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Sample records for resident tissue phagocytes

  1. Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1(+) DCs in mouse and human and distinguishes them from Langerhans cells.

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    Carpentier, Sabrina; Vu Manh, Thien-Phong; Chelbi, Rabie; Henri, Sandrine; Malissen, Bernard; Haniffa, Muzlifah; Ginhoux, Florent; Dalod, Marc

    2016-05-01

    Dendritic cells (DC) are mononuclear phagocytes which exhibit a branching (dendritic) morphology and excel at naïve T cell activation. DC encompass several subsets initially identified by their expression of cell surface molecules and later shown to possess distinct functions. DC subset differentiation is orchestrated by transcription factors, growth factors and cytokines. Identifying DC subsets is challenging as very few cell surface molecules are uniquely expressed on any one of these cell populations. There is no standard consensus to identify mononuclear phagocyte subsets; varying antigens are employed depending on the tissue and animal species studied and between laboratories. This has led to confusion in how to accurately define and classify DCs across tissues and between species. Here we report a comparative genomics strategy that enables universal definition of DC and other mononuclear phagocyte subsets across species. We performed a meta-analysis of several public datasets of human and mouse mononuclear phagocyte subsets isolated from blood, spleen, skin or cutaneous lymph nodes, including by using a novel and user friendly software, BubbleGUM, which generates and integrates gene signatures for high throughput gene set enrichment analysis. This analysis demonstrates the equivalence between human and mouse skin XCR1(+) DCs, and between mouse and human Langerhans cells. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  2. In vivo evaluation of the antibacterial capacity of tissue phagocytes

    International Nuclear Information System (INIS)

    Guerra, H.

    1975-01-01

    The phagocytic activity of guinea pig liver to deal with bacterial infection was investigated on 14 C- or 32 P-labelled Brucella melitensis. Some in vitro work has been started, using immunoglobulins (IgG, IgM) with antibody activity against whole Brucella

  3. The Phagocytic Function of Macrophage-Enforcing Innate Immunity and Tissue Homeostasis

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    Daisuke Hirayama

    2017-12-01

    Full Text Available Macrophages are effector cells of the innate immune system that phagocytose bacteria and secrete both pro-inflammatory and antimicrobial mediators. In addition, macrophages play an important role in eliminating diseased and damaged cells through their programmed cell death. Generally, macrophages ingest and degrade dead cells, debris, tumor cells, and foreign materials. They promote homeostasis by responding to internal and external changes within the body, not only as phagocytes, but also through trophic, regulatory, and repair functions. Recent studies demonstrated that macrophages differentiate from hematopoietic stem cell-derived monocytes and embryonic yolk sac macrophages. The latter mainly give rise to tissue macrophages. Macrophages exist in all vertebrate tissues and have dual functions in host protection and tissue injury, which are maintained at a fine balance. Tissue macrophages have heterogeneous phenotypes in different tissue environments. In this review, we focused on the phagocytic function of macrophage-enforcing innate immunity and tissue homeostasis for a better understanding of the role of tissue macrophages in several pathological conditions.

  4. Tissues Use Resident Dendritic Cells and Macrophages to Maintain Homeostasis and to Regain Homeostasis upon Tissue Injury: The Immunoregulatory Role of Changing Tissue Environments

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    Maciej Lech

    2012-01-01

    Full Text Available Most tissues harbor resident mononuclear phagocytes, that is, dendritic cells and macrophages. A classification that sufficiently covers their phenotypic heterogeneity and plasticity during homeostasis and disease does not yet exist because cell culture-based phenotypes often do not match those found in vivo. The plasticity of mononuclear phagocytes becomes obvious during dynamic or complex disease processes. Different data interpretation also originates from different conceptual perspectives. An immune-centric view assumes that a particular priming of phagocytes then causes a particular type of pathology in target tissues, conceptually similar to antigen-specific T-cell priming. A tissue-centric view assumes that changing tissue microenvironments shape the phenotypes of their resident and infiltrating mononuclear phagocytes to fulfill the tissue's need to maintain or regain homeostasis. Here we discuss the latter concept, for example, why different organs host different types of mononuclear phagocytes during homeostasis. We further discuss how injuries alter tissue environments and how this primes mononuclear phagocytes to enforce this particular environment, for example, to support host defense and pathogen clearance, to support the resolution of inflammation, to support epithelial and mesenchymal healing, and to support the resolution of fibrosis to the smallest possible scar. Thus, organ- and disease phase-specific microenvironments determine macrophage and dendritic cell heterogeneity in a temporal and spatial manner, which assures their support to maintain and regain homeostasis in whatever condition. Mononuclear phagocytes contributions to tissue pathologies relate to their central roles in orchestrating all stages of host defense and wound healing, which often become maladaptive processes, especially in sterile and/or diffuse tissue injuries.

  5. Diversity and functions of intestinal mononuclear phagocytes

    DEFF Research Database (Denmark)

    Joeris, Thorsten; Müller-Luda, K; Agace, William Winston

    2017-01-01

    The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation. In the curr......The intestinal lamina propria (LP) contains a diverse array of mononuclear phagocyte (MNP) subsets, including conventional dendritic cells (cDC), monocytes and tissue-resident macrophages (mφ) that collectively play an essential role in mucosal homeostasis, infection and inflammation....... In the current review we discuss the function of intestinal cDC and monocyte-derived MNP, highlighting how these subsets play several non-redundant roles in the regulation of intestinal immune responses. While much remains to be learnt, recent findings also underline how the various populations of MNP adapt...

  6. Tissue-resident memory T cells.

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    Shin, Haina; Iwasaki, Akiko

    2013-09-01

    Tissues such as the genital tract, skin, and lung act as barriers against invading pathogens. To protect the host, incoming microbes must be quickly and efficiently controlled by the immune system at the portal of entry. Memory is a hallmark of the adaptive immune system, which confers long-term protection and is the basis for efficacious vaccines. While the majority of existing vaccines rely on circulating antibody for protection, struggles to develop antibody-based vaccines against infections such as herpes simplex virus (HSV) and human immunodeficiency virus (HIV) have underscored the need to generate memory T cells for robust antiviral control. The circulating memory T-cell population is generally divided into two subsets: effector memory (TEM ) and central memory (TCM ). These two subsets can be distinguished by their localization, as TCM home to secondary lymphoid organs and TEM circulate through non-lymphoid tissues. More recently, studies have identified a third subset, called tissue-resident memory (TRM ) cells, based on its migratory properties. This subset is found in peripheral tissues that require expression of specific chemoattractants and homing receptors for T-cell recruitment and retention, including barrier sites such as the skin and genital tract. In this review, we categorize different tissues in the body based on patterns of memory T-cell migration and tissue residency. This review also describes the rules for TRM generation and the properties that distinguish them from circulating TEM and TCM cells. Finally, based on the failure of recent T-cell-based vaccines to provide optimal protection, we also discuss the potential role of TRM cells in vaccine design against microbes that invade through the peripheral tissues and highlight new vaccination strategies that take advantage of this newly described memory T-cell subset. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Innate Immunity to Leishmania Infection: Within Phagocytes

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    Marcela Freitas Lopes

    2014-01-01

    Full Text Available Infection by Leishmania takes place in the context of inflammation and tissue repair. Besides tissue resident macrophages, inflammatory macrophages and neutrophils are recruited to the infection site and serve both as host cells and as effectors against infection. Recent studies suggest additional important roles for monocytes and dendritic cells. This paper addresses recent experimental findings regarding the regulation of Leishmania major infection by these major phagocyte populations. In addition, the role of IL-4 on dendritic cells and monocytes is discussed.

  8. Transcriptional regulation of mononuclear phagocyte development

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    Roxane eTussiwand

    2015-10-01

    Full Text Available IntroductionThe mononuclear-phagocyte system (MPS, which comprises dendritic cells (DCs, macrophages and monocytes, is a heterogeneous group of myeloid cells. The complexity of the MPS is equally reflected by the plasticity in function and phenotype that characterizes each subset depending on their location and activation state. Specialized subsets of Mononuclear Phagocytes (MP reside in defined anatomical locations, are critical for the homeostatic maintenance of tissues, and provide the link between innate and adaptive immune responses during infections. The ability of MP to maintain or to induce the correct tolerogenic or inflammatory milieu also resides in their complex subset specialization. Such subset heterogeneity is obtained through lineage diversification and specification, which is controlled by defined transcriptional networks and programs. Understanding the MP biology means to define their transcriptional signature, which is required during lineage commitment, and which characterizes each subset’s features. This review will focus on the transcriptional regulation of the MPS; in particular what determines lineage commitment and functional identity; we will emphasizes recent advances in the field of single cell analysis and highlight unresolved questions in the field.

  9. Evaluating the potential of gold, silver, and silica nanoparticles to saturate mononuclear phagocytic system tissues under repeat dosing conditions.

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    Weaver, James L; Tobin, Grainne A; Ingle, Taylor; Bancos, Simona; Stevens, David; Rouse, Rodney; Howard, Kristina E; Goodwin, David; Knapton, Alan; Li, Xiaohong; Shea, Katherine; Stewart, Sharron; Xu, Lin; Goering, Peter L; Zhang, Qin; Howard, Paul C; Collins, Jessie; Khan, Saeed; Sung, Kidon; Tyner, Katherine M

    2017-07-17

    As nanoparticles (NPs) become more prevalent in the pharmaceutical industry, questions have arisen from both industry and regulatory stakeholders about the long term effects of these materials. This study was designed to evaluate whether gold (10 nm), silver (50 nm), or silica (10 nm) nanoparticles administered intravenously to mice for up to 8 weeks at doses known to be sub-toxic (non-toxic at single acute or repeat dosing levels) and clinically relevant could produce significant bioaccumulation in liver and spleen macrophages. Repeated dosing with gold, silver, and silica nanoparticles did not saturate bioaccumulation in liver or spleen macrophages. While no toxicity was observed with gold and silver nanoparticles throughout the 8 week experiment, some effects including histopathological and serum chemistry changes were observed with silica nanoparticles starting at week 3. No major changes in the splenocyte population were observed during the study for any of the nanoparticles tested. The clinical impact of these changes is unclear but suggests that the mononuclear phagocytic system is able to handle repeated doses of nanoparticles.

  10. Tissue-Resident Cytolytic Innate Lymphocytes in Cancer.

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    Nixon, Briana G; Li, Ming O

    2018-01-15

    Innate lymphoid cells (ILCs) are critical components of tissues in the body, providing a first line of defense against challenges to host integrity. In contrast to strictly cytokine-producing helper ILCs, resident innate lymphocyte populations with cytolytic potential have been identified in multiple tissues in both mouse and human. These cells express the transcription factor Tbet, NK cell receptors, granzymes, perforin, and death receptors, and can directly kill tumor cells. Signals in the tumor microenvironment may promote this response, including the cytokine IL-15 and stress-associated ligands for activating NK receptors. Although there is evidence that these cells are tissue and tumor resident, their lineage remains unclear. Whether they are derived from the NK or helper ILC lineages or represent a third differentiation pathway remains to be determined. A better understanding of their lineage will help clarify their regulation and function in the context of antitumor immunity. Copyright © 2018 by The American Association of Immunologists, Inc.

  11. Behavior and function of tissue-resident memory T cells.

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    Ariotti, Silvia; Haanen, John B; Schumacher, Ton N

    2012-01-01

    Our understanding of memory T cell function in mice and men is to date in large part restricted to the behavior of circulating memory T cells. Emerging evidence, however, suggests that in addition to such systemic memory T cell populations, a separate population of locally confined memory T cells is generated at former sites of antigen encounter. Here, we discuss the potential function of these long-term tissue-resident memory T cells (T(TRM)), how such local T cell memory can be maintained for prolonged periods of time, and how the induction of long-term tissue-resident memory T cells may potentially be exploited during vaccination. Copyright © 2012 Elsevier Inc. All rights reserved.

  12. Unravelling mononuclear phagocyte heterogeneity

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    Geissmann, Frédéric; Gordon, Siamon; Hume, David A.; Mowat, Allan M.; Randolph, Gwendalyn J.

    2011-01-01

    When Ralph Steinman and Zanvil Cohn first described dendritic cells (DCs) in 1973 it took many years to convince the immunology community that these cells were truly distinct from macrophages. Almost four decades later, the DC is regarded as the key initiator of adaptive immune responses; however, distinguishing DCs from macrophages still leads to confusion and debate in the field. Here, Nature Reviews Immunology asks five experts to discuss the issue of heterogeneity in the mononuclear phagocyte system and to give their opinion on the importance of defining these cells for future research. PMID:20467425

  13. Preoperative surgical rehearsal using cadaveric fresh tissue surgical simulation increases resident operative confidence.

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    Weber, Erin L; Leland, Hyuma A; Azadgoli, Beina; Minneti, Michael; Carey, Joseph N

    2017-08-01

    Rehearsal is an essential part of mastering any technical skill. The efficacy of surgical rehearsal is currently limited by low fidelity simulation models. Fresh cadaver models, however, offer maximal surgical simulation. We hypothesize that preoperative surgical rehearsal using fresh tissue surgical simulation will improve resident confidence and serve as an important adjunct to current training methods. Preoperative rehearsal of surgical procedures was performed by plastic surgery residents using fresh cadavers in a simulated operative environment. Rehearsal was designed to mimic the clinical operation, complete with a surgical technician to assist. A retrospective, web-based survey was used to assess resident perception of pre- and post-procedure confidence, preparation, technique, speed, safety, and anatomical knowledge on a 5-point scale (1= not confident, 5= very confident). Twenty-six rehearsals were performed by 9 residents (PGY 1-7) an average of 4.7±2.1 days prior to performance of the scheduled operation. Surveys demonstrated a median pre-simulation confidence score of 2 and a post-rehearsal score of 4 (Psafety, and anatomical knowledge improved as a result of simulation. Fresh tissue-based preoperative surgical rehearsal was effectively implemented in the residency program. Resident confidence and perception of technique improved. Survey results suggest that cadaveric simulation is beneficial for all levels of residents. We believe that implementation of preoperative surgical rehearsal is an effective adjunct to surgical training at all skill levels in the current environment of decreased work hours.

  14. Tissue-resident memory T cells play a key role in the efficacy of cancer vaccines.

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    Granier, C; Blanc, C; Karaki, S; Tran, T; Roussel, H; Tartour, E

    2017-01-01

    Resident memory CD8 + T cells (T RM ) usually defined by the CD103 marker represent a new subset of long-lived memory T cells that remain in the tissues. We directly demonstrate their specific role in cancer vaccine-induced tumor regression. In human, they also seem to play a major role in tumor immunosurveillance.

  15. The extent to which melanoma alters tissue-resident dendritic cell function correlates with tumorigenicity

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    Hargadon, Kristian Michael

    2015-01-01

    ABSTRACT We have shown that melanoma-derived factors alter the function of differentiated tissue-resident dendritic cells (DC) in a tumorigenicity-dependent manner. Soluble factors, including TGF?1 and VEGF-A, contributed to dendritic cell dysfunction associated with a highly-aggressive melanoma and conferred a phenotype upon DC likely to favor immune escape and tumor outgrowth.

  16. The extent to which melanoma alters tissue-resident dendritic cell function correlates with tumorigenicity.

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    Hargadon, Kristian Michael

    We have shown that melanoma-derived factors alter the function of differentiated tissue-resident dendritic cells (DC) in a tumorigenicity-dependent manner. Soluble factors, including TGFβ1 and VEGF-A, contributed to dendritic cell dysfunction associated with a highly-aggressive melanoma and conferred a phenotype upon DC likely to favor immune escape and tumor outgrowth.

  17. New Insights into the Immunobiology of Mononuclear Phagocytic Cells and Their Relevance to the Pathogenesis of Cardiovascular Diseases

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    Liliana Maria Sanmarco

    2018-01-01

    Full Text Available Macrophages are the primary immune cells that reside within the myocardium, suggesting that these mononuclear phagocytes are essential in the orchestration of cardiac immunity and homeostasis. Independent of the nature of the injury, the heart triggers leukocyte activation and recruitment. However, inflammation is harmful to this vital terminally differentiated organ with extremely poor regenerative capacity. As such, cardiac tissue has evolved particular strategies to increase the stress tolerance and minimize the impact of inflammation. In this sense, growing evidences show that mononuclear phagocytic cells are particularly dynamic during cardiac inflammation or infection and would actively participate in tissue repair and functional recovery. They respond to soluble mediators such as metabolites or cytokines, which play central roles in the timing of the intrinsic cardiac stress response. During myocardial infarction two distinct phases of monocyte influx have been identified. Upon infarction, the heart modulates its chemokine expression profile that sequentially and actively recruits inflammatory monocytes, first, and healing monocytes, later. In the same way, a sudden switch from inflammatory macrophages (with microbicidal effectors toward anti-inflammatory macrophages occurs within the myocardium very shortly after infection with Trypanosoma cruzi, the causal agent of Chagas cardiomyopathy. While in sterile injury, healing response is necessary to stop tissue damage; during an intracellular infection, the anti-inflammatory milieu in infected hearts would promote microbial persistence. The balance of mononuclear phagocytic cells seems to be also dynamic in atherosclerosis influencing plaque initiation and fate. This review summarizes the participation of mononuclear phagocyte system in cardiovascular diseases, keeping in mind that the immune system evolved to promote the reestablishment of tissue homeostasis following infection/injury, and

  18. A tissue phantom model for training residents in ultrasound-guided liver biopsy.

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    Sekhar, Aarti; Sun, Maryellen R; Siewert, Bettina

    2014-07-01

    The apprenticeship model for training of percutaneous liver biopsy has limitations, and costs of commercially available simulation models can be prohibitive. We created an inexpensive tissue phantom for liver biopsy simulation and evaluated the utility of this model for training radiology residents. A bovine-porcine tissue phantom was devised as a simulation model and consisted of bovine liver with a porcine rib layer and inserted pimento olives simulating target lesions. Training sessions (a 20-minute didactic lecture and a 90-minute practice session) were offered to all residents in a diagnostic radiology residency. Effect of training was assessed by questionnaire before and after training. Level of knowledge of topics covered in the didactic session, confidence in technical skills, and anxiety level were evaluated on a five-point scale (1, poor to 5, excellent). Thirty-five of 38 residents received training on the models (~$40). Mean reported value score for training was 4.88/5. Improvement was greatest for knowledge of technique (2.3-4.1/5, P Technical confidence increased (2.4-3.8/5, P < .001) and anxiety related to performing liver biopsy improved (2.7-3.7/5, P < .001). Residents with no prior experience in liver biopsy (n = 21) had significantly greater increases in all categories than residents with prior experience (n = 14), except for knowledge about obtaining informed consent and anxiety levels. Utilization of an inexpensively created bovine/porcine liver biopsy simulation model was well perceived by radiology residents and can be used as an educational tool during residency. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

  19. Homeostasis in the mononuclear phagocyte system.

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    Jenkins, Stephen J; Hume, David A

    2014-08-01

    The mononuclear phagocyte system (MPS) is a family of functionally related cells including bone marrow precursors, blood monocytes, and tissue macrophages. We review the evidence that macrophages and dendritic cells (DCs) are separate lineages and functional entities, and examine whether the traditional view that monocytes are the immediate precursors of tissue macrophages needs to be refined based upon evidence that macrophages can extensively self-renew and can be seeded from yolk sac/foetal liver progenitors with little input from monocytes thereafter. We review the role of the growth factor colony-stimulating factor (CSF)1, and present a model consistent with the concept of the MPS in which local proliferation and monocyte recruitment are connected to ensure macrophages occupy their well-defined niche in most tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Soluble glucomannan isolated from Candida utilis primes blood phagocytes.

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    Hájková, Veronika; Svobodová, Aneta; Krejcová, Daniela; Cíz, Milan; Velebný, Vladimír; Lojek, Antonín; El-Benna, Jamel; Kubala, Lukás

    2009-10-12

    It is well documented that the polysaccharide glucomannan (GM), an abundant constituent of the fungal cell wall, in the form of particulate induces strong activation of phagocytes, however, the effects of soluble GM are not known. Activation of phagocyte anti-microbial mechanisms is a crucial part of the innate host defense against invading pathogens. However, under uncontrolled inflammatory conditions they contribute to damage of surrounding tissues. Thus, to prevent these deleterious effects, the activation of phagocytes is a tightly regulated process. Therefore, in this study we analyzed the effect of soluble GM on some neutrophil functions such as reactive oxygen species production, degranulation, and receptor mobilization at the plasma membrane. Soluble GM at the tested concentrations did not stimulate oxidative burst of phagocytes directly but significantly potentiated oxidative burst in response to opsonized zymosan particles. GM induced significant phosphorylation of p47phox subunit of NADPH oxidase on Ser345. This priming effect of GM was accompanied by time and concentration dependent degranulation characterized by increased surface expression of receptors stored in neutrophil granules (CD10, CD11b, CD14, CD35, and CD66b). Degranulation was further confirmed by increase of elastase activity in media. Thus, it could be suggested that soluble GM induces priming of phagocytes connected with their degranulation, the increase of surface receptor expression, and potentiation of oxidative burst response to opsonized particles through the activation of NADPH oxidase.

  1. Evaluation of Metal Ion Concentration in Hard Tissues of Teeth in Residents of Central Poland

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    Piotr Wychowanski

    2017-01-01

    Full Text Available Objectives. The aim of the study was an assessment of the content of trace elements in enamel and dentin of teeth extracted in patients residing in urban and agricultural areas of Poland. Methods. The study included 30 generally healthy patients with retained third molars. 65 samples of enamel and dentin from individuals living in urban areas and 85 samples of enamel and dentin from individuals living in agricultural areas were prepared. The content of manganese, lead, cadmium, and chromium in the studied enamel and dentin samples from retained teeth was determined by Graphite Furnace Atomic Absorption Spectrometry. In the process of statistical hypothesis testing, the level of significance was assumed at α=0.05. Results. A comparative analysis of the data showed that enamel and dentin of inhabitants of industrialized areas contain significantly higher amounts of lead and cadmium than hard tissues of teeth in residents of agricultural areas and comparable amounts of manganese and chromium. Significance. It appears that hard tissues of retained teeth may constitute valuable material for assessment of long-term environmental exposure to metal ions. The study confirms that the risk of exposure to heavy metals depends on the place of residence and environmental pollution.

  2. Evaluation of Metal Ion Concentration in Hard Tissues of Teeth in Residents of Central Poland.

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    Wychowanski, Piotr; Malkiewicz, Konrad

    2017-01-01

    Objectives. The aim of the study was an assessment of the content of trace elements in enamel and dentin of teeth extracted in patients residing in urban and agricultural areas of Poland. Methods. The study included 30 generally healthy patients with retained third molars. 65 samples of enamel and dentin from individuals living in urban areas and 85 samples of enamel and dentin from individuals living in agricultural areas were prepared. The content of manganese, lead, cadmium, and chromium in the studied enamel and dentin samples from retained teeth was determined by Graphite Furnace Atomic Absorption Spectrometry. In the process of statistical hypothesis testing, the level of significance was assumed at α = 0.05. Results. A comparative analysis of the data showed that enamel and dentin of inhabitants of industrialized areas contain significantly higher amounts of lead and cadmium than hard tissues of teeth in residents of agricultural areas and comparable amounts of manganese and chromium. Significance. It appears that hard tissues of retained teeth may constitute valuable material for assessment of long-term environmental exposure to metal ions. The study confirms that the risk of exposure to heavy metals depends on the place of residence and environmental pollution.

  3. CD157 Marks Tissue-Resident Endothelial Stem Cells with Homeostatic and Regenerative Properties.

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    Wakabayashi, Taku; Naito, Hisamichi; Suehiro, Jun-Ichi; Lin, Yang; Kawaji, Hideya; Iba, Tomohiro; Kouno, Tsukasa; Ishikawa-Kato, Sachi; Furuno, Masaaki; Takara, Kazuhiro; Muramatsu, Fumitaka; Weizhen, Jia; Kidoya, Hiroyasu; Ishihara, Katsuhiko; Hayashizaki, Yoshihide; Nishida, Kohji; Yoder, Mervin C; Takakura, Nobuyuki

    2018-02-01

    The generation of new blood vessels via angiogenesis is critical for meeting tissue oxygen demands. A role for adult stem cells in this process remains unclear. Here, we identified CD157 (bst1, bone marrow stromal antigen 1) as a marker of tissue-resident vascular endothelial stem cells (VESCs) in large arteries and veins of numerous mouse organs. Single CD157 + VESCs form colonies in vitro and generate donor-derived portal vein, sinusoids, and central vein endothelial cells upon transplantation in the liver. In response to injury, VESCs expand and regenerate entire vasculature structures, supporting the existence of an endothelial hierarchy within blood vessels. Genetic lineage tracing revealed that VESCs maintain large vessels and sinusoids in the normal liver for more than a year, and transplantation of VESCs rescued bleeding phenotypes in a mouse model of hemophilia. Our findings show that tissue-resident VESCs display self-renewal capacity and that vascular regeneration potential exists in peripheral blood vessels. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Drug treatment of skin and soft tissue infections in elderly long-term care residents.

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    Lertzman, B H; Gaspari, A A

    1996-08-01

    Nursing home-acquired skin and soft tissue infections are common, with an estimated prevalence of approximately 5%. Such infections can be a cause of significant morbidity. The types of organisms that cause primary skin and soft tissue infections in the elderly are diverse, and include bacterial, viral and fungal infections, as well as infestations with scabies or lice. In the elderly, these infections or infestations may present with atypical signs and symptoms, so a high index of suspicion is necessary. These skin and soft tissue infections may complicate an underlying chronic skin disorder (such as a decubitus ulcer), further altering their clinical presentation. Treatment of skin infections and infestations is based on the appropriate diagnostic tests. Once the diagnosis has been confirmed, treatment with the standard drug therapy is usually associated with a favourable clinical outcome. This article summarises the major skin and soft tissue infections in the elderly, and the appropriate drug therapy, with emphasis on special considerations for long-term care residents and the unique environment of the nursing home that allows for the emergence of resistant organisms. These factors make the management of skin and soft tissue infections in this population unique and challenging.

  5. Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway.

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    Morizawa, Yosuke M; Hirayama, Yuri; Ohno, Nobuhiko; Shibata, Shinsuke; Shigetomi, Eiji; Sui, Yang; Nabekura, Junichi; Sato, Koichi; Okajima, Fumikazu; Takebayashi, Hirohide; Okano, Hideyuki; Koizumi, Schuichi

    2017-06-22

    Astrocytes become reactive following various brain insults; however, the functions of reactive astrocytes are poorly understood. Here, we show that reactive astrocytes function as phagocytes after transient ischemic injury and appear in a limited spatiotemporal pattern. Following transient brain ischemia, phagocytic astrocytes are observed within the ischemic penumbra region during the later stage of ischemia. However, phagocytic microglia are mainly observed within the ischemic core region during the earlier stage of ischemia. Phagocytic astrocytes upregulate ABCA1 and its pathway molecules, MEGF10 and GULP1, which are required for phagocytosis, and upregulation of ABCA1 alone is sufficient for enhancement of phagocytosis in vitro. Disrupting ABCA1 in reactive astrocytes result in fewer phagocytic inclusions after ischemia. Together, these findings suggest that astrocytes are transformed into a phagocytic phenotype as a result of increase in ABCA1 and its pathway molecules and contribute to remodeling of damaged tissues and penumbra networks.Astrocytic phagocytosis has been shown to play a role in synaptic pruning during development, but whether adult astrocytes possess phagocytic ability is unclear. Here the authors show that following brain ischemia, reactive astrocytes become phagocytic and engulf debris via the ABCA1 pathway.

  6. Tissue-Resident Memory CD8+ T Cells: From Phenotype to Function

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    David J. Topham

    2018-03-01

    Full Text Available Tissue-resident memory CD8+ T cells are an important first line of defense from infection in peripheral non-lymphoid tissues, such as the mucosal tissues of the respiratory, digestive, and urogenital tracts. This memory T cell subset is established late during resolution of primary infection of those tissues, has a distinct genetic signature, and is often defined by the cell surface expression of CD69, CD103, CD49a, and CD44 in both mouse and human studies. The stimuli that program or imprint the unique gene expression and cell surface phenotypes on TRM are beginning to be defined, but much work remains to be done. It is not clear, for example, when and where the TRM precursors receive these signals, and there is evidence that supports imprinting in both the lymph node and the peripheral tissue sites. In most studies, expression of CD49a, CD103, and CD69 on T cells in the tissues appears relatively late in the response, suggesting there are precise environmental cues that are not present at the height of the acute response. CD49a and CD103 are not merely biomarkers of TRM, they confer substrate specificities for cell adhesion to collagen and E-cadherin, respectively. Yet, little attention has been paid to how expression affects the positioning of TRM in the peripheral tissues. CD103 and CD49a are not mutually exclusive, and not always co-expressed, although whether they can compensate for one another is unknown. In fact, they may define different subsets of TRM in certain tissues. For instance, while CD49a+CD8+ memory T cells can be found in almost all peripheral tissues, CD103 appears to be more restricted. In this review, we discuss the evidence for how these hallmarks of TRM affect positioning of T cells in peripheral sites, how CD49a and CD103 differ in expression and function, and why they are important for immune protection conferred by TRM in mucosal tissues such as the respiratory tract.

  7. MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells.

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    Jones, Russell G; Pearce, Edward J

    2017-05-16

    Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells. We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts. Copyright © 2017. Published by Elsevier Inc.

  8. IL-15-Independent Maintenance of Tissue-Resident and Boosted Effector Memory CD8 T Cells.

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    Schenkel, Jason M; Fraser, Kathryn A; Casey, Kerry A; Beura, Lalit K; Pauken, Kristen E; Vezys, Vaiva; Masopust, David

    2016-05-01

    IL-15 regulates central and effector memory CD8 T cell (TCM and TEM, respectively) homeostatic proliferation, maintenance, and longevity. Consequently, IL-15 availability hypothetically defines the carrying capacity for total memory CD8 T cells within the host. In conflict with this hypothesis, previous observations demonstrated that boosting generates preternaturally abundant TEM that increases the total quantity of memory CD8 T cells in mice. In this article, we provide a potential mechanistic explanation by reporting that boosted circulating TEM do not require IL-15 for maintenance. We also investigated tissue-resident memory CD8 T cells (TRM), which protect nonlymphoid tissues from reinfection. We observed up to a 50-fold increase in the total magnitude of TRM in mouse mucosal tissues after boosting, suggesting that the memory T cell capacity in tissues is flexible and that TRM may not be under the same homeostatic regulation as primary central memory CD8 T cells and TEM Further analysis identified distinct TRM populations that depended on IL-15 for homeostatic proliferation and survival, depended on IL-15 for homeostatic proliferation but not for survival, or did not depend on IL-15 for either process. These observations on the numerical regulation of T cell memory indicate that there may be significant heterogeneity among distinct TRM populations and also argue against the common perception that developing vaccines that confer protection by establishing abundant TEM and TRM will necessarily erode immunity to previously encountered pathogens as the result of competition for IL-15. Copyright © 2016 by The American Association of Immunologists, Inc.

  9. Poised Regeneration of Zebrafish Melanocytes Involves Direct Differentiation and Concurrent Replenishment of Tissue-Resident Progenitor Cells.

    Science.gov (United States)

    Iyengar, Sharanya; Kasheta, Melissa; Ceol, Craig J

    2015-06-22

    Efficient regeneration following injury is critical for maintaining tissue function and enabling organismal survival. Cells reconstituting damaged tissue are often generated from resident stem or progenitor cells or from cells that have dedifferentiated and become proliferative. While lineage-tracing studies have defined cellular sources of regeneration in many tissues, the process by which these cells execute the regenerative process is largely obscure. Here, we have identified tissue-resident progenitor cells that mediate regeneration of zebrafish stripe melanocytes and defined how these cells reconstitute pigmentation. Nearly all regeneration melanocytes arise through direct differentiation of progenitor cells. Wnt signaling is activated prior to differentiation, and inhibition of Wnt signaling impairs regeneration. Additional progenitors divide symmetrically to sustain the pool of progenitor cells. Combining direct differentiation with symmetric progenitor divisions may serve as a means to rapidly repair injured tissue while preserving the capacity to regenerate. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Tissue-Resident Lymphocytes in Solid Organ Transplantation: Innocent Passengers or the Key to Organ Transplant Survival?

    Science.gov (United States)

    Prosser, Amy C; Kallies, Axel; Lucas, Michaela

    2018-03-01

    Short-term outcomes of solid organ transplantation have improved dramatically over the past several decades; however, long-term survival has remained static over the same period, and chronic rejection remains a major cause of graft failure. The importance of donor, or "passenger," lymphocytes to the induction of tolerance to allografts was recognized in the 1990s, but their precise contribution to graft acceptance or rejection has not been elucidated. Recently, specialized populations of tissue-resident lymphocytes in nonlymphoid organs have been described. These lymphocytes include tissue-resident memory T cells, regulatory T cells, γδ T cells, invariant natural killer T cells, and innate lymphoid cells. These cells reside in commonly transplanted solid organs, including the liver, kidneys, heart, and lung; however, their contribution to graft acceptance or rejection has not been examined in detail. Similarly, it is unclear whether tissue-resident cells derived from the pool of recipient-derived lymphocytes play a specific role in transplantation biology. This review summarizes the evidence for the roles of tissue-resident lymphocytes in transplant immunology, focussing on their features, functions, and relevance for solid organ transplantation, with specific reference to liver, kidney, heart, and lung transplantation.

  11. Melanoma-derived factors alter the maturation and activation of differentiated tissue-resident dendritic cells.

    Science.gov (United States)

    Hargadon, Kristian M; Bishop, Johnathan D; Brandt, John P; Hand, Zachary C; Ararso, Yonathan T; Forrest, Osric A

    2016-01-01

    Dendritic cells (DCs) are key regulators of host immunity that are capable of inducing either immune tolerance or activation. In addition to their well-characterized role in shaping immune responses to foreign pathogens, DCs are also known to be critical for the induction and maintenance of anti-tumor immune responses. Therefore, it is important to understand how tumors influence the function of DCs and the quality of immune responses they elicit. Although the majority of studies in this field to date have utilized either immortalized DC lines or DC populations that have been generated under artificial conditions from hematopoietic precursors in vitro, we wished to investigate how tumors impact the function of already differentiated, tissue-resident DCs. Therefore, we used both an ex vivo and in vivo model system to assess the influence of melanoma-derived factors on DC maturation and activation. In ex vivo studies with freshly isolated splenic DCs, we demonstrate that the extent to which DC maturation and activation are altered by these factors correlates with melanoma tumorigenicity, and we identify partial roles for tumor-derived transforming growth factor (TGF)β1 and vascular endothelial growth factor (VEGF)-A in the altered functionality of DCs. In vivo studies using a lung metastasis model of melanoma also demonstrate tumorigenicity-dependent alterations to the function of lung-resident DCs, and skewed production of proinflammatory cytokines and chemokines by these tumor-altered cells is associated with recruitment of an immune infiltrate that may ultimately favor tumor immune escape and outgrowth.

  12. Aging of tissue-resident adult stem/progenitor cells and their pathological consequences.

    Science.gov (United States)

    Mimeault, M; Batra, S K

    2009-06-01

    The fascinating discovery of tissue-resident adult stem/progenitor cells in recent years led to an explosion of interest in the development of novel stem cell-based therapies for improving the regenerative capacity of these endogenous immature cells or transplanted cells for the repair of damaged and diseased tissues. In counterbalance, a growing body of evidence has revealed that the changes in phenotypic and functional properties of human adult stem/progenitor cells may occur during chronological aging and have severe pathological consequences. Especially, intense oxidative and metabolic stress and chronic inflammation, enhanced telomere attrition and defects in DNA repair mechanisms may lead to severe DNA damages and genomic instability in adult stem/progenitor cells with advancing age that may in turn trigger their replicative senescence and/or programmed cell death. Moreover, the changes in the intrinsic and extrinsic factors involved in the stringent control of self-renewal and multilineage differentiation capacities of these regenerative cells, including deregulated signals from the aged niche, may also contribute to their dysfunctions or loss during chronological aging. This age-associated decline in the regenerative capacity and number of functional adult stem/progenitor cells may increase the risk to develop certain diseases. At opposed end, the telomerase reactivation and accumulation of genetic alterations leading to a down-regulation of numerous tumor suppressor genes concomitant with the enhanced expression of diverse oncogenic products may result in their malignant transformation into cancer-initiating cells. Therefore, the rescue or replacement of aged and dysfunctional endogenous adult stem/progenitor cells or molecular targeting of their malignant counterpart, cancer stem/progenitor cells may constitute potential anti-aging and cancer therapies. These therapeutic strategies could be used for treating diverse devastating premature aging and age

  13. Human and mouse mononuclear phagocyte networks: a tale of two species?

    Directory of Open Access Journals (Sweden)

    Gary eReynolds

    2015-06-01

    Full Text Available Dendritic cells (DCs, monocytes and macrophages are a heterogeneous population of mononuclear phagocytes that are involved in antigen processing and presentation to initiate and regulate immune responses to pathogens, vaccines, tumour and tolerance to self. In addition to their afferent sentinel function, DCs and macrophages are also critical as effectors and coordinators of inflammation and homeostasis in peripheral tissues. Harnessing DCs and macrophages for therapeutic purposes has major implications for infectious disease, vaccination, transplantation, tolerance induction, inflammation and cancer immunotherapy. There has been a paradigm shift in our understanding of the developmental origin and function of the cellular constituents of the mononuclear phagocyte system. Significant progress has been made in tandem in both human and mouse mononuclear phagocyte biology. This progress has been accelerated by comparative biology analysis between mouse and human, which has proved to be an exceptionally fruitful strategy to harmonise findings across species. Such analyses have provided unexpected insights and facilitated productive reciprocal and iterative processes to inform our understanding of human and mouse mononuclear phagocytes. In this review, we discuss the strategies, power and utility of comparative biology approaches to integrate recent advances in human and mouse mononuclear phagocyte biology and its potential to drive forward clinical translation of this knowledge. We also present a functional framework on the parallel organisation of human and mouse mononuclear phagocyte networks.

  14. IL-4 directly signals tissue-resident macrophages to proliferate beyond homeostatic levels controlled by CSF-1

    Science.gov (United States)

    Ruckerl, Dominik; Thomas, Graham D.; Hewitson, James P.; Duncan, Sheelagh; Brombacher, Frank; Maizels, Rick M.; Hume, David A.; Allen, Judith E.

    2013-01-01

    Macrophages (MΦs) colonize tissues during inflammation in two distinct ways: recruitment of monocyte precursors and proliferation of resident cells. We recently revealed a major role for IL-4 in the proliferative expansion of resident MΦs during a Th2-biased tissue nematode infection. We now show that proliferation of MΦs during intestinal as well as tissue nematode infection is restricted to sites of IL-4 production and requires MΦ-intrinsic IL-4R signaling. However, both IL-4Rα–dependent and –independent mechanisms contributed to MΦ proliferation during nematode infections. IL-4R–independent proliferation was controlled by a rise in local CSF-1 levels, but IL-4Rα expression conferred a competitive advantage with higher and more sustained proliferation and increased accumulation of IL-4Rα+ compared with IL-4Rα− cells. Mechanistically, this occurred by conversion of IL-4Rα+ MΦs from a CSF-1–dependent to –independent program of proliferation. Thus, IL-4 increases the relative density of tissue MΦs by overcoming the constraints mediated by the availability of CSF-1. Finally, although both elevated CSF1R and IL-4Rα signaling triggered proliferation above homeostatic levels, only CSF-1 led to the recruitment of monocytes and neutrophils. Thus, the IL-4 pathway of proliferation may have developed as an alternative to CSF-1 to increase resident MΦ numbers without coincident monocyte recruitment. PMID:24101381

  15. Aggregation of sea urchin phagocytes is augmented in vitro by lipopolysaccharide.

    Science.gov (United States)

    Majeske, Audrey J; Bayne, Christopher J; Smith, L Courtney

    2013-01-01

    Development of protocols and media for culturing immune cells from marine invertebrates has not kept pace with advancements in mammalian immune cell culture, the latter having been driven by the need to understand the causes of and develop therapies for human and animal diseases. However, expansion of the aquaculture industry and the diseases that threaten these systems creates the need to develop cell and tissue culture methods for marine invertebrates. Such methods will enable us to better understand the causes of disease outbreaks and to develop means to avoid and remedy epidemics. We report a method for the short-term culture of phagocytes from the purple sea urchin, Strongylocentrotus purpuratus, by modifying an approach previously used to culture cells from another sea urchin species. The viability of cultured phagocytes from the purple sea urchin decreases from 91.6% to 57% over six days and phagocyte morphology changes from single cells to aggregates leading to the formation of syncytia-like structures. This process is accelerated in the presence of lipopolysaccharide suggesting that phagocytes are capable of detecting this molecular pattern in culture conditions. Sea urchin immune response proteins, called Sp185/333, are expressed on the surface of a subset of phagocytes and have been associated with syncytia-like structures. We evaluated their expression in cultured phagocytes to determine their possible role in cell aggregation and in the formation of syncytia-like structures. Between 0 and 3 hr, syncytia-like structures were observed in cultures when only ~10% of the cells were positive for Sp185/333 proteins. At 24 hr, ~90% of the nuclei were Sp185/333-positive when all of the phagocytes had aggregated into syncytia-like structures. Consequently, we conclude that the Sp185/333 proteins do not have a major role in initiating the aggregation of cultured phagocytes, however the Sp185/333 proteins are associated with the clustered nuclei within the

  16. In vitro phagocytosis and intracellular survival of Campylobacter jejuni with phagocytes

    Energy Technology Data Exchange (ETDEWEB)

    Kiehlbauch, J.A.

    1986-01-01

    In vitro phagocytosis and intracellular survival of Campylobacter jejuni was studied using three types of mononuclear phagocytes: a J774G8 peritoneal macrophage line, resident BABL/c peritoneal macrophages and human peripheral blood monocytes. In phagocytosis assays using CFU determinations, phagocytosis increased steadily over an 8 hr time period. Results obtained using a /sup 51/Cr assay indicated no consistent significant difference between phagocytosis of C. jejuni between the three mononuclear phagocytes or PMN's and that maximum infection occurred prior to 0.5 hr and maintained throughout the 4 hr assay. Further investigation of the mechanism of attachment and entry of C. jejuni revealed this process required the expenditure of energy by the phagocyte, but was not inhibited by inhibitors of microfilament functions. In addition, phagocytosis was enhanced by the presence of 20% FCS,

  17. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.

    OpenAIRE

    Heng Giap Woon; Asolina Braun; Jane Li; Corey Smith; Jarem Edwards; Frederic Sierro; Carl G Feng; Rajiv Khanna; Michael Elliot; Andrew Bell; Andrew D Hislop; Stuart G Tangye; Alan B Rickinson; Thomas Gebhardt; Warwick J Britton

    2016-01-01

    Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV) and Cytomegalovirus (CMV). How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that...

  18. The effects of different lying positions on interface pressure, skin temperature, and tissue blood flow in nursing home residents.

    Science.gov (United States)

    Källman, Ulrika; Engström, Maria; Bergstrand, Sara; Ek, Anna-Christina; Fredrikson, Mats; Lindberg, Lars-Göran; Lindgren, Margareta

    2015-03-01

    Although repositioning is considered an important intervention to prevent pressure ulcers, tissue response during loading in different lying positions has not been adequately explored. To compare the effects of different lying positions on interface pressure, skin temperature, and tissue blood flow in nursing home residents. From May 2011 to August 2012, interface pressure, skin temperature, and blood flow at three tissue depths were measured for 1 hr over the sacrum in 30° supine tilt and 0° supine positions and over the trochanter major in 30° lateral and 90° lateral positions in 25 residents aged 65 years or older. Measurement of interface pressure was accomplished using a pneumatic pressure transmitter connected to a digital manometer, skin temperature using a temperature sensor, and blood flow using photoplethysmography and laser Doppler flowmetry. Interface pressure was significantly higher in the 0° supine and 90° lateral positions than in 30° supine tilt and 30° lateral positions. The mean skin temperature increased from baseline in all positions. Blood flow was significantly higher in the 30° supine tilt position compared to the other positions. A hyperemic response in the post pressure period was seen at almost all tissue depths and positions. The 30° supine tilt position generated less interface pressure and allowed greater tissue perfusion, suggesting that this position is the most beneficial. © The Author(s) 2014.

  19. Neutrophils and macrophages: The main partners of phagocyte cell systems

    Directory of Open Access Journals (Sweden)

    Manuel T. Silva

    2012-07-01

    Full Text Available Biological cellular systems are groups of cells sharing a set of characteristics, mainly key function and origin. Phagocytes are crucial in the host defense against microbial infection. The previously proposed phagocyte cell systems including the most recent and presently prevailing one, the Mononuclear Phagocyte System (MPS, grouped mononuclear cells but excluded neutrophils, creating an unacceptable situation. As neutrophils are archetypical phagocytes that must be members of comprehensive phagocyte systems, M. T. Silva recently proposed the creation of a Myeloid Phagocyte System (MYPS that adds neutrophils to the MPS. The phagocytes grouped in the MYPS include the leukocytes neutrophils, inflammatory monocytes, macrophages and immature myeloid DCs. Here the justifications behind the inclusion of neutrophils in a phagocyte system is expanded and the MYPS are further characterized as a group of dedicated phagocytic cells that function in an interacting and cooperative way in the host defense against microbial infection. Neutrophils and macrophages are considered the main arms of this system.

  20. Comparative anatomy of phagocytic and immunological synapses

    Directory of Open Access Journals (Sweden)

    Florence eNiedergang

    2016-01-01

    Full Text Available The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all critical features to build functional phagosomes and immunological synapses. Interestingly, both phagocytic cups and immunological synapses display particular spatial and temporal patterns of receptors and signaling molecules, leading to the notion of phagocytic synapse. Here we discuss both types of structures, their organization and the mechanisms by which they are generated and regulated.

  1. Oral administration of visceral adipose tissue antigens ameliorates metabolic disorders in mice and elevates visceral adipose tissue-resident CD4+CD25+Foxp3+regulatory T cells.

    Science.gov (United States)

    Chen, Xiangyu; Zhang, Dali; Chen, Xiaoling; Meng, Gang; Zheng, Qian; Mai, Wenli; Wu, Yuzhang; Ye, Lilin; Wang, Li

    2017-08-16

    Obesity and type 2 diabetes are linked with chronic, low-grade inflammation in visceral adipose tissue (VAT). A unique population of VAT-resident CD4 + Foxp3 + Tregs plays a crucial role in regulating VAT inflammation and metabolic homeostasis. VAT-resident Tregs display a highly restricted TCR repertoire, suggesting they recognize certain autoantigen(s) in VAT. A dramatic reduction of VAT-resident Tregs has been shown to closely correlate with obesity-related VAT chronic inflammation and metabolic disorders. Oral tolerance strategy may modulate inflammatory response to autoantigens by several mechanisms including induction of autoantigen-specific Tregs. Here, we explored the effects and cellular mechanism of oral administration of VAT pooled antigens on high-fat diet (HFD)-induced metabolic disorders in mice. Indeed, we found that oral treatment of VAT mixture antigens effectively inhibited gain in body weight and fat mass, ameliorated serum lipid parameters, and improved insulin sensitivity in HFD mice. This strategy was shown to significantly restore HFD-induced decrease of VAT-resident Tregs, accompanied by a hampered M2-type to M1-type macrophages phenotypic switch as well as decreased CD8 + T cells infiltration in VAT. Thus, oral administration of VAT antigens may be a novel and safe strategy against obesity and its related metabolic disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Human Induced Pluripotent Stem Cell-Derived Macrophages Share Ontogeny with MYB-Independent Tissue-Resident Macrophages

    Directory of Open Access Journals (Sweden)

    Julian Buchrieser

    2017-02-01

    Full Text Available Tissue-resident macrophages, such as microglia, Kupffer cells, and Langerhans cells, derive from Myb-independent yolk sac (YS progenitors generated before the emergence of hematopoietic stem cells (HSCs. Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes, as well as infiltrating, gut, and dermal macrophages, derive from Myb-dependent HSCs. These findings are derived from the mouse, using gene knockouts and lineage tracing, but their applicability to human development has not been formally demonstrated. Here, we use human induced pluripotent stem cells (iPSCs as a tool to model human hematopoietic development. By using a CRISPR-Cas9 knockout strategy, we show that human iPSC-derived monocytes/macrophages develop in an MYB-independent, RUNX1-, and SPI1 (PU.1-dependent fashion. This result makes human iPSC-derived macrophages developmentally related to and a good model for MYB-independent tissue-resident macrophages, such as alveolar and kidney macrophages, microglia, Kupffer cells, and Langerhans cells.

  3. Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites

    Directory of Open Access Journals (Sweden)

    Brahma V. Kumar

    2017-09-01

    Full Text Available Tissue-resident memory T cells (TRMs in mice mediate optimal protective immunity to infection and vaccination, while in humans, the existence and properties of TRMs remain unclear. Here, we use a unique human tissue resource to determine whether human tissue memory T cells constitute a distinct subset in diverse mucosal and lymphoid tissues. We identify a core transcriptional profile within the CD69+ subset of memory CD4+ and CD8+ T cells in lung and spleen that is distinct from that of CD69− TEM cells in tissues and circulation and defines human TRMs based on homology to the transcriptional profile of mouse CD8+ TRMs. Human TRMs in diverse sites exhibit increased expression of adhesion and inhibitory molecules, produce both pro-inflammatory and regulatory cytokines, and have reduced turnover compared with circulating TEM, suggesting unique adaptations for in situ immunity. Together, our results provide a unifying signature for human TRM and a blueprint for designing tissue-targeted immunotherapies.

  4. Tissue-resident adult stem cell populations of rapidly self-renewing organs

    NARCIS (Netherlands)

    Barker, N.; Bartfeld, S.; Clevers, H.

    2010-01-01

    The epithelial lining of the intestine, stomach, and skin is continuously exposed to environmental assault, imposing a requirement for regular self-renewal. Resident adult stem cell populations drive this renewal, and much effort has been invested in revealing their identity. Reliable adult stem

  5. Evidence for a dual function of monocyte-derived mononuclear phagocytes during chronic intestinal inflammation

    DEFF Research Database (Denmark)

    Rivollier, Aymeric Marie Christian; Pool, Lieneke; Frising, Ulrika

    Mononuclear phagocytes derived from tissue-infiltrating monocytes play diverse roles in immunity, ranging from pathogen killing to immune regulation. We and others showed that, upon recruitment to the intestinal mucosa, the differentiation of Ly6Chi monocytes into phagocytes with anti- versus pro...... cells pool in the inflamed intestinal mucosa. However, surprisingly, mice deficient for the chemokine receptor CCR2, which exhibit highly decreased amounts of intestinal MDP, develop an intestinal pathology similar to their wild type littermates. Preliminary experiments using the anti-CD40 colitis model...

  6. Wound repair in the Amphioxus (Branchiostoma platae), an animal deprived of inflammatory phagocytes.

    Science.gov (United States)

    Silva, J R; Mendes, E G; Mariano, M

    1995-03-01

    The existence of phagocytes in the Amphioxus is a matter of debate since early studies of Metchnikoff, who could not induce inflammation in this animal. To reinvestigate this important phenomenon, we sectioned the distal portion of the animal and analyzed, by morphological methods, the presence of phagocytes in the wound. The analysis of the wound by optical and electron microscopy did not detect cells with morphological characteristics of phagocytes in it. The wound is completely covered by the external cuticle of the animal 24 hr after the lesion was made. A second section of the animal leads to abnormal healing of the lesion. The insertion of a surgical silk thread in the muscle of the animals results--after 13 days--in a collection of cells surrounding the foreign body. The ultrastructural analysis of these cells showed they are endothelial cells rather than specialized phagocytes. Yet, the Amphioxus is able to mount an allograph rejection when the animals are tied together by suture. This intriguing capacity of the Amphioxus to cope with tissue healing, infection, and other pathologies without phagocytes is discussed.

  7. Incomplete Memories: The Natural Suppression of Tissue-Resident Memory CD8 T Cells in the Lung

    Directory of Open Access Journals (Sweden)

    Katie L. Reagin

    2018-01-01

    Full Text Available The yearly, cyclic impact of viruses like influenza on human health and the economy is due to the high rates of mutation of traditional antibody targets, which negate any preexisting humoral immunity. However, the seasonality of influenza infections can equally be attributed to an absent or defective memory CD8 T cell response since the epitopes recognized by these cells are derived from essential virus proteins that mutate infrequently. Experiments in mouse models show that protection from heterologous influenza infection is temporally limited and conferred by a population of tissue-resident memory (TRM cells residing in the lung and lung airways. TRM are elicited by a diverse set of pathogens penetrating mucosal barriers and broadly identified by extravascular staining and expression of the activation and adhesion molecules CD69 and CD103. Interestingly, lung TRM fail to express these molecules, which could limit tissue retention, resulting in airway expulsion or death with concomitant loss of heterologous protection. Here, we make the case that respiratory infections uniquely evoke a form of natural immunosuppression whereby specific cytokines and cell–cell interactions negatively impact memory cell programming and differentiation. Respiratory memory is not only short-lived but most of the memory cells in the lung parenchyma may not be bona fide TRM. Given the quantity of microbes humans inhale over a lifetime, limiting cellular residence could be a mechanism employed by the respiratory tract to preserve organismal vitality. Therefore, successful efforts to improve respiratory immunity must carefully and selectively breach these inherent tissue barriers.

  8. Evaluation of Metal Ion Concentration in Hard Tissues of Teeth in Residents of Central Poland

    OpenAIRE

    Wychowanski, Piotr; Malkiewicz, Konrad

    2017-01-01

    Objectives. The aim of the study was an assessment of the content of trace elements in enamel and dentin of teeth extracted in patients residing in urban and agricultural areas of Poland. Methods. The study included 30 generally healthy patients with retained third molars. 65 samples of enamel and dentin from individuals living in urban areas and 85 samples of enamel and dentin from individuals living in agricultural areas were prepared. The content of manganese, lead, cadmium, and chromium i...

  9. Trafficking of phagocytic peritoneal cells in hypoinsulinemic-hyperglycemic mice with systemic candidiasis.

    Science.gov (United States)

    Fraga-Silva, Thais Fernanda de Campos; Venturini, James; de Arruda, Maria Sueli Parreira

    2013-03-25

    Candidemia is a severe fungal infection that primarily affects hospitalized and/or immunocompromised patients. Mononuclear phagocytes have been recognized as pivotal immune cells which act in the recognition of pathogens, phagocytosis, inflammation, polarization of adaptive immune response and tissue repair. Experimental studies have showed that the systemic candidiasis could be controlled by activated peritoneal macrophages. However, the mechanism to explain how these cells act in distant tissue during a systemic fungal infection is still to be elucidated. In the present study we investigate the in vivo trafficking of phagocytic peritoneal cells into infected organs in hypoinsulinemic-hyperglycemic (HH) mice with systemic candidiasis. The red fluorescent vital dye PKH-26 PCL was injected into the peritoneal cavity of Swiss mice 24 hours before the intravenous inoculation with Candida albicans. After 24 and 48 hours and 7 days of infection, samples of the spleen, liver, kidneys, brain and lungs were submitted to the microbiological evaluation as well as to phagocytic peritoneal cell trafficking analyses by fluorescence microscopy. In the present study, PKH+ cells were observed in the peritoneum, kidney, spleen and liver samples from all groups. In infected mice, we also found PKH+ cells in the lung and brain. The HH condition did not affect this process. In the present study we have observed that peritoneal phagocytes migrate to tissues infected by C. albicans and the HH condition did not interfere in this process.

  10. Incorporation of resident macrophages in engineered tissues: Multiple cell type response to microenvironment controlled macrophage-laden gelatine hydrogels.

    Science.gov (United States)

    Dollinger, Camille; Ciftci, Sait; Knopf-Marques, Helena; Guner, Rabia; Ghaemmaghami, Amir M; Debry, Christian; Barthes, Julien; Vrana, Nihal Engin

    2018-02-01

    The success of tissue engineering strategy is strongly related to the inflammatory response, mainly through the activity of macrophages that are key cells in initial immune response to implants. For engineered tissues, the presence of resident macrophages can be beneficial for maintenance of homeostasis and healing. Thus, incorporation of macrophages in engineered tissues can facilitate the integration upon implantation. In this study, an in-vitro model of interaction was developed between encapsulated naive monocytes, macrophages induced with M1/M2 stimulation and incoming cells for immune assisted tissue engineering applications. To mimic the wound healing cascade, naive THP-1 monocytes, endothelial cells and fibroblasts were seeded on the gels as incoming cells. The interaction was first monitored in the absence of the gels. To mimic resident macrophages, THP-1 cells were encapsulated in the presence or absence of IL-4 to control their phenotype and then these hydrogels were seeded with incoming cells. Without encapsulation, activated macrophages induce apoptosis in endothelial cells. Once encapsulated no adverse effects were seen. Macrophage-laden hydrogels attracted more endothelial cells and fibroblasts compared to monocytes-laden hydrogels. The induction (M2 stimulation) of encapsulated macrophages did not change the overall number of attracted cells; but significantly affected their morphology. M1 stimulation by a defined media resulted in more secretion of both pro- and anti-inflammatory cytokines compared to M2 stimulation. It was demonstrated that there is a distinct effect of encapsulated macrophages on the behaviour of the incoming cells; this effect can be harnessed to establish a microenvironment more prone to regeneration upon implantation. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Determination of Pu-239, 240 tissue concentrations in non-occupationally exposed residents of New York City

    International Nuclear Information System (INIS)

    Wrenn, M.E.; Cohen, N.

    1977-01-01

    The study reports on the Pu-239, 240 concentrations in various tissues obtained from individuals residing in New York City. Twenty-six tissue samples have been analyzed for their Pu-239, 240 content, which include sections from the right lung, the liver, bone (4th and 5th vertebrae) and the kidney. The tissues were obtained at autopsy from a selected population not occupationally exposed to plutonium and whose deaths were the result of causes other than metabolic disorders. A detailed description is presented of the radiochemical procedures employed to separate Pu and electrochemically deposit plutonium isotopes prior to alpha spectrometry with Si surface-barrier detectors. Results of these measurements are given as activity per gram wet weight and activity per gram of calcium in the individual tissue. All results have been compared to similar measurements made at other laboratories and with estimates of concentration based on metabolic models. To date, the magnitudes and the distribution of the measured values are consistent with the values inferred from the ICRP lung model and measured concentrations of air

  12. Autophagy Proteins in Phagocyte Endocytosis and Exocytosis

    Directory of Open Access Journals (Sweden)

    Christian Münz

    2017-09-01

    Full Text Available Autophagy was initially described as a catabolic pathway that recycles nutrients of cytoplasmic constituents after lysosomal degradation during starvation. Since the immune system monitors products of lysosomal degradation via major histocompatibility complex (MHC class II restricted antigen presentation, autophagy was found to process intracellular antigens for display on MHC class II molecules. In recent years, however, it has become apparent that the molecular machinery of autophagy serves phagocytes in many more membrane trafficking pathways, thereby regulating immunity to infectious disease agents. In this minireview, we will summarize the recent evidence that autophagy proteins regulate phagocyte endocytosis and exocytosis for myeloid cell activation, pathogen replication, and MHC class I and II restricted antigen presentation. Selective stimulation and inhibition of the respective functional modules of the autophagy machinery might constitute valid therapeutic options in the discussed disease settings.

  13. High content analysis of phagocytic activity and cell morphology with PuntoMorph.

    Science.gov (United States)

    Al-Ali, Hassan; Gao, Han; Dalby-Hansen, Camilla; Peters, Vanessa Ann; Shi, Yan; Brambilla, Roberta

    2017-11-01

    Phagocytosis is essential for maintenance of normal homeostasis and healthy tissue. As such, it is a therapeutic target for a wide range of clinical applications. The development of phenotypic screens targeting phagocytosis has lagged behind, however, due to the difficulties associated with image-based quantification of phagocytic activity. We present a robust algorithm and cell-based assay system for high content analysis of phagocytic activity. The method utilizes fluorescently labeled beads as a phagocytic substrate with defined physical properties. The algorithm employs statistical modeling to determine the mean fluorescence of individual beads within each image, and uses the information to conduct an accurate count of phagocytosed beads. In addition, the algorithm conducts detailed and sophisticated analysis of cellular morphology, making it a standalone tool for high content screening. We tested our assay system using microglial cultures. Our results recapitulated previous findings on the effects of microglial stimulation on cell morphology and phagocytic activity. Moreover, our cell-level analysis revealed that the two phenotypes associated with microglial activation, specifically cell body hypertrophy and increased phagocytic activity, are not highly correlated. This novel finding suggests the two phenotypes may be under the control of distinct signaling pathways. We demonstrate that our assay system outperforms preexisting methods for quantifying phagocytic activity in multiple dimensions including speed, accuracy, and resolution. We provide a framework to facilitate the development of high content assays suitable for drug screening. For convenience, we implemented our algorithm in a standalone software package, PuntoMorph. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Phagocytic activity of peripheral blood and crevicular phagocytes in health and periodontal disease

    Directory of Open Access Journals (Sweden)

    Asif K

    2010-01-01

    Full Text Available Background: Neutrophils constitute the main phagocytic cell system in mammalian host defense against an infecting agent. Abnormalities in leukocyte number and function are associated with increased susceptibility to periodontal diseases. The purpose of this study is to evaluate the in vitro phagocytic properties of crevicular and peripheral blood neutrophils in healthy and periodontitis subjects. Patients and Methods: A total of 30 subjects, that is, 10 patients in each of the following three groups: healthy controls, chronic periodontitis (CP, and localized aggressive periodontitis (LAP, were included in the study. The neutrophils were isolated from the peripheral blood and gingival crevice and tested for phagocytosis of Candida albicans. The percentage of leukocytes with ingested C. albicans was determined by light microscopy. Results: A significant reduction in the phagocytic activity of crevicular fluid polymorphonuclear neutrophils (CF-PMN of LAP subjects (mean: 54.3±7(P< 0.001 was observed, compared to healthy controls (mean: 74.2±9 and chronic periodontitis subjects (mean: 69±9(P=0.352. The mean percentage of peripheral blood polymorphonuclear neutrophils (PMNs with phagocytosis of opsonized C. albicans in LAP patients was significantly reduced (mean: 74.9±5(P< 0.0068 compared to the phagocytic activity of neutrophils from controls (mean:82.1±3 and chronic periodontitis subjects (mean: 82.0±5(P=0.970. There was no significant reduction in the phagocytic activity of CF PMNs (mean: 69±9 (P=0.35 and peripheral blood PMNs (mean: 82.5(P=0.97 in the chronic periodontitis group when compared to the control group. Conclusion: The phagocytic activity of both crevicular and peripheral neutrophils in subjects with periodontitis is altered, increasing the susceptibility to periodontitis. Thus individual susceptibility may be an additional and important modifying factor in the pathogenesis of periodontal disease.

  15. Neutrophil Migration into the Infected Uroepithelium Is Regulated by the Crosstalk between Resident and Helper Macrophages

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    Kristina Zec

    2016-02-01

    Full Text Available The antibacterial defense against infections depends on the cooperation between distinct phagocytes of the innate immune system, namely macrophages and neutrophils. However, the mechanisms driving this cooperation are incompletely understood. In this study we describe the crosstalk between Ly6C+ and Ly6C− macrophage-subtypes and neutrophils in the context of urinary tract infection (UTI with uropathogenic E. coli (UPEC. Ly6C− macrophages acted as tissue resident sentinels and attracted circulating phagocytes by chemokines. Ly6C+ macrophages produced tumor necrosis factor (TNF that licensed Ly6C− macrophages to release preformed CXCL2, which in turn caused matrix metalloproteinases (MMP-9 secretion by neutrophils to enable transepithelial migration.

  16. Aggregation of sea urchin phagocytes is augmented in vitro by lipopolysaccharide.

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    Audrey J Majeske

    Full Text Available Development of protocols and media for culturing immune cells from marine invertebrates has not kept pace with advancements in mammalian immune cell culture, the latter having been driven by the need to understand the causes of and develop therapies for human and animal diseases. However, expansion of the aquaculture industry and the diseases that threaten these systems creates the need to develop cell and tissue culture methods for marine invertebrates. Such methods will enable us to better understand the causes of disease outbreaks and to develop means to avoid and remedy epidemics. We report a method for the short-term culture of phagocytes from the purple sea urchin, Strongylocentrotus purpuratus, by modifying an approach previously used to culture cells from another sea urchin species. The viability of cultured phagocytes from the purple sea urchin decreases from 91.6% to 57% over six days and phagocyte morphology changes from single cells to aggregates leading to the formation of syncytia-like structures. This process is accelerated in the presence of lipopolysaccharide suggesting that phagocytes are capable of detecting this molecular pattern in culture conditions. Sea urchin immune response proteins, called Sp185/333, are expressed on the surface of a subset of phagocytes and have been associated with syncytia-like structures. We evaluated their expression in cultured phagocytes to determine their possible role in cell aggregation and in the formation of syncytia-like structures. Between 0 and 3 hr, syncytia-like structures were observed in cultures when only ~10% of the cells were positive for Sp185/333 proteins. At 24 hr, ~90% of the nuclei were Sp185/333-positive when all of the phagocytes had aggregated into syncytia-like structures. Consequently, we conclude that the Sp185/333 proteins do not have a major role in initiating the aggregation of cultured phagocytes, however the Sp185/333 proteins are associated with the clustered

  17. CD49a Expression Defines Tissue-Resident CD8+ T Cells Poised for Cytotoxic Function in Human Skin

    DEFF Research Database (Denmark)

    Cheuk, Stanley; Schlums, Heinrich; Sérézal, Irène Gallais

    2017-01-01

    Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8+ Trm cells on a compartmental and functional basis. In human skin epithelia, CD8+CD49a+ Trm cells produced...... interferon-γ, whereas CD8+CD49a− Trm cells produced interleukin-17 (IL-17). In addition, CD8+CD49a+ Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response. In skin from patients...... in this skin disease. Overall, CD49a expression delineates CD8+ Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases....

  18. Compartmentalization of Total and Virus-Specific Tissue-Resident Memory CD8+ T Cells in Human Lymphoid Organs.

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    Heng Giap Woon

    2016-08-01

    Full Text Available Disruption of T cell memory during severe immune suppression results in reactivation of chronic viral infections, such as Epstein Barr virus (EBV and Cytomegalovirus (CMV. How different subsets of memory T cells contribute to the protective immunity against these viruses remains poorly defined. In this study we examined the compartmentalization of virus-specific, tissue resident memory CD8+ T cells in human lymphoid organs. This revealed two distinct populations of memory CD8+ T cells, that were CD69+CD103+ and CD69+CD103-, and were retained within the spleen and tonsils in the absence of recent T cell stimulation. These two types of memory cells were distinct not only in their phenotype and transcriptional profile, but also in their anatomical localization within tonsils and spleen. The EBV-specific, but not CMV-specific, CD8+ memory T cells preferentially accumulated in the tonsils and acquired a phenotype that ensured their retention at the epithelial sites where EBV replicates. In vitro studies revealed that the cytokine IL-15 can potentiate the retention of circulating effector memory CD8+ T cells by down-regulating the expression of sphingosine-1-phosphate receptor, required for T cell exit from tissues, and its transcriptional activator, Kruppel-like factor 2 (KLF2. Within the tonsils the expression of IL-15 was detected in regions where CD8+ T cells localized, further supporting a role for this cytokine in T cell retention. Together this study provides evidence for the compartmentalization of distinct types of resident memory T cells that could contribute to the long-term protection against persisting viral infections.

  19. Up-regulated expression of extracellular matrix remodeling genes in phagocytically challenged trabecular meshwork cells.

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    Kristine M Porter

    Full Text Available Cells in the trabecular meshwork (TM, the tissue responsible for draining aqueous humor out of the eye, are known to be highly phagocytic. Phagocytic function in TM cells is thought to play an important role in the normal functioning of the outflow pathway. Dysfunction of phagocytosis could lead to abnormalities of outflow resistance and increased intraocular pressure (IOP. However, the molecular mechanisms triggered by phagocytosis in TM cells are completely unknown.Gene expression profile analysis of human TM cells phagocytically challenged to E. coli or pigment under physiological and oxidative stress environment were performed using Affymetrix U133 plus 2.0 array and analyzed with Genespring GX. Despite the differential biological response elicited by E. coli and pigment particles, a number of genes, including MMP1, MMP3, TNFSF11, DIO2, KYNU, and KCCN2 showed differential expression with both phagocytic ligands in all conditions. Data was confirmed by qPCR in both human and porcine TM cells. Metacore pathway analysis and the usage of recombinant adenovirus encoding the dominant negative mutant of IkB identified NF-κB as a transcription factor mediating the up-regulation of at least MMP1 and MMP3 in TM cells with phagocytosis. In-gel zymography demonstrated increased collagenolytic and caseinolytic activities in the culture media of TM cells challenge to E. coli. In addition, collagenolytic I activity was further confirmed using the self-quenched fluorescent substrate DQ-Collagen I.Here we report for the first time the differential gene expression profile of TM cells phagocytically challenged with either E. coli or pigment. Our data indicate a potential role of phagocytosis in outflow pathway tissue homeostasis through the up-regulation and/or proteolytic activation of extracellular matrix remodeling genes.

  20. Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic and conventional splenic NK cells

    Science.gov (United States)

    Sojka, Dorothy K; Plougastel-Douglas, Beatrice; Yang, Liping; Pak-Wittel, Melissa A; Artyomov, Maxim N; Ivanova, Yulia; Zhong, Chao; Chase, Julie M; Rothman, Paul B; Yu, Jenny; Riley, Joan K; Zhu, Jinfang; Tian, Zhigang; Yokoyama, Wayne M

    2014-01-01

    Natural killer (NK) cells belong to the innate immune system; they can control virus infections and developing tumors by cytotoxicity and producing inflammatory cytokines. Most studies of mouse NK cells, however, have focused on conventional NK (cNK) cells in the spleen. Recently, we described two populations of liver NK cells, tissue-resident NK (trNK) cells and those resembling splenic cNK cells. However, their lineage relationship was unclear; trNK cells could be developing cNK cells, related to thymic NK cells, or a lineage distinct from both cNK and thymic NK cells. Herein we used detailed transcriptomic, flow cytometric, and functional analysis and transcription factor-deficient mice to determine that liver trNK cells form a distinct lineage from cNK and thymic NK cells. Taken together with analysis of trNK cells in other tissues, there are at least four distinct lineages of NK cells: cNK, thymic, liver (and skin) trNK, and uterine trNK cells. DOI: http://dx.doi.org/10.7554/eLife.01659.001 PMID:24714492

  1. Cathepsin B is up-regulated and mediates extracellular matrix degradation in trabecular meshwork cells following phagocytic challenge.

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    Kristine Porter

    Full Text Available Cells in the trabecular meshwork (TM, a tissue responsible for draining aqueous humor out of the eye, are known to be highly phagocytic. Phagocytic activity in TM cells is thought to play an important role in outflow pathway physiology. However, the molecular mechanisms triggered by phagocytosis in TM cells are unknown. Here we investigated the effects of chronic phagocytic stress on lysosomal function using different phagocytic ligands (E. coli, carboxylated beads, collagen I-coated beads, and pigment. Lysotracker red co-localization and electron micrographs showed the maturation of E. coli- and collagen I-coated beads-containing phagosomes into phagolysosomes. Maturation of phagosomes into phagolysosomes was not observed with carboxylated beads or pigment particles. In addition, phagocytosis of E. coli and collagen I-coated beads led to increased lysosomal mass, and the specific up-regulation and activity of cathepsin B (CTSB. Higher levels of membrane-bound and secreted CTSB were also detected. Moreover, in vivo zymography showed the intralysosomal degradation of ECM components associated with active CTSB, as well as an overall increased gelatinolytic activity in phagocytically challenged TM cells. This increased gelatinolytic activity with phagocytosis was partially blocked with an intracellular CTSB inhibitor. Altogether, these results suggest a potential role of phagocytosis in outflow pathway tissue homeostasis through the up-regulation and/or proteolytic activation of extracellular matrix remodeling genes.

  2. Nicotine attenuates activation of tissue resident macrophages in the mouse stomach through the β2 nicotinic acetylcholine receptor.

