Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mitogenic effect of Nafenopin, a hypolipidemic hepatic peroxisome proliferator, in mouse liver has been studied in acute and chronically treated mice. After 1, 6 and 32 weeks of treatment, the total hepatic DNA was increased 1.5-2.0-fold over controls. Mitotic and labeling indices were also increased 3-4 fold after 5 days, 6 weeks and 32 weeks of treatment. The increased mitotic activity in nafenopin fed animals was not associated with liver cell necrosis. The nafenopin induced hepatomegaly therefore appears to arise from a combination of cell proliferation, as well as, cellular hypertrophy, which is associated with peroxisome proliferation.
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PMID:Mitogenic effect in mouse liver induced by a hypolipidemic drug, nafenopin. 40 52

Male Swiss-Webster mice were fed diets containing four hypolipidemic agents which are known to induce proliferation of hepatic peroxisomes. Treatment with all four drugs (clofibrate; its structural analogue, nafenopin; and two drugs structurally unrelated to clofibrate, tibric acid and Wy-14,643) produced a marked hepatomegaly in the mice. The extent of the increase in liver weight correlated well with the increases in total hepatic DNA and in the collective volume of hepatocyte peroxisomes. Treatment with these drugs also produced similar increases in the activities of peroxisome-associated enzymes. The most dramatic increases were noted in the activities of the short-chain (8- to 26-fold) and medium-chain (4- to 11-fold) carnitine acyltransferase. Significant increases were also noted in the activities of catalase (twofold to threefold), alpha-glycerophosphate dehydrogenase (twofold to threefold) and the long-chain carnitine acyltransferase (twofold to fourfold). Activity of the latter enzyme, however, is not known to be associated with peroxisome fractions. Concomitant administration of actinomycin D or cycloheximide with a single oral dose of clofibrate diminished the increases in liver weight and carnitine acyltransferase which occurred with clofibrate treatment alone. The finding that the major increase in activity of peroxisome enzymes occurred in those associated with metabolism of acyl CoA groups supports the hypothesis that the hypolipidemic action of the drugs and the proliferation of hepatic peroxisomes are related functions.
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PMID:The hepatic effects of hypolipidemic drugs (clofibrate, nafenopin, tibric acid, and Wy-14,643) on hepatic peroxisomes and peroxisome-associated enzymes. 62 9

To determine whether chronic Schistosoma mansoni infection interferes with hepatitis B virus (HBV) immunization, 308 schoolchildren aged 6-12 years with no evidence of prior HBV infection (156 with active schistosomiasis) were vaccinated with three 5-micrograms injections of recombinant DNA-derived HBV vaccine. The vaccine was given in the deltoid muscle at time 0 and 1 and 7 months later. All vaccinees were examined 1 and 3 years after vaccination for quantitative antibody to hepatitis B surface antigen (anti-HBs). Seroconversion was detected in 284 vaccinated children (92%), of whom 271 had a good (51-300 mIU/mL) or excellent (greater than 300 mIU/mL) anti-HBs response. Sixteen other children (5%) had evidence of natural HBV infection (antibody to hepatitis B core antigen). Of those with good or excellent response, 99% retained high antibody titers for 3 years. Response was not influenced by S. mansoni infection. Hepatomegaly and splenomegaly were associated with reduced vaccine response.
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PMID:Efficacy of hepatitis B vaccination in primary school children from a village endemic for Schistosoma mansoni. 138 97

A 3-month-old girl was admitted to the hospital because of hypotonia and frequent vomiting. She had severe metabolic acidosis and her liver function was abnormal. Hepatomegaly and rapidly progressive liver failure developed, and she died at 4 months of age. Two half-siblings from a different mother had died in infancy of an undiagnosed myopathy. The liver was fatty and hepatocytes were filled with large and small lipid droplets. Other tissues were morphologically normal. The respiratory chain enzymes containing subunits encoded by mitochondrial DNA were markedly decreased in liver, partially decreased in muscle, but normal in other tissues. Southern blot analysis showed 90% depletion of mitochondrial DNA in liver, 53% depletion in muscle, and normal amounts in other tissues. This is the second case of fatal infantile liver failure associated with mitochondrial DNA depletion. This pathogenetic mechanism should be considered in infants with multiple respiratory chain defects and variable tissue expression.
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PMID:Fatal infantile liver failure associated with mitochondrial DNA depletion. 144 52

