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Sample records for lymphoid recovery hypothesis

  1. Postirradiation recovery of lymphoid cells in the rat

    International Nuclear Information System (INIS)

    Farnsworth, A.; Wotherspoon, J.S.; Dorsch, S.E.

    1988-01-01

    Whole-body irradiation has been extensively used to remove immune responsiveness in rodent recipients in adoptive allograft assays. This study was undertaken to determine the relative radioresistance and the tempo of regeneration, following whole-body irradiation, of cells involved in the allograft response. Six distinct cell populations have been identified in the lymphoid tissues of rats subjected to sublethal whole-body irradiation. The relative representation of these subpopulations was significantly different from that in nonirradiated controls. NK cells, macrophages, and plasma cells, which are present in very low numbers in cell suspensions prepared from normal lymphoid tissues, made up a significant proportion of the residual/regenerating population in the tissues of rats recovering from whole-body irradiation. More significantly perhaps, the mature T cell populations showed a significant increase in the T cytotoxic/suppressor to T helper cell ratio. These observations support the suggestion that a number of the cell types within the mixed cell population observed in the rejecting indicator grafts of irradiated recipients in adoptive allograft assays are host derived. The finding that the T cytotoxic/suppressor population is apparently more radioresistant than the T helper population supports a conclusion that graft rejection in irradiated recipients, restored with pure populations of T helper cells, may not be directly mediated by the injected cells but may be the result of collaboration between these and host-derived cytotoxic cell populations

  2. Recovery of Epstein--Barr virus from nonproducer neonatal human lymphoid cell transformants

    International Nuclear Information System (INIS)

    Wilson, G.; Miller, G.

    1979-01-01

    Lymphoid cell lines (LCL) were established by infection of two batches of human umbilical cord lymphocytes with low multiplicities of the B95-8 strain of Epstein--Barr virus. Three of the 17 lines released minute mounts of transforming virus. The rest did not, nor did they make capsid antigen. However virus could be regularly recovered by lethal x-irradiation of transformed cells followed by cocultivation with primary human umbilical cord leukocytes. By this technique transforming activity could be identified in 15 of the 17 lines. These data indicate that these nonproducer human neonatal cell transformants established by EBV infection in vitro possess sufficient genetic information to code for production of biologically active mature virions. X rays alone failed to cause a detectable increase in the number of cells with capsid antigen or to enhance extracellular virus production. EBV-positive human serum blocked rescue if it was added during the first 2 to 4 hr after cocultivation, but not thereafter. Transforming virus could be recovered from x-rayed cells which were immediately thereafter lysed by freezing and thawing. These results suggest that recovery of virus following x-ray and cocultivation is not due to activation of the intracellular virus genome. Rather, it is likely that the method detects small numbers of virions which are cell associated. While transforming virus could regularly be rescued from lymphoblastoid cell lines resulting from in vitro transformation, attempts to rescue virus from Raji or EBV-converted BJAB cells were unsuccessful. This discrepancy suggests differences in genome complexity or in genome-cell interactions in different types of EBV-transformed cells

  3. [Shengqifuzheng Injection promotes the recovery of B cells in gut-associated lymphoid tissues of mice treated with cyclophosphamide].

    Science.gov (United States)

    Deng, Xiangliang; Huang, Rongrong; Wen, Ruyan; Luo, Xia; Zhou, Lian

    2016-08-01

    Objective To investigate the effect of Shengqifuzheng Injection (SQFZ) on the number recovery of B cells in gut-associated lymphoid tissues (GALTs) of mice receiving cyclophosphamide-based chemotherapy. Methods BALB/c mice were randomly divided into control group, cyclophosphamide (Cy) group and SQFZ group. Mice in Cy group and SQFZ group were injected intraperitoneally with Cy (100 mg/kg), while the control mice were injected with an equal volume of normal saline. Twenty-four hours later, mice in SQFZ group were administrated intragastricly with 1 mL SQFZ once daily for 10 consecutive days, and mice in the other groups were given the same volume of normal saline. Body mass of all the mice was measured every day. Mice were killed on day 10, and the indexes of spleen and thymus were measured. Cell cycles of bone marrow cells and the percentage of B cells in lymphocytes in mesenteric lymph node (MLN) and Peyer's patch (PP) were detected by flow cytometry. In vitro, after being treated with SQFZ, activity of lymphocytes was evaluzed by MTT assay; expression of CD86 on B cell surface was analyzed by flow cytometry; and B cell proliferation was tested by carboxyfluorescein succinimidyl ester (CFSE)-based lymphocyte proliferation assay. Results SQFZ alleviated the loss of body mass caused by Cy and promoted the recovery of thymus indexes, spleen indexes and B cell number in MLN and PP. But it did not alleviate the bone marrow suppression of mice in this condition. In vitro, SQFZ enhanced lymphocyte activity, and improved the activation and proliferation of B cells. Conclusion SQFZ could accelerate the recovery of B cells in GALTs of mice receiving chemotherapy and it might act by promoting B cell proliferation.

  4. Thymic irradiation inhibits the rapid recovery of TH1 but not TH2-like functions of CD4+ T cells after total lymphoid irradiation

    International Nuclear Information System (INIS)

    Bass, H.; Adkins, B.; Strober, S.

    1991-01-01

    Four to six weeks after total lymphoid irradiation (TLI), there is a selective deficit in the CD4+ T cells which secrete IL-2, proliferate in the MLR, and induce GVHD (Th1-like functions). A similar deficit in CD4+ T cells which secrete IL-4 and help antibody responses (Th2-like functions) is not observed. In the present study, shielding of the thymus with lead during TLI increased the Th1-like functions of CD4+ cells. Mice without thymus shields showed a marked selective reduction in the medullary stromal cells identified with the monoclonal antibody, MD1, and the severe reduction was prevented with thymus shields. Thus, shielding the thymus prevents the depletion of thymic medullary stromal cells and allows for a rapid recovery of Th1-like functions in the mouse spleen after TLI. Th2-like functions recover rapidly after TLI whether or not the thymus is irradiated

  5. Market disruption, cascading effects, and economic recovery:a life-cycle hypothesis model.

    Energy Technology Data Exchange (ETDEWEB)

    Sprigg, James A.

    2004-11-01

    This paper builds upon previous work [Sprigg and Ehlen, 2004] by introducing a bond market into a model of production and employment. The previous paper described an economy in which households choose whether to enter the labor and product markets based on wages and prices. Firms experiment with prices and employment levels to maximize their profits. We developed agent-based simulations using Aspen, a powerful economic modeling tool developed at Sandia, to demonstrate that multiple-firm economies converge toward the competitive equilibria typified by lower prices and higher output and employment, but also suffer from market noise stemming from consumer churn. In this paper we introduce a bond market as a mechanism for household savings. We simulate an economy of continuous overlapping generations in which each household grows older in the course of the simulation and continually revises its target level of savings according to a life-cycle hypothesis. Households can seek employment, earn income, purchase goods, and contribute to savings until they reach the mandatory retirement age; upon retirement households must draw from savings in order to purchase goods. This paper demonstrates the simultaneous convergence of product, labor, and savings markets to their calculated equilibria, and simulates how a disruption to a productive sector will create cascading effects in all markets. Subsequent work will use similar models to simulate how disruptions, such as terrorist attacks, would interplay with consumer confidence to affect financial markets and the broader economy.

  6. Innate lymphoid cells in secondary lymphoid organs.

    Science.gov (United States)

    Bar-Ephraïm, Yotam E; Mebius, Reina E

    2016-05-01

    The family of innate lymphoid cells (ILCs) has attracted attention in recent years as its members are important regulators of immunity, while they can also cause pathology. In both mouse and man, ILCs were initially discovered in developing lymph nodes as lymphoid tissue inducer (LTi) cells. These cells form the prototypic members of the ILC family and play a central role in the formation of secondary lymphoid organs (SLOs). In the absence of LTi cells, lymph nodes (LN) and Peyer's Patches (PP) fail to form in mice, although the splenic white pulp can develop normally. Besides LTi cells, the ILC family encompasses helper-like ILCs with functional distinctions as seen by T-helper cells, as well as cytotoxic natural killer (NK) cells. ILCs are still present in adult SLOs where they have been shown to play a role in lymphoid tissue regeneration. Furthermore, ILCs were implicated to interact with adaptive lymphocytes and influence the adaptive immune response. Here, we review the recent literature on the role of ILCs in secondary lymphoid tissue from the formation of SLOs to mature SLOs in adults, during homeostasis and pathology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Human innate lymphoid cells

    NARCIS (Netherlands)

    Hazenberg, Mette D.; Spits, Hergen

    2014-01-01

    Innate lymphoid cells (ILCs) are lymphoid cells that do not express rearranged receptors and have important effector and regulatory functions in innate immunity and tissue remodeling. ILCs are categorized into 3 groups based on their distinct patterns of cytokine production and the requirement of

  8. Total lymphoid irradiation

    International Nuclear Information System (INIS)

    Sutherland, D.E.; Ferguson, R.M.; Simmons, R.L.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1983-01-01

    Total lymphoid irradiation by itself can produce sufficient immunosuppression to prolong the survival of a variety of organ allografts in experimental animals. The degree of prolongation is dose-dependent and is limited by the toxicity that occurs with higher doses. Total lymphoid irradiation is more effective before transplantation than after, but when used after transplantation can be combined with pharmacologic immunosuppression to achieve a positive effect. In some animal models, total lymphoid irradiation induces an environment in which fully allogeneic bone marrow will engraft and induce permanent chimerism in the recipients who are then tolerant to organ allografts from the donor strain. If total lymphoid irradiation is ever to have clinical applicability on a large scale, it would seem that it would have to be under circumstances in which tolerance can be induced. However, in some animal models graft-versus-host disease occurs following bone marrow transplantation, and methods to obviate its occurrence probably will be needed if this approach is to be applied clinically. In recent years, patient and graft survival rates in renal allograft recipients treated with conventional immunosuppression have improved considerably, and thus the impetus to utilize total lymphoid irradiation for its immunosuppressive effect alone is less compelling. The future of total lymphoid irradiation probably lies in devising protocols in which maintenance immunosuppression can be eliminated, or nearly eliminated, altogether. Such protocols are effective in rodents. Whether they can be applied to clinical transplantation remains to be seen

  9. Predicting recovery from acid rain using the micro-spatial heterogeneity of soil columns downhill the infiltration zone of beech stemflow: introduction of a hypothesis.

    Science.gov (United States)

    Berger, Torsten W; Muras, Alexander

    Release of stored sulfur may delay the recovery of soil pH from Acid Rain. It is hypothesized that analyzing the micro-spatial heterogeneity of soil columns downhill of a beech stem enables predictions of soil recovery as a function of historic acid loads and time. We demonstrated in a very simplified approach, how these two different factors may be untangled from each other using synthetic data. Thereafter, we evaluated the stated hypothesis based upon chemical soil data with increasing distance from the stem of beech trees. It is predicted that the top soil will recover from acid deposition, as already recorded in the infiltration zone of stemflow near the base of the stem. However, in the between trees areas and especially in deeper soil horizons recovery may be highly delayed.

  10. Human innate lymphoid cells.

    Science.gov (United States)

    Mjösberg, Jenny; Spits, Hergen

    2016-11-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune responses. As such, ILCs make up interesting therapeutic targets for several diseases. In patients with allergy and asthma, group 2 innate lymphoid cells produce high amounts of IL-5 and IL-13, thereby contributing to type 2-mediated inflammation. Group 3 innate lymphoid cells are implicated in intestinal homeostasis and psoriasis pathology through abundant IL-22 production, whereas group 1 innate lymphoid cells are accumulated in chronic inflammation of the gut (inflammatory bowel disease) and lung (chronic obstructive pulmonary disease), where they contribute to IFN-γ-mediated inflammation. Although the ontogeny of mouse ILCs is slowly unraveling, the development of human ILCs is far from understood. In addition, the growing complexity of the human ILC family in terms of previously unrecognized functional heterogeneity and plasticity has generated confusion within the field. Here we provide an updated view on the function and plasticity of human ILCs in tissue homeostasis and disease. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  11. Human innate lymphoid cells

    NARCIS (Netherlands)

    Mjösberg, Jenny; Spits, Hergen

    2016-01-01

    Innate lymphoid cells (ILCs) are increasingly acknowledged as important mediators of immune homeostasis and pathology. ILCs act as early orchestrators of immunity, responding to epithelium-derived signals by expressing an array of cytokines and cell-surface receptors, which shape subsequent immune

  12. Testing the additive versus the compensatory hypothesis of mortality from ring recovery data using a random effects model

    Directory of Open Access Journals (Sweden)

    Schaub, M.

    2004-06-01

    Full Text Available The interaction of an additional source of mortality with the underlying “natural” one strongly affects population dynamics. We propose an alternative way to test between two forms of interaction, total additivity and compensation. In contrast to existing approaches, only ring-recovery data where the cause of death of each recovered individual is known are needed. Cause-specific mortality proportions are estimated based on a multistate capture-recapture model. The hypotheses are tested by inspecting the correlation between the cause-specific mortality proportions. A variance decomposition is performed to obtain a proper estimate of the true process correlation. The estimation of the cause-specific mortality proportions is the most critical part of the approach. It works well if at least one of the two mortality rates varies across time and the two recovery rates are constant across time. We illustrate this methodology by a case study of White Storks Ciconia ciconia where we tested whether mortality induced by power line collision is additive to other forms of mortality.

  13. Bioengineering of artificial lymphoid organs

    OpenAIRE

    NOSENKO M.A.; DRUTSKAYA M.S.; MOISENOVICH M.M.; NEDOSPASOV S.A.

    2016-01-01

    This review addresses the issue of bioengineering of artificial lymphoid organs.Progress in this field may help to better understand the nature of the structure-function relations that exist in immune organs. Artifical lymphoid organs may also be advantageous in the therapy or correction of immunodefficiencies, autoimmune diseases, and cancer. The structural organization, development, and function of lymphoid tissue are analyzed with a focus on the role of intercellular contacts and on the cy...

  14. Bioengineering of Artificial Lymphoid Organs.

    Science.gov (United States)

    Nosenko, M A; Drutskaya, M S; Moisenovich, M M; Nedospasov, S A

    2016-01-01

    This review addresses the issue of bioengineering of artificial lymphoid organs.Progress in this field may help to better understand the nature of the structure-function relations that exist in immune organs. Artifical lymphoid organs may also be advantageous in the therapy or correction of immunodefficiencies, autoimmune diseases, and cancer. The structural organization, development, and function of lymphoid tissue are analyzed with a focus on the role of intercellular contacts and on the cytokine signaling pathways regulating these processes. We describe various polymeric materials, as scaffolds, for artificial tissue engineering. Finally, published studies in which artificial lymphoid organs were generated are reviewed and possible future directions in the field are discussed.

  15. Superficially located enlarged lymphoid follicles characterise nodular gastritis.

    Science.gov (United States)

    Okamura, Takuma; Sakai, Yasuhiro; Hoshino, Hitomi; Iwaya, Yugo; Tanaka, Eiji; Kobayashi, Motohiro

    2015-01-01

    Nodular gastritis is a form of chronic Helicobacter pylori gastritis affecting the gastric antrum and characterised endoscopically by the presence of small nodular lesions resembling gooseflesh. It is generally accepted that hyperplasia of lymphoid follicles histologically characterises nodular gastritis; however, quantitative analysis in support of this hypothesis has not been reported. Our goal was to determine whether nodular gastritis is characterised by lymphoid follicle hyperplasia.The number, size, and location of lymphoid follicles in nodular gastritis were determined and those properties compared to samples of atrophic gastritis. The percentages of high endothelial venule (HEV)-like vessels were also evaluated.The number of lymphoid follicles was comparable between nodular and atrophic gastritis; however, follicle size in nodular gastritis was significantly greater than that seen in atrophic gastritis. Moreover, lymphoid follicles in nodular gastritis were positioned more superficially than were those in atrophic gastritis. The percentage of MECA-79 HEV-like vessels was greater in areas with gooseflesh-like lesions in nodular versus atrophic gastritis.Superficially located hyperplastic lymphoid follicles characterise nodular gastritis, and these follicles correspond to gooseflesh-like nodular lesions observed endoscopically. These observations suggest that MECA-79 HEV-like vessels could play at least a partial role in the pathogenesis of nodular gastritis.

  16. Lymphoid Aggregates That Resemble Tertiary Lymphoid Organs Define a Specific Pathological Subset in Metal-on-Metal Hip Replacements

    Science.gov (United States)

    Barone, Francesca; Hardie, Debbie L.; Matharu, Gulraj S.; Davenport, Alison J.; Martin, Richard A.; Grant, Melissa; Mosselmans, Frederick; Pynsent, Paul; Sumathi, Vaiyapuri P.; Addison, Owen; Revell, Peter A.; Buckley, Christopher D.

    2013-01-01

    Aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL) has been used to describe the histological lesion associated with metal-on-metal (M-M) bearings. We tested the hypothesis that the lymphoid aggregates, associated with ALVAL lesions resemble tertiary lymphoid organs (TLOs). Histopathological changes were examined in the periprosthetic tissue of 62 M-M hip replacements requiring revision surgery, with particular emphasis on the characteristics and pattern of the lymphocytic infiltrate. Immunofluorescence and immunohistochemistry were used to study the classical features of TLOs in cases where large organized lymphoid follicles were present. Synchrotron X-ray fluorescence (XRF) measurements were undertaken to detect localisation of implant derived ions/particles within the samples. Based on type of lymphocytic infiltrates, three different categories were recognised; diffuse aggregates (51%), T cell aggregates (20%), and organised lymphoid aggregates (29%). Further investigation of tissues with organised lymphoid aggregates showed that these tissues recapitulate many of the features of TLOs with T cells and B cells organised into discrete areas, the presence of follicular dendritic cells, acquisition of high endothelial venule like phenotype by blood vessels, expression of lymphoid chemokines and the presence of plasma cells. Co-localisation of implant-derived metals with lymphoid aggregates was observed. These findings suggest that in addition to the well described general foreign body reaction mediated by macrophages and a T cell mediated type IV hypersensitivity response, an under-recognized immunological reaction to metal wear debris involving B cells and the formation of tertiary lymphoid organs occurs in a distinct subset of patients with M-M implants. PMID:23723985

  17. Why Innate Lymphoid Cells?

    Science.gov (United States)

    Kotas, Maya E; Locksley, Richard M

    2018-06-19

    Innate lymphoid cells (ILCs) are positioned in tissues perinatally, constitutively express receptors responsive to their organ microenvironments, and perform an arsenal of effector functions that overlap those of adaptive CD4 + T cells. Based on knowledge regarding subsets of invariant-like lymphocytes (e.g., natural killer T [NKT] cells, γδ T cells, mucosal-associated invariant T [MAIT] cells, etc.) and fetally derived macrophages, we hypothesize that immune cells established during the perinatal period-including, but not limited to, ILCs-serve intimate roles in tissue that go beyond classical understanding of the immune system in microbial host defense. In this Perspective, we propose mechanisms by which the establishment of ILCs and the tissue lymphoid niche during early development may have consequences much later in life. Although definitive answers require better tools, efforts to achieve deeper understanding of ILC biology across the mammalian lifespan have the potential to lift the veil on the unknown breadth of immune cell functions. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. The Innate Lymphoid Cell Precursor.

    Science.gov (United States)

    Ishizuka, Isabel E; Constantinides, Michael G; Gudjonson, Herman; Bendelac, Albert

    2016-05-20

    The discovery of tissue-resident innate lymphoid cell populations effecting different forms of type 1, 2, and 3 immunity; tissue repair; and immune regulation has transformed our understanding of mucosal immunity and allergy. The emerging complexity of these populations along with compounding issues of redundancy and plasticity raise intriguing questions about their precise lineage relationship. Here we review advances in mapping the emergence of these lineages from early lymphoid precursors. We discuss the identification of a common innate lymphoid cell precursor characterized by transient expression of the transcription factor PLZF, and the lineage relationships of innate lymphoid cells with conventional natural killer cells and lymphoid tissue inducer cells. We also review the rapidly growing understanding of the network of transcription factors that direct the development of these lineages.

  19. Lymphoid Tissue Grafts in Man

    Energy Technology Data Exchange (ETDEWEB)

    Kay, H. E.M. [Royal Marsden Hospital, Institute of Cancer Research, London (United Kingdom)

    1969-07-15

    Grafts of lymphoid tissue or of lymphoid stem cells may be appropriate in the treatment of some congenital immune deficiency disorders. The reasons for preferring tissues of foetal origin are discussed and the evidence for foetal immunocompetence is briefly summarized. Methods of storing foetal liver cells and cells or fragments of thymus are mentioned, and the organization of the Foetal Tissue Bank of the Royal Marsden Hospital is described. Clinical data from transplantation of lymphoid cells in various immune deficiency disorders are briefly presented. (author)

  20. Prions and lymphoid organs

    Science.gov (United States)

    O’Connor, Tracy; Aguzzi, Adriano

    2013-01-01

    Prion colonization of secondary lymphoid organs (SLOs) is a critical step preceding neuroinvasion in prion pathogenesis. Follicular dendritic cells (FDCs), which depend on both tumor necrosis factor receptor 1 (TNFR1) and lymphotoxin β receptor (LTβR) signaling for maintenance, are thought to be the primary sites of prion accumulation in SLOs. However, prion titers in RML-infected TNFR1−/− lymph nodes and rates of neuroinvasion in TNFR1−/− mice remain high despite the absence of mature FDCs. Recently, we discovered that TNFR1-independent prion accumulation in lymph nodes relies on LTβR signaling. Loss of LTβR signaling in TNFR1−/− lymph nodes coincided with the de-differentiation of high endothelial venules (HEVs)—the primary sites of lymphocyte entry into lymph nodes. These findings suggest that HEVs are the sites through which prions initially invade lymph nodes from the bloodstream. Identification of HEVs as entry portals for prions clarifies a number of previous observations concerning peripheral prion pathogenesis. However, a number of questions still remain: What is the mechanism by which prions are taken up by HEVs? Which cells are responsible for delivering prions to lymph nodes? Are HEVs the main entry site for prions into lymph nodes or do alternative routes also exist? These questions and others are considered in this article. PMID:23357827

  1. Total lymphoid irradiation

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    An outline review notes recent work on total lymphoid irradiation (TLI) as a means of preparing patients for grafts and particularly for bone-marrow transplantation. T.L.I. has proved immunosuppressive in rats, mice, dogs, monkeys and baboons; when given before bone-marrow transplantation, engraftment took place without, or with delayed rejection or graft-versus-host disease. Work with mice has indicated that the thymus needs to be included within the irradiation field, since screening of the thymus reduced skin-graft survival from 50 to 18 days, though irradiation of the thymus alone has proved ineffective. A more lasting tolerance has been observed when T.L.I. is followed by an injection of donor bone marrow. 50% of mice treated in this way accepted allogenic skin grafts for more than 100 days, the animals proving to be stable chimeras with 50% of their peripheral blood lymphocytes being of donor origin. Experiments of a similar nature with dogs and baboons were not so successful. (U.K.)

  2. Innate lymphoid cells and the skin

    OpenAIRE

    Salimi, Maryam; Ogg, Graham

    2014-01-01

    Innate lymphoid cells are an emerging family of effector cells that contribute to lymphoid organogenesis, metabolism, tissue remodelling and protection against infections. They maintain homeostatic immunity at barrier surfaces such as lung, skin and gut (Nature 464:1367?1371, 2010, Nat Rev Immunol 13: 145?149, 2013). Several human and mouse studies suggest a role for innate lymphoid cells in inflammatory skin conditions including atopic eczema and psoriasis. Here we review the innate lymphoid...

  3. Florid reactive lymphoid hyperplasia of terminal ileum

    OpenAIRE

    Kanakala, Venkatesh; Birch, Peter; Kasaraneni, Ramesh

    2010-01-01

    Florid lymphoid hyperplasia in the terminal ileum can present to surgeons as an acute abdominal pain. Only few cases were reported in the literature. Our case illustrates that a rare case of florid lymphoid hyperplasia can present to surgeons as acute appendicitis. During the operation the gross appearance may mimic Crohn’s disease. A limited resection is sufficient to clinch the diagnosis of florid lymphoid hyperplasia / Crohn’s disease. In florid lymphoid hyperplasia limited resection may b...

  4. Artificial engineering of secondary lymphoid organs.

    Science.gov (United States)

    Tan, Jonathan K H; Watanabe, Takeshi

    2010-01-01

    Secondary lymphoid organs such as spleen and lymph nodes are highly organized immune structures essential for the initiation of immune responses. They display distinct B cell and T cell compartments associated with specific stromal follicular dendritic cells and fibroblastic reticular cells, respectively. Interweaved through the parenchyma is a conduit system that distributes small antigens and chemokines directly to B and T cell zones. While most structural aspects between lymph nodes and spleen are common, the entry of lymphocytes, antigen-presenting cells, and antigen into lymphoid tissues is regulated differently, reflecting the specialized functions of each organ in filtering either lymph or blood. The overall organization of lymphoid tissue is vital for effective antigen screening and recognition, and is a feature which artificially constructed lymphoid organoids endeavor to replicate. Synthesis of artificial lymphoid tissues is an emerging field that aims to provide therapeutic application for the treatment of severe infection, cancer, and age-related involution of secondary lymphoid tissues. The development of murine artificial lymphoid tissues has benefited greatly from an understanding of organogenesis of lymphoid organs, which has delineated cellular and molecular elements essential for the recruitment and organization of lymphocytes into lymphoid structures. Here, the field of artificial lymphoid tissue engineering is considered including elements of lymphoid structure and development relevant to organoid synthesis. (c) 2010 Elsevier Inc. All rights reserved.

  5. Innate lymphoid cells and asthma.

    Science.gov (United States)

    Yu, Sanhong; Kim, Hye Young; Chang, Ya-Jen; DeKruyff, Rosemarie H; Umetsu, Dale T

    2014-04-01

    Asthma is a complex and heterogeneous disease with several phenotypes, including an allergic asthma phenotype characterized by TH2 cytokine production and associated with allergen sensitization and adaptive immunity. Asthma also includes nonallergic asthma phenotypes, such as asthma associated with exposure to air pollution, infection, or obesity, that require innate rather than adaptive immunity. These innate pathways that lead to asthma involve macrophages, neutrophils, natural killer T cells, and innate lymphoid cells, newly described cell types that produce a variety of cytokines, including IL-5 and IL-13. We review the recent data regarding innate lymphoid cells and their role in asthma. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  6. Innate lymphoid cells in atherosclerosis.

    Science.gov (United States)

    Engelbertsen, Daniel; Lichtman, Andrew H

    2017-12-05

    The family of innate lymphoid cells (ILCs) consisting of NK cells, lymphoid tissue inducer cells and the 'helper'-like ILC subsets ILC1, ILC2 and ILC3 have been shown to have important roles in protection against microbes, regulation of inflammatory diseases and involved in allergic reactions. ILC1s produce IFN-γ upon stimulation with IL-12 and IL-18, ILC2s produce IL-5 and IL-13 responding to IL-33 and IL-25 while ILC3s produce IL-17 and IL-22 after stimulation with IL-23 or IL-1. Although few studies have directly investigated the role for ILCs in atherosclerosis, several studies have investigated transcription factors and cytokines shared by ILCs and T helper cells. In this review we summarize our current understanding of the role of ILC in atherosclerosis and discuss future directions. Copyright © 2017. Published by Elsevier B.V.

  7. Histological and three dimensional organizations of lymphoid tubules in normal lymphoid organ of Penaeus monodon.

    Science.gov (United States)

    Duangsuwan, Pornsawan; Phoungpetchara, Ittipon; Tinikul, Yotsawan; Poljaroen, Jaruwan; Wanichanon, Chaitip; Sobhon, Prasert

    2008-04-01

    The normal lymphoid organ of Penaeus monodon (which tested negative for WSSV and YHV) was composed of two parts: lymphoid tubules and interstitial spaces, which were permeated with haemal sinuses filled with large numbers of haemocytes. There were three permanent types of cells present in the wall of lymphoid tubules: endothelial, stromal and capsular cells. Haemocytes penetrated the endothelium of the lymphoid tubule's wall to reside among the fixed cells. The outermost layer of the lymphoid tubule was covered by a network of fibers embedded in a PAS-positive extracellular matrix, which corresponded to a basket-like network that covered all the lymphoid tubules as visualized by a scanning electron microscope (SEM). Argyrophilic reticular fibers surrounded haemal sinuses and lymphoid tubules. Together they formed the scaffold that supported the lymphoid tubule. Using vascular cast and SEM, the three dimensional structure of the subgastric artery that supplies each lobe of the lymphoid organ was reconstructed. This artery branched into highly convoluted and blind-ending terminal capillaries, each forming the lumen of a lymphoid tubule around which haemocytes and other cells aggregated to form a cuff-like wall. Stromal cells which form part of the tubular scaffold were immunostained for vimentin. Examination of the whole-mounted lymphoid organ, immunostained for vimentin, by confocal microscopy exhibited the highly branching and convoluted lymphoid tubules matching the pattern of the vascular cast observed in SEM.

  8. Shaping Innate Lymphoid Cell Diversity

    Directory of Open Access Journals (Sweden)

    Qiutong Huang

    2017-11-01

    Full Text Available Innate lymphoid cells (ILCs are a key cell type that are enriched at mucosal surfaces and within tissues. Our understanding of these cells is growing rapidly. Paradoxically, these cells play a role in maintaining tissue integrity but they also function as key drivers of allergy and inflammation. We present here the most recent understanding of how genomics has provided significant insight into how ILCs are generated and the enormous heterogeneity present within the canonical subsets. This has allowed the generation of a detailed blueprint for ILCs to become highly sensitive and adaptive sensors of environmental changes and therefore exquisitely equipped to protect immune surfaces.

  9. Innate lymphoid cells in inflammation and immunity

    NARCIS (Netherlands)

    McKenzie, Andrew N. J.; Spits, Hergen; Eberl, Gerard

    2014-01-01

    Innate lymphoid cells (ILCs) were first described as playing important roles in the development of lymphoid tissues and more recently in the initiation of inflammation at barrier surfaces in response to infection or tissue damage. It has now become apparent that ILCs play more complex roles

  10. Transcriptional control of innate lymphoid cells

    NARCIS (Netherlands)

    Mjösberg, Jenny; Bernink, Jochem; Peters, Charlotte; Spits, Hergen

    2012-01-01

    Cells that belong to the family of innate lymphoid cells (ILCs) not only form a first line of defense against invading microbes, but also play essential roles in tissue remodeling and immune pathology. Ror?t+ ILCs, producing the cytokines IL-22 and IL-17, include lymphoid tissue inducer (LTi) cells

  11. Lymphoid cells in chicken intestinal epithelium

    DEFF Research Database (Denmark)

    Bjerregaard, P

    1975-01-01

    The intraepithelial lymphoid cells of chicken small intestine were studied by light microscopy using 1 mu Epon sections, and by electron microscopy. Three cell types were found: small lymphocytes, large lymphoid cells, and granular cells. These cells correspond to the theliolymphocytes and globule...

  12. Innate Lymphoid Cells in Tumor Immunity.

    Science.gov (United States)

    van Beek, Jasper J P; Martens, Anne W J; Bakdash, Ghaith; de Vries, I Jolanda M

    2016-02-25

    Innate lymphoid cells (ILCs) are a group of immune cells of the lymphoid lineage that do not possess antigen specificity. The group includes natural killer (NK) cells, lymphoid tissue inducer (LTi) cells and the recently identified ILC1s, ILC2s and ILC3s. Although the role of NK cells in the context of cancer has been well established, the involvement of other ILC subsets in cancer progression and resistance is just emerging. Here, we review the literature on the role of the different ILC subsets in tumor immunity and discuss its implications for cancer treatment and monitoring.

  13. The enigma of the lower gut-associated lymphoid tissue (GALT).

    Science.gov (United States)

    Butler, John E; Sinkora, Marek

    2013-08-01

    Artiodactyls possess GALT that appears in fetal life and is located at the extreme end of the ileum. These IPP contain mostly B cells and involute early in postnatal life. Rabbits have a similarly located lymphoid organ, called the sacculus rotundus. Studies in sheep and rabbits have led to the concept that the lower hindgut GALT represents primary lymphoid tissue for B cells and is necessary for normal B cell development, analogous to the bursa of Fabricius. This review traces the history of the observations and theories that have led to the existing concept concerning the role of lower GALT. We then review recent data from piglets with resected IPP that challenges the concept that the IPP is primary B cell lymphoid tissue and that artiodactyls and rabbits are members of the GALT group in the same context as gallinaceous birds. Eliminating the IPP as the primary lymphoid tissue for B cells leads to the hypothesis that the IPP acts as first-responder mucosal lymphoid tissue.

  14. Innate lymphoid cells and their stromal microenvironments.

    Science.gov (United States)

    Kellermayer, Zoltán; Vojkovics, Dóra; Balogh, Péter

    2017-09-01

    In addition to the interaction between antigen presenting cells, T and B lymphocytes, recent studies have revealed important roles for a diverse set of auxiliary cells that profoundly influence the induction and regulation of immune responses against pathogens. Of these the stromal cells composed of various non-hematopoietic constituents are crucial for the creation and maintenance of specialized semi-static three-dimensional lymphoid tissue microenvironment, whereas the more recently described innate lymphoid cells are generated by the diversification of committed lymphoid precursor cells independently from clonally rearranged antigen receptor genes. Recent findings have revealed important contributions by innate lymphoid cells in inflammation and protection against pathogens in a tissue-specific manner. Importantly, lymphoid stromal cells also influence the onset of immune responses in tissue-specific fashion, raising the possibility of tissue-specific stromal - innate lymphoid cell collaboration. In this review we summarize the main features and interactions between these two cells types, with particular emphasis on ILC type 3 cells and their microenvironmental partners. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  15. HCV Virus and Lymphoid Neoplasms

    Directory of Open Access Journals (Sweden)

    Yutaka Tsutsumi

    2011-01-01

    Full Text Available Hepatitis C virus (HCV is one of the viruses known to cause hepatic cancer. HCV is also believed to be involved in malignant lymphoma. In this paper, we investigated characteristics of malignant lymphoma cases that were anti-HCV antibody (HCV-Ab positive. We were able to perform pathological examinations on 13 out of 14 HCV-positive cases. Of these, lymphoid tissues of 10 stained positive for HCV-Ab. There was no significant correlation between the degree of HCV staining and the rate of recurrence or resistance to treatment. However, there did appear to be a consistent decrease in the amount of HCV-RNA between pre- and posttreatment among HCV-Ab-positive cases; that is, treatment-resistant cases that exhibited resistance from the first treatment and recurrent cases more frequently had a higher HCV level at treatment termination compared to the pretreatment level. This suggests that the HCV virus either accelerates oncogenesis by direct interaction with B cells or indirectly affects lymphoma prognosis.

  16. Isolation of Human Innate Lymphoid Cells.

    Science.gov (United States)

    Krabbendam, Lisette; Nagasawa, Maho; Spits, Hergen; Bal, Suzanne M

    2018-06-29

    Innate lymphoid cells (ILCs) are innate immune cells of lymphoid origin that have important effector and regulatory functions in the first line of defense against pathogens, but also regulate tissue homeostasis, remodeling, and repair. Their function mirrors T helper cells and cytotoxic CD8 + T lymphocytes, but they lack expression of rearranged antigen-specific receptors. Distinct ILC subsets are classified in group 1 ILCs (ILC1s), group 2 ILCs (ILC2s), and group 3 ILCs (ILC3s and lymphoid tissue-inducer cells), based on the expression of transcription factors and the cytokines they produce. As the frequency of ILCs is low, their isolation requires extensive depletion of other cell types. The lack of unique cell surface antigens further complicates the identification of these cells. Here, methods for ILC isolation and characterization from human peripheral blood and different tissues are described. © 2018 by John Wiley & Sons, Inc. © 2018 John Wiley & Sons, Inc.

  17. Colonic lymphoid follicles associated with colonic neoplasms

    International Nuclear Information System (INIS)

    Glick, S.N.; Teplick, S.K.; Ross, W.M.

    1986-01-01

    The authors prospectively evaluated 62 patients over 40 years old in whom lymphoid follicles were demonstrated on double-contrast enema examinations. Eighteen patients (29%) had no current radiographic evidence of, or history of, colonic neoplasms. Forty-four patients (71%) had an associated neoplasm. Fourteen patients had associated colonic carcinoma, and ten patients had a history of a previously resected colon cancer. One patient had previously undergone resection for ''polyps.'' Twenty-two patients had an associated ''polyp.'' There were no clinical or radiographic features that could reliably distinguish the neoplastic from the nonneoplastic groups. However, lymphoid follicles in the left colon or diffusely involving the colon were more likely to be associated with a colonic neoplasm. Lymphoid follicles were almost always identified near a malignant lesion

  18. TOX sets the stage for innate lymphoid cells

    NARCIS (Netherlands)

    Spits, Hergen

    2015-01-01

    Like T cells and B cells, innate lymphoid cells (ILCs) develop from common lymphoid progenitors, but how commitment to the ILC lineage is regulated has remained unclear. The transcriptional regulator TOX is important in this process

  19. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    OpenAIRE

    Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2011-01-01

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of ly...

  20. The biology of human innate lymphoid cells

    NARCIS (Netherlands)

    Bernink, J.H.J.

    2016-01-01

    In this thesis I performed studies to investigate the contribution of human innate lymphoid cells (ILCs) in maintaining the mucosal homeostasis, initiating and/or propagating inflammatory responses, but also - when not properly regulated - how these cells contribute to immunopathology. First I

  1. Total lymphoid irradiation of intractable rheumatoid arthritis

    International Nuclear Information System (INIS)

    Herbst, M.; Fritz, H.; Sauer, R.

    1986-01-01

    Eleven patients with intractable rheumatoid arthritis were treated with fractionated total lymphoid irradiation, (total dose 20 Gy). Lasting improvement in clinical symptoms was found in four patients during treatment and the remaining patients experienced similar benefit within 2 months of irradiation. There was marked reduction in exacerbations and number of joints involved. Morning stiffness, joint swelling and tenderness decreased. Complications included severe fatigue during treatment and acute bacterial arthritis in multiple joints in one patient. Four patients have since died, one of renal failure, another of cardiogenic shock following surgery 3 and 24 months after total lymphoid irradiation. Both had generalised amyloidosis. The third patient developed joint empyema and died of toxic cardiac failure. The fourth died 3 months after resection of a Kaposi's sarcoma complicated by wound infection which responded to treatment. Immunologically, total lymphoid irradiation resulted in suppression of the absolute lymphocyte count and reduction in T-helper cells, the number of T-suppressor cells remaining unchanged. These data provide evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis. Total lymphoid irradiation can induce sustained improvement in clinical disease activity, but severe, possibly fatal, side-effects cannot be ignored. (author)

  2. Innate lymphoid cells, precursors and plasticity.

    Science.gov (United States)

    Gronke, Konrad; Kofoed-Nielsen, Michael; Diefenbach, Andreas

    2016-11-01

    Innate lymphoid cells (ILC) have only recently been recognized as a separate entity of the lymphoid lineage. Their subpopulations share common characteristics in terms of early development and major transcriptional circuitry with their related cousins of the T cell world. It is currently hypothesized that ILCs constitute an evolutionary older version of the lymphoid immune system. They are found at all primary entry points for pathogens such as mucosal surfaces of the lung and gastrointestinal system, the skin and the liver, which is the central contact point for pathogens that breach the intestinal barrier and enter the circulation. There, ILC contribute to the first line defense as well as to organ homeostasis. However, ILC are not only involved in classical defense tasks, but also contribute to the organogenesis of lymphoid organs as well as tissue remodeling and even stem cell regeneration. ILC may, therefore, implement different functions according to their emergence in ontogeny, their development and their final tissue location. We will review here their early development from precursors of the fetal liver and the adult bone marrow as well as their late plasticity in adaptation to their environment. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  3. Radiotherapy of lymphoid diseases of the orbit

    International Nuclear Information System (INIS)

    Austin-Seymour, M.M.; Donaldson, S.S.; Egbert, P.R.; McDougall, I.R.; Kriss, J.P.

    1985-01-01

    Thirty-two patients with orbital pseudotumor (18), reactive lymphoid hyperplasia (2), atypical lymphoid infiltrate (4) or malignant lymphoma (8) were treated in the Division of Radiation Therapy at Stanford University between January 1973 and May 1983. Of the 20 patients with pseudotumor or reactive lymphoid hyperplasia, 10 had unilateral lesions and 10 had bilateral lesions. Biopsy samples were obtained in 15 patients; in five patients with bilateral disease the diagnosis was made on the basis of computed tomography (CT) and clinical findings. The majority of patients were referred because of disease refractory to treatment with corticosteroids. The patients were given a mean dose of 2360 rad using complex, individualized megavoltage techniques including lens shielding. Radiotherapy was well tolerated with no significant acute or late complications. Fifteen patients had complete resolution of symptoms after treatment; five had continued symptoms. Of the 12 patients with malignant lymphoma or atypical lymphoid infiltrate, four had systemic lymphoma with orbital involvement and eight had orbital involvement only. A mean dose of 3625 rad was delivered to the orbit only. Most of the patients received complex megavoltage treatment using bolus. All patients in this group had a complete response and local control. Two patients developed cataracts. Carefullly planned orbital radiotherapy provides local control without symptomatic sequelae for orbital masses ranging from pseudotumor to malignant lymphoma

  4. Total lymphoid irradiation of intractable rheumatoid arthritis

    Energy Technology Data Exchange (ETDEWEB)

    Herbst, M.; Fritz, H.; Sauer, R.

    1986-12-01

    Eleven patients with intractable rheumatoid arthritis were treated with fractionated total lymphoid irradiation, (total dose 20 Gy). Lasting improvement in clinical symptoms was found in four patients during treatment and the remaining patients experienced similar benefit within 2 months of irradiation. There was marked reduction in exacerbations and number of joints involved. Morning stiffness, joint swelling and tenderness decreased. Complications included severe fatigue during treatment and acute bacterial arthritis in multiple joints in one patient. Four patients have since died, one of renal failure, another of cardiogenic shock following surgery 3 and 24 months after total lymphoid irradiation. Both had generalised amyloidosis. The third patient developed joint empyema and died of toxic cardiac failure. The fourth died 3 months after resection of a Kaposi's sarcoma complicated by wound infection which responded to treatment. Immunologically, total lymphoid irradiation resulted in suppression of the absolute lymphocyte count and reduction in T-helper cells, the number of T-suppressor cells remaining unchanged. These data provide evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis. Total lymphoid irradiation can induce sustained improvement in clinical disease activity, but severe, possibly fatal, side-effects cannot be ignored.

  5. Homing of bone marrow lymphoid cells

    International Nuclear Information System (INIS)

    Yoshida, Y.; Osmond, D.G.

    1978-01-01

    DNA labeling, bone marrow fractionation, and radioautography were used to follow the fate of transfused, newly formed marrow lymphocytes in irradiated hosts. After infusing donor Hartley guinea pigs with 3 H-thymidine for 3 to 5 days, high concentrations of labeled small lymphocytes and large lymphoid cells were separated from marrow by sedimentation in sucrose-serum gradients and injected into lethally x-irradiated syngeneic recipients. Most labeled small lymphocytes and large lymphoid cells rapidly left the circulation. They appeared to be mainly in the marrow and spleen, increasing in incidence from 1 to 3 days, but declining in mean grain count. Labeled cells were scattered throughout the recipient marrow; in the spleen they localized initially in the red pulp, and subsequently in peripheral areas of white pulp, often in clusters. Labeled small lymphocytes showed a delayed migration into the mesenteric lymph node, mainly in the superficial cortex and medulla; they also appeared in small numbers in Peyer's patches, but rarely in the thymus or thoracic duct lymph. It is concluded that a rapid selective homing of newly formed marrow lymphoid cells occurs in both the marrow and certain areas of the spleen of irradiated hosts, followed by a continuing proliferation of large lymphoid cells and production of small lymphocytes. The results are discussed with respect to the life history of marrow lymphocytes and the use of adoptive immune assays of marrow cells to characterize B lymphocyte maturation

  6. The new WHO nomenclature: lymphoid neoplasms.

    Science.gov (United States)

    Leclair, Susan J; Rodak, Bernadette F

    2002-01-01

    The development of the WHO classification of lymphoid neoplasms is a remarkable example of cooperation and communication between pathologists and oncologists from around the world. Joint classification committees of the major hematopathology societies will periodically review and update this classification, facilitating further progress in the understanding and treatment of hematologic malignancies.

  7. Conjunctival lymphoma arising from reactive lymphoid hyperplasia

    Directory of Open Access Journals (Sweden)

    Fukuhara Junichi

    2012-09-01

    Full Text Available Abstract Extra nodal marginal zone B-cell lymphoma (EMZL of the conjunctiva typically arises in the marginal zone of mucosa-associated lymphoid tissue. The pathogenesis of conjunctival EMZL remains unknown. We describe an unusual case of EMZL arising from reactive lymphoid hyperplasia (RLH of the conjunctiva. A 35-year-old woman had fleshy salmon-pink conjunctival tumors in both eyes, oculus uterque (OU. Specimens from conjunctival tumors in the right eye, oculus dexter (OD, revealed a collection of small lymphoid cells in the stroma. Immunohistochemically, immunoglobulin (Ig light chain restriction was not detected. In contrast, diffuse atypical lymphoid cell infiltration was noted in the left eye, oculus sinister (OS, and positive for CD20, a marker for B cells OS. The tumors were histologically diagnosed as RLH OD, and EMZL OS. PCR analysis detected IgH gene rearrangement in the joining region (JH region OU. After 11 months, a re-biopsy specimen demonstrated EMZL based on compatible pathological and genetic findings OD, arising from RLH. This case suggests that even if the diagnosis of the conjunctival lymphoproliferative lesions is histologically benign, confirmation of the B-cell clonality by checking IgH gene rearrangement should be useful to predict the incidence of malignancy.

  8. Mapping of NKp46+ cells in healthy human lymphoid and non-lymphoid tissues

    Directory of Open Access Journals (Sweden)

    Elena eTomasello

    2012-11-01

    Full Text Available Understanding Natural Killer (NK cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs expressing the retinoic acid receptor-related orphan receptor t (RORt transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We also identified a novel cell subset of CD56dimNKp46low cells that includes RORt+ILCs with a lineage-CD94-CD117brightCD127bright phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases.

  9. Mapping of NKp46+ Cells in Healthy Human Lymphoid and Non-Lymphoid Tissues

    Science.gov (United States)

    Tomasello, Elena; Yessaad, Nadia; Gregoire, Emilie; Hudspeth, Kelly; Luci, Carmelo; Mavilio, Domenico; Hardwigsen, Jean; Vivier, Eric

    2012-01-01

    Understanding Natural Killer (NK) cell anatomical distribution is key to dissect the role of these unconventional lymphocytes in physiological and disease conditions. In mouse, NK cells have been detected in various lymphoid and non-lymphoid organs, while in humans the current knowledge of NK cell distribution at steady state is mainly restricted to lymphoid tissues. The translation to humans of findings obtained in mice is facilitated by the identification of NK cell markers conserved between these two species. The Natural Cytotoxicity Receptor (NCR) NKp46 is a marker of the NK cell lineage evolutionary conserved in mammals. In mice, NKp46 is also present on rare T cell subsets and on a subset of gut Innate Lymphoid Cells (ILCs) expressing the retinoic acid receptor-related orphan receptor γt (RORγt) transcription factor. Here, we documented the distribution and the phenotype of human NKp46+ cells in lymphoid and non-lymphoid tissues isolated from healthy donors. Human NKp46+ cells were found in splenic red pulp, in lymph nodes, in lungs, and gut lamina propria, thus mirroring mouse NKp46+ cell distribution. We also identified a novel cell subset of CD56dimNKp46low cells that includes RORγt+ ILCs with a lineage−CD94−CD117brightCD127bright phenotype. The use of NKp46 thus contributes to establish the basis for analyzing quantitative and qualitative changes of NK cell and ILC subsets in human diseases. PMID:23181063

  10. Stroma cell priming in enteric lymphoid organ morphogenesis

    Directory of Open Access Journals (Sweden)

    Manuela eFerreira

    2012-07-01

    Full Text Available The lymphoid system is equipped with a network of specialized platforms located at strategic sites, which grant strict immune-surveillance and efficient immune responses. The development of these peripheral secondary lymphoid organs occurs mainly in utero, while tertiary lymphoid structures can form in adulthood generally in response to persistent infection and inflammation. Regardless of the lymphoid tissue and intrinsic cellular and molecular differences, it is now well established that the recruitment of fully functional Lymphoid Tissue inducer (LTi cells to presumptive lymphoid organ sites, and their consequent close and reciprocal interaction with resident stroma cells, are central to secondary lymphoid organ formation. In contrast, the nature of events that initially prime resident sessile stroma cells to recruit and retain LTi cells remains poorly understood.

  11. Tertiary lymphoid structures in cancer and beyond.

    Science.gov (United States)

    Dieu-Nosjean, Marie-Caroline; Goc, Jérémy; Giraldo, Nicolas A; Sautès-Fridman, Catherine; Fridman, Wolf Herman

    2014-11-01

    Tertiary lymphoid structures (TLS) are ectopic lymphoid formations found in inflamed, infected, or tumoral tissues. They exhibit all the characteristics of structures in the lymph nodes (LN) associated with the generation of an adaptive immune response, including a T cell zone with mature dendritic cells (DC), a germinal center with follicular dendritic cells (FDC) and proliferating B cells, and high endothelial venules (HEV). In this review, we discuss evidence for the roles of TLS in chronic infection, autoimmunity, and cancer, and address the question of whether TLS present beneficial or deleterious effects in these contexts. We examine the relationship between TLS in tumors and patient prognosis, and discuss the potential role of TLS in building and/or maintaining local immune responses and how this understanding may guide therapeutic interventions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. STUDIES ON TRANSMISSIBLE LYMPHOID LEUCEMIA OF MICE.

    Science.gov (United States)

    Furth, J; Strumia, M

    1931-04-30

    Lymphoid leucemia of the mouse is readily transmitted by intravenous inoculations. The majority of the mice inoculated successfully develop leucemic, a smaller number of them, aleucemic lymphadenosis. The data presented favor the view that leucemic and aleucemic lymphadenosis are essentially the same condition. Leucemia produced by transmission is preceded by an aleucemic stage, in which the lymph nodes and the spleen are uniformly enlarged, and the white blood count and the percentage of lymphocytes are within the normal range but immature lymphocytes are numerous in the circulating blood. Young as well as old mice may develop leucemia if leucotic material enters their circulation. Studies of transmissible leucemia favor the view that leucemia of mammals is a neoplastic disease. The basic problem of leucemia would seem to be determination of the factors that bring about a malignant transformation of lymphoid cells.

  13. THE FRACTAL MARKET HYPOTHESIS

    OpenAIRE

    FELICIA RAMONA BIRAU

    2012-01-01

    In this article, the concept of capital market is analysed using Fractal Market Hypothesis which is a modern, complex and unconventional alternative to classical finance methods. Fractal Market Hypothesis is in sharp opposition to Efficient Market Hypothesis and it explores the application of chaos theory and fractal geometry to finance. Fractal Market Hypothesis is based on certain assumption. Thus, it is emphasized that investors did not react immediately to the information they receive and...

  14. Variability: A Pernicious Hypothesis.

    Science.gov (United States)

    Noddings, Nel

    1992-01-01

    The hypothesis of greater male variability in test results is discussed in its historical context, and reasons feminists have objected to the hypothesis are considered. The hypothesis acquires political importance if it is considered that variability results from biological, rather than cultural, differences. (SLD)

  15. Tertiary lymphoid organs in Takayasu Arteritis

    OpenAIRE

    Marc eClement; Marc eClement; Adrien eGaly; Patrick eBruneval; Marion eMorvan; Fabien eHyafil; Fabien eHyafil; Khadija eBenali; Nicoletta ePasi; Lydia eDeschamps; Quentin ePellenc; Quentin ePellenc; Thomas ePapo; Antonino eNicoletti; Antonino eNicoletti

    2016-01-01

    Objective: The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients.Methods: Hematoxylin and eosin–stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune cells from t...

  16. Tertiary Lymphoid Organs in Takayasu Arteritis

    OpenAIRE

    Clement, Marc; Galy, Adrien; Bruneval, Patrick; Morvan, Marion; Hyafil, Fabien; Benali, Khadija; Pasi, Nicoletta; Deschamps, Lydia; Pellenc, Quentin; Papo, Thomas; Nicoletti, Antonino; Sacre, Karim

    2016-01-01

    Objective The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. Methods Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune ce...

  17. Characteristic of innate lymphoid cells (ILC

    Directory of Open Access Journals (Sweden)

    Mateusz Adamiak

    2014-12-01

    Full Text Available Innate lymphoid cells (ILC is a newly described family of immune cells that are part of the natural immunity which is important not only during infections caused by microorganisms, but also in the formation of lymphoid tissue, tissue remodeling after damage due to injury and homeostasis tissue stromal cells. Family ILC cells form NK cells (natural killer and lymphoid tissue inducer T cells (LTi, which, although they have different functions, are evolutionarily related. NK cells are producing mainly IFN-γ, whereas LTi cells as NKR+LTi like, IL-17 and/or IL-22, which suggests that the last two cells, can also represent the innate versions of helper T cell - TH17 and TH22. Third population of ILC is formed by cells with characteristics such as NK cells and LTi (ILC22 - which are named NK22 cells, natural cytotoxicity receptor 22 (NCR22 cells or NK receptor-positive (LTi NKR+ LTi cells. Fourth population of ILC cells are ILC17 - producing IL-17, while the fifth is formed by natural helper type 2 T cells (nTH2, nuocyte, innate type 2 helper cells (IH2 and multi-potent progenitor type 2 cells (MPPtype2. Cells of the last population synthesize IL-5 and IL-13. It is assumed that an extraordinary functional diversity of ILC family, resembles T cells, probably because they are under the control of the corresponding transcription factors - as direct regulation factors, such as the family of lymphocytes T.

  18. THE FRACTAL MARKET HYPOTHESIS

    Directory of Open Access Journals (Sweden)

    FELICIA RAMONA BIRAU

    2012-05-01

    Full Text Available In this article, the concept of capital market is analysed using Fractal Market Hypothesis which is a modern, complex and unconventional alternative to classical finance methods. Fractal Market Hypothesis is in sharp opposition to Efficient Market Hypothesis and it explores the application of chaos theory and fractal geometry to finance. Fractal Market Hypothesis is based on certain assumption. Thus, it is emphasized that investors did not react immediately to the information they receive and of course, the manner in which they interpret that information may be different. Also, Fractal Market Hypothesis refers to the way that liquidity and investment horizons influence the behaviour of financial investors.

  19. Suitability of stratagene reference RNA for analysis of lymphoid tissues

    DEFF Research Database (Denmark)

    Dybkaer, Karen; Zhou, Guimei; Iqbal, Javeed

    2004-01-01

    acceptable gene coverage to serve as a comprehensive standard for gene expression profiling of lymphoid tissues. Our lymphoid standard was prepared from thymus, spleen, tonsil, and cell lines representing immature B cells, plasma cells, and natural killer (NK) cells, thus covering the entire spectrum...... of lymphoid cells and most stromal elements present in specialized lymphoid tissues. The two standards were co-hybridized on oligonucleotide microarrays containing 17,260 genes, and both had fluorescence intensities above background for approximately 85% of the genes. Despite the limited representation...... of lymphoid cells in the Stratagene standard, only 4.2% genes exhibited expression differences greater than 2-fold including only 0.35% with differences greater than 4-fold. Although the lymphoid standard reflected a more comprehensive representation of immune system-associated genes, the Stratagene standard...

  20. Stromal cell regulation of homeostatic and inflammatory lymphoid organogenesis

    Science.gov (United States)

    Kain, Matthew J W; Owens, Benjamin M J

    2013-01-01

    Summary Secondary lymphoid organs function to increase the efficiency of interactions between rare, antigen-specific lymphocytes and antigen presenting cells, concentrating antigen and lymphocytes in a supportive environment that facilitates the initiation of an adaptive immune response. Homeostatic lymphoid tissue organogenesis proceeds via exquisitely controlled spatiotemporal interactions between haematopoietic lymphoid tissue inducer populations and multiple subsets of non-haematopoietic stromal cells. However, it is becoming clear that in a range of inflammatory contexts, ectopic or tertiary lymphoid tissues can develop inappropriately under pathological stress. Here we summarize the role of stromal cells in the development of homeostatic lymphoid tissue, and assess emerging evidence that suggests a critical role for stromal involvement in the tertiary lymphoid tissue development associated with chronic infections and inflammation. PMID:23621403

  1. Physiopathological Hypothesis of Cellulite

    Science.gov (United States)

    de Godoy, José Maria Pereira; de Godoy, Maria de Fátima Guerreiro

    2009-01-01

    A series of questions are asked concerning this condition including as regards to its name, the consensus about the histopathological findings, physiological hypothesis and treatment of the disease. We established a hypothesis for cellulite and confirmed that the clinical response is compatible with this hypothesis. Hence this novel approach brings a modern physiological concept with physiopathologic basis and clinical proof of the hypothesis. We emphasize that the choice of patient, correct diagnosis of cellulite and the technique employed are fundamental to success. PMID:19756187

  2. Life Origination Hydrate Hypothesis (LOH-Hypothesis

    Directory of Open Access Journals (Sweden)

    Victor Ostrovskii

    2012-01-01

    Full Text Available The paper develops the Life Origination Hydrate Hypothesis (LOH-hypothesis, according to which living-matter simplest elements (LMSEs, which are N-bases, riboses, nucleosides, nucleotides, DNA- and RNA-like molecules, amino-acids, and proto-cells repeatedly originated on the basis of thermodynamically controlled, natural, and inevitable processes governed by universal physical and chemical laws from CH4, niters, and phosphates under the Earth's surface or seabed within the crystal cavities of the honeycomb methane-hydrate structure at low temperatures; the chemical processes passed slowly through all successive chemical steps in the direction that is determined by a gradual decrease in the Gibbs free energy of reacting systems. The hypothesis formulation method is based on the thermodynamic directedness of natural movement and consists ofan attempt to mentally backtrack on the progression of nature and thus reveal principal milestones alongits route. The changes in Gibbs free energy are estimated for different steps of the living-matter origination process; special attention is paid to the processes of proto-cell formation. Just the occurrence of the gas-hydrate periodic honeycomb matrix filled with LMSEs almost completely in its final state accounts for size limitation in the DNA functional groups and the nonrandom location of N-bases in the DNA chains. The slowness of the low-temperature chemical transformations and their “thermodynamic front” guide the gross process of living matter origination and its successive steps. It is shown that the hypothesis is thermodynamically justified and testable and that many observed natural phenomena count in its favor.

  3. The mechanism of radiation-induced interphase death of lymphoid cells: A new hypothesis

    International Nuclear Information System (INIS)

    Eidus, L.K.; Korystov, Yu.N.; Dobrovinskaja, O.R.; Shaposhnikova, V.V.

    1990-01-01

    The interphase death of irradiated rat thymocytes depends on their concentration during postirradiation incubation. The kinetics of pycnosis and cell death determined with the trypan blue exclusion test in the samples with the highest cell concentration (1-2 x 10(7) cells/ml) is consistent with the data available in the literature, whereas the samples with the lowest concentration (2 x 10(5) cells/ml) undergo almost no pycnosis and death after irradiation with doses up to 50 Gy. On the basis of these results, we suggest a new mechanism of interphase death involving an interaction between irradiated thymocytes and the fraction of thymus cells possessing cytocidal activity. The observed correlation between the cytocidal activity and interphase death of thymocytes from animals of different ages favors our mechanism. It was found that the inhibitors which prevent the conjugation of killer cells and their targets do not influence interphase death, while the substances which block the secretion of cytotoxic factors or their action on the target membrane do protect from interphase death. Thus we suggest that the irradiation activates the killer cells to secrete some cytotoxic factors which induce pycnosis and interphase death of thymocytes

  4. The Development of Adult Innate Lymphoid Cells

    Science.gov (United States)

    Yang, Qi; Bhandoola, Avinash

    2016-01-01

    Innate lymphoid cells (ILC) are a specialized family of effector lymphocytes that transcriptionally and functionally mirror effector subsets of T cells, but differ from T cells in that they lack clonally-distributed adaptive antigen receptors. Our understanding of this family of lymphocytes is still in its infancy. In this review, we summarize current understanding and discuss recent insights into the cellular and molecular events that occur during early ILC development in adult mice. We discuss how these events overlap and diverge with the early development of adaptive T cells, and how they may influence the molecular and functional properties of mature ILC. PMID:26871595

  5. Total lymphoid irradiation in rhesus monkeys

    International Nuclear Information System (INIS)

    Vriesendorp, H.M.; Maat, B.; Hogeweg, B.

    Total lymphoid irradiation (TLI) consists of three contiguous fields, a mantle, an inverted Y and a spleen field. TLI induces a state of immunosuppression in patients with Hodgkin disease or in small rodents. Infusion of allogeneic bone marrow cells into mice after TLI led to the development split haemopoietic chimerism and indefinite survival of skin grafts from the bone marrow donor. A protocol for TLI was developed for rhesus monkeys to attempt to verify these interesting observations in a pre-clinical animal model. (Auth.)

  6. Tertiary Lymphoid Organs in Central Nervous System Autoimmunity

    Directory of Open Access Journals (Sweden)

    Meike Mitsdoerffer

    2016-10-01

    Full Text Available Multiple sclerosis (MS is an autoimmune disease characterized by chronic inflammation in the central nervous system (CNS, which results in permanent neuronal damage and substantial disability in patients. Autoreactive T cells are important drivers of the disease, however, the efficacy of B cell depleting therapies uncovered an essential role for B cells in disease pathogenesis. They can contribute to inflammatory processes via presentation of autoantigen, secretion of pro-inflammatory cytokines and production of pathogenic antibodies. Recently, B cell aggregates reminiscent of tertiary lymphoid organs (TLOs were discovered in the meninges of MS patients, leading to the hypothesis that differentiation and maturation of autopathogenic B and T cells may partly occur inside the CNS. Since these structures were associated with a more severe disease course, it is extremely important to gain insight into the mechanism of induction, their precise function and clinical significance. Mechanistic studies in patiens are limited. However, a few studies in the MS animal model experimental autoimmune encephalomyelitis (EAE recapitulate TLO formation in the CNS and provide new insight into CNS TLO features, formation and function. This review summarizes what we know so far about CNS TLOs in MS and what we have learned about them from EAE models. It also highlights the areas that are in need of further experimental work, as we are just beginning to understand and evaluate the phenomenon of CNS TLOs.

