WorldWideScience

Sample records for cytokine environment permissive

  1. MULTI-AGENT CO-ORDINATION IN DISTRIBUTED E-LEARNING ENVIRONMENTS: PROVIDING ACCESS PERMISSIONS

    Directory of Open Access Journals (Sweden)

    Shantha Visalakshi. U

    2013-04-01

    Full Text Available E-Learning, the new technology of supporting education and training, in recent times has been gaining a lot of attention. Content retrieval in e-learning refers the way by which the learning content is provided by means of electronic medium. It is an effective web-based learning paradigm, where many agents can be assigned with unique responsibilities to cope-up with the content retrieval by various users. Agent based system can manage the information stored in the e-learning environment, accessing and granting access permissions. Each task can be carried out by an autonomous agent and various such agents are grouped to form a multi-agent based system. Existing architectures do not consider the enhanced security measures, where it holds security as one among the agents. In the proposed architecture, security is enhanced at the network level and it wraps up all the other agents providing an enhanced security.

  2. Pulmonary infection by Yersinia pestis rapidly establishes a permissive environment for microbial proliferation.

    Science.gov (United States)

    Price, Paul A; Jin, Jianping; Goldman, William E

    2012-02-21

    Disease progression of primary pneumonic plague is biphasic, consisting of a preinflammatory and a proinflammatory phase. During the long preinflammatory phase, bacteria replicate to high levels, seemingly uninhibited by normal pulmonary defenses. In a coinfection model of pneumonic plague, it appears that Yersinia pestis quickly creates a localized, dominant anti-inflammatory state that allows for the survival and rapid growth of both itself and normally avirulent organisms. Yersinia pseudotuberculosis, the relatively recent progenitor of Y. pestis, shows no similar trans-complementation effect, which is unprecedented among other respiratory pathogens. We demonstrate that the effectors secreted by the Ysc type III secretion system are necessary but not sufficient to mediate this apparent immunosuppression. Even an unbiased negative selection screen using a vast pool of Y. pestis mutants revealed no selection against any known virulence genes, demonstrating the transformation of the lung from a highly restrictive to a generally permissive environment during the preinflammatory phase of pneumonic plague.

  3. Leishmania Exosomes Deliver Preemptive Strikes to Create an Environment Permissive for Early Infection

    Directory of Open Access Journals (Sweden)

    Judith Maxwell Silverman

    2012-01-01

    Full Text Available Herein, we review evidence supporting a role for leishmania exosomes during early infection. We suggest a model in which leishmania secreted microvesicles released into the extracellular milieu deliver effector cargo to host target cells. This cargo mediates immunosuppression and functionally primes host cells for leishmania invasion. Leishmania ssp. release microvesicles and the amount of vesicle release and the specific protein cargo of the vesicles is sensitive to changes in environmental conditions that mimic infection. Leishmania exosomes influence the phenotype of treated immune cells. For example, ; wild-type (WT exosomes attenuate interferon-γ-induced pro-inflammatory cytokine production (TNF-α by leishmania-infected monocytes while conversely enhancing production of the anti-inflammatory cytokine IL-10. The leishmania proteins GP63 and elongation factor-1α (EF-1α are found in secreted vesicles and are likely important effectors responsible for these changes in phenotype. GP63 and EF-1α access host cell cytosol and activate multiple host protein tyrosine phosphatases (PTPs. Activation of these PTPs negatively regulates interferon-γ signaling and this prevents effective expression of the macrophage microbicidal arsenal, including TNF-α and nitric oxide. In addition to changing macrophage phenotype, WT vesicles dampen the immune response of monocyte-derived dendritic cells and CD4+ T lymphocytes. This capacity is lost when the protein cargo of the vesicles is modified, specifically when the amount of GP63 and EF-1α in the vesicles is reduced. It appears that exosome delivery of effector proteins results in activation of host PTPs and the negative regulatory effects of the latter creates a pro-parasitic environment. The data suggest that leishmania exosomes secreted upon initial infection are capable of delivering effector cargo to naïve target cells wherein the cargo primes host cells for infection by interfering with host cell

  4. Leishmania exosomes deliver preemptive strikes to create an environment permissive for early infection.

    Science.gov (United States)

    Silverman, Judith Maxwell; Reiner, Neil E

    2011-01-01

    Herein, we review evidence supporting a role for Leishmania exosomes during early infection. We suggest a model in which Leishmania secreted microvesicles released into the extracellular milieu deliver effector cargo to host target cells. This cargo mediates immunosuppression and functionally primes host cells for Leishmania invasion. Leishmania ssp. release microvesicles and the amount of vesicle release and the specific protein cargo of the vesicles is sensitive to changes in environmental conditions that mimic infection. Leishmania exosomes influence the phenotype of treated immune cells. For example, wild-type (WT) exosomes attenuate interferon-γ-induced pro-inflammatory cytokine production (TNF-α) by Leishmania-infected monocytes while conversely enhancing production of the anti-inflammatory cytokine IL-10. The Leishmania proteins GP63 and elongation factor-1α (EF-1α) are found in secreted vesicles and are likely important effectors responsible for these changes in phenotype. GP63 and EF-1α access host cell cytosol and activate multiple host protein-tyrosine phosphatases (PTPs). Activation of these PTPs negatively regulates interferon-γ signaling and this prevents effective expression of the macrophage microbicidal arsenal, including TNF-α and nitric oxide. In addition to changing macrophage phenotype, WT vesicles dampen the immune response of monocyte-derived dendritic cells and CD4+ T lymphocytes. This capacity is lost when the protein cargo of the vesicles is modified, specifically when the amount of GP63 and EF-1α in the vesicles is reduced. It appears that exosome delivery of effector proteins results in activation of host PTPs and the negative regulatory effects of the latter creates a pro-parasitic environment. The data suggest that Leishmania exosomes secreted upon initial infection are capable of delivering effector cargo to naïve target cells wherein the cargo primes host cells for infection by interfering with host cell signaling pathways.

  5. Meningeal cells and glia establish a permissive environment for axon regeneration after spinal cord injury in newts

    Directory of Open Access Journals (Sweden)

    Odelberg Shannon J

    2011-01-01

    Full Text Available Abstract Background Newts have the remarkable ability to regenerate their spinal cords as adults. Their spinal cords regenerate with the regenerating tail after tail amputation, as well as after a gap-inducing spinal cord injury (SCI, such as a complete transection. While most studies on newt spinal cord regeneration have focused on events occurring after tail amputation, less attention has been given to events occurring after an SCI, a context that is more relevant to human SCI. Our goal was to use modern labeling and imaging techniques to observe axons regenerating across a complete transection injury and determine how cells and the extracellular matrix in the injury site might contribute to the regenerative process. Results We identify stages of axon regeneration following a spinal cord transection and find that axon regrowth across the lesion appears to be enabled, in part, because meningeal cells and glia form a permissive environment for axon regeneration. Meningeal and endothelial cells regenerate into the lesion first and are associated with a loose extracellular matrix that allows axon growth cone migration. This matrix, paradoxically, consists of both permissive and inhibitory proteins. Axons grow into the injury site next and are closely associated with meningeal cells and glial processes extending from cell bodies surrounding the central canal. Later, ependymal tubes lined with glia extend into the lesion as well. Finally, the meningeal cells, axons, and glia move as a unit to close the gap in the spinal cord. After crossing the injury site, axons travel through white matter to reach synaptic targets, and though ascending axons regenerate, sensory axons do not appear to be among them. This entire regenerative process occurs even in the presence of an inflammatory response. Conclusions These data reveal, in detail, the cellular and extracellular events that occur during newt spinal cord regeneration after a transection injury and

  6. Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment.

    Science.gov (United States)

    Sekinaka, Tamotsu; Hayashi, Yohei; Noce, Toshiaki; Niwa, Hitoshi; Matsui, Yasuhisa

    2016-09-09

    Epigenetic modifications play crucial roles on establishment of tissue-specific transcription profiles and cellular characteristics. Direct conversions of fibroblasts into differentiated tissue cells by over-expression of critical transcription factors have been reported, but the epigenetic mechanisms underlying these conversions are still not fully understood. In addition, conversion of somatic cells into germ cells has not yet been achieved. To understand epigenetic mechanisms that underlie germ cell characteristics, we attempted to use defined epigenetic factors to directly convert mouse embryonic fibroblasts (MEFs) into germ cells. Here, we successfully induced germ cell-specific genes by inhibiting repressive epigenetic modifications via RNAi or small-molecule compounds. Under these conditions, some tissue-specific genes and stimulus-inducible genes were also induced. Meanwhile, the treatments did not result in genome-wide transcriptional activation. These results suggested that a permissive epigenetic environment resulted in selective de-repression of stimulus- and differentiation-inducible genes including germ cell-specific genes in MEFs.

  7. Fluid spatial dynamics of West Nile virus in the USA: Rapid spread in a permissive host environment

    Science.gov (United States)

    Di Giallonardo , Francesca; Geoghegan, Jemma L.; Docherty, Douglas E.; McLean, Robert G.; Zody, Michael C.; Qu, James; Yang, Xiao; Birren, Bruce W.; Malboeuf, Christine M.; Newman, R.; Ip, Hon S.; Holmes, Edward C.

    2016-01-01

    The introduction of West Nile virus (WNV) into North America in 1999 is a classical example of viral emergence in a new environment, with its subsequent dispersion across the continent having a major impact on local bird populations. Despite the importance of this epizootic, the pattern, dynamics and determinants of WNV spread in its natural hosts remain uncertain. In particular, it is unclear whether the virus encountered major barriers to transmission, or spread in an unconstrained manner, and if specific viral lineages were favored over others indicative of intrinsic differences in fitness. To address these key questions in WNV evolution and ecology we sequenced the complete genomes of approximately 300 avian isolates sampled across the USA between 2001-2012. Phylogenetic analysis revealed a relatively ‘star-like' tree structure, indicative of explosive viral spread in US, although with some replacement of viral genotypes through time. These data are striking in that viral sequences exhibit relatively limited clustering according to geographic region, particularly for those viruses sampled from birds, and no strong phylogenetic association with well sampled avian species. The genome sequence data analysed here also contain relatively little evidence for adaptive evolution, particularly on structural proteins, suggesting that most viral lineages are of similar fitness, and that WNV is well adapted to the ecology of mosquito vectors and diverse avian hosts in the USA. In sum, the molecular evolution of WNV in North America depicts a largely unfettered expansion within a permissive host and geographic population with little evidence of major adaptive barriers.

  8. Selective de-repression of germ cell-specific genes in mouse embryonic fibroblasts in a permissive epigenetic environment

    Science.gov (United States)

    Sekinaka, Tamotsu; Hayashi, Yohei; Noce, Toshiaki; Niwa, Hitoshi; Matsui, Yasuhisa

    2016-01-01

    Epigenetic modifications play crucial roles on establishment of tissue-specific transcription profiles and cellular characteristics. Direct conversions of fibroblasts into differentiated tissue cells by over-expression of critical transcription factors have been reported, but the epigenetic mechanisms underlying these conversions are still not fully understood. In addition, conversion of somatic cells into germ cells has not yet been achieved. To understand epigenetic mechanisms that underlie germ cell characteristics, we attempted to use defined epigenetic factors to directly convert mouse embryonic fibroblasts (MEFs) into germ cells. Here, we successfully induced germ cell-specific genes by inhibiting repressive epigenetic modifications via RNAi or small-molecule compounds. Under these conditions, some tissue-specific genes and stimulus-inducible genes were also induced. Meanwhile, the treatments did not result in genome-wide transcriptional activation. These results suggested that a permissive epigenetic environment resulted in selective de-repression of stimulus- and differentiation-inducible genes including germ cell-specific genes in MEFs. PMID:27608931

  9. Priming Sexual and Romantic Representations in Two Media Environments: Sex Encourages and Romance Discourages Sexual Permissiveness … Sometimes.

    Science.gov (United States)

    Dillman Carpentier, Francesca R

    2016-06-29

    Two experiments (Ns = 314, 447) were used to evaluate the effectiveness of sexual cues in temporarily increasing young adults' self-reported sexual permissiveness, as well as the effects of romantic cues in temporarily decreasing permissiveness. Participants were exposed to sexual or romantic cues embedded as a theme-defining component of an online game (Study 1) or in advertisements peripheral to the online game (Study 2). Sexual and romantic conditions were compared against a control condition. As hypothesized, participants in the romantic conditions rated themselves lower in sexual permissiveness, compared to participants in the sexual and control conditions, particularly when participants positively evaluated the online game experience. Findings suggest that exposure to entertaining media depictions of two people, as a committed couple, expressing love, as well as lust, for each other might deter young adults from considering engagement in casual sexual encounters indicative of "hookup culture."

  10. Synergistic Communication between CD4+ T Cells and Monocytes Impacts the Cytokine Environment

    Science.gov (United States)

    Schrier, Sarah B.; Hill, Abby S.; Plana, Deborah; Lauffenburger, Douglas A.

    2016-01-01

    Physiological cytokine environments arise from factors produced by diverse cell types in coordinated concert. Understanding the contributions of each cell type in the context of cell-cell communication is important for effectively designing disease modifying interventions. Here, we present multi-plexed measurement of 48 cytokines from a coculture system of primary human CD4+ T cells and monocytes across a spectrum of stimuli and for a range of relative T cell/monocyte compositions, coupled with corresponding measurements from PBMCs and plasma from the same donors. Computational analysis of the resulting data-sets elucidated communication-independent and communication-dependent contributions, including both positive and negative synergies. We find that cytokines in cell supernatants were uncorrelated to those found in plasma. Additionally, as an example of positive synergy, production levels of CXCR3 cytokines IP-10 and MIG, depend non-linearly on both IFNγ and TNFα levels in cross-talk between T cells and monocytes. Overall, this work demonstrates that communication between cell types can significantly impact the consequent cytokine environment, emphasizing the value of mixed cell population studies. PMID:27721433

  11. Th17 cells demonstrate stable cytokine production in a proallergic environment.

    Science.gov (United States)

    Glosson-Byers, Nicole L; Sehra, Sarita; Stritesky, Gretta L; Yu, Qing; Awe, Olufolakemi; Pham, Duy; Bruns, Heather A; Kaplan, Mark H

    2014-09-15

    Th17 cells are critical for the clearance of extracellular bacteria and fungi, but also contribute to the pathology of autoimmune diseases and allergic inflammation. After exposure to an appropriate cytokine environment, Th17 cells can acquire a Th1-like phenotype, but less is known about their ability to adopt Th2 and Th9 effector programs. To explore this in more detail, we used an IL-17F lineage tracer mouse strain that allows tracking of cells that formerly expressed IL-17F. In vitro-derived Th17 cells adopted signature cytokine and transcription factor expression when cultured under Th1-, Th2-, or Th9-polarizing conditions. In contrast, using two models of allergic airway disease, Th17 cells from the lungs of diseased mice did not adopt Th1, Th2, or Th9 effector programs, but remained stable IL-17 secretors. Although in vitro-derived Th17 cells expressed IL-4Rα, those induced in vivo during allergic airway disease did not, possibly rendering them unresponsive to IL-4-induced signals. However, in vitro-derived, Ag-specific Th17 cells transferred in vivo to OVA and aluminum hydroxide-sensitized mice also maintained IL-17 secretion and did not produce alternative cytokines upon subsequent OVA challenge. Thus, although Th17 cells can adopt new phenotypes in response to some inflammatory environments, our data suggest that in allergic inflammation, Th17 cells are comparatively stable and retain the potential to produce IL-17. This might reflect a cytokine environment that promotes Th17 stability, and allow a broader immune response at tissue barriers that are susceptible to allergic inflammation.

  12. Human Telomerase Reverse Transcriptase (hTERT) Transcription Requires Sp1/Sp3 Binding to the Promoter and a Permissive Chromatin Environment.

    Science.gov (United States)

    Cheng, De; Zhao, Yuanjun; Wang, Shuwen; Jia, Wenwen; Kang, Jiuhong; Zhu, Jiyue

    2015-12-11

    The transcription of human telomerase gene hTERT is regulated by transcription factors (TFs), including Sp1 family proteins, and its chromatin environment. To understand its regulation in a relevant chromatin context, we employed bacterial artificial chromosome reporters containing 160 kb of human genomic sequence containing the hTERT gene. Upon chromosomal integration, the bacterial artificial chromosomes recapitulated endogenous hTERT expression, contrary to transient reporters. Sp1/Sp3 expression did not correlate with hTERT promoter activity, and these TFs bound to the hTERT promoters in both telomerase-positive and telomerase-negative cells. Mutation of the proximal GC-box resulted in a dramatic decrease of hTERT promoter activity, and mutations of all five GC-boxes eliminated its transcriptional activity. Neither mutations of GC-boxes nor knockdown of endogenous Sp1 impacted promoter binding by other TFs, including E-box-binding proteins, and histone acetylation and trimethylation of histone H3K9 at the hTERT promoter in telomerase-positive and -negative cells. The result indicated that promoter binding by Sp1/Sp3 was essential, but not a limiting step, for hTERT transcription. hTERT transcription required a permissive chromatin environment. Importantly, our data also revealed different functions of GC-boxes and E-boxes in hTERT regulation; although GC-boxes were essential for promoter activity, factors bound to the E-boxes functioned to de-repress hTERT promoter.

  13. Permissible Delay in Payments

    Directory of Open Access Journals (Sweden)

    Yung-Fu Huang

    2007-01-01

    Full Text Available The main purpose of this paper wants to investigate the optimal retailer's lot-sizing policy with two warehouses under partially permissible delay in payments within the economic order quantity (EOQ framework. In this paper, we want to extend that fully permissible delay in payments to the supplier would offer the retailer partially permissible delay in payments. That is, the retailer must make a partial payment to the supplier when the order is received. Then the retailer must pay off the remaining balance at the end of the permissible delay period. In addition, we want to add the assumption that the retailer's storage space is limited. That is, the retailer will rent the warehouse to store these exceeding items when the order quantity is larger than retailer's storage space. Under these conditions, we model the retailer's inventory system as a cost minimization problem to determine the retailer's optimal cycle time and optimal order quantity. Three theorems are developed to efficiently determine the optimal replenishment policy for the retailer. Finally, numerical examples are given to illustrate these theorems and obtained a lot of managerial insights.

  14. Comparison of Effect of Two-Hour Exposure to Forest and Urban Environments on Cytokine, Anti-Oxidant, and Stress Levels in Young Adults

    National Research Council Canada - National Science Library

    Im, Su Geun; Choi, Han; Jeon, Yo-Han; Song, Min-Kyu; Kim, Won; Woo, Jong-Min

    2016-01-01

    The purpose of this study was to investigate the effect of two-hour exposure to a forest environment on cytokine, anti-oxidant and stress levels among university students and to compare the results...

  15. Identification of myeloproliferative neoplasm drug agents via predictive simulation modeling: assessing responsiveness with micro-environment derived cytokines.

    Science.gov (United States)

    Kobayashi, Susumu S; Vali, Shireen; Kumar, Ansu; Singh, Neeraj; Abbasi, Taher; Sayeski, Peter P

    2016-06-14

    Previous studies have shown that the bone marrow micro-environment supports the myeloproliferative neoplasms (MPN) phenotype including via the production of cytokines that can induce resistance to frontline MPN therapies. However, the mechanisms by which this occurs are poorly understood. Moreover, the ability to rapidly identify drug agents that can act as adjuvants to existing MPN frontline therapies is virtually non-existent. Here, using a novel predictive simulation approach, we sought to determine the effect of various drug agents on MPN cell lines, both with and without the micro-environment derived inflammatory cytokines. We first created individual simulation models for two representative MPN cell lines; HEL and SET-2, based on their genomic mutation and copy number variation (CNV) data. Running computational simulations on these virtual cell line models, we identified a synergistic effect of two drug agents on cell proliferation and viability; namely, the Jak2 kinase inhibitor, G6, and the Bcl-2 inhibitor, ABT737. IL-6 did not show any impact on the cells due to the predicted lack of IL-6 signaling within these cells. Interestingly, TNFα increased the sensitivity of the single drug agents and their use in combination while IFNγ decreased the sensitivity. In summary, this study predictively identified two drug agents that reduce MPN cell viability via independent mechanisms that was prospectively validated. Moreover, their efficacy is either potentiated or inhibited, by some of the micro-environment derived cytokines. Lastly, this study has validated the use of this simulation based technology to prospectively determine such responses.

  16. The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production.

    Science.gov (United States)

    Pellicer, A; Albert, C; Mercader, A; Bonilla-Musoles, F; Remohí, J; Simón, C

    1998-09-01

    To assess the endocrine, paracrine, and autocrine milieu in patients with endometriosis on the basis of the measurement of several cytokines in serum and follicular fluid (FF) and in vitro culture of granulosa luteal cells. Case-control study. In vitro fertilization program at the Instituto Valenciano de Infertilidad. Twenty patients with laparoscopically documented endometriosis and 18 controls. Fifteen subjects were studied in a natural cycle and 23 were investigated in a stimulated cycle while undergoing IVF. Individual follicle aspiration, oocyte isolation, FF storage, and preparation of luteinized granulosa cell cultures. Diagnostic laparoscopy in natural cycles. Serum (day of ovum pick-up or laparoscopy) and FF measurement of interleukin (IL)-1beta, IL-6, and vascular endothelial growth factor (VEGF). Secretion of IL-1beta, IL-6, and VEGF in the cell-conditioned medium. Results were compared between patients with endometriosis and controls. Interleukin-6 levels in serum were increased in the natural cycles of patients with endometriosis and modulated by ovarian stimulation, showing a significant decrease in hMG- and FSH-stimulated cycles and a significant increase after hCG administration. In addition, IL-6 levels were increased in the FF of patients with endometriosis and released in higher amounts by their granulosa luteal cells. Vascular endothelial growth factor was accumulated in lesser concentrations in the FF of patients with endometriosis. Interleukin-1beta levels did not show significant changes. Implantation rates were decreased significantly in patients with endometriosis who were undergoing IVF. The data demonstrate that cytokines are regulated differently in patients with endometriosis, who have increased IL-6 production, and suggest that fine hormonal modulation of this cytokine occurs at the systemic and local (ovarian) levels. These changes show that the endocrine, paracrine, and autocrine milieu is different in patients with endometriosis and

  17. 40 CFR 227.27 - Limiting permissible con-cen-tra-tion (LPC).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Limiting permissible con-cen-tra-tion (LPC). 227.27 Section 227.27 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Definitions § 227.27 Limiting permissible con-cen-tra-tion (LPC). (a) The limiting permissible concentration...

  18. Precise control of miR-125b levels is required to create a regeneration-permissive environment after spinal cord injury: a cross-species comparison between salamander and rat.

    Science.gov (United States)

    Diaz Quiroz, Juan Felipe; Tsai, Eve; Coyle, Matthew; Sehm, Tina; Echeverri, Karen

    2014-06-01

    Most spinal cord injuries lead to permanent paralysis in mammals. By contrast, the remarkable regenerative abilities of salamanders enable full functional recovery even from complete spinal cord transections. The molecular differences underlying this evolutionary divergence between mammals and amphibians are poorly understood. We focused on upstream regulators of gene expression as primary entry points into this question. We identified a group of microRNAs (miRNAs) that are conserved between the Mexican axolotl salamander (Ambystoma mexicanum) and mammals but show marked cross-species differences in regulation patterns following spinal cord injury. We found that precise post-injury levels of one of these miRNAs (miR-125b) is essential for functional recovery, and guides correct regeneration of axons through the lesion site in a process involving the direct downstream target Sema4D in axolotls. Translating these results to a mammalian model, we increased miR-125b levels in the rat through mimic treatments following spinal cord transection. These treatments downregulated Sema4D and other glial-scar-related genes, and enhanced the animal's functional recovery. Our study identifies a key regulatory molecule conserved between salamander and mammal, and shows that the expression of miR-125b and Sema4D must be carefully controlled in the right cells at the correct level to promote regeneration. We also show that these molecular components of the salamander's regeneration-permissive environment can be experimentally harnessed to improve treatment outcomes for mammalian spinal cord injuries.

  19. 40 CFR 26.406 - Requirements for permission by parents or guardians and for assent by children.

    Science.gov (United States)

    2010-07-01

    ... Requirements for permission by parents or guardians and for assent by children. (a) In addition to the... are made for soliciting the permission of each child's parents or guardian. Where parental permission... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Requirements for permission by...

  20. Comparison of Effect of Two-Hour Exposure to Forest and Urban Environments on Cytokine, Anti-Oxidant, and Stress Levels in Young Adults

    Directory of Open Access Journals (Sweden)

    Su Geun Im

    2016-06-01

    Full Text Available The purpose of this study was to investigate the effect of two-hour exposure to a forest environment on cytokine, anti-oxidant and stress levels among university students and to compare the results to those measured in urban environments. Forty-one subjects were recruited. For our crossover design, subjects were divided into two groups based on similar demographic characteristics. Group A remained in the urban environment and was asked to perform regular breathing for 2 h. Blood samples were collected and the serum levels of cytokines including interleukin-6 (IL-6, IL-8, tumor necrosis factor-α (TNF-α, and glutathione peroxidase (GPx were examined. Subjects were moved to a small town in a rural area for an equal amount of time to exclude carryover effects, and then remained for another 2 h in a forest environment. The second set of blood samples was collected to assess the effect of exposure to the forest environment. Using the same method, Group B was first exposed to the forest environment, followed by exposure to the urban environment. Blood samples collected after the subjects were exposed to the forest environment showed significantly lower levels of IL-8 and TNF-α compared to those in samples collected after urban environment exposure (10.76 vs. 9.21, t = 4.559, p < 0.001, and 0.97 vs. 0.87, t = 4.130, p < 0.001. The GPx concentration increased significantly after exposure to the forest environment (LnGPx = 5.09 vs. LnGPx = 5.21, t = −2.039, p < 0.05.

  1. Precise control of miR-125b levels is required to create a regeneration-permissive environment after spinal cord injury: a cross-species comparison between salamander and rat

    Directory of Open Access Journals (Sweden)

    Juan Felipe Diaz Quiroz

    2014-06-01

    Full Text Available Most spinal cord injuries lead to permanent paralysis in mammals. By contrast, the remarkable regenerative abilities of salamanders enable full functional recovery even from complete spinal cord transections. The molecular differences underlying this evolutionary divergence between mammals and amphibians are poorly understood. We focused on upstream regulators of gene expression as primary entry points into this question. We identified a group of microRNAs (miRNAs that are conserved between the Mexican axolotl salamander (Ambystoma mexicanum and mammals but show marked cross-species differences in regulation patterns following spinal cord injury. We found that precise post-injury levels of one of these miRNAs (miR-125b is essential for functional recovery, and guides correct regeneration of axons through the lesion site in a process involving the direct downstream target Sema4D in axolotls. Translating these results to a mammalian model, we increased miR-125b levels in the rat through mimic treatments following spinal cord transection. These treatments downregulated Sema4D and other glial-scar-related genes, and enhanced the animal’s functional recovery. Our study identifies a key regulatory molecule conserved between salamander and mammal, and shows that the expression of miR-125b and Sema4D must be carefully controlled in the right cells at the correct level to promote regeneration. We also show that these molecular components of the salamander’s regeneration-permissive environment can be experimentally harnessed to improve treatment outcomes for mammalian spinal cord injuries.

  2. Vagueness, truth and permissive consequence

    NARCIS (Netherlands)

    Cobreros, P.; Egré, P.; Ripley, D.; van Rooij, R.; Achourioti, D.; Galinon, H.; Martínez Fernández, J.; Fujimoto, K.

    2015-01-01

    We say that a sentence A is a permissive consequence of a set of premises Γ whenever, if all the premises of Γ hold up to some standard, then A holds to some weaker standard. In this paper, we focus on a three-valued version of this notion, which we call strict-to-tolerant consequence, and discuss

  3. The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Krakowski, M L; Owens, T

    1997-01-01

    In experimental allergic encephalomyelitis (EAE), CD4+ T cells infiltrate the central nervous system (CNS). We derived CD4+ T cell lines from SJL/J mice that were specific for encephalitogenic myelin basic protein (MBP) peptides and produced both Th1 and Th2 cytokines. These lines transferred EAE...

  4. Take control of permissions in Leopard

    CERN Document Server

    Tanaka, Brian

    2009-01-01

    Permissions problems got you down? Turn to Unix expert Brian Tanaka's unique guide to the permissions in Mac OS X 10.5 Leopard that control access to your files, folders, and disks. You'll learn how to keep files private, when to set Ignore Permissions, what happens when you repair permissions, how to delete stuck files, and the best ways to solve permissions-related problems. Advanced concepts include the sticky bit, Leopard's more-important access control lists, bit masks, and symbolic versus absolute ways to set permissions. The book covers how to take control of permissions via the Finder

  5. 'The ravages of permissiveness': sex education and the permissive society.

    Science.gov (United States)

    Hampshire, James; Lewis, Jane

    2004-01-01

    In this article we explore how sex education in schools has become an adversarial political issue. Although sex education has never been a wholly uncontroversial subject, we show that for two decades after the Second World War there was a broad consensus among policy-makers that it offered a solution to public health and social problems, especially venereal disease. From the late 1960s, this consensus came under attack. As part of a wider effort to reverse the changes associated with the 'permissive' society and legislation of the late 1960s, moral traditionalists and pro-family campaigners sought to problematize sex education. They depicted it as morally corrupting and redefined it as a problem rather than a public health solution. Henceforth, the politics of sex education became increasingly polarized and adversarial. We conclude that the fractious debates about sex education in the 1980s and 1990s are a legacy of this reaction against the permissive society.

  6. The central nervous system environment controls effector CD4+ T cell cytokine profile in experimental allergic encephalomyelitis

    DEFF Research Database (Denmark)

    Krakowski, M L; Owens, T

    1997-01-01

    in vitro. Although CNS antigen-presenting cells (APC) supported increased production of interferon (IFN)-gamma mRNA by these T cells, there was no increase in the interleukin (IL)-4 signal, whereas splenic APC induced increases in both IFN-gamma and IL-4. mRNA for IL-12 (p40 subunit) was up......-regulated in both infiltrating macrophages and resident microglia from mice with EAE. We have thus shown that a Th1 cytokine bias within the CNS can be induced by CNS APC, and that IL-12 is up-regulated in microglial cells within the CNS of mice with EAE. Microglia may therefore control Th1 cytokine responses...

  7. Dietary phytic acid modulates characteristics of the colonic luminal environment and reduces serum levels of proinflammatory cytokines in rats fed a high-fat diet.

    Science.gov (United States)

    Okazaki, Yukako; Katayama, Tetsuyuki

    2014-12-01

    Dietary phytic acid (PA; myo-inositol [MI] hexaphosphate) is known to inhibit colon carcinogenesis in rodents. Dietary fiber, which is a negative risk factor of colon cancer, improves characteristics of the colonic environment, such as the content of organic acids and microflora. We hypothesized that dietary PA would improve the colonic luminal environment in rats fed a high-fat diet. To test this hypothesis, rats were fed diets containing 30% beef tallow with 2.04% sodium PA, 0.4% MI, or 1.02% sodium PA + 0.2% MI for 3 weeks. Compared with the control diet, the sodium PA diet up-regulated cecal organic acids, including acetate, propionate, and n-butyrate; this effect was especially prominent for cecal butyrate. The sodium PA + MI diet also significantly increased cecal butyrate, although this effect was less pronounced when compared with the sodium PA diet. The cecal ratio of Lactobacillales, cecal and fecal mucins (an index of intestinal barrier function), and fecal β-glucosidase activity were higher in rats fed the sodium PA diet than in those fed the control diet. The sodium PA, MI, and sodium PA + MI diets decreased levels of serum tumor necrosis factor α, which is a proinflammatory cytokine. Another proinflammatory cytokine, serum interleukin-6, was also down-regulated by the sodium PA and sodium PA + MI diets. These data showed that PA may improve the composition of cecal organic acids, microflora, and mucins, and it may decrease the levels of serum proinflammatory cytokines in rats fed a high-fat, mineral-sufficient diet.

  8. Cytokine receptors and hematopoietic differentiation.

    Science.gov (United States)

    Robb, L

    2007-10-15

    Colony-stimulating factors and other cytokines signal via their cognate receptors to regulate hematopoiesis. In many developmental systems, inductive signalling determines cell fate and, by analogy with this, it has been postulated that cytokines, signalling via their cognate receptors, may play an instructive role in lineage specification in hematopoiesis. An alternative to this instructive hypothesis is the stochastic or permissive hypothesis. The latter proposes that commitment to a particular hematopoietic lineage is an event that occurs independently of extrinsic signals. It predicts that the role of cytokines is to provide nonspecific survival and proliferation signals. In this review, we look at the role of cytokine receptor signalling in hematopoiesis and consider the evidence for both hypotheses. Data from experiments that genetically manipulate receptor gene expression in vitro or in vivo are reviewed. Experiments in which cytokine receptors were installed in multipotential cells showed that, in some cases, stimulation with the cognate ligand could lead to alterations in lineage output. The creation of genetically manipulated mouse strains demonstrated that cytokine receptors are required for expansion and survival of single lineages but did not reveal a role in lineage commitment. We conclude that hematopoietic differentiation involves mainly stochastic events, but that cytokine receptors also have some instructive role.

  9. Serum exosomes and cytokines promote a T-helper cell type 2 environment in the peripheral blood of glioblastoma patients

    Science.gov (United States)

    Harshyne, Larry A.; Nasca, Brian J.; Kenyon, Lawrence C.; Andrews, David W.; Hooper, D. Craig

    2016-01-01

    Background Glioblastoma (GBM) is an aggressive infiltrative brain tumor with a particularly poor prognosis that is characterized by microvascular proliferation, necrotic tissue, and significant infiltration of M2-like monocytes. Compromised barrier function in tumor vasculature might be expected to permit communication between the tumor microenvironment and peripheral blood. Methods To ascertain whether tumor-derived vesicles and/or factors might reach the bloodstream and what effects these molecules have on the peripheral compartment, we analyzed blood samples collected from primary GBM patients. Results Notably, a significant number of patient sera samples contained tumor exosome-reactive immunoglobulin (Ig)G2 and IgG4 antibody isotypes, which are consistent with Th2 immunity. M2-like monocytes expressing CD14+ and CD163+, another indicator of Th2 bias, are elevated in GBM patient blood and associated with high serum concentrations of colony−stimulating factor 2 and 3, as well as interleukin-2, -4, and -13, the latter 2 cytokines being hallmarks of Th2 immunity. GBM patient sera samples induce high levels of CD163 expression when added to normal monocytes, providing mechanistic evidence of a basis for Th2 bias. Fractionation of GBM patient sera into samples enriched for exosomes or soluble factors proved that both fractions are capable of inducing CD163 expression in normal monocytes. Conclusions The results of the current study indicate a Th2 bias in the periphery of GBM patients, likely as a result of products elaborated by the tumor. Consequentially, through immune modulation these brain tumors exert systemic effects beyond the confines of the CNS. PMID:26180083

  10. Maximum permissible voltage of YBCO coated conductors

    Energy Technology Data Exchange (ETDEWEB)

    Wen, J.; Lin, B.; Sheng, J.; Xu, J.; Jin, Z. [Department of Electrical Engineering, Shanghai Jiao Tong University, Shanghai (China); Hong, Z., E-mail: zhiyong.hong@sjtu.edu.cn [Department of Electrical Engineering, Shanghai Jiao Tong University, Shanghai (China); Wang, D.; Zhou, H.; Shen, X.; Shen, C. [Qingpu Power Supply Company, State Grid Shanghai Municipal Electric Power Company, Shanghai (China)

    2014-06-15

    Highlights: • We examine three kinds of tapes’ maximum permissible voltage. • We examine the relationship between quenching duration and maximum permissible voltage. • Continuous I{sub c} degradations under repetitive quenching where tapes reaching maximum permissible voltage. • The relationship between maximum permissible voltage and resistance, temperature. - Abstract: Superconducting fault current limiter (SFCL) could reduce short circuit currents in electrical power system. One of the most important thing in developing SFCL is to find out the maximum permissible voltage of each limiting element. The maximum permissible voltage is defined as the maximum voltage per unit length at which the YBCO coated conductors (CC) do not suffer from critical current (I{sub c}) degradation or burnout. In this research, the time of quenching process is changed and voltage is raised until the I{sub c} degradation or burnout happens. YBCO coated conductors test in the experiment are from American superconductor (AMSC) and Shanghai Jiao Tong University (SJTU). Along with the quenching duration increasing, the maximum permissible voltage of CC decreases. When quenching duration is 100 ms, the maximum permissible of SJTU CC, 12 mm AMSC CC and 4 mm AMSC CC are 0.72 V/cm, 0.52 V/cm and 1.2 V/cm respectively. Based on the results of samples, the whole length of CCs used in the design of a SFCL can be determined.

  11. [Cytokines in bone diseases. What is cytokine?].

    Science.gov (United States)

    Murakami, Yousuke; Kohsaka, Hitoshi

    2010-10-01

    Cytokines have an essential role for cell-cell communication. They can regulate cell proliferation, differentiation, survival, and function. Interaction of cell surface receptor with cytokines is necessary for control of physiological responses. Activation of cytokine receptors transduces specific signal in the receptor-expressing cells, resulting that cytokines can regulate specific cell population. Thus, cytokines contribute directly or indirectly to morphogenesis, host defense and immune response, play critical roles for homeostasis and development.

  12. 12 CFR 703.14 - Permissible investments.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Permissible investments. 703.14 Section 703.14 Banks and Banking NATIONAL CREDIT UNION ADMINISTRATION REGULATIONS AFFECTING CREDIT UNIONS INVESTMENT.... A Federal credit union may invest in a registered investment company or collective investment fund...

  13. Maximum permissible voltage of YBCO coated conductors

    Science.gov (United States)

    Wen, J.; Lin, B.; Sheng, J.; Xu, J.; Jin, Z.; Hong, Z.; Wang, D.; Zhou, H.; Shen, X.; Shen, C.

    2014-06-01

    Superconducting fault current limiter (SFCL) could reduce short circuit currents in electrical power system. One of the most important thing in developing SFCL is to find out the maximum permissible voltage of each limiting element. The maximum permissible voltage is defined as the maximum voltage per unit length at which the YBCO coated conductors (CC) do not suffer from critical current (Ic) degradation or burnout. In this research, the time of quenching process is changed and voltage is raised until the Ic degradation or burnout happens. YBCO coated conductors test in the experiment are from American superconductor (AMSC) and Shanghai Jiao Tong University (SJTU). Along with the quenching duration increasing, the maximum permissible voltage of CC decreases. When quenching duration is 100 ms, the maximum permissible of SJTU CC, 12 mm AMSC CC and 4 mm AMSC CC are 0.72 V/cm, 0.52 V/cm and 1.2 V/cm respectively. Based on the results of samples, the whole length of CCs used in the design of a SFCL can be determined.

  14. Cytokines and cytokine-specific therapy in asthma.

    Science.gov (United States)

    Desai, Dhananjay; Brightling, Christopher

    2012-01-01

    Asthma is increasing in prevalence worldwide. It is characterized by typical symptoms and variable airway obstruction punctuated with episodes of worsening symptoms known as exacerbations. Underlying this clinical expression of disease is airway inflammation and remodeling. Cytokines and their networks are implicated in the innate and adaptive immune responses driving airway inflammation in asthma and are modulated by host-environment interactions. Asthma is a complex heterogeneous disease, and the paradigm of Th2 cytokine-mediated eosinophilic inflammation as a consequence of allergic sensitization has been challenged and probably represents a subgroup of asthma. Indeed, as attention has switched to the importance of severe asthma, which represents the highest burden both to the patient and health care provider, there is an increasing recognition of inflammatory subphenotypes that are likely to be driven by different cytokine networks. Interestingly, these networks may be specific to aspects of clinical expression as well as inflammatory cell profiles and therefore present novel phenotype-specific therapeutic strategies. Here, we review the breadth of cytokines implicated in the pathogenesis of asthma and focus upon the outcomes of early clinical trials conducted using cytokines or cytokine-blocking therapies.

  15. Rationalizing the Permissibility of Mosque Decoration

    Directory of Open Access Journals (Sweden)

    Spahic Omer

    2016-06-01

    Full Text Available This paper discusses the subject of mosque decoration and some of the criteria which determine its permissibility or otherwise. Some aspects of the matter are somewhat sensitive and double-edged. Thus, the paper presents an objective, balanced and scientific account of the theme, steering clear of the sentimental aspects of the evidences often put forth by both the proponents and opponents of mosque decoration. The main thrusts of the paper are the issues pertaining to the legitimacy of decoration in general, the subject of the function of mosques vis-à-vis their decoration, as well as the broad guidelines that regulate mosque decoration emphasizing the decoration of the mihrab (praying niche area and the qiblah wall. The paper concludes that in principle mosque decoration is permissible so long as it conforms to the requirements of the Islamic spirituality and the quintessence of genuine Islamic art and architecture.

