Biomedical subjects

Peter Wong

Publications and source records attributed to Peter Wong.

8 recordsLinked to original sources

PubMed2006

Improved proteomic discovery by sample pre-fractionation using dual-column ion-exchange high performance liquid chromatography.

Clinically relevant biomarkers are urgently needed for improving patient diagnosis, risk stratification, prognosis and therapeutic treatments. There is a particularly compelling motivation for identifying protein-based indicators of early-stage disease for more effective interventions. Despite recent progress, the proteomic discovery process remains a daunting challenge due to the sheer heterogeneity and skewed protein abundances in biofluids. Even the most advanced mass spectrometry systems exhibit limiting overall dynamic ranges and sensitivities relative to the needs of modern biomedical applications. To this end, we report the development of a robust, rapid, and reproducible high performance ion-exchange liquid chromatography pre-fractionation method that allows for improved proteomic detection coverage of complex biological specimens using basic tandem mass spectrometry screening procedures. This form of sample simplification prior to global proteomic profiling, which we refer to collectively as 'fractionomics', increases the number and diversity of proteins that can be confidently identified in tissue and cell lysates as compared to the straight analysis of unfractionated crude extracts.

Animals↗

PubMed2006

Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.

Identification of protein-protein interactions often provides insight into protein function, and many cellular processes are performed by stable protein complexes. We used tandem affinity purification to process 4,562 different tagged proteins of the yeast Saccharomyces cerevisiae. Each preparation was analysed by both matrix-assisted laser desorption/ionization-time of flight mass spectrometry and liquid chromatography tandem mass spectrometry to increase coverage and accuracy. Machine learning was used to integrate the mass spectrometry scores and assign probabilities to the protein-protein interactions. Among 4,087 different proteins identified with high confidence by mass spectrometry from 2,357 successful purifications, our core data set (median precision of 0.69) comprises 7,123 protein-protein interactions involving 2,708 proteins. A Markov clustering algorithm organized these interactions into 547 protein complexes averaging 4.9 subunits per complex, about half of them absent from the MIPS database, as well as 429 additional interactions between pairs of complexes. The data (all of which are available online) will help future studies on individual proteins as well as functional genomics and systems biology.

Biological Evolution↗

PubMed2005

Interactions of the Escherichia coli hydrogenase biosynthetic proteins: HybG complex formation.

Assembly of the active site of the [NiFe]-hydrogenase enzymes involves a multi-step pathway and the coordinated activity of many accessory proteins. To analyze complex formation between these factors in Escherichia coli, they were genomically tagged and native multi-protein complexes were isolated. This method validated multiple interactions reported in separate studies from several organisms and defined a new complex containing the putative chaperone HybG and the large subunit of hydrogenase 1 or 2. The complex also includes HypE and HypD, which interact with each other before joining the larger complex.

Escherichia coli↗

PubMed2004

Notch1-expressing cells are indispensable for prostatic branching morphogenesis during development and re-growth following castration and androgen replacement.

Notch expression is frequently associated with progenitor cells, and its function is crucial for development. Our recent work showing that Notch1 is selectively expressed in basal epithelial cells of the prostate and higher Notch1 expression during development suggests that Notch1-expressing cells may define progenitor cells in the prostate. To test this hypothesis, we have generated a transgenic mouse line in which the Notch1-expressing cells can be ablated in a controlled manner. Specific targeting was achieved by expressing the bacterial nitroreductase, an enzyme that catalyzes its substrate into a cytotoxin capable of inducing apoptosis, under the Notch1 promoter. Cell death in transgenic prostate was confirmed by histological analyses including terminal dUTP nick-end labeling and caspase 3 immunocytochemical staining. We evaluated the consequences of ablation of Notch1-expressing cells in two systems, organ culture of early postnatal prostates and re-growth of prostate in castrated mice triggered by hormone replacement. Our data show that elimination of Notch1-expressing cells inhibited the branching morphogenesis, growth, and differentiation of early postnatal prostate in culture and impaired prostate re-growth triggered by hormone replacement in castrated mice. Furthermore, we found that Notch1 expression following castration and hormone replacement was concomitant with known basal cell markers p63 and cytokeratin 14 and was high in the proliferative human prostate epithelial cells. Taken together, these data suggest that Notch1-expressing cells define the progenitor cells in the prostatic epithelial cell lineage, which are indispensable for prostatic development and re-growth.

Androgens↗

PubMed2004

Imbalanced gp130-dependent signaling in macrophages alters macrophage colony-stimulating factor responsiveness via regulation of c-fms expression.

