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For example, Denis F. Hochstrasser, head of the department of clinical pathology at the University Hospital of Geneva, Switzerland, presented a plenary lecture on proteomics and MS in medicine in which he called MS "the future of molecular medicine." He labeled his comment as a "provocative statement," but undoubtedly, few people in the audience found his words controversial. To push MS into clinical practice, Hochstrasser would like to see matrix-assisted laser desorption and ionization (MALDI) MS used as a "molecular scanner." In such a device, proteins are separated by gel electrophoresis and then transblotted through a trypsin membrane onto a capture membrane, rather than spots being cut out and digested for MS analysis. A rapid scan is done first to obtain the image of the membrane. A slower scan is used to identify proteins by their peptide fingerprint. If proteins still can't be identified at that point, tandem MS is used to sequence the peptides. Such methods are being developed for use in the clinic for the analysis of proteinuria (a condition in which urine contains an abnormal amount of protein) and tissue biopsies. Hochstrasser reminded the audience that dynamic range of protein concentration remains a challenge for MS analysis of biological samples. There are probably about 100,000 plasma proteins, he said, with concentrations ranging from the millimolar level for albumin down to the femtomolar level for proteins such as tumor necrosis factor. Many proteins are present at concentrations that are too low to be detected by a mass spectrometer, or they may simply be masked by high-concentration proteins. For example, with the use of two-dimensional gel electrophoresis on a crude plasma sample, only about 100 different proteins can be resolved. Removing albumin and immunoglobulins from the sample makes it possible to observe proteins at lower concentrations, extending the analysis to about 1,000 proteins, Hochstrasser said. |
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