  16. Control over Permissible Short Emergency Overloads in Power Transformers

    Directory of Open Access Journals (Sweden)

    V. A. Anischenko

    2010-01-01

    Full Text Available The paper proposes a method for determination a permissible duration of short intermittent overloads of power transformers that permits to avoid non-permissible over-heating of winding insulation and fully utilize overloading transformer ability.

  17. Cytokines as cellular communicators

    Directory of Open Access Journals (Sweden)

    R. Debets

    1996-01-01

    Full Text Available Cytokines and their receptors are involved in the pathophysiology of many diseases. Here we present a detailed review on cytokines, receptors and signalling routes, and show that one important lesson from cytokine biology is the complex and diverse regulation of cytokine activity. The activity of cytokines is controlled at the level of transcription, translation, storage, processing, posttranslational modification, trapping, binding by soluble proteins, and receptor number and/or function. Translation of this diverse regulation in strategies aimed at the control of cytokine activity will result in the development of more specific and selective drugs to treat diseases.

  18. A Comparison of Authoritarian and Permissive Wording of Hypnotic Suggestions.

    Science.gov (United States)

    Coyle, Robert B.; Church, Jay K.

    The authoritarian/permissive dimension of hypnosis refers to the manner in which hypnotic suggestions are phrased. In the authoritarian mode suggestions imply the subject is under control of the hypnotist; permissive suggestions are phrased to emphasize the subject's own thinking. To compare the permissive suggestions of the Creative Imagination…

  19. A Symbolic Approach to Permission Accounting for Concurrent Reasoning

    NARCIS (Netherlands)

    Huisman, Marieke; Mostowski, Wojciech

    2015-01-01

    Permission accounting is fundamental to modular, thread-local reasoning about concurrent programs. This paper presents a new, symbolic system for permission accounting. In existing systems, permissions are numeric value-based and refer to the current thread only. Our system is based on symbolic

  20. 25 CFR 169.4 - Permission to survey.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Permission to survey. 169.4 Section 169.4 Indians BUREAU... Permission to survey. Anyone desiring to obtain permission to survey for a right-of-way across individually... to cover twice the estimated damages which may be sustained as a result of the survey. With...

  1. Cytokines in Drosophila immunity.

    Science.gov (United States)

    Vanha-Aho, Leena-Maija; Valanne, Susanna; Rämet, Mika

    2016-02-01

    Cytokines are a large and diverse group of small proteins that can affect many biological processes, but most commonly cytokines are known as mediators of the immune response. In the event of an infection, cytokines are produced in response to an immune stimulus, and they function as key regulators of the immune response. Cytokines come in many shapes and sizes, and although they vary greatly in structure, their functions have been well conserved in evolution. The immune signaling pathways that respond to cytokines are remarkably conserved from fly to man. Therefore, Drosophila melanogaster, provides an excellent platform for studying the biology and function of cytokines. In this review, we will describe the cytokines and cytokine-like molecules found in the fly and discuss their roles in host immunity.

  2. Cytokines in bipolar disorder

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Vinberg, Maj; Vedel Kessing, Lars

    2012-01-01

    and 767 healthy controls, evaluating 15 different cytokines-, cytokine receptors- or cytokine antagonists. The levels of tumor necrosis factor-α (TNF-α), the soluble tumor necrosis factor receptor type 1 (sTNF-R1) and the soluble inlerleukin-2 receptor (sIL-2R) were elevated in manic patients compared...

  3. Deciphering conjugative plasmid permissiveness in wastewater microbiomes

    DEFF Research Database (Denmark)

    Jacquiod, Samuel Jehan Auguste; Brejnrod, Asker Daniel; Milani, Stefan Morberg

    2017-01-01

    Wastewater treatment plants (WWTPs) are designed to robustly treat polluted water. They are characterized by ceaseless flows of organic, chemical and microbial matter, followed by treatment steps before environmental release. WWTPs are hotspots of horizontal gene transfer between bacteria via...... still remains largely uncharted. Furthermore, current in vitro methods used to assess conjugation in complex microbiomes do not include in situ behaviours of recipient cells, resulting in partial understanding of transfers. We investigated the in vitro conjugation capacities of WWTP microbiomes from...... diversity of recipient bacterial phyla for the plasmid was observed, especially in WWTP outlets. We also identified permissive bacteria potentially able to cross WWTPs and engage in conjugation before and after water treatment. Bacterial activity and lifestyle seem to influence conjugation extent...

  4. Gender and Family as Moderators of the Relationship between Music Video Exposure and Adolescent Sexual Permissiveness.

    Science.gov (United States)

    Strouse, Jeremiah S.; And Others

    1995-01-01

    Examined family environment and gender as moderators of an hypothesized relationship between exposure to rock music videos and premarital sexual attitudes and behavior. Results of a survey of 214 adolescents revealed a stronger association between permissive sexual attitudes and behavior and reported exposure to music videos for females than for…

  5. Environment

    DEFF Research Database (Denmark)

    Valentini, Chiara

    2017-01-01

    The term environment refers to the internal and external context in which organizations operate. For some scholars, environment is defined as an arrangement of political, economic, social and cultural factors existing in a given context that have an impact on organizational processes and structures....... For others, environment is a generic term describing a large variety of stakeholders and how these interact and act upon organizations. Organizations and their environment are mutually interdependent and organizational communications are highly affected by the environment. This entry examines the origin...... and development of organization-environment interdependence, the nature of the concept of environment and its relevance for communication scholarships and activities....

  6. Prevention of Interapp Permission Leakage for Android Applications

    Directory of Open Access Journals (Sweden)

    Gayathri S

    2016-02-01

    Full Text Available Each and every application in android requires respective user approval for providing permission to app to install. Suppose each and every one the consents are accepted the application is installed and takes delivery of the assemblage association. Throughout runtime, the permissions are checkered by the collection association. The gone astray permissions will grounds the request to smash into and as well it appropriates the respective user individual information from the server. Numerous methods were urbanized to become aware of the second-hand and idle permissions. Other than they did not catalog out the idle permissions. Many android applications like appwrong were able to exchange a few words with peripheral servers because it is arranged the internet permission. Furthermore, appwrong had confirmed permission for the camera smooth though it is not using any code related to the camera. For the reason that of this permission, the aggressor can inscribe the code for using camera,then it will obtain image and propel that to a distant congregation in the Internet. Therefore, this paper recommends a new-fangled procedure to register out the unexploited permissions using the compositional investigation and describe chart cohort. In wrapping up, the idle permissions will be detached and the app will be mounting into the corresponding device.

  7. Cytokines and the Skin Barrier

    Directory of Open Access Journals (Sweden)

    Jens Malte Baron

    2013-03-01

    Full Text Available The skin is the largest organ of the human body and builds a barrier to protect us from the harmful environment and also from unregulated loss of water. Keratinocytes form the skin barrier by undergoing a highly complex differentiation process that involves changing their morphology and structural integrity, a process referred to as cornification. Alterations in the epidermal cornification process affect the formation of the skin barrier. Typically, this results in a disturbed barrier, which allows the entry of substances into the skin that are immunologically reactive. This contributes to and promotes inflammatory processes in the skin but also affects other organs. In many common skin diseases, including atopic dermatitis and psoriasis, a defect in the formation of the skin barrier is observed. In these diseases the cytokine composition within the skin is different compared to normal human skin. This is the result of resident skin cells that produce cytokines, but also because additional immune cells are recruited. Many of the cytokines found in defective skin are able to influence various processes of differentiation and cornification. Here we summarize the current knowledge on cytokines and their functions in healthy skin and their contributions to inflammatory skin diseases.

  8. Legal Permissibility of Unilateral Humanitarian Interventions

    Directory of Open Access Journals (Sweden)

    Petra Perisic

    2013-03-01

    Full Text Available The paper explores the status of unilateral humanitarian interventions in international law. The United Nations Charter prohibits the use of force, except in case of self-defense and the collective action authorized by the Security Council. The question is whether the non-existence of unilateral humanitarian intervention among these exceptions means that they are not in conformity with the Charter and if so, whether the right to such interventions exists as the part of customary law. The issue has become even more controversial after the adoption of the “responsibility to protect” principle. Findings of legal scholars on this issue differ significantly. This paper analyzes and interprets the Charter provisions in order to answer the question of compatibility of humanitarian interventions with the Charter and examines the state practice in order to conclude whether the customary law rule allowing the humanitarian intervention exists. The conclusion of the paper is that there is no evidence to support the contentions that interventions without the Security Council authorization are permissible, although there are elements which point to the possibility of the creation of customary law allowing them.

  9. Free choice permission as resource-sensitive reasoning

    Directory of Open Access Journals (Sweden)

    Chris Barker

    2010-09-01

    Full Text Available Free choice permission is a long-standing puzzle in deontic logic and in natural language semantics. It involves what appears to be a conjunctive use of "or": from "You may eat an apple or a pear", we can infer that "You may eat an apple" and that "You may eat a pear" -- though not that "You may eat an apple and a pear". Following Lokhorst (1997, I argue that because permission is a limited resource, a resource-sensitive logic such as Girard's Linear Logic is better suited to modeling permission talk than, say, classical logic. A resource-sensitive approach enables the semantics to track not only that permission has been granted and what sort of permission it is (i.e., permission to eat apples versus permission to eat pears, but also how much permission has been granted, i.e., whether there is enough permission to eat two pieces of fruit or only one. The account here is primarily semantic (as opposed to pragmatic, with no special modes of composition or special pragmatic rules. The paper includes an introduction to Linear Logic. doi:10.3765/sp.3.10 BibTeX info

  10. Establishment of hepatitis E virus infection-permissive and -non-permissive human hepatoma PLC/PRF/5 subclones.

    Science.gov (United States)

    Shiota, Tomoyuki; Li, Tian-Cheng; Yoshizaki, Sayaka; Kato, Takanobu; Wakita, Takaji; Ishii, Koji

    2015-02-01

    PLC/PRF/5 cells show limited permissiveness, meaning that almost all subclones are permissive; however, some subclones do not exhibit permissiveness for hepatitis E virus (HEV) infection. In this study, the single-cell cloning of PLC/PRF/5 was performed and heterogeneous subclones characterized. Notably, the efficiency of intracellular virus replication did not correlate with the permissiveness for HEV infection. However, as well as binding permissive subclones, virus-like particles bound non-permissive subclones on various levels, suggesting that these subclones have some deficiencies in the attachment and entry steps of infection. Our data would be useful for investigating the HEV life cycle. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  11. 12 CFR 703.13 - Permissible investment activities.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Permissible investment activities. 703.13... INVESTMENT AND DEPOSIT ACTIVITIES § 703.13 Permissible investment activities. (a) Regular way settlement and... funds transactions. (c) Investment repurchase transaction. A Federal credit union may enter into...

  12. 30 CFR 75.1103-7 - Electrical components; permissibility requirements.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electrical components; permissibility... Protection § 75.1103-7 Electrical components; permissibility requirements. The electrical components of each... dust when the electrical power is deenergized as required by § 75.313, but these components shall...

  13. 30 CFR 75.503 - Permissible electric face equipment; maintenance.

    Science.gov (United States)

    2010-07-01

    ...-General § 75.503 Permissible electric face equipment; maintenance. The operator of each coal mine shall... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Permissible electric face equipment; maintenance. 75.503 Section 75.503 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT...

  14. 45 CFR 1639.4 - Permissible representation of eligible clients.

    Science.gov (United States)

    2010-10-01

    ... 45 Public Welfare 4 2010-10-01 2010-10-01 false Permissible representation of eligible clients... CORPORATION WELFARE REFORM § 1639.4 Permissible representation of eligible clients. Recipients may represent an individual eligible client who is seeking specific relief from a welfare agency. ...

  15. 30 CFR 57.5039 - Maximum permissible concentration.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Maximum permissible concentration. 57.5039... Maximum permissible concentration. Except as provided by standard § 57.5005, persons shall not be exposed to air containing concentrations of radon daughters exceeding 1.0 WL in active workings. ...

  16. Insights into cytokine-receptor interactions from cytokine engineering.

    Science.gov (United States)

    Spangler, Jamie B; Moraga, Ignacio; Mendoza, Juan L; Garcia, K Christopher

    2015-01-01

    Cytokines exert a vast array of immunoregulatory actions critical to human biology and disease. However, the desired immunotherapeutic effects of native cytokines are often mitigated by toxicity or lack of efficacy, either of which results from cytokine receptor pleiotropy and/or undesired activation of off-target cells. As our understanding of the structural principles of cytokine-receptor interactions has advanced, mechanism-based manipulation of cytokine signaling through protein engineering has become an increasingly feasible and powerful approach. Modified cytokines, both agonists and antagonists, have been engineered with narrowed target cell specificities, and they have also yielded important mechanistic insights into cytokine biology and signaling. Here we review the theory and practice of cytokine engineering and rationalize the mechanisms of several engineered cytokines in the context of structure. We discuss specific examples of how structure-based cytokine engineering has opened new opportunities for cytokines as drugs, with a focus on the immunotherapeutic cytokines interferon, interleukin-2, and interleukin-4.

  17. Cytokines and Liver Diseases

    Directory of Open Access Journals (Sweden)

    Herbert Tilg

    2001-01-01

    Full Text Available Cytokines are pleiotropic peptides produced by virtually every nucleated cell in the body. In most tissues, including the liver, constitutive production of cytokines is absent or minimal. There is increasing evidence that several cytokines mediate hepatic inflammation, apoptosis and necrosis of liver cells, cholestasis and fibrosis. Interestingly, the same mediators also mediate the regeneration of liver tissue after injury. Among the various cytokines, the proinflammatory cytokine tumour necrosis factor-alpha (TNF-a has emerged as a key factor in various aspects of liver disease, such as cachexia and/or cholestasis. Thus, antagonism of TNF-a and other injury-related cytokines in liver diseases merits evaluation as a treatment of these diseases. However, because the same cytokines are also necessary for the regeneration of the tissue after the liver has been injured, inhibition of these mediators might impair hepatic recovery. The near future will bring the exiting clinical challenge of testing new anticytokine strategies in various liver diseases.

  18. A concept of dynamic permission mechanism on android

    Science.gov (United States)

    Aron, Lukas; Hanacek, Petr

    2016-02-01

    This paper discuss the main security topic in mobile security area and this topic is protect user against the leakage of data. This work primarily contains the proposal of concept of dynamic permission mechanism for Android operating system. This mechanism deals with assignment or enforcement permissions to the application according to files that the application works with. Application has set of permissions that can use, but if the user opens confident files the application permissions should change its permission set and there should not be possible leakage of this secret data. The permissions set should be stricter according to opened confidential file or more open (without restriction) if the file is not secret file. The concept proposes the solution for protecting this data leakage. Idea covers rule that user should be avoided of change this permissions himself, but this behavior should be dynamic, automatic and independent. This proposal is mainly aimed to Android operating system, but the concept can be applied to other mobile platforms with some implementation changes.

  19. Maximum permissible concentrations for water, sediment and soil derived from toxicity data for nine trace metals

    OpenAIRE

    Plassche EJ van de; Polder MD; Canton JH

    1992-01-01

    In this report Maximum Permissible Concentrations (MPC) are derived for 9 trace metals based on ecotoxicological data. The elements are: antimony, barium, beryllium, cobalt, molybdenum, selenium, thallium, tin, and vanadium The study was carried out in the framework of the project "Setting integrated environmental quality objectives". For the aquatic environment MPCs could be derived for all trace elements. These values were based on toxicity data for freshwater as well as saltwater...

  20. Android Security (Decompilation of APK File to Check Permissions

    Directory of Open Access Journals (Sweden)

    Hemant Bansal

    2016-01-01

    Full Text Available The world wide revolution in Android technology is changing our lives in term of the way we learn and use. Android Security fits into this because the technology has been around long enough and can provide various benefits for security in this area. The main objective of this paper is to Decompile the Android App And Check the permissions Used By That App (What The permissions any app is accessing Like reading messages, Using our internet data, reading our call logs. This Research Paper Helps Peoples To aware About the Un necessary Applications and Their Permissions That Are in Our Phone Stealing Our Credit Card details, secret details etc.

  1. Recombinant Cytokines from Plants

    OpenAIRE

    Patrycja Redkiewicz; Anna Góra-Sochacka; Tomas Vaněk; Agnieszka Sirko

    2011-01-01

    Plant-based platforms have been successfully applied for the last two decades for the efficient production of pharmaceutical proteins. The number of commercialized products biomanufactured in plants is, however, rather discouraging. Cytokines are small glycosylated polypeptides used in the treatment of cancer, immune disorders and various other related diseases. Because the clinical use of cytokines is limited by high production costs they are good candidates for plant-made pharmaceuticals. S...

  2. Cytokines and Blastocyst Hatching.

    Science.gov (United States)

    Seshagiri, Polani B; Vani, Venkatappa; Madhulika, Pathak

    2016-03-01

    Blastocyst implantation into the uterine endometrium establishes early pregnancy. This event is regulated by blastocyst- and/or endometrium-derived molecular factors which include hormones, growth factors, cell adhesion molecules, cytokines and proteases. Their coordinated expression and function are critical for a viable pregnancy. A rate-limiting event that immediately precedes implantation is the hatching of blastocyst. Ironically, blastocyst hatching is tacitly linked to peri-implantation events, although it is a distinct developmental phenomenon. The exact molecular network regulating hatching is still unclear. A number of implantation-associated molecular factors are expressed in the pre-implanting blastocyst. Among others, cytokines, expressed by peri-implantation blastocysts, are thought to be important for hatching, making blastocysts implantation competent. Pro-inflammatory (IL-6, LIF, GM-CSF) and anti-inflammatory (IL-11, CSF-1) cytokines improve hatching rates; they modulate proteases (MMPs, tPAs, cathepsins and ISP1). However, functional involvement of cytokines and their specific mediation of hatching-associated proteases are unclear. There is a need to understand mechanistic roles of cytokines and proteases in blastocyst hatching. This review will assess the available knowledge on blastocyst-derived pro-inflammatory and anti-inflammatory cytokines and their role in potentially regulating blastocyst hatching. They have implications in our understanding of early embryonic loss and infertility in mammals, including humans.

  3. A Biomedical Research Permissions Ontology: Cognitive and Knowledge Representation Considerations.

    Science.gov (United States)

    Obeid, Jihad; Gabriel, Davera; Sanderson, Iain

    2010-12-01

    In designing a comprehensive mechanism for managing informed consents and permissions for biomedical research involving human participants, a significant effort is dedicated to the development of standardized classification of these consents and permissions. In this paper, we describe the considerations and implications of this effort that should be addressed during the development of a Biomedical Research Permissions Ontology (RPO). It is hoped that this standardization will allow disparate research institutions to pool research data and associated consents and permissions in order to facilitate collaborative translational research projects across multiple institutions and subsequent new breakthroughs in medicine while providing: 1) essential built in protections for privacy and confidentiality of research participants and 2) a mechanism for insuring that researchers adhere to patient's intent whether to participate in research or not.

  4. 50 CFR 216.252 - Permissible methods of taking.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE... Mexico § 216.252 Permissible methods of taking. (a) Under Letters of Authorization issued pursuant...

  5. Pedestrian safety under permissive left-turn signal control

    Directory of Open Access Journals (Sweden)

    Yi Qi

    2017-06-01

    Full Text Available At intersections with permissive only signal control, pedestrians will move at the phase with the parallel through vehicular movement and the permissive left-turn movement. The left-turn vehicles have to yield to both opposing vehicles and pedestrians at the crosswalk. Under such complicated driving conditions, collision risks rise if left-turn vehicles make misjudgments and fail to yield to the pedestrians. In this research, driving-simulation based experiments were conducted for identifying and assessing the impacts of the factors that contribute to the collision between the left-turn vehicles and the pedestrians during the permissive left-turn phase. The results of this study showed that the percentage of left-turn trucks and the pedestrian volume has significant impacts on the pedestrian safety under permissive left-turn signal control.

  6. Permission to Speak: A Novel Formal Foundation for Access Control

    Science.gov (United States)

    2016-06-21

    Permission to Speak: A Novel Formal Foundation for Access Control Oleg Sokolsky Nikhil Dinesh, Insup Lee, Aravind Joshi Report Documentation Page...comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE 04 NOV 2009 2. REPORT TYPE 3...DATES COVERED 00-00-2009 to 00-00-2009 4. TITLE AND SUBTITLE Permission to Speak: A Novel Formal Foundation for Access Control 5a. CONTRACT

  7. [Cytokines and asthma].

    Science.gov (United States)

    Gani, F; Senna, G; Piglia, P; Grosso, B; Mezzelani, P; Pozzi, E

    1998-10-01

    Asthma is a chronic inflammatory lung disease in which eosinophils are one of the most important involved cells. These cells accumulate in the lung because of cytokines, which are able to regulate cellular responses. The role of cytokines is well known in allergic asthma: IL4, IL5, IL3, GMCSF are the principally cytokine involved. IL4 regulate IgE synthesis while IL5, (and IL3) cause the activation and accumulation of eosinophils. In non allergic asthma, whilst only IL5 seemed to be important recent data, shows that also IL4 plays an important role. Therefore nowadays no relevant difference seems to exist between allergic and non allergic asthma; instead the primer is different: the allergen in allergic asthma and often an unknown factor in the non allergic asthma. Recently other cytokines have been proved to play a role in the pathogenesis of asthma. IL8 is chemotactic not only for neutrophils but also for eosinophils and might cause chronic inflammation in severe asthma. IL13 works like IL4, while RANTES seems to be a more important chemotactic agent than IL5. Finally IL10, which immunoregulates T lymphocyte responses, may reduce asthma inflammation. In conclusion cytokine made us to learn more about the pathogenesis of asthma even if we do not yet know when and how asthma inflammation develops.

  8. Cytokiner og osteoporose

    DEFF Research Database (Denmark)

    Jørgensen, N R

    1997-01-01

    /testosterone, parathyroidhormone and 1,25(OH)2D3. Some of the cytokines primarily enhance osteoclastic bone resorption e.g. IL-1 (Interleukin-1), TNF (Tumor Necrosis Factor) and IL-6 (Interleukin-6), while others primarily stimulate bone formation e.g. TGF-beta (Transforming Growth Factor), IGF (Insulin-like Growth Factor......During the last few years, progress has been made towards the understanding of local regulation of bone remodelling especially in relation to osteoporosis. Cytokines have shown to be powerful regulators of bone resorption and formation, though under superior control from oestrogen...

  9. Cytokines in Sjogren's syndrome

    NARCIS (Netherlands)

    N. Roescher; P.P. Tak; G.G. Illei

    2009-01-01

    Cytokines play a central role in the regulation of immunity and are often found to be deregulated in autoimmune diseases. Sjogren's syndrome is a chronic autoimmune disease characterized by inflammation and loss of secretory function of the salivary and lachrymal glands. This review highlights the c

  10. Complement Activation Correlates With Disease Severity and Contributes to Cytokine Responses in Plasmodium falciparum Malaria.

    Science.gov (United States)

    Berg, Aase; Otterdal, Kari; Patel, Sam; Gonca, Miguel; David, Catarina; Dalen, Ingvild; Nymo, Stig; Nilsson, Margareta; Nordling, Sofia; Magnusson, Peetra U; Ueland, Thor; Prato, Mauro; Giribaldi, Giuliana; Mollnes, Tom Eirik; Aukrust, Pål; Langeland, Nina; Nilsson, Per H

    2015-12-01

    The impact of complement activation and its possible relation to cytokine responses during malaria pathology was investigated in plasma samples from patients with confirmed Plasmodium falciparum malaria and in human whole-blood specimens stimulated with malaria-relevant agents ex vivo. Complement was significantly activated in the malaria cohort, compared with healthy controls, and was positively correlated with disease severity and with certain cytokines, in particular interleukin 8 (IL-8)/CXCL8. This was confirmed in ex vivo-stimulated blood specimens, in which complement inhibition significantly reduced IL-8/CXCL8 release. P. falciparum malaria is associated with systemic complement activation and complement-dependent release of inflammatory cytokines, of which IL-8/CXCL8 is particularly prominent. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. Development of Hydrogel with Anti-Inflammatory Properties Permissive for the Growth of Human Adipose Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    R. Sánchez-Sánchez

    2016-01-01

    Full Text Available Skin wound repair requires the development of different kinds of biomaterials that must be capable of restoring the damaged tissue. Type I collagen and chitosan have been widely used to develop scaffolds for skin engineering because of their cell-related signaling properties such as proliferation, migration, and survival. Collagen is the major component of the skin extracellular matrix (ECM, while chitosan mimics the structure of the native polysaccharides and glycosaminoglycans in the ECM. Chitosan and its derivatives are also widely used as drug delivery vehicles since they are biodegradable and noncytotoxic. Regulation of the inflammatory response is crucial for wound healing and tissue regeneration processes; and, consequently, the development of biomaterials such as hydrogels with anti-inflammatory properties is very important and permissive for the growth of cells. In the last years, it has been shown that mesenchymal stem cells have clinical importance in the treatment of different pathologies, for example, skin injuries. In this paper, we describe the anti-inflammatory activity of collagen type 1/chitosan/dexamethasone hydrogel, which is permissive for the culture of human adipose-derived mesenchymal stem cells (hADMSC. Our results show that hADMSC cultured in the hydrogel are viable, proliferate, and secrete the anti-inflammatory cytokine interleukin-10 (IL-10 but not the inflammatory cytokine Tumor Necrosis Factor-alpha (TNF-α.

  12. 33 CFR 401.68 - Explosives Permission Letter.

    Science.gov (United States)

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Explosives Permission Letter. 401.68 Section 401.68 Navigation and Navigable Waters SAINT LAWRENCE SEAWAY DEVELOPMENT CORPORATION, DEPARTMENT OF TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Dangerous Cargo § 401.68...

  13. 46 CFR 176.700 - Permission for repairs and alterations.

    Science.gov (United States)

    2010-10-01

    ... (UNDER 100 GROSS TONS) INSPECTION AND CERTIFICATION Repairs and Alterations § 176.700 Permission for... refastening of deck or hull planking, plating, and structural members; repair of plate or frame cracks; damage repair or replacement, other than replacement in kind, of electrical wiring, fuel lines, tanks,...

  14. Autophagy and cytokines.

    Science.gov (United States)

    Harris, James

    2011-11-01

    Autophagy is a highly conserved homoeostatic mechanism for the lysosomal degradation of cytosolic constituents, including long-lived macromolecules, organelles and intracellular pathogens. Autophagosomes are formed in response to a number of environmental stimuli, including amino acid deprivation, but also by both host- and pathogen-derived molecules, including toll-like receptor ligands and cytokines. In particular, IFN-γ, TNF-α, IL-1, IL-2, IL-6 and TGF-β have been shown to induce autophagy, while IL-4, IL-10 and IL-13 are inhibitory. Moreover, autophagy can itself regulate the production and secretion of cytokines, including IL-1, IL-18, TNF-α, and Type I IFN. This review discusses the potentially pivotal roles of autophagy in the regulation of inflammation and the coordination of innate and adaptive immune responses.

  15. Coordinate cytokine regulatory sequences

    Science.gov (United States)

    Frazer, Kelly A.; Rubin, Edward M.; Loots, Gabriela G.

    2005-05-10

    The present invention provides CNS sequences that regulate the cytokine gene expression, expression cassettes and vectors comprising or lacking the CNS sequences, host cells and non-human transgenic animals comprising the CNS sequences or lacking the CNS sequences. The present invention also provides methods for identifying compounds that modulate the functions of CNS sequences as well as methods for diagnosing defects in the CNS sequences of patients.

  16. Cytokines and anti-cytokines as therapeutics--an update.

    Science.gov (United States)

    Tayal, Vandana; Kalra, Bhupinder Singh

    2008-01-28

    Cytokines which comprise of a family of proteins--interleukins, lymphokines, monokines, interferons, and chemokines, are important components of the immune system. They act in concert with specific cytokine inhibitors and soluble cytokine receptors to regulate the human immune response. Their physiologic role in inflammation and pathologic role in systemic inflammatory states are now well recognized. An imbalance in cytokine production or cytokine receptor expression and/or dysregulation of a cytokine process contributes to various pathological disorders. Research is progressing rapidly in the area of cytokines and their therapeutic targets, the two major therapeutic modalities being the administration of purified recombinant cytokines and the use of their antagonists in various inflammatory disorders. However, given the large number of cytokines, it is disappointing that only relatively few can be used clinically. In the present article, we have made an attempt to review and present a glimpse of the history as well as up to date information that is pertinent to cytokines and anti-cytokine therapies in the treatment of cancer, autoimmune disorders and various other related diseases.

  17. Cytokine Therapies in Neurological Disease.

    Science.gov (United States)

    Azodi, Shila; Jacobson, Steven

    2016-07-01

    Cytokines are a heterogeneous group of glycoproteins that coordinate physiological functions. Cytokine deregulation is observed in many neurological diseases. This article reviews current research focused on human clinical trials of cytokine and anticytokine therapies in the treatment of several neurological disease including stroke, neuromuscular diseases, neuroinfectious diseases, demyelinating diseases, and neurobehavioral diseases. This research suggests that cytokine therapy applications may play an important role in offering new strategies for disease modulation and treatment. Further, this research provides insights into the causal link between cytokine deregulation and neurological diseases.

  18. Detection of autoantibodies to cytokines

    DEFF Research Database (Denmark)

    Bendtzen, K; Hansen, M B; Ross, C;

    2000-01-01

    Autoantibodies to various cytokines have been reported in normal individuals and in patients with various infectious and immunoinflammatory disorders, and similar antibodies (Ab) may be induced in patients receiving human recombinant cytokines. The clinical relevance of these Ab is often difficult...... to evaluate. Not only are in vitro neutralizing cytokine Ab not necessarily neutralizing in vivo, but assays for binding and neutralizing Ab to cytokines are often difficult to interpret. For example, denaturation of immobilized cytokines in immunoblotting techniques and immunometric assays may leave Ab...

  19. Left-turn phase: permissive, protected, or both? A quasi-experimental design in New York City.

    Science.gov (United States)

    Chen, Li; Chen, Cynthia; Ewing, Reid

    2015-03-01

    The practice of left-turn phasing selection (permissive, protected-only, or both) varies from one locality to another. The literature evidence on this issue is equally mixed and insufficient. In this study, we evaluate the safety impacts of changing left-turn signal phasing from permissive to protected/permissive or protected-only at 68 intersections in New York City using a rigorous quasi-experimental design accompanied with regression modeling. Changes in police reported crashes including total crashes, multiple-vehicle crashes, left-turn crashes, pedestrian crashes and bicyclist crashes were compared between before period and after period for the treatment group and comparison group by means of negative binomial regression using a Generalized Estimating Equations (GEE) technique. Confounding factors such as the built environment characteristics that were not controlled in comparison group selection are accounted for by this approach. The results show that the change of permissive left-turn signal phasing to protected/permissive or protected-only signal phasing does not result in a significant reduction in intersection crashes. Though the protected-only signal phasing does reduce the left-turn crashes and pedestrian crashes, this reduction was offset by a possible increase in over-taking crashes. These results suggest that left-turn phasing should not be treated as a universal solution that is always better than the permissive control for left-turn vehicles. The selection and implementation of left-turn signal phasing needs to be done carefully, considering potential trade-offs between safety and delay, and many other factors such as geometry, traffic flows and operations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Permissiveness of soil microbial communities towards broad host range plasmids

    DEFF Research Database (Denmark)

    Klümper, Uli

    at high frequencies from diverse donors, I showed plasmid or donor dependence of plasmid transfer to other species. Additionally, environmental factors like stress also impact the permissiveness of phylogenetic groups towards plasmids. The developed method and results increase our ability to predict......Horizontal transfer of mobile genetic elements facilitates adaptive and evolutionary processes in bacteria. Among the known mobile genetic elements, plasmids can confer their hosts with accessory adaptive traits, such as antibiotic or heavy metal resistances, or additional metabolic pathways...... and the extent of bacterial phyla permissive towards plasmid receipt are largely unknown. Historically, methods exploring the underlying genetic and environmental factors of plasmid transfer have been heavily reliant on cultivation and expression of plasmid encoded phenotypes. This has provided an incomplete...

  1. [Cytokines and hematopoiesis].

    Science.gov (United States)

    Mannoni, P

    1993-03-01

    The identification and purification of haemopoietic growth regulators have resulted in a better understanding of control mechanisms. Cloning and expression of the corresponding genes have shown that most of the activities observed correspond to specific glycoproteins produced by cells from numerous tissues, including those of bone marrow stroma and immune system. These cytokines activate the responsive cells through specific receptors expressed on their membranes. They exert an accurate control of haematopoiesis in a network of synergistic and antagonistic factors. The exact identification of their biological activities, together with the possibility of producing them in large amounts by genetic recombination, have already resulted in their therapeutic use with, in certain cases, a remarkable efficiency.

  2. Permission-Based Separation Logic for Multithreaded Java Programs

    OpenAIRE

    Haack, Christian; Huisman, Marieke; Hurlin, C.

    2011-01-01

    This paper motivates and presents a program logic for reasoning about multithreaded Java-like programs with concurrency primitives such as dynamic thread creation, thread joining and reentrant object monitors. The logic is based on concurrent separation logic. It is the first detailed adaptation of concurrent separation logic to a multithreaded Java-like language. The program logic associates a unique static access permission with each heap location, ensuring exclusive write accesses and ruli...

  3. Permission-Based Separation Logic for Multithreaded Java Programs.

    OpenAIRE

    Amighi, Afshin; Haack, Christian; Huisman, Marieke; Hurlin, Clément

    2011-01-01

    This paper presents a program logic for reasoning about multithreaded Java-like programs with dynamic thread creation, thread joining and reentrant object monitors. The logic is based on concurrent separation logic. It is the first detailed adaptation of concurrent separation logic to a multithreaded Java-like language. The program logic associates a unique static access permission with each heap location, ensuring exclusive write accesses and ruling out data races. Concurrent reads are suppo...

  4. [Cytokines in bone diseases. Cytokine and postmenopausal osteoporosis].

    Science.gov (United States)

    Inada, Masaki; Miyaura, Chisato

    2010-10-01

    Bone resorption is regulated by various cytokines. In postmenopausal osteoporosis, bone loss due to estrogen deficiency is closely related to the production of bone-resorbing cytokine. Especially, the increased production of IL-1, IL-6 and TNF-α could induce the expression of RANKL in bone tissues to enhance osteoclastogenesis. Relationship between estrogen deficiency and various cytokines is important to clarify the pathogenesis of postmenopausal osteoporosis.

  5. Cytokine-producing T cell subsets in human leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, Kåre

    2000-01-01

    Leishmania specific Th1/Th2 cells have been identified in humans as well as in mice. There is a correlation between the clinical outcome of the infection and the cytokine response profile. Generally, the production of Th2 cytokines leads to severe infection, whereas the production of Th1 cytokine...... cells mutually down-regulate each other. However, the presence of antigen specific regulatory T cell subsets may provide an environment that allows the presence of both Th1 and Th2 cells....

  6. Post-Transcriptional Regulation of Cytokine Signaling by AU-Rich and GU-Rich Elements

    Science.gov (United States)

    Bohjanen, Paul R.

    2014-01-01

    Cytokines are necessary for cell communication to enable responses to external stimuli that are imperative for the survival and maintenance of homeostasis. Dysfunction of the cytokine network has detrimental effects on intra- and extracellular environments. Thus, it is critical that the expression of cytokines and the signals transmitted by cytokines to target cells are tightly regulated at numerous levels, including transcriptional and post-transcriptional levels. Here, we briefly summarize the role of AU-rich elements (AREs) in the regulation of cytokine gene expression at the post-transcriptional level and describe a role for GU-rich elements (GREs) in coordinating the regulation of cytokine signaling. GREs function as post-transcriptional regulators of proteins that control cellular activation, growth, and apoptosis. GREs and AREs work in concert to coordinate cytokine signal transduction pathways. The precise regulation of cytokine signaling is particularly important, because its dysregulation can lead to human diseases. PMID:24697201

  7. Parental feeding practices predict authoritative, authoritarian, and permissive parenting styles.

    Science.gov (United States)

    Hubbs-Tait, Laura; Kennedy, Tay Seacord; Page, Melanie C; Topham, Glade L; Harrist, Amanda W

    2008-07-01

    Our goal was to identify how parental feeding practices from the nutrition literature link to general parenting styles from the child development literature to understand how to target parenting practices to increase effectiveness of interventions. Stand-alone parental feeding practices could be targeted independently. However, parental feeding practices linked to parenting styles require interventions treating underlying family dynamics as a whole. To predict parenting styles from feeding practices and to test three hypotheses: restriction and pressure to eat are positively related whereas responsibility, monitoring, modeling, and encouraging are negatively related to an authoritarian parenting style; responsibility, monitoring, modeling, and encouraging are positively related whereas restriction and pressure to eat are negatively related to an authoritative parenting style; a permissive parenting style is negatively linked with all six feeding practices. Baseline data of a randomized-controlled intervention study. Two hundred thirty-nine parents (93.5% mothers) of first-grade children (134 boys, 105 girls) enrolled in rural public schools. Parental responses to encouraging and modeling questionnaires and the Child Feeding Questionnaire, as well as parenting styles measured by the Parenting Styles and Dimensions Questionnaire. Correlation and regression analyses. Feeding practices explained 21%, 15%, and 8% of the variance in authoritative, authoritarian, and permissive parenting, respectively. Restriction, pressure to eat, and monitoring (negative) significantly predicted an authoritarian style (Hypothesis 1); responsibility, restriction (negative), monitoring, and modeling predicted an authoritative style (Hypothesis 2); and modeling (negative) and restriction significantly predicted a permissive style (Hypothesis 3). Parental feeding practices with young children predict general parenting styles. Interventions that fail to address underlying parenting styles

  8. 7 CFR 51.1178 - Maximum anhydrous citric acid permissible for corresponding total soluble solids.

    Science.gov (United States)

    2010-01-01

    ... 7 Agriculture 2 2010-01-01 2010-01-01 false Maximum anhydrous citric acid permissible for... Sinensis (l) Osbeck) § 51.1178 Maximum anhydrous citric acid permissible for corresponding total soluble solids. For determining the grade of juice, the maximum permissible anhydrous citric acid content...

  9. Permissible limits for uncertainty of measurement in laboratory medicine.

    Science.gov (United States)

    Haeckel, Rainer; Wosniok, Werner; Gurr, Ebrhard; Peil, Burkhard

    2015-07-01

    The international standard ISO 15189 requires that medical laboratories estimate the uncertainty of their quantitative test results obtained from patients' specimens. The standard does not provide details how and within which limits the measurement uncertainty should be determined. The most common concept for establishing permissible uncertainty limits is to relate them on biological variation defining the rate of false positive results or to base the limits on the state-of-the-art. The state-of-the-art is usually derived from data provided by a group of selected medical laboratories. The approach on biological variation should be preferred because of its transparency and scientific base. Hitherto, all recommendations were based on a linear relationship between biological and analytical variation leading to limits which are sometimes too stringent or too permissive for routine testing in laboratory medicine. In contrast, the present proposal is based on a non-linear relationship between biological and analytical variation leading to more realistic limits. The proposed algorithms can be applied to all measurands and consider any quantity to be assured. The suggested approach tries to provide the above mentioned details and is a compromise between the biological variation concept, the GUM uncertainty model and the technical state-of-the-art.

  10. Quantitative Proteomics Analysis of the Hepatitis C Virus Replicon High-Permissive and Low-Permissive Cell Lines.

    Science.gov (United States)

    Ye, Fei; Xin, Zhongshuai; Han, Wei; Fan, Jingjing; Yin, Bin; Wu, Shuzhen; Yang, Wei; Yuan, Jiangang; Qiang, Boqin; Sun, Wei; Peng, Xiaozhong

    2015-01-01

    Chronic hepatitis C virus (HCV) infection is one of the leading causes of severe hepatitis. The molecular mechanisms underlying HCV replication and pathogenesis remain unclear. The development of the subgenome replicon model system significantly enhanced study of HCV. However, the permissiveness of the HCV subgenome replicon greatly differs among different hepatoma cell lines. Proteomic analysis of different permissive cell lines might provide new clues in understanding HCV replication. In this study, to detect potential candidates that might account for the differences in HCV replication. Label-free and iTRAQ labeling were used to analyze the differentially expressed protein profiles between Huh7.5.1 wt and HepG2 cells. A total of 4919 proteins were quantified in which 114 proteins were commonly identified as differentially expressed by both quantitative methods. A total of 37 differential proteins were validated by qRT-PCR. The differential expression of Glutathione S-transferase P (GSTP1), Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1), carboxylesterase 1 (CES1), vimentin, Proteasome activator complex subunit1 (PSME1), and Cathepsin B (CTSB) were verified by western blot. And over-expression of CTSB or knock-down of vimentin induced significant changes to HCV RNA levels. Additionally, we demonstrated that CTSB was able to inhibit HCV replication and viral protein translation. These results highlight the potential role of CTSB and vimentin in virus replication.

