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Paul Bankey

Publications and source records attributed to Paul Bankey.

8 recordsLinked to original sources
PubMed2006

Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways.

Monitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for the future of medicine. Patients with injuries severe enough to develop multiple organ dysfunction syndrome have multiple immune derangements, including T cell apoptosis and anergy combined with depressed monocyte antigen presentation. Genome-wide expression analysis of highly enriched circulating leukocyte subpopulations, combined with cell-specific pathway analyses, offers an opportunity to discover leukocyte regulatory networks in critically injured patients. Severe injury induced significant changes in T cell (5,693 genes), monocyte (2,801 genes), and total leukocyte (3,437 genes) transcriptomes, with only 911 of these genes common to all three cell populations (12%). T cell-specific pathway analyses identified increased gene expression of several inhibitory receptors (PD-1, CD152, NRP-1, and Lag3) and concomitant decreases in stimulatory receptors (CD28, CD4, and IL-2Ralpha). Functional analysis of T cells and monocytes confirmed reduced T cell proliferation and increased cell surface expression of negative signaling receptors paired with decreased monocyte costimulation ligands. Thus, genome-wide expression from highly enriched cell populations combined with knowledge-based pathway analyses leads to the identification of regulatory networks differentially expressed in injured patients. Importantly, application of cell separation, genome-wide expression, and cell-specific pathway analyses can be used to discover pathway alterations in human disease.

Gene Expression Profiling↗
PubMed2005

Application of genome-wide expression analysis to human health and disease.

The application of genome-wide expression analysis to a large-scale, multicentered program in critically ill patients poses a number of theoretical and technical challenges. We describe here an analytical and organizational approach to a systematic evaluation of the variance associated with genome-wide expression analysis specifically tailored to study human disease. We analyzed sources of variance in genome-wide expression analyses performed with commercial oligonucleotide arrays. In addition, variance in gene expression in human blood leukocytes caused by repeated sampling in the same subject, among different healthy subjects, among different leukocyte subpopulations, and the effect of traumatic injury, were also explored. We report that analytical variance caused by sample processing was acceptably small. Blood leukocyte gene expression in the same individual over a 24-h period was remarkably constant. In contrast, genome-wide expression varied significantly among different subjects and leukocyte subpopulations. Expectedly, traumatic injury induced dramatic changes in apparent gene expression that were greater in magnitude than the analytical noise and interindividual variance. We demonstrate that the development of a nation-wide program for gene expression analysis with careful attention to analytical details can reduce the variance in the clinical setting to a level where patterns of gene expression are informative among different healthy human subjects, and can be studied with confidence in human disease.

Cluster Analysis↗
PubMed2004

Prospective study of neutrophil chemokine responses in trauma patients at risk for pneumonia.

Neutrophil hyperactivity contributes to organ failure, whereas hypofunction permits sepsis. The chemokine receptors CXCR1 and CXCR2 are central to polymorphonuclear neutrophil (PMN) function. We prospectively assessed CXCR function and expression in PMNs from trauma patients at high risk for pneumonia and their matched volunteer controls. CXCR2-specific calcium flux and chemotaxis were desensitized by injury, returning toward normal after 1 week. CXCR1 responses were relatively maintained. These defects appeared to be caused by preferential suppression of CXCR2 surface expression. To evaluate potential mechanisms of in vivo chemokine receptor regulation further we studied cross-desensitization of chemokine receptors in normal PMNs. Susceptibility to desensitization was in the order CXCR2 > CXCR1 > formyl peptide or C5a receptors. Trauma desensitizes CXC receptors, with CXCR2 being especially vulnerable. Desensitization is most marked immediately postinjury, generally resolving by Day 7. High-affinity chemoattractant receptors responsible for PMN chemotaxis from bloodstream to tissue appear to be regulated by injury. Receptors for end-target chemoattractants regulate CXCR1 and CXCR2 but resist suppression themselves and respond normally after injury. CXCR2 desensitization occurs before pneumonia, which developed in 44% of these patients. Suppression of high-affinity PMN receptors, like CXCR2, may predispose to pneumonia after trauma or other inflammatory conditions that lead to systemic inflammatory response syndrome.

Adolescent↗
PubMed2004

Tree stand falls: a persistent cause of sports injury.

