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 effects of peroxisome proliferating agents have been implicated in their carcinogenicity. WY-14,643 stimulates an increase in hepatocellular DNA replication that persists with continued administration, but it is unclear if other peroxisome proliferators share this property. In these studies, WY-14,643 was compared to clofibric acid, nafenopin and LY171883 given to rats in the diet for up to 30 days. DNA replication in the rat liver was quantified by immunohistochemical methods after continuous s.c. infusion of bromodeoxyuridine by osmotic minipump. During the first 7 days of treatment, WY-14,643 (0.1% in diet) and nafenopin (0.05%) increased the percentage of bromodeoxyuridine-labeled hepatocytes to greater than 50%, from 3% in controls. Clofibric acid (0.5%) and LY171883 (0.3%) increased the labeling to approximately 33%. The replicative response to each of the compounds was localized primarily to the periportal region of the liver lobule. The time-course of replication induced by clofibric acid and WY-14,64.3 was examined over 3 day intervals. The peak of replication in response to clofibric acid occurred during days 4-6, whereas the effect of WY-14,643 peaked during days 1-3 and was much greater than clofibric acid. The replicative response to WY-14,643 persisted through 30 days at dietary concentrations of 0.1 and 0.005%. Nafenopin, LY171883 and clofibric acid were without effect on DNA replication on days 28-30 even though the hepatomegaly and induction of peroxisomal beta-oxidation persisted. Thus, under the conditions of these experiments, the persistent replicative effect through 30 days was unique to WY-14,643. Although sustained replication in the general population of hepatocytes may be involved in the carcinogenesis of WY-14,643, it does not appear to be a factor in the hepatocarcinogenesis of the other peroxisome proliferators.
Carcinogenesis 1991 Sep
PMID:Hepatocellular DNA synthesis in rats given peroxisome proliferating agents: comparison of WY-14,643 to clofibric acid, nafenopin and LY171883. 189 15

Hairless mice were exposed to UVB irradiation from a Philips T1 12 light source. Mice that were exposed to UV-light and not protected with 5% p-aminobenzoic acid (PABA) showed a significantly higher number of peripheral blood granulocytes (P less than 0.001) and a significantly higher mean weight of both the spleen and the liver (P less than 0.001) than the non-irradiated controls. Light microscopy of the histology of the enlarged liver and spleen showed a proliferation of granulocytes and the reticuloendothelial cells. Treatment with topical PABA during the whole period of UV-exposure prevented the peripheral blood granulocytosis. These protected mice also had a significantly (P less than 0.001) lower mean weight for the liver and spleen than UV-exposed and non-protected mice.
Br J Dermatol 1991 Sep
PMID:Ultraviolet light induction of peripheral granulocytosis with splenomegaly: protection of mice with topical p-aminobenzoic acid (PABA). 191 13

An endocrine cell carcinoma is a carcinoid tumor that has an especially malignant prognosis. We herein report on 2 cases of a biliary endocrine cell carcinoma. Case 1 involved a 68 year old man manifesting a fever, jaundice, hepatomegaly and a ballooned gallbladder. After decreasing the jaundice by PTCD, an exploratory abdominal operation was performed. As a tumor was found at the papilla of Vater, a pancreaticoduodenectomy was done. Case 2 involved a 72 year old woman who was diagnosed as having a gallbladder tumor and cholelithiasis. She was given a cholecystectomy and a choledocholithotomy. These 2 cases had hepatic metastasis within a year and subsequently died. Procedurally, an endocrine cell carcinoma should be treated separately from classical carcinoid tumors.
Gan No Rinsho 1990 Sep
PMID:[A biliary endocrine cell carcinoma: a report of two cases]. 223 74

The first twenty-one cases of Paediatric Acquired Immunodeficiency Syndrome (PAIDS) in Trinidad and Tobago were studied. An overwhelming majority of patients were of African descent. Most of the children presented within the first year of life, the average time between presentation and death was 4 1/2 months, and the majority presented with either diarrhoea or pneumonia or failure to thrive, common conditions in the West Indies. Fever lasting longer than two weeks as well as hepatomegaly were clues which led to a definitive diagnosis.
West Indian Med J 1990 Sep
PMID:Paediatric acquired immunodeficiency syndrome (PAIDS) in Trinidad and Tobago. 226 32

Three patients with amyloidosis in whom hepatomegaly was the main sign ara presented. In all cases jaundice coexisted which is regarded as a rare sign in amyloidosis. Attention is called to the diagnostic difficulties of amyloidosis especially without a preceding clinically overt disease process. The presence of a particularly high activity of alkaline phosphatase in the serum, and focal absence of 99Tc uptake by the hepatic macrophage system in liver scintigram suggested liver tumour. However, demonstration of monoclonal protein in blood, urine or ascitic fluid, or raised level of alpha 2 globulin, should call attention to the possibility of liver amyloidosis. The authors stress the usefulness of the method of preincubation of tissue biopsy specimens in potassium hypermanganate during routine staining with Congo red for differentiation of amyloid AA from amyloid AL.
Pol Arch Med Wewn 1990 Sep
PMID:[Diagnostic difficulties in hepatic amyloidosis--clinical analysis and autopsy data of 3 cases]. 226 76