  11. Quantitative Proteomics Analysis of the Hepatitis C Virus Replicon High-Permissive and Low-Permissive Cell Lines.

    Directory of Open Access Journals (Sweden)

    Fei Ye

    Full Text Available Chronic hepatitis C virus (HCV infection is one of the leading causes of severe hepatitis. The molecular mechanisms underlying HCV replication and pathogenesis remain unclear. The development of the subgenome replicon model system significantly enhanced study of HCV. However, the permissiveness of the HCV subgenome replicon greatly differs among different hepatoma cell lines. Proteomic analysis of different permissive cell lines might provide new clues in understanding HCV replication. In this study, to detect potential candidates that might account for the differences in HCV replication. Label-free and iTRAQ labeling were used to analyze the differentially expressed protein profiles between Huh7.5.1 wt and HepG2 cells. A total of 4919 proteins were quantified in which 114 proteins were commonly identified as differentially expressed by both quantitative methods. A total of 37 differential proteins were validated by qRT-PCR. The differential expression of Glutathione S-transferase P (GSTP1, Ubiquitin carboxyl-terminal hydrolase isozyme L1 (UCHL1, carboxylesterase 1 (CES1, vimentin, Proteasome activator complex subunit1 (PSME1, and Cathepsin B (CTSB were verified by western blot. And over-expression of CTSB or knock-down of vimentin induced significant changes to HCV RNA levels. Additionally, we demonstrated that CTSB was able to inhibit HCV replication and viral protein translation. These results highlight the potential role of CTSB and vimentin in virus replication.

  12. Cytokine-Induced Modulation of Colorectal Cancer.

    Science.gov (United States)

    Mager, Lukas F; Wasmer, Marie-Hélène; Rau, Tilman T; Krebs, Philippe

    2016-01-01

    The emergence of novel immunomodulatory cancer therapies over the last decade, above all immune checkpoint blockade, has significantly advanced tumor treatment. For colorectal cancer (CRC), a novel scoring system based on the immune cell infiltration in tumors has greatly improved disease prognostic evaluation and guidance to more specific therapy. These findings underline the relevance of tumor immunology in the future handling and therapeutic approach of malignant disease. Inflammation can either promote or suppress CRC pathogenesis and inflammatory mediators, mainly cytokines, critically determine the pro- or anti-tumorigenic signals within the tumor environment. Here, we review the current knowledge on the cytokines known to be critically involved in CRC development and illustrate their mechanisms of action. We also highlight similarities and differences between CRC patients and murine models of CRC and point out cytokines with an ambivalent role for intestinal cancer. We also identify some of the future challenges in the field that should be addressed for the development of more effective immunomodulatory therapies.

  13. Replenishment Decision Making with Permissible Shortage, Repairable Nonconforming Products and Random Equipment Failure

    Directory of Open Access Journals (Sweden)

    Huei-Hsin Chang

    2012-09-01

    Full Text Available This study is concerned with replenishment decision making with repairable nonconforming products, backordering and random equipment failure during production uptime. In real world manufacturing systems, due to different factors generation of nonconforming items and unexpected machine breakdown are inevitable. Also, in certain business environments various situations between vendor and buyer, the backordering of shortage stocks sometimes is permissible with extra cost involved. This study incorporates backlogging, random breakdown and rework into a production system, with the objective of determination of the optimal replenishment lot size and optimal level of backordering that minimizes the long-run average system costs. Mathematical modeling along with the renewal reward theorem is employed for deriving system cost function. Hessian matrix equations are used to prove its convexity. Research result can be directly adopted by practitioners in the production planning and control field to assist them in making their own robust production replenishment decision.

  14. Cytokine-Leukotriene Receptor Interactions

    Directory of Open Access Journals (Sweden)

    Marek Rola-Pleszczynski

    2007-01-01

    Full Text Available Biochemical and pharmacological studies have identified the structure of leukotrienes, the pathways that lead to their synthesis, and the signaling events they trigger when they interact with their cognate receptors. A privileged interaction exists between these lipid mediators and another group of molecules essential for inflammation and immune modulation, namely, cytokines. Whereas leukotrienes can trigger the synthesis and release of selected cytokines in distinct cell populations, many cytokines can affect cellular responsiveness to leukotrienes by modulating leukotriene receptor expression. As we progressively begin to unravel these complex interactions, new areas of cell-cell communication and eventual therapeutic interventions will emerge.

  15. Does an 'activity-permissive' workplace change office workers' sitting and activity time?

    Directory of Open Access Journals (Sweden)

    Erin Gorman

    Full Text Available INTRODUCTION: To describe changes in workplace physical activity, and health-, and work-related outcomes, in workers who transitioned from a conventional to an 'activity-permissive' workplace. METHODS: A natural pre-post experiment conducted in Vancouver, Canada in 2011. A convenience sample of office-based workers (n=24, 75% women, mean [SD] age = 34.5 [8.1] years were examined four months following relocation from a conventional workplace (pre to a newly-constructed, purpose-built, movement-oriented physical environment (post. Workplace activity- (activPAL3-derived stepping, standing, and sitting time, health- (body composition and fasting cardio-metabolic blood profile, and work- (performance; job satisfaction related outcomes were measured pre- and post-move and compared using paired t-tests. RESULTS: Pre-move, on average (mean [SD] the majority of the day was spent sitting (364 [43.0] mins/8-hr workday, followed by standing (78.2 [32.1] mins/8-hr workday and stepping (37.7 [15.6] mins/8-hr workday. The transition to the 'activity-permissive' workplace resulted in a significant increase in standing time (+18.5, 95% CI: 1.8, 35.2 mins/8-hr workday, likely driven by reduced sitting time (-19.7, 95% CI: -42.1, 2.8 mins/8-hr workday rather than increased stepping time (+1.2, 95% CI: -6.2, 8.5 mins/8-hr workday. There were no statistically significant differences observed in health- or work-related outcomes. DISCUSSION: This novel, opportunistic study demonstrated that the broader workplace physical environment can beneficially impact on standing time in office workers. The long-term health and work-related benefits, and the influence of individual, organizational, and social factors on this change, requires further evaluation.

  16. Does an 'activity-permissive' workplace change office workers' sitting and activity time?

    Science.gov (United States)

    Gorman, Erin; Ashe, Maureen C; Dunstan, David W; Hanson, Heather M; Madden, Ken; Winkler, Elisabeth A H; McKay, Heather A; Healy, Genevieve N

    2013-01-01

    To describe changes in workplace physical activity, and health-, and work-related outcomes, in workers who transitioned from a conventional to an 'activity-permissive' workplace. A natural pre-post experiment conducted in Vancouver, Canada in 2011. A convenience sample of office-based workers (n=24, 75% women, mean [SD] age = 34.5 [8.1] years) were examined four months following relocation from a conventional workplace (pre) to a newly-constructed, purpose-built, movement-oriented physical environment (post). Workplace activity- (activPAL3-derived stepping, standing, and sitting time), health- (body composition and fasting cardio-metabolic blood profile), and work- (performance; job satisfaction) related outcomes were measured pre- and post-move and compared using paired t-tests. Pre-move, on average (mean [SD]) the majority of the day was spent sitting (364 [43.0] mins/8-hr workday), followed by standing (78.2 [32.1] mins/8-hr workday) and stepping (37.7 [15.6] mins/8-hr workday). The transition to the 'activity-permissive' workplace resulted in a significant increase in standing time (+18.5, 95% CI: 1.8, 35.2 mins/8-hr workday), likely driven by reduced sitting time (-19.7, 95% CI: -42.1, 2.8 mins/8-hr workday) rather than increased stepping time (+1.2, 95% CI: -6.2, 8.5 mins/8-hr workday). There were no statistically significant differences observed in health- or work-related outcomes. This novel, opportunistic study demonstrated that the broader workplace physical environment can beneficially impact on standing time in office workers. The long-term health and work-related benefits, and the influence of individual, organizational, and social factors on this change, requires further evaluation.

  17. Robot Lies in Health Care: When Is Deception Morally Permissible?

    Science.gov (United States)

    Matthias, Andreas

    2015-06-01

    Autonomous robots are increasingly interacting with users who have limited knowledge of robotics and are likely to have an erroneous mental model of the robot's workings, capabilities, and internal structure. The robot's real capabilities may diverge from this mental model to the extent that one might accuse the robot's manufacturer of deceiving the user, especially in cases where the user naturally tends to ascribe exaggerated capabilities to the machine (e.g. conversational systems in elder-care contexts, or toy robots in child care). This poses the question, whether misleading or even actively deceiving the user of an autonomous artifact about the capabilities of the machine is morally bad and why. By analyzing trust, autonomy, and the erosion of trust in communicative acts as consequences of deceptive robot behavior, we formulate four criteria that must be fulfilled in order for robot deception to be morally permissible, and in some cases even morally indicated.

  18. Permissiveness of soil microbial communities towards broad host range plasmids

    DEFF Research Database (Denmark)

    Klümper, Uli

    larger than previously assumed. I was able to show abundant plasmid transfer from the Gram negative donor strains to a wide diversity of Gram positive soil bacteria, formerly thought to constitute distinct clusters of gene transfer. Moreover, among the observed transconjugants, I identified a core super...... environmental factors that modulate plasmid transfer in soil microbial communities. In order to attain these goals, I developed a high-throughput method that enabled me to evaluate the permissiveness of bacterial communities towards introduced plasmids. This new approach is based on the introduction...... fraction of soil the bacteria (up to 1 in 10,000) were able to take up any of these broad host range conjugal plasmids. The transconjugal pools comprised 11 bacterial phyla. This finding indicates that the realized transfer range of broad host range plasmids in environmental microbial communities is much...

  19. Exploring Permission-Induced Risk in Android Applications for Malicious Application Detection

    KAUST Repository

    Wang, Wei

    2014-10-07

    Android has been a major target of malicious applications (malapps). How to detect and keep the malapps out of the app markets is an ongoing challenge. One of the central design points of Android security mechanism is permission control that restricts the access of apps to core facilities of devices. However, it imparts a significant responsibility to the app developers with regard to accurately specifying the requested permissions and to the users with regard to fully understanding the risk of granting certain combinations of permissions. Android permissions requested by an app depict the app\\'s behavioral patterns. In order to help understanding Android permissions, in this paper, we explore the permission-induced risk in Android apps on three levels in a systematic manner. First, we thoroughly analyze the risk of an individual permission and the risk of a group of collaborative permissions. We employ three feature ranking methods, namely, mutual information, correlation coefficient, and T-test to rank Android individual permissions with respect to their risk. We then use sequential forward selection as well as principal component analysis to identify risky permission subsets. Second, we evaluate the usefulness of risky permissions for malapp detection with support vector machine, decision trees, as well as random forest. Third, we in depth analyze the detection results and discuss the feasibility as well as the limitations of malapp detection based on permission requests. We evaluate our methods on a very large official app set consisting of 310 926 benign apps and 4868 real-world malapps and on a third-party app sets. The empirical results show that our malapp detectors built on risky permissions give satisfied performance (a detection rate as 94.62% with a false positive rate as 0.6%), catch the malapps\\' essential patterns on violating permission access regulations, and are universally applicable to unknown malapps (detection rate as 74.03%).

  20. Plasma cytokines in acute stroke

    DEFF Research Database (Denmark)

    Christensen, Hanne Krarup; Boysen, Gudrun; Christensen, Erik

    2011-01-01

    GOALS: The aim of this study was to test the relations between plasma cytokines and the clinical characteristics, course, and risk factors in acute stroke. PATIENTS AND METHODS: The analysis was based on 179 patients with acute stroke included within 24 hours of stroke onset. On inclusion and 3...... measured by enzyme-linked immunoassay (ELISA). FINDINGS: The levels of most cytokines were significantly different in acute stroke from the levels 3 months later; but only IL-10 was positively associated with stroke severity. C-reactive protein and white blood cell count were positively associated...... with the cytokine response. CONCLUSIONS: We found a substantial overall cytokine reaction that reflected the stroke incident. However, these results do not, at present, suggest a potential for clinical use, as they do not seem to add to the information obtained from the clinical workup of the individual patient....

  1. Vasculogenic Cytokines in Wound Healing

    Directory of Open Access Journals (Sweden)

    Victor W. Wong

    2013-01-01

    Full Text Available Chronic wounds represent a growing healthcare burden that particularly afflicts aged, diabetic, vasculopathic, and obese patients. Studies have shown that nonhealing wounds are characterized by dysregulated cytokine networks that impair blood vessel formation. Two distinct forms of neovascularization have been described: vasculogenesis (driven by bone-marrow-derived circulating endothelial progenitor cells and angiogenesis (local endothelial cell sprouting from existing vasculature. Researchers have traditionally focused on angiogenesis but defects in vasculogenesis are increasingly recognized to impact diseases including wound healing. A more comprehensive understanding of vasculogenic cytokine networks may facilitate the development of novel strategies to treat recalcitrant wounds. Further, the clinical success of endothelial progenitor cell-based therapies will depend not only on the delivery of the cells themselves but also on the appropriate cytokine milieu to promote tissue regeneration. This paper will highlight major cytokines involved in vasculogenesis within the context of cutaneous wound healing.

  2. Th2 cytokines inhibit lymphangiogenesis.

    Directory of Open Access Journals (Sweden)

    Ira L Savetsky

    Full Text Available Lymphangiogenesis is the process by which new lymphatic vessels grow in response to pathologic stimuli such as wound healing, inflammation, and tumor metastasis. It is well-recognized that growth factors and cytokines regulate lymphangiogenesis by promoting or inhibiting lymphatic endothelial cell (LEC proliferation, migration and differentiation. Our group has shown that the expression of T-helper 2 (Th2 cytokines is markedly increased in lymphedema, and that these cytokines inhibit lymphatic function by increasing fibrosis and promoting changes in the extracellular matrix. However, while the evidence supporting a role for T cells and Th2 cytokines as negative regulators of lymphatic function is clear, the direct effects of Th2 cytokines on isolated LECs remains poorly understood. Using in vitro and in vivo studies, we show that physiologic doses of interleukin-4 (IL-4 and interleukin-13 (IL-13 have profound anti-lymphangiogenic effects and potently impair LEC survival, proliferation, migration, and tubule formation. Inhibition of these cytokines with targeted monoclonal antibodies in the cornea suture model specifically increases inflammatory lymphangiogenesis without concomitant changes in angiogenesis. These findings suggest that manipulation of anti-lymphangiogenic pathways may represent a novel and potent means of improving lymphangiogenesis.

  3. Permissivity of the NCI-60 cancer cell lines to oncolytic Vaccinia Virus GLV-1h68

    Directory of Open Access Journals (Sweden)

    Bedognetti Davide

    2011-10-01

    Full Text Available Abstract Background Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. We previously described GLV-1h68, a modified Vaccinia Virus with exclusive tropism for tumor cells, and we observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro and its ability to colonize and eliminate tumor in vivo. Methods In the current study we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines. Selected cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV strain. In order to identify correlates of permissity to viral infection, we measured transcriptional profiles of the cell lines prior infection. Results We observed highly heterogeneous permissivity to VACV infection amongst the cell lines. The heterogeneity of permissivity was independent of tissue with the exception of B cell derivation. Cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV strain and a significant correlation was found suggesting a common permissive phenotype. While no clear transcriptional pattern could be identified as predictor of permissivity to infection, some associations were observed suggesting multifactorial basis permissivity to viral infection. Conclusions Our findings have implications for the design of oncolytic therapies for cancer and offer insights into the nature of permissivity of tumor cells to viral infection.

  4. Circadian Rhythm in Cytokines Administration.

    Science.gov (United States)

    Trufakin, Valery A; Shurlygina, Anna V

    2016-01-01

    In recent times, a number of diseases involving immune system dysfunction have appeared. This increases the importance of research aimed at finding and developing optimized methods for immune system correction. Numerous studies have found a positive effect in using cytokines to treat a variety of diseases, yet the clinical use of cytokines is limited by their toxicity. Research in the field of chronotherapy, aimed at designing schedules of medicine intake using circadian biorhythms of endogenous production of factors, and receptors' expression to the factors on the target cells, as well as chronopharmacodynamics and chronopharmacokinetics of medicines may contribute to the solution of this problem. Advantages of chronotherapy include a greater effectiveness of treatment, reduced dose of required drugs, and minimized adverse effects. This review presents data on the presence of circadian rhythms of spontaneous and induced cytokine production, as well as the expression of cytokine receptors in the healthy body and in a number of diseases. The article reviews various effects of cytokines, used at different times of the day in humans and experimental animals, as well as possible mechanisms underlying the chronodependent effects of cytokines. The article presents the results of chronotherapeutic modes of administering IL-2, interferons, G-CSF, and GM-CSF in treatment of various types of cancer as well as in experimental models of immune suppression and inflammation, which lead to a greater effectiveness of therapy, the possibility of reducing or increasing the dosage, and reduced drug toxicity. Further research in this field will contribute to the effectiveness and safety of cytokine therapy.

  5. Cytokines in Sjogren's syndrome: potential therapeutic targets

    NARCIS (Netherlands)

    Roescher, N.; Tak, P.P.; Illei, G.G.

    2010-01-01

    The dysregulated cytokine network in Sjogren's Syndrome (SS) is reflected by local and systemic overexpression of pro-inflammatory cytokines and absent or low levels of anti-inflammatory cytokines. To date, the use of cytokine based therapies in SS has been disappointing. Oral administration of low

  6. Growth hormone is permissive for neoplastic colon growth.

    Science.gov (United States)

    Chesnokova, Vera; Zonis, Svetlana; Zhou, Cuiqi; Recouvreux, Maria Victoria; Ben-Shlomo, Anat; Araki, Takako; Barrett, Robert; Workman, Michael; Wawrowsky, Kolja; Ljubimov, Vladimir A; Uhart, Magdalena; Melmed, Shlomo

    2016-06-07

    Growth hormone (GH) excess in acromegaly is associated with increased precancerous colon polyps and soft tissue adenomas, whereas short-stature humans harboring an inactivating GH receptor mutation do not develop cancer. We show that locally expressed colon GH is abundant in conditions predisposing to colon cancer and in colon adenocarcinoma-associated stromal fibroblasts. Administration of a GH receptor (GHR) blocker in acromegaly patients induced colon p53 and adenomatous polyposis coli (APC), reversing progrowth GH signals. p53 was also induced in skin fibroblasts derived from short-statured humans with mutant GHR. GH-deficient prophet of pituitary-specific positive transcription factor 1 (Prop1)(-/-) mice exhibited induced colon p53 levels, and cross-breeding them with Apc(min+/-) mice that normally develop intestinal and colon tumors resulted in GH-deficient double mutants with markedly decreased tumor number and size. We also demonstrate that GH suppresses p53 and reduces apoptosis in human colon cell lines as well as in induced human pluripotent stem cell-derived intestinal organoids, and confirm in vivo that GH suppresses colon mucosal p53/p21. GH excess leads to decreased colon cell phosphatase and tensin homolog deleted on chromosome 10 (PTEN), increased cell survival with down-regulated APC, nuclear β-catenin accumulation, and increased epithelial-mesenchymal transition factors and colon cell motility. We propose that GH is a molecular component of the "field change" milieu permissive for neoplastic colon growth.

  7. Dealing with Actors and Compliance in Intervention Operations in a Non-permissive Hybrid Environment

    Science.gov (United States)

    2009-12-01

    Semiperiphery: I. Wallerstein : The Modern World-System II: Mercantilism and the Consolidation of the European World-Economy 1600-1750, New York 1980. C. Ragin...D. Chirot: World System of Immanuel Wallerstein , in: T. Skocpol (ed.): Vision and Method in Historical Sociology, Cambridge 1984, 296-299. 47 1

  8. Measuring Permissiveness in Parity Games: Mean-Payoff Parity Games Revisited

    CERN Document Server

    Bouyer, Patricia; Olschewski, Jörg; Ummels, Michael

    2011-01-01

    We study nondeterministic strategies in parity games with the aim of computing a most permissive winning strategy. Following earlier work, we measure permissiveness in terms of the average number/weight of transitions blocked by the strategy. Using a translation into mean-payoff parity games, we prove that the problem of computing (the permissiveness of) a most permissive winning strategy is in NP intersected coNP. Along the way, we provide a new study of mean-payoff parity games. In particular, we prove that the opponent player has a memoryless optimal strategy and give a new algorithm for solving these games.

  9. Measuring Permissiveness in Parity Games: Mean-Payoff Parity Games Revisited

    OpenAIRE

    Bouyer P.; Markey N.; Olschewski J.; Ummels M.

    2011-01-01

    We study nondeterministic strategies in parity games with the aim of computing a most permissive winning strategy. Following earlier work, we measure permissiveness in terms of the average number/weight of transitions blocked by the strategy. Using a translation into mean-payoff parity games, we prove that the problem of computing (the permissiveness of) a most permissive winning strategy is in NP intersected coNP. Along the way, we provide a new study of mean-payoff parity games. In particul...

  10. Cytokine profile in murine toxoplasmosis

    Institute of Scientific and Technical Information of China (English)

    Funda Dogruman-Al; Isil Fidan; Bekir Celebi; Emine Yesilyurt; Berna Erdal; Cahit Babur; Semra Kustimur

    2011-01-01

    Objective: To investigate which cytokines are produced after acute infection of mice withToxoplasma gondii (T. Gondii) RH strain. Methods: Mus domesticus domesticus mice in infected group were inoculated with with highly virulent T. Gondii RH strain by intraperitoneally. Serum samples were obtained from infected and non-infected mice for cytokine levels for ELISA assay. Results: The concentrations of tumor necrosis factor-α, interferonγ, interleukin (IL)-10 and IL-12 in the cardiac blood sample of the infected mice were significantly higher than those in uninfected controls (P0.05). Conclusions: According to our findings, immune response into T helper type 1 was predominant during acute T. gondii infection. Further characterization and purification of Toxoplasma molecule(s) implicated in the regulation of cytokines could lead to the development of new drug prospects to control Toxoplasma infection.

  11. Leucocytes, cytokines and satellite cells

    DEFF Research Database (Denmark)

    Paulsen, Gøran; Mikkelsen, Ulla Ramer; Raastad, Truls

    2012-01-01

    -damaging exercise', primarily eccentric exercise. We review the evidence for the notion that the degree of muscle damage is related to the magnitude of the cytokine response. In the third and final section, we look at the satellite cell response to a single bout of eccentric exercise, as well as the role...... damage. With the exception of IL-6, the sources of systemic cytokines following exercise remain unclear The satellite cell response to severe muscle damage is related to regeneration, whereas the biological significance of satellite cell proliferation after mild damage or non-damaging exercise remains...

  12. Cytokines, STATs and Liver Disease

    Institute of Scientific and Technical Information of China (English)

    BinGao

    2005-01-01

    The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, activated by more than 50 cytokines or growth factors, plays critical roles in a wide variety of cellular functions in the hematopoietic, immune, neuronal and hepatic systems. In the liver, this signaling pathway, activated by more than 20 cytokines, growth factors, hormones, and hepatitis viral proteins, plays critical roles in antiviral defense, acute phase response, hepatic injury, repair, inflammation, transformation, and hepatitis. This article reviews the biological significance of STAT1, 2, 3, 4, 5, 6 in hepatic functions and diseases. Cellular & Molecular Immunology. 2005;2(2):92-100.

  13. Cytokines, STATs and Liver Disease

    Institute of Scientific and Technical Information of China (English)

    Bin Gao

    2005-01-01

    The Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, activated by more than 50 cytokines or growth factors, plays critical roles in a wide variety of cellular functions in the hematopoietic, immune, neuronal and hepatic systems. In the liver, this signaling pathway, activated by more than 20 cytokines, growth factors, hormones, and hepatitis viral proteins, plays critical roles in antiviral defense, acute phase response, hepatic injury, repair, inflammation, transformation, and hepatitis. This article reviews the biological significance of STAT1, 2, 3, 4, 5, 6 in hepatic functions and diseases. Cellular & Molecular Immunology.2005;2(2):92-100.

  14. Cytokine crowdsourcing: multicellular production of TH17-associated cytokines.

    Science.gov (United States)

    Busman-Sahay, Kathleen O; Walrath, Travis; Huber, Samuel; O'Connor, William

    2015-03-01

    In the 2 decades since its discovery, IL-17A has become appreciated for mounting robust, protective responses against bacterial and fungal pathogens. When improperly regulated, however, IL-17A can play a profoundly pathogenic role in perpetuating inflammation and has been linked to a wide variety of debilitating diseases. IL-17A is often present in a composite milieu that includes cytokines produced by TH17 cells (i.e., IL-17F, IL-21, IL-22, and IL-26) or associated with other T cell lineages (e.g., IFN-γ). These combinatorial effects add mechanistic complexity and more importantly, contribute differentially to disease outcome. Whereas TH17 cells are among the best-understood cell types that secrete IL-17A, they are frequently neither the earliest nor dominant producers. Indeed, non-TH17 cell sources of IL-17A can dramatically alter the course and severity of inflammatory episodes. The dissection of the temporal regulation of TH17-associated cytokines and the resulting net signaling outcomes will be critical toward understanding the increasingly intricate role of IL-17A and TH17-associated cytokines in disease, informing our therapeutic decisions. Herein, we discuss important non-TH17 cell sources of IL-17A and other TH17-associated cytokines relevant to inflammatory events in mucosal tissues.

  15. Cytokines in Human Seminal Plasma and Their Effect on Male Fertility

    Institute of Scientific and Technical Information of China (English)

    Snje(z)ana (Z)idovec; Sanja Vujisi(c)

    2005-01-01

    Cytokines are a heterogeneous group of peptides that play an important role in intercellular communication, regulation of innate and specific immunity, hematopoiesis,interaction between the immune system and neuroendocrine network as well as in reproduction and development. Seminal plasma provides an immunological environment for the semen and contains important biological response mediators. Numerous studies investigated the presence of various cytokines in the seminal plasma and tried to correlate cytokine levels with sperm quality and male fertility. However, the pathophysiological significance of seminal cytokines in sperm function is still not completely understood. The purpose of this review is to provide a brief summary of the extensive literature dealing with cytokines in the seminal plasma and to discuss the contribution of local cytokine immunity to male fertility.

  16. Smoking as a permissive factor of periodontal disease in psoriasis.

    Directory of Open Access Journals (Sweden)

    Márk Antal

    Full Text Available BACKGROUND: Population-based studies have identified smoking as a pathogenetic factor in chronic periodontitis. At the same time, chronic periodontal disease has also been found to occur more often in persons suffering from psoriasis than in controls with no psoriasis. It is known that smoking aggravates both periodontal disease and psoriasis, but so far it has not been investigated how smoking influences the occurrence and severity of periodontal disease in psoriasis. METHODS: A hospital-based study was conducted to investigate this question. The study population consisted of 82 psoriasis patients and 89 controls. All patients received a full-mouth periodontal examination, and a published classification based on bleeding on probing, clinical attachment level and probing depth was utilized for staging. Both patients and controls were divided into smoker and non-smoker groups, and the resulting groups were compared in terms of periodontal status. Beyond the descriptive statistics, odds ratios were computed. RESULTS: Psoriasis in itself increased the likelihood of severe periodontal disease to 4.373 (OR, as compared to non-smoker controls, p<0.05, while smoking increased it to 24.278 (OR, as compared to non-smoker controls, p<0.001 in the studied population. In other words, the risk of severe periodontal disease in psoriasis turned out to be six times higher in smokers than in non-smokers. CONCLUSIONS: The results of this study corroborate those of other studies regarding the link between psoriasis and periodontal disease, but they also seem to reveal a powerful detrimental effect of smoking on the periodontal health of psoriasis patients, whereby the authors propose that smoking may have a permissive effect on the development of severe periodontal disease in psoriasis.

  17. On the Problem of Permissible Covariance and Variogram Models

    Science.gov (United States)

    Christakos, George

    1984-02-01

    The covariance and variogram models (ordinary or generalized) are important statistical tools used in various estimation and simulation techniques which have been recently applied to diverse hydrologic problems. For example, the efficacy of kriging, a method for interpolating, filtering, or averaging spatial phenomena, depends, to a large extent, on the covariance or variogram model chosen. The aim of this article is to provide the users of these techniques with convenient criteria that may help them to judge whether a function which arises in a particular problem, and is not included among the known covariance or variogram models, is permissible as such a model. This is done by investigating the properties of the candidate model in both the space and frequency domains. In the present article this investigation covers stationary random functions as well as intrinsic random functions (i.e., nonstationary functions for which increments of some order are stationary). Then, based on the theoretical results obtained, a procedure is outlined and successfully applied to a number of candidate models. In order to give to this procedure a more practical context, we employ "stereological" equations that essentially transfer the investigations to one-dimensional space, together with approximations in terms of polygonal functions and Fourier-Bessel series expansions. There are many benefits and applications of such a procedure. Polygonal models can be fit arbitrarily closely to the data. Also, the approximation of a particular model in the frequency domain by a Fourier-Bessel series expansion can be very effective. This is shown by theory and by example.

  18. Anesthesiology and the cytokine network

    Directory of Open Access Journals (Sweden)

    Barbara Lisowska

    2013-08-01

    Full Text Available The immune response is a highly specific reaction carried out by means of specialized cells that belong to the immune system. There are two types of immune response mechanisms aimed towards pathogens: non-specific, innate reactions, and specific, acquired reactions. Acquired immunity, characterized by its specificity, is comprised of lymphocytes, including both T cell and B cell populations. The role of B lymphocytes is not limited to the humoral response, though the cellular immune response is carried out mainly by various T lymphocyte subpopulations. The reactions of the humoral and cellular responses complement and stimulate one another mutually – cytokines are their common linking element. The attachment of cytokines to their specific receptors activates a sequence of signals – either intracellular or between the cells of various systems. This organization of respective connections and reactions, including the functional relations between cells of the immune response, in its complexity, is best described as a cytokine network. The response of the immune system to surgical trauma can be looked at from both a local and a general perspective. Not only surgical trauma caused by tissue damage, however, influences the functioning of the immune system, but also the drugs and techniques used during anesthesia. Our article is a presentation of the effects of medications used in anesthesia with respect to their influence on the cytokine network.

  19. Cytokines in human lung fibrosis.

    Science.gov (United States)

    Martinet, Y; Menard, O; Vaillant, P; Vignaud, J M; Martinet, N

    1996-01-01

    Fibrosis is a pathological process characterized by the replacement of normal tissue by mesenchymal cells and the extracellular matrix produced by these cells. The sequence of events leading to fibrosis of an organ involves the subsequent processes of injury with inflammation and disruption of the normal tissue architecture, followed by tissue repair with accumulation of mesenchymal cells in the area of derangement. The same sequence of events occurs in wound healing with normal granulation tissue and scar formation, but, while normal scar formation is very localized and transient, in contrast, in fibrosis, the repair process is exaggerated and usually widespread and can be chronic. Inflammatory cells (mainly mononuclear phagocytes), platelets, endothelial cells, and type II pneumocytes play a direct and indirect role in tissue injury and repair. The evaluation of three human fibrotic lung diseases, two diffuse [idiopathic pulmonary fibrosis (IPF), and the adult respiratory distress syndrome (ARDS)], and one focal (tumor stroma in lung cancer), has shown that several cytokines participate to the local injury and inflammatory reaction [interleukin-1 (IL-1), interleukin-8 (IL-8), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha)], while other cytokines are involved in tissue repair and fibrosis [platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-beta), and basic-fibroblast growth factor (b-FGF)]. A better understanding of the cytokines and cytokine networks involved in lung fibrosis leads to the possibility of new therapeutic approaches.

  20. Malaria: toxins, cytokines and disease

    DEFF Research Database (Denmark)

    Jakobsen, P H; Bate, C A; Taverne, J;

    1995-01-01

    In this review the old concept of severe malaria as a toxic disease is re-examined in the light of recent discoveries in the field of cytokines. Animal studies suggest that the induction of TNF by parasite-derived molecules may be partly responsible for cerebral malaria and anemia, while hypoglyc...

  1. Cytokine responses during chronic denervation

    Directory of Open Access Journals (Sweden)

    Olsson Tomas

    2005-11-01

    Full Text Available Abstract Background The aim of the present study was to examine inflammatory responses during Wallerian degeneration in rat peripheral nerve when the regrowth of axons was prevented by suturing. Methods Transected rat sciatic nerve was sutured and ligated to prevent reinnervation. The samples were collected from the left sciatic nerve distally and proximally from the point of transection. The endoneurium was separated from the surrounding epi- and perineurium to examine the expression of cytokines in both of these compartments. Macrophage invasion into endoneurium was investigated and Schwann cell proliferation was followed as well as the expression of cytokines IL-1β, IL-10, IFN-γ and TNF-α mRNA. The samples were collected from 1 day up to 5 weeks after the primary operation. Results At days 1 to 3 after injury in the epi-/perineurium of the proximal and distal stump, a marked expression of the pro-inflammatory cytokines TNF-α and IL-1β and of the anti-inflammatory cytokine IL-10 was observed. Concurrently, numerous macrophages started to gather into the epineurium of both proximal and distal stumps. At day 7 the number of macrophages decreased in the perineurium and increased markedly in the endoneurium of both stumps. At this time point marked expression of TNF-α and IFN-γ mRNA was observed in the endo- and epi-/perineurium of the proximal stump. At day 14 a marked increase in the expression of IL-1β could be noted in the proximal stump epi-/perineurium and in the distal stump endoneurium. At that time point many macrophages were observed in the longitudinally sectioned epineurium of the proximal 2 area as well as in the cross-section slides from the distal stump. At day 35 TNF-α, IL-1β and IL-10 mRNA appeared abundantly in the proximal epi-/perineurium together with macrophages. Conclusion The present studies show that even during chronic denervation there is a cyclic expression pattern for the studied cytokines. Contrary to the

  2. Formulation and stability of cytokine therapeutics.

    Science.gov (United States)

    Lipiäinen, Tiina; Peltoniemi, Marikki; Sarkhel, Sanjay; Yrjönen, Teijo; Vuorela, Heikki; Urtti, Arto; Juppo, Anne

    2015-02-01

    Cytokines are messenger proteins that regulate the proliferation and differentiation of cells and control immune responses. Interferons, interleukins, and growth factors have applications in cancer, autoimmune, and viral disease treatment. The cytokines are susceptible to chemical and physical instability. This article reviews the structure and stability issues of clinically used cytokines, as well as formulation strategies for improved stability. Some general aspects for identifying most probable stability concerns, selecting excipients, and developing stable cytokine formulations are presented. The vast group of cytokines offers possibilities for new biopharmaceuticals. The formulation approaches of the current cytokine products could facilitate development of new biopharmaceuticals.

  3. 19 CFR 122.66 - Clearance or permission to depart denied.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Clearance or permission to depart denied. 122.66 Section 122.66 Customs Duties U.S. CUSTOMS AND BORDER PROTECTION, DEPARTMENT OF HOMELAND SECURITY... Clearance or permission to depart denied. If advance electronic air cargo information is not received...

  4. Permissive Parenting and Mental Health in College Students: Mediating Effects of Academic Entitlement

    Science.gov (United States)

    Barton, Alison L.; Hirsch, Jameson K.

    2016-01-01

    Objective: Student mental health may suffer due to unreasonable expectations associated with academic entitlement; permissive parenting may be one source of these expectations. The authors examined the role of academic entitlement as a mediator of the relationship between permissive parenting and psychological functioning. Participants:…

  5. 20 CFR 416.1321 - Suspension for not giving us permission to contact financial institutions.

    Science.gov (United States)

    2010-04-01

    ... contact financial institutions. 416.1321 Section 416.1321 Employees' Benefits SOCIAL SECURITY....1321 Suspension for not giving us permission to contact financial institutions. (a) If you don't give us permission to contact any financial institution and request any financial records about you...

  6. 36 CFR 223.12 - Permission to cut, damage, or destroy trees without advertisement.

    Science.gov (United States)

    2010-07-01

    ... destroy trees without advertisement. 223.12 Section 223.12 Parks, Forests, and Public Property FOREST... § 223.12 Permission to cut, damage, or destroy trees without advertisement. Permission may be granted to... lands without advertisement when necessary for the occupancy of a right-of-way or other authorized...

  7. 12 CFR 714.2 - What are the permissible leasing arrangements?

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false What are the permissible leasing arrangements... CREDIT UNIONS LEASING § 714.2 What are the permissible leasing arrangements? (a) You may engage in direct leasing. In direct leasing, you purchase personal property from a vendor, becoming the owner of...

  8. 42 CFR 433.68 - Permissible health care-related taxes.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Permissible health care-related taxes. 433.68 Section 433.68 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Requirements State Financial Participation § 433.68 Permissible health care-related taxes. (a) General rule....

  9. 30 CFR 75.506-1 - Electric face equipment; permissible condition; maintenance requirements.

    Science.gov (United States)

    2010-07-01

    ... Equipment-General § 75.506-1 Electric face equipment; permissible condition; maintenance requirements. (a... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Electric face equipment; permissible condition; maintenance requirements. 75.506-1 Section 75.506-1 Mineral Resources MINE SAFETY AND HEALTH...

  10. 30 CFR 75.505 - Mines classed gassy; use and maintenance of permissible electric face equipment.

    Science.gov (United States)

    2010-07-01

    ... Electrical Equipment-General § 75.505 Mines classed gassy; use and maintenance of permissible electric face... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Mines classed gassy; use and maintenance of permissible electric face equipment. 75.505 Section 75.505 Mineral Resources MINE SAFETY AND...

  11. Optimal Inventory Planning under Permissible Delay in Payments When a Larger Order Quantity

    Science.gov (United States)

    Hsu, Kuang-Hua; Huang, Hung-Fu; Tu, Yu-Cheng; Huang, Yung-Fu

    In the previous related studies, the inventory replenishment problems under permissible delay in payments are independent of the order quantity. In this study, the restrictive assumption of the trade credit independent of the order quantity is relaxed. This study discusses the inventory policies under permissible delay in payments when a larger order quantity.

  12. Effect of short-term heat acclimation with permissive dehydration on thermoregulation and temperate exercise performance.

    Science.gov (United States)

    Neal, R A; Corbett, J; Massey, H C; Tipton, M J

    2016-08-01

    We examined the effect of short-term heat acclimation with permissive dehydration (STHADe) on heat acclimation (HA) and cycling performance in a temperate environment. Ten trained male cyclists [mean (SD) maximal oxygen uptake: 63.3(4.0) mL/kg/min; peak power output (PPO): 385(40) W; training: 10 (3) h/week] underwent a STHADe program consisting of 5 days of exercise (maximum 90 min/day) in a hot environment (40 °C, 50% RH) to elicit isothermic heat strain [rectal temperature 38.64(0.27) °C]. Participants abstained from fluids during, and 30 min after, HA sessions. Pre- and post-STHADe HA was evaluated during euhydrated fixed-intensity exercise (60 min) in hot conditions; the effect of STHADe on thermoregulation was also examined under temperate conditions (20 min fixed-intensity exercise; 22 °C, 60% RH). Temperate cycling performance was assessed by a graded exercise test (GXT) and 20-km time trial (TT). STHADe reduced thermal and cardiovascular strain in hot and temperate environments. Lactate threshold [Δ = 16 (17) W] and GXT PPO [Δ = 6 (7) W] were improved following STHADe (P  0.05), although there was a trend for a higher mean power (P = 0.06). In conclusion, STHADE can reduce thermal and cardiovascular strain under hot and temperate conditions and there is some evidence of ergogenic potential for temperate exercise, but longer HA regimens may be necessary for this to meaningfully influence performance.

  13. Nociceptive neurons detect cytokines in arthritis

    OpenAIRE

    Schaible, Hans-Georg

    2014-01-01

    Proinflammatory cytokines are major mediators in the pathogenesis of diseases of joints such as rheumatoid arthritis and osteoarthritis. This review emphasizes that proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1beta, interleukin-6 and interleukin-17 are also mediators of pain by directly acting on the nociceptive system. Proportions of nociceptive sensory neurons express receptors for these cytokines, and the application of cytokines rapidly changes the excitabil...

  14. Economic order quantity model for deteriorating items with imperfect quality and permissible delay on payment

    Directory of Open Access Journals (Sweden)

    Chandra K. Jaggi

    2011-04-01

    Full Text Available In the classical inventory models, most of the time the issue of quality has not been considered. However, in realistic environment, it can be observed that there may be some defective items in an ordered lot, because of these defective items retailer incurs additional cost due to rejection, repair and refund etc. Thus, inspection/screening of lot becomes indispensible in most of the organizations. Moreover, it plays a very essential role when items are of deteriorating in nature. Further, it is generally assumed that payment will be made to the supplier for the goods immediately after receiving the consignment. Whereas, in practice, supplier does offers a certain fixed period to the retailer for settling the account. During this period, supplier charges no interest, but beyond this period interest is being charged as has been agreed upon. On the other hand, retailer can earn interest on the revenue generated during this period. Keeping this scenario in mind, an attempt has been made to formulate an inventory model for deteriorating items with imperfect quality under permissible delay in payments. Results have been validated with the help of a numerical example using Matlab7.0.1. Comprehensive sensitivity analysis has also been presented.

