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)

2-Deoxy-D-galactose, in a dose of 3 mmol/kg, was administered intraperitoneally twice daily to young rats for periods up to 12 weeks. This dosage schedule resulted in recurrent phosphate trapping predominantly in liver. UTP deficiency was excluded by simultaneous uridine injections. Phosphate trapping was caused by the rapid accumulation of 2-deoxy-D-galactose 1-phosphate and was most pronounced in liver but also demonstrated in small intestine, brain, spleen, and thymus. The marked, although transient, drop in the hepatic content of inorganic phosphate triggered the catabolism of adenine nucleotides and a loss of ATP. Other metabolic pathways affected by phosphate deficiency include glycogenolysis and glycolysis. Increasing with time, repeated doses of the galactose analog led to retardation and arrest of growth, hepatomegaly, and splenomegaly. The average relative liver and spleen weights were elevated 2.5- and 4.5-fold, respectively, after 12 weeks of treatment. Liver damage was indicated by hyperbilirubinaemia and a progressive rise in the activity in plasma of sorbitol dehydrogenase, alkaline phosphatase, and gamma-glutamyltransferase. Examination by light and electron microscopy showed increasing numbers of vacuoles, surrounded by a single membrane, in hepatocytes, sinusoidal endothelial cells, and Kupffer cells. Focal cytoplasmic degeneration in hepatocytes was occasionally indicated by formation of autophagic vacuoles and finger print lysosomes. Hepatocytes of 2-deoxy-D-galactose-treated rats showed a dissociation and fragmentation of the rough endoplasmic reticulum. Sinusoidal endothelial cells and Kupffer cells were markedly enlarged, the latter contained a PAS-positive but amylase resistant substance. Extrahepatic changes included an increased occurrence of vacuolated cells in thymus. Phosphate trapping and its metabolic consequences are common phenomena in the experimental injury induced b 2-deoxy-D-galactose and in some hereditary diseases such as uridylyltransferase deficiency galactosaemia, fructose intolerance and glucose-6-phosphatase deficiency.
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PMID:Consequences of recurrent phosphate trapping induced by repeated injections of 2-deoxy-D-galactose. Biochemical and morphological studies in rats. 4 10

A case of hepatoma in a 79-year old woman is reported. The patient had an enlarged liver and a pathological liver scintigram. Percutaneous liver biopsies were performed both with Menghini-and fine needles. The most prominent feature was the presence of hyaline cytoplasmic PAS-negative inclusions in liver parenchymal cells. There was no nuclear atypia. Electron microscopy disclosed two types of cytoplasmic changes. One consisted of a lamellar ultrastructure and was interpreted as a hyperplasia of smooth-surfaced endoplasmic reticulum. The other change consisted of smooth globular non-membrane limited regions containing amorphous or finely fibrillar material. This was interpreted as corresponding to the hyaline inclusions visible in the light microscope. The presence of PAS-negative hyaline cytoplasmic inclusions may thus be a sign of hepatoma. This may be of relevance for the diagnostic considerations of material obtained by fine needle biopsy.
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PMID:Hyaline cytoplasmic inclusions in human hepatoma. A case report. 19 65

The effect of repeated (4 weeks) oral administration of 2,4-, 2,5- or 2,6-xylidine (at dose levels of 400--500 mg/kg/day) on the morphology and microsomal drug metabolising enzyme activity of the liver was studied in rats. All 3 isomers caused hepatomegaly which was considered to be due to proliferation of the smooth endoplasmic reticulum. Decreases in glycogen content and glucose-6-phosphatase activity were demonstrated histochemically. Biochemical investigations showed increases in microsomal protein and cytochrome P-450 content in rats dosed with 2,4- or 2,5-xylidine and in glucuronyltransferase activity in rats given 2,4-, 2,5- or 2,6-xylidine. Aniline hydroxylase activity was increased in all treated rats except males dosed with 2,6-xylidine. The results of the study indicate that all isomes of xylidine can be inducers of microsomal drug-metabolising enzyme activity, that they may be metabolised by oxidation and that the xylidine molecule may be eliminated as a conjugate with glucuronic acid.
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PMID:Hepatic effects of xylidine isomers in rats. 22 31

