Biomedical subjects

Michael P Hall

Publications and source records attributed to Michael P Hall.

4 recordsLinked to original sources

PubMed2007

Indications for rotator cuff repair: a systematic review.

Despite the popularity of surgical repair of rotator cuff tears, literature regarding the indications for and timing of surgery are sparse. We performed a systematic review of the literature to investigate factors influencing the decision to surgically repair symptomatic, full-thickness rotator cuff tears. Specifically, how do demographic variables, duration of symptoms, timing of surgery, physical examination findings, and size of tear affect treatment outcome and indications for surgery? We reviewed the best available evidence, which offers some guidelines for surgical decision making. Variables suggest earlier surgical intervention may be needed in the setting of weakness and substantial functional disability. With regard to demographic variables, the evidence is unclear regarding their association with treatment outcome. However, older chronological age does not seem to portend a worse outcome. Pending worker's compensation claims does seem to negatively affect treatment results. Further research is required to define the indications for surgery for full thickness rotator cuff tears. However, the design and conduct of an ethical study to obtain Level I evidence on this issue will be a major challenge.

Age Factors↗

PubMed2005

Stable isotope methods for high-precision proteomics.

Stable isotope tagging methods provide a useful means of determining the relative expression level of individual proteins between samples in a mass spectrometer with high precision (coefficients of variation less than 10%). Because two or more samples tagged with different numbers of stable isotopes can be mixed before any processing steps, sample-to-sample recovery differences are eliminated. Mass spectrometry also allows post-translational modifications, splice variations and mutations (often unnoticed in immunoassays) to be detected and identified, increasing the clinical relevance of the assay and avoiding the issues of non-specific binding and cross-reactivity observed in immunoassays. Several stable isotope tagging methods are available for use in proteomics research. We discuss the advantages and disadvantages of each technique with respect to biomarker discovery, target validation, efficacy and toxicology screening and clinical diagnostic applications.

Isotope Labeling↗

PubMed2004

Isotope-differentiated binding energy shift tags (IDBEST) for improved targeted biomarker discovery and validation.

Mass spectrometry has proved to be an important tool for protein biomarker discovery, identification and characterization. However, global proteomic profiling strategies often fail to identify known low-abundance biomarkers as a result of the limited dynamic range of mass spectrometry (two to three orders of magnitude) compared with the large dynamic range of protein concentrations in biologic fluids (11 to 12 orders of magnitude for serum). In addition, the number of peptides generated in such methods vastly overwhelms the resolution capacity of mass spectrometers, requiring extensive sample clean-up (e.g., affinity tag, retentate chromatography and/or high-performance liquid chromatography) before mass spectrometry analysis. Baiting and affinity pre-enrichment strategies, which overcome the dynamic range and sample complexity issues of global proteomic strategies, are very difficult to couple to mass spectrometry. This is due to the fact that it is nearly impossible to sort target peptides from those of the bait since there will be many cases of isobaric peptides. IDBEST (Target Discovery, Inc.) is a new tagging strategy that enables such pre-enrichment of specific proteins or protein classes as the resulting tagged peptides are distinguishable from those of the bait by a mass defect shift of approximately 0.1 atomic mass units. The special characteristics of these tags allow: resolution of tagged peptides from untagged peptides through incorporation of a mass defect element; high-precision quantitation of up- and downregulation by using stable isotope versions of the same tag; and potential analysis of protein isoforms through more complete peptide coverage from the proteins of interest.

Biomarkers↗

PubMed2003

"Mass defect" tags for biomolecular mass spectrometry.

We present a new class of "mass defect" tags with utility in biomolecular mass spectrometry. These tags, incorporating element(s) with atomic numbers between 17 (Cl) and 77 (Ir), have a substantially different nuclear binding energy (mass defect) from the elements common to biomolecules. This mass defect yields a readily resolvable mass difference between tagged and untagged species in high-resolution mass spectrometers. We present the use of a subset of these tags in a new protein sequencing application. This sequencing technique has advantages over existing mass spectral protein identification methodologies: intact proteins are quickly sequenced and unambiguously identified using only an inexpensive, robust mass spectrometer. We discuss the potential broader utility of these tags for the sequencing of other biomolecules, differential display applications and combinatorial methods.

Animals↗