  7. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bergomas, Francesca [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Grizzi, Fabio [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Doni, Andrea; Pesce, Samantha [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Laghi, Luigi [Laboratory of Molecular Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Gastroenterology, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Allavena, Paola [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Mantovani, Alberto [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy); Department of Translational Medicine, University of Milan, Milan 20089 (Italy); Marchesi, Federica, E-mail: federica.marchesi@humanitasresearch.it [Department of Immunology and Inflammation, IRCCS Humanitas Clinical Institute, Via Manzoni 56, 20089 Rozzano, Milan (Italy)

    2011-12-28

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21{sup +} follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  8. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    Directory of Open Access Journals (Sweden)

    Federica Marchesi

    2011-12-01

    Full Text Available Ectopic (or tertiary lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21+ follicular dendritic cells (FDC. We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS. B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV. Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response.

  9. Tertiary Intratumor Lymphoid Tissue in Colo-Rectal Cancer

    International Nuclear Information System (INIS)

    Bergomas, Francesca; Grizzi, Fabio; Doni, Andrea; Pesce, Samantha; Laghi, Luigi; Allavena, Paola; Mantovani, Alberto; Marchesi, Federica

    2011-01-01

    Ectopic (or tertiary) lymphoid tissue develops at sites of inflammation or infection in non lymphoid organs and is associated with chronic inflammation. In colon mucosa, small lymphoid aggregates are already present in homeostatic conditions, as part of the gut-associated lymphoid tissue and play an essential role in the immune response to perturbations of the mucosal microenvironment. Despite the recognized role of inflammation in tumor progression, the presence and biological function of lymphoid tissue in cancer has been poorly investigated. We identified aggregates of lymphocytes resembling tertiary lymphoid tissue in human colorectal cancer specimens; intratumor accumulations of lymphocytes display a high degree of compartmentalization, with B and T cells, mature dendritic cells and a network of CD21 + follicular dendritic cells (FDC). We analyzed the adaptation of colon lymphoid tissue in a murine model of colitis-associated cancer (AOM/DSS). B cell follicle formation increases in the context of the chronic inflammation associated to intestinal neoplasia, in this model. A network of lymphatic and haematic vessels surrounding B cell follicles is present and includes high endothelial venules (HEV). Future task is to determine whether lymphoid tissue contributes to the persistence of the tumor-associated inflammatory reaction, rather than represent a functional immune compartment, potentially participating to the anti tumor response

  10. Prion pathogenesis and secondary lymphoid organs (SLO)

    Science.gov (United States)

    Mabbott, Neil A.

    2012-01-01

    Prion diseases are subacute neurodegenerative diseases that affect humans and a range of domestic and free-ranging animal species. These diseases are characterized by the accumulation of PrPSc, an abnormally folded isoform of the cellular prion protein (PrPC), in affected tissues. The pathology during prion disease appears to occur almost exclusively within the central nervous system. The extensive neurodegeneration which occurs ultimately leads to the death of the host. An intriguing feature of the prion diseases, when compared with other protein-misfolding diseases, is their transmissibility. Following peripheral exposure, some prion diseases accumulate to high levels within lymphoid tissues. The replication of prions within lymphoid tissue has been shown to be important for the efficient spread of disease to the brain. This article describes recent progress in our understanding of the cellular mechanisms that influence the propagation of prions from peripheral sites of exposure (such as the lumen of the intestine) to the brain. A thorough understanding of these events will lead to the identification of important targets for therapeutic intervention, or alternatively, reveal additional processes that influence disease susceptibility to peripherally-acquired prion diseases. PMID:22895090

  11. Hypothesis analysis methods, hypothesis analysis devices, and articles of manufacture

    Science.gov (United States)

    Sanfilippo, Antonio P [Richland, WA; Cowell, Andrew J [Kennewick, WA; Gregory, Michelle L [Richland, WA; Baddeley, Robert L [Richland, WA; Paulson, Patrick R [Pasco, WA; Tratz, Stephen C [Richland, WA; Hohimer, Ryan E [West Richland, WA

    2012-03-20

    Hypothesis analysis methods, hypothesis analysis devices, and articles of manufacture are described according to some aspects. In one aspect, a hypothesis analysis method includes providing a hypothesis, providing an indicator which at least one of supports and refutes the hypothesis, using the indicator, associating evidence with the hypothesis, weighting the association of the evidence with the hypothesis, and using the weighting, providing information regarding the accuracy of the hypothesis.

  12. On the Keyhole Hypothesis

    DEFF Research Database (Denmark)

    Mikkelsen, Kaare B.; Kidmose, Preben; Hansen, Lars Kai

    2017-01-01

    simultaneously recorded scalp EEG. A cross-validation procedure was employed to ensure unbiased estimates. We present several pieces of evidence in support of the keyhole hypothesis: There is a high mutual information between data acquired at scalp electrodes and through the ear-EEG "keyhole," furthermore we......We propose and test the keyhole hypothesis that measurements from low dimensional EEG, such as ear-EEG reflect a broadly distributed set of neural processes. We formulate the keyhole hypothesis in information theoretical terms. The experimental investigation is based on legacy data consisting of 10...

  13. [Comparative study of lymphoid follicles in mucosa of pharynx and mucosal associated lymphoid tissues in paranasal sinuses].

    Science.gov (United States)

    Zhai, Weigang; Yao, Min; Chen, Jue

    2013-08-01

    To study the relationship between the lymphoid follicles in mucous membrane of pharynx and mucosal associated lymphoid tissues (MALT). Ten folliculi obtained from 10 patients of follicular pharyngitis and mucosa taken form 10 patients of paranasal sinusitis were fixed in neutral formalin and embedded in paraffin. Sections were prepared, stained by H. E and by immunohistochemical method staining with S-100,and observe by light microscopy. We observed the morphology of lymphoid follicles in mucous membrane of pharynx with MALT in mucosa of paranasal sinusitis as the contrast. Lymphoid follicles in mucosa of pharynx compared with MALT in the mucosa of paranasal sinuses, there was no mantle zone, no typical germinal center and no mucosal epithelium, immunological staining with S-100 was week. The lymphoid follicles in mucosa of pharynx does not belong to the MALT.

  14. Effects of HIV infection and ART on phenotype and function of circulating monocytes, natural killer, and innate lymphoid cells.

    Science.gov (United States)

    Nabatanzi, Rose; Cose, Stephen; Joloba, Moses; Jones, Sarah Rowland; Nakanjako, Damalie

    2018-03-15

    HIV infection causes upregulation of markers of inflammation, immune activation and apoptosis of host adaptive, and innate immune cells particularly monocytes, natural killer (NK) and innate lymphoid cells (ILCs). Although antiretroviral therapy (ART) restores CD4 T-cell counts, the persistent aberrant activation of monocytes, NK and ILCs observed likely contributes to the incomplete recovery of T-cell effector functions. A better understanding of the effects of HIV infection and ART on the phenotype and function of circulating monocytes, NK, and ILCs is required to guide development of novel therapeutic interventions to optimize immune recovery.

  15. Radiation effects on cultured human lymphoid cells

    International Nuclear Information System (INIS)

    Johansson, L.; Nilsson, K.; Carlsson, J.; Larsson, B.; Jakobsson, P.

    1981-01-01

    The cloning efficiency of human normal and malignant lymphoid cells is usually low. Radiation effects in vitro on such cells can therefore not be analysed with conventional cloning. However, this problem can be circumscribed by using the growth extrapolation method. A panel of human leukemia-lymphoma cell-lines representing Epstein-Barr virus carrying lymphoblastoid cells of presumed non-neoplastic derivation and neoplastic T- and B-lymphocytes was used to test the efficiency of this method. The sensitivity to radiation could be determined for all these cell types. The growth extrapolation method gave generally the same result as conventional cloning demonstrated by comparison with one exceptional cell-line with capacity for cloning in agar. The sensitivity varied largely between the different cell types. A common feature was that none of the cell lines had a good capacity to accumulate sublethal radiation injury. (Auth.)

  16. Innate lymphoid cells and the MHC.

    Science.gov (United States)

    Robinette, M L; Colonna, M

    2016-01-01

    Innate lymphoid cells (ILCs) are a new class of immune cells that include natural killer (NK) cells and appear to be the innate counterparts to CD4(+) helper T cells and CD8(+) cytotoxic T cells based on developmental and functional similarities. Like T cells, both NK cells and other ILCs also show connections to the major histocompatibility complex (MHC). In human and mouse, NK cells recognize and respond to classical and nonclassical MHC I molecules as well as structural homologues, whereas mouse ILCs have recently been shown to express MHC II. We describe the history of MHC I recognition by NK cells and discuss emerging roles for MHC II expression by ILC subsets, making comparisons between both mouse and human when possible. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Deciphering the Innate Lymphoid Cell Transcriptional Program

    Directory of Open Access Journals (Sweden)

    Cyril Seillet

    2016-10-01

    Full Text Available Innate lymphoid cells (ILCs are enriched at mucosal surfaces, where they provide immune surveillance. All ILC subsets develop from a common progenitor that gives rise to pre-committed progenitors for each of the ILC lineages. Currently, the temporal control of gene expression that guides the emergence of these progenitors is poorly understood. We used global transcriptional mapping to analyze gene expression in different ILC progenitors. We identified PD-1 to be specifically expressed in PLZF+ ILCp and revealed that the timing and order of expression of the transcription factors NFIL3, ID2, and TCF-1 was critical. Importantly, induction of ILC lineage commitment required only transient expression of NFIL3 prior to ID2 and TCF-1 expression. These findings highlight the importance of the temporal program that permits commitment of progenitors to the ILC lineage, and they expand our understanding of the core transcriptional program by identifying potential regulators of ILC development.

  18. Clinical epidemiological aspects of chronic lymphoid leukaemia

    International Nuclear Information System (INIS)

    Rodriguez Brunet, Marisol; Hernandez Galano, Geldris P; Suarez Beyries, Lidia C; Duverger Magdaleon, Ernesto

    2011-01-01

    A descriptive and retrospective study of 71 patients with chronic lymphoid leukemia, attended at the Hematology Service from 'Dr Juan Bruno Zayas Alfonso' Teaching General Hospital in Santiago de Cuba was carried out from January, 2001 to November, 2006, in order to identify some clinical epidemiological variables on them, to show the therapeutical variables more used, as well as to assess survival, mortality, and the main causes of the clinical entity. Elderly, male sex, and high risk category related to advanced stage were predominant in the series. The therapeutical schedule of chlorambucil and prednisone was the most used, achieving good results in the majority of the case material. The survival of patients, in general, ranged among 1-5 years, whereas deaths occurred due to disease progression, infectious respiratory processes, pro-lymphocytic transformation, second neoplasias, and strokes. (author)

  19. Tertiary lymphoid organs in Takayasu Arteritis

    Directory of Open Access Journals (Sweden)

    Marc eClement

    2016-04-01

    Full Text Available Objective: The role of B cells in the pathogenesis of Takayasu arteritis (TA is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs in the aortic wall of TA patients.Methods: Hematoxylin and eosin–stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20, follicular dendritic cells (FDCs, CD21, and high endothelial venules (HEVs, PNAd was investigated by immunohistochemistry. Immune cells from the adventitial layer of one patient were characterized by flow cytometry. Demographic, medical history, laboratory, imaging, treatment and follow up data were extracted from medical records.Results: Aorta specimens from Bentall procedures were available from 7 patients (five female, aged 22 to 57 years with TA. Surgical treatment was performed at TA diagnosis (n=4 or at a median of 108 months [84-156] after TA diagnosis. Disease was active at surgery in four patients according to NIH score. B cell aggregates-TLOs containing HEVs were observed in the adventitia of all but one patient.. Of note, ectopic follicles containing CD21+ FDCs were found in all patients (4/4 with increased aortic FDG uptake before surgery but were absent in all but one patients (2/3 with no FDG uptake. In addition, flow cytometry analysis confirmed the accumulation of memory/germinal center–like B cells in the adventitial layer and showed the presence of antigen-experienced T follicular helper cells.Conclusion: Ectopic lymphoid neogenesis displaying functional features can be found in the aortic wall of a subset of patients with active TA. The function of these local B cell clusters on the pathogenesis of TA remains to be elucidated.

  20. Tertiary Lymphoid Organs in Takayasu Arteritis.

    Science.gov (United States)

    Clement, Marc; Galy, Adrien; Bruneval, Patrick; Morvan, Marion; Hyafil, Fabien; Benali, Khadija; Pasi, Nicoletta; Deschamps, Lydia; Pellenc, Quentin; Papo, Thomas; Nicoletti, Antonino; Sacre, Karim

    2016-01-01

    The role of B cells in the pathogenesis of Takayasu arteritis (TA) is controversial. We aimed to study the presence of tertiary lymphoid organs (TLOs) in the aortic wall of TA patients. Hematoxylin and eosin-stained sections from aorta specimens from patients with TA were screened for TLOs. The presence of B cell aggregates (CD20), follicular dendritic cells (FDCs, CD21), and high endothelial venules (HEVs, PNAd) was investigated by immunohistochemistry. Immune cells from the adventitial layer of one patient were characterized by flow cytometry. Demographic, medical history, laboratory, imaging, treatment, and follow-up data were extracted from medical records. Aorta specimens from Bentall procedures were available from seven patients (5 females, aged 22-57 years) with TA. Surgical treatment was performed at TA diagnosis (n = 4) or at a median of 108 months (84-156) after TA diagnosis. Disease was active at surgery in four patients according to NIH score. B cell aggregates-TLOs containing HEVs were observed in the adventitia of all but one patient. Of note, ectopic follicles containing CD21(+) FDCs were found in all patients (4/4) with increased aortic (18)F-fluoro-deoxyglucose (FDG) uptake before surgery but were absent in all but one patients (2/3) with no FDG uptake. In addition, flow cytometry analysis confirmed the accumulation of memory/germinal center-like B cells in the adventitial layer and showed the presence of antigen-experienced T follicular helper cells. Ectopic lymphoid neogenesis displaying functional features can be found in the aortic wall of a subset of patients with active TA. The function of these local B cell clusters on the pathogenesis of TA remains to be elucidated.

  1. High-resolution CT of lymphoid interstitial pneumonia

    International Nuclear Information System (INIS)

    Vilgrain, V.; Frija, J.; Yana, C.; Couderc, L.J.; David, M.; Clauvel, J.P.; Laval-Jeantet, M.

    1989-01-01

    Three patients with lymphoid interstitial pneumonia (two HIV 1+ patients with chronic lymphadenopathic syndromes and one with a not-characterized autoimmune disease) have been studied with high-resolution computed tomography (HR-CT). This technique reveals septal lines, small reticulonodular opacities, polyhedral micronodular opacities, 'ground-glass' opacities and a dense, subpleural, curved broken line in one patient. The lesions dominate in the bases of the lungs. They are not characteristic for lymphoid interstitial pneumonia. If a patient presents with a chronic lymphadenopathic syndrome, the diagnosis of an opportunistic infection should not be automatically made, since the syndrome can be caused by lymphoid interstitial pneumonia [fr

  2. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus-infected macaques.

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A; Veazey, Ronald S

    2015-12-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit(+)IL-7Rα(+) (CD117(+)CD127(+)) cells. These ILC3 cells highly expressed CD90 (∼ 63%) and aryl hydrocarbon receptor and produced IL-17 (∼ 63%), IL-22 (∼ 36%), and TNF-α (∼ 72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4(+) T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues. © FASEB.

  3. The Qualitative Expectations Hypothesis

    DEFF Research Database (Denmark)

    Frydman, Roman; Johansen, Søren; Rahbek, Anders

    2017-01-01

    We introduce the Qualitative Expectations Hypothesis (QEH) as a new approach to modeling macroeconomic and financial outcomes. Building on John Muth's seminal insight underpinning the Rational Expectations Hypothesis (REH), QEH represents the market's forecasts to be consistent with the predictions...... of an economistís model. However, by assuming that outcomes lie within stochastic intervals, QEH, unlike REH, recognizes the ambiguity faced by an economist and market participants alike. Moreover, QEH leaves the model open to ambiguity by not specifying a mechanism determining specific values that outcomes take...

  4. The Qualitative Expectations Hypothesis

    DEFF Research Database (Denmark)

    Frydman, Roman; Johansen, Søren; Rahbek, Anders

    We introduce the Qualitative Expectations Hypothesis (QEH) as a new approach to modeling macroeconomic and financial outcomes. Building on John Muth's seminal insight underpinning the Rational Expectations Hypothesis (REH), QEH represents the market's forecasts to be consistent with the predictions...... of an economist's model. However, by assuming that outcomes lie within stochastic intervals, QEH, unlike REH, recognizes the ambiguity faced by an economist and market participants alike. Moreover, QEH leaves the model open to ambiguity by not specifying a mechanism determining specific values that outcomes take...

  5. Vitamin A Controls the Presence of RORγ+ Innate Lymphoid Cells and Lymphoid Tissue in the Small Intestine.

    Science.gov (United States)

    Goverse, Gera; Labao-Almeida, Carlos; Ferreira, Manuela; Molenaar, Rosalie; Wahlen, Sigrid; Konijn, Tanja; Koning, Jasper; Veiga-Fernandes, Henrique; Mebius, Reina E

    2016-06-15

    Changes in diet and microbiota have determining effects on the function of the mucosal immune system. For example, the active metabolite of vitamin A, retinoic acid (RA), has been described to maintain homeostasis in the intestine by its influence on both lymphocytes and myeloid cells. Additionally, innate lymphoid cells (ILCs), important producers of cytokines necessary for intestinal homeostasis, are also influenced by vitamin A in the small intestines. In this study, we show a reduction of both NCR(-) and NCR(+) ILC3 subsets in the small intestine of mice raised on a vitamin A-deficient diet. Additionally, the percentages of IL-22-producing ILCs were reduced in the absence of dietary vitamin A. Conversely, mice receiving additional RA had a specific increase in the NCR(-) ILC3 subset, which contains the lymphoid tissue inducer cells. The dependence of lymphoid tissue inducer cells on vitamin A was furthermore illustrated by impaired development of enteric lymphoid tissues in vitamin A-deficient mice. These effects were a direct consequence of ILC-intrinsic RA signaling, because retinoic acid-related orphan receptor γt-Cre × RARα-DN mice had reduced numbers of NCR(-) and NCR(+) ILC3 subsets within the small intestine. However, lymphoid tissue inducer cells were not affected in these mice nor was the formation of enteric lymphoid tissue, demonstrating that the onset of RA signaling might take place before retinoic acid-related orphan receptor γt is expressed on lymphoid tissue inducer cells. Taken together, our data show an important role for vitamin A in controlling innate lymphoid cells and, consequently, postnatal formed lymphoid tissues within the small intestines. Copyright © 2016 by The American Association of Immunologists, Inc.

  6. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Lackner, Andrew A.; Veazey, Ronald S.

    2015-01-01

    Innate lymphoid cells (ILCs) type 3, also known as lymphoid tissue inducer cells, plays a major role in both the development and remodeling of organized lymphoid tissues and the maintenance of adaptive immune responses. HIV/simian immunodeficiency virus (SIV) infection causes breakdown of intestinal barriers resulting in microbial translocation, leading to systemic immune activation and disease progression. However, the effects of HIV/SIV infection on ILC3 are unknown. Here, we analyzed ILC3 from mucosal and systemic lymphoid tissues in chronically SIV-infected macaques and uninfected controls. ILC3 cells were defined and identified in macaque lymphoid tissues as non-T, non-B (lineage-negative), c-Kit+IL-7Rα+ (CD117+CD127+) cells. These ILC3 cells highly expressed CD90 (∼63%) and aryl hydrocarbon receptor and produced IL-17 (∼63%), IL-22 (∼36%), and TNF-α (∼72%) but did not coexpress CD4 or NK cell markers. The intestinal ILC3 cell loss correlated with the reduction of total CD4+ T cells and T helper (Th)17 and Th22 cells in the gut during SIV infection (P lymphoid tissues in SIV-infected macaques, further contributing to the HIV-induced impairment of gut-associated lymphoid tissue structure and function, especially in mucosal tissues.—Xu, H., Wang, X., Lackner, A. A., Veazey, R. S. Type 3 innate lymphoid cell depletion is mediated by TLRs in lymphoid tissues of simian immunodeficiency virus–infected macaques. PMID:26283536

  7. Revisiting the Dutch hypothesis

    NARCIS (Netherlands)

    Postma, Dirkje S.; Weiss, Scott T.; van den Berge, Maarten; Kerstjens, Huib A. M.; Koppelman, Gerard H.

    The Dutch hypothesis was first articulated in 1961, when many novel and advanced scientific techniques were not available, such as genomics techniques for pinpointing genes, gene expression, lipid and protein profiles, and the microbiome. In addition, computed tomographic scans and advanced analysis

  8. The Lehman Sisters Hypothesis

    NARCIS (Netherlands)

    I.P. van Staveren (Irene)

    2014-01-01

    markdownabstract__Abstract__ This article explores the Lehman Sisters Hypothesis. It reviews empirical literature about gender differences in behavioral, experimental, and neuro-economics as well as in other fields of behavioral research. It discusses gender differences along three dimensions of

  9. 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.

  10. Bioengineering of Artificial Antigen Presenting Cells and Lymphoid Organs.

    Science.gov (United States)

    Wang, Chao; Sun, Wujin; Ye, Yanqi; Bomba, Hunter N; Gu, Zhen

    2017-01-01

    The immune system protects the body against a wide range of infectious diseases and cancer by leveraging the efficiency of immune cells and lymphoid organs. Over the past decade, immune cell/organ therapies based on the manipulation, infusion, and implantation of autologous or allogeneic immune cells/organs into patients have been widely tested and have made great progress in clinical applications. Despite these advances, therapy with natural immune cells or lymphoid organs is relatively expensive and time-consuming. Alternatively, biomimetic materials and strategies have been applied to develop artificial immune cells and lymphoid organs, which have attracted considerable attentions. In this review, we survey the latest studies on engineering biomimetic materials for immunotherapy, focusing on the perspectives of bioengineering artificial antigen presenting cells and lymphoid organs. The opportunities and challenges of this field are also discussed.

  11. Morphology of mucosa-associated lymphoid tissue in odontocetes.

    Science.gov (United States)

    Silva, Fernanda M O; Guimarães, Juliana P; Vergara-Parente, Jociery E; Carvalho, Vitor L; Carolina, Ana; Meirelles, O; Marmontel, Miriam; Oliveira, Bruno S S P; Santos, Silvanise M; Becegato, Estella Z; Evangelista, Janaina S A M; Miglino, Maria Angelica

    2016-09-01

    This study describes the mucosa-associated lymphoid tissue (MALT) in odontocetes from the Brazilian coast and freshwater systems. Seven species were evaluated and tissue samples were analyzed by light, scanning and transmission electron microscopy, and immunohistochemistry. Laryngeal tonsil was a palpable oval mass located in the larynx, composed of a lymphoepithelial complex. Dense collections of lymphocytes were found in the skin of male fetus and calf. Clusters of lymphoid tissue were found in the uterine cervix of a reproductively active juvenile female and along the pulmonary artery of an adult female. Lymphoid tissues associated with the gastrointestinal tract were characterized by diffusely arranged or organized lymphocytes. The anal tonsil was composed of an aggregate of lymphoid tissue occurring exclusively in the anal canal, being composed of squamous epithelium branches. MALT was present in different tissues and organic systems of cetaceans, providing constant protection against mucosal pathogens present in their environment. © 2016 Wiley Periodicals, Inc.

  12. Total lymphoid irradiation for treatment of intractable cardiac allograft rejection

    International Nuclear Information System (INIS)

    Hunt, S.A.; Strober, S.; Hoppe, R.T.; Stinson, E.B.

    1991-01-01

    The ability of postoperative total lymphoid irradiation to reverse otherwise intractable cardiac allograft rejection was examined in a group of 10 patients in whom conventional rejection therapy (including pulsed steroids and monoclonal or polyclonal anti-T-cell antibody therapy) had failed to provide sustained freedom from rejection. Follow-up periods range from 73 to 1119 days since the start of total lymphoid irradiation. No patient died or sustained serious morbidity because of the irradiation. Three patients have had no further rejection (follow-up periods, 105 to 365 days). Two patients died--one in cardiogenic shock during the course of total lymphoid irradiation, the other with recurrent rejection caused by noncompliance with his medical regimen. Total lymphoid irradiation appears to be a safe and a moderately effective immunosuppressive modality for 'salvage' therapy of cardiac allograft rejection unresponsive to conventional therapy

  13. Early lymphoid lesions: conceptual, diagnostic and clinical challenges

    OpenAIRE

    Ganapathi, Karthik A.; Pittaluga, Stefania; Odejide, Oreofe O.; Freedman, Arnold S.; Jaffe, Elaine S.

    2014-01-01

    There are no “benign lymphomas”, a fact due to the nature of lymphoid cells to circulate and home as part of their normal function. Thus, benign clonal expansions of lymphocytes are only rarely recognized when localized. Recent studies have identified a number of lymphoid proliferations that lie at the interface between benign and malignant. Some of these are clonal proliferations that carry many of the molecular hallmarks of their malignant counterparts, such as BCL2/IGH and CCND1/IGH transl...

  14. Bayesian Hypothesis Testing

    Energy Technology Data Exchange (ETDEWEB)

    Andrews, Stephen A. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Sigeti, David E. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-11-15

    These are a set of slides about Bayesian hypothesis testing, where many hypotheses are tested. The conclusions are the following: The value of the Bayes factor obtained when using the median of the posterior marginal is almost the minimum value of the Bayes factor. The value of τ2 which minimizes the Bayes factor is a reasonable choice for this parameter. This allows a likelihood ratio to be computed with is the least favorable to H0.

  15. The Drift Burst Hypothesis

    OpenAIRE

    Christensen, Kim; Oomen, Roel; Renò, Roberto

    2016-01-01

    The Drift Burst Hypothesis postulates the existence of short-lived locally explosive trends in the price paths of financial assets. The recent US equity and Treasury flash crashes can be viewed as two high profile manifestations of such dynamics, but we argue that drift bursts of varying magnitude are an expected and regular occurrence in financial markets that can arise through established mechanisms such as feedback trading. At a theoretical level, we show how to build drift bursts into the...

  16. Hypothesis in research

    Directory of Open Access Journals (Sweden)

    Eudaldo Enrique Espinoza Freire

    2018-01-01

    Full Text Available It is intended with this work to have a material with the fundamental contents, which enable the university professor to formulate the hypothesis, for the development of an investigation, taking into account the problem to be solved. For its elaboration, the search of information in primary documents was carried out, such as thesis of degree and reports of research results, selected on the basis of its relevance with the analyzed subject, current and reliability, secondary documents, as scientific articles published in journals of recognized prestige, the selection was made with the same terms as in the previous documents. It presents a conceptualization of the updated hypothesis, its characterization and an analysis of the structure of the hypothesis in which the determination of the variables is deepened. The involvement of the university professor in the teaching-research process currently faces some difficulties, which are manifested, among other aspects, in an unstable balance between teaching and research, which leads to a separation between them.

  17. Immunosuppressive effect of total lymphoid irradiation

    International Nuclear Information System (INIS)

    Bendel, V.; Medizinische Hochschule Hannover

    1981-01-01

    Contrary to the immunosuppression by means of wholebody irradiation which is known for a long while but connected with considerable side effects and risks, the total lymphoid irradiation (TLI) is a new possibility of immunosuppression the tolerance of which by man is known by virtue of long-standing experiences with the treatment of malignant lymphatic system diseases. In connexion with organ transplantations, TLI might possibly soon be important for the radiotherapeutist. In the experimentation on animals, the unspecific immunosuppression induced by TLI causes a prolonged survival time of allogeneic skin and organ grafts in certain mammals. Furthermore, a formation of blood chimeras combined with specific, permanent tolerance of organ grafts from the bone marrow donor can be caused by bone marrow transplantation after TLI. First experiences with man have been made. In the German literature, TLI has not been mentioned yet. In the present study, a summary is given on the Anglo-Saxon literature, and the first own experiments with regard to the problem of irradiation dose and transplantation interval are presented. (orig.) [de

  18. Epigenomic Views of Innate Lymphoid Cells.

    Science.gov (United States)

    Sciumè, Giuseppe; Shih, Han-Yu; Mikami, Yohei; O'Shea, John J

    2017-01-01

    The discovery of innate lymphoid cells (ILCs) with selective production of cytokines typically attributed to subsets of T helper cells forces immunologists to reassess the mechanisms by which selective effector functions arise. The parallelism between ILCs and T cells extends beyond these two cell types and comprises other innate-like T lymphocytes. Beyond the recognition of specialized effector functionalities in diverse lymphocytes, features typical of T cells, such as plasticity and memory, are also relevant for innate lymphocytes. Herein, we review what we have learned in terms of the molecular mechanisms underlying these shared functions, focusing on insights provided by next generation sequencing technologies. We review data on the role of lineage-defining- and signal-dependent transcription factors (TFs). ILC regulomes emerge developmentally whereas the much of the open chromatin regions of T cells are generated acutely, in an activation-dependent manner. And yet, these regions of open chromatin in T cells and ILCs have remarkable overlaps, suggesting that though accessibility is acquired by distinct modes, the end result is that convergent signaling pathways may be involved. Although much is left to be learned, substantial progress has been made in understanding how TFs and epigenomic status contribute to ILC biology in terms of differentiation, specification, and plasticity.

  19. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue.

    Science.gov (United States)

    Martinet, Kim Zita; Bloquet, Stéphane; Bourgeois, Christine

    2014-01-01

    CD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue (GALT), a crucial site of CD4 T cell accumulation. Primary, secondary and tertiary lymphoid organs of C57BL/6 animals were analysed at three intervals of ages: 2 to 6 months (young), 10 to 14 months (middle-aged) and 22 to 26 months (old). We confirmed that ageing preferentially impacted CD4 T cell compartment in secondary lymphoid organs. Importantly, a different picture emerged from gut associated mucosal sites: during ageing, CD4 T cell accumulation was progressively developing in colon and small intestine lamina propria and Peyer's patches. Similar trend was also observed in middle-aged SJL/B6 F1 mice. Interestingly, an inverse correlation was detected between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria of C57BL/6 mice whereas no increase in proliferation rate of GALT CD4 T cells was detected. In contrast to GALT, no CD4 T cell accumulation was detected in lungs and liver in middle-aged animals. Finally, the concomitant accumulation of CD4 T cell in GALT and depletion in secondary lymphoid organs during ageing was detected both in male and female animals. Our data thus demonstrate that T cell lymphopenia in secondary lymphoid organs currently associated to ageing is not sustained in gut or lung mucosa associated lymphoid tissues or non-lymphoid sites such as the liver. The inverse correlation between CD4 T cell numbers in secondary lymphoid organs and colonic lamina propria and the absence of overt proliferation in GALT suggest that marked CD4 T cell decay in secondary

  20. Total lymphoid irradiation for multiple sclerosis

    International Nuclear Information System (INIS)

    Devereux, C.K.; Vidaver, R.; Hafstein, M.P.; Zito, G.; Troiano, R.; Dowling, P.C.; Cook, S.D.

    1988-01-01

    Although chemical immunosuppression has been shown to benefit patients with chronic progressive multiple sclerosis (MS), it appears that chemotherapy has an appreciable oncogenic potential in patients with multiple sclerosis. Accordingly, we developed a modified total lymphoid irradiation (TLI) regimen designed to reduce toxicity and applied it to a randomized double blind trial of TLI or sham irradiation in MS. Standard TLI regimens were modified to reduce dose to 1,980 rad, lowering the superior mantle margin to midway between the thyroid cartilage and angle of the mandible (to avert xerostomia) and the lower margin of the mantle field to the inferior margin of L1 (to reduce gastrointestinal toxicity by dividing abdominal radiation between mantle and inverted Y), limiting spinal cord dose to 1,000 rad by custom-made spine blocks in the mantle and upper 2 cm of inverted Y fields, and also protecting the left kidney even if part of the spleen were shielded. Clinical efficacy was documented by the less frequent functional scale deterioration of 20 TLI treated patients with chronic progressive MS compared to to 20 sham-irradiated progressive MS patients after 12 months (16% versus 55%, p less than 0.03), 18 months (28% versus 63%, p less than 0.03), and 24 months (44% versus 74%, N.S.). Therapeutic benefit during 3 years follow-up was related to the reduction in lymphocyte count 3 months post-irradiation (p less than 0.02). Toxicity was generally mild and transient, with no instance of xerostomia, pericarditis, herpes zoster, or need to terminate treatment in TLI patients. However, menopause was induced in 2 patients and staphylococcal pneumonia in one

  1. Close Encounters of Lymphoid Cells and Bacteria

    Science.gov (United States)

    Cruz-Adalia, Aranzazu; Veiga, Esteban

    2016-01-01

    During infections, the first reaction of the host against microbial pathogens is carried out by innate immune cells, which recognize conserved structures on pathogens, called pathogen-associated molecular patterns. Afterward, some of these innate cells can phagocytose and destroy the pathogens, secreting cytokines that would modulate the immune response to the challenge. This rapid response is normally followed by the adaptive immunity, more specific and essential for a complete pathogen clearance in many cases. Some innate immune cells, usually named antigen-presenting cells, such as macrophages or dendritic cells, are able to process internalized invaders and present their antigens to lymphocytes, triggering the adaptive immune response. Nevertheless, the traditional boundary of separated roles between innate and adaptive immunity has been blurred by several studies, showing that very specialized populations of lymphocytes (cells of the adaptive immunity) behave similarly to cells of the innate immunity. These “innate-like” lymphocytes include γδ T cells, invariant NKT cells, B-1 cells, mucosal-associated invariant T cells, marginal zone B cells, and innate response activator cells, and together with the newly described innate lymphoid cells are able to rapidly respond to bacterial infections. Strikingly, our recent data suggest that conventional CD4+ T cells, the paradigm of cells of the adaptive immunity, also present innate-like behavior, capturing bacteria in a process called transinfection. Transinfected CD4+ T cells digest internalized bacteria like professional phagocytes and secrete large amounts of proinflammatory cytokines, protecting for further bacterial challenges. In the present review, we will focus on the data showing such innate-like behavior of lymphocytes following bacteria encounter. PMID:27774092

  2. Characterization of nasal cavity-associated lymphoid tissue in ducks.

    Science.gov (United States)

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2014-05-01

    The nasal mucosa is involved in immune defense, as it is the first barrier for pathogens entering the body through the respiratory tract. The nasal cavity-associated lymphoid tissue (NALT), which is found in the mucosa of the nasal cavity, is considered to be the main mucosal immune inductive site in the upper respiratory tract. NALT has been found in humans and many mammals, which contributes to local and systemic immune responses after intranasal vaccination. However, there are very few data on NALT in avian species, especially waterfowl. For this study, histological sections of the nasal cavities of Cherry Valley ducks were used to examine the anatomical location and histological characteristics of NALT. The results showed that several lymphoid aggregates are present in the ventral wall of the nasal cavity near the choanal cleft, whereas several more lymphoid aggregates were located on both sides of the nasal septum. In addition, randomly distributed intraepithelial lymphocytes and isolated lymphoid follicles were observed in the regio respiratoria of the nasal cavity. There were also a few lymphoid aggregates located in the lamina propria of the regio vestibularis, which was covered with a stratified squamous epithelium. This study focused on the anatomic and histological characteristics of the nasal cavity of the duck and performed a systemic overview of NALT. This will be beneficial for further understanding of immune mechanisms after nasal vaccination and the development of effective nasal vaccines for waterfowls. Copyright © 2014 Wiley Periodicals, Inc.

  3. [Dilemma of null hypothesis in ecological hypothesis's experiment test.

    Science.gov (United States)

    Li, Ji

    2016-06-01

    Experimental test is one of the major test methods of ecological hypothesis, though there are many arguments due to null hypothesis. Quinn and Dunham (1983) analyzed the hypothesis deduction model from Platt (1964) and thus stated that there is no null hypothesis in ecology that can be strictly tested by experiments. Fisher's falsificationism and Neyman-Pearson (N-P)'s non-decisivity inhibit statistical null hypothesis from being strictly tested. Moreover, since the null hypothesis H 0 (α=1, β=0) and alternative hypothesis H 1 '(α'=1, β'=0) in ecological progresses are diffe-rent from classic physics, the ecological null hypothesis can neither be strictly tested experimentally. These dilemmas of null hypothesis could be relieved via the reduction of P value, careful selection of null hypothesis, non-centralization of non-null hypothesis, and two-tailed test. However, the statistical null hypothesis significance testing (NHST) should not to be equivalent to the causality logistical test in ecological hypothesis. Hence, the findings and conclusions about methodological studies and experimental tests based on NHST are not always logically reliable.

  4. PrPC expression and prion seeding activity in the alimentary tract and lymphoid tissue of deer.

    Science.gov (United States)

    Davenport, Kristen A; Hoover, Clare E; Bian, Jifeng; Telling, Glenn C; Mathiason, Candace K; Hoover, Edward A

    2017-01-01

    The agent responsible for prion diseases is a misfolded form of a normal protein (PrPC). The prion hypothesis stipulates that PrPC must be present for the disease to manifest. Cervid populations across the world are infected with chronic wasting disease, a horizontally-transmissible prion disease that is likely spread via oral exposure to infectious prions (PrPCWD). Though PrPCWD has been identified in many tissues, there has been little effort to characterize the overall PrPC expression in cervids and its relationship to PrPCWD accumulation. We used immunohistochemistry (IHC), western blot and enzyme-linked immunosorbent assay to describe PrPC expression in naïve white-tailed deer. We used real-time, quaking-induced conversion (RT-QuIC) to detect prion seeding activity in CWD-infected deer. We assessed tissues comprising the alimentary tract, alimentary-associated lymphoid tissue and systemic lymphoid tissue from 5 naïve deer. PrPC was expressed in all tissues, though expression was often very low compared to the level in the CNS. IHC identified specific cell types wherein PrPC expression is very high. To compare the distribution of PrPC to PrPCWD, we examined 5 deer with advanced CWD infection. Using RT-QuIC, we detected prion seeding activity in all 21 tissues. In 3 subclinical deer sacrificed 4 months post-inoculation, we detected PrPCWD consistently in alimentary-associated lymphoid tissue, irregularly in alimentary tract tissues, and not at all in the brain. Contrary to our hypothesis that PrPC levels dictate prion accumulation, PrPC expression was higher in the lower gastrointestinal tissues than in the alimentary-associated lymphoid system and was higher in salivary glands than in the oropharyngeal lymphoid tissue. These data suggest that PrPC expression is not the sole driver of prion accumulation and that alimentary tract tissues accumulate prions before centrifugal spread from the brain occurs.

  5. [Rectal tonsil or lymphoid follicular hyperplasia of the rectum].

    Science.gov (United States)

    Trillo Fandiño, L; Arias González, M; Iglesias Castañón, A; Fernández Eire, M P

    2014-01-01

    The rectal tonsil is a reactive proliferation of lymphoid tissue located in the rectum. The morphology of the lymphoid proliferation of the colon is usually polypoid or, less commonly, nodular. Only in exceptional cases does lymphoid proliferation of the colon present as a mass in the rectum (rectal tonsil), although this is the most common presentation in middle-aged patients. It is important to be familiar with the rectal tonsil because in cases of exuberant growth it can be difficult to distinguish it from other types of masses. We present the case of rectal tonsil in a four-year-old girl. We describe the magnetic resonance imaging findings and review the literature. Copyright © 2011 SERAM. Published by Elsevier Espana. All rights reserved.

  6. Induction and Analysis of Bronchus-Associated Lymphoid Tissue.

    Science.gov (United States)

    Fleige, Henrike; Förster, Reinhold

    2017-01-01

    Bronchus-associated lymphoid tissue (BALT) forms spontaneously in the lung after pulmonary infection and has been identified as a highly organized lymphoid structure supporting the efficient priming of T cells in the lung. To explore the mechanisms and instructive signals controlling BALT neogenesis we used both, a single dose of vaccinia virus MVA and repeated inhalations of heat-inactivated Pseudomonas aeruginosa (P. aeruginosa). Intranasal administration of both pathogens induces highly organized BALT but distinct pathways and molecules are used to promote the development of BALT. Here, we describe the induction and phenotype of the distinct types of BALT as well as the immunofluorescence microscopy-based analysis of the induced lymphoid tissue in the lung.

  7. B lymphocyte autoimmunity in rheumatoid synovitis is independent of ectopic lymphoid neogenesis

    NARCIS (Netherlands)

    Cantaert, Tineke; Kolln, Johanna; Timmer, Trieneke; van der Pouw Kraan, Tineke C.; Vandooren, Bernard; Thurlings, Rogier M.; Cañete, Juan D.; Catrina, Anca I.; Out, Theo; Verweij, Cor L.; Zhang, Yiping; Tak, Paul P.; Baeten, Dominique

    2008-01-01

    B lymphocyte autoimmunity plays a crucial role in the pathogenesis of rheumatoid arthritis. The local production of autoantibodies and the presence of ectopic lymphoid neogenesis in the rheumatoid synovium suggest that these dedicated microenvironments resembling canonical lymphoid follicles may

  8. HIV Persistence in Gut-Associated Lymphoid Tissues: Pharmacological Challenges and Opportunities.

    Science.gov (United States)

    Thompson, Corbin G; Gay, Cynthia L; Kashuba, Angela D M

    2017-06-01

    An increasing amount of evidence suggests that HIV replication persists in gut-associated lymphoid tissues (GALT), despite treatment with combination antiretroviral therapy (cART). Residual replication in this compartment may propagate infection at other sites in the body and contribute to sustained immune dysregulation and delayed immune recovery. Therefore, it is important to focus efforts on eliminating residual replication at this site. There are several challenges to accomplishing this goal, including low antiretroviral (ARV) exposure at specific tissue locations within GALT, which might be overcome by using the tools of clinical pharmacology. Here, we summarize the evidence for GALT as a site of residual HIV replication, highlight the consequences of persistent infection in tissues, identify current pharmacologic knowledge of drug exposure in GALT, define the challenges that hinder eradication from this site, and propose several avenues for pharmacologic intervention.

  9. Pathologic characteristics of gut-associated lymphoid tissues and lymphocyte apoptosis in mouse intestine after neutron-and γ-irradiation

    International Nuclear Information System (INIS)

    Fu Kaifei; Peng Ruiyun; Gao Yabing; Wang Dewen; Chen Haoyu; Wu Xiaohong; Yang Yi; Hu Wenhua; Ma Junjie

    2004-01-01

    Objective: To compare the pathologic characteristics of gut-associated lymphoid tissues and lymphocyte apoptosis in neutron-irradiated mouse small intestines with those in γ-irradiated ones. Methods: Altogether 350 BALB/c mice were irradiated with different doses of neutrons or γ-rays, and were sacrificed on 6 h,12 h,125 d, 7 d, 14 d, 21 d and 28 d after irradiation and their total intestines were removed. Then the pathologic changes and death mode of lymphocytes in gut-associated lymphoid tissues were studied comparatively with light microscopy, electron microscopy and in situ terminal labeling method. Results: The basic pathologic changes of gut-associated lymphoid tissues after neutron irradiation included degeneration, apoptosis and necrosis of lymphocytes. The number of lymphocytes also decreased. There was no obvious regeneration after 4.0 and 5.5 Gy neutron irradiation, while after 2.5 Gy regeneration and recovery appeared, which were, there fore, dose-dependent. In the 2.5 Gy neutron group, the numbers of lymphocytes of intramucosal and submucous lymphoid tissues decreased, and karyopyknosis and a great quantity of nuclear fragments could also be observed at 6 h-3 d after irradiation. However, on the 3rd day regeneration of crypt epithelial cells appeared. On the 5th day hyperplasia of submucous lymphocytic tissues appeared, but recovery to normal level was not achieved till 14 d after irradiation. The basic pathologic changes after γ-irradiation were similar to that of neutron irradiation. Regeneration and recovery appeared in the 5.5 Gy group while no obvious regeneration in the 12.0 Gy group. The results of in situ terminal labeling indicated that at 6 h after irradiation the number of apoptotic cells in gut-associated lymphoid tissues of each group increased obviously, while in 4.0 Gy neutron group and 12.0 Gy γ-ray group it was more abundant. Conclusion: Both 2.5-5.5 Gy neutron and 5.5-12.0 Gy γ-ray irradiation can induce obvious injuries in gut

  10. Innate Lymphoid Cells in Intestinal Inflammation

    Science.gov (United States)

    Geremia, Alessandra; Arancibia-Cárcamo, Carolina V.

    2017-01-01

    Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD) and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC) in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an increased risk of

  11. Innate Lymphoid Cells in Intestinal Inflammation

    Directory of Open Access Journals (Sweden)

    Alessandra Geremia

    2017-10-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory disorder of the intestine that encompasses Crohn’s disease (CD and ulcerative colitis. The cause of IBD is unknown, but the evidence suggests that an aberrant immune response toward the commensal bacterial flora is responsible for disease in genetically susceptible individuals. Results from animal models of colitis and human studies indicate a role for innate lymphoid cells (ILC in the pathogenesis of chronic intestinal inflammation in IBD. ILC are a population of lymphocytes that are enriched at mucosal sites, where they play a protective role against pathogens including extracellular bacteria, helminthes, and viruses. ILC lack an antigen-specific receptor, but can respond to environmental stress signals contributing to the rapid orchestration of an early immune response. Several subsets of ILC reflecting functional characteristics of T helper subsets have been described. ILC1 express the transcription factor T-bet and are characterized by secretion of IFNγ, ILC2 are GATA3+ and secrete IL5 and IL13 and ILC3 depend on expression of RORγt and secrete IL17 and IL22. However, ILC retain a degree of plasticity depending on exposure to cytokines and environmental factors. IL23 responsive ILC have been implicated in the pathogenesis of colitis in several innate murine models through the production of IL17, IFNγ, and GM-CSF. We have previously identified IL23 responsive ILC in the human intestine and found that they accumulate in the inflamed colon and small bowel of patients with CD. Other studies have confirmed accumulation of ILC in CD with increased frequencies of IFNγ-secreting ILC1 in both the intestinal lamina propria and the epithelium. Moreover, IL23 driven IL22 producing ILC have been shown to drive bacteria-induced colitis-associated cancer in mice. Interestingly, our data show increased ILC accumulation in patients with IBD and primary sclerosing cholangitis, who carry an

  12. Apparent clusters of childhood lymphoid malignancy in Northern England

    International Nuclear Information System (INIS)

    Craft, A.W.; Openshaw, S.; Birch, J.

    1984-01-01

    The authors have reanalysed their previous data on the incidence of childhood malignancy in the North of England by very small geographical areas. Seascale, which ranks first by Poisson probability for all lymphoid malignancies is the village closest to the Sellafield plant. However, it is not unique in the region; nor are wards of apparent excess confined to coastal areas of Cumbria. The highest rate of lymphoid malignancies is in Whittingham, a village in north Northumberland. For other varieties of childhood cancer, there is a similar spread of 'Highly ranked', but different, wards throughout the region. (U.K.)

  13. Interactions between the intestinal microbiota and innate lymphoid cells

    Science.gov (United States)

    Chen, Vincent L; Kasper, Dennis L

    2014-01-01

    The mammalian intestine must manage to contain 100 trillion intestinal bacteria without inducing inappropriate immune responses to these microorganisms. The effects of the immune system on intestinal microorganisms are numerous and well-characterized, and recent research has determined that the microbiota influences the intestinal immune system as well. In this review, we first discuss the intestinal immune system and its role in containing and maintaining tolerance to commensal organisms. We next introduce a category of immune cells, the innate lymphoid cells, and describe their classification and function in intestinal immunology. Finally, we discuss the effects of the intestinal microbiota on innate lymphoid cells. PMID:24418741

  14. Mature lymphoid malignancies: origin, stem cells, and chronicity

    DEFF Research Database (Denmark)

    Husby, Simon; Grønbæk, Kirsten

    2017-01-01

    after treatment. Lately, the use of next-generation sequencing techniques has revealed essential information on the clonal evolution of lymphoid malignancies. Also, experimental xenograft transplantation point to the possible existence of an ancestral (stem) cell. Such a malignant lymphoid stem cell...... population could potentially evade current therapies and be the cause of chronicity and death in lymphoma patients; however, the evidence is divergent across disease entities and between studies. In this review we present an overview of genetic studies, case reports, and experimental evidence of the source...

  15. Introduction of transplantation tolerance after total lymphoid irradiation: cellular mechanisms

    International Nuclear Information System (INIS)

    Strober, S.; King, D.P.; Gottlieb, M.; Hoppe, R.T.; Kaplan, H.S.

    1981-01-01

    High-dose fractionated total lymphoid irradiation (TLI) is a safe, routine regimen used to treat patients with lymphoid malignancies. Although few side effects are associated with the regimen, a profound suppression of cell-mediated immunity is observed for several years after therapy, as judged by both in vivo and in vitro assays. A profound immunosuppression has also been observed in mice and rats given TLI. Recently, we have achieved similar results using TLI in nonmatched bone marrow transplantation in outbred dogs. The experimental work in animals and underlying cellular mechanisms are reviewed here

  16. The Bergschrund Hypothesis Revisited

    Science.gov (United States)

    Sanders, J. W.; Cuffey, K. M.; MacGregor, K. R.

    2009-12-01

    After Willard Johnson descended into the Lyell Glacier bergschrund nearly 140 years ago, he proposed that the presence of the bergschrund modulated daily air temperature fluctuations and enhanced freeze-thaw processes. He posited that glaciers, through their ability to birth bergschrunds, are thus able to induce rapid cirque headwall retreat. In subsequent years, many researchers challenged the bergschrund hypothesis on grounds that freeze-thaw events did not occur at depth in bergschrunds. We propose a modified version of Johnson’s original hypothesis: that bergschrunds maintain subfreezing temperatures at values that encourage rock fracture via ice lensing because they act as a cold air trap in areas that would otherwise be held near zero by temperate glacial ice. In support of this claim we investigated three sections of the bergschrund at the West Washmawapta Glacier, British Columbia, Canada, which sits in an east-facing cirque. During our bergschrund reconnaissance we installed temperature sensors at multiple elevations, light sensors at depth in 2 of the 3 locations and painted two 1 m2 sections of the headwall. We first emphasize bergschrunds are not wanting for ice: verglas covers significant fractions of the headwall and icicles dangle from the base of bödens or overhanging rocks. If temperature, rather than water availability, is the limiting factor governing ice-lensing rates, our temperature records demonstrate that the bergschrund provides a suitable environment for considerable rock fracture. At the three sites (north, west, and south walls), the average temperature at depth from 9/3/2006 to 8/6/2007 was -3.6, -3.6, and -2.0 °C, respectively. During spring, when we observed vast amounts of snow melt trickle in to the bergschrund, temperatures averaged -3.7, -3.8, and -2.2 °C, respectively. Winter temperatures are even lower: -8.5, -7.3, and -2.4 °C, respectively. Values during the following year were similar. During the fall, diurnal

  17. Functional differences between human NKp44(-) and NKp44(+) RORC+ innate lymphoid cells

    NARCIS (Netherlands)

    Hoorweg, Kerim; Peters, Charlotte P.; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M.; Spits, Hergen; Cupedo, Tom

    2012-01-01

    Human RORC+ lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human

  18. File list: InP.Bld.50.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.50.AllAg.Lymphoid_cells mm9 Input control Blood Lymphoid cells SRX021894,SR...X971601 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.50.AllAg.Lymphoid_cells.bed ...

  19. File list: ALL.Bld.20.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.20.AllAg.Lymphoid_cells mm9 All antigens Blood Lymphoid cells SRX658437,SRX...658389,SRX021894,SRX971603,SRX658419,SRX971601,SRX971602,SRX658405 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.20.AllAg.Lymphoid_cells.bed ...

  20. File list: ALL.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Bld.05.AllAg.Lymphoid_cells mm9 All antigens Blood Lymphoid cells SRX658419,SRX...658405,SRX658389,SRX658437,SRX971601,SRX971603,SRX021894,SRX971602 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Bld.05.AllAg.Lymphoid_cells.bed ...

  1. File list: InP.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Bld.05.AllAg.Lymphoid_cells mm9 Input control Blood Lymphoid cells SRX971601,SR...X021894 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Bld.05.AllAg.Lymphoid_cells.bed ...

  2. Locations of gut-associated lymphoid tissue in the 3-month-old chicken: a review.

    Science.gov (United States)

    Casteleyn, C; Doom, M; Lambrechts, E; Van den Broeck, W; Simoens, P; Cornillie, P

    2010-06-01

    The lymphoid tissue that is associated with the intestinal tract, the so-called gut-associated lymphoid tissue (GALT), is well developed in the chicken. Depending on the location, it is present as aggregations of lymphoid cells, or organized in lymphoid follicles and tonsils. From proximal to distal, the intestinal tract contains a pharyngeal tonsil, diffuse lymphoid tissue and lymphoid follicles in the cervical and thoracic parts of the oesophagus, an oesophageal tonsil, diffuse lymphoid tissue in the proventriculus, a pyloric tonsil, Peyer's patches, Meckel's diverticulum, two caecal tonsils, diffuse lymphoid tissue in the rectum, the bursa of Fabricius, and diffuse lymphoid tissue in the wall of the proctodeum. The lymphoid tissues are frequently covered by a lympho-epithelium that is infiltrated by lymphoid cells. Such an epithelium often contains M or microfold cells, which are specialized in antigen sampling and transport antigens to the underlying lymphoid tissue. A solid knowledge of the avian GALT could contribute to the development of vaccines to be administered orally. Additionally, immune stimulation via pre- and probiotics is based on the presence of a well-developed intestinal immune system.

  3. File list: ALL.Bld.50.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: InP.Bld.20.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: His.Bld.05.AllAg.Lymphoid_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Bld.05.AllAg.Lymphoid_cells mm9 Histone Blood Lymphoid cells SRX658419,SRX65840...5,SRX658389,SRX658437,SRX971603,SRX971602 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Bld.05.AllAg.Lymphoid_cells.bed ...

  6. THE EXTENT OF CLONAL STRUCTURE IN DIFFERENT LYMPHOID ORGANS

    NARCIS (Netherlands)

    HERMANS, MHA; WUBBENA, A; KROESE, FGM; HUNT, SV; COWAN, R; OPSTELTEN, D

    1992-01-01

    To gain insight into the clonal organization of lymphoid organs, we studied the distribution in situ of donor-derived cells in near-physiological chimeras. We introduced RT7b fetal liver cells into nonirradiated congenic RT7a neonatal rats. The chimerism 6-20 wk after injection ranged from 0.3 to

  7. Innate lymphoid cells and parasites: Ancient foes with shared history.

    Science.gov (United States)

    Neill, D R; Fallon, P G

    2018-02-01

    This special issue of Parasite Immunology charts the rapid advances made in our understanding of the myriad interactions between innate lymphoid cells and parasites and how these interactions have shaped our evolutionary history. Here, we provide an overview of the issue and highlight key findings from studies in mice and man. © 2017 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

  8. Developmental acquisition of regulomes underlies innate lymphoid cell functionality

    Science.gov (United States)

    Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and homeostasis, and they mirror adaptive CD4+ T helper (Th) cell subtypes in both usages of effector molecules and ·transcription factors. To better understand ILC subsets and their relationship with Th cells, we measur...

  9. Cytokine Networks between Innate Lymphoid Cells and Myeloid Cells.

    Science.gov (United States)

    Mortha, Arthur; Burrows, Kyle

    2018-01-01

    Innate lymphoid cells (ILCs) are an essential component of the innate immune system in vertebrates. They are developmentally rooted in the lymphoid lineage and can diverge into at least three transcriptionally distinct lineages. ILCs seed both lymphoid and non-lymphoid tissues and are locally self-maintained in tissue-resident pools. Tissue-resident ILCs execute important effector functions making them key regulator in tissue homeostasis, repair, remodeling, microbial defense, and anti-tumor immunity. Similar to T lymphocytes, ILCs possess only few sensory elements for the recognition of non-self and thus depend on extrinsic cellular sensory elements residing within the tissue. Myeloid cells, including mononuclear phagocytes (MNPs), are key sentinels of the tissue and are able to translate environmental cues into an effector profile that instructs lymphocyte responses. The adaptation of myeloid cells to the tissue state thus influences the effector program of ILCs and serves as an example of how environmental signals are integrated into the function of ILCs via a tissue-resident immune cell cross talks. This review summarizes our current knowledge on the role of myeloid cells in regulating ILC functions and discusses how feedback communication between ILCs and myeloid cells contribute to stabilize immune homeostasis in order to maintain the healthy state of an organ.

  10. ID’ing Innate and Innate-like Lymphoid Cells

    Science.gov (United States)

    Verykokakis, Mihalis; Zook, Erin C.; Kee, Barbara L.

    2014-01-01

    Summary The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. PMID:25123285

  11. Innate lymphoid cells--a proposal for uniform nomenclature

    NARCIS (Netherlands)

    Spits, Hergen; Artis, David; Colonna, Marco; Diefenbach, Andreas; Di Santo, James P.; Eberl, Gerard; Koyasu, Shigeo; Locksley, Richard M.; McKenzie, Andrew N. J.; Mebius, Reina E.; Powrie, Fiona; Vivier, Eric

    2013-01-01

    Innate lymphoid cells (ILCs) are a family of developmentally related cells that are involved in immunity and in tissue development and remodelling. Recent research has identified several distinct members of this family. Confusingly, many different names have been used to characterize these newly

  12. ID'ing innate and innate-like lymphoid cells.

    Science.gov (United States)

    Verykokakis, Mihalis; Zook, Erin C; Kee, Barbara L

    2014-09-01

    The immune system can be divided into innate and adaptive components that differ in their rate and mode of cellular activation, with innate immune cells being the first responders to invading pathogens. Recent advances in the identification and characterization of innate lymphoid cells have revealed reiterative developmental programs that result in cells with effector fates that parallel those of adaptive lymphoid cells and are tailored to effectively eliminate a broad spectrum of pathogenic challenges. However, activation of these cells can also be associated with pathologies such as autoimmune disease. One major distinction between innate and adaptive immune system cells is the constitutive expression of ID proteins in the former and inducible expression in the latter. ID proteins function as antagonists of the E protein transcription factors that play critical roles in lymphoid specification as well as B- and T-lymphocyte development. In this review, we examine the transcriptional mechanisms controlling the development of innate lymphocytes, including natural killer cells and the recently identified innate lymphoid cells (ILC1, ILC2, and ILC3), and innate-like lymphocytes, including natural killer T cells, with an emphasis on the known requirements for the ID proteins. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Innate lymphoid cells: the new kids on the block.

    Science.gov (United States)

    Withers, David R; Mackley, Emma C; Jones, Nick D

    2015-08-01

    The purpose of this article is to review recent advances in our understanding of innate lymphoid cell function and to speculate on how these cells may become activated and influence the immune response to allogeneic tissues and cells following transplantation. Innate lymphoid cells encompass several novel cell types whose wide-ranging roles in the immune system are only now being uncovered. Through cytokine production, cross-talk with both haematopoietic and nonhaematopoietic populations and antigen presentation to T cells, these cells have been shown to be key regulators in maintaining tissue integrity, as well as initiating and then sustaining immune responses. It is now clear that innate lymphoid cells markedly contribute to immune responses and tissue repair in a number of disease contexts. Although experimental and clinical data on the behaviour of these cells following transplantation are scant, it is highly likely that innate lymphoid cells will perform similar functions in the alloimmune response following transplantation and therefore may be potential therapeutic targets for manipulation to prevent allograft rejection.

  14. Synchronous high-risk melanoma and lymphoid neoplasia.

    LENUS (Irish Health Repository)

    Cahill, R A

    2012-02-03

    Large population-based studies have shown a significant association between melanoma and lymphoid neoplasia, particularly non-Hodgkin\\'s lymphoma (NHL) and chronic lymphocytic leukaemia (CLL), that is independent of any treatment received for the initial tumour. This study examines the presentation, diagnosis, treatment and progress of three patients who developed advanced melanoma concurrently with a lymphoid neoplasm (one NHL, two CLLs), in order to illustrate their association, discuss common aetiological factors and examine possible therapeutic options. As it is the melanoma rather than the lymphoid neoplasm that represents the bigger threat to overall survival, initial treatment should be targeted towards this cancer. However, because of the interplay between the diseases and the possible side-effects of the various treatments, the choice of adjuvant therapy requires careful consideration. Immunosuppression associated with chemotherapy may permit a more aggressive course for the melanoma, while locoregional radiotherapy is contraindicated following lymph node dissections. As immunotherapy is of benefit in the treatment of melanoma and has also been recently shown to be effective in the management of lymphoid neoplasia, we instituted interferon-alpha as adjuvant therapy for these patients, thereby utilizing a single agent to treat the dual pathologies. The three patients have now been followed-up for 6 months without evidence of disease recurrence or progression.

  15. 'Managing' the immune system with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Strober, S.

    1981-01-01

    Total lymphoid irradiation (TLI), which in the past was limited to the treatment of malignant disease, is now emerging as a practical technique in the management of unwanted immune reactions in the areas of transplant tolerance and various autoimmune diseases. Current studies are particularly promising for application of TLI in rheumatoid arthritis and lupus nephritis

  16. Innate lymphoid cells in autoimmunity: emerging regulators in rheumatic diseases

    NARCIS (Netherlands)

    Shikhagaie, Medya M.; Germar, Kristine; Bal, Suzanne M.; Ros, Xavier Romero; Spits, Hergen

    2017-01-01

    Innate lymphoid cells (ILCs) are important in the regulation of barrier homeostasis. These cells do not express T cell receptors but share many functional similarities with T helper cells and cytotoxic CD8(+) T lymphocytes. ILCs are divided into three groups, namely group 1 ILCs, group 2 ILCs and

  17. Occurrence of lymphoid cells in the intestine of the Goldfish

    NARCIS (Netherlands)

    Weinberg, Steven

    1975-01-01

    The Goldfish intestine normally contains a large number of lymphocytes, many of them being present in the epithelial layer. After stimulation with antigen, the number of lymphoid cells does not increase, but the proportion of large pyroninophilic cells and plasma cells does. It seems therefore that

  18. Induction of secondary and tertiary lymphoid structures in the skin.

    NARCIS (Netherlands)

    Cupedo, T.; Jansen, W.; Kraal, G.; Mebius, R.E.