  15. Permission-based Leadership and Change Management in Hong Kong's Nongovernment Organisations

    Directory of Open Access Journals (Sweden)

    Wong Michael

    2014-12-01

    Full Text Available This study addresses the management of transformational change by chief executives in nongovernment organisations (NGOs in Hong Kong. The study takes an exploratory approach with interviews of 18 chief executives from a cross section of Hong Kong's NGOs. The findings indicate that organisational transformation is driven by increasing competition within the NGO sector and from commercial firms, by a demand for greater transparency and by internal forces. These factors are countered by structural inertia. Leadership of the organisational transformation of an NGO is permission-based; agreement from the various stakeholders must be gained to execute a successful transformation. The chief executive should have a humanistic style and be visionary, ethical and participative. Constant communication and involvement facilitate this process. Through this approach, followers will have a greater commitment to the organisational transformation. Organisational change is a combination of planned and emergent processes. The chief executive should relax control and foster a nurturing environment for transformation. This research suggests a leadership style, behavioural approach and model for managing change that will provide chief executives and senior leaders with useful considerations and insights.

  16. Avian cytokines in health and disease

    Directory of Open Access Journals (Sweden)

    P Wigley

    2003-04-01

    Full Text Available Cytokines are proteins secreted by cells that play an important role in the activation and regulation of other cells and tissues during inflammation and immune responses. Although well described in several mammalian species, the role of cytokines and other related proteins is poorly understood in avian species. Recent advances in avian genetics and immunology have begun to allow the exploration of cytokines in health and disease. Cytokines may be classified in a number of ways, but may be conveniently arranged into four broad groups on the basis of their function. Proinflammatory cytokines such as interleukin-6 and interleukin-1beta play a role in mediating inflammation during disease or injury. Th1 cytokines, including interleukin-12 and interferon-gamma, are involved in the induction of cell-mediated immunity, whereas Th2 cytokines such as interleukin-4 are involved in the induction of humoral immunity. The final group Th3 or Tr cytokines play a role in regulation of immunity. The role of various cytokines in infectious and non-infectious diseases of chickens and turkeys is now being investigated. Although there are only a few reliable ELISAs or bioassays developed for avian cytokines, the use of molecular techniques, and in particular quantitative RT-PCR (Taqman has allowed investigation of cytokine responses in a number of diseases including salmonellosis, coccidiosis and autoimmune thyroiditis. In addition the use of recombinant cytokines as therapeutic agents or as vaccine adjuvants is now being explored.

  17. Can ‘Mobile Platform’ and ‘Permission Marketing’ dance a tango to the consumers' tune? Modeling adoption of ‘SMS based Permission Advertising’

    Directory of Open Access Journals (Sweden)

    Prerna Bamoriya

    2015-12-01

    Full Text Available Many a times situation of advertising clutter is further aggrieved by the markers’ intrusive practices i.e. not asking for consumer’s explicit permission. It results in consumers’ alienation and reduced advertising effectiveness. Solution could be integration of Permission Marketing with an innovative advertising platform like Mobile. This study aimed to develop and validate a comprehensive model for understanding consumers’ adoption behavior towards SMS Based Permission Advertising (SBPA. For this, data was collected using systematic random sampling from 524 respondents and was analyzed using Structural Equation Modeling. Study revealed some critical variables along with complex relationships among such variables, in form of an empirically validated model. At last, study made some important implications for practitioners and researchers.

  18. Cytokines, Neovascularization and Breast Cancer

    Science.gov (United States)

    1996-10-01

    obtained. Eight micron histologic sections were prepared and analyzed by immunohistochemistry using chicken-anti human IL-8 antibody and the Avidin -Biotin... Egg yolks containing antibody were processed as previously described (need ref). Antibody titer and specificity were assessed by double-immunodiffusion...vitro cytokine paper Scott H. Kurtzman, M.D. Hill, NJ) prepared in Hunger’s Titer Max (CYTRX Corp., Norcross, GA). Egg yolks containing antibody were

  19. Cytokines and perinatal brain injury.

    Science.gov (United States)

    Silverstein, F S; Barks, J D; Hagan, P; Liu, X H; Ivacko, J; Szaflarski, J

    1997-01-01

    A rapidly expanding body of data provides support for the hypothesis that pro-inflammatory cytokines including interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) are expressed acutely in injured brain and contribute to progressive neuronal damage. Little is known about the pathogenetic role of these cytokines in perinatal brain injury. Recent experimental studies have incorporated two closely related in vivo perinatal rodent brain injury models to evaluate the role(s) of pro-inflammatory cytokines in the progression of neuronal injury: a perinatal stroke model, elicited by unilateral carotid artery ligation and subsequent timed exposure to 8% oxygen in 7-day-old rats, and a model of excitotoxic injury, elicited by stereotactic intra-cerebral injection of the selective excitatory amino acid agonist NMDA. Each of these lesioning methods results in reproducible, quantifiable focal forebrain injury at this developmental stage. Acute brain injury, evoked by cerebral hypoxia-ischemia or excitotoxin lesioning, results in transient marked increases in expression of IL-1 beta, and TNF-alpha mRNA in brain regions susceptible to irreversible injury, and there is evidence that pharmacological antagonism of IL-1 receptors can attenuate injury in both models. Recent studies also suggest that complementary strategies, based on pharmacological antagonism of platelet activating factor and on neutrophil depletion can also limit the extent of irreversible injury. In summary, current data suggest that pro-inflammatory cytokines contribute to the progression of perinatal brain injury, and that these mediators are important targets for neuroprotective interventions in the acute post-injury period.

  20. A new model for deteriorating items with inflation under permissible delay in payments

    Directory of Open Access Journals (Sweden)

    R.P. Tripathi

    2014-05-01

    Full Text Available Inflation is an important factor influencing traditional economic order quality models. Marketing strategy depends on inflation due to public demand and availability of the materials. This paper presents an optimal inventory policy for deteriorating items using exponential demand rate under permissible delay in payments. Mathematical model has been derived under two cases: case I: cycle time is greater than or equal to permissible delay period, case II: cycle time is less than permissible delay period by considering holding cost as a function of time. Numerical examples and sensitivity analysis are given to reflect the numerical results. Mathematica software is used for finding optimal solutions.

  1. The role of cytokine deficiencies and cytokine autoantibodies in clinical dermatology

    DEFF Research Database (Denmark)

    Liszewski, Walter; Gniadecki, Robert

    2016-01-01

    Cytokines are small, secreted proteins that are essential for promoting and maintaining a normal immune response. Upregulation of cytokines frequently occurs in autoimmune and inflammatory diseases. Conversely, several immunodeficiency, autoimmune and autoinflammatory disorders are known to occur...... review the role of cytokine deficiencies and cytokine autoantibodies in immunodeficiency syndromes, as well as in autoimmune disorders. Finally, we will examine autoinflammatory disorders due to cytokine deficiencies....

  2. 76 FR 78085 - Permissible Investments for Federal and State Savings Associations: Corporate Debt Securities

    Science.gov (United States)

    2011-12-15

    ...), (E), or (F) of the Home Owners Loan Act (``HOLA''). The FDIC currently may require a state savings... (HOLA) (12 U.S.C. 1464 et seq.), as well as activities recognized as permissible for a Federal...

  3. The structure of the amygdala associates with human sexual permissiveness: evidence from voxel-based morphometry.

    Science.gov (United States)

    Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Hashizume, Hiroshi; Sekiguchi, Atsushi; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Sassa, Yuko; Kawashima, Ryuta

    2015-02-01

    Sexual behavior is a critical function of human procreation. Despite previous studies that investigated the neural mechanisms of basic human physiological sexual functions, the neural mechanisms that underlie individual differences in human sexual permissiveness remain unknown. We used voxel-based morphometry and a questionnaire (scale for sexual attitudes) to measure sexual permissiveness to investigate the gray matter and white matter structural correlates of sexual permissiveness. Sexual permissiveness was negatively correlated with regional gray matter density of the structures involving the right amygdala and surrounding areas, and positively correlated with regional white matter density of the white matter area that spread around the left amygdala to the hypothalamus area. There were no gender-specific relationships in the neural correlates of our findings. These findings suggest that structural variations in regions that play key roles in the basic physiological aspects of human sexuality underlie individual complex sexual attitudes in social life. © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

  4. Maximum permissible concentrations and negligible concentrations for antifouling substances. Irgarol 1051, dichlofluanid, ziram, chlorothalonil and TCMTB

    NARCIS (Netherlands)

    Wezel AP van; Vlaardingen P van; CSR

    2001-01-01

    This report presents maximum permissible concentrations and negligible concentrations that have been derived for various antifouling substances used as substitutes for TBT. Included here are Irgarol 1051, dichlofluanide, ziram, chlorothalonil and TCMTB.

  5. 19 CFR 162.62 - Permissible controlled substances on vessels, aircraft, and individuals.

    Science.gov (United States)

    2010-04-01

    ...), and the regulations of the Drug Enforcement Administration (21 CFR 1301.28, 1311.27), controlled... Controlled Substances, Narcotics, and Marihuana § 162.62 Permissible controlled substances on...

  6. Permissible Home Range Estimation (PHRE in Restricted Habitats: A New Algorithm and an Evaluation for Sea Otters.

    Directory of Open Access Journals (Sweden)

    L Max Tarjan

    Full Text Available Parametric and nonparametric kernel methods dominate studies of animal home ranges and space use. Most existing methods are unable to incorporate information about the underlying physical environment, leading to poor performance in excluding areas that are not used. Using radio-telemetry data from sea otters, we developed and evaluated a new algorithm for estimating home ranges (hereafter Permissible Home Range Estimation, or "PHRE" that reflects habitat suitability. We began by transforming sighting locations into relevant landscape features (for sea otters, coastal position and distance from shore. Then, we generated a bivariate kernel probability density function in landscape space and back-transformed this to geographic space in order to define a permissible home range. Compared to two commonly used home range estimation methods, kernel densities and local convex hulls, PHRE better excluded unused areas and required a smaller sample size. Our PHRE method is applicable to species whose ranges are restricted by complex physical boundaries or environmental gradients and will improve understanding of habitat-use requirements and, ultimately, aid in conservation efforts.

  7. Permissible Home Range Estimation (PHRE) in restricted habitats: A new algorithm and an evaluation for sea otters

    Science.gov (United States)

    Tarjan, Lily M; Tinker, M. Tim

    2016-01-01

    Parametric and nonparametric kernel methods dominate studies of animal home ranges and space use. Most existing methods are unable to incorporate information about the underlying physical environment, leading to poor performance in excluding areas that are not used. Using radio-telemetry data from sea otters, we developed and evaluated a new algorithm for estimating home ranges (hereafter Permissible Home Range Estimation, or “PHRE”) that reflects habitat suitability. We began by transforming sighting locations into relevant landscape features (for sea otters, coastal position and distance from shore). Then, we generated a bivariate kernel probability density function in landscape space and back-transformed this to geographic space in order to define a permissible home range. Compared to two commonly used home range estimation methods, kernel densities and local convex hulls, PHRE better excluded unused areas and required a smaller sample size. Our PHRE method is applicable to species whose ranges are restricted by complex physical boundaries or environmental gradients and will improve understanding of habitat-use requirements and, ultimately, aid in conservation efforts.

  8. Drug evaluation and the permissive principle: continuities and contradictions between standards and practices in antidepressant regulation.

    Science.gov (United States)

    Abraham, John; Davis, Courtney

    2009-08-01

    Pharmaceuticals are not permitted on to the market unless they are granted regulatory approval. The regulatory process is, therefore, crucial in whether or not a drug is widely prescribed. Regulatory agencies have developed standards of performance that pharmaceuticals are supposed to meet before entering the market. Regulation of technologies is often discussed by reference to the precautionary principle. In contrast, this paper develops the concept of the 'permissive principle' as a way of understanding the departure of regulators' practices from standards of drug efficacy to which regulatory agencies themselves subscribe. By taking a case study of antidepressant regulation in the UK and the USA, the mechanisms of permissive regulatory practices are examined. An STS methodology of both spatial (international) and temporal comparisons of regulatory practices with regulatory standards is employed to identify the nature and extent of the permissive regulation. It is found that the permissive principle was adopted by drug regulators in the UK and the USA, but more so by the former than the latter. Evidently, permissive regulation, which favours the commercial interests of the drug manufacturer, but is contrary to the interests of patients, may penetrate to the heart of regulatory science. On the other hand, permissive regulation of specific drugs should not be regarded as an inevitable result of marketing strategies and concomitant networks deployed by powerful pharmaceutical companies, because the extent of permissive regulation may vary according to the intra-institutional normative commitments of regulators to uphold their technical standards against the commercial interests of the manufacturer. Likely sociological factors that can account for such permissive regulatory practices are 'corporate bias', secrecy and excessive regulatory trust in the pharmaceutical industry in the UK, political expediency and ideological capture in the USA, combined in both countries

  9. Sodium chloride-enriched Diet Enhanced Inflammatory Cytokine Production and Exacerbated Experimental Colitis in Mice.

    Science.gov (United States)

    Monteleone, Ivan; Marafini, Irene; Dinallo, Vincenzo; Di Fusco, Davide; Troncone, Edoardo; Zorzi, Francesca; Laudisi, Federica; Monteleone, Giovanni

    2017-02-01

    Environmental factors are supposed to play a decisive role in the pathogenesis of inflammatory bowel diseases [IBDs]. Increased dietary salt intake has been linked with the development of autoimmune diseases, but the impact of a salt-enriched diet on the course of IBD remains unknown. In this study, we examined whether high salt intake alters mucosal cytokine production and exacerbates colitis. Normal intestinal lamina propria mononuclear cells [LPMCs] were activated with anti-CD3/CD28 in the presence or absence of increasing concentrations of sodium chloride [NaCl] and/or SB202190, a specific inhibitor of p38/MAP Kinase. For in vivo experiments, a high dose of NaCl was administered to mice 15 days before induction of trinitrobenzene-sulfonic acid [TNBS]-colitis or dextran sulfate sodium [DSS]-colitis. In parallel, mice were given SB202190 before induction of TNBS-colitis. Transcription factors and effector cytokines were evaluated by flow-cytometry and real-time PCR. IL-17A, IL-23R, TNF-α, and Ror-γT were significantly increased in human LPMCs following NaCl exposure, while there was no significant change in IFN-γ, T-bet or Foxp3. Pharmacologic inhibition of p38/MAPK abrogated the NaCl-inducing effect on LPMC-derived cytokines. Mice receiving the high-salt diet developed a more severe colitis than control mice, and this effect was preventable by SB202190. Our data indicated that exposure of intestinal mononuclear cells to a high-NaCl diet enhanced effector cytokine production and contributed to the exacerbation of experimental colitis in mice. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Usability of Security Management:Defining the Permissions of Guests

    Science.gov (United States)

    Johnson, Matthew; Stajano, Frank

    Within the scenario of a Smart Home, we discuss the issues involved in allowing limited interaction with the environment for unidentified principals, or guests. The challenges include identifying and authenticating guests on one hand and delegating authorization to them on the other. While the technical mechanisms for doing so in generic distributed systems have been around for decades, existing solutions are in general not applicable to the smart home because they are too complex to manage. We focus on providing both security and usability; we therefore seek simple and easy to understand approaches that can be used by a normal computer-illiterate home owner, not just by a trained system administrator. This position paper describes ongoing research and does not claim to have all the answers.

  11. Perceived realism moderates the relation between sexualized media consumption and permissive sexual attitudes in Dutch adolescents.

    Science.gov (United States)

    Baams, Laura; Overbeek, Geertjan; Dubas, Judith Semon; Doornwaard, Suzan M; Rommes, Els; van Aken, Marcel A G

    2015-04-01

    This study examined whether the development of sexualized media consumption and permissive sexual attitudes would be more strongly interrelated when adolescents perceived sexualized media images as highly realistic. We used data from a three-wave longitudinal sample of 444 Dutch adolescents aged 13-16 years at baseline. Results from parallel process latent growth modeling multigroup analyses showed that higher initial levels of sexualized media consumption were associated with higher initial level of permissive sexual attitudes. Moreover, increases of sexualized media consumption over time were associated with increases of permissive sexual attitudes over time. Considering the moderation by perceived realism, we found these effects only for those who perceived sexualized media as more realistic. Findings for male and female adolescents were similar except for the relations between initial levels and subsequent development. Among male adolescents who perceived sexualized media images to be realistic, higher initial levels of permissive sexual attitudes were related to subsequent less rapid development of sexualized media consumption. For male adolescents who perceived sexualized media to be less realistic, higher initial levels of sexualized media consumption were related to a subsequent less rapid development of permissive sexual attitudes. These relations were not found for female adolescents. Overall, our results suggest that, in male and female adolescents, those with a high level of perceived realism showed a correlated development of sexualized media consumption and permissive sexual attitudes. These findings point to a need for extended information on how to guide adolescents in interpreting and handling sexualized media in everyday life.

  12. 21 CFR 50.55 - Requirements for permission by parents or guardians and for assent by children.

    Science.gov (United States)

    2010-04-01

    ... Children in Clinical Investigations § 50.55 Requirements for permission by parents or guardians and for... determine that the permission of each child's parents or guardian is granted. (1) Where parental permission... reasonably available, or when only one parent has legal responsibility for the care and custody of the...

  13. 34 CFR 97.408 - Requirements for permission by parents or guardians and for assent by children.

    Science.gov (United States)

    2010-07-01

    ... § 97.408 Requirements for permission by parents or guardians and for assent by children. (a) In... permission of each child's parent(s) or guardian(s). If parental permission is to be obtained, the IRB may... reasonably available, or if only one parent has legal responsibility for the care and custody of the...

  14. Cytokine release assays: current practices and future directions.

    Science.gov (United States)

    Finco, D; Grimaldi, C; Fort, M; Walker, M; Kiessling, A; Wolf, B; Salcedo, T; Faggioni, R; Schneider, A; Ibraghimov, A; Scesney, S; Serna, D; Prell, R; Stebbings, R; Narayanan, P K

    2014-04-01

    As a result of the CD28 superagonist biotherapeutic monoclonal antibody (TGN 1412) "cytokine storm" incident, cytokine release assays (CRA) have become hazard identification and prospective risk assessment tools for screening novel biotherapeutics directed against targets having a potential risk for eliciting adverse pro-inflammatory clinical infusion reactions. Different laboratories may have different strategies, assay formats, and approaches to the reporting, interpretation, and use of data for either decision making or risk assessment. Additionally, many independent contract research organizations (CROs), academic and government laboratories are involved in some aspect of CRA work. As a result, while some pharmaceutical companies are providing CRA data as part of the regulatory submissions when necessary, technical and regulatory practices are still evolving to provide data predictive of cytokine release in humans and that are relevant to safety. This manuscript provides an overview of different approaches employed by the pharmaceutical industry and CROs, for the use and application of CRA based upon a survey and post survey follow up conducted by ILSI-Health and Environmental Sciences Institute (HESI) Immunotoxicology Committee CRA Working Group. Also discussed is ongoing research in the academic sector, the regulatory environment, current limitations of the assays, and future directions and recommendations for cytokine release assays.

  15. Cytokine Network Involvement in Subjects Exposed to Benzene

    Directory of Open Access Journals (Sweden)

    Paola Lucia Minciullo

    2014-01-01

    Full Text Available Benzene represents an ubiquitous pollutant both in the workplace and in the general environment. Health risk and stress posed by benzene have long been a concern because of the carcinogenic effects of the compound which was classified as a Group 1 carcinogen to humans and animals. There is a close correlation between leukemia, especially acute myeloid leukemia, and benzene exposure. In addition, exposure to benzene can cause harmful effects on immunological, neurological, and reproductive systems. Benzene can directly damage hematopoietic progenitor cells, which in turn could lead to apoptosis or may decrease responsiveness to cytokines and cellular adhesion molecules. Alternatively, benzene toxicity to stromal cells or mature blood cells could disrupt the regulation of hematopoiesis, including hematopoietic commitment, maturation, or mobilization, through the network of cytokines, chemokines, and adhesion molecules. Today there is mounting evidence that benzene may alter the gene expression, production, or processing of several cytokines in vitro and in vivo. The purpose of this review was to systematically analyze the published cases of cytokine effects on human benzene exposure, particularly hematotoxicity, and atopy, and on lungs.

  16. Bioanalytical chemistry of cytokines--a review.

    Science.gov (United States)

    Stenken, Julie A; Poschenrieder, Andreas J

    2015-01-01

    Cytokines are bioactive proteins produced by many different cells of the immune system. Due to their role in different inflammatory disease states and maintaining homeostasis, there is enormous clinical interest in the quantitation of cytokines. The typical standard methods for quantitation of cytokines are immunoassay-based techniques including enzyme-linked immusorbent assays (ELISA) and bead-based immunoassays read by either standard or modified flow cytometers. A review of recent developments in analytical methods for measurements of cytokine proteins is provided. This review briefly covers cytokine biology and the analysis challenges associated with measurement of these biomarker proteins for understanding both health and disease. New techniques applied to immunoassay-based assays are presented along with the uses of aptamers, electrochemistry, mass spectrometry, optical resonator-based methods. Methods used for elucidating the release of cytokines from single cells as well as in vivo collection methods are described.

  17. An Inventory Model for Two Warehouses with Constant Deterioration and Quadratic Demand Rate under Inflation and Permissible Delay in Payments

    Directory of Open Access Journals (Sweden)

    U. B. Gothi

    2016-07-01

    Full Text Available In this paper, we have analysed a two-warehouse inventory model for deteriorating items with quadratic demand with time varying holding cost. The effect of permissible delay in payments is also considered, which is usual practice in most of the businesses i.e. purchasers are allowed a period to pay back for the goods brought without paying any interest. To make it more suitable to the present environment the effect of inflation is also considered. Our objective is to minimize the average total cost per time unit under the influence of inflation. Numerical examples are provided to illustrate the model and sensitivity analysis is also carried out for the parameters

  18. CYTOKINE REGULATION OF ULCEROGENESIS IN GASTRODUODENAL MUCOSA

    Directory of Open Access Journals (Sweden)

    L. V. Matveeva

    2013-01-01

    Full Text Available Ulcerogenesis in gastroduodenal mucosa area is a complex multistep process. Its, phases arecontrolled by interaction and activation of pro­ and antiinflammatory cytokine cascade. Present review article summarizes scientific data on impact of cytokines upon ulcerative and reparatory processes, a variety of their diagnostic and therapeutic options is defined. Evaluation of cytokine status, or, in some cases, cytokine genotyping in patients with stomach and duodenal ulcers, may predict clinical course of the disease, as well as efficiency of basic and eradication therapy, correction of the treatment.

  19. Foetal immune programming: hormones, cytokines, microbes and regulatory T cells.

    Science.gov (United States)

    Hsu, Peter; Nanan, Ralph

    2014-10-01

    In addition to genetic factors, environmental cues play important roles in shaping the immune system. The first environment that the developing foetal immune system encounters is the uterus. Although physically the mother and the foetus are separated by the placental membranes, various factors such as hormones and cytokines may provide "environmental cues" to the foetal immune system. Additionally, increasing evidence suggests that prenatal maternal environmental factors, particularly microbial exposure, might significantly influence the foetal immune system, affecting long-term outcomes, a concept termed foetal immune programming. Here we discuss the potential mediators of foetal immune programming, focusing on the role of pregnancy-related hormones, cytokines and regulatory T cells, which play a critical role in immune tolerance.

  20. Cytokine profile of cervical cancer cells

    NARCIS (Netherlands)

    Hazelbag, S; Fleuren, GJ; Baelde, JJ; Schuuring, E; Kenter, GG; Gorter, A

    2001-01-01

    Objective. In patients with cervical carcinoma, the presence of cytokines produced by T(H)2 cells, and the presence of an eosinophilic inflammatory infiltrate, has been associated with a less effective immune response and tumor progression. In the present study, we have investigated the cytokine pro

  1. Cytokines and organ failure in acute pancreatitis

    DEFF Research Database (Denmark)

    Malmstrøm, Marie Louise; Hansen, Mark Berner; Andersen, Anders Møller

    2012-01-01

    We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP).......We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP)....

  2. Cytokines and mood in healthy young adults

    NARCIS (Netherlands)

    Jansen, J.; Fernstrand, A.M.; Van De Loo, A.J.A.E.; Garssen, J.; Verster, J.C.

    2015-01-01

    Purpose: A link between chronic inflammation and neuropsychiatric disorders has been demonstrated previously. For example, pro- and anti-inflammatory cytokines have shown to impact neurocircuits relevant to mood regulation. Elevated levels of inflammatory cytokines have been associated with the deve

  3. Cytokines and mood in healthy young adults

    NARCIS (Netherlands)

    Jansen, J.; Fernstrand, A.M.; Van De Loo, A.J.A.E.|info:eu-repo/dai/nl/369403649; Garssen, J.|info:eu-repo/dai/nl/086369962; Verster, J.C.|info:eu-repo/dai/nl/241442702

    2015-01-01

    Purpose: A link between chronic inflammation and neuropsychiatric disorders has been demonstrated previously. For example, pro- and anti-inflammatory cytokines have shown to impact neurocircuits relevant to mood regulation. Elevated levels of inflammatory cytokines have been associated with the deve

  4. Compartmentalized Cytokine Responses in Hidradenitis Suppurativa.

    Directory of Open Access Journals (Sweden)

    Theodora Kanni

    Full Text Available Favorable treatment outcomes with TNF blockade led us to explore cytokine responses in hidradenitis suppurativa (HS.Blood monocytes of 120 patients and 24 healthy volunteers were subtyped by flow cytometry. Isolated blood mononuclear cells (PBMCs were stimulated for cytokine production; this was repeated in 13 severe patients during treatment with etanercept. Cytokines in pus were measured.CD14brightCD16dim inflammatory monocytes and patrolling monocytes were increased in Hurley III patients. Cytokine production by stimulated PBMCs was low compared to controls but the cytokine gene copies did not differ, indicating post-translational inhibition. The low production of IL-17 was restored, when cells were incubated with adalimumab. In pus, high concentrations of pro-inflammatory cytokines were detected. Based on the patterns, six different cytokine profiles were discerned, which are potentially relevant for the choice of treatment. Clinical improvement with etanercept was predicted by increased production of IL-1β and IL-17 by PBMCs at week 8.Findings indicate compartmentalized cytokine expression in HS; high in pus but suppressed in PBMCs. This is modulated through blockade of TNF.

  5. Cytokines in clinical and experimental transplantation

    NARCIS (Netherlands)

    A.C.Th.M. Vossen (Ann); H.F.J. Savelkoul (Huub)

    1994-01-01

    textabstractAllograft rejection is a complex process, which requires interactions between different cell types and a variety of soluble factors, such as cytokines. In this review we discuss the role of cytokines in the induction and effector phases of the rejection process and in the induction and m

  6. Interactions between Autophagy and Inhibitory Cytokines

    Science.gov (United States)

    Wu, Tian-tian; Li, Wei-Min; Yao, Yong-Ming

    2016-01-01

    Autophagy is a degradative pathway that plays an essential role in maintaining cellular homeostasis. Most early studies of autophagy focused on its involvement in age-associated degeneration and nutrient deprivation. However, the immunological functions of autophagy have become more widely studied in recent years. Autophagy has been shown to be an intrinsic cellular defense mechanism in the innate and adaptive immune responses. Cytokines belong to a broad and loose category of proteins and are crucial for innate and adaptive immunity. Inhibitory cytokines have evolved to permit tolerance to self while also contributing to the eradication of invading pathogens. Interactions between inhibitory cytokines and autophagy have recently been reported, revealing a novel mechanism by which autophagy controls the immune response. In this review, we discuss interactions between autophagy and the regulatory cytokines IL-10, transforming growth factor-β, and IL-27. We also mention possible interactions between two newly discovered cytokines, IL-35 and IL-37, and autophagy. PMID:27313501

  7. Interactions between Autophagy and Inhibitory Cytokines.

    Science.gov (United States)

    Wu, Tian-Tian; Li, Wei-Min; Yao, Yong-Ming

    2016-01-01

    Autophagy is a degradative pathway that plays an essential role in maintaining cellular homeostasis. Most early studies of autophagy focused on its involvement in age-associated degeneration and nutrient deprivation. However, the immunological functions of autophagy have become more widely studied in recent years. Autophagy has been shown to be an intrinsic cellular defense mechanism in the innate and adaptive immune responses. Cytokines belong to a broad and loose category of proteins and are crucial for innate and adaptive immunity. Inhibitory cytokines have evolved to permit tolerance to self while also contributing to the eradication of invading pathogens. Interactions between inhibitory cytokines and autophagy have recently been reported, revealing a novel mechanism by which autophagy controls the immune response. In this review, we discuss interactions between autophagy and the regulatory cytokines IL-10, transforming growth factor-β, and IL-27. We also mention possible interactions between two newly discovered cytokines, IL-35 and IL-37, and autophagy.

  8. Cytokines in juvenile rheumatoid arthritis (JRA).

    Science.gov (United States)

    Mangge, H; Schauenstein, K

    1998-06-01

    Juvenile rheumatoid arthritis (JRA), unlike rheumatoid arthritis of adulthood (RA), is a heterogenous disease comprising at least five subtypes that differ in clinical course and prognosis, and require different therapeutical approaches. As compared to RA, the production of local and systemic cytokines in JRA have not yet been as extensively investigated. In this article we review the available literature on cytokine expression in serum and synovial fluid in all five different subtypes of JRA. Even though the data are still fragmentary, the evidence so far suggests that the determination of serum cytokines yields relevant information as to clinical subtype and inflammatory activity of the disease. Furthermore, the cytokine data suggest that the pathogenesis of JRA may even by more heterogenous than defined by the clinical subtypes. Finally, future directions of research in this area are proposed, and-based on the latest results-arguments for (anti)cytokine therapies in JRA are critically discussed.

  9. Cytokines and Immune Responses in Murine Atherosclerosis.

    Science.gov (United States)

    Kusters, Pascal J H; Lutgens, Esther

    2015-01-01

    Atherosclerosis is an inflammatory disease of the vessel wall characterized by activation of the innate immune system, with macrophages as the main players, as well as the adaptive immune system, characterized by a Th1-dominant immune response. Cytokines play a major role in the initiation and regulation of inflammation. In recent years, many studies have investigated the role of these molecules in experimental models of atherosclerosis. While some cytokines such as TNF or IFNγ clearly had atherogenic effects, others such as IL-10 were found to be atheroprotective. However, studies investigating the different cytokines in experimental atherosclerosis revealed that the cytokine system is complex with both disease stage-dependent and site-specific effects. In this review, we strive to provide an overview of the main cytokines involved in atherosclerosis and to shed light on their individual role during atherogenesis.

  10. Cytokine signalling in embryonic stem cells

    DEFF Research Database (Denmark)

    Kristensen, David Møbjerg; Kalisz, Mark; Nielsen, Jens Høiriis

    2006-01-01

    Cytokines play a central role in maintaining self-renewal in mouse embryonic stem (ES) cells through a member of the interleukin-6 type cytokine family termed leukemia inhibitory factor (LIF). LIF activates the JAK-STAT3 pathway through the class I cytokine receptor gp130, which forms a trimeric...... pathways seem to converge on c-myc as a common target to promote self-renewal. Whereas LIF does not seem to stimulate self-renewal in human embryonic stem cells it cannot be excluded that other cytokines are involved. The pleiotropic actions of the increasing number of cytokines and receptors signalling...... via JAKs, STATs and SOCS exhibit considerable redundancy, compensation and plasticity in stem cells in accordance with the view that stem cells are governed by quantitative variations in strength and duration of signalling events known from other cell types rather than qualitatively different stem...

  11. Cytokines and pregnancy in rheumatic disease.

    Science.gov (United States)

    Østensen, Monika; Förger, Frauke; Villiger, Peter M

    2006-06-01

    Cytokines are important mediators involved in the successful outcome of pregnancy. The concept of pregnancy as biased toward a Th2 immune response states that Th1 type cytokines are associated with pregnancy failure and that Th2 cytokines are protective and counteract pregnancy-related disorders. Studies at the level of the maternal-fetal interface, in the maternal circulation and in cells of peripheral blood have shown that the Th2 concept of pregnancy is an oversimplification. Both Th1 and Th2 type cytokines play a role at different stages of pregnancy and are adapted to the localization and function of cells and tissues. The changes of local and systemic cytokine patterns during pregnancy correspond to neuroendocrine changes with hormones as powerful modulators of cytokine expression. Several autoimmune disorders show a modulation of disease activity during and after pregnancy. In rheumatic diseases with a predominance of a Th1 immune response, a shift to a Th2 type immune response during pregnancy has been regarded as beneficial. Studies of pregnant patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have shown a cytokine expression similar to that found in healthy pregnant women. Significant differences were present only for a few cytokines and seemed related to the activity of the underlying disease. Interestingly, a gestational increase of cytokine inhibitors interleukin 1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFR) in the circulation corresponded to low disease activity in RA. The influence of hormones and cytokines on autoimmune disease is an issue for further study.

  12. Novel methods of cytokine detection: Real-time PCR, ELISPOT, and intracellular cytokine staining

    Directory of Open Access Journals (Sweden)

    Eliza Turlej

    2009-05-01

    Full Text Available Cytokines are small hormone-like proteins that play important roles in immune system control. Cytokines regulate the proliferation and differentiation of cells and hematopoiesis and act as mediators in the inflammatory reaction. Changes in cytokine levels are found in many diseases, such as sepsis, bowel inflammatory disease, autoimmune diseases, as well as graft-versus-host disease. Cytokines levels can be detected using in vivo, in vitro, and ex vivo techniques. The level of cytokine produced can be measured by immunoenzymatic test (ELISA in supernatant after cell culture with the addition of stimulant and in plasma by techniques that measure the level of cytokine secretion in cells (e.g. immunohistochemical staining, ELISPOT, and intracellular cytokine staining, and by molecular biological methods (RPA, real-time PCR, in situ hybridization, and Northern blot. Detection of cytokine mRNA in tissues is useful in the direct determination of heterogenic populations of cytokine-producing cells. Nowadays the most frequently used methods for measuring cytokine level are ELISPOT, intracellular cytokine staining with flow cytometry detection, and real-time PCR. These methods have an important clinical role in vaccine efficacy, in viral, bacterial, and verminous diagnostics, and in determining the efficacy of cancer treatment.

  13. Photonic crystal enhanced cytokine immunoassay.

    Science.gov (United States)

    Mathias, Patrick C; Ganesh, Nikhil; Cunningham, Brian T

    2009-01-01

    Photonic crystal surfaces are demonstrated as a means for enhancing the detection sensitivity and resolution for assays that use a fluorescent tag to quantify the concentration of an analyte protein molecule in a liquid test sample. Computer modeling of the spatial distribution of resonantly coupled electromagnetic fields on the photonic crystal surface are used to estimate the magnitude of enhancement factor compared to performing the same fluorescent assay on a plain glass surface, and the photonic crystal structure is fabricated and tested to experimentally verify the performance using a sandwich immunoassay for the protein Tumor Necrosis Factor-alpha (TNF-alpha). The demonstrated photonic crystal fabrication method utilizes a nanoreplica molding technique that allows for large-area inexpensive fabrication of the structure in a format that is compatible with confocal microarray laser scanners. The signal-to-noise ratio for fluorescent spots on the photonic crystal is increased by at least five-fold relative to the glass slide, allowing a TNF-alpha concentration of 1.6 pg/ml to be distinguished from noise on a photonic crystal surface. In addition, the minimum quantitative limit of detection on the photonic crystal surface is one-third the limit on the glass slide - a decrease from 18 pg/ml to 6 pg/ml. The increased performance of the immunoassay allows for more accurate quantitation of physiologically relevant concentrations of TNF-alpha in a protein microarray format that can be expanded to multiple cytokines.

  14. Inflammatory cytokines in newborn infants

    Directory of Open Access Journals (Sweden)

    A. Sarandakou

    1998-01-01

    Full Text Available Serum levels of IL-1β, IL-6 and TNF-α were measured in 48 healthy, termed neonates on the 1st (N1, 5th (N5 and 40th (N40 day after birth, compared with those in maternal serum (MS, umbilical cord (UC and adult controls. Cytokine values in N1 and N5 were significantly elevated, than those in UC and in controls (p<0.0001. IL-1β and IL-6 declined significantly from N1 to N40 (p<0.0001, while TNF-α increased significantly from N1 to N5 and declined thereafter. MS ∞ IL-1β and IL-6, but not MS ∞ TNF-α, were significantly higher than those of controls (p<0.0001. IL-1β values depended on the mode of delivery. In conclusion, the increased concentrations of IL-1 β, IL-6 and TNF-α during the perinatal period might suggest their involvement in an inflammation like process during normal parturition, and reflect also a newborn immune response to the stress of delivery and environmental changes.

  15. Maximum Permissible Concentrations and Negligible Concentrations for Rare Earth Elements (REEs)

    NARCIS (Netherlands)

    Sneller FEC; Kalf DF; Weltje L; Wezel AP van; CSR

    2000-01-01

    In this report maximum permissible concentrations (MPCs) and negligible concentrations (NCs) are derived for Rare Earth Elements (REEs), which are also known as lanthanides. The REEs selected for derivation of environmental risk limits in this report are Yttrium (Y), Lanthanum (La), Cerium (Ce), Pra

  16. 30 CFR 75.1002 - Installation of electric equipment and conductors; permissibility.

    Science.gov (United States)

    2010-07-01

    ... conductors; permissibility. 75.1002 Section 75.1002 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Wires and Trolley Feeder Wires § 75.1002 Installation of electric equipment and conductors... equipment is located within 150 feet of pillar workings or longwall faces. (b) Electric conductors...

  17. 34 CFR 682.202 - Permissible charges by lenders to borrowers.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Permissible charges by lenders to borrowers. 682.202 Section 682.202 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF POSTSECONDARY EDUCATION, DEPARTMENT OF EDUCATION FEDERAL FAMILY EDUCATION LOAN (FFEL) PROGRAM General...

  18. Corruption and the Other(s): Scope of Superordinate Identity Matters for Corruption Permissibility.

    Science.gov (United States)

    Pisor, Anne C; Gurven, Michael

    2015-01-01

    The decision to engage in corruption-public and private corruption, nepotism, and embezzlement-is often attributed to rational actors maximizing benefits to themselves. However, the importance of reciprocal relationships in humans suggests that an actor may weigh the costs of harms of her corrupt behavior to individuals who may generate future benefits for her. We hypothesize that actors who have a larger circle of actual and potential social partners will have more individuals to consider when generating harms and will thus be less likely to find corrupt acts permissible than actors with smaller circles of valued others. Using data from the World Values Survey and European Values Study (WVS), we explore whether participants with a larger geographic identity or a greater number of group memberships (i.e. a larger scope of actual and potential social partners) are less likely to find accepting bribes permissible. We find mixed support for our hypotheses, but consistently find that WVS participants with local, country, continent, or world geographic identities are less likely to find accepting a bribe permissible than those with regional identities-that is, actors whose primary identities that encompass more than their region find corruption less permissible. We discuss the importance of considering an actor's valuation of others when modeling corruption persistence, noting that establishing scopes of positive valuation is a precursor to predicting where actors will target benefits and shunt costs.

  19. AN OPTIMAL REPLENISHMENT POLICY FOR DETERIORATING ITEMS WITH RAMP TYPE DEMAND UNDER PERMISSIBLE DELAY IN PAYMENTS

    Directory of Open Access Journals (Sweden)

    Dr. Sanjay Jain

    2010-10-01

    Full Text Available The aim of this paper is to develop an optimal replenishment policy for inventory models of deteriorating items with ramp type demand under permissible delay in payments. Deterioration of items begins on their arrival in stock.  An example is also presented to illustrate the application of developed model.

  20. 20 CFR 416.207 - You do not give us permission to contact financial institutions.

    Science.gov (United States)

    2010-04-01

    ... financial institutions. 416.207 Section 416.207 Employees' Benefits SOCIAL SECURITY ADMINISTRATION... institutions. (a) To be eligible for SSI payments you must give us permission to contact any financial institution and request any financial records that financial institution may have about you. You must give...

  1. Maximum permissible concentrations for water, sediment and soil derived from toxicity data for nine trace metals

    NARCIS (Netherlands)

    van de Plassche EJ; Polder MD; Canton JH

    1992-01-01

    In this report Maximum Permissible Concentrations (MPC) are derived for 9 trace metals based on ecotoxicological data. The elements are: antimony, barium, beryllium, cobalt, molybdenum, selenium, thallium, tin, and vanadium The study was carried out in the framework of the project "Setting int

  2. 77 FR 17367 - Permissible Sharing of Client Records by Customs Brokers

    Science.gov (United States)

    2012-03-26

    ... SECURITY U.S. Customs and Border Protection 19 CFR Part 111 RIN 1651-AA80 Permissible Sharing of Client Records by Customs Brokers AGENCY: U.S. Customs and Border Protection, Department of Homeland Security... Customs and Border Protection (CBP) regulations that would allow brokers, upon the client's consent in...