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    Andrea Nemethova

    Full Text Available BACKGROUND: The cholinergic anti-inflammatory pathway is an endogenous mechanism by which the autonomic nervous system attenuates macrophage activation via nicotinic acetylcholine receptors (nAChR. This concept has however not been demonstrated at a cellular level in intact tissue. To this end, we have studied the effect of nicotine on the activation of resident macrophages in a mouse stomach preparation by means of calcium imaging. METHODS: Calcium transients ([Ca(2+]i in resident macrophages were recorded in a mouse stomach preparation containing myenteric plexus and muscle layers by Fluo-4. Activation of macrophages was achieved by focal puff administration of ATP. The effects of nicotine on activation of macrophages were evaluated and the nAChR involved was pharmacologically characterized. The proximity of cholinergic nerves to macrophages was quantified by confocal microscopy. Expression of β2 and α7 nAChR was evaluated by β2 immunohistochemistry and fluorophore-tagged α-bungarotoxin. RESULTS: In 83% of macrophages cholinergic varicose nerve fibers were detected at distances <900 nm. The ATP induced [Ca(2+]i increase was significantly inhibited in 65% or 55% of macrophages by 100 µM or 10 µM nicotine, respectively. This inhibitory effect was reversed by the β2 nAChR preferring antagonist dihydro-β-eryhtroidine but not by hexamethonium (non-selective nAChR-antagonist, mecamylamine (α3β4 nAChR-preferring antagonist, α-bungarotoxin or methyllycaconitine (both α7 nAChR-preferring antagonist. Macrophages in the stomach express β2 but not α7 nAChR at protein level, while those in the intestine express both receptor subunits. CONCLUSION: This study is the first in situ demonstration of an inhibition of macrophage activation by nicotine suggesting functional signaling between cholinergic neurons and macrophages in the stomach. The data suggest that the β2 subunit of the nAChR is critically involved in the nicotine-induced inhibition

  3. Vitamin D(3 availability and functional activity of peripheral blood phagocytes in experimental type 1 diabetes

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    D. О. Labudzynskyi

    2014-04-01

    Full Text Available The study was devoted to identifying the relation between vitamin D3 availability (assessed by the level of circulatory 25OHD3, content of vitamin D3 25-hydroxylase isozymes CYP27A1 and CYP2R1 in hepatic tissue and functional activity of peripheral blood phagocytes in mice with experimental type 1 diabetes. It has been shown that diabetes is accompanied by the development of vitamin D3-deficiency which is characterized by decreased 25OHD3 content in blood serum and determined by changes in tissue expression of the major isoforms of vitamin D3 25-hydroxylase. The level of hepatic CYP27A1 was revealed to be markedly reduced with a concurrent significant augmentation of CYP2R1. Cholecalciferol administration resulted in normalization of tissue levels of both isoforms of vitamin D3 25-hydroxylase and blood serum 25OHD3 content. Diabetes-associated vitamin D3 deficiency correlated with a decrease in phagocytic activity of granulocytes and monocytes, and their ability to produce antibacterial biooxidants such as reactive oxygen and nitrogen forms. Vitamin D3 efficacy to attenuate these abnormalities of immune function was established, indicating an important immunoregulatory role of cholecalciferol in the phagocytic mechanism of antigens elimination implemented by granulocytes and monocytes.

  4. Defining mononuclear phagocyte subset homology across several distant warm-blooded vertebrates through comparative transcriptomics

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    Thien eVu Manh

    2015-06-01

    Full Text Available Mononuclear phagocytes are organized in a complex system of ontogenically and functionally-distinct subsets, that has been best described in mouse and to some extent in human. Identification of homologous mononuclear phagocyte subsets in other vertebrate species of biomedical, economic and environmental interest is needed to improve our knowledge in physiologic and physio-pathologic processes, and to design intervention strategies against a variety of diseases, including zoonotic infections.We developed a streamlined approach combining refined cell sorting and integrated comparative transcriptomics analyses which revealed conservation of the mononuclear phagocyte organization across human, mouse, sheep, pigs and, in some respect, chicken. This strategy should help democratizing the use of omics analyses for the identification and study of cell types across tissues and species. Moreover we identified conserved gene signatures that enable robust identification and universal definition of these cell types. We identified new evolutionarily conserved gene candidates and gene interaction networks for the molecular regulation of the development or functions of these cell types, as well as conserved surface candidates for refined subset phenotyping throughout species. A phylogenetic analysis revealed that orthologous genes of the conserved signatures exist in teleost fishes and apparently not in Lamprey, indicating conservation of the genetic support for mononuclear phagocyte organization throughout jawed vertebrates but likely not in agnathans. Altogether this work provides molecular clues to the definition and functions of mononuclear phagocyte subsets across vertebrates which shall be useful to rigorously identify these cells and to design universal strategies to manipulate them in many target species towards the goal to reach and maintain global health.

  5. Human Lung Mononuclear Phagocytes in Health and Disease

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    Anna Smed-Sörensen

    2017-05-01

    Full Text Available The lungs are vulnerable to attack by respiratory insults such as toxins, allergens, and pathogens, given their continuous exposure to the air we breathe. Our immune system has evolved to provide protection against an array of potential threats without causing collateral damage to the lung tissue. In order to swiftly detect invading pathogens, monocytes, macrophages, and dendritic cells (DCs—together termed mononuclear phagocytes (MNPs—line the respiratory tract with the key task of surveying the lung microenvironment in order to discriminate between harmless and harmful antigens and initiate immune responses when necessary. Each cell type excels at specific tasks: monocytes produce large amounts of cytokines, macrophages are highly phagocytic, whereas DCs excel at activating naïve T cells. Extensive studies in murine models have established a division of labor between the different populations of MNPs at steady state and during infection or inflammation. However, a translation of important findings in mice is only beginning to be explored in humans, given the challenge of working with rare cells in inaccessible human tissues. Important progress has been made in recent years on the phenotype and function of human lung MNPs. In addition to a substantial population of alveolar macrophages, three subsets of DCs have been identified in the human airways at steady state. More recently, monocyte-derived cells have also been described in healthy human lungs. Depending on the source of samples, such as lung tissue resections or bronchoalveolar lavage, the specific subsets of MNPs recovered may differ. This review provides an update on existing studies investigating human respiratory MNP populations during health and disease. Often, inflammatory MNPs are found to accumulate in the lungs of patients with pulmonary conditions. In respiratory infections or inflammatory diseases, this may contribute to disease severity, but in cancer patients this may

  6. In vivo transfer of intracellular labels from locally implanted bone marrow stromal cells to resident tissue macrophages.

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    Edyta Pawelczyk

    Full Text Available Intracellular labels such as dextran coated superparamagnetic iron oxide nanoparticles (SPION, bromodeoxyuridine (BrdU or green fluorescent protein (GFP are frequently used to study the fate of transplanted cells by in vivo magnetic resonance imaging or fluorescent microscopy. Bystander uptake of labeled cells by resident tissue macrophages (TM can confound the interpretation of the presence of intracellular labels especially during direct implantation of cells, which can result in more than 70% cell death. In this study we determined the percentages of TM that took up SPION, BrdU or GFP from labeled bone marrow stromal cells (BMSCs that were placed into areas of angiogenesis and inflammation in a mouse model known as Matrigel plaque perfusion assay. Cells recovered from digested plaques at various time points were analyzed by fluorescence microscopy and flow cytometry. The analysis of harvested plaques revealed 5% of BrdU(+, 5-10% of GFP(+ and 5-15% of dextran(+ macrophages. The transfer of the label was not dependent on cell dose or viability. Collectively, this study suggests that care should be taken to validate donor origin of cells using an independent marker by histology and to assess transplanted cells for TM markers prior to drawing conclusions about the in vivo behavior of transplanted cells.

  7. CD103+CD8 T Cells in theToxoplasma-Infected Brain Exhibit a Tissue-Resident Memory Transcriptional Profile.

    Science.gov (United States)

    Landrith, Tyler A; Sureshchandra, Suhas; Rivera, Andrea; Jang, Jessica C; Rais, Maham; Nair, Meera G; Messaoudi, Ilhem; Wilson, Emma H

    2017-01-01

    During chronic infection, memory T cells acquire a unique phenotype and become dependent on different survival signals than those needed for memory T cells generated during an acute infection. The distinction between the role of effector and memory T cells in an environment of persistent antigen remains unclear. Here, in the context of chronic Toxoplasma gondii infection, we demonstrate that a population of CD8 T cells exhibiting a tissue-resident memory (T RM ) phenotype accumulates within the brain. We show that this population is distributed throughout the brain in both parenchymal and extraparenchymal spaces. Furthermore, this population is transcriptionally distinct and exhibits a transcriptional signature consistent with the T RM observed in acute viral infections. Finally, we establish that the CD103 + T RM population has an intrinsic capacity to produce both IFN-γ and TNF-α, cytokines critical for parasite control within the central nervous system (CNS). The contribution of this population to pro-inflammatory cytokine production suggests an important role for T RM in protective and ongoing immune responses in the infected CNS. Accession number:   GSE95105 .

  8. In vitro formation of osteoclasts from long-term cultures of bone marrow mononuclear phagocytes

    International Nuclear Information System (INIS)

    Burger, E.H.; Van der Meer, J.W.; van de Gevel, J.S.; Gribnau, J.C.; Thesingh, G.W.; van Furth, R.

    1982-01-01

    The origin of osteoclasts was studied in an in vitro model using organ cultures of periosteum-free embryonic mouse long-bone primordia, which were co-cultured with various cell populations. The bone rudiments were freed of their periosteum-perichondrium by collagenase treatment in a stage before cartilage erosion and osteoclast formation, and co-cultured for 7 d with either embryonic liver or mononuclear phagocytes from various sources. Light and electron microscopic examination of the cultures showed that mineralized matrix-resorbing osteoclasts developed only in bones co-cultured with embryonic liver or with cultured bone marrow mononuclear phagocytes but not when co-cultured with blood monocytes or resident or exudate peritoneal macrophages. Osteoclasts developed from the weakly adherent, but not from the strongly adherent cells of bone marrow cultures, whereas 1,000 rad irradiation destroyed the capacity of such cultures to form osteoclasts. In bone cultures to which no other cells were added, osteoclasts were virtually absent. Bone-resorbing activity of in vitro formed osteoclasts was demonstrated by 45 Ca release studies. These studies demonstrate that osteoclasts develop from cells present in cultures of proliferating mononuclear phagocytes and that, at least in our system, monocytes and macrophages are unable to form osteoclasts. The most likely candidates for osteoclast precursor cells seem to be monoblasts and promonocytes

  9. Eat-me signals: Keys to molecular phagocyte biology and “appetite” control

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    Li, Wei

    2011-01-01

    Hundreds of billions of cells undergo apoptosis in our body everyday and are removed by immunologically silent phagocytosis to maintain tissue homeostasis. Impairments in phagocytosis result in autoimmune and/or degenerative diseases. Eat-me signals are the key to the recognition of extracellular cargos and the initiation of the phagocytosis process by activating phagocytic receptors and signaling cascades, and are convenient targets for therapeutic modulation. Despite their importance, eat-me signals and other phagocytosis players are mostly identified on case-by-case basis with daunting challenges. This Commentary focuses on our latest knowledge of the extracellular players, highlights our approaches to systematically map unknown pathways by functional genetic and proteomic technologies, and discusses future direction to unravel the mystery of molecular phagocyte biology. PMID:21520079

  10. Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

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    Carlos Eduardo Tosta

    1983-03-01

    Full Text Available The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.

  11. Could a B-1 cell derived phagocyte "be one" of the peritoneal macrophages during LPS-driven inflammation?

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    Ana Flavia Popi

    Full Text Available The inflammatory response is driven by signals that recruit and elicit immune cells to areas of tissue damage or infection. The concept of a mononuclear phagocyte system postulates that monocytes circulating in the bloodstream are recruited to inflamed tissues where they give rise to macrophages. A recent publication demonstrated that the large increase in the macrophages observed during infection was the result of the multiplication of these cells rather than the recruitment of blood monocytes. We demonstrated previously that B-1 cells undergo differentiation to acquire a mononuclear phagocyte phenotype in vitro (B-1CDP, and we propose that B-1 cells could be an alternative origin for peritoneal macrophages. A number of recent studies that describe the phagocytic and microbicidal activity of B-1 cells in vitro and in vivo support this hypothesis. Based on these findings, we further investigated the differentiation of B-1 cells into phagocytes in vivo in response to LPS-induced inflammation. Therefore, we investigated the role of B-1 cells in the composition of the peritoneal macrophage population after LPS stimulation using osteopetrotic mice, BALB/Xid mice and the depletion of monocytes/macrophages by clodronate treatment. We show that peritoneal macrophages appear in op/op((-/- mice after LPS stimulation and exhibit the same Ig gene rearrangement (VH11 that is often found in B-1 cells. These results strongly suggest that op/op((-/- peritoneal "macrophages" are B-1CDP. Similarly, the LPS-induced increase in the macrophage population was observed even following monocyte/macrophage depletion by clodronate. After monocyte/macrophage depletion by clodronate, LPS-elicited macrophages were observed in BALB/Xid mice only following the transfer of B-1 cells. Based on these data, we confirmed that B-1 cell differentiation into phagocytes also occurs in vivo. In conclusion, the results strongly suggest that B-1 cell derived phagocytes are a component of

  12. A radiolabel release microassay for phagocytic killing of Candida albicans

    International Nuclear Information System (INIS)

    Bistoni, F.; Baccarini, M.; Blasi, E.; Marconi, P.; Puccetti, P.

    1982-01-01

    The chromium-51 release technique for quantifying intracellular killing of radiolabelled Candida albicans particles was exploited in a microassay in which murine and human phagocytes acted as effectors under peculiarly simple conditions. At appropriate effector: target ratios and with a 4 h incubation, up to 50% specific chromium release could be detected in the supernatant with no need for opsonization or lysis of phagocytes. This simple microassay permits easy-to-perform, simultaneous testing of a variety of different phagocytes even if only available in limited amounts, and provides an objective measurement of intracellular killing of Candida albicans. (Auth.)

  13. Iron inhibits respiratory burst of peritoneal phagocytes in vitro

    DEFF Research Database (Denmark)

    Gotfryd, Kamil; Jurek, Aleksandra; Kubit, Piotr

    2011-01-01

    Objective. This study examines the effects of iron ions Fe(3+) on the respiratory burst of phagocytes isolated from peritoneal effluents of continuous ambulatory peritoneal dialysis (CAPD) patients, as an in vitro model of iron overload in end-stage renal disease (ESRD). Material and Methods....... Respiratory burst of peritoneal phagocytes was measured by chemiluminescence method. Results. At the highest used concentration of iron ions Fe(3+) (100 µM), free radicals production by peritoneal phagocytes was reduced by 90% compared to control. Conclusions. Iron overload may increase the risk of infectious...

  14. The role of Tec family kinases in mononuclear phagocytes.

    Science.gov (United States)

    Koprulu, Afitap Derya; Ellmeier, Wilfried

    2009-01-01

    Mononuclear phagocytes, including monocytcs, macrophages, and dendritic cells, play an important role in innate and adaptive immune responses and are important regulators of the inflammatory response. Among these, monocytes/macrophages are involved in virtually all aspects of inflammation, ranging from the detection and phagocytosis of pathogens up to the resolution of inflammation and repair of tissue damage. The stimulation of cell surface receptors, such as Toll-like receptors, leads to the initiation of intracellular signal transduction pathways regulating macrophagc activation and effector functions. One group of signaling molecules stimulated on macrophage activation is formed by the Tec kinasc family, which consists of five members (Bmx, Btk, Itk, Rlk, and Tec) and constitutes the second-largest family of nonreceptor protein tyrosine kinases in the immune system. Some Tec kinases have been shown to be major regulators of antigen receptor signaling in lymphocytes, and deficiencies in Tec family kinases cause several immunological defects in humans and mice. Much less is known about the role of Tec family kinases in the myeloid branch of the hematopoietic system. In this review, we discuss the current knowledge about the role of Tec family kinases in monocytes/macrophages, in dendritic cells, and in osteoclasts.

  15. Survival and function of phagocytes in blood culture media

    DEFF Research Database (Denmark)

    Fischer, T K; Prag, J; Kharazmi, A

    1999-01-01

    The survival and function of human phagocytes in sterile aerobic and anaerobic blood culture media were investigated using neutrophil morphology, white blood cell count in a haemoanalyser, flow cytometry, oxidative burst response, and bactericidal effect in Colorbact and Septi-Chek blood culture...... media and Bact/Alert. When comparing agitation to stationary incubation no difference in phagocytic activity was found. The methods showed the same trends demonstrating that the phagocytes' viability and activity were prolonged by oxygen and shortened by anaerobic conditions and sodium polyethanol...... sulfonate (SPS). Best preserved activity and viability were found in the aerobic media containing less than 0.5 g/l SPS, in which significant phagocyte oxidative burst and bactericidal activity were found up to 4 days after inoculation. Considering that the majority of bacteremias are due to aerobic...

  16. Specific niches for lung-resident memory CD8+ T cells at the site of tissue regeneration enable CD69-independent maintenance

    Science.gov (United States)

    Hakata, Yoshiyuki; Motozono, Chihiro; McMaster, Sean R.; Masumoto, Tomoko; Fujisawa, Makoto; Chikaishi, Tomomi; Komeda, Junko; Itoh, Jun; Umemura, Miki; Kyusai, Ami; Woodland, David L.; Kohlmeier, Jacob E.; Miyazawa, Masaaki

    2016-01-01

    CD8+ tissue-resident memory T cells (TRM cells) reside permanently in nonlymphoid tissues and provide a first line of protection against invading pathogens. However, the precise localization of CD8+ TRM cells in the lung, which physiologically consists of a markedly scant interstitium compared with other mucosa, remains unclear. In this study, we show that lung CD8+ TRM cells localize predominantly in specific niches created at the site of regeneration after tissue injury, whereas peripheral tissue-circulating CD8+ effector memory T cells (TEM cells) are widely but sparsely distributed in unaffected areas. Although CD69 inhibited sphingosine 1–phosphate receptor 1–mediated egress of CD8+ T cells immediately after their recruitment into lung tissues, such inhibition was not required for the retention of cells in the TRM niches. Furthermore, despite rigid segregation of TEM cells from the TRM niche, prime-pull strategy with cognate antigen enabled the conversion from TEM cells to TRM cells by creating de novo TRM niches. Such damage site–specific localization of CD8+ TRM cells may be important for efficient protection against secondary infections by respiratory pathogens. PMID:27815325

  17. Zebrafish kidney phagocytes utilize macropinocytosis and Ca+-dependent endocytic mechanisms.

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    Claudia Hohn

    Full Text Available BACKGROUND: The innate immune response constitutes the first line of defense against invading pathogens and consists of a variety of immune defense mechanisms including active endocytosis by macrophages and granulocytes. Endocytosis can be used as a reliable measure of selective and non-selective mechanisms of antigen uptake in the early phase of an immune response. Numerous assays have been developed to measure this response in a variety of mammalian and fish species. The small size of the zebrafish has prevented the large-scale collection of monocytes/macrophages and granulocytes for these endocytic assays. METHODOLOGY/PRINCIPAL FINDINGS: Pooled zebrafish kidney hematopoietic tissues were used as a source of phagocytic cells for flow-cytometry based endocytic assays. FITC-Dextran, Lucifer Yellow and FITC-Edwardsiella ictaluri were used to evaluate selective and non-selective mechanisms of uptake in zebrafish phagocytes. CONCLUSIONS/SIGNIFICANCE: Zebrafish kidney phagocytes characterized as monocytes/macrophages, neutrophils and lymphocytes utilize macropinocytosis and Ca(2+-dependant endocytosis mechanisms of antigen uptake. These cells do not appear to utilize a mannose receptor. Heat-killed Edwardsiella ictaluri induces cytoskeletal interactions for internalization in zebrafish kidney monocytes/macrophages and granulocytes. The proposed method is easy to implement and should prove especially useful in immunological, toxicological and epidemiological research.

  18. Depletion of Phagocytic Cells during Nonlethal Plasmodium yoelii Infection Causes Severe Malaria Characterized by Acute Renal Failure in Mice.

    Science.gov (United States)

    Terkawi, Mohamad Alaa; Nishimura, Maki; Furuoka, Hidefumi; Nishikawa, Yoshifumi

    2016-01-11

    In the current study, we examined the effects of depletion of phagocytes on the progression of Plasmodium yoelii 17XNL infection in mice. Strikingly, the depletion of phagocytic cells, including macrophages, with clodronate in the acute phase of infection significantly reduced peripheral parasitemia but increased mortality. Moribund mice displayed severe pathological damage, including coagulative necrosis in liver and thrombi in the glomeruli, fibrin deposition, and tubular necrosis in kidney. The severity of infection was coincident with the increased sequestration of parasitized erythrocytes, the systematic upregulation of inflammation and coagulation, and the disruption of endothelial integrity in the liver and kidney. Aspirin was administered to the mice to minimize the risk of excessive activation of the coagulation response and fibrin deposition in the renal tissue. Interestingly, treatment with aspirin reduced the parasite burden and pathological lesions in the renal tissue and improved survival of phagocyte-depleted mice. Our data imply that the depletion of phagocytic cells, including macrophages, in the acute phase of infection increases the severity of malarial infection, typified by multiorgan failure and high mortality. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  19. Characterization and functional properties of gastric tissue-resident memory T cells from children, adults and the elderly

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    Jayaum S. Booth

    2014-06-01

    Full Text Available T cells are the main orchestrators of protective immunity in the stomach; however, limited information on the presence and function of the gastric T subsets is available mainly due to the difficulty in recovering high numbers of viable cells from human gastric biopsies. To overcome this shortcoming we optimized a cell isolation method that yielded high numbers of viable lamina propria mononuclear cells (LPMC from gastric biopsies. Classic memory T (TM subsets were identified in gastric LPMC and compared to peripheral blood mononuclear cells (PBMC obtained from children, adults and the elderly using an optimized 14 color flow cytometry panel. A dominant effector memory (TEM phenotype was observed in gastric LPMC CD4+ and CD8+ T cells in all age groups. We then evaluated whether these cells represented a population of gastric tissue-resident memory T (TRM cells by assessing expression of CD103 and CD69. The vast majority of gastric LPMC CD8+ T cells either co-expressed CD103/CD69 (>70% or expressed CD103 alone (~20%. Gastric LPMC CD4+ T cells also either co-expressed CD103/CD69 (>35% or expressed at least one of these markers. Thus, gastric LPMC CD8+ and CD4+ T cells had the characteristics of TRM cells. Gastric CD8+ and CD4+ TRM cells produced multiple cytokines (IFN-γ, IL-2, TNF-α, IL-17A, MIP-1β and up-regulated CD107a upon stimulation. However, marked differences were observed in their cytokine and multi-cytokine profiles when compared to their PBMC TEM counterparts. Furthermore, gastric CD8+ TRM and CD4+ TRM cells demonstrated differences in the frequency, susceptibility to activation and cytokine/multi-cytokine production profiles among the age groups. Most notably, children’s gastric TRM cells responded differently to stimuli than gastric TRM cells from adults or the elderly. In conclusion, we demonstrate the presence of gastric TRM which exhibit diverse functional characteristics in children, adults and the elderly.

  20. Retention of Ag-specific memory CD4+ T cells in the draining lymph node indicates lymphoid tissue resident memory populations.

    Science.gov (United States)

    Marriott, Clare L; Dutton, Emma E; Tomura, Michio; Withers, David R

    2017-05-01

    Several different memory T-cell populations have now been described based upon surface receptor expression and migratory capabilities. Here we have assessed murine endogenous memory CD4 + T cells generated within a draining lymph node and their subsequent migration to other secondary lymphoid tissues. Having established a model response targeting a specific peripheral lymph node, we temporally labelled all the cells within draining lymph node using photoconversion. Tracking of photoconverted and non-photoconverted Ag-specific CD4 + T cells revealed the rapid establishment of a circulating memory population in all lymph nodes within days of immunisation. Strikingly, a resident memory CD4 + T cell population became established in the draining lymph node and persisted for several months in the absence of detectable migration to other lymphoid tissue. These cells most closely resembled effector memory T cells, usually associated with circulation through non-lymphoid tissue, but here, these cells were retained in the draining lymph node. These data indicate that lymphoid tissue resident memory CD4 + T-cell populations are generated in peripheral lymph nodes following immunisation. © 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Cross-Tissue Transcriptomic Analysis of Human Secondary Lymphoid Organ-Residing ILC3s Reveals a Quiescent State in the Absence of Inflammation

    Directory of Open Access Journals (Sweden)

    Yotam E. Bar-Ephraim

    2017-10-01

    Full Text Available A substantial number of human and mouse group 3 innate lymphoid cells (ILC3s reside in secondary lymphoid organs, yet the phenotype and function of these ILC3s is incompletely understood. Here, we employed an unbiased cross-tissue transcriptomic approach to compare human ILC3s from non-inflamed lymph nodes and spleen to their phenotypic counterparts in inflamed tonsils and from circulation. These analyses revealed that, in the absence of inflammation, lymphoid organ-residing ILC3s lack transcription of cytokines associated with classical ILC3 functions. This was independent of expression of the natural cytotoxicity receptor NKp44. However, and in contrast to ILC3s from peripheral blood, lymphoid organ-residing ILC3s express activating cytokine receptors and have acquired the ability to be recruited into immune responses by inflammatory cytokines. This comprehensive cross-tissue dataset will allow for identification of functional changes in human lymphoid organ ILC3s associated with human disease.

  2. CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis

    DEFF Research Database (Denmark)

    Trebst, C; Sørensen, Torben Lykke; Kivisäkk, P

    2001-01-01

    and macrophage inflammatory protein-1alpha/CCL3. We analyzed expression of CCR1 and CCR5, the monocyte receptors for these chemokines, on circulating and cerebrospinal fluid CD14+ cells, and in MS brain lesions. Approximately 70% of cerebrospinal fluid monocytes were CCR1+/CCR5+, regardless of the presence...... of CNS pathology, compared to less than 20% of circulating monocytes. In active MS lesions CCR1+/CCR5+ monocytes were found in perivascular cell cuffs and at the demyelinating edges of evolving lesions. Mononuclear phagocytes in early demyelinating stages comprised CCR1+/CCR5+ hematogenous monocytes...... and CCR1-/CCR5- resident microglial cells. In later stages, phagocytic macrophages were uniformly CCR1-/CCR5+. Cultured in vitro, adherent monocytes/macrophages up-regulated CCR5 and down-regulated CCR1 expression, compared to freshly-isolated monocytes. Taken together, these findings suggest...

  3. Nanoparticles of barium induce apoptosis in human phagocytes.

    Science.gov (United States)

    Mores, Luana; França, Eduardo Luzia; Silva, Núbia Andrade; Suchara, Eliane Aparecida; Honorio-França, Adenilda Cristina

    2015-01-01

    Nutrients and immunological factors of breast milk are essential for newborn growth and the development of their immune system, but this secretion can contain organic and inorganic toxins such as barium. Colostrum contamination with barium is an important issue to investigate because this naturally occurring element is also associated with human activity and industrial pollution. The study evaluated the administration of barium nanoparticles to colostrum, assessing the viability and functional activity of colostral mononuclear phagocytes. Colostrum was collected from 24 clinically healthy women (aged 18-35 years). Cell viability, superoxide release, intracellular Ca(2+) release, and phagocyte apoptosis were analyzed in the samples. Treatment with barium lowered mononuclear phagocyte viability, increased superoxide release, and reduced intracellular calcium release. In addition, barium increased cell death by apoptosis. These data suggest that nanoparticles of barium in colostrum are toxic to cells, showing the importance of avoiding exposure to this element.

  4. Contrasting Inflammation Resolution during Atherosclerosis and post Myocardial Infarction at the Level of Monocyte/Macrophage Phagocytic Clearance

    Directory of Open Access Journals (Sweden)

    Edward eThorp

    2012-03-01

    Full Text Available In cardiovascular disorders including advanced atherosclerosis and myocardial infarction (MI, increased cell death and tissue destabilization is associated with recruitment of inflammatory monocyte subsets that give rise to differentiated macrophages. These phagocytic cells clear necrotic and apoptotic bodies and promote inflammation resolution and tissue remodeling. The capacity of macrophages for phagocytosis of apoptotic cells (efferocytosis, clearance of necrotic cell debris, and repair of damaged tissue are challenged and modulated by local cell stressors that include increased protease activity, oxidative stress, and hypoxia. The effectiveness, or lack thereof, of phagocyte-mediated clearance, in turn is linked to active inflammation resolution signaling pathways, susceptibility to atherothrombosis and potentially, adverse post-MI cardiac remodeling leading to heart failure. Previous reports indicate that in advanced atherosclerosis, defective efferocytosis is associated with atherosclerotic plaque destabilization. Post MI, the role of phagocytes and clearance in the heart is less appreciated. Herein we contrast the roles of efferocytosis in atherosclerosis and post MI and focus on how targeted modulation of clearance and accompanying resolution and reparative signaling may be a strategy to prevent heart failure post MI.

  5. Onset of apoprotein E secretion during differentiation of mouse bone marrow-derived mononuclear phagocytes

    International Nuclear Information System (INIS)

    Werb, Z.; Chin, J.R.

    1983-01-01

    A number of macrophage functions were sequentially expressed when the bone marrow precursors of mononuclear phagocytes differentiated in culture in the presence of a specific growth factor, colony-stimulating factor-1. The authors defined the expression of apoprotein E (ApoE), a major secreted protein of resident peritoneal macrophages, during maturation of adherent bone marrow-derived mononuclear phagocytes into macrophages. By 5 d the bone marrow macrophages were active secretory cells, but few cells contained intracellular immunoreactive ApoE, and little, if any, ApoE was secreted. ApoE secretion was initiated at 9 d, and this correlated with an increase in the percentage of macrophages containing intracellular ApoE. The onset of ApoE secretion was selective, and little change occurred in the other major secreted proteins detected by [ 35 S]methionine incorporation. In parallel, the high rate of plasminogen activator secretion, which peaked at 7 d, decreased markedly. ApoE secretion was not associated with altered expression of the macrophage surface antigen, la, or with secretion of fibronectin. Virtually all cells in independent colonies of bone marrow-derived macrophages eventually expressed ApoE. The proliferating monocyte/macrophage-like cell lines P388D1, J774.2, WHEI-3, RAW 264.1, and MGI.D + secreted little or no ApoE. These data establish that ApoE secretion is developmentally regulated

  6. DMPD: Regulation of phagocyte migration and recruitment by Src-family kinases. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18385944 Regulation of phagocyte migration and recruitment by Src-family kinases. B...how Regulation of phagocyte migration and recruitment by Src-family kinases. PubmedID 18385944 Title Regulation of phagocyte migratio

  7. Soluble glucomannan isolated from Candida utilis primes blood phagocytes

    Czech Academy of Sciences Publication Activity Database

    Hájková, V.; Svobodová, Aneta; Krejčová, Daniela; Číž, Milan; Velebný, V.; Lojek, Antonín; El-Benna, J.; Kubala, Lukáš

    2009-01-01

    Roč. 344, č. 15 (2009), s. 2036-2041 ISSN 0008-6215 R&D Projects: GA ČR(CZ) GA524/06/1197 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : phagocyte * glucans * degranulation Subject RIV: BO - Biophysics Impact factor: 2.025, year: 2009

  8. Survival and function of phagocytes in blood culture media

    DEFF Research Database (Denmark)

    Fischer, T K; Prag, J; Kharazmi, A

    1999-01-01

    The survival and function of human phagocytes in sterile aerobic and anaerobic blood culture media were investigated using neutrophil morphology, white blood cell count in a haemoanalyser, flow cytometry, oxidative burst response, and bactericidal effect in Colorbact and Septi-Chek blood culture...

  9. Adenylate Cyclase Toxin promotes bacterial internalisation into non phagocytic cells.

    Science.gov (United States)

    Martín, César; Etxaniz, Asier; Uribe, Kepa B; Etxebarria, Aitor; González-Bullón, David; Arlucea, Jon; Goñi, Félix M; Aréchaga, Juan; Ostolaza, Helena

    2015-09-08

    Bordetella pertussis causes whooping cough, a respiratory infectious disease that is the fifth largest cause of vaccine-preventable death in infants. Though historically considered an extracellular pathogen, this bacterium has been detected both in vitro and in vivo inside phagocytic and non-phagocytic cells. However the precise mechanism used by B. pertussis for cell entry, or the putative bacterial factors involved, are not fully elucidated. Here we find that adenylate cyclase toxin (ACT), one of the important toxins of B. pertussis, is sufficient to promote bacterial internalisation into non-phagocytic cells. After characterization of the entry route we show that uptake of "toxin-coated bacteria" proceeds via a clathrin-independent, caveolae-dependent entry pathway, allowing the internalised bacteria to survive within the cells. Intracellular bacteria were found inside non-acidic endosomes with high sphingomyelin and cholesterol content, or "free" in the cytosol of the invaded cells, suggesting that the ACT-induced bacterial uptake may not proceed through formation of late endolysosomes. Activation of Tyr kinases and toxin-induced Ca(2+)-influx are essential for the entry process. We hypothesize that B. pertussis might use ACT to activate the endocytic machinery of non-phagocytic cells and gain entry into these cells, in this way evading the host immune system.

  10. H1-antihistamines and oxidative burst of professional phagocytes

    Czech Academy of Sciences Publication Activity Database

    Nosál, R.; Drábiková, K.; Jančinová, V.; Moravcová, Jana; Lojek, Antonín; Číž, Milan; Mačičková, T.; Pečivová, J.

    2009-01-01

    Roč. 30, č. 1 (2009), s. 133-136 ISSN 0172-780X Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : chemiluminescence * H1- antihistamines * phagocytes Subject RIV: BO - Biophysics Impact factor: 1.047, year: 2009

  11. Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

    DEFF Research Database (Denmark)

    Rolandsson, Sara; Andersson Sjöland, Annika; Brune, Jan C

    2014-01-01

    in vitro MSC properties; however, xenotransplantation into non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice showed that lung MSC readily differentiated into adipocytes and stromal tissues, but lacked significant in vivo bone formation. CONCLUSIONS: These data clearly demonstrate...

  12. Studies on the role of mononuclear phagocytes in resistance to acute lymphocytic choriomeningitis virus infection

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Volkert, M

    1983-01-01

    killer response was also unimpaired by this treatment. Taken together, these findings suggest that resident macrophages constitute a barrier to the initial multiplication of LCMV. A breakdown of this macrophage barrier results in a more disseminated infection, which the specific immune response has...... with early events in the host response to the virus. Correspondingly, carrageenan enhanced early virus multiplication. Pretreatment with carrageenan apparently did not inhibit induction of the T-cell response and had little or no direct effect on T-cell-dependent anti-viral activity. The LCMV-induced natural......The role of mononuclear phagocytes in various phases of the acute lymphocytic choriomeningitis virus (LCMV) infection was studied. The anti-macrophage agent carrageenan delayed virus clearance. Carrageenan was most effective when given before virus inoculation, suggesting that it interfered...

  13. Environmental dimensionality controls the interaction of phagocytes with the pathogenic fungi Aspergillus fumigatus and Candida albicans.

    Science.gov (United States)

    Behnsen, Judith; Narang, Priyanka; Hasenberg, Mike; Gunzer, Frank; Bilitewski, Ursula; Klippel, Nina; Rohde, Manfred; Brock, Matthias; Brakhage, Axel A; Gunzer, Matthias

    2007-02-01

    The fungal pathogens Aspergillus fumigatus and Candida albicans are major health threats for immune-compromised patients. Normally, macrophages and neutrophil granulocytes phagocytose inhaled Aspergillus conidia in the two-dimensional (2-D) environment of the alveolar lumen or Candida growing in tissue microabscesses, which are composed of a three-dimensional (3-D) extracellular matrix. However, neither the cellular dynamics, the per-cell efficiency, the outcome of this interaction, nor the environmental impact on this process are known. Live imaging shows that the interaction of phagocytes with Aspergillus or Candida in 2-D liquid cultures or 3-D collagen environments is a dynamic process that includes phagocytosis, dragging, or the mere touching of fungal elements. Neutrophils and alveolar macrophages efficiently phagocytosed or dragged Aspergillus conidia in 2-D, while in 3-D their function was severely impaired. The reverse was found for phagocytosis of Candida. The phagocytosis rate was very low in 2-D, while in 3-D most neutrophils internalized multiple yeasts. In competitive assays, neutrophils primarily incorporated Aspergillus conidia in 2-D and Candida yeasts in 3-D despite frequent touching of the other pathogen. Thus, phagocytes show activity best in the environment where a pathogen is naturally encountered. This could explain why "delocalized" Aspergillus infections such as hematogeneous spread are almost uncontrollable diseases, even in immunocompetent individuals.

  14. Environmental dimensionality controls the interaction of phagocytes with the pathogenic fungi Aspergillus fumigatus and Candida albicans.

    Directory of Open Access Journals (Sweden)

    Judith Behnsen

    2007-02-01

    Full Text Available The fungal pathogens Aspergillus fumigatus and Candida albicans are major health threats for immune-compromised patients. Normally, macrophages and neutrophil granulocytes phagocytose inhaled Aspergillus conidia in the two-dimensional (2-D environment of the alveolar lumen or Candida growing in tissue microabscesses, which are composed of a three-dimensional (3-D extracellular matrix. However, neither the cellular dynamics, the per-cell efficiency, the outcome of this interaction, nor the environmental impact on this process are known. Live imaging shows that the interaction of phagocytes with Aspergillus or Candida in 2-D liquid cultures or 3-D collagen environments is a dynamic process that includes phagocytosis, dragging, or the mere touching of fungal elements. Neutrophils and alveolar macrophages efficiently phagocytosed or dragged Aspergillus conidia in 2-D, while in 3-D their function was severely impaired. The reverse was found for phagocytosis of Candida. The phagocytosis rate was very low in 2-D, while in 3-D most neutrophils internalized multiple yeasts. In competitive assays, neutrophils primarily incorporated Aspergillus conidia in 2-D and Candida yeasts in 3-D despite frequent touching of the other pathogen. Thus, phagocytes show activity best in the environment where a pathogen is naturally encountered. This could explain why "delocalized" Aspergillus infections such as hematogeneous spread are almost uncontrollable diseases, even in immunocompetent individuals.

  15. Animal Investigation Program 1976 annual report: Nevada test site and vicinity. [Radioanalysis of tissues from animals residing on or near NTS in 1976

    Energy Technology Data Exchange (ETDEWEB)

    Smith, D.D.; Giles, K.R.; Bernhardt, D.E.; Brown, K.W.

    1978-11-01

    Data are presented from the radioanalysis of tissues collected from cattle and mule deer, desert bighorn sheep, feral horses, and other wildlife that resided on or near the Nevada Test Site during 1976. Other than the naturally occurring potassium-40, gamma-emitting radionuclides were detected infrequently with the exception of /sup 131/I in animal thyroid samples collected after September 25 (the date of a Chinese nuclear test). Strontium-90 concentrations in bones from deer, cattle, and desert bighorn sheep continued the downward trend of recent years. Tritium concentrations were generally within ambient limits with the exception of animals exposed to sources of contamination; e.g., Sedan Crater, drainage ponds from Area 12 tunnels, etc. Analysis of actinide in tissues was emphasized during 1976. Graphs illustrate the /sup 239/P levels in lungs, livers, and femurs from Nevada Test Site beef cattle for the years 1971 through 1976. Femur and lung residue data are nearly identical for each year with liver concentrations being a factor of 2 or 3 lower. Hypothetical dose estimates to man were calculated on the basis of the daily consumption of 0.5 kilogram of liver or muscle from animals that contained peak actinide levels. The highest postulated dose was 11 millirem from tritium from tissues for a mule deer. This dose is about 2% of the 500 millirems/year guide for radiation doses to an individual in the general public. All other postulated doses for consumption of the tissue containing other radionuclides are less than 0.1% of this guide. The food habits of desert bighorn sheep were discussed according to the geographic locations of the animals at time of collection. Grasses made up approximately 60% of the diet at all locations, with shrubs content approaching 30%, and the remainder consisting of various forbs. The movement of 13 mule deer fitted with collars containing a radiotransmitter unit was monitored on a weekly basis.

  16. Phagocytic activity and the response to autovaccines in recurrent staphylococcal boils

    Directory of Open Access Journals (Sweden)

    A C Karnik

    1990-01-01

    Full Text Available The present study was aimed to see the relationship between the phagocytic function as determined by NBT reduction test and the response to the staphylococal boils. Of the 34 cases of recurrent staphylococcal cutaneous infections, 19 showed normal phagocytic activity while 2 had marginally diminished and 13 had grossly diminished phagocytic activity. Sixteen of the vaccines (84% with normal phagocytic funetion responded well to the vaccine therapy while only 3 of the 13 (23% with poor phagocytic function showed the beneficial effects of the autovaccines. Thus the findings recommend the use of staphyloccoccal autovaccines in the cases with adequate phagocytic activity as seen by NBT reduction test but not as much for those with inadequate phagocytic function.

  17. Modulation of rat blood phagocyte activity by serotonin

    Czech Academy of Sciences Publication Activity Database

    Okénková, Kateřina; Lojek, Antonín; Kubala, Lukáš; Číž, Milan

    2007-01-01

    Roč. 101, č. 14 (2007), s245-s246 E-ISSN 1213-7103. [Mezioborová česko-slovenská toxikologická konference /12./. Praha, 11.06.2007-13.06.2007] R&D Projects: GA ČR(CZ) GA524/04/0897 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : phagocytes * serotonin * reactive oxygen species Subject RIV: BO - Biophysics

  18. Selective Biological Responses of Phagocytes and Lungs to Purified Histones.

    Science.gov (United States)

    Fattahi, Fatemeh; Grailer, Jamison J; Lu, Hope; Dick, Rachel S; Parlett, Michella; Zetoune, Firas S; Nuñez, Gabriel; Ward, Peter A

    2017-01-01

    Histones invoke strong proinflammatory responses in many different organs and cells. We assessed biological responses to purified or recombinant histones, using human and murine phagocytes and mouse lungs. H1 had the strongest ability in vitro to induce cell swelling independent of requirements for toll-like receptors (TLRs) 2 or 4. These responses were also associated with lactate dehydrogenase release. H3 and H2B were the strongest inducers of [Ca2+]i elevations in phagocytes. Cytokine and chemokine release from mouse and human phagocytes was predominately a function of H2A and H2B. Double TLR2 and TLR4 knockout (KO) mice had dramatically reduced cytokine release induced in macrophages exposed to individual histones. In contrast, macrophages from single TLR-KO mice showed few inhibitory effects on cytokine production. Using the NLRP3 inflammasome protocol, release of mature IL-1β was predominantly a feature of H1. Acute lung injury following the airway delivery of histones suggested that H1, H2A, and H2B were linked to alveolar leak of albumin and the buildup of polymorphonuclear neutrophils as well as the release of chemokines and cytokines into bronchoalveolar fluids. These results demonstrate distinct biological roles for individual histones in the context of inflammation biology and the requirement of both TLR2 and TLR4. © 2017 S. Karger AG, Basel.

  19. Fungal invasion of normally non-phagocytic host cells.

    Directory of Open Access Journals (Sweden)

    Scott G Filler

    2006-12-01

    Full Text Available Many fungi that cause invasive disease invade host epithelial cells during mucosal and respiratory infection, and subsequently invade endothelial cells during hematogenous infection. Most fungi invade these normally non-phagocytic host cells by inducing their own uptake. Candida albicans hyphae interact with endothelial cells in vitro by binding to N-cadherin on the endothelial cell surface. This binding induces rearrangement of endothelial cell microfilaments, which results in the endocytosis of the organism. The capsule of Cryptococcus neoformans is composed of glucuronoxylomannan, which binds specifically to brain endothelial cells, and appears to mediate both adherence and induction of endocytosis. The mechanisms by which other fungal pathogens induce their own uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species and the Zygomycetes, invade endothelial cells from the abluminal surface during the initiation of invasive disease, and subsequently invade the luminal surface of endothelial cells during hematogenous dissemination. Invasion of normally non-phagocytic host cells has different consequences, depending on the type of invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial cells. This review summarizes the mechanisms by which diverse fungal pathogens invade normally non-phagocytic host cells and discusses gaps in our knowledge that provide opportunities for future research.

  20. Interactions of Pseudomonas aeruginosa and Corynebacterium spp. with non-phagocytic brain microvascular endothelial cells and phagocytic Acanthamoeba castellanii.

    Science.gov (United States)

    Siddiqui, Ruqaiyyah; Lakhundi, Sahreena; Khan, Naveed Ahmed

    2015-06-01

    Several lines of evidence suggest that Acanthamoeba interact with bacteria, which may aid in pathogenic bacterial transmission to susceptible hosts, and these interactions may have influenced evolution of bacterial pathogenicity. In this study, we tested if Gram-negative Pseudomonas aeruginosa and Gram-positive Corynebacterium spp. can associate/invade and survive inside Acanthamoeba castellanii trophozoites and cysts, as well as non-phagocytic human brain microvascular endothelial cells. The results revealed that both Corynebacterium spp. and P. aeruginosa were able to associate as well as invade and/or taken up by the phagocytic A. castellanii trophozoite. In contrast, P. aeruginosa exhibited higher association as well as invasion of non-phagocytic HBMEC compared with Corynebacterium spp. Notably, P. aeruginosa remained viable during the encystment process and exhibited higher levels of recovery from mature cysts (74.54 bacteria per amoebae) compared with Corynebacterium spp. (2.69 bacteria per amoeba) (P Acanthamoeba cysts can be airborne, these findings suggest that Acanthamoeba is a potential vector in the transmission of P. aeruginosa to susceptible hosts. When bacterial-ridden amoebae were exposed to favourable (nutrient-rich) conditions, A. castellanii emerged as vegetative trophozoites and remained viable, and likewise viable P. aeruginosa were also observed but rarely any Corynebacterium spp. were observed. Correspondingly, P. aeruginosa but not Corynebacterium spp. exhibited higher cytotoxicity to non-phagocytic HBMEC, producing more than 75% cell death in 24 h, compared to 20% cell death observed with Corynebacterium spp. Additionally, it was observed that the bacterial conditioned medium had no negative effect on A. castellanii growth. Further characterization of amoebal and bacterial interactions will assist in identifying the role of Acanthamoeba in the transmission and evolution of pathogenic bacteria.

  1. Cost and logistics of implementing a tissue-based American College of Surgeons/Association of Program Directors in Surgery surgical skills curriculum for general surgery residents of all clinical years.

    Science.gov (United States)

    Henry, Brandon; Clark, Philip; Sudan, Ranjan

    2014-02-01

    The cost and logistics of deploying the American College of Surgeons (ACS)/Association of Program Directors in Surgery (APDS) National Technical Skills Curriculum across all training years are not known. This information is essential for residency programs choosing to adopt similar curricula. A task force evaluated the authors' institution's existing simulation curriculum and enhanced it by implementing the ACS/APDS modules. A 35-module curriculum was administered to 35 general surgery residents across all 5 clinical years. The costs and logistics were noted, and resident satisfaction was assessed. The annual operational cost was $110,300 ($3,150 per resident). Cost per module, per resident was $940 for the cadaveric module compared with $220 and $240 for dry simulation and animal tissue-based modules, respectively. Resident satisfaction improved from 2.45 to 4.78 on a 5-point, Likert-type scale after implementing the ACS/APDS modules. The ACS/APDS skills curriculum was implemented successfully across all clinical years. Cadaveric modules were the most expensive. Animal and dry simulation modules were equivalent in cost. The addition of tissue-based modules was associated with high satisfaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Lung CD4 Tissue-Resident Memory T Cells Mediate Adaptive Immunity Induced by Previous Infection of Mice withBordetella pertussis.

    Science.gov (United States)

    Wilk, Mieszko M; Misiak, Alicja; McManus, Róisín M; Allen, Aideen C; Lynch, Marina A; Mills, Kingston H G

    2017-07-01

    Th1 and Th17 cells have an established role in protective immunity to Bordetella pertussis , but this evidence is based largely on peripheral T cells. There is emerging evidence that local tissue-resident memory T (T RM ) cells that accumulate in tissue following mucosal infection may be crucial for long-term immunity. In this study, we examined the role of respiratory CD4 T RM cells in immunity to B. pertussis Natural immunity to B. pertussis induced by infection is considered long lasting and effective at preventing reinfection. Consistent with this, we found that convalescent mice rapidly cleared the bacteria after reinfection. Furthermore, CD4 T cells with a T RM cell phenotype (CD44 + CD62L - CD69 + or CD44 + CD62L - CD69 + CD103 + ) accumulated in the lungs of mice during infection with B. pertussis and significantly expanded through local proliferation following reinfection. These CD4 T RM cells were B. pertussis specific and secreted IL-17 or IL-17 and IFN-γ. Treatment of mice with FTY720, which prevented migration of T and B cells from lymph nodes to the circulation, significantly exacerbated B. pertussis infection. This was associated with significantly reduced infiltration of central memory T cells and B cells into the lungs. However, the local expansion of T RM cells and the associated rapid clearance of the secondary infection were not affected by treatment with FTY720 before rechallenge. Moreover, adoptive transfer of lung CD4 T RM cells conferred protection in naive mice. Our findings reveal that Ag-specific CD4 T RM cells play a critical role in adaptive immunity against reinfection and memory induced by natural infection with B. pertussis . Copyright © 2017 by The American Association of Immunologists, Inc.

  3. Determining the Phagocytic Activity of Clinical Antibody Samples

    Science.gov (United States)

    McAndrew, Elizabeth G.; Dugast, Anne-Sophie; Licht, Anna F.; Eusebio, Justin R.; Alter, Galit; Ackerman, Margaret E.

    2011-01-01

    Antibody-driven phagocytosis is induced via the engagement of Fc receptors on professional phagocytes, and can contribute to both clearance as well as pathology of disease. While the properties of the variable domains of antibodies have long been considered critical to in vivo function, the ability of antibodies to recruit innate immune cells via their Fc domains has become increasingly appreciated as a major factor in their efficacy, both in the setting of recombinant monoclonal antibody therapy, as well as in the course of natural infection or vaccination1-3. Importantly, despite its nomenclature as a constant domain, the antibody Fc domain does not have constant function, and is strongly modulated by IgG subclass (IgG1-4) and glycosylation at Asparagine 2974-6. Thus, this method to study functional differences of antigen-specific antibodies in clinical samples will facilitate correlation of the phagocytic potential of antibodies to disease state, susceptibility to infection, progression, or clinical outcome. Furthermore, this effector function is particularly important in light of the documented ability of antibodies to enhance infection by providing pathogens access into host cells via Fc receptor-driven phagocytosis7. Additionally, there is some evidence that phagocytic uptake of immune complexes can impact the Th1/Th2 polarization of the immune response8. Here, we describe an assay designed to detect differences in antibody-induced phagocytosis, which may be caused by differential IgG subclass, glycan structure at Asn297, as well as the ability to form immune complexes of antigen-specific antibodies in a high-throughput fashion. To this end, 1 μm fluorescent beads are coated with antigen, then incubated with clinical antibody samples, generating fluorescent antigen specific immune complexes. These antibody-opsonized beads are then incubated with a monocytic cell line expressing multiple FcγRs, including both inhibitory and activating. Assay output can

  4. Hacker Within! Ehrlichia chaffeensis Effector Driven Phagocyte Reprogramming Strategy

    Directory of Open Access Journals (Sweden)

    Taslima Taher Lina

    2016-05-01

    Full Text Available Ehrlichia chaffeensis is a small, gram negative, obligately intracellular bacterium that preferentially infects mononuclear phagocytes. It is the etiologic agent of human monocytotropic ehrlichiosis (HME, an emerging life-threatening tick-borne zoonosis. Mechanisms by which E. chaffeensis establishes intracellular infection, and avoids host defenses are not well understood, but involve functionally relevant host-pathogen interactions associated with tandem and ankyrin repeat effector proteins. In this review, we discuss the recent advances in our understanding of the molecular and cellular mechanisms that underlie Ehrlichia host cellular reprogramming strategies that enable intracellular survival.

  5. Plasminogen activator inhibitor type 1 regulates microglial motility and phagocytic activity

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    Jeon Hyejin

    2012-06-01

    Full Text Available Abstract Background Plasminogen activator inhibitor type 1 (PAI-1 is the primary inhibitor of urokinase type plasminogen activators (uPA and tissue type plasminogen activators (tPA, which mediate fibrinolysis. PAI-1 is also involved in the innate immunity by regulating cell migration and phagocytosis. However, little is known about the role of PAI-1 in the central nervous system. Methods In this study, we identified PAI-1 in the culture medium of mouse mixed glial cells by liquid chromatography and tandem mass spectrometry. Secretion of PAI-1 from glial cultures was detected by ELISA and western blotting analysis. Cell migration was evaluated by in vitro scratch-wound healing assay or Boyden chamber assay and an in vivo stab wound injury model. Phagocytic activity was measured by uptake of zymosan particles. Results The levels of PAI-1 mRNA and protein expression were increased by lipopolysaccharide and interferon-γ stimulation in both microglia and astrocytes. PAI-1 promoted the migration of microglial cells in culture via the low-density lipoprotein receptor-related protein (LRP 1/Janus kinase (JAK/signal transducer and activator of transcription (STAT1 axis. PAI-1 also increased microglial migration in vivo when injected into mouse brain. PAI-1-mediated microglial migration was independent of protease inhibition, because an R346A mutant of PAI-1 with impaired PA inhibitory activity also promoted microglial migration. Moreover, PAI-1 was able to modulate microglial phagocytic activity. PAI-1 inhibited microglial engulfment of zymosan particles in a vitronectin- and Toll-like receptor 2/6-dependent manner. Conclusion Our results indicate that glia-derived PAI-1 may regulate microglial migration and phagocytosis in an autocrine or paracrine manner. This may have important implications in the regulation of brain microglial activities in health and disease.

  6. Impaired activity of phagocytic cells in Candida albicans infection after exposure to chronic varied stress.

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    Rodriguez-Galán, M C; Correa, S G; Cejas, H; Sotomayor, C E

    2001-01-01

    Candidiasis is a prototypic opportunistic fungal disease that may follow severe modulations of the immune system of the host. The purpose of this study was to evaluate which innate immune mechanisms involved in the protection against fungal invasion are impaired under stress conditions. Wistar rats were infected intraperitoneally with Candida albicans and immediately exposed to chronic varied stress (CVS) over 10 days (CVS; Ca-S); the fungal burden (CFU), histopathological lesion and ACTH levels were evaluated. Additionally, functional assessment of peritoneal cells (PC) included the phagocytic and anticandidacidal activities and the production of H(2)O(2) and NO. In the only infected animals (Ca), C. albicans colonization stimulated an efficient inflammatory response, while in Ca-S rats poor tissue reactions were associated with increased CFU in livers and kidneys (p process was not modified, the candidacidal activity of PC was significantly decreased after the application of CVS (p < 0.001, Ca vs. Ca-S). The H(2)O(2) production by macrophages and neutrophils was downregulated by the infection, and while at early intervals these cells possessed a residual oxidative capacity, by day 10, the production of this metabolite was blocked. Spontaneous NO production by macrophages was significantly increased in both Ca and Ca-S animals (p < 0.001), but in stressed rats, this reactive nitrogen intermediate was noticeably downregulated (p < 0.05, Ca vs. Ca-S). The hyperactivity of hypothalamus-pituitary-adrenal axis after exposure to stress was confirmed by an increase in baseline plasma ACTH levels. These results show that during infection with C. albicans, the exposure to CVS contributes to the spread of the fungus and downregulates critical functions of phagocytic cells involved in the control of this opportunistic pathogen. Copyright 2002 S. Karger AG, Basel

  7. Excision of an unstable pathogenicity island in Salmonella enterica serovar Enteritidis is induced during infection of phagocytic cells.

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    Tania S Quiroz

    Full Text Available The availability of the complete genome sequence of several Salmonella enterica serovars has revealed the presence of unstable genetic elements in these bacteria, such as pathogenicity islands and prophages. This is the case of Salmonella enterica serovar Enteritidis (S. Enteritidis, a bacterium that causes gastroenteritis in humans and systemic infection in mice. The whole genome sequence analysis for S. Enteritidis unveiled the presence of several genetic regions that are absent in other Salmonella serovars. These regions have been denominated "regions of difference" (ROD. In this study we show that ROD21, one of such regions, behaves as an unstable pathogenicity island. We observed that ROD21 undergoes spontaneous excision by two independent recombination events, either under laboratory growth conditions or during infection of murine cells. Importantly, we also found that one type of excision occurred at higher rates when S. Enteritidis was residing inside murine phagocytic cells. These data suggest that ROD21 is an unstable pathogenicity island, whose frequency of excision depends on the environmental conditions found inside phagocytic cells.

  8. Excision of an unstable pathogenicity island in Salmonella enterica serovar Enteritidis is induced during infection of phagocytic cells.

    Science.gov (United States)

    Quiroz, Tania S; Nieto, Pamela A; Tobar, Hugo E; Salazar-Echegarai, Francisco J; Lizana, Rodrigo J; Quezada, Carolina P; Santiviago, Carlos A; Araya, Daniela V; Riedel, Claudia A; Kalergis, Alexis M; Bueno, Susan M

    2011-01-01

    The availability of the complete genome sequence of several Salmonella enterica serovars has revealed the presence of unstable genetic elements in these bacteria, such as pathogenicity islands and prophages. This is the case of Salmonella enterica serovar Enteritidis (S. Enteritidis), a bacterium that causes gastroenteritis in humans and systemic infection in mice. The whole genome sequence analysis for S. Enteritidis unveiled the presence of several genetic regions that are absent in other Salmonella serovars. These regions have been denominated "regions of difference" (ROD). In this study we show that ROD21, one of such regions, behaves as an unstable pathogenicity island. We observed that ROD21 undergoes spontaneous excision by two independent recombination events, either under laboratory growth conditions or during infection of murine cells. Importantly, we also found that one type of excision occurred at higher rates when S. Enteritidis was residing inside murine phagocytic cells. These data suggest that ROD21 is an unstable pathogenicity island, whose frequency of excision depends on the environmental conditions found inside phagocytic cells.

  9. Reciprocal upregulation of scavenger receptors complicates interpretation of nanoparticle uptake in non-phagocytic cells

    NARCIS (Netherlands)

    Prapainop, Kanlaya; Miao, Rong; Åberg, Christoffer; Salvati, Anna; Dawson, Kenneth A

    2017-01-01

    Nanoparticles have great potential as drug delivery vehicles or as imaging agents for treatment and diagnosis of various diseases. It is therefore crucial to understand how nanoparticles are taken up by cells, both phagocytic and non-phagocytic. Small interference RNA has previously been used to

  10. Scrambled Eggs: Apoptotic Cell Clearance by Non-Professional Phagocytes in the Drosophila Ovary

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    Sandy B. Serizier

    2017-11-01

    Full Text Available For half of a century, it has been known that non-professional phagocytes, such as fibroblasts, endothelial, and epithelial cells, are capable of efferocytosis (engulfment of apoptotic cells. Non-professional phagocytes differ from professional phagocytes in the range and efficiency of engulfment. Much of the recognition and underlying signaling machinery between non-professional and professional phagocytes is the same, but it is not known how the engulfment capacity of non-professional phagocytes is controlled. Moreover, the signaling networks involved in cell corpse recognition, engulfment, and phagosome maturation are only partially understood. The Drosophila ovary provides an excellent system to investigate the regulation of phagocytic activity by epithelial cells, a major class of non-professional phagocytes. During Drosophila oogenesis, mid-stage egg chambers undergo apoptosis of the germline in response to nutrient deprivation. Epithelial follicle cells then undergo major cell shape changes and concomitantly engulf the germline material. Our previous work has established that Draper and the integrin α-PS3/β-PS heterodimer are required in follicle cells for germline cell clearance. In addition, we have characterized phagosome maturation pathways, and found that the JNK pathway amplifies the engulfment response. In this review, we discuss recent advances on the interplay between engulfment pathways in the follicular epithelium for cell clearance in the Drosophila ovary. We also provide a comparison to apoptotic cell clearance mechanisms in C. elegans and mammals, illustrating strong conservation of efferocytosis mechanisms by non-professional phagocytes.

  11. Scrambled Eggs: Apoptotic Cell Clearance by Non-Professional Phagocytes in the Drosophila Ovary.

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    Serizier, Sandy B; McCall, Kimberly

    2017-01-01

    For half of a century, it has been known that non-professional phagocytes, such as fibroblasts, endothelial, and epithelial cells, are capable of efferocytosis (engulfment of apoptotic cells). Non-professional phagocytes differ from professional phagocytes in the range and efficiency of engulfment. Much of the recognition and underlying signaling machinery between non-professional and professional phagocytes is the same, but it is not known how the engulfment capacity of non-professional phagocytes is controlled. Moreover, the signaling networks involved in cell corpse recognition, engulfment, and phagosome maturation are only partially understood. The Drosophila ovary provides an excellent system to investigate the regulation of phagocytic activity by epithelial cells, a major class of non-professional phagocytes. During Drosophila oogenesis, mid-stage egg chambers undergo apoptosis of the germline in response to nutrient deprivation. Epithelial follicle cells then undergo major cell shape changes and concomitantly engulf the germline material. Our previous work has established that Draper and the integrin α-PS3/β-PS heterodimer are required in follicle cells for germline cell clearance. In addition, we have characterized phagosome maturation pathways, and found that the JNK pathway amplifies the engulfment response. In this review, we discuss recent advances on the interplay between engulfment pathways in the follicular epithelium for cell clearance in the Drosophila ovary. We also provide a comparison to apoptotic cell clearance mechanisms in C. elegans and mammals, illustrating strong conservation of efferocytosis mechanisms by non-professional phagocytes.

  12. Microglia: unique and common features with other tissue macrophages.

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    Prinz, Marco; Tay, Tuan Leng; Wolf, Yochai; Jung, Steffen

    2014-09-01

    Microglia are highly specialized tissue macrophages of the brain with dedicated functions in neuronal development, homeostasis and recovery from pathology Despite their unique localization in the central nervous system (CNS), microglia are ontogenetically and functionally related to their peripheral counterparts of the mononuclear phagocytic system in the body, namely tissue macrophages and circulating myeloid cells. Recent developments provided new insights into the myeloid system in the body with microglia emerging as intriguing unique archetypes. Similar to other tissue macrophages, microglia develop early during embryogenesis from immature yolk sac progenitors. But in contrast to most of their tissue relatives microglia persist throughout the entire life of the organism without any significant input from circulating blood cells due to their longevity and their capacity of self-renewal. Notably, microglia share some features with short-lived blood monocytes to limit CNS tissue damage in pathologies, but only bone marrow-derived cells display the ability to become permanently integrated in the parenchyma. This emphasizes the therapeutic potential of bone marrow-derived microglia-like cells. Further understanding of both fate and function of microglia during CNS pathologies and considering their uniqueness among other tissue macrophages will be pivotal for potential manipulation of immune cell function in the CNS, thereby reducing disease burden. Here, we discuss new aspects of myeloid cell biology in general with special emphasis on the brain-resident macrophages and microglia.

  13. Modulation of metabolic activity of phagocytes by antihistamines

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    Lojek, Antonin; Číž, Milan; Pekarová, Michaela; Ambrožová, Gabriela; Vašíček, Ondřej; Moravcová, Jana; Kubala, Lukáš; Drábiková, Katarína; Jančinová, Viera; Perečko, Tomáš; Pečivová, Jana; Mačičková, Tatiana; Nosál, Radomír

    2011-01-01

    The purpose of the study was to investigate the effects of H1-antihistamines of the 1st generation (antazoline, bromadryl, brompheniramine, dithiaden, cyclizine, chlorcyclizine, chlorpheniramine, clemastine) and the 2nd generation (acrivastine, ketotifen, and loratadine) on the respiratory burst of phagocytes. Reactive oxygen species generation in neutrophils isolated from rat blood was measured using luminol-enhanced chemiluminescence. Changes in nitrite formation and iNOS protein expression by RAW 264.7 macrophages were analysed using Griess reaction and Western blotting. The antioxidative properties of drugs in cell-free systems were detected spectrophotometrically, luminometrically, fluorimetrically, and amperometrically. The majority of the H1-antihistamines tested (bromadryl, brompheniramine, chlorcyclizine, chlorpheniramine, clemastine, dithiaden, and ketotifen) exhibited a significant inhibitory effect on the chemiluminescence activity of phagocytes. H1-antihistamines did not show significant scavenging properties against superoxide anion and hydroxyl radical, thus this could not contribute to the inhibition of chemiluminescence. H1-antihistamines had a different ability to modulate nitric oxide production by LPS-stimulated macrophages. Bromadryl, clemastine, and dithiaden were the most effective since they inhibited iNOS expression, which was followed by a significant reduction in nitrite levels. H1-antihistamines had no scavenging activity against nitric oxide. It can be concluded that the effects observed in the H1-antihistamines tested are not mediated exclusively via H1-receptor pathway or by direct antioxidative properties. Based on our results, antihistamines not interfering with the microbicidal mechanisms of leukocytes (antazoline, acrivastine and cyclizine) could be used preferentially in infections. Other antihistamines should be used, under pathological conditions accompanied by the overproduction of reactive oxygen species. PMID:21577279

  14. Effect of ambient temperature on phenotype and functions of professional phagocytes of athymic nude mice.

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    Vetvicka, V; Holub, M; Houstek, J

    1993-02-01

    Cytofluorometric analysis of surface marker expression was performed on myeloid cells isolated from bone marrow, spleen and lymph nodes of nude mice and nu/+ and +/+ mice (haired controls) exposed for various time periods to ambient temperature of 22 degrees C or 28 degrees C. A rise in the proportion of cells bearing macrophage markers (MAC-1, MAC-3 and F4/80) in the spleen and of FcR+ cells in all tissues tested was found in 22 degrees C-exposed nudes with high nonshivering thermogenesis. Numbers of MAC-1+ macrophages and actively phagocytic cells increased also in peritoneal exudates. There was a conspicuous predominance of large macrophages in the exudates and the specific markers decreased in density on their surface. Ia expression declined in all tissues tested with the length of exposure to cold. In the granulocytic series (BP-2+ cells), there was a decrease in the bone marrow and lymph nodes and an increase in the spleen and circulation, which suggested an enhanced mobilization and increased production at extramedullary sites in cold-exposed nude mice. The changes in haired mice were negligible.

  15. Accumulation of 14C-5,6-dihydroxytryptamine-melanin in intrathecal and subependymal phagocytes of the rat CNS and possible routes of their elimination from brain

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    Baumgarten, H.G.; Moritz, F.; Schlossberger, H.G.

    1981-01-01

    14C-5,6-DHT-Melanin, a labelled synthetic polymer resembling the naturally occurring melanin formed in brain by autoxidation of dopamine, was injected into the left lateral ventricle of adult rats, and its fate followed by autoradiography and by transmission electron microscopy of structures identified as labelled in preceding light micrographs, and by EM-autoradiography. Shortly after injection, melanin particles (easily identified in the em because of their size, structure and electron opacity) were seen ingested by supraependymal and epiplexus cells, by cells residing in the piaarachnoid, i.e. free subarachnoidal cells and perivascular cells, and by subependymally located microglia-like cells with intraventricular processes. Up to day four, an increase in the number of labelled phagocytes in the CSF was noted which transformed into typical reactive macrophages. Beyond this time, many intraventricular melanin-loaded phagocytes formed rounded clusters; cells of such clusters were subsequently found to invade the brain parenchyma by penetrating the ependymal lining and to accumulate in the perivascular space of brain vessels. 14C-Melanin-storing macrophages were found in the marginal sinus of the deep jugular lymph nodes suggesting emigration of CNS-derived phagocytes via lymphatics or prelymphatics that contact the subarachnoidal space compartment. This does not exclude the possibility that some of the macrophages leave the brain via the systemic circulation by penetrating the vascular endothelium; these may be disposed of in peripheral organs other than the lymph nodes.

  16. Resident resistance.

    Science.gov (United States)

    Price, J L; Cleary, B

    1999-01-01

    Clearly, faculty must work hard with residents to explore the nature of their resistance to a program's learning and growth opportunities. Initial steps to a deeper, more effective, and longer-lasting change process must be pursued. If resident resistance is mishandled or misunderstood, then learning and professional growth may be sidetracked and the purposes of residency training defeated. Listening to the whole person of the resident and avoiding the trap of getting caught up in merely responding to select resident behaviors that irritate us is critical. Every faculty member in the family practice residency program must recognize resistance as a form of defense that cannot immediately be torn down or taken away. Resident defenses have important purposes to play in stress reduction even if they are not always healthy. Residents, especially interns, use resistance to avoid a deeper and more truthful look at themselves as physicians. A family practice residency program that sees whole persons in their residents and that respects resident defenses will effectively manage the stress and disharmony inherent to the resistant resident.

  17. Assessment of phagocytic activity of neutrophils in chronic obstructive pulmonary disease

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    Lalitha Shanmugam

    2015-01-01

    Full Text Available Aim: To assess the phagocytic activity of neutrophils in subjects with chronic obstructive pulmonary disease (COPD. Background/Need of Study: There is a paucity of data in relation to phagocytic function in COPD. By this multidisciplinary study, a better understanding about the etiology of lung destruction among COPD patients is being sought. Materials and Methods: The study was conducted among 28 subjects with COPD and 25 controls in a private tertiary hospital in Chennai after obtaining Institutional Ethical Clearance. Known cases of COPD as proven by clinical findings and spirometry were included in the study, and subjects with any other source of infection, recent surgery, or chronic granulomatous disease were excluded. The study subjects were divided into three groups based on the severity of COPD as determined by spirometry, and healthy volunteers were taken as Group 4. After obtaining informed consent, validated respiratory health questionnaire was administered. The phagocytic function was assessed by Candida phagocytic test and Nitroblue Tetrazolium (NBT Reduction Test. Results: Significantly impaired phagocytic function as indicated by lower phagocytic, lytic indices and decreased NBT reduction of neutrophils was seen in COPD subjects compared to normal healthy controls (P <.001. Conclusion: This study showed that there is phagocytic dysfunction in COPD subjects when compared with normal subjects. This could be due to underlying inflammation in human airway. Understanding the role of neutrophils may lead to improved understanding of the pathogenesis of COPD, which in turn may pave way for implementing modified therapeutic intervention strategies.

  18. NADPH phagocyte oxidase knockout mice control Trypanosoma cruzi proliferation, but develop circulatory collapse and succumb to infection.

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    Helton C Santiago

    Full Text Available (•NO is considered to be a key macrophage-derived cytotoxic effector during Trypanosoma cruzi infection. On the other hand, the microbicidal properties of reactive oxygen species (ROS are well recognized, but little importance has been attributed to them during in vivo infection with T. cruzi. In order to investigate the role of ROS in T. cruzi infection, mice deficient in NADPH phagocyte oxidase (gp91(phox (-/- or phox KO were infected with Y strain of T. cruzi and the course of infection was followed. phox KO mice had similar parasitemia, similar tissue parasitism and similar levels of IFN-γ and TNF in serum and spleen cell culture supernatants, when compared to wild-type controls. However, all phox KO mice succumbed to infection between day 15 and 21 after inoculation with the parasite, while 60% of wild-type mice were alive 50 days after infection. Further investigation demonstrated increased serum levels of nitrite and nitrate (NOx at day 15 of infection in phox KO animals, associated with a drop in blood pressure. Treatment with a NOS2 inhibitor corrected the blood pressure, implicating NOS2 in this phenomenon. We postulate that superoxide reacts with (•NO in vivo, preventing blood pressure drops in wild type mice. Hence, whilst superoxide from phagocytes did not play a critical role in parasite control in the phox KO animals, its production would have an important protective effect against blood pressure decline during infection with T. cruzi.

  19. Dynamic acquisition of HTLV-1 tax protein by mononuclear phagocytes: Role in neurologic disease.

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    Matsuura, Eiji; Enose-Akahata, Yoshimi; Yao, Karen; Oh, Unsong; Tanaka, Yuetsu; Takashima, Hiroshi; Jacobson, Steven

    2017-03-15

    Pathology of HTLV-1 associated myelopathy/Tropical spastic paraparesis (HAM/TSP) is believed to be the result of "bystander damage" involving effector CD8 (+) T lymphocytes (CTLs) killing of virus infected cells. But the specific cellular events leading up to tissue injury are still unclear. Here, we developed the Microscopy Imaging of Cytotoxic T lymphocyte assay with Fluorescence emission (MI-CaFé), an optimized visualization analysis to explore the interactions between CTLs and virus infected or viral antigen presenting target cells. Various cell-to-cell formations can be observed and our results demonstrate elevated frequencies of CTL-target cell conjugates in HAM/TSP patient PBMCs compared to control PBMCs. Furthermore, HTLV-1 Tax protein expression can be localized at the cell-cell junctions and also tracked moving from an infected cell to a CD14 (+) mononuclear phagocyte (MP). Activation of CD14 (+) MPs in HAM/TSP patient PBMCs and antigenic presentation of HTLV-1 Tax by MPs can be inferred by their spontaneous cytotoxicity after 18h of in vitro culture. Given that CD4 (+) T lymphocytes are the primary reservoirs of HTLV-1 and MPs are scavenger cells responsible for pathogen clearance, spontaneous cytotoxicity against MPs in HAM/TSP PBMCs suggests a mechanism of chronic inflammation, secondary to low level of persistent virus infection within the central nervous system. Published by Elsevier B.V.

  20. Streptococcus pyogenes CAMP factor attenuates phagocytic activity of RAW 264.7 cells.

    Science.gov (United States)

    Kurosawa, Mie; Oda, Masataka; Domon, Hisanori; Saitoh, Issei; Hayasaki, Haruaki; Terao, Yutaka

    2016-02-01

    Streptococcus pyogenes produces molecules that inhibit the function of human immune system, thus allowing the pathogen to grow and spread in tissues. It is known that S. pyogenes CAMP factor increases erythrocytosis induced by Staphylococcus aureus β-hemolysin. However, the effects of CAMP factor for immune cells are unclear. In this study, we investigated the effects of CAMP factor to macrophages. Western blotting analysis demonstrated that all examined strains expressed CAMP factor protein. In the presence of calcium or magnesium ion, CAMP factor was significantly released in the supernatant. In addition, both culture supernatant from S. pyogenes strain SSI-9 and recombinant CAMP factor dose-dependently induced vacuolation in RAW 264.7 cells, but the culture supernatant from Δcfa isogenic mutant strain did not. CAMP factor formed oligomers in RAW 264.7 cells in a time-dependent manner. CAMP factor suppressed cell proliferation via G2 phase cell cycle arrest without inducing cell death. Furthermore, CAMP factor reduced the uptake of S. pyogenes and phagocytic activity indicator by RAW 264.7 cells. These results suggest that CAMP factor works as a macrophage dysfunction factor. Therefore, we conclude that CAMP factor allows S. pyogenes to escape the host immune system, and contribute to the spread of streptococcal infection. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  1. Down-regulation of homing receptors: a mechanism for impaired recruitment of human phagocytes in sepsis.

