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 effects of feeding two compounds, dehydroepiandrosterone (DHEA), an adrenal steroid, and clofibrate (CLOF) to rats (which are both hypolipidemic, hepatomegaly inducing and hepatic peroxisome proliferating agents) on the binding of 7,12-dimethylbenz(a)anthracene (DMBA) to hepatic DNA in vivo is compared. Male Sprague Dawley rats (two-three months old) were fed either DHEA or CLOF for 14 days at a dietary level of 0.8%. Control rats were pair fed. An increase in liver weight followed by increases per whole liver in total protein, without much change in DNA content was observed. Subsequently, all the animals were given a single intraperitoneal dose of [3H]DMBA (133 mumol/kg body weight, 102 microCi/rat) in 250 microliters dimethyl sulfoxide. Forty-eight hours later, binding of DMBA to hepatic DNA was determined. The results indicate that DMBA binding to DNA was reduced by 67% in DHEA-fed rats whereas in clofibrate-fed rats it was not significantly different from that of the controls.
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PMID:Differential effects of dehydroepiandrosterone and clofibrate on the binding of 7,12-dimethyl benz(a)anthracene to hepatic DNA in vivo--a preliminary study. 253 80

A 60-year-old man born in Okinawa was admitted to our hospital because of epigastralgia. Physical examination revealed general lymphadenopathy, mild hepatomegaly and skin eruption. The peripheral blood leukocyte count was 168,600/microliters, with 93% abnormal lymphocytes showing convoluted or lobulated nuclei. Anti HTLV-1 antibody was positive with titer of 1: 1280 (PA). Leukemic cells had typical ATL cells' surface markers (OKT3; 97.2%, T4; 93.3%, T8; 2.8%, OKIA1; 39.6%, IL-2R; 41.8%) and complete monoclonal HTLV-1 provirus DNA. Endoscopic examination with biopsy revealed massive involvement of ATL cells into gastric mucosa. In the course of the treatment, he had extremely massive melena, and was saved by emergency operation. Multiple ulcers were found in the resected colon. Histological examination showed the marked infiltration of the ATL cells into the mucous or submucous membrane. Thereafter, he was treated well with ALG (Anti Lymphocyte Globulin), until hypercalcemia occurred. He died of acute renal failure after hypercalcemia.
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PMID:[Adult T-cell leukemia with massive melena due to marked gastrointestinal involvement]. 259 52

In the present study, the effects of chloroquine and ethanol administration during gestation have been investigated on the developing rat fetus. Intragastric administration of chloroquine (700 mg/kg body weight) resulted in several structural abnormalities. The incidence of hepatomegaly was increased by 30%, the liquification of visceral organs was increased by 15% and a 9% higher incidence of cleft palate, wrist drop, clubbed foot and brain liquification was observed in the fetuses from the chloroquine-treated group compared to the corresponding controls. Fetuses from the chloroquine-treated group also showed a decrease of about 40% in the body weight and a 30% reduction in the ossification of the sternum. The teratogenic effects of oral ethanol administration in several respects were similar to those of the chloroquine. Ethanol, when administered as 30% of the total daily calories, resulted in growth retardation, resorption, still births, liquification of the brain, wrist drop and clubbed foot. Additionally, ethanol resulted in the inhibition of several metabolic pathways in the liver and brain of the developing fetuses. This included the inhibition of protein, RNA and DNA metabolism in the fetal livers and brains. The feto-toxic effects of these two xenobiotics and their possible molecular mechanisms have been discussed.
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PMID:Toxicological consequences of chloroquine and ethanol on the developing fetus. 262 56

To determine if the carcinogenic potential of peroxisome proliferators is dependent upon their ability to induce cell proliferation, we have investigated the extent of cell proliferation in the livers of rats fed ciprofibrate, a peroxisome proliferator. Male rats were maintained on a diet containing ciprofibrate (0.025% w/w) and killed at selected intervals following 1 week of continuous [3H]thymidine labeling. Evaluation of labeling indices demonstrated a significant increase in cell proliferation during the first week but not in rats killed at the end of 5 and 20 weeks of treatment. Increases in hepatocyte nuclear labeling were found at 40 and 70 weeks of ciprofibrate administration which coincided with the appearance in livers of putative preneoplastic and neoplastic lesions. In a short-term feeding study, ciprofibrate and ethoxyquin were fed to rats at a dietary concentration of 0.025% and 0.5%, respectively, either alone or in combination for 7 days. Ciprofibrate and ethoxyquin either alone or in combination produced marked hepatomegaly and a significant increase in DNA synthesis as demonstrated by [3H]thymidine incorporation and autoradiographic studies. DNA synthesis in the group receiving ciprofibrate and ethoxyquin simultaneously, was slightly more than in animals that received either compound alone, suggesting a synergistic effect, although chronic feeding of these agents together resulted in inhibition of liver carcinogenesis (Rao, M. S. et al. (1984) Cancer Res., 44, 1072-1076). The results of this study further suggest that cell proliferation induced by peroxisome proliferators may be less important in carcinogenesis than peroxisome proliferation induced by these compounds.
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PMID:Evaluation of liver cell proliferation during ciprofibrate-induced hepatocarcinogenesis. 263 30

