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)

The metabolism of chemical carcinogens was investigated in liver preparations from 28 captive woodchucks (Marmota monax). Of these, 23 were naturally infected with the woodchuck hepatitis virus (WHV), and eight also had primary hepatocellular carcinoma (PHC). Twenty-nine parameters were investigated in liver subcellular fractions, including cross-reactivity with HBsAg, and biochemical parameters, such as gamma-glutamyl transpeptidase, cytochrome P-450 and microsomal monooxygenases (aryl hydrocarbon hydroxylase, ethoxycoumarin and ethoxyresorufin deethylases, aminopyrine and dimethylnitrosamine demethylases, and testosterone 7 alpha-, 16 alpha- and 6 beta-hydroxylases), uridine 5'-diphosphoglucuronosyl transferase, GSH and related enzymes (peroxidase, reductase and S-transferase), as well as other cytosolic enzyme activities (glucose 6-phosphate and 6-phosphogluconate dehydrogenases, NADPH- and NADH-dependent diaphorases, and DT diaphorase). In addition, liver preparations were used in order to quantify the metabolic activation into bacterial mutagens of five procarcinogens (aflatoxin B1, the pyrolysis products Trp-P-2 and MeIQ, 2-aminofluorene and dimethylnitrosamine) and the decrease of potency of three direct-acting mutagens (sodium dichromate, ICR 191 and 4-nitroquinoline 1-oxide). WHV infection produced a significant stimulation of carcinogen metabolism, as shown by the simultaneous change in detoxification parameters (GSH depletion) and activation indices (enhancement of microsomal monooxygenases and of procarcinogen activation into mutagenic metabolites). There were no significant differences between WHV-positive samples from animals without PHC and the noncancerous tissue of PHC-bearing animals, whereas a decrease of both activation and detoxification indices was recorded in the tumorous tissue. There was a considerable interindividual variability among WHV carriers, which was tentatively ascribed to genetic factors. Pregnancy was the only known factor influencing the results in WHV carriers. However, even by excluding pregnant animals, the effects on carcinogen metabolism produced by WHV infection were still statistically significant. These results, together with previous data obtained in humans, revealed that metabolic factors may play a role in the synergism between viral hepatitis and chemical hepatocarcinogens in the etiopathogenesis of PHC.
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PMID:Enhanced metabolic activation of chemical hepatocarcinogens in woodchucks infected with hepatitis B virus. 272 Sep 3

The safety of an antihaemophilic factor concentrate treated with the organic solvent tri-(n-butyl)phosphate and sodium cholate (factor VIII-SD) was assessed for transmission of non-A, non-B (NANB) hepatitis and human immunodeficiency virus (HIV). Patients enrolled in the study had no previous exposure to blood products made from plasma pools, although 5 had received small quantities of single-donor products. All but 1 had normal alanine aminotransferase (ALT) levels, none had markers of HIV infection, and all had been vaccinated against hepatitis B. After treatment with factor VIII-SD, serum ALT levels and HIV antibody were monitored for up to 1 year. 20 patients received 625 to greater than 40,000 U (total 163,000 U, median dose 3900 U), and 17 of these were followed up for at least 6 months: transmission of either NANB hepatitis or HIV was not observed.
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PMID:Virus safety of solvent/detergent-treated antihaemophilic factor concentrate. 289 62

