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

Two cases of gangliosidosis due to aggregates of Gm1 are described. The first patient was a female infant with noticeable retardation in psychomotor development, coarse facies, hepatomegaly, and X-rays showing skeletal anomalies in the large bones, vertebral column, cranium and ribs. She died at the age of 10 months of a septic condition. The second patient was a male infant; deterioration in psychomotor development was first noticed 8 months after birth and this progressed slowly to arrive at a vegetative state with convulsions and myoclonus. The child died at the age of 4 years. There were no signs of enlargement of visceral organs but a cherry red stain was observed in the ophthalmologic examination. In the first case, necropsy revealed the presence of a deposit substance in the histiocytes of the hepatic sinusoids, spleen, pancreas, thymus, septi and pulmonary alveoli, intestinal lamina propria, epithelial cells of the renal glomeruli, and in the neurons and glial cells of the brain. The same deposits were observed only in the neurons and glial cells in the second case. Ultrastructural examination showed the presence of typical cytoplasmic membranous bodies in the central nervous system of both patients. The beta-galactosidase activity in the urine of both patients during life was zero. There was a higher than normal total amount of gangliosides in brain tissue samples from both (1906.7 and 2459.9 NANA/g respectively) as compared with normal values (724.0). This increase was proportional to the rise in Gm1 ganglioside (76.8 and 89.6 percent molar respectively) as compared to control (27.0). These clinical, morphologic, and biochemical data characterize both types 1 and 2 of gangliosidosis due to Gm1 aggregates.
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PMID:[Gm1 gangliosidosis types 1 and 2 (author's transl)]. 10 76

Acute toxicity of individual PCBs, which were categorized as either phenobarbital (PB)- or 3-methylcholanthrene (MC)-type inducers, was examined in young male Wistar rats, comparing their effects on growth rate, organ weight and liver lipid content, 5 days after a single i.p. injection. PB-type PCBs (2,4,3',4'- and 2,5,2'5'-tetrachlorobiphenyl), which slightly increased a content of cytochrome P450, did not show any significant toxicity at a dose of 100 mg/kg. On the contrary, MC-type PCBs (3,4,5,3',4'-pentachloro- and 3,4,5,3',4',5'-hexachlorobiphenyl), which markedly increased a content of cytochrome P448, strongly reduced growth rate and weights of thymus and spleen at a dose of 10 mg/kg. Liver enlargement accompanied by fatty liver was also observed only with MC-type PCBs. 3,4,3',4'-Tetrachlorobiphenyl was also toxic at a dose of 50 mg/kg, in keeping with its weak MC-type-inducing ability. Pretreatment with MC affected neither growth rate, spleen weight, nor liver lipid content. These results suggest that the toxic potency of PCBs is related to their MC-type inducing ability, but the toxic characteristics are different from those of MC itself.
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PMID:Possible correlation between induction modes of hepatic enzymes by PCBs and their toxicity in rats. 11 Jan 91

Previous studies have indicated that mice which differ in their acute susceptibility to responses mediated by the Ah receptor have a pattern of suppression of the antibody response which is consistent with a role by the putative dioxin receptor. The objective of the present investigation was to compare the TCDD-induced suppression of the antibody response following acute and subchronic exposures in B6C3F1 mice, an Ah-high-responder strain, and DBA/2 mice, an Ah-low-responder strain. Results of our initial studies demonstrate that suppression of humoral immunity can be enhanced in DBA/2 mice approximately 10-fold following subchronic versus acute exposures to the same cumulative doses of TCDD. This change in suppression of the antibody response in DBA/2 mice was not accompanied by significant changes in liver weight (hepatomegaly), as was observed in the B6C3F1 strain when exposed under comparable conditions. In contrast, effects on thymus weight (involution) were enhanced in the DBA/2 mice following subchronic exposure and demonstrated a higher degree of atrophy than was seen in the B6C3F1 strain (68 versus 56% decrease in thymic weight at the 42 micrograms/kg cumulative dose). These findings suggest that multiple mechanisms may be operating to suppress humoral immunity in vivo and that the conditions of exposure can alter the toxic effects of TCDD in the DBA/2, Ah-low responsive, mouse strain.
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PMID:Enhanced suppression of humoral immunity in DBA/2 mice following subchronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). 131 Jan 64