OBJECTIVE: Tree stand falls are a well-known cause of hunting-related injury. Spine and brain injuries associated with these falls result in a significant incidence of permanent disability. Prior studies indicate that hunting tree stand injuries are largely preventable with the proper use of safety belts; however, compliance with safety belt use is variable. The purposes of this study were to determine 1) current compliance with safety belt use, 2) alterations in the spectrum of injury, and 3) causes of the falls. METHODS: From January 1996 to October 2001, 51 tree stand-related injuries referred to either of two regional trauma centers or their region's medical examiner's office were reviewed. Data had been recorded in each hospital's trauma registry, and the registries were searched for falls. Medical records were reviewed for additional data retrospectively, with an emphasis on determining the use of safety belts, and mechanisms contributing to the fall. RESULTS: Fifty-one cases of tree stand-associated injuries were identified. These injuries all occurred in men, with a mean age of 42.6 years (range, 22-69 years). Alcohol use was present in 10% of patients and in two of the three deaths. The mean Injury Severity Score was 18.1 (range, 2-75). The most common injuries were spinal fractures (51% of series) and extremity fractures (41% of series). Closed head injuries were identified in 24% and lung injuries were identified in 22% of patients. Abdominal visceral injuries were present in 8% and genitourinary injuries were present in 4%. Three patients died. In addition to injury from the fall, a significant number (six patients [12%]) had additional morbidity from exposure. Only two patients reported the use of a safety belt (4% of series). There were no cases of gunshot wounds in this review, either self-inflicted or hunter-related. The chief reasons reported for these falls were errors in placement that resulted in structural failure of the stand, or errors made while climbing into or out of the stand (50% of falls). CONCLUSION: Devastating spine and brain injuries continue to occur after falls from tree stands during recreational hunting when safety belts are not used. Our results suggest a continuing need for the education of hunters concerning safe tree stand hunting practices, including proper methods of stand placement, assessment of tree branch strength, avoidance of fatigue and alcohol, anticipation of firearm recoil, and proper methods of stand entrance and exit. Trauma prevention programs directed toward heightened public awareness of these injuries during hunting season are still needed.

Accidental Falls↗
PubMed2002

Down-regulated circulating PMN function after injury despite enhanced p38 MAPK activity.

BACKGROUND: Neutrophils (PMN) are initially primed by injury. However, remaining PMN found in the circulation postinjury demonstrate a down-regulated phenotype with inhibited apoptosis, CXCR2 expression, and endotoxin (LPS) responsiveness that may contribute to infectious complications and organ dysfunction. The p38 mitogen activated protein kinase (MAPK) signal transduction pathway has been implicated in regulating each of these PMN functions. We, therefore, hypothesize that p38 signaling is similarly down-regulated in postinjury circulating PMN. MATERIALS AND METHODS: PMN were isolated from trauma patients (ISS > 20, postinjury day 3) and concurrently from healthy volunteers (control). PMN were cultured with LPS (100 ng/mL) and p38 activity assessed by Western blotting of cell lysates using a dual phosphospecific antibody for phosphorylated, active p38. In separate experiments, PMN from healthy volunteers were cultured in plasma from either healthy or injured subjects +/- LPS and p38 activity assessed by a cell-free in vitro kinase assay using the transcription factor, ATF-2, as a substrate. Apoptosis and IL-1beta secretion of the cultured PMN from each experimental condition were also quantified. RESULTS: Circulating PMN from trauma patients have an upregulated LPS signaled p38 MAPK response (threefold) compared to PMN from healthy volunteers (p < 0.05). Furthermore, circulating factors present in trauma plasma can transfer this response to normal PMN. There was no significant alteration in apoptosis following LPS treatment between control and trauma patient's PMN (control: 62 +/- 3% vs. trauma: 55 +/- 5%), but there was decreased secretion of IL-1beta (control: 100 +/- 28 pg/mL vs. trauma: 12 +/- 5 pg/mL, p < 0.05). CONCLUSION: We conclude that injury down-regulates selective PMN function despite enhanced p38 activity. These results suggest a shift in the role of PMN p38 signal transduction following injury with additional critical regulation of LPS responses downstream to p38 MAPK activity.

Apoptosis↗