    2004-01-01

    During embryogenesis a developmental program leading to the formation of lymph nodes and Peyer's patches is initiated. We now show that lymph node-like structures as well as tertiary lymphoid structures can ectopically be induced by intradermal injection of newborn lymph node-derived cells.

  19. The E-Id Protein Axis Specifies Adaptive Lymphoid Cell Identity and Suppresses Thymic Innate Lymphoid Cell Development.

    Science.gov (United States)

    Miyazaki, Masaki; Miyazaki, Kazuko; Chen, Kenian; Jin, Yi; Turner, Jacob; Moore, Amanda J; Saito, Rintaro; Yoshida, Kenichi; Ogawa, Seishi; Rodewald, Hans-Reimer; Lin, Yin C; Kawamoto, Hiroshi; Murre, Cornelis

    2017-05-16

    Innate and adaptive lymphoid development is orchestrated by the activities of E proteins and their antagonist Id proteins, but how these factors regulate early T cell progenitor (ETP) and innate lymphoid cell (ILC) development remains unclear. Using multiple genetic strategies, we demonstrated that E proteins E2A and HEB acted in synergy in the thymus to establish T cell identity and to suppress the aberrant development of ILCs, including ILC2s and lymphoid-tissue-inducer-like cells. E2A and HEB orchestrated T cell fate and suppressed the ILC transcription signature by activating the expression of genes associated with Notch receptors, T cell receptor (TCR) assembly, and TCR-mediated signaling. E2A and HEB acted in ETPs to establish and maintain a T-cell-lineage-specific enhancer repertoire, including regulatory elements associated with the Notch1, Rag1, and Rag2 loci. On the basis of these and previous observations, we propose that the E-Id protein axis specifies innate and adaptive lymphoid cell fate. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Is the Aluminum Hypothesis Dead?

    Science.gov (United States)

    2014-01-01

    The Aluminum Hypothesis, the idea that aluminum exposure is involved in the etiology of Alzheimer disease, dates back to a 1965 demonstration that aluminum causes neurofibrillary tangles in the brains of rabbits. Initially the focus of intensive research, the Aluminum Hypothesis has gradually been abandoned by most researchers. Yet, despite this current indifference, the Aluminum Hypothesis continues to attract the attention of a small group of scientists and aluminum continues to be viewed with concern by some of the public. This review article discusses reasons that mainstream science has largely abandoned the Aluminum Hypothesis and explores a possible reason for some in the general public continuing to view aluminum with mistrust. PMID:24806729

  1. An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

    International Nuclear Information System (INIS)

    Park, Charn Il; Han, Man Chung

    1981-01-01

    The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 ± 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 ± 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers

  2. An experimental study of the effect of total lymphoid irradiation on the survival of skin allografts

    Energy Technology Data Exchange (ETDEWEB)

    Park, Charn Il; Han, Man Chung [College of Medicine, Seoul National University, Seoul (Korea, Republic of)

    1981-06-15

    The study was undertaken to determine the effect of fractionated high-dose total lymphoid irradiation (TLI) on the survival of skin allograft despite major histocompatibility difference. Total lymphoid irradiation is a relatively safe form of radiotherapy, has been used extensively to treat lymphoid malignancies in humans with few side effects. A total of 90 rats, Sprague-Dawley rat as recipient and Wistar rat as donor, were used for the experiment, of which 10 rats were used to determine mixed lymphocyte response (MLR) for antigenic difference and skin allografts was performed in 30 rats given total lymphoid irradiation to assess the immunosuppressive effect of total lymphoid irradiation despite major histocompatibility difference. In addition, the peripheral white blood cell counts and the proportion of lymphocytes was studied in 10 rats given total lymphoid irradiation but no skin graft to determine the effects of bone marrow suppression. The results obtained are summarized as follows. 1. The optimum dose of total lymphoid irradiation was between 1800 rads to 2400 rads. 2. The survival of skin graft on rats given total lymphoid irradiation (23.2 {+-} 6.0 days) was prolonged about three folds as compared to unirradiated control (8.7 {+-} 1.3 days). 3. Total lymphoid irradiation resulted in a severe leukopenia with marked lymphopenia, but the count was normal by the end of 3rd week. 4. The study suggests that total lymphoid irradiation is a nonlethal procedure that could be used successfully in animals to transplant allograft across major histocompatibility barriers.

  3. Functional and phenotypic heterogeneity of group 3 innate lymphoid cells.

    Science.gov (United States)

    Melo-Gonzalez, Felipe; Hepworth, Matthew R

    2017-03-01

    Group 3 innate lymphoid cells (ILC3), defined by expression of the transcription factor retinoid-related orphan receptor γt, play key roles in the regulation of inflammation and immunity in the gastrointestinal tract and associated lymphoid tissues. ILC3 consist largely of two major subsets, NCR + ILC3 and LTi-like ILC3, but also demonstrate significant plasticity and heterogeneity. Recent advances have begun to dissect the relationship between ILC3 subsets and to define distinct functional states within the intestinal tissue microenvironment. In this review we discuss the ever-expanding roles of ILC3 in the context of intestinal homeostasis, infection and inflammation - with a focus on comparing and contrasting the relative contributions of ILC3 subsets. © 2016 The Authors. Immunology published by John Wiley & Sons Ltd.

  4. Clinical outcomes of childhood x-irradiation for lymphoid hyperplasia

    International Nuclear Information System (INIS)

    Pottern, L.M.

    1987-01-01

    A prospective study was conducted to explore the relationship between childhood x-irradiation for lymphoid hyperplasia and the subsequent development of thyroid gland and other head and neck disorders. All individuals under 18 years of age who were x-irradiated for lymphoid hyperplasia during the years 1938-69 at Children's Hospital Medical Center, Boston comprised the exposed population. The comparison group consisted of non-exposed, surgically treated individuals. The study included a health questionnaire and a clinical examination component. A history of thyroid cancer was reported by 11 exposed subjects and no non-exposed subjects. Significantly elevated standardized incidence ratios of thyroid cancer were seen for both exposed males and females, 19.9 and 12.1, respectively. The average thyroid radiation dose was 25.8 rads and the mean latency period was 17.3 years

  5. Total lymphoid irradiation in refractory systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Ben-Chetrit, E.; Gross, D.J.; Braverman, A.; Weshler, Z.; Fuks, Z.; Slavin, S.; Eliakim, M.

    1986-01-01

    In two patients with systemic lupus erythematosus, conventional therapy was considered to have failed because of persistent disease activity and unacceptable side effects. Both were treated with total lymphoid irradiation without clinical benefit, despite adequate immunosuppression as documented by markedly reduced numbers of circulating T lymphocytes and T-lymphocyte-dependent proliferative responses in vitro. The first patient developed herpes zoster, gram-negative septicemia, neurologic symptoms, and deterioration of lupus nephritis. The second patient developed massive bronchopneumonia, necrotic cutaneous lesions, and progressive nephritis and died 2 weeks after completion of radiotherapy. These observations, although limited to two patients, indicate that total lymphoid irradiation in patients with severe systemic lupus erythematosus should be regarded as strictly experimental

  6. Beyond NK cells: the expanding universe of innate lymphoid cells.

    Science.gov (United States)

    Cella, Marina; Miller, Hannah; Song, Christina

    2014-01-01

    For a long time, natural killer (NK) cells were thought to be the only innate immune lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different innate lymphoid cell (ILC) populations found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. These ILC populations closely mirror the phenotype of adaptive T helper subsets in their repertoire of secreted soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response that is appropriate for the incoming insult. Here, we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.

  7. Beyond NK cells: the expanding universe of Innate Lymphoid Cells.

    Directory of Open Access Journals (Sweden)

    Marina eCella

    2014-06-01

    Full Text Available For a long time NK cells were thought to be the only immune innate lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different Innate Lymphoid Cells found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. ILC populations closely mirror the phenotype of adaptive Thelper subsets in their ability to secrete soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response appropriate to the incoming insult. Here we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development.

  8. Immunosuppression by fractionated total lymphoid irradiation in collagen arthritis

    International Nuclear Information System (INIS)

    McCune, W.J.; Buckley, J.A.; Belli, J.A.; Trentham, D.E.

    1982-01-01

    Treatments with fractionated total lymphoid irradiation (TLI) and cyclophosphamide were evaluated for rats injected with type II collagen. Preadministration of TLI and repeated injections of cyclophosphamide suppressed the severity of arthritis and lowered antibody titers to collagen significantly. TLI initiated at the onset of collagen arthritis decreased humoral and cellular responses to collagen but did not affect the severity of arthritis. These data demonstrate that both TLi and cyclophosphamide are immunosuppressive in an experimentally inducible autoimmune disease

  9. Total lymphoid irradiation in the Wistar rat: technique and dosimetry

    International Nuclear Information System (INIS)

    Hoogenhout, J.; Kazem, I.; de Jong, J.

    1983-01-01

    The technical and dosimetric aspects of total lymphoid irradiation (TLI) in the Wistar rat were evaluated as part of a set-up to develop a new model for tumor xenotransplantation. Information obtained from anatomical dissections, radionuclide imaging of the spleen, lymphography and chromolymphography was used to standardize the localization portals cut out in a lead plate. The two portals encompassed the lymphoid tissue above and below the diaphragm. A specially designed masonite phantom was used to measure the dose distribution in the simulated target volumes. Ionization chamber dosimetery, thermoluminescence dosimetry and film densitometry were used for measuring exposure and absorbed dose. Irradiation was performed with 250 kV X rays (HVL 3.1 mm Cu). The dose rate was regulated by adjusting the treatment distance. The dose inhomogeneity measured in the target volumes varied between 80-100%. The side scatter dose to non target tissues under the shielded area between the two portals ranged between 20-30%. The technique and dosimetry of total lymphoid irradiation in Wistar rats are now standardized and validated and pave the way for tumor xenotransplantation experiments

  10. Dysregulation of Innate Lymphoid Cells in Common Variable Immunodeficiency.

    Science.gov (United States)

    Maglione, Paul J; Cols, Montserrat; Cunningham-Rundles, Charlotte

    2017-10-05

    Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immune deficiency. With widespread use of immunoglobulin replacement therapy, non-infectious complications, such as autoimmunity, chronic intestinal inflammation, and lung disease, have replaced infections as the major cause of morbidity and mortality in this immune deficiency. The pathogenic mechanisms that underlie the development of these complications in CVID are not known; however, there have been numerous associated laboratory findings. Among the most intriguing of these associations is elevation of interferon signature genes in CVID patients with inflammatory/autoimmune complications, as a similar gene expression profile is found in systemic lupus erythematosus and other chronic inflammatory diseases. Linked with this heightened interferon signature in CVID is an expansion of circulating IFN-γ-producing innate lymphoid cells. Innate lymphoid cells are key regulators of both protective and pathogenic immune responses that have been extensively studied in recent years. Further exploration of innate lymphoid cell biology in CVID may uncover key mechanisms underlying the development of inflammatory complications in these patients and may inspire much needed novel therapeutic approaches.

  11. Human natural killer cell development in secondary lymphoid tissues

    Science.gov (United States)

    Freud, Aharon G.; Yu, Jianhua; Caligiuri, Michael A.

    2014-01-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34+CD45RA+ hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field. PMID:24661538

  12. Treatment of intractable lupus nephritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Strober, S.; Field, E.; Hoppe, R.T.; Kotzin, B.L.; Shemesh, O.; Engleman, E.; Ross, J.C.; Myers, B.D.

    1985-01-01

    Ten patients with lupus nephritis and marked proteinuria (3.9 g or more/d) that did not respond adequately to treatment with prednisone alone or prednisone in combination with azathioprine were treated with total lymphoid irradiation in an uncontrolled feasibility study. Within 6 weeks after the start of total lymphoid irradiation, the serum albumin level rose in all patients in association with a reduction in the serum level of anti-DNA antibodies, an increase in the serum complement level, or both. Improvement in these variables persisted in eight patients followed for more than 1 year, with the stabilization or reduction of the serum creatinine level. Urinary leakage of albumin was substantially reduced in all patients. Side effects associated with radiotherapy included transient constitutional complaints in ten patients, transient blood element depressions in three, localized viral and bacterial infections in four, and ovarian failure in one. The results suggest that total lymphoid irradiation may provide an alternative to cytotoxic drugs in the treatment of lupus nephritis

  13. Hypothesis Designs for Three-Hypothesis Test Problems

    OpenAIRE

    Yan Li; Xiaolong Pu

    2010-01-01

    As a helpful guide for applications, the alternative hypotheses of the three-hypothesis test problems are designed under the required error probabilities and average sample number in this paper. The asymptotic formulas and the proposed numerical quadrature formulas are adopted, respectively, to obtain the hypothesis designs and the corresponding sequential test schemes under the Koopman-Darmois distributions. The example of the normal mean test shows that our methods are qu...

  14. Tests of the lunar hypothesis

    Science.gov (United States)

    Taylor, S. R.

    1984-01-01

    The concept that the Moon was fissioned from the Earth after core separation is the most readily testable hypothesis of lunar origin, since direct comparisons of lunar and terrestrial compositions can be made. Differences found in such comparisons introduce so many ad hoc adjustments to the fission hypothesis that it becomes untestable. Further constraints may be obtained from attempting to date the volatile-refractory element fractionation. The combination of chemical and isotopic problems suggests that the fission hypothesis is no longer viable, and separate terrestrial and lunar accretion from a population of fractionated precursor planetesimals provides a more reasonable explanation.

  15. Ageing combines CD4 T cell lymphopenia in secondary lymphoid organs and T cell accumulation in gut associated lymphoid tissue

    OpenAIRE

    Martinet , Kim ,; Bloquet , Stéphane; Bourgeois , Christine

    2014-01-01

    International audience; BackgroundCD4 T cell lymphopenia is an important T cell defect associated to ageing. Higher susceptibility to infections, cancer, or autoimmune pathologies described in aged individuals is thought to partly rely on T cell lymphopenia. We hypothesize that such diverse effects may reflect anatomical heterogeneity of age related T cell lymphopenia. Indeed, no data are currently available on the impact of ageing on T cell pool recovered from gut associated lymphoid tissue ...

  16. Evaluating the Stage Learning Hypothesis.

    Science.gov (United States)

    Thomas, Hoben

    1980-01-01

    A procedure for evaluating the Genevan stage learning hypothesis is illustrated by analyzing Inhelder, Sinclair, and Bovet's guided learning experiments (in "Learning and the Development of Cognition." Cambridge: Harvard University Press, 1974). (Author/MP)

  17. The Purchasing Power Parity Hypothesis:

    African Journals Online (AJOL)

    2011-10-02

    Oct 2, 2011 ... reject the unit root hypothesis in real exchange rates may simply be due to the shortness ..... Violations of Purchasing Power Parity and Their Implications for Efficient ... Official Intervention in the Foreign Exchange Market:.

  18. Test of the hypothesis; a lymphoma stem cells exist which is capable of self-renewal

    DEFF Research Database (Denmark)

    Kjeldsen, Malene Krag

      Test of the hypothesis; a lymphoma stem cell exist which is capable of self-renewal   Malene Krag Pedersen, Karen Dybkaer, Hans E. Johnsen   The Research Laboratory, Department of Haematology, Aalborg Hospital, Århus University   Failure of current therapeutics in the treatment of diffuse large B...... and sustaining cells(1-3). My project is based on studies of stem and early progenitor cells in lymphoid cell lines from patients with advanced DLBCL. The cell lines are world wide recognised and generously provided by Dr. Hans Messner and colleagues.   Hypothesis and aims: A lymphoma stem and progenitor cell...

  19. Critical role of CD4 T cells in maintaining lymphoid tissue structure for immune cell homeostasis and reconstitution.

    Science.gov (United States)

    Zeng, Ming; Paiardini, Mirko; Engram, Jessica C; Beilman, Greg J; Chipman, Jeffrey G; Schacker, Timothy W; Silvestri, Guido; Haase, Ashley T

    2012-08-30

    Loss of the fibroblastic reticular cell (FRC) network in lymphoid tissues during HIV-1 infection has been shown to impair the survival of naive T cells and limit immune reconstitution after antiretroviral therapy. What causes this FRC loss is unknown. Because FRC loss correlates with loss of both naive CD4 and CD8 T-cell subsets and decreased lymphotoxin-β, a key factor for maintenance of FRC network, we hypothesized that loss of naive T cells is responsible for loss of the FRC network. To test this hypothesis, we assessed the consequences of antibody-mediated depletion of CD4 and CD8 T cells in rhesus macaques and sooty mangabeys. We found that only CD4 T-cell depletion resulted in FRC loss in both species and that this loss was caused by decreased lymphotoxin-β mainly produced by the CD4 T cells. We further found the same dependence of the FRC network on CD4 T cells in HIV-1-infected patients before and after antiretroviral therapy and in other immunodeficiency conditions, such as CD4 depletion in cancer patients induced by chemotherapy and irradiation. CD4 T cells thus play a central role in the maintenance of lymphoid tissue structure necessary for their own homeostasis and reconstitution.

  20. Bronchus-associated lymphoid tissue in pulmonary hypertension produces pathologic autoantibodies.

    Science.gov (United States)

    Colvin, Kelley L; Cripe, Patrick J; Ivy, D Dunbar; Stenmark, Kurt R; Yeager, Michael E

    2013-11-01

    Autoimmunity has long been associated with pulmonary hypertension. Bronchus-associated lymphoid tissue plays important roles in antigen sampling and self-tolerance during infection and inflammation. We reasoned that activated bronchus-associated lymphoid tissue would be evident in rats with pulmonary hypertension, and that loss of self-tolerance would result in production of pathologic autoantibodies that drive vascular remodeling. We used animal models, histology, and gene expression assays to evaluate the role of bronchus-associated lymphoid tissue in pulmonary hypertension. Bronchus-associated lymphoid tissue was more numerous, larger, and more active in pulmonary hypertension compared with control animals. We found dendritic cells in and around lymphoid tissue, which were composed of CD3(+) T cells over a core of CD45RA(+) B cells. Antirat IgG and plasma from rats with pulmonary hypertension decorated B cells in lymphoid tissue, resistance vessels, and adventitia of large vessels. Lymphoid tissue in diseased rats was vascularized by aquaporin-1(+) high endothelial venules and vascular cell adhesion molecule-positive vessels. Autoantibodies are produced in bronchus-associated lymphoid tissue and, when bound to pulmonary adventitial fibroblasts, change their phenotype to one that may promote inflammation. Passive transfer of autoantibodies into rats caused pulmonary vascular remodeling and pulmonary hypertension. Diminution of lymphoid tissue reversed pulmonary hypertension, whereas immunologic blockade of CCR7 worsened pulmonary hypertension and hastened its onset. Bronchus-associated lymphoid tissue expands in pulmonary hypertension and is autoimmunologically active. Loss of self-tolerance contributes to pulmonary vascular remodeling and pulmonary hypertension. Lymphoid tissue-directed therapies may be beneficial in treating pulmonary hypertension.

  1. Skin-associated lymphoid tissues (SALT): origins and functions

    International Nuclear Information System (INIS)

    Streilein, J.W.

    1983-01-01

    The skin has an unusual set of immunologic requirements. It is confronted by a specialized set of pathogenic organisms and environmental chemicals that represent a distinctive spectrum of antigenic specificities. Skin is subjected to physicochemical stresses such as irradiation with ultraviolet light that alter dramatically its immunologic properties. It is proposed that nature has provided skin with a unique collection of lymphoid cells, reticular cells, and organized lymphoid organs to deal with these special demands. Evidence in favor of the existence of skin-associated lymphoid tissues (SALT) includes (1) the cutaneous microenvironment is capable on its own of accepting, processing, and presenting nominal antigen; (2) strategically located peripheral lymph nodes are able to accept immunogenic signals derived from skin; (3) subsets of T lymphocytes display differential affinity for skin and its associated peripheral nodes; and (4) acquisition of this affinity by T cells is determined at least in part by differentiation signals received in situ from resident cutaneous cells. Responsibility for the establishment and integration of SALT rests with keratinocytes, Langerhans cells, and immunocompetent lymphocytes, each of which contributes uniquely to the synthesis. Together they provide skin with immune surveillance that effectively prejudices against the development of cutaneous neoplasms and persistent infection with intracellular pathogens. In patients who have been under long-term immunosuppressive therapy, the large majority of nonlymphoid malignancies arise within the skin, rather than other types of tissues. These data suggest that immune surveillance, once thought to be an immune defense operative in all somatic tissues, is a specialized immune function dedicated to the skin and mediated by SALT

  2. Development of venetoclax for therapy of lymphoid malignancies

    Directory of Open Access Journals (Sweden)

    Zhu H

    2017-03-01

    Full Text Available Huayuan Zhu,1,2 Alexandru Almasan1 1Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA; 2Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, People’s Republic of China Abstract: B-cell lymphoma-2 (BCL-2 family dysfunction and impairment of apoptosis are common in most B-cell lymphoid malignancies. Venetoclax (Venclexta™, formerly ABT-199, GDC-0199 is a highly selective BCL-2 inhibitor, which mimics its BCL-2 homology 3-domain to induce apoptosis. It was approved for treatment of previously treated chronic lymphocytic leukemia (CLL patients with 17p deletion early in 2016. It has also been in clinical trials for other B-cell lymphoid malignancies. Unlike the other recently approved targeted agents idelalisib and ibrutinib, so far there has been no relapse reported in some patients. Also, unlike the other targeted agents, it is effective against tumor cells that reside in the blood marrow. Despite its promising outcome in CLL, preclinical data have already uncovered mechanistic insights underlying venetoclax resistance, such as upregulation of MCL-1 or BCL-xL expression and protective signaling from the microenvironment. In this review, we describe the role of the BCL-2 family in the pathogenesis of B-cell lymphoid malignancies, the development of venetoclax, and its current clinical outcome in CLL and other B-cell malignancies. We also discuss the resistance mechanisms that develop following venetoclax therapy, potential strategies to overcome them, and how this knowledge can be translated into clinical applications. Keywords: BCL-2, BCL-xL, chronic lymphocytic leukemia, MCL-1, venetoclax

  3. Lymphoid follicles in children with Helicobacter pylori-negative gastritis

    Science.gov (United States)

    Broide, Efrat; Richter, Vered; Mendlovic, Sonia; Shalem, Tzippora; Eindor-Abarbanel, Adi; Moss, Steven F; Shirin, Haim

    2017-01-01

    Purpose The prevalence of Helicobacter pylori gastritis has been declining, whereas H. pylori-negative gastritis has become more common. We evaluated chronic gastritis in children with regard to H. pylori status and celiac disease (CD). Patients and methods Demographic, clinical, endoscopic, and histologic features of children who underwent elective esophagogastroduodenoscopy were reviewed retrospectively. Gastric biopsies from the antrum and corpus of the stomach were graded using the Updated Sydney System. H. pylori presence was defined by hematoxylin and eosin, Giemsa, or immunohistochemical staining and urease testing. Results A total of 184 children (61.9% female) met the study criteria with a mean age of 10 years. A total of 122 (66.3%) patients had chronic gastritis; 74 (60.7%) were H. pylori-negative. Children with H. pylori-negative gastritis were younger (p=0.003), were less likely to present with abdominal pain (p=0.02), and were mostly of non-Arabic origin (p=0.011). Nodular gastritis was found to be less prevalent in H. pylori-negative gastritis (6.8%) compared with H. pylori-positive gastritis (35.4%, pgastritis and lymphoid follicles were associated most commonly with H. pylori. Although less typical, lymphoid follicles were demonstrated in 51.3% of H. pylori-negative patients. The presence or absence of CD was not associated with histologic findings in H. pylori-negative gastritis. Conclusion Our findings suggest that lymphoid follicles are a feature of H. pylori-negative gastritis in children independent of their CD status. PMID:28860835

  4. The atomic hypothesis: physical consequences

    International Nuclear Information System (INIS)

    Rivas, Martin

    2008-01-01

    The hypothesis that matter is made of some ultimate and indivisible objects, together with the restricted relativity principle, establishes a constraint on the kind of variables we are allowed to use for the variational description of elementary particles. We consider that the atomic hypothesis not only states the indivisibility of elementary particles, but also that these ultimate objects, if not annihilated, cannot be modified by any interaction so that all allowed states of an elementary particle are only kinematical modifications of any one of them. Therefore, an elementary particle cannot have excited states. In this way, the kinematical group of spacetime symmetries not only defines the symmetries of the system, but also the variables in terms of which the mathematical description of the elementary particles can be expressed in either the classical or the quantum mechanical description. When considering the interaction of two Dirac particles, the atomic hypothesis restricts the interaction Lagrangian to a kind of minimal coupling interaction

  5. Disaster Debris Recovery Database - Recovery

    Data.gov (United States)

    U.S. Environmental Protection Agency — The US EPA Disaster Debris Recovery Database (DDRD) promotes the proper recovery, recycling, and disposal of disaster debris for emergency responders at the federal,...

  6. Isolation and characterization of mouse innate lymphoid cells.

    Science.gov (United States)

    Halim, Timotheus Y F; Takei, Fumio

    2014-08-01

    Innate lymphoid cells (ILCs) are rare populations of cytokine-producing lymphocytes and are divided into three groups, namely ILC1, ILC2, and ILC3, based on the cytokines that they produce. They comprise less than 1% of lymphocytes in mucosal tissues and express no unique cell surface markers. Therefore, they can only be identified by combinations of multiple cell surface markers and further characterized by cytokine production in vitro. Thus, multicolor flow cytometry is the only reliable method to purify and characterize ILCs. Here we describe the methods for cell preparation, flow cytometric analysis, and purification of murine ILC2 and ILC3. Copyright © 2014 John Wiley & Sons, Inc.

  7. Effect of total lymphoid irradiation in chronic progressive multiple sclerosis

    International Nuclear Information System (INIS)

    Cook, S.D.; Devereux, C.; Troiano, R.; Hafstein, M.P.; Zito, G.; Hernandez, E.; Lavenhar, M.; Vidaver, R.; Dowling, P.C.

    1986-01-01

    Total lymphoid irradiation (TLI; 1980 cGy) or sham irradiation was given to 40 patients with chronic progressive multiple sclerosis (MS) in a prospective, randomised, double-blind study. During mean follow-up of 21 months, MS patients treated with TLI has less functional decline than sham-irradiated MS patients (p<0.01). A significant relation was noted between absolute blood lymphocyte counts in the first year after TLI and subsequent course, patients with higher lymphocyte counts generally having a worse prognosis (p<0.01). TLI was well tolerated and associated with only mild short-term, and to date, long-term side-effects. (author)

  8. Multiple sclerosis: a geographical hypothesis.

    Science.gov (United States)

    Carlyle, I P

    1997-12-01

    Multiple sclerosis remains a rare neurological disease of unknown aetiology, with a unique distribution, both geographically and historically. Rare in equatorial regions, it becomes increasingly common in higher latitudes; historically, it was first clinically recognized in the early nineteenth century. A hypothesis, based on geographical reasoning, is here proposed: that the disease is the result of a specific vitamin deficiency. Different individuals suffer the deficiency in separate and often unique ways. Evidence to support the hypothesis exists in cultural considerations, in the global distribution of the disease, and in its historical prevalence.

  9. Discussion of the Porter hypothesis

    International Nuclear Information System (INIS)

    1999-11-01

    In the reaction to the long-range vision of RMNO, published in 1996, The Dutch government posed the question whether a far-going and progressive modernization policy will lead to competitive advantages of high-quality products on partly new markets. Such a question is connected to the so-called Porter hypothesis: 'By stimulating innovation, strict environmental regulations can actually enhance competitiveness', from which statement it can be concluded that environment and economy can work together quite well. A literature study has been carried out in order to determine under which conditions that hypothesis is endorsed in the scientific literature and policy documents. Recommendations are given for further studies. refs

  10. The thrifty phenotype hypothesis revisited

    DEFF Research Database (Denmark)

    Vaag, A A; Grunnet, L G; Arora, G P

    2012-01-01

    Twenty years ago, Hales and Barker along with their co-workers published some of their pioneering papers proposing the 'thrifty phenotype hypothesis' in Diabetologia (4;35:595-601 and 3;36:62-67). Their postulate that fetal programming could represent an important player in the origin of type 2...... of the underlying molecular mechanisms. Type 2 diabetes is a multiple-organ disease, and developmental programming, with its idea of organ plasticity, is a plausible hypothesis for a common basis for the widespread organ dysfunctions in type 2 diabetes and the metabolic syndrome. Only two among the 45 known type 2...

  11. Immunohistochemical detection of prion protein in lymphoid tissues of sheep with natural scrapie

    NARCIS (Netherlands)

    Keulen, van L.J.M.; Schreuder, B.E.C.; Meloen, R.H.; Mooij-Harkes, G.; Vromans, M.E.W.; Langeveld, J.P.M.

    1996-01-01

    The scrapie-associated form of the prion protein (PrP(Sc)) accumulates in the brain and lymphoid tissues of sheep with scrapie. In order to assess whether detecting PrP(Sc) in lymphoid tissue could he used as a diagnostic test for scrapie, we studied the localization and distribution of PrP(Sc) in

  12. [Histopathological Study of the Relationship between Lymphoid Follicles and Different Endoscopic Types of Nodular Gastritis].

    Science.gov (United States)

    Nagata, Takuo; Ishitake, Hisahito; Shimamoto, Fumio; Tamura, Tadamasa; Matsumura, Kazunori; Sumii, Masaharu; Nakai, Shirou

    2014-11-01

    Nodular gastritis is characterized histologically by hyperplasia and enlargement of lymphoid follicles in the lamina propria. With the objective of elucidating the relationship between different endoscopic types of nodular gastritis and lymphoid follicles, distributions of lymphoid follicles in the lamina propria were investigated in young gastric cancer patients with nodular gastritis. For the study, whole-mucosal step sectioning of each resected stomach was performed, the densities of lymphoid follicles of all specimens were measured microscopically, and the horizontal and depth distributions were calculated. For assessment in the horizontal direction, density distribution diagrams of lymphoid follicles were created. For assessment in the depth direction, the different endoscopic types of nodular gastritis were compared in the five different analysis sites. In the assessment of the horizontal distribution, no characteristic distribution tendencies were observed in either the granular type group or the scattered type group; however, it was found that areas with relatively high densities of lymphoid follicles generally coincided with the areas where nodular gastritis was observed endoscopically. These results suggested that hyperplasia and aggregation of lymphoid follicles in the lamina propria are involved at the sites where nodular gastritis is observed endoscopically. In the assessment of the depth distribution, lymphoid follicles tended to be more unevenly distributed in the upper lamina propria in the granular type group than in the scattered type at the three different analysis sites where nodular gastritis was observed endoscopically. These results suggested the possibility of a granular type characteristic.

  13. The expanding family of innate lymphoid cells: regulators and effectors of immunity and tissue remodeling

    NARCIS (Netherlands)

    Spits, Hergen; Di Santo, James P.

    2011-01-01

    Research has identified what can be considered a family of innate lymphoid cells (ILCs) that includes not only natural killer (NK) cells and lymphoid tissue-inducer (LTi) cells but also cells that produce interleukin 5 (IL-5), IL-13, IL-17 and/or IL-22. These ILC subsets are developmentally related,

  14. Innate Lymphoid Cells: Emerging Insights in Development, Lineage Relationships, and Function

    NARCIS (Netherlands)

    Spits, Hergen; Cupedo, Tom

    2012-01-01

    Innate lymphoid cells (ILCs) are immune cells that lack a specific antigen receptor yet can produce an array of effector cytokines that in variety match that of T helper cell subsets. ILCs function in lymphoid organogenesis, tissue remodeling, antimicrobial immunity, and inflammation, particularly

  15. Determination of the Fate and Function of Innate Lymphoid Cells Following Adoptive Transfer of Innate Lymphoid Cell Precursors.

    Science.gov (United States)

    O'Sullivan, Timothy E; Sun, Joseph C

    2018-01-01

    Innate lymphoid cells are a heterogeneous family of tissue-resident and circulating lymphocytes that play an important role in host immunity. Recent studies have profiled the developmental pathways of mature ILCs and have identified ILC progenitors in the bone marrow through the use of transcription factor reporter mice. Here we describe methodology to identify and isolate bone marrow CHILP and ILC2 progenitor (ILC2P) cells based on cell surface marker expression for adoptive transfer into lymphopenic mice to track the fate of developing ILCs.

  16. Innate Lymphoid Cells in HIV/SIV Infections

    Directory of Open Access Journals (Sweden)

    Spandan V. Shah

    2017-12-01

    Full Text Available Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  17. Sustained improvement of intractable rheumatoid arthritis after total lymphoid irradiation

    International Nuclear Information System (INIS)

    Field, E.H.; Strober, S.; Hoppe, R.T.

    1983-01-01

    Total lymphoid irradiation (TLI) was administered to 11 patients who had intractable rheumatoid arthritis that was unresponsive to conventional medical therapy, including aspirin, multiple nonsteroidal antiinflammatory drugs, gold salts, and D-penicillamine. Total lymphoid irradiation was given as an alternative to cytotoxic drugs such as azathioprine and cyclophosphamide. After radiotherapy, 9 of the 11 patients showed a marked improvement in clinical disease activity as measured by morning stiffness, joint tenderness, joint swelling, and overall functional abilities. The mean improvement of disease activity in all patients ranged from 40-70 percent and has persisted throughout a 13-28 month followup period. This improvement permitted the mean daily steroid dose to be reduced by 54%. Complications included severe fatigue and other constitutional symptoms during radiotherapy, development of Felty's syndrome in 1 patient, and an exacerbation of rheumatoid lung disease in another. After therapy, all patients exhibited a profound T lymphocytopenia, and a reversal in their T suppressor/cytotoxic cell to helper cell ratio. The proliferative responses of peripheral blood mononuclear cells to phytohemagglutinin, concanavalin A, and allogeneic leukocytes (mixed leukocyte reaction) were markedly reduced, as was in vitro immunoglobulin synthesis after stimulation with pokeweed mitogen. Alterations in T cell numbers and function persisted during the entire followup period, except that the mixed leukocyte reaction showed a tendency to return to normal values

  18. [The lymph nodes imprint for the diagnosis of lymphoid neoplasms].

    Science.gov (United States)

    Peniche-Alvarado, Carolina; Ramos-Peñafiel, Christian Omar; Martínez-Murillo, Carlos; Romero-Guadarrama, Mónica; Olarte-Carrillo, Irma; Rozen-Fuller, Etta; Martínez-Tovar, Adolfo; Collazo-Jaloma, Juan; Mendoza-García, Carlos Alberto

    2013-01-01

    lymphoma is the most frequent lymphoid neoplasm in our country. Its diagnosis is based on histopathological findings. The lymph node imprint has been used for more than 40 years. The aim was to establish the sensitivity, specificity, positive predictive value and negative predictive value of lymph node imprint and estimate the inter-observer rate. we did an observational, retrospective, prolective study, based on the lymph node imprint obtained by excisional biopsies over a period of 6 years. the inclusion criteria was met on 199 samples, 27.1 % were considered as reactive (n = 54), 16.1 % Hodgkin lymphoma (n = 32), 40.2 % (n = 80) non-Hodgkin lymphoma and 16.6 % (n = 33) as metastatic carcinoma. Comparing with the final histopathology report, the sensitivity and specificity of lymph node imprint were 88 % (0.81-0.95) and 64 % (0.55-0.73) respectively, the positive predictive value was 67 % (0.59-0.76) and the negative predictive value was 86 % (0.79-0.94). The interobserver kappa index was 0.467. the lymph node imprint remains as a useful tool for the diagnosis of lymphoid neoplasm. The agreement between observers was acceptable.

  19. Innate lymphoid cells in tissue homeostasis and diseases.

    Science.gov (United States)

    Ignacio, Aline; Breda, Cristiane Naffah Souza; Camara, Niels Olsen Saraiva

    2017-08-18

    Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells. They are a part of the innate immune system, but develop from the lymphoid lineage. They lack pattern-recognition receptors and rearranged receptors, and therefore cannot directly mediate antigen specific responses. The progenitors specifically associated with the ILCs lineage have been uncovered, enabling the distinction between ILCs and natural killer cells. Based on the requirement of specific transcription factors and their patterns of cytokine production, ILCs are categorized into three subsets (ILC1, ILC2 and ILC3). First observed in mucosal surfaces, these cell populations interact with hematopoietic and non-hematopoietic cells throughout the body during homeostasis and diseases, promoting immunity, commensal microbiota tolerance, tissue repair and inflammation. Over the last 8 years, ILCs came into the spotlight as an essential cell type able to integrate diverse host immune responses. Recently, it became known that ILC subsets play a key role in immune responses at barrier surfaces, interacting with the microbiota, nutrients and metabolites. Since the liver receives the venous blood directly from the intestinal vein, the intestine and liver are essential to maintain tolerance and can rapidly respond to infections or tissue damage. Therefore, in this review, we discuss recent findings regarding ILC functions in homeostasis and disease, with a focus on the intestine and liver.

  20. Human innate lymphoid cells (ILCs) in filarial infections.

    Science.gov (United States)

    Bonne-Année, S; Nutman, T B

    2018-02-01

    Filarial infections are characteristically chronic and can cause debilitating diseases governed by parasite-induced innate and adaptive immune responses. Filarial parasites traverse or establish niches in the skin (migrating infective larvae), in nonmucosal tissues (adult parasite niche) and in the blood or skin (circulating microfilariae) where they intersect with the host immune response. While several studies have demonstrated that filarial parasites and their antigens can modulate myeloid cells (monocyte, macrophage and dendritic cell subsets), T- and B-lymphocytes and skin resident cell populations, the role of innate lymphoid cells during filarial infections has only recently emerged. Despite the identification and characterization of innate lymphoid cells (ILCs) in murine helminth infections, little is actually known about the role of human ILCs during parasitic infections. The focus of this review will be to highlight the composition of ILCs in the skin, lymphatics and blood; where the host-parasite interaction is well-defined and to examine the role of ILCs during filarial infections. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  1. Innate lymphoid cells in normal and disease: An introductory overview.

    Science.gov (United States)

    Moretta, Lorenzo; Locatelli, Franco

    2016-11-01

    Innate lymphoid cells (ILC) represent a novel group of lymphocytes that, different from T and B-lymphocytes lack recombinant activating genes (RAG-1 or RAG-2) and thus do not express rearranged antigen-specific receptors. Members of this family, i.e. NK cells, have been known since long time, while the other ILCs have been discovered only in recent years, possibly because of their predominant localization in tissues, primarily in mucosal tissues, skin and mucosa-associated lymphoid organs. ILC have been grouped in three major subsets on the basis of their phenotypic and functional features as well as of their dependency on given transcription factors (TF). Briefly, ILC-1 are dependent on T-bet TF and produce interferon (IFN)-γ. Group 2 ILC (ILC2) express GATA-3 TF and produce IL-5, IL-4 and IL-13 (Type 2) cytokines while group 3 ILC (ILC3) express RORγt TF and produce IL-17 and IL-22. ILC provide early defenses against pathogens and intervene in the repair of damaged tissues. ILC activation is mediated by cytokines (specifically acting on different ILC groups) and/or by activating receptors that are, at least in part, the same that had been previously identified in NK cells [1]. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  2. The Yin and Yang of Innate Lymphoid Cells in Cancer.

    Science.gov (United States)

    Carrega, Paolo; Campana, Stefania; Bonaccorsi, Irene; Ferlazzo, Guido

    2016-11-01

    The recent appreciation of novel subsets of innate lymphoid cells (ILCs) as important regulators of tissue homeostasis, inflammation and repair, raise questions regarding the presence and role of these cells in cancer tissues. In addition to natural killer and fetal lymphoid tissue inducer (LTi) cells, the ILC family comprises non-cytolytic, cytokine-producing cells that are classified into ILC1, ILC2 and ILC3 based on phenotypic and functional characteristics. Differently from natural killer cells, which are the prototypical members of ILC1 and whose role in tumors is better established, the involvement of other ILC subsets in cancer progression or resistance is still fuzzy and in several instances controversial, since current studies indicate both context-dependent beneficial or pathogenic effects. Here, we review the current knowledge regarding the involvement of these novel ILC subsets in the context of tumor immunology, highlighting how ILC subsets might behave either as friends or foes. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  3. Emerging concepts and future challenges in innate lymphoid cell biology

    Science.gov (United States)

    Artis, David

    2016-01-01

    Innate lymphoid cells (ILCs) are innate immune cells that are ubiquitously distributed in lymphoid and nonlymphoid tissues and enriched at mucosal and barrier surfaces. Three major ILC subsets are recognized in mice and humans. Each of these subsets interacts with innate and adaptive immune cells and integrates cues from the epithelium, the microbiota, and pathogens to regulate inflammation, immunity, tissue repair, and metabolic homeostasis. Although intense study has elucidated many aspects of ILC development, phenotype, and function, numerous challenges remain in the field of ILC biology. In particular, recent work has highlighted key new questions regarding how these cells communicate with their environment and other cell types during health and disease. This review summarizes new findings in this rapidly developing field that showcase the critical role ILCs play in directing immune responses through their ability to interact with a variety of hematopoietic and nonhematopoietic cells. In addition, we define remaining challenges and emerging questions facing the field. Finally, this review discusses the potential application of basic studies of ILC biology to the development of new treatments for human patients with inflammatory and infectious diseases in which ILCs play a role. PMID:27811053

  4. Innate Lymphoid Cells in HIV/SIV Infections.

    Science.gov (United States)

    Shah, Spandan V; Manickam, Cordelia; Ram, Daniel R; Reeves, R Keith

    2017-01-01

    Over the past several years, new populations of innate lymphocytes have been described in mice and primates that are critical for mucosal homeostasis, microbial regulation, and immune defense. Generally conserved from mice to humans, innate lymphoid cells (ILC) have been divided primarily into three subpopulations based on phenotypic and functional repertoires: ILC1 bear similarities to natural killer cells; ILC2 have overlapping functions with TH2 cells; and ILC3 that share many functions with TH17/TH22 cells. ILC are specifically enriched at mucosal surfaces and are possibly one of the earliest responders during viral infections besides being involved in the homeostasis of gut-associated lymphoid tissue and maintenance of gut epithelial barrier integrity. Burgeoning evidence also suggests that there is an early and sustained abrogation of ILC function and numbers during HIV and pathogenic SIV infections, most notably ILC3 in the gastrointestinal tract, which leads to disruption of the mucosal barrier and dysregulation of the local immune system. A better understanding of the direct or indirect mechanisms of loss and dysfunction will be critical to immunotherapeutics aimed at restoring these cells. Herein, we review the current literature on ILC with a particular emphasis on ILC3 and their role(s) in mucosal immunology and the significance of disrupting the ILC niche during HIV and SIV infections.

  5. Trafficking of α-L-fucosidase in lymphoid cells

    International Nuclear Information System (INIS)

    DiCioccio, R.A.; Brown, K.S.

    1987-01-01

    The quantity of α-L-fucosidase in human serum is determined by heredity. The mechanism controlling levels of the enzyme in serum is unknown. To investigate this, lymphoid cell lines derived from individuals with either low, intermediate or high α-L-fucosidase in serum were established. Steady state levels of extracellular α-L-fucosidase protein and activity overlapped among the cell lines. Thus, in vivo serum phenotypes of α-L-fucosidase are not adequately expressed in this system. α-L-Fucosidase was also metabolically labelled with 35 S-methionine, immunoprecipitated, and examined by SDS-PAGE. Cells pulse-labelled from 0.25-2 h had a major intracellular form of enzyme (Mr = 58,000). Cells pulsed for 1.5 h and chased for 21 h with unlabeled methionine had an intracellular form of Mr = 60,000 and an extracellular form of Mr = 62,000. Cells treated with chloroquine had only the 58,000-form both intra- and extra-cellularly. Moreover, chloroquine did not effect the quantitative distribution of α-L-fucosidase between cells and medium. In fibroblasts, chloroquine enhanced the secretion of newly made lysosomal enzymes and blocked the processing of intercellular enzyme forms from a higher to a lower molecular mass. Thus, there are trafficking differences between α-L-fucosidase in lymphoid cells and lysosomal enzymes in fibroblasts. This suggests that alternative targeting mechanisms for lysosomal enzymes exist in these cells

  6. Gut-associated Lymphoid Tissue (GALT) Carcinoma or Dome Carcinoma?

    Science.gov (United States)

    Rubio, Carlos A; Schmidt, Peter T

    2016-10-01

    The vast majority of colorectal carcinomas (CRCs) evolve from mucosa not associated to lymphoid tissues aggregates via the adenoma-carcinoma sequence or via the serrated pathway. Rarely CRCs evolve from gut mucosa associated to lymphoid tissue (GALT). Based on the presence of a circumscribed elevation in the colorectal mucosa, GALT carcinomas are also referred to as dome carcinomas (DC). Descriptions of the surface mucosa covering 21 GALT-CRCs appearing in pathological reports were reviewed. Three of the 21 GALT-CRCs fulfilled the criteria of dome carcinoma. Of the remaining 18 GALT-CRCs, nine were described as polypoid lesions, five as plaque-like lesions, two as sessile elevated lesions or mass, one as ulcerated and one as histological finding. Hence, only 14.3% (n=3) of the 21 GALT-CRCs displayed a dome configuration, whereas the majority, 85.7% (n=18), exhibited structures other than dome shapes at gross or at histologic examination. It becomes apparent that by using "dome" in addressing carcinomas in the colorectal mucosa, many cases of GALT carcinomas might be overlooked. Another drawback of using the "dome" nomenclature is that dome-like outlines may be detected in small metastatic tumors in the submucosa or in small colorectal carcinomas not arising from GALT mucosa. Instead, by using "GALT carcinoma", that is the histologic diagnosis in addressing these neoplasias, all cases of GALT-CRCs will be included. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  7. Treatment of intractable rheumatoid arthritis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Kotzin, B.L.; Strober, S.; Engleman, E.G.; Calin, A.; Hoppe, R.T.; Kansas, G.S.; Terrell, C.P.; Kaplan, H.S.

    1981-01-01

    Eleven patients with intractable rheumatoid arthritis were treated with total lymphoid irradiation (total dose, 2000 rad) in an uncontrolled feasibility study, as an alternative to long-term therapy with cytotoxic drugs such as cyclophosphamide and azathioprine. During a follow-up period of five to 18 months after total lymphoid irradiation, there was a profound and sustained suppression of the absolute lymphocyte count and in vitro lymphocyte function, as well as an increase in the ratio of Leu-2 (suppressor/cytotoxic) to Leu-3 (helper) T cells in the blood. Persistent circulating suppressor cells of the mixed leukocyte response and of pokeweed mitogen-induced immunoglobulin secretion developed in most patients. In nine of the 11 patients, these changes in immune status were associated with relief of joint tenderness and swelling and with improvement in function scores. Maximum improvement occurred approximately six months after irradiation and continued for the remainder of the observation period. Few severe or chronic side effects were associated with the radiotherapy

  8. High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function

    Science.gov (United States)

    Ager, Ann

    2017-01-01

    The blood vasculature regulates both the development and function of secondary lymphoid organs by providing a portal for entry of hemopoietic cells. During the development of lymphoid organs in the embryo, blood vessels deliver lymphoid tissue inducer cells that initiate and sustain the development of lymphoid tissues. In adults, the blood vessels are structurally distinct from those in other organs due to the requirement for high levels of lymphocyte recruitment under non-inflammatory conditions. In lymph nodes (LNs) and Peyer’s patches, high endothelial venules (HEVs) especially adapted for lymphocyte trafficking form a spatially organized network of blood vessels, which controls both the type of lymphocyte and the site of entry into lymphoid tissues. Uniquely, HEVs express vascular addressins that regulate lymphocyte entry into lymphoid organs and are, therefore, critical to the function of lymphoid organs. Recent studies have demonstrated important roles for CD11c+ dendritic cells in the induction, as well as the maintenance, of vascular addressin expression and, therefore, the function of HEVs. Tertiary lymphoid organs (TLOs) are HEV containing LN-like structures that develop inside organized tissues undergoing chronic immune-mediated inflammation. In autoimmune lesions, the development of TLOs is thought to exacerbate disease. In cancerous tissues, the development of HEVs and TLOs is associated with improved patient outcomes in several cancers. Therefore, it is important to understand what drives the development of HEVs and TLOs and how these structures contribute to pathology. In several human diseases and experimental animal models of chronic inflammation, there are some similarities between the development and function of HEVs within LN and TLOs. This review will summarize current knowledge of how hemopoietic cells with lymphoid tissue-inducing, HEV-inducing, and HEV-maintaining properties are recruited from the bloodstream to induce the development and

  9. Immunological and clinical observations in diabetic kidney graft recipients pretreated with total-lymphoid irradiation

    International Nuclear Information System (INIS)

    Waer, M.; Vanrenterghem, Y.; Roels, L.

    1987-01-01

    In a feasibility study, twenty patients with end-stage diabetic nephropathy were treated with fractionated total-lymphoid irradiation (TLI, mean dose 25 Gy), before transplantation of a first cadaveric kidney. During radiotherapy, only one patient had a serious side effect (bone marrow depression). After transplantation four patients died (one of a myocardial infarction, one of ketoacidosis, and two of infections occurring during treatment of rejection crises). One graft was lost because of chronic rejection. The other 15 patients have a functioning graft (mean follow-up 24 months) and receive low-dose prednisone alone (less than 10 mg/day, n = 11) or in conjunction with cyclosporine (n = 4) as maintenance immunosuppressive therapy. A favorable clinical outcome after TLI (no, or only one, steroid-sensitive rejection crisis) was significantly correlated with a high pre-TLI helper/suppressor lymphocyte ratio, a short interval between TLI and the time of transplantation, and the occurrence of functional suppressor cells early after TLI. The most striking immunological changes provoked by TLI consisted of a long-term depression of the mixed lymphocyte reaction and of the phytohemagglutinin, and Concanavalin A or pokeweed-mitogen-induced blastogenesis. A rapid and complete recovery of the natural killer cell activity was observed after TLI. A permanent inversion of the OKT4+ (T helper/inducer) over OKT8+ (T suppressor/cytotoxic) lymphocyte ratio was provoked by a decrease of the OTK4+ subpopulation, together with a supranormal recovery of the OKT8+ lymphocytes. A majority of the latter lymphocytes did also express the Leu 7 and the Leu 15 phenotype

  10. Questioning the social intelligence hypothesis.

    Science.gov (United States)

    Holekamp, Kay E

    2007-02-01

    The social intelligence hypothesis posits that complex cognition and enlarged "executive brains" evolved in response to challenges that are associated with social complexity. This hypothesis has been well supported, but some recent data are inconsistent with its predictions. It is becoming increasingly clear that multiple selective agents, and non-selective constraints, must have acted to shape cognitive abilities in humans and other animals. The task now is to develop a larger theoretical framework that takes into account both inter-specific differences and similarities in cognition. This new framework should facilitate consideration of how selection pressures that are associated with sociality interact with those that are imposed by non-social forms of environmental complexity, and how both types of functional demands interact with phylogenetic and developmental constraints.

  11. Whiplash and the compensation hypothesis.

    Science.gov (United States)

    Spearing, Natalie M; Connelly, Luke B

    2011-12-01

    Review article. To explain why the evidence that compensation-related factors lead to worse health outcomes is not compelling, either in general, or in the specific case of whiplash. There is a common view that compensation-related factors lead to worse health outcomes ("the compensation hypothesis"), despite the presence of important, and unresolved sources of bias. The empirical evidence on this question has ramifications for the design of compensation schemes. Using studies on whiplash, this article outlines the methodological problems that impede attempts to confirm or refute the compensation hypothesis. Compensation studies are prone to measurement bias, reverse causation bias, and selection bias. Errors in measurement are largely due to the latent nature of whiplash injuries and health itself, a lack of clarity over the unit of measurement (specific factors, or "compensation"), and a lack of appreciation for the heterogeneous qualities of compensation-related factors and schemes. There has been a failure to acknowledge and empirically address reverse causation bias, or the likelihood that poor health influences the decision to pursue compensation: it is unclear if compensation is a cause or a consequence of poor health, or both. Finally, unresolved selection bias (and hence, confounding) is evident in longitudinal studies and natural experiments. In both cases, between-group differences have not been addressed convincingly. The nature of the relationship between compensation-related factors and health is unclear. Current approaches to testing the compensation hypothesis are prone to several important sources of bias, which compromise the validity of their results. Methods that explicitly test the hypothesis and establish whether or not a causal relationship exists between compensation factors and prolonged whiplash symptoms are needed in future studies.

  12. Autoimmunity and asthma: The dirt on the hygiene hypothesis.

    Science.gov (United States)

    Mannie, Mark D

    2010-04-01

    Self peptides shape T-cell development through selectional processes in the thymus and secondary lymphoid organs to promote a diverse and balanced repertoire of conventional and regulatory T cells. Foreign proteins and their derivative peptides permeate our mucosal tissues to constitute another diverse array of peptides that may specify and diversify the mucosal T-cell repertoire. Indeed, the distinction between self peptides and environmental foreign peptides may be academic if both are present constantly within the body. The premise here is that the plethora of foreign peptides, present ubiquitously in our environment and body, form homeostatic niches to foster highly diversified repertoires of conventional and regulatory T cells that recognize persistent environmental peptides as self. Highly diversified repertoires that recognize myriads of self and environmental foreign peptides as homeostatic ligands may be critical for adaptive distinctions of friend or foe in mucosal tissues. The change from our agrarian past to the highly sterile environments of today may adversely impact the diversity and concentrations of foreign peptides that shape the mucosal T-cell repertoire. Various hygiene hypotheses postulate that the lack of factors such as infectious pathogens, innate receptor engagement or Th1 bias is key to the marked increase in immunological disease in modern society. In this version of the hygiene hypothesis, highly diverse constellations of innocuous environmental peptides are postulated to be the critical factor for immune balance and homeostasis.

  13. Prolonged heart xenograft survival using combined total lymphoid irradiation and cyclosporine

    International Nuclear Information System (INIS)

    Knechtle, S.J.; Halperin, E.C.; Saad, T.; Bollinger, R.R.

    1986-01-01

    Total lymphoid irradiation and cyclosporine have profound immunosuppressive properties and permit successful heart allotransplantation. Cyclosporine used alone has not permitted consistently successful transplantation between species in all cases. Total lymphoid irradiation has not been applied to xenotransplantation. The efficacy of total lymphoid irradiation alone and in combination with cyclosporine was examined using an animal model of heart xenotransplantation. Heterotopic heart transplants were performed using inbred Syrian hamsters as donors and Lewis rats as recipients. Total lymphoid irradiation was administered preoperatively over 3 weeks for a total dose of 15 gray. Cyclosporine was started on the day of surgery and was given as a daily intramuscular injection of 2.5, 5, or 10 mg/kg/day until rejection was complete. Neither total lymphoid irradiation nor cyclosporine alone markedly prolonged graft survival. However, combined total lymphoid irradiation and cyclosporine, 5 or 10 mg/kg/day, dramatically prolonged graft survival to greater than 100 days in most recipients. There were no treatment-related deaths. In conclusion, combined total lymphoid irradiation and cyclosporine permit successful long-term survival of heart xenotransplants in this hamster-to-rat model

  14. Immunosuppression and tolerance after total lymphoid irradiation (TLI)

    International Nuclear Information System (INIS)

    Strober, S.; Gottlieb, M.; Slavin, S.; King, D.P.; Hoppe, R.T.; Fuks, Z.; Bieber, C.P.; Kaplan, H.S.

    1980-01-01

    The immunosuppressive effects of total lymphoid irradiation (TLI) in humans and in several species of inbred and outbred laboratory animals have been investigated. A unique property of TLI, the prevention of the graft vs. host disease, was used to induce transplantation tolerance in order to study the mechanism of altered immunity when the celluar basis of the TLI-induced immunosuppression was examined by means of the mixed lymphocyte response (MLR), no suppression of the MLR was observed when spleen cells from unirradiated or whole body-irradiated donors were used instead of donors given TLI. These results indicated that TLI induces a population of cells in the spleen that can nonspecifically suppress the MLR

  15. Innate Lymphoid Cell Biology: Lessons Learnt from Natural Killer Cells

    Directory of Open Access Journals (Sweden)

    Yuhao Jiao

    2016-10-01

    Full Text Available Group 1 innate lymphoid cells (ILC comprise the natural killer (NK cells and ILC1 which reside within peripheral tissues. Several different ILC1 subsets have recently been characterised, however no unique markers to define these subsets have been identified. Whether ILC1 and NK cells are in fact distinct lineages, or alternately exhibit transitional molecular programs, that allow them to adapt to different tissue niches remains an open question. NK cells are the prototypic member of the Group 1 ILC and have been historically assigned the functions of what now appears to be a multi-subset family that are distributed throughout the body. This raises the question of whether each of these populations mediate distinct functions during infection and tumour immunosurveillance. Here, we review the diversity in the Group 1 ILC subsets with regards to their transcriptional regulation, localization, mobility and receptor expression and highlight the challenges in unraveling the individual functions of these different populations of cells.

  16. Innate lymphoid cells in autoimmunity and chronic inflammatory diseases.

    Science.gov (United States)

    Xiong, Tingting; Turner, Jan-Eric

    2018-03-22

    Abnormal activation of the innate immune system is a common feature of autoimmune and chronic inflammatory diseases. Since their identification as a separate family of leukocytes, innate lymphoid cells (ILCs) have emerged as important effector cells of the innate immune system. Alterations in ILC function and subtype distribution have been observed in a variety of immune-mediated diseases in humans and evidence from experimental models suggests a subtype specific role of ILCs in the pathophysiology of autoimmune inflammation. In this review, we discuss recent advances in the understanding of ILC biology in autoimmune and chronic inflammatory disorders, including multiple sclerosis, inflammatory bowel diseases, psoriasis, and rheumatic diseases, with a special focus on the potential of ILCs as therapeutic targets for the development of novel treatment strategies in humans.

  17. Role of Type 2 Innate Lymphoid Cells in Allergic Diseases.

    Science.gov (United States)

    Cosmi, Lorenzo; Liotta, Francesco; Maggi, Laura; Annunziato, Francesco

    2017-09-11

    The adaptive immune response orchestrated by type 2 T helper (Th2) lymphocytes, strictly cooperates with the innate response of group 2 innate lymphoid cells (ILC2), in the protection from helminths infection, as well as in the pathogenesis of allergic disease. The aim of this review is to explore the pathogenic role of ILC2 in different type 2-mediated disorders. Recent studies have shown that epithelial cell-derived cytokines and their responding cells, ILC2, play a pathogenic role in bronchial asthma, chronic rhinosinusitis, and atopic dermatitis. The growing evidences of the contribution of ILC2 in the induction and maintenance of allergic inflammation in such disease suggest the possibility to target them in therapy. Biological therapies blocking ILC2 activation or neutralizing their effector cytokines are currently under evaluation to be used in patients with type 2-dominated diseases.

  18. Innate Lymphoid Cells: A Promising New Regulator in Fibrotic Diseases.

    Science.gov (United States)

    Zhang, Yi; Tang, Jun; Tian, Zhiqiang; van Velkinburgh, Jennifer C; Song, Jianxun; Wu, Yuzhang; Ni, Bing

    2016-09-02

    Fibrosis is a consequence of chronic inflammation and the persistent accumulation of extracellular matrix, for which the cycle of tissue injury and repair becomes a predominant feature. Both the innate and adaptive immune systems play key roles in the progress of fibrosis. The recently identified subsets of innate lymphoid cells (ILCs), which are mainly localize to epithelial surfaces, have been characterized as regulators of chronic inflammation and tissue remodeling, representing a functional bridge between the innate and adaptive immunity. Moreover, recent research has implicated ILCs as potential contributing factors to several kinds of fibrosis diseases, such as hepatic fibrosis and pulmonary fibrosis. Here, we will summarize and discuss the key roles of ILCs and their related factors in fibrotic diseases and their potential for translation to the clinic.

  19. Innate Lymphoid Cells: a new paradigm in immunology

    Science.gov (United States)

    Eberl, Gérard; Colonna, Marco; Di Santo, James P.; McKenzie, Andrew N.J.

    2016-01-01

    Summary Innate lymphoid cells (ILCs) are a growing family of immune cells that mirror the phenotypes and functions of T cells. However, in contrast to T cells, ILCs do not express acquired antigen receptors or undergo clonal selection and expansion when stimulated. Instead, ILCs react promptly to signals from infected or injured tissues and produce an array of secreted proteins termed cytokines that direct the developing immune response into one that is adapted to the original insult. The complex crosstalk between microenvironment, ILCs and adaptive immunity remains to be fully deciphered. Only by understanding these complex regulatory networks can the power of ILCs be controlled or unleashed to regulate or enhance immune responses in disease prevention and therapy. PMID:25999512

  20. Migration and Tissue Tropism of Innate Lymphoid Cells

    Science.gov (United States)

    Kim, Chang H.; Hashimoto-Hill, Seika; Kim, Myunghoo

    2016-01-01

    Innate lymphoid cell (ILCs) subsets differentially populate various barrier and non-barrier tissues, where they play important roles in tissue homeostasis and tissue-specific responses to pathogen attack. Recent findings have provided insight into the molecular mechanisms that guide ILC migration into peripheral tissues, revealing common features among different ILC subsets as well as important distinctions. Recent studies have also highlighted the impact of tissue-specific cues on ILC migration, and the importance of the local immunological milieu. We review these findings here and discuss how the migratory patterns and tissue tropism of different ILC subsets relate to the development and differentiation of these cells, and to ILC-mediated tissue-specific regulation of innate and adaptive immune responses. In this context we outline open questions and important areas of future research. PMID:26708278

  1. Development and function of secondary and tertiary lymphoid organs in the small intestine and the colon

    Directory of Open Access Journals (Sweden)

    Manuela Buettner

    2016-09-01

    Full Text Available The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer’s patches (PP in the small intestine and their colonic counterparts that develop in a programmed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT. In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP to large, mature isolated lymphoid follicles (ILF. Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi cells and the requirement for lymphotoxin beta (LTβ receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO. While so far it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation.

  2. Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon

    Science.gov (United States)

    Buettner, Manuela; Lochner, Matthias

    2016-01-01

    The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer’s patches (PP) in the small intestine and their colonic counterparts that develop in a programed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT). In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP) to large, mature isolated lymphoid follicles (ILF). Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi) cells and the requirement for lymphotoxin beta (LTβ) receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO). While, so far, it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation. PMID

  3. Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon.