Stillborn calves (80 animals) originating from one dairy herd were used for studies on allometric measures in newborn calves. In the first approach some factors were neglected and only the effect of the calves' sex was considered. Differences in mean birthweight between male and female calves were reflected in organ and other body constituent weights too, but with different relations between them. Enlarged thyroid glands could be observed in both sexes but more often in female calves meaning that there is no correlation between thyroid size and body weight. Strong correlations of bones, muscles and outer body measures and looser ones of internal organs (thymus, liver, lung, kidneys, spleen) and endocrine glands (adrenal glands) with body weight were found especially in male calves. In some calves the sometimes enlarged liver looked like a fatty liver with its pale yellowish appearance and crumbly consistency.
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PMID:[Birth weight and measurements of various body parts of stillborn calves of a large dairy cattle herd]. 145 35

Scurfy (sf), is an X-linked recessive lethal mutation that occurs spontaneously in the C3H mouse. The disease is characterized by lymphoid and hematopoietic dysfunction. Affected males are of small stature and exhibit scaliness and crusting of the eyelids, ears, tail, and feet, marked splenomegaly, moderate hepatomegaly, enlarged lymph nodes, and atrophy of the thymus. The average lifespan of the affected hemizygous males (sf/y) is 24 +/- 0.7 days. Total cellular proteins were extracted from pooled samples of thymus and spleen obtained from combined litters of mice. Tissue-specific protein profiles characteristic of either sf mutant or normal mice were analyzed by two dimensional polyacrylamide gel electrophoresis (2DPAGE) at different stages of the phenotypic expression of the sf mutation, to identify changes in protein patterns that might be associated with the progression of the disease. The resultant gels were silver stained, digitized, and analyzed, by image analysis utilizing a pipelined image processor connected to a host computer. At 14 +/- 1 days of age, protein patterns from sf mutant and normal mice control organs showed considerable homogeneity, although there were proteins identified unique to the sf mutant and to the normal controls. At 20 +/- 1 days of age, the pattern differences between the sf mutant and normal control increased markedly. Differences were expressed as the percent of proteins that were unique to either the sf mutant or the normal control from the total number of each type. The percent of proteins that increased or decreased in the three organs utilized in this study ranged between 21%-39% at 14 days and were between 25%-54% at 20 days. Differences in protein expression between the normal and sf mutant as the disorder progressed for each of the three tissues examined. In addition, thymus protein profiles from 9 day old littermates that were phenotypically normal but genotypically unknown were evaluated to determine if marker proteins could be identified for the sf mutation. Limited protein changes were noted at relative molecular weights of 66, 60, 54, 39, 37, 33, 25, 23, 27, and 11 kDa. These data suggest that the sf mutation follows a trackable pattern of protein expression and repression different than the normal control C3H mouse. Several potential marker proteins associated with the sf mutation were identified in 9 day thymus prior to the phenotypic expression of the disease. These putative biomarkers may be useful for characterizing the sf mutation and the mutant may act a possible model the Wiskott-Aldrich syndrome (WAS).
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PMID:Two-dimensional polyacrylamide gel electrophoretic characterization of proteins from organs of C3H mice expressing the scurfy (sf) genetic mutation during early and late stages of disease progression. 147 19

CD-1 mice were given oral doses of 0-16 ml/kg/day for five days of Prudhoe Bay (PBCO), South Louisiana and Arabian Light crude oils, Bunker C oil (BCO), mineral oil (MO) and corn oil. Minor decreases in packed cell volume and increases in mean corpuscular hemoglobin concentration occurred after ingestion of crude oils and BCO. Dietary depletion of vitamin E and selenium failed to enhance hematological changes. Pronounced liver enlargement and atrophy of thymus and spleen accompanied ingestion of all petroleum oils except MO and were shown to be dependent on dose of PBCO. Concentration of RNA and total RNA were increased while total DNA, but not concentration of DNA, was increased in enlarged livers. Liver enlargement was attributed primarily to hyperplasia with an additional contribution due to hypertrophy. The severe hemolytic anemia reported in marine birds that ingested PBCO was not reproduced in mice. Liver enlargement and lymphoid tissue atrophy were similar to those reported in other species exposed to petroleum oils.
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PMID:The systemic toxicity of Prudhoe Bay Crude and other petroleum oils to CD-1 mice. 169 Sep 73

