35 research outputs found
Pitfalls in the diagnosis of acoustic neuroma
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71894/1/j.1365-2273.1984.tb01490.x.pd
The effects of neural synchronization and peripheral compression on the acoustic-reflex threshold
False-negative brainstem auditory evoked potential recordings in a case of multiple acoustic neuroma
Time Course of the Human Acoustic Stapedius Reflex: A Comparison of Eight Different Measures in Normal-hearing Subjects
Quantitation of Spatially-Localized Proteins in Tissue Samples using MALDI-MRM Imaging
MALDI imaging allows the creation of a “molecular
image”
of a tissue slice. This image is reconstructed from the ion abundances
in spectra obtained while rastering the laser over the tissue. These
images can then be correlated with tissue histology to detect potential
biomarkers of, for example, aberrant cell types. MALDI, however, is
known to have problems with ion suppression, making it difficult to
correlate measured ion abundance with concentration. It would be advantageous
to have a method which could provide more accurate protein concentration
measurements, particularly for screening applications or for precise
comparisons between samples. In this paper, we report the development
of a novel MALDI imaging method for the localization and accurate
quantitation of proteins in tissues. This method involves optimization
of in situ tryptic digestion, followed by reproducible and uniform
deposition of an isotopically labeled standard peptide from a target
protein onto the tissue, using an aerosol-generating device. Data
is acquired by MALDI multiple reaction monitoring (MRM) mass spectrometry
(MS), and accurate peptide quantitation is determined from the ratio
of MRM transitions for the endogenous unlabeled proteolytic peptides
to the corresponding transitions from the applied isotopically labeled
standard peptides. In a parallel experiment, the quantity of the labeled
peptide applied to the tissue was determined using a standard curve
generated from MALDI time-of-flight (TOF) MS data. This external calibration
curve was then used to determine the quantity of endogenous peptide
in a given area. All standard curves generate by this method had coefficients
of determination greater than 0.97. These proof-of-concept experiments
using MALDI MRM-based imaging show the feasibility for the precise
and accurate quantitation of tissue protein concentrations over 2
orders of magnitude, while maintaining the spatial localization information
for the proteins