Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A large percentage of patients with advanced-stage hepatocellular carcinoma (HCC) have a recurrence of tumor in the liver or lung after primary resection and even after orthotopic liver transplantation. One reason for this may be the presence of small numbers of tumor cells circulating in the blood before surgery or the liberation of tumor cells into circulation during surgical manipulation. We tested this hypothesis by measuring messenger RNA (mRNA) for human albumin gene as a liver cell marker with the highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR) technique. Albumin mRNA was not found in peripheral blood from normal humans (0 of 6), from patients with liver cirrhosis (0 of 10), from other tumors metastatic to liver (0 of 10), or during liver transplant surgery for cirrhosis (0 of 10). In patients with advanced-stage HCC (TNM stages III and IV), albumin mRNA was detected (16 of 17) in peripheral blood. After liver transplantation in the HCC patients, the level of mRNA decreased below the detectable limit (0 of 9). Three of these patients again had detectable mRNA levels when they had recurrence of HCC after liver transplantation. Patients with stage I HCC did not have detectable expression. These results suggest that circulating tumor cells are present in patients with advanced-stage HCC, which may be one of the reasons why these patients have a high incidence of tumor recurrence after apparently definitive surgical resection and even after liver transplantation.
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PMID:Detection of liver cells in peripheral blood of patients with advanced-stage hepatocellular carcinoma. 784 13

Hepatocytes of F344 rat were transplanted into the liver of congenic analbuminemic rats by infusion into the mesenteric vein from once to four times at one-week intervals. The transplantability was confirmed by the increase in the number of albumin-positive cells and appearance of normal albumin mRNA within the recipient liver, and the elevated serum albumin level. When the normal albumin mRNA was quantitated by reverse transcriptase polymerase chain reaction (RT-PCR) using the abnormally spliced albumin mRNA of analbuminemic rats as an internal standard, the increase in normal mRNA was in good agreement with the serum albumin level and the number of albumin positive hepatocytes within the liver. These three markers proportionally increased with the number of infusion times. Our results demonstrate that the number of intrahepatically transplanted hepatocytes is able to be increased by repeated infusion.
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PMID:Increase in albumin mRNA by repeated intrahepatic transplantation of F344 rat hepatocytes into the liver of congenic analbuminemic rats. 834 47

SC-52151 is a potent, selective, tight-binding human immunodeficiency virus (HIV) protease inhibitor containing the novel (R)-(hydroxyethyl) urea isostere. The mean 50% effective concentration for lymphotropic, monocytotropic strains and field isolates of HIV type 1 (HIV-1), HIV-2, and simian immunodeficiency virus is 26 ng/ml (43 nM). The combination of SC-52151 and nucleoside reverse transcriptase inhibitors synergistically inhibited HIV-1 replication without additive toxicity. An extended postantiviral effect correlates with inhibition of gag and gag-pol polyprotein processing. SC-52151 is highly protein bound ( >90%) in human plasma, and the level of partitioning into erythrocytes is low. Physiological concentrations of alpha-1-acid glycoprotein, but not albumin, substantially affect the antiviral potency of SC-52151. The oral bioavailability of [14C]SC-52151 is 17% when it is administered as an elixir to the rat, dog, or monkey. Oxidation of the t-butyl moiety is the major route of biotransformation, and elimination is mainly by biliary excretion. No toxicologically significant effects have been observed in animals. Pharmacokinetic and metabolism studies in multiple animal species predict 20 to 30% systemic bioavailability, an elimination half-life of 1 to 2 h, and a volume of distribution of greater than 3 liters/kg in humans.
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PMID:SC-52151, a novel inhibitor of the human immunodeficiency virus protease. 861 73

The tumor suppresser p53 is a cell cycle checkpoint protein that contributes to the preservation of genetic stability by mediating either a G1 arrest or apoptosis in response to DNA damage. p53 causes growth arrest through transcriptional activation of the cyclin-dependent kinase inhibitor p21. During p53-mediated suppression of cell proliferation, p21 is important for coordinating cell cycle progression, DNA replication, and repair of damaged DNA. The purpose of this study is to investigate the expression of p53 and p21 mRNA in association with DNA damage and normal repair in acute immune complex alveolitis in mice. Male ICR mice were injected intravenously with IgG antibodies against oval albumin, aerosolized with oval albumin solution, and killed at 4, 6, 12, 24, and 48 hours and 1 week after aerosolization. We assessed the expression of p53 and p21 mRNA by reverse transcriptase (RT)-PCR and by RT in situ PCR. We also assessed DNA damage by terminal deoxynucleotidyl transferase mediated biotin-dUTP nick-end-labeling (TUNEL) and by gel electrophoresis of DNA extracted from lung tissues. The results of RT-PCR and RT in situ PCR showed that p53 and p21 mRNA were concurrently up-regulated at 4 to 48 hours after aerosolization in alveolar epithelial cells. Bronchial and alveolar epithelial cells were positively stained by TUNEL in this period but not at 1 week after aerosolization or in control mice. The result of electrophoretic analysis of DNA was compatible with that of TUNEL. These studies suggest that the responses of p53 and p21 mRNA are associated with physiologic processes of DNA damage and repair in acute immune complex alveolitis in mice.
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PMID:P53 and p21 (Waf1/Cip1) mRNA expression associated with DNA damage and repair in acute immune complex alveolitis in mice. 904 52