Echinococcosis is an infectious disease of humans caused by the larval (metacestode) stage of the cestode species Echinococcus granulosus (cystic echinococcosis or hydatid disease) or Echinococcus multilocularis (alveolar echinococcosis or alveolar hydatid disease). Clinical manifestations depend primarily on localization and size of hepatic lesions and may include hepatomegaly, obstructive jaundice, or cholangitis. Prognostically, alveolar echinococcosis is considered similar to liver malignancies, including a lethality rate of 90% for untreated cases. Diagnosis is based on imaging techniques coupled with immunodiagnostic procedures. Antibody detection tests for E. multilocularis have markedly improved with the use of affinity-purified Em2 antigen and recombinant antigen II/3-10 in enzyme immunoassays. Antigens of corresponding quality for E. granulosus are still unavailable. The detection of circulating antigens and immune complexes in the sera of patients with cystic echinococcosis, the demonstration of in vitro lymphocyte proliferation in response to stimulation with Echinococcus antigens, and the discrimination of serum immunoglobulin isotype activity to various Echinococcus antigens in both cystic and alveolar echinococcosis have been suggested for diagnostic purposes as well as for monitoring patients after treatment. New diagnostic molecular tools include DNA probes for Southern hybridization tests and polymerase chain reaction for the amplification of E. multilocularis and E. granulosus species-specific DNA fragments.
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PMID:Molecular and immunological diagnosis of echinococcosis. 149 67

Perfluoro-n-decanoic acid (PFDA) is a perfluorinated fatty acid that produces hepatomegaly and increased peroxisomal beta-oxidation when administered to rodents. Chlorotrifluoroethylene (CTFE) trimer acid and CTFE tetramer acid are metabolites of the six- and eight-carbon oligomers of CTFE, respectively. They are structurally related to PFDA, and CTFE tetramer acid has caused toxic effects in rodents that are similar to those observed following PFDA administration. Because of the correlation between peroxisome proliferation and hepatocarcinogenesis, CTFE trimer acid, CTFE tetramer acid, and PFDA were evaluated in in vitro and in vivo/in vitro bioassays to assess their potential genotoxic activity. The assays conducted were the Ames Salmonella/microsomal mutagenicity assay, the hypoxanthineguanine phosphoribosyltransferase (HGPRT) locus Chinese hamster ovary gene mutation assay, the sister chromatid exchange (SCE) assay, chromosomal aberration assay, and an in vivo/in vitro unscheduled DNA synthesis (UDS) and S-phase DNA synthesis assay. All test articles were negative in the Ames assay, the HGPRT assay, and the SCE assay. In the chromosomal aberration assay CTFE trimer acid and CTFE tetramer acid were negative in cultures with and without S9 metabolic activation. PFDA was also negative in the absence of metabolic activation, but chromosomal aberrations were observed when PFDA was incubated in the presence of S9 fraction. All test articles were negative for inducing UDS but all induced S-phase replicative DNA synthesis 16 hr after administration of the test article to the test animals; only CTFE tetramer acid and PFDA induced S-phase synthesis 48 hr after dosing: the usual timepoint examined for this response.
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PMID:Assessment of the potential genotoxicity of perfluorodecanoic acid and chlorotrifluoroethylene trimer and tetramer acids. 152 68

Earlier studies indicated that the hepatocarcinogenic activity of two peroxisome proliferators (PP) Wy-14,643 and di(2-ethylhexyl)phthalate (DEHP) correlated to the degree of lipofuscin accumulation and sustained cell replication rather than the level of peroxisome induction. This study extends the comparison of peroxisome proliferation, lipofuscin accumulation and cell replication responses in rats fed (i) clofibric acid at 5000 p.p.m. (CA), a regimen of moderate hepatocarcinogenicity; (ii) Wy-14,643 at 50 p.p.m. (WYLD), a dose of unknown hepatocarcinogenicity; and (iii) Wy-14,643 at 1000 p.p.m. (WYHD), as the highly hepatocarcinogenic regimen. Adult male F344 rats were fed the experimental diets for 1, 2, 5, 11 or 22 weeks. Relative liver weights (% of body weight) were increased in rats fed CA (1.6- to 1.7-fold), WYHD or WYLD (2.0- to 2.7-fold), compared to controls (approximately 3%) at all time points. All rats fed CA, WYHD or WYLD had similar hepatic peroxisome proliferation at all time points with large elevations in peroxisomal enzyme activities and number, size and mean volume of peroxisomes. In contrast, hepatocytic lipofuscin accumulation differed between treatments, with a decreasing order of accumulation observed in WYHD greater than WYLD approximately equal to CA greater than controls. Replicative DNA synthesis (as assessed by nuclear labeling index, LI) in nonlesion hepatocytes was markedly elevated at 1 week by both WYHD and WYLD (45- and 40-fold over controls respectively) while CA induced a 10-fold response over controls (control LI less than or equal to 1%). From week 2 to week 22 the hepatocytic LI was sustained in WYHD and WYLD rats (8- and 4-fold over controls respectively) but not in CA-rats, as compared to controls. In contrast to the cell replication response, apoptosis was elevated only in WYHD at 22 weeks. Collectively, this study supports the conclusion that neither hepatomegaly nor peroxisome proliferation are accurate predictors of carcinogenic activity for PP. Further, these results suggest that if lipofuscin accumulation or sustained cell turnover are indicators of PP-induced carcinogenesis, then WYLD should be at least as carcinogenic as CA. The moderate carcinogenic activity of CA also suggests that additional factor(s) may be necessary besides lipofuscin accumulation and sustained cell replication to determine the ultimate carcinogenic activity of PP.
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PMID:Contrasting hepatocytic peroxisome proliferation, lipofuscin accumulation and cell turnover for the hepatocarcinogens Wy-14,643 and clofibric acid. 160 Jun 4