We previously reported that streptococcal preparation (OK-432), which is a TNF inducer, inhibits insulitis and development of autoimmune diabetes in nonobese diabetic (NOD) mice and Bio-Breeding (BB) rats, as animal models of insulin-dependent diabetes mellitus. We have recently shown that recombinant human (h)TNF-alpha also suppresses development of diabetes in NOD mice. In this study we have extended our observation on TNF to BB rats in order to see whether TNF generally inhibits autoimmune diabetes. A total of 5 x 10(4) U of rhTNF-alpha was administered i.p., twice a week to male and female BB rats from 4 to 27 wk of age. The cumulative incidence of diabetes by 27 wk of age in nontreated rats was 36.4% (8/22), whereas that in hTNF-alpha-treated rats was 0% (0/21) (p less than 0.001). The hTNF-alpha-treated rats did not lose body weight and maintained normal blood glucose concentrations. Immunologic and histologic examinations were performed at the end of the experiment. Spleen cell cytotoxicities for NK-sensitive YAC-1 and rat insulinoma (RINm5F) cells in hTNF-alpha-treated rats significantly decreased in comparison with nontreated and nondiabetic BB rats. Intensity of insulitis was also inhibited in hTNF-alpha-treated rats. Interestingly, a huge hepatomegaly and splenomegaly was found in two of the 21 hTNF-alpha-treated rats. The latter consisted of W3/13dull+ and W3/25dull+ cells, which did not exhibit cytotoxicity for either YAC-1 or RINm5F cells. These results indicate that the chronic and systemic administration of TNF has a regulatory role in autoimmune diabetes in BB rats as well as in NOD mice, and that these animals may have a defect in TNF-mediated immunoregulation.
J Immunol 1990 Sep 01
PMID:Inhibition of type 1 diabetes in BB rats with recombinant human tumor necrosis factor-alpha. 238 63

The influence of ciprofibrate, a potent oxyisobutyrate derivative, on several hepatic enzyme parameters was studied in five rat strains following a 14-day treatment period. Ciprofibrate-dependent hepatomegaly was observed at two dose levels (2 and 20 mg/kg) in all rat strains examined. A 10- to 15-fold induction in the 12-hydroxylation of lauric acid with a less marked 1.5- to 5-fold induction of 11-hydroxylation was observed in treated animals. This dose-dependent increase in fatty acid hydroxylase activity was associated with a maximal 10-fold increase in the specific content of cytochrome P-450 IVA1 isoenzyme apoprotein, as assessed immunochemically using an ELISA technique. The activities of the cytochrome P-450 I (IA1 and IA2) and II (IIB1 and IIB2) families, as measured by ethoxyresorufin-O-deethylase and benzphetamine-N-demethylase activities respectively, were decreased on treatment. In the mitochondria, monoamine oxidase activity was significantly decreased at the higher dose level whereas alpha-glycerophosphate dehydrogenase activity was elevated. Total carnitine acetyltransferase activity (mitochondrial and peroxisomal) and peroxisomal beta-oxidation were markedly increased at both dose levels in all strains examined. Cytosolic glutathione peroxidase activity, measured using both t-butylhydroperoxide and hydrogen peroxide as substrates, was decreased on treatment to approximately 50% of the control value. In treated animals, a marked increase in mRNA levels coding for cytochrome P-450 IVA1 and the peroxisomal bifunctional protein of the fatty acid beta-oxidation spiral was observed. However, mRNA levels coding for glutathione peroxidase appeared unchanged following ciprofibrate administration, in contrast to the above-noted decrease of glutathione peroxidase enzyme activity. Taken collectively, our results have further substantiated a close association between the induction of microsomal cytochrome P-450 IVA1, peroxisomal beta-oxidation and total carnitine acetyltransferase activity in rat liver, and have performed a conceptual basis for the rationalization of the chronic toxicity of peroxisome proliferators in this species.
Biochem Pharmacol 1990 Sep 01
PMID:Characterization of the hepatic responses to the short-term administration of ciprofibrate in several rat strain. Co-induction of microsomal cytochrome P-450 IVA1 and peroxisome proliferation. 239 Jan 5

