Bone marrow transplantation in Niemann-Pick mice.
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Biomedical subjects
Publications and source records attributed to M Owada.
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Clinical pictures of 21 cases with I-cell disease patients, 12 males and 9 females, were analyzed. Characteristic coarse facial features and shortness of stature were observed in all cases. In general, the motor development was found to be more severely retarded than the mental development of the patients. Rather little involvement of the nervous system seemed to cause somewhat acceptable mental development in some cases, and also cause the absence of epileptic seizures in all cases. Involvement of the cardiovascular system, especially progressive hypertrophic cardiomyopathy, could be highly responsible for frequent sudden death of I-cell disease patients.
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The Niemann-Pick mice which received bone marrow transplants showed a decreased accumulation of sphingomyelin and cholesterol quantitatively in their spleen. The sphingomyelin deposit in the bone marrow was also reduced histochemically. However, the neurological manifestations were not improved by the bone marrow graft.
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Defects of neuraminidase activities towards sialyloligosaccharides in fibroblasts and leucocytes and enhanced excretion of sialyloligosaccharides in urine were shown in patients with adult type sialidosis with partial deficiency of beta-galactosidase and cherry red spot-myoclonus syndrome. No differences in their neuraminidase residual levels and urinary excretion patterns on thin-layer chromatography were found between these two disorders. In mucolipidosis II and III patients, the neuraminidase activities towards sialyloligosaccharides were almost normal in leucocytes, although decreased in fibroblasts. The discrepancy of neuraminidase activities towards 2 leads to 3 and 2 leads to 6 sialyloligosaccharide isomers was not noticed in all cases.
Prenatal diagnoses of I-cell disease were carried out by examination of the amniotic fluid and cultured amniotic cells in four cases of high-risk pregnancy in three different families. Three of the four fetuses were diagnosed as having I-cell disease, on the basis of observation of abnormally increased activity of lysosomal acid hydrolases in the amniotic fluid and their decreased activity in cultured amniotic cells, thus leading to therapeutic abortion. alpha-Mannosidase in the amniotic fluid of the fetuses with I-cell disease exhibited significant alterations in pH profile Km value, thermal stability and isoelectric focusing pattern, compared with the enzyme in normal controls. The results indicate that prenatal diagnosis of I-cell disease may be accomplished by demonstration of altered enzymological characteristics of alpha-mannosidase in the supernatant of amniotic fluid. The significance of the alteration of alpha-mannosidase in the amniotic fluid is not known.
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