Human liver glycogen phosphorylase deficiency, also known as glycogen storage disease type VI (GSD VI) or Hers disease, is characterized by hepatomegaly and reduced or absent glycogenolytic response to the injection of glucagon. The recently isolated cDNA encoding the liver isozyme of glycogen phosphorylase was used to map the gene and identify restriction-fragment polymorphisms in normal Caucasians as a prerequisite for detecting linked GSD VI abnormalities. Results of restriction-enzyme analysis using a downstream fragment of the liver glycogen phosphorylase cDNA indicated the existence of a single gene copy per haploid genome. Hybridization of this downstream liver phosphorylase probe to dual laser-excited, sorted human chromosomes localized the gene to human chromosome 14. When the downstream probe was tested on genomic DNA cut with seven different restriction enzymes, a single MspI restriction-fragment-length polymorphism (RFLP) was observed in a single individual. In contrast, similar Southern blots performed with an upstream portion of the cDNA encoding liver phosphorylase revealed common RFLPs for four of eight enzymes tested, with minor polymorphic allele frequencies ranging from 33% to 44%. One of the four enzymes (TaqI) revealed two independent polymorphisms. If random distribution of these haplotypes among normal and disease loci, is assumed, approximately 92% of fetuses at risk for Hers disease will be informative when tested with the upstream liver phosphorylase probe.
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PMID:The polymorphic locus for glycogen storage disease VI (liver glycogen phosphorylase) maps to chromosome 14. 288 91

Previously, we have established that some peroxisome proliferators, a class of nongenotoxic hepatocarcinogens, are able to induce replicative DNA synthesis (RDS) in cultured hepatocytes. Hepatomegaly observed after short-term in vivo treatment correlated better with the ability to induce RDS than with the potency as peroxisome proliferator assessed in vitro. To clarify the challenging question of the limited sensitivity of primates to peroxisome proliferators, primary cultures of marmoset hepatocytes have been treated with nafenopin for some days. As expected from in vivo observations, no evidence for peroxisome proliferation could be observed. However, nafenopin induced a dose-dependent increase in the amount of RDS, but this induction was measurable only when the serum was absent from the culture medium. These results confirm that peroxisome proliferation and mitogenicity might be independent properties of peroxisome proliferators. Since in vivo the ability of compounds to induce RDS in liver cells is relevant to at least one key parameter of the hepatocarcinogenic response, it is suggested that measurement of RDS inducibility in cultured hepatocytes from different species might be relevant and useful to assess species differences in the liver tumor potency of nondirectly genotoxic compounds.
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PMID:Assessment of peroxisome proliferation and liver growth-stimulating potential by nondirectly genotoxic compounds in cultured hepatocytes. 315 2

Flow cytometry using a DNA label can quantitate aneuploid clones in malignant tissue. We illustrated the clinical value of this technique in a 71-year-old woman with acute megakaryocytic leukemia, which was diagnosed by staining of the blasts with factor VIII antigen and their morphologic resemblance to megakaryoblasts. Marrow cells were removed from needle biopsies by vortexing in RPMI medium, centrifuged in Ficoll-Hypaque, stained with a propidium-iodide/NP-40 mixture, and analyzed at 488 nm using an argon laser. During 3 weeks of low-dose cytosine arabinoside (ara-c) infusion therapy, hyperdiploid peak A dropped from 35% (day 0) to 2.3% (day 14) to 0% (day 21), with development of marrow hypoplasia. Similarly, hyperdiploid peak B, went from 7.6% to 9.1% to 3.5%. Subsequently, her marrow recovered normal morphology and lost the aneuploid peaks. Her blood counts recovered to near normal. Four months later, she relapsed and had a return of the day-21, incompletely eradicated peak B. There was no evidence of peak A. Repeated treatment with ara-c resulted in temporary suppression of the disease, but she died 3 months later with progressive hepatosplenomegaly. Analysis of cells from her enlarged liver, heavily infiltrated with blasts, showed a large hyperdiploid peak B. In this patient, ara-c therapy induced a remission with permanent eradication of one clone, but incomplete eradication of a second clone, which ultimately led to her relapse and death.
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PMID:Flow cytometry shows recurrent aneuploid clone after remission in megakaryocytic leukemia. 319 26