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    Hasslen, S R; Nelson, R D; Kishimoto, T K; Warren, W E; Ahrenholz, D H; Solem, L D

    1991-05-01

    Receptors known as DREG adhesion molecules on human neutrophils and monocytes provide for homing of these phagocytic leukocytes to sites of inflammation. They mediate the initial adhesive interaction of the leukocytes to vascular endothelial cells and are then shed from the cell surface in response to chemotactic factors and inflammatory mediators. Systemic accumulation of these agents following major injury or sepsis may therefore promote shedding of DREG receptors from circulating leukocytes and impair their recruitment to sites of inflammation. To test this hypothesis, we have analyzed the expression of DREG receptors on neutrophils and monocytes from 25 patients admitted to the Surgical Intensive Care Unit. Receptor expression was measured by flow cytometry of cells stained with murine monoclonal DREG-56 anti-DREG antibody. For 14 nonseptic patients, mean monocyte positivity for DREG was reduced from 64% to 40%. For 11 septic patients, mean neutrophil and monocyte positivity for DREG was reduced from 94% to 82% and 64% to 34%, respectively. These results suggest that monocytes are more affected than neutrophils in vivo by conditions expected to stimulate shedding of DREG and that sepsis promotes shedding of these adherence receptors. Accumulation of DREG-negative monocytes in association with sepsis may be sufficient to impair their recruitment to inflammatory sites and limit their contribution to host defense against infection and tissue repair.

  2. Phagocytes, Antibiotics, and Self-Limiting Bacterial Infections.

    Science.gov (United States)

    Levin, Bruce R; Baquero, Fernando; Ankomah, Peter Pierre; McCall, Ingrid C

    2017-11-01

    Most antibiotic use in humans is to reduce the magnitude and term of morbidity of acute, community-acquired infections in immune competent patients, rather than to save lives. Thanks to phagocytic leucocytes and other host defenses, the vast majority of these infections are self-limiting. Nevertheless, there has been a negligible amount of consideration of the contribution of phagocytosis and other host defenses in the research for, and the design of, antibiotic treatment regimens, which hyper-emphasizes antibiotics as if they were the sole mechanism responsible for the clearance of infections. Here, we critically review this approach and its limitations. With the aid of a heuristic mathematical model, we postulate that if the rate of phagocytosis is great enough, for acute, normally self-limiting infections, then (i) antibiotics with different pharmacodynamic properties would be similarly effective, (ii) low doses of antibiotics can be as effective as high doses, and (iii) neither phenotypic nor inherited antibiotic resistance generated during therapy are likely to lead to treatment failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Effects of lethal and non-lethal malaria on the mononuclear phagocyte system

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    Carlos Eduardo Tosta

    1983-03-01

    Full Text Available The effects ofone non-lethal species ofmalarialparasite, Plasmodium yoelii, and one lethal species, P. berghei, on the mononuclear phagocyte system (MPS of BALB/c mice were studied. P. yoelii caused a greater and more sustained expansion and activation of the MPS, and the two major populations of spleen phagocytic cells-red pulp and marginal zone macrophages - exhibited a greater increase in numbers in this infection. During the course of P. berghei mataria, the spleen was progressively occupied by haematopoietic tissue and, at the terminal stage of infection, an extensive depletion of lymphocytes and macrophages was apparent. The possibility was suggested that the outcome of mataria may be inftuenced by the particular way the parasite interacts with the MPS.Estudou-se o efeito da infecção causada por espécie letal (Plasmodium berghei e não- letal (P. yoelii de plasmódio sobre o sistema de fagócitos mononucleares de camundongo BALB/c. O P. yoelii causou maior e mais prolongada expansão e ativação do sistema de macrófagos. As duas mais importantes populações de fagócitos esplênicos - macrófagos de polpa vermelha e da zona marginal - exibiam maior aumento do número de células nesta infecção. Durante a evolução da malária por P. berghei, o baço foi progressivamente ocupado por tecido hematopoiético e, na fase terminal da infecção, observou-se significativa depleção dos linfócitos e macrófagos esplênicos. Os dados apresentados indicam que a evolução da malária depende do tipo de interação entre o plasmódio e o sistema de fagócitos mononucleares.

  4. The Potency of Hyaluronan of Different Molecular Weights in the Stimulation of Blood Phagocytes

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    Barbora Safrankova

    2010-01-01

    Full Text Available The regulatory functions of glycosaminoglycan hyaluronan (HA are suggested to be dependent on its molecular weight (MW. Proinflammatory and stimulatory effects are proposed mainly for the low MW HA. However, the complex response of blood phagocytes to HA of different MW is unclear. Herein, the effects of highly purified HA of precisely defined MW (52, 250, and 970 kDa on human blood phagocytes were tested. All MW HA activated blood phagocytes, including the spontaneous production of ROS, degranulation, and the production of tumor necrosis factor alpha, with low MW HA 52 kDa having the highest potency and high MW HA 970 kDa having the lowest potency. Interestingly, HA inhibited ROS production stimulated by opsonized zymosan particles and, in contrast, potentiated starch-activated ROS production, mostly independent of MW. Data showed a significant effect of HA of different MW on blood phagocytes, including high MW HA.

  5. The potency of hyaluronan of different molecular weights in the stimulation of blood phagocytes.

    Science.gov (United States)

    Safrankova, Barbora; Gajdova, Silvie; Kubala, Lukas

    2010-01-01

    The regulatory functions of glycosaminoglycan hyaluronan (HA) are suggested to be dependent on its molecular weight (MW). Proinflammatory and stimulatory effects are proposed mainly for the low MW HA. However, the complex response of blood phagocytes to HA of different MW is unclear. Herein, the effects of highly purified HA of precisely defined MW (52, 250, and 970  kDa) on human blood phagocytes were tested. All MW HA activated blood phagocytes, including the spontaneous production of ROS, degranulation, and the production of tumor necrosis factor alpha, with low MW HA 52  kDa having the highest potency and high MW HA 970  kDa having the lowest potency. Interestingly, HA inhibited ROS production stimulated by opsonized zymosan particles and, in contrast, potentiated starch-activated ROS production, mostly independent of MW. Data showed a significant effect of HA of different MW on blood phagocytes, including high MW HA.

  6. Alarmins MRP8 and MRP14 Induce Stress Tolerance in Phagocytes under Sterile Inflammatory Conditions

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    Judith Austermann

    2014-12-01

    Full Text Available Hyporesponsiveness by phagocytes is a well-known phenomenon in sepsis that is frequently induced by low-dose endotoxin stimulation of Toll-like receptor 4 (TLR4 but can also be found under sterile inflammatory conditions. We now demonstrate that the endogenous alarmins MRP8 and MRP14 induce phagocyte hyporesponsiveness via chromatin modifications in a TLR4-dependent manner that results in enhanced survival to septic shock in mice. During sterile inflammation, polytrauma and burn trauma patients initially present with high serum concentrations of myeloid-related proteins (MRPs. Human neonatal phagocytes are primed for hyporesponsiveness by increased peripartal MRP concentrations, which was confirmed in murine neonatal endotoxinemia in wild-type and MRP14−/− mice. Our data therefore indicate that alarmin-triggered phagocyte tolerance represents a regulatory mechanism for the susceptibility of neonates during systemic infections and sterile inflammation.

  7. Phage-Phagocyte Interactions and Their Implications for Phage Application as Therapeutics

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    Jończyk-Matysiak, Ewa; Weber-Dąbrowska, Beata; Owczarek, Barbara; Międzybrodzki, Ryszard; Łusiak-Szelachowska, Marzanna; Łodej, Norbert; Górski, Andrzej

    2017-01-01

    Phagocytes are the main component of innate immunity. They remove pathogens and particles from organisms using their bactericidal tools in the form of both reactive oxygen species and degrading enzymes—contained in granules—that are potentially toxic proteins. Therefore, it is important to investigate the possible interactions between phages and immune cells and avoid any phage side effects on them. Recent progress in knowledge concerning the influence of phages on phagocytes is also important as such interactions may shape the immune response. In this review we have summarized the current knowledge on phage interactions with phagocytes described so far and their potential implications for phage therapy. The data suggesting that phage do not downregulate important phagocyte functions are especially relevant for the concept of phage therapy. PMID:28613272

  8. In Vitro Analysis of Nanoparticle Effects on the Zymosan Uptake by Phagocytic Cells.

    Science.gov (United States)

    Potter, Timothy M; Skoczen, Sarah L; Rodriguez, Jamie C; Neun, Barry W; Ilinskaya, Anna N; Cedrone, Edward; Dobrovolskaia, Marina A

    2018-01-01

    This chapter provides a protocol for analysis of nanoparticle effects on the function of phagocytic cells. The protocol relies on luminol chemiluminescence to detect zymosan uptake. Zymosan is an yeast particle which is typically eliminated by phagocytic cells via the complement receptor pathway. The luminol, co-internalized with zymosan, is processed inside the phagosome to generate a chemiluminescent signal. If a test nanoparticle affects the phagocytic function of the cell, the amount of phagocytosed zymosan and, proportionally, the level of generated chemiluminescent signal change. Comparing the zymosan uptake of untreated cells with that of cells exposed to a nanoparticle provides information about the nanoparticle's effects on the normal phagocytic function. This method has been described previously and is presented herein with several changes. The revised method includes details about nanoparticle concentration selection, updated experimental procedure, and examples of the method performance.

  9. THE RELATION BETWEEN PHAGOCYTIC ACTIVITY OF THE NEUTROPHILS (PMN AND THE GLICEMIC LEVEL AT THE SPORTSMAN

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    D. Cotuna

    1999-01-01

    Full Text Available We tried to find a relation between the phagocytes activity of the neutrophils and the level of glicemy in athletes applying the ANOVA test, taking into account the fact that hyperglicemy reduces the phagocytes activity of the neutrophils which becomes so more spherical and burden after the contact with foreign particles. The phagocyte activity of neutrophils (PMN had been established through NBT technique and the glicemy level was determined by Hagerdon – Jansen method. From these notices processed by ANOVA test applied on the values of phagocyte activity of PMN and on glicemy level we conclude that does not exist a tendency of association of these two parameters in a relationship.

  10. Effects of Levamisole on Phagocytic Activity of Rainbow Trout (Oncorhynchus mykiss W.

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    U. Ispir

    2007-01-01

    Full Text Available In this study, activation of phagocytic cells was examined in rainbow trout (Oncorhynchus mykiss W. exposed to 1, 5 and 10 μg ml-1 concentrations of levamisole solution. For this purpose, blood samples were taken from fish on days 1, 7 and 14 of exposure. Potential killing activity was determined by measuring oxidative radical production and phagocytic activity of neutrophils and superoxide anion production of phagocytic cells against Y. ruckeri. The activity of phagocytic cells in fish exposed to each of three concentrations was found higher than that in controls and the differences were statistically significant (p p -1 concentration of levamisole solution was determined on day 7, it was observed that all indicators increased on day 14 of exposure. The present results suggest that the application of levamisole in fish farms could increase non-specific immunity and resistance to infection of fish and offer economics benefits.

  11. Phagocytic and bactericidal activities of leukocytes in whole blood from atomic bomb survivors

    International Nuclear Information System (INIS)

    Sasagawa, S.; Yoshimoto, Y.; Toyota, E.; Neriishi, S.; Yamakido, M.; Matsuo, M.; Hosoda, Y.; Finch, S.C.

    1990-01-01

    This study evaluated the phagocytic and bactericidal activities of peripheral blood leukocytes from Hiroshima and Nagasaki atomic bomb survivors for Staphylococcus aureus. The data were analyzed by multiple linear regression for age, sex, radiation exposure, city of exposure, and neutrophil counts. No significant radiation effect was observed for either blood phagocytic or bactericidal activities. The only significant variable for these functions was the neutrophil count

  12. Pattern of mercury accumulation in different tissues of migratory and resident birds: Western reef heron (Egretta gularis) and Siberian gull (Larus heuglini) in Hara International Wetland-Persian Gulf.

    Science.gov (United States)

    Majidi, Yousef; Bahramifar, Nader; Ghasempouri, Seyed Mahmoud

    2015-01-01

    The Hara Mangrove Forest of the Persian Gulf is undergoing increasing pollution from industrial, municipal, and petroleum sources; however, little research in ecotoxicology has been carried out in this ecosystem. In the present study, mercury distribution and accumulation were investigated in muscle, liver, kidney, and feather of the resident Western reef heron (n = 15) and the migratory Siberian gull (n = 15). We also evaluated the relation between Hg concentrations, sex, and age (juvenile vs. adult). Results showed that the highest concentrations of Hg were recorded in the feather (35 ± 0.14-3.0 ± 0.27 mg kg(-1) dw) and at 3.7-, 1.6-, and 1.3-fold in muscle, kidney, and liver, respectively. Concentrations of mercury in tissues of migratory birds were two times higher than in resident birds; geographical differences and feeding habits were used to explain these variations. We found a weak relationship between Hg concentrations in feathers and internal tissues (r ≤ 0.50); conversely, liver presented strong positive correlations with other soft tissues, especially kidney (p > 0.05; r = 0.82). Results showed that sex and age have no significant effects on T-Hg accumulation in these birds (p > 0.05; r pollution in this region.

  13. Human hantavirus infection elicits pronounced redistribution of mononuclear phagocytes in peripheral blood and airways.

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    Saskia Scholz

    2017-06-01

    Full Text Available Hantaviruses infect humans via inhalation of virus-contaminated rodent excreta. Infection can cause severe disease with up to 40% mortality depending on the viral strain. The virus primarily targets the vascular endothelium without direct cytopathic effects. Instead, exaggerated immune responses may inadvertently contribute to disease development. Mononuclear phagocytes (MNPs, including monocytes and dendritic cells (DCs, orchestrate the adaptive immune responses. Since hantaviruses are transmitted via inhalation, studying immunological events in the airways is of importance to understand the processes leading to immunopathogenesis. Here, we studied 17 patients infected with Puumala virus that causes a mild form of hemorrhagic fever with renal syndrome (HFRS. Bronchial biopsies as well as longitudinal blood draws were obtained from the patients. During the acute stage of disease, a significant influx of MNPs expressing HLA-DR, CD11c or CD123 was detected in the patients' bronchial tissue. In parallel, absolute numbers of MNPs were dramatically reduced in peripheral blood, coinciding with viremia. Expression of CCR7 on the remaining MNPs in blood suggested migration to peripheral and/or lymphoid tissues. Numbers of MNPs in blood subsequently normalized during the convalescent phase of the disease when viral RNA was no longer detectable in plasma. Finally, we exposed blood MNPs in vitro to Puumala virus, and demonstrated an induction of CCR7 expression on MNPs. In conclusion, the present study shows a marked redistribution of blood MNPs to the airways during acute hantavirus disease, a process that may underlie the local immune activation and contribute to immunopathogenesis in hantavirus-infected patients.

  14. Bisphosphonates in vitro specifically inhibit, among the hematopoietic series, the development of the mouse mononuclear phagocyte lineage

    Energy Technology Data Exchange (ETDEWEB)

    Cecchini, M.G.; Fleisch, H. (Univ. of Bern (Switzerland))

    1990-10-01

    Bisphosphonates (BP) are powerful inhibitors of bone resorption. We have previously shown that 4-amino-1-hydroxybutylidene-1,1-bisphosphonate (AHBuBP), 3-amino-1-hydroxypropylidene-1,1-bisphosphonate (AHPrBP), and dichloromethylenebisphosphonate (Cl2MBP) inhibit the proliferation of macrophages in vitro at concentrations that do not affect the viability of nonproliferating cells. In this study we further investigated whether the antiproliferative effect of these three BP is, among the hematopoietic series, preferential to the mononuclear phagocyte lineage. BP were unable to inhibit more than 30-40% of the ({sup 3}H)thymidine ({sup 3}H-TdR) incorporation into bone marrow cells stimulated to proliferate by multilineage colony-stimulating activity containing conditioned medium (multi-CSA). From the analysis of the colonies induced in semisolid medium by multi-CSA and recombinant murine granulocyte-macrophage colony stimulating factor (rmGM-CSF), a dose-dependent disappearance specific to the macrophage-containing colonies emerged. In contrast, the number and composition of colonies other than macrophage and, in particular, the granulocyte colonies were not affected by these compounds, even at high concentrations (100 microM) previously also shown to be toxic for nonproliferating macrophages. Since the macrophages, differently from polymorphonuclear phagocytes, are known to be highly pinocytotic, it is possible that by this means they selectively concentrate BP intracellularly, leading to toxic concentrations. We postulate tht BP may also act in vivo in addition to their effect on osteoclast activity, by a similar mechanism on osteoclast precursors and on bone resident macrophages, a source of cytokines stimulating bone resorption and leading to impaired osteoclast recruitment and activity.

  15. Quantified F-Actin Morphology Is Predictive of Phagocytic Capacity of Stem Cell-Derived Retinal Pigment Epithelium

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    Claudia Müller

    2018-03-01

    Full Text Available Summary: With stem cell-derived retinal pigment epithelial (RPE replacement therapies in clinical testing, establishing potency of RPE prior to transplantation is imperative. Phagocytosis of photoreceptor outer segment fragments (POS is a key indicator of RPE functionality. Comparing RPE derived from different donor human adult RPE stem cell lines, we found that cells were either high-phagocytic or low-phagocytic despite sharing phagocytic receptors and ligands, junctional ZO-1, and lack of epithelial-mesenchymal transition. We found that low-phagocytic cells harbored F-actin stress fibers but lacked contiguous lateral circumferential F-actin and ezrin-rich microvilli of high-phagocytic cells. Rho kinase inhibition reversed the F-actin phenotype and restored phagocytic capacity to low-phagocytic RPE. Conversely, RhoA activation induced stress fiber formation and reduced phagocytic function of high-phagocytic RPE. These results demonstrate that a stress fiber-rich microfilament cytoskeleton causes phagocytic dysfunction of RPE cells. We propose F-actin assessment as a rapid, sensitive, and quantitative test to identify RPE populations lacking phagocytic capacity. : Here, Finnemann and colleagues demonstrate that F-actin stress fibers in adult stem cell-derived retinal pigment epithelial (RPE cells predict and cause poor phagocytic activity, a cardinal RPE function. ROCK inhibitor treatment of differentiated RPE monolayers suffices to revert F-actin phenotype and restore phagocytic function. The authors propose F-actin phenotype scoring as a rapid, sensitive, and quantitative assessment of RPE quality. Keywords: adult RPE stem cells, cytoskeleton, F-actin, phagocytosis, retinal pigment epithelium, RPE, RhoA/ROCK, stress fibers

  16. Evolutionary conservation of divergent pro-inflammatory and homeostatic responses in Lamprey phagocytes.

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    Jeffrey J Havixbeck

    Full Text Available In higher vertebrates, phagocytosis plays a critical role in development and immunity, based on the internalization and removal of apoptotic cells and invading pathogens, respectively. Previous studies describe the effective uptake of these particles by lower vertebrate and invertebrate phagocytes, and identify important molecular players that contribute to this internalization. However, it remains unclear if individual phagocytes mediate internalization processes in these ancient organisms, and how this impacts the balance of pro-inflammatory and homeostatic events within their infection sites. Herein we show that individual phagocytes of the jawless vertebrate Petromyzon marinus (sea lamprey, like those of teleost fish and mice, display the capacity for divergent pro-inflammatory and homeostatic responses following internalization of zymosan and apoptotic cells, respectively. Professional phagocytes (macrophages, monocytes, neutrophils were the primary contributors to the internalization of pro-inflammatory particles among goldfish (C. auratus and lamprey (P. marinus hematopoietic leukocytes. However, goldfish showed a greater ability for zymosan phagocytosis when compared to their jawless counterparts. Coupled to this increase was a significantly lower sensitivity of goldfish phagocytes to homeostatic signals derived from apoptotic cell internalization. Together, this translated into a significantly greater capacity for induction of antimicrobial respiratory burst responses compared to lamprey phagocytes, but also a decreased efficacy in apoptotic cell-driven leukocyte homeostatic mechanisms that attenuate this pro-inflammatory process. Overall, our results show the long-standing evolutionary contribution of intrinsic phagocyte mechanisms for the control of inflammation, and illustrate one effective evolutionary strategy for increased responsiveness against invading pathogens. In addition, they highlight the need for development of

  17. Characterization of NCR1+ cells residing in lymphoid tissues in the gut of lambs indicates that the majority are NK cells.

    Science.gov (United States)

    Olsen, Line; Boysen, Preben; Åkesson, Caroline Piercey; Gunnes, Gjermund; Connelley, Timothy; Storset, Anne K; Espenes, Arild

    2013-11-13

    Natural killer (NK) cells are important for immune protection of the gut mucosa. Previous studies have shown that under pathologic conditions NK cells, T cells and dendritic cells are found co-localised in secondary lymphoid organs where their interaction coordinates immune responses. However, in the gut-associated lymphoid tissues (GALTs), there are few detailed reports on the distribution of NK cells. Sheep harbour several types of organised lymphoid tissues in the gut that have different functions. The ileal Peyer's patch (IPP) functions as a primary lymphoid tissue for B cell generation, while the jejunal Peyer's patches (JPPs) and colon patches (CPs) are considered secondary lymphoid tissues. In the present study, we analysed tissues from healthy lambs by flow cytometry and in situ multicolour immunofluorescence, using recently described NCR1 antibodies to identify ovine NK cells. Most NCR1+ cells isolated from all tissues were negative for the pan T cell marker CD3, and thus comply with the general definition of NK cells. The majority of NCR1+ cells in blood as well as secondary lymphoid organs expressed CD16, but in the GALT around half of the NCR1+ cells were negative for CD16. A semi-quantitative morphometric study on tissue sections was used to compare the density of NK cells in four compartments of the IPPs, JPP and CPs. NCR1+ cells were found in all gut segments. Statistical analysis revealed significant differences between compartments of the primary lymphoid organ IPP and the secondary lymphoid organs of the JPPs and CP. NK cells co-localised and made close contact with T cells, dendritic cells and other NK cells, but did not show signs of proliferation. We conclude that NK cells are present in all investigated segments of the sheep gut, but that presence of other innate lymphoid cells expressing NCR1 cannot be excluded.

  18. Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease.

    Science.gov (United States)

    Gomez-Arboledas, Angela; Davila, Jose C; Sanchez-Mejias, Elisabeth; Navarro, Victoria; Nuñez-Diaz, Cristina; Sanchez-Varo, Raquel; Sanchez-Mico, Maria Virtudes; Trujillo-Estrada, Laura; Fernandez-Valenzuela, Juan Jose; Vizuete, Marisa; Comella, Joan X; Galea, Elena; Vitorica, Javier; Gutierrez, Antonia

    2018-03-01

    Reactive astrogliosis, a complex process characterized by cell hypertrophy and upregulation of components of intermediate filaments, is a common feature in brains of Alzheimer's patients. Reactive astrocytes are found in close association with neuritic plaques; however, the precise role of these glial cells in disease pathogenesis is unknown. In this study, using immunohistochemical techniques and light and electron microscopy, we report that plaque-associated reactive astrocytes enwrap, engulf and may digest presynaptic dystrophies in the hippocampus of amyloid precursor protein/presenilin-1 (APP/PS1) mice. Microglia, the brain phagocytic population, was apparently not engaged in this clearance. Phagocytic reactive astrocytes were present in 35% and 67% of amyloid plaques at 6 and 12 months of age, respectively. The proportion of engulfed dystrophic neurites was low, around 7% of total dystrophies around plaques at both ages. This fact, along with the accumulation of dystrophic neurites during disease course, suggests that the efficiency of the astrocyte phagocytic process might be limited or impaired. Reactive astrocytes surrounding and engulfing dystrophic neurites were also detected in the hippocampus of Alzheimer's patients by confocal and ultrastructural analysis. We posit that the phagocytic activity of reactive astrocytes might contribute to clear dysfunctional synapses or synaptic debris, thereby restoring impaired neural circuits and reducing the inflammatory impact of damaged neuronal parts and/or limiting the amyloid pathology. Therefore, potentiation of the phagocytic properties of reactive astrocytes may represent a potential therapy in Alzheimer's disease. © 2017 The Authors GLIA Published by Wiley Periodicals, Inc.

  19. Permanent resident

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    John F. Fisher

    2016-05-01

    Full Text Available The training of physicians in the past century was based primarily on responsibility and the chain-of-command. Those with the bulk of that responsibility in the fields of pediatrics and internal medicine were residents. Residents trained the medical students and supervised them carefully in caring for patients. Most attending physicians supervised their teams at arm's length, primarily serving as teachers of the finer points of diagnosis and treatment during set periods of the day or week with a perfunctory signature on write-ups or progress notes. Residents endeavored to protect the attending physician from being heavily involved unless they were unsure about a clinical problem. Before contacting the attending physician, a more senior resident would be called. Responsibility was the ultimate teacher. The introduction of diagnosis-related groups by the federal government dramatically changed the health care delivery system, placing greater emphasis on attending physician visibility in the medical record, ultimately resulting in more attending physician involvement in day-to-day care of patients in academic institutions. Without specified content in attending notes, hospital revenues would decline. Although always in charge technically, attending physicians increasingly have assumed the role once dominated by the resident. Using biographical experiences of more than 40 years, the author acknowledges and praises the educational role of responsibility in his own training and laments its declining role in today's students and house staff.

  20. Permanent resident.

    Science.gov (United States)

    Fisher, John F

    2016-01-01

    The training of physicians in the past century was based primarily on responsibility and the chain-of-command. Those with the bulk of that responsibility in the fields of pediatrics and internal medicine were residents. Residents trained the medical students and supervised them carefully in caring for patients. Most attending physicians supervised their teams at arm's length, primarily serving as teachers of the finer points of diagnosis and treatment during set periods of the day or week with a perfunctory signature on write-ups or progress notes. Residents endeavored to protect the attending physician from being heavily involved unless they were unsure about a clinical problem. Before contacting the attending physician, a more senior resident would be called. Responsibility was the ultimate teacher. The introduction of diagnosis-related groups by the federal government dramatically changed the health care delivery system, placing greater emphasis on attending physician visibility in the medical record, ultimately resulting in more attending physician involvement in day-to-day care of patients in academic institutions. Without specified content in attending notes, hospital revenues would decline. Although always in charge technically, attending physicians increasingly have assumed the role once dominated by the resident. Using biographical experiences of more than 40 years, the author acknowledges and praises the educational role of responsibility in his own training and laments its declining role in today's students and house staff.

  1. Neuropilin-1 Is Expressed on Lymphoid Tissue Residing LTi-like Group 3 Innate Lymphoid Cells and Associated with Ectopic Lymphoid Aggregates.

    Science.gov (United States)

    Shikhagaie, Medya Mara; Björklund, Åsa K; Mjösberg, Jenny; Erjefält, Jonas S; Cornelissen, Anne S; Ros, Xavier Romero; Bal, Suzanne M; Koning, Jasper J; Mebius, Reina E; Mori, Michiko; Bruchard, Melanie; Blom, Bianca; Spits, Hergen

    2017-02-14

    Here, we characterize a subset of ILC3s that express Neuropilin1 (NRP1) and are present in lymphoid tissues, but not in the peripheral blood or skin. NRP1 + group 3 innate lymphoid cells (ILC3s) display in vitro lymphoid tissue inducer (LTi) activity. In agreement with this, NRP1 + ILC3s are mainly located in proximity to high endothelial venules (HEVs) and express cell surface molecules involved in lymphocyte migration in secondary lymphoid tissues via HEVs. NRP1 was also expressed on mouse fetal LTi cells, indicating that NRP1 is a conserved marker for LTi cells. Human NRP1 + ILC3s are primed cells because they express CD45RO and produce higher amounts of cytokines than NRP1 - cells, which express CD45RA. The NRP1 ligand vascular endothelial growth factor A (VEGF-A) served as a chemotactic factor for NRP1 + ILC3s. NRP1 + ILC3s are present in lung tissues from smokers and patients with chronic obstructive pulmonary disease, suggesting a role in angiogenesis and/or the initiation of ectopic pulmonary lymphoid aggregates. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Spironolactone attenuates bleomycin-induced pulmonary injury partially via modulating mononuclear phagocyte phenotype switching in circulating and alveolar compartments.

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    Wen-Jie Ji

    Full Text Available BACKGROUND: Recent experimental studies provide evidence indicating that manipulation of the mononuclear phagocyte phenotype could be a feasible approach to alter the severity and persistence of pulmonary injury and fibrosis. Mineralocorticoid receptor (MR has been reported as a target to regulate macrophage polarization. The present work was designed to investigate the therapeutic potential of MR antagonism in bleomycin-induced acute lung injury and fibrosis. METHODOLOGY/PRINCIPAL FINDINGS: We first demonstrated the expression of MR in magnetic bead-purified Ly6G-/CD11b+ circulating monocytes and in alveolar macrophages harvested in bronchoalveolar lavage fluid (BALF from C57BL/6 mice. Then, a pharmacological intervention study using spironolactone (20 mg/kg/day by oral gavage revealed that MR antagonism led to decreased inflammatory cell infiltration, cytokine production (downregulated monocyte chemoattractant protein-1, transforming growth factor β1, and interleukin-1β at mRNA and protein levels and collagen deposition (decreased lung total hydroxyproline content and collagen positive area by Masson' trichrome staining in bleomycin treated (2.5 mg/kg, via oropharyngeal instillation male C57BL/6 mice. Moreover, serial flow cytometry analysis in blood, BALF and enzymatically digested lung tissue, revealed that spironolactone could partially inhibit bleomycin-induced circulating Ly6C(hi monocyte expansion, and reduce alternative activation (F4/80+CD11c+CD206+ of mononuclear phagocyte in alveoli, whereas the phenotype of interstitial macrophage (F4/80+CD11c- remained unaffected by spironolactone during investigation. CONCLUSIONS/SIGNIFICANCE: The present work provides the experimental evidence that spironolactone could attenuate bleomycin-induced acute pulmonary injury and fibrosis, partially via inhibition of MR-mediated circulating monocyte and alveolar macrophage phenotype switching.

  3. Infection-Mediated Priming of Phagocytes Protects against Lethal Secondary Aspergillus fumigatus Challenge.

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    Amélie Savers

    Full Text Available Phagocytes restrict the germination of Aspergillus fumigatus conidia and prevent the establishment of invasive pulmonary aspergillosis in immunecompetent mice. Here we report that immunecompetent mice recovering from a primary A. fumigatus challenge are protected against a secondary lethal challenge. Using RAGγc knock-out mice we show that this protection is independent of T, B and NK cells. In protected mice, lung phagocytes are recruited more rapidly and are more efficient in conidial phagocytosis and killing. Protection was also associated with an enhanced expression of CXCR2 and Dectin-1 on bone marrow phagocytes. We also show that protective lung cytokine and chemokine responses are induced more rapidly and with enhanced dynamics in protected mice. Our findings support the hypothesis that following a first encounter with a non-lethal dose of A. fumigatus conidia, the innate immune system is primed and can mediate protection against a secondary lethal infection.

  4. Blood phagocyte activity after race training sessions in Thoroughbred and Arabian horses.

    Science.gov (United States)

    Cywinska, Anna; Szarska, Ewa; Degorski, Andrzej; Guzera, Maciej; Gorecka, Renata; Strzelec, Katarzyna; Kowalik, Sylwester; Schollenberger, Antoni; Winnicka, Anna

    2013-10-01

    Intensive exercise and exertion during competition promote many changes that may result in the impairment of immunity and increased susceptibility to infections. The aim of this study was to evaluate the activity of "the first line of defense": neutrophils and monocytes in racing Thoroughbred and Arabian horses after routine training sessions. Twenty-three (12 Thoroughbred and 11 Arabian) horses were examined. Routine haematological (number of red blood cells - RBC, haemoglobin concentration - HGB, haematocrit - HCT, total number of white blood cells - WBC), biochemical (creatine phosphokinase activity - CPK and total protein concentration - TP) parameters, cortisol concentration as well as phagocytic and oxidative burst activity of neutrophils and monocytes were determined. The values of basic parameters and the activity of phagocytes differed between breeds and distinct patterns of exercise-induced changes were observed. The training sessions did not produce the decrease in phagocyte activity that might lead to the suppression of immunity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Upregulation of phagocyte-derived catecholamines augments the acute inflammatory response.

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    Michael A Flierl

    Full Text Available Following our recent report that phagocytic cells (neutrophils, PMNs, and macrophages are newly discovered sources of catecholamines, we now show that both epinephrine and norepinephrine directly activate NFkappaB in macrophages, causing enhanced release of proinflammatory cytokines (TNFalpha, IL-1beta, IL-6. Both adrenal-intact (AD+ and adrenalectomized (ADX rodents were used, because ADX animals had greatly enhanced catecholamine release from phagocytes, facilitating our efforts to understand the role of catecholamines released from phagocytes. Phagocytes isolated from adrenalectomized rats displayed enhanced expression of tyrosine-hydroxylase and dopamine-beta-hydroxylase, two key enzymes for catecholamine production and exhibited higher baseline secretion of norepinephrine and epinephrine. The effects of upregulation of phagocyte-derived catecholamines were investigated in two models of acute lung injury (ALI. Increased levels of phagocyte-derived catecholamines were associated with intensification of the acute inflammatory response, as assessed by increased plasma leak of albumin, enhanced myeloperoxidase content in lungs, augmented levels of proinflammatory mediators in bronchoalveolar lavage fluids, and elevated expression of pulmonary ICAM-1 and VCAM-1. In adrenalectomized rats, development of ALI was enhanced and related to alpha(2-adrenoceptors engagement but not to involvement of mineralocorticoid or glucocorticoid receptors. Collectively, these data demonstrate that catecholamines are potent inflammatory activators of macrophages, upregulating NFkappaB and further downstream cytokine production of these cells. In adrenalectomized animals, which have been used to further assess the role of catecholamines, there appears to be a compensatory increase in catecholamine generating enzymes and catecholamines in macrophages, resulting in amplification of the acute inflammatory response via engagement of alpha(2-adrenoceptors.

  6. Whole-blood phagocytic and bactericidal activities of atomic bomb survivors, Hiroshima and Nagasaki

    International Nuclear Information System (INIS)

    Sasagawa, Sumiko; Yoshimoto, Yasuhiko; Toyota, Emiko; Neriishi, Shotaro; Yamakido, Michio; Matsuo, Miyo; Hosoda, Yutaka; Finch, S.C.

    1989-04-01

    This in vitro study evaluated the phagocytic and bactericidal activities of leukocytes in aliquots of whole blood from Hiroshima and Nagasaki atomic bomb survivors for Staphylococcus aureus. The data were analyzed by multiple linear regression. Any significant effects of exposure to A-bomb radiation could not be detected for both phagocytic and bactericidal activities of whole blood from A-bomb survivors. In addition, there were no significant effects of age categories, sex or city, except in neutrophil counts. (J.P.N.)

  7. Efferocytosis and Outside-In Signaling by Cardiac Phagocytes. Links to Repair, Cellular Programming, and Intercellular Crosstalk in Heart

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    Matthew DeBerge

    2017-11-01

    Full Text Available Phagocytic sensing and engulfment of dying cells and extracellular bodies initiate an intracellular signaling cascade within the phagocyte that can polarize cellular function and promote communication with neighboring non-phagocytes. Accumulating evidence links phagocytic signaling in the heart to cardiac development, adult myocardial homeostasis, and the resolution of cardiac inflammation of infectious, ischemic, and aging-associated etiology. Phagocytic clearance in the heart may be carried out by professional phagocytes, such as macrophages, and non-professional cells, including myofibrolasts and potentially epithelial cells. During cardiac development, phagocytosis initiates growth cues for early cardiac morphogenesis. In diseases of aging, including myocardial infarction, heightened levels of cell death require efficient phagocytic debridement to salvage further loss of terminally differentiated adult cardiomyocytes. Additional risk factors, including insulin resistance and other systemic risk factors, contribute to inefficient phagocytosis, altered phagocytic signaling, and delayed cardiac inflammation resolution. Under such conditions, inflammatory presentation of myocardial antigen may lead to autoimmunity and even possible rejection of transplanted heart allografts. Increased understanding of these basic mechanisms offers therapeutic opportunities.

  8. TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis.

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    Kazuya Takahashi

    2007-04-01

    Full Text Available BACKGROUND: In multiple sclerosis, inflammation can successfully be prevented, while promoting repair is still a major challenge. Microglial cells, the resident phagocytes of the central nervous system (CNS, are hematopoietic-derived myeloid cells and express the triggering receptor expressed on myeloid cells 2 (TREM2, an innate immune receptor. Myeloid cells are an accessible source for ex vivo gene therapy. We investigated whether myeloid precursor cells genetically modified to express TREM2 affect the disease course of experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis. METHODS AND FINDINGS: EAE was induced in mice by immunization with a myelin autoantigen. Intravenous application of TREM2-transduced bone marrow-derived myeloid precursor cells at the EAE peak led to an amelioration of clinical symptoms, reduction in axonal damage, and prevention of further demyelination. TREM2-transduced myeloid cells applied intravenously migrated into the inflammatory spinal cord lesions of EAE-diseased mice, showed increased lysosomal and phagocytic activity, cleared degenerated myelin, and created an anti-inflammatory cytokine milieu within the CNS. CONCLUSIONS: Intravenously applied bone marrow-derived and TREM2-tranduced myeloid precursor cells limit tissue destruction and facilitate repair within the murine CNS by clearance of cellular debris during EAE. TREM2 is a new attractive target for promotion of repair and resolution of inflammation in multiple sclerosis and other neuroinflammatory diseases.

  9. Effect of H1-antihistamines on the oxidative burst of rat phagocytes

    Czech Academy of Sciences Publication Activity Database

    Králová, Jana; Číž, Milan; Nosál, R.; Drábiková, K.; Lojek, Antonín

    2006-01-01

    Roč. 55, č. 1 (2006), S15-S16 ISSN 1023-3830 R&D Projects: GA ČR(CZ) GA305/04/0896 Institutional research plan: CEZ:AV0Z50040507 Keywords : H1-antihistamines * reactive oxygen species * phagocytes Subject RIV: BO - Biophysics Impact factor: 1.485, year: 2006

  10. The potency of hyaluronan of different molecular weights in the stimulation of blood phagocytes

    Czech Academy of Sciences Publication Activity Database

    Šafaříková, Barbora; Gajdová, Silvie; Kubala, Lukáš

    Vol. 2010, ID 380948 (2010), s. 1-98 ISSN 0962-9351 R&D Projects: GA ČR(CZ) GA305/08/1704 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : phagocyte function * hyaluronan * inflammation Subject RIV: BO - Biophysics Impact factor: 2.059, year: 2010

  11. SURFACE MODIFICATION OF NANOPARTICLES TO OPPOSE UPTAKE BY THE MONONUCLEAR PHAGOCYTE SYSTEM

    NARCIS (Netherlands)

    STORM, G; BELLIOT, SO; DAEMEN, T; LASIC, DD

    1995-01-01

    An overview of recent advances in the surface modification of colloidal particles to oppose uptake by the mononuclear phagocyte system (MPS) is presented. First, we describe the colloidal particles and hydrophilic coating materials investigated, with particular focus on the literature concerning

  12. Pheniramines and oxidative burst of blood phagocytes during ischaemia/reperfusion

    Czech Academy of Sciences Publication Activity Database

    Nosál, R.; Jančinová, V.; Nosálová, V.; Perečko, T.; Číž, Milan; Lojek, Antonín

    2009-01-01

    Roč. 58, č. 1 (2009), S66-S67 ISSN 1023-3830 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : oxidative burst * phagocytes * pheniramines Subject RIV: BO - Biophysics Impact factor: 1.586, year: 2009

  13. Phagocytic activity of three Naegleria strains in the presence of erythrocytes of various types.

    Science.gov (United States)

    Alonso, P; Zubiaur, E

    1985-11-01

    The phagocytic activities of N. lovaniensis (Aq/9/1/45D) and N. gruberi (1518/1f and 1518/1e) were studied in the presence of erythrocytes of various species: chicken, rabbit, goat, and human (A+, B+, and AB+ were tested). The percentage of amoebae with ingested red cells, the phagocytic index (PhI), can be considered as an expression of phagocytic activity. Under given conditions (erythrocyte concentration, incubation time, age of amoebic cultures) each strain of Naegleria prefers one erythrocyte type. Thus, for 72-h cultures, N. lovaniensis ingested more A+ type erythrocytes than did N. gruberi strains but had very low affinity for rabbit red cells except when very high concentrations were tested. Naegleria gruberi 1f was the most active of the three strains towards rabbit and B+ and AB+ human erythrocytes, but very low PhIs were obtained with goat erythrocytes. Naegleria gruberi 1e exhibited high phagocytic activity for every erythrocyte type except for rabbit red cells.

  14. Lessons Learned from Phagocytic Function Studies in a Large Cohort of Patients with Recurrent Infections

    NARCIS (Netherlands)

    Wolach, Baruch; Gavrieli, Ronit; Roos, Dirk; Berger-Achituv, Sivan

    2012-01-01

    Background There is a paucity of data on the relationship between demographic characteristics, specific clinical manifestations, and neutrophil dysfunction, guiding physicians to decide which clinical signs and symptoms are a code for an underlying phagocytic disorder. Methods The data over a

  15. The phagocyte inhibitory receptor sirpα in the immune system

    NARCIS (Netherlands)

    Álvarez Zárate, J.

    2014-01-01

    Phagocytes play a central role in the host defense against pathogens, by virtue of amongst other things their ability to recognize and destroy them. These processes have to be tightly controlled to prevent unwanted inflammation that could harm the host. From previous studies it has become clear that

  16. Value of phagocyte function screening for immunotoxicity of nanoparticles in vivo.

    Science.gov (United States)

    Fröhlich, Eleonore

    2015-01-01

    Nanoparticles (NPs) present in the environment and in consumer products can cause immunotoxic effects. The immune system is very complex, and in vivo studies are the gold standard for evaluation. Due to the increased amount of NPs that are being developed, cellular screening assays to decrease the amount of NPs that have to be tested in vivo are highly needed. Effects on the unspecific immune system, such as effects on phagocytes, might be suitable for screening for immunotoxicity because these cells mediate unspecific and specific immune responses. They are present at epithelial barriers, in the blood, and in almost all organs. This review summarizes the effects of carbon, metal, and metal oxide NPs used in consumer and medical applications (gold, silver, titanium dioxide, silica dioxide, zinc oxide, and carbon nanotubes) and polystyrene NPs on the immune system. Effects in animal exposures through different routes are compared to the effects on isolated phagocytes. In addition, general problems in the testing of NPs, such as unknown exposure doses, as well as interference with assays are mentioned. NPs appear to induce a specific immunotoxic pattern consisting of the induction of inflammation in normal animals and aggravation of pathologies in disease models. The evaluation of particle action on several phagocyte functions in vitro may provide an indication on the potency of the particles to induce immunotoxicity in vivo. In combination with information on realistic exposure levels, in vitro studies on phagocytes may provide useful information on the health risks of NPs.

  17. Effect of thyme oil on small intestine integrity and antioxidant status, phagocytic activity and gastrointestinal microbiota in rabbits.

    Science.gov (United States)

    Placha, Iveta; Chrastinova, Lubica; Laukova, Andrea; Cobanova, Klaudia; Takacova, Jana; Strompfova, Viola; Chrenkova, Maria; Formelova, Zuzana; Faix, Stefan

    2013-06-01

    The effects of 0.5 g thyme oil per kg dry matter (DM) of diet on duodenal tissue integrity, antioxidant status, phagocytic activity and selected microbiota in the caecum and faeces of rabbits were studied. Twenty-four rabbits were divided into two groups and were fed a commercial granulated diet for growing rabbits (CD) with access to water ad libitum. The first group was fed the CD, while to the CD of the second group thyme oil was added. Intestinal integrity was tested by measuring the transepithelial electrical resistance (TEER). Thyme oil significantly increased the value of total antioxidant status (TAS) in the blood plasma and glutathione peroxidase (GPx) activity in the liver, and it decreased malondialdehyde (MDA) concentration in the duodenal tissue. Thyme oil resulted in strengthened intestinal integrity, as the essential oil supplementation significantly increased TEER values in the experiment. The faecal microbiota of rabbits was almost completely balanced in both groups, and only a slight decrease was found in the microbial population at day 42 of the trial. In both groups, the bacterial counts were generally lower in the caecum than in the faecal samples. In conclusion, dietary supplementation with 0.5 g/kg DM thyme oil may improve intestinal integrity, and it may have an antioxidant effect. A tendency was also found for thyme oil to stimulate the abundance of some microbes beneficial in the rabbit gut.

  18. MerTK Cleavage on Resident Cardiac Macrophages Compromises Repair After Myocardial Ischemia Reperfusion Injury.

    Science.gov (United States)

    DeBerge, Matthew; Yeap, Xin Yi; Dehn, Shirley; Zhang, Shuang; Grigoryeva, Lubov; Misener, Sol; Procissi, Daniel; Zhou, Xin; Lee, Daniel C; Muller, William A; Luo, Xunrong; Rothlin, Carla; Tabas, Ira; Thorp, Edward B

    2017-09-29

    Clinical benefits of reperfusion after myocardial infarction are offset by maladaptive innate immune cell function, and therapeutic interventions are lacking. We sought to test the significance of phagocytic clearance by resident and recruited phagocytes after myocardial ischemia reperfusion. In humans, we discovered that clinical reperfusion after myocardial infarction led to significant elevation of the soluble form of MerTK (myeloid-epithelial-reproductive tyrosine kinase; ie, soluble MER), a critical biomarker of compromised phagocytosis by innate macrophages. In reperfused mice, macrophage Mertk deficiency led to decreased cardiac wound debridement, increased infarct size, and depressed cardiac function, newly implicating MerTK in cardiac repair after myocardial ischemia reperfusion. More notably, Mertk(CR ) mice, which are resistant to cleavage, showed significantly reduced infarct sizes and improved systolic function. In contrast to other cardiac phagocyte subsets, resident cardiac MHCII LO CCR2 - (major histocompatibility complex II/C-C motif chemokine receptor type 2) macrophages expressed higher levels of MerTK and, when exposed to apoptotic cells, secreted proreparative cytokines, including transforming growth factor-β. Mertk deficiency compromised the accumulation of MHCII LO phagocytes, and this was rescued in Mertk(CR ) mice. Interestingly, blockade of CCR2-dependent monocyte infiltration into the heart reduced soluble MER levels post-ischemia reperfusion. Our data implicate monocyte-induced MerTK cleavage on proreparative MHCII LO cardiac macrophages as a novel contributor and therapeutic target of reperfusion injury. © 2017 American Heart Association, Inc.

  19. Value of phagocyte function screening for immunotoxicity of nanoparticles in vivo

    Directory of Open Access Journals (Sweden)

    Fröhlich E

    2015-05-01

    Full Text Available Eleonore Fröhlich Center for Medical Research, Medical University of Graz, Graz, Austria Abstract: Nanoparticles (NPs present in the environment and in consumer products can cause immunotoxic effects. The immune system is very complex, and in vivo studies are the gold standard for evaluation. Due to the increased amount of NPs that are being developed, cellular screening assays to decrease the amount of NPs that have to be tested in vivo are highly needed. Effects on the unspecific immune system, such as effects on phagocytes, might be suitable for screening for immunotoxicity because these cells mediate unspecific and specific immune responses. They are present at epithelial barriers, in the blood, and in almost all organs. This review summarizes the effects of carbon, metal, and metal oxide NPs used in consumer and medical applications (gold, silver, titanium dioxide, silica dioxide, zinc oxide, and carbon nanotubes and polystyrene NPs on the immune system. Effects in animal exposures through different routes are compared to the effects on isolated phagocytes. In addition, general problems in the testing of NPs, such as unknown exposure doses, as well as interference with assays are mentioned. NPs appear to induce a specific immunotoxic pattern consisting of the induction of inflammation in normal animals and aggravation of pathologies in disease models. The evaluation of particle action on several phagocyte functions in vitro may provide an indication on the potency of the particles to induce immunotoxicity in vivo. In combination with information on realistic exposure levels, in vitro studies on phagocytes may provide useful information on the health risks of NPs. Keywords: immunotoxicity, phagocytes, cytokines, respiratory burst, nitric oxide generation, phagocytosis

  20. The Peyer’s Patch Mononuclear Phagocyte System at Steady State and during Infection

    Directory of Open Access Journals (Sweden)

    Clément Da Silva

    2017-10-01

    Full Text Available The gut represents a potential entry site for a wide range of pathogens including protozoa, bacteria, viruses, or fungi. Consequently, it is protected by one of the largest and most diversified population of immune cells of the body. Its surveillance requires the constant sampling of its encounters by dedicated sentinels composed of follicles and their associated epithelium located in specialized area. In the small intestine, Peyer’s patches (PPs are the most important of these mucosal immune response inductive sites. Through several mechanisms including transcytosis by specialized epithelial cells called M-cells, access to the gut lumen is facilitated in PPs. Although antigen sampling is critical to the initiation of the mucosal immune response, pathogens have evolved strategies to take advantage of this permissive gateway to enter the host and disseminate. It is, therefore, critical to decipher the mechanisms that underlie both host defense and pathogen subversive strategies in order to develop new mucosal-based therapeutic approaches. Whereas penetration of pathogens through M cells has been well described, their fate once they have reached the subepithelial dome (SED remains less well understood. Nevertheless, it is clear that the mononuclear phagocyte system (MPS plays a critical role in handling these pathogens. MPS members, including both dendritic cells and macrophages, are indeed strongly enriched in the SED, interact with M cells, and are necessary for antigen presentation to immune effector cells. This review focuses on recent advances, which have allowed distinguishing the different PP mononuclear phagocyte subsets. It gives an overview of their diversity, specificity, location, and functions. Interaction of PP phagocytes with the microbiota and the follicle-associated epithelium as well as PP infection studies are described in the light of these new criteria of PP phagocyte identification. Finally, known alterations affecting the

  1. Residency training program: Perceptions of residents

    African Journals Online (AJOL)

    Abstract. Background: There is a phobia among doctors for the residency training program, since the establishment of ... Materials and Methods: Structured questionnaires were administered to residents at 3 training institutions in Nigeria. Results: ... Keywords: Decentralization, motivation, perception, remuneration, residents.

  2. Serum levels of RBP4 and adipose tissue levels of PTP1B are increased in obese men resident in northeast Scotland without associated changes in ER stress response genes

    Directory of Open Access Journals (Sweden)

    Hoggard N

    2012-05-01

    Full Text Available Nigel Hoggard1, Abdelali Agouni2, Nimesh Mody2, Mirela Delibegovic21Rowett Institute of Nutrition and Health, 2Integrative Physiology, University of Aberdeen, Aberdeen, UKBackground: Retinol-binding protein 4 (RBP4 is an adipokine identified as a marker of insulin resistance in mice and humans. Protein tyrosine phosphatase 1B (PTP1B expression levels as well as other genes involved in the endoplasmic reticulum (ER stress response are increased in adipose tissue of obese, high-fat-diet-fed mice. In this study we investigated if serum and/or adipose tissue RBP4 protein levels and expression levels of PTP1B and other ER stress-response genes are altered in obese and obese/diabetic men resident in northeast Scotland.Methods: We studied three groups of male volunteers: (1 normal/overweight (body mass index [BMI] < 30, (2 obese (BMI > 30, and (3 obese/diabetic (BMI > 30 controlling their diabetes either by diet or the antidiabetic drug metformin. We analyzed their serum and adipose tissue RBP4 protein levels as well as adipose tissue mRNA expression of PTP1B, binding immunoglobulin protein (BIP, activated transcription factor 4 (ATF4, and glucose-regulated protein 94 (GRP94 alongside other markers of adiposity (percentage body fat, leptin, cholesterol, triglycerides and insulin resistance (oral glucose tolerance tests, insulin, homeostatic model assessment–insulin resistance, C-reactive protein, and adiponectin.Results: We found that obese Scottish subjects had significantly higher serum RBP4 protein levels in comparison to the normal/overweight subjects (P < 0.01. Serum RBP4 levels were normalized in obese/diabetic subjects treated with diet or metformin (P < 0.05. Adipose tissue RBP4 protein levels were comparable between all three groups of subjects as were serum and adipose transthyretin levels. Adipose tissue PTP1B mRNA levels were increased in obese subjects in comparison to normal/overweight subjects (P < 0.05; however diet and/or metformin

  3. Evaluation of possible failure of the mononuclear phagocyte system after total splenectomy in rats

    Directory of Open Access Journals (Sweden)

    Marques Ruy Garcia

    2004-01-01

    Full Text Available Young and adult Wistar rats were submitted to total splenectomy and compared to animals not submitted to any surgical manipulation in order to evaluate the phagocytic function of spleen. The animals were infected with Escherichia coli labeled with technetium-99m and killed 20 minutes later. Liver, lung, spleen and a blood clot sample were taken. No significant differences were found in the percentage of bacterial radioactivity uptake in mononuclear phagocyte system (MPS organs in young and adult splenectomized rats. However, phagocytosis index by macrophages of MPS organs was smaller in splenectomized animals than in control group. Splenectomized rats were associated with a higher blood bacterial radioactivity uptake than animals of the control group (p<0.0001 due to a larger bacterial remnant in the bloodstream. This finding suggested that some failure in the MPS occurred in the absence of the spleen, demonstrating the need to develop alternative surgical techniques for total splenectomy.

  4. Brazilian Propolis: A Natural Product That Improved the Fungicidal Activity by Blood Phagocytes

    Science.gov (United States)

    Possamai, Muryllo Mendes; Honorio-França, Adenilda Cristina; Reinaque, Ana Paula Barcelos; França, Eduardo Luzia; Souto, Paula Cristina de Souza

    2013-01-01

    Natural product incorporation into microcarriers increases the bioavailability of these compounds, consequently improving their therapeutic properties. Natural products, particularly those from bees such as propolis, are widely used in popular medicine. Propolis is a powerful treatment for several diseases. In this context, the present study evaluated the effect of propolis Scaptotrigona sp. and its fractions, alone or adsorbed to polyethylene glycol (PEG) microspheres, on the activity of human phagocytes against Candida albicans. The results show that propolis exerts a stimulatory effect on these cells to assist in combating the fungus, especially as the crude extract is compared with the fractions. However, when incorporated into microspheres, these properties were significantly potentiated. These results suggest that propolis adsorbed onto PEG microspheres has immunostimulatory effects on phagocytes in human blood. Therefore, propolis may potentially be an additional natural product that can be used for a variety of therapies. PMID:23509737

  5. The role of nitrite ion in phagocyte function—perspectives and puzzles

    Science.gov (United States)

    Cape, Jonathan L.; Hurst, James K.

    2009-01-01

    Macrophages and neutrophils are essential elements of host cellular defense systems that function, at least in part, by generating respiration-driven oxidative toxins in response to external stimuli. In both cells, encapsulation by phagocytosis provides a mechanism to direct the toxins against the microbes. The toxic chemicals formed by these two phagocytic cells differ markedly, as do the enzymatic catalysts that generate them. Nitrite ion is microbicidal under certain conditions, is generated by activated macrophages, and is present at elevated concentration levels at infection sites. In this review, we consider potential roles that nitrite might play in cellular disinfection by these phagocytes within the context of available experimental information. Although the suggested roles are plausible, based upon the chemical and biochemical reactivity of NO2−, studies to date provide little support for their implementation within phagosomes. PMID:19402211

  6. Diversity and Versatility of Phagocytosis: Roles in Innate Immunity, Tissue Remodeling, and Homeostasis.

    Science.gov (United States)

    Lim, Justin J; Grinstein, Sergio; Roth, Ziv

    2017-01-01

    Phagocytosis, a critical early event in the microbicidal response of neutrophils, is now appreciated to serve multiple functions in a variety of cell types. Professional phagocytes play a central role in innate immunity by eliminating pathogenic bacteria, fungi and malignant cells, and contribute to adaptive immunity by presenting antigens to lymphocytes. In addition, phagocytes play a part in tissue remodeling and maintain overall homeostasis by disposing of apoptotic cells, a task shared by non-professional phagocytes, often of epithelial origin. This functional versatility is supported by a vast array of receptors capable of recognizing a striking variety of foreign and endogenous ligands. Here we present an abbreviated overview of the different types of phagocytes, their varied modes of signaling and particle engulfment, and the multiple physiological roles of phagocytosis.

  7. Dental Calculus Stimulates Interleukin-1β Secretion by Activating NLRP3 Inflammasome in Human and Mouse Phagocytes.

    Science.gov (United States)

    Montenegro Raudales, Jorge Luis; Yoshimura, Atsutoshi; Sm, Ziauddin; Kaneko, Takashi; Ozaki, Yukio; Ukai, Takashi; Miyazaki, Toshihiro; Latz, Eicke; Hara, Yoshitaka

    2016-01-01

    Dental calculus is a mineralized deposit associated with periodontitis. The bacterial components contained in dental calculus can be recognized by host immune sensors, such as Toll-like receptors (TLRs), and induce transcription of proinflammatory cytokines, such as IL-1β. Studies have shown that cellular uptake of crystalline particles may trigger NLRP3 inflammasome activation, leading to the cleavage of the IL-1β precursor to its mature form. Phagocytosis of dental calculus in the periodontal pocket may therefore lead to the secretion of IL-1β, promoting inflammatory responses in periodontal tissues. However, the capacity of dental calculus to induce IL-1β secretion in human phagocytes has not been explored. To study this, we stimulated human polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) with dental calculus collected from periodontitis patients, and measured IL-1β secretion by ELISA. We found that calculus induced IL-1β secretion in both human PMNs and PBMCs. Calculus also induced IL-1β in macrophages from wild-type mice, but not in macrophages from NLRP3- and ASC-deficient mice, indicating the involvement of NLRP3 and ASC. IL-1β induction was inhibited by polymyxin B, suggesting that LPS is one of the components of calculus that induces pro-IL-1β transcription. To analyze the effect of the inorganic structure, we baked calculus at 250°C for 1 h. This baked calculus failed to induce pro-IL-1β transcription. However, it did induce IL-1β secretion in lipid A-primed cells, indicating that the crystalline structure of calculus induces inflammasome activation. Furthermore, hydroxyapatite crystals, a component of dental calculus, induced IL-1β in mouse macrophages, and baked calculus induced IL-1β in lipid A-primed human PMNs and PBMCs. These results indicate that dental calculus stimulates IL-1β secretion via NLRP3 inflammasome in human and mouse phagocytes, and that the crystalline structure has a partial role in

  8. Dental Calculus Stimulates Interleukin-1β Secretion by Activating NLRP3 Inflammasome in Human and Mouse Phagocytes

    Science.gov (United States)

    Montenegro Raudales, Jorge Luis; Yoshimura, Atsutoshi; SM, Ziauddin; Kaneko, Takashi; Ozaki, Yukio; Ukai, Takashi; Miyazaki, Toshihiro; Latz, Eicke; Hara, Yoshitaka

    2016-01-01

    Dental calculus is a mineralized deposit associated with periodontitis. The bacterial components contained in dental calculus can be recognized by host immune sensors, such as Toll-like receptors (TLRs), and induce transcription of proinflammatory cytokines, such as IL-1β. Studies have shown that cellular uptake of crystalline particles may trigger NLRP3 inflammasome activation, leading to the cleavage of the IL-1β precursor to its mature form. Phagocytosis of dental calculus in the periodontal pocket may therefore lead to the secretion of IL-1β, promoting inflammatory responses in periodontal tissues. However, the capacity of dental calculus to induce IL-1β secretion in human phagocytes has not been explored. To study this, we stimulated human polymorphonuclear leukocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) with dental calculus collected from periodontitis patients, and measured IL-1β secretion by ELISA. We found that calculus induced IL-1β secretion in both human PMNs and PBMCs. Calculus also induced IL-1β in macrophages from wild-type mice, but not in macrophages from NLRP3- and ASC-deficient mice, indicating the involvement of NLRP3 and ASC. IL-1β induction was inhibited by polymyxin B, suggesting that LPS is one of the components of calculus that induces pro-IL-1β transcription. To analyze the effect of the inorganic structure, we baked calculus at 250°C for 1 h. This baked calculus failed to induce pro-IL-1β transcription. However, it did induce IL-1β secretion in lipid A-primed cells, indicating that the crystalline structure of calculus induces inflammasome activation. Furthermore, hydroxyapatite crystals, a component of dental calculus, induced IL-1β in mouse macrophages, and baked calculus induced IL-1β in lipid A-primed human PMNs and PBMCs. These results indicate that dental calculus stimulates IL-1β secretion via NLRP3 inflammasome in human and mouse phagocytes, and that the crystalline structure has a partial role in

  9. Cellular immune responses and phagocytic activity of fishes exposed to pollution of volcano mud.

    Science.gov (United States)

    Risjani, Yenny; Yunianta; Couteau, Jerome; Minier, Christophe

    2014-05-01

    Since May 29, 2006, a mud volcano in the Brantas Delta of the Sidoarjo district has emitted mud that has inundated nearby villages. Pollution in this area has been implicated in detrimental effects on fish health. In fishes, leukocyte and phagocytic cells play a vital role in body defenses. We report for the first time the effect of "LUSI" volcano mud on the immune systems of fish in the Brantas Delta. The aim of this study was to find biomarkers to allow the evaluation of the effects of volcanic mud and anthropogenic pollution on fish health in the Brantas Delta. The study took places at the Brantas Delta, which was polluted by volcano mud, and at reference sites in Karangkates and Pasuruan. Leukocyte numbers were determined using a Neubauer hemocytometer and a light microscope. Differential leukocyte counts were determined using blood smears stained with May Grunwald-Giemsa, providing neutrophil, lymphocyte and monocyte counts. Macrophages were taken from fish kidney, and their phagocytic activity was measured. In vitro analyses revealed that leukocyte and differential leukocyte counts (DLC) were higher in Channa striata and Chanos chanos caught from the polluted area. Macrophage numbers were higher in Oreochromis mossambicus than in the other species, indicating that this species is more sensitive to pollution. In areas close to volcanic mud eruption, all specimens had lower phagocytic activity. Our results show that immune cells were changed and phagocytic activity was reduced in the polluted area indicating cytotoxicity and alteration of the innate immune system in fishes exposed to LUSI volcano mud and anthropogenic pollution. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. The role of phagocytes and specific antibodies in gamma irradiated mice infected by intracellular bacterial pathogens

    International Nuclear Information System (INIS)

    Kovarova, H.; Stulik, J.; Ledvina, M.

    1987-01-01

    The activation of oxygen metabolism in peritoneal macrophages during the defence against Francisella tularensis infection was inhibited by gamma irradiation of mice with 4.0 Gy. The application of specific antibodies protected the irradiated mice from the lethal infection without reactivation of oxygen metabolism in mononuclear phagocytes. These results demonstrated that the protecting function of the specific antibodies in the defence system against intracellular bacterial pathogens will be mediated by the oxygen-independent mechanisms. (author)

  11. The effect of carvedilol on the oxidative burst of rat phagocytes

    Czech Academy of Sciences Publication Activity Database

    Moravcová, Aneta; Lojek, Antonín; Číž, Milan; Pečivová, J.; Jančinová, V.; Nosál, R.

    2007-01-01

    Roč. 101, č. 14 (2007), s232-s233 E-ISSN 1213-7103. [Mezioborová česko-slovenská toxikologická konference /12./. Praha, 11.06.2007-13.06.2007] R&D Projects: GA ČR(CZ) GA524/07/1511 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : carvedilol * phagocytes * oxidative burst Subject RIV: BO - Biophysics

  12. Alkalinity of neutrophil phagocytic vacuoles is modulated by HVCN1 and has consequences for myeloperoxidase activity.

    Science.gov (United States)

    Levine, Adam P; Duchen, Michael R; de Villiers, Simon; Rich, Peter R; Segal, Anthony W

    2015-01-01

    The NADPH oxidase of neutrophils, essential for innate immunity, passes electrons across the phagocytic membrane to form superoxide in the phagocytic vacuole. Activity of the oxidase requires that charge movements across the vacuolar membrane are balanced. Using the pH indicator SNARF, we measured changes in pH in the phagocytic vacuole and cytosol of neutrophils. In human cells, the vacuolar pH rose to ~9, and the cytosol acidified slightly. By contrast, in Hvcn1 knock out mouse neutrophils, the vacuolar pH rose above 11, vacuoles swelled, and the cytosol acidified excessively, demonstrating that ordinarily this channel plays an important role in charge compensation. Proton extrusion was not diminished in Hvcn1-/- mouse neutrophils arguing against its role in maintaining pH homeostasis across the plasma membrane. Conditions in the vacuole are optimal for bacterial killing by the neutral proteases, cathepsin G and elastase, and not by myeloperoxidase, activity of which was unphysiologically low at alkaline pH.

  13. Vermamoeba vermiformis-Aspergillus fumigatus relationships and comparison with other phagocytic cells.

    Science.gov (United States)

    Maisonneuve, Elodie; Cateau, Estelle; Kaaki, Sihem; Rodier, Marie-Hélène

    2016-11-01

    Free living amoebae (FLA) are protists ubiquitously present in the environment. Aspergillus fumigatus is a mould responsible for severe deep-seated infections, and that can be recovered in the same habitats as the FLA. By conducting coculture experiments and fungal incubation with amoebal supernatants, we report herein that Vermamoeba vermiformis, a FLA present in hospital water systems, promotes filamentation and growth of A. fumigatus. This finding is of particular importance to institutions whose water systems might harbor FLA and could potentially be used by immunocompromised patients. Also, the relationships between V. vermiformis and A. fumigatus were compared to those between this fungus and two other phagocytic cells: Acanthamoeba castellanii, another FLA, and macrophage-like THP-1 cells. After 4 h of coincubation, the percentages of the three phagocytic cell types with adhered conidia were similar, even though the types of receptors between FLA and macrophagic cell seemed different. However, the percentage of THP-1 with internalized conidia was considerably lower (40 %) in comparison with the two other cell types (100 %). Thus, this study revealed that interactions between A. fumigatus and these three phagocytic cell types show similarities, even though it is premature to extrapolate these results to interpret relationships between A. fumigatus and macrophages.

  14. Nano-sized and micro-sized polystyrene particles affect phagocyte function.

    Science.gov (United States)

    Prietl, B; Meindl, C; Roblegg, E; Pieber, T R; Lanzer, G; Fröhlich, E

    2014-02-01

    Adverse effect of nanoparticles may include impairment of phagocyte function. To identify the effect of nanoparticle size on uptake, cytotoxicity, chemotaxis, cytokine secretion, phagocytosis, oxidative burst, nitric oxide production and myeloperoxidase release, leukocytes isolated from human peripheral blood, monocytes and macrophages were studied. Carboxyl polystyrene (CPS) particles in sizes between 20 and 1,000 nm served as model particles. Twenty nanometers CPS particles were taken up passively, while larger CPS particles entered cells actively and passively. Twenty nanometers CPS were cytotoxic to all phagocytes, ≥500 nm CPS particles only to macrophages. Twenty nanometers CPS particles stimulated IL-8 secretion in human monocytes and induced oxidative burst in monocytes. Five hundred nanometers and 1,000 nm CPS particles stimulated IL-6 and IL-8 secretion in monocytes and macrophages, chemotaxis towards a chemotactic stimulus of monocytes and phagocytosis of bacteria by macrophages and provoked an oxidative burst of granulocytes. At very high concentrations, CPS particles of 20 and 500 nm stimulated myeloperoxidase release of granulocytes and nitric oxide generation in macrophages. Cytotoxic effect could contribute to some of the observed effects. In the absence of cytotoxicity, 500 and 1,000 nm CPS particles appear to influence phagocyte function to a greater extent than particles in other sizes.

  15. Molecular pharmacology of antihistamines in inhibition of oxidative burst of professional phagocytes.

    Science.gov (United States)

    Nosáľ, Radomír; Jančinová, Viera; Drábiková, Katarína; Perečko, Tomáš

    2015-04-01

    Antihistamines of the H₁and H₃/H₄groups interfere with oxidative burst of human professional phagocytes in vitro. In the concentration of 10 μM, H₁antihistamines of the 1st and 2nd generation inhibited oxidative burst of human neutrophils in the rank order of potency: dithiaden > loratadine > brompheniramine > chlorpheniramine > pheniramine. Of the H₁antihistamines, the most effective was dithiaden in suppressing oxidative burst of whole human blood and dose-dependently the chemiluminescence of isolated neutrophils at extra- and intracellular level. Inhibition of free oxygen radical generation in isolated neutrophils by dithiaden resulted from the inhibition of protein kinase C activation. The potentiation of recombinant caspase-3 by dithiaden is supportive of the antiinflammatory effect of dithiaden and suggestive of increasing the apoptosis of professional phagocytes. Of the H₃/H₄antihistamines, the most effective was JNJ7777120 in decreasing chemiluminescence in whole blood and also at extra- and intracellular sites of isolated neutrophils. JNJ 10191584 and thioperamide were less effective and the latter significantly potentiated free oxygen radical generation intracellularly. The results demonstrated that, compared with the H₃/H₄antihistamines investigated, H₁antihistamines were much more potent in inhibiting free oxygen radical generation in human professional phagocytes. This finding should be taken into account therapeutically.

  16. Tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors are the cellular source of fibrofatty infiltration in arrhythmogenic cardiomyopathy [v1; ref status: indexed, http://f1000r.es/17s

    Directory of Open Access Journals (Sweden)

    Ben Paylor

    2013-06-01

    Full Text Available Arrhythmogenic cardiomyopathy (AC is a disease of the heart involving myocardial dystrophy leading to fibrofatty scarring of the myocardium and is associated with an increased risk of both ventricular arrhythmias and sudden cardiac death. It often affects the right ventricle but may also involve the left. Although there has been significant progress in understanding the role of underlying desmosomal genetic defects in AC, there is still a lack of data regarding the cellular processes involved in its progression. The development of cardiac fibrofatty scarring is known to be a principal pathological process associated with ventricular arrhythmias, and it is vital that we elucidate the role of various cell populations involved in the disease if targeted therapeutics are to be developed. The known role of mesenchymal progenitor cells in the reparative process of both the heart and skeletal muscle has provided inspiration for the identification of the cellular basis of fibrofatty infiltration in AC. Here we hypothesize that reparative processes triggered by myocardial degeneration lead to the differentiation of tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors into adipocytes and fibroblasts, which compose the fibrofatty lesions characteristic of AC.

  17. Viable group A streptococci in macrophages during acute soft tissue infection.

    Directory of Open Access Journals (Sweden)

    Pontus Thulin

    2006-03-01

    Full Text Available Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells.We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria.This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis of streptococcal soft tissue infections

  18. Viable Group A Streptococci in Macrophages during Acute Soft Tissue Infection.

    Directory of Open Access Journals (Sweden)

    2006-01-01

    Full Text Available BACKGROUND: Group A streptococcal severe soft tissue infections, such as necrotizing fasciitis, are rapidly progressive infections associated with high mortality. Group A streptococcus is typically considered an extracellular pathogen, but has been shown to reside intracellularly in host cells. METHODS AND FINDINGS: We characterized in vivo interactions between group A streptococci (GAS and cells involved in innate immune responses, using human biopsies (n = 70 collected from 17 patients with soft tissue infections. Immunostaining and in situ image analysis revealed high amounts of bacteria in the biopsies, even in those collected after prolonged antibiotic therapy. Viability of the streptococci was assessed by use of a bacterial viability stain, which demonstrated viable bacteria in 74% of the biopsies. GAS were present both extracellularly and intracellularly within phagocytic cells, primarily within macrophages. Intracellular GAS were predominantly noted in biopsies from newly involved tissue characterized by lower inflammation and bacterial load, whereas purely extracellular GAS or a combination of intra- and extracellular GAS dominated in severely inflamed tissue. The latter tissue was also associated with a significantly increased amount of the cysteine protease streptococcal pyrogenic exotoxin SpeB. In vitro studies confirmed that macrophages serve as reservoirs for viable GAS, and infection with a speB-deletion mutant produced significantly lower frequencies of cells with viable GAS following infection as compared to the wild-type bacteria. CONCLUSIONS: This is the first study to demonstrate that GAS survive intracellularly in macrophages during acute invasive infections. This intracellular presence may have evolved as a mechanism to avoid antibiotic eradication, which may explain our finding that high bacterial load is present even in tissue collected after prolonged intravenous antibiotic therapy. This new insight into the pathogenesis

  19. PEPTIDASE DISTRIBUTION IN LYMPHATIC TISSUE

    Science.gov (United States)

    Doyle, William L.

    1955-01-01

    The lymphatic tissue of the rabbit contains a labile peptidase as measured by the hydrolysis of alanylglycine. Some characteristics of the enzyme were determined. This enzyme increases in amount when the numbers of macrophages in the tissue are increased and it is also present in the extracellular fluid in high concentration. The extracellular fluid value for this activity is calculated to be about 8 times the value for serum. Based on a correlation between the types of cells present and the amount of peptidase found in the tissue the following relative activities are assigned to the tissue components per unit volume: lymphocytes 1.0, tissue fluid 11.0, serum 1.4, phagocytes (macrophages) 30.0, reticular cells 12.0. The amount of chloride space varied from 35 to 55 per cent. The relative amounts of acid phosphatase per unit volume in the same elements were calculated to be: lymphocytes 1.0, tissue fluid 0, phagocytes 20.0, and reticular cells 4.0. Analysis of the distribution of peptidase was facilitated by simultaneous determination of acid phosphatase whose primary localization in one cell type was known. The over-all contribution of lymphocytes to the labile peptidase content of lymphatic tissue is relatively minor and was not found to exceed 5 per cent of the average value for the entire nodular tissue. In the absence of large numbers of macrophages the intercellular fluid of the nodule accounts for half or more of the peptidase content of the nodules. PMID:13242588

  20. Topical herpes simplex virus 2 (HSV-2) vaccination with human papillomavirus vectors expressing gB/gD ectodomains induces genital-tissue-resident memory CD8+ T cells and reduces genital disease and viral shedding after HSV-2 challenge.