Simple or combined D,T,P and inactivated polio vaccines adsorbed onto calcium phosphate are prepared according to two procedures. Antigens can be dialysed in a sodium phosphate solution and quickly mixed with an equal volume of an equimolar solution of calcium chloride, the pH is adjusted to 6.8-7. Toxoids added to the phosphate solution are in this way entrapped within the 3-dimensional network during the formation of the precipitate. Antigens can also be added to a calcium phosphate gel suspension prepared in advance. Results of animal experiments and of field trials using either combined vaccines or simultaneous immunization with diphtheria, tetanus, pertussis, meningococcal and several viral vaccines: polio, rabies, hepatitis-B, etc., will be presented. Several programs have been studied in developing countries, mainly with the aim at simplifying vaccination campaigns. The efficiency of a two-dose regimen with DT vaccine has been ascertained, this has also been applied to pregnant women. Adsorbed tetanus toxoid was successfully used as a diluent for freeze-dried measles, meningococcal polysaccharide and rabies vaccines. Levels of circulating antibodies and potency of vaccines have been measured by new in vivo and in vitro methods. The choice of detoxified purified toxins is desirable for the preparation of vaccines in order to prevent the occurrence of adverse reactions. Local and generalized reactions have been studied. Adverse Arthus-type reactions have been encountered and related with the presence of high levels of circulating tetanus antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preparation and use of calcium phosphate adsorbed vaccines. 354 96

Six woodchucks, 10 1/2 months of age, injected intramuscularly with 0.02 ml of woodchuck hepatitis virus (WHV)-positive serum and two woodchucks of similar age and origin injected with phosphate buffered saline were studied by serial blood samples and liver biopsy sections over an 18 week period. Serum samples were assayed for WHV surface antigen (WHsAg), its corresponding antibody (anti-WHs) and antibody to WHV core antigen (anti-WHc). WHV core antigen (WHcAg) was detected in liver biopsy sections by fluorescent labeled anti-WHc, and WHsAg was detected by the Victoria blue stain. All six experimentally infected woodchucks eventually developed anti-WHs and four developed serologic and histologic signs of acute hepatitis. Hepatic lesions resembled lesions described in the livers of chimpanzees and humans with acute hepatitis B viral infections. The first histologic signs of liver change coincided with the appearance of WHsAg within the serum and WHcAg within the cytoplasm of hepatocytes. After WHcAg was no longer detected in the serum, WHsAg appeared in the cytoplasm of hepatocytes. Microfocal areas of hepatic necrosis were associated with aggregates of lymphocytes, macrophages, and a few neutrophils and plasma cells. The periportal exudate became increasingly abundant during the 18-week study period in the four animals with acute hepatitis. The results from this study indicate that acute hepatitis may be induced in the woodchuck by experimental infection with WHV. Furthermore, the woodchuck might serve as an excellent model for the study of the pathogenesis of acute viral hepatitis in man.
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PMID:Experimental infection of the woodchuck (Marmota monax monax) with woodchuck hepatitis virus. 372 63

Use of the organic solvent, tri(n-butyl)phosphate (TNBP), and detergents for the inactivation of viruses in labile blood derivatives was evaluated by addition of marker viruses (VSV, Sindbis, Sendai, EMC) to anti-hemophilic factor (AHF) concentrates. The rate of virus inactivation obtained with TNBP plus Tween 80 was superior to that observed with ethyl ether plus Tween 80, a condition previously shown to inactivate greater than or equal to 10(6.9) CID50 of hepatitis B and greater than or equal to 10(4) CID50 of Hutchinson strain non-A, non-B hepatitis. The AHF recovery after TNBP/Tween treatment was greater than or equal to 90 percent. Following the reaction, TNBP could be removed from the protein by gel exclusion chromatography on Sephadex G25; however, because of its large micelle size, Tween 80 could not be removed from protein by this method. Attempts to remove Tween 80 by differential precipitation of protein were only partially successful. An alternate detergent, sodium cholate, when combined with TNBP, resulted in almost as efficient virus inactivation and an 80 percent recovery of AHF. Because sodium cholate forms small micelles, it could be removed by Sephadex G25 chromatography. Electrophoretic examination of TNBP/cholate-treated AHF concentrates revealed few, if any, changes in protein mobility, except for plasma lipoprotein(s).
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PMID:Inactivation of viruses in labile blood derivatives. I. Disruption of lipid-enveloped viruses by tri(n-butyl)phosphate detergent combinations. 393 1

