Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 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

Experimental evidence for the presence and biosynthesis of subviral, leukemogenic particles in the isolated mitochondria of spleen cells of mice infected with Rauscher murine leukemia (RML) virus is presented. These subviral particles sediment at a density of 1.27-1.29 g/ml and induce splenomegaly and RML three weeks after i.v. or i.p. administration to white mice. Virosomes have been labelled with [32P]phosphate in the isolated mitochondria from RML spleen cells and high molecular weight (70S) [32P]RNA has been isolated from these subviral, leukemogenic particles. Rauscher virus group specific antigens were detected by immunodiffusion in the inner membrane and matrix fraction of the mitochondria of RML spleen cells. These results together with our earlier findings strongly suggest that mitochondria of the transformed cells participate in the biosynthesis of RNA tumor viruses. Possible mechanism of the penetration of viral genetic information of RNA tumor viruses into mitochondria of tumor cells in vivo is discussed.
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PMID:Biosynthesis of subviral oncogenic particles (virosomes) in mitochondria of Rous sarcoma and Rauscher murine leukemia cells. 19 96

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

The onset of postpolycythemic myeoloid metaplasia or spent polycythemia has been recognized for many years. As the result of many different series, the development of postpolycythemic myeolid metaplasia might be expected in from 15%-20% of patients with postpolycythemia vera. It appears that an etiologic role for sodium phosphate 32P may exist in this evolutionary pattern. About 70% of patients with PPMM will have symptoms with the onset of the syndrome. The major mechanisms producing symptoms result from (1) anemia, (2) pressure from massive splenomegaly, and (3) bleeding problems. Iron deficiency is a frequent cause of anemia in patients with PPMM. The major mechanism of anemia in these patients, however, relates to ineffective erythropoiesis and shortened red cell survival. Androgen trials for ineffective erythropoiesis seem worthwhile, although data on this point is too limited to draw any firm conclusions. A steroid trial for those patients with major hemolytic episodes is indicated. In those patients in whom adrenal steroid therapy fails to control major hemolysis, a consideration for splenectomy exists. Pressure-related manifestations secondary to massive splenomegaly have been treated with radiation therapy and oral alkylators. Although there is data to document amelioration of painful symptoms with associated shrinking of the spleen, long-term control of this problem has not been forthcoming. Again, patients who are medical failures in control of pressure-related manifestations may be considered for splenectomy. Bleeding problems may arise with PPMM secondary to thrombocytopenia, thrombocythemia, or qualitative platelet dysfunction. Adrenal steroids have met with some success in improving platelet counts in patients with life-threatening thrombocytopenia. Those patients who are medical failures with adrenal steroids in terms of thrombocytopenia might be candidates for splenectomy. Control of thrombocythemia has been observed with oral alkylator therapy and chlorambucil may have a special role in managing this complication. Qualitative platelet defects leading to severe bleeding are best managed with fresh platelet transfusions. Patients with PPMM in contrast to patients with agnogenic myeoloid metaplasia have a more lethal syndrome and shortened survivorship. Causes of death in patients with PPMM include cardiac problems, transition to acute leukemia, hemorrhage, and infection.
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PMID:The evolution into and the treatment of late stage polycythemia vera. 125 Dec 24

We describe the unique clinical and histopathologic features of a child with biochemical and immunocytochemical features of Niemann-Pick disease type C (NPC). Clinically, she was found to have multiple xanthomas of the upper aerodigestive tract with dysphagia and expressive language delay, splenomegaly, bony infarcts, and type IIb hyperlipidemia. Neurologic examination was otherwise normal. Microscopy revealed foam cells in her bone marrow, liver, tongue, tonsils, glottis, and in normal-appearing peritonsillar mucosa. Lipid analysis of a liver biopsy specimen showed a small increase in phospholipids, a twofold increase in sphingomyelin, a fivefold increase in cholesterol, and a marked (25-fold) increase in bis(monoacylglycerol) phosphate. Lysosomal acid hydrolase activities in cultured skin fibroblasts were nondiagnostic. Biochemical and immunocytochemical studies of cultured fibroblasts demonstrated lysosomal accumulation of unesterified LDL-derived cholesterol as well as delayed induction of homeostatic responses to endogenous cholesterol consistent with a diagnosis of NPC. Based upon these observations, we speculate that this patient could have a new phenotypic expression of NPC or represents a new cholesterol lipidosis biochemically resembling NPC. The chance occurrence of two separate lipid disorders seems less likely.
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PMID:Clinical, pathologic, and biochemical features of a cholesterol lipidosis accompanied by hyperlipidemia and xanthomas. 151 68