    Science.gov (United States)

    Buettner, Manuela; Lochner, Matthias

    2016-01-01

    The immune system of the gut has evolved a number of specific lymphoid structures that contribute to homeostasis in the face of microbial colonization and food-derived antigenic challenge. These lymphoid organs encompass Peyer's patches (PP) in the small intestine and their colonic counterparts that develop in a programed fashion before birth. In addition, the gut harbors a network of lymphoid tissues that is commonly designated as solitary intestinal lymphoid tissues (SILT). In contrast to PP, SILT develop strictly after birth and consist of a dynamic continuum of structures ranging from small cryptopatches (CP) to large, mature isolated lymphoid follicles (ILF). Although the development of PP and SILT follow similar principles, such as an early clustering of lymphoid tissue inducer (LTi) cells and the requirement for lymphotoxin beta (LTβ) receptor-mediated signaling, the formation of CP and their further maturation into ILF is associated with additional intrinsic and environmental signals. Moreover, recent data also indicate that specific differences exist in the regulation of ILF formation between the small intestine and the colon. Importantly, intestinal inflammation in both mice and humans is associated with a strong expansion of the lymphoid network in the gut. Recent experiments in mice suggest that these structures, although they resemble large, mature ILF in appearance, may represent de novo-induced tertiary lymphoid organs (TLO). While, so far, it is not clear whether intestinal TLO contribute to the exacerbation of inflammatory pathology, it has been shown that ILF provide the critical microenvironment necessary for the induction of an effective host response upon infection with enteric bacterial pathogens. Regarding the importance of ILF for intestinal immunity, interfering with the development and maturation of these lymphoid tissues may offer novel means for manipulating the immune response during intestinal infection or inflammation.

  4. Role of lymphotoxin and homeostatic chemokines in the development and function of local lymphoid tissues in the respiratory tract.

    Science.gov (United States)

    Rangel-Moreno, Javier; Carragher, Damian; Randall, Troy D

    2007-01-01

    Secondary lymphoid organs are strategically placed to recruit locally activated antigen presenting cells (APCs) as well as naïve, recirculating T and B cells. The structure of secondary lymphoid organs - separated B and T zones, populations of specialized stromal cells, high endothelial venules and lymphatic vessles - has also evolved to maximize encounters between APCs and lymphocytes and to facilitate the expansion and differentiation of antigen-stimulated T and B cells. Many of the general mechanisms that govern the development and organization of secondary lymphoid organs have been identified over the last decade. However, the specific cellular and molecular interactions involved in the development and organization of each secondary lymphoid organ are slightly different and probably reflect the cell types available at that time and location. Here we review the mechanisms involved in the development, organization and function of local lymphoid tissues in the respiratory tract, including Nasal Associated Lymphoid Tissue (NALT) and inducible Bronchus Associated Lymphoid Tissue (iBALT).

  5. A Molecular–Structure Hypothesis

    Directory of Open Access Journals (Sweden)

    Jan C. A. Boeyens

    2010-11-01

    Full Text Available The self-similar symmetry that occurs between atomic nuclei, biological growth structures, the solar system, globular clusters and spiral galaxies suggests that a similar pattern should characterize atomic and molecular structures. This possibility is explored in terms of the current molecular structure-hypothesis and its extension into four-dimensional space-time. It is concluded that a quantum molecule only has structure in four dimensions and that classical (Newtonian structure, which occurs in three dimensions, cannot be simulated by quantum-chemical computation.

  6. Antiaging therapy: a prospective hypothesis

    Directory of Open Access Journals (Sweden)

    Shahidi Bonjar MR

    2015-01-01

    Full Text Available Mohammad Rashid Shahidi Bonjar,1 Leyla Shahidi Bonjar2 1School of Dentistry, Kerman University of Medical Sciences, Kerman Iran; 2Department of Pharmacology, College of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran Abstract: This hypothesis proposes a new prospective approach to slow the aging process in older humans. The hypothesis could lead to developing new treatments for age-related illnesses and help humans to live longer. This hypothesis has no previous documentation in scientific media and has no protocol. Scientists have presented evidence that systemic aging is influenced by peculiar molecules in the blood. Researchers at Albert Einstein College of Medicine, New York, and Harvard University in Cambridge discovered elevated titer of aging-related molecules (ARMs in blood, which trigger cascade of aging process in mice; they also indicated that the process can be reduced or even reversed. By inhibiting the production of ARMs, they could reduce age-related cognitive and physical declines. The present hypothesis offers a new approach to translate these findings into medical treatment: extracorporeal adjustment of ARMs would lead to slower rates of aging. A prospective “antiaging blood filtration column” (AABFC is a nanotechnological device that would fulfill the central role in this approach. An AABFC would set a near-youth homeostatic titer of ARMs in the blood. In this regard, the AABFC immobilizes ARMs from the blood while blood passes through the column. The AABFC harbors antibodies against ARMs. ARM antibodies would be conjugated irreversibly to ARMs on contact surfaces of the reaction platforms inside the AABFC till near-youth homeostasis is attained. The treatment is performed with the aid of a blood-circulating pump. Similar to a renal dialysis machine, blood would circulate from the body to the AABFC and from there back to the body in a closed circuit until ARMs were sufficiently depleted from the blood. The

  7. Early Bronchus-Associated Lymphoid Tissue Lymphoma Diagnosed with Immunoglobulin Heavy Chain Molecular Testing

    Directory of Open Access Journals (Sweden)

    Pen Li

    2016-01-01

    Full Text Available When extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue (MALT, a low grade B-cell lymphoma, arises in the lung it is referred to as bronchus-associated lymphoid tissue (BALT lymphoma. We describe a patient with a history of Sjögren’s syndrome and rheumatoid arthritis with dyspnea and imaging consistent with lymphoid interstitial pneumonia (LIP. However, while histology and immunohistochemistry lacked definitive features of a lymphoma, immunoglobulin heavy chain (IgH polymerase chain reaction testing demonstrated B-cell monoclonality, consistent with an early BALT lymphoma.

  8. The effect of ionizing radiation on lipid metabolism in lymphoid cells

    International Nuclear Information System (INIS)

    Kolomiytseva, I.K.; Novoselova, E.G.; Kulagina, T.P.; Kuzin, A.M.

    1987-01-01

    Lipid metabolism was studied in lymphoid tissues of rats after whole body irradiation with doses producing damage of different degrees to lymphoid cells (4-10 Gy). The content of free cholesterol, cholesterol esters, and total phospholipids was determined in peripheral blood lymphocytes and thymocytes 1-2 h after exposure. Simultaneously, the rate of in vitro incorporation of 2 14 C-acetate into total lipids, phospholipids, and cholesterol of lymphoid cells was estimated. It was shown that exposure of rats to ionizing radiation caused activation of lipogenesis. Cholesterol synthesis was activated after a dose of 4 Gy and decreased with increasing dose. (author)

  9. Long-term survival of skin allografts in mice treated with fractionated total lymphoid irradiation

    International Nuclear Information System (INIS)

    Slavin, S.; Strober, S.; Fuks, Z.; Kaplan, H.S.

    1976-01-01

    Treatment of recipient Balb/c mice with fractionated, high-dose total lymphoid irradiation, a procedure commonly used in the therapy of human malignant lymphomas, resulted in fivefold prolongation of the survival of C57BL/Ka skin allografts despite major histocompatibility differences between the strains (H-2/sup d/ and H-2/sup b/, respectively). Infusion of 10 7 (C57BL/Ka x Balb/c)F 1 bone marrow cells after total lymphoid irradiation further prolonged C57BL/Ka skin graft survival to more than 120 days. Total lymphoid irradiation may eventually prove useful in clinical organ transplantation

  10. Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation.

    Science.gov (United States)

    Emgård, Johanna; Kammoun, Hana; García-Cassani, Bethania; Chesné, Julie; Parigi, Sara M; Jacob, Jean-Marie; Cheng, Hung-Wei; Evren, Elza; Das, Srustidhar; Czarnewski, Paulo; Sleiers, Natalie; Melo-Gonzalez, Felipe; Kvedaraite, Egle; Svensson, Mattias; Scandella, Elke; Hepworth, Matthew R; Huber, Samuel; Ludewig, Burkhard; Peduto, Lucie; Villablanca, Eduardo J; Veiga-Fernandes, Henrique; Pereira, João P; Flavell, Richard A; Willinger, Tim

    2018-01-16

    Group 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Is PMI the Hypothesis or the Null Hypothesis?

    Science.gov (United States)

    Tarone, Aaron M; Sanford, Michelle R

    2017-09-01

    Over the past several decades, there have been several strident exchanges regarding whether forensic entomologists estimate the postmortem interval (PMI), minimum PMI, or something else. During that time, there has been a proliferation of terminology reflecting this concern regarding "what we do." This has been a frustrating conversation for some in the community because much of this debate appears to be centered on what assumptions are acknowledged directly and which are embedded within a list of assumptions (or ignored altogether) in the literature and in case reports. An additional component of the conversation centers on a concern that moving away from the use of certain terminology like PMI acknowledges limitations and problems that would make the application of entomology appear less useful in court-a problem for lawyers, but one that should not be problematic for scientists in the forensic entomology community, as uncertainty is part of science that should and can be presented effectively in the courtroom (e.g., population genetic concepts in forensics). Unfortunately, a consequence of the way this conversation is conducted is that even as all involved in the debate acknowledge the concerns of their colleagues, parties continue to talk past one another advocating their preferred terminology. Progress will not be made until the community recognizes that all of the terms under consideration take the form of null hypothesis statements and that thinking about "what we do" as a null hypothesis has useful legal and scientific ramifications that transcend arguments over the usage of preferred terminology. © The Authors 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. The Stoichiometric Divisome: A Hypothesis

    Directory of Open Access Journals (Sweden)

    Waldemar eVollmer

    2015-05-01

    Full Text Available Dividing Escherichia coli cells simultaneously constrict the inner membrane, peptidoglycan layer and outer membrane to synthesize the new poles of the daughter cells. For this, more than 30 proteins localize to mid-cell where they form a large, ring-like assembly, the divisome, facilitating division. Although the precise function of most divisome proteins is unknown, it became apparent in recent years that dynamic protein-protein interactions are essential for divisome assembly and function. However, little is known about the nature of the interactions involved and the stoichiometry of the proteins within the divisome. A recent study (Li et al., 2014 used ribosome profiling to measure the absolute protein synthesis rates in E. coli. Interestingly, they observed that most proteins which participate in known multiprotein complexes are synthesized proportional to their stoichiometry. Based on this principle we present a hypothesis for the stoichiometry of the core of the divisome, taking into account known protein-protein interactions. From this hypothesis we infer a possible mechanism for PG synthesis during division.

  13. Tissue Pharmacologic and Virologic Determinants of Duodenal and Rectal Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution in HIV-Infected Patients Initiating Antiretroviral Therapy.

    Science.gov (United States)

    Asmuth, David M; Thompson, Corbin G; Chun, Tae-Wook; Ma, Zhong-Min; Mann, Surinder; Sainz, Talia; Serrano-Villar, Sergio; Utay, Netanya S; Garcia, Juan Carlos; Troia-Cancio, Paolo; Pollard, Richard B; Miller, Christopher J; Landay, Alan; Kashuba, Angela D

    2017-10-17

    Plasma, duodenal, and rectal tissue antiretroviral therapy (ART) drug concentrations, human immunodeficiency virus (HIV) RNA and HIV DNA copy numbers, and recovery of mucosal immunity were measured before and 9 months after initiation of 3 different ART regimens in 26 subjects. Plasma and tissue HIV RNA correlated at baseline and when 9-month declines were compared, suggesting that these compartments are tightly associated. Antiretroviral tissue:blood penetration ratios were above the 50% inhibitory concentration values in almost 100% of cases. There were no correlations between drug concentrations and HIV DNA/RNA. Importantly, no evidence was found for residual viral replication or deficient tissue drug penetration to account for delayed gastrointestinal-associated lymphoid tissue immune recovery. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  14. The interbranchial lymphoid tissue of Atlantic Salmon (Salmo salar L) extends as a diffuse mucosal lymphoid tissue throughout the trailing edge of the gill filament

    DEFF Research Database (Denmark)

    Dalum, Alf S; Austbø, Lars; Bjørgen, Håvard

    2015-01-01

    in all gill segments investigated. Numerous major histocompatibility complex class II(+) -cells were distributed uniformly throughout the filament epithelial tissue. Few Ig(+) -cells were detected. Overall, the morphological features and comparable immune gene expression of the previously described ILT......The teleost gill forms an extensive, semipermeable barrier that must tolerate intimate contact with the surrounding environment and be able to protect the body from external pathogens. The recent discovery of the interbranchial lymphoid tissue (ILT) has initiated an anatomical and functional...... investigation of the lymphoid tissue of the salmonid gill. In this article, sectioning of gill arches in all three primary planes revealed an elongation of the ILT outward along the trailing edge of the primary filament to the very distal end, a finding not previously described. This newly found lymphoid tissue...

  15. Lymphotoxin organizes contributions to host defense and metabolic illness from innate lymphoid cells.

    Science.gov (United States)

    Upadhyay, Vaibhav; Fu, Yang-Xin

    2014-04-01

    The lymphotoxin (LT)-pathway is a unique constituent branch of the Tumor Necrosis Superfamily (TNFSF). Use of LT is a critical mechanism by which fetal innate lymphoid cells regulate lymphoid organogenesis. Within recent years, adult innate lymphoid cells have been discovered to utilize this same pathway to regulate IL-22 and IL-23 production for host defense. Notably, genetic studies have linked polymorphisms in the genes encoding LTα to several phenotypes contributing to metabolic syndrome. The role of the LT-pathway may lay the foundation for a bridge between host immune response, microbiota, and metabolic syndrome. The contribution of the LT-pathway to innate lymphoid cell function and metabolic syndrome will be visited in this review. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Characterization of lymphoid cells in the blood of healthy adults: sequential immunological, cytochemical and cytokinetic studies

    International Nuclear Information System (INIS)

    Hirt, A.; Wagner, H.P.

    1980-01-01

    With a new method, sequential immunological, cytochemical and cytokinetic studies were done on lymphoid cells in the peripheral blood of 12 healthy adults. Every single lymphoid cell could therefore be characterized by the following markers: surface immunoglobulins (sIg); rosetting with sheep red blood cells (E); unspecific acid alpha-naphthyl acetate esterase (ANAE); and 3HdT incorporation. Significantly more E+sIg-ANAE-cells (51% and 22% of all lymphoid cells, respectively). Of all ANAE+ cells 90% were E+, but 64% of all ANAE- cells were also E+. In all individuals a subpopulation of E+sIg+ cells was found. The esterase pattern of these cells was similar to that of E-sIg+ cells. The overall labeling index of the lymphoid cells examined was less than or equal to 0.2%

  17. Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma with a Nodular Opacity: Report of a Case.

    Science.gov (United States)

    Yoshino, Naoyuki; Hirata, Tomomi; Takeuchi, Chie; Usuda, Jitsuo; Hosone, Masaru

    2017-01-01

    Herein, we describe our experience in treating a case of primary pulmonary mucosa-associated lymphoid tissue lymphoma detected as a nodular opacity. A 79-year-old man was referred to our hospital. Computed tomography showed a nodular opacity measuring 20 mm in diameter with regular margins in segment 5 of the right middle lobe of the lung. Although the bronchoscopic brush cytology result was class III, the patient was tentatively diagnosed with suspected mucosa-associated lymphoid tissue lymphoma. A thoracoscopic right middle lobectomy was performed. The pathological findings showed nodular proliferation of small to medium-sized, mature-appearing atypical lymphoid cells, lymphoepithelial lesions, and vague follicles suggesting follicular colonization in some areas. The patient was diagnosed with low-grade small B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma. He has remained well to date, 23 months after surgery, without evidence of recurrence.

  18. Spectrum of lymphoid hyperplasia: colonic manifestations of sarcoidosis, infectious mononucleosis, and Crohn's disease

    Energy Technology Data Exchange (ETDEWEB)

    Ell, S.R.; Frank, P.H.

    1981-10-15

    The radiographic pattern of nodular lymphoid hyperplasia, perhaps better called the lymphoid follicular pattern, has variously been described as an indication of disease and as a normal variant in the adult, with current opinion favoring the latter. We report 3 cases wherein this pattern resulted from definite pathologic processes: sarcoidosis, infectious mononucleosis, and Crohn's disease. Although usually of no pathological significance, the benign follicular pattern may reflect a variety of diseases.

  19. Colonization and effector functions of innate lymphoid cells in mucosal tissues

    Science.gov (United States)

    Kim, Myunghoo; Kim, Chang H.

    2016-01-01

    Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. PMID:27365193

  20. Characterization of membranous (M) cells in normal feline conjunctiva-associated lymphoid tissue (CALT).

    Science.gov (United States)

    Giuliano, Elizabeth A; Finn, Kevin

    2011-09-01

    To characterize conjunctival lymphoid nodules obtained from the nictitans of healthy cats to determine if the follicle-associated epithelium (FAE) of conjunctiva-associated lymphoid tissue (CALT) in this species contains membranous (M)-cells analogous to those described in other regions of mucosa-associated lymphoid tissue (MALT). Lymphoid follicles from nictitan bulbar surfaces of 10 healthy cats (20 eyes total) were examined. Nictitans from five cats were harvested immediately post-mortem and a minimum of 12 lymphoid nodules from each third eyelid were isolated using a Zeiss operating microscope. At least three lymphoid follicles from each eye were examined using light microscopy (LM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM) using standard fixation and embedding protocols. Nictitan-lymphoid follicles from another five healthy cats were processed for immunohistochemistry to characterize the distribution of T- and B-lymphocytes present beneath the FAE. The FAE overlying CALT from 10 healthy cats demonstrated morphology characteristic of M-cells including attenuated apical cell surface with blunted microvilli and microfolds, invaginated basolateral membrane forming a cytoplasmic pocket, and diminished distance between the apical and pocket membrane. Immunohistochemistry of lymphoid tissue subtending the FAE demonstrated B-cell dependent regions in the germinal centers surrounded by T-cell dependent interfollicular zones. Healthy feline CALT contains morphologic features analogous to those described in other regions of MALT. Documentation of feline conjunctival M-cells is of clinical relevance in the study of primary infectious, allergic, and autoimmune ocular diseases, as well as a potential means of vaccination or drug delivery. © 2011 American College of Veterinary Ophthalmologists.

  1. Metabolic and physiologic studies of nonimmune lymphoid cells cytotoxic for fibroblastic cells in vitro

    International Nuclear Information System (INIS)

    Mayhew, E.; Bennett, M.

    1974-01-01

    An in vitro reaction between mouse lymphoid cells and target fibroblastic cells in wells of microtest plates, which appears to simulate the in vivo rejection of hemopoietic allografts, has been analyzed for metabolic and physiologic requirements. Protein synthesis was required for only the first few hours of culture. Inhibition of RNA synthesis and alteration of cell surface charge with various agents were without obvious effects. Metabolic slowing at 4 0 C or deviation of the pH of the culture medium suppressed the reaction. Thymus cells, which are not cytotoxic in this system, significantly but not completely inhibited the cytotoxicity of lymph node cells. Antiserum directed against target cells specifically protected them from the cytotoxic lymphoid cells in the absence of complement. Precursors of cytotoxic lymphoid cells were radiosensitive, unlike the cytotoxic cells themselves. BALB/c anti-C57BL/6 spleen cell serum and 89 Sr both are able to prevent rejection of marrow allografts in vivo. Lymphoid cells incubated with this antiserum plus complement lost much of their cytotoxicity but were still effective at high ratios of aggressor to target cells. Lymphoid cells of mice treated with 89 Sr were effectively cytotoxic but lost practically all of their cytotoxicity after incubation with the antiserum plus complement. Thus, it appears that this reaction detects two different cytotoxic lymphoid cells, either of which can function in vitro. Both cell types may need to cooperate in vivo during marrow allograft rejections

  2. A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells.

    Science.gov (United States)

    Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom

    2015-11-01

    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs. Copyright © 2015 by The American Association of Immunologists, Inc.

  3. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    Science.gov (United States)

    van de Pavert, Serge A.; Ferreira, Manuela; Domingues, Rita G.; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F.; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R.; Habani, Yasmin; Haak, Esther; Santori, Fabio R.; Littman, Dan R.; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J. Pedro; Mebius, Reina E.; Veiga-Fernandes, Henrique

    2014-04-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally programmed. Secondary lymphoid organ formation depends on a subset of type 3 innate lymphoid cells (ILC3) named lymphoid tissue inducer (LTi) cells. Here we show that mouse fetal ILC3s are controlled by cell-autonomous retinoic acid (RA) signalling in utero, which pre-sets the immune fitness in adulthood. We found that embryonic lymphoid organs contain ILC progenitors that differentiate locally into mature LTi cells. Local LTi cell differentiation was controlled by maternal retinoid intake and fetal RA signalling acting in a haematopoietic cell-autonomous manner. RA controlled LTi cell maturation upstream of the transcription factor RORγt. Accordingly, enforced expression of Rorgt restored maturation of LTi cells with impaired RA signalling, whereas RA receptors directly regulated the Rorgt locus. Finally, we established that maternal levels of dietary retinoids control the size of secondary lymphoid organs and the efficiency of immune responses in the adult offspring. Our results reveal a molecular link between maternal nutrients and the formation of immune structures required for resistance to infection in the offspring.

  4. Flt3 Ligand Regulates the Development of Innate Lymphoid Cells in Fetal and Adult Mice.

    Science.gov (United States)

    Baerenwaldt, Anne; von Burg, Nicole; Kreuzaler, Matthias; Sitte, Selina; Horvath, Edit; Peter, Annick; Voehringer, David; Rolink, Antonius G; Finke, Daniela

    2016-03-15

    Flt3 ligand (Flt3L) promotes survival of lymphoid progenitors in the bone marrow and differentiation of dendritic cells (DCs), but its role in regulating innate lymphoid cells (ILCs) during fetal and adult life is not understood. By using Flt3L knockout and transgenic mice, we demonstrate that Flt3L controls ILC numbers by regulating the pool of α4β7(-) and α4β7(+) lymphoid tissue inducer cell progenitors in the fetal liver and common lymphoid progenitors in the bone marrow. Deletion of flt3l severely reduced the number of fetal liver progenitors and lymphoid tissue inducer cells in the neonatal intestine, resulting in impaired development of Peyer's patches. In the adult intestine, NK cells and group 2 and 3 ILCs were severely reduced. This effect occurred independently of DCs as ILC numbers were normal in mice in which DCs were constitutively deleted. Finally, we could show that administration of Flt3L increased the number of NKp46(-) group 3 ILCs in wild-type and even in Il7(-/-) mice, which generally have reduced numbers of ILCs. Taken together, Flt3L significantly contributes to ILC and Peyer's patches development by targeting lymphoid progenitor cells during fetal and adult life. Copyright © 2016 by The American Association of Immunologists, Inc.

  5. The Role of TOX in the Development of Innate Lymphoid Cells.

    Science.gov (United States)

    Seehus, Corey R; Kaye, Jonathan

    2015-01-01

    TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4(+) T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

  6. Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells.

    Science.gov (United States)

    Hoorweg, Kerim; Peters, Charlotte P; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M; Spits, Hergen; Cupedo, Tom

    2012-01-01

    Human RORC(+) lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC(+) innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC(+) innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44(+) IL-22 producing cells are present in tonsils while NKp44(-) IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44(+) ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44(+) ILC are the main ILC subset producing IL-22. NKp44(-) ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.

  7. The Role of TOX in the Development of Innate Lymphoid Cells

    Directory of Open Access Journals (Sweden)

    Corey R. Seehus

    2015-01-01

    Full Text Available TOX, an evolutionarily conserved member of the HMG-box family of proteins, is essential for the development of various cells of both the innate and adaptive immune system. TOX is required for the development of CD4+ T lineage cells in the thymus, including natural killer T and T regulatory cells, as well as development of natural killer cells and fetal lymphoid tissue inducer cells, the latter required for lymph node organogenesis. Recently, we have identified a broader role for TOX in the innate immune system, demonstrating that this nuclear protein is required for generation of bone marrow progenitors that have potential to give rise to all innate lymphoid cells. Innate lymphoid cells, classified according to transcription factor expression and cytokine secretion profiles, derive from common lymphoid progenitors in the bone marrow and require Notch signals for their development. We discuss here the role of TOX in specifying CLP toward an innate lymphoid cell fate and hypothesize a possible role for TOX in regulating Notch gene targets during innate lymphoid cell development.

  8. Immunophenotype of cells within cervine rectoanal mucosa-associated lymphoid tissue and mesenteric lymph nodes.

    Science.gov (United States)

    Dagleish, M P; Finlayson, J; Steele, P J; Pang, Y; Hamilton, S; Eaton, S L; Sales, J; González, L; Chianini, F

    2012-05-01

    Rectoanal mucosa-associated lymphoid tissue (RAMALT) is a part of the lymphoid system that can be sampled easily in live animals, especially ruminants. RAMALT biopsy is useful for the diagnosis of transmissible spongiform encephalopathies, including scrapie in sheep and goats and chronic wasting disease (CWD) in cervids. Diagnosis is reliant on detection of abnormal prion protein (PrP(d)), which is associated with lymphoid follicles. For enzyme linked immunosorbent assays (ELISAs) detecting PrP(d) it is necessary to ensure that lymphoid follicles are present in biopsy samples to avoid false-negative results. Monoclonal antibodies known to recognize specific immune cell subsets present in lymphoid tissues of sheep were tested for cross-reactivity with cervine RAMALT and mesenteric lymph nodes (MLNs) preserved in zinc salts fixative. The distribution of cells expressing CD3, CD4, CD79, CD21 and class II molecules of the major histocompatibility complex was determined in these tissues. Cells of each immunophenotype had similar distributions in RAMALT and MLNs and these distributions were similar to those reported previously for sheep and cattle. The identification and validation of cervine lymphoid follicle cell markers (CD79 and CD21) may allow reduction in false-negative results during diagnosis of CWD by ELISA. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Tertiary Lymphoid Structures in Cancer: Drivers of Antitumor Immunity, Immunosuppression, or Bystander Sentinels in Disease?

    Science.gov (United States)

    Colbeck, Emily Jayne; Ager, Ann; Gallimore, Awen; Jones, Gareth Wyn

    2017-01-01

    Secondary lymphoid organs are integral to initiation and execution of adaptive immune responses. These organs provide a setting for interactions between antigen-specific lymphocytes and antigen-presenting cells recruited from local infected or inflamed tissues. Secondary lymphoid organs develop as a part of a genetically preprogrammed process during embryogenesis. However, organogenesis of secondary lymphoid tissues can also be recapitulated in adulthood during de novo lymphoid neogenesis of tertiary lymphoid structures (TLSs). These ectopic lymphoid-like structures form in the inflamed tissues afflicted by various pathological conditions, including cancer, autoimmunity, infection, or allograft rejection. Studies are beginning to shed light on the function of such structures in different disease settings, raising important questions regarding their contribution to progression or resolution of disease. Data show an association between the tumor-associated TLSs and a favorable prognosis in various types of human cancer, attracting the speculation that TLSs support effective local antitumor immune responses. However, definitive evidence for the role for TLSs in fostering immune responses in vivo are lacking, with current data remaining largely correlative by nature. In fact, some more recent studies have even demonstrated an immunosuppressive, tumor-promoting role for cancer-associated TLSs. In this review, we will discuss what is known about the development of cancer-associated TLSs and the current understanding of their potential role in the antitumor immune response. PMID:29312327

  10. Memory in astrocytes: a hypothesis

    Directory of Open Access Journals (Sweden)

    Caudle Robert M

    2006-01-01

    Full Text Available Abstract Background Recent work has indicated an increasingly complex role for astrocytes in the central nervous system. Astrocytes are now known to exchange information with neurons at synaptic junctions and to alter the information processing capabilities of the neurons. As an extension of this trend a hypothesis was proposed that astrocytes function to store information. To explore this idea the ion channels in biological membranes were compared to models known as cellular automata. These comparisons were made to test the hypothesis that ion channels in the membranes of astrocytes form a dynamic information storage device. Results Two dimensional cellular automata were found to behave similarly to ion channels in a membrane when they function at the boundary between order and chaos. The length of time information is stored in this class of cellular automata is exponentially related to the number of units. Therefore the length of time biological ion channels store information was plotted versus the estimated number of ion channels in the tissue. This analysis indicates that there is an exponential relationship between memory and the number of ion channels. Extrapolation of this relationship to the estimated number of ion channels in the astrocytes of a human brain indicates that memory can be stored in this system for an entire life span. Interestingly, this information is not affixed to any physical structure, but is stored as an organization of the activity of the ion channels. Further analysis of two dimensional cellular automata also demonstrates that these systems have both associative and temporal memory capabilities. Conclusion It is concluded that astrocytes may serve as a dynamic information sink for neurons. The memory in the astrocytes is stored by organizing the activity of ion channels and is not associated with a physical location such as a synapse. In order for this form of memory to be of significant duration it is necessary

  11. Recovery Spirituality

    Directory of Open Access Journals (Sweden)

    Ernest Kurtz

    2015-01-01

    Full Text Available There is growing interest in Alcoholics Anonymous (A.A. and other secular, spiritual, and religious frameworks of long-term addiction recovery. The present paper explores the varieties of spiritual experience within A.A., with particular reference to the growth of a wing of recovery spirituality promoted within A.A. It is suggested that the essence of secular spirituality is reflected in the experience of beyond (horizontal and vertical transcendence and between (connection and mutuality and in six facets of spirituality (Release, Gratitude, Humility, Tolerance, Forgiveness, and a Sense of Being-at-home shared across religious, spiritual, and secular pathways of addiction recovery. The growing varieties of A.A. spirituality (spanning the “Christianizers” and “Seculizers” reflect A.A.’s adaptation to the larger diversification of religious experience and the growing secularization of spirituality across the cultural contexts within which A.A. is nested.

  12. Robust and distributed hypothesis testing

    CERN Document Server

    Gül, Gökhan

    2017-01-01

    This book generalizes and extends the available theory in robust and decentralized hypothesis testing. In particular, it presents a robust test for modeling errors which is independent from the assumptions that a sufficiently large number of samples is available, and that the distance is the KL-divergence. Here, the distance can be chosen from a much general model, which includes the KL-divergence as a very special case. This is then extended by various means. A minimax robust test that is robust against both outliers as well as modeling errors is presented. Minimax robustness properties of the given tests are also explicitly proven for fixed sample size and sequential probability ratio tests. The theory of robust detection is extended to robust estimation and the theory of robust distributed detection is extended to classes of distributions, which are not necessarily stochastically bounded. It is shown that the quantization functions for the decision rules can also be chosen as non-monotone. Finally, the boo...

  13. The venom optimization hypothesis revisited.

    Science.gov (United States)

    Morgenstern, David; King, Glenn F

    2013-03-01

    Animal venoms are complex chemical mixtures that typically contain hundreds of proteins and non-proteinaceous compounds, resulting in a potent weapon for prey immobilization and predator deterrence. However, because venoms are protein-rich, they come with a high metabolic price tag. The metabolic cost of venom is sufficiently high to result in secondary loss of venom whenever its use becomes non-essential to survival of the animal. The high metabolic cost of venom leads to the prediction that venomous animals may have evolved strategies for minimizing venom expenditure. Indeed, various behaviors have been identified that appear consistent with frugality of venom use. This has led to formulation of the "venom optimization hypothesis" (Wigger et al. (2002) Toxicon 40, 749-752), also known as "venom metering", which postulates that venom is metabolically expensive and therefore used frugally through behavioral control. Here, we review the available data concerning economy of venom use by animals with either ancient or more recently evolved venom systems. We conclude that the convergent nature of the evidence in multiple taxa strongly suggests the existence of evolutionary pressures favoring frugal use of venom. However, there remains an unresolved dichotomy between this economy of venom use and the lavish biochemical complexity of venom, which includes a high degree of functional redundancy. We discuss the evidence for biochemical optimization of venom as a means of resolving this conundrum. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Alien abduction: a medical hypothesis.

    Science.gov (United States)

    Forrest, David V

    2008-01-01

    In response to a new psychological study of persons who believe they have been abducted by space aliens that found that sleep paralysis, a history of being hypnotized, and preoccupation with the paranormal and extraterrestrial were predisposing experiences, I noted that many of the frequently reported particulars of the abduction experience bear more than a passing resemblance to medical-surgical procedures and propose that experience with these may also be contributory. There is the altered state of consciousness, uniformly colored figures with prominent eyes, in a high-tech room under a round bright saucerlike object; there is nakedness, pain and a loss of control while the body's boundaries are being probed; and yet the figures are thought benevolent. No medical-surgical history was apparently taken in the above mentioned study, but psychological laboratory work evaluated false memory formation. I discuss problems in assessing intraoperative awareness and ways in which the medical hypothesis could be elaborated and tested. If physicians are causing this syndrome in a percentage of patients, we should know about it; and persons who feel they have been abducted should be encouraged to inform their surgeons and anesthesiologists without challenging their beliefs.

  15. The oxidative hypothesis of senescence

    Directory of Open Access Journals (Sweden)

    Gilca M

    2007-01-01

    Full Text Available The oxidative hypothesis of senescence, since its origin in 1956, has garnered significant evidence and growing support among scientists for the notion that free radicals play an important role in ageing, either as "damaging" molecules or as signaling molecules. Age-increasing oxidative injuries induced by free radicals, higher susceptibility to oxidative stress in short-lived organisms, genetic manipulations that alter both oxidative resistance and longevity and the anti-ageing effect of caloric restriction and intermittent fasting are a few examples of accepted scientific facts that support the oxidative theory of senescence. Though not completely understood due to the complex "network" of redox regulatory systems, the implication of oxidative stress in the ageing process is now well documented. Moreover, it is compatible with other current ageing theories (e.g., those implicating the mitochondrial damage/mitochondrial-lysosomal axis, stress-induced premature senescence, biological "garbage" accumulation, etc. This review is intended to summarize and critically discuss the redox mechanisms involved during the ageing process: sources of oxidant agents in ageing (mitochondrial -electron transport chain, nitric oxide synthase reaction- and non-mitochondrial- Fenton reaction, microsomal cytochrome P450 enzymes, peroxisomal β -oxidation and respiratory burst of phagocytic cells, antioxidant changes in ageing (enzymatic- superoxide dismutase, glutathione-reductase, glutathion peroxidase, catalase- and non-enzymatic glutathione, ascorbate, urate, bilirubine, melatonin, tocopherols, carotenoids, ubiquinol, alteration of oxidative damage repairing mechanisms and the role of free radicals as signaling molecules in ageing.

  16. Treatment of experimental myasthenia gravis with total lymphoid irradiation

    International Nuclear Information System (INIS)

    de Silva, S.; Blum, J.E.; McIntosh, K.R.; Order, S.; Drachman, D.B.

    1988-01-01

    Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented the primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis

  17. Clinical drawbacks of total lymphoid irradiation: the cons

    International Nuclear Information System (INIS)

    Myers, L.W.; Ellison, G.W.; Fahey, J.L.; Tesler, A.; Gottlieb, M.S.

    1988-01-01

    Success has been reported with use of total lymphoid irradiation (TLI) in organ transplant recipients and in patients with rheumatoid arthritis and other autoimmune diseases. In a well-conducted randomized double blind clinical trial, Cook et al have found that TLI was superior to sham irradiation of patients with multiple sclerosis (MS). However, it is clear from looking at this data that not all patients responded to TLI and that with time disease activity returned. Our own experience with TLI in two MS patients was very disappointing. Despite its apparent benefit in some conditions, considerable drawbacks are associated with TLI. These include high financial cost, unpleasant treatment-related side effects, and the possibility that more serious morbidity as well as mortality may be treatment-related. Furthermore, the optimum therapeutic regimen for TLI has not yet been established. Issues related to cumulative dose, dose per fraction, frequency of fractions, field of irradiation, and interaction with other therapies still need clarification. For these reasons we do not recommend TLI as a treatment for MS

  18. Role of innate lymphoid cells in obesity and metabolic disease

    Science.gov (United States)

    Saetang, Jirakrit; Sangkhathat, Surasak

    2018-01-01

    The immune system has previously been demonstrated to be associated with the pathophysiological development of metabolic abnormalities. However, the mechanisms linking immunity to metabolic disease remain to be fully elucidated. It has previously been suggested that innate lymphoid cells (ILCs) may be involved in the progression of numerous types of metabolic diseases as these cells act as suppressors and promoters for obesity and associated conditions, and are particularly involved in adipose tissue inflammation, which is a major feature of metabolic imbalance. Group 2 ILCs (ILC2s) have been revealed as anti-obese immune regulators by secreting anti-inflammatory cytokines and promoting the polarization of M2 macrophages, whereas group 1 ILCs (ILC1s), including natural killer cells, may promote adipose tissue inflammation via production of interferon-γ, which in turn polarizes macrophages toward the M1 type. The majority of studies to date have demonstrated the pathological association between ILCs and obesity in the context of adipose tissue inflammation, whereas the roles of ILCs in other organs which participate in obesity development have not been fully characterized. Therefore, identifying the roles of all types of ILCs as central components mediating obesity-associated inflammation, is of primary concern, and may lead to the discovery of novel preventative and therapeutic interventions. PMID:29138853

  19. Regulation of Innate Lymphoid Cells by Aryl Hydrocarbon Receptor

    Science.gov (United States)

    Li, Shiyang; Bostick, John W.; Zhou, Liang

    2018-01-01

    With striking similarity to their adaptive T helper cell counterparts, innate lymphoid cells (ILCs) represent an emerging family of cell types that express signature transcription factors, including T-bet+ Eomes+ natural killer cells, T-bet+ Eomes− group 1 ILCs, GATA3+ group 2 ILCs, RORγt+ group 3 ILCs, and newly identified Id3+ regulatory ILC. ILCs are abundantly present in barrier tissues of the host (e.g., the lung, gut, and skin) at the interface of host–environment interactions. Active research has been conducted to elucidate molecular mechanisms underlying the development and function of ILCs. The aryl hydrocarbon receptor (Ahr) is a ligand-dependent transcription factor, best known to mediate the effects of xenobiotic environmental toxins and endogenous microbial and dietary metabolites. Here, we review recent progresses regarding Ahr function in ILCs. We focus on the Ahr-mediated cross talk between ILCs and other immune/non-immune cells in host tissues especially in the gut. We discuss the molecular mechanisms of the action of Ahr expression and activity in regulation of ILCs in immunity and inflammation, and the interaction between Ahr and other pathways/transcription factors in ILC development and function with their implication in disease. PMID:29354125

  20. Regulation of Innate Lymphoid Cells by Aryl Hydrocarbon Receptor

    Directory of Open Access Journals (Sweden)

    Shiyang Li

    2018-01-01

    Full Text Available With striking similarity to their adaptive T helper cell counterparts, innate lymphoid cells (ILCs represent an emerging family of cell types that express signature transcription factors, including T-bet+ Eomes+ natural killer cells, T-bet+ Eomes− group 1 ILCs, GATA3+ group 2 ILCs, RORγt+ group 3 ILCs, and newly identified Id3+ regulatory ILC. ILCs are abundantly present in barrier tissues of the host (e.g., the lung, gut, and skin at the interface of host–environment interactions. Active research has been conducted to elucidate molecular mechanisms underlying the development and function of ILCs. The aryl hydrocarbon receptor (Ahr is a ligand-dependent transcription factor, best known to mediate the effects of xenobiotic environmental toxins and endogenous microbial and dietary metabolites. Here, we review recent progresses regarding Ahr function in ILCs. We focus on the Ahr-mediated cross talk between ILCs and other immune/non-immune cells in host tissues especially in the gut. We discuss the molecular mechanisms of the action of Ahr expression and activity in regulation of ILCs in immunity and inflammation, and the interaction between Ahr and other pathways/transcription factors in ILC development and function with their implication in disease.

  1. Innate lymphoid cells at the interface between obesity and asthma.

    Science.gov (United States)

    Everaere, Laetitia; Ait Yahia, Saliha; Bouté, Mélodie; Audousset, Camille; Chenivesse, Cécile; Tsicopoulos, Anne

    2018-01-01

    Obesity and asthma prevalence has dramatically and concomitantly increased over the last 25 years, and many epidemiological studies have highlighted obesity as an important risk factor for asthma. Although many studies have been performed, the underlying mechanisms remain poorly understood. Innate mechanisms have been involved in both diseases, in particular through the recently described innate lymphoid cells (ILCs). ILCs are subdivided into three groups that are defined by their cytokine production and by their master transcription factor expression, in sharp correlation with their T helper counterparts. However, unlike T helper cells, ILCs do not express antigen-specific receptors, but respond to damage-induced signals. ILCs have been found in target tissues of both diseases, and data have implicated these cells in the pathogenesis of both diseases. In particular group 2 ILCs (ILC2) are activated in both the adipose and lung tissues under the effect of interleukin-33 and interleukin-25 expression. However, counter-intuitively to the well-known association between obesity and asthma, ILC2 are beneficial for obesity but deleterious for asthma. This review will examine the roles of ILCs in each disease and recent data highlighting ILCs as a putative link between obesity and asthma. © 2017 John Wiley & Sons Ltd.

  2. Kidney allograft survival in dogs treated with total lymphoid irradiation

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    Howard, R.J.; Sutherland, D.E.R.; Lum, C.T.; Lewis, W.I.; Kim, T.H.; Slavin, S.; Najarian, J.S.

    1981-01-01

    Total lymphoid irradiation (TLI) is immunosuppressive and, in rodents, can induce a state where transplantation of allogenic bone marrow results in chimerism and permanent acceptance of organ allografts from the donor strain. Twelve splenectomized dogs were treated with TLI (150 rads per fraction, total dose 1950 to 3000 rads) before bilateral nephrectomy and renal allotransplantation. Eight dogs received bone marrow from the kidney donor. In 13 untreated control dogs renal allografts functioned for a mean +- (SE) of 4.7 +- 0.3 days. In the four TLI treated dogs who did not receive bone marrow the renal allografts functioned for 15 to 76 days (two dogs died with functioning grafts). In the eight TLI treated dogs who received donor bone marrow, two died immediately after transplantation, two rejected at 3 and 13 days, one died at 13 days with a functioning graft, and two have had the grafts function for longer than 500 days. Chimerism was not detected in the one dog tested. The response of peripheral blood lymphocytes to stimulation with phytohemaglutinin and in mixed lymphocyte culture was suppressed for at least one month after TLI. The results confirm the immunosuppressive effect of TLI. The absence of kidney rejection in two recipients of donor bone marrow show the potential of this approach to induce long-term immunologic unresponsiveness as to an organ allograft, but the outcome is unpredictable and further experiments are needed to define the optimal conditions for administration of TLI and bone marrow to the recipients

  3. Treatment of experimental myasthenia gravis with total lymphoid irradiation

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    de Silva, S.; Blum, J.E.; McIntosh, K.R.; Order, S.; Drachman, D.B.

    1988-07-01

    Total lymphoid irradiation (TLI) has been reported to be effective in the immunosuppressive treatment of certain human and experimental autoimmune disorders. We have investigated the effects of TLI in Lewis rats with experimental autoimmune myasthenia gravis (EAMG) produced by immunization with purified torpedo acetylcholine receptor (AChR). The radiation is given in 17 divided fractions of 200 rad each, and nonlymphoid tissues are protected by lead shielding. This technique suppresses the immune system, while minimizing side effects, and permits the repopulation of the immune system by the patient's own bone marrow cells. Our results show that TLI treatment completely prevented the primary antibody response to immunization with torpedo AChR, it rapidly abolished the ongoing antibody response in established EAMG, and it suppressed the secondary (anamnestic) response to a boost of AChR. No EAMG animals died during TLI treatment, compared with six control animals that died of EAMG. TLI produces powerful and prompt immunosuppression and may eventually prove useful in the treatment of refractory human myasthenia gravis.

  4. CT appearances of mucosa-associated lymphoid tissue (MALT) lymphoma

    International Nuclear Information System (INIS)

    Kessar, P.; Norton, A.; Rohatiner, A.Z.S.; Lister, T.A.; Reznek, R.H.

    1999-01-01

    Mucosa-associated lymphoid tissue (MALT) lymphoma is a low-grade lymphoma that differs from high-grade non-Hodgkin lymphoma both clinically and histologically. The CT appearances of MALT lymphoma are described. Of 40 patients referred with biopsy-proven MALT lymphoma, only seven had not had gastrectomy or chemotherapy prior to CT examination. The CT scans of these seven cases were analysed for the degree and extent of gastric wall thickening, enlargement of abdominal and extra-abdominal lymph nodes, and presence of extranodal disease. In all patients the stomach was distended with oral contrast medium and scans performed at narrow collimation, after intravenous administration of 20 mg hyoscine butylbromide. In six patients focal thickening of the gastric wall was 1 cm or less. One patient had thickening of over 4 cm. There was no enlargement of abdominal or extra-abdominal lymph nodes or extension to adjacent organs. Thus on CT, at presentation, MALT lymphoma results in minimal gastric wall thickening, unlike high-grade non-Hodgkin lymphoma, which typically causes bulky gastric disease, nodal enlargement and extension into adjacent organs. CT is therefore of limited value in monitoring response to treatment. With disease greater than minimal thickening, transformation to a higher grade should be considered. (orig.)

  5. Gut-associated Lymphoid Tissue (GALT) Carcinoma in Ulcerative Colitis.

    Science.gov (United States)

    Rubio, Carlos A; DE Petris, Giovanni; Puppa, Giacomo

    2018-02-01

    In ulcerative colitis (UC), the majority of colorectal carcinomas (CRC) arise in the vast colorectal mucosal domain built with mucus-producing goblet cells and columnar cells. Conversely, CRC in UC rarely evolve in the tiny, spotty gut-associated lymphoid tissue (GALT) mucosal domain. Here we review the four reported cases of colonic carcinoma developing in GALT mucosa in UC, searching for possible precursor lesions connected with the evolution of these tumours. The clinical history, age, gender, endoscopic descriptions, and the pathology (localization, gross and histological descriptions of the luminal surface) of the four UC-GALT carcinomas reported in the literature were reviewed. The luminal surface in three out of the four carcinomas revealed conventional (tubular/villous) adenomas or high-grade dysplasia. All four UC-GALT-carcinomas were detected at an early stage (T1N0). GALT carcinomas do occur, albeit infrequently, in patients with UC. The finding that three out of the four GALT carcinomas on record were covered by conventional adenomas or by high-grade dysplasia strongly suggests that non-invasive conventional neoplasias might often precede GALT carcinomas in UC. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. CT findings of pulmonary mucosa-associated lymphoid tissue lymphoma

    International Nuclear Information System (INIS)

    Zhang Weidong; Guan Yubao; Li Chuanxing; Wu Peihong

    2010-01-01

    Objective: To study the CT findings of pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma. Methods: The CT examinations of 12 patients with pathologically proven pulmonary MALT lymphoma were reviewed retrospectively. Evaluated imaging findings included number, distribution, shape, attenuation and other associated findings of each lesion were evaluated. Results: Thirty-two pulmonary lesions, including consolidations, masses, nodules and lesions with ground glass attenuation, were identified in 12 patients. Multiple lesions were founded in 10 of 12 patients and solitary lesion in 2 patients. Multiple lesions found in one lung in 2 patients, and multiple lesions found in both lungs in 8 patients. Ten cases demonstrated 21 consolidation lesions with air bronchogram, and one of the ten cases demonstrated two lesions with airway dilatation. Three cases demonstrated 5 masses or nodular lesions, 3 of these 5 lesions showed air bronchogram. Two cases demonstrated 6 ground glass attenuation lesions. One case showed mediastinal and hilar lymphadenopathy. Conclusion: Pulmonary MALT lymphoma usually appears as multiple bilateral consolidations, masses, nodules with air bronchogram or lesions with ground- glass attenuation at CT imaging. The imaging findings described above and with an indolent clinical course may suggest the diagnosis of pulmonary MALT lymphoma. (authors)

  7. Innate lymphoid cells and their role in immune response regulation

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    Bibiana Patricia Ruiz-Sánchez

    2017-10-01

    Full Text Available Innate lymphoid cells (ILCs are lymphocytes lacking antigen recognition receptors and become activated in response to cytokines and through microbe-associated molecular pattern (MAMP receptors. ILCs are found mainly in mucosal tissues and participate in the immune response against infections and in chronic inflammatory conditions. ILCs are divided in ILC-1, ILC-2 and ILC-3, and these cells have analogue functions to those of immune adaptive response lymphocytes Th1, Th2 and Th17. ILC-1 express T-bet, produce IFNγ, protect against infections with intracellular microorganisms and are related to inflammatory bowel disease immunopathology. ILC-2 express GATA3, produce IL-4, IL-5, IL-13 and amphiregulin, protect against parasitic infections and related to allergy and obesity immunopathology. ILC-3 express ROR(γt, produce IL-17 and IL-22, protect against fungal infections and contribute to tolerance to intestinal microbiota and intestinal repair. They are related to inflammatory bowel disease and psoriasis immunopathology. In general terms, ILCs maintain homeostasis and coadjuvate in the protection against infections.

  8. EVALUATION OF CYTOKINE GENE POLYMORPHISM IN B CELL LYMPHOID MALIGNANCIES

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    E. L. Nazarova

    2014-01-01

    Full Text Available Previous studies with some solid tumors has shown that polymorphisms of certain cytokine genes may be used as predictors of clinical outcome in the patients. It seemed important to evaluate potential correlations between production of certain pro- and anti-inflammatory cytokines and co-receptor molecules, and promoter polymorphism of the cytokine genes involved into regulation of cell proliferation, differentiation, apoptosis, lipid metabolism and blood clotting in the patients with hematological malignancies. The article contains our results concerning associations between of IL-1β, -2, -4, -10, -17, TNFα, and allelic polymorphisms of their genes in 62 patients with B cell lymphoid malignancies in an ethnically homogenous group (self-identified as Russians. We have shown that the GА and AA genotypes of the G-308A polymorphism in TNFα gene are significantly associated with increased production of this cytokine, being more common in aggressive non-Hodgkin lymphomas, more rare in multiple myeloma and in indolent non-Hodgkin lymphomas.

  9. Lymphocyte trafficking and HIV infection of human lymphoid tissue in a rotating wall vessel bioreactor

    Science.gov (United States)

    Margolis, L. B.; Fitzgerald, W.; Glushakova, S.; Hatfill, S.; Amichay, N.; Baibakov, B.; Zimmerberg, J.

    1997-01-01

    The pathogenesis of HIV infection involves a complex interplay between both the infected and noninfected cells of human lymphoid tissue, the release of free viral particles, the de novo infection of cells, and the recirculatory trafficking of peripheral blood lymphocytes. To develop an in vitro model for studying these various aspects of HIV pathogenesis we have utilized blocks of surgically excised human tonsils and a rotating wall vessel (RWV) cell culture system. Here we show that (1) fragments of the surgically excised human lymphoid tissue remain viable and retain their gross cytoarchitecture for at least 3 weeks when cultured in the RWV system; (2) such lymphoid tissue gradually shows a loss of both T and B cells to the surrounding growth medium; however, this cellular migration is reversible as demonstrated by repopulation of the tissue by labeled cells from the growth medium; (3) this cellular migration may be partially or completely inhibited by embedding the blocks of lymphoid tissue in either a collagen or agarose gel matrix; these embedded tissue blocks retain most of the basic elements of a normal lymphoid cytoarchitecture; and (4) both embedded and nonembedded RWV-cultured blocks of human lymphoid tissue are capable of productive infection by HIV-1 of at least three various strains of different tropism and phenotype, as shown by an increase in both p24 antigen levels and free virus in the culture medium, and by the demonstration of HIV-1 RNA-positive cells inside the tissue identified by in situ hybridization. It is therefore reasonable to suggest that gel-embedded and nonembedded blocks of human lymphoid tissue, cocultured with a suspension of tonsillar lymphocytes in an RWV culture system, constitute a useful model for simulating normal lymphocyte recirculatory traffic and provide a new tool for testing the various aspects of HIV pathogenesis.

  10. Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients.

    Science.gov (United States)

    Diaz, Alba; Alós, Llúcia; León, Agathe; Mozos, Anna; Caballero, Miguel; Martinez, Antonio; Plana, Montserrat; Gallart, Teresa; Gil, Cristina; Leal, Manuel; Gatell, Jose M; García, Felipe

    2010-08-24

    The factors associated with fibrosis in lymphoid tissue in long-term treated HIV-infected patients and their correlation with immune reconstitution were assessed. Tonsillar biopsies were performed in seven antiretroviral-naive patients and 29 successfully treated patients (median time on treatment, 61 months). Twenty patients received protease inhibitors-sparing regimens and nine protease inhibitor-containing regimens. Five tonsillar resections of HIV-negative individuals were used as controls. Lymphoid tissue architecture, collagen deposition (fibrosis) and the mean interfollicular CD4(+) cell count per mum were assessed. Naive and long-term treated HIV-infected patients had a higher proportion of fibrosis than did HIV-uninfected persons (P lymphoid tissue (P = 0.03) and smaller increase in peripheral CD4(+) T cells (r = -0.40, P = 0.05). The factors independently associated with fibrosis in lymphoid tissue were age (P lymphoid tissue viral load when compared with patients with undetectable lymphoid tissue viral load (median 5 vs. 12%, respectively, P = 0.017) and patients receiving a protease inhibitor-sparing vs. a protease inhibitor-containing regimen (median 8 vs. 2.5%, respectively, P = 0.04). Fibrosis in lymphoid tissue was associated with a poor reconstitution of CD4(+) T cells and long-term antiretroviral therapy did not reverse this abnormality. HIV infection, older age, a detectable level of lymphoid tissue viral load in treated patients and protease inhibitor-sparing regimens seem to favour fibrosis in lymphoid tissue.

  11. Epstein-Barr Virus-Positive Extranodal Marginal Zone Lymphoma of Bronchial-Associated Lymphoid Tissue in the Posttransplant Setting: An Immunodeficiency-Related (Posttransplant) Lymphoproliferative Disorder?

    Science.gov (United States)

    Cassidy, Daniel P; Vega, Francisco; Chapman, Jennifer R

    2017-12-20

    Posttransplant lymphoproliferative disorders (PTLDs) are a heterogeneous group of hematolymphoid proliferations arising in the context of chronic immunosuppression. The common and indolent B-cell lymphomas, including extranodal marginal zone lymphomas (ENMZLs) of mucosa-associated lymphoid tissue (MALT), are excluded from the category of PTLD in the current World Health Organization classification. We report a case of Epstein-Barr virus (EBV)-positive bronchial-associated lymphoid tissue (BALT) lymphoma involving the lungs of a transplant patient. Aside from history of cardiac transplant, young patient age, and EBV positivity, the histopathologic findings were indistinguishable from usual BALT lymphoma. We review the literature of ENMZL occurring in immunocompromised patients and present this case for consideration that this specific entity is a PTLD. We believe that additional studies might lend strength to the hypothesis that this particular group of EBV-positive, posttransplant ENMZLs merits classification and management as PTLDs. © American Society for Clinical Pathology, 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

  12. Group 2 innate lymphoid cell production of IL-5 is regulated by NKT cells during influenza virus infection.

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    Stacey Ann Gorski

    2013-09-01

    Full Text Available Respiratory virus infections, such as influenza, typically induce a robust type I (pro-inflammatory cytokine immune response, however, the production of type 2 cytokines has been observed. Type 2 cytokine production during respiratory virus infection is linked to asthma exacerbation; however, type 2 cytokines may also be tissue protective. Interleukin (IL-5 is a prototypical type 2 cytokine that is essential for eosinophil maturation and egress out of the bone marrow. However, little is known about the cellular source and underlying cellular and molecular basis for the regulation of IL-5 production during respiratory virus infection. Using a mouse model of influenza virus infection, we found a robust transient release of IL-5 into infected airways along with a significant and progressive accumulation of eosinophils into the lungs, particularly during the recovery phase of infection, i.e. following virus clearance. The cellular source of the IL-5 was group 2 innate lymphoid cells (ILC2 infiltrating the infected lungs. Interestingly, the progressive accumulation of eosinophils following virus clearance is reflected in the rapid expansion of c-kit⁺ IL-5 producing ILC2. We further demonstrate that the enhanced capacity for IL-5 production by ILC2 during recovery is concomitant with the enhanced expression of the IL-33 receptor subunit, ST2, by ILC2. Lastly, we show that NKT cells, as well as alveolar macrophages (AM, are endogenous sources of IL-33 that enhance IL-5 production from ILC2. Collectively, these results reveal that c-kit⁺ ILC2 interaction with IL-33 producing NKT and AM leads to abundant production of IL-5 by ILC2 and accounts for the accumulation of eosinophils observed during the recovery phase of influenza infection.

  13. Co-localization of lymphoid aggregates and lymphatic networks in nose- (NALT) and lacrimal duct-associated lymphoid tissue (LDALT) of mice.

    Science.gov (United States)

    Lohrberg, Melanie; Pabst, Reinhard; Wilting, Jörg

    2018-01-25

    The lymphatic vascular pattern in the head of mice has rarely been studied, due to problems of sectioning and immunostaining of complex bony structures. Therefore, the association of head lymphoid tissues with the lymphatics has remained unknown although the mouse is the most often used species in immunology. Here, we studied the association of nasal and nasolacrimal duct lymphatics with lymphoid aggregates in 14-day-old and 2-month-old mice. We performed paraffin sectioning of whole, decalcified heads, and immunostaining with the lymphatic endothelial cell-specific antibodies Lyve-1 and Podoplanin. Most parts of the nasal mucous membrane do not contain any lymphatics. Only the region of the inferior turbinates contains lymphatic networks, which are connected to those of the palatine. Nose-associated lymphoid tissue (NALT) is restricted to the basal parts of the nose, which contain lymphatics. NALT is continued occipitally and can be found at both sides along the sphenoidal sinus, again in close association with lymphatic networks. Nasal lymphatics are connected to those of the ocular region via a lymphatic network along the nasolacrimal duct (NLD). By this means, lacrimal duct-associated lymphoid tissue (LDALT) has a dense supply with lymphatics. NALT and LDALT play a key role in the immune system of the mouse head, where they function as primary recognition sites for antigens. Using the dense lymphatic networks along the NLD described in this study, these antigens reach lymphatics near the palatine and are further drained to lymph nodes of the head and neck region. NALT and LDALT develop in immediate vicinity of lymphatic vessels. Therefore, we suggest a causative connection of lymphatic vessels and the development of lymphoid tissues.

  14. Group 1 innate lymphoid cells in Toxoplasma gondii infection.

    Science.gov (United States)

    Dunay, I R; Diefenbach, A

    2018-02-01

    Innate lymphoid cells (ILCs) are a group of lymphocytes that carry out important functions in immunity to infections and in organ homeostasis at epithelial barrier surfaces. ILCs are innate immune cells that provide an early source of cytokines to initiate immune responses against pathogens. Cytotoxic ILCs (i.e. conventional (c)NK cells) and several subsets of helper-like ILCs are the major branches of the ILC family. Conventional NK cells and group 1 ILCs share several characteristics such as surface receptors and the ability to produce IFN-γ upon activation, but they differ in their developmental paths and in their dependence on specific transcription factors. Infection of mice with the intracellular parasite Toxoplasma gondii is followed by a strong Th1-mediated immune response. Previous studies indicate that NK1.1 + cells contribute to the production of IFN-γ and TNF and cytotoxicity during acute T. gondii infection. Upon oral infection, the parasite infects intestinal enterocytes, and within the lamina propria, innate immune responses lead to initial parasite control although the infection disseminates widely and persists long-term in immune privileged sites despite adaptive immunity. Upon parasite entry into the small intestine, during the acute stage, ILC1 produce high levels of IFN-γ and TNF protecting barrier surfaces, thus essentially contributing to early parasite control. We will discuss here the role of innate lymphocytes during T. gondii infection in the context of the only recently appreciated diversity of ILC subsets. © 2018 John Wiley & Sons Ltd.

  15. Scrapie-specific pathology of sheep lymphoid tissues.

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    Gillian McGovern

    Full Text Available Transmissible spongiform encephalopathies (TSEs or prion diseases often result in accumulation of disease-associated PrP (PrP(d in the lymphoreticular system (LRS, specifically in association with follicular dendritic cells (FDCs and tingible body macrophages (TBMs of secondary follicles. We studied the effects of sheep scrapie on lymphoid tissue in tonsils and lymph nodes by light and electron microscopy. FDCs of sheep were grouped according to morphology as immature, mature or regressing. Scrapie was associated with FDC dendrite hypertrophy and electron dense deposit or vesicles. PrP(d was located using immunogold labelling at the plasmalemma of FDC dendrites and, infrequently, mature B cells. Abnormal electron dense deposits surrounding FDC dendrites were identified as immunoglobulins suggesting that excess immune complexes are retained and are indicative of an FDC dysfunction. Within scrapie-affected lymph nodes, macrophages outside the follicle and a proportion of germinal centre TBMs accumulated PrP(d within endosomes and lysosomes. In addition, TBMs showed PrP(d in association with the cell membrane, non-coated pits and vesicles, and also with discrete, large and random endoplasmic reticulum networks, which co-localised with ubiquitin. These observations suggest that PrP(d is internalised via the caveolin-mediated pathway, and causes an abnormal disease-related alteration in endoplasmic reticulum structure. In contrast to current dogma, this study shows that sheep scrapie is associated with cytopathology of germinal centres, which we attribute to abnormal antigen complex trapping by FDCs and abnormal endocytic events in TBMs. The nature of the sub-cellular changes in FDCs and TBMs differs from those of scrapie infected neurones and glial cells suggesting that different PrP(d/cell membrane interactions occur in different cell types.

  16. Progressive alterations in multipotent hematopoietic progenitors underlie lymphoid cell loss in aging.

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    Young, Kira; Borikar, Sneha; Bell, Rebecca; Kuffler, Lauren; Philip, Vivek; Trowbridge, Jennifer J

    2016-10-17

    Declining immune function with age is associated with reduced lymphoid output of hematopoietic stem cells (HSCs). Currently, there is poor understanding of changes with age in the heterogeneous multipotent progenitor (MPP) cell compartment, which is long lived and responsible for dynamically regulating output of mature hematopoietic cells. In this study, we observe an early and progressive loss of lymphoid-primed MPP cells (LMPP/MPP4) with aging, concomitant with expansion of HSCs. Transcriptome and in vitro functional analyses at the single-cell level reveal a concurrent increase in cycling of aging LMPP/MPP4 with loss of lymphoid priming and differentiation potential. Impaired lymphoid differentiation potential of aged LMPP/MPP4 is not rescued by transplantation into a young bone marrow microenvironment, demonstrating cell-autonomous changes in the MPP compartment with aging. These results pinpoint an age and cellular compartment to focus further interrogation of the drivers of lymphoid cell loss with aging. © 2016 Young et al.

