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 the anticonvulsant mephenytoin is subject to a genetic polymorphism. In 2-5% of Caucasians and 18-23% of Japanese subjects a specific cytochrome P-450 isozyme, P-450 meph, is functionally deficient or missing. We have accumulated evidence that autoimmune antibodies observed in sera of patients with tienilic acid induced hepatitis (anti-liver kidney microsome 2 or anti-LKM2 antibodies) specifically recognize the cytochrome P-450 involved in the mephenytoin hydroxylation polymorphism. This is demonstrated by immunoinhibition and immunoprecipitation of microsomal (S)-mephenytoin 4-hydroxylation activity and by the recognition by anti-LKM2 antibodies of a single protein band on immunoblots of human liver microsomes after sodium dodecyl sulfate-polyacrylamide gel electrophoresis or isoelectric focusing. The cytochrome P-450 recognized by anti-LKM2 antibodies was immunopurified from microsomes derived from livers of extensive (EM) or poor metabolizers (PM) of (S)-mephenytoin. Comparison of the EM-type cytochrome P-450 to that isolated from PM livers revealed no difference in regard to immuno-cross-reactivity, molecular weight, isoelectric point, relative content in microsomes, two-dimensional tryptic peptide maps, one-dimensional peptide maps with three proteases, amino acid composition, and amino-terminal protein sequence. Finally, the same protein was precipitated from microsomes prepared from the liver biopsy of a subject phenotyped in vivo as a poor metabolizer of mephenytoin. These data strongly suggest that the mephenytoin hydroxylation deficiency is caused by a minor structural change leading to a functionally altered cytochrome P-450 isozyme.
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PMID:Genetic polymorphism of human cytochrome P-450 (S)-mephenytoin 4-hydroxylase. Studies with human autoantibodies suggest a functionally altered cytochrome P-450 isozyme as cause of the genetic deficiency. 344 70

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

A direct spectrophotometric assay for determination of the serum bile acid concentration in the woodchuck (Marmota monax) has been validated. The assay relies on the conversion of 3-hydroxy bile acids to 3-oxo bile acids by 3 alpha-hydroxysteroid dehydrogenase with concomitant reduction of NAD+ to NADH. Reduction of NAD+ is coupled via a diaphorase catalyst to the formation of a diformazan dye from nitrotetrazolium blue and the diformazan product is measured spectrophotometrically at 540 nm. Interfering endogenous dehydrogenase activity present in woodchuck sera was inactivated with sodium pyruvate. Mean recovery of seven exogenous bile acids added to woodchuck sera was 102.0 +/- 2.2%. Intra-assay precision was determined with ten replicate samples giving a mean +/- standard error of the mean of 1.94 +/- 0.12 micron/L with a coefficient of variation of 3.9%. The mean serum bile acid concentration determined in 33 clinically healthy animals was 5.52 +/- 0.81 micron/L. The serum bile acid concentration increased following surgical ligation of the bile duct from 3.78 +/- 0.58 micron/L to a maximum value of 148.0 +/- 30.7 micron/L and remained increased for the 42 day study period. In woodchucks treated with carbon tetrachloride, the serum bile acid concentration peaked at 16 hours following treatment at 72.7 +/- 29.3 micron/L, and returned to pretreatment concentration within 6 days. The serum bile acid concentration therefore appears to be a sensitive biochemical test of cholestasis and hepatocellular forms of hepatic injury and of potential value in the clinical assessment of hepatic disease associated with woodchuck hepatitis virus infection.
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PMID:Serum bile acid determination for assessment of hepatic injury in the woodchuck. 359 95