The effects of dietary phosphate binder on deoxycorticosterone (DOC)-salt-hypertensive rats were examined. DOC-treated and non-DOC-treated rats were fed the diet either with or without phosphate binder, dihydroxyaluminum aminoacetate. All rats drank 1% NaCl. DOC-salt-treated rats without binder demonstrated marked glomerular hypertrophy, many globally sclerosed glomeruli, severe proteinuria, focal cardiac fibrosis, and splenomegaly. A significant reduction of glomerular hypertrophy, glomerulosclerosis, severity of proteinuria, splenomegaly, and the myocardial lesion took place when the DOC-salt-treated rats were given phosphate binder. The globally sclerosed glomeruli exhibited remarkable hypertrophy while structurally preserved glomeruli showed little evidence of enlargement. The plasma phosphate level was low in rats with dietary phosphate binder. In conclusion, the dietary phosphate binder ameliorated glomerular hypertrophy, glomerulosclerosis, proteinuria, myocardial fibrosis, and splenomegaly occurring in DOC-salt-treated rats. The data indicated that there was an association between glomerular hypertrophy and glomerulosclerosis in this model. The exact mechanisms of action of the phosphate binder, however, remain far from clear.
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PMID:Prevention of 11-deoxycorticosterone-salt-induced glomerular hypertrophy and glomerulosclerosis by dietary phosphate binder. 231 24

Cyclic phosphate derivative of DHPG, 2'-nor-cGMP [9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]-guani ne phosphate-oxide] was evaluated for activity against guinea pig cytomegalovirus (GPCMV) infection in cultured guinea pig embryo cells and in guinea pigs. By virus yield reduction and plaque reduction assays, 2'-nor-cGMP was demonstrated to be 15- to 20-fold more potent against GPCMV infection than its parental drug DHPG. The selectivity index of 2-nor-cGMP was 110, which was 10-fold higher than that of DHPG. In cultured cells, 2'-nor-cGMP attained maximal antiviral activity when added to the cells within 12 h postinfection. In the studies on GPCMV infection in guinea pigs, 2'-nor-cGMP administered subcutaneously once daily (5 mg/kg per day) for 8 days, starting 24 after virus inoculation, significantly suppressed GPCMV infectivity titers in the blood, spleen, lung, and salivary gland during acute infection (10 days postinfection) as compared with sham-treated infected animals. A greater reduction of GPCMV infectivity titers in the salivary gland was noted during chronic infection (i.e., 24 days postinfection). Clinically, splenomegaly and peripheral lymphocytosis were significantly modified as compared with the sham-treated animals (P less than 0.05). The drug, administered at this dosage, was reasonably tolerated by the guinea pigs and showed clinical benefit.
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PMID:Effect of 2'-nor-cyclic GMP against guinea pig cytomegalovirus infection. 255

The human erythrocyte generates high-energy adenosine triphosphate by anaerobic glycolysis and cycles oxidized and reduced nicotinamide adenine dinucleotide phosphate by the aerobic pentose phosphate shunt pathway. Certain enzymopathies of the pentose phosphate shunt are associated with hemolysis resulting from oxidative denaturation of hemoglobin. Glucose-6-phosphate dehydrogenase deficiency, an X-chromosome-linked disorder, is the prototype of these diseases and is genetically and clinically polymorphic. Six enzymopathies of anaerobic glycolysis cause hemolytic anemia; lactate dehydrogenase deficiency does not. In 2,3-diphosphoglycerate mutase deficiency, 2,3-diphosphoglycerate is greatly reduced and asymptomatic polycythemia is noted. Pyrimidine-5'-nucleotidase deficiency, an enzymopathy of nucleotide metabolism, is characterized by intracellular accumulations of pyrimidine-containing nucleotides, marked basophilic stippling on the stained blood film, splenomegaly, and hemolysis. Lead inhibits the nucleotidase and an identical syndrome occurs during severe lead poisoning. Hemolysis also accompanies an unusual enzymopathy characterized by a 40- to 70-fold increase (not decrease) in adenosine deaminase activity.
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PMID:Hemolytic anemias and erythrocyte enzymopathies. 299 Feb 76

The biological activity and time of appearance of alveolar hydatid cyst induced splenic amyloid enhancing factor (AEF) with respect to amyloid deposition in the spleens were determined in C57BL/6J mice. Mice were infected intraperitoneally with 100 alveolar hydatid cysts (AHC) and killed bi-weekly between 2 and 14 weeks postinfection (p.i.). AHCs and spleens were excised, weighed and a portion of each spleen was sectioned and stained for quantitation of amyloid deposits and histological studies. The remaining spleen pieces were sonicated separately in cold phosphate buffered saline, pH 7.4 (I g/10 ml), centrifuged (27,000 g, 60 min, 4 degrees C) and the supernatant tested for AEF activity. Splenomegaly followed the progressive increase in the AHC biomass and AEF activity coincided with the appearance of amyloid deposits at 6 weeks p.i. A 2.5 mg intraperitoneal protein dosage of AEF in conjunction with a subcutaneous injection of 0.5 ml of a 0.11 M AgNO3 solution in mice, induced the maximum amount of splenic amyloid deposition at 48 h; the amount of splenic amyloid deposits decreased by either increasing or decreasing the AEF dosage. In vivo, 70% of the AEF activity was abolished by day 4 post-injection of AEF and completely by 3 weeks. These findings indicate that AHC-induced AEF is functionally analogous to casein-induced AEF and its appearance in the spleen coincides with neutrophilia, histiocytosis and amyloid deposition.
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PMID:Induction of amyloid enhancing factor and its biological properties in murine alveolar hydatidosis. 334 56


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