Search

illus bibliog

'What is necessary to change a person, is to change his awareness of himself.' -Abraham Maslow Sun Tzu is often quoted as having said; 'If you know the enemy and [...]

Introduction There are literally hundreds of articles, papers, and books that have been written to explain culture and why it is so important to become proficient or competent in all [...]

A tense encounter with a frenzied crowd in Najaf during Operation Iraqi Freedom (OIF) I began spiraling out of control with no apparent way out of direct conflict. The US [...]

When the New Orleans Museum of Art displayed Monet's lilies several years ago, people who had previously shown little interest in art rushed to the exhibit--even though here in southern [...]

INCREASE PRODUCTIVITY THROUGH NETWORKING What are the problems encountered in computerized accounting systems and what are some possible solutions? This article will present: 1) the advantages of networking, 2) some [...]

Transition to outpatient surgery has grown with an emphasis on delivery of safe, high-quality medical care. The purpose of this study is to compare 90-day emergency department (ED) visits, readmissions, and complications between patients undergoing outpatient versus inpatient pollicization surgery.

Adipose‐derived stromal/stem cells (ASCs) have anti‐inflammatory as well as immunosuppressive activities and are currently the focus of clinical trials for a number of inflammatory diseases. Acute lung injury (ALI) is an inflammatory condition of the lung for which standard treatment is mainly supportive due to lack of effective therapies. Our recent studies have demonstrated the ability of both human ASCs (hASCs) and mouse ASCs (mASCs) to attenuate lung damage and inflammation in a rodent model of lipopolysaccharide‐induced ALI, suggesting that ASCs may also be beneficial in treating ALI. To better understand how ASCs may act in ALI and to elucidate the mechanism(s) involved in ASC modulation of lung inflammation, gene expression analysis was performed in ASC‐treated (hASCs or mASCs) and control sham‐treated lungs. The results revealed a dramatic difference between the expression of anti‐inflammatory molecules by hASCs and mASCs. These data show that the beneficial effects of hASCs and mASCs in ALI may result from the production of different paracrine factors. Interleukin 6 (IL‐6) expression in the mASC‐treated lungs was significantly elevated as compared to sham‐treated controls 20 hours after delivery of the cells by oropharyngeal aspiration. Knockdown of IL‐6 expression in mASCs by RNA interference abrogated most of their therapeutic effects, suggesting that the anti‐inflammatory properties of mASCs in ALI are explained, at least in part, by activation of IL‐6 secretion. StemCells2014;32:1616–1628

There are an insufficient number of donor organs available to meet the demand for lung transplantation. This issue could be addressed by regenerating functional tissue from diseased or damaged lungs that would otherwise be deemed unsuitable for transplant. Detergent-mediated whole-lung decellularization produces a three-dimensional natural scaffold that can be repopulated with various cell types. In this study, we investigated the decellularization and initial recellularization of diseased lungs using a rat model of monocrotaline-induced pulmonary hypertension (MCT-PHT). Decellularization of control and MCT-PHT Sprague-Dawley rat lungs was accomplished by treating the lungs with a combination of Triton X-100, sodium deoxycholate, NaCl, and DNase. The resulting acellular matrices were characterized by DNA quantification, Western blotting, immunohistochemistry, and proteomic analyses revealing that decellularization was able to remove cells while leaving the extracellular matrix (ECM) components and lung ultrastructure intact. Decellularization significantly reduced DNA content (∼30-fold in MCT-PHT lungs and ∼50-fold in the control lungs) and enriched ECM components (>60-fold in both the control and MCT-PHT lungs) while depleting cellular proteins. MicroCT visualization of MCT-PHT rat lungs indicated that the vasculature was narrowed as a result of MCT treatment, and this characteristic was unchanged by decellularization. Mean arterial vessel diameter of representative decellularized MCT-PHT and control scaffolds was estimated to be 0.152±0.134 mm and 0.247±0.160 mm, respectively. Decellularized MCT-PHT lung scaffolds supported attachment and survival of rat adipose-derived stem cells (rASCs), seeded into the airspace or the vasculature, for at least 2 weeks. The cells seeded in MCT-PHT lung scaffolds proliferated and underwent apoptosis similar to control scaffolds; however, the initial percentage of apoptotic cells was slightly higher in MCT-PHT lungs (2.79±2.03% vs. 1.05±1.02% of airway-seeded rASCs, and 4.47±1.21% vs. 2.66±0.10% of vascular seeded rASCs). The ECM of cell-seeded scaffolds showed no signs of degradation by the cells after 14 days in culture. These data suggest that diseased hypertensive lungs can be efficiently decellularized similar to control lungs and have the potential to be recellularized with mesenchymal stem cells with the ultimate goal of generating healthy, functional pulmonary tissue.