  17. Group 3 innate lymphoid cells (ILC3s): Origin, differentiation, and plasticity in humans and mice.

    Science.gov (United States)

    Montaldo, Elisa; Juelke, Kerstin; Romagnani, Chiara

    2015-08-01

    Since their discovery, innate lymphoid cells (ILCs) have been the subject of intense research. As their name implies, ILCs are innate cells of lymphoid origin, and can be grouped into subsets based on their cytotoxic activity, cytokine profile, and the transcriptional requirements during ILC differentiation. The main ILC groups are "killer" ILCs, comprising NK cells, and "helper-like" ILCs (including ILC1s, ILC2s, and ILC3s). This review examines the origin, differentiation stages, and plasticity of murine and human ILC3s. ILC3s express the retinoic acid receptor (RAR) related orphan receptor RORγt and the signature cytokines IL-22 and IL-17. Fetal ILC3s or lymphoid tissue inducer cells are required for lymphoid organogenesis, while postnatally developing ILC3s are important for the generation of intestinal cryptopatches and isolated lymphoid follicles as well as for the defence against pathogens and epithelial homeostasis. Here, we discuss the transcription factors and exogenous signals (including cytokines, nutrients and cell-to-cell interaction) that drive ILC3 lineage commitment and acquisition of their distinctive effector program. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Homeostatic migration and distribution of innate immune cells in primary and secondary lymphoid organs with ageing.

    Science.gov (United States)

    Nikolich-Žugich, J; Davies, J S

    2017-03-01

    Ageing of the innate and adaptive immune system, collectively termed immune senescence, is a complex process. One method to understand the components of ageing involves dissociating the effects of ageing on the cells of the immune system, on the microenvironment in lymphoid organs and tissues where immune cells reside and on the circulating factors that interact with both immune cells and their microenvironment. Heterochronic parabiosis, a surgical union of two organisms of disparate ages, is ideal for this type of study, as it has the power to dissociate the age of the cell and the age of the microenvironment into which the cell resides or is migrating. So far, however, it has been used sparingly to study immune ageing. Here we review the limited literature on homeostatic innate immune cell trafficking in ageing in the absence of chronic inflammation. We also review our own recent data on trafficking of innate immune subsets between primary and secondary lymphoid organs in heterochronic parabiosis. We found no systemic bias in retention or acceptance of neutrophils, macrophages, dendritic cells or natural killer cells with ageing in primary and secondary lymphoid organs. We conclude that these four innate immune cell types migrate to and populate lymphoid organs (peripheral lymph nodes, spleen and bone marrow), regardless of their own age and of the age of lymphoid organs. © 2017 British Society for Immunology.

  19. Nasal associated lymphoid tissue of the Syrian golden hamster expresses high levels of PrPC.

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    Melissa D Clouse

    Full Text Available The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrPSc comes into contact with native prion protein (PrPC and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrPC levels. PrPC immunohistochemistry (IHC of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer's patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection.

  20. Nasal associated lymphoid tissue of the Syrian golden hamster expresses high levels of PrPC.

    Science.gov (United States)

    Clouse, Melissa D; Shikiya, Ronald A; Bartz, Jason C; Kincaid, Anthony E

    2015-01-01

    The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrPSc) comes into contact with native prion protein (PrPC) and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrPC levels. PrPC immunohistochemistry (IHC) of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer's patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection.

  1. The Conjunctiva-Associated Lymphoid Tissue in Chronic Ocular Surface Diseases.

    Science.gov (United States)

    Mastropasqua, Rodolfo; Agnifili, Luca; Fasanella, Vincenzo; Nubile, Mario; Gnama, Agbeanda A; Falconio, Gennaro; Perri, Paolo; Di Staso, Silvio; Mariotti, Cesare

    2017-08-01

    Ocular surface diseases (OSDs) represent a widely investigated field of research given their growing incidence and the negative impact on quality of life. During OSDs, cytokines generated by damaged epithelia trigger and deregulate the lymphoid cells composing the eye-associated lymphoid tissues, inducing an immune-mediated chronic inflammation that amplifies and propagates the disease during time. The conjunctiva-associated lymphoid tissue (CALT), given its particular position that permits immune cells covering the cornea, might play a crucial role in the development of OSDs. Despite the recognized inflammatory role of mucosa-associated lymphoid tissues in other stations taking contact with the external environment (gut or bronchus), CALT did not gain the deserved consideration. In the last years, the diffusion of the in vivo confocal microscopy (IVCM) stimulated the interest to CALT, especially in dry eye, ocular allergy, and glaucoma. Though the initial stimuli were different, IVCM documented similar changes, represented by increased lymphoid cells within the diffuse layer, follicles and interfollicular spaces. These findings, which need to be validated by immunohistology, support the CALT stimulation during OSDs. However, while an involvement of the CALT in OSDs is hypothesizable, the exact role of this structure in their pathogenesis remains unclear and warrants further investigations.

  2. Validity of Linder Hypothesis in Bric Countries

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    Rana Atabay

    2016-03-01

    Full Text Available In this study, the theory of similarity in preferences (Linder hypothesis has been introduced and trade in BRIC countries has been examined whether the trade between these countries was valid for this hypothesis. Using the data for the period 1996 – 2010, the study applies to panel data analysis in order to provide evidence regarding the empirical validity of the Linder hypothesis for BRIC countries’ international trade. Empirical findings show that the trade between BRIC countries is in support of Linder hypothesis.

  3. Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

    International Nuclear Information System (INIS)

    Trentham, D.E.; Belli, J.A.; Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.

    1981-01-01

    Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly after a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered

  4. Clinical and immunologic effects of fractionated total lymphoid irradiation in refractory rheumatoid arthritis

    International Nuclear Information System (INIS)

    Trentham, D.E.; Belli, J.A.; Anderson, R.J.; Buckley, J.A.; Goetzl, E.J.; David, J.R.; Austen, K.F.

    1981-01-01

    Ten patients with refractory rheumatoid arthritis were given 3000 rad of fractionated total lymphoid irradiation in an uncontrolled therapeutic trial. Total lymphoid irradiation was associated with objective evidence of considerable clinical improvement in eight patients and with reduced blood lymphocyte counts in all 10. On completion of irradiation, there was an abrogation of lymphocyte reactivity in vitro in the patients with clinical responses, but abnormal antibody activities characteristic of rheumatoid arthritis and normal components of humoral immunity were not suppressed. Partial recrudescence of arthritis occurred shortly before a year after the completion of irradiation and was paralleled by a restitution of lymphocyte concentrations and responsiveness to mitogens to levels similar to those observed before irradiation. These data provide further evidence of T-cell involvement in the pathogenesis of rheumatoid arthritis and demonstrate that total lymphoid irradiation can induce temporary relief, but they do not ascertain whether the natural history of this disease was altered

  5. Pathological and therapeutic roles of innate lymphoid cells in diverse diseases.

    Science.gov (United States)

    Kim, Jisu; Kim, Geon; Min, Hyeyoung

    2017-11-01

    Innate lymphoid cells (ILCs) are a recently defined type of innate-immunity cells that belong to the lymphoid lineage and have lymphoid morphology but do not express an antigen-specific B cell or T-cell receptor. ILCs regulate immune functions prior to the formation of adaptive immunity and exert effector functions through a cytokine release. ILCs have been classified into three groups according to the transcription factors that regulate their development and function and the effector cytokines they produce. Of note, ILCs resemble T helper (Th) cells, such as Th1, Th2, and Th17 cells, and show a similar dependence on transcription factors and distinct cytokine production. Despite their short history in immunology, ILCs have received much attention, and numerous studies have revealed biological functions of ILCs including host defense against pathogens, inflammation, tissue repair, and metabolic homeostasis. Here, we describe recent findings about the roles of ILCs in the pathogenesis of various diseases and potential therapeutic targets.

  6. Immunological tumor destruction in a murine melanoma model by targeted LTalpha independent of secondary lymphoid tissue

    DEFF Research Database (Denmark)

    Schrama, D.; Voigt, H.; Eggert, A.O.

    2008-01-01

    BACKGROUND: We previously demonstrated that targeting lymphotoxin alpha (LTalpha) to the tumor evokes its immunological destruction in a syngeneic B16 melanoma model. Since treatment was associated with the induction of peritumoral tertiary lymphoid tissue, we speculated that the induced immune...... response was initiated at the tumor site. METHODS AND RESULTS: In order to directly test this notion, we analyzed the efficacy of tumor targeted LTalpha in LTalpha knock-out (LTalpha(-/-)) mice which lack peripheral lymph nodes. To this end, we demonstrate that tumor-targeted LTalpha mediates the induction...... of specific T-cell responses even in the absence of secondary lymphoid organs. In addition, this effect is accompanied by the initiation of tertiary lymphoid tissue at the tumor site in which B and T lymphocytes are compartmentalized in defined areas and which harbor expanded numbers of tumor specific T cells...

  7. Twin Rectal Tonsils Mimicking Carcinoid or Mucosa-Associated Lymphoid Tissue Lymphoma.

    Science.gov (United States)

    Takehara, Masanori; Muguruma, Naoki; Kitamura, Shinji; Kimura, Tetsuo; Okamoto, Koichi; Miyamoto, Hiroshi; Bando, Yoshimi; Takayama, Tetsuji

    2017-09-01

    The rectal tonsil is a rare polypoid lesion exclusively found in the rectum and is considered a reactive proliferation of the lymphoid tissue. Although this lesion is benign, we recommend that it should be differentiated from carcinoid or polypoid type of mucosa-associated lymphoid tissue lymphomas, based on gross findings. In this case report, we describe a case of rectal lesions with a unique appearance in a 41-year-old man. Colonoscopy revealed two 5-mm-sized nodules located opposite from each other on the left and right sides of the lower rectum. Endoscopic mucosal resection was conducted. Histopathologically, both lesions were mainly located in the submucosa and consisted of prominent lymphoid follicles with germinal centers of various sizes. No immunoreactivity of Bcl-2 was seen in the germinal centers. Immunohistochemical staining for kappa and lambda light chains revealed a polyclonal pattern. Therefore, these lesions were diagnosed as rectal tonsils.

  8. Activation of vestibule-associated lymphoid tissue in localized provoked vulvodynia.

    Science.gov (United States)

    Tommola, Päivi; Bützow, Ralf; Unkila-Kallio, Leila; Paavonen, Jorma; Meri, Seppo

    2015-04-01

    Localized provoked vulvodynia (LPV) may have inflammatory etiology. We wanted to find out whether the cell-mediated immune system becomes activated in the vestibular mucosa in LPV. This was a controlled cross-sectional study. Vestibular mucosal specimens were obtained from 27 patients with severe LPV and 15 controls. Detailed clinical history of the patients was obtained. For immunohistochemistry, antibodies against CD3 (T cells), CD20 (B cells), IgA (mucosal plasma cells), CD163 (dendritic cells [DCs]), CD68 (macrophages), and CD117 (mast cells) were employed. Mann-Whitney U test and χ(2) test were used for statistical analyses. More B lymphocytes and mature mucosal IgA-plasma cells were found in patients than in controls (P associated lymphoid tissue analogous to mucosa-associated lymphoid tissue. Vestibule-associated lymphoid tissue may emerge as a response to local infection or inflammation in LPV. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Gut-associated lymphoid tissue, T cell trafficking, and chronic intestinal inflammation.

    Science.gov (United States)

    Koboziev, Iurii; Karlsson, Fridrik; Grisham, Matthew B

    2010-10-01

    The etiologies of the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) have not been fully elucidated. However, there is very good evidence implicating T cell and T cell trafficking to the gut and its associated lymphoid tissue as important components in disease pathogenesis. The objective of this review is to provide an overview of the mechanisms involved in naive and effector T cell trafficking to the gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes and intestine in response to commensal enteric antigens under physiological conditions as well as during the induction of chronic gut inflammation. In addition, recent data suggests that the GALT may not be required for enteric antigen-driven intestinal inflammation in certain mouse models of IBD. These new data suggest a possible paradigm shift in our understanding of how and where naive T cells become activated to yield disease-producing effector cells. © 2010 New York Academy of Sciences.

  10. A rear case of multilocular thymic cyst with follicular lymphoid hyperplasia; Radiologic and histopathologic features

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Suk; Cha, Eun Jung [Konyang University Hospital, Daejeon (Korea, Republic of)

    2016-06-15

    Multilocular thymic cysts are rare and acquired lesions induced by an inflammatory arising within the thymus. We report a rare case of multilocular thymic cyst with follicular lymphoid hyperplasia in a 59-year-old female. Chest CT and MRI revealed a large multilocular cystic mass, which contains thick septa and nodules in the thymus. F-18 FDG PET/CT showed almost no FDG uptake of the multilocular cystic mass but moderate FDG uptake of the solid nodules. Extended total thymectomy was performed. Histopathological findings revealed follicular lymphoid hyperplasia of thymic tissue but no neoplastic lesion. Based on these findings, diagnosis of multilocular thymic cyst with follicular lymphoid hyperplasia was made. This is a rare case that preoperatively was difficult to diagnose.

  11. Possible stimulation of anti-tumor immunity using repeated cold stress: a hypothesis

    Directory of Open Access Journals (Sweden)

    Radoja Sasa

    2007-11-01

    Full Text Available Abstract Background The phenomenon of hormesis, whereby small amounts of seemingly harmful or stressful agents can be beneficial for the health and lifespan of laboratory animals has been reported in literature. In particular, there is accumulating evidence that daily brief cold stress can increase both numbers and activity of peripheral cytotoxic T lymphocytes and natural killer cells, the major effectors of adaptive and innate tumor immunity, respectively. This type of regimen (for 8 days has been shown to improve survival of mice infected with intracellular parasite Toxoplasma gondii, which would also be consistent with enhanced cell-mediated immunity. Presentation of the hypothesis This paper hypothesizes that brief cold-water stress repeated daily over many months could enhance anti-tumor immunity and improve survival rate of a non-lymphoid cancer. The possible mechanism of the non-specific stimulation of cellular immunity by repeated cold stress appears to involve transient activation of the sympathetic nervous system, hypothalamic-pituitary-adrenal and hypothalamic-pituitary-thyroid axes, as described in more detail in the text. Daily moderate cold hydrotherapy is known to reduce pain and does not appear to have noticeable adverse effects on normal test subjects, although some studies have shown that it can cause transient arrhythmias in patients with heart problems and can also inhibit humoral immunity. Sudden immersion in ice-cold water can cause transient pulmonary edema and increase permeability of the blood-brain barrier, thereby increasing mortality of neurovirulent infections. Testing the hypothesis The proposed procedure is an adapted cold swim (5–7 minutes at 20 degrees Celsius, includes gradual adaptation to be tested on a mouse tumor model. Mortality, tumor size, and measurements of cellular immunity (numbers and activity of peripheral CD8+ T lymphocytes and natural killer cells of the cold-exposed group would be compared to

  12. MRI of idiopathic orbital inflammation and lymphoid disease with lesions in extraocular muscle

    International Nuclear Information System (INIS)

    Matsuda, Chiharu; Kotake, Fumio; Kawanishi, Masayuki; Saito, Kazuhiro; Abe, Kimihiko

    2004-01-01

    Of the disorders accompanied by hypertrophy of the extraocular muscles, differentiating between idiopathic orbital inflammation and malignant lymphoma is difficult but important to treatment and prognosis. In this study using MRI, shape, signal intensity, and enhancement effects were compared between idiopathic orbital inflammation and lymphoproliferative lesions. The subjects were 27 patients (8 with idiopathic orbital inflammation, 1 with reactive lymphoid hyperplasia, 3 with atypical lymphoid hyperplasia, and 15 with malignant lymphoma) and 10 normal controls. The evaluation items were: thickness of extraocular muscles, number of extraocular muscles involved signal intensity of extraocular muscles, and enhancement effects on extraocular muscles. When compared to control subjects (p<0.05) the attachment portion of extraocular muscles were significantly thicker in the patients with idiopathic orbital inflammation, atypical lymphoid hyperplasia, or malignant lymphoma; the most marked hypertrophy was observed in patients with malignant lymphoma. The number of extraocular muscles involved was 1.5 (mean) in the patients with idiopathic orbital inflammation, 1 in the patient with reactive lymphoid hyperplasia, 1.7 (mean) in the patients with atypical lymphoid hyperplasia, and 5.1 (mean) in those with malignant lymphoma. The signal intensity ratio on T1W-images did not significantly differ between the patients and controls for all the disorders investigated. Signal intensity ratio on T2W-images significantly differed between patients with atypical lymphoid hyperplasia or malignant lymphoma and the controls (p<0.05) but not between patients with idiopathic orbital inflammation and controls. Signal intensity ratio after contrast enhancement differed significantly only between patients with idiopathic orbital inflammation and controls (p<0.05). (author)

  13. Type 2 innate lymphoid cells-new members of the "type 2 franchise" that mediate allergic airway inflammation

    NARCIS (Netherlands)

    Mjösberg, Jenny; Spits, Hergen

    2012-01-01

    Type 2 innate lymphoid cells (ILC2s) are members of an ILCfamily, which contains NKcells and Ror?t+ ILCs, the latter including lymphoid tissue inducer (LTi) cells and ILCs producing IL-17 and IL-22. ILC2s are dedicated to the production of IL-5 and IL-13 and, as such, ILC2s provide an early and

  14. Regulation of Cytokine Secretion in Human CD127(+) LTi-like Innate Lymphoid Cells by Toll-like Receptor 2

    NARCIS (Netherlands)

    Crellin, Natasha K.; Trifari, Sara; Kaplan, Charles D.; Satoh-Takayama, Naoko; Di Santo, James P.; Spits, Hergen

    2010-01-01

    Lymphoid tissue inducer cells are members of an emerging family of innate lymphoid cells (ILC). Although these cells were originally reported to produce cytokines such as interleukin-17 (IL-17) and IL-22, we demonstrate here that human CD127(+)RORC(+) and CD56(+)CD127(+) LTi-like ILC also express

  15. Long-term followup of rheumatoid arthritis patients treated with total lymphoid irradiation

    International Nuclear Information System (INIS)

    Tanay, A.; Field, E.H.; Hoppe, R.T.; Strober, S.

    1987-01-01

    Total lymphoid irradiation was administered to 32 patients with intractable rheumatoid arthritis. Twenty-four patients showed at least a 25% improvement in 3 of 4 disease activity parameters, which persisted during the followup period of up to 48 months. Eight of the 32 patients required adjunctive immunosuppressive drug therapy to maintain improvement. Four patients died after total lymphoid irradiation; the causes of death were acute myocardial infarction (1 patient), pulmonary embolism (1 patient), and rheumatoid lung disease complicated by respiratory infection (2 patients). After therapy, patients exhibited a prolonged reduction in the number and function of circulating T helper cells

  16. The role of innate lymphoid cells in healthy and inflamed skin

    DEFF Research Database (Denmark)

    Bonefeld, Charlotte M.; Geisler, Carsten

    2016-01-01

    system. During the last years, it has become clear that innate lymphoid cells play a role in homeostasis and inflammation of the skin in humans and mice. In this review, we will discuss the role of innate lymphoid cells in healthy and inflamed skin with special focus on their role in atopic dermatitis.......The skin constitutes the interface between the organism and the environment, and it protects the body from harmful substances in the environment via physical, chemical and immunological barriers. The immunological barrier of the skin comprises both cells from the innate and the adaptive immune...

  17. Imaging Findings of Localized Lymphoid Hyperplasia of the Pancreas: a Case Report

    International Nuclear Information System (INIS)

    Kim, Jin Woong; Heo, Suk Hee; Jeong, Yong Yeon; Kang, Heoung Keun; Shin, Sang Soo; Choi, Yoo Duk

    2011-01-01

    We report here on a case of localized lymphoid hyperplasia of the pancreas in a 70-year-old man which manifested as double lesions (uncinate process and tail) in the organ. The lesions were incidentally detected as hypoechoic lesions on ultrasonography and they appeared as delayed enhancing lesions on the contrast-enhanced dynamic CT and MRI. Total pancreatectomy was performed, because malignant tumor could not be excluded according to the preoperative imaging studies and the endoscopic ultrasound-guided biopsy failed. Pathology revealed localized lymphoid hyperplasia. The patient had an uneventful postoperative course. He has been alive for 18 months after surgery.

  18. Colonization and effector functions of innate lymphoid cells in mucosal tissues.

    Science.gov (United States)

    Kim, Myunghoo; Kim, Chang H

    2016-10-01

    Innate lymphoid cells (ILCs) protect mucosal barrier tissues to fight infection and maintain tissue integrity. ILCs and their progenitors are developmentally programmed to migrate, differentiate and populate various mucosal tissues and associated lymphoid tissues. Functionally mature ILC subsets respond to diverse pathogens such as bacteria, viruses, fungi and parasites in subset-specific manners. In this review, we will discuss how ILCs populate mucosal tissues and regulate immune responses to distinct pathogens to protect the host and maintain tissue integrity. Copyright © 2016 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  19. Retinoic acid differentially regulates the migration of innate lymphoid cell subsets to the gut

    OpenAIRE

    Kim, Myung H.; Taparowsky, Elizabeth J.; Kim, Chang H.

    2015-01-01

    Distinct groups of innate lymphoid cells (ILCs) such as ILC1, ILC2 and ILC3 populate the intestine, but how these ILCs develop tissue tropism for this organ is unclear. We report that prior to migration to the intestine ILCs first undergo a `switch' in their expression of homing receptors from lymphoid to gut homing receptors. This process is regulated by mucosal dendritic cells and the gut-specific tissue factor retinoic acid (RA). This change in homing receptors is required for long-term po...

  20. Imaging Findings of Localized Lymphoid Hyperplasia of the Pancreas: a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Woong; Heo, Suk Hee; Jeong, Yong Yeon; Kang, Heoung Keun [Chonnam National University Hwasun Hospital and Medical School, Hwasun (Korea, Republic of); Shin, Sang Soo; Choi, Yoo Duk [Chonnam National University Hospital and Medical School, Gwangju (KR)

    2011-08-15

    We report here on a case of localized lymphoid hyperplasia of the pancreas in a 70-year-old man which manifested as double lesions (uncinate process and tail) in the organ. The lesions were incidentally detected as hypoechoic lesions on ultrasonography and they appeared as delayed enhancing lesions on the contrast-enhanced dynamic CT and MRI. Total pancreatectomy was performed, because malignant tumor could not be excluded according to the preoperative imaging studies and the endoscopic ultrasound-guided biopsy failed. Pathology revealed localized lymphoid hyperplasia. The patient had an uneventful postoperative course. He has been alive for 18 months after surgery.

  1. Allograft tolerance in pigs after fractionated lymphoid irradiation. II. Kidney graft after conventional total lymphoid irradiation and bone marrow cell grafting

    International Nuclear Information System (INIS)

    Fradelizi, D.; Mahouy, G.; de Riberolles, C.; Lecompte, Y.; Alhomme, P.; Douard, M.C.; Chotin, G.; Martelli, H.; Daburon, F.; Vaiman, M.

    1981-01-01

    Experiments with pigs have been performed in order to establish bone marrow chimerism and kidney graft tolerance between SLA genotyped semi-incompatible animals. Recipients were conditioned by means of conventional fractionated total lymphoid irradiation (TLI) delivered by a vertical cobalt source. The principal lymphoid regions of the pig, including thymus and spleen, were submitted to irradiation. Two protocols were tested: A = 250 cGy four times a week x 13 times (TLI) (two animals) and B = 350 cGy three times a week x 8 times (TLI) (four animals). Bone marrow cells were injected 24 h after the last irradiation. One day later, bilateral nephrectomy and the graft of one kidney from the bone marrow cell donor were performed simultaneously. Results convinced us that application of the TLI protocol to humans is not yet practicable and that further experimental work is needed

  2. Hypothesis Testing in the Real World

    Science.gov (United States)

    Miller, Jeff

    2017-01-01

    Critics of null hypothesis significance testing suggest that (a) its basic logic is invalid and (b) it addresses a question that is of no interest. In contrast to (a), I argue that the underlying logic of hypothesis testing is actually extremely straightforward and compelling. To substantiate that, I present examples showing that hypothesis…

  3. Error probabilities in default Bayesian hypothesis testing

    NARCIS (Netherlands)

    Gu, Xin; Hoijtink, Herbert; Mulder, J,

    2016-01-01

    This paper investigates the classical type I and type II error probabilities of default Bayes factors for a Bayesian t test. Default Bayes factors quantify the relative evidence between the null hypothesis and the unrestricted alternative hypothesis without needing to specify prior distributions for

  4. Reassessing the Trade-off Hypothesis

    DEFF Research Database (Denmark)

    Rosas, Guillermo; Manzetti, Luigi

    2015-01-01

    Do economic conditions drive voters to punish politicians that tolerate corruption? Previous scholarly work contends that citizens in young democracies support corrupt governments that are capable of promoting good economic outcomes, the so-called trade-off hypothesis. We test this hypothesis based...

  5. Mastery Learning and the Decreasing Variability Hypothesis.

    Science.gov (United States)

    Livingston, Jennifer A.; Gentile, J. Ronald

    1996-01-01

    This report results from studies that tested two variations of Bloom's decreasing variability hypothesis using performance on successive units of achievement in four graduate classrooms that used mastery learning procedures. Data do not support the decreasing variability hypothesis; rather, they show no change over time. (SM)

  6. Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation.

    Science.gov (United States)

    Wells, James W; Evans, Christopher H; Scott, Milcah C; Rütgen, Barbara C; O'Brien, Timothy D; Modiano, Jaime F; Cvetkovic, Goran; Tepic, Slobodan

    2013-01-01

    Rapidly growing tumor cells require a nutrient-rich environment in order to thrive, therefore, restricting access to certain key amino acids, such as arginine, often results in the death of malignant cells, which frequently display defective cell cycle check-point control. Healthy cells, by contrast, become quiescent and remain viable under arginine restriction, displaying full recovery upon return to arginine-rich conditions. The use of arginase therapy to restrict available arginine for selectively targeting malignant cells is currently under investigation in human clinical trials. However, the suitability of this approach for veterinary uses is unexplored. As a prelude to in vivo studies in canine malignancies, we examined the in vitro effects of arginine-deprivation on canine lymphoid and osteosarcoma cell lines. Two lymphoid and 2 osteosarcoma cell lines were unable to recover following 6 days of arginine deprivation, but all remaining cell lines displayed full recovery upon return to arginine-rich culture conditions. These remaining cell lines all proved susceptible to cell death following the addition of arginase to the cultures. The lymphoid lines were particularly sensitive to arginase, becoming unrecoverable after just 3 days of treatment. Two of the osteosarcoma lines were also susceptible over this time-frame; however the other 3 lines required 6-8 days of arginase treatment to prevent recovery. In contrast, adult progenitor cells from the bone marrow of a healthy dog were able to recover fully following 9 days of culture in arginase. Over 3 days in culture, arginase was more effective than asparaginase in inducing the death of lymphoid lines. These results strongly suggest that short-term arginase treatment warrants further investigation as a therapy for lymphoid malignancies and osteosarcomas in dogs.

  7. Arginase treatment prevents the recovery of canine lymphoma and osteosarcoma cells resistant to the toxic effects of prolonged arginine deprivation.

    Directory of Open Access Journals (Sweden)

    James W Wells

    Full Text Available Rapidly growing tumor cells require a nutrient-rich environment in order to thrive, therefore, restricting access to certain key amino acids, such as arginine, often results in the death of malignant cells, which frequently display defective cell cycle check-point control. Healthy cells, by contrast, become quiescent and remain viable under arginine restriction, displaying full recovery upon return to arginine-rich conditions. The use of arginase therapy to restrict available arginine for selectively targeting malignant cells is currently under investigation in human clinical trials. However, the suitability of this approach for veterinary uses is unexplored. As a prelude to in vivo studies in canine malignancies, we examined the in vitro effects of arginine-deprivation on canine lymphoid and osteosarcoma cell lines. Two lymphoid and 2 osteosarcoma cell lines were unable to recover following 6 days of arginine deprivation, but all remaining cell lines displayed full recovery upon return to arginine-rich culture conditions. These remaining cell lines all proved susceptible to cell death following the addition of arginase to the cultures. The lymphoid lines were particularly sensitive to arginase, becoming unrecoverable after just 3 days of treatment. Two of the osteosarcoma lines were also susceptible over this time-frame; however the other 3 lines required 6-8 days of arginase treatment to prevent recovery. In contrast, adult progenitor cells from the bone marrow of a healthy dog were able to recover fully following 9 days of culture in arginase. Over 3 days in culture, arginase was more effective than asparaginase in inducing the death of lymphoid lines. These results strongly suggest that short-term arginase treatment warrants further investigation as a therapy for lymphoid malignancies and osteosarcomas in dogs.

  8. Peripheral tissue homing receptor control of naïve, effector, and memory CD8 T cell localization in lymphoid and non-lymphoid tissues.

    Science.gov (United States)

    Brinkman, C Colin; Peske, J David; Engelhard, Victor Henry

    2013-01-01

    T cell activation induces homing receptors that bind ligands on peripheral tissue vasculature, programing movement to sites of infection and injury. There are three major types of CD8 effector T cells based on homing receptor expression, which arise in distinct lymphoid organs. Recent publications indicate that naïve, effector, and memory T cell migration is more complex than once thought; while many effectors enter peripheral tissues, some re-enter lymph nodes (LN), and contain central memory precursors. LN re-entry can depend on CD62L or peripheral tissue homing receptors. Memory T cells in LN tend to express the same homing receptors as their forebears, but often are CD62Lneg. Homing receptors also control CD8 T cell tumor entry. Tumor vasculature has low levels of many peripheral tissue homing receptor ligands, but portions of it resemble high endothelial venules (HEV), enabling naïve T cell entry, activation, and subsequent effector activity. This vasculature is associated with positive prognoses in humans, suggesting it may sustain ongoing anti-tumor responses. These findings reveal new roles for homing receptors expressed by naïve, effector, and memory CD8 T cells in controlling entry into lymphoid and non-lymphoid tissues.

  9. Regular character of chromatin degradation in lymphoid tissues after treatment with biological alkylating agents in vivo

    International Nuclear Information System (INIS)

    Matyasova, J.; Skalka, M.; Cejkova, M.

    1979-01-01

    The chromatin changes are reevaluated occurring in lymphoid tissues of mice treated with alkylating agents of the nitrogen-mustard type in relation to recent evidence on the nucleosomal organization of chromatin and to our new data on the regular character of chromatin degradation in lymphoid tissues of irradiated mice. DNA was isolated from nuclei at various intervals (1 to 18 h) after treatment of mice and subjected to gel electrophoresis in polyacrylamide gels. Thymus chromatin from treated mice has been shown to degrade in a regular fashion and to yield discrete DNA fragments, resembling those that originate in lymphoid tissues of irradiated mice or in thymus nuclei digested with micrococcal nuclease in vitro. With increasing interval after treatment higher amounts of smaller DNA fragments appear. Chromatin in spleen cells responds to treatment in a similar way, whilst no degradation in vivo takes place in liver chromatin. Chromatin of LS/BL lymphosarcoma cells in mice treated with alkylating agents or with irradiation suffers from a similar regular degradation. The results stress the significance of the action of liberated or activated endogenous nuclease(s) in the development of chromatin damage in lymphoid cells after treatment with alkylating agents. (author)

  10. Case of CML lymphoid blast crisis presenting as bilateral breast masses.

    Science.gov (United States)

    Hossain, Aneesha; Gupta, Kanika; Mener, Andrew; Tabbara, Imad

    2016-08-10

    A woman aged 42 years with a 1-month history of rapidly expanding bilateral breast masses presented with severe leucocytosis, anaemia, blurry vision, headaches and shortness of breath. Evaluation revealed chronic myeloid leukaemia in lymphoid blast crisis with extramedullary leukaemia involving her breasts. 2016 BMJ Publishing Group Ltd.

  11. Treatment of severe aplastic anaemia with total lymphoid irradiation and methylprednisolone

    International Nuclear Information System (INIS)

    Mehta, J.; Singhal, S.; Huilgol, N.; Merchant, R.; Mehta, B.C.

    1992-01-01

    This case report briefly summarizes the treatment of aplastic anaemia with total lymphoid irradiation and methylprednisolone and recommends that this procedure should be considered a therapeutic option in patients who are not candidates for bone marrow transplantation or antithymocyte globulin, or those who have failed one course of the latter. (Author)

  12. The 2016 revision of the World Health Organization classification of lymphoid neoplasms | Center for Cancer Research

    Science.gov (United States)

    A revision of the nearly 8-year-old World Health Organization classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists, and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities.

  13. Genotypic and phenotypic aspects of primary immunodeficiency diseases of the lymphoid system

    NARCIS (Netherlands)

    J.G. Noordzij

    2002-01-01

    textabstractThis thesis focuses on the immunological phenotype, the mutation analysis, and the residual activity of mutated proteins in patients with PID of the lymphoid system. During this project, we have investigated possible genotype-(immuno)phenotype relationships in patients with antibody

  14. Microscopic aspects of lymphoid organs in the guinea pig (Cavia porcellus

    Directory of Open Access Journals (Sweden)

    Fernanda Menezes de Oliveira e Silva

    2013-10-01

    Full Text Available http://dx.doi.org/10.5007/2175-7925.2013v26n4p233 Microscopy of lymphoid organs was studied in the guinea pig at different developmental stages – fetus, pup, and adult. Liver is a lobed organ, coated with a mesothelium, and it consists of sinusoids and cell plates in its parenchyma, named hepatocytes. Thymus is covered by a thin capsule of connective tissue which is protruded as septa into the entire organ. The parenchyma of each lobule is not clearly separated into a cortex and medulla. Hassall’s corpuscles are abundant. Lymph nodes are arranged into cortex and medulla. The cortex has germinal centers or lymphoid nodules, surrounded by diffuse lymphoid tissue. Spleen is divided into red and white pulp. Trabeculae of connective tissue are protruded into the spleen from the capsule; however, they are sparsely found around the red and white pulps. Germinal centers were found in the white pulp, where small and large lymphocytes and lymphoblasts can be found. Since the guinea pig is regarded as an important model for morphological studies due to its closeness to human beings, this article raises relevant information on the structural components of the lymphoid system in these animals, providing a new source of data to other knowledge fields.

  15. Microscopic aspects of lymphoid organs in the guinea pig (Cavia porcellus

    Directory of Open Access Journals (Sweden)

    Fernanda Menezes de Oliveira e Silva

    2013-11-01

    Full Text Available Microscopy of lymphoid organs was studied in the guinea pig at different developmental stages – fetus, pup, and adult. Liver is a lobed organ, coated with a mesothelium, and it consists of sinusoids and cell plates in its parenchyma, named hepatocytes. Thymus is covered by a thin capsule of connective tissue which is protruded as septa into the entire organ. The parenchyma of each lobule is not clearly separated into a cortex and medulla. Hassall’s corpuscles are abundant. Lymph nodes are arranged into cortex and medulla. The cortex has germinal centers or lymphoid nodules, surrounded by diffuse lymphoid tissue. Spleen is divided into red and white pulp. Trabeculae of connective tissue are protruded into the spleen from the capsule; however, they are sparsely found around the red and white pulps. Germinal centers were found in the white pulp, where small and large lymphocytes and lymphoblasts can be found. Since the guinea pig is regarded as an important model for morphological studies due to its closeness to human beings, this article raises relevant information on the structural components of the lymphoid system in these animals, providing a new source of data to other knowledge fields.

  16. Context-Dependent Development of Lymphoid Stroma from Adult CD34+ Adventitial Progenitors

    DEFF Research Database (Denmark)

    Sitnik, Katarzyna Maria; Wendland, Kerstin; Weishaupt, Holger

    2016-01-01

    Despite the key role of primary and secondary lymphoid organ stroma in immunity, our understanding of the heterogeneity and ontogeny of these cells remains limited. Here, we identify a functionally distinct subset of BP3-PDPN+PDGFRβ+/α+CD34+ stromal adventitial cells in both lymph nodes (LNs...

  17. Serious Infections in Patients Receiving Ibrutinib for Treatment of Lymphoid Malignancies.

    Science.gov (United States)

    Varughese, Tilly; Taur, Ying; Cohen, Nina; Palomba, M Lia; Seo, Susan K; Hohl, Tobias M; Redelman-Sidi, Gil

    2018-03-02

    Ibrutinib is a Bruton's tyrosine kinase inhibitor that is used for the treatment of lymphoid malignancies, including chronic lymphocytic leukemia (CLL), Waldenström's macroglobulinemia and mantle cell lymphoma (MCL). Several case series have described opportunistic infections among ibrutinib recipients, but the full extent of these infections is unknown. We sought to determine the spectrum of serious infections associated with ibrutinib treatment. We reviewed the electronic medical records of patients with lymphoid malignancies at Memorial Sloan Kettering Cancer Center who received ibrutinib during a five-year period from January 1, 2012 to December 31, 2016. Serious infections were identified by review of the relevant microbiology, clinical laboratory, and radiology data. Risk factors for infection were determined by univariate and multivariate analyses. 378 patients with lymphoid malignancies who received ibrutinib were analyzed. The most common underlying malignancies were CLL and MCL. 84% of patients received ibrutinib as monotherapy. Serious infection developed in 43 patients (11.4%), primarily during the first year of ibrutinib treatment. Of these, 23 (53.5%) developed invasive bacterial infections, and 16 (37.2%) developed invasive fungal infections (IFI). The majority of those who developed IFI on ibrutinib therapy (62.5%) lacked classical clinical risk factors for fungal infection (i.e., neutropenia, lymphopenia, and receipt of corticosteroids). Infection resulted in death in six of the 43 patients (14%). Patients with lymphoid malignancies receiving ibrutinib treatment are at risk for serious infections, including IFI.

  18. Disseminated Cryptococcosis With Brain Involvement in Patients With Chronic Lymphoid Malignancies on Ibrutinib.

    Science.gov (United States)

    Messina, Julia A; Maziarz, Eileen K; Spec, Andrej; Kontoyiannis, Dimitrios P; Perfect, John R

    2017-01-01

    We report 2 cases of disseminated cryptococcosis with central nervous system involvement in patients with chronic lymphoid malignancies occurring within 1 month of starting on ibrutinib. Characteristically, in both cases, no inflammation was seen in the cerebrospinal fluid. Central nervous system mycoses should be considered as a potential complication of ibrutinib.

  19. Disseminated Cryptococcosis With Brain Involvement in Patients With Chronic Lymphoid Malignancies on Ibrutinib

    OpenAIRE

    Messina, Julia A.; Maziarz, Eileen K.; Spec, Andrej; Kontoyiannis, Dimitrios P.; Perfect, John R.

    2017-01-01

    Abstract We report 2 cases of disseminated cryptococcosis with central nervous system involvement in patients with chronic lymphoid malignancies occurring within 1 month of starting on ibrutinib. Characteristically, in both cases, no inflammation was seen in the cerebrospinal fluid. Central nervous system mycoses should be considered as a potential complication of ibrutinib.

  20. Treatment of Mucosa-associated Lymphoid Tissue Lymphoma in Sjogren's Syndrome : A Retrospective Clinical Study

    NARCIS (Netherlands)

    Pollard, Rodney P. E.; Pijpe, Justin; Bootsma, Hendrika; Spijkervet, Fred K. L.; Kluin, Philip M.; Roodenburg, Jan L. N.; Kallenberg, Cees G. M.; Vissink, Arjan; van Imhoff, Gustaaf W.

    2011-01-01

    Objective. To retrospectively analyze the clinical course of patients with mucosa-associated lymphoid tissue (MALT)-type lymphoma of the parotid gland and associated Sjogren's syndrome (SS). Methods. All consecutive patients with SS and MALT lymphoma (MALT-SS) diagnosed in the University Medical

  1. S1P dependent inter organ trafficking of group 2 innate lymphoid cells suppots host defense

    Science.gov (United States)

    Innate lymphoid cells (ILCs) are considered to be the innate counterparts of adaptive T lymphocytes and play important roles in host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs are generally thought of as tissue-resident cells, but whether ILCs strictly behave in a...

  2. Establishment and function of tissue-resident innate lymphoid cells in the skin

    Directory of Open Access Journals (Sweden)

    Jie Yang

    2017-03-01

    Full Text Available ABSTRACT Innate lymphoid cells (ILCs are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lymphoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mechanisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood. We herein review the up-to-date understanding of tissue-specific relevance of ILCs. Particularly we will focus on resident ILCs of the skin, the outmost barrier tissue critical in protection against various foreign hazardous agents and maintenance of thermal and water balance. In addition, we will discuss remaining outstanding questions yet to be addressed.

  3. Th1- and Th2-like subsets of innate lymphoid cells

    NARCIS (Netherlands)

    Bernink, Jochem; Mjösberg, Jenny; Spits, Hergen

    2013-01-01

    Innate lymphoid cells (ILCs) constitute a family of effectors in innate immunity and regulators of tissue remodeling that have a cytokine and transcription factor expression pattern that parallels that of the T-helper (Th) cell family. Here, we discuss how ILCs can be categorized and summarize the

  4. Establishment and function of tissue-resident innate lymphoid cells in the skin.

    Science.gov (United States)

    Yang, Jie; Zhao, Luming; Xu, Ming; Xiong, Na

    2017-07-01

    Innate lymphoid cells (ILCs) are a newly classified family of immune cells of the lymphoid lineage. While they could be found in both lymphoid organs and non-lymphoid tissues, ILCs are preferentially enriched in barrier tissues such as the skin, intestine, and lung where they could play important roles in maintenance of tissue integrity and function and protection against assaults of foreign agents. On the other hand, dysregulated activation of ILCs could contribute to tissue inflammatory diseases. In spite of recent progress towards understanding roles of ILCs in the health and disease, mechanisms regulating specific establishment, activation, and function of ILCs in barrier tissues are still poorly understood. We herein review the up-to-date understanding of tissue-specific relevance of ILCs. Particularly we will focus on resident ILCs of the skin, the outmost barrier tissue critical in protection against various foreign hazardous agents and maintenance of thermal and water balance. In addition, we will discuss remaining outstanding questions yet to be addressed.

  5. Innate Lymphoid Cells (ILCs): Cytokine Hubs Regulating Immunity and Tissue Homeostasis

    NARCIS (Netherlands)

    Nagasawa, Maho; Spits, Hergen; Ros, Xavier Romero

    2017-01-01

    Innate lymphoid cells (ILCs) have emerged as an expanding family of effector cells particularly enriched in the mucosal barriers. ILCs are promptly activated by stress signals and multiple epithelial- and myeloid-cell-derived cytokines. In response, ILCs rapidly secrete effector cytokines, which

  6. NFIL3 Orchestrates the Emergence of Common Helper Innate Lymphoid Cell Precursors

    Directory of Open Access Journals (Sweden)

    Wei Xu

    2015-03-01

    Full Text Available Innate lymphoid cells (ILCs are a family of effectors that originate from a common innate lymphoid cell progenitor. However, the transcriptional program that sets the identity of the ILC lineage remains elusive. Here, we show that NFIL3 is a critical regulator of the common helper-like innate lymphoid cell progenitor (CHILP. Cell-intrinsic Nfil3 ablation led to variably impaired development of fetal and adult ILC subsets. Conditional gene targeting demonstrated that NFIL3 exerted its function prior to ILC subset commitment. Accordingly, NFIL3 ablation resulted in loss of ID2+ CHILP and PLZF+ ILC progenitors. Nfil3 expression in lymphoid progenitors was under the control of the mesenchyme-derived hematopoietin IL-7, and NFIL3 exerted its function via direct Id2 regulation in the CHILP. Moreover, ectopic Id2 expression in Nfil3-null precursors rescued defective ILC lineage development in vivo. Our data establish NFIL3 as a key regulator of common helper-like ILC progenitors as they emerge during early lymphopoiesis.

  7. Another Armament in Gut Immunity: Lymphotoxin-Mediated Crosstalk between Innate Lymphoid and Dendritic Cells

    NARCIS (Netherlands)

    Spits, H.

    2011-01-01

    Innate lymphoid cells (ILCs) are novel players in innate immunity. Tumanov et al. (Tumanov et al., 2011) demonstrate that crosstalk between ILCs and dendritic cells involving membrane-bound lymphotoxin in ILCs and its receptor is critical for protection against colitogenic bacteria

  8. Differential protective effects of immune lymphoid cells against transplanted line Ib leukemia and immune polioencephalomyelitis

    International Nuclear Information System (INIS)

    Duffey, P.S.; Lukasewycz, O.A.; Olson, D.S.; Murphy, W.H.

    1978-01-01

    The capacity of immune cells obtained from the major lymphoid compartments to protect C58 mice from transplanted line Ib leukemia, and from an age-dependent autoimmune CNS disease (immune polioencephalomyelitis = IPE) elicited by immunizing old C58 mice with inactivated Ib cells was quantified. Cells used for comparative adoptive protection tests were harvested from the major lymphoid compartments 14 to 15 days after young C58 mice were immunized with inactivated Ib cell preparations. Regression curves were plotted from survival data and the log 10 PD 50 values were determined. Immune spleen (ISC) and peritoneal cells (IPEC) were significantly more protective against transplanted Ib cells than immune lymph node (ILNC), thymic (ITC), and marrow cells (IMC). In contrast, IPEC and IMC were not protective against IPE and ITC were only marginally protective. ILNC afforded significant protection to transplantable leukemia but were only marginally protective to IPE. When ISC were treated with anti-thy 1.2 serum and complement, protection against transplanted leukemia and IPE was reduced > 99%. When donors of immune lymphoid cells were treated with 12.5 mg of cortisone acetate daily for 2 days before lymphoid cells were harvested, protection against transplanted Ib cells by ISC was reduced by approximately 90% whereas protection against IPE was totally eliminated. Considered together, these results indicate that the protective mechanisms to transplantable leukemia and IPE differ significantly in the same indicator mouse strain

  9. Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors.

    Science.gov (United States)

    Horton, Sarah J; Giotopoulos, George; Yun, Haiyang; Vohra, Shabana; Sheppard, Olivia; Bashford-Rogers, Rachael; Rashid, Mamunur; Clipson, Alexandra; Chan, Wai-In; Sasca, Daniel; Yiangou, Loukia; Osaki, Hikari; Basheer, Faisal; Gallipoli, Paolo; Burrows, Natalie; Erdem, Ayşegül; Sybirna, Anastasiya; Foerster, Sarah; Zhao, Wanfeng; Sustic, Tonci; Petrunkina Harrison, Anna; Laurenti, Elisa; Okosun, Jessica; Hodson, Daniel; Wright, Penny; Smith, Ken G; Maxwell, Patrick; Fitzgibbon, Jude; Du, Ming Q; Adams, David J; Huntly, Brian J P

    2017-09-01

    Loss-of-function mutations of cyclic-AMP response element binding protein, binding protein (CREBBP) are prevalent in lymphoid malignancies. However, the tumour suppressor functions of CREBBP remain unclear. We demonstrate that loss of Crebbp in murine haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphomas. This is preceded by accumulation of hyperproliferative lymphoid progenitors with a defective DNA damage response (DDR) due to a failure to acetylate p53. We identify a premalignant lymphoma stem cell population with decreased H3K27ac, which undergoes transcriptional and genetic evolution due to the altered DDR, resulting in lymphomagenesis. Importantly, when Crebbp is lost later in lymphopoiesis, cellular abnormalities are lost and tumour generation is attenuated. We also document that CREBBP mutations may occur in HSPCs from patients with CREBBP-mutated lymphoma. These data suggest that earlier loss of Crebbp is advantageous for lymphoid transformation and inform the cellular origins and subsequent evolution of lymphoid malignancies.

  10. Ocular adnexal mucosa-associated lymphoid tissue lymphoma treated with radiotherapy

    International Nuclear Information System (INIS)

    Ejima, Yasuo; Sasaki, Ryohei; Okamoto, Yoshiaki; Maruta, Tsutomu; Azumi, Atsushi; Hayashi, Yoshitake; Demizu, Yusuke; Ota, Yosuke; Soejima, Toshinori; Sugimura, Kazuro

    2006-01-01

    Forty-two patients with stage IE ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma were retrospectively analyzed. Five-year local control and progression-free survival rates were 100 and 77%, respectively. The most common relapsed site was the contralateral orbit. Thirty Gy of local irradiation seemed to be quite effective and safe

  11. Tracheal involvement of bronchus-associated lymphoid tissue lymphoma: a case report

    International Nuclear Information System (INIS)

    Sohn, Kyung Sik; Jeon, Kyung Neough; Kang, Duk Sik

    2002-01-01

    Primary malignant tumors of the trachea are rare, the most prevalent histologies beeing squamous cell and adenoid cystic carcinoma. A review of the literature revealed only ten cases of primary tracheal or bronchial non-Hodgkin's lymphoma. We describe a case in which tracheal involvement of bronchus-associated lymphoid tissue lymphoma, a subtype of non-Hodgkin's lymphoma, occurred

  12. Most B cells in non-lymphoid tissues are naïve.

    Science.gov (United States)

    Inman, Charlotte F; Murray, Tamsin Zangerle; Bailey, Mick; Cose, Stephen

    2012-02-01

    The current view of lymphocyte migration states that naïve lymphocytes re-circulate between the blood and the lymph via the lymph nodes, but are not able to access non-lymphoid tissues. We examined B lymphocytes in peripheral tissues and found that the majority were phenotypically similar to naïve B cells in lymphoid tissues and were located within the parenchyma, not associated with blood vessels. The mutation rate within the Vh region of these cells was substantially less than the rate attributed to somatic hypermutation and was identical to that observed in naïve B cells isolated from the lymph nodes, showing the presence of naïve B cells in the non-lymphoid organs. Further, using FTY720-treated mice, we showed that naïve B cells migrate through the peripheral tissues and, using pertussis toxin, that the entry of B cells was not controlled by chemokine-mediated signalling events. Overall, these results show that naïve B lymphocytes constitute the majority of the total B-cell population in non-lymphoid tissues and suggest that these cells may re-circulate through the periphery as part of their normal migration pathway. This has implications for the current view of the role of naïve B cells in priming and tolerance.

  13. Peripheral Lymphoid Volume Expansion and Maintenance Are Controlled by Gut Microbiota via RALDH+ Dendritic Cells.

    Science.gov (United States)

    Zhang, Zongde; Li, Jianjian; Zheng, Wencheng; Zhao, Guang; Zhang, Hong; Wang, Xiaofei; Guo, Yaqian; Qin, Chuan; Shi, Yan

    2016-02-16

    Lymphocyte homing to draining lymph nodes is critical for the initiation of immune responses. Secondary lymphoid organs of germ-free mice are underdeveloped. How gut commensal microbes remotely regulate cellularity and volume of secondary lymphoid organs remains unknown. We report here that, driven by commensal fungi, a wave of CD45(+)CD103(+)RALDH(+) cells migrates to the peripheral lymph nodes after birth. The arrival of these cells introduces high amounts of retinoic acid, mediates the neonatal to adult addressin switch on endothelial cells, and directs the homing of lymphocytes to both gut-associated lymphoid tissues and peripheral lymph nodes. In adult mice, a small number of these RALDH(+) cells might serve to maintain the volume of secondary lymphoid organs. Homing deficiency of these cells was associated with lymph node attrition in vitamin-A-deficient mice, suggesting a perpetual dependence on retinoic acid signaling for structural and functional maintenance of peripheral immune organs. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Ultrasound Findings of Lymphoid Hyperplasia of the Appendix in Children: Differentiation from Acute Appendicitis

    International Nuclear Information System (INIS)

    Kim, Bong Jae; Seo, Jung Wook; Lee, Byung Hoon

    2009-01-01

    To evaluate the ultrasound (US) findings that can help differentiate lymphoid hyperplasia in the appendix from acute appendicitis. A total of 1230 patients (below 20 years old) suspected of having appendicitis received an appendectomy between November, 1999, and March, 2008, with US findings in 27 patients with pathologically proven lymphoid hyperplasia of the appendix. Of 167 patients that received an appendectomy from January, 2007, to December, 2007, 52 patients with acute appendicitis were retrospectively reviewed as a control group. Retrospective review of US images was performed by two radiologists who were blinded to the pathologic results. The review was based on 12 ultrasonographic criteria derived from reports on the diagnostic findings of the appendicitis. Compared with acute appendicitis, lymphoid hyperplasia in appendix had a smaller diameter (7.14±1.22 mm vs 9.37±1.80 mm, p < 0.001) and less wall thickening(1.38±0.36 mm vs 1.74 ± 0.56 mm, p =0.001). Periappendicular inflammation (p < 0.001), intraluminal air (p = 0.006), round shape in transverse scan (p = 0.002),increased blood flow on color Doppler US (p = 0.03) were also different. US is a useful modality to differentiate lymphoid hyperplasia in the appendix from acute appendicitis

  15. Maternal retinoids control type 3 innate lymphoid cells and set the offspring immunity

    NARCIS (Netherlands)

    van de Pavert, Serge A; Ferreira, Manuela; Domingues, Rita G; Ribeiro, Hélder; Molenaar, Rosalie; Moreira-Santos, Lara; Almeida, Francisca F; Ibiza, Sales; Barbosa, Inês; Goverse, Gera; Labão-Almeida, Carlos; Godinho-Silva, Cristina; Konijn, Tanja; Schooneman, Dennis; O'Toole, Tom; Mizee, Mark R; Habani, Yasmin; Haak, Esther; Santori, Fabio R; Littman, Dan R; Schulte-Merker, Stefan; Dzierzak, Elaine; Simas, J Pedro; Mebius, Reina E; Veiga-Fernandes, Henrique

    2014-01-01

    The impact of nutritional status during fetal life on the overall health of adults has been recognized; however, dietary effects on the developing immune system are largely unknown. Development of secondary lymphoid organs occurs during embryogenesis and is considered to be developmentally

  16. Ectopic Tertiary Lymphoid Tissue in Inflammatory Bowel Disease: Protective or Provocateur?

    Directory of Open Access Journals (Sweden)

    Eoin Neil McNamee

    2016-08-01

    Full Text Available Organized lymphoid tissues like the thymus first appeared in jawed vertebrates around 500 million years ago and have evolved to equip the host with a network of specialized sites, strategically located to orchestrate strict immune-surveillance and efficient immune responses autonomously. The gut-associated lymphoid tissues (GALT maintain a mostly tolerant environment to dampen our responses to daily dietary and microbial products in the intestine. However, when this homeostasis is perturbed by chronic inflammation, the intestine is able to develop florid organized tertiary lymphoid tissues (TLT, which heralds the onset of regional immune dysregulation. While TLT are a pathologic hallmark of Crohn’s disease (CD, their role in the overall process remains largely enigmatic. A critical question remains; are intestinal TLT generated by the immune infiltrated intestine to modulate immune responses and rebuild tolerance to the microbiota or are they playing a more sinister role by generating dysregulated responses that perpetuate disease? Herein we discuss the main theories of intestinal tertiary lymphoid tissue neogenesis and focus on the most recent findings that open new perspectives to their role in inflammatory bowel disease.

  17. Ultrasound Findings of Lymphoid Hyperplasia of the Appendix in Children: Differentiation from Acute Appendicitis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bong Jae; Seo, Jung Wook; Lee, Byung Hoon [Inje University Ilsan Paik Hospital, Koyang (Korea, Republic of)

    2009-12-15

    To evaluate the ultrasound (US) findings that can help differentiate lymphoid hyperplasia in the appendix from acute appendicitis. A total of 1230 patients (below 20 years old) suspected of having appendicitis received an appendectomy between November, 1999, and March, 2008, with US findings in 27 patients with pathologically proven lymphoid hyperplasia of the appendix. Of 167 patients that received an appendectomy from January, 2007, to December, 2007, 52 patients with acute appendicitis were retrospectively reviewed as a control group. Retrospective review of US images was performed by two radiologists who were blinded to the pathologic results. The review was based on 12 ultrasonographic criteria derived from reports on the diagnostic findings of the appendicitis. Compared with acute appendicitis, lymphoid hyperplasia in appendix had a smaller diameter (7.14{+-}1.22 mm vs 9.37{+-}1.80 mm, p < 0.001) and less wall thickening(1.38{+-}0.36 mm vs 1.74 {+-} 0.56 mm, p =0.001). Periappendicular inflammation (p < 0.001), intraluminal air (p = 0.006), round shape in transverse scan (p = 0.002),increased blood flow on color Doppler US (p = 0.03) were also different. US is a useful modality to differentiate lymphoid hyperplasia in the appendix from acute appendicitis

  18. Derangements of lacrimal drainage-associated lymphoid tissue (LDALT) in human chronic dacryocystitis.

    Science.gov (United States)

    Ali, Mohammad Javed; Mulay, Kaustubh; Pujari, Aditi; Naik, Milind N

    2013-12-01

    To study the changes in the lacrimal drainage-associated lymphoid tissue of the lacrimal sac in human chronic dacryocystitis and its possible implications in understanding the immune defense mechanisms and etiopathogenesis of primary acquired nasolacrimal duct obstruction. Retrospective interventional study involving 200 lacrimal sacs of 164 consecutive patients seen between July 2009 and July 2012. Data collected include demographics, clinical presentation, laterality, age at presentation, duration of symptoms, diagnostic irrigation, indications for a dacyrocystectomy, pattern and severity of lymphoid infiltrate, types of lymphoid follicles and their locations, plasma cells, and other cellular infiltrates. The associated epithelial, stromal, and luminal changes with an emphasis on acini, mucosal glands, blood vessels, lymphatics, and goblet cells were also noted. Immunohistochemistry using CD3, CD20, CD138, and immunoglobulin A were used to substantiate the lymphoid tissues of the lacrimal sac. A total of 200 lacrimal sacs were obtained from dacryocystectomy of 164 patients. The patients included 60.5% (99/164) females and 39.6% (65/164) males, with a mean age of 58.4 years at presentation. Laterality showed a predominance of left lacrimal sacs (55%, 110/200) as compared to the right lacrimal sacs (45%, 90/200). Symptoms of epiphora and discharge of more than 6 months duration were considered to be chronic. Lymphoid infiltrate pattern was diffuse in majority of the sacs (81%, 162/200), with subepithelial and intraepithelial together being the commonest location (46.5%, 93/200). Distinct lymphoid follicles were seen in 28% (56/200). Most of the sacs showed mild plasma cell infiltration (66.5%, 133/200). IgA-rich secretions were noted in the lumen and the lining epithelium in 34.5% (69/200). Other common changes noted include increase in the goblet cells (82%, 164/200), dilated lymphatics (94%, 188/200), proliferating blood vessels (99%, 198/200), thickened

  19. Implications of the Bohm-Aharonov hypothesis

    International Nuclear Information System (INIS)

    Ghirardi, G.C.; Rimini, A.; Weber, T.

    1976-01-01

    It is proved that the Bohm-Aharonov hypothesis concerning largerly separated subsystems of composite quantum systems implies that it is impossible to express the dynamical evolution in terms of the density operator

  20. Multi-agent sequential hypothesis testing

    KAUST Repository

    Kim, Kwang-Ki K.; Shamma, Jeff S.

    2014-01-01

    incorporate costs of taking private/public measurements, costs of time-difference and disagreement in actions of agents, and costs of false declaration/choices in the sequential hypothesis testing. The corresponding sequential decision processes have well

  1. Lacrimal drainage-associated lymphoid tissue (LDALT): a part of the human mucosal immune system.

    Science.gov (United States)

    Knop, E; Knop, N

    2001-03-01

    Mucosa-associated lymphoid tissue (MALT) specifically protects mucosal surfaces. In a previous study of the human conjunctiva, evidence was also found for the presence of MALT in the lacrimal sac. The present study, therefore, aims to investigate its morphology and topographical distribution in the human lacrimal drainage system. Lacrimal drainage systems (n = 51) obtained from human cadavers were investigated by clearing flat wholemounts or by serial sections of tissue embedded in paraffin, OCT compound, or epoxy resin. These were further analyzed by histology, immunohistochemistry, and electron microscopy. All specimens showed the presence of lymphocytes and plasma cells as a diffuse lymphoid tissue in the lamina propria, together with intraepithelial lymphocytes and occasional high endothelial venules (HEV). It formed a narrow layer along the canaliculi that became thicker in the cavernous parts. The majority of lymphocytes were T cells, whereas B cells were interspersed individually or formed follicular centers. T cells were positive for CD8 and the human mucosa lymphocyte antigen (HML-1). Most plasma cells were positive for IgA and the overlying epithelium expressed its transporter molecule secretory component (SC). Basal mucous glands were present in the lacrimal canaliculi and in the other parts accompanied by alveolar and acinar glands, all producing IgA-rich secretions. Primary and secondary lymphoid follicles possessing HEV were present in about half of the specimens. The term lacrimal drainage-associated lymphoid tissue (LDALT) is proposed here to describe the lymphoid tissue that is regularly present and belongs to the common mucosal immune system and to the secretory immune system. It is suggested that it may form a functional unit together with the lacrimal gland and conjunctiva, connected by tear flow, lymphocyte recirculation, and probably the neural reflex arc, and play a major role in preserving ocular surface integrity.

  2. Disaster Debris Recovery Database - Recovery

    Science.gov (United States)

    The US EPA Region 5 Disaster Debris Recovery Database includes public datasets of over 6,000 composting facilities, demolition contractors, transfer stations, landfills and recycling facilities for construction and demolition materials, electronics, household hazardous waste, metals, tires, and vehicles in the states of Illinois, Indiana, Iowa, Kentucky, Michigan, Minnesota, Missouri, North Dakota, Ohio, Pennsylvania, South Dakota, West Virginia and Wisconsin.In this update, facilities in the 7 states that border the EPA Region 5 states were added to assist interstate disaster debris management. Also, the datasets for composters, construction and demolition recyclers, demolition contractors, and metals recyclers were verified and source information added for each record using these sources: AGC, Biocycle, BMRA, CDRA, ISRI, NDA, USCC, FEMA Debris Removal Contractor Registry, EPA Facility Registry System, and State and local listings.

  3. The (not so) Immortal Strand Hypothesis

    OpenAIRE

    Tomasetti, Cristian; Bozic, Ivana

    2015-01-01

    Background: Non-random segregation of DNA strands during stem cell replication has been proposed as a mechanism to minimize accumulated genetic errors in stem cells of rapidly dividing tissues. According to this hypothesis, an “immortal” DNA strand is passed to the stem cell daughter and not the more differentiated cell, keeping the stem cell lineage replication error-free. After it was introduced, experimental evidence both in favor and against the hypothesis has been presented. Principal...