The mechanisms by which interleukin-6 (IL-6) family cytokines, which utilize the common receptor signaling subunit gp130, influence monocyte/macrophage development remain unclear. Here we have utilized macrophages devoid of either gp130-dependent STAT1/3 (gp130(Delta STAT/Delta STAT)) or extracellular signal-regulated kinases 1 and 2 (ERK1/2) mitogen-activated protein (MAP) kinase (gp130(Y757F/Y757F)) activation to assess the individual contribution of each pathway to macrophage formation. While the inhibition by IL-6 of macrophage colony-stimulating factor (M-CSF)-induced colony formation observed in gp130(wt/wt) mice was abolished in gp130(Delta STAT/Delta STAT) mice, inhibition of macrophage colony formation was enhanced in gp130(Y757F/Y757F) mice. In gp130(Delta STAT/Delta STAT) bone marrow-derived macrophages (BMMs), both IL-6- and M-CSF-induced ERK1/2 tyrosine phosphorylation was enhanced. By contrast, tyrosine phosphorylation of ERK1/2 in response to M-CSF was reduced in gp130(Y757F/Y757F) BMMs, and the pattern of ERK1/2 activation in gp130 mutant BMMs correlated with their opposing responsiveness to M-CSF-induced proliferation. When compared to the level of expression in gp130(wt/wt) BMMs, c-fms expression was elevated in gp130(Delta STAT/Delta STAT) BMMs but reduced in gp130(Y757F/Y757F) BMMs. Finally, an ERK1/2 inhibitor suppressed M-CSF-induced BMM proliferation, and this result corresponded to a reduction in c-fms expression. Collectively, these results provide a functional and causal correlation between gp130-dependent ERK MAP kinase signaling and c-fms gene activation, a finding that provides a potential mechanism underlying the inhibition of M-CSF-dependent macrophage development by IL-6 family cytokines in mice.

Animals↗

PubMed2002

Differences in neointima formation between impervious and porous polytetrafluoroethylene vascular patch material.

The aim of this study was to compare the neointima formation and blood loss of an impervious ePTFE with those of the porous ePTFE patch. Ten mongrel dogs were selected for the study. Both the impervious and porous ePTFE patches were implanted into the common iliac arteries in each dog. The blood loss of each patch was recorded and the patches were explanted 30-60 days later for microscopic analysis. The arteries with either the impervious or the porous ePTFE patch were all patent at the end of the study. The impervious ePTFE patch had a significant reduction in blood loss when compared with the porous ePTFE patch (p = 0.04). The neointima covering both patches showed no statistically significant difference in its thickness or in its cellular composition. It has been speculated that wall porosity is essential for tissue ingrowth, endothelial cell proliferation, and neointima formation. In this study, the impervious ePTFE patch did not inhibit neointima formation. Our study shows that graft porosity does not improve neointima formation or patency. Neointimization of the impervious ePTFE patch is the result of pannus ingrowth and deposition of circulating blood elements. There is a statistically significant reduction in blood loss (p = 0.04) with impervious ePTFE patch, compared with that of the porous ePTFE patch.

Animals↗

PubMed2002

Providing the right infrastructure to lead the culture change for patient safety.

BACKGROUND: In early 2000 the hospital leadership of Good Samaritan Hospital (GSH), a community teaching hospital in Dayton, Ohio, made patient safety a strategic priority and devoted resources to incorporate safety as a part of the hospital's culture and care processes. The vice president of clinical effectiveness and performance improvement, as a champion for safety, led a consensus-building effort to enlist the support of key physician and hospital leaders to a safety program. GSH added a Safety Board to its administrative infrastructure, which was to serve as an oversight body to ensure the advance of the safety program and to produce policies and procedures that are associated with safety. ADDRESSING PATIENT SAFETY AIMS: To assess GSH's progress toward achieving three aims--demonstrate patient safety as a top leadership priority, promote a nonpunitive culture for sharing information and lessons learned, and implement an integrated patient safety program throughout the organization--the Safety Board evaluates GSH's performance bimonthly, using a 5-point-scaled self-assessment tool. For example, for the third aim, the Safety Board oversaw the formation of three subcommittees, which were to test ideas and achieve improvements in three areas--medication, clinical, and environmental. DISCUSSION: The administrative structure provides the leadership and momentum necessary to fuel a cultural change in the way that patient safety issues are perceived and acted on throughout the organization. "To err" may be human, but so is the ability to increase patient safety awareness, to promote cultural change within existing systems, and to improve the patient care processes and outcomes.

Consensus↗

PubMed2002

Acute cardiogenic shock immediately after successful intervention for failed thrombolysis.

We report the case of a 60-year-old female with a history of hypertension who was admitted with an acute inferior myocardial infarction. She received rescue percutaneous transluminal coronary angioplasty/stenting of an occluded right coronary artery for failed thrombolysis with a good initial result. However, this was immediately complicated by cardiogenic shock characterized by left ventricular outflow tract (LVOT) gradient. She was treated with intravenous fluids and adrenaline. Predischarge echocardiography showed no LVOT gradient and features of left ventricular hypertrophy that mainly affected the septum.

Cardiomyopathy, Hypertrophic↗