Globoid cell leukodystrophy (GLD) is a common neurodegenerative lysosomal storage disorder caused by a deficiency in galactocerebrosidase (GALC), an enzyme that cleaves galactocerebroside during myelination. Bone marrow transplantation has shown promise when administered to late‐onset GLD patients. However, the side effects (e.g., graft vs. host disease), harsh conditioning regimens (e.g., myelosuppression), and variable therapeutic effects make this an unsuitable option for infantile GLD patients. We previously reported modest improvements in the twitcher mouse model of GLD after intracerebroventricular (ICV) injections of a low‐dose of multipotent stromal cells (MSCs). Goals of this study were to improve bone marrow‐derived MSC (BMSC) therapy for GLD by increasing the cell dosage and comparing cell type (e.g., transduced vs. native), treatment timing (e.g., single vs. weekly), and administration route (e.g., ICV vs. intraperitoneal [IP]). Neonatal twitcher mice received (a) 2 × 105BMSCs by ICV injection, (b) 1 × 106BMSCs by IP injection, (c) weekly IP injections of 1 × 106BMSCs, or (d) 1 × 106lentiviral‐transduced BMSCs overexpressing GALC (GALC‐BMSC) by IP injection. All treated mice lived longer than untreated mice. However, the mice receiving peripheral MSC therapy had improved motor function (e.g., hind limb strength and rearing ability), twitching symptoms, and weight compared to both the untreated and ICV‐treated mice. Inflammatory cell, globoid cell, and apoptotic cell levels in the sciatic nerves were significantly decreased as a result of the GALC‐BMSC or weekly IP injections. The results of this study indicate a promising future for peripheral MSC therapy as a noninvasive, adjunct therapy for patients affected with GLD. STEMCells2013;31:1523–1534

Currently, patients with end-stage lung disease are limited to lung transplantation as their only treatment option. Unfortunately, the lungs available for transplantation are few. Moreover, transplant recipients require life-long immune suppression to tolerate the transplanted lung. A promising alternative therapeutic strategy is decellularization of whole lungs, which permits the isolation of an intact scaffold comprised of innate extracellular matrix (ECM) that can theoretically be recellularized with autologous stem or progenitor cells to yield a functional lung. Nonhuman primates (NHP) provide a highly relevant preclinical model with which to assess the feasibility of recellularized lung scaffolds for human lung transplantation. Our laboratory has successfully accomplished lung decellularization and initial stem cell inoculation of the resulting ECM scaffold in an NHP model. Decellularization of normal adult rhesus macaque lungs as well as the biology of the resulting acellular matrix have been extensively characterized. Acellular NHP matrices retained the anatomical and ultrastructural properties of native lungs with minimal effect on the content, organization, and appearance of ECM components, including collagen types I and IV, laminin, fibronectin, and sulfated glycosaminoglycans (GAG), due to decellularization. Proteomics analysis showed enrichment of ECM proteins in total tissue extracts due to the removal of cells and cellular proteins by decellularization. Cellular DNA was effectively removed after decellularization (∼92% reduction), and the remaining nuclear material was found to be highly disorganized, very-low-molecular-weight fragments. Both bone marrow- and adipose-derived mesenchymal stem cells (MSC) attach to the decellularized lung matrix and can be maintained within this environment in vitro, suggesting that these cells may be promising candidates and useful tools for lung regeneration. Analysis of decellularized lung slice cultures to which MSC were seeded showed that the cells attached to the decellularized matrix, elongated, and proliferated in culture. Future investigations will focus on optimizing the recellularization of NHP lung scaffolds toward the goal of regenerating pulmonary tissue. Bringing this technology to eventual human clinical application will provide patients with an alternative therapeutic strategy as well as significantly reduce the demand for transplantable organs and patient wait-list time.