  3. 75 FR 66050 - Permissible Sharing of Client Records by Customs Brokers

    Science.gov (United States)

    2010-10-27

    ... SECURITY U.S. Customs and Border Protection 19 CFR Part 111 RIN 1651-AA80 Permissible Sharing of Client Records by Customs Brokers AGENCIES: Customs and Border Protection, Department of Homeland Security. ACTION: Notice of proposed rulemaking. SUMMARY: This document proposes to amend Customs and...

  4. 15 CFR 270.322 - Voluntary permission to enter and inspect property where building components, materials...

    Science.gov (United States)

    2010-01-01

    ... inspect property where building components, materials, artifacts, and records with respect to a building... Voluntary permission to enter and inspect property where building components, materials, artifacts, and... components, materials, artifacts, and records with respect to the building failure are located, and take...

  5. Corruption and the Other(s: Scope of Superordinate Identity Matters for Corruption Permissibility.

    Directory of Open Access Journals (Sweden)

    Anne C Pisor

    Full Text Available The decision to engage in corruption-public and private corruption, nepotism, and embezzlement-is often attributed to rational actors maximizing benefits to themselves. However, the importance of reciprocal relationships in humans suggests that an actor may weigh the costs of harms of her corrupt behavior to individuals who may generate future benefits for her. We hypothesize that actors who have a larger circle of actual and potential social partners will have more individuals to consider when generating harms and will thus be less likely to find corrupt acts permissible than actors with smaller circles of valued others. Using data from the World Values Survey and European Values Study (WVS, we explore whether participants with a larger geographic identity or a greater number of group memberships (i.e. a larger scope of actual and potential social partners are less likely to find accepting bribes permissible. We find mixed support for our hypotheses, but consistently find that WVS participants with local, country, continent, or world geographic identities are less likely to find accepting a bribe permissible than those with regional identities-that is, actors whose primary identities that encompass more than their region find corruption less permissible. We discuss the importance of considering an actor's valuation of others when modeling corruption persistence, noting that establishing scopes of positive valuation is a precursor to predicting where actors will target benefits and shunt costs.

  6. The study on the adaptation for regulation - the permission of a radioisotope

    Energy Technology Data Exchange (ETDEWEB)

    Park, Byoung Il; Choi, Won Seok; Jung, Yong Moon [Gallup Korea, Seoul (Korea, Republic of)

    2003-08-15

    The restriction -the permission of a radioisotope keeps satisfaction with almost parts for example, awareness, observance and so on. Moreover two concepts are considered fully -too strict about certain specific control rules and needed more discriminated application standards to each organization related to KINS, it's preserved and controlled properly even if the penalties are downsized.

  7. 42 CFR 433.67 - Limitations on level of FFP for permissible provider-related donations.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Limitations on level of FFP for permissible... General Administrative Requirements State Financial Participation § 433.67 Limitations on level of FFP for... the amount of bona fide provider-related donations that a State may receive without a reduction in...

  8. Permissiveness toward divorce: The influence of divorce experiences in three social contexts

    NARCIS (Netherlands)

    Sieben, I.J.P.; Verbakel, C.M.C.

    2013-01-01

    In this study, we assess whether divorce experiences in three social contexts shape individual's permissiveness toward divorce. Using European Values Study data from 44 countries, we find that--net of personal divorce experience--parental divorce before the age of 18 (socialization context);

  9. Guidance document on the derivation of maximum permissible risk levels for human intake of soil contaminants

    NARCIS (Netherlands)

    Janssen PJCM; Speijers GJA; CSR

    1997-01-01

    This report contains a basic step-to-step description of the procedure followed in the derivation of the human-toxicological Maximum Permissible Risk (MPR ; in Dutch: Maximum Toelaatbaar Risico, MTR) for soil contaminants. In recent years this method has been applied for a large number of compounds

  10. Permission to contact (PTC)--a strategy to enhance patient engagement in translational research.

    Science.gov (United States)

    Cheah, Stefanie; O'Donoghue, Sheila; Daudt, Helena; Dee, Simon; LeBlanc, Jodi; Braun, Lauren; Barnes, Rebecca; Vercauteren, Suzanne; Boone, Robert H; Watson, Peter H

    2013-08-01

    Improving patient recruitment and consent to participate in clinical studies is an important issue. The process of consent involves three steps: patient referral for contact, the preliminary interview to determine patient interest, and the informed consent discussion. We hypothesized that putting the first step of the consent process into a 'Permission to Contact' (PTC) platform would improve patient engagement, would improve the efficiency of the other steps of the process, and would be acceptable to diverse patient groups. To test this hypothesis, four PTC platforms were established in three types of outpatient health clinics (cancer, cardiac, maternal health) in different British Columbia health centers. Each began as a research project where clinic personnel were engaged, clinic flow processes were mapped, and a design for each PTC was derived by consensus. All patients at these clinics were asked for 'permission to be contacted for future research purposes.' Patient approach and permission response rates were assessed and operational costs were estimated. Overall permission rates were high for all projects, but ranged from 94% of 'cancer' patients to 80% of 'congenital heart' patients who were approached (pPTC platform is a feasible mechanism to engage patients in research programs such as biobanking. It is well supported by clinic staff and receives high engagement and acceptance from patients. Patient-approach rates vary in different clinics, likely due to both clinic and PTC process factors, but this strategy provides an efficient means of engaging patients in research and sets the stage for enhanced enrollment into translational research programs.

  11. Permissiveness toward divorce: The influence of divorce experiences in three social contexts

    NARCIS (Netherlands)

    Sieben, I.J.P.; Verbakel, C.M.C.

    2013-01-01

    In this study, we assess whether divorce experiences in three social contexts shape individual's permissiveness toward divorce. Using European Values Study data from 44 countries, we find that--net of personal divorce experience--parental divorce before the age of 18 (socialization context); parenta

  12. 12 CFR 347.105 - Permissible financial activities outside the United States.

    Science.gov (United States)

    2010-01-01

    ... consulting services, provided that such services when rendered with respect to the domestic market must be... REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING § 347.105 Permissible financial activities... and credit health insurance. (6) Performing services for other direct or indirect operations of...

  13. 17 CFR 240.12f-1 - Applications for permission to reinstate unlisted trading privileges.

    Science.gov (United States)

    2010-04-01

    ... reinstate unlisted trading privileges. 240.12f-1 Section 240.12f-1 Commodity and Securities Exchanges... Rules and Regulations Under the Securities Exchange Act of 1934 Unlisted Trading § 240.12f-1 Applications for permission to reinstate unlisted trading privileges. (a) An application to reinstate...

  14. Hypotensive hemostatis (permissive hypotension) for ruptured abdominal aortic aneurysm: are we really in control?

    NARCIS (Netherlands)

    Vliet, J.A. van der; Aalst, D.L. van; Kool, L.J.; Wever, J.J.; Blankensteijn, J.D.

    2007-01-01

    The purpose of this study was to investigate whether a protocol for permissive hypotension was feasible for patients admitted with a ruptured abdominal aortic aneurysm (RAAA). It was aimed to limit prehospital intravenous fluid administration to 500 mL and to maintain systolic blood pressure at a ra

  15. Cytokine medicines in clinical practice: current issues.

    Science.gov (United States)

    Barnes, Theresa; Moots, Robert J; Goodacre, John

    2005-10-21

    Cytokine medicines have been licensed for the treatment of rheumatoid arthritis since 2000. The rheumatology community has accrued a large amount of experience in the use of these medications. This experience has led to the development of guidelines for their use that include ongoing vigilance for long term adverse events and efficacy using the Biologics Register. Delivery of these expensive therapies has prompted extensive system developments within rheumatology. The cytokine medicines have provided important tools to probe the pathogenesis of rheumatoid and other inflammatory diseases. Further cytokine medicines, in various stages of development, are on the horizon and continue to stimulate excitement within this fast expanding field.

  16. Th17 cytokines induce pro-fibrotic cytokines release from human eosinophils.

    Science.gov (United States)

    Al-Muhsen, Saleh; Letuve, Severine; Vazquez-Tello, Alejandro; Pureza, Mary Angeline; Al-Jahdali, Hamdan; Bahammam, Ahmed S; Hamid, Qutayba; Halwani, Rabih

    2013-03-13

    Subepithelial fibrosis is one of the most critical structural changes affecting bronchial airway function during asthma. Eosinophils have been shown to contribute to the production of pro-fibrotic cytokines, TGF-β and IL-11, however, the mechanism regulating this process is not fully understood. In this report, we investigated whether cytokines associated with inflammation during asthma may induce eosinophils to produce pro-fibrotic cytokines. Eosinophils were isolated from peripheral blood of 10 asthmatics and 10 normal control subjects. Eosinophils were stimulated with Th1, Th2 and Th17 cytokines and the production of TGF-β and IL-11 was determined using real time PCR and ELISA assays. The basal expression levels of eosinophil derived TGF-β and IL-11 cytokines were comparable between asthmatic and healthy individuals. Stimulating eosinophils with Th1 and Th2 cytokines did not induce expression of pro-fibrotic cytokines. However, stimulating eosinophils with Th17 cytokines resulted in the enhancement of TGF-β and IL-11 expression in asthmatic but not healthy individuals. This effect of IL-17 on eosinophils was dependent on p38 MAPK activation as inhibiting the phosphorylation of p38 MAPK, but not other kinases, inhibited IL-17 induced pro-fibrotic cytokine release. Th17 cytokines might contribute to airway fibrosis during asthma by enhancing production of eosinophil derived pro-fibrotic cytokines. Preventing the release of pro-fibrotic cytokines by blocking the effect of Th17 cytokines on eosinophils may prove to be beneficial in controlling fibrosis for disorders with IL-17 driven inflammation such as allergic and autoimmune diseases.

  17. Cytokines and HCV-Related Disorders

    Directory of Open Access Journals (Sweden)

    Poupak Fallahi

    2012-01-01

    However, HCV interferes with cytokines at various levels and escapes immune response by inducing a T-helper (Th2/T cytotoxic 2 cytokine profile. Inability to control infection leads to the recruitment of inflammatory infiltrates into the liver parenchyma by interferon (IFN-gamma-inducible CXC chemokine ligand (CXCL-9, -10, and -11 chemokines, which results in sustained liver damage and eventually in liver cirrhosis. The most important systemic HCV-related extrahepatic diseases—mixed cryoglobulinemia, lymphoproliferative disorders, thyroid autoimmune disorders, and type 2 diabetes—are associated with a complex dysregulation of the cytokine/chemokine network, involving proinflammatory and Th1 chemokines. The therapeutical administration of cytokines such as IFN-alpha may result in viral clearance during persistent infection and reverts this process.

  18. Dynamical Systems, Cytokine Storms, and Blood Filtration

    Science.gov (United States)

    Foster, Glenn; Hubler, Alfred

    2008-03-01

    Various infections and non-infectious diseases can trigger immune cells and the proteins (cytokines) the cells use to communicate with each other to be caught in a positive feedback loop; this ``cytokine storm'' is frequently fatal. By examining the network of cytokine-immune cell interactions we will illustrate why anti-mediator drugs have been generally ineffective in stopping this feedback. A more effective approach may be to try and reduce interactions by dampening many signals at once by filtering the cytokines out of the blood directly (think dialysis). We will argue that feedback on an out of control nonlinear dynamical system is easier to understand than its normal healthy state and apply filtration to a toy model of immune response.

  19. Treatment of Cancer Pain by Targeting Cytokines

    OpenAIRE

    Vendrell, I.; Macedo, D.; I. Alho; Dionísio, M. R.; Costa, L.

    2015-01-01

    Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be relate...

  20. Plasma Cytokines and Chemokines in Zambian Children With Measles: Innate Responses and Association With HIV-1 Coinfection and In-Hospital Mortality.

    Science.gov (United States)

    Lin, Wen-Hsuan W; Nelson, Ashley N; Ryon, Judith J; Moss, William J; Griffin, Diane E

    2017-03-01

    To identify immune factors present during the acute rash phase of measles and associations with outcome and human immunodeficiency virus type 1 (HIV-1) coinfection, we measured the plasma levels of 22 cytokines and chemokines in Zambian children hospitalized with measles (n = 148) and control children (n = 44). Children with measles had higher levels of innate cytokines tumor necrosis factor (TNF) α, interleukin 1β (IL-1β), interleukin 18, and interleukin 6; chemokines CCL2, CCL4, CCL11, CCL22, CXCL8, and CXCL10; and T-cell cytokines interferon γ, and interleukin 2, 10, and 17. Children who died in the hospital had higher levels of TNF-α, IL-1β, interleukin 12p70; CCL2, CCL4, CCL13, CCL17, CXCL8, CXCL10; and interleukin 2 and interferon γ than children who survived, and lower levels of interleukin 4. Children coinfected with HIV-1 had higher levels of TNF-α and IL-1β than HIV-uninfected children with measles, and lower levels of interleukin 4 and 5. Therefore, acute measles was characterized by activation of macrophages and T cells producing type 1, but not type 2, cytokines, which was more pronounced in fatal disease. © 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.

  1. [Proinflammatory cytokines in patients with pyelonephritis].

    Science.gov (United States)

    Gaĭseniuk, F Z; Driianskaia, V E; Drannik, G N; Rudenko, M Iu; Lavrenchuk, O V; Stepanova, N M; Stashevskaia, N V; Busygina, Iu S

    2013-09-01

    The antiinflammatory cytokines participate in antiinfective immunity, that is why it is advisable to study their peculiarities in determination of the role in immunologic pathogenesis of pyelonephritis. Of the work is to study the levels of pro-inflammatory blood cytokines in the patients with pyelonephritis (PN), to determine the peculiarities in acute and chronic its course in children and adults. The immuno-enzymic method ELISA and the corresponding test-systems were used to study the levels of cytokines in blood. There were studied the levels of pro-inflammatory cytokines (TNF, MCP and IL-23) in blood serum of patients with acute (APN) and chronic (CPN) pyelonephritis. The analysis showed the reliable increase in levels of all studied findings in both forms of PN--both in all 173 patients and in every group--children (87) and adults (86). The MCP-1 levels in APN are reliably higher than in CPN, while in TNF-b and IL-23--do not differ. The levels of all three cytokines in blood of adults were higher than in children in APN, but TNF--in CPN as well. The high level of TNF, MCP-1 and IL-23 in blood of adults and children confirm their important role both in APN and CPN, but MCP-1 can be considered as a predictor of acute/exacerbation of chronic pyelonephritis. By the findings of the studied cytokines, more expressed immune response was noted in the adults.

  2. Classroom Resiliency--A Comparison of Navajo Elementary Students' Perceptions of Their Classroom Environment

    Science.gov (United States)

    Piechowski, Alta Begay

    2011-01-01

    The purpose of this study was to determine if there was a gender difference in how students perceived their classroom environment on the Navajo Nation public school. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be…

  3. The Neglected Role of Non-Profit Organizations in the Intellectual-Commons Environment

    Science.gov (United States)

    Lee, Jyh-An

    2009-01-01

    Intellectual commons are intellectual resources, which anyone can use either without permission, or with permission granted in advance. Since intellectual commons are crucially important to creativity, innovation, and human development, the shrinkage of the intellectual-commons environment will be a profound loss for our cultural freedom.…

  4. Classroom Resiliency--A Comparison of Navajo Elementary Students' Perceptions of Their Classroom Environment

    Science.gov (United States)

    Piechowski, Alta Begay

    2011-01-01

    The purpose of this study was to determine if there was a gender difference in how students perceived their classroom environment on the Navajo Nation public school. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be…

  5. 12 CFR 584.2-2 - Permissible bank holding company activities of savings and loan holding companies.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 5 2010-01-01 2010-01-01 false Permissible bank holding company activities of savings and loan holding companies. 584.2-2 Section 584.2-2 Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY SAVINGS AND LOAN HOLDING COMPANIES § 584.2-2 Permissible bank holding...

  6. 45 CFR 46.408 - Requirements for permission by parents or guardians and for assent by children.

    Science.gov (United States)

    2010-10-01

    ... Subpart A, that adequate provisions are made for soliciting the permission of each child's parents or... parent has legal responsibility for the care and custody of the child. (c) In addition to the provisions... 45 Public Welfare 1 2010-10-01 2010-10-01 false Requirements for permission by parents...

  7. 11 CFR 114.15 - Permissible use of corporate and labor organization funds for certain electioneering communications.

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Permissible use of corporate and labor organization funds for certain electioneering communications. 114.15 Section 114.15 Federal Elections FEDERAL ELECTION COMMISSION GENERAL CORPORATE AND LABOR ORGANIZATION ACTIVITY § 114.15 Permissible use of...

  8. The Family Educational Rights and Privacy Act and Permissive Disclosure: What Information Are Post-Secondary Institutions Disclosing and Why?

    Science.gov (United States)

    Greer, Christine Glah

    2012-01-01

    This study focuses on the response of universities to the permissive disclosure clauses of the Family Educational Rights and Privacy Act (FERPA). FERPA has been amended nine times; some of these amendments permit universities to disclose personally identifiable information without the permission of students. The purpose of this study is to…

  9. 75 FR 1384 - Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that...

    Science.gov (United States)

    2010-01-11

    ... Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under... engage de novo, or to acquire or control voting securities or assets of a company, including...

  10. 76 FR 30941 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-05-27

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...), to engage de novo, or to acquire or control voting securities or assets of a company, including...

  11. 75 FR 20849 - Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that...

    Science.gov (United States)

    2010-04-21

    ... Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under... engage de novo, or to acquire or control voting securities or assets of a company, including...

  12. 76 FR 40366 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-07-08

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...) to engage de novo, or to acquire or control voting securities or assets of a company, including...

  13. 75 FR 32780 - Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that...

    Science.gov (United States)

    2010-06-09

    ... Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under... engage de novo, or to acquire or control voting securities or assets of a company, including...

  14. 75 FR 1621 - Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that...

    Science.gov (United States)

    2010-01-12

    ... Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under... engage de novo, or to acquire or control voting securities or assets of a company, including...

  15. 76 FR 22705 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-04-22

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under... engage de novo, or to acquire or control voting securities or assets of a company, including...

  16. 76 FR 35218 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-06-16

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...) to engage de novo, or to acquire or control voting securities or assets of a company, including...

  17. 76 FR 53900 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-08-30

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...) to engage de novo, or to acquire or control voting securities or assets of a company, including...

  18. 75 FR 32182 - Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that...

    Science.gov (United States)

    2010-06-07

    ... Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under... engage de novo, or to acquire or control voting securities or assets of a company, including...

  19. 76 FR 9781 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-02-22

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...) to engage de novo, or to acquire or control voting securities or assets of a company, including...

  20. 76 FR 38178 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-06-29

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...) to engage de novo, or to acquire or control voting securities or assets of a company, including...

  1. 75 FR 69079 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2010-11-10

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...) to engage de novo, or to acquire or control voting securities or assets of a company, including...

  2. 76 FR 46808 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-08-03

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...) to engage de novo, or to acquire or control voting securities or assets of a company, including...

  3. 76 FR 30169 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-05-24

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...) to engage de novo, or to acquire or control voting securities or assets of a company, including...

  4. 75 FR 60749 - Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that...

    Science.gov (United States)

    2010-10-01

    ... Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...) to engage de novo, or to acquire or control voting securities or assets of a company, including...

  5. 75 FR 29760 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2010-05-27

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under... engage de novo, or to acquire or control voting securities or assets of a company, including...

  6. 76 FR 54469 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-09-01

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...) to engage de novo, or to acquire or control voting securities or assets of a company, including...

  7. 76 FR 55388 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-09-07

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under...) to engage de novo, or to acquire or control voting securities or assets of a company, including...

  8. 75 FR 2544 - Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that...

    Science.gov (United States)

    2010-01-15

    ... Notice of Proposals to Engage in Permissible Nonbanking Activities or to Acquire Companies that are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under... engage de novo, or to acquire or control voting securities or assets of a company, including...

  9. 75 FR 24701 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2010-05-05

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under... engage de novo, or to acquire or control voting securities or assets of a company, including...

  10. 30 CFR 77.1909 - Explosives and blasting; use of permissible explosives and shot-firing units.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Explosives and blasting; use of permissible explosives and shot-firing units. 77.1909 Section 77.1909 Mineral Resources MINE SAFETY AND HEALTH... blasting; use of permissible explosives and shot-firing units. Except as provided in § 77.1909-1,...

  11. Inflammatory cytokines suppress arylamine N-acetyltransferase 1 in cholangiocarcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the effect of inflammatory cytokines on arylamine N-acetyltransferase 1 (NAT1), which is a phase-Ⅱ enzyme involved in the biotransformation of aromatic and heterocyclic amines found in food, drugs and the environment.METHODS: Human cholangiocarcinoma KKU-100 cells were treated with a mixture of proinflammatory cytokines (interferon-y, interleukin-1β and tumor necrosis factor-α)for 48 h, and the effect on NAT1 activity was assessed by high performance liquid chromatography, while NAT1 expression was determined by reverse-transcription polymerase chain reaction. The oxidative stress on the cells was examined by the formation of nitric oxide,superoxide anion and glutathione (GSH) levels. The cells were also treated with S-nitroso-glutathione (GSNO), a nitric oxide donor, to see if the responses were similar to those obtained with the inflammatory cytokines.RESULTS: Cytokines suppressed NAT1 activity,reducing the Vmax without affecting the Km. Cytokines also had a significant impact on the induction of nitric oxide production and in reducing the redox ratios of glutathione (GSH) and GSH disulfide. Treatment with GSNO for 2-48 h reduced NAT1 activity without affecting the GSH ratio. Moreover, inflammatory cytokines and GSNO suppressed NAT1 mRNA expression.CONCLUSION: These findings indicate an association between inflammation and suppression of NAT1, which perhaps contributes to chemical-mediated toxicity and carcinogenesis.

  12. Comparative Evaluation of Permissiveness to Dengue Virus Serotype 2 Infection in Primary Rodent Macrophages

    Directory of Open Access Journals (Sweden)

    Jeanette Prada-Arismendy

    2012-01-01

    Full Text Available Infection with dengue virus presents a broad clinical spectrum, which can range from asymptomatic cases to severe cases that are characterised by haemorrhagic syndrome and/or shock. The reason for such variability remains unknown. This work evaluated the in vitro permissiveness of mouse, rat, hamster and guinea pig macrophages to infection by dengue virus 2 (DENV2. The results established that macrophages derived from the BALB/c mouse strain showed higher permissiveness to DENV2 infection than macrophages from other rodent species, although all rodent species studied had the C820T mutation in the oligoadenylate synthetase 1b gene, indicating no relationship to the different in vitro susceptibilities of mouse cells at this locus. Other molecular mechanisms related to flavivirus susceptibility remain to be explored.

  13. Eosinophil secretion of granule-derived cytokines

    Directory of Open Access Journals (Sweden)

    Lisa A Spencer

    2014-10-01

    Full Text Available Eosinophils are tissue-dwelling leukocytes, present in the thymus, and gastrointestinal and genitourinary tracts of healthy individuals at baseline, and recruited, often in large numbers, to allergic inflammatory foci and sites of active tissue repair. The biological significance of eosinophils is vast and varied. In health, eosinophils support uterine and mammary gland development, and maintain bone marrow plasma cells and adipose tissue alternatively activated macrophages, while in response to tissue insult eosinophils function as inflammatory effector cells, and, in the wake of an inflammatory response, promote tissue regeneration and wound healing. One common mechanism driving many of the diverse eosinophil functions is the regulated and differential secretion of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished from most other leukocytes in that many, if not all, of the over three dozen eosinophil-derived cytokines are pre-synthesized and stored within intracellular granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged in cytokine secretion in situ utilize distinct pathways of cytokine release that include: classical exocytosis, whereby granules themselves fuse with the plasma membrane and release their entire contents extracellularly; piecemeal degranulation, whereby granule-derived cytokines are selectively mobilized into vesicles that emerge from granules, traverse the cytoplasm and fuse with the plasma membrane to release discrete packets of cytokines; and eosinophil cytolysis, whereby intact granules are extruded from eosinophils, and deposited within tissues. In this latter scenario, extracellular granules can themselves function as stimulus-responsive secretory-competent organelles within the tissue. Here we review the distinctive processes of differential secretion of eosinophil granule-derived cytokines.

  14. Determination of Permissible Short-Time Emergency Overloading of Turbo-Generators and Synchronous Compensators

    Directory of Open Access Journals (Sweden)

    V. A. Anischenko

    2011-01-01

    Full Text Available The paper shows that failure to take into account variable ratio of short-time emergency overloading of turbo-generators (synchronous compensators that can lead to underestimation of overloading capacity or impermissible insulation over-heating.A method has been developed for determination of permissible duration of short-time emergency over-loading that takes into account changes of over-loading ratio in case of a failure.

  15. High Permissivity of Human HepG2 Hepatoma Cells for Influenza Viruses

    OpenAIRE

    Ollier, Laurence; Caramella, Anne; Giordanengo, Valérie; Lefebvre, Jean-Claude

    2004-01-01

    Human HepG2 hepatoma cells are highly permissive for influenza virus type A and type B, even without the addition of trypsin, and they exhibit a marked cytopathic effect. This property greatly facilitates the primary isolation of influenza viruses. Virus replication was significantly reduced by the plasmin(ogen)-specific inhibitor tranexamic acid, and this suggests a potential role played by the plasminogen/tissue plasminogen activator complex at the surface of HepG2 cells. This might represe...

  16. Th9 cytokines response and its possible implications in the immunopathogenesis of leprosy.

    Science.gov (United States)

    de Sousa, Jorge Rodrigues; Pagliari, Carla; de Almeida, Dandara Simone Maia; Barros, Luiz Fernando Lima; Carneiro, Francisca Regina Oliveira; Dias, Leonidas Braga; de Souza Aarão, Tinara Leila; Quaresma, Juarez Antonio Simões

    2017-06-01

    Leprosy is an infectious-contagious disease whose clinical evolution depends on the interaction of the infectious agent with the immune response of the host, leading to a clinical spectrum that ranges from lepromatous leprosy (susceptibility, LL) to tuberculoid leprosy (resistance, TT). The immune response profile will depend on the pattern of cytokine production and on the activity of macrophages during infection. Classically, the clinical evolution of leprosy has been associated with Th1/Th2 cytokine profiles, but the role of new cytokine profiles such as T helper 9 (Th9) remains to be elucidated. To evaluate the tissue expression profile of these cytokines, a cross-sectional study was conducted using a sample of 30 leprosy skin lesion biopsies obtained from patients with leprosy, 16 TT and 14 lepromatous LL. Immunohistochemical analysis revealed a significant difference in interleukin (IL)-9, IL-4 transforming growth factor (TGF)-β and IL-10 levels between the two groups. IL-9 was more expressed in TT lesions compared with LL lesions. Higher expression of IL-4, IL-10 and TGF-β was observed in LL compared with TT. IL-4, IL-10 and TGF-β tended to be negatively correlated with the expression of IL-9, indicating a possible antagonistic activity in tissue. The results suggest that Th9 lymphocytes may be involved in the response to Mycobacterium leprae, positively or negatively regulating microbicidal activity of the local immune system in the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. A genetic contribution to circulating cytokines and obesity in children

    Science.gov (United States)

    Cytokines are considered to be involved in obesity-related metabolic diseases. Study objectives are to determine the heritability of circulating cytokine levels, to investigate pleiotropy between cytokines and obesity traits, and to present genome scan results for cytokines in 1030 Hispanic children...

  18. Influence of a loop electrosurgical excision procedure (LEEP) on levels of cytokines in cervical secretions.

    Science.gov (United States)

    Saftlas, Audrey F; Spracklen, Cassandra N; Ryckman, Kelli K; Stockdale, Colleen K; Penrose, Kerri; Ault, Kevin; Rubenstein, Linda M; Pinto, Ligia A

    2015-06-01

    Over the past decade, there has been heightened interest in determining if there is an increased risk of adverse reproductive outcomes among women who had a loop electrosurgical excision procedure (LEEP) to remove cervical intraepithelial neoplasia (CIN). The objective of this exploratory study was to determine if the treatment of CIN with a LEEP is associated with changes in cervical soluble immune markers. Cervical cytokine concentrations were measured in women treated with LEEP and a control group of women who had colposcopy only and did not undergo LEEP. Cytokines were examined in cervical secretions collected in Merocel(®) sponges at study entry and at 6-month follow-up. Cytokines were measured using a Luminex 18-plex cytokine bead assay. The mean cytokine levels were not significantly changed from baseline to follow-up in either group, with the exception of TNF-α, which decreased among women who underwent a LEEP. When the mean levels of cytokines of the treated and untreated groups at baseline or follow-up were compared, cytokine levels tended to be lower in the treated group (particularly IFN-γ, IL-6, IL-8, and MCP-1). Findings from adjusted repeated measures analyses revealed no differences between the two groups with regard to changes in cytokine levels over time. Overall, women undergoing a LEEP showed few changes in the cervical microenvironment relative to untreated women. Future studies with additional cervical environment markers and larger sample sizes are needed to determine if a LEEP is associated with dysregulation of the cervical microenvironment.

  19. Role of laminin bioavailability in the astroglial permissivity for neuritic outgrowth

    Directory of Open Access Journals (Sweden)

    TARDY MARCIENNE

    2002-01-01

    Full Text Available The mechanisms involved in the failure of an adult brain to regenerate post-lesion remain poorly understood. The reactive gliosis which occurs after an injury to the CNS and leads to the glial scar has been considered as one of the major impediments to neurite outgrowth and axonal regeneration. A glial scar consists mainly of reactive, hypertrophic astrocytes. These reactive cells acquire new properties, leading to A non-permissive support for neurons. Astrogial reactivity is mainly characteriized by a high overexpression of the major component of the gliofilaments, the glial fibrillary acidic protein (GFAP. This GFAP overexpression is related to the astroglial morphological response to injury. We hypothesized that modulation of GFAP synthesis, reversing the hypertrophic phenotype, might also reverse the blockage of neuritic outgrowth observed after a lesion. In this article, we review findings of our group, confirming our hypothesis in a model of lesioned neuron-astrocyte cocultures. We demonstrate that permissivity for neuritic outgrowth is related to phenotypic changes induced in reactive astrocytes transfected by antisense GFAP-mRNA. We also found that this permissivity was related to a neuron-regulated extracellular laminin bioavailability.

  20. PROBABILISTIC APPROACH FOR THE DETERMINATION OF CUTS PERMISSIBLE BRAKING MODES ON THE GRAVITY HUMPS

    Directory of Open Access Journals (Sweden)

    Volodymyr BOBROVSKYI

    2016-03-01

    Full Text Available The paper presents the research results of cuts braking modes on the gravity humps. The objective of this paper is developing the methods for assessment of braking modes of cuts under conditions of fuzziness of their rolling properties, as well as selecting the permissible starting speed range of cuts from retardant positions. As a criterion for assessing the modes of target control of cut rolling speed, it was proposed to use an average gap size on a classification track at the established norms of probable exceeding of permissible speed of cars collision and their stop in retarders. As a criterion for evaluating the modes of interval control of cuts rolling speed, using the risk of their non-separation on the switches was proposed. Using the simulation modeling and mathematical statistics, the configuration of the range of permissible speed of cuts coming out from retardant positions has been set. The conducted researches allow simplifying the choice of cut braking modes in systems of automatic control of cut rolling speed.

  1. PATHOGENETIC ROLE OF CYTOKINES IN CHILDHOOD ROTAVIRUS INFECTION

    Directory of Open Access Journals (Sweden)

    S. N. Benyova

    2007-01-01

    Full Text Available Abstract. Results of cytokine network studies system in children with rotavirus infection are presented. Concentrations of cytokines were determined at both local and systemic levels. Analysis of cytokine levels was performed at initial terms (day 1 to 3, and in the course of disease (day 7 to 10. It was revealed that mild and mid-severe cases of rotavirus infection in the children are characterized by early increase in proinflammatory cytokines with restricted overshoot of proinflammatory cytokines at early recovery period. Meanwhile, the patients with severe forms of viral gastroenteritis exhibited high levels of proinflammatory cytokines. However, this balance was shifted towards anti-inflammatory cytokines during early reconvalescence.

  2. Th1 cytokine-based immunotherapy for cancer

    Institute of Scientific and Technical Information of China (English)

    Hong-Mei Xu

    2014-01-01

    Cytokine-based immunotherapy is executed by harnessing cytokines to activate the immune system to suppress tumors. Th1-type cytokines including IL-1, IL-2, IL-12 and granulocyte-macrophage colony-stimulating factor are potent stimulators of Th1 differentiation and Th1-based antitumor response. Many preclinical studies demonstrated the antitumor effects of Th1 cytokines but their clinical efficacy is limited. Multiple factors influence the efficacy of immunotherapy for tumors. For instance immunosuppressive cells in the tumor microenvironment can produce inhibitory cytokines which suppress antitumor immune response. Most studies on cytokine immunotherapy focused on how to boost Th1 response; many studies combined cytokine-based therapy with other treatments to reverse immunosuppression in tumor microenvironment. In addition, cytokines have pleiotropic functions and some cytokines show paradoxical activities under different settings. Better understanding the physiological and pathological functions of cytokines helps clinicians to design Th1-based cancer therapy in clinical practice.

  3. Antibody-cytokine fusion proteins for treatment of cancer: engineering cytokines for improved efficacy and safety.

    Science.gov (United States)

    Young, Patricia A; Morrison, Sherie L; Timmerman, John M

    2014-10-01

    The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing interleukin (IL)-2, IL-12, IL-21, tumor necrosis factor (TNF)α, and interferons (IFNs) α, β, and γ have been constructed and have shown anti-tumor activity in preclinical and early-phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results.

  4. Cytokines in Neuropathic Pain and Associated Depression.

    Science.gov (United States)

    Lees, Justin G; Fivelman, Brett; Duffy, Samuel S; Makker, Preet G S; Perera, Chamini J; Moalem-Taylor, Gila

    2015-01-01

    Neuropathic pain occurs as a result of lesion or disease affecting the somatosensory nervous system and is present in a diverse set of peripheral and central pathologies such as nerve trauma, diabetic neuropathy, post-herpetic neuralgia, chemotherapy-induced peripheral neuropathy, spinal cord injury and multiple sclerosis. Debilitating symptoms including allodynia, hyperalgesia and spontaneous pain have a substantial negative impact on patients' quality of life. The currently available therapeutic treatments are generally ineffective and characterised by poor response rates. Accumulating evidence suggests that neuroinflammation and cytokine signalling play a critical role in neuropathic pain. Numerous experimental studies have demonstrated that certain pro-inflammatory cytokines are elevated in neuropathic pain conditions, and administration of these cytokines can elicit pain hypersensitivity in the absence of injury or disease. This phenomenon is also apparent in the 'sickness response', which encompasses a broad inflammatory response to disease and injury and involves a series of physiological and behavioural changes including pain hypersensitivity. Interestingly, the 'sickness response' is also similar in nature to some of the defining characteristics of the depressed state of affective disorder. In this review, we explore links that may relate the co-existence of depression in neuropathic pain patients with the activity of cytokines and discuss the role of several key pro-inflammatory and anti-inflammatory cytokines in neuropathic pain.

  5. Interleukin-1 Family Cytokines in Liver Diseases.

    Science.gov (United States)

    Tsutsui, Hiroko; Cai, Xianbin; Hayashi, Shuhei

    2015-01-01

    The gene encoding IL-1 was sequenced more than 30 years ago, and many related cytokines, such as IL-18, IL-33, IL-36, IL-37, IL-38, IL-1 receptor antagonist (IL-1Ra), and IL-36Ra, have since been identified. IL-1 is a potent proinflammatory cytokine and is involved in various inflammatory diseases. Other IL-1 family ligands are critical for the development of diverse diseases, including inflammatory and allergic diseases. Only IL-1Ra possesses the leader peptide required for secretion from cells, and many ligands require posttranslational processing for activation. Some require inflammasome-mediated processing for activation and release, whereas others serve as alarmins and are released following cell membrane rupture, for example, by pyroptosis or necroptosis. Thus, each ligand has the proper molecular process to exert its own biological functions. In this review, we will give a brief introduction to the IL-1 family cytokines and discuss their pivotal roles in the development of various liver diseases in association with immune responses. For example, an excess of IL-33 causes liver fibrosis in mice via activation and expansion of group 2 innate lymphoid cells to produce type 2 cytokines, resulting in cell conversion into pro-fibrotic M2 macrophages. Finally, we will discuss the importance of IL-1 family cytokine-mediated molecular and cellular networks in the development of acute and chronic liver diseases.

  6. Methodological issues in cytokine measurement in schizophrenia

    Directory of Open Access Journals (Sweden)

    Maju Mathew Koola

    2016-01-01

    Full Text Available There is mounting evidence that inflammation is a major factor in the pathophysiology of schizophrenia. Inflammatory status is commonly ascertained by measuring peripheral cytokine concentrations. An issue concerning research on inflammation and schizophrenia relates to assay methodology. Enzyme-linked immunosorbent assay (ELISA is the most widely used and the gold standard method used to measure cytokine concentrations. ELISA has a number of limitations. Both ELISA and multiplex are limited by not being able to distinguish between bioactive and inactive molecules and the matrix and heterophilic (auto- antibody interference. Multiplex assays when combined with gene expression analysis and flow cytometry techniques such as fluorescence-activated cell sorting may be useful to detect abnormalities in specific immune pathways. Peripheral blood mononuclear cells cultures, to evaluate in vitro lipopolysaccharide-induced cytokine production, may be a better technology than measuring cytokines in the serum. The purpose of this paper is to shed light on major methodological issues that need to be addressed in order to advance the study of cytokines in schizophrenia. We make a few recommendations on how to address these issues.

  7. Cytokines in rheumatoid arthritis and osteoarthrosis

    Directory of Open Access Journals (Sweden)

    Petrović-Rackov Ljiljana

    2005-01-01

    Full Text Available The aim of this research was to determine the clinical significance of tumor necrosis factor-alpha (TNF-alpha, IL-12, IL-15 and IL-18 in evaluation of the activity of rheumatoid arthritis. Cytokine concentrations in serum samples and synovial fluid were measured by immnnoenzymatic methods using kits for human interleukins and the Disease Activity Score 28 in 64 patients with active disease. The control group consisted of 25 subjects with arthritis of the knee and osteoarthrosis. Patients with rheumatoid arthritis have significantly high (p<0.01 concentrations of examined cytokines in relation to patients with osteoarthritis. By comparing concentrations in 30 patients with high, 14 patients with moderate and 20 patients with mild activity of rheumatoid arthritis, it was established that patients with high degree of disease activity have significantly high (p<0.01; p<0.05 concentrations of examined cytokines in the blood and synovial fluid in relation to patients with moderate and mild disease. We have concluded that cytokine concentrations are good indicators of the degree of rheumatoid arthritis activity. This research is a contribution to understanding the insufficiently known pathogenetic mechanisms of cytokines, especially IL-18, in active disease. .

  8. Regulation of human cytokines by Cordyceps militaris

    Directory of Open Access Journals (Sweden)

    Yong Sun

    2014-12-01

    Full Text Available Cordyceps (Cordyceps militaris exhibits many biological activities including antioxidant, inhibition of inflammation, cancer prevention, hypoglycemic, and antiaging properties, etc. However, a majority of studies involving C. militaris have focused only on in vitro and animal models, and there is a lack of direct translation and application of study results to clinical practice (e.g., health benefits. In this study, we investigated the regulatory effects of C. militaris micron powder (3 doses on the human immune system. The study results showed that administration of C. militaris at various dosages reduced the activity of cytokines such as eotaxin, fibroblast growth factor-2, GRO, and monocyte chemoattractant protein-1. In addition, there was a significant decrease in the activity of various cytokines, including GRO, sCD40L, and tumor necrosis factor-α, and a significant downregulation of interleukin-12(p70, interferon-γ inducible protein 10, and macrophage inflammatory protein-1β activities, indicating that C. militaris at all three dosages downregulated the activity of cytokines, especially inflammatory cytokines and chemokines. Different dosages of C. militaris produced different changes in cytokines.