Male Swiss Webster mice were fed a diet containing 2.5 percent griseofulvin (GF). Serially progressive light and electron microscopic hepatic altertions were present from one day on and grossly visible hepatomegaly from two weeks until termination at 22 weeks. GF induced liver changes included hepatocyte nuclear and cytoplasmic hypertrophy, increased incidence of necrosis and mitosis, Kupffer cell activation, bile duct proliferation and portal fibrosis. Protoporphyrin crystals were present in hepatocyte cytoplasm as early as one day after GF feeding. Hepatocellular hyalin was initially noted at seven weeks. Thereafter, the hyalin increased in prominence and frequency of occurrence. Ultrastructurally, three types of hyalin have been presently demonstrated to correspond to Mallory bodies (MB) reported in human liver disease. Forms intermediate in appearance between various MB types suggested transition from one to another. Areas of organelle free cytosol with abundant, loosely scattered filamentous elements as well as vesicular, smooth surfaced endoplasmic reticulum and ribosomes appeared preceding and closely associated with MB formation. Similarities of hepatocellular MB observed in GF fed mice and reported earlier in human alcoholic liver disease suggest a common pathway in its formation as a response to divergent noxious insults.
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PMID:Light and electron microscopy of hepatocellular changes in griseofulvin fed mice. Particular reference to Mallory bodies. 42 May 10

Administration of BR-931, an ethanolamine derivative of Wy-14,643 [4-chloro-6-(2,3-xylidino)-2-pyrimidinythio]acetic acid, at a dietary concentration of 0.125% for 3 weeks to male F-344 rats, resulted in a significant enlargement of the liver. The hepatomegaly appeared to be due to liver cell hyperplasia and hypertrophy resulting, in part, from peroxisome and smooth endoplasmic reticulum proliferation. The hepatic catalase and carnitine acetyltransferase activities increased significantly in association with peroxisome proliferation. The hepatomegaly and peroxisome proliferation induced by BR-931 were comparable in degree to those resulting from feeding of an equivalent dose of Wy-14,643. All these hepatic effects were reversible when the drugs were withdrawn from the diet. Screening of new compounds for hepatic peroxisome proliferation and for increases in peroxisome-associated enzymes may prove to be an adjunct to evaluating their potency as hypolipidemic agents, in view of frequent association between hepatic peroxisome proliferation and hypolipidemia.
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PMID:Hepatic peroxisome proliferation: induction by BR-931, a hypolipidemic analog of WY-14,643. 70 42

Authors in 1968 performing the periodoc observation of persons, working in toluene-containing athmosphera noticed the presence of hepatomegaly. Laboratory tests performed in 1968--1976 have revealed increase of the level of GOT. At 22 workers out of 170 liver biopsy was performed. By electron microscopy pathologic alterations in the mitochondria and in the rough-surfaced endoplasmic reticulum could be observed, -since these organella contain the two-third of the GOT of hepatocytes. It is assumed that mitochondria as sources of energy take part in the process of the oxydation of toulene, ribosomes of the rough-surfaced endoplasmic reticulum in the conjugation of benzoic-acid with glycine. Authors assume that there is a correlation between the damage of the organella and the detoxication of the toluene by hepatocytes.
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PMID:[Current data on toluene toxicity based on liver biopsy studies]. 71 45

Some hepatic effects of the hypolipidemic agents 3,9-di-3-pyridyl-2,4,8,10-tetraoxaspiro-5,5-undecane (compound A) and 2-(4-dibenzofuranyloxy)-2-methylpropionic acid (compound B) were investigated in male rats. The animals were treated orally with these drugs and a reference compound-clofibrate for 10 weeks, the daily doses being 250, 300 and 300 mg/kg body weight respectively. All three drugs caused hepatomegaly with a normal microscopic appearance in liver cells. In rats given compound A, part of some liver cells could be occupied by numerous membranes of smooth endoplasmic reticulum. The hepatocytes of the rats treated with compound B or clofibrate showed a marked increase in microbody profiles and an elevated hepatic catalase activity in comparison to the control animals. Neither the microbodies nor the catalase activity were affected by compound A. Hypolipidemic effects were demonstrated with all three compounds, the most potent activity being shown by compound B. Treatment with this agent resulted in significantly higher catalse activity than with clofibrate.
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PMID:Hepatic effect of two hypolipidemic drugs in rats. 91 35

