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

Daily, for 14 days, rabbits of one group were injected with corticotropin, i.e. ACTH-zinc-phosphate (10 units/kg), whereas rabbits of another group were given (in addition) sodium ribonucleate (40 mg/kg) through a tube into the stomach. Formation of lysyl-tRNA, leucyl-tRNA, and alanyl-tRNA in the liver and the skeletal muscles proved to be significantly greater in the animals which received ACTH together with sodium ribonucleate, as compared to that in the animals given the hormone alone. Hyperglycemia, hepatomegaly, and emaciation were less pronounced in the animals given both the preparations.
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PMID:[Effect of enteral administration of sodium ribonucleate on the synthesis of amino acyl t RNA in the liver and skeletal muscles of rabbits in experimental hypercorticism]. 19 79

Clinical and biochemical diagnostic studies concerned 17 cases of galactosemia coming from 15 not consauguineous families. Galactosemia was diagnosed between 1-st day and 11-th month of life. Tentative diagnosis based on clinical picture was made in 12 infants, others were detected through family history of galactosemia and/or biochemical newborn screening carried out at the National Research Institute of Mother and Child since 1969. Clinical symptoms of galactosemia occurred in most patients in the first week of life. They were the following (tab. II): hepatomegaly (in 94%), jaundice (81%), splenomegaly (79%), vomitus (62%) and diarrhoea in 56% of patients. Cataract was found in 6 infants (38%). Biochemical diagnosis was based on the results of enzymatic estimation of galactose-1-phosphate uridyl transferase activity in blood, galactose-1-phosphate in red blood cells and galactose in blood and urine. No activity of galactose-1-phosphate uridyl transferase was found in all patients, and the concentration of galactose-1-phosphate was higher than 25 mg/100 ml of red blood cells. High galactose level was observed in blood and urine in all patients with typical clinical course of galactosemia. In 2 patients however without clinical symptoms of the disease only trace amounts of galactose was detected in blood and urine. All these patients were treated with galactose free diet.
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PMID:[Clinical and biochemical diagnosis of galactosemia among our cases]. 26 27

Clinical data on 24 civilian patients hospitalized for malaria in The New York Hospital were analyzed. Of 16 patients infected with Plasmodium falciparum, 14 acquired the disease in West Africa. Only three of the 24 had taken recommended courses of prophylaxis. Diagnosis was invariably, and often dangerously, delayed because physicians often made diagnoses of viral syndromes or used antibiotics; only one patient had a blood smear taken by a personal physician. Although all patients had fever and chills, classic malarial fever was seen in only seven patients; nausea, vomiting and diarrhea were common. Hepatomegaly and splenomegaly occurred in about half the patients. Blood smears stained in routine fashion by Wright's stain were positive in 23 of 24 patients. A normal leukocyte count was present in 19 of the 24 patients and thrombocytopenia in 16 of 23. The most frequent complications were those of central nervous system involvement. Therapy consisted mainly of chloroquine phosphate but other drugs, including quinine, pyrimethamine, sulfonamides and primaquine, were used in special situations. Suggestions for prophylaxis, diagnosis and therapy were made.
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PMID:Malaria - the mime. Recent lessons from a group of civilian travellers. 78 38

Infantile Refsum's disease was diagnosed in three male patients, presenting with facial dysmorphia, retinitis pigmentosa, neurosensory hearing loss, hepatomegaly, osteopenia and delayed growth and psychomotor development. An elevated plasma phytanic acid concentration and a deficient phytanic acid oxidase activity in fibroblasts were found with an accumulation of very long chain fatty acids in plasma and fibroblasts. There were elevated pipecolic acid levels in plasma, urine and CSF, and abnormal bile acid metabolites in plasma. Deficient activity of acylCoA: dihydroxyacetone phosphate acyl transferase was found in thrombocytes and fibroblasts of these patients as well as an impaired de novo plasmalogen biosynthesis in fibroblasts. These biochemical abnormalities, previously described in the Zellweger syndrome, suggest multiple peroxisomal dysfunction in our patients.
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PMID:Infantile Refsum's disease: biochemical findings suggesting multiple peroxisomal dysfunction. 242 95

The hepatic glucose-6-phosphatase system was studied with a novel microanalytical technique in adult patients undergoing liver biopsy. 4 patients were diagnosed as having type 1 glycogen storage disease (GSD). 3 of these patients, who had hypoglycaemic symptoms, had variations of type 1a GSD, which is caused by a defect in the hepatic microsomal glucose-6-phosphatase enzyme. The fourth, with hepatomegaly and no hypoglycaemic symptoms, had a normal glucose-6-phosphatase enzyme but a defect in the hepatic microsomal phosphate/pyrophosphate translocase T2; this is the first report of an adult with type 1c GSD. Adult type 1 GSD should be considered in patients with unresolved hypoglycaemic symptoms and/or unresolved hepatomegaly.
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PMID:Diagnosis of type 1a and type 1c glycogen storage diseases in adults. 288 97

