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)

Congenital parvovirus infection was diagnosed in two liveborn premature infants born at 24 and 35 weeks of gestational age. The illnesses were associated with placentomegaly, petechial rash, edema, hepatomegaly, anemia and thrombocytopenia, respiratory insufficiency, and death at 5 and 6 days of age. The syndromes exhibited by these cases shared common but nonspecific features with other life-threatening congenital infections. Serological studies in one case supported the diagnosis of parvoviral infection. Postmortem examination of both revealed nuclear inclusions in erythroid precursor cells characteristic of parvovirus infection. Use of the polymerase chain reaction confirmed the presence of parvovirus DNA in one of the cases. Intrauterine parvovirus B19 infection is most commonly associated with hydrops fetalis, "transient" hydrops, or a favorable outcome in infants found to be viremic after birth. These and previously reported examples of congenital B19 disease exemplify an exceptional form of human parvovirus infection.
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PMID:Congenital parvovirus infection. 935 30

Chronic administration of peroxisome proliferators to mice and rats results in hepatomegaly and ultimately carcinogenesis. The mechanism underlying the carcinogenic effect of nongenotoxic peroxisome proliferators is not well understood. To determine whether nongenotoxic carcinogenesis is receptor mediated, we evaluated the effect of the prototypical peroxisome proliferator Wy-14,643 on replicative DNA synthesis and carcinogenesis in the PPAR alpha-null mouse line. Male mice (F4, Sv/129 ter) of both genotypes (+/+) and (-/-) were fed either a control diet or one containing 0.1% Wy-14,643 for either 1 week, 5 weeks, or 11 months. Wild-type mice fed the Wy-14,643 diet for 1 or 5 weeks showed increased hepatic labeling by bromodeoxyuridine (BrDU) compared to untreated controls. In contrast, there was no increase in hepatic BrDU labeling index in (-/-) mice fed the Wy-14,643 diet for the same time periods compared to controls. After 11 months, 100% of the (+/+) mice fed the Wy-14,643 diet had multiple hepatocellular neoplasms, including adenomas and carcinomas, while the (-/-) mice fed the Wy-14,643 diet were unaffected. This work demonstrates that the effects of Wy-14,643 on replicative DNA synthesis and hepatocarcinogenesis are mediated by PPAR alpha.
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PMID:Role of PPAR alpha in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643. 939 98

Large cell change (LCC), characterized by cellular enlargement, nuclear pleomorphism and hyperchromasia, and multinucleation of hepatocytes, is a common lesion in cirrhotic livers, but its nature, significance, and pathogenesis remain uncertain. Therefore, we assessed the prognostic value of LCC as a marker of subsequent hepatocellular carcinoma (HCC) through a case-control study that compared pretransplant liver biopsy specimens from 37 cirrhotic liver transplant recipients with HCC to specimens from a control group of recipients without HCC, matched for sex, age (+/-5 years), and cause of cirrhosis. LCC was identified in 16 (43%) of the study and 7 (19%) of the control group biopsy specimens. By matched-pair analysis, LCC conveyed a moderately increased risk of later HCC with an estimated odds ratio of 3.3 (95% CI, 1.2-15; P = .038). However, a pathology review of 45 HCCs showed adjoining LCC in only 12 (27%) and did not suggest a morphological transition or a histogenetic association between the two lesions. LCC hepatocytes displayed a low proliferative rate by Ki-67 or proliferating cell nuclear antigen immunostaining (labeling indices of 0.27 and 0.73) but showed a greater degree of apoptosis than normal hepatocytes (labeling indices of 1.9 and 0.23; P = .03) To reconcile these findings, we propose that LCC derives from derangements in the hepatocyte's normal process of polyploidization. Such derangements, possibly caused by chronic inflammation-induced DNA damage, could yield a population of enlarged liver cells with nuclear atypia and pleomorphism, frequent binuclearity, and minimal proliferation. According to this hypothesis, LCC would be a habitual feature of cirrhosis and a regular accompaniment of HCC but would not represent a direct malignant precursor.
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PMID:Large cell change (liver cell dysplasia) and hepatocellular carcinoma in cirrhosis: matched case-control study, pathological analysis, and pathogenetic hypothesis. 979 34

A 4-year-old German girl was diagnosed as having glycogen storage disease type la and showed no other marked symptoms except hepatomegaly. The glucose-6-phosphatase activity in the liver was approximately 1.5% to 5.0% of normal values, and molecular analysis revealed compound heterozygosity for R83C and the novel mutation N264K. This result indicates that there is a wide clinical variation of glucose-6-phosphatase deficiency. DNA analysis is helpful for confirmation of the diagnosis, as well as establishment of the genotype and phenotype correlation in glycogen storage disease type 1a.
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PMID:A new mutation of the glucose-6-phosphatase gene in a 4-year-old girl with oligosymptomatic glycogen storage disease type 1a. 950 59