CD-1 mice were given oral doses of 0-16 ml/kg/day for five days of Prudhoe Bay (PBCO), South Louisiana and Arabian Light crude oils, Bunker C oil (BCO), mineral oil (MO) and corn oil. Minor decreases in packed cell volume and increases in mean corpuscular hemoglobin concentration occurred after ingestion of crude oils and BCO. Dietary depletion of vitamin E and selenium failed to enhance hematological changes. Pronounced liver enlargement and atrophy of thymus and spleen accompanied ingestion of all petroleum oils except MO and were shown to be dependent on dose of PBCO. Concentration of RNA and total RNA were increased while total DNA, but not concentration of DNA, was increased in enlarged livers. Liver enlargement was attributed primarily to hyperplasia with an additional contribution due to hypertrophy. The severe hemolytic anemia reported in marine birds that ingested PBCO was not reproduced in mice. Liver enlargement and lymphoid tissue atrophy were similar to those reported in other species exposed to petroleum oils.
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PMID:The systemic toxicity of Prudhoe Bay Crude and other petroleum oils to CD-1 mice. 169 Sep 73

The present study determined the composition and nucleic-acid content of livers obtained from 11-wk-old, broiler-strain pullets infused with pituitary-derived chicken growth hormone (p-cGH) in either a pulsatile (Study 1) or continuous (Study 2) manner for 21 days. Pulsatile p-cGH administration resulted in a decrease in ratios for liver DNA to wet weight (P less than .01), DNA to protein (P less than .03), and DNA to RNA (P less than .002), compared with controls. Total RNA-to-liver ratio (P less than .003) and liver weight (P less than .007) were significantly elevated, compared with controls. Total grams of protein (P less than .0007), water (P less than .004), and ash (P less than .01) were also elevated, with no significant differences in the percentage of composition. Continuous growth-hormone (GH) administration resulted in a decrease in the DNA-to-protein ratio (P less than .04) and a modest increase in the mass of liver protein (P less than .11) in comparison with controls, suggestive of cell hypertrophy. On a mass and percentage basis, liver composition was otherwise unaffected by the continuous administration of GH. In summary, pulsatile administration of GH induced hepatomegaly, largely due to cell hypertrophy, with no change in relative tissue composition. The continuous administration of GH had no effect on liver size, tissue composition, or most nucleic-acid-based indicators of cell hypertrophy or hyperplasia. Thus, previously observed differences in overall growth performance due to pattern of GH administration were also reflected in selected target-tissue response.
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PMID:Hepatomegaly induced by the pulsatile, but not continuous, intravenous administration of purified chicken growth hormone in broiler pullets: liver composition and nucleic-acid content. 169 89

Studies with hepatocyte cultures have defined four hepatocyte mitogens which can transmit a complete mitogenic signal in cultures kept in completely defined conditions. These four mitogens are epidermal growth factor (EGF), acidic fibroblast growth factor (aFGF), hepatopoietin A/hepatocyte growth factor (HPTA/HGF) and hepatopoietin B (HPTB). In this study, we investigated the effect of aFGF, HGF and the mito-inhibitor transforming growth factor beta (TGF-beta) on cultured hepatocytes isolated from livers of rats treated with the xenobiotic hepatic tumor promoters phenobarbital (PB) and alpha-hexachlorocyclohexane (alpha-HCH). Male F344 rats were treated with each of these two xenobiotics to stimulate hepatic DNA synthesis and augmentative hepatomegaly. At different times on the regimens with tumor promoters, hepatocytes were isolated and placed in primary culture. DNA synthesis of hepatocytes in culture stimulated by these two growth factors and the suppression of DNA synthesis affected by TGF-beta were examined as a function of time of treatment in vivo with these two promoters. Following day 10, hepatocytes from both promoter regimens became unresponsive to these two growth factors for the rest of the duration of the treatment (day 90). TGF-beta suppressed DNA synthesis stimulated by growth factors but did not affect the high background DNA synthesis stimulated by xenobiotics themselves.
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PMID:Long-term treatment with hepatic tumor promoters inhibits mitogenic responses of hepatocytes to acidic fibroblast growth factor and hepatocyte growth factor. 171 12


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