Although hepatitis C virus (HCV) is a leading cause of morbidity and mortality worldwide, the role of viral cytopathic effects remains unclear. To study the biosynthesis of HCV structural proteins and their pathogenic role, we constructed transgenic mice, expressing type 1b HCV structural proteins (core, E1, and E2) in liver tissues. Two liver-specific promoters were used. The mouse major urinary protein (MUP) promoter has been shown to be developmentally regulated with little or no expression in utero but high-level expression after birth. The albumin (Alb) promoter provides constitutive, high levels of transgenes in live. Expression of both HCV transgenes was detected in several lines by Northern blots, HCV-specific reverse transcriptase-polymerase chain reactions (RT-PCR), and Western immunoblotting. Alb HCV lines showed higher levels of HCV expression than the MUP HCV lines. Immunohistochemical analysis revealed a predominantly cytoplasmic presence of core protein with occasional nuclear staining, and both cytoplasmic and membrane expression of the E2 protein in the transgenic livers. In both transgenes, the highest levels of both antigens were seen in perivenular hepatocytes, suggesting potential processing specificity in those cells. At six months of age, the livers of all transgenic lineages remained histologically normal. We concluded that HCV structural proteins are not directly cytopathic in this animal model.
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PMID:Transgenic expression of hepatitis C virus structural proteins in the mouse. 909 13

Hepatocellular carcinoma (HCC) is one of the most common and rapidly fatal malignancies worldwide. Treatment options are severely limited by the frequent presence of metastases. If hepatocyte-specific mRNAs are detected in the circulation, it is possible to infer the presence of circulating, presumably malignant, liver cells. If these can be quantified, it is possible to predict the likelihood of haematogenous metastasis. In this investigation, we have attempted to gain an index of the mass of circulating HCC cells (with reference to the number of hepatoblastoma cells) by measuring the amounts of PCR products for albumin (alb) mRNA and alpha-fetoprotein (afp) mRNA by reverse transcriptase polymerase chain reaction (RT-PCR) and Southern blot analysis. For calibration, total RNA from 1-10(6) HepG2 cells was mixed with total RNA from 10(6) normal peripheral mononuclear cells. A linear relationship was demonstrated between the amount of alb- or afp PCR product and the level of HepG2 total RNA spiked. The assay is sensitive down to a detection level of one HepG2 cell. Alb mRNA was detected in 50% of 18 normal subjects and afp mRNA in only two normal subjects. The alb mRNA cut-off level for the normal was exceeded by seven normal subjects and 34 out of 64 HCC patients, and that for afp mRNA was exceeded by six HCC patients but none of the normal subjects. The level of alb mRNA detected was not linearly proportional to the amount of afp mRNA detected in peripheral blood of the same patients, suggesting heterogeneous expression of alb and afp genes in different circulating tumour cells. In addition, no significant linear association between the levels of afp mRNA and serum AFP was observed. Semiquantification of both mRNA markers for HCC cell detection may prove useful in prediction of metastases.
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PMID:Semiquantification of circulating hepatocellular carcinoma cells by reverse transcriptase polymerase chain reaction. 930 62

Deoxyribonucleic acid (DNA) strand breaks as a characteristic of apoptosis, and Fas antigen (Fas)/Fas ligand (FasL) expression may participate in acute immune complex alveolitis in mice. Male Institute for Cancer Research (ICR) mice were injected intravenously with immunoglobulin G (IgG) antibodies against ovalbumin and inhaled an aerosolized oval albumin (OA) solution. They were killed at 4, 6, 12, 24, 48 h and 7 days after aerosolization. We assessed DNA fragmentation by agarose gel electrophoresis and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labelling (TUNEL). The expression of Fas and FasL messenger ribonucleic acid (mRNA) in lung tissues was assessed by reverse transcriptase (RT) polymerase chain reaction, and by in situ hybridization (ISH) to localize Fas mRNA, and RT in situ polymerase chain reaction to localize FasL mRNA. The fragmentation of DNA extracted from lung tissue was found 6-24 h after OA inhalation. TUNEL detected positive signals in bronchial and alveolar epithelial, endothelial and inflammatory cells in the lung tissue. These positive signals had disappeared 7 days after OA inhalation. TUNEL also detected positive signals in apoptotic neutrophils in bronchoalveolar lavage fluid at 6-12 h. Fas mRNA was expressed in the alveolar epithelial and inflammatory cells, while the expression of FasL mRNA appeared to be upregulated in infiltrating inflammatory cells at 6-24 h. These results suggest that apoptosis may be associated with the resolution of inflammation and with tissue repair and also suggest the involvement of the Fas antigen/Fas ligand pathway in acute immune complex alveolitis in mice.
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PMID:Apoptosis and Fas/Fas ligand mRNA expression in acute immune complex alveolitis in mice. 938 64