    Science.gov (United States)

    Çuburu, Nicolas; Wang, Kening; Goodman, Kyle N; Pang, Yuk Ying; Thompson, Cynthia D; Lowy, Douglas R; Cohen, Jeffrey I; Schiller, John T

    2015-01-01

    No herpes simplex virus 2 (HSV-2) vaccine has been licensed for use in humans. HSV-2 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and T cells, but clinical trials involving intramuscular (i.m.) injection of HSV-2 gB and gD in adjuvants have not been effective. Here we evaluated intravaginal (ivag) genetic immunization of C57BL/6 mice with a replication-defective human papillomavirus pseudovirus (HPV PsV) expressing HSV-2 gB (HPV-gB) or gD (HPV-gD) constructs to target different subcellular compartments. HPV PsV expressing a secreted ectodomain of gB (gBsec) or gD (gDsec), but not PsV expressing a cytoplasmic or membrane-bound form, induced circulating and intravaginal-tissue-resident memory CD8(+) T cells that were able to secrete gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) as well as moderate levels of serum HSV neutralizing antibodies. Combined immunization with HPV-gBsec and HPV-gDsec (HPV-gBsec/gDsec) vaccines conferred longer survival after vaginal challenge with HSV-2 than immunization with HPV-gBsec or HPV-gDsec alone. HPV-gBsec/gDsec ivag vaccination was associated with a reduced severity of genital lesions and lower levels of viral shedding in the genital tract after HSV-2 challenge. In contrast, intramuscular vaccination with a soluble truncated gD protein (gD2t) in alum and monophosphoryl lipid A (MPL) elicited high neutralizing antibody titers and improved survival but did not reduce genital lesions and viral shedding. Vaccination combining ivag HPV-gBsec/gDsec and i.m. gD2t-alum-MPL improved survival and reduced genital lesions and viral shedding. Finally, high levels of circulating HSV-2-specific CD8(+) T cells, but not serum antibodies, correlated with reduced viral shedding. Taken together, our data underscore the potential of HPV PsV as a platform for a topical mucosal vaccine to control local manifestations of primary HSV-2 infection. Genital herpes is a highly prevalent chronic disease caused by

  1. CpG in Combination with an Inhibitor of Notch Signaling Suppresses Formalin-Inactivated Respiratory Syncytial Virus-Enhanced Airway Hyperresponsiveness and Inflammation by Inhibiting Th17 Memory Responses and Promoting Tissue-Resident Memory Cells in Lungs.

    Science.gov (United States)

    Zhang, Lei; Li, Hongyong; Hai, Yan; Yin, Wei; Li, Wenjian; Zheng, Boyang; Du, Xiaomin; Li, Na; Zhang, Zhengzheng; Deng, Yuqing; Zeng, Ruihong; Wei, Lin

    2017-05-15

    Respiratory syncytial virus (RSV) is the leading cause of childhood hospitalizations. The formalin-inactivated RSV (FI-RSV) vaccine-enhanced respiratory disease (ERD) has been an obstacle to the development of a safe and effective killed RSV vaccine. Agonists of Toll-like receptor (TLR) have been shown to regulate immune responses induced by FI-RSV. Notch signaling plays critical roles during the differentiation and effector function phases of innate and adaptive immune responses. Cross talk between TLR and Notch signaling pathways results in fine-tuning of TLR-triggered innate inflammatory responses. We evaluated the impact of TLR and Notch signaling on ERD in a murine model by administering CpG, an agonist of TLR9, in combination with L685,458, an inhibitor of Notch signaling during FI-RSV immunization. Activation with CpG or deficiency of MyD88-dependent TLR signaling did not alleviate airway inflammation in FI-RSV-immunized mice. Activation or inhibition of Notch signaling with Dll4, one of the Notch ligands, or L685,458 did not suppress FI-RSV-enhanced airway inflammation either. However, the CpG together with L685,458 markedly inhibited FI-RSV-enhanced airway hyperresponsiveness, weight loss, and lung inflammation. Interestingly, CpG plus L685,458 completely inhibited FI-RSV-associated Th17 and Th17-associated proinflammatory chemokine responses in lungs following RSV challenge but not Th1 or Th2, memory responses. In addition, FI-RSV plus CpG plus L685,458 promoted protective CD8 + lung tissue-resident memory (TRM) cells. These results indicate that activation of TLR signaling combined with inhibition of Notch signaling prevent FI-RSV ERD, and the mechanism appears to involve suppressing proinflammatory Th17 memory responses and promoting protective TRM in lungs. IMPORTANCE RSV is the most important cause of lower respiratory tract infections in infants. The FI-RSV-enhanced respiratory disease (ERD) is a major impediment to the development of a safe and

  2. Residency Allocation Database

    Data.gov (United States)

    Department of Veterans Affairs — The Residency Allocation Database is used to determine allocation of funds for residency programs offered by Veterans Affairs Medical Centers (VAMCs). Information...

  3. Enhanced alveolar monocytic phagocyte (macrophage) proliferation in tobacco and marijuana smokers

    Energy Technology Data Exchange (ETDEWEB)

    Barbers, R.G.; Evans, M.J.; Gong, H. Jr.; Tashkin, D.P. (Univ. of California-Los Angeles School of Medicine (USA))

    1991-05-01

    We tested the hypothesis that enhanced cell division accounted for the augmented numbers of monocytic phagocytes with characteristics attributed to alveolar macrophages (AM) found in the lungs of habitual tobacco (T) and marijuana (M) smokers. The monocytic phagocytes, that is, alveolar macrophages, were obtained by bronchoalveolar lavage (BAL) from 12 nonsmoking subjects; 10 subjects who smoked T only (TS); 13 subjects who smoked M only (MS); and 6 smokers of both T and M (MTS). The replication of these cells was determined by measuring the incorporation of ({sup 3}H)thymidine into the DNA of dividing cells and visually counting 2,000 cells on autoradiographically prepared cytocentrifuge cell preparations. This study demonstrated that the number of ({sup 3}H)thymidine-labeled monocytic phagocytes with characteristics of alveolar macrophages from either TS or MS have a higher proliferative index compared to cells (macrophages) from nonsmokers, p less than 0.05 by one-way ANOVA. The total number of BAL macrophages that are in mitosis in TS (17.90 +/- 4.50 labeled AM x 10(3)/ml) or MTS (10.50 +/- 4.20 labeled AM x 10(3)/ml) are 18- and 10-fold greater, respectively, than the number obtained from nonsmokers (1.01 +/- 0.18 labeled AM x 10(3)/ml). Interestingly, the number of ({sup 3}H)thymidine-labeled macrophages from MS (2.90 +/- 0.66 labeled AM x 10(3)/ml) are also greater than the number obtained from nonsmokers, although this is not statistically significant. The stimulus augmenting alveolar macrophage replication is as yet unknown but may likely be found in the T or M smoke.

  4. Enhanced alveolar monocytic phagocyte (macrophage) proliferation in tobacco and marijuana smokers

    International Nuclear Information System (INIS)

    Barbers, R.G.; Evans, M.J.; Gong, H. Jr.; Tashkin, D.P.

    1991-01-01

    We tested the hypothesis that enhanced cell division accounted for the augmented numbers of monocytic phagocytes with characteristics attributed to alveolar macrophages (AM) found in the lungs of habitual tobacco (T) and marijuana (M) smokers. The monocytic phagocytes, that is, alveolar macrophages, were obtained by bronchoalveolar lavage (BAL) from 12 nonsmoking subjects; 10 subjects who smoked T only (TS); 13 subjects who smoked M only (MS); and 6 smokers of both T and M (MTS). The replication of these cells was determined by measuring the incorporation of [ 3 H]thymidine into the DNA of dividing cells and visually counting 2,000 cells on autoradiographically prepared cytocentrifuge cell preparations. This study demonstrated that the number of [ 3 H]thymidine-labeled monocytic phagocytes with characteristics of alveolar macrophages from either TS or MS have a higher proliferative index compared to cells (macrophages) from nonsmokers, p less than 0.05 by one-way ANOVA. The total number of BAL macrophages that are in mitosis in TS (17.90 +/- 4.50 labeled AM x 10(3)/ml) or MTS (10.50 +/- 4.20 labeled AM x 10(3)/ml) are 18- and 10-fold greater, respectively, than the number obtained from nonsmokers (1.01 +/- 0.18 labeled AM x 10(3)/ml). Interestingly, the number of [ 3 H]thymidine-labeled macrophages from MS (2.90 +/- 0.66 labeled AM x 10(3)/ml) are also greater than the number obtained from nonsmokers, although this is not statistically significant. The stimulus augmenting alveolar macrophage replication is as yet unknown but may likely be found in the T or M smoke

  5. A Protocol for the Comprehensive Flow Cytometric Analysis of Immune Cells in Normal and Inflamed Murine Non-Lymphoid Tissues

    Science.gov (United States)

    Yu, Yen-Rei A.; O’Koren, Emily G.; Hotten, Danielle F.; Kan, Matthew J.; Kopin, David; Nelson, Erik R.; Que, Loretta; Gunn, Michael D.

    2016-01-01

    Flow cytometry is used extensively to examine immune cells in non-lymphoid tissues. However, a method of flow cytometric analysis that is both comprehensive and widely applicable has not been described. We developed a protocol for the flow cytometric analysis of non-lymphoid tissues, including methods of tissue preparation, a 10-fluorochrome panel for cell staining, and a standardized gating strategy, that allows the simultaneous identification and quantification of all major immune cell types in a variety of normal and inflamed non-lymphoid tissues. We demonstrate that our basic protocol minimizes cell loss, reliably distinguishes macrophages from dendritic cells (DC), and identifies all major granulocytic and mononuclear phagocytic cell types. This protocol is able to accurately quantify 11 distinct immune cell types, including T cells, B cells, NK cells, neutrophils, eosinophils, inflammatory monocytes, resident monocytes, alveolar macrophages, resident/interstitial macrophages, CD11b- DC, and CD11b+ DC, in normal lung, heart, liver, kidney, intestine, skin, eyes, and mammary gland. We also characterized the expression patterns of several commonly used myeloid and macrophage markers. This basic protocol can be expanded to identify additional cell types such as mast cells, basophils, and plasmacytoid DC, or perform detailed phenotyping of specific cell types. In examining models of primary and metastatic mammary tumors, this protocol allowed the identification of several distinct tumor associated macrophage phenotypes, the appearance of which was highly specific to individual tumor cell lines. This protocol provides a valuable tool to examine immune cell repertoires and follow immune responses in a wide variety of tissues and experimental conditions. PMID:26938654

  6. A Protocol for the Comprehensive Flow Cytometric Analysis of Immune Cells in Normal and Inflamed Murine Non-Lymphoid Tissues.

    Directory of Open Access Journals (Sweden)

    Yen-Rei A Yu

    Full Text Available Flow cytometry is used extensively to examine immune cells in non-lymphoid tissues. However, a method of flow cytometric analysis that is both comprehensive and widely applicable has not been described. We developed a protocol for the flow cytometric analysis of non-lymphoid tissues, including methods of tissue preparation, a 10-fluorochrome panel for cell staining, and a standardized gating strategy, that allows the simultaneous identification and quantification of all major immune cell types in a variety of normal and inflamed non-lymphoid tissues. We demonstrate that our basic protocol minimizes cell loss, reliably distinguishes macrophages from dendritic cells (DC, and identifies all major granulocytic and mononuclear phagocytic cell types. This protocol is able to accurately quantify 11 distinct immune cell types, including T cells, B cells, NK cells, neutrophils, eosinophils, inflammatory monocytes, resident monocytes, alveolar macrophages, resident/interstitial macrophages, CD11b- DC, and CD11b+ DC, in normal lung, heart, liver, kidney, intestine, skin, eyes, and mammary gland. We also characterized the expression patterns of several commonly used myeloid and macrophage markers. This basic protocol can be expanded to identify additional cell types such as mast cells, basophils, and plasmacytoid DC, or perform detailed phenotyping of specific cell types. In examining models of primary and metastatic mammary tumors, this protocol allowed the identification of several distinct tumor associated macrophage phenotypes, the appearance of which was highly specific to individual tumor cell lines. This protocol provides a valuable tool to examine immune cell repertoires and follow immune responses in a wide variety of tissues and experimental conditions.

  7. Microparticles from apoptotic platelets promote resident macrophage differentiation.

    Science.gov (United States)

    Vasina, E M; Cauwenberghs, S; Feijge, M A H; Heemskerk, J W M; Weber, C; Koenen, R R

    2011-09-29

    Platelets shed microparticles not only upon activation, but also upon ageing by an apoptosis-like process (apoptosis-induced platelet microparticles, PM(ap)). While the activation-induced microparticles have widely been studied, not much is known about the (patho)physiological consequences of PM(ap) formation. Flow cytometry and scanning electron microscopy demonstrated that PM(ap) display activated integrins and interact to form microparticle aggregates. PM(ap) were chemotactic for monocytic cells, bound to these cells, an furthermore stimulated cell adhesion and spreading on a fibronectin surface. After prolonged incubation, PM(ap) promoted cell differentiation, but inhibited proliferation. Monocyte membrane receptor analysis revealed increased expression levels of CD11b (integrin α(M)β(2)), CD14 and CD31 (platelet endothelial cell adhesion molecule-1), and the chemokine receptors CCR5 and CXCR4, but not of CCR2. This indicated that PM(ap) polarized the cells into resident M2 monocytes. Cells treated with PM(ap) actively consumed oxidized low-density lipoprotein (oxLDL), and released matrix metalloproteinases and hydrogen peroxide. Further confirmation for the differentiation towards resident professional phagocytes came from the finding that PM(ap) stimulated the expression of the (ox)LDL receptors, CD36 and CD68, and the production of proinflammatory and immunomodulating cytokines by monocytes. In conclusion, interaction of PM(ap) with monocytic cells has an immunomodulating potential. The apoptotic microparticles polarize the cells into a resident M2 subset, and induce differentiation to resident professional phagocytes.

  8. The modulatory role of cytokines IL-4 and IL-17 in the functional activity of phagocytes in diabetic pregnant women.

    Science.gov (United States)

    Fagundes, Danny L G; França, Eduardo L; Gonzatti, Michelangelo B; Rugde, Marilza V C; Calderon, Iracema M P; Honorio-França, Adenilda C

    2018-01-01

    The study investigated the role of cytokines IL-4 and IL-17 in the modulation of the functional activity of mononuclear phagocytes in diabetic pregnant women with hyperglycemia. Sixty pregnant women were assigned to the following groups: nondiabetic (ND), mild gestational hyperglycemia (MGH), gestational diabetes mellitus (GDM), or type 2 diabetes mellitus (DM2). The functional activity of phagocytes from maternal blood, cord blood, and colostrum was assessed by determining their superoxide release, phagocytosis, microbicidal activity, and intracellular Ca 2+ release. Irrespective of glycemic status, colostrum and blood cells treated with IL-4 and IL-17 increased superoxide release in the presence of enteropathogenic Escherichia coli (EPEC). The highest phagocytosis rate was observed in cells from the DM2 group treated with IL-4. In all the groups, phagocytes from colostrum, maternal blood, and cord blood exhibited higher microbicidal activity against EPEC when treated with cytokines. IL-17 increased intracellular Ca 2+ release by colostrum phagocytes in diabetic groups. The results indicate that the IL-4 and IL-17 modulate the functional activity of phagocytes in the maternal blood, cord blood, and colostrum of diabetic mother. The natural immunity resulting from the interaction between the cells and cytokines tested may be an alternative procedure to improve the prognosis of maternal and newborn infections. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  9. Lipopolysaccharides Derived from Pantoea agglomerans Can Promote the Phagocytic Activity of Amyloid β in Mouse Microglial Cells.

    Science.gov (United States)

    Kobayashi, Yutaro; Inagawa, Hiroyuki; Kohchi, Chie; Okazaki, Katsuichiro; Zhang, Ran; Kobara, Hideki; Masaki, Tsutomu; Soma, Gen-Ichiro

    2017-07-01

    Recent studies reported that lipopolysaccharide (LPS) exhibits beneficial effects on prevention of immune-related diseases by activating macrophages. We previously demonstrated that pre-treatment with LPS derived from Pantoea agglomerans (LPSp) activated amyloid β (Aβ) phagocytosis in mouse primary microglia. In the present study, we further examined the promotory effect on phagocytosis of phagocytic particles in the C8-B4 microglia cell line. Phagocytic analysis of C8-B4 cells was evaluated using phagocytic particles (latex beads or HiLyte™ Fluor 488-conjugated Aβ 1-42 ). The phagocytic activity of latex beads was dependent on the concentration of beads and incubation time. LPSp, at as low as 100 pg/ml, significantly increased phagocytosis against the beads. In the experiment of Aβ 1-42 phagocytosis, LPSp significantly increased Aβ phagocytic activity. LPSp treatment was confirmed to enhance Aβ 1-42 phagocytosis by mouse microglia. It is suggested that the use of LPSp may be a potential promising candidate for the prevention of Alzheimer's disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Respon Fagositosis Leukosit Polimorf Babi (in vitro Terhadap Streptoccocus equi Subsp. Zooepidemicus (PHAGOCYTIC RESPONSE OF SWINE POLYMORPH LEUCOCYTES (IN VITRO TO STREPTOCCOCUS EQUI SUBSP. ZOOEPIDEMICUS

    Directory of Open Access Journals (Sweden)

    Iwan Harjono Utama

    2016-08-01

    Full Text Available Respon Fagositosis Leukosit Polimorf Babi (in vitro Terhadap Streptoccocus equi Subsp. Zooepidemicus (PHAGOCYTIC RESPONSE OF SWINE POLYMORPH LEUCOCYTES (IN VITRO TO STREPTOCCOCUS EQUI SUBSP. ZOOEPIDEMICUS

  11. African Trypanosomiasis-Associated Anemia: The Contribution of the Interplay between Parasites and the Mononuclear Phagocyte System

    Directory of Open Access Journals (Sweden)

    Benoit Stijlemans

    2018-02-01

    Full Text Available African trypanosomosis (AT is a chronically debilitating parasitic disease of medical and economic importance for the development of sub-Saharan Africa. The trypanosomes that cause this disease are extracellular protozoan parasites that have developed efficient immune escape mechanisms to manipulate the entire host immune response to allow parasite survival and transmission. During the early stage of infection, a profound pro-inflammatory type 1 activation of the mononuclear phagocyte system (MPS, involving classically activated macrophages (i.e., M1, is required for initial parasite control. Yet, the persistence of this M1-type MPS activation in trypanosusceptible animals causes immunopathology with anemia as the most prominent pathological feature. By contrast, in trypanotolerant animals, there is an induction of IL-10 that promotes the induction of alternatively activated macrophages (M2 and collectively dampens tissue damage. A comparative gene expression analysis between M1 and M2 cells identified galectin-3 (Gal-3 and macrophage migration inhibitory factor (MIF as novel M1-promoting factors, possibly acting synergistically and in concert with TNF-α during anemia development. While Gal-3 enhances erythrophagocytosis, MIF promotes both myeloid cell recruitment and iron retention within the MPS, thereby depriving iron for erythropoiesis. Hence, the enhanced erythrophagocytosis and suppressed erythropoiesis lead to anemia. Moreover, a thorough investigation using MIF-deficient mice revealed that the underlying mechanisms in AT-associated anemia development in trypanosusceptible and tolerant animals are quite distinct. In trypanosusceptible animals, anemia resembles anemia of inflammation, while in trypanotolerant animals’ hemodilution, mainly caused by hepatosplenomegaly, is an additional factor contributing to anemia. In this review, we give an overview of how trypanosome- and host-derived factors can contribute to trypanosomosis

  12. Quantitation of microbicidal activity of mononuclear phagocytes: an in vitro technique.

    Directory of Open Access Journals (Sweden)

    Rege N

    1993-01-01

    Full Text Available An in vitro assay technique was set up to determine the phagocytic and microbicidal activity of a monocyte-macrophage cell line using Candida species as test organisms. The norms were determined for the activity of peritoneal macrophages of rats (24.69 +/- 2.6% phagocytosis and 35.4 +/- 5.22% ICK and human (27.89 +/- 3.63% phagocytosis and 50.91 +/- 6.3% ICK. The assay technique was used to test the degree of activation of macrophages induced by metronidazole, Tinospora cordifolia and Asparaqus racemousus and to compare their effects with a standard immunomodulator muramyl-dipeptide. All the three test agents increased the phagocytic and killing capacity of macrophages in a dose dependent manner upto a certain dose, beyond which either these activities were found to have plateaued or decreased. The optimal doses for MDP, Metronidazole, Asparagus racemosus and Tinospora cordifolia were found to be 100 micrograms, 300 mg/kg, 200 mg/kg and 100 mg/kg respectively. Patients with cirrhosis were screened for defects in monocyte function. The depressed monocyte function (20.58 +/- 5% phago and 41.24 +/- 12.19% ICK; P < 0.05 was observed indicating a compromised host defense. The utility of this candidicidal assay in experimental and clinical studies is discussed.

  13. Chemical composition and phagocyte immunomodulatory activity of Ferula iliensis essential oils.

    Science.gov (United States)

    Özek, Gulmira; Schepetkin, Igor A; Utegenova, Gulzhakhan A; Kirpotina, Liliya N; Andrei, Spencer R; Özek, Temel; Başer, Kemal Hüsnü Can; Abidkulova, Karime T; Kushnarenko, Svetlana V; Khlebnikov, Andrei I; Damron, Derek S; Quinn, Mark T

    2017-06-01

    Essential oil extracts from Ferula iliensis have been used traditionally in Kazakhstan for treatment of inflammation and other illnesses. Because little is known about the biologic activity of these essential oils that contributes to their therapeutic properties, we analyzed their chemical composition and evaluated their phagocyte immunomodulatory activity. The main components of the extracted essential oils were ( E )-propenyl sec -butyl disulfide (15.7-39.4%) and ( Z )-propenyl sec -butyl disulfide (23.4-45.0%). Ferula essential oils stimulated [Ca 2+ ] i mobilization in human neutrophils and activated ROS production in human neutrophils and murine bone marrow phagocytes. Activation of human neutrophil [Ca 2+ ] i flux by Ferula essential oils was dose-dependently inhibited by capsazepine, a TRPV1 channel antagonist, indicating that TRPV1 channels mediate this response. Furthermore, Ferula essential oils stimulated Ca 2+ influx in TRPV1 channel-transfected HEK293 cells and desensitized the capsaicin-induced response in these cells. Additional molecular modeling with known TRPV1 channel agonists suggested that the active component is likely to be ( Z )-propenyl sec -butyl disulfide. Our results provide a cellular and molecular basis to explain at least part of the beneficial therapeutic properties of FEOs. © Society for Leukocyte Biology.

  14. Dictyostelium discoideum as a novel host system to study the interaction between phagocytes and yeasts

    Directory of Open Access Journals (Sweden)

    Barbara Koller

    2016-10-01

    Full Text Available The social amoeba Dictyostelium discoideum is a well-established model organism to study the interaction between bacteria and phagocytes. In contrast, research using D. discoideum as a host model for fungi is rare. We describe a comprehensive study, which uses D. discoideum as a host model system to investigate the interaction with apathogenic (Saccharomyces cerevisiae and pathogenic (Candida sp. yeast. We show that Dictyostelium can be co-cultivated with yeasts on solid media, offering a convenient test to study the interaction between fungi and phagocytes. We demonstrate that a number of D. discoideum mutants increase (atg1-, kil1-, kil2- or decrease (atg6- the ability of the amoebae to predate yeast cells. On the yeast side, growth characteristics, reduced phagocytosis rate, as well as known virulence factors of C. albicans (EFG1, CPH1, HGC1, ICL1 contribute to the resistance of yeast cells against predation by the amoebae. Investigating haploid C. albicans strains, we suggest using the amoebae plate test for screening purposes after random mutagenesis. Finally, we discuss the potential of our adapted amoebae plate test to use D. discoideum for risk assessment of yeast strains.

  15. Aminopeptidase N (CD13 Is Involved in Phagocytic Processes in Human Dendritic Cells and Macrophages

    Directory of Open Access Journals (Sweden)

    Mónica I. Villaseñor-Cardoso

    2013-01-01

    Full Text Available Aminopeptidase N (APN or CD13 is a membrane ectopeptidase expressed by many cell types, including myelomonocytic lineage cells: monocytes, macrophages, and dendritic cells. CD13 is known to regulate the biological activity of various peptides by proteolysis, and it has been proposed that CD13 also participates in several functions such as angiogenesis, cell adhesion, metastasis, and tumor invasion. We had previously reported that, in human monocytes and macrophages, CD13 modulates the phagocytosis mediated by receptors for the Fc portion of IgG antibodies (FcγRs. In this work, we analyzed the possible interaction of CD13 with other phagocytic receptors. We found out that the cross-linking of CD13 positively modulates the phagocytosis mediated by receptors of the innate immune system, since a significant increase in the phagocytosis of zymosan particles or heat-killed E. coli was observed when CD13 was cross-linked using anti-CD13 antibodies, in both macrophages and dendritic cells. Also, we observed that, during the phagocytosis of zymosan, CD13 redistributes and is internalized into the phagosome. These findings suggest that, besides its known functions, CD13 participates in phagocytic processes in dendritic cells and macrophages.

  16. Cell-Type Specific Determinants of NRAMP1 Expression in Professional Phagocytes

    Directory of Open Access Journals (Sweden)

    Mathieu F. M. Cellier

    2013-01-01

    Full Text Available The Natural resistance-associated macrophage protein 1 (Nramp1 or Solute carrier 11 member 1, Slc11a1 transports divalent metals across the membrane of late endosomes and lysosomes in professional phagocytes. Nramp1 represents an ancient eukaryotic cell-autonomous defense whereas the gene duplication that yielded Nramp1 and Nramp2 predated the origin of Sarcopterygians (lobe-finned fishes and tetrapods. SLC11A1 genetic polymorphisms associated with human resistance to tuberculosis consist of potential regulatory variants. Herein, current knowledge of the regulation of SLC11A1 gene expression is reviewed and comprehensive analysis of ENCODE data available for hematopoietic cell-types suggests a hypothesis for the regulation of SLC11A1 expression during myeloid development and phagocyte functional polarization. SLC11A1 is part of a 34.6 kb CTCF-insulated locus scattered with predicted regulatory elements: a 3' enhancer, a large 5' enhancer domain and four elements spread around the transcription start site (TSS, including several C/EBP and PU.1 sites. SLC11A1 locus ends appear mobilized by ETS-related factors early during myelopoiesis; activation of both 5' and 3' enhancers in myelo-monocytic cells correlate with transcription factor binding at the TSS. Characterizing the corresponding cis/trans determinants functionally will establish the mechanisms involved and possibly reveal genetic variation that impacts susceptibility to infectious or immune diseases.

  17. A Simple, Reproducible, Inexpensive, Yet Old-Fashioned Method for Determining Phagocytic and Bactericidal Activities of Macrophages.

    Science.gov (United States)

    Kaneko, Masakazu; Emoto, Yoshiko; Emoto, Masashi

    2016-03-01

    Macrophages (Mφ) play a pivotal role in the protection system by recognizing and eliminating invading pathogenic bacteria. Phagocytosis and the killing of invading bacteria are major effector functions of Mφ. Although the phagocytic and bactericidal activities of Mφ have been analyzed via several methods using a light microscope, a fluorescence microscope, or a fluorescence-activated cell sorter, expensive materials and equipment are usually required, and the methods are rather complicated. Moreover, it is impossible to determine both the phagocytic and bactericidal activities of Mφ simultaneously using these methods. In this review, we describe a simple, reproducible, inexpensive, yet old-fashioned method (antibiotic protection assay) for determining the phagocytic and bactericidal activities of Mφ.

  18. Rat macrophage C-type lectin is an activating receptor expressed by phagocytic cells.

    Directory of Open Access Journals (Sweden)

    Ana Lobato-Pascual

    Full Text Available Macrophage C-type lectin (MCL is a membrane surface receptor encoded by the Antigen Presenting Lectin-like gene Complex (APLEC. We generated a mouse monoclonal antibody for the study of this receptor in the rat. We demonstrate that rat MCL is expressed on blood monocytes and neutrophils, as well as on several tissue macrophage populations, including alveolar and peritoneal cavity macrophages. We also demonstrate MCL expression on a subset of resident spleen macrophages. Immunohistochemistry analysis of the spleen showed staining specifically in the marginal zone and red pulp. Exposure to pro-inflammatory mediators or to yeast cell wall extract (zymosan increased surface MCL expression on peritoneal macrophages. We characterized a rat myeloid cell line, RMW, which expresses high levels of MCL. We found that MCL co-immunoprecipitated with the activating adaptor protein FcεRIγ in these cells. Moreover, beads coated with anti-MCL antibody increased phagocytosis in the RMW cells. Together, these observations indicate that rat MCL is a receptor that activates phagocytosis in myeloid cells under inflammatory conditions.

  19. Primary phagocytosis of viable neurons by microglia activated with LPS or Aβ is dependent on calreticulin/LRP phagocytic signalling

    Directory of Open Access Journals (Sweden)

    Fricker Michael

    2012-08-01

    Full Text Available Abstract Background Microglia are resident brain macrophages that can phagocytose dead, dying or viable neurons, which may be beneficial or detrimental in inflammatory, ischaemic and neurodegenerative brain pathologies. Cell death caused by phagocytosis of an otherwise viable cell is called ‘primary phagocytosis’ or ‘phagoptosis’. Calreticulin (CRT exposure on the surface of cancer cells can promote their phagocytosis via LRP (low-density lipoprotein receptor-related protein on macrophages, but it is not known whether this occurs with neurons and microglia. Methods We used primary cultures of cerebellar neurons, astrocytes and microglia to investigate the potential role of CRT/LRP phagocytic signalling in the phagocytosis of viable neurons by microglia stimulated with lipopolysaccharide (LPS or nanomolar concentrations of amyloid-β peptide1-42 (Aβ. Exposure of CRT on the neuronal surface was investigated using surface biotinylation and western blotting. A phagocytosis assay was also developed using BV2 and PC12 cell lines to investigate CRT/LRP signalling in microglial phagocytosis of apoptotic cells. Results We found that BV2 microglia readily phagocytosed apoptotic PC12 cells, but this was inhibited by a CRT-blocking antibody or LRP-blocking protein (receptor-associated protein: RAP. Activation of primary rat microglia with LPS or Aβ resulted in loss of co-cultured cerebellar granule neurons, and this was blocked by RAP or antibodies against CRT or against LRP, preventing all neuronal loss and death. CRT was present on the surface of viable neurons, and this exposure did not change in inflammatory conditions. CRT antibodies prevented microglia-induced neuronal loss when added to neurons, while LRP antibodies prevented neuronal loss when added to the microglia. Pre-binding of CRT to neurons promoted neuronal loss if activated microglia were added, but pre-binding of CRT to microglia or both cell types prevented microglia

  20. Residency training program: Perceptions of residents

    African Journals Online (AJOL)

    This study was carried out to ascertain the perception of the residency ... the time of the study. Analysis of the respondents showed similar findings for both senior and junior levels of training. Discussion. The introduction of the residency training program .... Overseas training/ attachment should be re-introduced. 12. (10.1).

  1. Tissue distribution of radiolabeled phosphatidylserine-containing liposome in mice

    Energy Technology Data Exchange (ETDEWEB)

    Borborema, Samanta E.T.; Nascimento, Nanci do [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia], e-mail: samanta@usp.br, e-mail: nnascime@ipen.br; Andrade Junior, Heitor F. de [Instituto de Medicina Tropical de Sao Paulo (IMTSP), Sao Paulo, SP (Brazil)], e-mail: hfandrad@usp.br; Osso Junior, Joao A. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia], e-mail: jaosso@ipen.br

    2009-07-01

    Liposomes are used as drug delivery systems to modify pharmacokinetic of drugs and also to improve their action in target cells. Liposomes containing phosphatidylserine are efficiently eliminated from the blood by cells of the mononuclear phagocytic system (MPS), predominantly Kupffer cells in the liver. In this way, this is a valuable approach to treat infectious diseases involving MPS, especially leishmaniasis. Leishmaniasis is a severe parasitic disease, caused by intramacrophage protozoa Leishmania sp., and is fatal if left untreated. Leishmania resides mainly in the liver and the spleen. Antileishmanial agents containing-liposomes showed more effective therapies with reduction of toxicity and adverse side effects. The purpose of this study was to investigate the tissue distribution of radioactive meglumine antimoniate encapsulated in phosphatidylserine-containing liposome. Meglumine antimoniate was neutron irradiated inside the IEA-R1 nuclear reactor to produce antimony radiotracers, {sup 122}Sb and {sup 124}Sb, and encapsulated in liposome. Healthy mice received a single intraperitoneal dose of the radiolabeled drug. Analysis of the mean radioactive tissue concentration-time data curves showed that liver and spleen had the highest levels of radioactivity. In addition these levels of drug remained for more than 48 hours. The dominant route of elimination was via biliary excretion with slow rate. Small fraction of the drug was found in the kidneys with very fast elimination. In conclusion, the phosphatidylserine-containing liposome showed to be a very useful tool to target antileishmanial agents to MPS and to sustain the drug levels for longer times. Besides, radiolabeled liposome is the easiest approach to perform biodistribution evaluation. (author)

  2. DMPD: CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multipleligand specificities and functions. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 8485905 CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multipleligand specificities...) (.html) (.csml) Show CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multipleligand specificities...d NK cell membrane receptor with multipleligand specificities and functions. Authors Ross GD, Vetvicka V. Pu

  3. A specific primed immune response in Drosophila is dependent on phagocytes.

    Directory of Open Access Journals (Sweden)

    Linh N Pham

    2007-03-01

    Full Text Available Drosophila melanogaster, like other invertebrates, relies solely on its innate immune response to fight invading microbes; by definition, innate immunity lacks adaptive characteristics. However, we show here that priming Drosophila with a sublethal dose of Streptococcus pneumoniae protects against an otherwise-lethal second challenge of S. pneumoniae. This protective effect exhibits coarse specificity for S. pneumoniae and persists for the life of the fly. Although not all microbial challenges induced this specific primed response, we find that a similar specific protection can be elicited by Beauveria bassiana, a natural fly pathogen. To characterize this primed response, we focused on S. pneumoniae-induced protection. The mechanism underlying this protective effect requires phagocytes and the Toll pathway. However, activation of the Toll pathway is not sufficient for priming-induced protection. This work contradicts the paradigm that insect immune responses cannot adapt and will promote the search for similar responses overlooked in organisms with an adaptive immune response.

  4. Resident Characteristics Report

    Data.gov (United States)

    Department of Housing and Urban Development — The Resident Characteristics Report summarizes general information about households who reside in Public Housing, or who receive Section 8 assistance. The report...

  5. Genetic Phagocyte NADPH Oxidase Deficiency Enhances Nonviable Candida albicans-Induced Inflammation in Mouse Lungs.

    Science.gov (United States)

    Endo, Daiki; Fujimoto, Kenta; Hirose, Rika; Yamanaka, Hiroko; Homme, Mizuki; Ishibashi, Ken-Ichi; Miura, Noriko; Ohno, Naohito; Aratani, Yasuaki

    2017-02-01

    Patients with chronic granulomatous disease (CGD) have mutated phagocyte NADPH oxidase, resulting in reduced production of reactive oxygen species (ROS). While the mechanism underlying hyperinfection in CGD is well understood, the basis for inflammatory disorders that arise in the absence of evident infection has not been fully explained. This study aimed to evaluate the effect of phagocyte NADPH oxidase deficiency on lung inflammation induced by nonviable Candida albicans (nCA). Mice deficient in this enzyme (CGD mice) showed more severe neutrophilic pneumonia than nCA-treated wild-type mice, which exhibited significantly higher lung concentrations of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and keratinocyte-derived chemokine (KC). Neutralization of these proinflammatory mediators significantly reduced neutrophil infiltration. In vitro, production of IL-1β and TNF-α from neutrophils and that of KC from macrophages was enhanced in nCA-stimulated neutrophils from CGD mice. Expression of IL-1β mRNA was higher in the stimulated CGD neutrophils than in the stimulated wild-type cells, concomitant with upregulation of nuclear factor (NF)-κB and its upstream regulator extracellular-signal regulated kinase (ERK) 1/2. Pretreatment with an NADPH oxidase inhibitor significantly enhanced IL-1β production in the wild-type neutrophils stimulated with nCA. These results suggest that lack of ROS production because of NADPH oxidase deficiency results in the production of higher levels of proinflammatory mediators from neutrophils and macrophages, which may at least partly contribute to the exacerbation of nCA-induced lung inflammation in CGD mice.

  6. A new non-phagocytic TLR6 with broad recognition ligands from Pacific oyster Crassostrea gigas.

    Science.gov (United States)

    Wang, Weilin; Zhang, Tao; Wang, Lingling; Xu, Jiachao; Li, Meijia; Zhang, Anguo; Qiu, Limei; Song, Linsheng

    2016-12-01

    Toll like receptors (TLRs) are evolutionarily prevalent recognition molecules in the Animalia and Plantae kingdom, which play vital roles in immune defense and homeostasis maintenance. Recently, the expansion of TLRs has been reported in invertebrate genomes, but the characters and immune functions of these expanded TLRs were still not well known. In the present study, a new member of TLR family with five LRR domains was identified in Crassostrea gigas (designated CgTLR6). It shared homology with TLRs from other organisms with the closest phylogenic relationship with molluscan TLRs. The recombinant protein of CgTLR6 (rCgTLR6) displayed direct bind activity to gram-negative bacteria Vibrio anguillarum and Vibrio splendidus, gram-positive bacteria Staphylococci aureus and Micrococcus luteus, and fungi Pichia pastoris, but not to fungi Yarrowia lipolytica. It also exhibited affinity to lipopolysaccharide (LPS) and peptidoglycan (PGN), while no affinity to mannan (MAN). The mRNA of CgTLR6 was mainly detected in hemocytes and hepatopancreas, and was significantly induced (p < 0.01) in hemocytes after the oyster was stimulated with LPS, PGN or bacteria V. splendidus. Immunofluorescence analysis indicated that CgTLR6 was mainly located at the membrane of hemocytes. The blockage of CgTLR6 by anti-rCgTLR6 antibody did not significantly inhibit the phagocytic rates of hemocytes toward recognized gram-negative bacteria V. anguillarum and V. splendidus, and unrecognized fungi Y. lipolytica. These results collectively implied that CgTLR6 was a novel non-phagocytic receptor of C. gigas to mediate humoral immune response by recognizing pathogen-associated molecular patterns on the invaders. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Mononuclear Phagocytes Are Dispensable for Cardiac Remodeling in Established Pressure-Overload Heart Failure.

    Directory of Open Access Journals (Sweden)

    Bindiya Patel

    Full Text Available Although cardiac and splenic mononuclear phagocytes (MPs, i.e., monocytes, macrophages and dendritic cells (DCs, are key contributors to cardiac remodeling after myocardial infarction, their role in pressure-overload remodeling is unclear. We tested the hypothesis that these immune cells are required for the progression of remodeling in pressure-overload heart failure (HF, and that MP depletion would ameliorate remodeling.C57BL/6 mice were subjected to transverse aortic constriction (TAC or sham operation, and assessed for alterations in MPs. As compared with sham, TAC mice exhibited expansion of circulating LyC6hi monocytes and pro-inflammatory CD206- cardiac macrophages early (1 w after pressure-overload, prior to significant hypertrophy and systolic dysfunction, with subsequent resolution during chronic HF. In contrast, classical DCs were expanded in the heart in a biphasic manner, with peaks both early, analogous to macrophages, and late (8 w, during established HF. There was no significant expansion of circulating DCs, or Ly6C+ monocytes and DCs in the spleen. Periodic systemic MP depletion from 2 to 16 w after TAC in macrophage Fas-induced apoptosis (MaFIA transgenic mice did not alter cardiac remodeling progression, nor did splenectomy in mice with established HF after TAC. Lastly, adoptive transfer of splenocytes from TAC HF mice into naïve recipients did not induce immediate or long-term cardiac dysfunction in recipient mice.Mononuclear phagocytes populations expand in a phasic manner in the heart during pressure-overload. However, they are dispensable for the progression of remodeling and failure once significant hypertrophy is evident and blood monocytosis has normalized.

  8. Expanding the tools for identifying mononuclear phagocyte subsets in swine: Reagents to porcine CD11c and XCR1

    Czech Academy of Sciences Publication Activity Database

    Deloizy, Ch.; Bouguyon, E.; Fossum, E.; Šebo, Peter; Osička, Radim; Bole, A.; Pierres, M.; Biacchesi, S.; Dalod, M.; Bogen, B.; Bertho, N.; Schwartz-Cornil, I.

    2016-01-01

    Roč. 65, December 2016 (2016), s. 31-40 ISSN 0145-305X R&D Projects: GA ČR GA15-09157S Institutional support: RVO:61388971 Keywords : Mononuclear phagocytes * Dendritic cells * Pig model Subject RIV: EE - Microbiology, Virology Impact factor: 3.218, year: 2016

  9. Effect of Lipopolysaccharide Derived from Pantoea agglomerans on the Phagocytic Activity of Amyloid β by Primary Murine Microglial Cells.

    Science.gov (United States)

    Kobayashi, Yutaro; Inagawa, Hiroyuki; Kohchi, Chie; Okazaki, Katsuichiro; Zhang, Ran; Soma, Gen-Ichiro

    2016-07-01

    Monophosphoryl lipid A, lipopolysaccharide (LPS)-derived Toll-like receptor (TLR) 4 agonist, has been shown to be effective in the prevention of Alzheimer's disease (AD) by enhancing phagocytosis of amyloid β (Aβ) by brain microglia. Our recent study demonstrated that oral administration of LPS derived from Pantoea agglomerans (LPSp) activates peritoneal macrophages and enhances the phagocytic activity via TLR4 signaling pathway; however, the effect of LPSp on Aβ phagocytosis in microglia is still unknown. Primary microglial cells were isolated from adult mouse brain by enzymatic digestion, following myelin removal and magnetic separation of cluster of differentiation (CD) 11b. Phagocytic analysis of the primary microglia was measured by using HiLyte™ Fluor 488-conjugated Aβ1-42 RESULTS: Using our protocols, the average yield of isolated CD11b(+) cells was around 2.2×10(5) cells per brain. CD11b(+)CD45(+)CD39(+) cells were defined here as microglia. The phagocytic activity of Aβ1-42 by the isolated microglia was confirmed. LPSp (10 ng/ml) pre-treatment for 18 h significantly increased Aβ phagocytic activity. The enhancement of Aβ1-42 phagocytosis by LPSp treatment in the primary mouse microglia was demonstrated for the first time. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  10. Phagocytic and oxidative-burst activity of blood leukocytes in rats fed a protein-free diet

    DEFF Research Database (Denmark)

    Sawosz, Ewa; Winnicka, Anna; Chwalibog, André

    2009-01-01

    The objective of this study was to evaluate the effects of two weeks' protein deprivation on the cellular parameters of non-specific immunity in rats. Wistar rats (200-250 g) were divided into two groups (2x12) and were fed two isoenergetic (control and protein-free) diets. The phagocytic activit...

  11. Comparative investigations of the influence of H1-antihistamines on the generation of reactive oxygen species by phagocytes

    Czech Academy of Sciences Publication Activity Database

    Králová, Jana; Nosál, R.; Drábiková, K.; Jančinová, V.; Denev, P.; Moravcová, Aneta; Kubala, Lukáš; Číž, Milan; Lojek, Antonín

    2008-01-01

    Roč. 57, č. 1 (2008), S01-S02 ISSN 1023-3830 R&D Projects: GA AV ČR(CZ) 1QS500040507 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : H1- antihistamines * phagocytes * ROS Subject RIV: BO - Biophysics Impact factor: 1.457, year: 2008

  12. Calcium influx rescues adenylate cyclase-hemolysin from rapid cell membrane removal and enables phagocyte permeabilization by toxin pores.

    Directory of Open Access Journals (Sweden)

    Radovan Fiser

    Full Text Available Bordetella adenylate cyclase toxin-hemolysin (CyaA penetrates the cytoplasmic membrane of phagocytes and employs two distinct conformers to exert its multiple activities. One conformer forms cation-selective pores that permeabilize phagocyte membrane for efflux of cytosolic potassium. The other conformer conducts extracellular calcium ions across cytoplasmic membrane of cells, relocates into lipid rafts, translocates the adenylate cyclase enzyme (AC domain into cells and converts cytosolic ATP to cAMP. We show that the calcium-conducting activity of CyaA controls the path and kinetics of endocytic removal of toxin pores from phagocyte membrane. The enzymatically inactive but calcium-conducting CyaA-AC⁻ toxoid was endocytosed via a clathrin-dependent pathway. In contrast, a doubly mutated (E570K+E581P toxoid, unable to conduct Ca²⁺ into cells, was rapidly internalized by membrane macropinocytosis, unless rescued by Ca²⁺ influx promoted in trans by ionomycin or intact toxoid. Moreover, a fully pore-forming CyaA-ΔAC hemolysin failed to permeabilize phagocytes, unless endocytic removal of its pores from cell membrane was decelerated through Ca²⁺ influx promoted by molecules locked in a Ca²⁺-conducting conformation by the 3D1 antibody. Inhibition of endocytosis also enabled the native B. pertussis-produced CyaA to induce lysis of J774A.1 macrophages at concentrations starting from 100 ng/ml. Hence, by mediating calcium influx into cells, the translocating conformer of CyaA controls the removal of bystander toxin pores from phagocyte membrane. This triggers a positive feedback loop of exacerbated cell permeabilization, where the efflux of cellular potassium yields further decreased toxin pore removal from cell membrane and this further enhances cell permeabilization and potassium efflux.

  13. Phagocytic activities of hemocytes from the deep-sea symbiotic mussels Bathymodiolus japonicus, B. platifrons, and B. septemdierum.

    Science.gov (United States)

    Tame, Akihiro; Yoshida, Takao; Ohishi, Kazue; Maruyama, Tadashi

    2015-07-01

    Deep-sea mytilid mussels harbor symbiotic bacteria in their gill epithelial cells that are horizontally or environmentally transmitted to the next generation of hosts. To understand the immune defense system in deep-sea symbiotic mussels, we examined the hemocyte populations of the symbiotic Bathymodiolus mussel species Bathymodiolus japonicus, Bathymodiolus platifrons, and Bathymodiolus septemdierum, and characterized three types of hemocytes: agranulocytes (AGs), basophilic granulocytes (BGs), and eosinophilic granulocytes (EGs). Of these, the EG cells were the largest (diameter, 8.4-10.0 μm) and had eosinophilic cytoplasm with numerous eosinophilic granules (diameter, 0.8-1.2 μm). Meanwhile, the BGs were of medium size (diameter, 6.7-8.0 μm) and contained small basophilic granules (diameter, 0.3-0.4 μm) in basophilic cytoplasm, and the AGs, the smallest of the hemocytes (diameter, 4.8-6.0 μm), had basophilic cytoplasm lacking granules. A lectin binding assay revealed that concanavalin A bound to all three hemocyte types, while wheat germ agglutinin bound exclusively to EGs and BGs. The total hemocyte population densities within the hemolymph of all three Bathymodiolus mussel species were similar (8.4-13.3 × 10(5) cells/mL), and the percentages of circulating AGs, BGs, and EGs in the hemolymph of these organisms were 44.7-48.5%, 14.3-17.6%, and 34.3-41.0%, respectively. To analyze the functional differences between these hemocytes, the phagocytic activity and post-phagocytic phagosome-lysosome fusion events were analyzed in each cell type using a fluorescent Alexa Fluor(®) 488-conjugated Escherichia coli bioparticle and a LysoTracker(®) lysosomal marker, respectively. While the AGs exhibited no phagocytic activity, both types of granulocytes were phagocytic. Of the three hemocyte types, the EGs exhibited the highest level of phagocytic activity as well as rapid phagosome-lysosome fusion, which occurred within 2 h of incubation. Meanwhile, the BGs showed

  14. Suppression of annexin A2 by prostaglandin E₂ impairs phagocytic ability of peritoneal macrophages in women with endometriosis.

    Science.gov (United States)

    Wu, Meng-Hsing; Chuang, Pei-Chin; Lin, Yiu-Juian; Tsai, Shaw-Jenq

    2013-04-01

    Is annexin A2 involved in the reduced phagocytic ability of macrophages in endometriosis? Data from women with endometriosis and a murine model of the disease show that expression of annexin A2 in peritoneal macrophages is inhibited by prostaglandin E2 (PGE2) and this impairs the phagocytic ability of macrophages. Endometriosis is a chronic inflammatory disease that recruits many immune cells, especially macrophages, to the peritoneal cavity. The phagocytic ability of peritoneal macrophages isolated from women with endometriosis is reduced. A laboratory study. Thirty-five patients (20 with and 15 without endometriosis) of reproductive age with normal menstrual cycles were recruited. Peritoneal macrophages isolated from women with or without endometriosis were cultured and treated with vehicle, PGE2 and different EP receptor agonists, and the expression of annexin A2 was quantified by RT-PCR and western blotting. Annexin A2 was knocked down (by small interfering RNA) in normal macrophages or overexpressed (by treatment with recombinant protein) in endometriotic macrophages and their phagocytic ability was measured by flow cytometry. Peritoneal macrophages were isolated from a mouse model of endometriosis and treated with PGE2 or cyclo-oxygenase (COX) inhibitors, and annexin A2 mRNA was quantified. Levels of annexin A2 were markedly reduced in peritoneal macrophages from women with endometriosis versus controls (mRNA: P endometriosis versus control) via the EP2/EP4 receptor-dependent signaling pathway. Treatment with PGE2 or knockdown of annexin A2 inhibited the phagocytic ability of macrophages (P peritoneal macrophages were markedly reduced in mice treated with PGE2 (P peritoneal macrophages (P peritoneal cells from patients with endometriosis or that their endometriotic fluid contains increased amounts of PGE2 when compared with control subjects. Inhibiting PGE2 signaling, in order to restore or enhance the phagocytic capability of macrophages, may represent a new

  15. Immune Defenses of the Invasive Apple Snail Pomacea canaliculata (Caenogastropoda, Ampullariidae): Phagocytic Hemocytes in the Circulation and the Kidney.

    Science.gov (United States)

    Cueto, Juan A; Rodriguez, Cristian; Vega, Israel A; Castro-Vazquez, Alfredo

    2015-01-01

    Hemocytes in the circulation and kidney islets, as well as their phagocytic responses to microorganisms and fluorescent beads, have been studied in Pomacea canaliculata, using flow cytometry, light microscopy (including confocal laser scanning microscopy) and transmission electron microscopy (TEM). Three circulating hemocyte types (hyalinocytes, agranulocytes and granulocytes) were distinguished by phase contrast microscopy of living cells and after light and electron microscopy of fixed material. Also, three different populations of circulating hemocytes were separated by flow cytometry, which corresponded to the three hemocyte types. Hyalinocytes showed a low nucleus/cytoplasm ratio, and no apparent granules in stained material, but showed granules of moderate electron density under TEM (L granules) and at least some L granules appear acidic when labeled with LysoTracker Red. Both phagocytic and non-phagocytic hyalinocytes lose most (if not all) L granules when exposed to microorganisms in vitro. The phagosomes formed differed whether hyalinocytes were exposed to yeasts or to Gram positive or Gram negative bacteria. Agranulocytes showed a large nucleus/cytoplasm ratio and few or no granules. Granulocytes showed a low nucleus/cytoplasm ratio and numerous eosinophilic granules after staining. These granules are electron dense and rod-shaped under TEM (R granules). Granulocytes may show merging of R granules into gigantic ones, particularly when exposed to microorganisms. Fluorescent bead exposure of sorted hemocytes showed phagocytic activity in hyalinocytes, agranulocytes and granulocytes, but the phagocytic index was significantly higher in hyalinocytes. Extensive hemocyte aggregates ('islets') occupy most renal hemocoelic spaces and hyalinocyte-like cells are the most frequent component in them. Presumptive glycogen deposits were observed in most hyalinocytes in renal islets (they also occur in the circulation but less frequently) and may mean that hyalinocytes

  16. Immune Defenses of the Invasive Apple Snail Pomacea canaliculata (Caenogastropoda, Ampullariidae: Phagocytic Hemocytes in the Circulation and the Kidney.

    Directory of Open Access Journals (Sweden)

    Juan A Cueto

    Full Text Available Hemocytes in the circulation and kidney islets, as well as their phagocytic responses to microorganisms and fluorescent beads, have been studied in Pomacea canaliculata, using flow cytometry, light microscopy (including confocal laser scanning microscopy and transmission electron microscopy (TEM. Three circulating hemocyte types (hyalinocytes, agranulocytes and granulocytes were distinguished by phase contrast microscopy of living cells and after light and electron microscopy of fixed material. Also, three different populations of circulating hemocytes were separated by flow cytometry, which corresponded to the three hemocyte types. Hyalinocytes showed a low nucleus/cytoplasm ratio, and no apparent granules in stained material, but showed granules of moderate electron density under TEM (L granules and at least some L granules appear acidic when labeled with LysoTracker Red. Both phagocytic and non-phagocytic hyalinocytes lose most (if not all L granules when exposed to microorganisms in vitro. The phagosomes formed differed whether hyalinocytes were exposed to yeasts or to Gram positive or Gram negative bacteria. Agranulocytes showed a large nucleus/cytoplasm ratio and few or no granules. Granulocytes showed a low nucleus/cytoplasm ratio and numerous eosinophilic granules after staining. These granules are electron dense and rod-shaped under TEM (R granules. Granulocytes may show merging of R granules into gigantic ones, particularly when exposed to microorganisms. Fluorescent bead exposure of sorted hemocytes showed phagocytic activity in hyalinocytes, agranulocytes and granulocytes, but the phagocytic index was significantly higher in hyalinocytes. Extensive hemocyte aggregates ('islets' occupy most renal hemocoelic spaces and hyalinocyte-like cells are the most frequent component in them. Presumptive glycogen deposits were observed in most hyalinocytes in renal islets (they also occur in the circulation but less frequently and may mean that

  17. Δ6-fatty acid desaturase and fatty acid elongase mRNA expression, phagocytic activity and weight-to-length relationships in channel catfish (Ictalurus punctatus) fed alternative diets with soy oil and a probiotic.

    Science.gov (United States)

    Santerre, A; Téllez-Bañuelos, M C; Casas-Solís, J; Castro-Félix, P; Huízar-López, M R; Zaitseva, G P; Horta-Fernández, J L; Trujillo-García, E A; de la Mora-Sherer, D; Palafox-Luna, J A; Juárez-Carrillo, E

    2015-09-22

    A time-course feeding trial was conducted for 120 days on juvenile channel catfish (Ictalurus punctatus) to study the effects of diets differing in oil source (fish oil or soy oil) and supplementation with a commercial probiotic. Relative levels of Δ6-fatty acid desaturase (Δ6-FAD) and fatty acid elongase (FAE) expression were assessed in brain and liver tissues. Both genes showed similar expression levels in all groups studied. Fish weight-to-length relationships were evaluated using polynomial regression analyses, which identified a burst in weight and length in the channel catfish on day 105 of treatment; this increase was related to an increase in gene expression. Mid-intestinal lactic acid bacterium (LAB) count was determined according to morphological and biochemical criteria using API strips. There was no indication that intestinal LAB count was affected by the modified diets. The Cunningham glass adherence method was applied to evaluate phagocytic cell activity in peripheral blood. Reactive oxygen species (ROS) generation was assessed through the respiratory burst activity of spleen macrophages by the NBT reduction test. Probiotic-supplemented diets provided a good substrate for innate immune system function; the phagocytic index was significantly enhanced in fish fed soy oil and the probiotic, and at the end of the experimental period, ROS production increased in fish fed soy oil. The substitution of fish oil by soy oil is recommended for food formulation and will contribute to promoting sustainable aquaculture. Probiotics are also recommended for channel catfish farming as they may act as immunonutrients.

  18. Cortactin is involved in the entry of Coxiella burnetii into non-phagocytic cells.

    Directory of Open Access Journals (Sweden)

    Eliana M Rosales

    Full Text Available BACKGROUND: Cortactin is a key regulator of the actin cytoskeleton and is involved in pathogen-host cell interactions. Numerous pathogens exploit the phagocytic process and actin cytoskeleton to infect host cells. Coxiella burnetii, the etiologic agent of Q fever, is internalized by host cells through a molecular mechanism that is poorly understood. METHODOLOGY/PRINCIPAL FINDING: Here we analyzed the role of different cortactin motifs in the internalization of C. burnetii by non-phagocytic cells. C. burnetii internalization into HeLa cells was significantly reduced when the cells expressed GFP-cortactin W525K, which carries a mutation in the SH3 domain that renders the protein unable to bind targets such as N-WASP. However, internalization was unaffected when the cells expressed the W22A mutant, which has a mutation in the N-terminal acidic region that destroys the protein's ability to bind and activate Arp2/3. We also determined whether the phosphorylation status of cortactin is important for internalization. Expression of GFP-cortactin 3F, which lacks phosphorylatable tyrosines, significantly increased internalization of C. burnetii, while expression of GFP-cortactin 3D, a phosphotyrosine mimic, did not affect it. In contrast, expression of GFP-cortactin 2A, which lacks phosphorylatable serines, inhibited C. burnetii internalization, while expression of GFP-cortactin SD, a phosphoserine mimic, did not affect it. Interestingly, inhibitors of Src kinase and the MEK-ERK kinase pathway blocked internalization. In fact, both kinases reached maximal activity at 15 min of C. burnetii infection, after which activity decreased to basal levels. Despite the decrease in kinase activity, cortactin phosphorylation at Tyr421 reached a peak at 1 h of infection. CONCLUSIONS/SIGNIFICANCE: Our results suggest that the SH3 domain of cortactin is implicated in C. burnetii entry into HeLa cells. Furthermore, cortactin phosphorylation at serine and dephosphorylation

  19. [Burnout in nursing residents].

    Science.gov (United States)

    Franco, Gianfábio Pimentel; de Barros, Alba Lúcia Bottura Leite; Nogueira-Martins, Luiz Antônio; Zeitoun, Sandra Salloum

    2011-03-01

    Nursing residents may experience physical and emotional exhaustion from the daily life of attending the Program. The aim of this study was to determine the Burnout incidence among Nursing Residents. An investigative, descriptive, analytical, longitudinal-prospective study was conducted with 16 Residents over two years. The Maslach Burnout Inventory was used, translated and validated for Brazil, as well as a sociodemographic/occupational data tool. Of all residents, 17.2% showed high rates in Emotional Exhaustion and Depersonalization; 18.8% showed impaired commitment in Personal Accomplishment, 75% of which belonged to specialty areas, such as Emergency Nursing, Adult and Pediatric Intensive Care. Age and specialty area were positively correlated with Personal Accomplishment. One of the Residents was identified with changes in three subscales of the Maslach Burnout Inventory, thus characterized as a Burnout Syndrome patient. Nursing Residents have profiles of disease. Knowing these factors can minimize health risks of these workers.

  20. Dichotomy between factors inducing the immunosuppressive enzyme IL-4-induced gene 1 (IL4I1) in B lymphocytes and mononuclear phagocytes.

    Science.gov (United States)

    Marquet, Jeanine; Lasoudris, Fanette; Cousin, Céline; Puiffe, Marie-Line; Martin-Garcia, Nadine; Baud, Véronique; Chereau, Fanny; Farcet, Jean-Pierre; Molinier-Frenkel, Valérie; Castellano, Flavia

    2010-09-01

    MPhi and DC are key elements in the control of tissue homeostasis and response to insult. In this work, we demonstrate that MPhi and DC are the major producers of the phenylalanine catabolizing enzyme IL-4-induced gene 1 (IL4I1) under inflammatory conditions. IL4I1 was first described in B cells, which indeed can produce IL4I1 in vitro, although at much lower levels. In vivo, IL4I1 is highly expressed by MPhi and DC of Th1 granulomas (sarcoidosis, tuberculosis) but poorly detected in Th2 granulomas (schistosomiasis). In vitro, expression of the enzyme is induced in mononuclear phagocytes by various pro-inflammatory stimuli through the activation of the transcription factors NF-kappaB and/or STAT1. B cells also express IL4I1 in response to NF-kappaB-activating stimuli such as CD40L; however, in contrast to myeloid cells, B cells are insensitive to IFN-gamma but respond to stimulation of the IL-4/STAT6 axis. As we show that the expression of IL4I1 by a monocytic cell line inhibits T-cell proliferation and production of IFN-gamma and inflammatory cytokines, we propose that IL4I1 participates in the downregulation of Th1 inflammation in vivo.

  1. The mononuclear phagocyte system of the mouse defined by immunohistochemical localisation of antigen F4/80: macrophages associated with epithelia.

    Science.gov (United States)

    Hume, D A; Perry, V H; Gordon, S

    1984-11-01

    The tissue distribution of the murine macrophage-specific antigen F4/80 has been analysed using an immunohistochemical technique. The antigen is observed on all known macrophage populations (including Kupffer cells and bronchoalveolar macrophages) and is absent from any cell types that are definitely not mononuclear phagocytes. Microglial cells from brain express F4/80. F4/80+ macrophages observed associated with epithelia can be divided into two categories, intraepithelial and periepithelial. The former includes epidermal Langerhans cells and cells with similar morphology in other stratified squamous epithelia (cervix, oesophagus), pseudostratified epithelium (trachea), transitional epithelium of urinary bladder, and simple epithelia lining various ducts (salivary gland, common bile duct, tracheobronchial gland). Periepithelial F4/80+ cells, apparently spread immediately below the basal lamina, are associated with simple epithelia throughout the gastrointestinal, respiratory, and male and female reproductive tract as well as the brain ependyma. A major class of periepithelial F4/80+ cells is associated with capillaries throughout the microcirulation. The role of these macrophage populations in control of epithelial function is discussed.

  2. Redundant Catalases Detoxify Phagocyte Reactive Oxygen and Facilitate Histoplasma capsulatum Pathogenesis

    Science.gov (United States)

    Holbrook, Eric D.; Smolnycki, Katherine A.; Youseff, Brian H.

    2013-01-01

    Histoplasma capsulatum is a respiratory pathogen that infects phagocytic cells. The mechanisms allowing Histoplasma to overcome toxic reactive oxygen molecules produced by the innate immune system are an integral part of Histoplasma's ability to survive during infection. To probe the contribution of Histoplasma catalases in oxidative stress defense, we created and analyzed the virulence defects of mutants lacking CatB and CatP, which are responsible for extracellular and intracellular catalase activities, respectively. Both CatB and CatP protected Histoplasma from peroxide challenge in vitro and from antimicrobial reactive oxygen produced by human neutrophils and activated macrophages. Optimal protection required both catalases, as the survival of a double mutant lacking both CatB and CatP was lower than that of single-catalase-deficient cells. Although CatB contributed to reactive oxygen species defenses in vitro, CatB was dispensable for lung infection and extrapulmonary dissemination in vivo. Loss of CatB from a strain also lacking superoxide dismutase (Sod3) did not further reduce the survival of Histoplasma yeasts. Nevertheless, some catalase function was required for pathogenesis since simultaneous loss of both CatB and CatP attenuated Histoplasma virulence in vivo. These results demonstrate that Histoplasma's dual catalases comprise a system that enables Histoplasma to efficiently overcome the reactive oxygen produced by the innate immune system. PMID:23589579

  3. Mycobacterium leprae phenolglycolipid-1 expressed by engineered M. bovis BCG modulates early interaction with human phagocytes.

    Directory of Open Access Journals (Sweden)

    Guillaume Tabouret

    2010-10-01

    Full Text Available The species-specific phenolic glycolipid 1 (PGL-1 is suspected to play a critical role in the pathogenesis of leprosy, a chronic disease of the skin and peripheral nerves caused by Mycobacterium leprae. Based on studies using the purified compound, PGL-1 was proposed to mediate the tropism of M. leprae for the nervous system and to modulate host immune responses. However, deciphering the biological function of this glycolipid has been hampered by the inability to grow M. leprae in vitro and to genetically engineer this bacterium. Here, we identified the M. leprae genes required for the biosynthesis of the species-specific saccharidic domain of PGL-1 and reprogrammed seven enzymatic steps in M. bovis BCG to make it synthesize and display PGL-1 in the context of an M. leprae-like cell envelope. This recombinant strain provides us with a unique tool to address the key questions of the contribution of PGL-1 in the infection process and to study the underlying molecular mechanisms. We found that PGL-1 production endowed recombinant BCG with an increased capacity to exploit complement receptor 3 (CR3 for efficient invasion of human macrophages and evasion of inflammatory responses. PGL-1 production also promoted bacterial uptake by human dendritic cells and dampened their infection-induced maturation. Our results therefore suggest that M. leprae produces PGL-1 for immune-silent invasion of host phagocytic cells.

  4. Heterophil Phagocytic Activity Stimulated by L61 and L55 Supplementation in Broilers with Infection

    Directory of Open Access Journals (Sweden)

    Pairat Sornplang

    2015-11-01

    Full Text Available Newborn chicks are susceptible to Salmonella enterica serovar Enteritidis (SE. The objective of this study was to evaluate the effect of Lactobacillus probiotic isolated from chicken feces on heterophil phagocytosis in broiler chicks. A total of 150 newborn broiler chicks were divided into 5 groups (30 chicks per group as follows: group 1 (normal control, given feed and water only, group 2 (positive control given feed, water and SE infection, group 3 (L61 treated given feed, water, SE infection followed by Lactobacillus salivarius L61 treatment, group 4 (L55 treated given feed, water, SE infection followed by L. salivarius L55 treatment, and group 5 given feed, water, SE infection followed by L. salivarius L61 + L55 combination treatment. After SE infection, L. salivarius treatment lasted for 7 days. The results showed that L. salivarius L61 and L. salivarius L55 treatment, either alone or combination of both, increased the survival rate after SE infection, and upregulated heterophil phagocytosis and phagocytic index (PI. Conversely, chick groups treated with Lactobacillus showed lower SE recovery rate from cecal tonsils than that of the positive control group. The PI values of the chicken group with SE infection, followed by the combination of L. salivarius L61 and L. salivarius L55 were the highest as compared to either positive control or normal control group. Two Lactobacillus strains supplementation group showed significantly (p<0.05 higher PI value at 48 h than 24 h after treatment.

  5. Alzheimer's associated β-amyloid protein inhibits influenza A virus and modulates viral interactions with phagocytes.

    Directory of Open Access Journals (Sweden)

    Mitchell R White

    Full Text Available Accumulation of β-Amyloid (βA is a key pathogenetic factor in Alzheimer's disease; however, the normal function of βA is unknown. Recent studies have shown that βA can inhibit growth of bacteria and fungi. In this paper we show that βA also inhibits replication of seasonal and pandemic strains of H3N2 and H1N1 influenza A virus (IAV in vitro. The 42 amino acid fragment of βA (βA42 had greater activity than the 40 amino acid fragment. Direct incubation of the virus with βA42 was needed to achieve optimal inhibition. Using quantitative PCR assays βA42 was shown to reduce viral uptake by epithelial cells after 45 minutes and to reduce supernatant virus at 24 hours post infection. βA42 caused aggregation of IAV particles as detected by light transmission assays and electron and confocal microscopy. βA42 did not stimulate neutrophil H2O2 production or extracellular trap formation on its own, but it increased both responses stimulated by IAV. In addition, βA42 increased uptake of IAV by neutrophils. βA42 reduced viral protein synthesis in monocytes and reduced IAV-induced interleukin-6 production by these cells. Hence, we demonstrate for the first time that βA has antiviral activity and modulates viral interactions with phagocytes.

  6. Phagocytic Index of Peritoneal Macrophages after Propolis Suplementation in Mice (Mus musculus

    Directory of Open Access Journals (Sweden)

    Siti Eva Mustafiah

    2011-12-01

    Design and Method: This research is an experiment with post test study design randomized control group design. This study used mice that were divided into four groups randomly. The first group / Group-I were for negative control (standard feed and aquadest; The second group/Group-II were fed standard-feed, aquadest, and propolis at a dose of 1.25 mg/kgBM; the third group/group-III were fed standard-feed, water, and propolis at a dose of 2.5 mg/KgBM; The fourth group/Group-IV were fed standard feed, water, and propolis at a dose of 5 mg/KgBM. Treatment where conducted for 3 days. Result: The average macrophage phagocytic index, were at the highest level of it (7.82 1.63 while the lowest one were the first group 3.43 0.13. The Kruskall Wallis result stated that there is index difference among various groups with p 0.002 (p < 0.05. Conclusion: Propolis effected on mice peritoneal macrophage phagocytosis index (Sains Medika, 3(2:121-128.

  7. Regulation of human mononuclear phagocyte migration by cell surface-binding proteins for advanced glycation end products.

    OpenAIRE

    Schmidt, A M; Yan, S D; Brett, J; Mora, R; Nowygrod, R; Stern, D

    1993-01-01

    Nonenzymatic glycation of proteins occurs at an accelerated rate in diabetes and can lead to the formation of advanced glycation end products of proteins (AGEs), which bind to mononuclear phagocytes (MPs) and induce chemotaxis. We have isolated two cell surface-associated binding proteins that mediate the interaction of AGEs with bovine endothelial cells. One of these proteins is a new member of the immunoglobulin superfamily of receptors (termed receptor for AGEs or RAGE); and the second is ...

  8. Stimulus-dependent regulation of the phagocyte NADPH oxidase by a VAV1, Rac1, and PAK1 signaling axis

    DEFF Research Database (Denmark)

    Roepstorff, Kirstine; Rasmussen, Izabela Zorawska; Sawada, Makoto

    2008-01-01

    proteins in the formyl-methionyl-leucyl-phenylalanine-induced activation of endogenous PAK1. In contrast, PAK1 mutants had no effect on superoxide generation downstream of FcgammaR signaling during phagocytosis of IgG-immune complexes. We further present evidence that the effect of PAK1 on the respiratory...... on NADPH oxidase activation. Collectively, our findings define a VAV1-Rac1-PAK1 signaling axis in mononuclear phagocytes regulating superoxide production in a stimulus-dependent manner....

  9. Caffeic acid and quercetin exert caspases-independent apoptotic effects on Leishmania major promastigotes, and reactivate the death of infected phagocytes derived from BALB/c mice

    Directory of Open Access Journals (Sweden)

    Radia Belkhelfa-Slimani

    2017-04-01

    Conclusions: The leishmanicidal effect of caffeic acid and quercetin on promastigotes and amastigotes, as well as reactivation of infected phagocytes apoptosis, suggested a potential therapeutic role against cutaneous leishmaniasis.

  10. Melatonin signaling affects the timing in the daily rhythm of phagocytic activity by the retinal pigment epithelium.

    Science.gov (United States)

    Laurent, Virgine; Sengupta, Anamika; Sánchez-Bretaño, Aída; Hicks, David; Tosini, Gianluca

    2017-12-01

    Earlier studies in Xenopus have indicated a role for melatonin in the regulation of retinal disk shedding, but the role of melatonin in the regulation of daily rhythm in mammalian disk shedding and phagocytosis is still unclear. We recently produced a series of transgenic mice lacking melatonin receptor type 1 (MT 1 ) or type 2 (MT 2 ) in a melatonin-proficient background and have shown that removal of MT 1 and MT 2 receptors induces significant effects on daily and circadian regulation of the electroretinogram as well as on the viability of photoreceptor cells during aging. In this study we investigated the daily rhythm of phagocytic activity by the retinal pigment epithelium in MT 1 and MT 2 knock-out mice. Our data indicate that in MT 1 and MT 2 knock-out mice the peak of phagocytosis is advanced by 3 h with respect to wild-type mice and occurred in dark rather than after the onset of light, albeit the mean phagocytic activity over the 24-h period did not change among the three genotypes. Nevertheless, this small change in the profile of daily phagocytic rhythms may produce a significant effect on retinal health since MT 1 and MT 2 knock-out mice showed a significant increase in lipofuscin accumulation in the retinal pigment epithelium. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Far beyond Phagocytosis: Phagocyte-Derived Extracellular Traps Act Efficiently against Protozoan Parasites In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Liliana M. R. Silva

    2016-01-01

    Full Text Available Professional mononuclear phagocytes such as polymorphonuclear neutrophils (PMN, monocytes, and macrophages are considered as the first line of defence against invasive pathogens. The formation of extracellular traps (ETs by activated mononuclear phagocytes is meanwhile well accepted as an effector mechanism of the early host innate immune response acting against microbial infections. Recent investigations showed evidence that ETosis is a widely spread effector mechanism in vertebrates and invertebrates being utilized to entrap and kill bacteria, fungi, viruses, and protozoan parasites. ETs are released in response to intact protozoan parasites or to parasite-specific antigens in a controlled cell death process. Released ETs consist of nuclear DNA as backbone adorned with histones, antimicrobial peptides, and phagocyte-specific granular enzymes thereby producing a sticky extracellular matrix capable of entrapping and killing pathogens. This review summarizes recent data on protozoa-induced ETosis. Special attention will be given to molecular mechanisms of protozoa-induced ETosis and on its consequences for the parasites successful reproduction and life cycle accomplishment.

