Defective regulation of intracellular cholesterol metabolism has been investigated in cultured fibroblasts from two subtypes of Niemann-Pick type II disease: the panethnic Niemann-Pick type C (NPC) and the Nova Scotia type D (NPD). Cell extracts from NPC and NPD fibroblasts cultured in lipoprotein-deficient medium exhibited activities of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase that were two-fold greater than in normal cells. Addition of serum resulted in only a 15% decrease in HMG-CoA reductase activity within 6 h in these cells, compared with a decrease of 80% in normal fibroblasts. The initial rate of return to maximal values for the first 6 h after removal of serum was similar in all three cell types; thereafter, the rate was faster in the mutant fibroblasts. Binding and internalization of 125I-labeled low density lipoprotein (LDL) was not decreased within 12 h of incubation of NPC fibroblasts with serum, while a decrease of 50% was observed for both NPD and normal fibroblasts over this time period. Northern blot analysis also indicated a slower decrease in steady-state LDL receptor mRNA in NPC relative to normal and NPD cells. In all three cell types, inhibition of HMG-CoA reductase with mevinolin had no effect on serum-stimulated cholesterol esterification, while inhibition of acyl-CoA:cholesterol acyltransferase with Sandoz 58-035 did not influence HMG-CoA reductase activity, indicating that defects in these regulatory mechanisms are independent.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood↗

PubMedDate not supplied

Evaluation of the cost-effectiveness of various passive monitors and active monitors for industrial hygiene sampling.

A framework for evaluating passive or active industrial hygiene air sampling monitors on a cost-effectiveness basis is described. Five passive monitors and one active monitor (charcoal tube with pump) were compared in several hypothetical scenarios. Using certain assumptions regarding method validation costs, sampling equipment costs, and labor costs, both a per sample cost and a total annual cost were calculated for each type of sampling monitor as a function of total samples taken per year. The results of this study indicate that even when the additional expense of full validation of the passive sampling monitor is required, these monitors are more cost-effective than active monitors. A specific type of passive monitor utilizing replaceable capsules is the most cost-effective when more than 500 samples per year are taken.

Air Pollution, Indoor↗