  4. B-lymphocyte differentiation in lethally irradiated and reconstituted mice. II. Recovery of humoral immune responsiveness

    International Nuclear Information System (INIS)

    Rozing, J.; Brons, N.H.C.; Benner, R.

    1977-01-01

    The recovery of humoral immune responsiveness was studied in lethally irradiated, fetal liver-reconstituted mice. By means of both membrane fluorescence and antibody formation to sheep red blood cells (SRBC) as a functional assay, the rate of recovery of the compartments of B and T lymphocytes was determined in various lymphoid organs. The recovery of the immunoglobulin-positive (B) cell compartment after irradiation and reconstitution started in the spleen. This organ was also found to be the first in which the recovery of the B-cell population was completed. The interval between the recovery of the B-cell population in the spleen and that in the other organs tested was found to increase when the irradiated mice were reconstituted with spleen colony cells instead of fetal liver cells. This proved to be caused by the number and nature of the reconstituting hemopoietic stem cells. The immunoglobulin-positive (B) cells were found to appear before SRBC-reactive B cells could be demonstrated in spleen, lymph nodes, and Peyer's patches. The appearance of T lymphocytes in the various lymphoid organs required even more time. By means of cell transfer experiments, a sequential appearance of the precursors of anti-SRBC IgM-, IgG-, and IgA-plaque-forming cells could be demonstrated in spleen, bone marrow, lymph nodes, and Peyer's patches

  5. Multiple hypothesis tracking for the cyber domain

    Science.gov (United States)

    Schwoegler, Stefan; Blackman, Sam; Holsopple, Jared; Hirsch, Michael J.

    2011-09-01

    This paper discusses how methods used for conventional multiple hypothesis tracking (MHT) can be extended to domain-agnostic tracking of entities from non-kinematic constraints such as those imposed by cyber attacks in a potentially dense false alarm background. MHT is widely recognized as the premier method to avoid corrupting tracks with spurious data in the kinematic domain but it has not been extensively applied to other problem domains. The traditional approach is to tightly couple track maintenance (prediction, gating, filtering, probabilistic pruning, and target confirmation) with hypothesis management (clustering, incompatibility maintenance, hypothesis formation, and Nassociation pruning). However, by separating the domain specific track maintenance portion from the domain agnostic hypothesis management piece, we can begin to apply the wealth of knowledge gained from ground and air tracking solutions to the cyber (and other) domains. These realizations led to the creation of Raytheon's Multiple Hypothesis Extensible Tracking Architecture (MHETA). In this paper, we showcase MHETA for the cyber domain, plugging in a well established method, CUBRC's INFormation Engine for Real-time Decision making, (INFERD), for the association portion of the MHT. The result is a CyberMHT. We demonstrate the power of MHETA-INFERD using simulated data. Using metrics from both the tracking and cyber domains, we show that while no tracker is perfect, by applying MHETA-INFERD, advanced nonkinematic tracks can be captured in an automated way, perform better than non-MHT approaches, and decrease analyst response time to cyber threats.

  6. Aminoglycoside antibiotics and autism: a speculative hypothesis

    Directory of Open Access Journals (Sweden)

    Manev Hari

    2001-10-01

    Full Text Available Abstract Background Recently, it has been suspected that there is a relationship between therapy with some antibiotics and the onset of autism; but even more curious, some children benefited transiently from a subsequent treatment with a different antibiotic. Here, we speculate how aminoglycoside antibiotics might be associated with autism. Presentation We hypothesize that aminoglycoside antibiotics could a trigger the autism syndrome in susceptible infants by causing the stop codon readthrough, i.e., a misreading of the genetic code of a hypothetical critical gene, and/or b improve autism symptoms by correcting the premature stop codon mutation in a hypothetical polymorphic gene linked to autism. Testing Investigate, retrospectively, whether a link exists between aminoglycoside use (which is not extensive in children and the onset of autism symptoms (hypothesis "a", or between amino glycoside use and improvement of these symptoms (hypothesis "b". Whereas a prospective study to test hypothesis "a" is not ethically justifiable, a study could be designed to test hypothesis "b". Implications It should be stressed that at this stage no direct evidence supports our speculative hypothesis and that its main purpose is to initiate development of new ideas that, eventually, would improve our understanding of the pathobiology of autism.

  7. Testing competing forms of the Milankovitch hypothesis

    DEFF Research Database (Denmark)

    Kaufmann, Robert K.; Juselius, Katarina

    2016-01-01

    We test competing forms of the Milankovitch hypothesis by estimating the coefficients and diagnostic statistics for a cointegrated vector autoregressive model that includes 10 climate variables and four exogenous variables for solar insolation. The estimates are consistent with the physical...... ice volume and solar insolation. The estimated adjustment dynamics show that solar insolation affects an array of climate variables other than ice volume, each at a unique rate. This implies that previous efforts to test the strong form of the Milankovitch hypothesis by examining the relationship...... that the latter is consistent with a weak form of the Milankovitch hypothesis and that it should be restated as follows: Internal climate dynamics impose perturbations on glacial cycles that are driven by solar insolation. Our results show that these perturbations are likely caused by slow adjustment between land...

  8. Rejecting the equilibrium-point hypothesis.

    Science.gov (United States)

    Gottlieb, G L

    1998-01-01

    The lambda version of the equilibrium-point (EP) hypothesis as developed by Feldman and colleagues has been widely used and cited with insufficient critical understanding. This article offers a small antidote to that lack. First, the hypothesis implicitly, unrealistically assumes identical transformations of lambda into muscle tension for antagonist muscles. Without that assumption, its definitions of command variables R, C, and lambda are incompatible and an EP is not defined exclusively by R nor is it unaffected by C. Second, the model assumes unrealistic and unphysiological parameters for the damping properties of the muscles and reflexes. Finally, the theory lacks rules for two of its three command variables. A theory of movement should offer insight into why we make movements the way we do and why we activate muscles in particular patterns. The EP hypothesis offers no unique ideas that are helpful in addressing either of these questions.

  9. The linear hypothesis and radiation carcinogenesis

    International Nuclear Information System (INIS)

    Roberts, P.B.

    1981-10-01

    An assumption central to most estimations of the carcinogenic potential of low levels of ionising radiation is that the risk always increases in direct proportion to the dose received. This assumption (the linear hypothesis) has been both strongly defended and attacked on several counts. It appears unlikely that conclusive, direct evidence on the validity of the hypothesis will be forthcoming. We review the major indirect arguments used in the debate. All of them are subject to objections that can seriously weaken their case. In the present situation, retention of the linear hypothesis as the basis of extrapolations from high to low dose levels can lead to excessive fears, over-regulation and unnecessarily expensive protection measures. To offset these possibilities, support is given to suggestions urging a cut-off dose, probably some fraction of natural background, below which risks can be deemed acceptable

  10. Rayleigh's hypothesis and the geometrical optics limit.

    Science.gov (United States)

    Elfouhaily, Tanos; Hahn, Thomas

    2006-09-22

    The Rayleigh hypothesis (RH) is often invoked in the theoretical and numerical treatment of rough surface scattering in order to decouple the analytical form of the scattered field. The hypothesis stipulates that the scattered field away from the surface can be extended down onto the rough surface even though it is formed by solely up-going waves. Traditionally this hypothesis is systematically used to derive the Volterra series under the small perturbation method which is equivalent to the low-frequency limit. In this Letter we demonstrate that the RH also carries the high-frequency or the geometrical optics limit, at least to first order. This finding has never been explicitly derived in the literature. Our result comforts the idea that the RH might be an exact solution under some constraints in the general case of random rough surfaces and not only in the case of small-slope deterministic periodic gratings.

  11. Effect of alkaline and acidic fractions of industrial effluents on some lymphoid cells of the fish Rasbora daniconius

    Energy Technology Data Exchange (ETDEWEB)

    Elizabeth, T K; Balasubramanian, N K; John, P A

    1981-01-01

    The percentage frequency of the different types of lymphoid cell found in the head-kidney of Rasbora daniconius exposed for 24 h to lc/sub 50/ levels of the ammonia (alkali), phosphoric and sulphuric acid fractions of the effluent from a fertiliser factory was determined by the imprint method. 'T' tests showed that both the alkaline and the acidic fractions could significantly affect the composition of the lymphoid cell population. Different types of lymphoid cell reacted differently to the different fractions; some cell types increased in number while others decreased. Some cell types were not affected. This indicated some sort of specificity in the action of the fractions on the lymphoid cells.

  12. Primary mucosa-associated lymphoid tissue (MALT) lymphoma of thyroid gland arising from coexisting Hashimoto's thyroiditis: a case report

    International Nuclear Information System (INIS)

    Lee, Sang Kwon; Kwon, Sun Young; Kim, Young Hwan; Choi, Jin Soo; Sohn, Chul Ho; Lee, Hee Jung; Woo, Seong Ku; Suh, Soo Ji

    2006-01-01

    We report herein on a case of primary mucosa-associated lymphoid tissue (MALT) lymphoma of the thyroid gland in a 57-year-old woman with coexisting Hashimoto's thyroiditis, and we include its characteristic imaging, histopathologic and immunohistochemical findings

  13. In vitro and in vivo infectivity and pathogenicity of the lymphoid cell-derived woodchuck hepatitis virus.

    Science.gov (United States)

    Lew, Y Y; Michalak, T I

    2001-02-01

    Woodchuck hepatitis virus (WHV) and human hepatitis B virus are closely related, highly hepatotropic mammalian DNA viruses that also replicate in the lymphatic system. The infectivity and pathogenicity of hepadnaviruses propagating in lymphoid cells are under debate. In this study, hepato- and lymphotropism of WHV produced by naturally infected lymphoid cells was examined in specifically established woodchuck hepatocyte and lymphoid cell cultures and coculture systems, and virus pathogenicity was tested in susceptible animals. Applying PCR-based assays discriminating between the total pool of WHV genomes and covalently closed circular DNA (cccDNA), combined with enzymatic elimination of extracellular viral sequences potentially associated with the cell surface, our study documents that virus replicating in woodchuck lymphoid cells is infectious to homologous hepatocytes and lymphoid cells in vitro. The productive replication of WHV from lymphoid cells in cultured hepatocytes was evidenced by the appearance of virus-specific DNA, cccDNA, and antigens, transmissibility of the virus through multiple passages in hepatocyte cultures, and the ability of the passaged virus to infect virus-naive animals. The data also revealed that WHV from lymphoid cells can initiate classical acute viral hepatitis in susceptible animals, albeit small quantities (approximately 10(3) virions) caused immunovirologically undetectable (occult) WHV infection that engaged the lymphatic system but not the liver. Our results provide direct in vitro and in vivo evidence that lymphoid cells in the infected host support propagation of infectious hepadnavirus that has the potential to induce hepatitis. They also emphasize a principal role of the lymphatic system in the maintenance and dissemination of hepadnavirus infection, particularly when infection is induced by low virus doses.

  14. IL-33-responsive innate lymphoid cells are an important source of IL-13 in chronic rhinosinusitis with nasal polyps.

    Science.gov (United States)

    Shaw, Joanne L; Fakhri, Samer; Citardi, Martin J; Porter, Paul C; Corry, David B; Kheradmand, Farrah; Liu, Yong-Jun; Luong, Amber

    2013-08-15

    Chronic rhinosinusitis (CRS) without nasal polyps (CRSsNP) and CRS with nasal polyps (CRSwNP) are associated with Th1 and Th2 cytokine polarization, respectively; however, the pathophysiology of CRS remains unclear. The importance of innate lymphoid cells in Th2-mediated inflammatory disease has not been clearly defined. The objective of this study was to investigate the role of the epithelial cell-derived cytokine IL-33 and IL-33-responsive innate lymphoid cells in the pathophysiology of CRS. Relative gene expression was evaluated using quantitative real-time polymerase chain reaction. Innate lymphoid cells in inflamed ethmoid sinus mucosa from patients with CRSsNP and CRSwNP were characterized using flow cytometry. Cytokine production from lymphoid cells isolated from inflamed mucosa of patients with CRS was examined using ELISA and intracellular cytokine staining. Elevated expression of ST2, the ligand-binding chain of the IL-33 receptor, was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP and healthy control subjects. An increased percentage of innate lymphoid cells was observed in inflamed sinonasal mucosa from CRSwNP compared with CRSsNP. ST2(+) innate lymphoid cells are a consistent source of IL-13 in response to IL-33 stimulation. Significant induction of IL-33 was observed in epithelial cells derived from patients with CRSwNP compared with patients with CRSsNP in response to stimulation with Aspergillus fumigatus extract. These data suggest a role for sinonasal epithelial cell-derived IL-33 and an IL-33-responsive innate lymphoid cell population in the pathophysiology of CRSwNP demonstrating the functional importance of innate lymphoid cells in Th2-mediated inflammatory disease.

  15. Central Role of Core Binding Factor β2 in Mucosa-Associated Lymphoid Tissue Organogenesis in Mouse.

    Science.gov (United States)

    Nagatake, Takahiro; Fukuyama, Satoshi; Sato, Shintaro; Okura, Hideaki; Tachibana, Masashi; Taniuchi, Ichiro; Ito, Kosei; Shimojou, Michiko; Matsumoto, Naomi; Suzuki, Hidehiko; Kunisawa, Jun; Kiyono, Hiroshi

    2015-01-01

    Mucosa-associated lymphoid tissue (MALT) is a group of secondary and organized lymphoid tissue that develops at different mucosal surfaces. Peyer's patches (PPs), nasopharynx-associated lymphoid tissue (NALT), and tear duct-associated lymphoid tissue (TALT) are representative MALT in the small intestine, nasal cavity, and lacrimal sac, respectively. A recent study has shown that transcriptional regulators of core binding factor (Cbf) β2 and promotor-1-transcribed Runt-related transcription factor 1 (P1-Runx1) are required for the differentiation of CD3-CD4+CD45+ lymphoid tissue inducer (LTi) cells, which initiate and trigger the developmental program of PPs, but the involvement of this pathway in NALT and TALT development remains to be elucidated. Here we report that Cbfβ2 plays an essential role in NALT and TALT development by regulating LTi cell trafficking to the NALT and TALT anlagens. Cbfβ2 was expressed in LTi cells in all three types of MALT examined. Indeed, similar to the previous finding for PPs, we found that Cbfβ2-/- mice lacked NALT and TALT lymphoid structures. However, in contrast to PPs, NALT and TALT developed normally in the absence of P1-Runx1 or other Runx family members such as Runx2 and Runx3. LTi cells for NALT and TALT differentiated normally but did not accumulate in the respective lymphoid tissue anlagens in Cbfβ2-/- mice. These findings demonstrate that Cbfβ2 is a central regulator of the MALT developmental program, but the dependency of Runx proteins on the lymphoid tissue development would differ among PPs, NALT, and TALT.

  16. Tertiary Lymphoid Tissue Forms in Retinas of Mice with Spontaneous Autoimmune Uveitis and Has Consequences on Visual Function.

    Science.gov (United States)

    Kielczewski, Jennifer L; Horai, Reiko; Jittayasothorn, Yingyos; Chan, Chi-Chao; Caspi, Rachel R

    2016-02-01

    During chronic inflammation, tertiary lymphoid tissue (TLT) can form within an inflamed organ, including the CNS. However, little is known about TLT formation in the neuroretina. In a novel spontaneous autoimmune mouse model of uveitis (R161H), we identified well-organized lymphoid aggregates in the retina and examined them for TLT characteristics. Presence of immune cells, tissue-specific markers, and gene expression patterns typically associated with germinal centers and T follicular helper cells were examined using immunohistochemistry and gene analysis of laser capture microdissected retina. Our data revealed the retinal lymphoid structures contained CD4(+) T cells and B cells in well-defined zonal areas that expressed classic germinal center markers, peanut lectin (agglutinin) and GL-7. Gene expression analysis showed upregulation of T follicular helper cell markers, most notably CXCR5 and its ligand CXCL13, and immunohistochemical analysis confirmed CXCR5 expression, typically associated with CD4(+) T follicular helper cells. Highly organized stromal cell networks, a hallmark of organized lymphoid tissue, were also present. Positive staining for phospho-Zap70 in retina-specific T cells indicated CD4(+) T cells were being activated within these lymphoid structures. CD138(+)/B220(+) plasma cells were detected, suggesting the retinal lymphoid aggregates give rise to functional germinal centers, which produce Abs. Interestingly, eyes with lymphoid aggregates exhibited lower inflammatory scores by fundus examination and a slower initial rate of loss of visual function by electroretinography, compared with eyes without these structures. Our findings suggest that the lymphoid aggregates in the retina of R161H mice represent organized TLT, which impact the course of chronic uveitis.

  17. Safe and successful birth following pelvic radiotherapy for rectal mucosa-associated lymphoid tissue lymphoma: a case report.

    Science.gov (United States)

    Hatayama, Yoshiomi; Aoki, Masahiko; Kawaguchi, Hideo; Hirose, Katsumi; Sato, Mariko; Akimoto, Hiroyoshi; Tanaka, Mitsuki; Fujioka, Ichitaro; Ono, Shuichi; Takai, Yoshihiro

    2017-02-01

    Mucosa-associated lymphoid tissue lymphomas can occur in various parts of the body, and half of mucosa-associated lymphoid tissue lymphomas occur in the gastrointestinal tract. Gastric mucosa-associated lymphoid tissue lymphoma is the most common lymphoma of the gastrointestinal tract and primary rectal mucosa-associated lymphoid tissue lymphoma is very rare. Because of the high radiosensitivity of mucosa-associated lymphoid tissue lymphomas, this condition can be controlled with radiotherapy of approximately 30 Gy alone. However, ovarian dysfunction as an adverse event of radiotherapy for pelvic lesions can become a problem in girls and women. We report a case of a 28-year-old woman with rectal mucosa-associated lymphoid tissue lymphoma who safely gave birth to a baby following 30.6 Gy radiotherapy to her whole rectum. A 28-year-old Japanese woman became aware of bloody stools and was diagnosed as having Lugano I rectal mucosa-associated lymphoid tissue lymphoma. She was referred to our institute and initiated on radiotherapy. However, she expressed a desire to bear children. We used horizontally opposed pair fields for radiotherapy to minimize the irradiation to her endometrium and ovary. A total dose of 30.6 Gy was given in 17 fractions of 1.8 Gy by 10-Megavolt X-ray linear accelerator. As a result, one-third of her uterus and half of her ovary were outside the irradiation field. After approximately 1 year of treatment, positive pregnancy was confirmed and finally she safely gave birth to a baby girl without congenital abnormalities. This report provides hope for girls and women who have undergone irradiation for pelvic mucosa-associated lymphoid tissue lymphomas and who desire to bear children.

  18. Deficiency in Mucosa-associated Lymphoid Tissue Lymphoma Translocation 1: A Novel Cause of IPEX-Like Syndrome.

    Science.gov (United States)

    Charbit-Henrion, Fabienne; Jeverica, Anja K; Bègue, Bernadette; Markelj, Gasper; Parlato, Marianna; Avčin, Simona Lucija; Callebaut, Isabelle; Bras, Marc; Parisot, Mélanie; Jazbec, Janez; Homan, Matjaz; Ihan, Alojz; Rieux-Laucat, Frédéric; Stolzenberg, Marie-Claude; Ruemmele, Frank M; Avčin, Tadej; Cerf-Bensussan, Nadine

    2017-03-01

    Early-onset inflammatory bowel diseases can result from a wide spectrum of rare mendelian disorders. Early molecular diagnosis is crucial in defining treatment and in improving life expectancy. Herein we aimed at defining the mechanism of an immunodeficiency-polyendrocrinopathy and enteropathy-X-linked (IPEX)-like disease combined with a severe immunodeficiency in 2 siblings born from distantly related parents. Whole exome sequencing was performed on blood-extracted genomic DNA from the 2 affected children and their parents on the genomic platform of Institut IMAGINE. Candidate gene mutation was identified using the in-house software PolyWeb and confirmed by Sanger sequencing. Protein expression was determined by western blot. Flow cytometry was used to assess consequences of the mutation on lymphocyte phenotype and nuclear factor-kappa B (NF-κB) activation at diagnosis and after treatment by hematopoietic stem cell transplantation. We identified a homozygous missense mutation in mucosa-associated lymphoid tissue lymphoma translocation 1 gene (MALT1), which precluded protein expression. In keeping with the known function of MALT1, NF-κB-dependent lymphocyte activation was severely impaired. Moreover, there was a drastic reduction in Forkhead box P3 (FOXP3) regulatory T cells accounting for the IPEX-like phenotype. Following identification of the mutation, both children received hematopoietic stem cell transplantation, which permitted full clinical recovery. Immunological workup at 6 and 12 months after transplantation showed normal NF-κB activation and correction of regulatory T cells frequency. Along with FOXP3, interleukin 2 receptor alpha chain (IL2RA), and cytotoxic T-lymphocyte protein 4 precursor (CTLA-4) mutations, MALT1 deficiency should now be considered as a possible cause of IPEX-like syndrome associated with immunodeficiency that can be cured by hematopoietic stem cell transplantation.

  19. Tumor xenotransplantation in Wistar rats after treatment with cyclophosphamide and total lymphoid irradiation

    International Nuclear Information System (INIS)

    Hoogenhout, J.; Kazem, I.; Jerusalem, C.R.; Bakkeren, J.A.J.; de Jong, J.; Kal, H.B.; van Munster, P.J.J.

    1982-01-01

    Three-month-old male Wistar rats were treated with cyclophosphamide and total lymphoid irradiation, and C22LR mouse osteosarcoma was transplanted into the rats. The effects of immunosuppression were monitored by lymphocyte counts, serum IgG determinations, phytohemagglutinin (PHA) and concanavalin A (Con A) responses, measurement of the proportion of B cells, and histopathological studies of the lymphoid organs. At eight days after treatment, the lymphocyte counts, IgG levels, and PHA and Con A values were decreased. Mitotic activity started in the depleted B and T cell areas of the peripheral lymphatic organs two weeks after treatment. There was a 94% graft take of the osteosarcoma. It was determined that the optimum time for tumor xenograft transplantation is 4 days after treatment. The duration of growth was 11 days, and this was followed by regression up to day 21

  20. Lymphoid cell kinetics under continuous low dose-rate gamma irradiation: A comparison study

    Science.gov (United States)

    Foster, B. R.

    1975-01-01

    A comparison study was conducted of the effects of continuous low dose-rate gamma irradiation on cell population kinetics of lymphoid tissue (white pulp) of the mouse spleen with findings as they relate to the mouse thymus. Experimental techniques employed included autoradiography and specific labeling with tritiated thymidine (TdR-(h-3)). The problem studied involved the mechanism of cell proliferation of lymphoid tissue of the mouse spleen and thymus under the stress of continuous irradiation at a dose rate of 10 roentgens (R) per day for 105 days (15 weeks). The aim was to determine whether or not a steady state or near-steady state of cell population could be established for this period of time, and what compensatory mechanisms of cell population were involved.

  1. Type 2 Innate Lymphoid Cells: Friends or Foes—Role in Airway Allergic Inflammation and Asthma

    Science.gov (United States)

    Pishdadian, Abbas; Varasteh, Abdol-Reza; Sankian, Mojtaba

    2012-01-01

    Innate-like lymphocytes (ILLs) and innate lymphoid cells (ILCs) are two newly characterized families of lymphocytes with limited and no rearranged antigen receptors, respectively. These soldiers provide a first line of defense against foreign insults by triggering a prompt innate immune response and bridging the gap of innate and adaptive immunity. Type 2 innate lymphoid cells (ILCs2) are newly identified members of the ILC family that play a key role in type 2 immune responses by prompt production of type 2 cytokines (especially IL-5 and IL-13) in response to antigen-induced IL-25/33 and by recruiting type 2 “immune franchise.” Regarding the two different roles of type 2 cytokines, helminth expulsion and type 2-related diseases, here we review the latest advances in ILC2 biology and examine the pivotal role of resident ILCs2 in allergen-specific airway inflammation and asthma. PMID:23209480

  2. Characteristics of innate lymphoid cells (ILCs) and their role in immunological disorders (an update).

    Science.gov (United States)

    Yazdani, Reza; Sharifi, Mehri; Shirvan, Aylar Saba; Azizi, Gholamreza; Ganjalikhani-Hakemi, Mazdak

    2015-01-01

    Innate lymphoid cells (ILCs) are a novel family of hematopoietic effectors and regulators of innate immunity. Although these cells are morphologically similar to B cells and T cells, however they do not express antigen receptors. ILCs seems to have emerging roles in innate immune responses against infectious or non-infectious microorganisms, protection of the epithelial barrier, lymphoid organogenesis and inflammation, tissue remodeling and regulating homeostasis of tissue stromal cells. In addition, it has recently been reported that ILCs have a crucial role in several disorders such as allergy and autoimmunity. Based on their phenotype and functions, ILCs are classified into three major groups called ILCs1, ILCs2, and ILCs3. Here we reviewed the most recent data concerning diverse ILC phenotypes, subclasses, functions in immune responses as well as in immune mediated disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Back to the drawing board: Understanding the complexity of hepatic innate lymphoid cells.

    Science.gov (United States)

    Marotel, Marie; Hasan, Uzma; Viel, Sébastien; Marçais, Antoine; Walzer, Thierry

    2016-09-01

    Recent studies of immune populations in nonlymphoid organs have highlighted the great diversity of the innate lymphoid system. It has also become apparent that mouse and human innate lymphoid cells (ILCs) have distinct phenotypes and properties. In this issue of the European Journal of Immunology, Harmon et al. [Eur. J. Immunol. 2016. 46: 2111-2120] characterized human hepatic NK-cell subsets. The authors report that hepatic CD56(bright) NK cells resemble mouse liver ILC1s in that they express CXCR6 and have an immature phenotype. However, unlike mouse ILC1s, they express high levels of Eomes and low levels of T-bet, and upon stimulation with tumor cells, secrete low amounts of cytokines. These unexpected findings further support the differences between human and mouse immune populations and prompt the study of the role of hepatic ILC subsets in immune responses. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Transcription Factor Networks Directing the Development, Function, and Evolution of Innate Lymphoid Effectors

    Science.gov (United States)

    Kang, Joonsoo; Malhotra, Nidhi

    2015-01-01

    Mammalian lymphoid immunity is mediated by fast and slow responders to pathogens. Fast innate lymphocytes are active within hours after infections in mucosal tissues. Slow adaptive lymphocytes are conventional T and B cells with clonal antigen receptors that function days after pathogen exposure. A transcription factor (TF) regulatory network guiding early T cell development is at the core of effector function diversification in all innate lymphocytes, and the kinetics of immune responses is set by developmental programming. Operational units within the innate lymphoid system are not classified by the types of pathogen-sensing machineries but rather by discrete effector functions programmed by regulatory TF networks. Based on the evolutionary history of TFs of the regulatory networks, fast effectors likely arose earlier in the evolution of animals to fortify body barriers, and in mammals they often develop in fetal ontogeny prior to the establishment of fully competent adaptive immunity. PMID:25650177

  5. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen

    DEFF Research Database (Denmark)

    Rodrigues, Celso Arrais; Rocha, Vanderson; Dreger, Peter

    2014-01-01

    We have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who received...... an allogeneic unrelated donor transplant using umbilical cord blood (n=104) or mobilized peripheral blood stem cells (n=541) after a reduced-intensity conditioning regimen. Unrelated cord blood recipients had more refractory disease. Median follow-up time was 30 months. Neutrophil engraftment (81% vs. 97......%, respectively; Pblood than after matched unrelated donor, whereas no differences were observed in grade II-IV acute graft-versus-host disease (29% vs. 32%), non-relapse mortality (29% vs. 28...

  6. Inducible Bronchus-Associated Lymphoid Tissue: Taming Inflammation in the Lung.

    Science.gov (United States)

    Hwang, Ji Young; Randall, Troy D; Silva-Sanchez, Aaron

    2016-01-01

    Following pulmonary inflammation, leukocytes that infiltrate the lung often assemble into structures known as inducible Bronchus-Associated Lymphoid Tissue (iBALT). Like conventional lymphoid organs, areas of iBALT have segregated B and T cell areas, specialized stromal cells, high endothelial venules, and lymphatic vessels. After inflammation is resolved, iBALT is maintained for months, independently of inflammation. Once iBALT is formed, it participates in immune responses to pulmonary antigens, including those that are unrelated to the iBALT-initiating antigen, and often alters the clinical course of disease. However, the mechanisms that govern immune responses in iBALT and determine how iBALT impacts local and systemic immunity are poorly understood. Here, we review our current understanding of iBALT formation and discuss how iBALT participates in pulmonary immunity.

  7. Bystander CD4+ T lymphocytes survive in HIV-infected human lymphoid tissue

    Science.gov (United States)

    Grivel, Jean-Charles; Biancotto, Angelique; Ito, Yoshinori; Lima, Rosangela G.; Margolis, Leonid B.

    2003-01-01

    HIV infection is associated with depletion of CD4(+) T cells. The mechanisms of this phenomenon remain to be understood. In particular, it remains controversial whether and to what extent uninfected ("bystander") CD4(+) T cells die in HIV-infected individuals. We address this question using a system of human lymphoid tissue ex vivo. Tissue blocks were inoculated with HIV-1. After productive infection was established, they were treated with the reverse transcriptase inhibitor nevirapine to protect from infection those CD4(+) T cells that had not yet been infected. These CD4(+) T cells residing in HIV-infected tissue are by definition bystanders. Our results demonstrate that after nevirapine application the number of bystander CD4(+) T cells is conserved. Thus, in the context of HIV-infected human lymphoid tissue, productive HIV infection kills infected cells but is not sufficient to cause the death of a significant number of uninfected CD4(+) T cells.

  8. Protruding and non-protruding colon carcinomas originating in gut-associated lymphoid tissue.

    Science.gov (United States)

    Rubio, Carlos A; Lindh, Claes; Björk, Jan; Törnblom, Hans; Befrits, Ragnar

    2010-07-01

    Colon carcinomas arising in gut-associated lymphoid tissue (GALTC) are termed dome carcinomas (DC) because of their protruding phenotype. Only 8 GALTC cases have been reported in the literature. A female patient, aged 53, having a familial pedigree of colon cancer, uterine cervix cancer and brain tumour developed a signet-ring carcinoma in the cecum and 10 years later endometrial cancer. While asymptomatic, a plaque-like protrusion in the colon was detected at surveillance colonoscopy. Histology demonstrated a protruding GALTC. The surgical specimen showed four additional carcinomas: 2 GALTC (non-protruding) and 2 carcinomas in lymphoid-free colonic mucosa (LFCMC). Since adenomas could not be demonstrated neither previously nor in the colectomy specimen, it is suggested that the GALTCs in this patient may have followed the GALT-carcinoma pathway.

  9. Generation of Immunoglobulin diversity in human gut-associated lymphoid tissue.

    Science.gov (United States)

    Spencer, Jo; Barone, Francesca; Dunn-Walters, Deborah

    2009-06-01

    The organised gut associated lymphoid tissue (GALT) exists adjacent to an extensive and diverse luminal flora. The follicle associated epithelium and associated dendritic cells and lymphocytes form a tightly fortified gateway between the flora and the host that permits connectivity between them and chronic activation of the lymphoid compartment. As a consequence, plasma cell precursors are generated continuously, and in abundance, in GALT by clonal proliferation. Clonal proliferation alone on this scale would reduce the spectrum of B cell specificity. To compensate, GALT also houses molecular machinery that diversifies the receptor repertoire by somatic hypermutation, class switch recombination and receptor revision. These three processes of enhancing the diversity of mature B cells ensure that although clonally related plasma cells may secrete immunoglobulin side by side in the mucosa they rarely have identical antigen binding sites.

  10. Establishment of an in vitro system representing the chicken gut-associated lymphoid tissue.

    Science.gov (United States)

    Alitheen, Noorjahan Banu; McClure, Susan Jane; Yeap, Swee Keong; Kristeen-Teo, Ye Wen; Tan, Sheau Wei; McCullagh, Peter

    2012-01-01

    The bursa of Fabricius is critical for B cell development and differentiation in chick embryos. This study describes the production in vitro, from dissociated cell suspensions, of cellular agglomerates with functional similarities to the chicken bursa. Co-cultivation of epithelial and lymphoid cells obtained from embryos at the appropriate developmental stage regularly led to agglomerate formation within 48 hours. These agglomerates resembled bursal tissue in having lymphoid clusters overlaid by well organized epithelium. Whereas lymphocytes within agglomerates were predominantly Bu-1a(+), a majority of those emigrating onto the supporting membrane were Bu-1a(-) and IgM(+). Both agglomerates and emigrant cells expressed activation-induced deaminase with levels increasing after 24 hours. Emigrating cells were actively proliferating at a rate in excess of both the starting cell population and the population of cells remaining in agglomerates. The potential usefulness of this system for investigating the response of bursal tissue to avian Newcastle disease virus (strain AF2240) was examined.

  11. Abnormal Wnt signaling and stem cell activation in reactive lymphoid tissue and low-grade marginal zone lymphoma.

    Science.gov (United States)

    Zhang, Da; O'neil, Maura F; Cunningham, Mark T; Fan, Fang; Olyaee, Mojtaba; Li, Linheng

    2010-05-01

    The variable natural history of mucosa-associated lymphoid tissue (MALT) lymphoma poses a challenge in predicting clinical outcome. Since Wnt signaling, as indicated by nuclear localization of beta-catenin, is believed to be key in stem cell activation and stem cell self-renewal, we explored the possibility that it might have a predictive value in marginal zone lymphoma. We chose to analyze pbeta-catenin-S552 because its nuclear localization by immunohistochemistry appears to coincide with Wnt signaling-initiated tumorigenesis in intestinal and hematopoietic tissues. Wnt signaling and activation was studied in 22 tissue samples of extranodal marginal zone lymphoma, atypical lymphoid hyperplasia, reactive lymphoid hyperplasia, and normal lymphoid tissue to determine whether Wnt signaling could help distinguish MALT lymphoma from benign lesions. Compared to normal or reactive lymphoid tissue, we found increased nuclear expression of localized pbeta-catenin-S552 in atypical lymphoid hyperplasia and extranodal marginal zone lymphoma. We show that the anti-pbeta-catenin-S552 antibody may be useful in diagnosing and monitoring the progression of or response to therapy of MALT lymphoma.

  12. Nasal-associated lymphoid tissues (NALTs) support the recall but not priming of influenza virus-specific cytotoxic T cells.

    Science.gov (United States)

    Pizzolla, Angela; Wang, Zhongfang; Groom, Joanna R; Kedzierska, Katherine; Brooks, Andrew G; Reading, Patrick C; Wakim, Linda M

    2017-05-16

    The lymphoid tissue that drains the upper respiratory tract represents an important induction site for cytotoxic T lymphocyte (CTL) immunity to airborne pathogens and intranasal vaccines. Here, we investigated the role of the nasal-associated lymphoid tissues (NALTs), which are mucosal-associated lymphoid organs embedded in the submucosa of the nasal passage, in the initial priming and recall expansion of CD8 + T cells following an upper respiratory tract infection with a pathogenic influenza virus and immunization with a live attenuated influenza virus vaccine. Whereas NALTs served as the induction site for the recall expansion of memory CD8 + T cells following influenza virus infection or vaccination, they failed to support activation of naïve CD8 + T cells. Strikingly, NALTs, unlike other lymphoid tissues, were not routinely surveyed during the steady state by circulating T cells. The selective recruitment of memory T cells into these lymphoid structures occurred in response to infection-induced elevation of the chemokine CXCL10, which attracted CXCR3 + memory CD8 + T cells. These results have significant implications for intranasal vaccines, which deliver antigen to mucosal-associated lymphoid tissue and aim to elicit protective CTL-mediated immunity.

  13. Mucosal vaccination by the intranasal route. Nose-associated lymphoid tissue (NALT)-Structure, function and species differences.

    Science.gov (United States)

    Pabst, Reinhard

    2015-08-26

    The advantage of mucosal vaccination in viral and bacterial infections in different age groups is of enormous clinical relevance. The advantages and potential hazards of intranasal vaccination have always to be considered. The intranasal route for vaccination is very successful for some antigens. Specific adjuvants are necessary. In the nose of rodents there is a structured lymphoid tissue (nose-associated lymphoid tissue (NALT)). This abbreviation should not be used for nasopharynx-associated lymphoid tissue, as this includes parts of the tonsils. In children lymphoid tissue is more dispersed in the nose and not concentrated at the bottom of the dorsal nose ducts as in rodents. There are no data on organized lymphoid tissue in the nose of adults. In NALT of rodents there is a unique structure of adhesion molecule expression; the postnatal development and the different composition of T and B lymphocytes in comparison with Peyer's patches document the uniqueness of this lymphoid organ. There is also a mucosa in the nose with antigen-presenting dendritic cells. Thus, it is often unclear whether intranasal vaccination is initiated via NALT or the diffuse nasal mucosa. There are still many open questions e. g., which adjuvant is necessary for a specific virus, bacterium or other allergen, how many doses are critical for an effective nasal vaccination. Species differences are of major importance when extrapolating results from rodents to humans. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Morphological Studies on the Postnatal Development of the Gut-associated Lymphoid Tissues of the Rabbit Cecum

    Directory of Open Access Journals (Sweden)

    Abdelmohaimen M. Saleh

    2012-10-01

    Full Text Available The macroscopic, morphometric, light and scanning electron microscopic structure of gut-associated lymphoid tissue (GALT of cecum were studied in the rabbits aged from birth to 16 weeks. The GALT were formed of lymph follicles covered by low columnar epithelium containing intraepithelial lymphocytes and leukocytes. They were concentrated at the ileocecal entrance (ileocecal patch and in the blind end of the cecum vermiform appendix. In the ileocecal patch, GALT were in direct contact with the lumen, while those of the appendix were covered by the interval intestinal villi in young rabbits and mucosal folds in the adult rabbits. The lymphoid follicles of the ileocecal patch were composed of dome region and germinal center and were separated by narrow inter-follicular areas. Whereas, the lymphoid follicles of the appendix were composed dome region and germinal center in the newly born rabbits and up to the 2nd week of age, the follicles became composed of four different sites: dome region, germinal center, coronal area, and a wide interfollicular area between neighboring follicles. Morphometrically; the dimensions of the lymphoid follicles of the cecal GALT increased in size with the advancement of the age. By SEM the lymphoid structures covered with special epithelium consisted of two types of cell absorptive enterocytes and M cells. The M cells in the cecal patch were microvilliated and present on the tips and sides of the dome lymphoid regions while in the appendix were non-microvilliated and present only on the sides of the dome regions.

  15. Classical swine fever virus induces pyroptosis in the peripheral lymphoid organs of infected pigs.

    Science.gov (United States)

    Yuan, Jin; Zhu, Mengjiao; Deng, Shaofeng; Fan, Shuangqi; Xu, Hailuan; Liao, Jiedan; Li, Peng; Zheng, Jingfang; Zhao, Mingqiu; Chen, Jinding

    2018-05-02

    Classical swine fever virus (CSFV) causes a highly lethal disease in pigs, which is characterized by immunosuppression. Leukopenia is known to be a possible mechanism of immunosuppression during CSFV infection. As a new and specialized form of cell death, pyroptosis is the key response of the innate immune system to pathogens, and is widely involved in the occurrence and development of infectious diseases. However, the relationship between CSFV and pyroptosis has not been explored. In this study, we investigated the occurrence of pyroptosis in pigs following CSFV infection. According to qRT-PCR assay results, the prevalence of this virus in peripheral lymphoid organs (tonsils, lymph nodes, and spleen) was much higher than that in other organs. Severe bleeding, necrosis, and a significant reduction in lymphocytes were found in the peripheral lymphoid organs of CSFV-infected pigs based on histological examination. In-depth studies showed that an increased ratio of deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive cells were present in the peripheral lymphoid organs of the CSFV-infected group according to immunohistochemistry. Meanwhile, the p10 subunit and activity of caspase-1, which is a regulator of pyroptosis, the N-terminal domain of gasdermin D, which is an executor of pyroptosis, and the cleavage and secretion of IL-1b, which is a product of pyroptosis were increased in the peripheral lymphoid organs of the CSFV-infected group. Together, these results demonstrated that pyroptosis is involved in CSFV-induced cell death in vivo, which provides a new understanding of the mechanism associated with lymphocyte depletion and immunosuppression in pigs infected with this virus. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Clinical Impact of the Immunome in Lymphoid Malignancies: The Role of Myeloid-Derived Suppressor Cells

    Science.gov (United States)

    Vetro, Calogero; Romano, Alessandra; Ancora, Flavia; Coppolino, Francesco; Brundo, Maria V.; Raccuia, Salvatore A.; Puglisi, Fabrizio; Tibullo, Daniele; La Cava, Piera; Giallongo, Cesarina; Parrinello, Nunziatina L.

    2015-01-01

    The better definition of the mutual sustainment between neoplastic cells and immune system has been translated from the bench to the bedside acquiring value as prognostic factor. Additionally, it represents a promising tool for improving therapeutic strategies. In this context, myeloid-derived suppressor cells (MDSCs) have gained a central role in tumor developing with consequent therapeutic implications. In this review, we will focus on the biological and clinical impact of the study of MDSCs in the settings of lymphoid malignancies. PMID:26052505

  17. Spectrum of lymphoid hyperplasia: Colonic manifestations of sarcoidosis, infectious mononucleosis, and Crohn's disease

    International Nuclear Information System (INIS)

    Ell, S.R.; Frank, P.H.

    1981-01-01

    The radiographic pattern of nodular lmyphoid hyperplasia, perhaps better called the lymphoid follicular pattern, has variously been described as an indication of disease and as a normal variant in the adult, with current opinion favoring the latter. We report 3 cases wherein this pattern resulted from definite pathologic processes: sarcoidosis, infectious mononucleosis, and Crohn's disease. Although usually of no pathological significance, the benign follicular pattern may reflect a variety of diseases. (orig.)

  18. Distribution of Hydroxychloroquine in Lymphoid Tissue in a Rabbit Model for HIV Infection

    Science.gov (United States)

    González-Hernández, Iliana; Aguirre-Cruz, Lucinda; Sotelo, Julio; López-Arellano, Raquel; Morales-Hipólito, Adriana

    2014-01-01

    Hydroxychloroquine has been proposed for HIV treatment; however, little is known about its disposition in the lymphatic system, where replication takes place. Therefore, its distribution in lymphoid tissues (Peyer's patches and popliteal, submandibular, femoral, splenic, and prescapular lymph nodes) was evaluated and compared with that in blood. Results showed a high affinity of hydroxychloroquine for all of these tissues, with higher affinity for the splenic and submandibular lymph nodes, suggesting its potential use as a coadjuvant in HIV therapy. PMID:24145523

  19. Immunofluorescent staining of nuclear antigen in lymphoid cells transformed by Herpesvirus papio (HVP).

    Science.gov (United States)

    Schmitz, H

    1981-01-01

    An improved fixation method for antigen detection in lymphoblastoid cells is described. Herpesvirus papio nuclear antigen (HUPNA) could be stained in several transformed lymphoid cell lines by anti-complement immunofluorescence (ACIF). Antibody to HUPNA was detected in many human sera containing antibodies to Epstein-Barr virus capsid and nuclear antigen (EBNA). Rheumatoid arthritis sera showed a high incidence of both anti-EBNA and anti-HUPNA antibodies.

  20. High Endothelial Venules and Lymphatic Vessels in Tertiary Lymphoid Organs: Characteristics, Functions, and Regulation

    Directory of Open Access Journals (Sweden)

    Nancy H Ruddle

    2016-11-01

    Full Text Available High endothelial venules (HEVs and lymphatic vessels (LVs are essential for the function of the immune system, by providing communication between the body and lymph nodes (LNs, specialized sites of antigen presentation and recognition. HEVs bring in naïve and central memory cells and LVs transport antigen, antigen presenting cells, and lymphocytes in and out of LNs. Tertiary lymphoid organs (TLOs are accumulations of lymphoid and stromal cells that arise and organize at ectopic sites in response to chronic inflammation in autoimmunity, microbial infection, graft rejection, and cancer. TLOs are distinguished from primary lymphoid organs-the thymus and bone marrow, and secondary lymphoid organs (SLOs-the LNs, spleen, and Peyer’s patches, in that they arise in response to inflammatory signals, rather than in ontogeny. TLOs usually do not have a capsule, but are rather contained within the confines of another organ. Their structure, cellular composition, chemokine expression, and vascular and stromal support resemble SLOs and are the defining aspects of TLOs. T and B cells, antigen presenting cells, fibroblast reticular cells and other stromal cells and vascular elements including HEVs and LVs are all typical components of TLOS. A key question is whether the HEVs and LVs play comparable roles and are regulated similarly to those in LNs. Data are presented that support this concept, especially with regard to TLO HEVs. Emerging data suggest that the functions and regulation of TLO LVs are also similar to those in LNs. These observations support the concept that TLOs are not merely cellular accumulations, but are functional entities that provide sites to generate effector cells, and that their HEVs and LVs are crucial elements in those activities.

  1. Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency.

    Science.gov (United States)

    Cols, Montserrat; Rahman, Adeeb; Maglione, Paul J; Garcia-Carmona, Yolanda; Simchoni, Noa; Ko, Huai-Bin M; Radigan, Lin; Cerutti, Andrea; Blankenship, Derek; Pascual, Virginia; Cunningham-Rundles, Charlotte

    2016-04-01

    Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobulin; however, patients can have noninfectious inflammatory conditions that lead to heightened morbidity and mortality. Modular analyses of RNA transcripts in whole blood previously identified an upregulation of many interferon-responsive genes. In this study we sought the cell populations leading to this signature. Lymphoid cells were measured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune complications) by using mass cytometry and flow cytometry. Surface markers, cytokines, and transcriptional characteristics of sorted innate lymphoid cells (ILCs) were defined by using quantitative PCR. Gastrointestinal and lung biopsy specimens of subjects with inflammatory disease were stained to seek ILCs in tissues. The linage-negative, CD127(+), CD161(+) lymphoid population containing T-box transcription factor, retinoic acid-related orphan receptor (ROR) γt, IFN-γ, IL-17A, and IL-22, all hallmarks of type 3 innate lymphoid cells, were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs). ILCs contained detectable amounts of the transcription factors inhibitor of DNA binding 2, T-box transcription factor, and RORγt and increased mRNA transcripts for IL-23 receptor (IL-23R) and IL-26, demonstrating inflammatory potential. In gastrointestinal and lung biopsy tissues of patients with CVID, numerous IFN-γ(+)RORγt(+)CD3(-) cells were identified, suggesting a role in these mucosal inflammatory states. An expansion of this highly inflammatory ILC population is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon signature are markers for the uncontrolled inflammatory state in these patients. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system

    Directory of Open Access Journals (Sweden)

    Enrique Montalvillo

    2014-05-01

    Full Text Available The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity. Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  3. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system.

    Science.gov (United States)

    Montalvillo, Enrique; Garrote, José Antonio; Bernardo, David; Arranz, Eduardo

    2014-05-01

    The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity.Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  4. Innate lymphoid cells contribute to allergic airway disease exacerbation by obesity.

    Science.gov (United States)

    Everaere, Laetitia; Ait-Yahia, Saliha; Molendi-Coste, Olivier; Vorng, Han; Quemener, Sandrine; LeVu, Pauline; Fleury, Sebastien; Bouchaert, Emmanuel; Fan, Ying; Duez, Catherine; de Nadai, Patricia; Staels, Bart; Dombrowicz, David; Tsicopoulos, Anne

    2016-11-01

    Epidemiologic and clinical observations identify obesity as an important risk factor for asthma exacerbation, but the underlying mechanisms remain poorly understood. Type 2 innate lymphoid cells (ILC2s) and type 3 innate lymphoid cells (ILC3s) have been implicated, respectively, in asthma and adipose tissue homeostasis and in obesity-associated airway hyperresponsiveness (AHR). We sought to determine the potential involvement of innate lymphoid cells (ILCs) in allergic airway disease exacerbation caused by high-fat diet (HFD)-induced obesity. Obesity was induced by means of HFD feeding, and allergic airway inflammation was subsequently induced by means of intranasal administration of house dust mite (HDM) extract. AHR, lung and visceral adipose tissue inflammation, humoral response, cytokines, and innate and adaptive lymphoid populations were analyzed in the presence or absence of ILCs. HFD feeding exacerbated allergic airway disease features, including humoral response, airway and tissue eosinophilia, AHR, and T H 2 and T H 17 pulmonary profiles. Notably, nonsensitized obese mice already exhibited increased lung ILC counts and tissue eosinophil infiltration compared with values in lean mice in the absence of AHR. The numbers of total and cytokine-expressing lung ILC2s and ILC3s further increased in HDM-challenged obese mice compared with those in HDM-challenged lean mice, and this was accompanied by high IL-33 and IL-1β levels and decreased ILC markers in visceral adipose tissue. Furthermore, depletion of ILCs with an anti-CD90 antibody, followed by T-cell reconstitution, led to a profound decrease in allergic airway inflammatory features in obese mice, including T H 2 and T H 17 infiltration. These results indicate that HFD-induced obesity might exacerbate allergic airway inflammation through mechanisms involving ILC2s and ILC3s. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  5. Identification of novel genes associated with renal tertiary lymphoid organ formation in aging mice.

    Science.gov (United States)

    Huang, Yuan; Caputo, Christina R; Noordmans, Gerda A; Yazdani, Saleh; Monteiro, Luiz Henrique; van den Born, Jaap; van Goor, Harry; Heeringa, Peter; Korstanje, Ron; Hillebrands, Jan-Luuk

    2014-01-01

    A hallmark of aging-related organ deterioration is a dysregulated immune response characterized by pathologic leukocyte infiltration of affected tissues. Mechanisms and genes involved are as yet unknown. To identify genes associated with aging-related renal infiltration, we analyzed kidneys from aged mice (≥20 strains) for infiltrating leukocytes followed by Haplotype Association Mapping (HAM) analysis. Immunohistochemistry revealed CD45+ cell clusters (predominantly T and B cells) in perivascular areas coinciding with PNAd+ high endothelial venules and podoplanin+ lymph vessels indicative of tertiary lymphoid organs. Cumulative cluster size increased with age (analyzed at 6, 12 and 20 months). Based on the presence or absence of clusters in male and female mice at 20 months, HAM analysis revealed significant associations with loci on Chr1, Chr2, Chr8 and Chr14 in male mice, and with loci on Chr4, Chr7, Chr13 and Chr14 in female mice. Wisp2 (Chr2) showed the strongest association (P = 5.00×10(-137)) in male mice; Ctnnbip1 (P = 6.42×10(-267)) and Tnfrsf8 (P = 5.42×10(-245)) (both on Chr4) showed the strongest association in female mice. Both Wisp2 and Ctnnbip1 are part of the Wnt-signaling pathway and the encoded proteins were expressed within the tertiary lymphoid organs. In conclusion, this study revealed differential lymphocytic infiltration and tertiary lymphoid organ formation in aged mouse kidneys across different inbred mouse strains. HAM analysis identified candidate genes involved in the Wnt-signaling pathway that may be causally linked to tertiary lymphoid organ formation.

  6. The Role of Radiotherapy in the Treatment of Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

    OpenAIRE

    Nam, Taek-Keun; Ahn, Jae-Sook; Choi, Yoo-Duk; Jeong, Jae-Uk; Kim, Yong-Hyeob; Yoon, Mee Sun; Song, Ju-Young; Ahn, Sung-Ja; Chung, Woong-Ki

    2014-01-01

    Purpose To assess radiotherapy for patients with early stage gastric mucosa-associated lymphoid tissue (MALT) lymphoma with respect to survival, treatment response, and complications. Materials and Methods Enrolled into this study were 48 patients diagnosed with gastric MALT lymphoma from January 2000 to September 2012. Forty-one patients had low grade and seven had mixed component with high grade. Helicobacter pylori eradication was performed in 33 patients. Thirty-four patients received rad...

  7. Characteristics of nasal-associated lymphoid tissue (NALT) and nasal absorption capacity in chicken.

    Science.gov (United States)

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2013-01-01

    As the main mucosal immune inductive site of nasal cavity, nasal-associated lymphoid tissue (NALT) plays an important role in both antigen recognition and immune activation after intranasal immunization. However, the efficiency of intranasal vaccines is commonly restricted by the insufficient intake of antigen by the nasal mucosa, resulting from the nasal mucosal barrier and the nasal mucociliary clearance. The distribution of NALT and the characteristic of nasal cavity have already been described in humans and many laboratory rodents, while data about poultry are scarce. For this purpose, histological sections of the chicken nasal cavities were used to examine the anatomical structure and histological characteristics of nasal cavity. Besides, the absorptive capacity of chicken nasal mucosa was also studied using the materials with different particle size. Results showed that the NALT of chicken was located on the bottom of nasal septum and both sides of choanal cleft, which mainly consisted of second lymphoid follicle. A large number of lymphocytes were distributed under the mucosal epithelium of inferior nasal meatus. In addition, there were also diffuse lymphoid tissues located under the epithelium of the concha nasalis media and the walls of nasal cavity. The results of absorption experiment showed that the chicken nasal mucosa was capable to absorb trypan blue, OVA, and fluorescent latex particles. Inactivated avian influenza virus (IAIV) could be taken up by chicken nasal mucosa except for the stratified squamous epithelium sites located on the forepart of nasal cavity. The intake of IAIV by NALT was greater than that of the nasal mucosa covering on non-lymphoid tissue, which could be further enhanced after intranasal inoculation combined with sodium cholate or CpG DNA. The study on NALT and nasal absorptive capacity will be benefit for further understanding of immune mechanisms after nasal vaccination and development of nasal vaccines for poultry.

  8. Lymphoid tissue neoplasms in the neck region - epidemiological and clinical analysis over 15 years.

    Science.gov (United States)

    Rzepakowska, Anna; Zwierzyńska, Klaudyna; Osuch-Wójcikiewicz, Ewa; Niemczyk, Kazimierz

    2017-06-30

    Epidemiological and clinical analysis of lymphoid tissue neoplasms in the neck region over a 15-year period. There was performed retrospective analysis of 97 patients, aged 17 to 88 years, mean age of 60.3 years. The analysis included data from subjective study, physical examination, image and histopathological studies Results: Almost all cases were lymphoid neoplasms - 95 patients (98%). B cell lymphoma was the most commonly diagnosed lymphoma - 74 cases (76%), followed by Hodgkin's lymphoma- 19 cases (20%). Only two patients had T-cell lymphoma (2%). There was observed prevalence among women, K: M ratio for the whole group was 51: 46, while male predominance was reported in Hodgkin's lymphoma patients (K: M = 7: 12). Over the 15-year period, there was an increase in the number of lymphoid tumors. The most common location on the neck were lymph nodes - 71 (73.2%). Extranodal localizations (26.8%) were most often associated with salivary glands: parotid and submandibular involvement and with the dominant lymphoma of the marginal zone MALT (14 cases). In 57% of patients the fine needle aspiration biopsy (FNAB) results were false, with positive results only in 32% of patients. Tumors from lymphoid tissue in the neck region are most commonly B-cell lymphomas or Hodgkin,s lymphomas. Non-specific clinical signs and non-specific radiological images, as well as non-diagnostic results o FNAB, make it difficult to effectively differentiate lymphomas with cancer metastasis in neck lymph nodes. Histopathology results of the excised lymph nodes remains a standard for lymphoma diagnosis.

  9. Identification and characterization of novel gut-associated lymphoid tissues in rat small intestine.

    Science.gov (United States)

    Hitotsumatsu, Osamu; Hamada, Hiromasa; Naganuma, Makoto; Inoue, Nagamu; Ishii, Hiromasa; Hibi, Toshifumi; Ishikawa, Hiromichi

    2005-10-01

    The crypt lamina propria of the mouse small intestine has been shown to harbor multiple tiny clusters filled with c-kit- and interleukin 7 receptor (IL-7R)-positive lympho-hemopoietic cells (cryptopatches; CPs). However, it has remained an open question whether similar lymphoid tissue are present in the gastrointesitinal tract in other animals. In the present study, we investigated whether the small intestine of rats harbored lymphoid tissues similar to mouse CPs. Immunohistochemical and flow cytometric analyses were carried out using various antibodies, including those to c-kit and IL-7R molecules. Lymphocyte-filled villi (LFVs), populated predominantly with c-kit- and IL-7 receptor (IL-7R)-positive cells and less with T cell receptor (TCR)-alphabeta T cells were found throughout the small intestine of young adult rats. Although LFVs were absent from fetal rat intestine, they were first detected at around 2 weeks after birth. Notably, in most LFVs that settled in the antimesenteric wall of the small intestine in young adult rats, immunoglobulin M-positive B cells were also detectable at the bottom of the LFVs. In aged rats, lymphocytes in some LFVs displayed a different phenotype, comprising a large B-cell area that included a germinal center. Thus, these clusters represent the first description of isolated lymphoid follicles (ILFs) in the rat small intestine. The present study provides the first evidence for c-kit- and IL-7R-positive lymphocyte clusters in the rat small intestine. Our data also indicating that LFVs and ILFs may constitute novel organized gut-associated lymphoid tissues in lamina propria of the rat small intestine.

  10. Bone marrow transplantation in aplastic anaemia using cyclophosphamide and total lymphoid irradiation

    International Nuclear Information System (INIS)

    Jansen, J.; Zwaan, F.E.; Noordijk, E.M.

    1980-01-01

    Six patients with severe aplastic anaemia received a bone-marrow graft after conditioning with cyclophosphamide and total lymphoid irradiation (TLI). No rejections occurred. Acute graft-versus-host disease developed in 3 patients and was fatal in one. Another patient died from systemic aspergillus infection. Chronic GVHD of the skin developed in a patient who was grafted with bone marrow from her HLA-phenotypically identical father. These data suggest that conditioning with cyclophosphamide and TLI is a promising regimen. (orig.) [de

  11. Identification of Cytological Features Distinguishing Mucosa-Associated Lymphoid Tissue Lymphoma from Reactive Lymphoid Proliferation Using Thyroid Liquid-Based Cytology

    Science.gov (United States)

    Suzuki, Ayana; Hirokawa, Mitsuyoshi; Ito, Aki; Takada, Nami; Higuchi, Miyoko; Hayashi, Toshitetsu; Kuma, Seiji; Miyauchi, Akira

    2018-01-01

    Objective To identify cytological differences between mucosa-associated lymphoid tissue lymphoma (MALT-L) and nonneoplastic lymphocytes using thyroid liquid-based cytology (LBC). Study Design We observed LBC and conventional specimens from 35 MALT-L cases, 3 diffuse large B-cell cell lymphoma (DLBCL) cases, and 44 prominent nonneoplastic lymphocytic infiltration cases. Results In MALT-L cases, the incidence of lymphoglandular bodies in the LBC specimens was lower than that in the conventional specimens (p 10% of the lymphoid cells in LBC specimens. Two cases with prominent nonneoplastic lymphocytic infiltration also exhibited these findings. In LBC specimens, swollen naked nuclei with less punctate chromatin patterns and thin nuclear margins were observed in 92.1% of lymphoma and 20.5% of prominent nonneoplastic lymphocytic infiltration. Elongated nuclei were significantly more apparent in thyroid lymphoma than in prominent nonneoplastic lymphocytic infiltration (p < 0.001), with a significantly higher incidence in LBC specimens than in conventional specimens (p < 0.001). Conclusions Lymphoglandular bodies are not reliable markers for lymphoma diagnosis using LBC specimens. Large, swollen naked, and elongated nuclei are useful in distinguishing thyroid lymphoma from nonneoplastic lymphocytes in LBC specimens. PMID:29597203

  12. Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.

    Science.gov (United States)

    Chu, Coco; Moriyama, Saya; Li, Zhi; Zhou, Lei; Flamar, Anne-Laure; Klose, Christoph S N; Moeller, Jesper B; Putzel, Gregory G; Withers, David R; Sonnenberg, Gregory F; Artis, David

    2018-06-26

    The intestinal tract is constantly exposed to various stimuli. Group 3 innate lymphoid cells (ILC3s) reside in lymphoid organs and in the intestinal tract and are required for immunity to enteric bacterial infection. However, the mechanisms that regulate the ILC3s in vivo remain incompletely defined. Here, we show that GPR183, a chemotactic receptor expressed on murine and human ILC3s, regulates ILC3 migration toward its ligand 7α,25-dihydroxycholesterol (7α,25-OHC) in vitro, and GPR183 deficiency in vivo leads to a disorganized distribution of ILC3s in mesenteric lymph nodes and decreased ILC3 accumulation in the intestine. GPR183 functions intrinsically in ILC3s, and GPR183-deficient mice are more susceptible to enteric bacterial infection. Together, these results reveal a role for the GPR183-7α,25-OHC pathway in regulating the accumulation, distribution, and anti-microbial and tissue-protective functions of ILC3s and define a critical role for this pathway in promoting innate immunity to enteric bacterial infection. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Identification of Cytological Features Distinguishing Mucosa-Associated Lymphoid Tissue Lymphoma from Reactive Lymphoid Proliferation Using Thyroid Liquid-Based Cytology.

    Science.gov (United States)

    Suzuki, Ayana; Hirokawa, Mitsuyoshi; Ito, Aki; Takada, Nami; Higuchi, Miyoko; Hayashi, Toshitetsu; Kuma, Seiji; Miyauchi, Akira

    2018-01-01

    To identify cytological differences between mucosa-associated lymphoid tissue lymphoma (MALT-L) and nonneoplastic lymphocytes using thyroid liquid-based cytology (LBC). We observed LBC and conventional specimens from 35 MALT-L cases, 3 diffuse large B-cell cell lymphoma (DLBCL) cases, and 44 prominent nonneoplastic lymphocytic infiltration cases. In MALT-L cases, the incidence of lymphoglandular bodies in the LBC specimens was lower than that in the conventional specimens (p 10% of the lymphoid cells in LBC specimens. Two cases with prominent nonneoplastic lymphocytic infiltration also exhibited these findings. In LBC specimens, swollen naked nuclei with less punctate chromatin patterns and thin nuclear margins were observed in 92.1% of lymphoma and 20.5% of prominent nonneoplastic lymphocytic infiltration. Elongated nuclei were significantly more apparent in thyroid lymphoma than in prominent nonneoplastic lymphocytic infiltration (p < 0.001), with a significantly higher incidence in LBC specimens than in conventional specimens (p < 0.001). Lymphoglandular bodies are not reliable markers for lymphoma diagnosis using LBC specimens. Large, swollen naked, and elongated nuclei are useful in distinguishing thyroid lymphoma from nonneoplastic lymphocytes in LBC specimens. © 2018 The Author(s) Published by S. Karger AG, Basell.