  12. Facility Focus: Residence Halls.

    Science.gov (United States)

    College Planning & Management, 2003

    2003-01-01

    Describes four examples of residence hall design, one renovation and three new residence halls, that exemplify design principles that meet student and institutional requirements. The examples are at (1) the University of Illinois at Chicago; (2) Bowdoin College; (3) Muhlenberg College; and (4) Spring Arbor University. (SLD)

  13. Rain Forest Dance Residency.

    Science.gov (United States)

    Watson, Dawn

    1997-01-01

    Outlines the author's experience as a dancer and choreographer artist-in-residence with third graders at a public elementary school, providing a cultural arts experience to tie in with a theme study of the rain forest. Details the residency and the insights she gained working with students, teachers, and theme. (SR)

  14. Psychologic effects of residency.

    Science.gov (United States)

    Reuben, D B

    1983-03-01

    The intense situational and physiologic stresses that accompany postgraduate training may have serious psychosocial ramifications. Although only a small proportion of residents have overt psychiatric illness, virtually all display some psychologic impairment. Contributing factors include life-changes, stresses associated with providing patient care, loss of social support, long working hours, sleep deprivation, and underlying personality traits of residents. The manifestations of this impairment are variable and may be subtle. In response to these problems, residency programs have taken steps to provide psychosocial support. Unfortunately, most programs do not offer formal support groups or seminars to discuss difficulties that accompany residency. Further definition of the psychosocial effects of residency may prompt changes that make the training of physicians a more humane process.

  15. Development of an In Vitro Model for the Multi-Parametric Quantification of the Cellular Interactions between Candida Yeasts and Phagocytes

    OpenAIRE

    Dementhon, Karine; El-Kirat-Chatel, Sofiane; Noël, Thierry

    2012-01-01

    We developed a new in vitro model for a multi-parameter characterization of the time course interaction of Candida fungal cells with J774 murine macrophages and human neutrophils, based on the use of combined microscopy, fluorometry, flow cytometry and viability assays. Using fluorochromes specific to phagocytes and yeasts, we could accurately quantify various parameters simultaneously in a single infection experiment: at the individual cell level, we measured the association of phagocytes to...

  16. Development of an in vitro model for the multi-parametric quantification of the cellular interactions between Candida yeasts and phagocytes.

    Science.gov (United States)

    Dementhon, Karine; El-Kirat-Chatel, Sofiane; Noël, Thierry

    2012-01-01

    We developed a new in vitro model for a multi-parameter characterization of the time course interaction of Candida fungal cells with J774 murine macrophages and human neutrophils, based on the use of combined microscopy, fluorometry, flow cytometry and viability assays. Using fluorochromes specific to phagocytes and yeasts, we could accurately quantify various parameters simultaneously in a single infection experiment: at the individual cell level, we measured the association of phagocytes to fungal cells and phagocyte survival, and monitored in parallel the overall phagocytosis process by measuring the part of ingested fungal cells among the total fungal biomass that changed over time. Candida albicans, C. glabrata, and C. lusitaniae were used as a proof of concept: they exhibited species-specific differences in their association rate with phagocytes. The fungal biomass uptaken by the phagocytes differed significantly according to the Candida species. The measure of the survival of fungal and immune cells during the interaction showed that C. albicans was the more aggressive yeast in vitro, destroying the vast majority of the phagocytes within five hours. All three species of Candida were able to survive and to escape macrophage phagocytosis either by the intraphagocytic yeast-to-hyphae transition (C. albicans) and the fungal cell multiplication until phagocytes burst (C. glabrata, C. lusitaniae), or by the avoidance of phagocytosis (C. lusitaniae). We demonstrated that our model was sensitive enough to quantify small variations of the parameters of the interaction. The method has been conceived to be amenable to the high-throughput screening of mutants in order to unravel the molecular mechanisms involved in the interaction between yeasts and host phagocytes.

  17. Development of an in vitro model for the multi-parametric quantification of the cellular interactions between Candida yeasts and phagocytes.

    Directory of Open Access Journals (Sweden)

    Karine Dementhon

    Full Text Available We developed a new in vitro model for a multi-parameter characterization of the time course interaction of Candida fungal cells with J774 murine macrophages and human neutrophils, based on the use of combined microscopy, fluorometry, flow cytometry and viability assays. Using fluorochromes specific to phagocytes and yeasts, we could accurately quantify various parameters simultaneously in a single infection experiment: at the individual cell level, we measured the association of phagocytes to fungal cells and phagocyte survival, and monitored in parallel the overall phagocytosis process by measuring the part of ingested fungal cells among the total fungal biomass that changed over time. Candida albicans, C. glabrata, and C. lusitaniae were used as a proof of concept: they exhibited species-specific differences in their association rate with phagocytes. The fungal biomass uptaken by the phagocytes differed significantly according to the Candida species. The measure of the survival of fungal and immune cells during the interaction showed that C. albicans was the more aggressive yeast in vitro, destroying the vast majority of the phagocytes within five hours. All three species of Candida were able to survive and to escape macrophage phagocytosis either by the intraphagocytic yeast-to-hyphae transition (C. albicans and the fungal cell multiplication until phagocytes burst (C. glabrata, C. lusitaniae, or by the avoidance of phagocytosis (C. lusitaniae. We demonstrated that our model was sensitive enough to quantify small variations of the parameters of the interaction. The method has been conceived to be amenable to the high-throughput screening of mutants in order to unravel the molecular mechanisms involved in the interaction between yeasts and host phagocytes.

  18. Immunohistochemical characterization of gastrointestinal macrophages/phagocytes in dogs with inflammatory bowel disease (IBD) and non-IBD dogs.

    Science.gov (United States)

    Wagner, Anna; Junginger, Johannes; Lemensieck, Frederik; Hewicker-Trautwein, Marion

    2018-03-01

    Intestinal Mϕ play a pivotal role in the maintenance of gut homeostasis, but can also contribute to inflammation such as inflammatory bowel disease (IBD). In contrast to human tissues, little is known about phenotypes of Mϕ in the canine gastrointestinal tract. Therefore, an immunohistochemical study was performed using Abs against Mϕ-associated molecules (Cluster of differentiation (CD)64, CD163, CD204, ionized calcium-binding adaptor molecule 1, L1 Ag, and MHC II) on stomach, duodenum, jejunum, ileum and colon from non-IBD dogs. In addition, marker-expression in the stomach, duodenum and colon of the non-IBD dogs was compared to that in dogs with IBD. Results revealed predominance of resident Mϕ displaying an anti-inflammatory phenotype represented by expression of CD163 as well as CD204 in the gut of non-IBD dogs with high Mϕ numbers especially present in the small intestinal villus area. Compared to non-IBD tissue counterparts, stomach, duodenum, and colon from dogs with IBD showed reduced Mϕ numbers with the exception of slightly increased numbers of CD64+ Mϕ. Correlation analyses between marker-expression of Mϕ and the Canine Inflammatory Bowel Disease Activity Index as well as histological scores failed to reveal relevant relationships. The present study provides evidence of the canine steady state gastrointestinal tract being dominated by Mϕ with anti-inflammatory properties maintaining gut homeostasis. A significant reduction in these resident Mϕ may reflect disturbances in homeostatic capacity that could contribute to the development of canine IBD. In contrast to human IBD and murine disease models, infiltration of pro-inflammatory Mϕ does not significantly contribute to the inflammatory process of canine IBD, which may illustrate possible species-specific differences in IBD pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Residents in difficulty

    DEFF Research Database (Denmark)

    Christensen, Mette Krogh; O'Neill, Lotte; Hansen, Dorthe Høgh

    2016-01-01

    Background The majority of studies on prevalence and characteristics of residents in difficulty have been conducted in English-speaking countries and the existing literature may not reflect the prevalence and characteristics of residents in difficulty in other parts of the world such as the Scand......Background The majority of studies on prevalence and characteristics of residents in difficulty have been conducted in English-speaking countries and the existing literature may not reflect the prevalence and characteristics of residents in difficulty in other parts of the world...... such as the Scandinavian countries, where healthcare systems are slightly different. The aim of this study was to examine prevalence and characteristics of residents in difficulty in one out of three postgraduate medical training regions in Denmark, and to produce both a quantifiable overview and in-depth understanding...... of the topic. Methods We performed a mixed methods study. All regional residency program directors (N = 157) were invited to participate in an e-survey about residents in difficulty. Survey data were combined with database data on demographical characteristics of the background population (N = 2399...

  20. Role of bacterial surface structures on the interaction of Klebsiella pneumoniae with phagocytes.

    Directory of Open Access Journals (Sweden)

    Catalina March

    Full Text Available Phagocytosis is a key process of the immune system. The human pathogen Klebsiella pneumoniae is a well known example of a pathogen highly resistant to phagocytosis. A wealth of evidence demonstrates that the capsule polysaccharide (CPS plays a crucial role in resistance to phagocytosis. The amoeba Dictyostelium discoideum shares with mammalian macrophages the ability to phagocytose and kill bacteria. The fact that K. pneumoniae is ubiquitous in nature and, therefore, should avoid predation by amoebae, poses the question whether K. pneumoniae employs similar means to counteract amoebae and mammalian phagocytes. Here we developed an assay to evaluate K. pneumoniae-D. discoideum interaction. The richness of the growth medium affected the threshold at which the cps mutant was permissive for Dictyostelium and only at lower nutrient concentrations the cps mutant was susceptible to predation by amoebae. Given the critical role of bacterial surface elements on host-pathogen interactions, we explored the possible contribution of the lipopolysaccharide (LPS and outer membrane proteins (OMPs to combat phagoyctosis by D. discoideum. We uncover that, in addition to the CPS, the LPS O-polysaccharide and the first core sugar participate in Klebsiella resistance to predation by D. discoideum. K. pneumoniae LPS lipid A decorations are also necessary to avoid predation by amoebae although PagP-dependent palmitoylation plays a more important role than the lipid A modification with aminoarabinose. Mutants lacking OMPs OmpA or OmpK36 were also permissive for D. discoideium growth. Except the LPS O-polysaccharide mutants, all mutants were more susceptible to phagocytosis by mouse alveolar macrophages. Finally, we found a correlation between virulence, using the pneumonia mouse model, and resistance to phagocytosis. Altogether, this work reveals novel K. pneumoniae determinants involved in resistance to phagocytosis and supports the notion that Dictyostelium amoebae

  1. Evidence that leishmania donovani utilizes a mannose receptor on human mononuclear phagocytes to establish intracellular parasitism

    International Nuclear Information System (INIS)

    Wilson, M.E.; Pearson, R.D.

    1986-01-01

    The pathogenic protozoan Leishmania donovani must gain entrance into mononuclear phagocytes to successfully parasitize man. The parasite's extracellular promastigote stage is ingested by human peripheral blood monocytes or monocyte-derived macrophages in the absence of serum, in a manner characteristic of receptor-mediated endocytosis. Remarkable similarities have been found between the macrophage receptor(s) for promastigotes and a previously characterized eucaryotic receptor system, the mannose/fucose receptor (MFR), that mediates the binding of zymosan particles and mannose- or fucose-terminal glycoconjugates to macrophages. Ingestion of promastigotes by monocyte-derived macrophages was inhibited by several MFR ligands; that is mannan, mannose-BSA and fucose-BSA. In contrast, promastigote ingestion by monocytes was unaffected by MFR ligands. Furthermore, attachment of promastigotes to macrophages, assessed by using cytochalasin D to prevent phagocytosis, was reduced 49.8% by mannan. Reorientation of the MFR to the ventral surface of the cell was achieved by plating macrophages onto mannan-coated coverslips, reducing MFR activity on the exposed cell surface by 94% as assessed by binding of 125 I-mannose-BSA. Under these conditions, ingestion of promastigotes was inhibited by 71.4%. Internalization of the MFR by exposure of macrophages to zymosan before infection with promastigotes resulted in a 62.3% decrease in parasite ingestion. Additionally, NH 4 Cl decreased macrophage ingestion of promastigotes by 38.2%. Subinhibitory concentration of NH 4 Cl (10 mM) and of mannan (0.25 mg/ml) together inhibited parsite ingestion by 76.4%

  2. Mononuclear phagocytes contribute to intestinal invasion and dissemination of Yersinia enterocolitica.

    Science.gov (United States)

    Drechsler-Hake, Doreen; Alamir, Hanin; Hahn, Julia; Günter, Manina; Wagner, Samuel; Schütz, Monika; Bohn, Erwin; Schenke-Layland, Katja; Pisano, Fabio; Dersch, Petra; Autenrieth, Ingo B; Autenrieth, Stella E

    2016-09-01

    Enteropathogenic Yersinia enterocolitica (Ye) enters the host via contaminated food. After colonisation of the small intestine Ye invades the Peyer's patches (PPs) via M cells and disseminates to the mesenteric lymph nodes (MLNs), spleen and liver. Whether Ye uses other invasion routes and which pathogenicity factors are required remains elusive. Oral infection of lymphotoxin-β-receptor deficient mice lacking PPs and MLNs with Ye revealed similar bacterial load in the spleen 1h post infection as wild-type mice, demonstrating a PP-independent dissemination route for Ye. Immunohistological analysis of the small intestine revealed Ye in close contact with mononuclear phagocytes (MPs), specifically CX3CR1(+) monocyte-derived cells (MCs) as well as CD103(+) dendritic cells (DCs). This finding was confirmed by flow cytometry and imaging flow cytometry analysis of lamina propria (LP) leukocytes showing CD103(+) DCs and MCs with intracellular Ye. Uptake of Ye by LP CD103(+) DCs and MCs was dependent on the pathogenicity factor invasin, whereas the adhesin YadA was dispensable as demonstrated by Ye deletion mutants. Furthermore, Ye were found exclusively associated with CD103(+) DCs in the MLNs from wild-type mice, but not from CCR7(-/-) mice, demonstrating a CCR7 dependent transport of Ye by CD103(+) DCs from LP to the MLNs. In contrast, dissemination of Ye to the spleen was dependent on MCs as significantly less Ye could be recovered from the spleen of CX3CR1(GFP/GFP) mice compared to wild-type mice. Altogether, MCs and CD103(+) DCs contribute to immediate invasion and dissemination of Ye. This together with data from other bacteria suggests MPs as general pathogenic entry site in the intestine. Copyright © 2016 Elsevier GmbH. All rights reserved.

  3. Technology in Residence.

    Science.gov (United States)

    Fox, Jordan

    1999-01-01

    Discusses the necessity for incorporating current technology in today's college residence halls to meet the more diverse and continued activities of its students. Technology addressed covers data networking and telecommunications, heating and cooling systems, and fire-safety systems. (GR)

  4. Satisfaction among residents in ASHP-accredited pharmacy residency programs.

    Science.gov (United States)

    VanDenBerg, C; Murphy, J E

    1997-07-01

    The level of work satisfaction among pharmacists in ASHP-accredited residencies was studied. In March 1996 a questionnaire designed to measure residency satisfaction was mailed to 697 individuals in ASHP-accredited pharmacy practice and specialty practice residencies. Subjects responded to 16 statements relating to intrinsic and extrinsic determinants of work satisfaction on a scale of 1 to 5, where 1 = strongly disagree and 5 = strongly agree. Questionnaires were returned by 413 (59%) of the residents. The respondents were predominantly women (76%), and most (86%) had at least a Pharm. D. degree. Hospitals were the primary work setting (88%). Of the 413 residents, 305 were in pharmacy practice residencies and 108 were in specialized residencies. None of the mean scores indicated disagreement (scores 3) with the negatively worded statements. The median and mode were equal to 2 (disagree) for the three negatively worded items and 4 (agree) for all but three positively worded items. Only 8% of the residents indicated that they would not accept the residency again if given the chance. Specialized residents tended to rate positively worded statements higher and negatively worded statements lower than pharmacy practice residents. Female residents indicated greater satisfaction than male residents. Pay and benefits were rated slightly better than neutral. Pharmacy residents appeared generally satisfied with their residencies. Specialized pharmacy residents were more satisfied than pharmacy practice residents, and women were more satisfied than men.

  5. Burnout Syndrome During Residency.

    Science.gov (United States)

    Turgut, Namigar; Karacalar, Serap; Polat, Cengiz; Kıran, Özlem; Gültop, Fethi; Kalyon, Seray Türkmen; Sinoğlu, Betül; Zincirci, Mehmet; Kaya, Ender

    2016-10-01

    The aim of this study is identified the degree of Burnout Syndrome (BOS) and find out its correlation with years of recidency and sociodemograpfic chareacteristics, training, sleeping habits, such as smoking and alcohol consumption. After approval from the Hospital Ethics Committee and obtaining informed consent, First, second, third, fourth and fifth year of recidency staff (n=127) working in our hospital were involved in this study. The standardized Maslach Burnout Inventory (MBI) was used in this study. Fifty six male (44.1%) and seventy one female (55.9%) residents were enroled in this study (Coranbach Alfa(α)=0.873). 57% of the first year residents smokes cigaret and 54% of them use alcohol. 2% of them gets one day off after hospital night shift, 61% of them suffers from disturbed sleep. 60% of them had been stated that they willingly selected their profession. 61% of them prefers talking to friends and 32% of them prefers shopping to overcome stress. There were statistical difference acording to years of recidency in MBI, Emotional Burnout (EB) and desensitisation scale (DS) points. EB scale points of the second year of residency group was statisticaly higher than fourth year of residency group. DS points of second year of residency group was also statisticaly higher than the third and fourth year of residency group. There was no statistical difference between any groups in Personal Success. BOS is a frequent problem during residency in anaesthesia. Appropriate definition and awareness are the first important steps to prevent this syndrome. Further administrative approaches should be evaluated with regard to their effects.

  6. HIV impairs opsonic phagocytic clearance of pregnancy-associated malaria parasites.

    Directory of Open Access Journals (Sweden)

    Jessica Keen

    2007-05-01

    Full Text Available BACKGROUND: Primigravid (PG women are at risk for pregnancy-associated malaria (PAM. Multigravid (MG women acquire protection against PAM; however, HIV infection impairs this protective response. Protection against PAM is associated with the production of IgG specific for variant surface antigens (VSA-PAM expressed by chondroitin sulfate A (CSA-adhering parasitized erythrocytes (PEs. We hypothesized that VSA-PAM-specific IgG confers protection by promoting opsonic phagocytosis of PAM isolates and that HIV infection impairs this response. METHODS AND FINDINGS: We assessed the ability of VSA-PAM-specific IgG to promote opsonic phagocytosis of CSA-adhering PEs and the impact of HIV infection on this process. Opsonic phagocytosis assays were performed using the CSA-adherent parasite line CS2 and human and murine macrophages. CS2 PEs were opsonized with plasma or purified IgG subclasses from HIV-negative or HIV-infected PG and MG Kenyan women or sympatric men. Levels of IgG subclasses specific for VSA-PAM were compared in HIV-negative and HIV-infected women by flow cytometry. Plasma from HIV-negative MG women, but not PG women or men, promoted the opsonic phagocytosis of CSA-binding PEs (p < 0.001. This function depended on VSA-PAM-specific plasma IgG1 and IgG3. HIV-infected MG women had significantly lower plasma opsonizing activity (median phagocytic index 46 [interquartile range (IQR 18-195] versus 251 [IQR 93-397], p = 0.006 and levels of VSA-PAM-specific IgG1 (mean fluorescence intensity [MFI] 13 [IQR 11-20] versus 30 [IQR 23-41], p < 0.001 and IgG3 (MFI 17 [IQR 14-23] versus 28 [IQR 23-37], p < 0.001 than their HIV-negative MG counterparts. CONCLUSIONS: Opsonic phagocytosis may represent a novel correlate of protection against PAM. HIV infection may increase the susceptibility of multigravid women to PAM by impairing this clearance mechanism.

  7. Delayed polarization of mononuclear phagocyte transcriptional program by type I interferon isoforms

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    Wang Ena

    2005-06-01

    Full Text Available Abstract Background Interferon (IFN-α is considered a key modulator of immunopathological processes through a signature-specific activation of mononuclear phagocytes (MPs. This study utilized global transcript analysis to characterize the effects of the entire type I IFN family in comparison to a broad panel of other cytokines on MP previously exposed to Lipopolysaccharide (LPS stimulation in vitro. Results Immature peripheral blood CD14+ MPs were stimulated with LPS and 1 hour later with 42 separate soluble factors including cytokines, chemokines, interleukins, growth factors and IFNs. Gene expression profiling of MPs was analyzed 4 and 9 hours after cytokine stimulation. Four hours after stimulation, the transcriptional analysis of MPs revealed two main classes of cytokines: one associated with the alternative and the other with the classical pathway of MP activation without a clear polarization of type I IFNs effects. In contrast, after 9 hours of stimulation most type I IFN isoforms induced a characteristic and unique transcriptional pattern separate from other cytokines. These "signature" IFNs included; IFN-β, IFN-α2b/α2, IFN-αI, IFN-α2, IFN-αC, IFN-αJ1, IFN-αH2, and INF-α4B and induced the over-expression of 44 genes, all of which had known functional relationships with IFN such as myxovirus resistance (Mx-1, Mx-2, and interferon-induced hepatitis C-associated microtubular aggregation protein. A second group of type I IFNs segregated separately and in closer association with the type II IFN-γ. The phylogenetic relationship of amino acid sequences among type I IFNs did not explain their sub-classification, although differences at positions 94 through 109 and 175 through 189 were present between the signature and other IFNs. Conclusion Seven IFN-α isoforms and IFN-β participate in the late phase polarization of MPs conditioned by LPS. This information broadens the previous view of the central role played by IFN-α in

  8. Behçet's disease heterogeneity: cytokine production and oxidative burst of phagocytes are altered in patients with severe manifestations.

    Science.gov (United States)

    Perazzio, Sandro F; Soeiro-Pereira, Paulo Vitor; de Souza, Alexandre Wagner S; Condino-Neto, Antônio; Andrade, Luis Eduardo C

    2015-01-01

    To test the hypothesis that classical phagocytic functions are constitutively stimulated in patients with Behçet's disease (BD). Four study groups were analysed: active BD (aBD; n=30), inactive BD (iBD; n=31); septic patients (SP; n=25); healthy controls (HC; n=30). Microbicide activity against Streptococcus pneumoniae, Streptococcus sanguinis and Candida albicans was determined by means of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and absorbance read by ELISA. Flow cytometry analysis evaluated phagocytosis (zymosan particles and microrganisms) and oxidative burst by dihidrorhodamine oxidation before and after stimulation with phorbol myristate acetate (PMA). The supernatant of PBMC cultures under TLR or microbial stimuli and of neutrophil cultures under PMA, LPS or microbial stimuli were used for determination of cytokine production by ELISA. We found no significant differences between the BD patient groups and control groups with regard to oxidative burst, phagocytic activity, microbicide activity or cytokine production. However, the cells from patients with severe BD (based on clinical manifestation) exhibit significantly higher oxidative burst activity, both before and after PMA stimulation, compared to cells from patients with mild BD. Furthermore, we found significant correlations between the BD patients' scores on the simplified Behçet's Disease Current Activity Form adapted for Portuguese (BR-BDCAFs) and Streptococcus sanguinis-stimulated production of IL23 by PBMC and IL8 by neutrophils, and between BR-BDCAFs score and constitutive production of TNF-α, IFNγ, IL6 and IL23 by PBMC. Patients with severe active BD do exhibit phagocytic dysfunction and some evidence of constitutive activation regarding oxidative burst and cytokine production.

  9. Analysis of Resident Case Logs in an Anesthesiology Residency Program

    DEFF Research Database (Denmark)

    Yamamoto, Satoshi; Tanaka, Pedro; Madsen, Matias Vested

    2016-01-01

    Our goal in this study was to examine Accreditation Council for Graduate Medical Education case logs for Stanford anesthesia residents graduating in 2013 (25 residents) and 2014 (26 residents). The resident with the fewest recorded patients in 2013 had 43% the number of patients compared with the...

  10. Residents as teachers: survey of Canadian family medicine residents.

    Science.gov (United States)

    Ng, Victor K; Burke, Clarissa A; Narula, Archna

    2013-09-01

    To examine Canadian family medicine residents' perspectives surrounding teaching opportunities and mentorship in teaching. A 16-question online survey. Canadian family medicine residency programs. Between May and June 2011, all first- and second-year family medicine residents registered in 1 of the 17 Canadian residency programs as of September 2010 were invited to participate. A total of 568 of 2266 residents responded. Demographic characteristics, teaching opportunities during residency, and resident perceptions about teaching. A total of 77.7% of family medicine residents indicated that they were either interested or highly interested in teaching as part of their future careers, and 78.9% of family medicine residents had had opportunities to teach in various settings. However, only 60.1% of respondents were aware of programs within residency intended to support residents as teachers, and 33.0% of residents had been observed during teaching encounters. It appears that most Canadian family medicine residents have the opportunity to teach during their residency training. Many are interested in integrating teaching as part of their future career goals. Family medicine residencies should strongly consider programs to support and further develop resident teaching skills.

  11. RpoS contributes to phagocyte oxidase-mediated stress resistance during urinary tract infection by Escherichia coli CFT073.

    Science.gov (United States)

    Hryckowian, Andrew J; Welch, Rodney A

    2013-02-12

    Uropathogenic Escherichia coli (UPEC) is the most common causative agent of community-acquired urinary tract infection (UTI). In order to cause UTI, UPEC must endure stresses ranging from nutrient limitation to host immune components. RpoS (σ(S)), the general stress response sigma factor, directs gene expression under a variety of inhibitory conditions. Our study of rpoS in UPEC strain CFT073 began after we discovered an rpoS-frameshift mutation in one of our laboratory stocks of "wild-type" CFT073. We demonstrate that an rpoS-deletion mutation in CFT073 leads to a colonization defect during UTI of CBA/J mice at 48 hours postinfection (hpi). There is no difference between the growth rates of CFT073 and CFT073 rpoS in urine. This indicates that rpoS is needed for replication and survival in the host rather than being needed to address limitations imposed by urine nutrients. Consistent with previous observations in E. coli K-12, CFT073 rpoS is more sensitive to oxidative stress than the wild type. We demonstrate that peroxide levels are elevated in voided urine from CFT073-infected mice compared to urine from mock-infected mice, which supports the notion that oxidative stress is generated by the host in response to UPEC. In mice that lack phagocyte oxidase, the enzyme complex expressed by phagocytes that produces superoxide, the competitive defect of CFT073 rpoS in bladder colonization is lost. These results demonstrate that σ(S) is important for UPEC survival under conditions of phagocyte oxidase-generated stress during UTI. Though σ(S) affects the pathogenesis of other bacterial species, this is the first work that directly implicates σ(S) as important for UPEC pathogenesis. UPEC must cope with a variety of stressful conditions in the urinary tract during infection. RpoS (σ(S)), the general stress response sigma factor, is known to direct the expression of many genes under a variety of stressful conditions in laboratory-adapted E. coli K-12. Here, we show that

  12. Trastuzumab triggers phagocytic killing of high HER2 cancer cells in vitro and in vivo by interaction with Fcγ receptors on macrophages.

    Science.gov (United States)

    Shi, Yun; Fan, Xuejun; Deng, Hui; Brezski, Randall J; Rycyzyn, Michael; Jordan, Robert E; Strohl, William R; Zou, Quanming; Zhang, Ningyan; An, Zhiqiang

    2015-05-01

    Trastuzumab has been used for the treatment of HER2-overexpressing breast cancer for more than a decade, but the mechanisms of action for the therapy are still being actively investigated. Ab-dependent cell-mediated cytotoxicity mediated by NK cells is well recognized as one of the key mechanisms of action for trastuzumab, but trastuzumab-mediated Ab-dependent cellular phagocytosis (ADCP) has not been established. In this study, we demonstrate that macrophages, by way of phagocytic engulfment, can mediate ADCP and cancer cell killing in the presence of trastuzumab. Increased infiltration of macrophages in the tumor tissue was associated with enhanced efficacy of trastuzumab whereas depletion of macrophages resulted in reduced antitumor efficacy in mouse xenograft tumor models. Among the four mouse FcγRs, FcγRIV exhibits the strongest binding affinity to trastuzumab. Knockdown of FcγRIV in mouse macrophages reduced cancer cell killing and ADCP activity triggered by trastuzumab. Consistently, an upregulation of FcγRIV expression by IFN-γ triggered an increased ADCP activity by trastuzumab. In an analogous fashion, IFN-γ priming of human macrophages increased the expression of FcγRIII, the ortholog of murine FcγRIV, and increased trastuzumab-mediated cancer cell killing. Thus, in two independent systems, the results indicated that activation of macrophages in combination with trastuzumab can serve as a therapeutic strategy for treating high HER2 breast cancer by boosting ADCP killing of cancer cells. Copyright © 2015 by The American Association of Immunologists, Inc.

  13. Isolation and functional characterization of mononuclear phagocytes from human lepromatous lesions

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    Euzenir Nunes Sarno

    1987-12-01

    Full Text Available In the present study, inflammatory cells from human lepromatous lesions were isolated by enzymatic dissociation of tissue. They were maintained in culture up to five days and their morphologic, cythochemicaland functional characteristics were described.

  14. ROLE OF MONOCYTE PHAGOCYTIC SYSTEM IN FORMATION OF ANTIVIRAL RESISTANCE IN MICE AFTER PRELIMINARY INJECTION OF CRYOPRESERVED CORD BLOOD

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    Kozhina OYu

    2013-03-01

    Full Text Available Now the task of preventive maintenance and search of biologically active substances, capable to make active the nonspecific immune response, remains an actual during flu epidemic. It has been previously established, that cryopreserved leucoconcentrate of human cord blood (cLHCB can act as modulator of activity of immunity. In the given work there was estimated influence of preventive injection of cLHCB and its components on functional activity of monocyte phagocytic system cells (MPSC in mice in the conditions of the induced influenzal infection. Preliminary introduction of cLHCB and its components 6 months prior to infection by flu virus makes 2 times increase of functional activity of macrophages, preventing inhibition of a nonspecific link of immunity. Thus, cLHCB inhibit of secondary immune deficiency development. The found increase in phagocytic activity of peritoneal cavity cells and 3 times increasesing of CD11b-marker expression after preventive injection of cLHCB testifies to rise of adherence and protective potential of MPSC that is one of possible mechanisms of formation of resistance to a flu virus. It is shown, that intranasal cLHCB injection before development of viral infection it can be o recommended as the method of preventive maintenance of flu.

  15. The Use of Selected Biomarkers, Phagocytic and Cholinesterase Activity to Detect the Effects of Dimethoate on Marine Mussel (Mytilus edulis

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    KHUSNUL YAQIN

    2008-03-01

    Full Text Available Effects of organophosphorous pesticide, dimethoate on blue mussels, Mytilus edulis using selected biomarkers have been studied. Mussels were exposed to serial dilutions of dimethoate, 7.88, 15.75, 31.35, and 63.00 µg/l including positive and negative controls for 14 days. The suppression effects of dimethoate on phagocytic activity significantly occurred at two lowest concentrations of dimethoate (7.88 and 15.75 µg/l, but stimulation effects significantly emerged at the following highest concentrations (31.35 and 63.00 µg/l. The declining tendency of the cholinesterase (ChE activity (23% lower than the control appeared when mussels exposed to 7.88 and 15.75 µg/l dimethoate. Moreover, the significant inhibition of the ChE activity occurred at 31.35 µg/l dimethoate exposure. This study suggested that the phagocytic and the ChE activity are useful biomarkers for assessing the affects of organophosporous pesticide, dimethoate on neuro-immune system of blue mussels, M. edulis.

  16. Phagocytic response to fully controlled plural stimulation of antigens on macrophage using on-chip microcultivation system

    Directory of Open Access Journals (Sweden)

    Wakamoto Yuichi

    2006-08-01

    Full Text Available Abstract To understand the control mechanism of innate immune response in macrophages, a series of phagocytic responses to plural stimulation of antigens on identical cells was observed. Two zymosan particles, which were used as antigens, were put on different surfaces of a macrophage using optical tweezers in an on-chip single-cell cultivation system, which maintains isolated conditions of each macrophage during their cultivation. When the two zymosan particles were attached to the macrophage simultaneously, the macrophage responded and phagocytosed both of the antigens simultaneously. In contrast, when the second antigen was attached to the surface after the first phagocytosis had started, the macrophage did not respond to the second stimulation during the first phagocytosis; the second phagocytosis started only after the first process had finished. These results indicate that (i phagocytosis in a macrophage is not an independent process when there are plural stimulations; (ii the response of the macrophage to the second stimulation is related to the time" delay from the first stimulation. Stimulations that occur at short time intervals resulted in simultaneous phagocytosis, while a second stimulation that is delayed long enough might be neglected until the completion of the first phagocytic process.

  17. Change in Performance of BALB/c Mouse Pulmonary Macrophage Surface Receptor after Exercise and its Influence on Phagocytic Activity

    Directory of Open Access Journals (Sweden)

    Ming Zhang

    2015-09-01

    Full Text Available Objective: To study the effect of exercise on phagocytosis by pulmonary bronchoalveolar macrophages (BAMs. Methods: A total of 120 seven- to nine-week-old male BALB/c mice were randomly assigned into the following groups based on exercise intensity on a treadmill: control exercise (CE group, acute moderate exercise (ME group, and strenuous exercise group. Lung lavage was conducted to collect BAMs from the mice. Phagocytic behavior and surface receptor expression on BALB/c mouse BAMs were analyzed through fluorescence microscopy and flow cytometry. Results: In the SE group, expression levels of macrophage scavenger receptors (surface receptor [SR-A] type I/II and macrophage receptor [MARCO], complement receptor3 (CR3, and intercellular adhesion molecule 1 (ICAM-1 were upregulated; by contrast, expression level of extensive G-type immune globulin receptor (Fc Rs was not upregulated. The promoting percentage of phagocytosis in the CE group was 100%; the highest promoting percentage of phagocytosis was 161% observed in MARCO, followed by 116% detected in CR3; the promoting percentage of phagocytosis found in SR-A type I/II and ICAM-1 increased by approximately 65%. Indeed, these scavenger receptors were involved in phagocytosis induced by macrophages. MARCO was also necessary to elicit a stimulatory effect on macrophage phagocytic activity. Conclusions: The phagocytosis of unopsonized particles was possibly mediated by MARCO expression.

  18. The Staphylococcal Toxins γ-Hemolysin AB and CB Differentially Target Phagocytes by Employing Specific Chemokine Receptors

    Science.gov (United States)

    Spaan, András N.; Vrieling, Manouk; Wallet, Pierre; Badiou, Cédric; Reyes-Robles, Tamara; Ohneck, Elizabeth A.; Benito, Yvonne; de Haas, Carla J.C.; Day, Christopher J.; Jennings, Michael P.; Lina, Gérard; Vandenesch, François; van Kessel, Kok P.M.; Torres, Victor J.; van Strijp, Jos A.G.; Henry, Thomas

    2014-01-01

    Evasion of the host phagocyte response by Staphylococcus aureus is crucial to successful infection with the pathogen. γ-Hemolysin AB and CB (HlgAB, HlgCB) are bicomponent pore-forming toxins present in almost all human S. aureus isolates. Cellular tropism and contribution of the toxins to S. aureus pathophysiology are poorly understood. Here, we identify the chemokine receptors CXCR1, CXCR2 and CCR2 as targets for HlgAB, and the complement receptors C5aR and C5L2 as targets for HlgCB. The receptor expression patterns allow the toxins to efficiently and differentially target phagocytic cells. Murine neutrophils are resistant to HlgAB and HlgCB. CCR2 is the sole murine receptor orthologue compatible with γ-Hemolysin. In a murine peritonitis model, HlgAB contributes to S. aureus bacteremia in a CCR2-dependent manner. HlgAB-mediated targeting of CCR2+ cells highlights the involvement of inflammatory macrophages during S. aureus infection. Functional quantification identifies HlgAB and HlgCB as major secreted staphylococcal leukocidins. PMID:25384670

  19. Effects of creosote exposure on rainbow trout pronephros phagocyte activity and the percentage of lymphoid B cells.

    Science.gov (United States)

    Karrow, N A; Bols, N C; Whyte, J J; Solomon, K R; Dixon, D G; Boermans, H J

    2001-07-06

    An outdoor microcosm study was conducted in order to evaluate the kinetics of immunomodulation in rainbow trout (Oncorhynchus mykiss) exposed to liquid creosote. Fish were sampled on d 7, 14, 21, and 28 from microcosms dosed initially with 0, 3, and 10 microl/L of creosote. Pronephros leukocytes were monitored for phagocytic activity, oxidative burst, and surface immunoglobulin-positive (Slg+) B-cell counts. Oxidative burst was inhibited by creosote exposure; however, by sampling d 28, the burst response returned to near control levels. Phagocytic activity, on the other hand, was stimulated, peaking on sampling d 7, then returning to near control levels by d 28. Although control Slg+ B-cell counts were quite variable across sampling days, Slg+ B-cell counts were also elevated in creosote-exposed fish after seven days of exposure. Slg+ B-cell numbers decreased significantly to near control levels during the remainder of the study. The overall results from this study confirm that creosote has the potential to alter certain immune parameters, and emphasize the importance of monitoring changes in the immune system during exposure. Polycyclic aromatic hydrocarbons (PAHs), a major constituent of liquid creosote, are the suspected immune-altering agents.

  20. Resident fatigue in otolaryngology residents: a Web based survey.

    Science.gov (United States)

    Nida, Andrew M; Googe, Benjamin J; Lewis, Andrea F; May, Warren L

    2016-01-01

    Resident fatigue has become a point of emphasis in medical education and its effects on otolaryngology residents and their patients require further study. The purpose of our study was to evaluate the prevalence and nature of fatigue in otolaryngology residents, evaluate various quality of life measures, and investigate associations of increased fatigue with resident safety. Anonymous survey. Internet based. United States allopathic otolaryngology residents. None. The survey topics included demographics, residency structure, sleep habits and perceived stress. Responses were correlated with a concurrent Epworth Sleep Scale questionnaire to evaluate effects of fatigue on resident training and quality of life. 190 residents responded to the survey with 178 completing the Epworth Sleep Scale questionnaire. Results revealed a mean Epworth Sleep Scale score of 9.9±5.1 with a median of 10.0 indicating a significant number of otolaryngology residents are excessively sleepy. Statistically significant correlations between Epworth Sleep Scale and sex, region, hours of sleep, and work hours were found. Residents taking in-house call had significantly fewer hours of sleep compared to home call (p=0.01). Residents on "head and neck" (typically consisting of a large proportion of head and neck oncologic surgery) rotations tended to have higher Epworth Sleep Scale and had significantly fewer hours of sleep (p=.003) and greater work hours (potolaryngology residents are excessively sleepy. Our data suggest that the effects of fatigue play a role in resident well-being and resident safety. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Comparative opsonic activity for Steptococcus mutans in oral fluids, and phagocytic activity of blood, crevicular, and salivary polymorphonuclear leucocytes in rhesus monkeys.

    Science.gov (United States)

    Scully, C M

    1980-01-01

    The opsonic activity for Streptococcus mutans was assayed in serum, gingival crevicular fluid, parotid saliva and mixed saliva from rhesus monkeys immunized against dental caries with a vaccine of Streptococcus mutans in Freund's incomplete adjuvant. The phagocytic activities of polymorphonuclear leucocytes from the blood and gingival crevice were compared, and the effects of gingival crevicular fluid and mixed saliva on blood polymorphonuclear leucocyte viability and phagocytic activity were assessed. Heat-stable opsonic activity was detected in sera, crevicular fluid, and mixed saliva of immunized animals. Polymorphonuclear leucocytes from the gingival crevice and saliva retained viability, although this was lower than in cells from blood. Exposure of blood polymorphonuclear leucocytes to crevicular fluid or mixed saliva for 30 min resulted in no loss of cell viability or phagocytic activity, but saliva was cytotoxic on prolonged exposure. These results support the hypothesis that the opsonization and phagocytosis of cariogenic bacteria might be a mechanism involved in the immunological protection against dental caries.

  2. Enhancing effects of gamma interferon on phagocytic cell association with and killing of Trypanosoma cruzi

    Science.gov (United States)

    Wirth, J. J.; Kierszenbaum, F.; Sonnenfeld, G.; Zlotnik, A.

    1985-01-01

    Results are reported from a study of the influence gamma interferon (GIFN) and interleukin 2 (IL2) have on the capability of P388D1 cells and mouse resident peritoneal macrophages (MPM) to attach to the blood-resident parasites Trypanosoma cruzi and kill them. Cultures of trypomastigote forms of the Tulahuen strain of T. cruzi grown in bovine serum were introduced into peritoneal cells of mice, along with P388D1 cells incubated with GIFN, IL2 and both. Control cells were also maintained. Statistical analysis were then performed on data on counts of the number of dead T. Cruzi cells. The GIFN enhanced the interaction of MPM and P388D1 cells with the surface of T. Cruzi, provided the interaction was given over 12 hr to take place. A depression of the cytotoxicity of P388D1 cells was attributed to mediation by H2O2, an effect partially offset by incubation with the lymphokine GIFN.

  3. Leadership Training in Otolaryngology Residency.

    Science.gov (United States)

    Bent, John P; Fried, Marvin P; Smith, Richard V; Hsueh, Wayne; Choi, Karen

    2017-06-01

    Although residency training offers numerous leadership opportunities, most residents are not exposed to scripted leadership instruction. To explore one program's attitudes about leadership training, a group of otolaryngology faculty (n = 14) and residents (n = 17) was polled about their attitudes. In terms of self-perception, more faculty (10 of 14, 71.4%) than residents (9 of 17, 52.9%; P = .461) considered themselves good leaders. The majority of faculty and residents (27 of 31) thought that adults could be taught leadership ability. Given attitudes about leadership ability and the potential for improvement through instruction, consideration should be given to including such training in otolaryngology residency.

  4. High content analysis of phagocytic activity and cell morphology with PuntoMorph

    DEFF Research Database (Denmark)

    Al-Ali, Hassan; Gao, Han; Dalby-Hansen, Camilla

    2017-01-01

    Background Phagocytosis is essential for maintenance of normal homeostasis and healthy tissue. As such, it is a therapeutic target for a wide range of clinical applications. The development of phenotypic screens targeting phagocytosis has lagged behind, however, due to the difficulties associated......, PuntoMorph....

  5. Lawful Permanent Residents - Annual Report

    Data.gov (United States)

    Department of Homeland Security — A lawful permanent resident (LPR) or 'green card' recipient is defined by immigration law as a person who has been granted lawful permanent residence in the United...

  6. Interaction between Salmonella typhimurium and phagocytic cells in pigs - Phagocytosis, oxidative burst and killing in polymorphonuclear leukocytes and monocytes

    DEFF Research Database (Denmark)

    Riber, Ulla; Lind, Peter

    1999-01-01

    with the exhaustion of oxidative burst in non-adherent monocytes were performed by prestimulation with PMA, heat-killed Salmonella or buffer. Prestimulation with PMA led to a strong reduction in oxidative burst induced by living opsonized Salmonella bacteria, whereas prestimulation with heat-killed bacteria gave rise......Interactions between Salmonella typhimurium and peripheral blood leucocytes from healthy, Salmonella-free pigs were investigated in vitro. Both granulocytes and monocytes phagocytized FITC-labelled heat-killed Salmonella bacteria as shown by flow cytometry. Phagocytosis in whole blood and isolated...... leucocytes was measured as acquired fluorescence in the leukocytes and was both time and dose related. Living, serum-opsonized Salmonella bacteria induced a dose-dependent oxidative burst in PMNs and monocytes as measured by luminol-enhanced chemiluminescence (LC). When opsonized in normal serum...

  7. Lipofuscin-mediated photic stress inhibits phagocytic activity of ARPE-19 cells; effect of donors' age and antioxidants.

    Science.gov (United States)

    Olchawa, Magdalena M; Furso, Justyna A; Szewczyk, Grzegorz M; Sarna, Tadeusz J

    2017-10-01

    The risk of chronic oxidative stress in the retinal pigment epithelium (RPE) increases with age due to accumulation of the photoreactive age pigment lipofuscin (LFG). Here, we asked whether sublethal and weakly lethal photic stress, induced by irradiation of ARPE-19 cells containing phagocytised LFG, affected the cell specific phagocytic activity, which is critically important for proper functioning and survival of the retina, and if natural antioxidants could modify the observed outcomes. ARPE-19 cells preloaded with LFG isolated from human donors of different age or containing LFG enriched with zeaxanthin and α-tocopherol (LFG-A), were irradiated with blue light. Phagocytosis of fluorescein-5-isothiocyanate (FITC)-labelled photoreceptor outer segments was determined by flow cytometry. Photoreactivity of LFG and LFG-A was analysed by measuring photoconsumption of oxygen and photogeneration of singlet oxygen mediated by the granules. LFG-mediated photic stress in ARPE-19 cells induced significant inhibition of their specific phagocytosis. The inhibitory effect increased with age of LFG donors and was reduced by enrichment of the granules with antioxidants. Oxygen consumption and generation of singlet oxygen induced by the photoexcited LFG increased with donor's age and was partially quenched by antioxidants. Although the phototoxic potential of lipofuscin increased with age, natural antioxidants reduced photoreactivity of LFG and their efficiency to induce oxidative stress. This study has demonstrated, for the first time, that mild oxidative stress, mediated by the age pigment lipofuscin, impairs specific phagocytic activity of RPE, and that natural antioxidants can protect this important cellular function by reducing lipofuscin photoreactivity.

  8. The specificity of immune priming in silkworm, Bombyx mori, is mediated by the phagocytic ability of granular cells.

    Science.gov (United States)

    Wu, Gongqing; Li, Mei; Liu, Yi; Ding, Ying; Yi, Yunhong

    2015-10-01

    In the past decade, the phenomenon of immune priming was documented in many invertebrates in a large number of studies; however, in most of these studies, behavioral evidence was used to identify the immune priming. The underlying mechanism and the degree of specificity of the priming response remain unclear. We studied the mechanism of immune priming in the larvae of the silkworm, Bombyx mori, and analyzed the specificity of the priming response using two closely related Gram-negative pathogenic bacteria (Photorhabdus luminescens TT01 and P. luminescens H06) and one Gram-positive pathogenic bacterium (Bacillus thuringiensis HD-1). Primed with heat-killed bacteria, the B. mori larvae were more likely to survive subsequent homologous exposure (the identical bacteria used in the priming and in the subsequent challenge) than heterologous (different bacteria used in the priming and subsequent exposure) exposure to live bacteria. This result indicated that the B. mori larvae possessed a strong immune priming response and revealed a degree of specificity to TT01, H06 and HD-1 bacteria. The degree of enhanced immune protection was positively correlated with the level of phagocytic ability of the granular cells and the antibacterial activity of the cell-free hemolymph. Moreover, the granular cells of the immune-primed larvae increased the phagocytosis of a previously encountered bacterial strain compared with other bacteria. Thus, the enhanced immune protection of the B. mori larvae after priming was mediated by the phagocytic ability of the granular cells and the antibacterial activity of the hemolymph; the specificity of the priming response was primarily attributed to the phagocytosis of bacteria by the granular cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Profiling the lymphoid-resident T cell pool reveals modulation by age and microbiota.

    Science.gov (United States)

    Durand, Aurélie; Audemard-Verger, Alexandra; Guichard, Vincent; Mattiuz, Raphaël; Delpoux, Arnaud; Hamon, Pauline; Bonilla, Nelly; Rivière, Matthieu; Delon, Jérôme; Martin, Bruno; Auffray, Cédric; Boissonnas, Alexandre; Lucas, Bruno

    2018-01-04

    Despite being implicated in non-lymphoid tissues, non-recirculating T cells may also exist in secondary lymphoid organs (SLO). However, a detailed characterization of this lymphoid-resident T cell pool has not yet been done. Here we show that a substantial proportion of CD4 regulatory (Treg) and memory (Tmem) cells establish long-term residence in the SLOs of specific pathogen-free mice. Of these SLOs, only T cell residence within Peyer's patches is affected by microbiota. Resident CD4 Treg and CD4 Tmem cells from lymph nodes and non-lymphoid tissues share many phenotypic and functional characteristics. The percentage of resident T cells in SLOs increases considerably with age, with S1PR1 downregulation possibly contributing to this altered homeostasis. Our results thus show that T cell residence is not only a hallmark of non-lymphoid tissues, but can be extended to secondary lymphoid organs.

  10. Inhibitory Effects of Standardized Extracts of Phyllanthus amarus and Phyllanthus urinaria and Their Marker Compounds on Phagocytic Activity of Human Neutrophils

    Directory of Open Access Journals (Sweden)

    Yuandani

    2013-01-01

    Full Text Available The standardized methanol extracts of Phyllanthus amarus and P. urinaria, collected from Malaysia and Indonesia, and their isolated chemical markers, phyllanthin and hypophyllanthin, were evaluated for their effects on the chemotaxis, phagocytosis and chemiluminescence of human phagocytes. All the plant extracts strongly inhibited the migration of polymorphonuclear leukocytes (PMNs with the Malaysian P. amarus showing the strongest inhibitory activity (IC50 value, 1.1 µg/mL. There was moderate inhibition by the extracts of the bacteria engulfment by the phagocytes with the Malaysian P. amarus exhibiting the highest inhibition (50.8% of phagocytizing cells. The Malaysian P. amarus and P. urinaria showed strong reactive oxygen species (ROS inhibitory activity, with both extracts exhibiting IC50 value of 0.7 µg/mL. Phyllanthin and hypophyllanthin exhibited relatively strong activity against PMNs chemotaxis, with IC50 values slightly lower than that of ibuprofen (1.4 µg/mL. Phyllanthin exhibited strong inhibitory activity on the oxidative burst with an IC50 value comparable to that of aspirin (1.9 µg/mL. Phyllanthin exhibited strong engulfment inhibitory activity with percentage of phagocytizing cells of 14.2 and 27.1% for neutrophils and monocytes, respectively. The strong inhibitory activity of the extracts was due to the presence of high amounts of phyllanthin and hypophyllanthin although other constituents may also contribute.

  11. The effect of core and lanthanide ion dopants in sodium fluoride-based nanocrystals on phagocytic activity of human blood leukocytes

    Energy Technology Data Exchange (ETDEWEB)

    Sojka, Bartlomiej [Wroclaw University of Science and Technology, Department of Experimental Physics (Poland); Liskova, Aurelia; Kuricova, Miroslava [Slovak Medical University, Medical Faculty, Department of Immunology and Immunotoxicology (Slovakia); Banski, Mateusz; Misiewicz, Jan [Wroclaw University of Science and Technology, Department of Experimental Physics (Poland); Dusinska, Maria [Norwegian Institute for Air Research, Health Effects Laboratory, Department of Environmental Chemistry (Norway); Horvathova, Mira; Ilavska, Silvia; Szabova, Michaela [Slovak Medical University, Medical Faculty, Department of Immunology and Immunotoxicology (Slovakia); Rollerova, Eva [Slovak Medical University, Faculty of Public Health, Department of Toxicology (Slovakia); Podhorodecki, Artur, E-mail: artur.p.podhorodecki@pwr.edu.pl [Wroclaw University of Science and Technology, Department of Experimental Physics (Poland); Tulinska, Jana, E-mail: jana.tulinska@szu.sk [Slovak Medical University, Medical Faculty, Department of Immunology and Immunotoxicology (Slovakia)

    2017-02-15

    Sodium fluoride-based β-NaLnF4 nanoparticles (NPs) doped with lanthanide ions are promising materials for application as luminescent markers in bio-imaging. In this work, the effect of NPs doped with yttrium (Y), gadolinium (Gd), europium (Eu), thulium (Tm), ytterbium (Yb) and terbium (Tb) ions on phagocytic activity of monocytes and granulocytes and the respiratory burst was examined. The surface functionalization of <10-nm NPs was performed according to our variation of patent pending ligand exchange method that resulted in meso-2,3-dimercaptosuccinic acid (DMSA) molecules on their surface. Y-core-based NCs were doped with Eu ions, which enabled them to be excited with UV light wavelengths. Cultures of human peripheral blood (n = 8) were in vitro treated with five different concentrations of eight NPs for 24 h. In summary, neither type of nanoparticles is found toxic with respect to conducted test; however, some cause toxic effects (they have statistically significant deviations compared to reference) in some selected doses tested. Both core types of NPs (Y-core and Gd-core) impaired the phagocytic activity of monocytes the strongest, having minimal or none whatsoever influence on granulocytes and respiratory burst of phagocytic cells. The lowest toxicity was observed in Gd-core, Yb, Tm dopants and near-infrared nanoparticles. Clear dose-dependent effect of NPs on phagocytic activity of leukocytes and respiratory burst of cells was observed for limited number of samples.

  12. Isolation and functional characterization of mononuclear phagocytes from human lepromatous lesions

    Directory of Open Access Journals (Sweden)

    Euzenir Nunes Sarno

    1987-12-01

    Full Text Available In the present study, inflammatory cells from human lepromatous lesions were isolated by enzymatic dissociation of tissue. They were maintained in culture up to five days and their morphologic, cythochemicaland functional characteristics were described.Células inflamatórias presentes em lesões Virchowianas humanas foram isoladas do tecido por um processo de digestão enzimática. Elas foram mantidas em cultura por cerca de 5 dias e suas características morfológicas citoquímicas efuncionaisforam descritas.

  13. Tissue engineering

    CERN Document Server

    Fisher, John P; Bronzino, Joseph D

    2007-01-01

    Increasingly viewed as the future of medicine, the field of tissue engineering is still in its infancy. As evidenced in both the scientific and popular press, there exists considerable excitement surrounding the strategy of regenerative medicine. To achieve its highest potential, a series of technological advances must be made. Putting the numerous breakthroughs made in this field into a broad context, Tissue Engineering disseminates current thinking on the development of engineered tissues. Divided into three sections, the book covers the fundamentals of tissue engineering, enabling technologies, and tissue engineering applications. It examines the properties of stem cells, primary cells, growth factors, and extracellular matrix as well as their impact on the development of tissue engineered devices. Contributions focus on those strategies typically incorporated into tissue engineered devices or utilized in their development, including scaffolds, nanocomposites, bioreactors, drug delivery systems, and gene t...

  14. Education Research: Neurology resident education

    Science.gov (United States)

    Mayans, David; Schneider, Logan; Adams, Nellie; Khawaja, Ayaz M.; Engstrom, John

    2016-01-01

    Objective: To survey US-trained graduating neurology residents who are American Academy of Neurology members, in an effort to trend perceived quality and completeness of graduate neurology education. Methods: An electronic survey was sent to all American Academy of Neurology members graduating from US neurology residency programs in the Spring of 2014. Results: Of 805 eligible respondents, 24% completed the survey. Ninety-three percent of adult neurology residents and 56% of child neurology residents reported plans to pursue fellowship training after residency. Respondents reported a desire for additional training in neurocritical care, neuro-oncology, neuromuscular diseases, botulinum toxin injection, and nerve blocks. There remains a clear deficit in business training of neurology residents, although there was notable improvement in knowledge of coding and office management compared to previous surveys. Discussion: Although there are still areas of perceived weakness in neurology training, graduating neurology residents feel generally well prepared for their chosen careers. However, most still pursue fellowship training for reasons that are little understood. In addition to certain subspecialties and procedures, practice management remains deficient in neurology training and is a point of future insecurity for most residents. Future curriculum changes should consider resident-reported gaps in knowledge, with careful consideration of improving business training. PMID:26976522

  15. Factors Influencing Resident Choice of Prosthodontic Residency Program.

    Science.gov (United States)

    Wojnarwsky, Pandora Keala Lee; Wang, Yan; Shah, Kumar; Koka, Sreenivas

    2017-06-01

    The decision by prosthodontic residency program directors to employ the Match process highlights the need to understand applicant priorities that influence their choice of which programs to rank highly. The purpose of this study is to determine the factors that were most important to residents when choosing from among nonmilitary based prosthodontics dental residency programs in the United States. Following completion of a pilot study, all currently enrolled prosthodontic residents at nonmilitary residency programs were invited to participate via the internet. The study consisted of a survey instrument asking residents to rank 26 possible factors that might impact an applicant's choice of residency program. In addition, the instrument collected other possible influencing variables including gender and debt load. Mean rank scores were compared to determine the most and least important factors. Kruskal-Wallis test was used to compare specific factors between the possible influencing variables. Two hundred and thirty residents completed the survey instrument, representing a 54.1% response rate of possible participants. With regard to factors influencing program choice, reputation of the residency program was the factor ranked the highest by participants, followed in descending order by the program director's personality, curriculum content, access to use of the latest digital technology, and opportunities for dental implant placement. Quality of schools for children, community outreach opportunities, and the ability to moonlight were ranked as the least important factors. Male and female residents ranked factors such as tuition/stipend, curriculum content, and community outreach opportunities significantly differently. Depending on debt load, residents ranked the factors tuition/stipend, ability to moonlight, curriculum content, and safety of the area where the program is differently. Current prosthodontic residents valued the reputation of the program as the most

  16. Pathology Informatics Essentials for Residents

    Science.gov (United States)

    Karcher, Donald S.; Harrison, James H.; Sinard, John H.; Riben, Michael W.; Boyer, Philip J.; Plath, Sue; Thompson, Arlene; Pantanowitz, Liron

    2016-01-01

    Context: Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics has been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. Objective: To develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills, and meets Accreditation Council for Graduate Medical Education Informatics Milestones. Design: The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. Results: Pathology Informatics Essentials for Residents (PIER) is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http://www.apcprods.org/PIER (accessed April 6, 2016). Conclusions: PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time. PMID:28725772

  17. Pathology Informatics Essentials for Residents

    Directory of Open Access Journals (Sweden)

    Walter H. Henricks MD

    2016-07-01

    Full Text Available Context: Recognition of the importance of informatics to the practice of pathology has surged. Training residents in pathology informatics has been a daunting task for most residency programs in the United States because faculty often lacks experience and training resources. Nevertheless, developing resident competence in informatics is essential for the future of pathology as a specialty. Objective: To develop and deliver a pathology informatics curriculum and instructional framework that guides pathology residency programs in training residents in critical pathology informatics knowledge and skills, and meets Accreditation Council for Graduate Medical Education Informatics Milestones. Design: The College of American Pathologists, Association of Pathology Chairs, and Association for Pathology Informatics formed a partnership and expert work group to identify critical pathology informatics training outcomes and to create a highly adaptable curriculum and instructional approach, supported by a multiyear change management strategy. Results: Pathology Informatics Essentials for Residents (PIER is a rigorous approach for educating all pathology residents in important pathology informatics knowledge and skills. PIER includes an instructional resource guide and toolkit for incorporating informatics training into residency programs that vary in needs, size, settings, and resources. PIER is available at http://www.apcprods.org/PIER (accessed April 6, 2016. Conclusions: PIER is an important contribution to informatics training in pathology residency programs. PIER introduces pathology trainees to broadly useful informatics concepts and tools that are relevant to practice. PIER provides residency program directors with a means to implement a standardized informatics training curriculum, to adapt the approach to local program needs, and to evaluate resident performance and progress over time.

  18. Incorporating resident research into the dermatology residency program

    Science.gov (United States)

    Wagner, Richard F; Raimer, Sharon S; Kelly, Brent C

    2013-01-01

    Programmatic changes for the dermatology residency program at The University of Texas Medical Branch were first introduced in 2005, with the faculty goal incorporating formal dermatology research projects into the 3-year postgraduate training period. This curriculum initially developed as a recommendation for voluntary scholarly project activity by residents, but it evolved into a program requirement for all residents in 2009. Departmental support for this activity includes assignment of a faculty mentor with similar interest about the research topic, financial support from the department for needed supplies, materials, and statistical consultation with the Office of Biostatistics for study design and data analysis, a 2-week elective that provides protected time from clinical activities for the purpose of preparing research for publication and submission to a peer-reviewed medical journal, and a departmental award in recognition for the best resident scholarly project each year. Since the inception of this program, five classes have graduated a total of 16 residents. Ten residents submitted their research studies for peer review and published their scholarly projects in seven dermatology journals through the current academic year. These articles included three prospective investigations, three surveys, one article related to dermatology education, one retrospective chart review, one case series, and one article about dermatopathology. An additional article from a 2012 graduate about dermatology education has also been submitted to a journal. This new program for residents was adapted from our historically successful Dermatology Honors Research Program for medical students at The University of Texas Medical Branch. Our experience with this academic initiative to promote dermatology research by residents is outlined. It is recommended that additional residency programs should consider adopting similar research programs to enrich resident education. PMID:23901305

  19. [Alternatively activated macrophages/mononuclear phagocytes promote growth and invasion of breast cancer cell line SKBR3].

    Science.gov (United States)

    Guo, Ju-jiang; Su, Feng-xi; Yao, He-rui; Chen, Ji-sheng

    2007-04-01

    To study the effect of alternatively activated macrophages /mononuclear phagocytes(MNP) on breast cancer cells and explore the mechanisms for the action of tumor-associated macrophages in breast cancer. Human peripheral blood monocytes were isolated and cultured in vitro and divided into 3 groups, namely classically activated monocytes (CAM) which were induced by lipopolysaccharide, alternatively activated monocytes (AAM) induce by IL-4, and control cells treated with the culture medium only. After cell culture for 48-72 h, the mRNA of tumor necrosis factor-alpha (TNF-alpha), alternative monocytes activation- associated CC-chemokine 1 (AMAC-1), and beta-actin of the 3 groups were extracted for RT-PCR, or the cells were cocultured with breast cancer cell line SKBR3, or seeded in chicken chorioallantoic membrane along with SKBR3. TNF-alpha mRNA was significantly increased in CAM, and AMAC-1 was highly expressed in AAM. The coculture experiments showed that CAM exhibited obvious inhibitory effect on SKBR3 cells after a 3-day culture whereas AAM significantly promoted the growth of SKBR3 cells after a 5-day culture. In chicken on chorioallantoic membrane experiment, the macrophages promoted tumor angiogenesis and AAM showed the most obvious effect. IL-4 induces high expression of AMAC-1, a molecular marker of AAM, in the macrophages, and AAM can promote the growth of SKBR3 cells and tumor angiogenesis.

  20. Effects of environmental concentrations of atrazine on hemocyte density and phagocytic activity in the pond snail Lymnaea stagnalis (Gastropoda, Pulmonata)

    Energy Technology Data Exchange (ETDEWEB)

    Russo, Jacqueline; Lagadic, Laurent

    2004-01-01

    Immunotoxicological effects of environmentally relevant concentrations (10, 23, 50, 100 {mu}g/l) of atrazine were studied in Lymnaea stagnalis. Individual hemolymph sampling was performed at 0, 24, 48, 72, 96, 168, 336, 504 and 672 h during exposure. Every atrazine concentration induced a significant increase in the mean number of circulating hemocytes, without any concentration-response relation. A peak (1.6-fold increase) of hemocyte density was observed after 96 h of exposure. After 504 h, the number of hemocytes remained higher only in the snails exposed to the two highest concentrations. Granulocytes contributed most to the increase in hemocyte density in herbicide-exposed snails. Both short- (24 and 96 h) and long-term (504 h) exposures resulted in significant inhibition of hemocyte phagocytic activity upon E. coli. Over the long-term, phagocytosis recovered for the two lowest concentrations. After 504 h of exposure, every herbicide level resulted in a significant reduction of reactive oxygen species production in E. coli-stimulated hemocytes, which was not observed for short-term exposures. - Phagocytosis and oxidative burst of hemocytes may be a functional biomarker for atrazine effects on snails.

  1. Development, standardisation and application of radiometric assays for measuring interaction of phagocytes, serum substances and fungal organisms

    International Nuclear Information System (INIS)

    Yamamura, M.

    1978-03-01

    Objective radiometric methods for measuring independently opsonisation, phagocytosis and intracellular killing of Candida albicans and Saccharomyces cerevisiae have been developed and standardised. Opsonisation and phagocytosis were measured as inhibition of 3 H-uridine uptake into the microorganisms caused by phagocytosis. Intracellular killing of C. albicans was measured by 51 Cr release assay. The methods are suitable for clinical application. It was shown that using human sera neither antibody nor complement were required for opsonisation of S. cerevisiae required the activation of the alternative complement pathway. Intracellular killing of C. albicans was found to be dependent on the presence of C3. Thus in the absence of C3, C. albicans was normally ingested but not killed. It was therefore concluded that C3 participates directly in the intracellular processes leading to phagocytic killing of C. albicans. Using S. cerevisiae, it was possible to measure selectively the opsonising capacity of the alternative pathway (APOC assay). Preliminary clinical application of the APOC assay suggested that a large proportion (30-40%) of patients with recurrent infection and suspected immune deficiency, without other detectable immunological abnormality, have decreased opsonising capacity of the alternative complement pathway. (author)

  2. Titanium dioxide nanoparticles stimulate sea urchin immune cell phagocytic activity involving TLR/p38 MAPK-mediated signalling pathway

    Science.gov (United States)

    Pinsino, Annalisa; Russo, Roberta; Bonaventura, Rosa; Brunelli, Andrea; Marcomini, Antonio; Matranga, Valeria

    2015-01-01

    Titanium dioxide nanoparticles (TiO2NPs) are one of the most widespread-engineered particles in use for drug delivery, cosmetics, and electronics. However, TiO2NP safety is still an open issue, even for ethical reasons. In this work, we investigated the sea urchin Paracentrotus lividus immune cell model as a proxy to humans, to elucidate a potential pathway that can be involved in the persistent TiO2NP-immune cell interaction in vivo. Morphology, phagocytic ability, changes in activation/inactivation of a few mitogen-activated protein kinases (p38 MAPK, ERK), variations of other key proteins triggering immune response (Toll-like receptor 4-like, Heat shock protein 70, Interleukin-6) and modifications in the expression of related immune response genes were investigated. Our findings indicate that TiO2NPs influence the signal transduction downstream targets of p38 MAPK without eliciting an inflammatory response or other harmful effects on biological functions. We strongly recommend sea urchin immune cells as a new powerful model for nano-safety/nano-toxicity investigations without the ethical normative issue. PMID:26412401

  3. Relationship between enhanced macrophage phagocytic activity and the induction of interferon by Newcastle disease virus in mice.

    Science.gov (United States)

    Hamburg, S I; Cassell, G H; Rabinovitch, M

    1980-03-01

    The relationship between phagocytic activity of peritoneal macrophages and serum interferon (IF) titers was evaluated in mice challenged with Newcastle disease virus (NDV). Time course studies indicated peak serum IF titers between 6 and 12 hr, whereas Fc receptor-mediated macrophage phagocytosis was maximal 18 hr after viral administration. Both responses decreased in parallel as the inoculated dose of the virus was reduced. Splenectomy, shown by others to decrease the NDV-induced serum IF titers, significantly decreased the stimulation of phagocytosis. The role of T cells in the response to the virus was studied with nude mice raised under germfree conditions. NDV-induced serum IF titers and macrophage phagocytosis were both diminished in BALB/c nudes compared with their heterozygous littermates. Both responses could be partially restored by transfer of thymocytes obtained from heterozygous mice. The results provide further evidence that in vivo macrophage stimulation by NDV is mediated by induced IF. The experiments with nude mice also indicate that the IF response to NDV is regulated by T lymphocytes.

  4. Burnout among Dutch medical residents

    NARCIS (Netherlands)

    Prins, J.T.; Hoekstra-Weebers, J.E.; Van De Wiel, H.B.; Gazendam-Donofrio, S.M.; Sprangers, F.; Jaspers, F.C.; van der Heijden, F.M.

    2007-01-01

    We examined levels of burnout and relationships between burnout, gender, age, years in training, and medical specialty in 158 medical residents working at the University Medical Center Groningen, the Netherlands. Thirteen percent of the residents met the criteria for burnout, with the highest

  5. Surgical residency: A tenant's view

    African Journals Online (AJOL)

    'To sleep: perchance to dream', is the frequent mantra of the surgical resident. However, unlike. Hamlet, there is no ensuing speculation as to what dreams may come as there are seldom any!! Surgical residency has been both vilified and immortalized, but the fact remains that it is one of the most challenging, provocative ...

  6. The effect of core and lanthanide ion dopants in sodium fluoride-based nanocrystals on phagocytic activity of human blood leukocytes

    Science.gov (United States)

    Sojka, Bartlomiej; Liskova, Aurelia; Kuricova, Miroslava; Banski, Mateusz; Misiewicz, Jan; Dusinska, Maria; Horvathova, Mira; Ilavska, Silvia; Szabova, Michaela; Rollerova, Eva; Podhorodecki, Artur; Tulinska, Jana

    2017-02-01

    Sodium fluoride-based β-NaLnF4 nanoparticles (NPs) doped with lanthanide ions are promising materials for application as luminescent markers in bio-imaging. In this work, the effect of NPs doped with yttrium (Y), gadolinium (Gd), europium (Eu), thulium (Tm), ytterbium (Yb) and terbium (Tb) ions on phagocytic activity of monocytes and granulocytes and the respiratory burst was examined. The surface functionalization of leukocytes and respiratory burst of cells was observed for limited number of samples.

  7. Tissue types (image)

    Science.gov (United States)

    There are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue ... and binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of ...

  8. Killer whale prey - Determining prey selection by southern resident killer whales (SRKW)

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Prey selectivity by southern resident killer whales is being determined by analyses of fish scales and tissue from predation events and feces. Information on killer...

  9. The PGE2/IL-10 Axis Determines Susceptibility of B-1 Cell-Derived Phagocytes (B-1CDP to Leishmania major Infection.

    Directory of Open Access Journals (Sweden)

    Angélica F Arcanjo

    Full Text Available B-1 cells can be differentiated from B-2 cells because they are predominantly located in the peritoneal and pleural cavities and have distinct phenotypic patterns and activation properties. A mononuclear phagocyte derived from B-1 cells (B-1CDP has been described. As the B-1CDP cells migrate to inflammatory/infectious sites and exhibit phagocytic capacity, the microbicidal ability of these cells was investigated using the Leishmania major infection model in vitro. The data obtained in this study demonstrate that B-1CDP cells are more susceptible to infection than peritoneal macrophages, since B-1CDP cells have a higher number of intracellular amastigotes forms and consequently release a larger number of promastigotes. Exacerbated infection by L. major required lipid bodies/PGE2 and IL-10 by B-1CDP cells. Both infection and the production of IL-10 were decreased when PGE2 production was blocked by NSAIDs. The involvement of IL-10 in this mechanism was confirmed, since B-1CDP cells from IL-10 KO mice are more competent to control L. major infection than cells from wild type mice. These findings further characterize the B-1CDP cells as an important mononuclear phagocyte that plays a previously unrecognized role in host responses to L. major infection, most likely via PGE2-driven production of IL-10.

  10. Effects of the antitumor agents from various natural sources on drug-metabolizing system, phagocytic activity and complement system in sarcoma 180-bearing mice.

    Science.gov (United States)

    Ito, H

    1986-03-01

    Correlation between antitumor activity and effects on some biological properties, such as phagocytic activity of the reticuloendothelial system, the third component of complement (C3) activation, hepatic drug-metabolizing activities and pentobarbital-induced narcosis, of antitumor agents from various natural sources such as B B (Broncasma Berna), GU-P (Grifora umbellata polysaccharide), OK-432, PS-K (Polysaccharide Kureha), and RA-P (Rumex acetosa polysaccharide) were studied with female ICR mice implanted with Sarcoma 180 solid tumor. All of these agents depressed aniline hydroxylase and aminopyrine demethylase activities, prolonged the duration of pentobarbital-induced narcosis, and significantly enhanced the phagocytic activity and C3 activity. Especially, RA-P which has the strongest antitumor activity was the most effective in changing these activities. The biological activities of GU-P at a dose of 10 mg/kg reached the same level as that found with PS-K at a dose of 100 mg/kg. a possible mechanism of inhibition of Sarcoma 180 solid tumor growth by the treatment with the antitumor agents could be interpreted as due to the C3 activation, the stimulation of phagocytic activity and depression of the hepatic microsomal drug-metabolizing system in tumor-bearing mice.

  11. Early resident-to-resident physics education in diagnostic radiology.

    Science.gov (United States)

    Kansagra, Akash P

    2014-01-01

    The revised ABR board certification process has updated the method by which diagnostic radiology residents are evaluated for competency in clinical radiologic physics. In this work, the author reports the successful design and implementation of a resident-taught physics course consisting of 5 weekly, hour-long lectures intended for incoming first-year radiology residents in their first month of training. To the author's knowledge, this is the first description of a course designed to provide a very early framework for ongoing physics education throughout residency without increasing the didactic burden on faculty members. Twenty-six first-year residents spanning 2 academic years took the course and reported subjective improvement in their knowledge (90%) and interest (75%) in imaging physics and a high level of satisfaction with the use of senior residents as physics educators. Based on the success of this course and the minimal resources required for implementation, this work may serve as a blueprint for other radiology residency programs seeking to develop revised physics curricula. Copyright © 2014 American College of Radiology. Published by Elsevier Inc. All rights reserved.