  9. Permissiveness of human hepatocellular carcinoma cell lines for hepatitis C virus entry and replication.

    Science.gov (United States)

    Coto-Llerena, Mairene; Koutsoudakis, George; Boix, Loreto; López-Oliva, Juan Manuel; Caro-Pérez, Noelia; Fernández-Carrillo, Carlos; González, Patricia; Gastaminza, Pablo; Bruix, Jordi; Forns, Xavier; Pérez-Del-Pulgar, Sofía

    2017-07-24

    Hepatitis C virus (HCV) is a globally prevalent pathogen and is associated with high death rates and morbidity. Since its discovery in 1989, HCV research has been impeded by the lack of a robust infectious cell culture system and thus in vitro studies on diverse genetic backgrounds are hampered because of the limited number of hepatoma cell lines which are able to support different aspects of the HCV life cycle. In the current study, we sought to expand the limited number of permissive cells capable of supporting the diverse phases of the HCV life cycle. Initially, we screened a panel of new hepatoma-derived cell lines, designated BCLC-1, -2, -3, -4, -5, -6, -9 and -10 cells, for their ability to express essential HCV receptors and subsequently to support HCV entry by using the well-characterized HCV pseudoparticle system (HCVpp). Apart from BCLC-9, all BCLC cell lines were permissive for HCVpp infection. Next, BCLC cells were subjected to short- and long-term HCV RNA replication studies using HCV subgenomic replicons. Interestingly, only BCLC-1, -5 and -9 cells, supported short-term HCV RNA replication, but the latter were excluded from further studies since they were refractory for HCV entry. BCLC-1, -5 were able to support long-term HCV replication too; yet BCLC-5 cells supported the highest long-term HCV RNA replication levels. Furthermore, cured BCLC-5 clones from HCV subgenomic replicon, showed increased permissiveness for HCV RNA replication. Strikingly, we were unable to detect endogenous BCLC-5 miR122 expression - an important HCV host factor- and as expected, the exogenous expression of miR122 in BCLC-5 cells increased their permissiveness for HCV RNA replication. However, this cell line was unable to produce HCV infectious particles despite ectopic expression of apolipoprotein E, which in other hepatoma cell lines has been shown to be sufficient to enable the HCV secretion process, suggesting a lack of other host cellular factor(s) and/or the presence of

  10. Cytokines and Pancreatic β-Cell Apoptosis

    DEFF Research Database (Denmark)

    Berchtold, L A; Prause, M; Størling, J

    2016-01-01

    The discovery 30 years ago that inflammatory cytokines cause a concentration, activity, and time-dependent bimodal response in pancreatic β-cell function and viability has been a game-changer in the fields of research directed at understanding inflammatory regulation of β-cell function and survival...... and the causes of β-cell failure and destruction in diabetes. Having until then been confined to the use of pathophysiologically irrelevant β-cell toxic chemicals as a model of β-cell death, researchers could now mimic endocrine and paracrine effects of the cytokine response in vitro by titrating concentrations...... to gene expressional changes, endoplasmic reticulum stress, and triggering of mitochondrial dysfunction. Preclinical studies have shown preventive effects of cytokine antagonism in animal models of diabetes, and clinical trials demonstrating proof of concept are emerging. The full clinical potential...

  11. Cytokine production associated with smallpox vaccine responses.

    Science.gov (United States)

    Simon, Whitney L; Salk, Hannah M; Ovsyannikova, Inna G; Kennedy, Richard B; Poland, Gregory A

    2014-01-01

    Smallpox was eradicated 34 years ago due to the success of the smallpox vaccine; yet, the vaccine continues to be studied because of its importance in responding to potential biological warfare and the adverse events associated with current smallpox vaccines. Interindividual variations in vaccine response are observed and are, in part, due to genetic variation. In some cases, these varying responses lead to adverse events, which occur at a relatively high rate for the smallpox vaccine compared with other vaccines. Here, we aim to summarize the cytokine responses associated with smallpox vaccine response to date. Along with a description of each of these cytokines, we describe the genetic and adverse event data associated with cytokine responses to smallpox vaccination.

  12. The role of cytokines in postmenopausal osteoporosis.

    Science.gov (United States)

    Brincat, S D; Borg, M; Camilleri, G; Calleja-Agius, J

    2014-08-01

    Postmenopausal osteoporosis is a silent systemic progressive disease characterised by a decrease in bone mass per unit volume. This condition compromises the physical strength of the skeleton and increases the susceptibility to fractures on minor trauma. The imbalance between bone formation and bone resorption is known to be responsible for postmenopausal bone loss. Estrogen deficiency contributes to bone loss by increasing the production of pro-inflammatory cytokines by bone marrow and bone cells. Clinical and molecular evidence indicates that estrogen-regulated cytokines exert regulatory effects on bone turnover implicating their role as being the primary mediators of the accelerated bone loss at menopause. The current perspective on the role and interaction of cytokines such as IL-1, IL-4, IL-6, IL-17, TNF, IFN-γ and TGF-β in bone loss linked with estrogen deficiency is reviewed. Current treatment options and emerging drug therapies in the management of postmenopausal osteoporosis are also evaluated.

  13. Th1/Th2 Cytokines in Psoriasis

    Directory of Open Access Journals (Sweden)

    Z Jadali

    2007-08-01

    Full Text Available Background: The aim of this study was to determine the Th1 and Th2 serum cytokines, in patients with psoriasis and to com¬pare their cytokine levels with those of normal control subjects. Methods: Serum levels of Interferon-gamma (IFN-γ, Interleukin-2 (IL-2, Interleukin-4 (IL-4, and Interleukin-10 (IL-10 were measured by enzyme linked immunosorbent assay in 40 patients with psoriasis and in 40 normal controls. Results: Compared with control subjects, patients with psoriasis had elevated levels of IFN-γ and IL-2 (P<0.001. In addi¬tion a positive correlation was found between the levels of IFN-γ, IL-2 and disease severity. Conclusion: Th1 secreting inflammatory cytokines may contribute to the pathogenesis of psoriasis.

  14. Cytokine and lipid mediator networks in tuberculosis.

    Science.gov (United States)

    Mayer-Barber, Katrin D; Sher, Alan

    2015-03-01

    A major approach for immunologic intervention in tuberculosis involves redirecting the outcome of the host immune response from the induction of disease to pathogen control. Cytokines and lipid mediators known as eicosanoids play key roles in regulating this balance and as such represent important targets for immunologic intervention. While the evidence for cytokine/eicosanoid function derives largely from the investigation of murine and zebrafish experimental infection models, clinical studies have confirmed the existence of many of the same pathways in tuberculosis patients. Here, we summarize new data that reveal important intersections between the cytokine and eicosanoid networks in the host response to mycobacteria and discuss how targeting this crosstalk can promote resistance to lethal Mycobacterium tuberculosis infection. This approach could lead to new host-directed therapies to be used either as an adjunct for improving the efficacy of standard antibiotic treatment or for the management of drug-resistant infections.

  15. Treatment of Cancer Pain by Targeting Cytokines.

    Science.gov (United States)

    Vendrell, I; Macedo, D; Alho, I; Dionísio, M R; Costa, L

    2015-01-01

    Inflammation is one of the most important causes of the majority of cancer symptoms, including pain, fatigue, cachexia, and anorexia. Cancer pain affects 17 million people worldwide and can be caused by different mediators which act in primary efferent neurons directly or indirectly. Cytokines can be aberrantly produced by cancer and immune system cells and are of particular relevance in pain. Currently, there are very few strategies to control the release of cytokines that seems to be related to cancer pain. Nevertheless, in some cases, targeted drugs are available and in use for other diseases. In this paper, we aim to review the importance of cytokines in cancer pain and targeted strategies that can have an impact on controlling this symptom.

  16. Cytokines in relation to autoantibodies before onset of symptoms for systemic lupus erythematosus.

    Science.gov (United States)

    Eriksson, C; Rantapää-Dahlqvist, S

    2014-06-01

    A number of cytokines and chemokines were analysed and related to autoantibodies in blood samples pre-dating the onset of symptoms of systemic lupus erythematosus. Thirty-five patients with systemic lupus erythematosus (American College of Rheumatology criteria) were identified as having donated blood samples, prior to symptom onset, to the Biobank of northern Sweden. Altogether, 140 age- and sex-matched controls were also identified. The concentrations of interferon-α, interleukin-4, interleukin-9, interleukin-10, interferon inducible protein-10 and monocyte chemotactic protein-1 were analysed using multiplex technology and related to autoantibodies (ANA, ENA, anti-dsDNA and anti-histone antibodies) analysed from the same blood sample. The interferon-γ inducible protein-10 levels were higher in the pre-symptomatic individuals than in controls (p systemic lupus erythematosus. An increased concentration of interferon-γ inducible protein-10 pre-dated the onset of systemic lupus erythematosus and was related to autoantibodies before the onset of disease. The levels of interferon-γ inducible protein-10 and interferon-α were correlated. These findings support the proposal that the interferon system is important early in the pathogenesis of systemic lupus erythematosus and autoantibody formation. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. Terrorism, Diasporas, and Permissive Threat Environments. A Study of Hizballah’s Fundraising Operations in Paraguay and Ecuador

    Science.gov (United States)

    2004-12-01

    poblacion de Guayaquil, considerados sus habitants nacionalidades, December 31, 1890”, Informe y memoria estadistica de la Intendencia de provincial...la poblacion de Guayaquil, considerados sus habitants nacionalidades, December 31, 1890”, Informe y memoria estadistica de la Intendencia de

  18. Cytokine polymorphisms in silicosis and other pneumoconioses

    Energy Technology Data Exchange (ETDEWEB)

    Yucesoy, B.; Vallyathan, V.; Landsittel, D.P.; Simeonova, P.; Luster, M.I. [NIOSH, Morgantown, WV (United States). Health Effects & Laboratory Division

    2002-06-01

    Silicosis and coal workers' pneumoconiosis are complex multifactorial lung diseases whose etiopathogenesis are not well defined. It is generally accepted that fibrotic lung disorders are mediated by macrophage-derived cytokines and growth factors. There is evidence showing a crucial role for tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) in inflammation caused by silica dust and in the transition from simple to progressive massive fibrosis. In this review genetic polymorphisms responsible for regulating the production of these proinflammatory cytokines and their role in modifying silicosis severity are discussed.

  19. Cytokine inhibition in the treatment of COPD

    Directory of Open Access Journals (Sweden)

    Caramori G

    2014-04-01

    Full Text Available Gaetano Caramori,1 Ian M Adcock,2,3 Antonino Di Stefano,4 Kian Fan Chung2,3 1Dipartimento di Scienze Mediche, Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO, Sezione di Medicina Interna e Cardiorespiratoria, Università di Ferrara, Ferrara, Italy; 2Airway Diseases Section, National Heart and Lung Institute, Imperial College London, UK; 3Biomedical Research Unit, Royal Brompton and Harefield NHS Trust, London, UK; 4Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio-Respiratorio, Fondazione Salvatore Maugeri, IRCCS, Veruno, Italy Abstract: Cytokines play an important part in many pathobiological processes of chronic obstructive pulmonary disease (COPD, including the chronic inflammatory process, emphysema, and altered innate immune response. Proinflammatory cytokines of potential importance include tumor necrosis factor (TNF-α, interferon-γ, interleukin (IL-1β, IL-6, IL-17, IL-18, IL-32, and thymic stromal lymphopoietin (TSLP, and growth factors such as transforming growth factor-β. The current objectives of COPD treatment are to reduce symptoms, and to prevent and reduce the number of exacerbations. While current treatments achieve these goals to a certain extent, preventing the decline in lung function is not currently achievable. In addition, reversal of corticosteroid insensitivity and control of the fibrotic process while reducing the emphysematous process could also be controlled by specific cytokines. The abnormal pathobiological process of COPD may contribute to these fundamental characteristics of COPD, and therefore targeting cytokines involved may be a fruitful endeavor. Although there has been much work that has implicated various cytokines as potentially playing an important role in COPD, there have been very few studies that have examined the effect of specific cytokine blockade in

  20. Proinflammatory Cytokines as Regulators of Vaginal Microbiota.

    Science.gov (United States)

    Kremleva, E A; Sgibnev, A V

    2016-11-01

    It was shown that IL-1β, IL-8, and IL-6 in concentrations similar to those in the vagina of healthy women stimulated the growth of normal microflora (Lactobacillus spp.) and suppressed the growth and biofilm production by S. aureus and E. coli. On the contrary, these cytokines in higher concentrations typical of vaginal dysbiosis suppressed normal microflora and stimulated the growth of opportunistic microorganisms. TGF-β1 in both doses produced a stimulating effects on study vaginal microsymbionts. It is hypothesized that pro-inflammatory cytokines serve as the molecules of interspecies communication coordinating the interactions of all components of the vaginal symbiotic system.

  1. Credit financing in economic ordering policies for non-instantaneous deteriorating items with price dependent demand under permissible delay in payments: A new approach

    Directory of Open Access Journals (Sweden)

    Chandra K. Jaggi

    2015-09-01

    Full Text Available In the existing literature of inventory modeling under the conditions of permissible delay in payments, researchers have assumed that the retailers have to settle their accounts at the end of credit period i.e. supplier accept only full amount at the end of the credit period. However in reality, supplier may either accept the partial amount at the end of the credit period and unpaid balance subsequently or the full amount at a fix point of time after the expiry of the credit period, if the retailer finances the inventory from the supplier itself. Further, in the classical deteriorating inventory models, the common unrealistic assumption is that all the items start to deteriorate as soon as they arrive in the system. However, in realistic environment, it is observed that there are several non-instantaneous deteriorating items that have a shelf life and start to deteriorate after a time lag, like dry fruits, potatoes, yams and even some fruits and vegetables etc. Considering the importance of above mentioned facts, the present study formulates a fuzzy inventory model for non-instantaneous deteriorating items under conditions of permissible delay in payments. The paper discusses all the possible cases which may arise and yet not considered in the previous inventory models under permissible delay in payments. Further, this paper also considers price-dependent demand and the possibility of higher interest earn rate than interest payable rate. The objective of this study is to determine the optimal decision policies for the retailer which maximizes the total profit. Finally, the numerical examples are solved by using the proposed algorithm to show the validity of the model followed by the sensitivity analysis.

  2. The Potential of GMP-Compliant Platelet Lysate to Induce a Permissive State for Cardiovascular Transdifferentiation in Human Mediastinal Adipose Tissue-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Camilla Siciliano

    2015-01-01

    Full Text Available Human adipose tissue-derived mesenchymal stem cells (ADMSCs are considered eligible candidates for cardiovascular stem cell therapy applications due to their cardiac transdifferentiation potential and immunotolerance. Over the years, the in vitro culture of ADMSCs by platelet lysate (PL, a hemoderivate containing numerous growth factors and cytokines derived from platelet pools, has allowed achieving a safe and reproducible methodology to obtain high cell yield prior to clinical administration. Nevertheless, the biological properties of PL are still to be fully elucidated. In this brief report we show the potential ability of PL to induce a permissive state of cardiac-like transdifferentiation and to cause epigenetic modifications. RTPCR results indicate an upregulation of Cx43, SMA, c-kit, and Thy-1 confirmed by immunofluorescence staining, compared to standard cultures with foetal bovine serum. Moreover, PL-cultured ADMSCs exhibit a remarkable increase of both acetylated histones 3 and 4, with a patient-dependent time trend, and methylation at lysine 9 on histone 3 preceding the acetylation. Expression levels of p300 and SIRT-1, two major regulators of histone 3, are also upregulated after treatment with PL. In conclusion, PL could unravel novel biological properties beyond its routine employment in noncardiac applications, providing new insights into the plasticity of human ADMSCs.

  3. The Potential of GMP-Compliant Platelet Lysate to Induce a Permissive State for Cardiovascular Transdifferentiation in Human Mediastinal Adipose Tissue-Derived Mesenchymal Stem Cells

    Science.gov (United States)

    Siciliano, Camilla; Chimenti, Isotta; Bordin, Antonella; Ponti, Donatella; Iudicone, Paola; Peruzzi, Mariangela; Rendina, Erino Angelo; Calogero, Antonella; Pierelli, Luca; Ibrahim, Mohsen; De Falco, Elena

    2015-01-01

    Human adipose tissue-derived mesenchymal stem cells (ADMSCs) are considered eligible candidates for cardiovascular stem cell therapy applications due to their cardiac transdifferentiation potential and immunotolerance. Over the years, the in vitro culture of ADMSCs by platelet lysate (PL), a hemoderivate containing numerous growth factors and cytokines derived from platelet pools, has allowed achieving a safe and reproducible methodology to obtain high cell yield prior to clinical administration. Nevertheless, the biological properties of PL are still to be fully elucidated. In this brief report we show the potential ability of PL to induce a permissive state of cardiac-like transdifferentiation and to cause epigenetic modifications. RTPCR results indicate an upregulation of Cx43, SMA, c-kit, and Thy-1 confirmed by immunofluorescence staining, compared to standard cultures with foetal bovine serum. Moreover, PL-cultured ADMSCs exhibit a remarkable increase of both acetylated histones 3 and 4, with a patient-dependent time trend, and methylation at lysine 9 on histone 3 preceding the acetylation. Expression levels of p300 and SIRT-1, two major regulators of histone 3, are also upregulated after treatment with PL. In conclusion, PL could unravel novel biological properties beyond its routine employment in noncardiac applications, providing new insights into the plasticity of human ADMSCs. PMID:26495284

  4. Cytokine profile of murine malaria: stage-related production of inflammatory and anti-inflammatory cytokines.

    Science.gov (United States)

    Bakir, Hanaa Y; Tomiyama, Chikako; Abo, Toru

    2011-06-01

    Balance between inflammatory and anti-inflammatory cytokines may be important in malaria presentation and outcome. To clarify cytokine interactions that produce pathology of malaria and control infection, C57BL/6 mice were infected with 10(4) parasitized RBCs from a non-lethal strain of Plasmodium yoelii. Kinetics was monitored showing the course of parasitemia, and cytokines were determined by RT-PCR from liver and spleen tissues. Inflammatory cytokines such as interferon-γ (IFNγ), interleukin (IL)-12, IL-6, tumor necrosis factor-α (TNFα) and anti-inflammatory cytokines, including IL-4 and IL-10, were investigated as key molecules that interact with immune cells in the activation of the immune responses. The production of IFNγ mRNA was found to be higher on day 7 than on day 21 after infection, and IL-12 and IL-6 showed higher expression in the liver than in the spleen. Though TNFα was highly expressed on day 14 after infection and on day 21 in the liver, such expression was decreased on day 21 in the spleen. Anti-inflammatory cytokines showed high expression in both the liver and spleen. The results suggest that a relative balance between inflammatory and anti-inflammatory cytokines is crucial and that the increase of inflammatory cytokine levels during the acute phase of malaria may reflect an early and effective immune response.The counteraction effect of anti-inflammatory cytokines is thought to play a role in limiting progression from uncomplicated malaria to severe life-threatening complications.

  5. The Moral Permissibility of Suicide%论自杀的道德合理性

    Institute of Scientific and Technical Information of China (English)

    徐家琦; 罗艳

    2014-01-01

    Suicide raises several ethical questions .And the most fundamental one is about the moral permissibility of sui-cide.It is widely believed that duties to others constitute the primary consideration that limits the permissibility of suicide .But one of the opposing view argues that the principle that suicide is a right limited by overriding duties to others does not remove the difficul -ty of knowing whether or not one ’ s suicide would be morally acceptable .While the other opposing view considers that suicide is purely personal decision which cannot be condemned on the basis of the suicide ’ s relations to others .However , no matter from al-truistic factor or from selfish reason , suicide can be morally permissible under special circumstance .%关于自杀,引起了很多伦理学上的讨论,其中最基本的是关于自杀的道德合理性问题,普遍认为个体对他人的义务是限制自杀合理性的主要因素。其中一种反对观点认为,将自杀看作一种权利的观点并没有很好地解决自杀的道德许可性问题;另一种反对观点则认为自杀是一个纯粹的私人问题,所以对他人的义务不能成为限制自杀的理由。然而,无论从利他因素考虑还是从利己因素考虑,在特定条件下自杀是可以被允许的,自杀的合理性可以得到辩护。

  6. Attitudes of adolescents toward suicidal behavior: permissiveness of suicidal behavior as a risk factor

    Directory of Open Access Journals (Sweden)

    Urška Arnautovska

    2008-04-01

    Full Text Available Throughout history, the social convictions and norms have influenced the recognition and presence of suicidal behaviour in different ways. However, previous research findings regarding the connection between suicidal behaviour and attitudes towards suicide have not arrived at a clear conclusion. The present research explores adolescents' attitudes toward suicide. The aim was to examine the relation between the permissive attitude toward suicide on one side and certain suicide risk factors and satisfaction in different domains of psychical functioning on the other side. Data was collected on 423high school students in three Slovenian cities, chosen on the basis of different regional suicide rates, with an Attitudes towards Suicide Questionnaire ATTS, Psychological Well-Being Scales PWBS, and questions about suicidal behaviour of adolescents and their surroundings. The results showed that the acceptance of suicide is proportional to the suicide rates of different regions. We concluded that permissive attitudes towards suicide could potentially lead to the increased risk of suicidal behaviour. Furthermore, the acceptance of suicide was, inter alia, significantly positively related to the self-reported probability of committing suicide, the presence of suicidal behaviour of the adolescent and his/her friends or other people he/she knows, while the connection with the subjective life satisfaction was negative. Considering the fact that there has been a trend of growing permissiveness towards suicide in society in the last few decades, the findings raise a question regarding the positive effects of such tolerance on suicide rates and support the justification of restrictive attitudes towards suicide as a protective factor of suicidal behaviour.

  7. The VP1u Receptor Restricts Parvovirus B19 Uptake to Permissive Erythroid Cells

    Science.gov (United States)

    Leisi, Remo; Von Nordheim, Marcus; Ros, Carlos; Kempf, Christoph

    2016-01-01

    Parvovirus B19 (B19V) is a small non-enveloped virus and known as the causative agent for the mild childhood disease erythema infectiosum. B19V has an extraordinary narrow tissue tropism, showing only productive infection in erythroid precursor cells in the bone marrow. We recently found that the viral protein 1 unique region (VP1u) contains an N-terminal receptor-binding domain (RBD), which mediates the uptake of the virus into cells of the erythroid lineage. To further investigate the role of the RBD in connection with a B19V-unrelated capsid, we chemically coupled the VP1u of B19V to the bacteriophage MS2 capsid and tested the internalization capacity of the bioconjugate on permissive cells. In comparison, we studied the cellular uptake and infection of B19V along the erythroid differentiation. The results showed that the MS2-VP1u bioconjugate mimicked the specific internalization of the native B19V into erythroid precursor cells, which further coincides with the restricted infection profile. The successful mimicry of B19V uptake demonstrates that the RBD in the VP1u is sufficient for the endocytosis of the viral capsid. Furthermore, the recombinant VP1u competed with B19V uptake into permissive cells, thus excluding a significant alternative uptake mechanism by other receptors. Strikingly, the VP1u receptor appeared to be expressed only on erythropoietin-dependent erythroid differentiation stages that also provide the necessary intracellular factors for a productive infection. Taken together, these findings suggest that the VP1u binds to a yet-unknown erythroid-specific cellular receptor and thus restricts the virus entry to permissive cells. PMID:27690083

  8. Permissive hypotension in the extremely low birthweight infant with signs of good perfusion.

    LENUS (Irish Health Repository)

    Dempsey, E M

    2012-01-31

    INTRODUCTION: Many practitioners routinely treat infants whose mean arterial blood pressure in mm Hg is less than their gestational age in weeks (GA). OBJECTIVE: To assess the effectiveness of utilising a combined approach of clinical signs, metabolic acidosis and absolute blood pressure (BP) values when deciding to treat hypotension in the extremely low birthweight (ELBW) infant. METHODS: Retrospective cohort study of all live born ELBW infants admitted to our neonatal intensive care unit over a 4-year period. Patients were grouped as either normotensive (BP never less than GA), hypotensive and not treated (BPpermissive hypotension) and hypotensive treated (BPpermissive hypotension had similar outcomes. Mean blood pressure in the permissive group increased from 26 mm Hg at 6 h to 31 mm Hg at 24 h. In a logistic regression model, treated hypotension is independently associated with mortality, odds ratio 8.0 (95% CI 2.3 to 28, p<0.001). CONCLUSIONS: Blood pressure spontaneously improves in ELBW infants during the first 24 h. Infants hypotensive on GA criteria but with clinical evidence of good perfusion had as good an outcome as normotensive patients. Treated low blood pressure was associated with adverse outcome.

  9. Different Responses of Two Highly Permissive Cell Lines Upon HCV Infection

    Institute of Scientific and Technical Information of China (English)

    Honghe Chen; Rongjuan Pei; Xinwen Chen

    2013-01-01

    The construction of the first infectious clone JFH-1 speeds up the research on hepatitis C virus (HCV).However,Huh7 cell line was the only highly permissive cell line for HCV infection and only a few clones were fully permissive.In this study,two different fully permissive clones of Huh7 cells,Huh7.5.1 and Huh7-Lunet-CD81 (Lunet-CD81) cells were compared for their responses upon HCV infection.The virus replication level was found slightly higher in Huh7.5.1 cells than that in Lunet-CD81 cells.Viability of Huh7.5.1 cells but not of Lunet-CD81 cells was reduced significantly after HCV infection.Further analysis showed that the cell cycle of infected Huh7.5.1 cells was arrested at G1 phase.The G1/S transition was blocked by HCV infection in Huh7.5.1 cells as shown by the cell cycle synchronization analysis.Genes related to cell cycle regulation was modified by HCV infection and gene interaction analysis in GeneSpring GX in Direct Interactions mode highlighted 31 genes.In conclusion,the responses of those two cell lines were different upon HCV infection.HCV infection blocked G1/S transition and cell cycle progress,thus reduced the cell viability in Huh7.5.1 cells but not in Lunet-CD81 cells.Lunet-CD81 cells might be suitable for long term infection studies of HCV.

  10. Cytokines and Organ Failure in Acute Pancreatitis

    DEFF Research Database (Denmark)

    Malmstrøm, Marie Louise; Hansen, Mark Berner; Andersen, Anders Møller

    2012-01-01

    Objectives: We aimed at synchronously examining the early time course of 4 proinflammatory cytokines as predictive factors for development of organ failure in patients with acute pancreatitis (AP). Methods: Interleukin (IL) 6, IL-8, IL-18, and tumor necrosis factor > were measured on admission...

  11. Role of cytokines in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), rep- resents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with a relapsing and remitting clinical course. Mucosal mac- rophages play an important role in the mucosal im- mune system, and an increase in the number of newly recruited monocytes and activated macrophages has been noted in the inflamed gut of patients with IBD. Activated macrophages are thought to be major con- tributors to the production of inflammatory cytokines in the gut, and imbalance of cytokines is contributing to the pathogenesis of IBD. The intestinal inflammation in IBD is controlled by a complex interplay of innate and adaptive immune mechanisms. Cytokines play a key role in IBD that determine T cell differentiation of Th1, Th2, T regulatory and newly described Th17 cells. Cytokines levels in time and space orchestrate the development, recurrence and exacerbation of theinflammatory process in IBD. Therefore, several cyto- kine therapies have been developed and tested for the treatment of IBD patients.

  12. Cytokines in atherosclerosis: an intricate balance

    NARCIS (Netherlands)

    Boshuizen, M.C.S.

    2016-01-01

    Atherosclerosis is the underlying pathology in the majority of clinical manifestations of cardiovascular diseases, which are nowadays the main global cause of mortality. Atherosclerosis is a lipid-driven chronic inflammatory disease of the arterial wall. This inflammatory response, with cytokines as

  13. Cytokines and immune surveillance in humans

    Science.gov (United States)

    Sonnenfeld, Gerald

    1994-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. Among the parameters shown, by us and others, to be affected is the production of interferons. Interferons are a family of cytokines that are antiviral and play a major role in regulating immune responses that control resistance to infection. Alterations in interferon and other cytokine production and activity could result in changes in immunity and a possible compromise of host defenses against both opportunistic and external infections. The purpose of the present study is to explore further the effects of space flight on cyotokines and cytokine-directed immunological function. Among the tests carried out are interferon-alpha production, interferon-gamma production, interleukin-1 and -2 production, signal transduction in neutrophils, signal transduction in monocytes, and monocyte phagocytic activity. The experiments will be performed using peripheral blood obtained from human subjects. It is our intent to eventually carry out these experiments using astronauts as subjects to determine the effects of space flight on cytokine production and activity. However, these subjects are not currently available. Until they become available, we will carry out these experiments using subjects maintained in the bed-rest model for microgravity.

  14. IFN-gamma: Novel antiviral cytokines

    DEFF Research Database (Denmark)

    Ank, Nina; West, Hans; Paludan, Søren Riis

    2006-01-01

    and adaptive immune responses. Recently, a novel class of cytokines was discovered and named IFN-lambda (alternatively type III IFN or interleukin-28/29 [IL- 28/29]), based on IFN-like antiviral activity and induction of typical IFN-inducible genes. Here, we review the literature on IFN-lambda and discuss...

  15. Murine cytokine patterns following rubella vaccination.

    Science.gov (United States)

    Farzaneh, Parvarich; Ebtekar, Massoumeh; Hassan, Z M; Rafati, Sima

    2003-06-01

    Although thorough studies on the immune reponse to rubella have been performed, less attention has been given to the cellular mechanism and mediators that shape the process. Specifically, information concerning the nature ofcytokine patterns involved in the immune response to Rubella vaccination is not avaliable. This study deals with cytokine production patterns of spleen cells from Balb/c mice following vaccination with the Takahashi strain of Rubella vaccine. Mice were injected intraperitonealy with Rubella virus and PBS and 7, 10 or 14 days later, spleen cells were separated and cultured with varying doses of virus, con A or only the medium. ELISA assays were performed on supernatants for measurement of IL-4, INF-gamma and IL-5. LTT (Lymphocyte Transformation Test) was also performed. The data indicate variation in cytokine patterns during the time periods after vaccination. On day 7 a type 1 pattern was observed. The LTT response was also indicative of CMI (Cell Mediated Immunity) response on the 7th and 14th days while a transient suppression on day 10 was observed. These results indicate a time dependent cytokine response with variation ultimately leading o a dominant type 1 (Ti) cytokine response.

  16. High permissivity of human HepG2 hepatoma cells for influenza viruses.

    Science.gov (United States)

    Ollier, Laurence; Caramella, Anne; Giordanengo, Valérie; Lefebvre, Jean-Claude

    2004-12-01

    Human HepG2 hepatoma cells are highly permissive for influenza virus type A and type B, even without the addition of trypsin, and they exhibit a marked cytopathic effect. This property greatly facilitates the primary isolation of influenza viruses. Virus replication was significantly reduced by the plasmin(ogen)-specific inhibitor tranexamic acid, and this suggests a potential role played by the plasminogen/tissue plasminogen activator complex at the surface of HepG2 cells. This might represent a new approach for study of the interrelations of this complex with influenza viruses.

  17. An inventory model for deteriorating items under the condition of permissible delay in payments

    Directory of Open Access Journals (Sweden)

    Chang Horng-Jinh

    2002-01-01

    Full Text Available In economic order quantity (EOQ models, it is often assumed that the payment of an order is made on the receipt of items by the inventory system. However, such an assumption is not quite practical in the real world. Under most market behaviors, it can be easily found that a vendor provides a credit period for buyers to stimulate demand. In this paper, a varying rate of determination and the condition of permissible delay in payments used in conjunction with the economic order quantity model are the focus of discussion. Numerical examples are presented to illustrate the proposed models.

  18. Young People's More Permissive Views About Marijuana: Local Impact of State Laws or National Trend?

    OpenAIRE

    Schmidt, LA; Jacobs, LM; Spetz, J

    2016-01-01

    To determine whether state medical marijuana laws "send the wrong message," that is, have a local influence on the views of young people about the risks of using marijuana.We performed multilevel, serial, cross-sectional analyses on 10 annual waves of the US National Survey on Drug Use and Health (2004-2013) nationally and for states with marijuana laws using individual- and state-level controls.Living in medical marijuana states was associated with more permissive views regarding marijuana a...

  19. Two warehouse inventory model for deteriorating item with exponential demand rate and permissible delay in payment

    Directory of Open Access Journals (Sweden)

    Kaliraman Naresh Kumar

    2017-01-01

    Full Text Available A two warehouse inventory model for deteriorating items is considered with exponential demand rate and permissible delay in payment. Shortage is not allowed and deterioration rate is constant. In the model, one warehouse is rented and the other is owned. The rented warehouse is provided with better facility for the stock than the owned warehouse, but is charged more. The objective of this model is to find the best replenishment policies for minimizing the total appropriate inventory cost. A numerical illustration and sensitivity analysis is provided.

  20. Cytokines in Endocrine Dysfunction of Plasma Cell Disorders.

    Science.gov (United States)

    Feigerlová, Eva; Battaglia-Hsu, Shyue-Fang

    2017-01-01

    Monoclonal gammopathies (MG) are classically associated with lytic bone lesions, hypercalcemia, anemia, and renal insufficiency. However, in some cases, symptoms of endocrine dysfunction are more prominent than these classical signs and misdiagnosis can thus be possible. This concerns especially the situation where the presence of M-protein is limited and the serum protein electrophoresis (sPEP) appears normal. To understand the origin of the endocrine symptoms associated with MG, we overview here the current knowledge on the complexity of interactions between cytokines and the endocrine system in MG and discuss the perspectives for both the diagnosis and treatments for this class of diseases. We also illustrate the role of major cytokines and growth factors such as IL-6, IL-1β, TNF-α, and VEGF in the endocrine system, as these tumor-relevant signaling molecules not only help the clonal expansion and invasion of the tumor cells but also influence cellular metabolism through autocrine, paracrine, and endocrine mechanisms. We further discuss the broader impact of these tumor environment-derived molecules and proinflammatory state on systemic hormone signaling. The diagnostic challenges and clinical work-up are illustrated from the point of view of an endocrinologist.

  1. Permissive attitude towards drug use, life satisfaction, and continuous drug use among psychoactive drug users in Hong Kong

    National Research Council Canada - National Science Library

    Cheung, Nicole WT; Cheung, Yuet-Wah; Chen, Xi

    2016-01-01

    Objectives: To examine the effects of a permissive attitude towards regular and occasional drug use, life satisfaction, self-esteem, depression, and other psychosocial variables in the drug use of psychoactive drug users...

  2. Neuropathic pain and cytokines: current perspectives

    Directory of Open Access Journals (Sweden)

    Clark AK

    2013-11-01

    Full Text Available Anna K Clark, Elizabeth A Old, Marzia Malcangio Wolfson Centre for Age Related Diseases, King's College London, London, UK Abstract: Neuropathic pain represents a major problem in clinical medicine because it causes debilitating suffering and is largely resistant to currently available analgesics. A characteristic of neuropathic pain is abnormal response to somatic sensory stimulation. Thus, patients suffering peripheral neuropathies may experience pain caused by stimuli which are normally nonpainful, such as simple touching of the skin or by changes in temperature, as well as exaggerated responses to noxious stimuli. Convincing evidence suggests that this hypersensitivity is the result of pain remaining centralized. In particular, at the first pain synapse in the dorsal horn of the spinal cord, the gain of neurons is increased and neurons begin to be activated by innocuous inputs. In recent years, it has become appreciated that a remote damage in the peripheral nervous system results in neuronal plasticity and changes in microglial and astrocyte activity, as well as infiltration of macrophages and T cells, which all contribute to central sensitization. Specifically, the release of pronociceptive factors such as cytokines and chemokines from neurons and non-neuronal cells can sensitize neurons of the first pain synapse. In this article we review the current evidence for the role of cytokines in mediating spinal neuron–non-neuronal cell communication in neuropathic pain mechanisms following peripheral nerve injury. Specific and selective control of cytokine-mediated neuronal–glia interactions results in attenuation of the hypersensitivity to both noxious and innocuous stimuli observed in neuropathic pain models, and may represent an avenue for future therapeutic intervention. Keywords: anti-inflammatory cytokines, proinflammatory cytokines, microglia, astrocytes, first pain synapse

  3. Expression of Cytokines in Acute Heart Transplantation Rejection

    Institute of Scientific and Technical Information of China (English)

    XIA Jiahong; XU Lei; YANG Chenyuan

    2006-01-01

    The expression and changes of local cytokines network were detected in heart transplantation in rats, so as to determine the role of cytokines in the acute rejection of rats of heart transplantation. Allografts were divided into 4 groups (n=12 in each group): group A (control), group B (IL-2 monoclonal antibody-treated), group C (CsA-treated) and group D (IL-2 monoclonal antibody+CsA-treated). Hearts from DA rats were transplanted into a cervical location in Wistar recipients. The local expression of IL-1β, IL-2, CD25, IL-4, IL-5, IL-6, IL-10, TNFα and INFγ was detected at day 1, 3, 5, 7, 9, 11 and 14 by reverse transcription polymerase chain reaction. The results showed that the survival time of allografts was 8.3±1.7, 29.2±7.1 (P<0.05), 26.4±5.7 (P<0.05) and 55.0±10.6 (P<0.01) days respectively in groups A, B, C and D. The expression of IL-1β, IL-4, IL-10and IFNγ was up-regulated, and that of IL-2, CD25, IL-5, IL-6 and TNFα was significantly inhibited in group A; The expression of IL-1β, IL-5, IL-6, IL-10 and IFNγ was up-regulated, and that of IL-2,IL-4 and TNFα was significantly down-regulated in group B; The expression of IL-1β, IL-2, CD25,IL-5, TNFα and IFNγ was up-regulated, and that of IL-4, IL-6 and IL-10 was significantly down-regulated in group C; The expression of IL-14, Il-5, IL-6 and Il-10 was up-regulated, and that of IL-1β, IL-2, CD25, TNFα and IFNγ was significantly down-regulated in group D. In conclusion,cytokines play an important role in the development of acute transplantation rejection. Different cytokines play different roles in different local environments.

  4. Activation of liver X receptor suppresses the production of the IL-12 family of cytokines by blocking nuclear translocation of NF-κBp50.

    Science.gov (United States)

    Canavan, Mary; McCarthy, Ciara; Larbi, Nadia Ben; Dowling, Jennifer K; Collins, Laura; O'Sullivan, Finbarr; Hurley, Grainne; Murphy, Carola; Quinlan, Aoife; Moloney, Gerry; Darby, Trevor; MacSharry, John; Kagechika, Hiroyuki; Moynagh, Paul; Melgar, Silvia; Loscher, Christine E

    2014-10-01

    There is now convincing evidence that liver X receptor (LXR) is an important modulator of the inflammatory response; however, its mechanism of action remains unclear. This study aimed to examine the effect of LXR on the IL-12 family of cytokines and examined the mechanism by which LXR exerted this effect. We first demonstrated that activation of murine-derived dendritic cells (DC) with a specific agonist to LXR enhanced expression of LXR following activation with LPS, suggesting a role in inflammation. Furthermore, we showed LXR expression to be increased in vivo in dextrane sulphate sodium-induced colitis. LXR activation also suppressed production of IL-12p40, IL-12p70, IL-27 and IL-23 in murine-derived DC following stimulation with LPS, and specifically targeted the p35, p40 and EBI3 subunits of the IL-12 cytokine family, which are under the control of the NF-κB subunit p50 (NF-κBp50). Finally, we demonstrated that LXR can associate with NF-κBp50 in DC and that LXR activation prevents translocation of the p50 subunit into the nucleus. In summary, our study indicates that LXR can specifically suppress the IL-12 family of cytokines though its association with NF-κBp50 and highlights its potential as a therapeutic target for chronic inflammatory diseases. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  5. Cytokine balance and cytokine-driven natural killer cell dysfunction in systemic juvenile idiopathic arthritis.

    Science.gov (United States)

    Avau, Anneleen; Put, Karen; Wouters, Carine H; Matthys, Patrick

    2015-02-01

    Systemic juvenile idiopathic arthritis (sJIA) is a severe inflammatory childhood disorder, characterized by a specific pattern of systemic features and a typical cytokine profile. Patients are at risk to develop macrophage activation syndrome (MAS), an acute life-threatening condition defined by excessive proliferation and activation of macrophages and T cells. Defects of unknown cause in the natural killer (NK) cell cytotoxic capacity are presumed to underlie the pathogenesis of MAS and have been detected in sJIA patients. Here, we provide an overview of the cytokine profiles in sJIA and related mouse models. We discuss the influence of cytokines on NK cell function, and hypothesize that NK cell dysfunction in sJIA is caused by altered cytokine profiles.

  6. Permissive human cytomegalovirus infection of a first trimester extravillous cytotrophoblast cell line

    Directory of Open Access Journals (Sweden)

    LaMarca Heather L

    2004-11-01

    Full Text Available Abstract Human cytomegalovirus (HCMV is the leading cause of congenital viral infection in the United States and Europe. Despite the significant morbidity associated with prenatal HCMV infection, little is known about how the virus infects the fetus during pregnancy. To date, primary human cytotrophoblasts (CTBs have been utilized to study placental HCMV infection and replication; however, the minimal mitotic potential of these cells restricts experimentation to a few days, which may be problematic for mechanistic studies of the slow-replicating virus. The aim of this study was to determine whether the human first trimester CTB cell line SGHPL-4 was permissive for HCMV infection and therefore could overcome such limitations. HCMV immediate early (IE protein expression was detected as early as 3 hours post-infection in SGHPL-4 cells and progressively increased as a function of time. HCMV growth assays revealed the presence of infectious virus in both cell lysates and culture supernatants, indicating that viral replication and the release of progeny virus occurred. Compared to human fibroblasts, viral replication was delayed in CTBs, consistent with previous studies reporting delayed viral kinetics in HCMV-infected primary CTBs. These results indicate that SGHPL-4 cells are fully permissive for the complete HCMV replicative cycle. Our findings suggest that these cells may serve as useful tools for future mechanistic studies of HCMV pathogenesis during early pregnancy.

