Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antithrombin III is of potential value for replacement therapy in patients with acquired or congenital deficiencies. Pasteurization of the purified inhibitor for 10 h at 60 degrees C can reduce the risk of transfusion hepatitis. Addition of appropriate stabilizers can largely prevent the loss of antithrombin activity which otherwise occurs during pasteurization. Studies of the mechanism of denaturation and stabilization have been facilitated by the use of 8-anilino-1-naphthalene sulfonate which binds weakly to the inhibitor and whose fluorescence undergoes a sigmoidal response to increasing temperature. The extent of the increase in 8-anilino-1-naphthalene sulfonate fluorescence correlates roughly with the loss of antithrombin activity and with the extent of protein aggregation as determined by high pressure liquid chromatography. The midpoint, Td, of the thermal denaturation curve increases by 13 degrees C and 19 degrees C in the presence of 0.5 M and 1.0 M sodium citrate, respectively. Phosphate, sulfate, and EDTA are also strong stabilizers while the chaotropic anions, iodide and thiocyanate are potent destabilizers. Heparin at 10 mg/ml increases Td by 7 degrees C, presumably through a direct binding mechanism; chondroitin sulfate and hyaluronic acid have no effect. Samples pasteurized for 10 h at 60 degrees C in the presence of 0.5 M and 1.0 M citrate retain essentially full activity but exhibit evidence of minor alterations in their interaction with heparin.
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PMID:Thermal denaturation of antithrombin III. Stabilization by heparin and lyotropic anions. 729 49

We report here the nonenzymatic self-ligation of transcripts corresponding to the peach latent mosaic viroid (PLMVd). This is the first description of this process with viroid sequences, although it has been reported to occur with human hepatitis delta virus RNA. Self-ligation occurs when the 5'-hydroxyl and the 2',3'-cyclic phosphate termini produced by the hammerhead self-cleavage of the viroid RNA are juxtaposed by the viroid rod-like structure, and a phosphodiester bond is formed between the two following hydrolysis of the cyclic phosphate. Unit-length transcripts undergo intramolecular folding, and their subsequent self-ligation produces circular molecules. The self-ligation observed in vitro may contribute to PLMVd circularization during rolling circle replication; however, this does not exclude the possibility that a host RNA ligase catalyzes the ligation steps in vivo. Like self-cleavage, self-ligation is probably an ancestral reaction, and the enzyme-catalyzed ligation most likely evolved from this primitive mechanism. Furthermore, the intermolecular self-ligation of annealed transcripts derived from PLMVd is demonstrated, suggesting a possible mechanism for sequence reassortment in viroids.
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PMID:Intra- and intermolecular nonenzymatic ligations occur within transcripts derived from the peach latent mosaic viroid. 757 40

Although the hepatitis delta virus genome contains multiple open reading frames, only one of these reading frames is known to be expressed during replication of the virus. This open reading frame encodes two distinct molecular species of hepatitis delta antigen (HDAg), p24 delta and p27 delta, depending on the location of the stop codon which terminates translation. We found antibody specific for p27 delta to be capable of precipitating p24 delta in extracts of infected liver, indicating that p27 delta and p24 delta form heterologous complexes in vivo. After cross-linking with 0.05% glutaraldehyde, specific HDAg dimers were detected in antigen prepared from both the liver and serum of an HDV-infected woodchuck carrier of woodchuck hepatitis virus. Guanidine HCl-denatured HDAg extracted from liver and dialyzed against phosphate-buffered saline sedimented in rate-zonal sucrose density gradients as 15S multimeric complexes. These 15S multimers were stable in the presence of 1.2% Nonidet P-40. After RNase digestion, the 15S complex was reduced to a 12S complex without associated RNA, while boiling for 3 min in 1% sodium dodecyl sulfate-0.5% 2-mercaptoethanol further reduced the 15S complex to 3S HDAg monomers. In the absence of glutaraldehyde cross-linking, HDAg extracted from liver migrated as monomer species in reducing and nonreducing gels, suggesting that the conserved cysteine residue present in p27 delta does not play a role in the formation of either dimers or multimers. On the other hand, an amino-terminal chymotrypsin-digested HDAg fragment, with a predicted length of 81 or less amino acids, retained the ability to form dimers, consistent with the hypothesis that a coiled-coil motif present between residues 27 and 58 may play a role in HDAg protein interactions in vivo.
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PMID:Hepatitis delta virus antigen forms dimers and multimeric complexes in vivo. 767 57

