ABSTRACT
A novel mass spectrometry system is described here comprising a quadrupole-multireflecting time-of-flight design. The new multireflecting time-of-flight analyzer has an effective path length of 48 m and employs planar, gridless ion mirrors providing fourth-order energy focusing resulting in resolving power over 200â¯000 fwhm and sub-ppm mass accuracy. We show how these attributes are maintained with relatively fast acquisition speeds, setting the system apart from other high resolution mass spectrometers. We have integrated this new system into both liquid chromatography-mass spectrometry and mass spectrometry imaging workflows to demonstrate how the instrument characteristics are of benefit to these applications.
Subject(s)
Cryptococcosis/diagnosis , Cryptococcus gattii/isolation & purification , Eye Infections, Fungal/diagnosis , Retinitis/diagnosis , Administration, Oral , Adult , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Choroiditis/diagnosis , Choroiditis/microbiology , Cryptococcosis/drug therapy , Cryptococcosis/microbiology , Drug Therapy, Combination , Eye Diseases/diagnosis , Eye Diseases/microbiology , Eye Infections, Fungal/drug therapy , Eye Infections, Fungal/microbiology , Fluconazole/therapeutic use , Flucytosine/therapeutic use , HIV Infections/diagnosis , Humans , Infusions, Intravenous , Male , Meningitis, Cryptococcal/diagnosis , Meningitis, Cryptococcal/drug therapy , Meningitis, Cryptococcal/microbiology , Retinitis/drug therapy , Retinitis/microbiology , Tomography, Optical Coherence , Vitreous Body/microbiology , Vitreous Body/pathologyABSTRACT
Three siblings developed bilateral, visually significant posterior subcapsular cataracts in their teenage years and were implanted with the SA40N Array Multifocal IOL. A recall examination was performed on the siblings at 12, 10, and 9 years, respectively, after implantation.
Subject(s)
Cataract Extraction , Lens Implantation, Intraocular/methods , Vision, Ocular/physiology , Adolescent , Adult , Female , Humans , Refraction, Ocular/physiology , Siblings , Visual Acuity/physiology , Young AdultABSTRACT
This study elucidates the factors underlying the enhancement in efflux of human fibroblast unesterified cholesterol and phospholipid (PL) by lipid-free apolipoprotein (apo) A-I that is induced by cholesterol enrichment of the cells. Doubling the unesterified cholesterol content of the plasma membrane by incubation for 24 h with low density lipoprotein and lipid/cholesterol dispersions increases the pools of PL and cholesterol available for removal by apoA-I from about 0.8-5%; the initial rates of mass release of cholesterol and PL are both increased about 6-fold. Expression of the ATP binding cassette transporter A1 (ABCA1) is critical for this increased efflux of lipids, and cholesterol loading of the fibroblasts over 24 h increases ABCA1 mRNA about 12-fold. The presence of more ABCA1 and cholesterol in the plasma membrane results in a 2-fold increase in the level of specific binding of apoA-I to the cells with no change in binding affinity. Characterization of the species released from either control or cholesterol-enriched cells indicates that the plasma membrane domains from which lipids are removed are cholesterol-enriched with respect to the average plasma membrane composition. Cholesterol enrichment of fibroblasts also affects PL synthesis, and this leads to enhanced release of phosphatidylcholine (PC) relative to sphingomyelin (SM); the ratios of PC to SM solubilized from control and cholesterol-enriched fibroblasts are approximately 2/1 and 5/1, respectively. Biosynthesis of PC is critical for this preferential release of PC and the enhanced cholesterol efflux because inhibition of PC synthesis by choline depletion reduces cholesterol efflux from cholesterol-enriched cells. Overall, it is clear that enrichment of fibroblasts with unesterified cholesterol enhances efflux of cholesterol and PL to apoA-I because of three effects, 1) increased PC biosynthesis, 2) increased PC transport via ABCA1, and 3) increased cholesterol in the plasma membrane.
