Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A simple one-vial-method was developed for the quantitative determination of sphingomyelinase activity in human leukocytes and urine, using [14C-methyl] sphingomyelin. The measured activities of healthy control persons show a higher scatter in (n=50) urine (1.2 +/- 0.5 nmol/h . ml urine) than in (n=9) leukocytes (2.15 +/- 0.35 nmol/h . mg protein). Long term tests showed that the enzyme activities in urine can best be correlated to the 24-h-creatinine excretion. A distinct loss of enzyme activity was found in dialyzed urine starting at about the third day; this did not occur in undialyzed urine. The method also shows good reproducibility in micro-tests. It is therefore suitable for screening tests (urine of persons suffering from Niemann Pick disease) and for the prenatal diagnosis of sphingomyelinosis. For one out of two children with symptoms of sphingomyelinosis (hepatosplenomegaly, mental retardation, and neurological deterioration) the diagnosis was confirmed by morphological examination of tissues obtained by biopsy. In both cases leukocytes and urine revealed normal sphingomyelinase activity. These biochemical results in conjunction with the clinical and morphological picture were indicative of type C Niemann-Pick disease.
 ...
PMID:An improved and simple micro-method of sphingomyelinase assay in leukocytes and urine. 21 Nov 76

Mice with sphingomyelinosis (spm) with a C57BL/KsJ inbred background showed hepatosplenomegaly as early as four weeks (wk) of age and cerebellar signs around seven wk. Almost all animals died by 14 wk. Sudanophilic lipid accumulated in the liver, spleen, and lymph nodes as well as in the brain. The striking neuropathological change was a marked atrophy of the cerebellum, where Purkinje cells were predominantly involved. Loss of Purkinje cells started at the age of six wk before the cerebellar signs had become evident clinically. The cell loss appeared to be more marked in the vermis than in the hemispheres. Cytoplasmic inclusions in most cells consisted of myelin figures composed of concentric membranous lamellae. These inclusions were found mainly in the Purkinje cells at an early stage; thereafter, they were widely distributed in the granule cells, Golgi cells, some glial cells, macrophages and endothelial cells. The neuronal inclusions were frequently located in the vicinity of the Golgi apparatus; there were no unusual mitochondrial configurations. The clinicopathological characteristics of the mutant mice are similar to those of the human Niemann-Pick disease type C.
 ...
PMID:Cerebellar involvement in murine sphingomyelinosis: a new model of Niemann-Pick disease. 313 Apr 65

A new autosomal recessive gene causing sphingomyelinosis in mice is described. The name sphingomyelinosis is proposed for this mutant with the gene symbol spm. The disease syndrome caused by this gene has been diagnosed as an analogue of Niemann-Pick disease in humans. Affected mice cannot breed. They show neurological symptoms and weight loss beginning from around 7 weeks of age, and die at 12-14 weeks. By 8 weeks of age striking hepatosplenomegaly and marked enlargement of lymph nodes are present. Large areas of the liver and spleen are replaced by clusters of foam cells. Purkinje cells in the cerebellum are severely depleted. The contents of sphingomyelin and free cholesterol in the liver and spleen are markedly elevated. But the brain shows no obvious changes in lipid concentrations. Sphingomyelinase activity is reduced to about 30 percent that of the homozygous normal controls in the liver, 50 percent in the spleen and 70-80 percent in the brain. Heterozygotes are normal in both lipid concentrations and sphingomyelinase activity. The syndrome produced by spm is different in several ways from that produced by fm, which has been reported to cause sphingomyelinosis in mice.
 ...
PMID:Sphingomyelinosis, a new mutation in the mouse: a model of Niemann-Pick disease in humans. 720 25