Manganese (II) N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'-bis(phosphate) (DPDP) is a paramagnetic magnetic resonance (MR) contrast agent that enhances the liver and is predominantly excreted through the biliary tree. The authors evaluated its utility in diffuse liver disease by assessing liver and gallbladder enhancement in 24 rabbits. Total (n = 6) or segmental (n = 6) biliary occlusion or galactosamine-induced hepatitis (n = 6) was induced 3 days before imaging. Six rabbits served as normal controls. T1- and T2-weighted axial MR images were acquired at baseline, followed by T1-weighted images every 10 minutes for 1 hour after the intravenous administration of 20 mumol/kg Mn-DPDP. Except for the segmental occlusion group, the baseline study did not allow distinction between normal and abnormal livers. The temporal hepatic enhancement pattern was statistically different for each group. The normal, segmental occlusion, and hepatitis groups showed patterns similar to one another but markedly higher signal intensity than the total-occlusion group throughout the observation period. In contrast, the gallbladder showed a greater difference in both degree of enhancement and time to peak enhancement among the four groups. Mn-DPDP produces a temporal hepatic enhancement pattern that allows recognition of markedly impaired livers, and gallbladder enhancement patterns that allow distinction of more subtly impaired livers.
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PMID:MR imaging assessment of experimental hepatic dysfunction with Mn-DPDP. 769

The mannose 6-phosphate/insulin-like growth factor II receptor (M6P/IGFIIr) is required for the activation of transforming growth factor beta, and previously we have found its expression to be significantly reduced in both rat and human hepatocellular carcinomas (HCCs). Therefore, we have postulated that loss of the M6P/IGFIIr gene may be mechanistically involved in liver carcinogenesis. Using the polymerase chain reaction, we utilized two polymorphisms in the 3' untranslated region of the M6P/IGFIIr gene to screen non-cirrhotic, hepatitis virus negative patients with hepatocellular tumors for LOH. Twenty-two of 36 (61%) patients were informative (heterozygous), and 14/22 (64%) liver tumors had LOH; 11/16 (69%) carcinomas, 1/3 (33%) fibrolamellar tumors and 2/3 (67%) adenomas. This is the first report of LOH at the M6P/IGFIIr locus in human hepatocellular tumors, and the presence of LOH in adenomas suggests that allelic loss may be an early event in the etiology of HCCs. These results support the hypothesis that the M6P/IGFIIr gene may function as a tumor suppressor gene in the liver.
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PMID:Frequent loss of heterozygosity on 6q at the mannose 6-phosphate/insulin-like growth factor II receptor locus in human hepatocellular tumors. 775 49

Neurospora VS RNA performs an RNA-mediated self-cleavage reaction whose products contain 2',3'-cyclic phosphate and 5'-hydroxyl termini. This reaction is similar to those of hammerhead, hairpin, and hepatitis delta virus ribozymes; however, VS RNA is not similar in sequence to these other self-cleaving motifs. Here we propose a model for the secondary structure of the self-cleaving region of VS RNA, supported by site-directed mutagenesis and chemical modification structure probing data. The secondary structure of VS RNA is distinct from those of the other naturally occurring RNA self-cleaving domains. In addition to a unique secondary structure, several Mg-dependent interactions occur during the folding of VS RNA into its active tertiary conformation.
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PMID:A secondary-structure model for the self-cleaving region of Neurospora VS RNA. 775 65