We have examined, relative to clofibric acid (CPIB), the effects of a chemical series of phenoxyacetic acids and of two asymmetric CPIB analogues, the R(+)- and S(-)-enantiomers of 2-(4-chlorophenoxy)propionic acid (4-CPPA) and 2-(4-chlorophenoxy)butyric acid (4-CPBA), on hepatic peroxisome proliferation both in vivo and in vitro utilizing cholesterol-fed rats and primary cultured rat hepatocytes respectively. Peroxisome proliferation was assessed by measuring changes in peroxisomal fatty acyl-CoA oxidase (FACO) and microsomal laurate hydroxylase (LH) activities as well as by electron microscopic examination of 3,3'-diaminobenzidine-stained liver slices. CPIB and enantiomers of 4-CPPA and 4-CPBA (0.6 mmol/kg/day for 7 days) produced hepatomegaly, lowered serum cholesterol levels, and caused 4.7- to 12.9-fold and 2.9- to 6.1-fold increases in hepatic FACO and LH activities, respectively, in cholesterol-fed rats. Electron micrographs of liver cells showed an increased number of peroxisomes from cholesterol-fed rats given S(-)-4-CPBA and CPIB. Likewise, these compounds (0.03 to 1.0 mM) induced FACO and LH in primary rat hepatocyte cultures after 72 hr. R(+)- and S(-)-Enantiomers of 4-CPPA produced similar concentration-dependent and maximal increases in both FACO and LH activities, whereas enantiomeric selectivity [S(-) greater than R(+)] for the induction of these two enzymes was observed with the isomers of 4-CPBA. The increases in the activities of FACO and LH caused by S(-)-4-CPBA were similar to those elicited by 1.0 mM CPIB (58.6- and 9.8-fold respectively). These results show that the enantiomers of 4-CPPA and 4-CPBA induce the peroxisome proliferation-associated enzymes FACO and LH in vivo and in vitro, and that the S(-)-isomer of 4-CPBA causes a greater induction of FACO and LH in vitro than its corresponding R(+)-isomer, indicating that these two enzymes are induced in an enantioselective manner. Optimal induction of the peroxisome proliferation-associated enzymes FACO and LH in rat hepatocyte cultures was produced by phenoxyacetic acids possessing (1) a chlorine atom at the 4-position of the phenyl ring, (2) a dimethyl or mono-ethyl substitution at the alpha-carbon atom of the carboxylic acid side chain; and (3) an S(-)-orientation for chiral analogues possessing a mono-ethyl group at the alpha-carbon atom of the carboxylic acid side chain.(ABSTRACT TRUNCATED AT 400 WORDS)
Biochem Pharmacol 1990 Sep 15
PMID:In vivo and in vitro peroxisome proliferation properties of selected clofibrate analogues in the rat. Structure-activity relationships. 240 80

The pattern of illness in 60 consecutive children with homozygous sickle cell disease who attended the Paediatric Emergency Room of a busy Lagos hospital with acute illness was studied prospectively. Their ages ranged from 3 months to 13 years with a peak in the 2nd year. There were twice as many boys as girls. The commonest symptoms were fever, limb or abdominal pain and cough, and the commonest signs were pallor and hepatomegaly. Painful crises occurred in 27, anaemic crises in 11, and a combination of these in 12 children. Infection was detected in 76% of subjects in crises. Infection was found in 82% of all the children and was mainly bacterial. The commonest infections were pneumonia (35%), bacteraemia (32%), tonsillitis/pharyngitis (17%) and osteomyelitis (8%). The predominant bacteria isolated were Klebsiella spp (38%), E. coli (23%), Staph. aureus (23%), Staph. albus (23%) and Pseudomonas spp (23%). Some children had multiple isolates. Bacterial infection was a major cause of morbidity in very young children and merits appropriate control and preventive measures in this age group. The spectrum of bacteria isolated makes it unlikely that the specific anti-pneumococcal measures widely advocated in Europe and America for young children with SCA would be appropriate in Nigeria.
Ann Trop Paediatr 1987 Sep
PMID:Acute illness in Nigerian children with sickle cell anaemia. 244 66

Three patients affected by infantile Refsum disease are described with mental retardation, minor facial dysmorphia, chorioretinopathy, sensorineural hearing deficit, hepatomegaly, failure to thrive and hypocholesterolaemia. Initially, only an accumulation of phytanic acid was thought to be present. More recent findings showed a biochemical profile very similar to that found in classical Zellweger syndrome or neonatal adrenoleukodystrophy. Morphologically typical peroxisomes were absent in the liver. All three disorders are associated with multiple peroxisomal dysfunction. Because of these similarities pertinent clinical data of our three patients are compared with those of reported patients diagnosed as having infantile Refsum disease, neonatal adrenoleukodystrophy or Zellweger syndrome who survived for several years. Attention is drawn to the difference in severity of clinical features, ranging from infantile Refsum's disease to neonatal adrenoleukodystrophy and, finally, to Zellweger syndrome.
Eur J Pediatr 1987 Sep
PMID:Infantile Refsum disease: an inherited peroxisomal disorder. Comparison with Zellweger syndrome and neonatal adrenoleukodystrophy. 244 76


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