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Biomedical subjects

Michael Buckley

Publications and source records attributed to Michael Buckley.

5 recordsLinked to original sources
PubMed2006

Interactive feature finding in liquid chromatography mass spectrometry data.

We propose a method for finding features in liquid chromatography mass spectrometry data that is based on the isotopic pattern of peaks. Our interactive approach to feature finding is carried out across many samples simultaneously and aligns features concurrently. Our scale-independent approach prioritises potential features and is easily adaptable to look for features of a particular mass and charge, paired features in isotopically labeled samples, or differentially expressed features. We demonstrate this by identifying features from normal human adult plasma. We highlight properties of plasma data that illustrate the need to visually check the quality of features found prior to further statistical analysis.

Blood Proteins↗
PubMed2005

Novel biomarkers of human growth hormone action from serum proteomic profiling using protein chip mass spectrometry.

CONTEXT: The detection of exogenous human GH (hGH) administration in athletes poses unique analytical problems, because its short circulating half-life provides only a brief opportunity to detect the administered hormone above endogenous levels. Measurement of novel GH-regulated serum protein biomarkers might provide an indirect method to detect exogenous GH. OBJECTIVE: The objective of this study was to identify new serum biomarkers of GH administration using proteomic profiling. DESIGN: Sera from a previously reported, double-blind, placebo-controlled GH administration trial were analyzed by protein chip mass spectrometry. SETTING: The study was performed at clinical research centers. SUBJECTS: Sixty healthy subjects, aged 18-40 yr, who were not elite athletes, were studied. INTERVENTIONS: Placebo or recombinant hGH treatment (0.1 or 0.2 IU/kg.d; 20 subjects/group) was administered for 4 wk, followed by an 8-wk washout period. MAIN OUTCOME MEASURES: Protein mass profiles were determined on immobilized Cu(2+) chips on d 0 and 21 of GH administration, and multivariate analysis was used to classify subjects into GH and placebo administration groups. RESULTS: When assessed by cross-validation, the classification performance of classifiers based on multivariate analysis of several GH-regulated peaks performed no better than classifiers based on the single best peak. This peak, a prominent biomarker of 15.1 kDa, was purified and identified as hemoglobin alpha-chain. The time course of the GH response of this biomarker is similar to that of other GH-dependent markers, such as IGF-I. CONCLUSION: This study demonstrates that protein mass profiling is an effective tool for the detection of GH administration and suggests that measurement of hemoglobin alpha-chain may have utility as a novel serum biomarker of GH action.

Adolescent↗
PubMed2002

PS-341, a novel proteasome inhibitor, induces Bcl-2 phosphorylation and cleavage in association with G2-M phase arrest and apoptosis.

Treatment with the proteasome inhibitor, PS-341 resulted in concentration- and time-dependent effects on Bcl-2 phosphorylation and cleavage in H460 cells that coincided with the PS-341-induced G2-M phase arrest. The observed Bcl-2 cleavage paralleled the degree of PS-341-induced apoptosis but was detected to a similar extent with comparable concentrations of two other proteasome inhibitors (MG-132 and PSI). Calpain inhibitors, ALLM and ALLN, and the caspase inhibitors, Z-VAD and AC-YVAD did not induce BcI-2 phosphorylation and cleavage. Exposure to PS-341 resulted in an additional Mr 25,000 cleavage fragment of Bcl-2, whereas only a Mr 23,000 fragment was observed with other anticancer agents. The formation of the Mr 25,000 fragment was not prevented by caspase inhibitors unlike the Mr 23,000 fragment, which suggests mediation by a caspase-independent pathway. Cell fractionation studies revealed that the Bcl-2 cleaved fragments localize within membrane structures and was an early event (at approximately 12 h, posttreatment), and before the observed cleavage of poly(ADP-ribose) polymerase (PARP), beta-catenin, and DNA fragmentation (at approximately 36 h posttreatment). The Mr 23,000 Bcl-2 cleavage product was inhibited by the pan-caspase inhibitor and the inhibitors of capase-3, -8, -9; but the PARP cleavage was prevented only by the pan-caspase and caspase-3 inhibitors, which suggests that the Mr 23,000 Bcl-2 cleavage occurred at both the initiation and execution stages of apoptosis. The inhibition of the ubiquitin/proteasome pathway by PS-341 leads, at an early stage of apoptosis, to Bcl-2 phosphorylation and a unique proteolytic cleavage product, which are associated with G2-M phase arrest and the induction of apoptosis.

Amino Acid Chloromethyl Ketones↗