  7. Permissible wearing times for rescue personnel using a new self-contained breathing apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Graveling, R.A.; Miller, B.G.

    1989-08-01

    British Coal's Central Mines Rescue Service has developed a new compressed oxygen breathing apparatus, the Selected Elevated Flow Apparatus (SEFA) to improve the wearability/tolerability of self-contained breathing apparatus in terms of breathing resistance and inspiratory temperature. Climate chamber studies were carried out of the physiological responses to wearing the SEFA apparatus in the heat, to determine new permissible working time charts. Ninety-three subjects completed a total of 428 wearings. The data for all wearings were summarized either to the time at which core temperature, heartrate or personal discomfort led to withdrawal of the subject from the chamber (withdrawal time), or to the limiting time (60 or 120 minutes, depending on selected flowrate) at which the wearing was terminated if withdrawal had not occurred. Plots of the 'limiting times' against climatic temperature were analysed statistically; As a result of this analysis, it was decided by British Coal Mines Rescue and Medical Services, in consultation with the Mines and Quarries Inspectorate and the Institute, to adopt working times which combined the two data from this and the previous trial. Support for this decision was provided by the lack of any evidence of heat-related problems with the operational use of the Proto apparatus since the introduction of the charts more than 30 years ago. A chart of permissible wearing times for the SEFA apparatus was produced in accordance with this decision. 22 refs., 13 tabs., 11 figs.

  8. Bioluminescence tomography using eigenvectors expansion and iterative solution for the optimized permissible source region.

    Science.gov (United States)

    Naser, Mohamed A; Patterson, Michael S

    2011-11-01

    A reconstruction algorithm for bioluminescence tomography (BLT) has been developed. The algorithm numerically calculates the Green's function at different wavelengths using the diffusion equation and finite element method. The optical properties used in calculating the Green's function are reconstructed using diffuse optical tomography (DOT) and assuming anatomical information is provided by x-ray computed tomography or other methods. A symmetric system of equations is formed using the Green's function and the measured light fluence rate and the resulting eigenvalue problem is solved to get the eigenvectors of this symmetric system of equations. A space can be formed from the eigenvectors obtained and the reconstructed source is written as an expansion of the eigenvectors corresponding to non-zero eigenvalues. The coefficients of the expansion are found to obtain the reconstructed BL source distribution. The problem is solved iteratively by using a permissible source region that is shrunk by removing nodes with low probability to contribute to the source. Throughout this process the permissible region shrinks from the entire object to just a few nodes. The best estimate of the reconstructed source is chosen that which minimizes the difference between the calculated and measured light fluence rates. 3D simulations presented here show that the reconstructed source is in good agreement with the actual source in terms of locations, magnitudes, sizes, and total powers for both localized multiple sources and large inhomogeneous source distributions.

  9. [Securing the therapy management during the leave permissions for the elderly patients].

    Science.gov (United States)

    Veyrier, M; Bachalat, N; Guenegou, A-L; Anne, B; Leglise, P; Huchon Becel, D

    2016-05-01

    Leave permission can be granted over a limited period of hospitalisation during which the patient can return home under the responsibility of the hospital. Despite its frequency, this practice is not evaluated in terms of maintaining the security of medication. This complex process involves several actors, processes and locations. In that case, the drug iatrogenic risk is not at all negligible, especially for the elderly. Patient comprehension of medication is not always easy and must be evaluated before leaving the hospital. Therefore, a risk analysis has been initiated to ensure the medical practice's security of our geriatric hospital. Multidisciplinary working group meetings were dedicated to analyse and overcome 21 unacceptable failure modes. The establishment of traceability nurse/patient for the medication intake, information and evaluation of drug monitoring allowed the patient's medication compliance. In the meanwhile, the role of the working group on the security of the internal drug circuit in the hospital has integrated the harmonization of practices, a unique source of information and a variety of comprehensible, readable and informative materials to propose to the patients. These preventive actions have been formulated to secure, optimize and to individualize drug management during the leave permission. In the context of optimization during transit period home/hospital, this process reorganized by the working group can be integrated in a public health approach to reduce the number of preventable readmissions.

  10. Permissible radionuclide loading for organic ion exchange resins from nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    MacKenzie, D.R.; Lin, M.; Barletta, R.E.

    1983-10-01

    A questionnaire on the use of ion exchange resins in nuclear power plants was sent to all operating reactors in the US. Responses were received from 23 of the 48 utilities approached. Information was sought concerning the amounts of radionuclides held by the resins, and the effects of its radiation on the resins both during operation and after removal from service. Relevant information from the questionnaires is summarized and discussed. Available literature on the effects of ionizing radiation on organic ion exchange resins has been reviewed. On the basis of published data on damage to resins by radiation, the technical rationale is given to support NRC's draft branch technical position on a maximum permissible radionuclide loading. It is considered advisable to formulate the rule in terms of a delivered dose rather than a curie loading. A maximum permissible dose of 10/sup 8/ rad is chosen because, while it is large enough that a measurable amount of damage will be done to the resin, it is small enough that the damage will be negligible at a power plant or disposal site. A test procedure has been written which a generator could use to qualify a specific resin for service at a higher dose than permitted by the general rule.

  11. NASA Space Radiation Protection Strategies: Risk Assessment and Permissible Exposure Limits

    Science.gov (United States)

    Huff, J. L.; Patel, Z. S.; Simonsen, L. C.

    2017-01-01

    Permissible exposure limits (PELs) for short-term and career astronaut exposures to space radiation have been set and approved by NASA with the goal of protecting astronauts against health risks associated with ionizing radiation exposure. Short term PELs are intended to prevent clinically significant deterministic health effects, including performance decrements, which could threaten astronaut health and jeopardize mission success. Career PELs are implemented to control late occurring health effects, including a 3% risk of exposure induced death (REID) from cancer, and dose limits are used to prevent cardiovascular and central nervous system diseases. For radiation protection, meeting the cancer PEL is currently the design driver for galactic cosmic ray and solar particle event shielding, mission duration, and crew certification (e.g., 1-year ISS missions). The risk of cancer development is the largest known long-term health consequence following radiation exposure, and current estimates for long-term health risks due to cardiovascular diseases are approximately 30% to 40% of the cancer risk for exposures above an estimated threshold (Deep Space one-year and Mars missions). Large uncertainties currently exist in estimating the health risks of space radiation exposure. Improved understanding through radiobiology and physics research allows increased accuracy in risk estimation and is essential for ensuring astronaut health as well as for controlling mission costs, optimization of mission operations, vehicle design, and countermeasure assessment. We will review the Space Radiation Program Element's research strategies to increase accuracy in risk models and to inform development and validation of the permissible exposure limits.

  12. Permissiveness of freshly isolated environmental strains of amoebae for growth of Legionella pneumophila.

    Science.gov (United States)

    Dupuy, Mathieu; Binet, Marie; Bouteleux, Celine; Herbelin, Pascaline; Soreau, Sylvie; Héchard, Yann

    2016-03-01

    Legionella pneumophila is a pathogenic bacterium commonly found in water and responsible for severe pneumonia. Free-living amoebae are protozoa also found in water, which feed on bacteria by phagocytosis. Under favorable conditions, some L. pneumophila are able to resist phagocytic digestion and even multiply within amoebae. However, it is not clear whether L. pneumophila could infect at a same rate a large range of amoebae or if there is some selectivity towards specific amoebal genera or strains. Also, most studies have been performed using collection strains and not with freshly isolated strains. In our study, we assess the permissiveness of freshly isolated environmental strains of amoebae, belonging to three common genera (i.e. Acanthamoeba, Naegleria and Vermamoeba), for growth of L. pneumophila at three different temperatures. Our results indicated that all the tested strains of amoebae were permissive to L. pneumophila Lens and that there was no significant difference between the strains. Intracellular proliferation was more efficient at a temperature of 40°C. In conclusion, our work suggests that, under favorable conditions, virulent strains of L. pneumophila could equally infect a large number of isolates of common freshwater amoeba genera.

  13. Access to a Loaded Gun Without Adult Permission and School-Based Bullying.

    Science.gov (United States)

    Simckes, Maayan S; Simonetti, Joseph A; Moreno, Megan A; Rivara, Frederick P; Oudekerk, Barbara A; Rowhani-Rahbar, Ali

    2017-09-01

    Gun access and bullying are risk factors for sustaining or perpetrating violence among adolescents. Our knowledge of gun access among bullied students is limited. We used data on students, aged 12-18 years, from the 2011 and 2013 School Crime Supplement to the National Crime Victimization Survey to assess the association between self-reported bullying victimization (traditional and cyber) and access to a loaded gun without adult permission. Prevalence ratios (PRs) and confidence intervals (CIs) were obtained from multivariable Poisson regression using the Taylor series after controlling for student age, sex, family income, public/private school, and race. Of 10,704 participants, 4.2% (95% CI: 3.8%-4.6%) reported gun access. Compared with nonbullied students, those who reported traditional bullying (PR = 2.2; 95% CI: 1.7-2.4), cyberbullying (PR = 2.8; 95% CI: 1.6-4.9), and both (PR = 5.9; 95% CI: 4.6-7.7) were more likely to also report gun access. Adolescents who experience bullying, particularly those who report both traditional bullying and cyberbullying, are more likely to report access to a loaded gun without adult permission. These findings highlight the importance of developing interventions focused on these modifiable risk factors for preventing self-directed or interpersonal violence among youth. Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  14. Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication

    Science.gov (United States)

    Aagaard, Kjersti M.; Lahon, Anismrita; Suter, Melissa A.; Arya, Ravi P.; Seferovic, Maxim D.; Vogt, Megan B.; Hu, Min; Stossi, Fabio; Mancini, Michael A.; Harris, R. Alan; Kahr, Maike; Eppes, Catherine; Rac, Martha; Belfort, Michael A.; Park, Chun Shik; Lacorazza, Daniel; Rico-Hesse, Rebecca

    2017-01-01

    Zika virus (ZIKV) is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (n = 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations. PMID:28128342

  15. Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus

    Directory of Open Access Journals (Sweden)

    Weber Friedemann

    2006-03-01

    Full Text Available Abstract Background SARS coronavirus (SARS-CoV is the etiologic agent of the severe acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. Here, we investigated the cytokine response of two human non-lymphatic cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV. Results A comparison with established cytokine-inducing viruses revealed that SARS-CoV only weakly triggered a cytokine response. In particular, SARS-CoV did not activate significant transcription of the interferons IFN-α, IFN-β, IFN-λ1, IFN-λ2/3, as well as of the interferon-induced antiviral genes ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly, however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293. Conclusion Our data indicate that SARS-CoV suppresses the antiviral cytokine system of non-immune cells to a large extent, thus buying time for dissemination in the host. However, synthesis of IP-10 and IL-8, which are established markers for acute-stage SARS, escapes the virus-induced silencing at least in some cell types. Therefore, the progressive infiltration of immune cells into the infected lungs observed in SARS patients could be due to the production of these chemokines by the infected tissue cells.

  16. Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases.

    Science.gov (United States)

    Lai, Yuping; Dong, Chen

    2016-04-01

    Inflammatory cytokines are key regulators of immune responses. Persistent and excessive production of inflammatory cytokines underscores the development of autoimmune diseases. Therefore, neutralizing inflammatory cytokines or antagonizing their receptor function is considered as a useful therapeutic strategy to treat autoimmune diseases. To achieve the success of such a strategy, understanding of the complex actions of these cytokines and cytokine networks is required. In this review we focus on four inflammatory cytokines--tumor necrosis factor α (TNFα), interleukin-6 (IL-6), IL-23 and IL-17--and dissect how the dysregulation of these cytokines regulates autoimmune diseases. On the basis of pre-clinical and clinical data, we specifically discuss the therapeutic rationale for targeting these cytokines and describe the potential adverse effects.

  17. Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain.

    Science.gov (United States)

    Neziri, Alban Y; Bersinger, Nick A; Andersen, Ole K; Arendt-Nielsen, Lars; Mueller, Michael D; Curatolo, Michele

    2014-01-01

    Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis. Six parameters assessing central pain processes were recorded. Positive correlations between concentration of some cytokines in the peritoneal fluid and amplification of central pain processing were found. The results suggest that inflammatory mechanisms may be important in the pathophysiology of altered central pain processes and that cytokines produced in the environment of endometriosis could act as mediators between the peripheral lesion and changes in central nociceptive processes.

  18. Mechanism of cytokine modulation of epithelial tight junction barrier

    OpenAIRE

    Al-Sadi, Rana; Boivin, Michel; Ma, Thomas

    2009-01-01

    Cytokines play a crucial role in the modulation of inflammatory response in the gastrointestinal tract. Pro-inflammatory cytokines including tumor necrosis factor-α, interferon-γ, interleukin-1β (IL-1β), and interleukin-12 are essential in mediating the inflammatory response, while anti-inflammatory cytokines including interleukin-10 and transforming growth factor-β are important in the attenuation or containment of inflammatory process. It is increasingly recognized that cytokines have an im...

  19. Cytokines gene expression in newly diagnosed multiple sclerosis patients.

    OpenAIRE

    Seyed Javad Hasheminia; Sepideh Tolouei; Sayyed Hamid Zarkesh-Esfahani; Vahid Shaygannejad; Hedaiat Allah Shirzad; Reza Torabi; Morteza Hashem Zadeh Chaloshtory

    2015-01-01

    Multiple Sclerosis (MS) is characterized by multiple areas of inflammation, demyelination and neurodegeneration. Infiltrating Th1 CD4+ T cells secrete proinflammatory cytokines. They stimulate the release of some cytokines, expression of adhesion molecules and these cytokines may cause damage to the myelin sheath and axons. In this study, we analyzed plasma levels and gene expressions of five important cytokines in the new diagnosed MS Patients by ELISA and Real time PCR. PCR amplifications w...

  20. Proinflammatory and anti-inflammatory cytokines in meningococcal disease.

    OpenAIRE

    Riordan, F A; Marzouk, O; Thomson, A. P.; Sills, J A; Hart, C. A.

    1996-01-01

    Interleukin-10 (IL-10), an anti-inflammatory cytokine, was measured in 131 children with meningococcal disease. IL-10 concentrations were significantly higher in children who died and correlated positively with proinflammatory cytokines. Children who die from meningococcal disease have high IL-10 concentrations, which do not suppress proinflammatory cytokines.

  1. Intragraft Cytokine mRNA Expression After Clinical Organ Transplantation

    NARCIS (Netherlands)

    C.C. Baan (Carla)

    1998-01-01

    textabstractAs the knowledge of the cytokine network in experimental transplant models grows, we need to understand how and to what extent cytokines mediate the various donordirected immune events in clinical situations. This overview on clinical cytokine measurements shows that specific intragraft

  2. Screening the cytokines for diagnosis of tuberculous meningitis

    Institute of Scientific and Technical Information of China (English)

    王丽豪

    2014-01-01

    Objective To select cytokines for diagnosis of tuber-culous meningitis.Methods One hundred and twenty kinds of cytokines were detected with protein chips among two tuberculous meningitis cases,two viral meningitis cases and two noninfectious neurologic disease cases.The results were compared among different disease groups to select the differential cytokines,which were

  3. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    raises TNF-α and IL-6 to moderate levels, has only identified IL-6 as a potent cytokine, decreasing systemic amino acid levels and muscle protein metabolism. The marked decrease in circulatory and muscle amino acid concentrations was observed with a concomitant reduction in both the rates of muscle...... of IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability. SUMMARY: Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However...... protein synthesis and breakdown, that is, reduced turnover with a minor increase in net muscle degradation. Very similar observations have been made in models of acute inflammation, induced by high-dose endotoxin injection. However, these changes were suggested not to be attributed to a direct effect...

  4. Salivary cytokine levels in early gingival inflammation

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Damgaard, Christian; Könönen, Eija

    2017-01-01

    chemoattractant protein (MCP)-1, IL-1β, and IL-1 receptor antagonist (IL-1Ra) in gingival inflammation. Twenty-eight systemically and orally healthy nonsmokers abstained from oral hygiene protocols for 10 days. After that, self-performed cleaning was resumed for 14 days. Plaque and gingival indexes were measured......Salivary protein levels have been studied in periodontitis. However, there is lack of information on salivary cytokine levels in early gingival inflammation. The aim of this study was to determine salivary levels of vascular endothelial growth factor (VEGF), interleukin (IL)-8, monocyte......, and saliva samples were collected at days 1, 4, 7, 10, and 24. Salivary cytokines were detected with Luminex®-xMAP™. Salivary IL-1β, IL-1Ra, and VEGF levels decreased after 10 days' development of experimental gingivitis and reached baseline levels at the end of the 2-week resolution period. Salivary IL-8...

  5. Cytokines: muscle protein and amino acid metabolism

    DEFF Research Database (Denmark)

    van Hall, Gerrit

    2012-01-01

    raises TNF-α and IL-6 to moderate levels, has only identified IL-6 as a potent cytokine, decreasing systemic amino acid levels and muscle protein metabolism. The marked decrease in circulatory and muscle amino acid concentrations was observed with a concomitant reduction in both the rates of muscle...... protein synthesis and breakdown, that is, reduced turnover with a minor increase in net muscle degradation. Very similar observations have been made in models of acute inflammation, induced by high-dose endotoxin injection. However, these changes were suggested not to be attributed to a direct effect...... of IL-6 on the regulation of muscle protein metabolism but indirectly via IL-6 reducing amino acid availability. SUMMARY: Recent studies suggest that the best described cytokines TNF-α and IL-6 are unlikely to be the major direct mediators of muscle protein loss in inflammatory diseases. However...

  6. Effects of hemorrhage on cytokine gene transcription.

    Science.gov (United States)

    Shenkar, R; Abraham, E

    1993-08-01

    Injury and blood loss are often followed by infection and the rapid development of organ system dysfunction, frequently involving mucosal sites, such as the lung and intestine. To examine possible mechanisms contributing to these conditions, we used semiquantitative polymerase chain reactions to determine cytokine mRNA expression among cellular populations isolated from mucosal and systemic anatomic sites of mice at predetermined time points following 30% blood volume hemorrhage with resuscitation 1 hr later. Within 1 hr after hemorrhage, significant increases were observed in mRNA levels for IL-1 alpha, IL-1 beta, IL-5, and TGF-beta in intraparenchymal pulmonary mononuclear cells. The levels of TGF-beta transcripts among alveolar macrophages were increased 1 hr following blood loss, and increase in IL-1 alpha transcripts was found starting 2 hr posthemorrhage. Cells from Peyer's patches showed significant increases in mRNA levels for IL-1 beta, IL-2, IL-5, IL-6, IFN-gamma, and TGF-beta during the 4 hr following hemorrhage. Significant increases in mRNA levels for IL-1 beta, TNF-alpha, and TGF-beta were present within 4 hr of blood loss among cells isolated from mesenteric lymph nodes. The expression of mRNA for most cytokines was not significantly altered in splenocytes or peripheral blood mononuclear cells at any time point following hemorrhage. These experiments demonstrate that blood loss, even if resuscitated, produces significant increases in proinflammatory and immunoregulatory cytokine gene transcription as early as 1 hr following hemorrhage. These posthemorrhage alterations in cytokine mRNA expression were particularly prominent at mucosal sites, suggesting a mechanism for the increased incidence of pulmonary and intestinal involvement in organ system failure following severe blood loss and injury.

  7. Acute pancreatitis and fibromyalgia: Cytokine link

    Directory of Open Access Journals (Sweden)

    Sadat Muzammil

    2011-01-01

    Full Text Available Context: Fibromyalgia is a widespread musculoskeletal pain disorder found in 2% of the general population and with a preponderance of 85% in females, and has both genetic and environmental contribution. Acute pancreatitis is a severe condition and in most cases gallstones disease represents approximately half of the cases of acute pancreatitis, and 20-25% are related to alcohol abuse. Small numbers of cases are caused by a variety of other reasons but a few cases have no obvious cause, referred to as ′idiopathic′. Here we present a case where fibromyalgia might be linked to acute pancreatitis. We believe this has not been reported in this context in literature. Case Report: Fibromyalgia is a widespread musculoskeletal pain disorder found in 2% of the general population and with a preponderance of 85% in females, and has both genetic and environmental contribution. Patient had a cholecystectomy eight years previously. Patient feels tired almost all the time due to her fibromyalgia and requires family support for daily routine. Patient′s blood results showed alanine transaminase 527 IU/L, alkaline phosphatase 604 IU/L, bilirubin 34 μmol/L, amylase 2257 IU/L, C-reactive protein 19 mg/L, Gamma-Glutamyl transpeptidase 851 IU/L, renal function and electrolytes were within normal limits. The patient was admitted to the high dependency unit with a diagnosis of acute pancreatitis. Conclusion: There is a known increase in levels of cytokines in patients with fibromyalgia. Part of the pathophysiology of acute pancreatitis is related to raised cytokines and immune deregulations. We hypothesize that elevated levels of cytokines in fibromyalgia has led to acute pancreatitis in our patient. Further epidemiological research on the incidence of pancreatitis in cytokine mediated conditions such as fibromyalgia is required.

  8. Permissive Attitude Towards Drug Use, Life Satisfaction, and Continuous Drug Use Among Psychoactive Drug Users in Hong Kong.

    Science.gov (United States)

    Cheung, N Wt; Cheung, Y W; Chen, X

    2016-06-01

    To examine the effects of a permissive attitude towards regular and occasional drug use, life satisfaction, self-esteem, depression, and other psychosocial variables in the drug use of psychoactive drug users. Psychosocial factors that might affect a permissive attitude towards regular / occasional drug use and life satisfaction were further explored. We analysed data of a sample of psychoactive drug users from a longitudinal survey of psychoactive drug abusers in Hong Kong who were interviewed at 6 time points at 6-month intervals between January 2009 and December 2011. Data of the second to the sixth time points were stacked into an individual time point structure. Random-effects probit regression analysis was performed to estimate the relative contribution of the independent variables to the binary dependent variable of drug use in the last 30 days. A permissive attitude towards drug use, life satisfaction, and depression at the concurrent time point, and self-esteem at the previous time point had direct effects on drug use in the last 30 days. Interestingly, permissiveness to occasional drug use was a stronger predictor of drug use than permissiveness to regular drug use. These 2 permissive attitude variables were affected by the belief that doing extreme things shows the vitality of young people (at concurrent time point), life satisfaction (at concurrent time point), and self-esteem (at concurrent and previous time points). Life satisfaction was affected by sense of uncertainty about the future (at concurrent time point), self-esteem (at concurrent time point), depression (at both concurrent and previous time points), and being stricken by stressful events (at previous time point). A number of psychosocial factors could affect the continuation or discontinuation of drug use, as well as the permissive attitude towards regular and occasional drug use, and life satisfaction. Implications of the findings for prevention and intervention work targeted at

  9. Cytokines as biomarkers in rheumatoid arthritis.

    Science.gov (United States)

    Burska, Agata; Boissinot, Marjorie; Ponchel, Frederique

    2014-01-01

    RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria) and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge's relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA.

  10. Cytokines as Biomarkers in Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Agata Burska

    2014-01-01

    Full Text Available RA is a complex disease that develops as a series of events often referred to as disease continuum. RA would benefit from novel biomarker development for diagnosis where new biomarkers are still needed (even if progresses have been made with the inclusion of ACPA into the ACR/EULAR 2010 diagnostic criteria and for prognostic notably in at risk of evolution patients with autoantibody-positive arthralgia. Risk biomarkers for rapid evolution or cardiovascular complications are also highly desirable. Monitoring biomarkers would be useful in predicting relapse. Finally, predictive biomarkers for therapy outcome would allow tailoring therapy to the individual. Increasing numbers of cytokines have been involved in RA pathology. Many have the potential as biomarkers in RA especially as their clinical utility is already established in other diseases and could be easily transferable to rheumatology. We will review the current knowledge’s relation to cytokine used as biomarker in RA. However, given the complexity and heterogeneous nature of RA, it is unlikely that a single cytokine may provide sufficient discrimination; therefore multiple biomarker signatures may represent more realistic approach for the future of personalised medicine in RA.

  11. The role of cytokines in skin aging.

    Science.gov (United States)

    Borg, M; Brincat, S; Camilleri, G; Schembri-Wismayer, P; Brincat, M; Calleja-Agius, J

    2013-10-01

    Cutaneous aging is one of the major noticeable menopausal complications that most women want to fight in their quest for an eternally youthful skin appearance. It may contribute to some maladies that occur in aging which, despite not being life-threatening, affect the well-being, psychological state and quality of life of aged women. Skin aging is mainly affected by three factors: chronological aging, decreased levels of estrogen after menopause, and environmental factors. Aged skin is characterized by a decrease in collagen content and skin thickness which result in dry, wrinkled skin that is easily bruised and takes a longer time to heal. Cytokines play a crucial role in the manifestation of these features of old skin. The pro-inflammatory cytokine tumor necrosis factor-alpha inhibits collagen synthesis and enhances collagen degradation by increasing the production of MMP-9. It also lowers the skin immunity and thus increases the risk of cutaneous infections in old age. Deranged levels of several interleukins and interferons also affect the aging process. The high level of CCN1 protein in aged skin gives dermal fibroblasts an 'age-associated secretory phenotype' that causes abnormal homeostasis of skin collagen and leads to the loss of the function and integrity of skin. Further research is required especially to establish the role of cytokines in the treatment of cutaneous aging.

  12. Aggressive periodontitis and chronic arthritis: blood mononuclear cell gene expression and plasma protein levels of cytokines and cytokine inhibitors

    DEFF Research Database (Denmark)

    Sørensen, Lars K; Havemose-Poulsen, Anne; Bendtzen, Klaus

    2009-01-01

    BACKGROUND: Cytokines and cytokine inhibitors have been associated with many immunoinflammatory diseases. In the present study, we examined whether peripheral blood mononuclear cell (PBMC) gene expression mirrors the corresponding plasma levels of clinically important pro- and anti-inflammatory c......BACKGROUND: Cytokines and cytokine inhibitors have been associated with many immunoinflammatory diseases. In the present study, we examined whether peripheral blood mononuclear cell (PBMC) gene expression mirrors the corresponding plasma levels of clinically important pro- and anti...

  13. Informal transborder trade between México and Guatemala from permissive border perspective

    Directory of Open Access Journals (Sweden)

    Carlos Ernesto Ruiz Juárez

    2015-01-01

    Full Text Available This paper analyzes processes of interaction, tension, conflict and economic interests in one of the major border areas between Mexico and Guatemala. Informal transborder trade involves several actors who have been building these processes pursuant to agency initiatives. Among these actors, Guatemalan transborder traders who come to buy goods from their Mexican counterparts (retail and wholesale shop owners play a prominent role, as do the camareros who transport the traders and their merchandise across the Suchiate River on rafts and other actors such as moneychangers and rickshaw drivers who participate in economic and social interaction in the region. From a conceptual perspective, supported by the dialectical relationship between the notions of a border the behavior of transborder actors, it is concluded that in the study area, an informal border-trade integration process has developed and its actors transcend the border, rendering that border permissive.

  14. Anorexia nervosa complicated by diabetes mellitus: the case for permissive hyperglycemia.

    Science.gov (United States)

    Brown, Carrie; Mehler, Philip S

    2014-09-01

    The coexistence of Type 1 Diabetes Mellitus and anorexia nervosa results in an increased incidence of known diabetic complications such as retinopathy and nephropathy, presumably because blood glucose is difficult to control within the throes of comorbid anorexia nervosa. In addition, even when a diabetic patient with anorexia nervosa has committed to resolving his or her eating disorder, glucose control is again difficult and fraught with complexity and peril as will be highlighted in the following case report. Prudence dictates that strict glucose control is not indicated for the relatively short period of time that constitutes the early stage of refeeding in a patient with severe anorexia nervosa. Rather, "permissive hyperglycemia" may be the more optimal course to pursue, as a clinical strategy which is considerate of both the criticality of the refeeding treatment plan and of the long-term nature of the diabetic illness.

  15. [Probabilistic assessment of radionuclide accumulation in agricultural products and permissible levels of soil radioactive contamination].

    Science.gov (United States)

    Spiridonov, S I; Ivanov, V V

    2013-01-01

    A number of models have been developed to assess the risks of radionuclide accumulation in agricultural products and to determine the permissible levels of soil radioactive contamination. The proposed approach takes into account uncertainties of some parameters that describe the radionuclide content in different links of food chains. The models are implemented in the form of software for on-line computations. The validity of applying the probabilistic methods for assessing the impacts of radioactive fallout as compared with the deterministic ones is demonstrated on some specific examples. A universal nature of the dependence between the risks of radionuclide content in products and the density of soil contamination is shown. Contamination limits of the agricultural land are found to vary significantly as a function of the risk size. Directions for further research are defined within the framework of this research.

  16. Permissivity of insect cells to Waddlia chondrophila, Estrella lausannensis and Parachlamydia acanthamoebae.

    Science.gov (United States)

    Kebbi-Beghdadi, Carole; Fatton, Morgane; Greub, Gilbert

    2015-01-01

    Recent large scale studies questioning the presence of intracellular bacteria of the Chlamydiales order in ticks and fleas revealed that arthropods, similarly to mammals, reptiles, birds or fishes, can be colonized by Chlamydia-related bacteria with a predominant representation of the Rhabdochlamydiaceae and Parachlamydiaceae families. We thus investigated the permissivity of two insect cell lines towards Waddlia chondrophila, Estrella lausannensis and Parachlamydia acanthamoebae, three bacteria representative of three distinct families within the Chlamydiales order, all documented in ticks and/or in other arthropods. We demonstrated that W. chondrophila and E. lausannensis are able to very efficiently multiply in these insect cell lines. E. lausannensis however induced a rapid cytopathic effect, which somehow restricted its replication. P. acanthamoebae was not able to grow in these cell lines even if inclusions containing a few replicating bacteria could occasionally be observed.

  17. An EPQ model under cash discount and permissible delay in payments derived without derivatives

    Directory of Open Access Journals (Sweden)

    Huang Yung-Fu

    2007-01-01

    Full Text Available The main purpose of this paper is to investigate the case where the retailer’s unit selling price and the purchasing price per unit are not necessarily equal within the economic production quantity (EPQ framework under cash discount and permissible delay in payments. We establish the retailer’s inventory system as a cost minimization problem to determine the retailer’s optimal inventory cycle time, optimal order quantity and optimal payment time. This paper provides an algebraic approach to determine the optimal cycle time, optimal order quantity and optimal payment time. This approach provides one theorem to efficiently determine the optimal solution. Some previously published results of other researchers are deduced as special cases. Finally, numerical examples are given to illustrate the result and the managerial insights are also obtained.

  18. Analysis of Customary Institutions’ Position and Roles in Business Permission Bureaucracy: Case of Bali

    Directory of Open Access Journals (Sweden)

    Buddi Wibowo

    2016-12-01

    Full Text Available Uneven investment activities distribution in Bali result in economic disparity which causes not only social tension but also endanger cultural heritage. Preservation of Balinese culture could be threatened if economic and business activities are not managed properly and in line with efforts to preserve the culture of Bali in the long term. This study aims to assess the empirical and normative sociological legal jurisdiction over existing regulations related to economic and business activities in the Province of Bali which can be considered a potential threat to the preservation of Balinese culture and tradition. Based on the problem mapping that is the result of the empirical and normative juridical study, we are able to do the analysis of regulatory and institutional rearrangement of business and investment permission bureaucracy in the Bali province by considering the preservation of cultural and traditional law enforcement in Bali.

  19. Oral keratinocytes support non-replicative infection and transfer of harbored HIV-1 to permissive cells

    Directory of Open Access Journals (Sweden)

    Giacaman Rodrigo A

    2008-07-01

    Full Text Available Abstract Background Oral keratinocytes on the mucosal surface are frequently exposed to HIV-1 through contact with infected sexual partners or nursing mothers. To determine the plausibility that oral keratinocytes are primary targets of HIV-1, we tested the hypothesis that HIV-1 infects oral keratinocytes in a restricted manner. Results To study the fate of HIV-1, immortalized oral keratinocytes (OKF6/TERT-2; TERT-2 cells were characterized for the fate of HIV-specific RNA and DNA. At 6 h post inoculation with X4 or R5-tropic HIV-1, HIV-1gag RNA was detected maximally within TERT-2 cells. Reverse transcriptase activity in TERT-2 cells was confirmed by VSV-G-mediated infection with HIV-NL4-3Δenv-EGFP. AZT inhibited EGFP expression in a dose-dependent manner, suggesting that viral replication can be supported if receptors are bypassed. Within 3 h post inoculation, integrated HIV-1 DNA was detected in TERT-2 cell nuclei and persisted after subculture. Multiply spliced and unspliced HIV-1 mRNAs were not detectable up to 72 h post inoculation, suggesting that HIV replication may abort and that infection is non-productive. Within 48 h post inoculation, however, virus harbored by CD4 negative TERT-2 cells trans infected co-cultured peripheral blood mononuclear cells (PBMCs or MOLT4 cells (CD4+ CCR5+ by direct cell-to-cell transfer or by releasing low levels of infectious virions. Primary tonsil epithelial cells also trans infected HIV-1 to permissive cells in a donor-specific manner. Conclusion Oral keratinocytes appear, therefore, to support stable non-replicative integration, while harboring and transmitting infectious X4- or R5-tropic HIV-1 to permissive cells for up to 48 h.

  20. Retailer’s replenishment policies under conditions of permissible delay in payments

    Directory of Open Access Journals (Sweden)

    Huang Yung-Fu

    2004-01-01

    Full Text Available Goyal (1985 is frequently cited when the inventory systems under conditions of permissible delay in payments are discussed. Goyal implicitly assumed that: 1. The unit selling price and the unit purchasing price are equal; 2. At the end of the credit period, the account is settled. The retailer starts paying for higher interest charges on the items in stock and returns money of the remaining balance immediately when the items are sold. But these assumptions are debatable in real-life situations. The main purpose of this paper is to modify Goyal’s model to allow the unit selling price and the unit purchasing price not necessarily be equal to reflect the real-life situations. Furthermore, this paper will adopt different payment rule. We assume that the retailer uses sales revenue during the permissible credit period to make payment to the supplier at the end of the credit period. If it is not enough to pay off the purchasing cost of all items, the retailer will pay off the remaining balance by taking loan from the bank. So, the retailer starts paying for the interest charges on the amount of loan from the bank after the account is settled. Then the retailer will return money to the bank at the end of the inventory cycle. Under these conditions, we model the retailer’s inventory system as a cost minimization problem to determine the retailer’s optimal cycle time and optimal order quantity. Four cases are developed to efficiently determine the optimal cycle time and the optimal order quantity. Numerical examples are given to illustrate these cases. Comparing with Goyal’s model, we also find that the optimal cycle times in this paper are not longer than those of Goyal’s model.

  1. Between reason and coercion: ethically permissible influence in health care and health policy contexts.

    Science.gov (United States)

    Blumenthal-Barby, J S

    2012-12-01

    In bioethics, the predominant categorization of various types of influence has been a tripartite classification of rational persuasion (meaning influence by reason and argument), coercion (meaning influence by irresistible threats-or on a few accounts, offers), and manipulation (meaning everything in between). The standard ethical analysis in bioethics has been that rational persuasion is always permissible, and coercion is almost always impermissible save a few cases such as imminent threat to self or others. However, many forms of influence fall into the broad middle terrain-and this terrain is in desperate need of conceptual refining and ethical analysis in light of recent interest in using principles from behavioral science to influence health decisions and behaviors. This paper aims to address the neglected space between rational persuasion and coercion in bioethics. First, I argue for conceptual revisions that include removing the "manipulation" label and relabeling this space "nonargumentative influence," with two subtypes: "reason-bypassing" and "reason-countering." Second, I argue that bioethicists have made the mistake of relying heavily on the conceptual categories themselves for normative work and instead should assess the ethical permissibility of a particular instance of influence by asking several key ethical questions, which I elucidate, that relate to (1) the impact of the form of influence on autonomy and (2) the relationship between the influencer and the influenced. Finally, I apply my analysis to two examples of nonargumentative influence in health care and health policy: (1) governmental agencies such as the Food and Drug Administration (FDA) trying to influence the public to be healthier using nonargumentative measures such as vivid images on cigarette packages to make more salient the negative effects of smoking, and (2) a physician framing a surgery in terms of survival rates instead of mortality rates to influence her patient to consent to

  2. Rheumatoid arthritis pathophysiology: update on emerging cytokine and cytokine-associated cell targets.

    Science.gov (United States)

    Furst, Daniel E; Emery, Paul

    2014-09-01

    Biologic therapies that target pathogenic cytokines such as TNF, IL-1β or IL-6 have greatly improved the treatment of RA. Unfortunately, not all RA patients respond to current biologic therapies and responses are not always maintained, suggesting that there are alternative drivers of RA pathogenesis that might serve as promising therapeutic targets. Discovery of the new Th17 subset of Th cells, and their role in autoimmune disease development, has implicated the proinflammatory IL-12 and IL-17 families of cytokines in RA disease pathogenesis. Members of these cytokine families are elevated in the blood and joints of RA patients and have been shown to remain elevated in patients who do not respond to current biologics. In addition, these cytokines have been shown to play roles in joint destruction and erosion. A new subclass of biologics that target the IL-12 and/or IL-17 signalling pathways are under development. Here we review evidence for a role of Th17 cells as well as IL-12 and IL-17 cytokines in RA pathogenesis as the rationale for a subsequent discussion of the ongoing and completed clinical trials of newly emerging biologic therapies directed at IL-12 or IL-17 pathway inhibition.

  3. Cytokines profile in hypertensive patients with left ventricular remodeling and dysfunction.

    Science.gov (United States)

    Kuznetsova, Tatiana; Haddad, Francois; Knez, Judita; Rosenberg-Hasson, Yael; Sung, Janine; Cauwenberghs, Nicholas; Thijs, Lutgarde; Karakikes, Ioannis; Maecker, Holden; Mahaffey, Kenneth W; Wu, Joseph C; Staessen, Jan A

    2015-12-01

    There is strong evidence that inflammatory mediators play a key role in the progression to heart failure in patients with systemic hypertension (HTN). The present study aimed to identify a set of cytokines that are associated with early left ventricular (LV) remodeling and dysfunction as captured by echocardiography in patients with HTN in a cross-sectional case-control study nested within the FLEMish study on ENvironment, Genes and Health Outcome. We identified three groups of participants from the cohort: normotensive subjects (normotension; n = 30), HTN with normal LV structure and function (HTN [LV-]; n = 30), and HTN with evidence of adverse LV remodeling (HTN [LV+]; n = 50). We measured cytokines using a 63-plex Luminex platform. Using partial least squares-discriminant analysis, we constructed three latent variables from the measured cytokines that explained 35%-45% of the variance between groups. We identified five common cytokines (interleukin 18, monokine induced by gamma interferon, hepatocyte growth factor, epithelial neutrophil-activating peptide 78, and vascular endothelial growth factor D) with a stable signal which had a major impact on the construction of the latent variables. Among these cytokines, after adjustment for confounders, interleukin 18 remained significantly different between HTN participants with and without LV involvement (P = .02). Moreover, granulocyte-macrophage colony-stimulating factor and leptin showed a consistent upward trend in all HTN patients compared with normotensive subjects. In conclusion, in HTN patients with LV remodeling or/and dysfunction, we identified a set of cytokines strongly associated with LV maladaptation. We also found a distinct profile of inflammatory biomarkers that characterize HTN.

  4. Modulation of PBMC-decay accelerating factor (PBMC-DAF) and cytokines in rheumatoid arthritis.

    Science.gov (United States)

    Pahwa, Roma; Kumar, Uma; Das, Nibhriti

    2016-03-01

    Studies have suggested that abnormal expression of complement regulatory proteins and cytokines contribute significantly to the path-physiology of rheumatoid arthritis. In this context, Decay accelerating factor (DAF) a complement regulatory protein is gaining increased attention. With the notion that immune effecter mechanisms are all interlinked and circulating peripheral blood mononuclear cells (PBMCs) should have a role in a systemic disease like rheumatoid arthritis, we studied the modulation and significance of PBMC-DAF and cytokines in RA. Seventy-five RA patients and 75 healthy controls were recruited. Expression of DAF and cytokines (IFN-γ, IL-17A and IL-10) in the PBMCs of patients and controls was determined. Correlations among DAF, cytokines, and disease activity were evaluated by standard statistical methods. The effect of IFN-γ, IL-17A, and IL-10 on the expression of DAF in patients and controls was studied in vitro. Expression of PBMC-DAF declined in patients both at mRNA and surface level and correlated negatively with the disease activity. Expression of IFN-γ also declined in patients but correlated positively with DAF and negatively with disease activity. Expression of IL-17A and IL-10 was higher in patients. The levels correlated positively with disease activity and negatively with DAF both in patients and controls. In vitro studies indicated that IFN-γ up-regulated DAF expression in PBMCs, whereas IL-17A and IL-10 had negative effect on the same. The decline in the PBMC-DAF is a contributing factor in manifestations of RA. Cytokine environment contributes to this decline. These findings brought novel insights into the complement-cytokine axis in the path-physiology of RA.