Weanling male Fischer 344 rats were exposed daily by gastric intubation for up to 15 weeks to the polychlorinated biphenyl (PCB) Aroclor 1254 at 0.1, 1, 10, or 25 mg/kg body weight. At 5, 10 and 15 weeks groups of rats were killed and immune functions were evaluated. The immune parameters examined included the following: body and lymphoid organ weights, mitogen-stimulated lymphoproliferative (LP) responses, natural killer (NK) cell activity, mixed lymphocyte reaction (MLR), and cytotoxic T lymphocyte (CTL) response. After 15 weeks of dosing body weights were reduced in rats receiving 25 mg/kg PCB while thymus weights were decreased in rats receiving 10 and 25 mg/kg. NK cell activity was reduced in rats dosed for 15 weeks at 10 and 25 mg/kg. The LP response to phytohemagglutinin was enhanced in rats dosed for 15 weeks at 25 mg/kg PCB. Exposure of rats to PCB did not affect the MLR or CTL responses. Other groups of rats were exposed to cyclophosphamide (CY) and served as positive controls for the immune assays employed. CY induced alterations in all of the immune parameters measured, indicating that this is an appropriate battery of immune function tests which is capable of detecting immune alterations in the rat. Alterations in immune function induced by daily gastric intubation with PCB were accompanied by reductions in body weight and/or hepatomegaly. These results suggest that the observed immune alterations may be related to the overt toxicity of this PCB in the rat.
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PMID:Evaluation of the immunotoxicity of low level PCB exposure in the rat. 249 55

T-2 toxin (T-2), a trichothecene mycotoxin, produced by several members of the genus Fusarium is a cytotoxic feed contaminant and has been shown to by immunomodulatory. It is suspected that T-2 associated immunomodulation is mediated partly through the hypothalamic-pituitary-adrenal (HPA) axis. T-2, prepared in 4% ethanol/corn oil, was administered orally to male CD-1 mice. Endotoxemia was evident 24 h after a single, oral exposure to T-2. Blood levels of corticosterone, indicative of the stress-response, increased 24 h after T-2 exposure. Hypothalamic norepinephrine and serum corticosterone levels increased in a dose-related manner after 2 weeks of T-2 exposure. Endotoxin, detected in the serum of animals exposed to 2.5 mg/kg T-2 for 1 week, was not associated with bacteremia. Neither endotoxin nor bacteremia were detectable after 2 or 4 weeks of T-2 exposure. Exposure to 2.5 mg/kg T-2 also affected several organs. The forestomach was ulcerated, with lymphocytic infiltration, epithelial proliferation, and hyperkeratinization. Increased spleen weight was associated with a proliferative red pulp. No histological changes were observed in the enlarged liver. Gastritis has been associated with increased corticosteroid production; cortical depletion and reduced mass of the thymus are phenomena attributable to increased corticosteroid levels. An increased corticosteroid level has been associated with thymic involution leading potentially to decreased T-dependent antibody response, a known effect of T-2.
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PMID:Relationship of the hypothalamic-pituitary-adrenal axis with chemically induced immunomodulation. I. Stress-like response after exposure to T-2 toxin. 254 45

The organic phase of the leachate (OPL) from the Love Canal chemical dump site contains more than 100 organic compounds including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The immunotoxic potential of OPL was determined in two mouse strains which differ in their sensitivity to aromatic hydrocarbon (Ah) receptor-mediated toxicity. OPL was administered in corn oil in a single oral gavage to male BALB/cByJ (Ahb/Ahb) mice (0.5, 0.8, or 1.1 g/kg) and DBA/2J (Ahd/Ahd) mice (0.6, 0.9, or 1.3 g/kg). TCDD was similarly administered at 0.25, 1.0, 4.0, or 16.0 micrograms/kg. Two days later all mice were immunized with sheep erythrocytes (SRBC). The antibody response (PFC) and organ weights were evaluated 4 days later. OPL produced thymic atrophy and hepatomegaly in both strains at all dose levels. The PFC/spleen in BALB/cByJ mice was significantly reduced at the three doses to 34, 13, and 15%, respectively, of the control response. Serum anti-SRBC antibody levels and relative spleen weights were also reduced. The only immune effect in the DBA/2J mice was a decrease of the PFC/spleen to 58% of the control at the highest dose. TCDD decreased the relative thymus and spleen weights only in BALB/cByJ mice. However, TCDD produced hepatomegaly, a decrease in serum antibody, and a decrease in PFC/spleen in both BALB/cByJ and DBA/2J mice to 3 and 15%, respectively, at 16 micrograms/kg. Thus, the TCDD dose required to cause a 50% suppression (ED50) of PFC/spleen for the BALB/cByJ and DBA/2J strains was 1.84 and 3.89 micrograms/kg, respectively. The ED50 for OPL was 0.24 g/kg in BALB/cByJ mice. The TCDD concentration in the OPL was estimated to be 7.6 ppm, which agrees closely with the chemical analysis (3 ppm). The results suggest that the immunosuppression caused by OPL in BALB/cByJ mice was primarily due to TCDD, that the non-TCDD components of OPL diminished the TCDD immunotoxicity in the DBA/2J strain, and that the thymic atrophy and hepatomegaly were caused primarily by the non-TCDD components of the OPL.
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PMID:Immunotoxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in a complex environmental mixture from the Love Canal. 271 30


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