An automated fluorescence microscopy assay using a nontoxic cholesterol binding protein, toxin domain 4, (D4), was developed in order to identify chemical compounds modifying intracellular cholesterol metabolism and distribution. Using this method, we screened a library of 1,056 compounds and identified 35 compounds that decreased D4 binding to the cell surface. Among them, 8 compounds were al...

The Golgi apparatus is a key element in the ordered movement of secretory polypeptides from the rough endoplasmic reticulum to the plasma membrane during secretion. It has been shown that cisternae that receive membranes from the reticulum are morphologically similar to the latter and that cisternae liberating secretory granules resemble that plasma membrane. By using an ultrastructural probe f...

Wide differences exist among the polyene antibiotics, nystatin, rimocidin, filipin, pimaricin, and amphotericin B, with reference to steroid interference with their antifungal activities against Candida albicans. Of the numerous steroids tested, ergosterol was the only one which effectively antagonized the antifungal activity of all five polyene antibiotics. The antifungal activities of nystati...

A series of LM cell variants resistant to filipin, but not auxotrophic for sterol, was isolated by plating mutagenized, filipin-treated cells on soft agar medium containing no sterol. Cloned variants were assayed for growth in the presence and absence of sterol or unsaturated fatty acid. Filipin-resistant clones whose growth rate was unaffected by the addition of sterol to the medium were furth...

Kinsky, Stephen C. (Washington University, St. Louis, Mo.). Effect of polyene antibiotics on protoplasts of Neurospora crassa. J. Bacteriol. 83:351-358. 1962.-The polyene antibiotics nystatin, amphotericin B, and filipin induced shrinkage of Neurospora crassa protoplasts stabilized in sucrose. At low concentrations of filipin (5 mug per ml), or higher concentrations of nystatin and amphotericin...

Niemann-Pick type C is a lysosomal storage disease associated with mutations in NPC1 or NPC2, resulting in an accumulation of cholesterol in the endosomal-lysosomal system. Niemann-Pick type C has a clinical spectrum that ranges from a neonatal rapidly fatal disorder to an adult-onset chronic neurodegenerative disease combined with remarkably, in some cases, hematological defects such as thromb...

BACKGROUND AND PURPOSE Variable alterations to the structure of the corpus callosum have been described in adults with NPC, a neurometabolic disorder known to result in both white and gray matter pathology. This study sought to examine the structure of the callosum in a group of adult patients with NPC and compared callosal structure with a group of matched controls, and to relate callosal stru...

Fatty acids cause a decrease in the absorption spectra of the antifungal polyene macrolide antibiotics nystatin, filipin, candicidin, and amphotericin B. For nystatin, filipin, and candicidin, this decrease in absorption could be correlated with the activity of the fatty acids in protecting the yeast Saccharomyces cerevisiae against the action of these antibiotics. With amphotericin B a correla...

Niemann–Pick C (NPC) disease is rare, neurodegenerative, lysosomal cholesterol storage disorder. Diagnosis of the disease is often delayed due to disease heterogeneity, non-specific early visceral and neurological symptoms, and lack of a rapid and reliable diagnostic assay. As a result, the disease progresses and opportunities to intervene tragically are lost. Until recently, the principal diag...