  14. On the generalized gravi-magnetic hypothesis

    International Nuclear Information System (INIS)

    Massa, C.

    1989-01-01

    According to a generalization of the gravi-magnetic hypothesis (GMH) any neutral mass moving in a curvilinear path with respect to an inertial frame creates a magnetic field, dependent on the curvature radius of the path. A simple astrophysical consequence of the generalized GMH is suggested considering the special cases of binary pulsars and binary neutron stars

  15. Remarks about the hypothesis of limiting fragmentation

    International Nuclear Information System (INIS)

    Chou, T.T.; Yang, C.N.

    1987-01-01

    Remarks are made about the hypothesis of limiting fragmentation. In particular, the concept of favored and disfavored fragment distribution is introduced. Also, a sum rule is proved leading to a useful quantity called energy-fragmentation fraction. (author). 11 refs, 1 fig., 2 tabs

  16. Multiple hypothesis clustering in radar plot extraction

    NARCIS (Netherlands)

    Huizing, A.G.; Theil, A.; Dorp, Ph. van; Ligthart, L.P.

    1995-01-01

    False plots and plots with inaccurate range and Doppler estimates may severely degrade the performance of tracking algorithms in radar systems. This paper describes how a multiple hypothesis clustering technique can be applied to mitigate the problems involved in plot extraction. The measures of

  17. The (not so immortal strand hypothesis

    Directory of Open Access Journals (Sweden)

    Cristian Tomasetti

    2015-03-01

    Significance: Utilizing an approach that is fundamentally different from previous efforts to confirm or refute the immortal strand hypothesis, we provide evidence against non-random segregation of DNA during stem cell replication. Our results strongly suggest that parental DNA is passed randomly to stem cell daughters and provides new insight into the mechanism of DNA replication in stem cells.

  18. A Developmental Study of the Infrahumanization Hypothesis

    Science.gov (United States)

    Martin, John; Bennett, Mark; Murray, Wayne S.

    2008-01-01

    Intergroup attitudes in children were examined based on Leyen's "infrahumanization hypothesis". This suggests that some uniquely human emotions, such as shame and guilt (secondary emotions), are reserved for the in-group, whilst other emotions that are not uniquely human and shared with animals, such as anger and pleasure (primary…

  19. Morbidity and Infant Development: A Hypothesis.

    Science.gov (United States)

    Pollitt, Ernesto

    1983-01-01

    Results of a study conducted in 14 villages of Sui Lin Township, Taiwan, suggest the hypothesis that, under conditions of extreme economic impoverishment and among children within populations where energy protein malnutrition is endemic, there is an inverse relationship between incidence of morbidity in infancy and measures of motor and mental…

  20. Diagnostic Hypothesis Generation and Human Judgment

    Science.gov (United States)

    Thomas, Rick P.; Dougherty, Michael R.; Sprenger, Amber M.; Harbison, J. Isaiah

    2008-01-01

    Diagnostic hypothesis-generation processes are ubiquitous in human reasoning. For example, clinicians generate disease hypotheses to explain symptoms and help guide treatment, auditors generate hypotheses for identifying sources of accounting errors, and laypeople generate hypotheses to explain patterns of information (i.e., data) in the…

  1. Multi-hypothesis distributed stereo video coding

    DEFF Research Database (Denmark)

    Salmistraro, Matteo; Zamarin, Marco; Forchhammer, Søren

    2013-01-01

    for stereo sequences, exploiting an interpolated intra-view SI and two inter-view SIs. The quality of the SI has a major impact on the DVC Rate-Distortion (RD) performance. As the inter-view SIs individually present lower RD performance compared with the intra-view SI, we propose multi-hypothesis decoding...

  2. [Resonance hypothesis of heart rate variability origin].

    Science.gov (United States)

    Sheĭkh-Zade, Iu R; Mukhambetaliev, G Kh; Cherednik, I L

    2009-09-01

    A hypothesis is advanced of the heart rate variability being subjected to beat-to-beat regulation of cardiac cycle duration in order to ensure the resonance interaction between respiratory and own fluctuation of the arterial system volume for minimization of power expenses of cardiorespiratory system. Myogenic, parasympathetic and sympathetic machanisms of heart rate variability are described.

  3. In Defense of Chi's Ontological Incompatibility Hypothesis

    Science.gov (United States)

    Slotta, James D.

    2011-01-01

    This article responds to an article by A. Gupta, D. Hammer, and E. F. Redish (2010) that asserts that M. T. H. Chi's (1992, 2005) hypothesis of an "ontological commitment" in conceptual development is fundamentally flawed. In this article, I argue that Chi's theoretical perspective is still very much intact and that the critique offered by Gupta…

  4. Vacuum counterexamples to the cosmic censorship hypothesis

    International Nuclear Information System (INIS)

    Miller, B.D.

    1981-01-01

    In cylindrically symmetric vacuum spacetimes it is possible to specify nonsingular initial conditions such that timelike singularities will (necessarily) evolve from these conditions. Examples are given; the spacetimes are somewhat analogous to one of the spherically symmetric counterexamples to the cosmic censorship hypothesis

  5. A novel hypothesis splitting method implementation for multi-hypothesis filters

    DEFF Research Database (Denmark)

    Bayramoglu, Enis; Ravn, Ole; Andersen, Nils Axel

    2013-01-01

    The paper presents a multi-hypothesis filter library featuring a novel method for splitting Gaussians into ones with smaller variances. The library is written in C++ for high performance and the source code is open and free1. The multi-hypothesis filters commonly approximate the distribution tran...

  6. The Income Inequality Hypothesis Revisited : Assessing the Hypothesis Using Four Methodological Approaches

    NARCIS (Netherlands)

    Kragten, N.; Rözer, J.

    The income inequality hypothesis states that income inequality has a negative effect on individual’s health, partially because it reduces social trust. This article aims to critically assess the income inequality hypothesis by comparing several analytical strategies, namely OLS regression,

  7. Lymphoid irradiation in intractable rheumatoid arthritis: effects on the production of immunoglobulins and rheumatoid factors

    International Nuclear Information System (INIS)

    Hanly, J.G.; Bresnihan, B.; Hassan, J.; Whelan, A.; Feighery, C.; Moriarty, M.

    1985-01-01

    Changes in the production of immunoglobulins and rheumatoid factors (RF's) were studied in 20 patients with intractable rheumatoid arthritis (RA) following total doses of 750 rad or 2,000 rad lymphoid irradiation. Over a 12 month follow up period there was no consistent change in absolute serum or synovial fluid levels, or in synovial membrane production of either total IgG, IgA or IgM, or the corresponding RF fractions. The in-vitro production of immunoglobulins and IgM RF by peripheral blood mononuclear cells was also unaltered, except for one patient who had a dramatic rise in IgM RF production. Over the same period there was a significant overall reduction in disease activity following both doses of radiotherapy. It is concluded that the clinical response which occurs following lymphoid irradiation is not due to a reduction in RF production. Furthermore, the production of RF's appears to be unaffected by the changes in T cell immunity which occur following lymphoid irradiation. (author)

  8. Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia.

    Science.gov (United States)

    Kikushige, Yoshikane; Miyamoto, Toshihiro

    2015-11-01

    Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies.

  9. Type two innate lymphoid cells; the Janus cells in health and disease

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-01-01

    Summary Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2 and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by costimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. PMID:28658553

  10. Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis

    Directory of Open Access Journals (Sweden)

    Barbara C. Mindt

    2018-04-01

    Full Text Available Group 2 innate lymphoid cells (ILC2 represent an evolutionary rather old but only recently identified member of the family of innate lymphoid cells and have received much attention since their detailed description in 2010. They can orchestrate innate as well as adaptive immune responses as they interact with and influence several immune and non-immune cell populations. Moreover, ILC2 are able to rapidly secrete large amounts of type 2 cytokines that can contribute to protective but also detrimental host immune responses depending on timing, location, and physiological context. Interestingly, ILC2, despite their scarcity, are the dominant innate lymphoid cell population in the lung, indicating a key role as first responders and amplifiers upon immune challenge at this site. In addition, the recently described tissue residency of ILC2 further underlines the importance of their respective microenvironment. In this review, we provide an overview of lung physiology including a description of the most prominent pulmonary resident cells together with a review of known and potential ILC2 interactions within this unique environment. We will further outline recent observations regarding pulmonary ILC2 during immune challenge including respiratory infections and discuss different models and approaches to study ILC2 biology in the lung.

  11. NK Cells and Other Innate Lymphoid Cells in Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Vacca, Paola; Montaldo, Elisa; Croxatto, Daniele; Moretta, Francesca; Bertaina, Alice; Vitale, Chiara; Locatelli, Franco; Mingari, Maria Cristina; Moretta, Lorenzo

    2016-01-01

    Natural killer (NK) cells play a major role in the T-cell depleted haploidentical hematopoietic stem cell transplantation (haplo-HSCT) to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILCs). At variance with NK cells, the other ILC populations (ILC1/2/3) are non-cytolytic, while they secrete different patterns of cytokines. ILCs provide host defenses against viruses, bacteria, and parasites, drive lymphoid organogenesis, and contribute to tissue remodeling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD) but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defenses that are reconstituted more rapidly than the adaptive ones. In this context, ILCs may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodeling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILCs. Of note, CD34(+) cells isolated from different sources of HSC may differentiate in vitro toward various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g., IL-1β) may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

  12. Group 2 Innate Lymphoid Cells in Pulmonary Immunity and Tissue Homeostasis.

    Science.gov (United States)

    Mindt, Barbara C; Fritz, Jörg H; Duerr, Claudia U

    2018-01-01

    Group 2 innate lymphoid cells (ILC2) represent an evolutionary rather old but only recently identified member of the family of innate lymphoid cells and have received much attention since their detailed description in 2010. They can orchestrate innate as well as adaptive immune responses as they interact with and influence several immune and non-immune cell populations. Moreover, ILC2 are able to rapidly secrete large amounts of type 2 cytokines that can contribute to protective but also detrimental host immune responses depending on timing, location, and physiological context. Interestingly, ILC2, despite their scarcity, are the dominant innate lymphoid cell population in the lung, indicating a key role as first responders and amplifiers upon immune challenge at this site. In addition, the recently described tissue residency of ILC2 further underlines the importance of their respective microenvironment. In this review, we provide an overview of lung physiology including a description of the most prominent pulmonary resident cells together with a review of known and potential ILC2 interactions within this unique environment. We will further outline recent observations regarding pulmonary ILC2 during immune challenge including respiratory infections and discuss different models and approaches to study ILC2 biology in the lung.

  13. Long-term Persistence of Innate Lymphoid Cells in the Gut After Intestinal Transplantation.

    Science.gov (United States)

    Weiner, Joshua; Zuber, Julien; Shonts, Brittany; Yang, Suxiao; Fu, Jianing; Martinez, Mercedes; Farber, Donna L; Kato, Tomoaki; Sykes, Megan

    2017-10-01

    Little is known about innate lymphoid cell (ILC) populations in the human gut, and the turnover of these cells and their subsets after transplantation has not been described. Intestinal samples were taken from 4 isolated intestine and 3 multivisceral transplant recipients at the time of any operative resection, such as stoma closure or revision. ILCs were isolated and analyzed by flow cytometry. The target population was defined as being negative for lineage markers and double-positive for CD45/CD127. Cells were further stained to define ILC subsets and a donor-specific or recipient-specific HLA marker to analyze chimerism. Donor-derived ILCs were found to persist greater than 8 years after transplantation. Additionally, the percentage of cells thought to be lymphoid tissue inducer cells among donor ILCs was far higher than that among recipient ILCs. Our findings demonstrate that donor-derived ILCs persist long-term after transplantation and support the notion that human lymphoid tissue inducer cells may form in the fetus and persist throughout life, as hypothesized in rodents. Correlation between chimerism and rejection, graft failure, and patient survival requires further study.

  14. Type two innate lymphoid cells: the Janus cells in health and disease.

    Science.gov (United States)

    Maazi, Hadi; Akbari, Omid

    2017-07-01

    Innate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti-helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co-stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Common-Lymphoid-Progenitor-Independent Pathways of Innate and T Lymphocyte Development

    Directory of Open Access Journals (Sweden)

    Maryam Ghaedi

    2016-04-01

    Full Text Available All lymphocytes are thought to develop from common lymphoid progenitors (CLPs. However, lymphoid-primed multipotent progenitors (LMPPs are more efficient than CLPs in differentiating into T cells and group 2 innate lymphoid cells (ILC2s. Here, we have divided LMPPs into CD127− (LMPP−s and CD127+ (LMPP+s subsets and compared them with Ly6D− and Ly6D+ CLPs. Adult LMPP+s differentiated into T cells and ILCs more rapidly and efficiently than other progenitors in transplantation assays. The development of T cells and ILC2s is highly active in the neonatal period. Neonatal CLPs are rare and, unlike prominent neonatal LMPP+s, do not efficiently differentiate into T cells and ILC2s. ILC2s generated in the neonatal period are long lived and persist in adult tissues. These results suggest that some ILCs and T cells may develop from LMPP+s via CLP-independent pathways.

  16. Effect of thumus cell injections on germinal center formation in lymphoid tissues of nude (thymusless) mice

    International Nuclear Information System (INIS)

    Jacobson, E.B.; Caporale, L.H.; Thorbecke, G.J.

    1974-01-01

    Nude mice, partially backcrossed to Balb/c or DBA/2, were injected iv with 5 x 10 7 thymus cells from the respective inbred strain. The response of these mice to immunization with Brucella abortus antigen was studied, with respect to both antibody production and the formation of germinal centers in their lymphoid tissues. The results were compared to those obtained with nude mice to which no thymus cells were given, as well as to Balb/c, DBA/2, or +/question litter mate controls. Nude mice formed less 19S as well as 7S antibody than did litter mate controls and completely lacked germinal centers in lymph nodes and gut-associated lymphoid tissue. Those nude mice which had been injected with thymus cells made a much better secondary response, both for 19S and for 7S antibody, and had active germinal centers in their lymph nodes as early as 3 wk after thymus cell injection. Intestinal lymphoid tissue in nude mice showed only slight reconstitution of germinal center activity several months after thymus cell injection and none at earlier times. Irradiated (3000 R) thymus cells appeared as effective as normal cells in facilitating germinal center appearance and 7S antibody production in the nude mice

  17. Activation of the Arterial Program Drives Development of Definitive Hemogenic Endothelium with Lymphoid Potential

    Directory of Open Access Journals (Sweden)

    Mi Ae Park

    2018-05-01

    Full Text Available Summary: Understanding the pathways guiding the development of definitive hematopoiesis with lymphoid potential is essential for advancing human pluripotent stem cell (hPSC technologies for the treatment of blood diseases and immunotherapies. In the embryo, lymphoid progenitors and hematopoietic stem cells (HSCs arise from hemogenic endothelium (HE lining arteries but not veins. Here, we show that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhanced the formation of arterial-type HE expressing DLL4 and CXCR4. Blood cells generated from arterial HE were more than 100-fold enriched in T cell precursor frequency and possessed the capacity to produce B lymphocytes and red blood cells expressing high levels of BCL11a and β-globin. Together, these findings provide an innovative strategy to aid in the generation of definitive lymphomyeloid progenitors and lymphoid cells from hPSCs for immunotherapy through enhancing arterial programming of HE. : Park et al. find that activation of the arterial program through ETS1 overexpression or by modulating MAPK/ERK signaling pathways at the mesodermal stage of development dramatically enhances formation of arterial-type hemogenic endothelium (HE from hPSCs. Blood cells generated from arterial HE are highly enriched in definitive lymphomyeloid progenitors. Keywords: human pluripotent stem cells, hemogenic endothelium, T cells, hematopoietic stem cells, hematopoiesis, ETS1, MAPK/ERK signaling

  18. In vivo confocal microscopy of conjunctiva-associated lymphoid tissue in healthy humans.

    Science.gov (United States)

    Agnifili, Luca; Mastropasqua, Rodolfo; Fasanella, Vincenzo; Di Staso, Silvio; Mastropasqua, Alessandra; Brescia, Lorenza; Mastropasqua, Leonardo

    2014-07-29

    To investigate modifications with aging of the presence, distribution and morphologic features of conjunctiva-associated lymphoid tissue (CALT) in healthy human subjects using laser scanning in vivo confocal microscopy (IVCM). A total of 108 (age range, 17-75 years) subjects were enrolled. In vivo confocal microscopy of the tarsal and bulbar conjunctiva, and impression cytology (IC) with CD3 (intra-epithelial T-lymphocytes) and CD20 (intra-epithelial B-lymphocytes) antibody immunofluorescence staining were performed. The main outcomes were subepithelial lymphocyte density (LyD), follicular density (FD), and follicular area (FA). The secondary outcomes were follicular reflectivity (FR), and lymphocyte density (FLyD), and CD3 and CD20 positivity. Conjunctiva-associated lymphoid tissue was observed in all subjects (97% only superior and 3% in both superior and inferior tarsum). Lymphocyte density ranged from 7.8 to 165.8 cells/mm(2) (46.42 [18.37]; mean [SD]), FD from 0.5 to 19.4 follicles/mm(2) (5.3 [3.6]), and FA from 1110 to 96,280 mm(2) (26,440 [26,280]). All three parameters showed a highly significant inverse cubic relationship with age (P lymphoid structures. These modifications may account for the decrease of mucosal immune response and increase of ocular surface diseases in the elderly. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  19. Morphological and functional development of the interbranchial lymphoid tissue (ILT) in Atlantic salmon (Salmo salar L).

    Science.gov (United States)

    Dalum, Alf Seljenes; Griffiths, David James; Valen, Elin Christine; Amthor, Karoline Skaar; Austbø, Lars; Koppang, Erling Olaf; Press, Charles McLean; Kvellestad, Agnar

    2016-11-01

    The interbranchial lymphoid tissue (ILT) of Atlantic salmon originates from an embryological location that in higher vertebrates gives rise to both primary and secondary lymphoid tissues. Still much is unknown about the morphological and functional development of the ILT. In the present work a standardized method of organ volume determination was established to study its development in relation to its containing gill and the thymus. Based on morphological findings and gene transcription data, the ILT shows no signs of primary lymphoid function. In contrast to the thymus, an ILT-complex first became discernible after the yolk-sac period. After its appearance, the ILT-complex constitutes 3-7% of the total volume of the gill (excluding the gill arch) with the newly described distal ILT constituting a major part, and in adult fish it is approximately 13 times larger than the thymus. Confined regions of T-cell proliferation are present within the ILT. Communication with systemic circulation through the distal ILT is also highly plausible thus offering both internal and external recruitment of immune cells in the growing ILT. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Ectopic Tertiary Lymphoid Tissue in Inflammatory Bowel Disease: Protective or Provocateur?

    Science.gov (United States)

    McNamee, Eóin N.; Rivera-Nieves, Jesús

    2016-01-01

    Organized lymphoid tissues like the thymus first appeared in jawed vertebrates around 500 million years ago and have evolved to equip the host with a network of specialized sites, strategically located to orchestrate strict immune-surveillance and efficient immune responses autonomously. The gut-associated lymphoid tissues maintain a mostly tolerant environment to dampen our responses to daily dietary and microbial products in the intestine. However, when this homeostasis is perturbed by chronic inflammation, the intestine is able to develop florid organized tertiary lymphoid tissues (TLT), which heralds the onset of regional immune dysregulation. While TLT are a pathologic hallmark of Crohn’s disease (CD), their role in the overall process remains largely enigmatic. A critical question remains; are intestinal TLT generated by the immune infiltrated intestine to modulate immune responses and rebuild tolerance to the microbiota or are they playing a more sinister role by generating dysregulated responses that perpetuate disease? Herein, we discuss the main theories of intestinal TLT neogenesis and focus on the most recent findings that open new perspectives to their role in inflammatory bowel disease. PMID:27579025

  1. Understanding Immune Cells in Tertiary Lymphoid Organ Development: It Is All Starting to Come Together

    Science.gov (United States)

    Jones, Gareth W.; Hill, David G.; Jones, Simon A.

    2016-01-01

    Tertiary lymphoid organs (TLOs) are frequently observed in tissues affected by non-resolving inflammation as a result of infection, autoimmunity, cancer, and allograft rejection. These highly ordered structures resemble the cellular composition of lymphoid follicles typically associated with the spleen and lymph node compartments. Although TLOs within tissues show varying degrees of organization, they frequently display evidence of segregated T and B cell zones, follicular dendritic cell networks, a supporting stromal reticulum, and high endothelial venules. In this respect, they mimic the activities of germinal centers and contribute to the local control of adaptive immune responses. Studies in various disease settings have described how these structures contribute to either beneficial or deleterious outcomes. While the development and architectural organization of TLOs within inflamed tissues requires homeostatic chemokines, lymphoid and inflammatory cytokines, and adhesion molecules, our understanding of the cells responsible for triggering these events is still evolving. Over the past 10–15 years, novel immune cell subsets have been discovered that have more recently been implicated in the control of TLO development and function. In this review, we will discuss the contribution of these cell types and consider the potential to develop new therapeutic strategies that target TLOs. PMID:27752256

  2. Detection of Mycobacterium avium subspecies in the gut associated lymphoid tissue of slaughtered rabbits.

    Science.gov (United States)

    Arrazuria, Rakel; Sevilla, Iker A; Molina, Elena; Pérez, Valentín; Garrido, Joseba M; Juste, Ramón A; Elguezabal, Natalia

    2015-06-11

    Rabbits are susceptible to infection by different species of the genus Mycobacterium. Particularly, development of specific lesions and isolation of Mycobacterium avium subsp. avium and Mycobacterium avium subsp. paratuberculosis, both subspecies of the M. avium complex, has been reported in wildlife conditions. Although, rabbit meat production worldwide is 200 million tons per year, microbiological data on this source of meat is lacking and more specifically reports of mycobacterial presence in industrially reared rabbit for human consumption have not been published. To this end, we sought mycobacteria by microbiological and histopathological methods paying special attention to Mycobacterium avium subsp. paratuberculosis in rabbits from commercial rabbitries from the North East of Spain. M. avium subsp. paratuberculosis was not detected either by culture or PCR. However, Mycobacterium avium subsp. avium was detected in 15.15% (10/66) and Mycobacterium avium subsp. hominissuis was detected in 1.51% (1/66) of gut associated lymphoid tissue of sampled animals by PCR, whereas caecal contents were negative. 9% (6/66) of the animals presented gross lesions suggestive of lymphoid activation, 6% (4/66) presented granulomatous lesions and 3% (2/66) contained acid fast bacilli. Mycobacterial isolation from samples was not achieved, although colonies of Thermoactinomycetes sp. were identified by 16s rRNA sequencing in 6% (4/66) of sampled animals. Apparently healthy farmed rabbits that go to slaughter may carry M. avium subspecies in gut associated lymphoid tissue.

  3. Retinoic Acid Differentially Regulates the Migration of Innate Lymphoid Cell Subsets to the Gut.

    Science.gov (United States)

    Kim, Myung H; Taparowsky, Elizabeth J; Kim, Chang H

    2015-07-21

    Distinct groups of innate lymphoid cells (ILCs) such as ILC1, ILC2, and ILC3 populate the intestine, but how these ILCs develop tissue tropism for this organ is unclear. We report that prior to migration to the intestine ILCs first undergo a "switch" in their expression of homing receptors from lymphoid to gut homing receptors. This process is regulated by mucosal dendritic cells and the gut-specific tissue factor retinoic acid (RA). This change in homing receptors is required for long-term population and effector function of ILCs in the intestine. Only ILC1 and ILC3, but not ILC2, undergo the RA-dependent homing receptor switch in gut-associated lymphoid tissues. In contrast, ILC2 acquire gut homing receptors in a largely RA-independent manner during their development in the bone marrow and can migrate directly to the intestine. Thus, distinct programs regulate the migration of ILC subsets to the intestine for regulation of innate immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Ectopic Tertiary Lymphoid Tissue in Inflammatory Bowel Disease: Protective or Provocateur?

    Science.gov (United States)

    McNamee, Eóin N; Rivera-Nieves, Jesús

    2016-01-01

    Organized lymphoid tissues like the thymus first appeared in jawed vertebrates around 500 million years ago and have evolved to equip the host with a network of specialized sites, strategically located to orchestrate strict immune-surveillance and efficient immune responses autonomously. The gut-associated lymphoid tissues maintain a mostly tolerant environment to dampen our responses to daily dietary and microbial products in the intestine. However, when this homeostasis is perturbed by chronic inflammation, the intestine is able to develop florid organized tertiary lymphoid tissues (TLT), which heralds the onset of regional immune dysregulation. While TLT are a pathologic hallmark of Crohn's disease (CD), their role in the overall process remains largely enigmatic. A critical question remains; are intestinal TLT generated by the immune infiltrated intestine to modulate immune responses and rebuild tolerance to the microbiota or are they playing a more sinister role by generating dysregulated responses that perpetuate disease? Herein, we discuss the main theories of intestinal TLT neogenesis and focus on the most recent findings that open new perspectives to their role in inflammatory bowel disease.

  5. Saccharomyces boulardii administration can inhibit the formation of gastric lymphoid follicles induced by Helicobacter suis infection.

    Science.gov (United States)

    Yang, Lin; Tian, Zi-Bin; Yu, Ya-Nan; Zhang, Cui-Ping; Li, Xiao-Yu; Mao, Tao; Jing, Xue; Zhao, Wen-Jun; Ding, Xue-Li; Yang, Ruo-Ming; Zhang, Shuai-Qing

    2017-01-01

    Helicobacter suis has a greater tendency to induce gastric mucosa-associated lymphoid tissue lymphoma compared with other Helicobacter species in humans and animals. Saccharomyces boulardii has been established as an adjunct to H. pylori eradication treatment, but the effect of S. boulardii administration alone on Helicobacter infection remains unclear. Here, we found that S. boulardii administration effectively decreased the bacterial load of H. suis and inhibited the formation of lymphoid follicles in the stomach post-infection. The levels of H. suis-specific immunoglobulin A (IgA) and secretory IgA in the gastric juice and small intestinal secretions and the production of mouse β-defensin-3 in the small intestinal secretions were significantly increased by S. boulardii administration at 12 weeks after H. suis infection. In addition, feeding with S. boulardii inhibited the expression of inflammatory cytokines and lymphoid follicle formation-related factors after H. suis infection. These results suggested that S. boulardii may be useful for the prevention and treatment of Helicobacter infection-related diseases in humans. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Recombinase, chromosomal translocations and lymphoid neoplasia: targeting mistakes and repair failures.

    Science.gov (United States)

    Marculescu, Rodrig; Vanura, Katrina; Montpellier, Bertrand; Roulland, Sandrine; Le, Trang; Navarro, Jean-Marc; Jäger, Ulrich; McBlane, Fraser; Nadel, Bertrand

    2006-09-08

    A large number of lymphoid malignancies is characterized by specific chromosomal translocations, which are closely linked to the initial steps of pathogenesis. The hallmark of these translocations is the ectopic activation of a silent proto-oncogene through its relocation at the vicinity of an active regulatory element. Due to the unique feature of lymphoid cells to somatically rearrange and mutate receptor genes, and to the corresponding strong activity of the immune enhancers/promoters at that stage of cell development, B- and T-cell differentiation pathways represent propitious targets for chromosomal translocations and oncogene activation. Recent progress in the understanding of the V(D)J recombination process has allowed a more accurate definition of the translocation mechanisms involved, and has revealed that V(D)J-mediated translocations result both from targeting mistakes of the recombinase, and from illegitimate repair of the V(D)J recombination intermediates. Surprisingly, V(D)J-mediated translocations turn out to be restricted to two specific sub-types of lymphoid malignancies, T-cell acute lymphoblastic leukemias, and a restricted set of mature B-cell Non-Hodgkin's lymphomas.

  7. Einstein's Revolutionary Light-Quantum Hypothesis

    Science.gov (United States)

    Stuewer, Roger H.

    2005-05-01

    The paper in which Albert Einstein proposed his light-quantum hypothesis was the only one of his great papers of 1905 that he himself termed ``revolutionary.'' Contrary to widespread belief, Einstein did not propose his light-quantum hypothesis ``to explain the photoelectric effect.'' Instead, he based his argument for light quanta on the statistical interpretation of the second law of thermodynamics, with the photoelectric effect being only one of three phenomena that he offered as possible experimental support for it. I will discuss Einstein's light-quantum hypothesis of 1905 and his introduction of the wave-particle duality in 1909 and then turn to the reception of his work on light quanta by his contemporaries. We will examine the reasons that prominent physicists advanced to reject Einstein's light-quantum hypothesis in succeeding years. Those physicists included Robert A. Millikan, even though he provided convincing experimental proof of the validity of Einstein's equation of the photoelectric effect in 1915. The turning point came after Arthur Holly Compton discovered the Compton effect in late 1922, but even then Compton's discovery was contested both on experimental and on theoretical grounds. Niels Bohr, in particular, had never accepted the reality of light quanta and now, in 1924, proposed a theory, the Bohr-Kramers-Slater theory, which assumed that energy and momentum were conserved only statistically in microscopic interactions. Only after that theory was disproved experimentally in 1925 was Einstein's revolutionary light-quantum hypothesis generally accepted by physicists---a full two decades after Einstein had proposed it.

  8. A Dopamine Hypothesis of Autism Spectrum Disorder.

    Science.gov (United States)

    Pavăl, Denis

    2017-01-01

    Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. While several theories have emerged, the pathogenesis of ASD remains unknown. Although studies report dopamine signaling abnormalities in autistic patients, a coherent dopamine hypothesis which could link neurobiology to behavior in ASD is currently lacking. In this paper, we present such a hypothesis by proposing that autistic behavior arises from dysfunctions in the midbrain dopaminergic system. We hypothesize that a dysfunction of the mesocorticolimbic circuit leads to social deficits, while a dysfunction of the nigrostriatal circuit leads to stereotyped behaviors. Furthermore, we discuss 2 key predictions of our hypothesis, with emphasis on clinical and therapeutic aspects. First, we argue that dopaminergic dysfunctions in the same circuits should associate with autistic-like behavior in nonautistic subjects. Concerning this, we discuss the case of PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) which displays behaviors similar to those of ASD, presumed to arise from dopaminergic dysfunctions. Second, we argue that providing dopamine modulators to autistic subjects should lead to a behavioral improvement. Regarding this, we present clinical studies of dopamine antagonists which seem to have improving effects on autistic behavior. Furthermore, we explore the means of testing our hypothesis by using neuroreceptor imaging, which could provide comprehensive evidence for dopamine signaling dysfunctions in autistic subjects. Lastly, we discuss the limitations of our hypothesis. Along these lines, we aim to provide a dopaminergic model of ASD which might lead to a better understanding of the ASD pathogenesis. © 2017 S. Karger AG, Basel.

  9. Efficacy of total lymphoid irradiation for chronic allograft rejection following double lung transplantation

    International Nuclear Information System (INIS)

    Diamond, David A.; Michalski, Jeff M.; Trulock, Elbert M.; Lynch, John P.

    1997-01-01

    Purpose: The purpose of this study was to assess the safety and efficacy of total lymphoid irradiation in a series of patients experiencing chronic rejection following bilateral lung transplantation. Patients and Materials: Eleven patients (10 males, 1 female) received total lymphoid irradiation for chronic allograft rejection (bronchiolitis obliterans syndrome) refractory to conventional treatment modalities. Treatment was delivered between March, 1995, and September, 1996. Mean patient age was 33 years (range 15-51). Indications for transplantation included cystic fibrosis (7 patients), alpha 1 anti-trypsin deficiency (2 patients), primary pulmonary hypertension (1 patient), and emphysema (1 patient). Radiation therapy was prescribed as 800 cGy delivered in ten 80 cGy fractions, 2 fractions per week, via AP/PA mantle and inverted-Y fields. Radiation was withheld for total wbc count 3 , absolute neutrophil count 3 , or platelets 3 . Serial pre- and post-radiation therapy pulmonary function values, complete blood counts, and immunosuppressive augmentation requirements (use of methylprednisolone, azathioprine, mycophenolate mofetil, OKT3, and FK506) were monitored. Results: In the 3 months preceding total lymphoid irradiation, the average decrease in FEV 1 was 34% (range 0-75%) and the median number of immunosuppression augmentations was 3 (range 0-5). At initiation of radiation therapy, the average FEV 1 was 1.4 liters (range 0.77-2.28). Only (4(11)) patients completed all 10 treatment fractions. Reasons for discontinuation included unabated rejection (4 patients), worsening pulmonary infection (2 patients), and persistent thrombocytopenia (1 patient). No treatment course was discontinued because of persistent neutropenia or leukopenia. Seven of the 11 patients failed within 8 weeks of treatment cessation. One patient had unabated rejection and received bilateral living related donor transplants. He is alive and well. Six patients died. Two of these deaths were due

  10. Tests of the Giant Impact Hypothesis

    Science.gov (United States)

    Jones, J. H.

    1998-01-01

    The giant impact hypothesis has gained popularity as a means of explaining a volatile-depleted Moon that still has a chemical affinity to the Earth. As Taylor's Axiom decrees, the best models of lunar origin are testable, but this is difficult with the giant impact model. The energy associated with the impact would be sufficient to totally melt and partially vaporize the Earth. And this means that there should he no geological vestige of Barber times. Accordingly, it is important to devise tests that may be used to evaluate the giant impact hypothesis. Three such tests are discussed here. None of these is supportive of the giant impact model, but neither do they disprove it.

  11. The discovered preference hypothesis - an empirical test

    DEFF Research Database (Denmark)

    Lundhede, Thomas; Ladenburg, Jacob; Olsen, Søren Bøye

    Using stated preference methods for valuation of non-market goods is known to be vulnerable to a range of biases. Some authors claim that these so-called anomalies in effect render the methods useless for the purpose. However, the Discovered Preference Hypothesis, as put forth by Plott [31], offers...... an nterpretation and explanation of biases which entails that the stated preference methods need not to be completely written off. In this paper we conduct a test for the validity and relevance of the DPH interpretation of biases. In a choice experiment concerning preferences for protection of Danish nature areas...... as respondents evaluate more and more choice sets. This finding supports the Discovered Preference Hypothesis interpretation and explanation of starting point bias....

  12. The Hypothesis-Driven Physical Examination.

    Science.gov (United States)

    Garibaldi, Brian T; Olson, Andrew P J

    2018-05-01

    The physical examination remains a vital part of the clinical encounter. However, physical examination skills have declined in recent years, in part because of decreased time at the bedside. Many clinicians question the relevance of physical examinations in the age of technology. A hypothesis-driven approach to teaching and practicing the physical examination emphasizes the performance of maneuvers that can alter the likelihood of disease. Likelihood ratios are diagnostic weights that allow clinicians to estimate the post-probability of disease. This hypothesis-driven approach to the physical examination increases its value and efficiency, while preserving its cultural role in the patient-physician relationship. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. MOLIERE: Automatic Biomedical Hypothesis Generation System.

    Science.gov (United States)

    Sybrandt, Justin; Shtutman, Michael; Safro, Ilya

    2017-08-01

    Hypothesis generation is becoming a crucial time-saving technique which allows biomedical researchers to quickly discover implicit connections between important concepts. Typically, these systems operate on domain-specific fractions of public medical data. MOLIERE, in contrast, utilizes information from over 24.5 million documents. At the heart of our approach lies a multi-modal and multi-relational network of biomedical objects extracted from several heterogeneous datasets from the National Center for Biotechnology Information (NCBI). These objects include but are not limited to scientific papers, keywords, genes, proteins, diseases, and diagnoses. We model hypotheses using Latent Dirichlet Allocation applied on abstracts found near shortest paths discovered within this network, and demonstrate the effectiveness of MOLIERE by performing hypothesis generation on historical data. Our network, implementation, and resulting data are all publicly available for the broad scientific community.

  14. The Method of Hypothesis in Plato's Philosophy

    Directory of Open Access Journals (Sweden)

    Malihe Aboie Mehrizi

    2016-09-01

    Full Text Available The article deals with the examination of method of hypothesis in Plato's philosophy. This method, respectively, will be examined in three dialogues of Meno, Phaedon and Republic in which it is explicitly indicated. It will be shown the process of change of Plato’s attitude towards the position and usage of the method of hypothesis in his realm of philosophy. In Meno, considering the geometry, Plato attempts to introduce a method that can be used in the realm of philosophy. But, ultimately in Republic, Plato’s special attention to the method and its importance in the philosophical investigations, leads him to revise it. Here, finally Plato introduces the particular method of philosophy, i.e., the dialectic

  15. Debates—Hypothesis testing in hydrology: Introduction

    Science.gov (United States)

    Blöschl, Günter

    2017-03-01

    This paper introduces the papers in the "Debates—Hypothesis testing in hydrology" series. The four articles in the series discuss whether and how the process of testing hypotheses leads to progress in hydrology. Repeated experiments with controlled boundary conditions are rarely feasible in hydrology. Research is therefore not easily aligned with the classical scientific method of testing hypotheses. Hypotheses in hydrology are often enshrined in computer models which are tested against observed data. Testability may be limited due to model complexity and data uncertainty. All four articles suggest that hypothesis testing has contributed to progress in hydrology and is needed in the future. However, the procedure is usually not as systematic as the philosophy of science suggests. A greater emphasis on a creative reasoning process on the basis of clues and explorative analyses is therefore needed.

  16. Multi-agent sequential hypothesis testing

    KAUST Repository

    Kim, Kwang-Ki K.

    2014-12-15

    This paper considers multi-agent sequential hypothesis testing and presents a framework for strategic learning in sequential games with explicit consideration of both temporal and spatial coordination. The associated Bayes risk functions explicitly incorporate costs of taking private/public measurements, costs of time-difference and disagreement in actions of agents, and costs of false declaration/choices in the sequential hypothesis testing. The corresponding sequential decision processes have well-defined value functions with respect to (a) the belief states for the case of conditional independent private noisy measurements that are also assumed to be independent identically distributed over time, and (b) the information states for the case of correlated private noisy measurements. A sequential investment game of strategic coordination and delay is also discussed as an application of the proposed strategic learning rules.

  17. Hypothesis testing of scientific Monte Carlo calculations

    Science.gov (United States)

    Wallerberger, Markus; Gull, Emanuel

    2017-11-01

    The steadily increasing size of scientific Monte Carlo simulations and the desire for robust, correct, and reproducible results necessitates rigorous testing procedures for scientific simulations in order to detect numerical problems and programming bugs. However, the testing paradigms developed for deterministic algorithms have proven to be ill suited for stochastic algorithms. In this paper we demonstrate explicitly how the technique of statistical hypothesis testing, which is in wide use in other fields of science, can be used to devise automatic and reliable tests for Monte Carlo methods, and we show that these tests are able to detect some of the common problems encountered in stochastic scientific simulations. We argue that hypothesis testing should become part of the standard testing toolkit for scientific simulations.

  18. Reverse hypothesis machine learning a practitioner's perspective

    CERN Document Server

    Kulkarni, Parag

    2017-01-01

    This book introduces a paradigm of reverse hypothesis machines (RHM), focusing on knowledge innovation and machine learning. Knowledge- acquisition -based learning is constrained by large volumes of data and is time consuming. Hence Knowledge innovation based learning is the need of time. Since under-learning results in cognitive inabilities and over-learning compromises freedom, there is need for optimal machine learning. All existing learning techniques rely on mapping input and output and establishing mathematical relationships between them. Though methods change the paradigm remains the same—the forward hypothesis machine paradigm, which tries to minimize uncertainty. The RHM, on the other hand, makes use of uncertainty for creative learning. The approach uses limited data to help identify new and surprising solutions. It focuses on improving learnability, unlike traditional approaches, which focus on accuracy. The book is useful as a reference book for machine learning researchers and professionals as ...

  19. Exploring heterogeneous market hypothesis using realized volatility

    Science.gov (United States)

    Chin, Wen Cheong; Isa, Zaidi; Mohd Nor, Abu Hassan Shaari

    2013-04-01

    This study investigates the heterogeneous market hypothesis using high frequency data. The cascaded heterogeneous trading activities with different time durations are modelled by the heterogeneous autoregressive framework. The empirical study indicated the presence of long memory behaviour and predictability elements in the financial time series which supported heterogeneous market hypothesis. Besides the common sum-of-square intraday realized volatility, we also advocated two power variation realized volatilities in forecast evaluation and risk measurement in order to overcome the possible abrupt jumps during the credit crisis. Finally, the empirical results are used in determining the market risk using the value-at-risk approach. The findings of this study have implications for informationally market efficiency analysis, portfolio strategies and risk managements.

  20. Water Taxation and the Double Dividend Hypothesis

    OpenAIRE

    Nicholas Kilimani

    2014-01-01

    The double dividend hypothesis contends that environmental taxes have the potential to yield multiple benefits for the economy. However, empirical evidence of the potential impacts of environmental taxation in developing countries is still limited. This paper seeks to contribute to the literature by exploring the impact of a water tax in a developing country context, with Uganda as a case study. Policy makers in Uganda are exploring ways of raising revenue by taxing environmental goods such a...

  1. [Working memory, phonological awareness and spelling hypothesis].

    Science.gov (United States)

    Gindri, Gigiane; Keske-Soares, Márcia; Mota, Helena Bolli

    2007-01-01

    Working memory, phonological awareness and spelling hypothesis. To verify the relationship between working memory, phonological awareness and spelling hypothesis in pre-school children and first graders. Participants of this study were 90 students, belonging to state schools, who presented typical linguistic development. Forty students were preschoolers, with the average age of six and 50 students were first graders, with the average age of seven. Participants were submitted to an evaluation of the working memory abilities based on the Working Memory Model (Baddeley, 2000), involving phonological loop. Phonological loop was evaluated using the Auditory Sequential Test, subtest 5 of Illinois Test of Psycholinguistic Abilities (ITPA), Brazilian version (Bogossian & Santos, 1977), and the Meaningless Words Memory Test (Kessler, 1997). Phonological awareness abilities were investigated using the Phonological Awareness: Instrument of Sequential Assessment (CONFIAS - Moojen et al., 2003), involving syllabic and phonemic awareness tasks. Writing was characterized according to Ferreiro & Teberosky (1999). Preschoolers presented the ability of repeating sequences of 4.80 digits and 4.30 syllables. Regarding phonological awareness, the performance in the syllabic level was of 19.68 and in the phonemic level was of 8.58. Most of the preschoolers demonstrated to have a pre-syllabic writing hypothesis. First graders repeated, in average, sequences of 5.06 digits and 4.56 syllables. These children presented a phonological awareness of 31.12 in the syllabic level and of 16.18 in the phonemic level, and demonstrated to have an alphabetic writing hypothesis. The performance of working memory, phonological awareness and spelling level are inter-related, as well as being related to chronological age, development and scholarity.

  2. Privacy on Hypothesis Testing in Smart Grids

    OpenAIRE

    Li, Zuxing; Oechtering, Tobias

    2015-01-01

    In this paper, we study the problem of privacy information leakage in a smart grid. The privacy risk is assumed to be caused by an unauthorized binary hypothesis testing of the consumer's behaviour based on the smart meter readings of energy supplies from the energy provider. Another energy supplies are produced by an alternative energy source. A controller equipped with an energy storage device manages the energy inflows to satisfy the energy demand of the consumer. We study the optimal ener...

  3. Box-particle probability hypothesis density filtering

    OpenAIRE

    Schikora, M.; Gning, A.; Mihaylova, L.; Cremers, D.; Koch, W.

    2014-01-01

    This paper develops a novel approach for multitarget tracking, called box-particle probability hypothesis density filter (box-PHD filter). The approach is able to track multiple targets and estimates the unknown number of targets. Furthermore, it is capable of dealing with three sources of uncertainty: stochastic, set-theoretic, and data association uncertainty. The box-PHD filter reduces the number of particles significantly, which improves the runtime considerably. The small number of box-p...

  4. Quantum effects and hypothesis of cosmic censorship

    International Nuclear Information System (INIS)

    Parnovskij, S.L.

    1989-01-01

    It is shown that filamentary characteristics with linear mass of less than 10 25 g/cm distort slightly the space-time at distances, exceeding Planck ones. Their formation doesn't change vacuum energy and doesn't lead to strong quantum radiation. Therefore, the problem of their occurrence can be considered within the framework of classical collapse. Quantum effects can be ignored when considering the problem of validity of cosmic censorship hypothesis

  5. The (not so) immortal strand hypothesis.

    Science.gov (United States)

    Tomasetti, Cristian; Bozic, Ivana

    2015-03-01

    Non-random segregation of DNA strands during stem cell replication has been proposed as a mechanism to minimize accumulated genetic errors in stem cells of rapidly dividing tissues. According to this hypothesis, an "immortal" DNA strand is passed to the stem cell daughter and not the more differentiated cell, keeping the stem cell lineage replication error-free. After it was introduced, experimental evidence both in favor and against the hypothesis has been presented. Using a novel methodology that utilizes cancer sequencing data we are able to estimate the rate of accumulation of mutations in healthy stem cells of the colon, blood and head and neck tissues. We find that in these tissues mutations in stem cells accumulate at rates strikingly similar to those expected without the protection from the immortal strand mechanism. Utilizing an approach that is fundamentally different from previous efforts to confirm or refute the immortal strand hypothesis, we provide evidence against non-random segregation of DNA during stem cell replication. Our results strongly suggest that parental DNA is passed randomly to stem cell daughters and provides new insight into the mechanism of DNA replication in stem cells. Copyright © 2015. Published by Elsevier B.V.

  6. A test of the orthographic recoding hypothesis

    Science.gov (United States)

    Gaygen, Daniel E.

    2003-04-01

    The Orthographic Recoding Hypothesis [D. E. Gaygen and P. A. Luce, Percept. Psychophys. 60, 465-483 (1998)] was tested. According to this hypothesis, listeners recognize spoken words heard for the first time by mapping them onto stored representations of the orthographic forms of the words. Listeners have a stable orthographic representation of words, but no phonological representation, when those words have been read frequently but never heard or spoken. Such may be the case for low frequency words such as jargon. Three experiments using visually and auditorily presented nonword stimuli tested this hypothesis. The first two experiments were explicit tests of memory (old-new tests) for words presented visually. In the first experiment, the recognition of auditorily presented nonwords was facilitated when they previously appeared on a visually presented list. The second experiment was similar, but included a concurrent articulation task during a visual word list presentation, thus preventing covert rehearsal of the nonwords. The results were similar to the first experiment. The third experiment was an indirect test of memory (auditory lexical decision task) for visually presented nonwords. Auditorily presented nonwords were identified as nonwords significantly more slowly if they had previously appeared on the visually presented list accompanied by a concurrent articulation task.

  7. Consumer health information seeking as hypothesis testing.

    Science.gov (United States)

    Keselman, Alla; Browne, Allen C; Kaufman, David R

    2008-01-01

    Despite the proliferation of consumer health sites, lay individuals often experience difficulty finding health information online. The present study attempts to understand users' information seeking difficulties by drawing on a hypothesis testing explanatory framework. It also addresses the role of user competencies and their interaction with internet resources. Twenty participants were interviewed about their understanding of a hypothetical scenario about a family member suffering from stable angina and then searched MedlinePlus consumer health information portal for information on the problem presented in the scenario. Participants' understanding of heart disease was analyzed via semantic analysis. Thematic coding was used to describe information seeking trajectories in terms of three key strategies: verification of the primary hypothesis, narrowing search within the general hypothesis area and bottom-up search. Compared to an expert model, participants' understanding of heart disease involved different key concepts, which were also differently grouped and defined. This understanding provided the framework for search-guiding hypotheses and results interpretation. Incorrect or imprecise domain knowledge led individuals to search for information on irrelevant sites, often seeking out data to confirm their incorrect initial hypotheses. Online search skills enhanced search efficiency, but did not eliminate these difficulties. Regardless of their web experience and general search skills, lay individuals may experience difficulty with health information searches. These difficulties may be related to formulating and evaluating hypotheses that are rooted in their domain knowledge. Informatics can provide support at the levels of health information portals, individual websites, and consumer education tools.

  8. Low CXCL13 expression, splenic lymphoid tissue atrophy and germinal center disruption in severe canine visceral leishmaniasis.

    Directory of Open Access Journals (Sweden)

    Joselli S Silva

    Full Text Available Visceral leishmaniasis is associated with atrophy and histological disorganization of splenic compartments. In this paper, we compared organized and disorganized splenic lymphoid tissue from dogs naturally infected with Leishmania infantum assessing the size of the white pulp compartments, the distribution of T, B and S100+ dendritic cells, using immunohistochemistry and morphometry and the expression of CCR7 and the cytokines, CXCL13, lymphotoxin (LT-α, LT-β, CCL19, CCL21, TNF-α, IL-10, IFN-γ and TGF-β, using by real time RT-PCR. The lymphoid follicles and marginal zones were smaller (3.2 and 1.9 times, respectively; Mann-Whitney, P<0.02 in animals with disorganized splenic tissue in comparison to those with organized splenic lymphoid tissue. In spleens with disorganized lymphoid tissue, the numbers of T cells and S100+ dendritic cells were decreased in the follicles, and the numbers of B cells were reduced in both the follicles and marginal zones. CXCL13 mRNA expression was lower in animals with disorganized lymphoid tissue (0.5±0.4 compared to those with organized lymphoid tissue (2.7±2.9, both relative to 18S expression, P = 0.01. These changes in the spleen were associated with higher frequency of severe disease (7/12 in the animals with disorganized than in animals with organized (2/13, Chi-square, P = 0.01 splenic lymphoid tissue. The data presented herein suggest that natural infection with Leishmania infantum is associated with the impairment of follicular dendritic cells, CXCL13 expression, B cell migration and germinal center formation and associates these changes with severe clinical forms of visceral leishmaniasis. Furthermore the fact that this work uses dogs naturally infected with Leishmania infantum emphasizes the relevance of the data presented herein for the knowledge on the canine and human visceral leishmaniasis.

  9. Recovery from schizophrenia and the recovery model.

    Science.gov (United States)

    Warner, Richard

    2009-07-01

    The recovery model refers to subjective experiences of optimism, empowerment and interpersonal support, and to a focus on collaborative treatment approaches, finding productive roles for user/consumers, peer support and reducing stigma. The model is influencing service development around the world. This review will assess whether optimism about outcome from serious mental illness and other tenets of the recovery model are borne out by recent research. Remission of symptoms has been precisely defined, but the definition of 'recovery' is a more diffuse concept that includes such factors as being productive and functioning independently. Recent research and a large, earlier body of data suggest that optimism about outcome from schizophrenia is justified. A substantial proportion of people with the illness will recover completely and many more will regain good social functioning. Outcome is better for people in the developing world. Mortality for people with schizophrenia is increasing but is lower in the developing world. Working appears to help people recover from schizophrenia, and recent advances in vocational rehabilitation have been shown to be effective in countries with differing economies and labor markets. A growing body of research supports the concept that empowerment is an important component of the recovery process. Key tenets of the recovery model - optimism about recovery from schizophrenia, the importance of access to employment and the value of empowerment of user/consumers in the recovery process - are supported by the scientific research. Attempts to reduce the internalized stigma of mental illness should enhance the recovery process.

  10. Recovery during radiation mutagenesis

    International Nuclear Information System (INIS)

    Deen, D.F.; Shaw, E.I.

    1976-01-01

    Many variables (e.g. cell inoculum size, mutagen dose, expression time, and concentration of the selective agent) are known to affect the induced mutation frequency obtained in cultured mammalian cells. The authors have studied the effects of several parameters on the frequency of radiation-induced resistance to 8-azaguanine in asynchronous V79-171B hamster cells. Inoculation with 10 5 cells was followed by graded doses of radiation, expression times were optimized to maximize mutation frequency, and then the treated cells were challenged with 8-azaguanine for ten days. The optimal expression times which maximized mutation frequency were dose dependent and are in the range of 14-24, 24, and 24-36 hours respectively for doses of 250, 40 and 800 rads. A time interval of 24 hours between two 250-rad fractions resulted in a mutation frequency smaller than that obtained from administration of a single 500-rad dose. With 36 hours between halves of the dose, the induced mutation frequency was an order of magnitude lower than that produced by a single dose and actually below the unirradiated (spontaneous) frequency. Maintenance of cells after irradation first at 18 0 C for 24 hours, and then allowance of expression at 37 0 C for 24 hours, increased both the spontaneous and induced mutation frequency. A one-hour postirradiation balanced salt-solution treatment did not affect the number of spontaneous mutants that arose, but reduced the number of induced mutants. Thus, the balanced salt treatment lowers the induced mutation frequency about a factor of two. The possible significance of these results are discussed with respect to the role of radiation repair mechanisms during mutagenesis, and to recovery at low dose rates. A working hypothesis is advanced to explain the possible mechanism which causes expression time to vary as a function of the dose of mutagen. (author)

  11. Heart Attack Recovery FAQs

    Science.gov (United States)

    ... recommendations to make a full recovery. View an animation of a heart attack . Heart Attack Recovery Questions ... Support Network Popular Articles 1 Understanding Blood Pressure Readings 2 Sodium and Salt 3 Heart Attack Symptoms ...

  12. Water Recovery Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The AES Water Recovery Project (WRP) is advancing environmental control and life support systems water recovery technologies to support human exploration beyond low...

  13. EPA Recovery Mapper

    Data.gov (United States)

    U.S. Environmental Protection Agency — The EPA Recovery Mapper is an Internet interactive mapping application that allows users to discover information about every American Recovery and Reinvestment Act...

  14. Incidence of lymphoid neoplasms by subtype among six Asian ethnic groups in the United States, 1996-2004.

    Science.gov (United States)

    Carreon, J Daniel; Morton, Lindsay M; Devesa, Susan S; Clarke, Christina A; Gomez, Scarlett L; Glaser, Sally L; Sakoda, Lori C; Linet, Martha S; Wang, Sophia S

    2008-12-01

    To establish baseline data for lymphoid neoplasm incidence by subtype for six Asian-American ethnic groups. Incident rates were estimated by age and sex for six Asian ethnic groups--Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, Vietnamese--in five United States cancer registry areas during 1996-2004. For comparison, rates for non-Hispanic Whites were also estimated. During 1996-2004, Filipinos had the highest (24.0) and Koreans had the lowest incidence (12.7) of total lymphoid neoplasms. By subtype, Vietnamese and Filipinos had the highest incidence for diffuse large B-cell lymphoma (DLBCL) (8.0 and 7.2); Japanese had the highest incidence of follicular lymphoma (2.3). Although a general male predominance of lymphoid neoplasms was observed, this pattern varied by lymphoid neoplasm subtype. Whites generally had higher rates than all Asian ethnic groups for all lymphoid neoplasms and most lymphoma subtypes, although the magnitude of the difference varied by both ethnicity and lymphoma subtype. The observed variations in incidence patterns among Asian ethnic groups in the United States suggest that it may be fruitful to pursue studies that compare Asian populations for postulated environmental and genetic risk factors.

  15. Updating the lamellar hypothesis of hippocampal organization

    Directory of Open Access Journals (Sweden)

    Robert S Sloviter

    2012-12-01

    Full Text Available In 1971, Andersen and colleagues proposed that excitatory activity in the entorhinal cortex propagates topographically to the dentate gyrus, and on through a trisynaptic circuit lying within transverse hippocampal slices or lamellae [Andersen, Bliss, and Skrede. 1971. Lamellar organization of hippocampal pathways. Exp Brain Res 13, 222-238]. In this way, a relatively simple structure might mediate complex functions in a manner analogous to the way independent piano keys can produce a nearly infinite variety of unique outputs. The lamellar hypothesis derives primary support from the lamellar distribution of dentate granule cell axons (the mossy fibers, which innervate dentate hilar neurons and area CA3 pyramidal cells and interneurons within the confines of a thin transverse hippocampal segment. Following the initial formulation of the lamellar hypothesis, anatomical studies revealed that unlike granule cells, hilar mossy cells, CA3 pyramidal cells, and Layer II entorhinal cells all form axonal projections that are more divergent along the longitudinal axis than the clearly lamellar mossy fiber pathway. The existence of pathways with translamellar distribution patterns has been interpreted, incorrectly in our view, as justifying outright rejection of the lamellar hypothesis [Amaral and Witter. 1989. The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31, 571-591]. We suggest that the functional implications of longitudinally-projecting axons depend not on whether they exist, but on what they do. The observation that focal granule cell layer discharges normally inhibit, rather than excite, distant granule cells suggests that longitudinal axons in the dentate gyrus may mediate "lateral" inhibition and define lamellar function, rather than undermine it. In this review, we attempt a reconsideration of the evidence that most directly impacts the physiological concept of hippocampal lamellar

  16. Hypothesis Testing as an Act of Rationality

    Science.gov (United States)

    Nearing, Grey

    2017-04-01

    Statistical hypothesis testing is ad hoc in two ways. First, setting probabilistic rejection criteria is, as Neyman (1957) put it, an act of will rather than an act of rationality. Second, physical theories like conservation laws do not inherently admit probabilistic predictions, and so we must use what are called epistemic bridge principles to connect model predictions with the actual methods of hypothesis testing. In practice, these bridge principles are likelihood functions, error functions, or performance metrics. I propose that the reason we are faced with these problems is because we have historically failed to account for a fundamental component of basic logic - namely the portion of logic that explains how epistemic states evolve in the presence of empirical data. This component of Cox' (1946) calculitic logic is called information theory (Knuth, 2005), and adding information theory our hypothetico-deductive account of science yields straightforward solutions to both of the above problems. This also yields a straightforward method for dealing with Popper's (1963) problem of verisimilitude by facilitating a quantitative approach to measuring process isomorphism. In practice, this involves data assimilation. Finally, information theory allows us to reliably bound measures of epistemic uncertainty, thereby avoiding the problem of Bayesian incoherency under misspecified priors (Grünwald, 2006). I therefore propose solutions to four of the fundamental problems inherent in both hypothetico-deductive and/or Bayesian hypothesis testing. - Neyman (1957) Inductive Behavior as a Basic Concept of Philosophy of Science. - Cox (1946) Probability, Frequency and Reasonable Expectation. - Knuth (2005) Lattice Duality: The Origin of Probability and Entropy. - Grünwald (2006). Bayesian Inconsistency under Misspecification. - Popper (1963) Conjectures and Refutations: The Growth of Scientific Knowledge.

  17. The conscious access hypothesis: Explaining the consciousness.

    Science.gov (United States)

    Prakash, Ravi

    2008-01-01

    The phenomenon of conscious awareness or consciousness is complicated but fascinating. Although this concept has intrigued the mankind since antiquity, exploration of consciousness from scientific perspectives is not very old. Among myriad of theories regarding nature, functions and mechanism of consciousness, off late, cognitive theories have received wider acceptance. One of the most exciting hypotheses in recent times has been the "conscious access hypotheses" based on the "global workspace model of consciousness". It underscores an important property of consciousness, the global access of information in cerebral cortex. Present article reviews the "conscious access hypothesis" in terms of its theoretical underpinnings as well as experimental supports it has received.

  18. Interstellar colonization and the zoo hypothesis

    International Nuclear Information System (INIS)

    Jones, E.M.

    1978-01-01

    Michael Hart and others have pointed out that current estimates of the number of technological civilizations arisen in the Galaxy since its formation is in fundamental conflict with the expectation that such a civilization could colonize and utilize the entire Galaxy in 10 to 20 million years. This dilemma can be called Hart's paradox. Resolution of the paradox requires that one or more of the following are true: we are the Galaxy's first technical civilization; interstellar travel is immensely impractical or simply impossible; technological civilizations are very short-lived; or we inhabit a wildnerness preserve. The latter is the zoo hypothesis

  19. RANDOM WALK HYPOTHESIS IN FINANCIAL MARKETS

    Directory of Open Access Journals (Sweden)

    Nicolae-Marius JULA

    2017-05-01

    Full Text Available Random walk hypothesis states that the stock market prices do not follow a predictable trajectory, but are simply random. If you are trying to predict a random set of data, one should test for randomness, because, despite the power and complexity of the used models, the results cannot be trustworthy. There are several methods for testing these hypotheses and the use of computational power provided by the R environment makes the work of the researcher easier and with a cost-effective approach. The increasing power of computing and the continuous development of econometric tests should give the potential investors new tools in selecting commodities and investing in efficient markets.

  20. Confluence Model or Resource Dilution Hypothesis?

    DEFF Research Database (Denmark)

    Jæger, Mads

    have a negative effect on educational attainment most studies cannot distinguish empirically between the CM and the RDH. In this paper, I use the different theoretical predictions in the CM and the RDH on the role of cognitive ability as a partial or complete mediator of the sibship size effect......Studies on family background often explain the negative effect of sibship size on educational attainment by one of two theories: the Confluence Model (CM) or the Resource Dilution Hypothesis (RDH). However, as both theories – for substantively different reasons – predict that sibship size should...

  1. Set theory and the continuum hypothesis

    CERN Document Server

    Cohen, Paul J

    2008-01-01

    This exploration of a notorious mathematical problem is the work of the man who discovered the solution. The independence of the continuum hypothesis is the focus of this study by Paul J. Cohen. It presents not only an accessible technical explanation of the author's landmark proof but also a fine introduction to mathematical logic. An emeritus professor of mathematics at Stanford University, Dr. Cohen won two of the most prestigious awards in mathematics: in 1964, he was awarded the American Mathematical Society's Bôcher Prize for analysis; and in 1966, he received the Fields Medal for Logic.

