Niemann-Pick cells

The thesis advanced by Epstein (1932) that lipid in liver cells and kidney epithelium results from passive infiltration, while glial cells, ganglion cells, and histiocytes store lipid actively, has been convincingly repudiated by Letterer (1939, 1947). 

While the typical cells in Gaucher s disease are usually limited to a few organs, NPC may be found almost everywhere in the body. However, corresponding to the distribution of the reticulo-endothelial system they will be most abundant in tissues of this system which therefore should preferably be biopsied for diagnostic purposes. As a rule, NPC cannot be recovered from circulating blood, and, according to Bloom (1928), the vascular endothelium is not a precursor for these cells. 

Accessory spleens were described by Crocker and Farber (1958) in three out of 14 cases their detection is facilitated by an increase in size, which parallels that of the main organ. 

The liver is enlarged, although rarely as much as the spleen. The average increase in weight of ten livers was 1.5 times (range 0.8—2.7) the age-corrected normal (Crocker and Farber 1958). Hepatomegaly is less in older patients. 

The organ is usually firmer than normal, although Pick (1927, 1933), in addition to very hard livers, also found organs of a doughy consistency. The cut surface is greyish-yellow, yellow or salmon colored. According to Niemann (1914) its color resembles that of the fatty liver observed in phosphorus poisoning. 

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Otterbach, B., and Stoffel, W., 1995, Acid sphingomyelinase-deficient mice mimic the neurovisceral form of human lysosomal storage disease (Niemann-Pick). Cell 81 1053-1061. 

Moussa M, Landrier JF, Reboul E, Ghiringhelli O, Comera C, Collet X, Frohlich K, Bohm V and Borel P. 2008. Lycopene absorption in human intestinal cells and in mice involves scavenger receptor class B type I but not Niemann-Pick Cl-like 1. J Nutr 138 1432-1436. 

Arora S, Beaudry C, Bisanz KM et al (2010) A high-content RNAi-screening assay to identify modulators of cholesterol accumulation in Niemann-Pick type C cells. Assay Drug Dev Technol 8 295-320... 

Niemann-Pick disease. Kolodny, E.H. (2000). Curr Opin Hematol, 7 1 48-52. [647919] Intracerebral transplantation of adult mouse neural progenitor cells into the Niemann-Pick-A mouse leads to a marked decrease in lysosomal storage pathology. Shihabuddin, L.S., Numan, S., Huff, M.R., Dodge, J.C., Clarke, J., Macauley, S.L., Yang, W., Taksir, T.V., Parsons, G., Passini, M.A., Gage, F.H., Stewart, G.R. (2004). J Neurosci, 24 (47) 10642-10651. 

Accumulation of lipids in spleen cells from a patient with Niemann-Pick disease. 

The receptors can be recycled, whereas the lipoprotein remnants in the vesicle are transferred to lysosomes and degraded by lysosomal (hydrolytic) enzymes, releasing free cholesterol, amro acids, fatty acids, and phospholipids. These compounds can be reutilized by the cell. [Note Rare autosomal recessive deficiencies in the ability to hydrolyze lysosomal cholesteryl esters (Wolman disease), or to transport unesterified cholesterol out of the lyso some (Niemann-Pick disease, type C) have been identified.]... 

In the very rare and fatal Niemann-Pick Cl disease lysosomes in cells of the central nervous system and the viscera accumulate LDL-derived cholesterol. Study of the DNA of patients led to discovery of a 1278-residue integral membrane protein, which may be required for the Golgi-mediated transport of unest-erified cholesterol from lysosomes to the ER.189/232 234c... 

The deficiency of any lysosomal enzyme results in accumulation of its substrate in lysosomes. Some of these diseases include Hurler syndrome, Hunter syndrome, I-cell disease, Niemann-Pick disease,... 

Jin, H. K. and Schuchman, E. H. (2003). Ex vivo gene therapy using bone marrow-derived cells Combined effects of intracerebral and intravenous transplantation in a mouse model of Niemann-Pick disease. Mol. Ther. 8, 876-885. 

The second major class of sphingoglycolipids found in mammalian cells is the ganglioside. It was first isolated from the brains of humans who died as the result of Niemann-Pick disease and later was also identified in those persons who were diagnosed with Tay-Sachs disorder. The gangliosides are present in... 

Acid sphingomyelinase is a lysosomal enzyme that catalyzes the breakdown of sphingomyelin to ceramide and phosphoryl-choline.A deficiency of this enzyme leads to lysosomal accumulation of sphingomyelin in patients with Niemann-Pick disease. Recent data indicate that correct intracellular targeting of acid sphingomyelinase to lysosomes is dependent on the mannose 6-phosphate-mediated pathway. Does this imply that the I-cell patient will present with Niemann-Pick symptoms Can I-cell disease be viewed as a constellation of many lysosomal storage diseases ... 

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