Thirty-six wild-caught woodchucks (Marmota monax) were characterized according to sex, weight, trapping locality, liver pathology, and serum or hepatic markers of woodchuck hepatitis virus. Liver subcellular fractions were assayed for microsomal cytochromes P-450, aryl hydrocarbon hydroxylase, glutathione, cytosolic enzymes involved in its metabolism (glutathione S-transferase, glutathione peroxidase, and glutathione reductase), in the hexose monophosphate shunt (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), NADH- and NADPH-dependent diaphorases, and DT diaphorase. Moreover, liver postmitochondrial fractions were assayed for their ability to activate procarcinogens [i.e., a tryptophan pyrolysate product, aflatoxin B1, 2-aminofluorene, and trans-7,8-dihydrobenzo(a)pyrene] to mutagenic metabolites in the Ames reversion test and to decrease the activity of direct-acting mutagens [i.e., 4-nitroquinoline N-oxide, 2-methoxy-6-chloro-9-[3-(2-chloroethyl)aminopropylamino]acridine X 2HCl, and sodium dichromate]. A considerable interindividual variability in metabolism was observed among the examined woodchucks. Some of the investigated parameters were more elevated in virus carriers, especially in those suffering from chronic active hepatitis, but only a few of the recorded differences (i.e., oxidized glutathione reductase and NADPH-dependent diaphorase) were statistically significant. The comparison of the monitored activities in woodchucks and in other rodent species (rat and mouse) led to the conclusion that the liver metabolism of mutagens and carcinogens in woodchucks is more oriented in the sense of activation, while detoxification mechanisms are more efficient in rats and mice.
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PMID:Metabolism of mutagens and carcinogens in woodchuck liver and its relationship with hepatitis virus infection. 360 50

A case of phenytoin-induced hepatitis with mononucleosis is reported, and syndromes associated with phenytoin hypersensitivity reactions are discussed. A 23-year-old black woman with a two-month history of seizure disorder was admitted to a hospital with nausea, vomiting, fever, lymphadenopathy, diffuse maculopapular rash, left-upper-quadrant tenderness, and hepatomegaly. She was receiving phenytoin sodium 300 mg/day; carbamazepine 200 mg four times daily had been discontinued four days before admission because of leukopenia. Phenytoin was discontinued after admission; however, phenytoin 1 g i.v. was given for a tonic-clonic seizure two days after admission, after which swelling of the face and legs and pruritus developed. Over the next few days, signs and symptoms of hepatotoxicity progressed, and she became comatose. Seizures were treated with diazepam. She began to recover after 10 days of supportive therapy and was discharged several weeks later on primidone therapy. Serious phenytoin hypersensitivity reactions may appear as dermatologic, lymphoid, or hepatic syndromes. Fever, rash, and lymphadenopathy often accompany hepatic injury. Encephalopathy and death may occur. Proposed mechanisms for phenytoin hypersensitivity include antigen-antibody reactions, alteration of lymphocyte function, and an enzyme abnormality causing the production of toxic metabolites. Treatment is supportive; phenobarbital and carbamazepine may be used with caution as alternate anticonvulsant therapy. The possibility of phenytoin hypersensitivity reactions should be considered when patients receiving phenytoin have unusual symptoms, particularly fever, rash, and lymphadenopathy.
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PMID:Phenytoin-induced hypersensitivity reactions. 367 71

Treatment of serum precipitates with sodium thiocyanate in patients with hepatitis B virus (HBV) replication results in liberation of circulating hepatitis core antigen (HBcAg) which can be demonstrated radioimmunologically. Follow-up investigations were performed in 80 patients with acute hepatitis B. Sera were examined for HBcAg. HBV DNA and conventional HBV markers. At the time of admission to hospital 34 of 80 (42%) patients were HBeAg positive. Twenty-six (76%) of the 34 HBcAg positive patients were HBV DNA positive, and circulating HBcAg was detectable in 25 of 34 (73%) HBcAg positive cases. In patients with uncomplicated courses of acute hepatitis B the serological HBcAg assay and HBV DNA became negative 1 to 8 weeks before elimination of HBeAg and up to 12 weeks earlier than the sera became negative for HBsAg. Five patients (6%) showed transition to chronic hepatitis B with persistence of HBsAg, HBeAg, HBV DNA and HBcAg in serum. One patient with acute hepatitis B and development of chronic hepatitis suffered from acquired immunodeficiency syndrome and showed delayed formation of anti-HBc. In this case uncomplexed HBcAg was demonstrable during the acute phase of hepatitis B. With the appearance of anti-HBc HBcAg circulated in a complexed form. The data indicate that serological determinations of HBcAg and HBV DNA can serve as prognostic markers in the early phase of acute hepatitis B. The demonstration of uncomplexed HBcAg in serum of a patient with inadequate formation of anti-HBc supports the hypothesis that circulating HBcAg is usually complexed by specific antibodies.
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PMID:Serological assessment of HBcAg and HBV DNA: its prognostic relevance in acute hepatitis B. 369 17