  12. Needs Assessment for Incoming PGY-1 Residents in Neurosurgical Residency.

    Science.gov (United States)

    Brandman, David M; Haji, Faizal A; Matte, Marie C; Clarke, David B

    2015-01-01

    Residents must develop a diverse range of skills in order to practice neurosurgery safely and effectively. The purpose of this study was to identify the foundational skills required for neurosurgical trainees as they transition from medical school to residency. Based on the CanMEDS competency framework, a web-based survey was distributed to all Canadian academic neurosurgical centers, targeting incoming and current PGY-1 neurosurgical residents as well as program directors. Using Likert scale and free-text responses, respondents rated the importance of various cognitive (e.g. management of raised intracranial pressure), technical (e.g. performing a lumbar puncture) and behavioral skills (e.g. obtaining informed consent) required for a PGY-1 neurosurgical resident. Of 52 individuals contacted, 38 responses were received. Of these, 10 were from program directors (71%), 11 from current PGY-1 residents (58%) and 17 from incoming PGY-1 residents (89%). Respondents emphasized operative skills such as proper sterile technique and patient positioning; clinical skills such as lesion localization and interpreting neuro-imaging; management skills for common scenarios such as raised intracranial pressure and status epilepticus; and technical skills such as lumbar puncture and external ventricular drain placement. Free text answers were concordant with the Likert scale results. We surveyed Canadian neurosurgical program directors and PGY-1 residents to identify areas perceived as foundational to neurosurgical residency education and training. This information is valuable for evaluating the appropriateness of a training program's goals and objectives, as well as for generating a national educational curriculum for incoming PGY-1 residents.

  13. Mesenchymal Stromal Cells and Tissue-Specific Progenitor Cells: Their Role in Tissue Homeostasis

    Directory of Open Access Journals (Sweden)

    Aleksandra Klimczak

    2016-01-01

    Full Text Available Multipotent mesenchymal stromal/stem cells (MSCs reside in many human organs and comprise heterogeneous population of cells with self-renewal ability. These cells can be isolated from different tissues, and their morphology, immunophenotype, and differentiation potential are dependent on their tissue of origin. Each organ contains specific population of stromal cells which maintain regeneration process of the tissue where they reside, but some of them have much more wide plasticity and differentiate into multiple cells lineage. MSCs isolated from adult human tissues are ideal candidates for tissue regeneration and tissue engineering. However, MSCs do not only contribute to structurally tissue repair but also MSC possess strong immunomodulatory and anti-inflammatory properties and may influence in tissue repair by modulation of local environment. This paper is presenting an overview of the current knowledge of biology of tissue-resident mesenchymal stromal and progenitor cells (originated from bone marrow, liver, skeletal muscle, skin, heart, and lung associated with tissue regeneration and tissue homeostasis.

  14. Myelin down-regulates myelin phagocytosis by microglia and macrophages through interactions between CD47 on myelin and SIRPα (signal regulatory protein-α on phagocytes

    Directory of Open Access Journals (Sweden)

    Reichert Fanny

    2011-03-01

    Full Text Available Abstract Background Traumatic injury to axons produces breakdown of axons and myelin at the site of the lesion and then further distal to this where Wallerian degeneration develops. The rapid removal of degenerated myelin by phagocytosis is advantageous for repair since molecules in myelin impede regeneration of severed axons. Thus, revealing mechanisms that regulate myelin phagocytosis by macrophages and microglia is important. We hypothesize that myelin regulates its own phagocytosis by simultaneous activation and down-regulation of microglial and macrophage responses. Activation follows myelin binding to receptors that mediate its phagocytosis (e.g. complement receptor-3, which has been previously studied. Down-regulation, which we test here, follows binding of myelin CD47 to the immune inhibitory receptor SIRPα (signal regulatory protein-α on macrophages and microglia. Methods CD47 and SIRPα expression was studied by confocal immunofluorescence microscopy, and myelin phagocytosis by ELISA. Results We first document that myelin, oligodendrocytes and Schwann cells express CD47 without SIRPα and further confirm that microglia and macrophages express both CD47 and SIRPα. Thus, CD47 on myelin can bind to and subsequently activate SIRPα on phagocytes, a prerequisite for CD47/SIRPα-dependent down-regulation of CD47+/+ myelin phagocytosis by itself. We then demonstrate that phagocytosis of CD47+/+ myelin is augmented when binding between myelin CD47 and SIRPα on phagocytes is blocked by mAbs against CD47 and SIRPα, indicating that down-regulation of phagocytosis indeed depends on CD47-SIRPα binding. Further, phagocytosis in serum-free medium of CD47+/+ myelin is augmented after knocking down SIRPα levels (SIRPα-KD in phagocytes by lentiviral infection with SIRPα-shRNA, whereas phagocytosis of myelin that lacks CD47 (CD47-/- is not. Thus, myelin CD47 produces SIRPα-dependent down-regulation of CD47+/+ myelin phagocytosis in phagocytes

  15. PVA matches human liver in needle-tissue interaction

    NARCIS (Netherlands)

    de Jong, T.L.; Pluymen, L.H.; van Gerwen, D.J.; Kleinrensink, GJ; Dankelman, J.; van den Dobbelsteen, J.J.

    2017-01-01

    Medical phantoms can be used to study needle-tissue interaction and to train medical residents. The purpose of this research is to study the suitability of polyvinyl alcohol (PVA) as a liver tissue mimicking material in terms of needle-tissue interaction. Insertions into ex-vivo human livers were

  16. The stress-response factor SigH modulates the interaction between Mycobacterium tuberculosis and host phagocytes.

    Directory of Open Access Journals (Sweden)

    Noton K Dutta

    Full Text Available The Mycobacterium tuberculosis stress response factor SigH plays a crucial role in modulating the pathogen's response to heat, oxidative-stress, envelope damage and hypoxia. We hypothesized that the lack of this key stress response factor would alter the interaction between the pathogen and its host cells. We compared the interaction of Mtb, Mtb:Δ-sigH and a strain where the mutation had been genetically complemented (Mtb: Δ-sigH:CO with primary rhesus macaque bone marrow derived macrophages (Rh-BMDMs. The expression of numerous inducible and homeostatic (CCL β-chemokines and several apoptotic markers was induced to higher levels in the cells infected with Mtb:Δ-sigH, relative to Mtb or the complemented strain. The differential expression of these genes manifested into functional differences in chemotaxis and apoptosis in cells infected with these two strains. The mutant strain also exhibited reduced late-stage survival in Rh-BMDMs. We hypothesize that the product of one or more SigH-dependent genes may modulate the innate interaction of Mtb with host cells, effectively reducing the chemokine-mediated recruitment of immune effector cells, apoptosis of infected monocytes and enhancing the long-term survival and replication of the pathogen in this milieu The significantly higher induction of Prostaglandin Synthetase 2 (PTGS2 or COX2 in Rh-BMDMs infected with Mtb relative to Mtb: Δ-sigH may explain reduced apoptosis in Mtb-infected cells, as PTGS2 is known to inhibit p53-dependent apoptosis.The SigH-regulon modulates the innate interaction of Mtb with host phagocytes, perhaps as part of a strategy to limit its clearance and prolong its survival. The SigH regulon appears to be required to modulate innate immune responses directed against Mtb.

  17. Helping Residents Protect Water Sources

    Science.gov (United States)

    Building on the successful early engagement of the Plain Sect agricultural community, the Eastern Lancaster County Source Water Protection Collaborative is expanding its efforts to involve local residents in the work of protecting drinking water sources.

  18. the contribution of resident physicians

    OpenAIRE

    Trusch, Klaus

    2011-01-01

    A telephone survey of resident physicians to the basic conditions in which they work has been conducted in 14 of the 16 federal states. In the center of the survey stood the general medicine within the prisons. This limitation was necessary in order to achieve comparability to primary medical care outside of correctional services. There are 140 salaried and tenured resident pysicians and 97 contract doctors in the general medical care of approx. 70000 prisoners in 185 independent prisons ...

  19. Minimum Data Set Active Resident Information Report

    Data.gov (United States)

    U.S. Department of Health & Human Services — The MDS Active Resident Report summarizes information for residents currently in nursing homes. The source of these counts is the residents MDS assessment record....

  20. Sleep Quality Among Psychiatry Residents.

    Science.gov (United States)

    Carvalho Aguiar Melo, Matias; das Chagas Medeiros, Francisco; Meireles Sales de Bruin, Veralice; Pinheiro Santana, José Abraão; Bastos Lima, Alexandre; De Francesco Daher, Elizabeth

    2016-01-01

    Medical residency programs are traditionally known for long working hours, which can be associated with a poor quality of sleep and daytime sleepiness. However, few studies have focused on this theme. Our objective was to investigate sleep quality, daytime sleepiness, and their relation with anxiety, social phobia, and depressive symptoms. This cross-sectional observational study involved 59 psychiatry residents. The Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) were used to measure the quality of sleep and excessive daytime sleepiness ([EDS] and ESS > 10), respectively. Among the 59 psychiatry residents, 59.3% had poor sleep quality (PSQI > 5) and 28.8% had EDS. Poor sleep quality was associated with higher EDS (P = 0.03) and the year of residency program (P = 0.03). Only 20% of residents with poor sleep had consulted at least once for sleep problems; 54.2% had used medications for sleep; and 16.9% were using medications at the time of interview. Only 30% obtained medication during medical consultations. Poor sleep was associated with irregular sleep hours (P = 0.001) and long periods lying down without sleep (P = 0.03). Poor sleep quality was also associated with high scores of anxiety symptoms (P Psychiatry residents frequently have poor sleep quality and EDS. Considering that sleep disorders can affect quality of life, predispose to metabolic syndrome, and be associated with worse performance at work, attention to this clinical problem is needed. © The Author(s) 2016.

  1. Selection criteria of residents for residency programs in Kuwait.

    Science.gov (United States)

    Marwan, Yousef; Ayed, Adel

    2013-01-19

    In Kuwait, 21 residency training programs were offered in the year 2011; however, no data is available regarding the criteria of selecting residents for these programs. This study aims to provide information about the importance of these criteria. A self-administered questionnaire was used to collect data from members (e.g. chairmen, directors, assistants …etc.) of residency programs in Kuwait. A total of 108 members were invited to participate. They were asked to rate the importance level (scale from 1 to 5) of criteria that may affect the acceptance of an applicant to their residency programs. Average scores were calculated for each criterion. Of the 108 members invited to participate, only 12 (11.1%) declined to participate. Interview performance was ranked as the most important criteria for selecting residents (average score: 4.63/5.00), followed by grade point average (average score: 3.78/5.00) and honors during medical school (average score: 3.67/5.00). On the other hand, receiving disciplinary action during medical school and failure in a required clerkship were considered as the most concerning among other criteria used to reject applicants (average scores: 3.83/5.00 and 3.54/5.00 respectively). Minor differences regarding the importance level of each criterion were noted across different programs. This study provided general information about the criteria that are used to accept/reject applicants to residency programs in Kuwait. Future studies should be conducted to investigate each criterion individually, and to assess if these criteria are related to residents' success during their training.

  2. Morfologia e função fagocitária de implante esplênico autógeno regenerado em ratos Morphology and phagocytic function of regenerated autogenous splenic implant in rats

    Directory of Open Access Journals (Sweden)

    Ruy Garcia Marques

    2004-12-01

    Full Text Available Objetivo: O objetivo deste trabalho é analisar a regeneração morfológica de tecido esplênico auto-implantado em ratos Wistar, verificando a função fagocitária bacteriana de seus macrófagos. Métodos: Utilizou-se um modelo experimental com ratos jovens e adultos, de ambos os sexos, submetidos a esplenectomia total combinada com auto-implante de fatias de toda a massa esplênica no omento maior. Dezesseis semanas após, os animais foram inoculados por via intravenosa com suspensão de Escherichia coli AB1157 e, após 20 minutos, foram mortos por dose letal de halotano, sendo submetidos a laparotomia para retirada dos auto-implantes esplênicos. A análise estatística foi realizada com o teste t de Student, com ênfase na comparação da massa de auto-implante esplênico regenerada entre animais jovens e adultos de ambos os sexos. Resultados: Ocorreu regeneração do auto-implante esplênico em todos os animais. Machos jovens e fêmeas adultas apresentaram maior percentual de regeneração. Observou-se aspecto morfológico microscópico semelhante em todos os animais. O tecido esplênico regenerado mostrou as polpas vermelha e branca, com desarranjo arquitetural moderado, bem como folículos linfóides. Os vasos sangüíneos mostravam paredes preservadas, sem sinais de vasculite ou trombose. Foram encontrados macrófagos contendo grumos de bactérias, bem como macrófagos contendo pigmento de hemossiderina intracitoplasmáticos. Conclusão: O auto-implante esplênico, no omento maior, em ratos, adquire a arquitetura macro e microscópica de um baço normal, de dimensão menor e preserva a função fagocitária bacteriana.Purpose: To analyze the morphologic regeneration of autotransplanted splenic tissue in Wistar rats and to determine the bacterial phagocytic function of their macrophages. Methods: We utilized an experimental model including young and adult rats, of both sexes, submitted to total splenectomy combined with

  3. Applying Expectancy Theory to residency training: proposing opportunities to understand resident motivation and enhance residency training

    Directory of Open Access Journals (Sweden)

    Shweiki E

    2015-04-01

    Full Text Available Ehyal Shweiki,1 Niels D Martin,2 Alec C Beekley,1 Jay S Jenoff,1 George J Koenig,1 Kris R Kaulback,1 Gary A Lindenbaum,1 Pankaj H Patel,1 Matthew M Rosen,1 Michael S Weinstein,1 Muhammad H Zubair,2 Murray J Cohen1 1Department of Surgery, Thomas Jefferson University Hospital, Philadelphia, PA, USA; 2Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA Abstract: Medical resident education in the United States has been a matter of national priority for decades, exemplified initially through the Liaison Committee for Graduate Medical Education and then superseded by the Accreditation Council for Graduate Medical Education. A recent Special Report in the New England Journal of Medicine, however, has described resident educational programs to date as prescriptive, noting an absence of innovation in education. Current aims of contemporary medical resident education are thus being directed at ensuring quality in learning as well as in patient care. Achievement and work-motivation theories attempt to explain people's choice, performance, and persistence in tasks. Expectancy Theory as one such theory was reviewed in detail, appearing particularly applicable to surgical residency training. Correlations between Expectancy Theory as a work-motivation theory and residency education were explored. Understanding achievement and work-motivation theories affords an opportunity to gain insight into resident motivation in training. The application of Expectancy Theory in particular provides an innovative perspective into residency education. Afforded are opportunities to promote the development of programmatic methods facilitating surgical resident motivation in education. Keywords: learning, education, achievement

  4. Tissue Classification

    DEFF Research Database (Denmark)

    Van Leemput, Koen; Puonti, Oula

    2015-01-01

    Computational methods for automatically segmenting magnetic resonance images of the brain have seen tremendous advances in recent years. So-called tissue classification techniques, aimed at extracting the three main brain tissue classes (white matter, gray matter, and cerebrospinal fluid), are now...... well established. In their simplest form, these methods classify voxels independently based on their intensity alone, although much more sophisticated models are typically used in practice. This article aims to give an overview of often-used computational techniques for brain tissue classification....... Although other methods exist, we concentrate on Bayesian modeling approaches, in which generative image models are constructed and subsequently ‘inverted’ to obtain automated segmentations. This general framework encompasses a large number of segmentation methods, including those implemented in widely used...

  5. Tissue Classification

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, David Gerald [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-01-01

    The project began as a e ort to support InLight and Lumidigm. With the sale of the companies to a non-New Mexico entity, the project then focused on supporting a new company Medici Technologies. The Small Business (SB) is attempting to quantify glucose in tissue using a series of short interferometer scans of the nger. Each scan is produced from a novel presentation of the nger to the device. The intent of the project is to identify and, if possible, implement improved methods for classi cation, feature selection, and training to improve the performance of predictive algorithms used for tissue classi cation.

  6. Evaluating Dermatology Residency Program Websites.

    Science.gov (United States)

    Ashack, Kurt A; Burton, Kyle A; Soh, Jonathan M; Lanoue, Julien; Boyd, Anne H; Milford, Emily E; Dunnick, Cory; Dellavalle, Robert P

    2016-03-16

    Internet resources play an important role in how medical students access information related to residency programs.Evaluating program websites is necessary in order to provide accurate information for applicants and provide information regarding areas of website improvement for programs. To date, dermatology residency websites (D  WS) have not been evaluated.This paper evaluates dermatology residency websites based on availability of predefined measures. Using the FREIDA (Fellowship and Residency Electronic Interactive Database) Online database, authors searched forall accredited dermatology program websites. Eligible programs were identified through the FREIDA Online database and had a functioning website. Two authors independently extracted data with consensus or third researcher resolution of differences. This data was accessed and archived from July 15th to July 17th, 2015.Primary outcomes measured were presence of content on education, resident and faculty information, program environment, applicant recruitment, schedule, salary, and website quality evaluated using an online tool (WooRank.com). Out of 117 accredited dermatology residencies, 115 had functioning webpages. Of these, 76.5% (75) had direct links found on the FRIEDA Online database. Most programs contained information on education, faculty, program environment, and applicant recruitment. However, website quality and marketing effectiveness were highly variable; most programs were deemed to need improvements in the functioning of their webpages. Also, additional information on current residents and about potential away rotations were lacking from most websites with only 52.2% (60) and 41.7% (48) of programs providing this content, respectively. A majority of dermatology residency websites contained adequate information on many of the factors we evaluated. However, many were lacking in areas that matter to applicants. We hope this report will encourage dermatology residencyprograms

  7. Phagocytic activity of granulocytes and bactericidal properties of the blood plasma in the course of radiotherapy of cancer of the lung

    International Nuclear Information System (INIS)

    Wysocka, J.; Kemona, H.; Kiluk, S.; Prokopowicz, J.

    1986-01-01

    Functional condition of granulocytes and bactericidal properties of blood plasma in patients with lung cancer, as well as the effect of radiotherapy on these parameters has been evaluated. Prior to the treatment decrease of the phagocytic activity and bactericidal properties of the blood plasma have been noticed. Application of radiotherapy is not resulting in total restitution of normal functional condition of granulocytes and even deteriorates temporarily the condition of the humoral resistance. Definition of the condition of non specific resistance is important for evaluation of the degree of exposure of patients with bacterial infections. 30 refs. (author)

  8. Anti-Pseudomonas aeruginosa IgY antibodies promote bacterial opsonization and augment the phagocytic activity of polymorphonuclear neutrophils

    DEFF Research Database (Denmark)

    Thomsen, Kim; Christophersen, Lars; Jensen, Peter Østrup

    2016-01-01

    Moderation of polymorphonuclear neutrophils (PMNs) as part of a critical defense against invading pathogens may offer a promising therapeutic approach to supplement the antibiotic eradication of Pseudomonas aeruginosa infection in non-chronically infected cystic fibrosis (CF) patients. We have...... observed that egg yolk antibodies (IgY) harvested from White leghorn chickens that target P. aeruginosa opsonize the pathogen and enhance the PMN-mediated respiratory burst and subsequent bacterial killing in vitro. The effects on PMN phagocytic activity were observed in different Pseudomonas aeruginosa...

  9. Potential Link between the Sphingosine-1-Phosphate (S1P System and Defective Alveolar Macrophage Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD.

    Directory of Open Access Journals (Sweden)

    Jameel Barnawi

    Full Text Available We previously reported that alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD are defective in their ability to phagocytose apoptotic cells, with a similar defect in response to cigarette smoke. The exact mechanisms for this defect are unknown. Sphingolipids including ceramide, sphingosine and sphingosine-1-phosphate (S1P are involved in diverse cellular processes and we hypothesised that a comprehensive analysis of this system in alveolar macrophages in COPD may help to delineate the reasons for defective phagocytic function.We compared mRNA expression of sphingosine kinases (SPHK1/2, S1P receptors (S1PR1-5 and S1P-degrading enzymes (SGPP1, SGPP2, SGPL1 in bronchoalveolar lavage-derived alveolar macrophages from 10 healthy controls, 7 healthy smokers and 20 COPD patients (10 current- and 10 ex-smokers using Real-Time PCR. Phagocytosis of apoptotic cells was investigated using flow cytometry. Functional associations were assessed between sphingosine signalling system components and alveolar macrophage phagocytic ability in COPD. To elucidate functional effects of increased S1PR5 on macrophage phagocytic ability, we performed the phagocytosis assay in the presence of varying concentrations of suramin, an antagonist of S1PR3 and S1PR5. The effects of cigarette smoking on the S1P system were investigated using a THP-1 macrophage cell line model.We found significant increases in SPHK1/2 (3.4- and 2.1-fold increases respectively, S1PR2 and 5 (4.3- and 14.6-fold increases respectively, and SGPL1 (4.5-fold increase in COPD vs. controls. S1PR5 and SGPL1 expression was unaffected by smoking status, suggesting a COPD "disease effect" rather than smoke effect per se. Significant associations were noted between S1PR5 and both lung function and phagocytosis. Cigarette smoke extract significantly increased mRNA expression of SPHK1, SPHK2, S1PR2 and S1PR5 by THP-1 macrophages, confirming the results in patient

  10. Potential Link between the Sphingosine-1-Phosphate (S1P) System and Defective Alveolar Macrophage Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD).

    Science.gov (United States)

    Barnawi, Jameel; Tran, Hai; Jersmann, Hubertus; Pitson, Stuart; Roscioli, Eugene; Hodge, Greg; Meech, Robyn; Haberberger, Rainer; Hodge, Sandra

    2015-01-01

    We previously reported that alveolar macrophages from patients with chronic obstructive pulmonary disease (COPD) are defective in their ability to phagocytose apoptotic cells, with a similar defect in response to cigarette smoke. The exact mechanisms for this defect are unknown. Sphingolipids including ceramide, sphingosine and sphingosine-1-phosphate (S1P) are involved in diverse cellular processes and we hypothesised that a comprehensive analysis of this system in alveolar macrophages in COPD may help to delineate the reasons for defective phagocytic function. We compared mRNA expression of sphingosine kinases (SPHK1/2), S1P receptors (S1PR1-5) and S1P-degrading enzymes (SGPP1, SGPP2, SGPL1) in bronchoalveolar lavage-derived alveolar macrophages from 10 healthy controls, 7 healthy smokers and 20 COPD patients (10 current- and 10 ex-smokers) using Real-Time PCR. Phagocytosis of apoptotic cells was investigated using flow cytometry. Functional associations were assessed between sphingosine signalling system components and alveolar macrophage phagocytic ability in COPD. To elucidate functional effects of increased S1PR5 on macrophage phagocytic ability, we performed the phagocytosis assay in the presence of varying concentrations of suramin, an antagonist of S1PR3 and S1PR5. The effects of cigarette smoking on the S1P system were investigated using a THP-1 macrophage cell line model. We found significant increases in SPHK1/2 (3.4- and 2.1-fold increases respectively), S1PR2 and 5 (4.3- and 14.6-fold increases respectively), and SGPL1 (4.5-fold increase) in COPD vs. controls. S1PR5 and SGPL1 expression was unaffected by smoking status, suggesting a COPD "disease effect" rather than smoke effect per se. Significant associations were noted between S1PR5 and both lung function and phagocytosis. Cigarette smoke extract significantly increased mRNA expression of SPHK1, SPHK2, S1PR2 and S1PR5 by THP-1 macrophages, confirming the results in patient-derived macrophages

  11. Simulation Activity in Otolaryngology Residencies.

    Science.gov (United States)

    Deutsch, Ellen S; Wiet, Gregory J; Seidman, Michael; Hussey, Heather M; Malekzadeh, Sonya; Fried, Marvin P

    2015-08-01

    Simulation has become a valuable tool in medical education, and several specialties accept or require simulation as a resource for resident training or assessment as well as for board certification or maintenance of certification. This study investigates current simulation resources and activities in US otolaryngology residency programs and examines interest in advancing simulation training and assessment within the specialty. Web-based survey. US otolaryngology residency training programs. An electronic web-based survey was disseminated to all US otolaryngology program directors to determine their respective institutional and departmental simulation resources, existing simulation activities, and interest in further simulation initiatives. Descriptive results are reported. Responses were received from 43 of 104 (43%) residency programs. Simulation capabilities and resources are available in most respondents' institutions (78.6% report onsite resources; 73.8% report availability of models, manikins, and devices). Most respondents (61%) report limited simulation activity within otolaryngology. Areas of simulation are broad, addressing technical and nontechnical skills related to clinical training (94%). Simulation is infrequently used for research, credentialing, or systems improvement. The majority of respondents (83.8%) expressed interest in participating in multicenter trials of simulation initiatives. Most respondents from otolaryngology residency programs have incorporated some simulation into their curriculum. Interest among program directors to participate in future multicenter trials appears high. Future research efforts in this area should aim to determine optimal simulators and simulation activities for training and assessment as well as how to best incorporate simulation into otolaryngology residency training programs. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

  12. Plagiarism in residency application essays.

    Science.gov (United States)

    Segal, Scott; Gelfand, Brian J; Hurwitz, Shelley; Berkowitz, Lori; Ashley, Stanley W; Nadel, Eric S; Katz, Joel T

    2010-07-20

    Anecdotal reports suggest that some residency application essays contain plagiarized content. To determine the prevalence of plagiarism in a large cohort of residency application essays. Retrospective cohort study. 4975 application essays submitted to residency programs at a single large academic medical center between 1 September 2005 and 22 March 2007. Specialized software was used to compare residency application essays with a database of Internet pages, published works, and previously submitted essays and the percentage of the submission matching another source was calculated. A match of more than 10% to an existing work was defined as evidence of plagiarism. Evidence of plagiarism was found in 5.2% (95% CI, 4.6% to 5.9%) of essays. The essays of non-U.S. citizens were more likely to demonstrate evidence of plagiarism. Other characteristics associated with the prevalence of plagiarism included medical school location outside the United States and Canada; previous residency or fellowship; lack of research experience, volunteer experience, or publications; a low United States Medical Licensing Examination Step 1 score; and non-membership in the Alpha Omega Alpha Honor Medical Society. The software database is probably incomplete, the 10%-match threshold for defining plagiarism has not been statistically validated, and the study was confined to applicants to 1 institution. Evidence of matching content in an essay cannot be used to infer the applicant's intent and is not sensitive to variations in the cultural context of copying in some societies. Evidence of plagiarism in residency application essays is more common in international applicants but was found in those by applicants to all specialty programs, from all medical school types, and even among applicants with significant academic honors. No external funding.

  13. 38 CFR 51.70 - Resident rights.

    Science.gov (United States)

    2010-07-01

    ... FOR NURSING HOME CARE OF VETERANS IN STATE HOMES Standards § 51.70 Resident rights. The resident has a... legal representative. (5) Conveyance upon death. Upon the death of a resident with a personal fund...; (iii) Physicians of the resident's choice (to provide care in the nursing home, physicians must meet...

  14. Mentorship in orthopaedic and trauma residency training ...

    African Journals Online (AJOL)

    Background: Mentorship is important in residency training as it is necessary for personal and professional development of the resident trainees. Objectives: This study documents mentorship in orthopaedic residency training programme in Nigeria by assessing the awareness of orthopaedic residents on the role of a mentor, ...

  15. Surgery resident learning styles and academic achievement.

    Science.gov (United States)

    Contessa, Jack; Ciardiello, Kenneth A; Perlman, Stacie

    2005-01-01

    To determine if surgical residents share a preferred learning style as measured by Kolb's Learning Style Inventory (LSI) and if a relationship exists between resident learning style and achievement as measured by a standardized examination (AME). Also, core faculty learning styles were assessed to determine if faculty and residents share a preferred learning style. Kolb's LSI, Version 3, was administered to 16 surgical residents and the residency program's core faculty of 6 attending physicians. To measure academic achievement, the American Medical Education (AME) examination was administered to residents. The Hospital of Saint Raphael, General Surgery Residency Program, New Haven, Connecticut. Both instruments were administered to residents during protected core curriculum time. Core faculty were administered the LSI on an individual basis. Surgical residents of the Hospital of Saint Raphael's General Surgery Residency Program and 6 core faculty members Analysis of resident learning style preference revealed Converging as the most commonly occurring style for residents (7) followed by Accommodating (5), Assimilating (3), and Diverging (1). The predominant learning style for core faculty was also Converging (4) with 2 Divergers. The average score for the Convergers on the AME was 62.6 compared with 42 for the next most frequently occurring learning style, Accommodators. In this surgical residency program, a preferred learning style for residents seems to exist (Converging), which confirms what previous studies have found. Additionally, residents with this learning style attained a higher average achievement score as measured by the AME. Also, core faculty share the same preferential learning style as this subset of residents.

  16. The resident's view of residency training in Canada.

    Science.gov (United States)

    Fish, D G

    1966-04-09

    In the view of residents in their last year of specialty training, the Fellowship is now becoming the operative standard for obtaining hospital privileges in urban centres and they felt that this implied that the two standards, the Certificate and the Fellowship of the Royal College, were not achieving the purpose for which they were designed. Although 80% of the residents intended to write the Fellowship, few viewed a year in a basic science department or in research as of intrinsic value in terms of their future practice.The examinations of the Royal College were the subject of criticism, most residents feeling that the examinations did not test the knowledge and ability gained in training. Most expressed a desire for ongoing evaluation during the training period.Service responsibilities were generally regarded as too heavy.Despite the criticism of both training and examination, most residents felt that their training had provided them with the experience and background they needed to practise as specialists.

  17. Conversations with Holocaust survivor residents.

    Science.gov (United States)

    Hirst, Sandra P; LeNavenec, Carole Lynne; Aldiabat, Khaldoun

    2011-03-01

    Traumatic events in one's younger years can have an impact on how an individual copes with later life. One traumatic experience for Jewish individuals was the Holocaust. Some of these people are moving into long-term care facilities. It was within this context that the research question emerged: What are Holocaust survivor residents' perceptions of a life lived as they move into a long-term care facility? For this qualitative study, Holocaust survivors were individually interviewed. Findings emphasize that nursing care needs to ensure that Holocaust survivor residents participate in activities, receive timely health care, and receive recognition of their life experiences. Copyright 2011, SLACK Incorporated.

  18. Analysis of lung tissue using ion beams

    International Nuclear Information System (INIS)

    Alvarez, J.L.; Barrera, R.; Miranda, J.

    2002-01-01

    In this work a comparative study is presented of the contents of metals in lung tissue from healthy patients and with lung cancer, by means of two analytical techniques: Particle Induced X-ray Emission (PIXE) and Rutherford Backscattering Spectrometry (RBS). The samples of cancerous tissue were taken from 26 autopsies made to individuals died in the National Institute of Respiratory Disease (INER), 22 of cancer and 4 of other non-cancer biopsies. When analyzing the entirety of the samples, in the cancerous tissues, there were increments in the concentrations of S (4%), K (635%), Co (85%) and Cu (13%). Likewise, there were deficiencies in the concentrations of Cl (59%), Ca (6%), Fe (26%) and Zn (7%). Only in the cancerous tissues there were appearances of P, Ca, Ti, V, Cr, Mn, Ni, Br and Sr. The tissue samples were classified according to cancer types (adenocarcinomas, epidermoides and of small cell carcinoma), personal habits (smokers and alcoholic), genetic predisposition and residence place. There was a remarkable decrease in the concentration of Ca and a marked increment in the Cu in the epidermoide tissue samples with regard to those of adenocarcinoma or of small cells cancer. Also, decrements were detected in K and increments of Fe, Co and Cu in the sample belonging to people that resided in Mexico City with regard to those that resided in the State of Mexico

  19. Analysis of Lung Tissue Using Ion Beams

    Science.gov (United States)

    Alvarez, J. L.; Barrera, R.; Miranda, J.

    2002-08-01

    In this work a comparative study is presented of the contents of metals in lung tissue from healthy patients and with lung cancer, by means of two analytical techniques: Particle Induced X-ray Emission (PIXE) and Rutherford Backscattering Spectrometry (RBS). The samples of cancerous tissue were taken from 26 autopsies made to individuals died in the National Institute of Respiratory Disease (INER), 22 of cancer and 4 of other non-cancer biopsies. When analyzing the entirety of the samples, in the cancerous tissues, there were increments in the concentrations of S (4%), K (635%), Co (85%) and Cu (13%). Likewise, there were deficiencies in the concentrations of Cl (59%), Ca (6%), Fe (26%) and Zn (7%). Only in the cancerous tissues there were appearances of P, Ca, Ti, V, Cr, Mn, Ni, Br and Sr. The tissue samples were classified according to cancer types (adenocarcinomas, epidermoides and of small cell carcinoma), personal habits (smokers and alcoholic), genetic predisposition and residence place. There was a remarkable decrease in the concentration of Ca and a marked increment in the Cu in the epidermoide tissue samples with regard to those of adenocarcinoma or of small cells cancer. Also, decrements were detected in K and increments of Fe, Co and Cu in the sample belonging to people that resided in Mexico City with regard to those that resided in the State of Mexico.

  20. Stable isotopes as tracers of residency for fish on inshore coral reefs

    Science.gov (United States)

    Davis, Jean P.; Pitt, Kylie A.; Fry, Brian; Connolly, Rod M.

    2015-12-01

    Understanding the migratory movements of fish between habitats is an important priority for fisheries management. Carbon (C) and nitrogen (N) stable isotopes were used to evaluate the degree of movement and residency for five fish species collected from coral reefs in Queensland, Australia. Isotope values of fish were measured and compared between slow-turnover muscle tissue and fast-turnover liver tissue, with isotopic agreement between liver and muscle generally indicating resident animals, and relatively low C isotope values in muscle indicating migrants. Three fish species, rabbitfish (Siganus fuscescens), painted sweetlips (Diagramma labiosum) and Guenther's wrasse (Pseudolabrus guentheri) showed relatively consistent carbon isotope values between muscle and liver tissue as expected for resident populations. One quarter of bream (Acanthopagrus australis) individuals showed much lower δ13C values in muscle than liver. These low values diverged from the -10 to -15‰ values of residents and were more similar to the -20‰ values of fish collected from coastal riverine habitats, the presumed migration source. Moses perch (Lutjanus russelli) also showed substantial differences between muscle and liver C isotopes for about a quarter of individuals, but the overall higher C values of these individuals indicated they may have switched diets within island habitats rather than migrating. Our results were consistent with previous studies of fish residency and indicate that measuring stable isotopes in multiple tissues provides a useful methodology for characterizing fish residency in inshore areas.

  1. Model Legislation on Student Residency.

    Science.gov (United States)

    Higher Education in the States, 1971

    1971-01-01

    Because of the radical variance in residency requirements from state to state and sometimes from institution to institution, and because of several court cases involving this issue, the Education Commission of the States appointed a Committee to develop (1) a statement of principles for consideration in drafting legislation in connection with…

  2. From Residency to Lifelong Learning.

    Science.gov (United States)

    Brandt, Keith

    2015-11-01

    The residency training experience is the perfect environment for learning. The university/institution patient population provides a never-ending supply of patients with unique management challenges. Resources abound that allow the discovery of knowledge about similar situations. Senior teachers provide counseling and help direct appropriate care. Periodic testing and evaluations identify deficiencies, which can be corrected with future study. What happens, however, when the resident graduates? Do they possess all the knowledge they'll need for the rest of their career? Will medical discovery stand still limiting the need for future study? If initial certification establishes that the physician has the skills and knowledge to function as an independent physician and surgeon, how do we assure the public that plastic surgeons will practice lifelong learning and remain safe throughout their career? Enter Maintenance of Certification (MOC). In an ideal world, MOC would provide many of the same tools as residency training: identification of gaps in knowledge, resources to correct those deficiencies, overall assessment of knowledge, feedback about communication skills and professionalism, and methods to evaluate and improve one's practice. This article discusses the need; for education and self-assessment that extends beyond residency training and a commitment to lifelong learning. The American Board of Plastic Surgery MOC program is described to demonstrate how it helps the diplomate reach the goal of continuous practice improvement.

  3. Effects of the in vitro administered ethanol and lipopolysaccharide toxin on membrane properties, intracellular free calcium and phagocytic function of isolated rat kupffer cells

    Energy Technology Data Exchange (ETDEWEB)

    Victorov, A.; Smith, T.; Abril, E.; Hamlin, E.; Earnest, D. (Univ. of Arizona, Tucson (United States))

    1991-03-11

    Low concentrations of ethanol slightly stimulated phagocytosis of cultured Kupffer cells (KC), producing practically no effect on membrane microviscosity and cytosolic free (Ca{sup 2+}){sub i}. On the contrary, high concentrations of ethanol significantly suppressed phagocytic function, increased fluidity of membrane lipids and caused a sustained rise in (Ca{sup 2}){sub i}; above the resting level of 41-85 nM. Treatment of KC with colchicine and cytochalasin B dramatically destructurized the plasma membrane lipids. Short term preincubation of KC with high doses of alcohol stimulated the disordering effects of both drugs, suggesting direct interaction of ethanol with microtubule and microfilament structures. The authors hypothesize that ethanol impairs phagocytosis of KC by concerted actions on membrane lipid fluidity, cytosolic free Ca{sup 2+} and functioning of cytoskeleton. On the other hand, incubation of KC with low concentrations of lipopolysaccharide (LPS) produced no changes in (Ca{sup 2+}){sub i}; or plasma membrane fluidity but reduced by several fold the fluidizing effect of subsequently added ethanol. They suggested that low doses of LPS, by activating second messengers other than Ca{sup 2+}, alter the functioning of the cytoskeleton and cause reorganization of the plasma membrane thus making KC membranes more resistent to the fluidizing action of ethanol and partially restoring the phagocytic function.

  4. Pro-phagocytic Effects of Thymoquinone on Cigarette Smoke-exposed Macrophages Occur by Modulation of the Sphingosine-1-phosphate Signalling System.

    Science.gov (United States)

    Barnawi, Jameel; Tran, Hai B; Roscioli, Eugene; Hodge, Greg; Jersmann, Hubertus; Haberberger, Rainer; Hodge, Sandra

    2016-10-01

    Oxidative stress, inflammation, increased bronchial epithelial cell apoptosis, and deficient phagocytic clearance of these cells (efferocytosis) by the alveolar macrophages are present in chronic obstructive pulmonary disease (COPD) and in response to cigarette smoke. We previously showed that the macrophage dysfunction is associated with changes to the sphingosine-1-phosphate (S1P) signalling system. We hypothesized that the antioxidant/anti-inflammatory agent, thymoquinone, would improve macrophage phagocytosis via modulation of the S1P system and protect bronchial epithelial cells from cigarette smoke or lipopolysaccharide (LPS)-induced apoptosis. Phagocytosis was assessed using flow cytometry, S1P mediators by Real-Time PCR, and apoptosis of 16HBE bronchial epithelial cells using flow cytometry and immunohistochemistry. Cigarette smoke and LPS decreased phagocytosis and increased S1P receptor (S1PR)-5 mRNA in THP-1 macrophages. Thymoquinone enhanced efferocytic/phagocytic ability, antagonized the effects of cigarette smoke extract and LPS on phagocytosis and S1PR5, and protected bronchial epithelial cells from cigarette smoke-induced apoptosis. Thymoquinone is worth further investigating as a potential therapeutic strategy for smoking-related lung diseases.

  5. Effects of Glycated Whey Protein Concentrate on Pro-inflammatory Cytokine Expression and Phagocytic Activity in RAW264.7 Macrophages.

    Science.gov (United States)

    Chun, Su-Hyun; Lee, Hyun Ah; Lee, Keon Bong; Kim, Sae Hun; Park, Kun-Young; Lee, Kwang-Won

    2016-01-01

    The aim of this study was to determine the stimulatory effects of Maillard reaction, a non-enzymatic browning reaction on the expression of pro-inflammatory cytokines and phagocytic activity induced by whey protein concentrate (WPC). Glycated WPC (G-WPC) was prepared by a reaction between WPC and the lactose it contained. The fluorescence intensity of G-WPC dramatically increased after one day, and high molecular weight complexes formed via the Maillard reaction were also observed in the sodium dodecyl sulfate-polyacrylamide gel electrophoresis profiles. G-WPC demonstrated immunomodulatory effects, including stimulation of increased nitric oxide production and cytokine expressions (i.e., tumor necrosis factor-α, interleukin (IL)-1β, and IL-6), compared to WPC. Furthermore, the phagocytic activity of RAW264.7 cells was significantly increased upon treatment with G-WPC, compared to WPC. Therefore, we suggest that G-WPC can be utilized as an improved dietary source for providing immune modulating activity.

  6. Student Expenses in Residency Interviewing.

    Science.gov (United States)

    Walling, Anne; Nilsen, Kari; Callaway, Paul; Grothusen, Jill; Gillenwater, Cole; King, Samantha; Unruh, Gregory

    2017-08-01

    The student costs of residency interviewing are of increasing concern but limited current information is available. Updated, more detailed information would assist students and residency programs in decisions about residency selection. The study objective was to measure the expenses and time spent in residency interviewing by the 2016 graduating class of the University of Kansas School of Medicine and assess the impact of gender, regional campus location, and primary care application. All 195 students who participated in the 2016 National Residency Matching Program (NRMP) received a 33 item questionnaire addressing interviewing activity, expenses incurred, time invested and related factors. Main measures were self-reported estimates of expenses and time spent interviewing. Descriptive analyses were applied to participant characteristics and responses. Multivariate analysis of variance (MANOVA) and chi-square tests compared students by gender, campus (main/regional), and primary care/other specialties. Analyses of variance (ANOVA) on the dependent variables provided follow-up tests on significant MANOVA results. A total of 163 students (84%) completed the survey. The average student reported 38 (1-124) applications, 16 (1-54) invitations, 11 (1-28) completed interviews, and spent $3,500 ($20-$12,000) and 26 (1-90) days interviewing. No significant differences were found by gender. After MANOVA and ANOVA analyses, non-primary care applicants reported significantly more applications, interviews, and expenditures, but less program financial support. Regional campus students reported significantly fewer invitations, interviews, and days interviewing, but equivalent costs when controlled for primary care application. Cost was a limiting factor in accepting interviews for 63% and time for 53% of study respondents. Students reported investing significant time and money in interviewing. After controlling for other variables, primary care was associated with significantly

  7. A survey of dermatology resident education in cosmetic procedures.

    Science.gov (United States)

    Kirby, Joslyn S; Adgerson, Cheri N; Anderson, Bryan E

    2013-02-01

    The demands for cosmetic procedures are increasing. Dermatologists perform many of these procedures, therefore adequate education and training during residency is important. Surveys demonstrate dermatology residents desire more training even while faculty members believe this has already become a more prominent feature of resident education. We sought to assess the time and methods dedicated to education and training of cosmetic procedures in dermatology residency. A 26-question survey was developed and electronically distributed in May 2010 to dermatology program directors via the Association of Professors of Dermatology list-serve with their approval. Program directors were asked to forward the e-mail to their instructors of cosmetic/procedural dermatology, and chief residents. Responses were anonymous. A total of 86 responses were collected. In all, 67% (n = 54) of respondents had formal lectures focusing on cosmetic dermatology. Lecture topics reported by more than 50% of respondents included botulinum toxin injection, lasers, soft tissue augmentation, chemical peels, and sclerotherapy. Topics such as dermabrasion, liposuction, and scar revision were less commonly taught. The most commonly encountered and performed procedures were botulinum toxin injection and lasers (100%, n = 86); 98.8% (n = 85) encounter soft tissue augmentation and 95.4% (n = 82) encounter both chemical peels and sclerotherapy. Resident experience performing procedures as the first assistant or as the first surgeon varied widely. The limitations of this study are that the data were subjectively reported so results may differ from the true amount of time spent in any activity. The data may be biased by the population that responded as they may have strong opinions supporting or opposing training in cosmetic procedures. The data also may have been skewed by the small percentage of participants who were instructors of cosmetic dermatology (21%), chief residents (20%), and others respondents (8

  8. The paradox of the neutrophil's role in tissue injury.

    Science.gov (United States)

    Segel, George B; Halterman, Marc W; Lichtman, Marshall A

    2011-03-01

    The neutrophil is an essential component of the innate immune system, and its function is vital to human life. Its production increases in response to virtually all forms of inflammation, and subsequently, it can accumulate in blood and tissue to varying degrees. Although its participation in the inflammatory response is often salutary by nature of its normal interaction with vascular endothelium and its capability to enter tissues and respond to chemotactic gradients and to phagocytize and kill microrganisms, it can contribute to processes that impair vascular integrity and blood flow. The mechanisms that the neutrophil uses to kill microorganisms also have the potential to injure normal tissue under special circumstances. Its paradoxical role in the pathophysiology of disease is particularly, but not exclusively, notable in seven circumstances: 1) diabetic retinopathy, 2) sickle cell disease, 3) TRALI, 4) ARDS, 5) renal microvasculopathy, 6) stroke, and 7) acute coronary artery syndrome. The activated neutrophil's capability to become adhesive to endothelium, to generate highly ROS, and to secrete proteases gives it the potential to induce local vascular and tissue injury. In this review, we summarize the evidence for its role as a mediator of tissue injury in these seven conditions, making it or its products potential therapeutic targets.

  9. Teaching residents to write a research paper.

    Science.gov (United States)

    Coleridge, S T

    1993-09-01

    Medical writing and publications are important in developing a scholarly basis for residency programs and in providing a learning experience for both resident and faculty mentors. Residency directors must provide the stimulus and support for both faculty and residents' varied creative activities. This support manifests itself in a commitment to scholarly activity (including a dedicated research person), the procurement of available research materials, the establishment of a process or plan for beginning a research project, and the development of a method for rewarding or recognizing faculty and residents who produce scholarly works. Some osteopathic residency programs may need to train faculty in research skills at the same time that residents are learning to write. Trained faculty are better models and coaches for residents engaged in research. Beginning with a fundamental, but disciplined, writing program, both faculty and residents may learn methods for sharing new knowledge or acquiring those skills necessary to critically analyze the medical literature.

  10. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells

    NARCIS (Netherlands)

    Watanabe, Rei; Gehad, Ahmed; Yang, Chao; Scott, Laura L.; Teague, Jessica E.; Schlapbach, Christoph; Elco, Christopher P.; Huang, Victor; Matos, Tiago R.; Kupper, Thomas S.; Clark, Rachael A.

    2015-01-01

    The skin of an adult human contains about 20 billion memory T cells. Epithelial barrier tissues are infiltrated by a combination of resident and recirculating T cells in mice, but the relative proportions and functional activities of resident versus recirculating T cells have not been evaluated in

  11. A patient safety curriculum for medical residents based on the perspectives of residents and supervisors

    NARCIS (Netherlands)

    Jansma, J.D.; Wagner, C.; Bijnen, A.B.

    2011-01-01

    Objectives: To develop a patient safety course for medical residents based on the views of medical residents and their supervisors. Methods: In 2007, questionnaires were distributed to investigate residents' and supervisors' perspectives on the current patient safety performance and educational

  12. Soft tissue appearance of a bone-seeker radiopharmaceutical

    International Nuclear Information System (INIS)

    Kertesz, L.; Hafenscher, I.; Baranyai, T.

    1994-01-01

    In the course of our routine whole body skeletal imaging - mainly done for metastatic screening - we were often faced with the nonosseous appearance of the polyphosphate-bound technetium /Foszfon/ as the tracer. A Toshiba GCA-901A/SA digital camera has been used in whole body scan mode. The paradoxity of bone-seekers' accumulation in soft tissues leads to the assumption that not only osteoblasts are able to incorporate the radiotracer but also cells in excited phagocytic state, too. Such states can be induced by inflammatory processes-no matter whether sterile or not - accompanied by some increase in local perfusion. Documentative cases of mastopathy, indurative trombo phlebitis, subacute and chronic postoperative wound healing will be shown with quite different imaging intensity. This should call also attention to avoid misinterpretations. (author)

  13. Tissue irradiator

    International Nuclear Information System (INIS)

    Hungate, F.P.; Riemath, W.F.; Bunnell, L.R.

    1975-01-01

    A tissue irradiator is provided for the in-vivo irradiation of body tissue. The irradiator comprises a radiation source material contained and completely encapsulated within vitreous carbon. An embodiment for use as an in-vivo blood irradiator comprises a cylindrical body having an axial bore therethrough. A radioisotope is contained within a first portion of vitreous carbon cylindrically surrounding the axial bore, and a containment portion of vitreous carbon surrounds the radioisotope containing portion, the two portions of vitreous carbon being integrally formed as a single unit. Connecting means are provided at each end of the cylindrical body to permit connections to blood-carrying vessels and to provide for passage of blood through the bore. In a preferred embodiment, the radioisotope is thulium-170 which is present in the irradiator in the form of thulium oxide. A method of producing the preferred blood irradiator is also provided, whereby nonradioactive thulium-169 is dispersed within a polyfurfuryl alcohol resin which is carbonized and fired to form the integral vitreous carbon body and the device is activated by neutron bombardment of the thulium-169 to produce the beta-emitting thulium-170

  14. Feasibility of an innovative third-year chief resident system: an internal medicine residency leadership study.

    Science.gov (United States)

    Kolade, Victor O; Staton, Lisa J; Jayarajan, Ramesh; Bentley, Nanette K; Huang, Xiangke

    2014-01-01

    The role of the internal medicine chief resident includes various administrative, academic, social, and educational responsibilities, fulfillment of which prepares residents for further leadership tasks. However, the chief resident position has historically only been held by a few residents. As fourth-year chief residents are becoming less common, we considered a new model for rotating third-year residents as the chief resident. Online surveys were given to all 29 internal medicine residents in a single university-based program after implementation of a leadership curriculum and specific job description for the third-year chief resident. Chief residents evaluated themselves on various aspects of leadership. Participation was voluntary. Descriptive statistics were generated using SPSS version 21. Thirteen junior (first- or second-year) resident responses reported that the chief residents elicited input from others (mean rating 6.8), were committed to the team (6.8), resolved conflict (6.7), ensured efficiency, organization and productivity of the team (6.7), participated actively (7.0), and managed resources (6.6). Responses from senior residents averaged 1 point higher for each item; this pattern repeated itself in teaching evaluations. Chief resident self-evaluators were more comfortable running a morning report (8.4) than with being chief resident (5.8). The feasibility of preparing internal medicine residents for leadership roles through a rotating PGY-3 (postgraduate year) chief residency curriculum was explored at a small internal medicine residency, and we suggest extending the study to include other programs.

  15. Epimorphic regeneration approach to tissue replacement in adult mammals

    Science.gov (United States)

    Urodeles and fetal mammals are capable of impressive epimorphic regeneration in a variety of tissues, whereas the typical default response to injury in adult mammals consists of inflammation and scar tissue formation. One component of epimorphic regeneration is the recruitment of resident progenitor...

  16. Phagocyte activity in the peripheral blood of pregnant women with systemic lupus erythematosus and in the cord blood of their newborns.

    Science.gov (United States)

    Sukhikh, Gennady T; Safronova, Valentina G; Vanko, Ludmila V; Matveeva, Nataliya K; Belyaeva, Anastasiya S; Fedorova, Ekaterina V; Nikolaeva, Marina A; Klimenchenko, Nataliya I; Krechetova, Lyubov V

    2017-05-01

    To detect faults in phagocytosis in peripheral blood cells of pregnant women with systemic lupus erythematosus (SLE) and in cord blood of their newborns. Pregnant women fulfilled ≥ 4 American College of Rheumatology criteria for SLE and their newborns were recruited. Pregnant women without SLE and their newborns constituted controls. Phagocytosis and respiratory burst were measured using PHAGOTEST and BURSTTEST kits (Biotechnology GmbH, Germany) on FACSCalibur™ flow cytometer. Expression of CD11b was estimated with antibodies (BD Biosciences, San Jose, CA, USA). Mann-Whitney rank-sum test was used to compare SLE group and controls. Phagocytosis and respiratory burst were estimated in blood of 31 SLE women (29.5 ± 3.3 years) and in cord blood of 26 newborns. Controls were 21 health women (29.8 ± 2.8 years) and their 21 babies. Median reactive oxygen species (ROS) production was reduced in the SLE group versus controls (arbitrary units): women, 2315 versus 3316 (P = 0.034); babies, 1051 versus 1791 (P = 0.041), respectively. Proportion of ROS-producing granulocytes decreased in the SLE group: women, 72.5% versus 94.0% (P = 0.025); babies, 46.8% versus 90.7% (P = 0.008). Proportion of phagocytes which engulfed Escherichia coli and bacteria number per phagocyte also decreased in SLE women. Monocyte activity was suppressed in newborns from the SLE group (RLU): 224 versus 507 (P = 0.022). CD11b expression was reduced in SLE women (RLU): granulocytes, 588 versus 1448.5 (P < 0.001); monocytes, 1017 versus 1619 (P = 0.002). Pregnant SLE women have low ingesting capacity of phagocytes. Suppression of phagocytosis in their newborns is mainly due to reduced number of cells producing ROS. © 2017 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.

  17. Deficient Surveillance and Phagocytic Activity of Myeloid Cells Within Demyelinated Lesions in Aging Mice Visualized byEx VivoLive Multiphoton Imaging.

    Science.gov (United States)

    Rawji, Khalil S; Kappen, Janson; Tang, Weiwen; Teo, Wulin; Plemel, Jason R; Stys, Peter K; Yong, V Wee

    2018-02-21

    Aging impairs regenerative processes including remyelination, the synthesis of a new myelin sheath. Microglia and other infiltrating myeloid cells such as macrophages are essential for remyelination through mechanisms that include the clearance of inhibitory molecules within the lesion. Prior studies have shown that the quantity of myeloid cells and the clearance of inhibitory myelin debris are deficient in aging, contributing to the decline in remyelination efficiency with senescence. It is unknown, however, whether the impaired clearance of debris is simply the result of the reduced number of phagocytes or if the dynamic activity of myeloid cells within the demyelinating plaque also declines with aging and this question is relevant to the proper design of therapeutics to mobilize myeloid cells for repair. Herein, we describe a high-resolution multiphoton ex vivo live imaging protocol that visualizes individual myelinated/demyelinated axons and lipid-containing myeloid cells to investigate the demyelinated lesion of aging female mice. We found that aging lesions have fewer myeloid cells and that these have reduced phagocytosis of myelin. Although the myeloid cells are actively migratory within the lesion of young mice and have protrusions that seem to survey the environment, this motility and surveillance is significantly reduced in aging mice. Our results emphasize the necessity of not only increasing the number of phagocytes, but also enhancing their activity once they are within demyelinated lesions. The high-resolution live imaging of demyelinated lesions can serve as a platform with which to discover pharmacological agents that rejuvenate intralesional remodeling that promotes the repair of plaques. SIGNIFICANCE STATEMENT The repair of myelin after injury depends on myeloid cells that clear debris and release growth factors. As organisms age, remyelination becomes less efficient correspondent with fewer myeloid cells that populate the lesions. It is unknown

  18. Lung toxicity of hard metal particles and production of interleukin-1, tumor necrosis factor-alpha, fibronectin, and cystatin-c by lung phagocytes.

    Science.gov (United States)

    Huaux, F; Lasfargues, G; Lauwerys, R; Lison, D

    1995-05-01

    Hard metal alloys (WC-Co) are made of a mixture of cobalt (Co; 6%) and tungsten carbide (WC; 94%) particles. Chronic inhalation of hard metal dust can lead to the development of a fibrosing alveolitis, the pathogenesis of which is still undefined. The present investigation was undertaken to assess the effect of Co, WC, and WC-Co particles on the release by lung phagocytes of interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), fibronectin, and cystatin-c. The responses were compared with those induced by two other lung toxicants, i.e., crystalline silica (DQ12) and arsenic trioxide (As2O3). IL-1 and TNF-alpha activities produced in the presence and absence of LPS stimulation were measured with the aid of bioassays while fibronectin and cystatin-c were determined by latex immunoassays. In vitro, maximal noncytotoxic doses of As2O3, Co, WC, or WC-Co did not significantly affect the production of these mediators by rat alveolar macrophages. In contrast, DQ12 enhanced the production of TNF-alpha (with and without LPS stimulation) and IL-1 (after LPS stimulation) and decreased cystatin-c release (in the absence of LPS). Following a single intratracheal instillation of the different test preparations in the rat, the response of the lung phagocytes obtained by bronchoalveolar lavage (BAL) 24 hr later was examined. We were unable to detect any consistent effect of Co (0.06 mg/100 g body wt), WC (1 mg/100 g body wt), or WC-Co treatment (1 mg/100 g body wt) on the production of the above mediators. In contrast, after LPS stimulation, As2O3 (0.5 mg/100 g body wt) and DQ12 (1 mg/100 g body wt) stimulated the production of TNF-alpha and IL-1. In the absence of LPS, As2O3 stimulated fibronectin and cystatin-c production and DQ12 stimulated cystatin-c release. Since the dose of WC-Co used in vivo (1 mg/100 g body wt) caused pronounced lung inflammation (increased LDH, protein, and albumin levels in BAL fluid), we conclude that the acute lung toxicity of WC-Co particles

  19. Lawful Permanent Residents Fiscal Year 2011 Country

    Data.gov (United States)

    Department of Homeland Security — Lawful permanet residents (LPRs) are foreign nationals who have been gratned the right to reside permanently in the United States. LPRs are also known as 'permanent...

  20. Lawful Permanent Residents Fiscal Year 2014 Country

    Data.gov (United States)

    Department of Homeland Security — Lawful permanent residents (LPRs) are foreign nationals who have been granted the right to reside permanently in the United States. LPRs are also known as 'permanent...

  1. Lawful Permanent Residents Fiscal Year 2015 State

    Data.gov (United States)

    Department of Homeland Security — Lawful permanent residents (LPRs) are foreign nationals who have been granted the right to reside permanently in the United States. LPRs are also known as 'permanent...

  2. Lawful Permanent Residents Fiscal Year 2014 State

    Data.gov (United States)

    Department of Homeland Security — Lawful permanent residents (LPRs) are foreign nationals who have been granted the right to reside permanently in the United States. LPRs are also known as 'permanent...

  3. Lawful Permanent Residents Fiscal Year 2011 State

    Data.gov (United States)

    Department of Homeland Security — Lawful permanent residents (LPRs) are foreign nationals who have been granted the right to reside permanently in the United States. LPRs are also known as 'permanent...

  4. Lawful Permanent Residents Fiscal Year 2016 State

    Data.gov (United States)

    Department of Homeland Security — Lawful permanent residents (LPRs) are foreign nationals who have been granted the right to reside permanently in the United States. LPRs are also known as 'permanent...

  5. Lawful Permanent Residents Fiscal Year 2015 Country

    Data.gov (United States)

    Department of Homeland Security — Lawful permanent residents (LPRs) are foreign nationals who have been granted the right to reside permanently in the United States. LPRs are also known as 'permanent...

  6. The Chief Resident Role in Emergency Medicine Residency Programs

    Directory of Open Access Journals (Sweden)

    Hafner, John W. Jr., MD, MPH

    2010-05-01

    Full Text Available Study Objectives: Although other specialties have examined the role of the chief resident (CR, the role and training of the emergency medicine (EM CR has largely been undefined.Methods: A survey was mailed to all EM CRs and their respective program directors (PD in 124 EM residency programs. The survey consisted of questions defining demographics, duties of the typical CR, and opinions regarding the level of support and training received. Multiple choice, Likert scale (1 strong agreement, 5 strong disagreement and short-answer responses were used. We analyzed associations between CR and PD responses using Chi-square, Student’s T and Mann-Whitney U tests.Results: Seventy-six percent of CRs and 65% of PDs responded and were similar except for age (31 vs. 42 years; p<0.001. CR respondents were most often male, in year 3 of training and held the position for 12 months. CRs and PDs agreed that the assigned level of responsibility is appropriate (2.63 vs. 2.73, p=0.15; but CRs underestimate their influence in the residency program (1.94 vs. 2.34, p=0.002 and the emergency department (2.61 vs. 3.03, p=0.002. The majority of CRs (70% and PDs (77% report participating in an extramural training program, and those CRs who participated in training felt more prepared for their job duties (2.26 vs. 2.73; p=0.03.Conclusion: EM CRs feel they have appropriate job responsibility but believe they are less influential in program and department administration than PD respondents. Extramural training programs for incoming CRs are widely used and felt to be helpful. [West J Emerg Med. 2010; 11(2:120-125.

  7. Pediatric Program Leadership's Contribution Toward Resident Wellness.

    Science.gov (United States)

    Carson, Savanna L; Perkins, Kate; Reilly, Maura R; Sim, Myung-Shin; Li, Su-Ting T

    2018-02-27

    Residency program leaders are required to support resident well-being, but often do not receive training in how to do so. Determine frequency in which program leadership provides support for resident well-being, comfort in supporting resident well-being, and factors associated with need for additional training in supporting resident well-being. National cross-sectional web-based survey of pediatric program directors, associate program directors, and coordinators in June 2015, on their experience supporting resident well-being. Univariate and bivariate descriptive statistics compared responses between groups. Generalized linear modeling, adjusting for program region, size, program leadership role, and number of years in role determined factors associated with need for additional training. 39.3% (322/820) of participants responded. Most respondents strongly agreed that supporting resident well-being is an important part of their role, but few reported supporting resident well-being as part of their job description. Most reported supporting residents' clinical, personal, and health issues at least annually, and in some cases weekly, with 72% spending >10% of their time on resident well-being. Most program leaders desired more training. After adjusting for level of comfort in dealing with resident well-being issues, program leaders more frequently exposed to resident well-being issues were more likely to desire additional training (pProgram leaders spend a significant amount of time supporting resident well-being. While they feel that supporting resident well-being is an important part of their job, opportunities exist for developing program leaders through including resident wellness on job descriptions and training program leaders how to support resident well-being. Copyright © 2018 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

  8. Photochemical tissue bonding

    Science.gov (United States)

    Redmond, Robert W [Brookline, MA; Kochevar, Irene E [Charlestown, MA

    2012-01-10

    Photochemical tissue bonding methods include the application of a photosensitizer to a tissue and/or tissue graft, followed by irradiation with electromagnetic energy to produce a tissue seal. The methods are useful for tissue adhesion, such as in wound closure, tissue grafting, skin grafting, musculoskeletal tissue repair, ligament or tendon repair and corneal repair.

  9. Phagocytic and chemiluminescent responses of mouse peritoneal macrophages to living and killed Salmonella typhimurium and other bacteria

    International Nuclear Information System (INIS)

    Tomita, T.; Blumenstock, E.; Kanegasaki, S.

    1981-01-01

    In the presence of luminol, resident as well as thioglycolate-induced and immunized macrophages emitted chemiluminescence more efficiently when the cells were exposed to living Salmonella typhimurium than when they were exposed to the same bacterium killed by ultraviolet light or heat. This phenomenon was observed whether or not the bacterium was opsonized. The different response to living and killed bacteria was also found with Escherichia coli, Pseudomonas aeruginosa, Proteus morganii, and Enterobacter aerogenes, but not with Shigella sonnei, Klebsiella pneumoniae, and Propionibacterium acnes. The results suggest that macrophages respond better to living, motile bacteria than to nonmotile or killed bacteria. The experimental results obtained with motility mutants of S. typhimurium, E. coli, and P. aeruginosa confirm that macrophages exposed to the motile bacteria emit chemiluminescence more efficiently and ingest the motile bacteria at a much faster rate than the nonmotile bacteria

  10. 45 CFR 233.40 - Residence.

    Science.gov (United States)

    2010-10-01

    .... For purposes of this section: (1) A resident of a State is one: (i) Who is living in the State... resident of the State in which he or she is living other than on a temporary basis. Residence may not depend upon the reason for which the individual entered the State, except insofar as it may bear upon...

  11. Breaking Bad News - Perceptions of Pediatric Residents.

    Science.gov (United States)

    Geeta, M G; Krishnakumar, P

    2017-08-15

    The present study evaluated the perceptions and practice of 92 final year pediatric residents with regard to breaking bad news. Only 16% of residents had received any training in communication skills. Majority (65%) of the residents were not comfortable while breaking bad news.

  12. 8 CFR 325.3 - Residence.

    Science.gov (United States)

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Residence. 325.3 Section 325.3 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY NATIONALITY REGULATIONS NATIONALS BUT NOT CITIZENS OF THE UNITED STATES; RESIDENCE WITHIN OUTLYING POSSESSIONS § 325.3 Residence. (a) For purposes of applying the...

  13. Sexual Health Education: A Psychiatric Resident's Perspective

    Science.gov (United States)

    Waineo, Eva; Arfken, Cynthia L.; Morreale, Mary K.

    2010-01-01

    Objective: This report discusses psychiatric residents' perceptions of sexual health education and their opinions regarding curricular improvements. Methods: An anonymous, web-based survey was sent to residents in one general psychiatry program (N = 33). The response rate was 69.7%. Results: Residents reported inadequate experience in multiple…

  14. Pioneering partnerships: Resident involvement from multiple perspectives

    NARCIS (Netherlands)

    Baur, V.E.; Abma, T.A.; Boelsma, F.; Woelders, S.

    2013-01-01

    Resident involvement in residential care homes is a challenge due to shortcomings of consumerist and formal approaches such as resident councils. The PARTNER approach aims to involve residents through collective action to improve their community life and wellbeing. The purpose of this article is to

  15. 24 CFR 206.39 - Principal residence.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Principal residence. 206.39 Section... CONVERSION MORTGAGE INSURANCE Eligibility; Endorsement Eligible Mortgagors § 206.39 Principal residence. The property must be the principal residence of each mortgagor at closing. For purposes of this section, the...

  16. 25 CFR 700.97 - Residence.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Residence. 700.97 Section 700.97 Indians THE OFFICE OF NAVAJO AND HOPI INDIAN RELOCATION COMMISSION OPERATIONS AND RELOCATION PROCEDURES General Policies and Instructions Definitions § 700.97 Residence. (a) Residence is established by proving that the head of household...

  17. Suicidal Thoughts Among Medical Residents with Burnout

    NARCIS (Netherlands)

    van der Heijden, Frank; Dillingh, Gea; Bakker, Arnold; Prins, Jelle

    2008-01-01

    Objectives: Recent research showed that medical residents have a high risk for developing burnout. The present study investigates the prevalence of burnout and its relationship with suicidal thoughts among medical residents. Methods: All Dutch medical residents (n = 5126) received a self-report

  18. Does Targeted Training Improve Residents' Teaching Skills?

    Science.gov (United States)

    Polreis, Sean; D'Eon, Marcel F.; Premkumar, Kalyani; Trinder, Krista; Bonnycastle, Deirdre

    2015-01-01

    Resident doctors have an important and integral responsibility of teaching a number of individuals. The purpose of this study was to measure the effectiveness of the University of Saskatchewan's resident-as-teacher training course--Teaching Improvement Project Systems (TIPS). Residents who attended the TIPS course from January, 2010 through June,…

  19. Negotiations of Acknowledgement among Middle Class Residents

    DEFF Research Database (Denmark)

    Andersen, Nina Blom

    2013-01-01

    The article presents an analysis of communication processes between residents, between residents and people in the broader societal context as well as of media coverage of a fireworks disaster in a Danish suburb. It demonstrates how residents (all members of the Danish middle class) were able...

  20. Tissue Photolithography

    Science.gov (United States)

    Wade, Lawrence A.; Kartalov, Emil; Shibata, Darryl; Taylor, Clive

    2011-01-01

    Tissue lithography will enable physicians and researchers to obtain macromolecules with high purity (greater than 90 percent) from desired cells in conventionally processed, clinical tissues by simply annotating the desired cells on a computer screen. After identifying the desired cells, a suitable lithography mask will be generated to protect the contents of the desired cells while allowing destruction of all undesired cells by irradiation with ultraviolet light. The DNA from the protected cells can be used in a number of downstream applications including DNA sequencing. The purity (i.e., macromolecules isolated form specific cell types) of such specimens will greatly enhance the value and information of downstream applications. In this method, the specific cells are isolated on a microscope slide using photolithography, which will be faster, more specific, and less expensive than current methods. It relies on the fact that many biological molecules such as DNA are photosensitive and can be destroyed by ultraviolet irradiation. Therefore, it is possible to protect the contents of desired cells, yet destroy undesired cells. This approach leverages the technologies of the microelectronics industry, which can make features smaller than 1 micrometer with photolithography. A variety of ways has been created to achieve identification of the desired cell, and also to designate the other cells for destruction. This can be accomplished through chrome masks, direct laser writing, and also active masking using dynamic arrays. Image recognition is envisioned as one method for identifying cell nuclei and cell membranes. The pathologist can identify the cells of interest using a microscopic computerized image of the slide, and appropriate custom software. In one of the approaches described in this work, the software converts the selection into a digital mask that can be fed into a direct laser writer, e.g. the Heidelberg DWL66. Such a machine uses a metalized glass plate (with

  1. Response of a phagocyte cell system to products of macrophage breakdown as a probable mechanism of alveolar phagocytosis adaptation to deposition of particles of different cytotoxicity.

    Science.gov (United States)

    Privalova, L I; Katsnelson, B A; Osipenko, A B; Yushkov, B N; Babushkina, L G

    1980-04-01

    The adaptation of the alveolar phagocytosis response to the quantitative and qualitative features of dust deposited during inhalation consists not only in enhanced recruitment of alveolar macrophages (AM), but also in adding a more or less pronounced neutrophil leukocyte (NL) recruitment as an auxiliary participant of particle clearance. The NL contribution to clearance is especially typical for response to cytotoxic particles (quartz, in particular). An important feature of the adaptation considered is the limitation of the number of AM and NL recruited when an efficient clearance can be achieved by a lesser number of cells due to increased AM reistance to the damaging actin of phagocytized particles. The main mechanism providing the adequacy of the alveolar phagocytosis response is its self-regulation thrugh the products of macrophage breakdown (PMB). In a series of experiments with intraperitoneal and intratracheal injections of syngenetic PMB into rats and mice, it was shown that these products stimulate respiration and migration of phagocytic cells, their dose-dependent attraction to the site of PMB formation with the predominant NL contribution, increasing with the increase of amount of PMB, the AM and NL precursor cells recruitment from reserve pools, and the replenishment of these reserves in the process of hemopoiesis. At least some of the above effects are connected with the action of the lipid components of PMB. The action of specialized regulative systems of the organism can modify the response to PMB, judging by the results obtained by hydrocortisone injection. Autocontrol of alveolar phagocytosis requires great care in attempts at artificial stimulation of this process, as an excessive cell recruitment may promote the retention of particles in lungs.

  2. In vivo tissue engineering of musculoskeletal tissues.

    Science.gov (United States)

    McCullen, Seth D; Chow, Andre G Y; Stevens, Molly M

    2011-10-01

    Tissue engineering of musculoskeletal tissues often involves the in vitro manipulation and culture of progenitor cells, growth factors and biomaterial scaffolds. Though in vitro tissue engineering has greatly increased our understanding of cellular behavior and cell-material interactions, this methodology is often unable to recreate tissue with the hierarchical organization and vascularization found within native tissues. Accordingly, investigators have focused on alternative in vivo tissue engineering strategies, whereby the traditional triad (cells, growth factors, scaffolds) or a combination thereof are directly implanted at the damaged tissue site or within ectopic sites capable of supporting neo-tissue formation. In vivo tissue engineering may offer a preferential route for regeneration of musculoskeletal and other tissues with distinct advantages over in vitro methods based on the specific location of endogenous cultivation, recruitment of autologous cells, and patient-specific regenerated tissues. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Ultrastructural changes in bronchoalveolar lavage cells in sarcoidosis and comparison with the tissue granuloma.

    Science.gov (United States)

    Danel, C.; Dewar, A.; Corrin, B.; Turner-Warwick, M.; Chretien, J.

    1983-01-01

    The authors undertook this study to determine whether there were any morphologic changes in bronchoalveolar lavage lymphocytes and macrophages in sarcoidosis and, in particular, to determine whether changes described previously in the mononuclear phagocytes of sarcoid granulomas were also evident in such cells obtained by lavage. Lavage cells from 28 sarcoidosis patients were studied by transmission electron microscopy and compared with lavage cells from 17 control subjects and with lung tissue granulomas from 5 sarcoidosis patients. Interactions between mononuclear phagocytes, especially subplasmalemmal linear densities, and between these cells and lymphocytes were observed in both the tissue granulomas and lavage specimens from sarcoidosis patients. Subplasmalemmal linear densities were never observed in control lavage specimens. Fully developed epitheloid cells were not identified in lavage specimens, but differences were nevertheless found between the lavage cells from sarcoidosis patients and control subjects: in particular, alveolar macrophages in sarcoidosis were larger and showed better developed pseudopodia, more marked polarity, less nuclear heterochromatin, and lysosomes that were larger and more numerous but less electron-dense than normal. Lymphocytes were also enlarged and contained more lysosomes. It is concluded that although there are only a few similarities between the cells of the granuloma and those obtained by bronchoalveolar lavage in sarcoidosis, there are noticeable differences between the lavage cells of sarcoidosis patients and control subjects. In sarcoidosis, a variable proportion (10-70%) of the lavage cells show morphologic features of "activation." Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 10 Figure 11 PMID:6859231

  4. 2003 survey of Canadian radiation oncology residents

    International Nuclear Information System (INIS)

    Yee, Don; Fairchild, Alysa; Keyes, Mira; Butler, Jim; Dundas, George

    2005-01-01

    Purpose: Radiation oncology's popularity as a career in Canada has surged in the past 5 years. Consequently, resident numbers in Canadian radiation oncology residencies are at all-time highs. This study aimed to survey Canadian radiation oncology residents about their opinions of their specialty and training experiences. Methods and Materials: Residents of Canadian radiation oncology residencies that enroll trainees through the Canadian Resident Matching Service were identified from a national database. Residents were mailed an anonymous survey. Results: Eight of 101 (7.9%) potential respondents were foreign funded. Fifty-two of 101 (51.5%) residents responded. A strong record of graduating its residents was the most important factor residents considered when choosing programs. Satisfaction with their program was expressed by 92.3% of respondents, and 94.3% expressed satisfaction with their specialty. Respondents planning to practice in Canada totaled 80.8%, and 76.9% plan to have academic careers. Respondents identified job availability and receiving adequate teaching from preceptors during residency as their most important concerns. Conclusions: Though most respondents are satisfied with their programs and specialty, job availability and adequate teaching are concerns. In the future, limited time and resources and the continued popularity of radiation oncology as a career will magnify the challenge of training competent radiation oncologists in Canada

  5. Operative Landscape at Canadian Neurosurgery Residency Programs.

    Science.gov (United States)

    Tso, Michael K; Dakson, Ayoub; Ahmed, Syed Uzair; Bigder, Mark; Elliott, Cameron; Guha, Daipayan; Iorio-Morin, Christian; Kameda-Smith, Michelle; Lavergne, Pascal; Makarenko, Serge; Taccone, Michael S; Wang, Bill; Winkler-Schwartz, Alexander; Sankar, Tejas; Christie, Sean D

    2017-07-01

    Background Currently, the literature lacks reliable data regarding operative case volumes at Canadian neurosurgery residency programs. Our objective was to provide a snapshot of the operative landscape in Canadian neurosurgical training using the trainee-led Canadian Neurosurgery Research Collaborative. Anonymized administrative operative data were gathered from each neurosurgery residency program from January 1, 2014, to December 31, 2014. Procedures were broadly classified into cranial, spine, peripheral nerve, and miscellaneous procedures. A number of prespecified subspecialty procedures were recorded. We defined the resident case index as the ratio of the total number of operations to the total number of neurosurgery residents in that program. Resident number included both Canadian medical and international medical graduates, and included residents on the neurosurgery service, off-service, or on leave for research or other personal reasons. Overall, there was an average of 1845 operative cases per neurosurgery residency program. The mean numbers of cranial, spine, peripheral nerve, and miscellaneous procedures were 725, 466, 48, and 193, respectively. The nationwide mean resident case indices for cranial, spine, peripheral nerve, and total procedures were 90, 58, 5, and 196, respectively. There was some variation in the resident case indices for specific subspecialty procedures, with some training programs not performing carotid endarterectomy or endoscopic transsphenoidal procedures. This study presents the breadth of neurosurgical training within Canadian neurosurgery residency programs. These results may help inform the implementation of neurosurgery training as the Royal College of Physicians and Surgeons residency training transitions to a competence-by-design curriculum.