Glycogen storage disease type VI (GSD6) defines a group of disorders that cause hepatomegaly and hypoglycemia with reduced liver phosphorylase activity. The course of these disorders is generally mild, but definitive diagnosis requires invasive procedures. We analyzed a Mennonite kindred with an autosomal recessive form of GSD6 to determine the molecular defect and develop a non-invasive diagnostic test. Linkage analysis was performed using genetic markers flanking the liver glycogen phosphorylase gene ( PYGL ), which was suspected to be the cause of the disorder on biochemical grounds. Mennonite GSD6 was linked to the PYGL locus with a multipoint LOD score of 4.7. The PYGL gene was analyzed for mutations by sequencing genomic DNA. Sequencing of genomic DNA revealed a splice site abnormality of the intron 13 splice donor. Confirmation of the genomic mutation was performed by sequencing RT-PCR products, which showed heterogeneous PYGL mRNA lacking all or part of exon 13 in affected persons. This study is the first to demonstrate that a mutation in the PYGL gene can cause GSD6. This mutation is estimated to be present on 3% of Mennonite chromosomes and the disease affects 0.1% of that population. Determination of this mutation provides a basis for the development of a simple and non-invasive diagnostic test for the disease and the carrier state in this population and confirms biochemical data showing the importance of this gene in glucose homeostasis.
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PMID:Identification of a mutation in liver glycogen phosphorylase in glycogen storage disease type VI. 953 91

We demonstrate in this study the cytotoxic effects of inorganic arsenicals, arsenite and arsenate, and organic arsenic compounds, monomethylarsonic acid (MAA), dimethylarsinic acid (DMAA), and trimethylarsine oxide (TMAO), which are metabolites of inorganic arsenicals in human bodies, using murine macrophages in vitro. Inorganic arsenicals, both arsenite and arsenate, are strongly toxic to macrophages, and the concentration that decreased the number of surviving cells to 50% of that in untreated controls (IC50) was 5 or 500 microM, respectively. These inorganic arsenicals mainly caused necrotic cell death with partially apoptotic cell death; about 80% of dead cells were necrotic, and 20% were apoptotic. The inorganic arsenicals also induced marked release of an inflammatory cytokine, tumor necrosis factor alpha (TNF alpha), at cytotoxic doses. This strong cytotoxicity of an inorganic arsenical, arsenite, might be mediated via active oxygen and protease activation because it was inhibited by the addition of some antioxidant reagents, such as superoxide dismutase (SOD), catalase, and GSH, or by a peptide inhibitor of interleukin-1 beta-converting enzyme (ICE). It is likely that these immunotoxic effects of inorganic arsenicals may evoke both immunosuppression and inflammation, and they may be central factors causing carcinogenesis and severe inflammatory responses, such as hepatomegaly and splenomegaly, in chronic arsenicosis patients who daily ingested arsenic-contaminated well water. In contrast, the cytotoxic effects of methylated arsenic compounds were lower than those of inorganic arsenicals. The IC50 value of DMAA was about 5 mM, and MAA and TMAO had no toxicity even at concentrations over 10 mM. Additionally, these methylated chemicals suppressed the TNFalpha release from macrophages. DMAA induced mainly apoptotic cell death in macrophages as indicated by cellular morphological changes, condensed nuclei, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL), and DNA fragmentation. However, the cytotoxicity of DMAA might be induced via a different mechanism from that of inorganic arsenicals because it was not abolished by the additions of SOD, catalase, or ICE inhibitor. Conversely, GSH enhanced the toxicity of DMAA. These data suggest that methylation of inorganic arsenicals in mammals plays an important role in suppression of both severe immunosuppression and inflammatory responses caused by inorganic arsenicals.
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PMID:Inorganic and methylated arsenic compounds induce cell death in murine macrophages via different mechanisms. 954 97

