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)

Copper (Cu), iron (Fe), zinc (Zn) and manganese (Mn) levels in organs of LEC rats (Long-Evans rats with a cinnamon-like coat color), which develop spontaneous jaundice with hereditary hepatitis, were determined by instrumental neutron activation analysis method. Unusual accumulations of Cu in the liver of LEC rats were found, depending on the age of the animals, the metal concentration being more than approximately 20-40 times those of normal LEA rats (Long-Evans rats with an agouti coat color). Fe and Zn were also accumulated, in addition to Cu, significantly in the LEC rats. The unusual Cu accumulations in the liver of LEC rats were associated with the induction of metallothionein, estimated by radioimmunoassay method, in the liver of LEC rats, rather than that of superoxide dismutase, estimated by electron spin resonance -spin trapping method. These findings suggest that the unusual Cu accumulation in LEC rats is involved in the development of jaundice, hepatic injury and hepatocellular carcinoma.
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PMID:Unusual accumulation of copper related to induction of metallothionein in the liver of LEC rats. 131 72

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

Long-Evans Cinnamon (LEC) rats are characterized by the sudden onset of hepatitis around 4 months after birth and the gross accumulation of hepatic copper (Cu) accompanied by metallothionein (MT). The biliary excretion of manganese (Mn) and cadmium (Cd) injected intravenously was studied in 3-month-old LEC rats without signs of hepatitis. Injected Mn was excreted into the bile in LEC and Fischer rats used for comparison. However, increased biliary excretion of Cd was found not in the LEC rat but in the Fischer rat. Excretion of horseradish peroxidase (HRP) injected along with the metal mixture was significantly lower in the LEC group than in the Fischer group. Our results suggest that Mn excretion is not related to the existence of a gross amount of Cu-MT. Reduced excretion of Cd may be partly due to binding to Cu-MT in the liver. Decreased excretion of HRP implies the existence of an inherent defect in the bile excretion route for endo- and exogenous substances.
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PMID:Biliary excretion of exogenous cadmium and manganese in Long-Evans Cinnamon (LEC) rats characterized by an inherently gross amount of copper-metallothionein in the liver. 780 94

9 cases (males) of primary sclerosing cholangitis (PSC) were studied clinico-morphologically. In puncture liver biopsies, sclerosis of walls of big ducts and portal tracts was found in 2 cases only; cell infiltration was minimal. Lobular hepatitis with intralobular fibrosis and moderate sclerosis of portal stroma was found in 3 patients, monolobular inactive liver cirrhosis in 4 patients. In all cases mild intralobular cholestasis was found which was followed with a considerable increase of copper and manganese in the liver and serum. The accumulation of a large amount of collagen of different types was observed around bile ducts which ultrastructurally was seen as fibrillar structures and homogeneous substance similar to the basal membrane. The elements of the epithelium destruction were found in foci of the duct basal membrane alteration, in the absence of cell infiltration. Progressing fibrosis of both portal tracts without inflammation and individual segments of the bile ducts and the intralobular stroma is at the basis of PSC.
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PMID:[Morphological changes in the liver in primary sclerosing cholangitis (a histological and electron microscopic study)]. 794 63

To identify the divalent metal ions that can support the self-cleavage activity of the genomic ribozyme of human hepatitis delta virus (HDV), we tested the activity of various divalent metal ions in the ribozyme reactions catalyzed by HDV88 (683-770 nt) and 88DI3 (HDV88 with the sequence from 740-752 nt deleted). Among various metal ions tested, Mg2+, Mn2+, Ca2+ and Sr2+ efficiently supported the self-cleavage reactions of the HDV88 and 88DI3 ribozymes. In the case of the 88DI3 ribozyme, other divalent metal ions, such as Cd2+, Ba2+, Co2+, Pb2+ and Zn2+, were also able to support the self-cleavage reaction to some extent (< 10%). In the presence of spermidine (0.5 mM), the cleavage reaction was promoted at lower concentrations of effective divalent metal ions. The HDV ribozyme represents the only example of ribozyme to date of a ribozyme that catalyzes the self-cleavage reaction in the presence of Ca2+ ions as efficiently as it does in the presence of Mg2+ ions.
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PMID:Self-cleavage activity of the genomic HDV ribozyme in the presence of various divalent metal ions. 834 2

The hepatocyte-specific paramagnetic magnetic resonance (MR) contrast agents manganese-DPDP [N,N'-dipyridoxylethylenediamine-N,N'-diacetate 5,5'bis-(phosphate)] and gadobenate dimeglumine were used for diagnosing chemically induced hepatitis in rats. Ex vivo liver tissue relaxation times and in vivo MR image signal-to-noise ratios were compared before and after contrast agent administration. Ex vivo relaxometry and in vivo MR imaging showed that Mn-DPDP enhanced normal and diseased livers to the same degree at all time points from 5 to 120 minutes. Gadobenate dimeglumine showed reduced T1 and T2 enhancements in hepatitis relative to those of normal liver, in the early phase (5-30 minutes). However, these effects are offsetting, and as a result, MR imaging failed to allow distinction of diseased from normal livers. This surprising result observed in vivo was in fact predicted by applying the Bloch equation to our ex vivo data. Our results show that detection and quantitation of hepatitis with MR imaging enhanced with paramagnetic cell-specific contrast agents will be more difficult than anticipated.
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PMID:Evaluation of hepatocyte-specific paramagnetic contrast media for MR imaging of hepatitis. 840 May 66