  6. Resident-Led Palliative Care Education Project.

    Science.gov (United States)

    Karlen, Naomi; Cruz, Brian; Leigh, A E

    2016-04-01

    Despite the growth of palliative medicine, 39% of hospitals do not have palliative care teams for consultation or to provide resident education. We examined the impact of resident-led education in palliative care principles on attitudes toward and comfort with palliative medicine and end-of-life care among internal medicine residents. An educational module designed by the authors was presented to other internal medicine residents in the program. Pre- and post-intervention survey data measuring residents' agreement with various statements regarding palliative medicine and end-of-life care were analyzed. Residents' agreement with various statements regarding palliative medicine and end-of-life care on a 5-point Likert scale was analyzed. Following the intervention, participants reported improved comfort with general knowledge of palliative medicine (p palliative care and end-of-life care (p curriculum in palliative medicine can improve resident comfort within this still-under-represented area of medicine.

  7. Tissue engineering; strategies, tissues, and biomaterials.

    Science.gov (United States)

    Bakhshandeh, Behnaz; Zarrintaj, Payam; Oftadeh, Mohammad Omid; Keramati, Farid; Fouladiha, Hamideh; Sohrabi-Jahromi, Salma; Ziraksaz, Zarrintaj

    2017-10-01

    Current tissue regenerative strategies rely mainly on tissue repair by transplantation of the synthetic/natural implants. However, limitations of the existing strategies have increased the demand for tissue engineering approaches. Appropriate cell source, effective cell modification, and proper supportive matrices are three bases of tissue engineering. Selection of appropriate methods for cell stimulation, scaffold synthesis, and tissue transplantation play a definitive role in successful tissue engineering. Although the variety of the players are available, but proper combination and functional synergism determine the practical efficacy. Hence, in this review, a comprehensive view of tissue engineering and its different aspects are investigated.

  8. Serratia marcescens Is Able to Survive and Proliferate in Autophagic-Like Vacuoles inside Non-Phagocytic Cells

    Science.gov (United States)

    Colombo, María Isabel; García Véscovi, Eleonora

    2011-01-01

    Serratia marcescens is an opportunistic human pathogen that represents a growing problem for public health, particularly in hospitalized or immunocompromised patients. However, little is known about factors and mechanisms that contribute to S. marcescens pathogenesis within its host. In this work, we explore the invasion process of this opportunistic pathogen to epithelial cells. We demonstrate that once internalized, Serratia is able not only to persist but also to multiply inside a large membrane-bound compartment. This structure displays autophagic-like features, acquiring LC3 and Rab7, markers described to be recruited throughout the progression of antibacterial autophagy. The majority of the autophagic-like vacuoles in which Serratia resides and proliferates are non-acidic and have no degradative properties, indicating that the bacteria are capable to either delay or prevent fusion with lysosomal compartments, altering the expected progression of autophagosome maturation. In addition, our results demonstrate that Serratia triggers a non-canonical autophagic process before internalization. These findings reveal that S. marcescens is able to manipulate the autophagic traffic, generating a suitable niche for survival and proliferation inside the host cell. PMID:21901159

  9. A Time Study of Plastic Surgery Residents.

    Science.gov (United States)

    Lau, Frank H; Sinha, Indranil; Jiang, Wei; Lipsitz, Stuart R; Eriksson, Elof

    2016-05-01

    Resident work hours are under scrutiny and have been subject to multiple restrictions. The studies supporting these changes have not included data on surgical residents. We studied the workday of a team of plastic surgery residents to establish prospective time-study data of plastic surgery (PRS) residents at a single tertiary-care academic medical center. Five trained research assistants observed all residents (n = 8) on a PRS service for 10 weeks and produced minute-by-minute activity logs. Data collection began when the team first met in the morning and continued until the resident being followed completed all non-call activities. We analyzed our data from 3 perspectives: 1) time spent in direct patient care (DPC), indirect patient care, and didactic activities; 2) time spent in high education-value activities (HEAs) versus low education-value activities; and 3) resident efficiency. We defined HEAs as activities that surgeons must master; other activities were LEAs. We quantified resident efficiency in terms of time fragmentation and time spent waiting. A total of 642.4 hours of data across 50 workdays were collected. Excluding call, residents worked an average of 64.2 hours per week. Approximately 50.7% of surgical resident time was allotted to DPC, with surgery accounting for the largest segment of this time (34.8%). Time spent on HEAs demonstrated trended upward with higher resident level (P = 0.086). Time in spent in surgery was significantly associated with higher resident levels (P time study of PRS residents, we found that compared with medicine trainees, surgical residents spent 3.23 times more time on DPC. High education-value activities comprised most of our residents' workdays. Surgery was the leading component of both DPC and HEAs. Our residents were highly efficient and fragmented, with the majority of all activities requiring 4 minutes or less. Residents spent a large portion of their time waiting for other services. In light of these data, we

  10. Neurocritical care education during neurology residency

    Science.gov (United States)

    Drogan, O.; Manno, E.; Geocadin, R.G.; Ziai, W.

    2012-01-01

    Objective: Limited information is available regarding the current state of neurocritical care education for neurology residents. The goal of our survey was to assess the need and current state of neurocritical care training for neurology residents. Methods: A survey instrument was developed and, with the support of the American Academy of Neurology, distributed to residency program directors of 132 accredited neurology programs in the United States in 2011. Results: A response rate of 74% (98 of 132) was achieved. A dedicated neuroscience intensive care unit (neuro-ICU) existed in 64%. Fifty-six percent of residency programs offer a dedicated rotation in the neuro-ICU, lasting 4 weeks on average. Where available, the neuro-ICU rotation was required in the vast majority (91%) of programs. Neurology residents' exposure to the fundamental principles of neurocritical care was obtained through a variety of mechanisms. Of program directors, 37% indicated that residents would be interested in performing away rotations in a neuro-ICU. From 2005 to 2010, the number of programs sending at least one resident into a neuro-ICU fellowship increased from 14% to 35%. Conclusions: Despite the expansion of neurocritical care, large proportions of US neurology residents have limited exposure to a neuro-ICU and neurointensivists. Formal training in the principles of neurocritical care may be highly variable. The results of this survey suggest a charge to address the variability of resident education and to develop standardized curricula in neurocritical care for neurology residents. PMID:22573636

  11. PNEUMONIA IN NURSING HOME RESIDENTS

    Directory of Open Access Journals (Sweden)

    Renato Eržen

    2002-10-01

    Full Text Available Background. Pneumonia remains one of the leading causes of morbidity and mortality worldwide, especially in advanced age. Prognosis of the disease depends on premorbid condition and immune competence of the patient, severity of the disease and causative microorganism. In our analysis we wanted to establish clinical, x-ray and microbiological characteristics of pneumonia in nursing home residents, estimate suitability of therapeutic measures and find out risk factors for adverse outcome in this group of patients.Material and methods. This retrospective study includes all nursing home residents hospitalised due to CAP in Hospital Golnik in 2000. Clinical data was/were evaluated according to case history. Microbiological data and laboratory results were gathered from the patients files. Chi-square test was used for statistical analysis.Results. 30 patients, 17 women were included, aged 82.5 ± 11.7 years. 60% of patients had at least 2 accompanying diseases, most frequently cardiovascular and neurologic diseases. At admittance 83% of patients presented with severe form of the disease. Dispnea (93%, tachypnea, cough (67% and confusion (47% dominate clinical picture. Patients rarely expectorate, are frequently hypoxemic (93%, have leucocytosis (63%, electrolyte disturbances and elevated urea (67%. According to the microbiologic results most frequent causative agents are Enterobacteriae, S. pneumoniae, H. influenzae and also some multiresistant bacteria. Amoxycillin with clavulanic acid was the most frequently used antibiotic, followed by macrolides and 3rd generation cephalosporines.9 patients died, mortality rate was 30%. Their average age was 83,4 years, 67% of them had more than 2 accompanying diseases, all of them severe form of the disease, 89% severe respiratory insufficiency and 22% positive hemoculture.Conclusions. Patients are characterised with numerous comorbidities and advanced age. Clinical presentation is unspecific. Mortality is high

  12. Learning environment: assessing resident experience.

    Science.gov (United States)

    Byszewski, Anna; Lochnan, Heather; Johnston, Donna; Seabrook, Christine; Wood, Timothy

    2017-06-01

    Given their essential role in developing professional identity, academic institutions now require formal assessment of the learning environment (LE). We describe the experience of introducing a novel and practical tool in postgraduate programmes. The Learning Environment for Professionalism (LEP) survey, validated in the undergraduate setting, is relatively short, with 11 questions balanced for positive and negative professionalism behaviours. LEP is anonymous and focused on rotation setting, not an individual, and can be used on an iterative basis. We describe how we implemented the LEP, preliminary results, challenges encountered and suggestions for future application. Academic institutions now require formal assessment of the learning environment METHODS: The study was designed to test the feasibility of introducing the LEP in the postgraduate setting, and to establish the validity and the reliability of the survey. Residents in four programmes completed 187 ratings using LEP at the end of one of 11 rotations. The resident response rate was 87 per cent. Programme and rotation ratings were similar but not identical. All items rated positively (favourably), but displays of altruism tended to have lower ratings (meaning less desirable behaviour was witnessed), as were ratings for derogatory comments (again meaning that less desirable behaviour was witnessed). We have shown that the LEP is a feasible and valid tool that can be implemented on an iterative basis to examine the LE. Two LEP questions in particular, regarding derogatory remarks and demonstrating altruism, recorded the lowest scores, and these areas deserve attention at our institution. Implementation in diverse programmes is planned at our teaching hospitals to further assess reliability. This work may influence other postgraduate programmes to introduce this assessment tool. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

  13. Case-Logging Practices in Otolaryngology Residency Training: National Survey of Residents and Program Directors.

    Science.gov (United States)

    Dermody, Sarah M; Gao, William; McGinn, Johnathan D; Malekzadeh, Sonya

    2017-06-01

    Objective (1) Evaluate the consistency and manner in which otolaryngology residents log surgical cases. (2) Assess the extent of instruction and guidance provided by program directors on case-logging practices. Study Design Cross-sectional national survey. Setting Accreditation Council for Graduate Medical Education otolaryngology residency programs in the United States. Subjects and Methods US otolaryngology residents, postgraduate year 2 through graduating chiefs as of July 2016, were recruited to respond to an anonymous questionnaire designed to characterize surgical case-logging practices. Program directors of US otolaryngology residency programs were recruited to respond to an anonymous questionnaire to elucidate how residents are instructed to log cases. Results A total of 272 residents and 53 program directors completed the survey, yielding response rates of 40.6% and 49.5%, respectively. Perceived accuracy of case logs is low among residents and program directors. Nearly 40% of residents purposely choose not to log certain cases, and 65.1% of residents underreport cases performed. More than 80% of program directors advise residents to log procedures performed outside the operating room, yet only 16% of residents consistently log such cases. Conclusion Variability in surgical case-logging behaviors and differences in provided instruction highlight the need for methods to improve consistency of logging practices. It is imperative to standardize practices across otolaryngology residency programs for case logs to serve as an accurate measure of surgical competency. This study provides a foundation for reform efforts within residency programs and for the Resident Case Log System.

  14. Understanding how residents' preferences for supervisory methods change throughout residency training: a mixed-methods study.

    Science.gov (United States)

    Olmos-Vega, Francisco; Dolmans, Diana; Donkers, Jeroen; Stalmeijer, Renée E

    2015-10-16

    A major challenge for clinical supervisors is to encourage their residents to be independent without jeopardising patient safety. Residents' preferences according to level of training on this regard have not been completely explored. This study has sought to investigate which teaching methods of the Cognitive Apprenticeship (CA) model junior, intermediate and senior residents preferred and why, and how these preferences differed between groups. We invited 301 residents of all residency programmes of Javeriana University, Bogotá, Colombia, to participate. Each resident was asked to complete a Maastricht Clinical Teaching Questionnaire (MCTQ), which, being based on the teaching methods of CA, asked residents to rate the importance to their learning of each teaching method and to indicate which of these they preferred the most and why. A total of 215 residents (71 %) completed the questionnaire. All concurred that all CA teaching methods were important or very important to their learning, regardless of their level of training. However, the reasons for their preferences clearly differed between groups: junior and intermediate residents preferred teaching methods that were more supervisor-directed, such as modelling and coaching, whereas senior residents preferred teaching methods that were more resident-directed, such as exploration and articulation. The results indicate that clinical supervision (CS) should accommodate to residents' varying degrees of development by attuning the configuration of CA teaching methods to each level of residency training. This configuration should initially vest more power in the supervisor, and gradually let the resident take charge, without ever discontinuing CS.

  15. Feasibility of an innovative third-year chief resident system: an internal medicine residency leadership study

    Directory of Open Access Journals (Sweden)

    Victor O. Kolade

    2014-07-01

    Full Text Available Introduction: The role of the internal medicine chief resident includes various administrative, academic, social, and educational responsibilities, fulfillment of which prepares residents for further leadership tasks. However, the chief resident position has historically only been held by a few residents. As fourth-year chief residents are becoming less common, we considered a new model for rotating third-year residents as the chief resident. Methods: Online surveys were given to all 29 internal medicine residents in a single university-based program after implementation of a leadership curriculum and specific job description for the third-year chief resident. Chief residents evaluated themselves on various aspects of leadership. Participation was voluntary. Descriptive statistics were generated using SPSS version 21. Results: Thirteen junior (first- or second-year resident responses reported that the chief residents elicited input from others (mean rating 6.8, were committed to the team (6.8, resolved conflict (6.7, ensured efficiency, organization and productivity of the team (6.7, participated actively (7.0, and managed resources (6.6. Responses from senior residents averaged 1 point higher for each item; this pattern repeated itself in teaching evaluations. Chief resident self-evaluators were more comfortable running a morning report (8.4 than with being chief resident (5.8. Conclusion: The feasibility of preparing internal medicine residents for leadership roles through a rotating PGY-3 (postgraduate year chief residency curriculum was explored at a small internal medicine residency, and we suggest extending the study to include other programs.

  16. What is an anesthesiology resident worth?

    Science.gov (United States)

    Ferrera, Marisa H; Beaman, Shawn T; Metro, David G; Handley, Linda J; Walker, James E

    2009-08-01

    To determine the cost of replacing an anesthesiology resident with a certified registered nurse anesthetist (CRNA) for equal operating room (OR) work. Retrospective financial analysis. Academic anesthesiology department. Clinical anesthesia (CA)-1 through CA-3 residents. Cost of replacing anesthesiology residents with CRNAs for equal OR work was determined. The cost of replacing one anesthesiology resident with a CRNA for the same number of OR hours ranged from $9,940.32 to $43,300 per month ($106,241.68 to $432,937.50 per yr). Numbers varied depending on the CRNA pay scale and whether the calculations were based on the number of OR hours worked at our residency program or OR hours worked in a maximum duty hour model. A CRNA is paid substantially more per OR hour worked, at all pay levels, than an anesthesiology resident.

  17. Understanding macrophage activation in the adipose tissue: at the crossroads of immunology and metabolism

    NARCIS (Netherlands)

    Boutens, Lily

    2018-01-01

    Macrophages and their monocyte precursors continuously patrol the bloodstream and tissues, ready to eliminate unwelcome visitors such as pathogens or foreign particles. Tissue-resident macrophages are crucial during development and for maintaining tissue homeostasis as well. The engulfment of

  18. γδ T cells in homeostasis and host defence of epithelial barrier tissues

    DEFF Research Database (Denmark)

    Nielsen, Morten M.; Witherden, Deborah A.; Havran, Wendy L.

    2017-01-01

    Epithelial surfaces line the body and provide a crucial interface between the body and the external environment. Tissue-resident epithelial γδ T cells represent a major T cell population in the epithelial tissues and are ideally positioned to carry out barrier surveillance and aid in tissue...

  19. Motherhood during residency training: challenges and strategies.

    Science.gov (United States)

    Walsh, Allyn; Gold, Michelle; Jensen, Phyllis; Jedrzkiewicz, Michelle

    2005-07-01

    To determine what factors enable or impede women in a Canadian family medicine residency program from combining motherhood with residency training. To determine how policies can support these women, given that in recent decades the number of female family medicine residents has increased. Qualitative study using in-person interviews. McMaster University Family Medicine Residency Program. Twenty-one of 27 family medicine residents taking maternity leave between 1994 and 1999. Semistructured interviews. The research team reviewed transcripts of audiotaped interviews for emerging themes; consensus was reached on content and meaning. NVIVO software was used for data analysis. Long hours, unpredictable work demands, guilt because absences from work increase workload for colleagues, and residents' high expectations of themselves cause pregnant residents severe stress. This stress continues upon return to work; finding adequate child care is an added stress. Residents report receiving less support from colleagues and supervisors upon return to work; they associate this with no longer being visibly pregnant. Physically demanding training rotations put additional strain on pregnant residents and those newly returned to work. Flexibility in scheduling rotations can help accommodate needs at home. Providing breaks, privacy, and refrigerators at work can help maintain breastfeeding. Allowing residents to remain involved in academic and clinical work during maternity leave helps maintain clinical skills, build new knowledge, and promote peer support. Pregnancy during residency training is common and becoming more common. Training programs can successfully enhance the experience of motherhood during residency by providing flexibility at work to facilitate a healthy balance among the competing demands of family, work, and student life.

  20. [Heart failure in nursing home residents].

    Science.gov (United States)

    Daamen, M A M J; Hamers, J P H; Brunner-la Rocca, H P; Schols, J M G A

    2016-01-01

    To determine the prevalence of heart failure (HF) in nursing home residents and to gain insight into the clinical characteristics of residents with heart failure. Multi-centre, observational, cross-sectional study. 501 nursing home residents aged 65 years and over, in a department for chronic somatic diseases or a psychogeriatric department, participated in this study. The diagnosis of HF and the related characteristics were based on data collected from clinical examinations for heart failure (including history, physical examination, ECG, cardiac markers and echocardiography), patient records and questionnaires. A panel of two cardiologists and an internist-geriatrician made the final diagnosis of HF. The prevalence of HF in nursing home residents was 33%. Dyspnoea, oedema and a history of cardiac disease were more common in residents with heart failure. Diabetes mellitus and chronic obstructive pulmonary disease also appeared to be more prevalent in this group. In 54% of the residents with HF, the diagnosis had not previously been made. Diagnosis of HF was not confirmed by the expert panel in 31% of residents with a history of HF. Heart failure does indeed appear to be very prevalent in nursing home residents. Heart failure had not been previously diagnosed in many cases but also a previous diagnosis of heart failure could be disproved in many participants. It is therefore important that the diagnostic process for heart failure in nursing home residents be improved.

  1. Radiology residents' experience with intussusception reduction.

    Science.gov (United States)

    Bateni, Cyrus; Stein-Wexler, Rebecca; Wootton-Gorges, Sandra L; Li, Chin-Shang

    2011-06-01

    Residents should be exposed to adequate procedural volume to act independently upon completion of training. Informal inquiry led us to question whether residents encounter enough intussusception reductions to become comfortable with the procedure. We sought to determine radiology residents' exposure to intussusception reductions, and whether their experiences vary by region or institution. U.S. radiology residency program directors were asked to encourage their residents to complete a 12-question online survey describing characteristics of their pediatric radiology department, experiences with intussusception reduction, and confidence in their own ability to perform the procedure. Six hundred sixty-four residents responded during the study period. Of those, 308 (46.4%) had not experienced an intussusception reduction, and 228 (34%) had experienced only one or two. Twenty-two percent of fourth-year residents had never experienced an intussusception reduction, and 21% had experienced only one. Among second- through fourth-year residents, only 99 (18.3%) felt confident that they could competently reduce an intussusception (P Radiology residents have limited opportunity to learn intussusception reduction and therefore lack confidence. Most think they would benefit from additional training with a computer-simulation model.

  2. Internal medicine residency training in Turkey.

    Science.gov (United States)

    Sahin, Hatice; Akcicek, Fehmi

    2005-12-01

    Medical school entrance depends on passing a central examination that is given annually by the National Selection and Placement Center. Undergraduate medical education takes 6 years. About 5000 students graduate from medical faculties annually. The central exam necessary for residency training is given by the National Selection and Placement Center. A Specialist Training Regulation regulates residency training. Internal medicine residency training takes 4 years and includes inpatient and outpatient care in wards and rotations. Residents prepare a dissertation that is used in the evaluation of residency competency. At the end of the residency period, residents who have been successful in previous evaluations take an oral exam followed by a written exam, which lead to their certification in internal medicine. Residents' scientific knowledge and skills are assessed by a jury consisting of five people, four from the same department and one from the equivalent department in another training institution. The title of specialist is granted after a certification exam given by training institutions and approved by the Ministry of Health. Internists are mainly employed in state hospitals, which are under the Ministry of Health. Subspecialty areas in internal medicine include gastroenterology, geriatrics, endocrinology, nephrology, hematology, rheumatology, immunology, allergology, and oncology. The training period for a subspecialty is 2 years. A substantial effort is being made all over the country to improve regulations and health care service delivery. These changes will also affect the residency training and manpower planning and employment of internists.

  3. The challenges of residents teaching neurology.

    Science.gov (United States)

    Frank, Samuel A; Józefowicz, Ralph F

    2004-07-01

    Teaching is integrated into the daily practice of residents, and it is a skill necessary for practice as well as academics. The settings in which teaching and learning take place are ubiquitous but include classrooms, small groups, bedside rounds, and grand rounds. Given the learning environment of residency, neurology residents should have working knowledge of basic principles of effective teaching to make learning successful. Teaching also reinforces knowledge, and residents will likely be better practitioners if some basic skills of teaching are practiced. Neurology teaching techniques for residents are rarely addressed in the medical literature. Although information regarding teaching principles in medicine exists, there is little information regarding how residents teach. We examine and review some of the more effective methods and appreciated qualities in teachers, with a particular emphasis for the neurology resident. We also review whom neurologists need to teach and the various settings in which teaching may take place. Neurology residents encounter a variety of audiences in a variety of settings that require diverse teaching skills to effectively convey information to other providers as well as patients. The majority of these skills should be learned in residency to establish a foundation for teaching, regardless of future practice settings.

  4. Activation of phagocytic activity in astrocytes by reduced expression of the inflammasome component ASC and its implication in a mouse model of Alzheimer disease.

    Science.gov (United States)

    Couturier, Julien; Stancu, Ilie-Cosmin; Schakman, Olivier; Pierrot, Nathalie; Huaux, François; Kienlen-Campard, Pascal; Dewachter, Ilse; Octave, Jean-Noël

    2016-01-27

    The proinflammatory cytokine interleukin-1β (IL-1β) is overexpressed in Alzheimer disease (AD) as a key regulator of neuroinflammation. Amyloid-β (Aβ) peptide triggers activation of inflammasomes, protein complexes responsible for IL-1β maturation in microglial cells. Downregulation of NALP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome has been shown to decrease amyloid load and rescue cognitive deficits in a mouse model of AD. Whereas activation of inflammasome in microglial cells has been described in AD, no data are currently available concerning activation of inflammasome in astrocytes, although they are involved in inflammatory response and phagocytosis. Here, by targeting the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD domain), we investigated the influence of activation of the inflammasome on the phagocytic activity of astrocytes. We used an ASC knockout mouse model, as ASC is a central protein in the inflammasome, acting as an adaptor and stabilizer of the complex and thus critical for its activation. Lipopolysaccharide (LPS)-primed primary cultures of astrocytes from newborn mice were utilized to evaluate Aβ-induced inflammasome activation by measuring IL-1β release by ECLIA (electro-chemiluminescence immunoassay). Phagocytosis efficiency was measured by incorporation of bioparticles, and the release of the chemokine CCL3 (C-C motif ligand 3) was measured by ECLIA. ASC mice were crossbred with 5xFAD (familial Alzheimer disease) mice and tested for spatial reference memory using the Morris water maze (MWM) at 7-8 months of age. Amyloid load and CCL3 were quantified by thioflavine S staining and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. Cultured astrocytes primed with LPS and treated with Aβ showed an ASC-dependent production of IL-1β resulting from inflammasome activation mediated by Aβ phagocytosis and cathepsin B enzymatic activity. ASC

  5. Identification of Scedosporium boydii catalase A1 gene, a reactive oxygen species detoxification factor highly expressed in response to oxidative stress and phagocytic cells.

    Science.gov (United States)

    Mina, Sara; Staerck, Cindy; d'Almeida, Sènan M; Marot, Agnès; Delneste, Yves; Calenda, Alphonse; Tabiasco, Julie; Bouchara, Jean-Philippe; Fleury, Maxime J J

    2015-12-01

    Scedosporium boydii is an opportunistic filamentous fungus which may be responsible for a large variety of infections in both immunocompetent and immunocompromised individuals. This fungus belongs to the Scedosporium apiospermum species complex which usually ranks second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). Species of the S. apiospermum complex are able to chronically colonize the CF airways suggesting pathogenic mechanisms allowing persistence and growth of these fungi in the respiratory tract. Few putative virulence factors have been purified and characterized so far in the S. apiospermum complex including a cytosolic Cu,Zn-superoxide dismutase (SOD) and a monofunctional catalase (catalase A1). Upon microbial infection, host phagocytes release reactive oxygen species (ROS), such as hydrogen peroxide, as part of the antimicrobial response. Catalases are known to protect pathogens against ROS by degradation of the hydrogen peroxide. Here, we identified the S. boydii catalase A1 gene (CATA1) and investigated its expression in response to the environmental conditions encountered in the CF airways and to the oxidative stress. Results showed that S. boydii CATA1 gene expression is not affected by hypoxia, hypercapnia or pH changes. In contrast, CATA1 gene was overexpressed in response to a chemically induced oxidative stress with a relative gene expression 37-fold higher in the presence of 250 μM H(2)O(2), 20-fold higher with 250 μM menadione and 5-fold higher with 2 mM paraquat. Moreover, S. boydii CATA1 gene expression progressively increased upon exposure to activated THP-1-derived macrophages, reaching a maximum after 12 h (26 fold). Activated HL60-derived neutrophils and activated human peripheral blood neutrophils more rapidly induced S. boydii CATA1 gene overexpression, a maximum gene expression level being reached at 75 min (17 fold) and 60 min (15 fold), respectively. In contrast expression of the gene

  6. Integration of Surgical Residency Training With US Military Humanitarian Missions.

    Science.gov (United States)

    Jensen, Shane; Tadlock, Matthew D; Douglas, Trent; Provencher, Matthew; Ignacio, Romeo C

    2015-01-01

    To describe how the US Navy integrates surgical resident training during hospital ship-based humanitarian activities and discuss the potential operative and educational benefits during these missions. Retrospective review of predeployment surgical plans, operative case logs, and after-action reports from United States Naval Ship (USNS) Mercy humanitarian deployments from 2006 to 2012. The USNS Mercy hospital ship. We enrolled 24 surgical residents from different surgical specialties including general surgery, obstetrics and gynecology, urology, otolaryngology, and ophthalmology. During 4 planned deployments (2006-2012), 2887 surgical procedures were performed during 20 humanitarian missions conducted by the USNS Mercy in 9 different Southeast Asian countries. Of all the general surgery eligible procedures performed, 1483 (79%) were defined categories under the current general surgery Accreditation Council for Graduate Medical Education guidelines, including abdominal (31%); skin, soft tissue, and breast (21%); ear, nose, and throat (20.5%); plastic surgery (15.5%); and pediatric (12%) cases. The number of surgical cases completed by each resident ranged from 30 to 67 cases over a period of 4 to 6 weeks during the overseas humanitarian rotation. The US Navy's humanitarian experience provides a unique educational opportunity for young military surgeons to experience various global health systems, diverse cultures, and complex logistical planning without sacrificing the breadth and depth of surgical training. This model may provide a framework to develop future international electives for other general surgery training programs. Copyright © 2015. Published by Elsevier Inc.

  7. Contemporary Trends in Radiation Oncology Resident Research

    Energy Technology Data Exchange (ETDEWEB)

    Verma, Vivek [Department of Radiation Oncology, University of Nebraska, Omaha, Nebraska (United States); Burt, Lindsay [Department of Radiation Oncology, University of Utah, Salt Lake City, Utah (United States); Gimotty, Phyllis A. [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Ojerholm, Eric, E-mail: eric.ojerholm@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

    2016-11-15

    Purpose: To test the hypothesis that recent resident research productivity might be different than a decade ago, and to provide contemporary information about resident scholarly activity. Methods and Materials: We compiled a list of radiation oncology residents from the 2 most recent graduating classes (June 2014 and 2015) using the Association of Residents in Radiation Oncology annual directories. We queried the PubMed database for each resident's first-authored publications from postgraduate years (PGY) 2 through 5, plus a 3-month period after residency completion. We abstracted corresponding historical data for 2002 to 2007 from the benchmark publication by Morgan and colleagues (Int J Radiat Oncol Biol Phys 2009;74:1567-1572). We tested the null hypothesis that these 2 samples had the same distribution for number of publications using the Wilcoxon rank-sum test. We explored the association of demographic factors and publication number using multivariable zero-inflated Poisson regression. Results: There were 334 residents publishing 659 eligible first-author publications during residency (range 0-17; interquartile range 0-3; mean 2.0; median 1). The contemporary and historical distributions were significantly different (P<.001); contemporary publication rates were higher. Publications accrued late in residency (27% in PGY-4, 59% in PGY-5), and most were original research (75%). In the historical cohort, half of all articles were published in 3 journals; in contrast, the top half of contemporary publications were spread over 10 journals—most commonly International Journal of Radiation Oncology • Biology • Physics (17%), Practical Radiation Oncology (7%), and Radiation Oncology (4%). Male gender, non-PhD status, and larger residency size were associated with higher number of publications in the multivariable analysis. Conclusion: We observed an increase in first-author publications during training compared with historical data from the mid-2000s. These

  8. Contemporary Trends in Radiation Oncology Resident Research.

    Science.gov (United States)

    Verma, Vivek; Burt, Lindsay; Gimotty, Phyllis A; Ojerholm, Eric

    2016-11-15

    To test the hypothesis that recent resident research productivity might be different than a decade ago, and to provide contemporary information about resident scholarly activity. We compiled a list of radiation oncology residents from the 2 most recent graduating classes (June 2014 and 2015) using the Association of Residents in Radiation Oncology annual directories. We queried the PubMed database for each resident's first-authored publications from postgraduate years (PGY) 2 through 5, plus a 3-month period after residency completion. We abstracted corresponding historical data for 2002 to 2007 from the benchmark publication by Morgan and colleagues (Int J Radiat Oncol Biol Phys 2009;74:1567-1572). We tested the null hypothesis that these 2 samples had the same distribution for number of publications using the Wilcoxon rank-sum test. We explored the association of demographic factors and publication number using multivariable zero-inflated Poisson regression. There were 334 residents publishing 659 eligible first-author publications during residency (range 0-17; interquartile range 0-3; mean 2.0; median 1). The contemporary and historical distributions were significantly different (Pcontemporary publication rates were higher. Publications accrued late in residency (27% in PGY-4, 59% in PGY-5), and most were original research (75%). In the historical cohort, half of all articles were published in 3 journals; in contrast, the top half of contemporary publications were spread over 10 journals-most commonly International Journal of Radiation Oncology • Biology • Physics (17%), Practical Radiation Oncology (7%), and Radiation Oncology (4%). Male gender, non-PhD status, and larger residency size were associated with higher number of publications in the multivariable analysis. We observed an increase in first-author publications during training compared with historical data from the mid-2000s. These contemporary figures may be useful to medical students considering

  9. Contemporary Trends in Radiation Oncology Resident Research

    International Nuclear Information System (INIS)

    Verma, Vivek; Burt, Lindsay; Gimotty, Phyllis A.; Ojerholm, Eric

    2016-01-01

    Purpose: To test the hypothesis that recent resident research productivity might be different than a decade ago, and to provide contemporary information about resident scholarly activity. Methods and Materials: We compiled a list of radiation oncology residents from the 2 most recent graduating classes (June 2014 and 2015) using the Association of Residents in Radiation Oncology annual directories. We queried the PubMed database for each resident's first-authored publications from postgraduate years (PGY) 2 through 5, plus a 3-month period after residency completion. We abstracted corresponding historical data for 2002 to 2007 from the benchmark publication by Morgan and colleagues (Int J Radiat Oncol Biol Phys 2009;74:1567-1572). We tested the null hypothesis that these 2 samples had the same distribution for number of publications using the Wilcoxon rank-sum test. We explored the association of demographic factors and publication number using multivariable zero-inflated Poisson regression. Results: There were 334 residents publishing 659 eligible first-author publications during residency (range 0-17; interquartile range 0-3; mean 2.0; median 1). The contemporary and historical distributions were significantly different (P<.001); contemporary publication rates were higher. Publications accrued late in residency (27% in PGY-4, 59% in PGY-5), and most were original research (75%). In the historical cohort, half of all articles were published in 3 journals; in contrast, the top half of contemporary publications were spread over 10 journals—most commonly International Journal of Radiation Oncology • Biology • Physics (17%), Practical Radiation Oncology (7%), and Radiation Oncology (4%). Male gender, non-PhD status, and larger residency size were associated with higher number of publications in the multivariable analysis. Conclusion: We observed an increase in first-author publications during training compared with historical data from the mid-2000s. These

  10. Lawful Permanent Residents Fiscal Year 2014 Core Based Statistical Area (CBSA) of Residence

    Data.gov (United States)

    Department of Homeland Security — Lawful permanent residents (LPRs) are foreign nationals who have been granted the right to reside permanently in the United States. LPRs are also known as 'permanent...

  11. Lawful Permanent Residents Fiscal Year 2015 Core Based Statistical Area (CBSA) of Residence

    Data.gov (United States)

    Department of Homeland Security — Lawful permanent residents (LPRs) are foreign nationals who have been granted the right to reside permanently in the United States. LPRs are also known as 'permanent...

  12. Lawful Permanent Residents Fiscal Year 2016 Core Based Statistical Area (CBSA) of Residence

    Data.gov (United States)

    Department of Homeland Security — Lawful permanet residents (LPRs) are foreign nationals who have been gratned the right to reside permanently in the United States. LPRs are also known as 'permanent...

  13. Lawful Permanent Residents Fiscal Year 2011 Core Based Statistical Area (CBSA) of Residence

    Data.gov (United States)

    Department of Homeland Security — Lawful permanent residents (LPRs) are foreign nationals who have been granted the right to reside permanently in the United States. LPRs are also known as 'permanent...

  14. Radiology residents as teachers: Current status of teaching skills training in United States residency programs.

    Science.gov (United States)

    Donovan, Andrea

    2010-07-01

    Radiology residents often teach medical students and other residents. Workshops developed with the goal of improving resident teaching skills are becoming increasingly common in various fields of medicine. The purpose of this study was to determine the prevalence and structure of resident-teacher training opportunities within radiology programs in the United States. Program directors with membership in the Association of Program Directors in Radiology (APDR) were surveyed to determine views on a panel of topics related to resident-teacher training programs. A total of 114 (56%) of 205 APDR members completed an online survey. Approximately one-third (32%) stated that their program provided instruction to residents on teaching skills. The majority of these programs (72%) were established within the last 5 years. Residents provided teaching to medical students (94%) and radiology residents (90%). The vast majority of program directors agreed that it is important for residents to teach (98%) and that these teaching experiences helped residents become better radiologists (85%). Ninety-four percent of program directors felt that the teaching skills of their residents could be improved, and 85% felt that residents would benefit from instruction on teaching methods. Only one-third of program directors felt their program adequately recognized teaching provided by residents. Program directors identified residents as being active contributors to teaching in most programs. Although teaching was viewed as an important skill to develop, few programs had instituted a resident-teacher curriculum. Program directors felt that residents would benefit from structured training to enhance teaching skills. Future studies are needed to determine how best to provide teaching skills training for radiology trainees. 2010 AUR. Published by Elsevier Inc. All rights reserved.

  15. Radiology resident teaching skills improvement: impact of a resident teacher training program.

    Science.gov (United States)

    Donovan, Andrea

    2011-04-01

    Teaching is considered an essential competency for residents to achieve during their training. Instruction in teaching skills may assist radiology residents in becoming more effective teachers and increase their overall satisfaction with teaching. The purposes of this study were to survey radiology residents' teaching experiences during residency and to assess perceived benefits following participation in a teaching skills development course. Study participants were radiology residents with membership in the American Alliance of Academic Chief Residents in Radiology or the Siemens AUR Radiology Resident Academic Development Program who participated in a 1.5-hour workshop on teaching skills development at the 2010 Association of University Radiologists meeting. Participants completed a self-administered, precourse questionnaire that addressed their current teaching strategies, as well as the prevalence and structure of teaching skills training opportunities at their institutions. A second postcourse questionnaire enabled residents to evaluate the seminar and assessed new knowledge and skill acquisition. Seventy-eight residents completed the precourse and postcourse questionnaires. The vast majority of respondents indicated that they taught medical students (72 of 78 [92.3%]). Approximately 20% of residency programs (17 of 78) provided residents with formal didactic programs on teaching skills. Fewer than half (46.8%) of the resident respondents indicated that they received feedback on their teaching from attending physicians (36 of 77), and only 18% (13 of 78) routinely gave feedback to their own learners. All of the course participants agreed or strongly agreed that this workshop was helpful to them as teachers. Few residency programs had instituted resident teacher training curricula. A resident teacher training workshop was perceived as beneficial by the residents, and they reported improvement in their teaching skills. Copyright © 2011 AUR. Published by

  16. Designing the stem cell microenvironment for guided connective tissue regeneration.

    Science.gov (United States)

    Bogdanowicz, Danielle R; Lu, Helen H

    2017-12-01

    Adult mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine because of their ability to self-renew and their capacity for multilineage differentiation and tissue regeneration. For connective tissues, such as ligaments or tendons, MSCs are vital to the modulation of the inflammatory response following acute injury while also interacting with resident fibroblasts to promote cell proliferation and matrix synthesis. To date, MSC injection for connective tissue repair has yielded mixed results in vivo, likely due to a lack of appropriate environmental cues to effectively control MSC response and promote tissue healing instead of scar formation. In healthy tissues, stem cells reside within a complex microenvironment comprising cellular, structural, and signaling cues that collectively maintain stemness and modulate tissue homeostasis. Changes to the microenvironment following injury regulate stem cell differentiation, trophic signaling, and tissue healing. Here, we focus on models of the stem cell microenvironment that are used to elucidate the mechanisms of stem cell regulation and inspire functional approaches to tissue regeneration. Recent studies in this frontier area are highlighted, focusing on how microenvironmental cues modulate MSC response following connective tissue injury and, more importantly, how this unique cell environment can be programmed for stem cell-guided tissue regeneration. © 2017 New York Academy of Sciences.

  17. Soft Tissue Sarcoma

    Science.gov (United States)

    ... muscles, tendons, fat, and blood vessels. Soft tissue sarcoma is a cancer of these soft tissues. There ... have certain genetic diseases. Doctors diagnose soft tissue sarcomas with a biopsy. Treatments include surgery to remove ...

  18. Invitational Engineering in the Residence Halls.

    Science.gov (United States)

    Murphy, Jack; Purkey, William

    1981-01-01

    Presents various ways in which a residence hall environment may be specifically engineered to encourage individual participation in the process of education. Invitational engineering is defined as one way to transpose psychological principles to residence halls so they contribute to the developmental life of students. (RC)

  19. Emotional intelligence in orthopedic surgery residents

    Science.gov (United States)

    Chan, Kevin; Petrisor, Brad; Bhandari, Mohit

    2014-01-01

    Background Emotional intelligence (EI) is the ability to understand and manage emotions in oneself and others. It was originally popularized in the business literature as a key attribute for success that was distinct from cognitive intelligence. Increasing focus is being placed on EI in medicine to improve clinical and academic performance. Despite the proposed benefits, to our knowledge, there have been no previous studies on the role of EI in orthopedic surgery. We evaluated baseline data on EI in a cohort of orthopedic surgery residents. Methods We asked all orthopedic surgery residents at a single institution to complete an electronic version of the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT). We used completed questionnaires to calculate total EI scores and 4 branch scores. Data were analyzed according to a priori cutoff values to determine the proportion of residents who were considered competent on the test. Data were also analyzed for possible associations with age, sex, race and level of training. Results Thirty-nine residents (100%) completed the MSCEIT. The mean total EI score was 86 (maximum score 145). Only 4 (10%) respondents demonstrated competence in EI. Junior residents (p = 0.026), Caucasian residents (p = 0.009) and those younger than 30 years (p = 0.008) had significantly higher EI scores. Conclusion Our findings suggest that orthopedic residents score low on EI based on the MSCEIT. Optimizing resident competency in noncognitive skills may be enhanced by dedicated EI education, training and testing. PMID:24666445

  20. Sedation practice among Nigerian radiology residents | Omisore ...

    African Journals Online (AJOL)

    Background: Providing safe and effective sedation to patients, especially those with multiple medical problems, can be challenging for radiology residents and fellows. This study aimed to determine knowledge, attitude and practice of Nigerian radiology residents concerning sedation. Keywords: anaesthetist, guidelines ...

  1. Emotional intelligence in orthopedic surgery residents.

    Science.gov (United States)

    Chan, Kevin; Petrisor, Brad; Bhandari, Mohit

    2014-04-01

    Emotional intelligence (EI) is the ability to understand and manage emotions in oneself and others. It was originally popularized in the business literature as a key attribute for success that was distinct from cognitive intelligence. Increasing focus is being placed on EI in medicine to improve clinical and academic performance. Despite the proposed benefits, to our knowledge, there have been no previous studies on the role of EI in orthopedic surgery. We evaluated baseline data on EI in a cohort of orthopedic surgery residents. We asked all orthopedic surgery residents at a single institution to complete an electronic version of the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). We used completed questionnaires to calculate total EI scores and 4 branch scores. Data were analyzed according to a priori cutoff values to determine the proportion of residents who were considered competent on the test. Data were also analyzed for possible associations with age, sex, race and level of training. Thirty-nine residents (100%) completed the MSCEIT. The mean total EI score was 86 (maximum score 145). Only 4 (10%) respondents demonstrated competence in EI. Junior residents (p = 0.026), Caucasian residents (p = 0.009) and those younger than 30 years (p = 0.008) had significantly higher EI scores. Our findings suggest that orthopedic residents score low on EI based on the MSCEIT. Optimizing resident competency in noncognitive skills may be enhanced by dedicated EI education, training and testing.

  2. 42 CFR 483.10 - Resident rights.

    Science.gov (United States)

    2010-10-01

    ... to Medicaid benefits, in writing, at the time of admission to the nursing facility or, when the resident becomes eligible for Medicaid of— (A) The items and services that are included in nursing facility... eligibility for Medicaid or SSI. (6) Conveyance upon death. Upon the death of a resident with a personal fund...

  3. Tax treaty entitlement issues concerning dual residents

    NARCIS (Netherlands)

    Sanghavi, D.

    2014-01-01

    The question whether a dual resident taxpayer is entitled to tax treaties concluded by each residence state with a third state has been controversial. Since 2008, the Organisation for Economic Co-operation and Development (OECD) Commentary on Article 4(1) of the OECD Model states that such a

  4. Displacing Media: LCD LAB Artistic Residency

    Directory of Open Access Journals (Sweden)

    Filipe Pais

    2012-12-01

    Full Text Available This review refers to an artistic residency which took place at LCD LAB -  CAAA at Guimarães, in March, exploring a strategy for media art called Media Displacement. The text introduces the strategy very briefly and describes the residency's organization, structure, processses and the results produced.

  5. 20th Annual Residence Hall Construction Report

    Science.gov (United States)

    Agron, Joe

    2009-01-01

    Even in difficult economic times, colleges and universities continue to invest in residence hall construction projects as a way to attract new students and keep existing ones on campus. According to data from "American School & University"'s 20th annual Residence Hall Construction Report, the median new project completed in 2008 was…

  6. 38 CFR 3.653 - Foreign residence.

    Science.gov (United States)

    2010-07-01

    ... 38 Pensions, Bonuses, and Veterans' Relief 1 2010-07-01 2010-07-01 false Foreign residence. 3.653 Section 3.653 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS ADJUDICATION Pension, Compensation, and Dependency and Indemnity Compensation Adjustments and Resumptions § 3.653 Foreign residence...

  7. Medication Refusal: Resident Rights, Administration Dilemma.

    Science.gov (United States)

    Haskins, Danielle R; Wick, Jeannette Y

    2017-12-01

    Occasionally, residents actively or passively refuse to take medications. Residents may refuse medication for a number of reasons, including religious beliefs, dietary restrictions, misunderstandings, cognitive impairment, desire to self-harm, or simple inconvenience. This action creates a unique situation for pharmacists and long-term facility staff, especially if patients have dementia. Residents have the legal right to refuse medications, and long-term care facilities need to employ a process to resolve disagreement between the health care team that recommends the medication and the resident who refuses it. In some cases, simple interventions like selecting a different medication or scheduling medications in a different time can address and resolve the resident's objection. If the medical team and the resident cannot resolve their disagreement, often an ethics consultation is helpful. Documenting the resident's refusal to take any or all medications, the health care team's actions and any other outcomes are important. Residents' beliefs may change over time, and the health care team needs to be prepared to revisit the issue as necessary.

  8. 42 CFR 436.403 - State residence.

    Science.gov (United States)

    2010-10-01

    ...) Definition. For purposes of this section—Institution has the same meaning as Institution and Medical... intention to remain there permanently or for an indefinite period. (2) For any individual not residing in an... of residence is the State where the individual is— (i) Living with the intention to remain there...

  9. 42 CFR 435.403 - State residence.

    Science.gov (United States)

    2010-10-01

    ... set forth in § 431.52 of this chapter. (b) Definition. For purposes of this section—Institution has... intent, the State of residence is the State where the individual is living with the intention to remain...), the State of residence is the State where the individual is— (i) Living with the intention to remain...

  10. Adult neurology training during child neurology residency.

    Science.gov (United States)

    Schor, Nina F

    2012-08-21

    As it is currently configured, completion of child neurology residency requires performance of 12 months of training in adult neurology. Exploration of whether or not this duration of training in adult neurology is appropriate for what child neurology is today must take into account the initial reasons for this requirement and the goals of adult neurology training during child neurology residency.

  11. Teaching Forensic Psychiatry to General Psychiatry Residents

    Science.gov (United States)

    Lewis, Catherine F.

    2004-01-01

    Objective: The Accreditation Council on Graduate Medical Education (ACGME) requires that general psychiatry residency training programs provide trainees with exposure to forensic psychiatry. Limited information is available on how to develop a core curriculum in forensic psychiatry for general psychiatry residents and few articles have been…

  12. INFLUENCE OF LOCAL RONKOLEIKIN TREATMENT UPON CLINICAL COURSE OF PURULENT WOUNDS AND FUNCTIONAL ACTIVITY OF WOUND PHAGOCYTES IN PATIENTS WITH ODONTOGENIC PHLEGMONAE

    Directory of Open Access Journals (Sweden)

    I. I. Dolgushin

    2009-01-01

    Full Text Available Abstract. The aim of the work was to evaluate clinical features of purulent wounds trend and functional activity of local wound phagocytes in the patients with odontogenic phlegmones in the course of local treatment with Ronkoleukin. A randomized clinical study was performed which included sixty-five patients with odontogenic phlegmones. Their age ranged from 18 to 74 years old. The group was divided in two parts, i.e., patients of a comparison group (n = 33 receiving a conventional combined drug therapy, and the persons from study group (n = 32 who were subject to local immunotherapy with Ronkoleukin, applied along with conventional therapy. It was established that the local therapy with Ronkoleikin exerts distinct positive effects, i.e., increase in wound-located lymphocytes and macrophages, acceleration of phasic dynamics of inflammatory events, augmentation of an lysosomal luminescence index (2.3-fold, enhancement of phagocytosis intensity in wound neutrophiles and macrophages (1.9-2-fold, strengthening the reserve abilities of wound neutrophils (1.3-fold. These effects create favorable conditions for elimination of pathogen and optimal healing of purulent wounds in the patients with odontogenic phlegmones.

  13. Endosomal pH modulation by peptide-gold nanoparticle hybrids enables potent anti-inflammatory activity in phagocytic immune cells.

    Science.gov (United States)

    Yang, Hong; Kozicky, Lisa; Saferali, Aabida; Fung, Shan-Yu; Afacan, Nicole; Cai, Bing; Falsafi, Reza; Gill, Erin; Liu, Mingyao; Kollmann, Tobias R; Hancock, R E W; Sly, Laura M; Turvey, Stuart E

    2016-12-01

    Toll-like receptor (TLR) signaling plays a central role in the pathophysiology of many acute and chronic human inflammatory diseases, and pharmacological regulation of TLR responses is anticipated to be beneficial in many inflammatory conditions. Currently there are no specific TLR inhibitors in clinical use. To overcome this challenge, we have developed a nano-based TLR inhibitor (peptide-gold nanoparticle hybrids) that inhibits a broad spectrum of TLR responses. Through mechanistic studies, we established that specific peptide decorated-gold nanoparticles that display high cellular uptake in phagocytic immune cells modulate endosomal pH, leading to significant attenuation of signaling through multiple TLRs. Using a global transcriptomic approach, we defined the broad anti-inflammatory activity of the nanoparticle in human peripheral blood mononuclear cells. In vivo studies confirmed the beneficial immunomodulatory activity since treatment with the nanoparticle significantly reduced weight loss, improved the disease activity index, and ameliorated colonic inflammation in a murine model of intestinal inflammation. This work enhances our fundamental understanding of the role of peptide coatings on the nanoparticle surface in regulating innate immune signaling, and identifies specific peptide decorated nanoparticles that may represent a novel class of anti-inflammatory therapeutics for human inflammatory diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Influence of platelet-activating factor receptor (PAFR) on Brucella abortus infection: implications for manipulating the phagocytic strategy of B. abortus.

    Science.gov (United States)

    Lee, Jin Ju; Simborio, Hannah Leah; Reyes, Alisha Wehdnesday Bernardo; Hop, Huynh Tan; Arayan, Lauren Togonon; Lee, Hu Jang; Min, Wongi; Her, Moon; Rhee, Man Hee; Watarai, Masahisa; Chang, Hong Hee; Kim, Suk

    2016-04-21

    Brucella abortus is an intracellular pathogen which can infect and persist in host cells through multiple interactions. Above all, its interaction to host cell receptor is important to understand the pathogenic mechanisms of B. abortus. Accordingly, we demonstrated that platelet-activating factor receptor (PAFR) affects host cell response against B. abortus infection. First of all, B. abortus infection to macrophage induces secretion of platelet-activating factor (PAF), which is a PAFR agonist. The stimulation of PAFR by PAF remarkably increases B. abortus uptake into macrophages. It induces Janus kinase 2 (JAK2) and p38α phosphorylation, indicating that PAFR-mediated activation of JAK2 signaling leads to enhanced uptake of B. abortus. Moreover, the dynamics of F-actin polymerization revealed that PAFR-mediated B. abortus uptake is related with the reorganization of F-actin and JAK2. Upon B. abortus phagocytosis, reduced PAFR in the membrane and subsequently increased levels of PAFR colocalization with endosomes were observed which indicate that B. abortus uptake into macrophages allowed PAFR trafficking to endosomes. This study demonstrated that PAFR has a compelling involvement in B. abortus uptake as a promoter of phagocytosis, which is associated with JAK2 activation. Thus, our findings establish a novel insight into a receptor-related phagocytic mechanism of B. abortus.

  15. Inhibitory effect of red ginseng acidic polysaccharide from Korean red ginseng on phagocytic activity and intracellular replication of Brucella abortus in RAW 264.7 cells.

    Science.gov (United States)

    Reyes, Alisha Wehdnesday Bernardo; Simborio, Hannah Leah Tadeja; Hop, Huynh Tan; Arayan, Lauren Togonon; Min, Won Gi; Lee, Hu Jang; Rhee, Man Hee; Chang, Hong Hee; Kim, Suk

    2016-09-30

    Korean red ginseng (KRG) has long been used in traditional Korean and Oriental medicine. However, the anti-bacterial mechanism and therapeutic efficiency of KGR for intracellular Brucella infection are still unclear. In this study, the bactericidal activity of Korean red ginseng acidic polysaccharide (RGAP) on Brucella (B.) abortus and its cytotoxic effects on RAW 264.7 cells were evaluated. In addition, B. abortus internalization and intracellular replication in macrophages were investigated after RGAP treatment. RGAP-incubated cells displayed a marked reduction in the adherence, internalization and intracellular growth of B. abortus in macrophages. Furthermore, decreased F-actin fluorescence was observed relative to untreated B. abortus-infected cells. Western blot analysis of intracellular signaling proteins revealed reduced ERK, JNK and p38α phosphorylation levels in B. abortus-infected RGAP-treated cells compared to the control. Moreover, elevated co-localization of B. abortus-containing phagosomes with lysosome-associated membrane protein 1 (LAMP-1) were observed in RGAP-treated cells compared with the control. Overall, the results of this study suggest that RGAP can disrupt phagocytic activity of B. abortus via suppression of mitogen-activated protein kinases (MAPKs) signaling proteins ERK, JNK and p38 levels and inhibit intracellular replication of B. abortus by enhancing phagolysosome fusion, which may provide an alternative control of brucellosis.

  16. Decreased Fc receptor expression on innate immune cells is associated with impaired antibody-mediated cellular phagocytic activity in chronically HIV-1 infected individuals.

    Science.gov (United States)

    Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T; Ackerman, Margaret E; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

    2011-07-05

    In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. Decreased Fc-Receptor expression on innate immune cells is associated with impaired antibody mediated cellular phagocytic activity in chronically HIV-1 infected individuals

    Science.gov (United States)

    Dugast, Anne-Sophie; Tonelli, Andrew; Berger, Christoph T.; Ackerman, Margaret E.; Sciaranghella, Gaia; Liu, Qingquan; Sips, Magdalena; Toth, Ildiko; Piechocka-Trocha, Alicja; Ghebremichael, Musie; Alter, Galit

    2011-01-01

    In addition to neutralization, antibodies mediate other antiviral activities including antibody-dependent cellular-phagocytosis (ADCP), antibody dependent cellular-cytotoxicity (ADCC), as well as complement deposition. While it is established that progressive HIV infection is associated with reduced ADCC and ADCP, the underlying mechanism for this loss of function is unknown. Here we report considerable changes in FcR expression over the course of HIV infection on both mDCs and monocytes, including elevated FcγRI expression in acute HIV infection and reduced expression of FcγRII and FcγRIIIa in chronic HIV infection. Furthermore, selective blockade of FcγRII alone was associated with a loss in ADCP activity, suggesting that FcγRII plays a central role in modulating ADCP. Overall, HIV infection is associated with a number of changes in FcR expression on phagocytic cells that are associated with changes in their ability to respond to antibody-opsonized targets, potentially contributing to a failure in viral clearance in progressive HIV-1 infection. PMID:21565376

  18. Interactions of Neuropathogenic Escherichia coli K1 (RS218 and Its Derivatives Lacking Genomic Islands with Phagocytic Acanthamoeba castellanii and Nonphagocytic Brain Endothelial Cells

    Directory of Open Access Journals (Sweden)

    Farzana Abubakar Yousuf

    2014-01-01

    Full Text Available Here we determined the role of various genomic islands in E. coli K1 interactions with phagocytic A. castellanii and nonphagocytic brain microvascular endothelial cells. The findings revealed that the genomic islands deletion mutants of RS218 related to toxins (peptide toxin, α-hemolysin, adhesins (P fimbriae, F17-like fimbriae, nonfimbrial adhesins, Hek, and hemagglutinin, protein secretion system (T1SS for hemolysin, invasins (IbeA, CNF1, metabolism (D-serine catabolism, dihydroxyacetone, glycerol, and glyoxylate metabolism showed reduced interactions with both A. castellanii and brain microvascular endothelial cells. Interestingly, the deletion of RS218-derived genomic island 21 containing adhesins (P fimbriae, F17-like fimbriae, nonfimbrial adhesins, Hek, and hemagglutinin, protein secretion system (T1SS for hemolysin, invasins (CNF1, metabolism (D-serine catabolism abolished E. coli K1-mediated HBMEC cytotoxicity in a CNF1-independent manner. Therefore, the characterization of these genomic islands should reveal mechanisms of evolutionary gain for E. coli K1 pathogenicity.

  19. The Entamoeba histolytica, Arp2/3 Complex Is Recruited to Phagocytic Cups through an Atypical Kinase EhAK1.

    Directory of Open Access Journals (Sweden)

    Mrigya Babuta

    2015-12-01

    Full Text Available The parasite Entamoeba histolytica is the etiological agent of amoebiasis and phagocytosis plays a key role in virulence of this organism. Signaling pathways involved in activation of cytoskeletal dynamics required for phagocytosis remain to be elucidated. Phagocytosis is initiated with sequential recruitment of EhC2PK, EhCaBP1, EhCaBP3 and an atypical kinase EhAK1 after particle attachment. Here we show that EhARPC1, an essential subunit of the actin branching complex Arp 2/3 is recruited to the phagocytic initiation sites by EhAK1. Imaging, expression knockdown of different molecules and pull down experiments suggest that EhARPC1 interacts with EhAK1 and that it is required during initiation of phagocytosis and phagosome formation. Moreover, recruitment of EhARPC2 at the phagocytosis initiation by EhAK1 is also observed, indicating that the Arp 2/3 complex is recruited. In conclusion, these results suggests a novel mechanism of recruitment of Arp 2/3 complex during phagocytosis in E. histolytica.

  20. Engineering complex orthopaedic tissues via strategic biomimicry.

    Science.gov (United States)

    Qu, Dovina; Mosher, Christopher Z; Boushell, Margaret K; Lu, Helen H

    2015-03-01

    The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, wherein overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g., bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g., bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g., bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

  1. Engineering Complex Orthopaedic Tissues via Strategic Biomimicry

    Science.gov (United States)

    Qu, Dovina; Mosher, Christopher Z.; Boushell, Margaret K.; Lu, Helen H.

    2014-01-01

    The primary current challenge in regenerative engineering resides in the simultaneous formation of more than one type of tissue, as well as their functional assembly into complex tissues or organ systems. Tissue-tissue synchrony is especially important in the musculoskeletal system, whereby overall organ function is enabled by the seamless integration of bone with soft tissues such as ligament, tendon, or cartilage, as well as the integration of muscle with tendon. Therefore, in lieu of a traditional single-tissue system (e.g. bone, ligament), composite tissue scaffold designs for the regeneration of functional connective tissue units (e.g. bone-ligament-bone) are being actively investigated. Closely related is the effort to re-establish tissue-tissue interfaces, which is essential for joining these tissue building blocks and facilitating host integration. Much of the research at the forefront of the field has centered on bioinspired stratified or gradient scaffold designs which aim to recapitulate the structural and compositional inhomogeneity inherent across distinct tissue regions. As such, given the complexity of these musculoskeletal tissue units, the key question is how to identify the most relevant parameters for recapitulating the native structure-function relationships in the scaffold design. Therefore, the focus of this review, in addition to presenting the state-of-the-art in complex scaffold design, is to explore how strategic biomimicry can be applied in engineering tissue connectivity. The objective of strategic biomimicry is to avoid over-engineering by establishing what needs to be learned from nature and defining the essential matrix characteristics that must be reproduced in scaffold design. Application of this engineering strategy for the regeneration of the most common musculoskeletal tissue units (e.g. bone-ligament-bone, muscle-tendon-bone, cartilage-bone) will be discussed in this review. It is anticipated that these exciting efforts will

  2. Simulation and resident education in spinal neurosurgery.

    Science.gov (United States)

    Bohm, Parker E; Arnold, Paul M

    2015-01-01

    A host of factors have contributed to the increasing use of simulation in neurosurgical resident education. Although the number of simulation-related publications has increased exponentially over the past two decades, no studies have specifically examined the role of simulation in resident education in spinal neurosurgery. We performed a structured search of several databases to identify articles detailing the use of simulation in spinal neurosurgery education in an attempt to catalogue potential applications for its use. A brief history of simulation in medicine is given, followed by current trends of spinal simulation utilization in residency programs. General themes from the literature are identified that are integral for implementing simulation into neurosurgical residency curriculum. Finally, various applications are reported. The use of simulation in spinal neurosurgery education is not as ubiquitous in comparison to other neurosurgical subspecialties, but many promising methods of simulation are available for augmenting resident education.

  3. Introducing "optimal challenges" in resident training

    DEFF Research Database (Denmark)

    Sørensen, Anette Bagger; Christensen, Mette Krogh

    Background: Residents are often caught between two interests: the resident’s desire to participate in challenging learning situations and the department’s work planning. However, these interests may clash if they are not coordinated by the senior doctors, and challenging learning situations risk...... being subject to work planning. Summary of work: Inspired by Csikszentmihalyi’s concept of optimal challenges, an intervention study aimed at introducing a more suitable planning of residents' learning in terms of optimal allocation of educational patient contacts. The objective was to coordinating...... residents’ individual competences and learning needs with patient characteristics in order to match each resident with a case (an outpatient or a patient) that meets the learning needs of the resident and thus pose an optimal challenge to the resident. Summary of results: The preliminary results show...

  4. Child Neurology Education for Pediatric Residents.

    Science.gov (United States)

    Albert, Dara V F; Patel, Anup D; Behnam-Terneus, Maria; Sautu, Beatriz Cunill-De; Verbeck, Nicole; McQueen, Alisa; Fromme, H Barrett; Mahan, John D

    2017-03-01

    The aim of this study was to evaluate whether the current state of child neurology education during pediatric residency provides adequate preparation for pediatric practice. A survey was sent to recent graduates from 3 pediatric residency programs to assess graduate experience, perceived level of competence, and desire for further education in child neurology. Responses from generalists versus subspecialists were compared. The response rate was 32%, half in general pediatric practice. Only 22% feel very confident in approaching patients with neurologic problems. This may represent the best-case scenario as graduates from these programs had required neurology experiences, whereas review of Accreditation Council of Graduate Medical Education-accredited residency curricula revealed that the majority of residencies do not. Pediatric neurologic problems are common, and pediatric residency graduates do encounter such problems in practice. The majority of pediatricians report some degree of confidence; however, some clear areas for improvement are apparent.

  5. Pregnancy and the Plastic Surgery Resident.

    Science.gov (United States)

    Garza, Rebecca M; Weston, Jane S; Furnas, Heather J

    2017-01-01

    Combining pregnancy with plastic surgery residency has historically been difficult. Two decades ago, 36 percent of plastic surgery program directors surveyed actively discouraged pregnancy among residents, and 33 percent of women plastic surgeons suffered from infertility. Most alarmingly, 26 percent of plastic surgery trainees had had an elective abortion during residency. With increasing numbers of women training in plastic surgery, this historical lack of support for pregnancy deserves further attention. To explore the current accommodations made for the pregnant plastic surgery resident, an electronic survey was sent to 88 plastic surgery program directors in the United States. Fifty-four responded, for a response rate of 61.36 percent. On average, a director trained a total of 7.91 women among 17.28 residents trained over 8.19 years. Of the women residents, 1.43 were pregnant during a director's tenure, with 1.35 of those residents taking maternity leave. An average 1.75 male residents took paternity leave. Approximately one-third of programs had a formal maternity/paternity leave policy (36.54 percent) which, in most cases, was limited to defining allowed weeks of leave, time required to fulfill program requirements, and remuneration during leave. This survey of plastic surgery directors is a first step in defining the challenges training programs face in supporting the pregnant resident. Directors provided comments describing their challenges accommodating an absent resident in a small program and complying with the American Board of Plastic Surgery's required weeks of training per year. A discussion of these challenges is followed by suggested solutions.

  6. Evaluation of stress experienced by pharmacy residents.

    Science.gov (United States)

    Le, Hung M; Young, Shardae D

    2017-04-15

    Results of a study of stress and negative affect levels in postgraduate year 1 (PGY1) and postgraduate year 2 (PGY2) pharmacy residents are presented. A cross-sectional approach was used. Pharmacy residency program directors received e-mailed invitation letters requesting that they ask their residents to participate in an online survey in 2011. The main study outcomes included evaluation of resident scores on the 10-item Perceived Stress Scale (PSS10) and the Multiple Affect Adjective Checklist-Revised (MAACL-R) anxiety, depression, hostility, and dysphoria subscales. Of the 524 pharmacy residents included in the study, 75.4% were female, 41.2% were under 26 years of age, and 41% reported working more than 60 hours per week. There were no significant differences between PGY1 and PGY2 residents in stress levels, as assessed with the PSS10 (mean ± S.D. score, 19.05 ± 5.96 versus 19.09 ± 5.77). MAACL-R scores for hostility were, on average, higher among PGY2 residents (mean ± S.D., 50.83 ± 10.02) than among PGY1 residents (48.62 ± 8.96), while there were no significant differences in anxiety, depression, and dysphoria levels. Relative to residents who worked 60 or fewer hours per week, those who worked more than 60 hours had higher perceived stress levels as well as higher depression, hostility, and dysphoria scores. Pharmacy residents exhibited high levels of perceived stress, especially those who worked more than 60 hours per week. Perceived stress was highly correlated to negative affect levels. Copyright © 2017 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  7. Evolution of the Pathology Residency Curriculum

    Science.gov (United States)

    Powell, Suzanne Z.; Black-Schaffer, W. Stephen

    2016-01-01

    The required medical knowledge and skill set for the pathologist of 2020 are different than in 2005. Pathology residency training curriculum must accordingly change to fulfill the needs of these ever-changing requirements. In order to make rational curricular adjustments, it is important for us to know the current trajectory of resident training in pathology—where we have been, what our actual current training curriculum is now—to understand how that might change in anticipation of meeting the needs of a changing patient and provider population and to fit within the evolving future biomedical and socioeconomic health-care setting. In 2013, there were 143 Accreditation Council for Graduate Medical Education-accredited pathology residency training programs in the United States, with approximately 2400 residents. There is diversity among residency training programs not only with respect to the number of residents but also in training venue(s). To characterize this diversity among pathology residency training programs, a curriculum survey was conducted of pathology residency program directors in 2013 and compared with a similar survey taken almost 9 years previously in 2005 to identify trends in pathology residency curriculum. Clinical pathology has not changed significantly in the number of rotations over 9 years; however, anatomic pathology has changed dramatically, with an increase in the number of surgical pathology rotations coupled with a decline in stand-alone autopsy rotations. With ever-expanding medical knowledge that the graduating pathology resident must know, it is necessary to (1) reflect upon what are the critical need subjects, (2) identify areas that have become of lesser importance, and then (3) prioritize training accordingly. PMID:28725779

  8. Enhancing teamwork between chief residents and residency program directors: description and outcomes of an experiential workshop.

    Science.gov (United States)

    McPhillips, Heather A; Frohna, John G; Murad, M Hassan; Batra, Maneesh; Panda, Mukta; Miller, Marsha A; Brigham, Timothy P; Doughty, Robert A

    2011-12-01

    An effective working relationship between chief residents and residency program directors is critical to a residency program's success. Despite the importance of this relationship, few studies have explored the characteristics of an effective program director-chief resident partnership or how to facilitate collaboration between the 2 roles, which collectively are important to program quality and resident satisfaction. We describe the development and impact of a novel workshop that paired program directors with their incoming chief residents to facilitate improved partnerships. The Accreditation Council for Graduate Medical Education sponsored a full-day workshop for residency program directors and their incoming chief residents. Sessions focused on increased understanding of personality styles, using experiential learning, and open communication between chief residents and program directors, related to feedback and expectations of each other. Participants completed an anonymous survey immediately after the workshop and again 8 months later to assess its long-term impact. Participants found the workshop to be a valuable experience, with comments revealing common themes. Program directors and chief residents expect each other to act as a role model for the residents, be approachable and available, and to be transparent and fair in their decision-making processes; both groups wanted feedback on performance and clear expectations from each other for roles and responsibilities; and both groups identified the need to be innovative and supportive of changes in the program. Respondents to the follow-up survey reported that workshop participation improved their relationships with their co-chiefs and program directors. Participation in this experiential workshop improved the working relationships between chief residents and program directors. The themes that were identified can be used to foster communication between incoming chief residents and residency directors and to

  9. A Review of the Tissue Residue Approach for Organic and Organometallic Compounds in Aquatic Organisms

    Science.gov (United States)

    This paper reviews the tissue residue approach (TRA) for toxicity assessment as it applies to organic chemicals and some organometallic compounds (tin, mercury, and lead). Specific emphasis was placed on evaluating key factors that influence interpretation of critical body resid...

  10. Comparison of Emergency Medicine Malpractice Cases Involving Residents to Non-Resident Cases.

    Science.gov (United States)

    Gurley, Kiersten L; Grossman, Shamai A; Janes, Margaret; Yu-Moe, C Winnie; Song, Ellen; Tibbles, Carrie D; Shapiro, Nathan I; Rosen, Carlo L

    2018-04-17

    Data are lacking on how emergency medicine (EM) malpractice cases with resident involvement differs from cases that do not name a resident. To compare malpractice case characteristics in cases where a resident is involved (resident case) to cases that do not involve a resident (non-resident case) and to determine factors that contribute to malpractice cases utilizing EM as a model for malpractice claims across other medical specialties. We used data from the Controlled Risk Insurance Company (CRICO) Strategies' division Comparative Benchmarking System (CBS) to analyze open and closed EM cases asserted from 2009-2013. The CBS database is a national repository that contains professional liability data on > 400 hospitals and > 165,000 physicians, representing over 30% of all malpractice cases in the U.S (> 350,000 claims). We compared cases naming residents (either alone or in combination with an attending) to those that did not involve a resident (non-resident cohort). We reported the case statistics, allegation categories, severity scores, procedural data, final diagnoses and contributing factors. Fisher's exact test or t-test was used for comparisons (alpha set at 0.05). Eight hundred and forty-five EM cases were identified of which 732 (87%) did not name a resident (non-resident cases), while 113 (13%) included a resident (resident cases) (Figure 1). There were higher total incurred losses for non-resident cases (Table 1). The most frequent allegation categories in both cohorts were "Failure or Delay in Diagnosis/Misdiagnosis" and "Medical Treatment" (non-surgical procedures or treatment regimens i.e. central line placement). Allegation categories of Safety and Security, Patient Monitoring, Hospital Policy and Procedure and Breach of Confidentiality were found in the non-resident cases. Resident cases incurred lower payments on average ($51,163 vs. $156,212 per case). Sixty six percent (75) of resident vs 57% (415) of non-resident cases were high severity claims

  11. Assessment of heavy metal residues in water, fish tissue and human ...

    African Journals Online (AJOL)

    MICHAEL HORSFALL

    ABSTRACT: Residual levels of lead, chromium, cadmium and zinc in water and fish tissue from. Ubeji River, Warri and blood samples from residents of Ubeji were analysed. Control water and fish samples were obtained from Eleyele River and blood from residents of Ibadan. All the samples collected were digested using a ...