Synthesis of a number of rat liver proteins, including albumin, fibrinogen, apolipoprotein AI, and transferrin, is elevated in the nephrotic syndrome (NS). Increased synthesis of these proteins is regulated at the transcriptional level and occurs in the context of increased mRNA encoding each protein. Changes in albumin, fibrinogen, apolipoprotein AI, and transferrin mRNA levels in total cellular RNA isolated from the livers of normal rats and rats with passive Heymann nephritis were measured using a kinetically monitored, reverse transcriptase-initiated PCR (kRT-PCR) assay. The kRT-PCR assay rapidly quantitated changes in rat liver mRNA levels with an accuracy comparable to that of more labor-intensive mRNA quantitation methods. The relative levels of beta-actin, apolipoprotein AI, fibrinogen, and albumin mRNAs were very similar in total cellular RNA isolated from rat liver versus H4C3 hepatocytes in culture, suggesting that the H4C3 hepatocyte is an appropriate model for studying expression of genes encoding proteins secreted by the liver. Taken together, the results demonstrate the feasibility of using the kRT-PCR assay for isolation and characterization of a soluble factor responsible for elevated synthesis of hepatocyte mRNAs associated with the nephrotic syndrome.
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PMID:Rat liver transcript profiling in normal and disease states using a kinetic polymerase chain reaction assay. 948 Jul 87

The use of combinations of anti-human immunodeficiency virus (anti-HIV) agents targeted to different molecular targets will most likely result in increased viral suppression and may also delay or prevent the emergence of resistant HIV strains. The purpose of the present study was to develop information on the in vitro anti-HIV activities of combinations of the reverse transcriptase inhibitor 1592U89 and the protease inhibitor 141W94 to help guide the choice of dosages in clinical trials. Triplicate in vitro dose-response matrices were prepared with MT-2 cells infected with HIV type 1 (HIV-1) strain IIIB. In order to account for the effects of protein binding, tissue culture medium with 10% fetal bovine serum was supplemented with the human serum proteins alpha1 acid glycoprotein (1 mg/ml) and albumin (40 mg/ml). The three-dimensional drug interaction surface for 1592U89 and 141W94 was constructed with the program MacSynergy II. As analyzed relative to a Bliss Independence null reference model, this combination was synergistic, with volumes of synergy exceeding 100 (99% confidence). Analysis of the data set with a fully parametric form of an equation for the quantitation of drug interaction developed by Greco et al. (W. R. Greco, G. Bravo, and J. C. Parsons, Pharmacol. Rev. 47:331-385, 1995) resulted in an interaction term statistically significantly greater than 0.0, indicating true synergy. Both methods concur that this combination is significantly synergistic. These data, with favorable findings from phase I/II trials for each drug alone, suggest that the combination of 1592U89 plus 141W94 should be further evaluated in clinical trials.
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PMID:Nucleoside analog 1592U89 and human immunodeficiency virus protease inhibitor 141W94 are synergistic in vitro. 973 27

Advanced glycation end products (AGEs) have been identified as relevant mediators of late diabetic complications such as atherosclerotic disease. The endothelial migration of monocytes is one of the first steps in atherogenesis and monocyte-endothelial interaction itself is linked to the expression of adhesion molecules like vascular cell adhesion molecule-1 (VCAM-1). Recently, stimulation of VCAM-1 by AGEs has been demonstrated. Since endothelial stimulation by AGEs is followed by generation of oxygen free radicals with subsequent activation of nuclear transcription factor kappaB, we investigated the influence of alpha-lipoic acid on the expression of VCAM-1 and monocyte adherence to endothelial cells in vitro by means of cell-associated chemiluminescence assays and quantitative reverse transcriptase polymerase chain reaction using a constructed recombinant RNA standard. We found that alpha-lipoic acid was able to decrease the number of VCAM-1 transcripts from 41. 0+/-11.2 to 9.5+/-4.7 RNA copies per cell in AGE-stimulated cell cultures. Furthermore, expression of VCAM-1 was suppressed in a time- and dose-dependent manner by alpha-lipoic acid as shown by chemiluminescence endothelial cell assay. Pretreatment of endothelial cells with 0.5 mM or 5 mM alpha-lipoic acid reduced AGE-induced endothelial binding of monocytes from 22.5+/-2.9% to 18. 3+/-1.9% and 13.8+/-1.8% respectively. Thus, we suggest that extracellularly administered alpha-lipoic acid reduces AGE-albumin-induced endothelial expression of VCAM-1 and monocyte binding to endothelium in vitro. These in vitro results may contribute to the understanding of a potential antioxidative treatment of atherosclerosis.
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PMID:Alpha-lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. 985 9


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