A retrospective analysis of staging results from 308 patients with Hodgkin's disease (HD) was performed in order to relate clinico-pathological findings with respect to the liver to other staging results and to prognosis. Thirty-four patients had clinically enlarged liver, 80 had increased serum-enzyme levels indicating possible liver damage, but only 10 patients had biopsy-proven histologic evidence of HD in the liver (7 primary biopsies, 3 re-biopsies). Among the prognostic correlations not only advanced stage and liver infiltrates were connected to poor prognosis, but also--even in early stages--elevated serum enzyme values (S-GOT and alkaline phosphate).
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PMID:The liver in Hodgkin's disease--I. Clinico-pathological relations. 688 20

Cancer cachexia contributes to the demise of a significant number of cancer patients, and severe loss of adipose tissue is a prominent component of this syndrome. One of the products of fat catabolism is glycerol, and its turnover is elevated in the cancerous state. Since glycerol is also one of the most important gluconeogenic substrates, its role in the augmented and abnormal gluconeogenesis of cancer hosts needs to be defined. In the present study, we examined hepatic glycerol metabolism in livers of Fischer 344 rats bearing s.c. nonmetastatic adenocarcinoma R3230AC. Five weeks after tumor inoculation, the liver was removed and perfused with 5 mM [2-13C]glycerol while 13C nuclear magnetic resonance spectroscopy was performed. In the livers of tumorous rats, we found: (a) lipogenesis from glycerol was augmented; (b) the rate of hepatic glycerol uptake was unchanged; (c) glucose production from glycerol was not altered; and (d) conversion of glycerol 3-phosphate to dihydroxyacetone phosphate remains the rate-limiting step. Therefore, it appears that, in cancer hosts, diminished glycerol clearance is not due to reduction in hepatic glycerol uptake or metabolism, and the abnormal gluconeogenesis involves the pathway prior to the entry of glycerol. The exaggerated lipolysis is probably used for the pathological hepatomegaly, and the availability of the cytosolic hydrogen acceptor remains the rate-limiting factor for glycerol metabolism.
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PMID:Hepatic glycerol metabolism in tumorous rats: a 13C nuclear magnetic resonance study. 785 Jul 86

An 8-year-old boy with galactose-1-phosphate uridyl transferase (GALT) deficiency presented with hypotonia, muscle hypotrophy, hepatomegaly, bilateral cataract and mild mental retardation. Two brothers showed a GALT activity consistent with a homozygotic condition and both parents were found to be heterozygotes for this defect. Histological and ultrastructural examination of muscle biopsy specimens showed several necrotic fibres. GALT activity was undetectable in skeletal muscle and muscle tissue cultures; myotubes converted galactose to CO2 at a lower rate than controls. Galactose-1-phosphate was increased in the patient's red cells and muscle tissue. GALT deficiency, not previously described in muscle, may be of pathogenic relevance in determining the myopathic features present in GALT deficiency syndrome.
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PMID:Clinical and biochemical evidence of skeletal muscle involvement in galactose-1-phosphate uridyl transferase deficiency. 832 30

The effects of ciprofibrate and fenofibrate, which are more potent peroxisome proliferators than clofibrate, on the activities of dihydroxyacetone-phosphate acyl-transferase (DHAP-AT) and glycerol-3-phosphate acyl-transferase (G3P-AT) were studied at the two pH optima 5.5 and 7.4 in subcellular fractions of rat liver, and in solubilized peroxisomal membranes (PMP) as well. Protein was also analyzed by gel electrophoresis. 1) Under the conditions of the specific activity of peroxisomal acyl-CoA oxidase (CN(-)-ACO) being increased (8 to 9-fold), there was no specific induction of the DHAP-AT activity when measured at pH 5.5 in purified peroxisomes and PMP. However, the total activities of DHAP-AT in these two fractions were increased by 6 to 11 times, as a result of hepatomegaly and peroxisome proliferation. In contrast, they were only slightly enhanced (x 1.1 to 2.2-fold) when determined at pH 7.4. The magnitude of the effects of a fibrate treatment was, therefore, dependent on the pH of the incubation medium. 2) Experiments of reversibility of enzyme induction reinforced the finding that the peroxisomal DHAP-AT activity is not specifically induced by ciprofibrate and fenofibrate. 3) Our results suggest the existence of a peroxisomal G3P-AT, non-inducible by fibrates, in the rat liver. 4) Induction of peroxisomal membrane-associated polypeptides with apparent molecular masses of 26- and 36-kDa was evidenced in stained electrophoretic gels of protein.
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PMID:Effects of two peroxisome proliferators (ciprofibrate and fenofibrate) on peroxisomal membrane proteins and dihydroxyacetone-phosphate acyl-transferase activity in rat liver. 846 41


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