The relationship between liver enlargement and drug metabolism was investigated in female rats. Hepatomegaly (e.g., 31% increase in liver weight in a 17-day experiment) was induced by injection of lyophylized anterior pituitary (LAP) extract. The liver enlargement seemed to be due to an increase in the number and the size (enhanced water content and PAS-positive material) of hepatocytes. Electron microscopic examination of the liver revealed slight proliferation of the smooth endoplasmic reticulum and pronounced fragmentation and dilation of the rough endoplasmic reticulum. Zoxazolamine paralysis time was significantly prolonged (+55% and +102%) after 4 and 17 days, respectively, of treatment with LAP. Metabolism of zoxazolamine by the 9000 g supernatant fraction of the liver of rats given LAP for 17 days was reduced by 73%. Thus, the marked hepatomegaly induced by LAP was associated with a prolonged action of the drug which may result from a decrease in hepatic drug metabolism.
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PMID:Massive liver enlargement accompanied by decreased drug metabolism. Effect of anterior pituitary extract on hepatic ultrastructure, zoxazolamine paralysis, and metabolism in the rat. 92 87

Lysinuric protein intolerance (LPI), an autosomal recessive defect of diamino acid transport, is characterized chemically by renal hyperdiaminoaciduria, especially lysinuria, and by impaired formation of urea with hyperammonemia after protein ingestion. Our 20 patients thrived during breast-feeding, but ingestion of cow's milk caused diarrhea and vomiting. When able to select their diet, they rejected all protein-rich foods. They were short staturated and had weak atrophic muscles, osteoporosis, hepatomegaly and often splenomegaly. Four patients were mentally retarded. Fifteen patients had leukocyte counts below 4,000/mm3, and 17 patients had platelet counts below 150,000/mm3. Serum lactate dehydrogenase activity was constantly increased, and transaminase and aldolase activities were often increased. In the infants' livers, changes were only revealed by electron microscopy: increased and vesicular smooth endoplasmic reticulum, and abundance of glycogen particles in the hepatocytes. In the older patients, light microscopy demonstrated clearly limited areas where hepatocytes had large pale cytoplasm and small pyknotic nuclei. The diamino acids lysine, arginine and ornithine had plasma concentrations only one-third to one-half the normal mean; the renal clearances were clearly increased. Oral diamino acid loading tests suggested impaired intestinal absorption. Urea is built in the liver through transformation of ornithine to arginine, and cleavage of arginine to ornithine and urea. The addition of ornithine to an intravenous I-alanine loading prevented the hyperammonemia and normalized the urea production. Therefore, the diet has been supplemented with arginine, and more protein has been added. This therapy has lead to a remarkable catch-up growth in some patients. The pathophysiology of LPI is explained. Because of defective intestinal absorption and incrased renal loss, the diamino acids have a low plasma concentration. Their transport from plasma to hepatocytes is also impaired, and the liver becomes deficient in ornithine. This retards the urea cycle, and leads to postprandial hyperammonemia and protein aversion. The presence of the transport defect in the hepatocytes distinguishes LPI from other hyperdibasicaminoacidurias.
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PMID:Lysinuric protein intolerance. 115 80

Spontaneous lymphomas from a strain of hereditary cataract (CAC-nct/+) mice were examined by light and electron microscopy and by immunohistochemical reaction for the mouse heavy and light immunoglobulin chains. Lymphomas occurred in 28 out of 45 male cataract mice and in 34 out of 52 females at 25 to 65 weeks of age. All of the lymphoma-bearing mice showed an enlargement of the spleen and mesenteric lymph nodes, and some mice also had hepatomegaly. Morphologically, all tumors were composed of a mixed population of small and large cells. Neoplastic cells had features of follicular center cell lymphomas, such as scant to moderate amounts of cytoplasm and cleaved and/or round nuclei with a large nuclear-to-cytoplasmic ratio. Large cells were often admixed with small cells, and had vesicular nuclei with prominent nucleoli juxtaposed to the nuclear membrane. Intracytoplasmic eosinophilic inclusions were observed in occasional cells, but Golgi apparatus was poorly developed and rough-surfaced endoplasmic reticulum was scant, unlike those in plasma cells. C-particles were seen in all lymphoma-bearing mice by electron microscopy. Intracisternal A-particles were detected in some mice. Immunohistochemically, neoplastic lymphoid cells were positive for the kappa light chain and the surface/cytoplasmic immunoglobulin M. These results indicate that lymphoid cell neoplasms found in hereditary cataract mice originate from follicular center B cells.
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PMID:Spontaneous follicular center cell lymphomas of B cell origin in cataract mice. 158 91


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