The mean coefficient of variation for replicate determinations was 23% for Quantiplex and 45% for MONITOR (P =.13). Conclusions: Despite a positive correlation, systematic differences exist between the two methods for quantitation of HCV RNA and they cannot be used interchangeably.
Mol Diagn 1997 Mar
PMID:Evaluation of Two Methods for Quantitation of Hepatitis C Virus RNA. 1046 90

4-hydroxy-2,3-alkenals (HAKs) are major end products of oxidative decomposition of omega-3 and omega-6 polyunsaturated fatty acids of membrane phospholipids, a process usually referred to as lipid peroxidation. These reactive aldehydic compounds have been unequivocally detected in vivo in either clinical or experimental conditions of chronic liver damage, suggesting an involvement of lipid peroxidation processes, elicited by either reactive oxygen intermediates (ROI) or by pro-oxidant agents, in the pathogenesis of liver fibrosis. Literature data provided by experimental studies with animal models of liver fibrosis or by studies performed on primary culture of human hepatic stellate cells (hHSC), which are known to play a major role in liver fibrogenesis, indicate that HAKs may sustain at molecular level the fibrogenic development of chronic liver diseases. These compounds may act as ultimate mediators of oxidative stress able to up-regulate the synthesis of extracellular matrix components and of growth factors, chemokines and cytokines, as well as to modulate functional responses of hepatic cell types involved in the progression of chronic liver diseases and to sustain chronic hepatitis.
Int J Mol Med 1999 Oct
PMID:4-hydroxy-2,3-alkenals as molecular mediators of oxidative stress in the pathogenesis of liver fibrosis (review). 1049 86

Hepatic vitronectin expression was assessed in 27 patients with chronic hepatitis C before and after interferon alpha treatment and in 7 control patients. Before interferon therapy, vitronectin was localized in the hepatocytes and in the portal and central venous regions. A high correlation was found for the vitronectin expression level with the histological grading and staging scores in the hepatocytes as well as in the portal region. After interferon therapy, the hepatic vitronectin was significantly decreased in the sustained and transient responders, but it was not as markedly decreased in the nonresponders and the non-treated group. A good correlation was found for the vitronectin expression with the staging scores but not with the grading scores in the portal region. These findings suggest that hepatic vitronectin is influenced by interferon therapy and that it may play an important role as a hepatic adhesion molecule through the improvement of inflammation, necrosis and fibrogenesis.
Res Commun Mol Pathol Pharmacol 1999
PMID:Changes of hepatic vitronectin levels in patients with chronic hepatitis C treated with interferon alpha. 1074 76

We assessed differences in the pattern of HCV RNA decrease for HCV genotypes 1, 2, and 3 during interferon treatment to determine if the lower response rates observed among genotype 1 patients were related to a slower decrease in HCV clearance. Serum HCV RNA values of 472 chronic hepatitis C patients treated with either consensus interferon (CIFN) or interferon alfa-2b (IFN alfa-2b) were evaluated. Neither virological sustained responders nor relapsers differed in the pattern of serum HCV RNA decrease based on genotype. Virological sustained responders infected with genotype 1 cleared HCV RNA as rapidly as sustained responders who were infected with genotype 2 or 3. Relapsers had a slower rate of serum HCV RNA decrease than did virological sustained responders. Nonresponders differed in the pattern of serum HCV RNA decrease based on genotype: HCV genotype 3 patients had the greatest decrease in serum HCV RNA; genotype 2 patients had an intermediate decrease; and genotype 1 patients had the least serum HCV RNA decrease. HCV genotype 1 patients treated with CIFN had a greater decrease in serum HCV RNA during therapy than did patients treated with IFN alfa-2b. However, there was no difference in the magnitude of serum HCV RNA decrease between the two interferon treatments for patients infected with genotype 2 or 3. In summary, both genotype and ultimate response to treatment are determinants of the pattern and rate of serum HCV RNA change during interferon therapy of chronic hepatitis C.
Cytokines Cell Mol Ther 1999 Dec
PMID:Genotype does not affect pattern of HCV RNA decrease among responders during interferon treatment of chronic hepatitis C. Consensus Interferon Study Group. 1085 Mar 85

The interferon-gamma (IFN-gamma) transgenic mouse expresses the exogenous IFN-gamma gene in the liver and develops chronic hepatitis. For the present experiment, four IFN-gamma transgene (+) mice of 48 weeks of age and 16 IFN-gamma transgene (+) mice of 8 weeks of age were used. The four IFN-gamma transgene (+) mice of 48 weeks of age showed significantly elevated plasma alanine aminotransferase (ALT) and expressed the inducible form of nitric oxide synthase (iNOS) mRNA in the liver. Of the 16 IFN-gamma transgene (+) mice of 8 weeks of age, iNOS mRNA was expressed in the livers of three. These three mice exhibited higher plasma ALT levels than the other mice of 8 weeks of age. The present results suggest that iNOS mRNA expression in the liver might be correlated with the progression of hepatitis.
Int J Mol Med 2000 Sep
PMID:Expression of the inducible form of the nitric oxide synthase gene in the livers of mice with chronic hepatitis. 1093 96

Although many drugs have been developed by pharmaceutical companies, there are many diseases which can not be cured with these drugs. In order to overcome this problem, the combination of Western and Eastern medicine has been proposed. Ayurveda is traditional Indian medicine established B.C. and is accepted throughout the world today. Due to its effectiveness and fewer side effects, Ayurveda will provide us with many hints for drug development. In the present review, we discuss the possible application of Ayurveda in drug development taking into account the following two points, i) herbs used in Ayurveda contain many unknown active components, and ii) Ayurveda provides new therapeutic approaches. In the case of drugs for the treatment of chronic hepatitis, we get hints from active components in the herbs used in Ayurveda. For rheumatism, we obtain hints for new pharmacological approaches from this medicinal approach.
Int J Mol Med 2000 Dec
PMID:Drug development with hints from traditional Indian Ayurveda medicine: hepatitis and rheumatoid as an example. 1107 18

Granulocytopenia is commonly observed in interferon-alpha (IFN-alpha) therapy. Granulocyte colony-stimulating factor (G-CSF) has been identified as a primary cytokine that regulates neutrophil production, but the kinetics of G-CSF in IFN-alpha-induced granulocytopenia remains unclear. We investigated the effects of IFN-alpha on serum G-CSF levels and peripheral neutrophil counts (NC) in 15 chronic hepatitis C patients treated with standard-dose (10 MU) recombinant IFN-alpha for 24 weeks by using a chemiluminescent enzyme immunoassay for G-CSF. The time course of change after a single IFN-alpha injection showed that mean serum G-CSF levels and NC increased significantly compared with pretreatment values (p < 0.05), and were statistically correlated (r = 0.914, p = 0.0015). On repeating IFN-alpha administration, this change gradually became unclear, and granulocytopenia occurred, accompanied by a significant increase in serum G-CSF (p < 0.01). Both values reached a plateau within 2 weeks after starting treatment, and recovered rapidly after the cessation of therapy. Although continuous administration of IFN-alpha caused a time-dependent granulocytopenia, our results suggest that a single injection of IFN-alpha would be a potent inducer of G-CSF and NC in vivo as a short-term effect and that there would be negative-feedback regulation between them during long-term IFN-alpha therapy.
Cytokines Cell Mol Ther 2000 Sep
PMID:Effects of interferon-alpha on peripheral neutrophil counts and serum granulocyte colony-stimulating factor levels in chronic hepatitis C patients. 1114 Aug 84


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