Properties of a hepatitis delta virus (HDV) RNA ribozyme system, which consists of three RNA oligomer strands (substrate 8-mer; enzyme 16-mer plus 35-mer) and contains a hybrid sequence of genomic and antigenomic RNA cores, are reported. Effects of Mg2+ concentration, divalent metal ion species, pH, and temperature on the cleavage activity were examined. The substrate cleavage activity increased with increasing Mg2+ concentration (0-100 mM). Ca2+ and Mn2+ ions were the most effective divalent cations and Mg2+ was less effective. The cleavage activity increased with increasing pH (5-7.5). The optimum temperature for the cleavage activity was 25-40 degrees C. The Mg2+ concentration, pH and temperature dependencies are different from those reported for the single-strand ribozymes (about 90-mer) although the divalent metal ion preference is very similar. Conformational change induced by Mg2+ ion titration was monitored by CD. The CD data and the activity-Mg2+ concentration data were analyzed by curve-fitting analysis using equations derived for multiple metal ion binding mechanisms. The data can be explained by a model in which three Mg2+ ions bind to one ribozyme unit.
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PMID:Properties of hepatitis delta virus ribozyme, which consists of three RNA oligomer strands. 935 86

The natural substrate cleaved by the hepatitis delta virus (HDV) ribozyme contains a 3',5'-phosphodiester linkage at the cleavage site; however, a 2',5'-linked ribose-phosphate backbone can also be cleaved by both trans-acting and self-cleaving forms of the HDV ribozyme. With substrates containing either linkage, the HDV ribozyme generated 2',3'-cyclic phosphate and 5'-hydroxyl groups suggesting that the mechanisms of cleavage in both cases were by a nucleophilic attack on the phosphorus center by the adjacent hydroxyl group. Divalent metal ion was required for cleavage of either linkage. However, although the 3',5'-linkage was cleaved slightly faster in Ca2+ than in Mg2+, the 2',5'-linkage was cleaved in Mg2+ (or Mn2+) but not Ca2+. This dramatic difference in metal-ion specificity is strongly suggestive of a crucial metal-ion interaction at the active site. In contrast to the HDV ribozymes, cleavage at a 2',5'-phosphodiester bond was not efficiently catalyzed by the hammerhead ribozyme. The relaxed linkage specificity of the HDV ribozymes may be due in part to lack of a rigid binding site for sequences 5' to the cleavage site.
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PMID:Ribozyme cleavage of a 2,5-phosphodiester linkage: mechanism and a restricted divalent metal-ion requirement. 1049 15

A new DNA enzyme, the "Bipartite DNAzyme", suitable for the sequence-specific cleavage of RNA, was obtained from a random DNA library by in vitro selection. Only a single family of catalytic molecules emerged from the selection, and a 22 nucleotide consensus sequence common to all clones defined a putative catalytic core. The most abundant clone self-cleaved at a single internal ribonucleotide phosphodiester with a relatively fast k(obs) value of 1.7 min(-1), in 10 mM MgCl(2) at 23 degrees C. This DNAzyme ("Bipartite I") required divalent cations, with magnesium and manganese most optimally supporting cleavage. A reselection from a mutagenized DNAzyme pool for the ability to cleave at extended RNA substrates yielded an unchanged catalytic core sequence. From this re-selection a DNAzyme ("Bipartite II") capable of sequence-specifically cleaving extended stretches of RNA was derived. A rate versus pH analysis of the Bipartite II DNAzyme revealed a two-phase profile, similar to that reported for the hepatitis delta virus (HDV) ribozyme, suggesting that the Bipartite II DNAzyme and the HDV ribozyme may share similar catalytic strategies. Multiple-turnover kinetics, measured in 30 mM MgCl(2), at 37 degrees C, with an HIV-1-derived RNA substrate, yielded a k(cat) value of approximately 1.4 min(-1) and a K(M) value of approximately 230 nM, which were of the same order as k(cat) and K(M )values measured for other ribozymes and DNAzymes in general use for RNA cleavage. The Bipartite DNAzyme therefore represents a new and potentially useful reagent, both for the processing of RNA transcripts in vitro and for mRNA ablation procedures in vivo.
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PMID:A new and efficient DNA enzyme for the sequence-specific cleavage of RNA. 1180 May 57

The performance of hepatocyte-targeted magnetic resonance (MR) contrast agents in the detection of liver tumor was tested in rats with hepatitis. Hepatocyte-targeted MR contrast agents (paramagnetic hepatobiliary complex [manganese-DPDP] and superparamagnetic iron oxide coated with arabinogalactan [SPIO-AG]) were injected into normal rats and rats with carbon tetrachloride-induced hepatitis. Before and after injection of either contrast agent, ex vivo relaxometry (0.94T) or in vivo MR imaging (1.0T) were performed. The obtained liver and tumor T1 and T2 relaxation times, liver and tumor signal-to-noise ratios (SNR), and tumor-liver contrast-to-noise ratios (CNR) of control rats and rats with hepatitis were compared. Both relaxometry and MR imaging showed that MnDPDP and SPIO-AG selectively enhanced liver tissue in controls and in rats with hepatitis to the same degree, and little tumor enhancement was seen in either group. As a result, no significant difference between control rats and rats with hepatitis was observed in the postcontrast tumor-liver CNR. For a MnDPDP-enhanced CNR with spin echo (SE) of 310/15, the results were -10.4+/-3.6 in control rats vs. -11.5+/-1.4 in rats with hepatitis; for a SPIO-AG-enhanced CNR with SE 2000/45 and 2000/90, respectively, the results were 30.7+/-9.2 and 18.7+/-4.7 in control rats vs. 31.9+/-7.1 and 17.7+/-2.4 in rats with hepatitis. These results indicate that hepatocyte-targeted contrast agents effectively enhance liver tissue and enhance liver-tumor image contrast despite hepatocellular dysfunction.
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PMID:Hepatocyte-targeted MR contrast agents: contrast enhanced detection of liver cancer in diffusely damaged liver. 1634 Jan 58


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