  12. Pediatric dermatology training during residency: a survey of the 2014 graduating residents.

    Science.gov (United States)

    Akhavan, Alaleh; Murphy-Chutorian, Blair; Friedman, Adam

    2015-01-01

    Knowledge of pediatric dermatology is considered a core competency of dermatology training and should be expected of all practicing dermatologists. While the numbers of both pediatric dermatology fellowships and board certified pediatric dermatologists in the workforce have increased over the years, recent reports suggest that there is a gap in pediatric dermatology education during dermatology residency. The goal of this study is to assess the current state of pediatric education during residency, as well as the clinical experience, satisfaction and expectations of graduating dermatology residents. A 31-question self-report survey was distributed electronically to 294 third-year dermatology residents with questions pertaining to demographics, didactic education, resident experience in pediatric dermatology training, satisfaction with pediatric training and future plans. One hundred and twenty-three residents responded (41.8% response rate) representing approximately 29.1% of the total number of graduating residents. 69 (56.1%) residents reported academic time specifically devoted to pediatric dermatology, the majority (79.7%) of which was led by pediatric dermatologists. 82% of residents reported dedicated pediatric dermatology clinics at their program. 86.8% of respondents felt that their training in pediatric dermatology will allow them to confidently see pediatric dermatology patients in practice. This survey highlights a promising state of pediatric dermatology training among current graduating dermatology residents. The majority of current graduating dermatology residents are satisfied with their pediatric dermatology education, feel confident treating pediatric patients, and plan to see pediatric patients in clinical practice. © 2015 Wiley Periodicals, Inc.

  13. Do otolaryngology residency applicants relocate for training?

    Science.gov (United States)

    Gebhard, Grant M; Hauser, Leah J; Dally, Miranda J; Weitzenkamp, David A; Cabrera-Muffly, Cristina

    2016-04-01

    To determine whether there is an association between the geographic location of an applicant's undergraduate school, medical school, and residency program among matched otolaryngology residency applicants. Observational. Otolaryngology residency program applications to our institution from 2009 to 2013 were analyzed. The geographic location of each applicant's undergraduate education and medical education were collected. Online public records were queried to determine the residency program location of matched applicants. Applicants who did not match or who attended medical school outside the United States were excluded. Metro area, state, and region were determined according to US Census Bureau definitions. From 2009 to 2013, 1,089 (78%) of 1,405 applicants who matched into otolaryngology residency applied to our institution. The number of subjects who attended medical school and residency in the same geographic region was 241 (22%) for metropolitan area, 305 (28%) for state, and 436 (40%) for region. There was no difference in geographic location retention by gender or couples match status of the subject. United States Medical Licensing Exam step 1 scores correlated with an increased likelihood of subjects staying within the same geographic region (P = .03). Most otolaryngology applicants leave their previous geographic area to attend residency. Based on these data, the authors recommend against giving weight to geography as a factor when inviting applicants to interview. NA. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  14. Neurosurgery resident leadership development: an innovative approach.

    Science.gov (United States)

    Pettit, Jeffrey E; Dahdaleh, Nader S; Albert, Gregory W; Greenlee, Jeremy D

    2011-02-01

    A great deal of time and resources go into the development and training of neurosurgeons. One area that has minimal literature and assessment is leadership development. Under the core competency of interpersonal and communication skills, the Accreditation Council for Graduate Medical Education has indicated that residents are expected to work effectively as a member or leader of a healthcare team. This article reveals how a structured leadership program was developed so that residents are better prepared for the role of chief resident and future leadership roles. Beginning in October 2006, residents attended a series of 1-hour workshops conducted monthly. Topics included leadership style, conflict management, effective feedback, team building, team leadership, motivation, and moving from peer to leader. A retrospective pretest was conducted at the end of the program. Residents reported a significant knowledge gain for the majority of topics. Resident comments indicated a greater awareness of the impact of leading and ways to improve their personal leadership. Quantitatively and qualitatively, residents and faculty reported that the leadership program made a significant impact on the development of future neurosurgical leaders.

  15. Problem neurology residents: a national survey.

    Science.gov (United States)

    Tabby, David S; Majeed, Muhammed H; Schwartzman, Robert J

    2011-06-14

    Problem residents are found across most medical specialties at a prevalence of about 10%. This study was designed to explore the prevalence and causes of problem neurology residents and to compare neurology programs' responses and outcomes. Directors of 126 US neurology residency programs were sent an electronic survey. We collected data on demographics, first and all "identifiers" of problem residents, and year of training in which the problem was found. We asked about observable signs, etiology, and who performed remediation. We asked what resources were used and what outcomes occurred. Ninety-five program directors completed surveys (75% response rate). Almost all neurology programs have problem residents (81%). Age, sex, marital status, being a US native, or attending a US medical school had no effect on problem status. Being a parent carried a lower likelihood of problems (32%). Most commonly the problem is acted on during the first year of training. Faculty members without defined educational roles were the most frequent first identifiers. Program directors were the most common remediators. The most common remediation techniques were increasing supervision and assigning a faculty mentor. Graduate medical education office and psychiatric or psychological counseling services were most often used. Eleven percent of problem residents required a program for impaired physicians and 14% required a leave of absence. Sixteen percent were dismissed from their programs. The prevalence of problem residents in neurology is similar to other disciplines, and various resources are available to remediate them.

  16. Are neurology residents interested in headache?

    Science.gov (United States)

    Gago-Veiga, A B; Santos-Lasaosa, S; Viguera Romero, J; Pozo-Rosich, P

    The years of residency are the pillars of the subsequent practice in every medical specialty. The aim of our study is to evaluate the current situation, degree of involvement, main interests, and perceived quality of the training received by Spanish residents of neurology, specifically in the area of headache. A self-administered survey was designed by the Headache Study Group of the Spanish Society of Neurology (GECSEN) and was sent via e-mail to all residents who were members of the Society as of May 2015. Fifty-three residents completed the survey (N = 426, 12.4%): 6% were first year residents, 25.5% second year, 23.5% third year, and 45% fourth year residents, all from 13 different Spanish autonomous communities. The areas of greatest interest are, in this order: Vascular neurology, headache, and epilepsy. Of them, 85% believe that the area of headache is undervalued. More than half of residents (52.8%) do not rotate in specific Headache Units and only 35.8% complete their training dominating anaesthetic block and toxin infiltration techniques. Of them, 81.1% believe that research is scarce or absent; 69.8% have never made a poster/presentation, 79.3% have not published and only 15% collaborate on research projects in this area. Lastly, 40% believe that they have not received adequate training. Headache is among the areas that interest our residents the most; however, we believe that we must improve their training both at a patient healthcare level and as researchers. Thus, increasing the number of available courses, creating educational web pages, involving residents in research, and making a rotation in a specialised unit mandatory are among the fundamental objectives of the GECSEN. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  17. Program for developing leadership in pharmacy residents.

    Science.gov (United States)

    Fuller, Patrick D

    2012-07-15

    An innovative, structured approach to incorporating leadership development activities into pharmacy residency training is described. The American Society of Health-System Pharmacists (ASHP) has called for increased efforts to make leadership development an integral component of the training of pharmacy students and new practitioners. In 2007, The Nebraska Medical Center (TNMC) took action to systematize leadership training in its pharmacy residency programs by launching a new Leadership Development Series. Throughout the residency year, trainees at TNMC participate in a variety of activities: (1) focused group discussions of selected articles on leadership concepts written by noted leaders of the past and present, (2) a two-day offsite retreat featuring trust-building exercises and physical challenges, (3) a self-assessment designed to help residents identify and use their untapped personal strengths, (4) training on the effective application of different styles of communication and conflict resolution, and (5) education on the history and evolution of health-system pharmacy, including a review and discussion of lectures by recipients of ASHP's Harvey A. K. Whitney Award. Feedback from residents who have completed the series has been positive, with many residents indicating that it has stimulated their professional growth and helped prepared them for leadership roles. A structured Leadership Development Series exposes pharmacy residents to various leadership philosophies and principles and, through the study of Harvey A. K. Whitney Award lectures, to the thoughts of past and present pharmacy leaders. Residents develop an increased self-awareness through a resident fall retreat, a StrengthsFinder assessment, and communication and conflict-mode assessment tools.

  18. Tissue bionics: examples in biomimetic tissue engineering

    International Nuclear Information System (INIS)

    Green, David W

    2008-01-01

    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic

  19. Tissue bionics: examples in biomimetic tissue engineering.

    Science.gov (United States)

    Green, David W

    2008-09-01

    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

  20. Tissue bionics: examples in biomimetic tissue engineering

    Energy Technology Data Exchange (ETDEWEB)

    Green, David W [Bone and Joint Research Group, Developmental Origins of Health and Disease, General Hospital, University of Southampton, SO16 6YD (United Kingdom)], E-mail: Hindoostuart@googlemail.com

    2008-09-01

    Many important lessons can be learnt from the study of biological form and the functional design of organisms as design criteria for the development of tissue engineering products. This merging of biomimetics and regenerative medicine is termed 'tissue bionics'. Clinically useful analogues can be generated by appropriating, modifying and mimicking structures from a diversity of natural biomatrices ranging from marine plankton shells to sea urchin spines. Methods in biomimetic materials chemistry can also be used to fabricate tissue engineering scaffolds with added functional utility that promise human tissues fit for the clinic.

  1. 26 CFR 25.2702-5 - Personal residence trusts.

    Science.gov (United States)

    2010-04-01

    ... a portion of the residence is used in an activity meeting the requirements of section 280A(c) (1) or... provision of lodging (e.g. a hotel or a bed and breakfast). A residence is not a personal residence if... portion of their interests in the residence) to the same personal residence trust, provided that the...

  2. 0 + 5 Vascular Surgery Residents' Operative Experience in General Surgery: An Analysis of Operative Logs from 12 Integrated Programs.

    Science.gov (United States)

    Smith, Brigitte K; Kang, P Chulhi; McAninch, Chris; Leverson, Glen; Sullivan, Sarah; Mitchell, Erica L

    2016-01-01

    Integrated (0 + 5) vascular surgery (VS) residency programs must include 24 months of training in core general surgery. The Accreditation Council for Graduate Medical Education currently does not require specific case numbers in general surgery for 0 + 5 trainees; however, program directors have structured this time to optimize operative experience. The aim of this study is to determine the case volume and type of cases that VS residents are exposed to during their core surgery training. Accreditation council for graduate medical education operative logs for current 0 + 5 VS residents were obtained and retrospectively reviewed to determine general surgery case volume and distribution between open and laparoscopic cases performed. Standard statistical methods were applied. A total of 12 integrated VS residency programs provided operative case logs for current residents. A total of 41 integrated VS residents in clinical years 2 through 5. During the postgraduate year-1 training year, residents participated in significantly more open than laparoscopic general surgery cases (p surgery cases are hernia repair (20%), skin and soft tissue (7.4%), and breast (6.3%). Residents in programs with core surgery over 3 years participated in significantly more general surgery operations compared with residents in programs with core surgery spread out over 4 years (p = 0.035). 0 + 5 VS residents perform significantly more open operations than laparoscopic operations during their core surgery training. The majority of these operations are minor, nonabdominal procedures. The 0 + 5 VS residency program general surgery operative training requirements should be reevaluated and case minimums defined. The general surgery training component of 0 + 5 VS residencies may need to be restructured to meet the needs of current and future trainees. Copyright © 2016 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

  3. Perspectives of Residents of Mashhad School of Dentistry about the Curriculum of Residency Program

    Directory of Open Access Journals (Sweden)

    Javad Sarabadani

    2015-09-01

    Full Text Available Introduction: This study was carried out to analyze the viewpoint of the residents of school of dentistry about the curriculum presented in the residency program to students of Mashhad School of Dentistry. Methods: To evaluate the perspectives of residents of dental school about the curriculum and regulations of residency program, a questionnaire was designed whose validity and reliability were confirmed by the authorities of School of Dentistry and test-retest reliability, respectively. The questionnaire was distributed among 100 residents and 80 of them completed the questionnaires. The data were analyzed by SPSS software (version 11.5. Results: A total of 43% of residents were informed of the curriculum (e.g. academic leave, transfer, removal of semester, etc.. As for the ability to write research proposal, 42.7% of residents were reported to have a favorable status, i.e. they were able to write more than 80% of their proposal. From among the residents, 30.4% had specialized English language certificate. Most of them (77% were satisfied with the professional staff, faculty members, of the faculty. Many students liked to participate in the teaching method courses of the residency program. Conclusion: Residents maintained that the curriculum in such domains as educational and research issues and special capabilities had some weak points. Thus, appropriate strategies are recommended to be applied to revise the curriculum using the residents’ views on these programs.

  4. Confidence, knowledge, and skills at the beginning of residency. A survey of pathology residents.

    Science.gov (United States)

    Hsieh, Cindy M; Nolan, Norris J

    2015-01-01

    To document the pathology learning experiences of pathology residents prior to residency and to determine how confident they were in their knowledge and technical skills. An online survey was distributed to all pathology residency program directors in the United States, who were requested to forward the survey link to their residents. Data were obtained on pathology electives, grossing experience, and frozen section experience. Likert scale questions assessed confidence level in knowledge and skills. In total, 201 pathology residents responded (8% of residents in the United States). Prior to starting residency, most respondents had exposure to anatomic pathology through elective rotations. Few respondents had work-related experience. Most did not feel confident in their pathology-related knowledge or skills, and many did not understand what pathology resident duties entail. Respondents gained exposure to pathology primarily through elective rotations, and most felt the elective experience prepared them for pathology residency. However, elective time may be enhanced by providing opportunities for students to increase hands-on experience and understanding of resident duties. Copyright© by the American Society for Clinical Pathology.

  5. Changes in Personal Relationships During Residency and Their Effects on Resident Wellness: A Qualitative Study.

    Science.gov (United States)

    Law, Marcus; Lam, Michelle; Wu, Diana; Veinot, Paula; Mylopoulos, Maria

    2017-11-01

    Residency poses challenges for residents' personal relationships. Research suggests residents rely on family and friends for support during their training. The authors explored the impact of residency demands on residents' personal relationships and the effects changes in those relationships could have on their wellness. The authors used a constructivist grounded theory approach. In 2012-2014, they conducted semistructured interviews with a purposive and theoretical sample of 16 Canadian residents from various specialties and training levels. Data analysis occurred concurrently with data collection, allowing authors to use a constant comparative approach to explore emergent themes. Transcripts were coded; codes were organized into categories and then themes to develop a substantive theory. Residents perceived their relationships to be influenced by their evolving professional identity: Although personal relationships were important, being a doctor superseded them. Participants suggested they were forced to adapt their personal relationships, which resulted in the evolution of a hierarchy of relationships that was reinforced by the work-life imbalance imposed by their training. This poor work-life balance seemed to result in relationship issues and diminish residents' wellness. Participants applied coping mechanisms to manage the conflict arising from the adaptation and protect their relationships. To minimize the effects of identity dissonance, some gravitated toward relationships with others who shared their professional identity or sought social comparison as affirmation. Erosion of personal relationships could affect resident wellness and lead to burnout. Educators must consider how educational programs impact relationships and the subsequent effects on resident wellness.

  6. Emergency Medicine Residency Applicant Characteristics Associated with Measured Adverse Outcomes During Residency

    Directory of Open Access Journals (Sweden)

    Jesse Bohrer-Clancy

    2017-12-01

    Full Text Available Introduction Negative outcomes in emergency medicine (EM programs use a disproportionate amount of educational resources to the detriment of other residents. We sought to determine if any applicant characteristics identifiable during the selection process are associated with negative outcomes during residency. Methods Primary analysis consisted of looking at the association of each of the descriptors including resident characteristics and events during residency with a composite measure of negative outcomes. Components of the negative outcome composite were any formal remediation, failure to complete residency, or extension of residency. Results From a dataset of 260 residents who completed their residency over a 19-year period, 26 (10% were osteopaths and 33 (13% were international medical school graduates A leave of absence during medical school (p <.001, failure to send a thank-you note (p=.008, a failing score on United States Medical Licensing Examination Step I (p=.002, and a prior career in health (p=.034 were factors associated with greater likelihood of a negative outcome. All four residents with a “red flag” during their medicine clerkships experienced a negative outcome (p <.001. Conclusion “Red flags” during EM clerkships, a leave of absence during medical school for any reason and failure to send post-interview thank-you notes may be associated with negative outcomes during an EM residency.

  7. Does operative experience during residency correlate with reported competency of recent general surgery graduates?

    Science.gov (United States)

    Safavi, Arash; Lai, Sarah; Butterworth, Sonia; Hameed, Morad; Schiller, Dan; Skarsgard, Erik

    2012-01-01

    Background Identification of attributes of residency training that predict competency would improve surgical education. We hypothesized that case experience during residency would correlate with self-reported competency of recent graduates. Methods Aggregate case log data of residents enrolled in 2 general surgery programs were collected over a 12-month period and stratified into Surgical Council on Resident Education (SCORE) categories. We surveyed recent (surgery (4, 0.04%), and the least common EU procedure was abdomen–spleen (1, 0.1%). The questionnaire response rate was 45%. For EC procedures, self-reported competency was highest in skin and soft tissue, thoracic and head and neck (each 100%) and lowest in vascular–venous (54%), whereas for EU procedures it was highest in abdomen–general (100%) and lowest in vascular–arterial (62%). The correlation between case volume and self-reported competency was poor (R = 0.2 for EC procedures). Conclusion Self-reported competency correlates poorly with operative case experience during residency. Other curriculum factors, including specific rotations and timing, balance between inpatient and outpatient surgical experience and competition for cases, may contribute to procedural competency acquisition during residency. PMID:22854144

  8. The impact of an acute care surgery team on general surgery residency.

    Science.gov (United States)

    Hatch, Quinton; McVay, Derek; Johnson, Eric K; Maykel, Justin A; Champagne, Bradley J; Steele, Scott R

    2014-11-01

    Acute care surgical teams (ACSTs) have limited data in residency. We sought to determine the impact of an ACST on the depth and breadth of general surgery resident training. One year prior to and after implementation of an ACST, Accreditation Council for Graduate Medical Education case logs spanning multiple postgraduate year levels were compared for numbers, case types, and complexity. We identified 6,009 cases, including 2,783 after ACST implementation. ACSTs accounted for 752 cases (27%), with 39.2% performed laparoscopically. ACST cases included biliary (19.4%), skin/soft tissue (10%), hernia (9.8%), and appendix (6.5%). Second-year residents performed a lower percentage of laparoscopic cases after the creation of the ACST (20.4% vs 26.3%; P = .003), while chief residents performed a higher percentage (42.1 vs 37.4; P = .04). Case numbers and complexity following ACST development were unchanged within all year groups (P > .1). ACST in a residency program does not sacrifice resident case complexity, diversity, or volume. Published by Elsevier Inc.

  9. Effectiveness of resident as teacher curriculum in preparing emergency medicine residents for their teaching role.

    Science.gov (United States)

    Hosein Nejad, Hooman; Bagherabadi, Mehdi; Sistani, Alireza; Dargahi, Helen

    2017-01-01

    Over the past 30 years, recognizing the need and importance of training residents in teaching skills has resulted in several resident-as-teacher programs. The purpose of this study was to explore the impact of this teaching initiative and investigate the improvement in residents' teaching skills through evaluating their satisfaction and perceived effectiveness as well as assessing medical students' perception of the residents' teaching quality. This research is a quasi-experimental study with pre- and post-tests, continuing from Dec 2010 to May 2011 in Imam Hospital, Tehran University of Medical Sciences. In this survey, Emergency Medicine Residents (n=32) participated in an 8-hour workshop. The program evaluation was performed based on Kirkpatrick's model by evaluation of residents in two aspects: self-assessment and evaluation by interns who were trained by these residents. Content validity of the questionnaires was judged by experts and reliability was carried out by test re-test. The questionnaires were completed before and after the intervention. Paired sample t-test was applied to analyze the effect of RAT curriculum and workshop on the improvement of residents' teaching skills based on their self-evaluation and Mann-Whitney U test was used to identify significant differences between the two evaluator groups before and after the workshop. The results indicated that residents' attitude towards their teaching ability was improved significantly after participating in the workshop (pTeacher for emergency medicine residents resulted in favorable outcomes in the second evaluated level of Kirkpatrick's model, i.e. it showed measurable positive changes in the self-assessments of medical residents about different aspects of teaching ability and performance. However, implementing training sessions for resident physicians, although effective in improving their confidence and self-assessment of their teaching skills, seems to cause no positive change in the third

  10. Identifying Gaps and Launching Resident Wellness Initiatives: The 2017 Resident Wellness Consensus Summit

    Directory of Open Access Journals (Sweden)

    Nicole Battaglioli

    2018-02-01

    Full Text Available Introduction: Burnout, depression, and suicidality among residents of all specialties have become a critical focus for the medical education community, especially among learners in graduate medical education. In 2017 the Accreditation Council for Graduate Medical Education (ACGME updated the Common Program Requirements to focus more on resident wellbeing. To address this issue, one working group from the 2017 Resident Wellness Consensus Summit (RWCS focused on wellness program innovations and initiatives in emergency medicine (EM residency programs. Methods: Over a seven-month period leading up to the RWCS event, the Programmatic Initiatives workgroup convened virtually in the Wellness Think Tank, an online, resident community consisting of 142 residents from 100 EM residencies in North America. A 15-person subgroup (13 residents, two faculty facilitators met at the RWCS to develop a public, central repository of initiatives for programs, as well as tools to assist programs in identifying gaps in their overarching wellness programs. Results: An online submission form and central database of wellness initiatives were created and accessible to the public. Wellness Think Tank members collected an initial 36 submissions for the database by the time of the RWCS event. Based on general workplace, needs-assessment tools on employee wellbeing and Kern’s model for curriculum development, a resident-based needs-assessment survey and an implementation worksheet were created to assist residency programs in wellness program development. Conclusion: The Programmatic Initiatives workgroup from the resident-driven RWCS event created tools to assist EM residency programs in identifying existing initiatives and gaps in their wellness programs to meet the ACGME’s expanded focus on resident wellbeing.

  11. Anesthesiology resident personality type correlates with faculty assessment of resident performance.

    Science.gov (United States)

    Schell, Randall M; Dilorenzo, Amy N; Li, Hsin-Fang; Fragneto, Regina Y; Bowe, Edwin A; Hessel, Eugene A

    2012-11-01

    To study the association between anesthesiology residents' personality preference types, faculty evaluations of residents' performance, and knowledge. Convenience sample and prospective study. Academic department of anesthesiology. Consenting anesthesiology residents (n = 36). All participants completed the Myers Briggs Type Indicator® (MBTI®). All residents' 6-month summation of daily focal evaluations completed by faculty [daily performance score (DPS); 1 = unsatisfactory, 2 = needs improvement, 3 = meets expectations, 4 = exceeds expectations], as well as a global assessment of performance (GAP) score based on placement of each resident into perceived quartile compared with their peers (ie,1 = first, or top, quartile) by senior faculty (n = 7) who also completed the MBTI, were obtained. The resident MBTI personality preferences were compared with the DPS and GAP scores, the United States Medical Licensing Examination (USMLE) I and II scores, and faculty MBTI personality type. There was no association between personality preference type and performance on standardized examinations (USMLE I, II). The mean GAP score was better (higher quartile score) for Extraverts than Introverts (median 2.0 vs 2.6, P = 0.0047) and for Sensing versus Intuition (median 2.0 vs 2.6, P = 0.0206) preference. Faculty evaluator MBTI preference type did not influence the GAP scores they assigned residents. Like GAP, the DPS was better for residents with Sensing versus Intuition preference (median 3.5 vs 3.3, P = 0.0111). No difference in DPS was noted between Extraverts and Introverts. Personality preference type was not associated with resident performance on standardized examinations, but it was associated with faculty evaluations of resident performance. Residents with Sensing personality preference were evaluated more favorably on global and focal faculty evaluations than those residents who chose the Intuition preference. Extraverted residents were evaluated more favorably on

  12. Vaccination against canine leishmaniosis increases the phagocytic activity, nitric oxide production and expression of cell activation/migration molecules in neutrophils and monocytes.

    Science.gov (United States)

    Moreira, Marcela L; Costa-Pereira, Christiane; Alves, Marina Luiza Rodrigues; Marteleto, Bruno H; Ribeiro, Vitor M; Peruhype-Magalhães, Vanessa; Giunchetti, Rodolfo C; Martins-Filho, Olindo A; Araújo, Márcio S S

    2016-04-15

    Visceral leishmaniasis (VL) is transmitted by phlebotomine sandfly vectors and domestic dogs serve as a reservoir. The elimination of seropositive dogs has been a recommended strategy for managing the disease in Brazil. A protective canine vaccine would be an important tool for controlling the disease, reducing the parasites available to sandfly vectors and, consequently, reducing the number of human VL cases. Leishmune(®) is an anti-canine Leishmaniosis (VL Canine) vaccine produced by Zoetis (Pfizer, Brazil) that was commercially available in Brazil until 2014. The main goal of the present study was to investigate the protective immunological events induced by vaccination with Leishmune(®) in the time frame of one year. Healthy, non-vaccinated dogs and dogs of 1, 6 and 10 months post-vaccination were evaluated. Results showed that Leishmune(®) induced an increase in phagocytic activity of neutrophils and monocytes and also increased NO production. Immunological events were correlated with functional responses, as high levels of IgG and an increase of the receptor Fcγ were detected. Vaccination induced an increased expression of TLR (2, 4, 5, 9), integrin (CD29, CD49f), activation (MHCII) and co-stimulatory (CD80, CD81) molecules by neutrophils and monocytes. Vaccination led to decrease of IL-4 and an increase of IL-8 production by monocytes and higher IFN-γ and IL-17 production by T-cells. The results suggested that Leishmune(®) was able to induce a long-lasting change in immune response, mediated by supportive immunological events that may be participating in protective immunity against CL. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Detection and analysis of human serum albumin nanoparticles within phagocytic cells at the resolution of individual live cell or single 3D multicellular spheroid

    Energy Technology Data Exchange (ETDEWEB)

    Afrimzon, Elena; Zurgil, Naomi; Sobolev, Maria; Shafran, Yana [Bar-Ilan University, The Biophysical Interdisciplinary Schottenstein Center for the Research and Technology of the Cellome (Israel); Langer, Klaus; Zlatev, Iavor [Westfälischen Wilhelms-Universität Münster, Institut für Pharmazeutische Technologie und Biopharmazie (Germany); Wronski, Robert; Windisch, Manfred [QPS Austria GmbH (Austria); Briesen, Hagen von [Fraunhofer Institute for Biomedical Engineering IBMT, Department of Cell Biology & Applied Virology (Germany); Schmidt, Reinhold [Medical University of Graz, Department of Neurology (Austria); Pietrzik, Claus [University Medical Center of the Johannes Gutenberg University of Mainz, Institute of Pathobiochemistry (Germany); Deutsch, Mordechai, E-mail: motti.jsc@gmail.com [Bar-Ilan University, The Biophysical Interdisciplinary Schottenstein Center for the Research and Technology of the Cellome (Israel)

    2015-12-15

    Since nanoparticles (NPs) have shown great potential in various biomedical applications, live cell response to NPs should be thoroughly explored prior to their in vivo use. In the current study, live cell array (LCA) methodology and unique cell-based assays were used to study the interaction of magnetite (HSA-Mag NP) loaded human serum albumin NPs with phagocytic cells. The LCA enabled cell culturing during HSA-Mag NP accumulation and monolayer or spheroid formation, concomitantly with on-line monitoring of NP internalization. These platforms were also utilized for imaging intercellular links between living cells preloaded with HSA-Mag NP in 2D and 3D resolution. HSA-Mag NP uptake by cells was quantified by imaging, and analyzed using time-resolved measurements. Image analysis of the individual cells in cell populations showed accumulation of HSA-Mag NP by promonocytes and glial cells in a dose- and time-dependent manner. High variability of NP accumulation in individual cells within cell populations, as well as cell subgroups, was evident in both cell types. Following 24 h interaction, uptake of HSA-Mag NP was about 10 times more efficient in glial cells than in activated promonocytes. The presented assays may facilitate detection and analysis of the amount of NPs within individual cells, as well as the rate of NP accumulation and processing in different subsets of living cells. Such data are crucial for estimating predicted drug dosage delivered by NPs, as well as to study possible mechanisms for NP interference with live cells.

  14. Capsules from pathogenic and non-pathogenic Cryptococcus spp. manifest significant differences in structure and ability to protect against phagocytic cells.

    Directory of Open Access Journals (Sweden)

    Glauber de S Araujo

    Full Text Available Capsule production is common among bacterial species, but relatively rare in eukaryotic microorganisms. Members of the fungal Cryptococcus genus are known to produce capsules, which are major determinants of virulence in the highly pathogenic species Cryptococcus neoformans and Cryptococcus gattii. Although the lack of virulence of many species of the Cryptococcus genus can be explained solely by the lack of mammalian thermotolerance, it is uncertain whether the capsules from these organisms are comparable to those of the pathogenic cryptococci. In this study, we compared the characteristic of the capsule from the non-pathogenic environmental yeast Cryptococcus liquefaciens with that of C. neoformans. Microscopic observations revealed that C. liquefaciens has a capsule visible in India ink preparations that was also efficiently labeled by three antibodies generated to specific C. neoformans capsular antigens. Capsular polysaccharides of C. liquefaciens were incorporated onto the cell surface of acapsular C. neoformans mutant cells. Polysaccharide composition determinations in combination with confocal microscopy revealed that C. liquefaciens capsule consisted of mannose, xylose, glucose, glucuronic acid, galactose and N-acetylglucosamine. Physical chemical analysis of the C. liquefaciens polysaccharides in comparison with C. neoformans samples revealed significant differences in viscosity, elastic properties and macromolecular structure parameters of polysaccharide solutions such as rigidity, effective diameter, zeta potential and molecular mass, which nevertheless appeared to be characteristics of linear polysaccharides that also comprise capsular polysaccharide of C. neoformans. The environmental yeast, however, showed enhanced susceptibility to the antimicrobial activity of the environmental phagocytes, suggesting that the C. liquefaciens capsular components are insufficient in protecting yeast cells against killing by amoeba. These results

  15. Nitroxide Tempol down-regulates kinase activities associated with NADPH oxidase function in phagocytic cells and potentially decreases their fungicidal response.

    Science.gov (United States)

    Santos, Gérsika B; Ribeiro, Ana C G; Lima, Samuel N P; Trostchansky, Andrés; Cerdeira, Cláudio Daniel; Brigagão, Maísa R P L

    2018-01-05

    The identification of novel targets to control inflammation in humans is probably the primary challenge that impairs the development of new anti-inflammatory drugs. Therefore, the modulation of intracellular signaling pathways in phagocytes may be an interesting means of achieving this goal. However, this change to signaling can compromise the host's susceptibility to invading pathogens. We investigated whether the antioxidant nitroxide Tempol regulates the activity of kinases associated with the production of oxidants in neutrophils, which affects the fungicidal capability of these cells. The effects of Tempol on PMA- or fMLP-activated neutrophils were examined by oxygen consumption as an index of the oxidative burst, a release of extracellular and total Reactive Oxygen Species (ROS) by chemiluminescence, kinase activities through analysis of ATP consumption during enzyme activities and the dot blot immunoassay and, finally, by neutrophil capacity of killing Candida albicans. Tempol significantly inhibited the neutrophil oxidative burst in a concentration-dependent manner and decreased oxygen consumption (IC50 = 45 μM) and extracellular/total ROS formation with an increase on the lag period response. In addition, Tempol inhibited neutrophil kinase activities (i.e., a decrease in protein phosphorylation) elicited through different biochemical pathways and consequently impaired the fungicidal activity of these cells. Although Tempol has potential anti-inflammatory activity that acts on different intracellular pathways (such as those involving kinases), researchers should be cautious, since this nitroxide down-regulated oxidants production and the fungicidal response of neutrophils. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. General Surgery Resident Satisfaction on Cardiothoracic Rotations.

    Science.gov (United States)

    Lussiez, Alisha; Bevins, Jack; Plaska, Andrew; Rosin, Vadim; Reddy, Rishindra M

    2016-01-01

    General surgery residents' exposure to cardiothoracic (CT) surgery rotations has decreased, which may affect resident satisfaction. We surveyed general surgery graduates to assess the relationships among rotation satisfaction, CT disease exposure, rotation length, mentorship, and mistreatment. A survey assessing CT curriculum, exposure, mentorship, and satisfaction was forwarded to general surgery graduates from 17 residency programs. A Wilcoxon rank-sum test was used to assess statistical significance of ordinal level data. Statistical significance was defined as p surgery residency programs who graduated between the years of 1999 to 2014. A total of 94 responses were completed and received. Receiving adequate exposure to CT procedures and disease management was significantly associated with higher satisfaction ratings for all procedures, particularly thoracotomy incisions (p Surgery. Published by Elsevier Inc. All rights reserved.

  17. Introducing "optimal challenges" in resident training

    DEFF Research Database (Denmark)

    Sørensen, Anette Bagger; Christensen, Mette Krogh

    Background: Residents are often caught between two interests: the resident’s desire to participate in challenging learning situations and the department’s work planning. However, these interests may clash if they are not coordinated by the senior doctors, and challenging learning situations risk...... that the residents benefit from the intervention because they experienced more optimal challenges than before the intervention. However, the matching of resident and case seems to work against the established culture in the department: The daily work has for many years been organized so that senior doctors have...... relationships in order to meet the health system’s and the patients’ call for continuity in the treatment. Take-home message: The matching of resident and case stimulates optimal learning situations, but cultural and organizational values concerning the doctor-patient continuity are challenged....

  18. Drug target residence time: a misleading concept.

    Science.gov (United States)

    Folmer, Rutger H A

    2018-01-01

    Since the importance of drug target residence time was first highlighted more 10 years ago, slow binding kinetics has received much attention in the drug discovery literature, and indeed within pharmaceutical research. However, the residence concept as presented in most papers is supported by rather misleading simulations and arguments, and by examples where compounds are taken out of their pharmacokinetic context. Moreover, fast association is typically more desirable than slow, and advantages of long residence time, notably a potential disconnect between pharmacodynamics (PD) and pharmacokinetics (PK), would be partially or completely offset by slow on-rate. Therefore, plain potency is likely a better predictor of drug development success than is residence time. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Resident Station Contact Information for Application Developers

    Data.gov (United States)

    Social Security Administration — SSA provides a web service and downloadable file for SSA Resident Station locations, telephone numbers, and hours of operation. (Note: If you think an office might...

  20. Request by the Resident Representative of Iraq

    International Nuclear Information System (INIS)

    1990-01-01

    The attached clarification by a spokesman of the Iraqi Ministry of Foreign Affairs is being circulated for the information of Member States pursuant to a request made by the Resident Representative of Iraq

  1. Mainframe computer use and residency cohort data.

    Science.gov (United States)

    Hotch, D; Helford, M; Rivers, D

    1987-01-01

    This paper describes a computer based method that was developed to prepare a profile of the patient care experiences of a cohort in a three-year, university based family practice residency. Sample pages from the report produced by this method and a description of the computer program are presented. This method of presenting patient encounter information may be particularly useful for program-level evaluation and for monitoring resident training.

  2. Thoracic surgical resident education: a costly endeavor.

    Science.gov (United States)

    Calhoon, John H; Baisden, Clint; Holler, Ben; Hicks, George L; Bove, Ed L; Wright, Cameron D; Merrill, Walter H; Fullerton, Dave A

    2014-12-01

    We sought to define an accurate measure of thoracic surgical education costs. Program directors from six distinct and differently sized and geographically located thoracic surgical training programs used a common template to provide estimates of resident educational costs. These data were reviewed, clarifying questions or discrepancies when noted and using best estimates when exact data were unavailable. Subsequently, a composite of previously published cost-estimation products was used to capture accurate cost data. Data were then compiled and averaged to provide an accurate picture of all costs associated with thoracic surgical education. Before formal accounting was performed, the estimated average for all programs was approximately $250,000 per year per resident. However, when formal evaluations by the six programs were performed, the annual cost of resident education ranged from $330,000 to $667,000 per year per resident. The average cost of $483,000 per year was almost double the initial estimates. Variability was noted by region and size of program. Faculty teaching costs varied from $208,000 to $346,000 per year. Simulation costs ranged from $0 to $80,000 per year. Resident savings to program ranged from $0 to $135,000 per year and averaged $37,000 per year per resident. Thoracic surgical education costs are considerably higher than initial estimates from program directors and probably represent an unappreciated source of financial burden for cardiothoracic surgical educational programs. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  3. Ambulatory Care Skills: Do Residents Feel Prepared?

    Directory of Open Access Journals (Sweden)

    Denise Bonds

    2002-10-01

    Full Text Available Objective: To determine resident comfort and skill in performing ambulatory care skills. Methods: Descriptive survey of common ambulatory care skills administered to internal medicine faculty and residents at one academic medical center. Respondents were asked to rate their ability to perform 12 physical exam skills and 6 procedures, and their comfort in performing 7 types of counseling, and obtaining 6 types of patient history (4 point Likert scale for each. Self-rated ability or comfort was compared by gender, status (year of residency, faculty, and future predicted frequency of use of the skill. Results: Residents reported high ability levels for physical exam skills common to both the ambulatory and hospital setting. Fewer felt able to perform musculoskeletal, neurologic or eye exams easily alone. Procedures generally received low ability ratings. Similarly, residents’ comfort in performing common outpatient counseling was also low. More residents reported feeling very comfortable in obtaining history from patients. We found little variation by gender, year of training, or predicted frequency of use. Conclusion: Self-reported ability and comfort for many common ambulatory care skills is low. Further evaluation of this finding in other training programs is warranted.

  4. Informatics and Technology in Resident Education.

    Science.gov (United States)

    Niehaus, William

    2017-05-01

    Biomedical or clinical informatics is the transdisciplinary field that studies and develops effective uses of biomedical data, information technology innovations, and medical knowledge for scientific inquiry, problem solving, and decision making, with an emphasis on improving human health. Given the ongoing advances in information technology, the field of informatics is becoming important to clinical practice and to residency education. This article will discuss how informatics is specifically relevant to residency education and the different ways to incorporate informatics into residency education, and will highlight applications of current technology in the context of residency education. How informatics can optimize communication for residents, promote information technology use, refine documentation techniques, reduce medical errors, and improve clinical decision making will be reviewed. It is hoped that this article will increase faculty and trainees' knowledge of the field of informatics, awareness of available technology, and will assist practitioners to maximize their ability to provide quality care to their patients. This article will also introduce the idea of incorporating informatics specialists into residency programs to help practitioners deliver more evidenced-based care and to further improve their efficiency. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  5. Urology residents training in laparoscopic surgery. Development of a virtual reality model.

    Science.gov (United States)

    Gutiérrez-Baños, J L; Ballestero-Diego, R; Truan-Cacho, D; Aguilera-Tubet, C; Villanueva-Peña, A; Manuel-Palazuelos, J C

    2015-11-01

    The training and learning of residents in laparoscopic surgery has legal, financial and technological limitations. Simulation is an essential tool in the training of residents as a supplement to their training in laparoscopic surgery. The training should be structured in an appropriate environment, with previously established and clear objectives, taught by professionals with clinical and teaching experience in simulation. The training should be conducted with realistic models using animals and ex-vivo tissue from animals. It is essential to incorporate mechanisms to assess the objectives during the residents' training progress. We present the training model for laparoscopic surgery for urology residents at the University Hospital Valdecilla. The training is conducted at the Virtual Hospital Valdecilla, which is associated with the Center for Medical Simulation in Boston and is accredited by the American College of Surgeons. The model is designed in 3 blocks, basic for R1, intermediate for R2-3 and advanced for R4-5, with 9 training modules. The training is conducted in 4-hour sessions for 4 afternoons, for 3 weeks per year of residence. Residents therefore perform 240 hours of simulated laparoscopic training by the end of the course. For each module, we use structured objective assessments to measure each resident's training progress. Since 2003, 9 urology residents have been trained, in addition to the 5 who are currently in training. The model has undergone changes according to the needs expressed in the student feedback. The acquisition of skills in a virtual reality model has enabled the safe transfer of those skills to actual practice. A laparoscopic surgery training program designed in structured blocks and with progressive complexity provides appropriate training for transferring the skills acquired using this model to an actual scenario while maintaining patient safety. Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. Canadian Plastic Surgery Resident Work Hour Restrictions: Practices and Perceptions of Residents and Program Directors.

    Science.gov (United States)

    McInnes, Colin W; Vorstenbosch, Joshua; Chard, Ryan; Logsetty, Sarvesh; Buchel, Edward W; Islur, Avinash

    2018-02-01

    The impact of resident work hour restrictions on training and patient care remains a highly controversial topic, and to date, there lacks a formal assessment as it pertains to Canadian plastic surgery residents. To characterize the work hour profile of Canadian plastic surgery residents and assess the perspectives of residents and program directors regarding work hour restrictions related to surgical competency, resident wellness, and patient safety. An anonymous online survey developed by the authors was sent to all Canadian plastic surgery residents and program directors. Basic summary statistics were calculated. Eighty (53%) residents and 10 (77%) program directors responded. Residents reported working an average of 73 hours in hospital per week with 8 call shifts per month and sleep 4.7 hours/night while on call. Most residents (88%) reported averaging 0 post-call days off per month and 61% will work post-call without any sleep. The majority want the option of working post-call (63%) and oppose an 80-hour weekly maximum (77%). Surgical and medical errors attributed to post-call fatigue were self-reported by 26% and 49% of residents, respectively. Residents and program directors expressed concern about the ability to master surgical skills without working post-call. The majority of respondents oppose duty hour restrictions. The reason is likely multifactorial, including the desire of residents to meet perceived expectations and to master their surgical skills while supervised. If duty hour restrictions are aggressively implemented, many respondents feel that an increased duration of training may be necessary.

  7. The Resident Academic Project Program: A Structured Approach to Inspiring Academic Development During Residency Training.

    Science.gov (United States)

    Eckert, Jill; Vaida, Sonia J; Bezinover, Dmitri; McCloskey, Diane E; Mets, Berend

    2016-02-15

    We report the successful implementation of structured resident academic projects in our Department of Anesthesiology at the Penn State Hershey Medical Center. Beginning with the graduating class of 2010, we adopted an expectation that each resident complete a project that results in a manuscript of publishable quality. Defining a clear timeline for all steps in the project and providing research education, as well as the necessary infrastructure and ongoing support, has helped grow the academic productivity of our anesthesia residents.

  8. Assessment of medical residents technology readiness for an online residents-as-teachers curriculum.

    Science.gov (United States)

    Silva, Débora; Lewis, Kadriye O

    2014-06-01

    The University of Puerto Rico School of Medicine has a need to expand the current Residents-as-Teachers workshops into a comprehensive curriculum. One way to do so is to implement an online curriculum, but prior to this, the readiness of the medical residents to participate in such a curriculum should be assessed. Our objective was to determine whether the residents at the University of Puerto Rico School of Medicine are prepared to engage in an online Residents-as-Teachers program. This was a descriptive, mixed-method-design study that collected qualitative and quantitative data using an online survey and a focus-group interview. The study was conducted with students from 11 of the residency programs at the University of Puerto Rico School of Medicine. More than 80% of the participating residents had the technical knowledge to engage in an online program; 90.5% thought an online Residents-as-Teachers course would be a good alternative to what was currently available; 87.5% would be willing to participate in an online program, and 68.6% of the residents stated that they preferred an online course to a traditional one. Determinants of readiness for online learning at the University of Puerto Rico School of Medicine were identified and discussed. Our results suggest that the majority of the residents who participated in this study are ready to engage in an online Residents-as-Teachers program. The only potential barrier found was that one-third of the residents still preferred a traditional curriculum, even when they thought an online Residents-as-Teachers curriculum was a good alternative and were willing to participate in the course or courses forming part of such a curriculum. Therefore, prior to wide-spread implementation of such a curriculum, a pilot test should be conducted to maximize the presumed and eventual success of that curriculum.

  9. Personal Therapy in Psychiatry Residency Training: A National Survey of Canadian Psychiatry Residents.

    Science.gov (United States)

    Hadjipavlou, George; Halli, Priyanka; Hernandez, Carlos A Sierra; Ogrodniczuk, John S

    2016-02-01

    The authors collected nationally representative data on Canadian residents' experiences with and perspectives on personal psychotherapy in their psychiatric training. A 43-item questionnaire was distributed electronically to all current psychiatry residents in Canada (N = 839). Four hundred residents from every program across Canada returned the survey (response rate 47.7%). The prevalence of personal therapy at any time was 55.3%, with 42.8% receiving personal therapy during residency. Of residents who undertook personal psychotherapy, 59.3% engaged in weekly therapy, 74.1% received psychodynamic psychotherapy, and 81.5% participated in long-term therapy (>1 year). Personal growth, self-understanding, and professional development were the most common reasons for engaging in personal therapy; however, one-third of residents did so to alleviate symptoms of depression, anxiety, or other mental health concerns. Time was the most important factor impeding residents from personal therapy; only 8.8% found stigma to act as a barrier. The vast majority of residents rated their experience with personal therapy as having a positive or very positive impact on their personal life (84.8%) and overall development as psychiatrists (81.8%). For 64% of respondents, personal therapy had an important or very important role in psychiatry residency training. Residents who received personal therapy rated themselves as better able to understand what happens moment by moment during therapy sessions, detect and deal with patients' emotional reactions, and constructively use their personal reactions to patients. Interest in personal therapy remains strong among psychiatry trainees in Canada. Residents who engaged in psychotherapy endorsed greater confidence in psychotherapy and rated their psychotherapy skills more favorably than those who had never been in the patient role, supporting the view of personal therapy as an important adjunct to psychotherapy training during residency.

  10. Local Determinants of Crime: Distinguishing Between Resident and Non-resident Offenders

    OpenAIRE

    Spengler, Hannes; Büttner, Thiess

    2003-01-01

    The paper revisits the local determinants of crime using a spatial model distinguishing between resident and non-resident offenders. Employing data for German municipalities, the model is estimated by means of a spatial GMM approach. Focusing on resident offenders legal earnings opportunities and the expected gain from offenses are found to be important determinants of crime. Also the socio-economic background in terms of unemployment, poverty, and inequality proves significant for both prope...

  11. Evaluation of otolaryngology residency program websites.

    Science.gov (United States)

    Svider, Peter F; Gupta, Amar; Johnson, Andrew P; Zuliani, Giancarlo; Shkoukani, Mahdi A; Eloy, Jean Anderson; Folbe, Adam J

    2014-10-01

    Prior to applying or interviewing, most prospective applicants turn to the Internet when evaluating residency programs, making maintenance of a comprehensive website critical. While certain "intangibles" such as reputation may not be communicated effectively online, residency websites are invaluable for conveying other aspects of a program. Prior analyses have reported that certain criteria such as research experience and didactics are important considerations for applicants. To evaluate the comprehensiveness of otolaryngology residency websites. Review of otolaryngology residency program websites. Websites of 99 civilian residency programs were searched for the presence of 23 criteria. Presence of 23 criteria for application process, incentives, instruction, research, clinical training, and other. Only 5 programs contained at least three-quarters of the criteria analyzed; on average programs reported less than 50% of information sought. Among the 99 residency program websites, a description of the following criteria was noted: comprehensive faculty listing (88%), didactics (80%), contact e-mail (77%), current residents (74%), description of facilities (70%), intern schedule (70%), research requirements (69%), otolaryngology rotation schedule (64%), other courses (61%), ERAS (Electronic Residency Application Service) link (55%), year-to-year responsibility progression (47%), call schedule (40%), active/past research projects (37%), area information (34%), message from the program director (33%) or chair (23%), selection criteria (30%), salary (directly on site) (23%), surgical statistics (18%), parking (9%), and meal allowance (7%). The mean (SD) percentage present of factors encompassing "clinical training" was 55% (23%), significantly higher than the mean (SD) percentage of factors covered under the "incentives" category (19% [11%]; P = .01). The proportion of overall criteria present on websites did not differ on organizing programs by region (range, 42

  12. Career Interests of Canadian Psychiatry Residents: What Makes Residents Choose a Research Career?

    Science.gov (United States)

    Laliberté, Vincent; Rapoport, Mark J; Andrew, Melissa; Davidson, Marla; Rej, Soham

    2016-02-01

    Training future clinician-researchers remains a challenge faced by Canadian psychiatry departments. Our objectives were to determine the prevalence of residents interested in pursuing research and other career options as part of their practice, and to identify the factors associated with interest in research. Data from a national online survey of 207 Canadian psychiatry residents from a total of 853 (24.3% response rate) were examined. The main outcome was interest in research as part of residents' future psychiatrist practice. Bivariate and multivariate analyses were performed to identify demographic and vocational variables associated with research interest. Interest in research decreases by 76% between the first and fifth year of psychiatry residency (OR 0.76 per year, 95% CI 0.60 to 0.97). Training in a department with a residency research track did not correlate with increased research interest (χ2 = 0.007, df = 1, P = 0.93). Exposing and engaging psychiatry residents in research as early as possible in residency training appears key to promoting future research interest. Psychiatry residency programs and research tracks could consider emphasizing research training initiatives and protected research time early in residency. © The Author(s) 2015.

  13. International Programs in the Education of Residents: Benefits for the Resident and the Home Program.

    Science.gov (United States)

    Rodriguez, Abigail; Ho, Trung; Verheyden, Charles

    2015-11-01

    There is a significant need for basic surgical care worldwide. In recent years, modest improvement in fulfilling this demand has been achieved through international medical mission trips from various organizations. These humanitarian endeavors and global health experiences have generated increasing interest in participating in international missions from surgical residents. However, many academic institutions currently do not have the infrastructure or desire to support surgical residents participating in medical missions. This paper aims to illustrate that careful, planned integration of medical mission trips into the residency curriculum will develop and enhance resident education and experience by fulfilling all six Accreditation Council for Graduate Medical Education (ACGME) core competencies and by benefitting the native program.

  14. Elective time during dermatology residency: A survey of residents and program directors.

    Science.gov (United States)

    Uppal, Pushpinder; Shantharam, Rohini; Kaufmann, Tara Lynn

    2017-12-15

    Elective time during residency training provides residents with exposure to different subspecialties. This opportunity gives residents the chance tonurture growth in particular areas of interest and broaden their knowledge base in certain topics in dermatology by having the chance to work withexperts in the field. The purpose of this study was to assess the views of residency program directors and dermatology residents on the value of elective time through a cross sectional survey. An eight-questionIRB exempt survey was sent out to 113 residency program directors via email through the American Professors of Dermatology (APD) program director listserv. Program directors were asked to forward a separate set of 9 questions to their residents. The majority of programs that responded allowed for some elective time within their schedule, often duringthe PGY 4 (3rd year of dermatology training), but the amount of time allowed widely varied among many residency programs. Overall, residents and program directors agree that elective is important in residencytraining, but no standardization is established across programs.

  15. Resident Macrophages and Lymphocytes in the Canine Endometrium.

    Science.gov (United States)

    Pires, M A; Payan-Carreira, R

    2015-10-01

    Resident immune cells play a major role in endometrial immunity and in tissue homoeostasis. This study aimed to analyse the distribution of macrophages, B and T lymphocytes (respectively, Mø, B-Lym and T-Lym) in the canine endometrium throughout the oestrous cycle and in late involution (at the proestrus stage post-parturition). An immunohistochemistry technique was used on samples from 50 post-pubertal healthy female dogs, of which five in late post-partum. The distribution of resident immune cells was analysed in three endometrial layers (superficial, intermediate and basal areas). Mø, B-Lym and T-Lym were demonstrated to reside in the endometrium in all the stages of the canine cycle; their numbers being considerably higher during late involution. T-Lym were scattered in the stroma or amidst the glandular epithelium, constituting the predominant immune cell population in anestrus and proestrus, but decreased in number at all other stages. Endometrial B-Lym remained fairly constant during the canine cycle, although its numbers were higher in late involution. Mø counts were higher during anestrus compared to the other stages, the cells being displaced into the superficial endometrial layer. Mø demonstrated the highest level in late involution samples, forming small aggregates below the surface epithelium. The number of immune cells was not normally distributed, suggesting the influence of individual factors, such as age or parity, not explored herein due to limited sample availability. Still, this study provides important information for the interpretation of endometrial biopsies in dogs and for the understanding of the increased susceptibility to uterine infection during dioestrus found in the bitch. © 2015 Blackwell Verlag GmbH.

  16. Neuroscience and humanistic psychiatry: a residency curriculum.

    Science.gov (United States)

    Griffith, James L

    2014-04-01

    Psychiatry residencies with a commitment to humanism commonly prioritize training in psychotherapy, cultural psychiatry, mental health policy, promotion of human rights, and similar areas reliant upon dialogue and collaborative therapeutic relationships. The advent of neuroscience as a defining paradigm for psychiatry has challenged residencies with a humanistic focus due to common perceptions that it would entail constriction of psychiatric practice to diagnostic and psychopharmacology roles. The author describes a neuroscience curriculum that has taught psychopharmacology effectively, while also advancing effectiveness of language-based and relationship-based therapeutics. In 2000, the George Washington University psychiatry residency initiated a neuroscience curriculum consisting of (1) a foundational postgraduate year 2 seminar teaching cognitive and social neuroscience and its integration into clinical psychopharmacology, (2) advanced seminars that utilized a neuroscience perspective in teaching specific psychotherapeutic skill sets, and (3) case-based teaching in outpatient clinical supervisions that incorporated a neuroscience perspective into traditional psychotherapy supervisions. Curricular assessment was conducted by (1) RRC reaccreditation site visit feedback, (2) examining career trajectories of residency graduates, (3) comparing PRITE exam Somatic Treatments subscale scores for 2010-2012 residents with pre-implementation residents, and (4) postresidency survey assessment by 2010-2012 graduates. The 2011 RRC site visit report recommended a "notable practice" citation for "innovative neurosciences curriculum." Three of twenty 2010-2012 graduates entered neuroscience research fellowships, as compared to none before the new curriculum. PRITE Somatic Treatments subscale scores improved from the 23rd percentile to the 62nd percentile in pre- to post-implementation of curriculum (p neuroscience curriculum for a residency committed to humanistic psychiatry

  17. [Evaluation in medical residency training programs].

    Science.gov (United States)

    Kolokythas, O; Patzwahl, R; Straka, M; Binkert, C

    2016-01-01

    For resident doctors the acquisition of technical and professional competence is decisive for the successful practice of their activities. Competency and professional development of resident doctors benefit from regular self-reflection and assessment by peers. While often promoted and recommended by national educational authorities, the implementation of a robust evaluation process in the clinical routine is often counteracted by several factors. The aim of the study was to test a self-developed digital evaluation system for the assessment of radiology residents at our institute for practicality and impact with regard to the radiological training. The intranet-based evaluation system was implemented in January 2014, which allowed all Radiology consultants to submit a structured assessment of the Radiology residents according to standardized criteria. It included 7 areas of competency and 31 questions, as well as a self-assessment module, both of which were filled out electronically on a 3-month basis using a 10-point scale and the opportunity to make free text comments. The results of the mandatory self-evaluation by the residents were displayed beside the evaluation by the supervisor. Access to results was restricted and quarterly discussions with the residents were conducted confidentially and individually. The system was considered to be practical to use and stable in its functionality. The centrally conducted anonymous national survey of residents revealed a noticeable improvement of satisfaction with the institute assessment for the criterion "regular feedback"compared to the national average. Since its implementation the system has been further developed and extended and is now available for other institutions.

  18. Learning styles in two otolaryngology residency programs.

    Science.gov (United States)

    Laeeq, Kulsoom; Weatherly, Robert A; Carrott, Alice; Pandian, Vinciya; Cummings, Charles W; Bhatti, Nasir I

    2009-12-01

    Kolb portrays four learning styles depending on how an individual grasps or transforms experience: accommodating, assimilating, diverging, and converging. Past studies in surgery, medicine, and anesthesia identified the predominant learning style in each of these specialties. The prevalence of different learning styles and existence of a predominant style, if any, has not been reported for otolaryngology residency programs. The purpose of our study was to determine if otolaryngology residents have a preferred learning style that is different from the predominant learning styles reported for other specialties. We conducted a survey of the otolaryngology-head and neck surgery residents at two residency programs. Kolb's Learning Style Index (LSI) version 3.1 was administered to 46 residents from Johns Hopkins University and Kansas University Otolaryngology-Head and Neck Surgery programs. LSI is a widely used 12-item questionnaire, with each item followed by four options. The subjects graded the options depending on how the options applied to them. Forty-three otolaryngology residents completed the survey, with a response rate of 93.47%. The predominant learning style was converging (55.81%) followed by accommodating (18.61%), accounting for the learning styles of 74.42% of the total population. There were only 13.95% assimilating and 6.98% diverging learning styles. Two residents (4.65%) had their preference balanced across four learning styles. The predominant learning styles in otolaryngology were converging and accommodating, accounting for three fourths of the population. It would be desirable to modify our curriculum in a way that will optimize and facilitate learning.

  19. Under the microscope: assessing surgical aptitude of otolaryngology residency applicants.

    Science.gov (United States)

    Carlson, Matthew L; Archibald, David J; Sorom, Abraham J; Moore, Eric J

    2010-06-01

    Application to otolaryngology residency is a highly competitive process. Programs identify the best candidates by evaluating academic performance in medical school, board scores, research experience, performance during an interview, and letters of recommendation. Unfortunately, none of these metrics completely assess an applicant's capacity to learn and perform surgical skills. We describe a direct assessment of an applicant's ability for rapid surgical skill acquisition, manual dexterity, and response to stress that can be performed during the interview process. A retrospective study at an academic otolaryngology residency program. After orientation, applicants were seated at a microsurgical training station and allotted 20 minutes to suture an incision using 10-0 nylon suture on a latex practice card. Their performance was graded using a 1-to-5 scoring system for the following categories: microscope use, respect for tissue, instrument handling, knot tying and suture control, skills acquisition, and attitude toward the exercise. Applicants were given some instruction and assessed on their ability to incorporate what they had learned into their technique. The average total applicant score was 23.2, standard deviation (SD) 3.6 (maximum 30); 13.4% of applicants scored 1 SD above the mean. The value of applicant screening tests in predicting surgical competency is controversial. We describe a direct assessment tool that may prove useful in identifying outliers, both high and low, to aid in final applicant ranking.

  20. FRD tissue archive

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The fishery genetics tissue collection has over 80,000 tissues stored in 95% ethanol representing fishes and invertebrates collected globally but with a focus on the...

  1. Plant tissue culture techniques

    Directory of Open Access Journals (Sweden)

    Rolf Dieter Illg

    1991-01-01

    Full Text Available Plant cell and tissue culture in a simple fashion refers to techniques which utilize either single plant cells, groups of unorganized cells (callus or organized tissues or organs put in culture, under controlled sterile conditions.

  2. Breast Cancer Tissue Repository

    National Research Council Canada - National Science Library

    Iglehart, J

    1997-01-01

    The Breast Tissue Repository at Duke enters its fourth year of finding. The purpose of the Repository at Duke is to provide substantial quantities of frozen tissue for explorative molecular studies...

  3. Use and utility of Web-based residency program information: a survey of residency applicants.

    Science.gov (United States)

    Embi, Peter J; Desai, Sima; Cooney, Thomas G

    2003-01-01

    The Internet has become essential to the residency application process. In recent years, applicants and residency programs have used the Internet-based tools of the National Residency Matching Program (NRMP, the Match) and the Electronic Residency Application Service (ERAS) to process and manage application and Match information. In addition, many residency programs have moved their recruitment information from printed brochures to Web sites. Despite this change, little is known about how applicants use residency program Web sites and what constitutes optimal residency Web site content, information that is critical to developing and maintaining such sites. To study the use and perceived utility of Web-based residency program information by surveying applicants to an internal medicine program. Our sample population was the applicants to the Oregon Health & Science University Internal Medicine Residency Program who were invited for an interview. We solicited participation using the group e-mail feature available through the Electronic Residency Application Service Post-Office application. To minimize the possibility for biased responses, the study was confined to the period between submission of National Residency Matching Program rank-order lists and release of Match results. Applicants could respond using an anonymous Web-based form or by reply to the e-mail solicitation. We tabulated responses, calculated percentages for each, and performed a qualitative analysis of comments. Of the 431 potential participants, 218 responded (51%) during the study period. Ninety-nine percent reported comfort browsing the Web; 52% accessed the Web primarily from home. Sixty-nine percent learned about residency Web sites primarily from residency-specific directories while 19% relied on general directories. Eighty percent found these sites helpful when deciding where to apply, 69% when deciding where to interview, and 36% when deciding how to rank order programs for the Match. Forty

  4. The "resident's dilemma"? Values and strategies of medical residents for education interactions: a cellular automata simulation.

    Science.gov (United States)

    Heckerling, P S; Gerber, B S; Weiner, S J

    2006-01-01

    Medical residents engage in formal and informal education interactions with fellow residents during the working day, and can choose whether to spend time and effort on such interactions. Time and effort spent on such interactions can bring learning and personal satisfaction to residents, but may also delay completion of clinical work. Using hypothetical cases, we assessed the values and strategies of internal medicine residents at one hospital for both cooperative and non-cooperative education interactions with fellow residents. We then used these data and cellular automata models of two-person games to simulate repeated interactions between residents, and to determine which strategies resulted in greatest accrued value. We conducted sensitivity analyses on several model parameters, to test the robustness of dominant strategies to model assumptions. Twenty-nine of the 57 residents (50.9%) valued cooperation more than non-cooperation no matter what the other resident did during the current interaction. Similarly, thirty-six residents (63.2%) endorsed an unconditional always-cooperate strategy no matter what the other resident had done during their previous interaction. In simulations, an always-cooperate strategy accrued more value (776.42 value units) than an aggregate of strategies containing non-cooperation components (675.0 value units, p = 0.052). Only when the probability of strategy errors reached 50%, or when values were re-ordered to match those of a Prisoner's Dilemma, did non-cooperation-based strategies accrue the most value. Cooperation-based values and strategies were most frequent among our residents, and dominated in simulations of repeated education interactions between them.

  5. Pregnancy during otolaryngology residency: experience and recommendations.

    Science.gov (United States)

    Cole, Stephanie; Arnold, Michelle; Sanderson, Alicia; Cupp, Craig

    2009-05-01

    Pregnancy during graduate medical training became a pertinent issue in the United States during the 10-year interval between 1992 and 2002 as the number of female residents trended steadily upward to over 25 per cent. Surgical training programs characteristically present unique challenges and stressors for all trainees, and pregnancy introduces additional physical, professional, and emotional demands for the pregnant woman and her coworkers. A qualitative study was performed using in-person interviews of female otolaryngology residents who had given birth within the previous 12 months. Items addressed included the pregnancy course and its complications, specific stressors during and after pregnancy, and solutions implemented by the resident and her program director. Reactions and level of support from coworkers were also discussed. Five pregnancies were reported among three residents interviewed. One resident experienced preterm delivery, which necessitated a week-long stay in the neonatal intensive care unit for her infant. Another had chorioamnionitis during delivery of two infants. One child had low birth weight. The third resident had a miscarriage during the first trimester of her first pregnancy and sustained a minor head injury after fainting in the operating room during her second pregnancy. Overall, long hours, unpredictable work demands, and guilt over colleagues' increased workloads and altered schedules were noted as significant sources of stress among these residents; the women also described high expectations of themselves, along with misgivings over their ability to balance pregnancy and parenthood with career demands. The most significant postpartum stress indicator was the matter of child care, especially as it related to finding adequate coverage for on-call periods ranging from 3 to 14 days per month. Maintaining breastfeeding was an additional concern in the postpartum period. Pregnancy during surgical residency is a significant source of

  6. Vascularization Tissue Engineering

    NARCIS (Netherlands)

    Rouwkema, Jeroen; Rivron, N.C.; van Blitterswijk, Clemens

    2008-01-01

    Tissue engineering has been an active field of research for several decades now. However, the amount of clinical applications in the field of tissue engineering is still limited. One of the current limitations of tissue engineering is its inability to provide sufficient blood supply in the initial

  7. Plant Tissue Culture

    Indian Academy of Sciences (India)

    Admin

    The success of plant biotechnology relies on the fundamental techniques of plant tissue culture. Understanding basic biol- ogy of plants is a prerequisite for proper utilization of the plant system or parts thereof. Plant tissue culture helps in providing a basic understanding of physical and chemical requirements of cell, tissue, ...

  8. Tissue engineering of reproductive tissues and organs.

    Science.gov (United States)

    Atala, Anthony

    2012-07-01

    Regenerative medicine and tissue engineering technology may soon offer new hope for patients with serious injuries and end-stage reproductive organ failure. Scientists are now applying the principles of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured reproductive tissues. In addition, the stem cell field is advancing, and new discoveries in this field will lead to new therapeutic strategies. For example, newly discovered types of stem cells have been retrieved from uterine tissues such as amniotic fluid and placental stem cells. The process of therapeutic cloning and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. Although stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous adult cells have already entered the clinic. This article discusses these tissue engineering strategies for various organs in the male and female reproductive tract. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Teacher in Residence: Bringing Science to Students

    CERN Multimedia

    Daisy Yuhas

    CERN welcomes its first Teacher in Residence, Terrence Baine of the University of Oslo. Baine, who originally hails from Canada, will be concurrently completing his PhD in Physics Education during his time at CERN. Like CERN’s High School Teacher Programme (HST), of which Baine is an alumnus, the Teacher in Residence position is designed to help educators spread the science of CERN in a form that is accessible to students and can encourage them to pursue physics throughout their education.   Terrence Baine, first 'teacher in residence' at CERN Baine explains, “It’s very important to have a teacher present who can be that middle person between the young peoplecoming here, whom we are trying to enlighten, and the physicists who work at CERN. The Teacher in Residence can act as an on-site educational consultant.” As Teacher in Residence, Baine’s primary project will be to develop teaching modules, or a series of lesson plans, that can help high schoo...

  10. Murine Neonates Infected with Yersinia enterocolitica Develop Rapid and Robust Proinflammatory Responses in Intestinal Lymphoid Tissues

    Science.gov (United States)

    Siefker, David T.; Echeverry, Andrea; Brambilla, Roberta; Fukata, Masayuki; Schesser, Kurt

    2014-01-01

    Neonatal animals are generally very susceptible to infection with bacterial pathogens. However, we recently reported that neonatal mice are highly resistant to orogastric infection with Yersinia enterocolitica. Here, we show that proinflammatory responses greatly exceeding those in adults arise very rapidly in the mesenteric lymph nodes (MLN) of neonates. High-level induction of proinflammatory gene expression occurred in the neonatal MLN as early as 18 h postinfection. Marked innate phagocyte recruitment was subsequently detected at 24 h postinfection. Enzyme-linked immunosorbent spot assay (ELISPOT) analyses indicated that enhanced inflammation in neonatal MLN is contributed to, in part, by an increased frequency of proinflammatory cytokine-secreting cells. Moreover, both CD11b+ and CD11b− cell populations appeared to play a role in proinflammatory gene expression. The level of inflammation in neonatal MLN was also dependent on key bacterial components. Y. enterocolitica lacking the virulence plasmid failed to induce innate phagocyte recruitment. In contrast, tumor necrosis factor alpha (TNF-α) protein expression and neutrophil recruitment were strikingly higher in neonatal MLN after infection with a yopP-deficient strain than with wild-type Y. enterocolitica, whereas only modest increases occurred in adults. This hyperinflammatory response was associated with greater colonization of the spleen and higher mortality in neonates, while there was no difference in mortality among adults. This model highlights the dynamic levels of inflammation in the intestinal lymphoid tissues and reveals the protective (wild-type strain) versus harmful (yopP-deficient strain) consequences of inflammation in neonates. Moreover, these results reveal that the neonatal intestinal lymphoid tissues have great potential to rapidly mobilize innate components in response to infection with bacterial enteropathogens. PMID:24478090

  11. Mononuclear phagocyte system depletion blocks interstitial tonicity-responsive enhancer binding protein/vascular endothelial growth factor C expression and induces salt-sensitive hypertension in rats.

    Science.gov (United States)

    Machnik, Agnes; Dahlmann, Anke; Kopp, Christoph; Goss, Jennifer; Wagner, Hubertus; van Rooijen, Nico; Eckardt, Kai-Uwe; Müller, Dominik N; Park, Joon-Keun; Luft, Friedrich C; Kerjaschki, Dontscho; Titze, Jens

    2010-03-01

    We showed recently that mononuclear phagocyte system (MPS) cells provide a buffering mechanism for salt-sensitive hypertension by driving interstitial lymphangiogenesis, modulating interstitial Na(+) clearance, and increasing endothelial NO synthase protein expression in response to very high dietary salt via a tonicity-responsive enhancer binding protein/vascular endothelial growth factor C regulatory mechanism. We now tested whether isotonic saline and deoxycorticosterone acetate (DOCA)-salt treatment leads to a similar regulatory response in Sprague-Dawley rats. Male rats were fed a low-salt diet and received tap water (low-salt diet LSD), 1.0% saline (high-salt diet HSD), or DOCA+1.0% saline (DOCA-HSD). To test the regulatory role of interstitial MPS cells, we further depleted MPS cells with clodronate liposomes. HSD and DOCA-HSD led to Na(+) accumulation in the skin, MPS-driven tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated hyperplasia of interstitial lymph capillaries, and increased endothelial NO synthase protein expression in skin interstitium. Clodronate liposome MPS cell depletion blocked MPS infiltration in the skin interstitium, resulting in unchanged tonicity-responsive enhance binding protein/vascular endothelial growth factor C levels and absent hyperplasia of the lymph capillary network. Moreover, no increased skin endothelial NO synthase protein expression occurred in either clodronate liposome-treated HSD or DOCA-salt rats. Thus, absence of the MPS-cell regulatory response converted a salt-resistant blood-pressure state to a salt-sensitive state in HSD rats. Furthermore, salt-sensitive hypertension in DOCA-salt rats was aggravated. We conclude that MPS cells act as onsite controllers of interstitial volume and blood pressure homeostasis, providing a local regulatory salt-sensitive tonicity-responsive enhancer binding protein/vascular endothelial growth factor C-mediated mechanism in the skin to maintain

  12. Inhibitory effect of immature dendritic cells (iDCs phagocytizing apoptotic lymphocytes on LPS-mediated activation of iDCs

    Directory of Open Access Journals (Sweden)

    Yu-xiang WEI

    2013-09-01

    Full Text Available Objective To investigate the inhibitory effect of immature dendritic cells(iDCs on LPS-mediated maturation of iDCs phagocytizing allogeneic spleen lymphocytes after being treated bypsoralen plus ultraviolet A(PUVA. Methods Bone marrow-derived DCs were obtained from bone marrow cells of C57BL/6 mice by co-cultivation with recombinant mouse IL-4 and GM-CSF. Spleenlymphocytes(SLP of BALB/c mice were isolated and transformed to PUVA-SLP by treatment with 8-methoxy PUVA irradiation.The bone marrow-derived iDCs of C57BL/6 were co-cultured with PUVA-SLP of BALB/c mice to obtain PUVA¬SLPDCs. After incubation, iDCs and PUVA-SP DCs were induced to maturation by LPS(10ng/ml,24h, and then they were analyzed by flow cytometry.At the same time,the concentrations of the immunoreactive proteins IL-12p70,IL-12p40andIL-10 in cell supernatants were determined by ELISA kits according to the manufacturer's recommendations. Results PUVA-SLP DCs and iDCs were compared in terms of LPS responsiveness.The phenotype of iDCs(CD40,CD80, andCD86 was 50.58%, 66.29%, 71.20%, respectively, showed more rapid changes from immature to mature statein response to LPS stimulation compared with PUVA-SP DCs, the phenotype of which was 21.26%,38.50% and 39.78%, respectively(P0.05.PUVA-SPDCs secreted high levels of IL-10(435.6±13.9, but lowlevels of IL-12(p7018.56±1.3,p4015.22±1.2, as compared with those of iDCs (132.6±2.8, p70192.1±5.9, p40999.8±26.9, P<0.01 after LPS stimulation. Conclusions Although PUVA-SLPDCs do not express as immature phenotype, they can be readily induced to differentiate into mature DCs in the presence of antigen or LPS. It may be suitable to use iDCs clinically in autoimmune diseases and transplantation.

  13. Factors influencing resident's decision to reside in gated and guarded community

    Science.gov (United States)

    Shamsudin, Zarina; Shamsudin, Shafiza; Zainal, Rozlin

    2017-10-01

    Gated communities are residential areas developed with restricted access with strictly controlled entrances and surrounded by a close perimeter of wall or fences. Developers, conscious of the need to fulfill the requirement of living in modern and sophisticated lifestyle and gated properties become the trend and mushroomed over the past decade. Nowadays, it is obvious that gated and guarded communities become almost a dominant feature of Malaysia housing development projects. The focus of this paper is to identify the factors contribute resident's decision to reside in gated and guarded community and to study social interaction among gated communities' residents. 150 questionnaires were distributed to the residents of selected gated and guarded community area in order to achieve the objectives and analyzed by using Statistical Package for Social Science (SPSS) and descriptive analysis. The result was tabulated and presented in charts and graphs for a clear and better understanding. The five main factors contribute to resident decision to reside in gated communities were identified and ranked; there are privacy, security, location, lifestyle and prestige. Besides, the residents are feeling neutral towards the facilities and services provided in their gated and guarded residential area. A comprehensive improvement towards the facilities and services is needed to reach higher satisfaction from the residents.

  14. Four Residents' Narratives on Abortion Training: A Residency Climate of Reflection, Support, and Mutual Respect.

    Science.gov (United States)

    Singer, Janet; Fiascone, Stephen; Huber, Warren J; Hunter, Tiffany C; Sperling, Jeffrey

    2015-07-01

    The decision on the part of obstetrics and gynecology residents to opt in or out of abortion training is, for many, a complex one. Although the public debate surrounding abortion can be filled with polarizing rhetoric, residents often discover that the boundaries between pro-choice and pro-life beliefs are not so neatly divided. We present narratives from four residents, training at a 32-resident program in the Northeast, who have a range of views surrounding abortion. Their stories reveal how some struggle with the real-life experience of providing abortions, while others feel angst over lacking the skills to terminate a life-threatening pregnancy. Thes