The effects of aevite and riboflavin on electrolyte balance in the vessel wall were studied in toxic hepatitis in the cat. Significant changes in the contents of Na+, K+, Ca2+ and Mg2+ ions in the hepatic blood vessels were found in all periods of observation. The treatment of toxic hepatitis with aevite and riboflavin results in normalization of electrolyte balance of the vessel wall.
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PMID:[Effect of aevite and riboflavin on the electrolyte balance in the wall of the hepatic blood vessels in experimental toxic hepatitis]. 370 81

Lipid molecules in lipoprotein surfaces exchange with their counterparts in cell plasma membranes. In human or experimental liver disease, plasma lipoprotein surfaces are enriched in cholesterol and deficient in arachidonate; corresponding alterations occur in membrane lipids of erythrocytes. To determine whether similar changes take place in membranes of nucleated cells, the lipid content of plasma and of erythrocyte, liver and kidney membranes was measured in rats with acute (3-day) galactosamine-induced hepatitis or chronic (3-week) biliary obstruction. In both models of liver injury the cholesterol:phospholipid ratio in plasma and in erythrocytes was significantly increased (P less than 0.001). Although this ratio was also elevated in liver and kidney microsomes, only in liver microsomes of obstructed rats was the increase significant (P less than 0.001). However, the cholesterol:phospholipid ratio of kidney brush-border membranes, was significantly higher in bile-duct-ligated rats; presumably, compensating mechanisms limit cholesterol accumulation in intracellular membranes. Kidney brush-border membranes from obstructed rats were deficient in arachidonate as were plasma and erythrocytes. However, arachidonate levels were unchanged in kidney microsomes; renal delta 6-desaturase, the rate-limiting enzyme in the conversion of linoleic acid to arachidonic acid, was increased by 50% (P less than 0.001) and may have counteracted a reduced supply of exogenous lipoprotein arachidonate. We conclude that in experimental liver disease lipoprotein-induced lipid abnormalities can occur in renal membranes, although compensatory mechanisms may operate; the alterations seen, cholesterol accumulation and arachidonate depletion, would be expected to interfere with sodium transport and prostaglandin production, respectively. Our findings support the hypothesis that lipid abnormalities in kidney membranes contribute to the renal dysfunction which is a frequent complication of human liver disease.
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PMID:Membrane lipid changes in erythrocytes, liver and kidney in acute and chronic experimental liver disease in rats. 379 May 85

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

The toxic effect of insect iridescent virus type 6 - chilo iridescent virus - (CIV) was investigated using Balb/c mice (strain ByJ Ico and Kisslegg). The animals were inoculated with CIV intraperitoneally (1 X 10(9) to 9.2 X 10(11) TCID50/animal). The animals which were administered with 1 X 10(11) to 9 X 10(11) TCID50 of CIV per animal, developed acute clinical illness and died during 18 to 80 h post infection. Histopathological and electronmicroscopic examinations of the liver tissues of those animals which died and/or were sacrificed when moribund showed acute degenerative hepatitis leading to death. No evidence for viral replication was found in the liver cells affected. A mortality rate between 21.1% and 100% was recorded for CIV, depending on the strain and number of mice used and the dose of virus administered. The toxic effect of CIV was eliminated or reduced extensively using heat denaturation or treatment of CIV with sodium dodecylsulphate or proteinase K. This indicates that the nature of the factor causing toxic degenerative cell damage is a protein.
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PMID:Insect iridescent virus type 6 induced toxic degenerative hepatitis in mice. 395 91


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