The ratio of mtDNA and a nuclear reference gene was estimated by Southern blotting in the skeletal muscle DNA of a 3-year-old girl who suffered from congenital brain damage, focal epilepsy, hepatomegaly, malabsorption syndrome and severe myopathy. The signal ratio of mtDNA versus 18S rDNA was 22% of the mean value obtained from controls. No major deletions or insertions were found and the MERRF, MELAS and NARP mutations were ruled out. Mitochondrial DNA-encoded enzyme activities and mitochondrial respiration were reduced. The analysis of the NAD(P)H and flavoprotein redox states of intact fibres revealed the presence of mitochondrial dysfunction. In tissue sections a moderate elevation of type I and type II fibre diameter variation was detected, aberrant NADH- and succinate dehydrogenase staining and some ragged red fibres. This suggested that a mitochondrial disorder caused by a decrease in the amount of intact wild-type mtDNA was responsible for the severe myopathy.
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PMID:mtDNA depletion and impairment of mitochondrial function in a case of a multisystem disorder including severe myopathy. 970 May 97

The first case of Q fever endocarditis that has been diagnosed in Mexico is presented. A 10-year-old girl with discrete subaortic stenosis (SAS) and patent ductus arteriosus (PDA) was seen in December of 1996 with fever, hepatomegaly and splenomegaly. She presented also anemia, leukopenia, hypergammaglobulinemia, positive rheumatoid factor, cryoglobulinemia, antinuclear and anticytoplasmic antibodies (anti-RNA-proteins and anti-DNA). An aortic valve vegetation was seen by echocardiogram. Blood-cultures were negative. Antibody test for Coxiella burnetii was positive. Treatment with doxicyclin was initiated as soon the diagnosis was done. PDA was closed, SAS was liberated and two aortic vegetations were resected. Endocarditis in Q fever occurs when there is predisposing heart disease and/or immunodeficiency. Effective therapy has not yet been established. The diagnosis of Q fever endocarditis is difficult; it should be considered, in case of clinical suspicion of endocarditis with negative blood-cultures.
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PMID:[Coxiella burnetii endocarditis. A report of the first case diagnosed in Mexico]. 981 Mar 69

During cardiac surgery for transposition of the great arteries at age 7 weeks, a female infant received blood, fresh frozen plasma and platelet transfusions. Eleven days postoperatively, she developed bloody diarrhoea, fever, an erythematous macular rash, hepatomegaly, seizures and pancytopaenia. A clinical diagnosis of transfusion related graft-versus-host disease (GVHD) was supported by skin histopathology. DNA polymorphism studies confirmed that circulating lymphocytes in peripheral blood and infiltrating cells in the skin were foreign in origin and were derived from transfused blood cells. No underlying immunodeficiency was identified. Treatment with steroids cyclosporin and antithymocyte globulin was unsuccessful and death occurred 2 months after surgery. The features of fever, rash, diarrhoea, liver dysfunction and pancytopaenia which characterize GVHD may mimic drug reactions or viral infection. In addition to histological features on skin biopsy. DNA polymorphism studies on skin and blood samples provide a unique and sensitive method to confirm GVHD. Irradiation of blood products should be considered for acutely compromised infants requiring urgent cardiac surgery.
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PMID:DNA polymorphism analysis in transfusion-associated graft-versus-host disease. 1023 46

Insulin-dependent diabetes mellitus in both humans and animals leads to structural and functional changes including hepatomegaly. This study examined hypertrophy, hyperplasia, and apoptosis, three basic aspects of tissue growth, in livers of Sprague-Dawley and Wistar rats made diabetic by iv injection of streptozotocin 8, 30, or 90 days previously. Immunohistochemical measurement of proliferating cell nuclear antigen revealed that hepatic DNA labeling indices were similar in normal control animals and diabetic rats 30 or 90 days post diabetic induction, but were reduced to 45 to 50% of control in insulin-treated diabetic animals, perhaps due to altered receptor activity or to partial insulin resistance, as reported previously. Flow cytometry indicated a 613% increase in diploid hepatocytes in the livers of diabetic rats 30 days after the onset of diabetes, compared to control. Diabetic livers contained 29% fewer tetraploid cells, 81% fewer octaploid cells, and 20% more binucleated hepatocytes than normal controls. At 90 days, the overall smaller size of hepatocytes in diabetic tissue was evidenced by more cells per area. Insulin treatment prevented some of these changes, but did not restore ploidy to a normal distribution. Mitosis, while 300% of normal at 8 days after streptozotocin injection, was reduced to 25% of normal after 90 days of diabetes. The morphological evidence of apoptosis was decreased by 23% to 76% in the diabetic liver, and was reversed but not normalized by insulin treatment. This study indicates that the hepatomegaly observed in streptozotocin-induced experimental diabetes may be due primarily to early hyperplasia, and later decreased apoptosis.
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PMID:Decreased apoptosis as a mechanism for hepatomegaly in streptozotocin-induced diabetic rats. 1044 63


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