  2. Statistical hypothesis testing with SAS and R

    CERN Document Server

    Taeger, Dirk

    2014-01-01

    A comprehensive guide to statistical hypothesis testing with examples in SAS and R When analyzing datasets the following questions often arise:Is there a short hand procedure for a statistical test available in SAS or R?If so, how do I use it?If not, how do I program the test myself? This book answers these questions and provides an overview of the most commonstatistical test problems in a comprehensive way, making it easy to find and performan appropriate statistical test. A general summary of statistical test theory is presented, along with a basicdescription for each test, including the

  3. Immature Reticulocyte Fraction and Absolute Neutrophil Count as Predictor of Hemopoietic Recovery in Patients with Acute Lymphoblastic Leukemia on Remission Induction Chemotherapy

    Directory of Open Access Journals (Sweden)

    Shan E. Rauf

    2016-05-01

    Full Text Available Objective: Acute lymphoblastic leukemia (ALL encompasses a group of lymphoid neoplasms that are more common in children and arise from B-and T-lineage lymphoid precursor cells. The immature reticulocyte fraction (IRF, a new routine parameter in hematology analyzers, can give an indication of hemopoietic recovery like absolute neutrophil count (ANC. The purpose of this study was to evaluate IRF in excess of 5% was considered as IRF recovery. Materials and Methods: In this descriptive study, 2.5 to 3 mL of EDTA blood of 45 ALL patients undergoing the remission induction phase of their treatment was sampled and analyzed with a Sysmex XE-5000 on day 1 and every second day thereafter until the day of recovery. ANC of >0.5x109/L on the day corresponding to the first of the three consecutive counts was considered as the day of ANC recovery. IRF recovery was an IRF in excess of 5%. Results: The mean age of the patients was 12.04±5.30 years; 25 patients (55.6% were male and 20 patients (44.4% were female. On day 1 of induction remission, the mean IRF value was 9.68±1.41, while the mean ANC value was 0.077±0.061. Mean recovery day for IRF was 11.84±7.44 and mean recovery day for ANC was 17.67±8.77 (twotailed p-value <0.0001 with 95% confidence interval. By day 28, out of 45 patients 36 (80% showed ANC recovery, while 41 (91% showed IRF recovery. The remaining patients who had not shown recovery by day 28 were further followed up and all of them showed recovery of both parameters by day 39. Conclusion: This study concluded that postinduction bone marrow hemopoietic recovery was earlier by IRF than ANC in children with ALL on chemotherapy

  4. Recovery from mental illness

    DEFF Research Database (Denmark)

    Petersen, Kirsten Schultz; Friis, Vivi Soegaard; Haxholm, Birthe Lodahl

    2015-01-01

    Mental health services strive to implement a recovery-oriented approach to rehabilitation. Little is known about service users' perception of the recovery approach. The aim is to explore the service user's perspectives on facilitators and barriers associated with recovery. Twelve residents living...

  5. Improving sample recovery

    International Nuclear Information System (INIS)

    Blanchard, R.J.

    1995-09-01

    This Engineering Task Plan (ETP) describes the tasks, i.e., tests, studies, external support and modifications planned to increase the recovery of the recovery of the waste tank contents using combinations of improved techniques, equipment, knowledge, experience and testing to better the recovery rates presently being experienced

  6. Lymphoid Precursor Cells and their Differentiation; Kletki-predshestvenniki v limfoidnoj tkani i ikh differentsirovka

    Energy Technology Data Exchange (ETDEWEB)

    Chertkov, I. L. [Central' Nyj Institut Gematologii I Perelivanija Krovi, Moskva, SSSR (Russian Federation); Fridenshtejn, A. Ja. [Institut Epidemiologii, Mikrobiologii i Immunologii Im. N.F.Gamaleja, Moskva, SSSR (Russian Federation)

    1968-08-15

    The authors discuss present-day ideas concerning precursor cells in lymphoid tissues and suggest that the stem cells' decision in regard to proliferation and the path of further differentiation may be a multi-stage process, occurring at various successive phases in the histogenesis of lymphoid cells. They propose that only those elements which are capable of actively deciding (under the influence of suitable stimuli or factors inherent in the cell) in which direction the successor cells are to differentiate should be regarded as precursor cells. It is shown that there are in lymphoid tissue at least three stages with the properties of precursor cells: the stem haemopoietic cell, the antigen-sensitive cell and the immunological memory cell. The authors suggest that the working cells of immune response are transformed into immunological memory cells, and discuss the morphological characteristics of the precursor cells. (author) [Russian] V doklade rassmatrivajutsja sovremennye predstavlenija o kletkah-pred- shestvennjakah v limfoidnoj tkani. Predpolagaetsja, chto prinjatie stvolovymi kletkami reshenija o proliferacii i napravlenii dal'nejshej differencirovki mozhet predstavljat' soboj mnogostadijnyj process, proishodjashhij posledovatel'no na raznyh jetapah gistogenez a limfoidnyh kletok. Predlagaetsja rassmatrivat' v kach estv e kletok-predshestvennikov tol'ko te jelementy, kotorye sposobny aktivno (pod vlijaniem sootvetstvujushhih induktorov ili vnutrennih dlja kletki faktorov) prinimat' reshenie o napravlenii differencirovki kletok-potomkov. Dok azyvaet sja nalichie v limfoidnoj tkani, po men'shej mere, treh stadij so svojstvami kletok-predshestvennikov: stvolovaja krovetvornaja kletka, antigen-chuvstvitel'naja kletka i kletka immunologicheskoj pamjati. Vyskazyvaet sja gi poteza o transformacii rabochih kletok immunnogo otvet a v kletki immunologicheskoj pamjati. Obsuzhdaetsja morfologicheskaja harakteristika kletok-predshestvennikov. (author)

  7. Ozone-Induced Nasal Type 2 Immunity in Mice Is Dependent on Innate Lymphoid Cells.

    Science.gov (United States)

    Kumagai, Kazuyoshi; Lewandowski, Ryan; Jackson-Humbles, Daven N; Li, Ning; Van Dyken, Steven J; Wagner, James G; Harkema, Jack R

    2016-06-01

    Epidemiological studies suggest that elevated ambient concentrations of ozone are associated with activation of eosinophils in the nasal airways of atopic and nonatopic children. Mice repeatedly exposed to ozone develop eosinophilic rhinitis and type 2 immune responses. In this study, we determined the role of innate lymphoid cells (ILCs) in the pathogenesis of ozone-induced eosinophilic rhinitis by using lymphoid-sufficient C57BL/6 mice, Rag2(-/-) mice that are devoid of T cells and B cells, and Rag2(-/-)Il2rg(-/-) mice that are depleted of all lymphoid cells including ILCs. The animals were exposed to 0 or 0.8 ppm ozone for 9 consecutive weekdays (4 h/d). Mice were killed 24 hours after exposure, and nasal tissues were selected for histopathology and gene expression analysis. ILC-sufficient C57BL/6 and Rag2(-/-) mice exposed to ozone developed marked eosinophilic rhinitis and epithelial remodeling (e.g., epithelial hyperplasia and mucous cell metaplasia). Chitinase-like proteins and alarmins (IL-33, IL-25, and thymic stromal lymphopoietin) were also increased morphometrically in the nasal epithelium of ozone-exposed C57BL/6 and Rag2(-/-) mice. Ozone exposure elicited increased expression of Il4, Il5, Il13, St2, eotaxin, MCP-2, Gob5, Arg1, Fizz1, and Ym2 mRNA in C57BL/6 and Rag2(-/-) mice. In contrast, ozone-exposed ILC-deficient Rag2(-/-)Il2rg(-/-) mice had no nasal lesions or overexpression of Th2- or ILC2-related transcripts. These results indicate that ozone-induced eosinophilic rhinitis, nasal epithelial remodeling, and type 2 immune activation are dependent on ILCs. To the best of our knowledge, this is the first study to demonstrate that ILCs play an important role in the nasal pathology induced by repeated ozone exposure.

  8. NK cells and other innate lymphoid cells in haematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Paola eVacca

    2016-05-01

    Full Text Available Natural Killer (NK cells play a major role in the T-cell depleted haploidentical haematopoietic stem cell transplantation (haplo-HSCT to cure high-risk leukemias. NK cells belong to the expanding family of innate lymphoid cells (ILC. At variance with NK cells, the other ILC populations (ILC1/2/3 are non-cytolytic, while they secrete different patterns of cytokines. ILC provide host defences against viruses, bacteria and parasites, drive lymphoid organogenesis, and contribute to tissue remodelling. In haplo-HSCT patients, the extensive T-cell depletion is required to prevent graft-versus-host disease (GvHD but increases risks of developing a wide range of life-threatening infections. However, these patients may rely on innate defences that are reconstituted more rapidly than the adaptive ones. In this context, ILC may represent important players in the early phases following transplantation. They may contribute to tissue homeostasis/remodelling and lymphoid tissue reconstitution. While the reconstitution of NK cell repertoire and its role in haplo-HSCT have been largely investigated, little information is available on ILC. Of note, CD34+ cells isolated from different sources of HSC, may differentiate in vitro towards various ILC subsets. Moreover, cytokines released from leukemia blasts (e.g. IL-1β may alter the proportions of NK cells and ILC3, suggesting the possibility that leukemia may skew the ILC repertoire. Further studies are required to define the timing of ILC development and their potential protective role after HSCT.

  9. Effect of total lymphoid irradiation and pretransplant blood transfusion on pancreatic islet allograft survival

    International Nuclear Information System (INIS)

    Mendez-Picon, G.; McGeorge, M.

    1983-01-01

    Total lymphoid irradiation (TLI) has been shown to have a strong immunosuppressive effect both experimentally and clinically. Pretransplant blood transfusions have also been shown to have a strong beneficial effect in the outcome of organ transplantation. A study was made of the effect of TLI and pretransplant blood transfusions, alone and in combination, as an immunosuppressive modality in the isolated pancreatic islet transplant in the rat model. Donor rats (Fischer RT1v1) were kept on a 50% DL-ethionine supplemented diet for 4-6 weeks prior to pancreas removal. Recipient rats (Lewis RT1) were made diabetics prior to transplantation by iv injection of streptozotocin (45 mg/kg). Transfusion protocol consisted of a biweekly transfusion of 2 ml of either donor specific or third party transfusions. Total lymphoid irradiation was carried out by daily administration of 200 rads during one week prior to transplantation. Transplantation of the isolated islets was performed by intraportal injection. Syngeneic transplant of one and a half donor pancreata in each recipient reverted the diabetic condition indefinitely (greater than 100 days). Untreated allogenic grafts had a mean survival time (MST) of 5.2 days. Total lymphoid irradiation in dosages of 800, 1000, and 1200 rads, as the only immunosuppressive regimen, prolonged the MST of allografts to 15.3, 16.5, and 21.8 days, respectively (P less than .05). Pretransplant third party blood transfusion had no effect on allograft survival (MST 6.0). When donor specific blood transfusions were given, the MST was prolonged to 25.3 days (P less than .05). When TLI was administered to recipients of donor specific transfusions, the MST of the allografts did not show any statistical significant difference when compared with untreated animals. This abrogation of the beneficial effect of specific blood transfusion was observed in all dosages of TLI employed: 800 rad (MST 3.0), 1000 rad (MST 8.0), 1200 rad (MST 5.18)

  10. Clonality analysis of lymphoid proliferations using the BIOMED-2 clonality assays: a single institution experience

    Science.gov (United States)

    Kokovic, Ira; Novakovic, Barbara Jezersek; Cerkovnik, Petra; Novakovic, Srdjan

    2014-01-01

    Background Clonality determination in patients with lymphoproliferative disorders can improve the final diagnosis. The aim of our study was to evaluate the applicative value of standardized BIOMED-2 gene clonality assay protocols for the analysis of clonality of lymphocytes in a group of different lymphoid proliferations. Materials and methods. With this purpose, 121 specimens from 91 patients with suspected lymphoproliferations submitted for routine diagnostics from January to December 2011 were retrospectively analyzed. According to the final diagnosis, our series comprised 32 cases of B-cell lymphomas, 38 cases of non-Hodgkin’s T-cell lymphomas and 51 cases of reactive lymphoid proliferations. Clonality testing was performed using the BIOMED-2 clonality assays. Results The determined sensitivity of the TCR assay was 91.9%, while the sensitivity of the IGH assay was 74.2%. The determined specificity of the IGH assay was 73.3% in the group of lymphomas and 87.2% in the group of reactive lesions. The determined specificity of the TCR assay was 62.5% in the group of lymphomas and 54.3% in the group of reactive lesions. Conclusions In the present study, we confirmed the utility of standardized BIOMED-2 clonality assays for the detection of clonality in a routine diagnostical setting of non-Hodgkin’s lymphomas. Reactions for the detection of the complete IGH rearrangements and reactions for the detection of the TCR rearrangements are a good choice for clonality testing of a wide range of lymphoid proliferations and specimen types while the reactions for the detection of incomplete IGH rearrangements have not shown any additional diagnostic value. PMID:24991205

  11. Estradiol Synthesis in Gut-Associated Lymphoid Tissue: Leukocyte Regulation by a Sexually Monomorphic System.

    Science.gov (United States)

    Oakley, Oliver R; Kim, Kee Jun; Lin, Po-Ching; Barakat, Radwa; Cacioppo, Joseph A; Li, Zhong; Whitaker, Alexandra; Chung, Kwang Chul; Mei, Wenyan; Ko, CheMyong

    2016-12-01

    17β-estradiol is a potent sex hormone synthesized primarily by gonads in females and males that regulates development and function of the reproductive system. Recent studies show that 17β-estradiol is locally synthesized in nonreproductive tissues and regulates a myriad of events, including local inflammatory responses. In this study, we report that mesenteric lymph nodes (mLNs) and Peyer's patches (Pps) are novel sites of de novo synthesis of 17β-estradiol. These secondary lymphoid organs are located within or close to the gastrointestinal tract, contain leukocytes, and function at the forefront of immune surveillance. 17β-estradiol synthesis was initially identified using a transgenic mouse with red fluorescent protein coexpressed in cells that express aromatase, the enzyme responsible for 17β-estradiol synthesis. Subsequent immunohistochemistry and tissue culture experiments revealed that aromatase expression was localized to high endothelial venules of these lymphoid organs, and these high endothelial venule cells synthesized 17β-estradiol when isolated and cultured in vitro. Both mLNs and Pps contained 17β-estradiol with concentrations that were significantly higher than those of peripheral blood. Furthermore, the total amount of 17β-estradiol in these organs exceeded that of the gonads. Mice lacking either aromatase or estrogen receptor-β had hypertrophic Pps and mLNs with more leukocytes than their wild-type littermates, demonstrating a role for 17β-estradiol in leukocyte regulation. Importantly, we did not observe any sex-dependent differences in aromatase expression, 17β-estradiol content, or steroidogenic capacity in these lymphoid organs.

  12. Dynamics of viral replication in blood and lymphoid tissues during SIVmac251 infection of macaques

    Directory of Open Access Journals (Sweden)

    Mannioui Abdelkrim

    2009-01-01

    Full Text Available Abstract Background Extensive studies of primary infection are crucial to our understanding of the course of HIV disease. In SIV-infected macaques, a model closely mimicking HIV pathogenesis, we used a combination of three markers -- viral RNA, 2LTR circles and viral DNA -- to evaluate viral replication and dissemination simultaneously in blood, secondary lymphoid tissues, and the gut during primary and chronic infections. Subsequent viral compartmentalization in the main target cells of the virus in peripheral blood during the chronic phase of infection was evaluated by cell sorting and viral quantification with the three markers studied. Results The evolutions of viral RNA, 2LTR circles and DNA levels were correlated in a given tissue during primary and early chronic infection. The decrease in plasma viral load principally reflects a large decrease in viral replication in gut-associated lymphoid tissue (GALT, with viral RNA and DNA levels remaining stable in the spleen and peripheral lymph nodes. Later, during chronic infection, a progressive depletion of central memory CD4+ T cells from the peripheral blood was observed, accompanied by high levels of viral replication in the cells of this subtype. The virus was also found to replicate at this point in the infection in naive CD4+ T cells. Viral RNA was frequently detected in monocytes, but no SIV replication appeared to occur in these cells, as no viral DNA or 2LTR circles were detected. Conclusion We demonstrated the persistence of viral replication and dissemination, mostly in secondary lymphoid tissues, during primary and early chronic infection. During chronic infection, the central memory CD4+ T cells were the major site of viral replication in peripheral blood, but viral replication also occurred in naive CD4+ T cells. The role of monocytes seemed to be limited to carrying the virus as a cargo because there was an observed lack of replication in these cells. These data may have important

  13. The Notch Signaling Pathway Is Balancing Type 1 Innate Lymphoid Cell Immune Functions

    Directory of Open Access Journals (Sweden)

    Thibaut Perchet

    2018-06-01

    Full Text Available The Notch pathway is one of the canonical signaling pathways implicated in the development of various solid tumors. During carcinogenesis, the Notch pathway dysregulation induces tumor expression of Notch receptor ligands participating to escape the immune surveillance. The Notch pathway conditions both the development and the functional regulation of lymphoid subsets. Its importance on T cell subset polarization has been documented contrary to its action on innate lymphoid cells (ILC. We aim to analyze the effect of the Notch pathway on type 1 ILC polarization and functions after disruption of the RBPJk-dependent Notch signaling cascade. Indeed, type 1 ILC comprises conventional NK (cNK cells and type 1 helper innate lymphoid cells (ILC1 that share Notch-related functional characteristics such as the IFNg secretion downstream of T-bet expression. cNK cells have strong antitumor properties. However, data are controversial concerning ILC1 functions during carcinogenesis with models showing antitumoral capacities and others reporting ILC1 inability to control tumor growth. Using various mouse models of Notch signaling pathway depletion, we analyze the effects of its absence on type 1 ILC differentiation and cytotoxic functions. We also provide clues into its role in the maintenance of immune homeostasis in tissues. We show that modulating the Notch pathway is not only acting on tumor-specific T cell activity but also on ILC immune subset functions. Hence, our study uncovers the intrinsic Notch signaling pathway in ILC1/cNK populations and their response in case of abnormal Notch ligand expression. This study help evaluating the possible side effects mediated by immune cells different from T cells, in case of multivalent forms of the Notch receptor ligand delta 1 treatments. In definitive, it should help determining the best novel combination of therapeutic strategies in case of solid tumors.

  14. Service Recovery Sebagai Upaya Peningkatan Kualitas Layanan Perbankan

    OpenAIRE

    Liestyana, Yuli

    2008-01-01

    This study focused on an empirical investigation of service failure and service recoveryin retail banking. Different types of failures and recovery strategies used by banks wereidentified by using critical incident interviews. A survey questionnaire was then developed tomeasure customers' perceptions of the magnitude of service failure and the effectiveness ofservice recovery strategies. A number of research hypothesis were tested relating to thecustomers' evaluations of particular banking fa...

  15. Rorγt+ innate lymphoid cells in intestinal homeostasis and immunity.

    Science.gov (United States)

    Aparicio-Domingo, Patricia; Cupedo, Tom

    2011-01-01

    Innate lymphoid cells (ILC) combine innate and adaptive immune functions and are part of the first line of defense against mucosal infections. ILC are set apart from adaptive lymphocytes by their independence on RAG genes and the resulting absence of specific antigen receptors. In this review, we will discuss the biology and function of intestinal ILC that express the nuclear hormone receptor Rorγt (encoded by the Rorc gene) and highlight their role in intestinal homeostasis and immunity. Copyright © 2011 S. Karger AG, Basel.

  16. Clinical impact of the immunome in lymphoid malignancies: the role of Myeloid-Derived Suppressor Cells

    Directory of Open Access Journals (Sweden)

    Calogero eVetro

    2015-05-01

    Full Text Available The better definition of the mutual sustainment between neoplastic cells and immune system has been translated from the bench to the bedside acquiring value as prognostic factor. Additionally, it represents a promising tool for improving therapeutic strategies. In this context, myeloid-derived suppressor cells have gained a central role in tumor developing with consequent therapeutic implications. In this review, we will focus on the biological and clinical impact of the study of myeloid-derived suppressor cells in the settings of lymphoid malignancies.

  17. Lymphoid nodular hyperplasia in a patient with severe combined immunodeficiency disease

    International Nuclear Information System (INIS)

    Sanchez-Alegre, M. L.; Casanova, A.; Delgado, J.; Relanzon, S.

    2001-01-01

    We describe a case of lymphoid nodular hyperplasia in a woman with severe combined immunodeficiency disease. the patient complained of constipation and episodes of abdominal pain, and examination revealed the presence of a large abdominal mass. The diagnosis was suspected on the basis of the initial radiological studies, but intestinal biopsy was necessary to rule out lymphomatous involvement. We point out the radiological features of this entity which, despite the fact that it may be a chance finding of no pathological significance, requires special attention, especially in immuno deficient individuals. (Author) 10 refs

  18. Total lymphoid irradiation in multiple sclerosis: blood lymphocytes and clinical course

    International Nuclear Information System (INIS)

    Cook, S.D.; Devereux, C.; Troiano, R.; Zito, G.; Hafstein, M.; Lavenhar, M.; Hernandez, E.; Dowling, P.C.

    1987-01-01

    We have found a significant relationship between blood lymphocyte count and prognosis in 45 patients receiving either total lymphoid irradiation or sham irradiation for chronic progressive multiple sclerosis. Patients with sustained lymphocyte counts less than 900 mm-3 for prolonged periods after treatment showed less rapid progression over the ensuing 3 years than did patients with multiple sclerosis who had lymphocyte counts above this level (p less than 0.01). Our results suggest that a simple laboratory test, the absolute blood lymphocyte count, may serve as a valuable barometer for monitoring the amount of immunosuppressive therapy needed to prevent progression in patients with multiple sclerosis, and possibly other autoimmune diseases

  19. Increased number and frequency of group 3 innate lymphoid cells in nonlesional psoriatic skin

    DEFF Research Database (Denmark)

    Dyring-Andersen, B; Geisler, Carsten; Agerbeck, C

    2014-01-01

    BACKGROUND: Psoriasis is a common immune-mediated inflammatory disease that affects the skin and joints. The interleukin (IL)-23/IL-17A axis and IL-22 play key roles in the pathogenesis of psoriasis. IL-23-responsive innate lymphoid cells (ILCs) with a high capacity to produce IL-17 and/or IL-22....... METHODS: Skin biopsies were taken from healthy skin, nonlesional and lesional psoriatic skin, and nickel- and petrolatum-exposed skin from patients with contact allergy to nickel, and lymphocytes were isolated. The cells were stained and characterized by flow cytometry. Cytokine and ligand mRNA expression...

  20. Immune modules shared by innate lymphoid cells and T cells.

    Science.gov (United States)

    Robinette, Michelle L; Colonna, Marco

    2016-11-01

    In recent years, innate lymphoid cells (ILCs) have emerged as innate correlates to T cells. The similarities between ILCs and T cells indicate that lymphocytes of fundamentally distinct lineages can share core "immune modules" that encompass transcriptional circuitry and effector functions while using nonredundant complementary mechanisms of pattern recognition to enact these functions. We review modules currently recognized to be shared between ILCs and T cells. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. Endoscopic features of lymphoid follicles in Helicobacter pylori-associated chronic gastritis.

    Science.gov (United States)

    Hayashi, Seishu; Imamura, Jun; Kimura, Kiminori; Saeki, Shunichi; Hishima, Tsunekazu

    2015-01-01

    Small, round, yellowish-white nodules (YWN) are frequently observed in Helicobacter pylori-associated gastritis. The aim of the present study was to investigate the clinical significance of these YWN. Participants comprised 211 patients with H. pylori-associated gastritis, ranging in age from 23 to 86 years. YWN were detected in 23% of participants, more frequently in women (33%) than in men (12%; P gastritis, and represented histological lymphoid follicles. © 2014 The Authors. Digestive Endoscopy © 2014 Japan Gastroenterological Endoscopy Society.

  2. Primary mucosa-associated lymphoid tissue lymphoma of the breast: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jong Heon; Kim, Dae Bong; Shin, Mi Kyung; Jang, Suk Ki; Kang, Su Min; Ahn, In Oak [Bundang Jesaeng General Hospital, Seongnam (Korea, Republic of)

    2007-11-15

    A primary mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the breast is extremely rare. We report a case of a MALT lymphoma of the breast that presented as a palpable left breast mass in a 37-year-old woman. A physical examination revealed a large firm, and fixed mass in the left inner breast. Mammograms showed a large, isodense mass in the lower inner quadrant of the left breast and an enlarged lymph node in the axilla. A sonogram demonstrated a 5 cm sized, oval, circumscribed, and heterogeneously hypoechoic mass with posterior acoustic enhancement. A surgical biopsy was performed, and the pathology revealed a MALT lymphoma.

  3. Distribution of Interleukin-22-secreting Immune Cells in Conjunctival Associated Lymphoid Tissue.

    Science.gov (United States)

    Yoon, Chang Ho; Lee, Daeseung; Jeong, Hyun Jeong; Ryu, Jin Suk; Kim, Mee Kum

    2018-04-01

    Interleukin (IL)-22 is a cytokine involved in epithelial cell regeneration. Currently, no research studies have analyzed the distribution of the three distinct IL-22-secreting cell populations in human or mouse conjunctiva. This study investigated the distribution of the three main populations of IL-22-secreting immune cells, αβ Th cells, γδ T cells, or innate cells (innate lymphoid cells [ILCs] or natural killer cells), in conjunctival associated lymphoid tissues (CALTs) in human and mouse models. We collected discarded cadaveric bulbar conjunctival tissue specimens after preservation of the corneo-limbal tissue for keratoplasty from four enucleated eyes of the domestic donor. The bulbar conjunctiva tissue, including the cornea from normal (n = 27) or abraded (n = 4) B6 mice, were excised and pooled in RPMI 1640 media. After the lymphoid cells were gated in forward and side scattering, the αβ Th cells, γδ T cells, or innate lymphoid cells were positively or negatively gated using anti-CD3, anti-γδ TCR, and anti-IL-22 antibodies, with a FACSCanto flow cytometer. In normal human conjunctiva, the percentage and number of cells were highest in αβ Th cells, followed by γδ T cells and CD3- γδ TCR- IL-22+ innate cells (presumed ILCs, pILCs) (Kruskal-Wallis test, p = 0.012). In normal mice keratoconjunctiva, the percentage and total number were highest in γδ T cells, followed by αβ Th cells and pILCs (Kruskal-Wallis test, p = 0.0004); in corneal abraded mice, the population of αβ Th cells and pILCs tended to increase. This study suggests that three distinctive populations of IL-22-secreting immune cells are present in CALTs of both humans and mice, and the proportions of IL-22+αβ Th cells, γδ T cells, and pILCs in CALTs in humans might be differently distributed from those in normal mice. © 2018 The Korean Ophthalmological Society.

  4. Primary mucosa-associated lymphoid tissue lymphoma of the breast: a case report

    International Nuclear Information System (INIS)

    Park, Jong Heon; Kim, Dae Bong; Shin, Mi Kyung; Jang, Suk Ki; Kang, Su Min; Ahn, In Oak

    2007-01-01

    A primary mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the breast is extremely rare. We report a case of a MALT lymphoma of the breast that presented as a palpable left breast mass in a 37-year-old woman. A physical examination revealed a large firm, and fixed mass in the left inner breast. Mammograms showed a large, isodense mass in the lower inner quadrant of the left breast and an enlarged lymph node in the axilla. A sonogram demonstrated a 5 cm sized, oval, circumscribed, and heterogeneously hypoechoic mass with posterior acoustic enhancement. A surgical biopsy was performed, and the pathology revealed a MALT lymphoma

  5. Radiation response of mouse lymphoid and myeloid cell lines. Pt. 1

    International Nuclear Information System (INIS)

    Radford, I.R.

    1994-01-01

    The sensitivity of 10 mouse lymphoid or myeloid cell lines to γ-ray- and DNA-associated 125 I-decay-induced clonogenic cell killing have been compared with their rate of loss of viability (membrane integrity) and with their putative cell type of origin. The increased sensitivity of haematopoietic cell lines to killing by DNA dsb may be related to their mode of death (apoptosis versus necrosis). Mode of cell death may thus be an important factor in determining the 'inherent radiosensitivity' of normal cells/tissues. Haematopoietic cell lines that undergo rapid interphase apoptotic death showed extreme sensitivity to DNA dsb. (author)

  6. Gut microbiota and probiotics in modulation of epithelium and gut-associated lymphoid tissue function.

    Science.gov (United States)

    Sanz, Yolanda; De Palma, Giada

    2009-01-01

    The intestinal tract mucosa is exposed to a vast number of environmental antigens and a large community of commensal bacteria. The mucosal immune system has to provide both protection against pathogens and tolerance to harmless bacteria. Immune homeostasis depends on the interaction of indigenous commensal and transient bacteria (probiotics) with various components of the epithelium and the gut-associated lymphoid tissue. Herein, an update is given of the mechanisms by which the gut microbiota and probiotics are translocated through the epithelium, sensed via pattern-recognition receptors, and activate innate and adaptive immune responses.

  7. Gut-associated lymphoid tissues for the development of oral vaccines.

    Science.gov (United States)

    Kunisawa, Jun; Kurashima, Yosuke; Kiyono, Hiroshi

    2012-05-01

    Oral vaccine has been considered to be a prospective vaccine against many pathogens especially invading across gastrointestinal tracts. One key element of oral vaccine is targeting efficient delivery of antigen to gut-associated lymphoid tissue (GALT), the inductive site in the intestine where antigen-specific immune responses are initiated. Various chemical and biological antigen delivery systems have been developed and some are in clinical trials. In this review, we describe the immunological features of GALT and the current status of antigen delivery system candidates for successful oral vaccine. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. Reduced lymphoid response to skin allotransplants in cows with hepatic lipidosis.

    Science.gov (United States)

    Wentink, G H; van den Ingh, T S; Rutten, V P; Müller, K E; Wensing, T

    1999-04-01

    The immune responsiveness of cows with hepatic lipidosis (fatty liver) in comparison to control cows with a normal liver fat content was tested by applying skin allotransplants to the skin of the back of cows on day 3 after parturition. Immunoreactivity was determined by semiquantitative counting of the number of infiltrating lymphocytes in the recipient skin adjacent to the allotransplants during a period of 21 days. There were more invading lymphocytes in samples from control cows than there were in samples from cows with hepatic lipidosis. It was concluded that cows with hepatic lipidosis have a reduced lymphoid response to skin allotransplants.

  9. Primary mucosa-associated lymphoid tissue thyroid lymphoma: a rare thyroid neoplasm of extrathyroid origin

    Directory of Open Access Journals (Sweden)

    Dimitrios Hadjidakis

    2012-01-01

    Full Text Available Primary thyroid lymphoma is a rare malignancy, representing 2-8% of all thyroid malignancies and 1-2% of all extranodal lymphomas. The majority of cases concern non-Hodgkin`s lymphoma of B cell origin, following by Hodgkin’s disease, T cell lymphomas and rarely marginal zone B-cell mucosa-associated lymphoid tissue (MALT lymphomas. MALT lymphomas have been associated with long-standing autoimmune Hashimoto`s thyroiditis. We present the case of a 44-years-old woman with thyroid MALT lymphoma in the background of multinodular goiter of autoimmune origin.

  10. Transplantation tolerance in primates following total lymphoid irradiation and allogeneic bone marrow injection. II. Renal allographs

    International Nuclear Information System (INIS)

    Myburgh, J.A.; Smit, J.A.; Hill, R.R.H.; Browde, S.

    1980-01-01

    A modified regimen of fractionated total lymphoid irradiation and allogeneic bone marrow (BM) injection in chacma baboons produced transplantation tolerance for allografted kidneys from the BM donors, and substantial chimerism without evidence of graft-versus-host disease. Increasing the dose of nucleated BM cells injected 4-fold over that used in liver transplantation resulted consistently in normal graft function in the early weeks after transplantation. Bone marrow injection and challenge with renal allografts could be delayed for at least 3 weeks after completion of irradiation. If it can be shown that this period can be extended even further, the protocols will be relevant to the circumstances of clinical cadaveric renal transplantation

  11. Hypothesis-driven physical examination curriculum.

    Science.gov (United States)

    Allen, Sharon; Olson, Andrew; Menk, Jeremiah; Nixon, James

    2017-12-01

    Medical students traditionally learn physical examination skills as a rote list of manoeuvres. Alternatives like hypothesis-driven physical examination (HDPE) may promote students' understanding of the contribution of physical examination to diagnostic reasoning. We sought to determine whether first-year medical students can effectively learn to perform a physical examination using an HDPE approach, and then tailor the examination to specific clinical scenarios. Medical students traditionally learn physical examination skills as a rote list of manoeuvres CONTEXT: First-year medical students at the University of Minnesota were taught both traditional and HDPE approaches during a required 17-week clinical skills course in their first semester. The end-of-course evaluation assessed HDPE skills: students were assigned one of two cardiopulmonary cases. Each case included two diagnostic hypotheses. During an interaction with a standardised patient, students were asked to select physical examination manoeuvres in order to make a final diagnosis. Items were weighted and selection order was recorded. First-year students with minimal pathophysiology performed well. All students selected the correct diagnosis. Importantly, students varied the order when selecting examination manoeuvres depending on the diagnoses under consideration, demonstrating early clinical decision-making skills. An early introduction to HDPE may reinforce physical examination skills for hypothesis generation and testing, and can foster early clinical decision-making skills. This has important implications for further research in physical examination instruction. © 2016 John Wiley & Sons Ltd and The Association for the Study of Medical Education.

  12. A default Bayesian hypothesis test for mediation.

    Science.gov (United States)

    Nuijten, Michèle B; Wetzels, Ruud; Matzke, Dora; Dolan, Conor V; Wagenmakers, Eric-Jan

    2015-03-01

    In order to quantify the relationship between multiple variables, researchers often carry out a mediation analysis. In such an analysis, a mediator (e.g., knowledge of a healthy diet) transmits the effect from an independent variable (e.g., classroom instruction on a healthy diet) to a dependent variable (e.g., consumption of fruits and vegetables). Almost all mediation analyses in psychology use frequentist estimation and hypothesis-testing techniques. A recent exception is Yuan and MacKinnon (Psychological Methods, 14, 301-322, 2009), who outlined a Bayesian parameter estimation procedure for mediation analysis. Here we complete the Bayesian alternative to frequentist mediation analysis by specifying a default Bayesian hypothesis test based on the Jeffreys-Zellner-Siow approach. We further extend this default Bayesian test by allowing a comparison to directional or one-sided alternatives, using Markov chain Monte Carlo techniques implemented in JAGS. All Bayesian tests are implemented in the R package BayesMed (Nuijten, Wetzels, Matzke, Dolan, & Wagenmakers, 2014).

  13. Gaussian Hypothesis Testing and Quantum Illumination.

    Science.gov (United States)

    Wilde, Mark M; Tomamichel, Marco; Lloyd, Seth; Berta, Mario

    2017-09-22

    Quantum hypothesis testing is one of the most basic tasks in quantum information theory and has fundamental links with quantum communication and estimation theory. In this paper, we establish a formula that characterizes the decay rate of the minimal type-II error probability in a quantum hypothesis test of two Gaussian states given a fixed constraint on the type-I error probability. This formula is a direct function of the mean vectors and covariance matrices of the quantum Gaussian states in question. We give an application to quantum illumination, which is the task of determining whether there is a low-reflectivity object embedded in a target region with a bright thermal-noise bath. For the asymmetric-error setting, we find that a quantum illumination transmitter can achieve an error probability exponent stronger than a coherent-state transmitter of the same mean photon number, and furthermore, that it requires far fewer trials to do so. This occurs when the background thermal noise is either low or bright, which means that a quantum advantage is even easier to witness than in the symmetric-error setting because it occurs for a larger range of parameters. Going forward from here, we expect our formula to have applications in settings well beyond those considered in this paper, especially to quantum communication tasks involving quantum Gaussian channels.

  14. Inoculation stress hypothesis of environmental enrichment.

    Science.gov (United States)

    Crofton, Elizabeth J; Zhang, Yafang; Green, Thomas A

    2015-02-01

    One hallmark of psychiatric conditions is the vast continuum of individual differences in susceptibility vs. resilience resulting from the interaction of genetic and environmental factors. The environmental enrichment paradigm is an animal model that is useful for studying a range of psychiatric conditions, including protective phenotypes in addiction and depression models. The major question is how environmental enrichment, a non-drug and non-surgical manipulation, can produce such robust individual differences in such a wide range of behaviors. This paper draws from a variety of published sources to outline a coherent hypothesis of inoculation stress as a factor producing the protective enrichment phenotypes. The basic tenet suggests that chronic mild stress from living in a complex environment and interacting non-aggressively with conspecifics can inoculate enriched rats against subsequent stressors and/or drugs of abuse. This paper reviews the enrichment phenotypes, mulls the fundamental nature of environmental enrichment vs. isolation, discusses the most appropriate control for environmental enrichment, and challenges the idea that cortisol/corticosterone equals stress. The intent of the inoculation stress hypothesis of environmental enrichment is to provide a scaffold with which to build testable hypotheses for the elucidation of the molecular mechanisms underlying these protective phenotypes and thus provide new therapeutic targets to treat psychiatric/neurological conditions. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Athlete's Heart: Is the Morganroth Hypothesis Obsolete?

    Science.gov (United States)

    Haykowsky, Mark J; Samuel, T Jake; Nelson, Michael D; La Gerche, Andre

    2018-05-01

    In 1975, Morganroth and colleagues reported that the increased left ventricular (LV) mass in highly trained endurance athletes versus nonathletes was primarily due to increased end-diastolic volume while the increased LV mass in resistance trained athletes was solely due to an increased LV wall thickness. Based on the divergent remodelling patterns observed, Morganroth and colleagues hypothesised that the increased "volume" load during endurance exercise may be similar to that which occurs in patients with mitral or aortic regurgitation while the "pressure" load associated with performing a Valsalva manoeuvre (VM) during resistance exercise may mimic the stress imposed on the heart by systemic hypertension or aortic stenosis. Despite widespread acceptance of the four-decade old Morganroth hypothesis in sports cardiology, some investigators have questioned whether such a divergent "athlete's heart" phenotype exists. Given this uncertainty, the purpose of this brief review is to re-evaluate the Morganroth hypothesis regarding: i) the acute effects of resistance exercise performed with a brief VM on LV wall stress, and the patterns of LV remodelling in resistance-trained athletes; ii) the acute effects of endurance exercise on biventricular wall stress, and the time course and pattern of LV and right ventricular (RV) remodelling with endurance training; and iii) the value of comparing "loading" conditions between athletes and patients with cardiac pathology. Copyright © 2018. Published by Elsevier B.V.

  16. The Debt Overhang Hypothesis: Evidence from Pakistan

    Directory of Open Access Journals (Sweden)

    Shah Muhammad Imran

    2016-04-01

    Full Text Available This study investigates the debt overhang hypothesis for Pakistan in the period 1960-2007. The study examines empirically the dynamic behaviour of GDP, debt services, the employed labour force and investment using the time series concepts of unit roots, cointegration, error correlation and causality. Our findings suggest that debt-servicing has a negative impact on the productivity of both labour and capital, and that in turn has adversely affected economic growth. By severely constraining the ability of the country to service debt, this lends support to the debt-overhang hypothesis in Pakistan. The long run relation between debt services and economic growth implies that future increases in output will drain away in form of high debt service payments to lender country as external debt acts like a tax on output. More specifically, foreign creditors will benefit more from the rise in productivity than will domestic producers and labour. This suggests that domestic labour and capital are the ultimate losers from this heavy debt burden.

  17. Roots and Route of the Artification Hypothesis

    Directory of Open Access Journals (Sweden)

    Ellen Dissanayake

    2017-08-01

    Full Text Available Over four decades, my ideas about the arts in human evolution have themselves evolved, from an original notion of art as a human behaviour of “making special” to a full-fledged hypothesis of artification. A summary of the gradual developmental path (or route of the hypothesis, based on ethological principles and concepts, is given, and an argument presented in which artification is described as an exaptation whose roots lie in adaptive features of ancestral mother–infant interaction that contributed to infant survival and maternal reproductive success. I show how the interaction displays features of a ritualised behavior whose operations (formalization, repetition, exaggeration, and elaboration can be regarded as characteristic elements of human ritual ceremonies as well as of art (including song, dance, performance, literary language, altered surroundings, and other examples of making ordinary sounds, movement, language, environments, objects, and bodies extraordinary. Participation in these behaviours in ritual practices served adaptive ends in early Homo by coordinating brain and body states, and thereby emotionally bonding members of a group in common cause as well as reducing existential anxiety in individuals. A final section situates artification within contemporary philosophical and popular ideas of art, claiming that artifying is not a synonym for or definition of art but foundational to any evolutionary discussion of artistic/aesthetic behaviour.

  18. Hypothesis: does ochratoxin A cause testicular cancer?

    Science.gov (United States)

    Schwartz, Gary G

    2002-02-01

    Little is known about the etiology of testicular cancer, which is the most common cancer among young men. Epidemiologic data point to a carcinogenic exposure in early life or in utero, but the nature of the exposure is unknown. We hypothesize that the mycotoxin, ochratoxin A, is a cause of testicular cancer. Ochratoxin A is a naturally occurring contaminant of cereals, pigmeat, and other foods and is a known genotoxic carcinogen in animals. The major features of the descriptive epidemiology of testicular cancer (a high incidence in northern Europe, increasing incidence over time, and associations with high socioeconomic status, and with poor semen quality) are all associated with exposure to ochratoxin A. Exposure of animals to ochratoxin A via the diet or via in utero transfer induces adducts in testicular DNA. We hypothesize that consumption of foods contaminated with ochratoxin A during pregnancy and/or childhood induces lesions in testicular DNA and that puberty promotes these lesions to testicular cancer. We tested the ochratoxin A hypothesis using ecologic data on the per-capita consumption of cereals, coffee, and pigmeat, the principal dietary sources of ochratoxin A. Incidence rates for testicular cancer in 20 countries were significantly correlated with the per-capita consumption of coffee and pigmeat (r = 0.49 and 0.54, p = 0.03 and 0.01). The ochratoxin A hypothesis offers a coherent explanation for much of the descriptive epidemiology of testicular cancer and suggests new avenues for analytic research.

  19. Urbanization and the more-individuals hypothesis.

    Science.gov (United States)

    Chiari, Claudia; Dinetti, Marco; Licciardello, Cinzia; Licitra, Gaetano; Pautasso, Marco

    2010-03-01

    1. Urbanization is a landscape process affecting biodiversity world-wide. Despite many urban-rural studies of bird assemblages, it is still unclear whether more species-rich communities have more individuals, regardless of the level of urbanization. The more-individuals hypothesis assumes that species-rich communities have larger populations, thus reducing the chance of local extinctions. 2. Using newly collated avian distribution data for 1 km(2) grid cells across Florence, Italy, we show a significantly positive relationship between species richness and assemblage abundance for the whole urban area. This richness-abundance relationship persists for the 1 km(2) grid cells with less than 50% of urbanized territory, as well as for the remaining grid cells, with no significant difference in the slope of the relationship. These results support the more-individuals hypothesis as an explanation of patterns in species richness, also in human modified and fragmented habitats. 3. However, the intercept of the species richness-abundance relationship is significantly lower for highly urbanized grid cells. Our study confirms that urban communities have lower species richness but counters the common notion that assemblages in densely urbanized ecosystems have more individuals. In Florence, highly inhabited areas show fewer species and lower assemblage abundance. 4. Urbanized ecosystems are an ongoing large-scale natural experiment which can be used to test ecological theories empirically.

  20. A cholinergic hypothesis of the unconscious in affective disorders.

    Directory of Open Access Journals (Sweden)

    Costa eVakalopoulos

    2013-11-01

    Full Text Available The interactions between distinct pharmacological systems are proposed as a key dynamic in the formation of unconscious memories underlying rumination and mood disorder, but also reflect the plastic capacity of neural networks that can aid recovery. An inverse and reciprocal relationship is postulated between cholinergic and monoaminergic receptor subtypes. M1-type muscarinic receptor transduction facilitates encoding of unconscious, prepotent behavioural repertoires at the core of affective disorders and ADHD. Behavioural adaptation to new contingencies is mediated by the classic prototype receptor: 5-HT1A (Gi/o and its modulation of m1-plasticity. Reversal of learning is dependent on increased phasic activation of midbrain monoaminergic nuclei and is a function of hippocampal theta. Acquired hippocampal dysfunction due to abnormal activation of the hypothalamic-pituitary-adrenal (HPA axis predicts deficits in hippocampal-dependent memory and executive function and further impairments to cognitive inhibition. Encoding of explicit memories is mediated by Gq/11 and Gs signalling of monoamines only. A role is proposed for the phasic activation of the basal forebrain cholinergic nucleus by cortical projections from the complex consisting of the insula and claustrum. Although controversial. recent studies suggest a common ontogenetic origin of the two structures and a functional coupling. Lesions of the region result in loss of motivational behaviour and familiarity based judgements. A major hypothesis of the paper is that these lost faculties result indirectly, from reduced cholinergic tone.

  1. The Younger Dryas impact hypothesis: A requiem

    Science.gov (United States)

    Pinter, Nicholas; Scott, Andrew C.; Daulton, Tyrone L.; Podoll, Andrew; Koeberl, Christian; Anderson, R. Scott; Ishman, Scott E.

    2011-06-01

    The Younger Dryas (YD) impact hypothesis is a recent theory that suggests that a cometary or meteoritic body or bodies hit and/or exploded over North America 12,900 years ago, causing the YD climate episode, extinction of Pleistocene megafauna, demise of the Clovis archeological culture, and a range of other effects. Since gaining widespread attention in 2007, substantial research has focused on testing the 12 main signatures presented as evidence of a catastrophic extraterrestrial event 12,900 years ago. Here we present a review of the impact hypothesis, including its evolution and current variants, and of efforts to test and corroborate the hypothesis. The physical evidence interpreted as signatures of an impact event can be separated into two groups. The first group consists of evidence that has been largely rejected by the scientific community and is no longer in widespread discussion, including: particle tracks in archeological chert; magnetic nodules in Pleistocene bones; impact origin of the Carolina Bays; and elevated concentrations of radioactivity, iridium, and fullerenes enriched in 3He. The second group consists of evidence that has been active in recent research and discussions: carbon spheres and elongates, magnetic grains and magnetic spherules, byproducts of catastrophic wildfire, and nanodiamonds. Over time, however, these signatures have also seen contrary evidence rather than support. Recent studies have shown that carbon spheres and elongates do not represent extraterrestrial carbon nor impact-induced megafires, but are indistinguishable from fungal sclerotia and arthropod fecal material that are a small but common component of many terrestrial deposits. Magnetic grains and spherules are heterogeneously distributed in sediments, but reported measurements of unique peaks in concentrations at the YD onset have yet to be reproduced. The magnetic grains are certainly just iron-rich detrital grains, whereas reported YD magnetic spherules are

  2. Approaches to informed consent for hypothesis-testing and hypothesis-generating clinical genomics research.

    Science.gov (United States)

    Facio, Flavia M; Sapp, Julie C; Linn, Amy; Biesecker, Leslie G

    2012-10-10

    Massively-parallel sequencing (MPS) technologies create challenges for informed consent of research participants given the enormous scale of the data and the wide range of potential results. We propose that the consent process in these studies be based on whether they use MPS to test a hypothesis or to generate hypotheses. To demonstrate the differences in these approaches to informed consent, we describe the consent processes for two MPS studies. The purpose of our hypothesis-testing study is to elucidate the etiology of rare phenotypes using MPS. The purpose of our hypothesis-generating study is to test the feasibility of using MPS to generate clinical hypotheses, and to approach the return of results as an experimental manipulation. Issues to consider in both designs include: volume and nature of the potential results, primary versus secondary results, return of individual results, duty to warn, length of interaction, target population, and privacy and confidentiality. The categorization of MPS studies as hypothesis-testing versus hypothesis-generating can help to clarify the issue of so-called incidental or secondary results for the consent process, and aid the communication of the research goals to study participants.

  3. Learning-Related Changes in Adolescents' Neural Networks during Hypothesis-Generating and Hypothesis-Understanding Training

    Science.gov (United States)

    Lee, Jun-Ki; Kwon, Yongju

    2012-01-01

    Fourteen science high school students participated in this study, which investigated neural-network plasticity associated with hypothesis-generating and hypothesis-understanding in learning. The students were divided into two groups and participated in either hypothesis-generating or hypothesis-understanding type learning programs, which were…

  4. Mucosal immunity in HIV infection: what can be done to restore gastrointestinal-associated lymphoid tissue function?

    Science.gov (United States)

    George, Michael D; Asmuth, David M

    2014-06-01

    This review describes the impact of HIV infection on gut-associated lymphoid tissue, the mechanisms for persistent gut-associated lymphoid tissue dysfunction despite effective antiretroviral therapy, and potential strategies to restore gut-associated lymphoid tissue function and promote immune reconstitution. Recent studies indicate that unresolved microbial translocation and intestinal dysbiosis may continue to promote enteropathy as well as HIV-associated and non-HIV-associated conditions in many HIV patients who otherwise maintain therapeutic control of systemic viral replication. Several novel therapeutic approaches to reduce intestinal inflammation and mitigate microbial translocation may hold promise for restoring gastrointestinal health and thereby increasing the efficacy of immune reconstitution in HIV-infected patients undergoing antiretroviral therapy.

  5. Rac1 augments Wnt signaling by stimulating β-catenin–lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import

    Science.gov (United States)

    Jamieson, Cara; Lui, Christina; Brocardo, Mariana G.; Martino-Echarri, Estefania; Henderson, Beric R.

    2015-01-01

    ABSTRACT β-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate β-catenin-dependent transcription of Wnt target genes and we confirmed this activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling by enhancing β-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of β-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1–β-catenin protein complexes redistribute from the plasma membrane to the nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to stimulate the formation of nuclear β-catenin–lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of β-catenin stimulates Wnt-dependent gene transactivation by enhancing β-catenin–LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/β-catenin signaling. PMID:26403202

  6. Battleground Energy Recovery Project

    Energy Technology Data Exchange (ETDEWEB)

    Bullock, Daniel [USDOE Gulf Coast Clean Energy Application Center, Woodlands, TX (United States)

    2011-12-31

    In October 2009, the project partners began a 36-month effort to develop an innovative, commercial-scale demonstration project incorporating state-of-the-art waste heat recovery technology at Clean Harbors, Inc., a large hazardous waste incinerator site located in Deer Park, Texas. With financial support provided by the U.S. Department of Energy, the Battleground Energy Recovery Project was launched to advance waste heat recovery solutions into the hazardous waste incineration market, an area that has seen little adoption of heat recovery in the United States. The goal of the project was to accelerate the use of energy-efficient, waste heat recovery technology as an alternative means to produce steam for industrial processes. The project had three main engineering and business objectives: Prove Feasibility of Waste Heat Recovery Technology at a Hazardous Waste Incinerator Complex; Provide Low-cost Steam to a Major Polypropylene Plant Using Waste Heat; and Create a Showcase Waste Heat Recovery Demonstration Project.

  7. Alternative donor hematopoietic stem cell transplantation for mature lymphoid malignancies after reduced-intensity conditioning regimen: Similar outcomes with umbilical cord blood and unrelated donor peripheral blood

    NARCIS (Netherlands)

    C.A. Rodrigues (Celso Arrais); V. Rocha (Vanderson); P. Dreger (Peter); C.G. Brunstein (Claudio); H. Sengeloev (Henrik); J. Finke (Jürgen); M. Mohty (Mohamad); B. Rio (Bernard); E. Petersen (Eefke); F. Guilhot (François); D. Niederwieser (Dietger); J.J. Cornelissen (Jan); P. Jindra (Pavel); A. Nagler (Arnon); N. Fegueux (Nathalie); H. Schoemans (Hélène); A. Ruggeri (Annelisa); S.P. Robinson (Stephen); E. Gluckman (Eliane); C. Canals (Carmen); A. Sureda (Anna)

    2014-01-01

    textabstractWe have reported encouraging results of unrelated cord blood transplantation for patients with lymphoid malignancies. Whether those outcomes are comparable to matched unrelated donor transplants remains to be defined. We studied 645 adult patients with mature lymphoid malignancies who

  8. Synergistic effects of combined immunosuppressive modulation. I. Unresponsiveness to dendritic cell-depleted renal allografts in dogs exposed to total-lymphoid irradiation

    International Nuclear Information System (INIS)

    Rapaport, F.T.; Meek, A.; Miura, S.; Hayashi, R.; Arnold, A.N.; Strober, S.

    1988-01-01

    Attenuation of the allogeneic stimulus provided by dendritic cells (DC) was achieved by irradiation of the donors, followed by their reconstitution with bone marrow from the prospective DLA-identical recipient. Following long-term (131-187 days) recovery free of graft-versus-host (GVH) disease, the chimeric kidneys were placed into the corresponding recipients; such allografts were rejected at 55, 55, and 60 days, respectively. Four other recipients were conditioned with 1750-1790 cgy of total lymphoid irradiation (TLI) and were then given a similar chimeric kidney from the corresponding partner. These allografts currently survive for 296, 295, 290, and 252 days, respectively. A third group of four dogs was exposed to TLI prior to transplantation of a normal DLA-identical kidney. These grafts were rejected at 20, 42, 46, and 242 days, respectively. Thirteen DLA-identical renal allografts transplanted into normal dogs survived for 13-38 days (mean survival time = 28.6 days). Depletion of allogeneic DC alone, or TLI alone, produced relative prolongations in allograft survival in canine recipients. Combined use of these two modalities, however, resulted in long-term allogeneic unresponsiveness in the recipients

  9. Resistance to mycobacteria in mice treated with fractionated total lymphoid irradiation (TLI) and in mice reconstituted with allogeneic bone marrow cells following radiotherapy

    International Nuclear Information System (INIS)

    Mor, N.; Lutsky, I.; Weiss, L.; Morecki, S.; Slavin, S.

    1985-01-01

    The increased clinical use of total lymphoid irradiation (TLI) as an immunosuppressive adjunct in transplantation suggested the need for determining the effects of TLI on the in vivo susceptibility of animals to infections controlled by cell-mediated immunity. TLI-treated, TLI-treated and splenectomized, and chimeric mice prepared with TLI were inoculated in the hind foot pad with Mycobacterium marinum or Mycobacterium leprae. Although M. marinum organisms multiplied in greater numbers in the TLI mice, ultimately they were destroyed as effectively in TLI mice as in the non-irradiated control mice. M. leprae multiplied at the same rate and to the same maximum in TLI mice as in controls. Mice previously challenged with M. marinum in one hind foot pad, and challenged subsequently with the same organism in the opposite hind foot pad, showed a solid immunity against this reinfection. It appears that upon recovery from the immediate effects of radiotherapy TLI-treated mice are able to mount an effective immune response to experimental infection with M. marinum and M. leprae

  10. Resistance to mycobacteria in mice treated with fractionated total lymphoid irradiation (TLI) and in mice reconstituted with allogeneic bone marrow cells following radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mor, N.; Lutsky, I.; Weiss, L.; Morecki, S.; Slavin, S.

    1985-01-01

    The increased clinical use of total lymphoid irradiation (TLI) as an immunosuppressive adjunct in transplantation suggested the need for determining the effects of TLI on the in vivo susceptibility of animals to infections controlled by cell-mediated immunity. TLI-treated, TLI-treated and splenectomized, and chimeric mice prepared with TLI were inoculated in the hind foot pad with Mycobacterium marinum or Mycobacterium leprae. Although M. marinum organisms multiplied in greater numbers in the TLI mice, ultimately they were destroyed as effectively in TLI mice as in the non-irradiated control mice. M. leprae multiplied at the same rate and to the same maximum in TLI mice as in controls. Mice previously challenged with M. marinum in one hind foot pad, and challenged subsequently with the same organism in the opposite hind foot pad, showed a solid immunity against this reinfection. It appears that upon recovery from the immediate effects of radiotherapy TLI-treated mice are able to mount an effective immune response to experimental infection with M. marinum and M. leprae.

  11. Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-Infection in the Absence of Viral Suppression

    DEFF Research Database (Denmark)

    Kløverpris, Henrik N.; Kazer, Samuel W.; Mjösberg, Jenny

    2016-01-01

    Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-on ILCs remains unknown. We found that human blood...... upregulation of genes associated with cell death, temporally linked with a strong IFN acute-phase response and evidence of gut barrier breakdown. We found no evidence of tissue redistribution in chronic disease and remaining circulating ILCs were activated but not apoptotic. These data provide a potential...... mechanistic link between acute HIV-infection, lymphoid tissue breakdown, and persistent immune dysfunction....

  12. Apoptosis of gut-associated lymphoid tissue in rainbow trout Oncorhynchus mykiss after incubation with Candida albicans and bacterial lipopolysaccharide.

    Science.gov (United States)

    Passantino, L; Ostillio, A; Cianciotta, A; Russo, C; Carrassi, M; Patruno, R; Dhaskali, L; Passantino, G F; Passantino, A

    2011-06-01

    Until now a few studies have been carried out on the gut lymphoid system in fish despite its protective role in the host. Here, we have evaluated the effects of Candida albicans (Ca) and lipopolysaccaride (LPS) on the pyloric and terminal segments of gut in the rainbow trout Oncorhynchus mykiss. In particular, data show that both Ca and LPS are able to cause apoptosis of intestinal lymphoid cells as detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) procedure. These findings suggest a further modality of gut response in fish to environmental antigens.

  13. Alternatives to the linear risk hypothesis

    International Nuclear Information System (INIS)

    Craig, A.G.

    1976-01-01

    A theoretical argument is presented which suggests that in using the linear hypothesis for all values of LET the low dose risk is overestimated for low LET but that it is underestimated for very high LET. The argument is based upon the idea that cell lesions which do not lead to cell death may in fact lead to a malignant cell. Expressions for the Surviving Fraction and the Cancer Risk based on this argument are given. An advantage of this very general approach is that is expresses cell survival and cancer risk entirely in terms of the cell lesions and avoids the rather contentious argument as to how the average number of lesions should be related to the dose. (U.K.)

  14. Large numbers hypothesis. II - Electromagnetic radiation

    Science.gov (United States)

    Adams, P. J.

    1983-01-01

    This paper develops the theory of electromagnetic radiation in the units covariant formalism incorporating Dirac's large numbers hypothesis (LNH). A direct field-to-particle technique is used to obtain the photon propagation equation which explicitly involves the photon replication rate. This replication rate is fixed uniquely by requiring that the form of a free-photon distribution function be preserved, as required by the 2.7 K cosmic radiation. One finds that with this particular photon replication rate the units covariant formalism developed in Paper I actually predicts that the ratio of photon number to proton number in the universe varies as t to the 1/4, precisely in accord with LNH. The cosmological red-shift law is also derived and it is shown to differ considerably from the standard form of (nu)(R) - const.

  15. Artistic talent in dyslexia--a hypothesis.

    Science.gov (United States)

    Chakravarty, Ambar

    2009-10-01

    The present article hints at a curious neurocognitive phenomenon of development of artistic talents in some children with dyslexia. The article also takes note of the phenomenon of creating in the midst of language disability as observed in the lives of such creative people like Leonardo da Vinci and Albert Einstein who were most probably affected with developmental learning disorders. It has been hypothesised that a developmental delay in the dominant hemisphere most likely 'disinhibits' the non-dominant parietal lobe to unmask talents, artistic or otherwise, in some such individuals. The present hypothesis follows the phenomenon of paradoxical functional facilitation described earlier. It has been suggested that children with learning disorders be encouraged to develop such hidden talents to full capacity, rather than be subjected to overemphasising on the correction of the disturbed coded symbol operations, in remedial training.

  16. Tissue misrepair hypothesis for radiation carcinogenesis

    International Nuclear Information System (INIS)

    Kondo, Sohei

    1991-01-01

    Dose-response curves for chronic leukemia in A-bomb survivors and liver tumors in patients given Thorotrast (colloidal thorium dioxide) show large threshold effects. The existence of these threshold effects can be explained by the following hypothesis. A high dose of radiation causes a persistent wound in a cellrenewable tissue. Disorder of the injured cell society partly frees the component cells from territorial restraints on their proliferation, enabling them to continue development of their cellular functions toward advanced autonomy. This progression might be achieved by continued epigenetic and genetic changes as a result of occasional errors in the otherwise concerted healing action of various endogeneous factors recruited for tissue repair. Carcinogenesis is not simply a single-cell problem but a cell-society problem. Therefore, it is not warranted to estimate risk at low doses by linear extrapolation from cancer data at high doses without knowledge of the mechanism of radiation carcinogenesis. (author) 57 refs

  17. Statistical hypothesis tests of some micrometeorological observations

    International Nuclear Information System (INIS)

    SethuRaman, S.; Tichler, J.

    1977-01-01

    Chi-square goodness-of-fit is used to test the hypothesis that the medium scale of turbulence in the atmospheric surface layer is normally distributed. Coefficients of skewness and excess are computed from the data. If the data are not normal, these coefficients are used in Edgeworth's asymptotic expansion of Gram-Charlier series to determine an altrnate probability density function. The observed data are then compared with the modified probability densities and the new chi-square values computed.Seventy percent of the data analyzed was either normal or approximatley normal. The coefficient of skewness g 1 has a good correlation with the chi-square values. Events with vertical-barg 1 vertical-bar 1 vertical-bar<0.43 were approximately normal. Intermittency associated with the formation and breaking of internal gravity waves in surface-based inversions over water is thought to be the reason for the non-normality

  18. The hexagon hypothesis: Six disruptive scenarios.

    Science.gov (United States)

    Burtles, Jim

    2015-01-01

    This paper aims to bring a simple but effective and comprehensive approach to the development, delivery and monitoring of business continuity solutions. To ensure that the arguments and principles apply across the board, the paper sticks to basic underlying concepts rather than sophisticated interpretations. First, the paper explores what exactly people are defending themselves against. Secondly, the paper looks at how defences should be set up. Disruptive events tend to unfold in phases, each of which invites a particular style of protection, ranging from risk management through to business continuity to insurance cover. Their impact upon any business operation will fall into one of six basic scenarios. The hexagon hypothesis suggests that everyone should be prepared to deal with each of these six disruptive scenarios and it provides them with a useful benchmark for business continuity.

  19. Novae, supernovae, and the island universe hypothesis

    International Nuclear Information System (INIS)

    Van Den Bergh, S.

    1988-01-01

    Arguments in Curtis's (1917) paper related to the island universe hypothesis and the existence of novae in spiral nebulae are considered. It is noted that the maximum magnitude versus rate-of-decline relation for novae may be the best tool presently available for the calibration of the extragalactic distance scale. Light curve observations of six novae are used to determine a distance of 18.6 + or - 3.5 MPc to the Virgo cluster. Results suggest that Type Ia supernovae cannot easily be used as standard candles, and that Type II supernovae are unsuitable as distance indicators. Factors other than precursor mass are probably responsible for determining the ultimate fate of evolving stars. 83 references

  20. Extra dimensions hypothesis in high energy physics

    Directory of Open Access Journals (Sweden)

    Volobuev Igor

    2017-01-01

    Full Text Available We discuss the history of the extra dimensions hypothesis and the physics and phenomenology of models with large extra dimensions with an emphasis on the Randall- Sundrum (RS model with two branes. We argue that the Standard Model extension based on the RS model with two branes is phenomenologically acceptable only if the inter-brane distance is stabilized. Within such an extension of the Standard Model, we study the influence of the infinite Kaluza-Klein (KK towers of the bulk fields on collider processes. In particular, we discuss the modification of the scalar sector of the theory, the Higgs-radion mixing due to the coupling of the Higgs boson to the radion and its KK tower, and the experimental restrictions on the mass of the radion-dominated states.