A phosphorothioate substitution interference assay was used to investigate the role of the pro-Rp oxygens of phosphate groups in the self-cleavage reaction of the genomic human hepatitis delta virus (HDV) ribozyme. Incorporation of several different phosphorothioates (NTP alpha S) into the HDV ribozyme inhibited the self-cleavage activity. Incorporation of uridine 5' phosphorothioate or adenosine 5' phosphorothioate maintained 72% of the original self-cleavage activity whereas incorporation of guanosine 5' phosphorothioate or cytosine 5' phosphorothioate into the precursor reduced self-cleavage activity to about 20% in each case. Using partially substituted phosphorothioate-modified transcripts, we identified the pro-Rp oxygens that are important for the ribozyme activity, and they are located at positions 0, 1, 4, 5, 21, 24, 25, 27, 28, 30-34, 40, 43 and 75. In particular, the pro-Rp oxygens at positions 0, 1 and 21 are appear to be critical for the self-cleavage activity of the HDV ribozyme.
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PMID:Identification of phosphate oxygens that are important for self-cleavage activity of the HDV ribozyme by phosphorothioate substitution interference analysis. 793 83

Two different virus inactivated plasma preparations are available in Germany. Methylene blue ephotoxidized (MB) plasma is plasma from a single donation, which is photoxidized using 1 microM methylene blue and visible light (1 hour 60,000 Lux). Photochemical inactivation reduces HIV by at least 5 log10, but also fibrinogen is altered. To date, the clinical significance of this finding is still unclear, since prospective clinical studies are lacking. Solvent detergent (SD) plasma is manufactured from a pool of about 2000 plasma donations, and triton-X-100 and tri-n-butyl-phosphate (TNBP) are added for virus inactivation. HIV and hepatitis viruses are thus reduced by 5 to 6 log10. SD treatment reduces protein S and alpha-2-antiplasmin by about 40%. Clinical studies have already demonstrated, that SD plasma is comparable with untreated, native fresh frozen plasma in terms of efficacy.
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PMID:[Virus inactivated plasma]. 800 Feb 59

The effect of Gomisi (dried ripe fruit of schizandra chinensis) on chlorodifluoroethylene (CDE) and chlorotrifluoroethane (CTE) formation was investigated. The incubation mixtures for the measurement of reductive metabolites of halothane consisted of liver microsomal suspensions, 3 mM NADPH, extract solution of Gomisi and halothane in 0.1 M potassium phosphate buffer (pH 7.4). The production of CDE and CTE was inhibited by Gomisi in a dose-dependent way. The production were reduced to half in the presence of 0.5% Gomisi extract in the reaction mixture. The results suggest that Gomisi can inhibit the reductive metabolism of halothane in vitro; thus it may protect against halothane-induced hepatitis.
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PMID:Inhibitory effect of gomisi on reductive metabolism of halothane. 828 41

The main objective of this study was to determine the applicability of the polymerase chain reaction (PCR) to detection of hepatitis E virus (HEV) in sewage treatment plants and establishment of the prevalence of hepatitis viral diseases in a population. Epidemics of HEV infection because of inadequate public sanitation have been reported in several developing countries. A procedure for concentration of HEV in sewage samples through adsorption to membrane filters, elution with urea-arginine phosphate buffer, and subsequent reconcentration with magnesium chloride enabled us to concentrate HEV to volumes in the microliter range. HEV-specific cDNA was prepared by reverse transcription of the total RNA extracted from samples. Specific DNA amplification by PCR in combination with slot blot hybridization was used to demonstrate the presence of HEV in sewage samples from the inlets and outlets of three sewage treatment plants. The assay was specific for HEV, and a 240-bp amplified product was visualized by ethidium bromide fluorescence. Sewage samples adjusted to pH 5.0 for adsorption of viruses to membrane filters were PCR positive, while samples adjusted to pH 3.5 were PCR negative.
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PMID:Detection of hepatitis E virus in raw and treated wastewater with the polymerase chain reaction. 836 44


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