Cellular proliferation and differentiation of the mammalian mammary gland requires a medley of hormones including the anterior pituitary hormone, PRL. Recent evidence extends the role of PRL as a mammalian mitogen to cells in several physiological systems not directly involved in reproductive functions, such as liver and lymphocytes. PRL administration induces biochemical markers expressed during the G1 phase of cell cycle and activates DNA synthesis in rat liver. Chronic PRL treatment causes hepatomegaly, reflecting its stimulation of the proliferative process. In vitro, a lactogen-dependent cell line, the Nb2 rat node lymphoma cell, serves as a useful paradigm to study PRL action on mitogenesis. These cells, when cultured in the presence of lactogens, proliferate in a dose-dependent manner. The effects of various pharmacological agents on discrete phases of the cell cycle may be readily assessed in these cells since PRL-stimulated entry into cycle is signalled by an elevation of ODC activity at 6 hr and entry into S-phase at 6-12 hr. The parallel effects of phorbol ester tumor promoters and PRL on cell cycle progression in Nb2 lymphoma cells and in hepatic proliferation suggest that PRL may likewise mediate proliferation in aberrant growth conditions such as neoplasia. The data presented support the hypothesis that PRL is capable of promoting hepatocarcinogenesis. Its chronic administration after a hepatic initiating agent stimulated the development of histochemical and biochemical markers characteristic of preneoplasia. Further, the effect of PRL was comparable to that of the hepatocarcinogen when either was administered alone. Thus, hyperprolactinemia may serve to promote the development of hepatic tumors. Phorbol esters are thought to promote tumorigenesis by directly activating PKC. In the Nb2 lymphoma cell model, tumor promoting phorbol esters mimic the effects of PRL. Similarly, PRL-stimulated enzyme induction in liver is mirrored by phorbol ester treatment, and inhibitors of PKC block PRL-stimulated mitogenesis in Nb2 cells. Further, PRL or TPA administration to rats causes translocation of PKC activity from the hepatic cytosol to the membrane fraction, reflecting kinase activation. Therefore, PRL activation of PKC appears to be a physiological phenomenon of general significance, occurring as the result of lactogen receptor stimulation and serving to transmit intracellular signals linked to the regulation of mitogenesis. Further study is required to more fully define the scope of PRL-mediated mitogenic actions as well as its effects on the expression of differentiated products in tissues and cells.
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PMID:Prolactin as a mammalian mitogen and tumor promoter. 325 Feb 31

An increase in bile flow after phenobarbital administration occurs in the rat and other species; however, the mechanism(s) of the choleretic effect is incompletely understood and the role of the increase in liver weight is controversial. We therefore measured bile flow, bile acid secretion and pool size in male Sprague-Dawley rats pretreated with phenobarbital (75 mg/kg/day) for 6 days; liver weight, liver cell volume and DNA content were also evaluated. Phenobarbital treatment increased liver weight and mean hepatocyte volume by 39 and 26%, respectively, while total DNA content did not change, thus indicating that the hepatomegaly results principally from hypertrophy rather than hyperplasia. Bile flow was significantly higher in treated rats when expressed per unit of body weight (64.6 +/- 2.4 (S.E.) vs 53.3 +/- 1.6 microliter/min/kg; P less than 0.05) but was unchanged when expressed per gram of liver (1.40 +/- 0.04 vs 1.37 +/- 0.06 microliter/min/g; P greater than 0.5). The initial bile acid secretion rate and pool size were both significantly reduced in the phenobarbital group compared to controls (1224.2 +/- 110.4 vs 1656.6 +/- 163.2 nmol/kg/min and 562.8 +/- 41.5 vs 814.3 +/- 78.3 mumol/kg; both P less than 0.05), whereas the basal synthetic rate was unchanged. These findings suggest that the enlarged, phenobarbital-treated hepatocyte produces more bile than the normal cell, despite the decreased secretion of bile acids. Therefore, the drug-induced choleresis involves a selective increase in the bile acid-independent fraction of bile flow.
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PMID:Bile acid secretion and pool size during phenobarbital induced hypercholeresis. 334 Jun 28

Fifty-one asymptomatic Chinese hepatitis B surface antigen (HBsAg) carrier children (34 boys, 17 girls), age 1 to 15 years (median: 10 years), were prospectively followed for up to 4 years (median: 30 months) to determine the natural evolution of clinical, biochemical and virological features during the early phase of chronic hepatitis B virus infection. Hepatomegaly was the only abnormal finding on examination, being present in five children initially and four at follow-up. Serum ALT levels were normal in 80% of the children at presentation and remained within the normal range during the study in 60%. Fluctuations in ALT levels were mild. In four of 12 instances, transient elevations in ALT levels were associated with a fall in serum hepatitis B virus DNA levels. At presentation, 43 (84%) children were hepatitis B e antigen (HBeAg) positive; only two (7%) cleared HBeAg on follow-up. None of the eight children who were initially positive for the antibody to HBeAg reverted back to HBeAg positivity. All the children remained HBsAg positive. In this study, we demonstrated that chronic hepatitis B virus infection in asymptomatic Chinese children is usually associated with a mild and stable liver disease despite high levels of hepatitis B virus replication. This may reflect an immunological tolerance to the hepatitis B virus induced by early exposure to the virus and accounts for the persistently high levels of hepatitis B virus replication on follow-up.
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PMID:A longitudinal follow-up of asymptomatic hepatitis B surface antigen-positive Chinese children. 341 35


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