Recellularization of whole decellularized lung scaffolds provides a novel approach for generating functional lung tissue ex vivofor subsequent clinical transplantation. To explore the potential utility of stem and progenitor cells in this model, we investigated recellularization of decellularized whole mouse lungs after intratracheal inoculation of bone marrow-derived mesenchymal stromal cells (MSCs). The decellularized lungs maintained structural features of native lungs, including intact vasculature, ability to undergo ventilation, and an extracellular matrix (ECM) scaffold consisting primarily of collagens I and IV, laminin, and fibronectin. However, even in the absence of intact cells or nuclei, a number of cell-associated (non-ECM) proteins were detected using mass spectroscopy, western blots, and immunohistochemistry. MSCs initially homed and engrafted to regions enriched in types I and IV collagen, laminin, and fibronectin, and subsequently proliferated and migrated toward regions enriched in types I and IV collagen and laminin but not provisional matrix (fibronectin). MSCs cultured for up to 1 month in either basal MSC medium or in a small airways growth media (SAGM) localized in both parenchymal and airway regions and demonstrated several different morphologies. However, while MSCs cultured in basal medium increased in number, MSCs cultured in SAGM decreased in number over 1 month. Under both media conditions, the MSCs predominantly expressed genes consistent with mesenchymal and osteoblast phenotype. Despite a transient expression of the lung precursor TTF-1, no other airway or alveolar genes or vascular genes were expressed. These studies highlight the power of whole decellularized lung scaffolds to study functional recellularization with MSCs and other cells.

Chloride anion is essential for myeloperoxidase (MPO) to produce hypochlorous acid (HOCl) in polymorphonuclear neutrophils (PMNs). To define whether chloride availability to PMNs affects their HOCl production and microbicidal capacity, we examined how extracellular chloride concentration affects killing of Pseudomonas aeruginosa(PsA) by normal neutrophils. PMN‐mediated bacterial killing was strongly dependent on extracellular chloride concentration. Neutrophils in a chloride‐deficient medium killed PsA poorly. However, as the chloride level was raised, the killing efficiency increased in a dose‐dependent manner. By using specific inhibitors to selectively block NADPH oxidase, MPO, and cystic fibrosis transmembrane conductance regulator (CFTR) functions, neutrophil‐mediated killing of PsA could be attributed to three distinct mechanisms: CFTR‐dependent and oxidant‐dependent; chloride‐dependent but not CFTR‐ and oxidant‐dependent; and independent of any of the tested factors. Therefore, chloride anion is involved in oxidant‐ and nonoxidant‐mediated bacterial killing. We previously reported that neutrophils from CF patients are defective in chlorination of ingested bacteria [1], suggesting that the chloride channel defect might impair the MPO‐hydrogen peroxide‐chloride microbicidal function. Here, we compared the competence of killing PsA by neutrophils from normal donors and CF patients. The data demonstrate that the killing rate by CF neutrophils was significantly lower than that by normal neutrophils. CF neutrophils in a chloride‐deficient environment had only one‐third of the bactericidal capacity of normal neutrophils in a physiological chloride environment. These results suggest that CFTR‐dependent chloride anion transport contributes significantly to killing PsA by normal neutrophils and when defective as in CF, may compromise the ability to clear PsA.

The article focuses on deliberate practice for developing expert soccer players. Topics discussed include views of author Ander Ericsson on deliberate practice; estimation of hours of soccer training for a soccer player; the Ohio High School Athletic Association preventing club soccer playing; and views of auhtor Shawn Mitchell on focus of students on club soccer.

The article presents the author's views on the difference between competing and playing. He explores the impact between the two words to the youth soccer players as he gives their definition. He also examines the work of Jay Martin, men's soccer coach at Ohio Wesleyan University, and Terry Michler, boy's soccer coach at St. Louis, Missouri Christian Brothers College Preparatory High School, about playing versus competing.

An interview is presented with cinematographer Michael Bonvillain. He discusses the influence of the film "The Wizard of Oz" and the work of cinematographers Bob Richardson, Gordon Willis, and Roger Deakins on his career. Other topics covered include his education at the University of Texas at Austin, his early work with commercial director Steve Horn, and his interest in dramatic films.