This report describes advances in techniques for analyzing cellular and humoral immune components in the cerebrospinal fluid (CSF) of the mouse that are applicable to other laboratory animals. CSF studies undertaken during experimental infection of mice with JHM strain virus (JHMV) of mouse hepatitis virus are presented. A critical pitfall which can lead to erroneous or invalid results is contamination of the CSF by even minute quantities of blood. Means of avoiding this contamination are attention to anatomical reference points, the use of a micropipet, and prior intracardiac perfusion of animals with phosphate-buffered saline. Cells in the CSF were typed as either B, T, polymorphonuclear, or mononuclear cells by the combination of a microcytotoxicity assay and histologic stains. A radioimmunoassay (RIA) allowed quantification of antibodies to JHMV in the CSF and indicated the presence of intrathecal synthesis of antibody in chronically infected mice. The combined use of these sensitive methods makes possible CSF analysis in individual mice rather than in pooled groups.
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PMID:Improvements in obtaining and characterizing mouse cerebrospinal fluid. Application to mouse hepatitis virus-induced encephalomyelitis. 630 Jan 86

We report the cases of four adult patients suffering from acute hepatitis due to isaxonine phosphate (Nerfactor), a drug recently proposed for the treatment of the lesions of peripheral nerves. Hepatitis developed 14 to 166 days after the beginning of the administration of the drug. In all the patients, predominantly centrilobular hepatocytic necrosis was present. In two of our patients, the course of hepatitis was fatal. Hepatitis induced by isaxonine phosphate is likely to be due to an immuno-allergic mechanism.
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PMID:[Acute hepatitis caused by isaxonine phosphate (Nerfactor)]. 630 99

The case history of a 4 year old girl with primary hypoparathyroidism is reported. Treatment with oral 1 alpha-hydroxyvitamin D3 did not result in normal calcium and phosphate levels, whereas treatment with oral 1 alpha,25-dihydroxyvitamin D3 did. During the treatment period, the patient developed signs of severe liver disease and died in a picture of increased intracranial pressure. Post-mortem examination revealed a giant cell hepatitis and severe cirrhosis. The clinical course is consistent with a liver vitamin D3 hydroxylation defect.
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PMID:Hypoparathyroidism and liver disease--evidence for a vitamin D hydroxylation defect. A case report. 654 65

Isaxonine phosphate is known to induce acute hepatitis which in most cases is reversible after withdrawal of the drug. The authors describe 4 new cases of hepatitis which differ from those previously reported by their evolutive and pathological features. In 3 cases, the outcome was fatal within a delay of 15-40 days despite discontinuation of the drug, and was associated with hepatic encephalopathy and ascites. In the 4 cases plasma concentration of alanine- and aspartate-aminotransferases were initially increased (up to 33 X upper normal range) and decreased to normal values in 2 cases. Plasma bilirubin levels were also elevated at first and continued to increase during the first 15 days of evolution. Pathological examination of the liver showed mild necrosis, sometimes with a piecemeal or a bridging aspect, marked fibrosis infiltrated with mononuclear and neutrophil polymorphonuclear cells and a conspicuous biliary neogenesis. In these particular cases of hepatitis due to isaxonine phosphate, occurrence in women, increased serum immunoglobulin levels, presence of autoantibodies, clinical and pathological aspects resembling those observed in iproniazid hepatitis may be suggestive of an immunological, or even autoimmune, mechanism.
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PMID:[Hepatotoxicity of isaxonine phosphate: 4 cases of severe subacute hepatitis]. 654

Two patients abruptly developed congestive heart failure and elevation in serum transaminase levels when given disopyramide phosphate; enzyme abnormalities and hemodynamic status corrected upon withdrawal of the drug. Both patients had underlying ischemic cardiomyopathy. Myocardial infarction, pulmonary embolism, and viral hepatitis were ruled out in both patients. One patient had a liver biopsy documenting central hepatic necrosis with congestion, consistent with hepatic ischemia and not toxic hepatitis. In the other patient, cardiac decompensation and hepatocellular enzyme elevation were reproduced on rechallenge with the drug. Disopyramide should be used with caution in patients with heart failure.
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PMID:Acute cardiac failure and hepatic ischemia induced by disopyramide phosphate. 722 41


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