  5. Associations of health risk behaviors with school absenteeism. Does having permission for the absence make a difference?

    Science.gov (United States)

    Eaton, Danice K; Brener, Nancy; Kann, Laura K

    2008-04-01

    Nearly 10% of students enrolled in US public schools are absent daily. Although previous research has shown associations of school absenteeism with participation in risk behaviors, it is unclear if these associations vary by whether the absence was excused. The purpose of this study was to examine the associations of health risk behaviors with being absent from school with and without permission among high school students. During spring 2004, questionnaires similar to the Youth Risk Behavior Survey questionnaire were completed by 4517 ninth- and eleventh-grade students. Responses to items assessing frequency of school absences during the past 30 days for any reason and without permission were combined to create a variable coded as absent on: 0 days; > or =1 day, all with permission (WP); and > or =1 day, at least 1 day without permission (WOP). Logistic regression analyses controlling for gender, grade, and race/ethnicity examined the association of risk behaviors with absenteeism. Controlling for demographic variables, compared to students who were absent 0 days, students who were absent WP had significantly higher odds of engaging in 25 of 55 risk behaviors examined and students who were absent WOP had significantly higher odds of engaging in 43 of the 55 behaviors. Students who were absent WOP also had approximately twice the odds of engaging in risk behaviors compared to students who were absent WP. School absenteeism, with and without permission, is associated with risk behaviors. Schools should recognize absenteeism for any reason as a warning sign for a variety of risk behaviors.

  6. Cytokines: The Good, the Bad, and the Deadly.

    Science.gov (United States)

    Ramani, Thulasi; Auletta, Carol S; Weinstock, Daniel; Mounho-Zamora, Barbara; Ryan, Patricia C; Salcedo, Theodora W; Bannish, Gregory

    2015-01-01

    Over the past 30 years, the world of pharmaceutical toxicology has seen an explosion in the area of cytokines. An overview of the many aspects of cytokine safety evaluation currently in progress and evolving strategies for evaluating these important entities was presented at this symposium. Cytokines play a broad role to help the immune system respond to diseases, and drugs which modulate their effect have led to some amazing therapies. Cytokines may be "good" when stimulating the immune system to fight a foreign pathogen or attack tumors. Other "good" cytokine effects include reduction of an immune response, for example interferon β reduction of neuron inflammation in patients with multiple sclerosis. They may be "bad" when their expression causes inflammatory diseases, such as the role of tumor necrosis factor α in rheumatoid arthritis or asthma and Crohn's disease. Therapeutic modulation of cytokine expression can help the "good" cytokines to generate or quench the immune system and block the "bad" cytokines to prevent damaging inflammatory events. However, care must be exercised, as some antibody therapeutics can cause "ugly" cytokine release which can be deadly. Well-designed toxicology studies should incorporate careful assessment of cytokine modulation that will allow effective therapies to treat unmet needs. This symposium discussed lessons learned in cytokine toxicology using case studies and suggested future directions.

  7. Regulation of cytokines by small RNAs during skin inflammation

    Directory of Open Access Journals (Sweden)

    Mikkelsen Jacob G

    2010-07-01

    Full Text Available Abstract Intercellular signaling by cytokines is a vital feature of the innate immune system. In skin, an inflammatory response is mediated by cytokines and an entwined network of cellular communication between T-cells and epidermal keratinocytes. Dysregulated cytokine production, orchestrated by activated T-cells homing to the skin, is believed to be the main cause of psoriasis, a common inflammatory skin disorder. Cytokines are heavily regulated at the transcriptional level, but emerging evidence suggests that regulatory mechanisms that operate after transcription play a key role in balancing the production of cytokines. Herein, we review the nature of cytokine signaling in psoriasis with particular emphasis on regulation by mRNA destabilizing elements and the potential targeting of cytokine-encoding mRNAs by miRNAs. The proposed linkage between mRNA decay mediated by AU-rich elements and miRNA association is described and discussed as a possible general feature of cytokine regulation in skin. Moreover, we describe the latest attempts to therapeutically target cytokines at the RNA level in psoriasis by exploiting the cellular RNA interference machinery. The applicability of cytokine-encoding mRNAs as future clinical drug targets is evaluated, and advances and obstacles related to topical administration of RNA-based drugs targeting the cytokine circuit in psoriasis are described.

  8. How does Chinese medicine target cytokine imbalance in rheumatoid arthritis?

    Science.gov (United States)

    Liu, Jian; Sun, Yue

    2013-11-01

    Rheumatoid arthritis (RA) manifests as an imbalance between pro- and anti-inflammatory cytokines. Cytokine imbalance is suggested to play critical roles in the development of RA. Currently, various treatments for RA, including biological agents such as antibodies against inflammation mediators, or Chinese herbal medicines, intervene the disease by restoring the balance of cytokines. Chinese medicine (CM) can not only suppress the expression of pro-inflammatory cytokines, but also induce the expression of cytokines with anti-inflammatory and immunomodulatory effects. Thus, Chinese medicine can effectively reduce inflammatory cell infiltration into synovial tissue, pannus formation, and degradation of the extracellular matrix surrounding cartilage cells, thereby reducing subchondral bone damage. This paper reviews the changes of cytokine profiling during development of RA and discuss the mechanisms by which Chinese medicine restores the cytokine balance.

  9. Cytokines: Names and Numbers You Should Care About.

    Science.gov (United States)

    Holdsworth, Stephen R; Gan, Poh-Yi

    2015-12-07

    Cytokines play an important role in host defense against microorganisms. They orchestrate innate immunity by inducing protective local inflammation and systemic acute phase responses. Cytokines are important in initiating, amplifying, directing, mediating, and regulating adaptive immunity. Unfortunately, they may also direct tissue damage if excessive responses occur or if they are involved in directing and mediating autoimmunity. Under these circumstances, cytokines are potential therapeutic targets. Over the last 20 years, we have seen the successful development and clinical implementation of biologic strategies that target key cytokines in specific inflammatory diseases with efficacy, specificity, and toxicity profiles challenging conventional drug therapies. These therapies are finding new applications and many new agents show promise. Unfortunately, these new cytokine-based therapies have had little effect on renal disease. This review provides evidence that common renal diseases, including those causing AKI and the autoimmune proliferative and crescentic forms of GN, have cytokine mediation profiles that suggest they would be susceptible to cytokine-targeting therapeutic strategies.

  10. Modulation of monocyte/macrophage-derived cytokine and chemokine profile by persistent Hepatitis C virus (HCV infection leads to chronic inflammation

    Directory of Open Access Journals (Sweden)

    Penelope Mavromara

    2012-02-01

    Full Text Available HCV infection presents a major public health problem, with more than 170 million people infected worldwide. Chronicity and persistence of infection constitute the hallmark of the disease. Although HCV is a hepatotropic virus, subsets of immune cells have been found to be permissive to infection and viral replication. Peripheral blood monocytes, attracted to the site of infection and differentiated into macrophages, and resident hepatic macrophages, known as Kupffer cells, are important mediators of innate immunity, through production of several chemokines and cytokines in addition to their phagocytic activity. HCV proteins have been shown to modulate the cytokine and chemokine production profile of monocytes/macrophages, as it is suggested by both in vitro and clinical studies. This modified expression profile appears crucial for the establishment of aberrant inflammation that leads to liver cirrhosis and hepatocellular carcinoma.

  11. Cytokines, cytokine gene polymorphisms and Helicobacter pylori infection: friend or foe?

    Science.gov (United States)

    Figueiredo, Camila A; Marques, Cintia Rodrigues; Costa, Ryan dos Santos; da Silva, Hugo Bernardino F; Alcantara-Neves, Neuza M

    2014-05-14

    Helicobacter pylori (H. pylori) is a flagellated, spiral-shaped, microaerophilic Gram-negative bacillus that colonises the gastric mucosa of more than 50% of the human population. Infection is a risk factor for gastritis, ulcer disease and stomach cancer. Immunity against H. pylori is mainly related to Th1/Th17 skewing, and the activation of regulatory T cells is the main strategy used to limit inflammatory responses, which can result in the pathogen persistence and can lead to chronic gastrointestinal diseases, including cancer. Furthermore, host genetic factors that affect cytokines may determine differences in the susceptibility to many diseases. In this review, we present the cytokine profiles and the main cytokine gene polymorphisms associated with resistance/susceptibility to H. pylori and discuss how such polymorphisms may influence infection/disease outcomes.

  12. Herpesvirus saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor.

    Science.gov (United States)

    Yao, Zhengbin; Fanslow, William C; Seldin, Michael F; Rousseau, Anne-Marie; Painter, Sally L; Comeau, Michael R; Cohen, Jeffrey I; Spriggs, Melanie K

    2011-11-01

    Herpesvirus Saimiri gene 13 (HVS13) exhibits 57% identity with the predicted sequence of a T cell-derived molecule termed CTLA8. Recombinant HVS13 and CTLA8 stimulate transcriptional factor NF-kappaB activity and Interleukin-6 (IL-6) secretion in fibroblasts, and costimulate T cell proliferation. An HVS13.Fc fusion protein was used to isolate a cDNA encoding a novel receptor that also binds CTLA8. This receptor is unrelated to previously identified cytokine receptor families. A recombinant soluble receptor inhibited T cell proliferation and IL-2 production induced by PHA, concanavalin A (conA), and anti-TCR MAb. These results define CTLA8 and HVS13 as novel cytokines that bind to a novel cytokine receptor. We propose to call these molecules IL-17, vIL-17, and IL-17R, respectively.

  13. Solution assembly of cytokine receptor ectodomain complexes

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zining; Ciardelli, T.L. [Dartmouth Medical School, Hanover, NH (United States). Dept. of Pharmacology and Toxicology; Johnson, K.W. [Chiron Corp., Emeryville, CA (United States)] [and others

    1995-09-01

    For the majority of single transmembrane-spanning cell surface receptors, signal transmission across the lipid bilayer barrier involves several discrete components of molecular recognition. The interaction between ligand and the extracellular segment of its cognate receptor (ectodomain) initiates either homomeric or heteromeric association of receptor subunits. Specific recognition among these subunits may then occur between ectodomain regions, within the membrane by interhelical contact or inside the cell between cytoplasmic domains. Any or all of these interactions may contribute to the stability of the signaling complex. It is the characteristics of ligand binding by the ectodomains of these receptors that controls the heteromeric or homomeric nature and the stoichiometry of the complex. Cytokines and their receptors belong to a growing family of macromolecular systems that exhibit these functional features and share many structural similarities as well. Interleukin-2 is a multifunctional cytokine that represents, perhaps, the most complex example to date of ligand recognition among the hematopoietin receptor family. It is the cooperative binding of IL-2 by all three proteins on the surface of activated T-lymphocytes, however, that ultimately results in crosslinking of the {beta}- and {gamma}-subunits and signaling via association of their cytoplasmic domains. Although the high-affinity IL-2R functions as a heterotrimer, heterodimers of the receptor subunits are also physiologically important. The {alpha}/{beta} heterodimer or {open_quotes}pseudo-high affinity{close_quotes} receptor captures IL-2 as a preformed cell surface complex while the {beta}/{gamma} intermediate affinity site exists, in the absence of the {alpha} subunit, on the majority of natural killer cells. We have begun to study stable complexes of cytokine receptor ectodomains of defined composition and that mimic the ligand binding characteristics of the equivalent cell surface receptor sites.

  14. Cytokines in the modulation of eosinophilia

    Directory of Open Access Journals (Sweden)

    Faccioli Lúcia H

    1997-01-01

    Full Text Available In this review we discuss our recently results showing interleukin 5 (IL-5 involvement in eosinophil migration and in the maintenance of eosinophilia in blood, bone marrow, lung and peritoneal cavity, in a visceral larva migrans syndrome model using guinea-pigs infected with Toxocara canis. We also describe the sequential release of TNF-alpha and IL-8 during the course of infection, and the interaction between these cytokines and IL-5 during infection. Finally we propose a new biological role for IL-5, at least in our model, as a modulator of IL-8 release and secretion.

  15. Chronic pain: cytokines, lymphocytes and chemokines.

    Science.gov (United States)

    de Miguel, Marcia; Kraychete, Durval Campos; Meyer Nascimento, Roberto Jose

    2014-01-01

    Chronic pain is a debilitating condition and, in most cases, difficult to treat. A prominent example of this is neuropathic pain. Understanding pathophysiological mechanisms of pain and, therefore, making this knowledge into an effective treatment is still a challenge to experts. Pain can now be considered as a neuro-immune disorder, since recent data indicate critical involvement of innate and adaptive immune responses following injury, and this interaction plays an important role in the onset and perpetuation of chronic pain. The aim of this article is to review the relationship between immune system and chronic pain, especially about neuropathic pain, and focusing on cytokines, chemokines and lymphocytes.

  16. AUTOPHAGY AND IL-1 FAMILY CYTOKINES

    Directory of Open Access Journals (Sweden)

    James Harris

    2013-01-01

    Full Text Available Autophagy is an important intracellular homeostatic mechanism for the targeting of cytosolic constituents, including organelles, for lysosomal degradation. Autophagy plays roles in numerous physiological processes, include immune cell responses to endogenous and exogenous pathogenic stimuli. Moreover, autophagy has a potentially pivotal role in the regulation of inflammatory responses. In particular, autophagy regulates endogenous inflammasome activators, as well as inflammasome components and pro-IL-1β. This review focuses specifically on the role autophagy plays in regulating the production, processing and secretion of IL-1 family cytokines.

  17. Standardization of cytokine flow cytometry assays

    Directory of Open Access Journals (Sweden)

    Cox Josephine

    2005-06-01

    Full Text Available Abstract Background Cytokine flow cytometry (CFC or intracellular cytokine staining (ICS can quantitate antigen-specific T cell responses in settings such as experimental vaccination. Standardization of ICS among laboratories performing vaccine studies would provide a common platform by which to compare the immunogenicity of different vaccine candidates across multiple international organizations conducting clinical trials. As such, a study was carried out among several laboratories involved in HIV clinical trials, to define the inter-lab precision of ICS using various sample types, and using a common protocol for each experiment (see additional files online. Results Three sample types (activated, fixed, and frozen whole blood; fresh whole blood; and cryopreserved PBMC were shipped to various sites, where ICS assays using cytomegalovirus (CMV pp65 peptide mix or control antigens were performed in parallel in 96-well plates. For one experiment, antigens and antibody cocktails were lyophilised into 96-well plates to simplify and standardize the assay setup. Results (CD4+cytokine+ cells and CD8+cytokine+ cells were determined by each site. Raw data were also sent to a central site for batch analysis with a dynamic gating template. Mean inter-laboratory coefficient of variation (C.V. ranged from 17–44% depending upon the sample type and analysis method. Cryopreserved peripheral blood mononuclear cells (PBMC yielded lower inter-lab C.V.'s than whole blood. Centralized analysis (using a dynamic gating template reduced the inter-lab C.V. by 5–20%, depending upon the experiment. The inter-lab C.V. was lowest (18–24% for samples with a mean of >0.5% IFNγ + T cells, and highest (57–82% for samples with a mean of Conclusion ICS assays can be performed by multiple laboratories using a common protocol with good inter-laboratory precision, which improves as the frequency of responding cells increases. Cryopreserved PBMC may yield slightly more

  18. Cytokines and Pancreatic β-Cell Apoptosis.

    Science.gov (United States)

    Berchtold, L A; Prause, M; Størling, J; Mandrup-Poulsen, T

    The discovery 30 years ago that inflammatory cytokines cause a concentration, activity, and time-dependent bimodal response in pancreatic β-cell function and viability has been a game-changer in the fields of research directed at understanding inflammatory regulation of β-cell function and survival and the causes of β-cell failure and destruction in diabetes. Having until then been confined to the use of pathophysiologically irrelevant β-cell toxic chemicals as a model of β-cell death, researchers could now mimic endocrine and paracrine effects of the cytokine response in vitro by titrating concentrations in the low to the high picomolar-femtomolar range and vary exposure time for up to 14-16h to reproduce the acute regulatory effects of systemic inflammation on β-cell secretory responses, with a shift to inhibition at high picomolar concentrations or more than 16h of exposure to illustrate adverse effects of local, chronic islet inflammation. Since then, numerous studies have clarified how these bimodal responses depend on discrete signaling pathways. Most interest has been devoted to the proapoptotic response dependent upon mainly nuclear factor κ B and mitogen-activated protein kinase activation, leading to gene expressional changes, endoplasmic reticulum stress, and triggering of mitochondrial dysfunction. Preclinical studies have shown preventive effects of cytokine antagonism in animal models of diabetes, and clinical trials demonstrating proof of concept are emerging. The full clinical potential of anticytokine therapies has yet to be shown by testing the incremental effects of appropriate dosing, timing, and combinations of treatments. Due to the considerable translational importance of enhancing the precision, specificity, and safety of antiinflammatory treatments of diabetes, we review here the cellular, preclinical, and clinical evidence of which of the death pathways recently proposed in the Nomenclature Committee on Cell Death 2012

  19. An EOQ model for three parameter Weibull deterioration with permissible delay in payments and associated salvage value

    Directory of Open Access Journals (Sweden)

    L. M. Pradhan

    2012-01-01

    Full Text Available This paper deals with the development of an inventory model for Weibull deteriorating items with constant demand when delay in payments is allowed to the retailer to settle the account against the purchases made. Shortages are not allowed and the salvage value is associated with the deteriorated units. In this paper, we consider two cases; those are for the case payment within the permissible time and for payment after the expiry of permissible time with interest. Numerical examples are provided to illustrate our results. Sensitivity analysis are carried out to analyze the effect of changes in the optimal solution with respect to change in one parameter at a time.

  20. Cheap and Effective System for Parking Avoidance of the Car Without Permission at Disabled Parking Permit Spaces

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2013-10-01

    Full Text Available Cheap and effective system for parking avoidance of the car without permission at Disabled Parking Permit: DPP spaces is proposed. The proposed system is validated through some experiments. Multiple methods for detection of car in the DPP space using ultrasound sensors, Near Infrared: NIR cameras, RFID writer and reader with IC card, IC chip and IC tag as well as ETC system and GPS receiver are proposed. It is found that these proposed car detection systems work well. Furthermore, it is effective if more than two systems out of the proposed car detection systems are used for avoid car parking without permission.

  1. HIV-1 imposes rigidity on blood and semen cytokine networks.

    Science.gov (United States)

    Lisco, Andrea; Introini, Andrea; Munawwar, Arshi; Vanpouille, Christophe; Grivel, Jean-Charles; Blank, Paul; Singh, Sarman; Margolis, Leonid

    2012-12-01

    Although it is established that the levels of individual cytokines are altered by HIV-1 infection, the changes in cytokine interrelations that organize them into networks have been poorly studied. Here, we evaluated these networks in HIV-infected and HIV-uninfected individuals in fluid compartments that are critical for HIV-1 pathogenesis and transmission, namely blood and semen. In samples collected from therapy-naïve HIV-1-infected and HIV-1-uninfected individuals, we measured HIV-1-load, CD4 cell count, and levels of 21 cytokines using a multiplex bead assay. Cytokine networks in blood and semen were different for HIV-1-infected and HIV-1-uninfected individuals. In both compartments of HIV-1-infected individuals, the cytokine networks were more interlocked than in controls: HIV-1 infection resulted in the establishment of new correlations and in the strengthening of pre-existing correlations between different cytokines. In blood and semen of HIV-infected patients, there were, respectively, 68 and 72 statistically significant correlations between cytokines, while in uninfected individuals, there were 18 and 21 such correlations. HIV-1 infection reorganizes the cytokine networks, establishing new strong correlations between various cytokines and thus imposes a high rigidity on the cytokine network. This rigidity may reflect the impairment of the ability of the immune system to respond to microbial challenges. © 2012 John Wiley & Sons A/S.

  2. Macrophage cytokines: Involvement in immunity and infectious diseases

    Directory of Open Access Journals (Sweden)

    Guillermo eArango Duque

    2014-10-01

    Full Text Available The evolution of macrophages has made them primordial for both development and immunity. Their functions range from the shaping of body plans to the ingestion and elimination of apoptotic cells and pathogens. Cytokines are small soluble proteins that confer instructions and mediate communication among immune and non-immune cells. A portfolio of cytokines is central to the role of macrophages as sentries of the innate immune system that mediate the transition from innate to adaptive immunity. In concert with other mediators, cytokines bias the fate of macrophages into a spectrum of inflammation-promoting ‘classically activated’, to anti-inflammatory or ‘alternatively activated’ macrophages. Deregulated cytokine secretion is implicated in several disease states ranging from chronic inflammation to allergy. Macrophages release cytokines via a series of beautifully orchestrated pathways that are spatiotemporally regulated. At the molecular level, these exocytic cytokine secretion pathways are coordinated by multi-protein complexes that guide cytokines from their point of synthesis to their ports of exit into the extracellular milieu. These trafficking proteins, many of which were discovered in yeast and commemorated in the 2013 Nobel Prize in Physiology or Medicine, coordinate the organelle fusion steps that are responsible for cytokine release. This review discusses the functions of cytokines secreted by macrophages, and summarizes what is known about their release mechanisms. This information will be used to delve into how selected pathogens subvert cytokine release for their own survival.

  3. Obesity Related Alterations in Plasma Cytokines and Metabolic Hormones in Chimpanzees

    Directory of Open Access Journals (Sweden)

    Pramod Nehete

    2014-01-01

    Full Text Available Obesity is characterized by chronic low-grade inflammation and serves as a major risk factor for hypertension, coronary artery disease, dyslipidemias, and type-2 diabetes. The purpose of this study was to examine changes in metabolic hormones, inflammatory cytokines, and immune function, in lean, overweight, and obese chimpanzees in a controlled environment. We observed increased plasma circulating levels of proinflammatory TH-1 cytokines, Interferon gamma, interleukin-6, interleukin-12p40, tumor necrosis factor, soluble CD40 ligand, and Interleukin-1β and anti-inflammatory TH-2 cytokines, Interleukin-4, Interleukin-RA, Interleukin-10, and Interleukin-13 in overweight and obese chimpanzees. We also observed increased levels of metabolic hormones glucagon-like-peptide-1, glucagon, connecting peptide, insulin, pancreatic peptide YY3–36, and leptin in the plasma of overweight and obese chimpanzees. Chemokine, eotaxin, fractalkine, and monocyte chemoattractant protein-1 were higher in lean compared to obese chimpanzees, while chemokine ligand 8 increased in plasma of obese chimpanzees. We also observed an obesity-related effect on immune function as demonstrated by lower mitogen induced proliferation, and natural killer activity and higher production of IFN-γ by PBMC in Elispot assay, These findings suggest that lean, overweight, and obese chimpanzees share circulating inflammatory cytokines and metabolic hormone levels with humans and that chimpanzees can serve as a useful animal model for human studies.

  4. Ghrelin's Effects on Proinflammatory Cytokine Mediated Apoptosis and Their Impact on β-Cell Functionality

    Science.gov (United States)

    Diaz-Ganete, Antonia; Baena-Nieto, Gloria; Lomas-Romero, Isabel M.; Lopez-Acosta, Jose Francisco; Cozar-Castellano, Irene; Medina, Francisco; Segundo, Carmen; Lechuga-Sancho, Alfonso M.

    2015-01-01

    Ghrelin is a peptidic hormone, which stimulates cell proliferation and inhibits apoptosis in several tissues, including pancreas. In preclinical stage of type 1 diabetes, proinflammatory cytokines generate a destructive environment for β-cells known as insulitis, which results in loss of β-cell mass and impaired insulin secretion, leading to diabetes. Our aim was to demonstrate that ghrelin could preserve β-cell viability, turnover rate, and insulin secretion acting as a counter balance of cytokines. In the present work we reproduced proinflammatory milieu found in insulitis stage by treating murine cell line INS-1E and rat islets with a cytokine cocktail including IL-1β, IFNγ, and TNFα and/or ghrelin. Several proteins involved in survival pathways (ERK 1/2 and Akt/PKB) and apoptosis (caspases and Bcl-2 protein family and endoplasmic reticulum stress markers) as well as insulin secretion were analyzed. Our results show that ghrelin alone has no remarkable effects on β-cells in basal conditions, but interestingly it activates cell survival pathways, downregulates apoptotic mediators and endoplasmic reticulum stress, and restores insulin secretion in response to glucose when beta-cells are cytokine-exposed. These data suggest a potential role of ghrelin in preventing or slowing down the transition from a preclinical to clinically established diabetes by ameliorating the effects of insulitis on β-cells. PMID:26257781

  5. In vitro investigation of the roles of the proinflammatory cytokines tumor necrosis factor-α and interleukin-1 in murine osteoclastogenesis.

    Science.gov (United States)

    Jules, Joel; Feng, Xu

    2014-01-01

    Whereas the monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator of NF-кB ligand (RANKL) are essential and sufficient for osteoclastogenesis, a number of other cytokines including two proinflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1 (IL-1), can exert profound effects on the osteoclastogenic process. However, the precise mode of action of TNF-α and IL-1 in osteoclastogenesis remains controversial. While some groups demonstrated that these two cytokines can promote murine osteoclastogenesis in vitro in the presence of M-CSF only, we and others showed that TNF-α-/IL-1-mediated osteoclastogenesis requires permissive levels of RANKL. This chapter describes the method that we have used to investigate the effects of TNF-α and IL-1 on osteoclast formation in in vitro osteoclastogenesis assays using primary murine bone marrow macrophages (BMMs). Detailed experimental conditions are provided and critical points are discussed to help the reader use the method to independently evaluate the roles of TNF-α and IL-1 in osteoclastogenesis in vitro. Moreover, this method can be used to further elucidate the signaling mechanisms by which these two cytokines act in concert with RANKL or with each other to modulate osteoclastogenesis.

  6. Relationship of cytokines and cytokine signaling to immunodeficiency disorders in the mouse

    Directory of Open Access Journals (Sweden)

    Morawetz R.A.

    1998-01-01

    Full Text Available The contributions of cytokines to the development and progression of disease in a mouse model of retrovirus-induced immunodeficiency (MAIDS are controversial. Some studies have indicated an etiologic role for type 2 cytokines, while others have emphasized the importance of type 1 cytokines. We have used mice deficient in expression of IL-4, IL-10, IL-4 and IL-10, IFN-g, or ICSBP - a transcriptional protein involved in IFN signaling - to examine their contributions to this disorder. Our results demonstrate that expression of type 2 cytokines is an epiphenomenon of infection and that IFN-g is a driving force in disease progression. In addition, exogenously administered IL-12 prevents many manifestations of disease while blocking retrovirus expression. Interruption of the IFN signaling pathways in ICSBP-/- mice blocks induction of MAIDS. Predictably, ICSBP-deficient mice exhibit impaired responses to challenge with several other viruses. This immunodeficiency is associated with impaired production of IFN-g and IL-12. Unexpectedly, however, the ICSBP-/- mice also develop a syndrome with many similarities to chronic myelogenous leukemia in humans. The chronic phase of this disease is followed by a fatal blast crisis characterized by clonal expansions of undifferentiated cells. ICSBP is thus an important determinant of hematopoietic growth and differentiation as well as a prominent signaling molecule for IFNs

  7. Boswellia carterii extract inhibits TH1 cytokines and promotes TH2 cytokines in vitro.

    Science.gov (United States)

    Chevrier, Marc R; Ryan, Abigail E; Lee, David Y-W; Zhongze, Ma; Wu-Yan, Zhang; Via, Charles S

    2005-05-01

    Traditional herbal formulas used to treat inflammatory arthritis in China and India include Boswellia carterii or Boswellia serrata. They both contain boswellic acids (BAs) which have been shown to exhibit anti-inflammatory and antiarthritic properties. This study tests the hypothesis that mixtures of BAs derived from B. carterii have immunomodulatory properties. B. carterii plant resin obtained from China was prepared as an ethanol extract, and the presence of seven BAs was confirmed by column chromatography, high-performance liquid chromatography, and UV laser desorption/ionization tandem mass spectroscopy. The extract was then tested for its ability to alter in vitro production of TH1 cytokines (interleukin-2 [IL-2] and gamma interferon) and TH2 cytokines (IL-4 and IL-10) by murine splenocytes. Delivery of the resin extract using ethanol as a solvent resulted in significant cellular toxicity not seen with the addition of ethanol alone. By contrast, delivery of the resin extract using a sesame oil solvent resulted in a dose-dependent inhibition of TH1 cytokines coupled with a dose-dependent potentiation of TH2 cytokines. These results indicate that a purified mixture of BAs from B. carterii plant resin exhibits carrier-dependent immunomodulatory properties in vitro.

  8. Permissible level of toxaphene residues in fish from the German market based on in vivo and in vitro effects to tumor promotion.

    Science.gov (United States)

    Ekici, Perihan; Friess, Albrecht; Parlar, Harun

    2008-07-01

    Toxaphene is a chlorinated pesticide consisting of more than 200 congeners that are mainly chlorobornanes and chlorocamphenes. As the congeners exhibit different stability properties in the environment, only between 20 and 30 compounds can be observed in, e.g., fish, which are represented by technical toxaphene as a mixture. In human body, the congeners Parlar #26, #40, #41, #44, #50, and #62 are detected frequently. Three of them, #26, #50, and #62, pose a potential risk to human health due to their persistent characteristic. By using experimental results of a European Union study (MATT, 2000. Investigation into the Monitoring, Analysis and Toxicity of Toxaphene in Marine Foodstuffs, European Union, Brussels, Final report, FAIR CT PL.96.3131. Investigation into the Monitoring, Analysis and Toxicity of Toxaphene in Marine Foodstuffs), a reference dose related to tumor promotion was calculated for these representative persistent toxaphene congeners. In Germany, the sum of the congeners #26, #50, and #62 is defined as the official standard for toxaphene residues in food. In this work, different fish samples obtained from German markets were studied regarding their contamination with toxaphene congeners, presented either in sum, or as single constitutes. The obtained data were used to define the acceptable total concentration of the sum of Parlar #26, #50, and #62 with regard to prevention of tumor promotion in human. The results showed that the currently existing permissible level of the sum of these congeners (0.1 mg/kg) is higher than the acceptable concentration in fish samples determined by this work and calculated at ca. 0.090 mg/kg. It is therefore recommended to improve the permissible level of toxaphene in German food samples.

  9. Characterization of potential mineralization in Afghanistan: four permissive areas identified using imaging spectroscopy data

    Science.gov (United States)

    King, Trude V.V.; Berger, Byron R.; Johnson, Michaela R.

    2014-01-01

    As part of the U.S. Geological Survey and Department of Defense Task Force for Business and Stability Operations natural resources revitalization activities in Afghanistan, four permissive areas for mineralization, Bamyan 1, Farah 1, Ghazni 1, and Ghazni 2, have been identified using imaging spectroscopy data. To support economic development, the areas of potential mineralization were selected on the occurrence of selected mineral assemblages mapped using the HyMap™ data (kaolinite, jarosite, hydrated silica, chlorite, epidote, iron-bearing carbonate, buddingtonite, dickite, and alunite) that may be indicative of past mineralization processes in areas with limited or no previous mineral resource studies. Approximately 30 sites were initially determined to be candidates for areas of potential mineralization. Additional criteria and material used to refine the selection and prioritization process included existing geologic maps, Landsat Thematic Mapper data, and published literature. The HyMapTM data were interpreted in the context of the regional geologic and tectonic setting and used the presence of alteration mineral assemblages to identify areas with the potential for undiscovered mineral resources. Further field-sampling, mapping, and supporting geochemical analyses are necessary to fully substantiate and verify the specific deposit types in the four areas of potential mineralization.

  10. Resident alveolar macrophages are susceptible to and permissive of Coxiella burnetii infection.

    Directory of Open Access Journals (Sweden)

    Matthew Calverley

    Full Text Available Coxiella burnetii, the causative agent of Q fever, is a zoonotic disease with potentially life-threatening complications in humans. Inhalation of low doses of Coxiella bacteria can result in infection of the host alveolar macrophage (AM. However, it is not known whether a subset of AMs within the heterogeneous population of macrophages in the infected lung is particularly susceptible to infection. We have found that lower doses of both phase I and phase II Nine Mile C. burnetii multiply and are less readily cleared from the lungs of mice compared to higher infectious doses. We have additionally identified AM resident within the lung prior to and shortly following infection, opposed to newly recruited monocytes entering the lung during infection, as being most susceptible to infection. These resident cells remain infected up to twelve days after the onset of infection, serving as a permissive niche for the maintenance of bacterial infection. A subset of infected resident AMs undergo a distinguishing phenotypic change during the progression of infection exhibiting an increase in surface integrin CD11b expression and continued expression of the surface integrin CD11c. The low rate of phase I and II Nine Mile C. burnetii growth in murine lungs may be a direct result of the limited size of the susceptible resident AM cell population.

  11. Human Endometrial Stromal Cells Are Highly Permissive To Productive Infection by Zika Virus

    Science.gov (United States)

    Pagani, Isabel; Ghezzi, Silvia; Ulisse, Adele; Rubio, Alicia; Turrini, Filippo; Garavaglia, Elisabetta; Candiani, Massimo; Castilletti, Concetta; Ippolito, Giuseppe; Poli, Guido; Broccoli, Vania; Panina-Bordignon, Paola; Vicenzi, Elisa

    2017-01-01

    Zika virus (ZIKV) is a recently re-emerged flavivirus transmitted to humans by mosquito bites but also from mother to fetus and by sexual intercourse. We here show that primary human endometrial stromal cells (HESC) are highly permissive to ZIKV infection and support its in vitro replication. ZIKV envelope expression was detected in the endoplasmic reticulum whereas double-stranded viral RNA colocalized with vimentin filaments to the perinuclear region. ZIKV productive infection also occurred in the human T-HESC cell line together with the induction of interferon-β (IFN-β) and of IFN-stimulated genes. Notably, in vitro decidualization of T-HESC with cyclic AMP and progesterone upregulated the cell surface expression of the ZIKV entry co-receptor AXL and boosted ZIKV replication by ca. 100-fold. Thus, endometrial stromal cells, particularly if decidualized, likely represent a crucial cell target of ZIKV reaching them, either via the uterine vasculature in the viremic phase of the infection or by sexual viral transmission, and a potential source of virus spreading to placental trophoblasts during pregnancy. PMID:28281680

  12. Valganciclovir Inhibits Human Adenovirus Replication and Pathology in Permissive Immunosuppressed Female and Male Syrian Hamsters

    Directory of Open Access Journals (Sweden)

    Karoly Toth

    2015-03-01

    Full Text Available Adenovirus infections of immunocompromised pediatric hematopoietic stem cell transplant patients can develop into serious and often deadly multi-organ disease. There are no drugs approved for adenovirus infections. Cidofovir (an analog of 2-deoxycytidine monophosphate is used at times but it can be nephrotoxic and its efficacy has not been proven in clinical trials. Brincidofovir, a promising lipid-linked derivative of cidofovir, is in clinical trials. Ganciclovir, an analog of 2-deoxyguanosine, has been employed occasionally but with unknown efficacy in the clinic. In this study, we evaluated valganciclovir against disseminated adenovirus type 5 (Ad5 infection in our permissive immunosuppressed Syrian hamster model. We administered valganciclovir prophylactically, beginning 12 h pre-infection or therapeutically starting at Day 1, 2, 3, or 4 post-infection. Valganciclovir significantly increased survival, reduced viral replication in the liver, and mitigated the pathology associated with Ad5 infection. In cultured cells, valganciclovir inhibited Ad5 DNA replication and blocked the transition from early to late stage of infection. Valganciclovir directly inhibited Ad5 DNA polymerase in vitro, which may explain, at least in part, its mechanism of action. Ganciclovir and valganciclovir are approved to treat infections by certain herpesviruses. Our results support the use of valganciclovir to treat disseminated adenovirus infections in immunosuppressed patients.

  13. Valganciclovir inhibits human adenovirus replication and pathology in permissive immunosuppressed female and male Syrian hamsters.

    Science.gov (United States)

    Toth, Karoly; Ying, Baoling; Tollefson, Ann E; Spencer, Jacqueline F; Balakrishnan, Lata; Sagartz, John E; Buller, Robert Mark L; Wold, William S M

    2015-03-23

    Adenovirus infections of immunocompromised pediatric hematopoietic stem cell transplant patients can develop into serious and often deadly multi-organ disease. There are no drugs approved for adenovirus infections. Cidofovir (an analog of 2-deoxycytidine monophosphate) is used at times but it can be nephrotoxic and its efficacy has not been proven in clinical trials. Brincidofovir, a promising lipid-linked derivative of cidofovir, is in clinical trials. Ganciclovir, an analog of 2-deoxyguanosine, has been employed occasionally but with unknown efficacy in the clinic. In this study, we evaluated valganciclovir against disseminated adenovirus type 5 (Ad5) infection in our permissive immunosuppressed Syrian hamster model. We administered valganciclovir prophylactically, beginning 12 h pre-infection or therapeutically starting at Day 1, 2, 3, or 4 post-infection. Valganciclovir significantly increased survival, reduced viral replication in the liver, and mitigated the pathology associated with Ad5 infection. In cultured cells, valganciclovir inhibited Ad5 DNA replication and blocked the transition from early to late stage of infection. Valganciclovir directly inhibited Ad5 DNA polymerase in vitro, which may explain, at least in part, its mechanism of action. Ganciclovir and valganciclovir are approved to treat infections by certain herpesviruses. Our results support the use of valganciclovir to treat disseminated adenovirus infections in immunosuppressed patients.

  14. The gamma-2-herpesvirus bovine herpesvirus 4 causes apoptotic infection in permissive cell lines.

    Science.gov (United States)

    Sciortino, M T; Perri, D; Medici, M A; Foti, M; Orlandella, B M; Mastino, A

    2000-11-10

    Increasing evidence suggests that regulation of apoptosis in infected cells is associated with several viral infections. The gammaherpesvirus bovine herpesvirus 4 (BHV-4) has been shown to harbor genes with antiapoptotic potentialities. However, here we have demonstrated that productive infection of adherent, permissive cell lines by BHV-4 resulted in a cytopathic effect characterized by induction of apoptosis. This phenomenon was confirmed using different techniques to detect apoptosis and using different virus strains and cell targets. Apoptosis induced by BHV-4 was inhibited by (1) treatment with doses of heparin, which completely inhibited virus attachment and infectivity; (2) UV treatment, which completely abrogated infectivity; and (3) treatment with a dose of phosphonoacetic acid, which blocked virus replication. Virus-induced apoptosis was associated with a down-regulation of Bcl-2 expression and was reduced by Z-VAD-FMK, but not by Z-DEVD-FMK (caspase-3-specific) caspase inhibitors. Inhibition of apoptosis by Z-VAD-FMK treatment during infection did not modify virus yield. Therefore, despite the presence of antiapoptotic genes in its genoma, BHV-4 could complete its cycle of productive infection while inducing apoptosis of infected cells. This finding might have implications for the pathobiology of BHV-4 and other gammaherpesviruses in vivo. Copyright 2000 Academic Press.

  15. Experimental verification of the imposing principle for maximum permissible levels of multicolor laser radiation

    Directory of Open Access Journals (Sweden)

    Ivashin V.A.

    2013-12-01

    Full Text Available Aims. The study presents the results of experimental research to verify the principle overlay for maximum permissible levels (MPL of multicolor laser radiation single exposure on eyes. This principle of the independence of the effects of radiation with each wavelength (the imposing principle, was founded and generalized to a wide range of exposure conditions. Experimental verification of this approach in relation to the impact of laser radiation on tissue fundus of an eye, as shows the analysis of the literature was not carried out. Material and methods. Was used in the experimental laser generating radiation with wavelengths: Л1 =0,532 microns, A2=0,556to 0,562 microns and A3=0,619to 0,621 urn. Experiments were carried out on eyes of rabbits with evenly pigmented eye bottom. Results. At comparison of results of processing of the experimental data with the calculated data it is shown that these levels are close by their parameters. Conclusions. For the first time in the Russian Federation had been performed experimental studies on the validity of multi-colored laser radiation on the organ of vision. In view of the objective coincidence of the experimental data with the calculated data, we can conclude that the mathematical formulas work.

  16. Crayfish hematopoietic tissue cells but not hemocytes are permissive for white spot syndrome virus replication.

    Science.gov (United States)

    Wu, Junjun; Li, Fang; Huang, Jiajun; Xu, Limei; Yang, Feng

    2015-03-01

    Hemocytes are the major immune cells of crustaceans which are believed to be essential for the pathogenesis of white spot syndrome virus (WSSV) infection. Crayfish hemocytes and hematopoietic tissue (HPT) cells have been found to be susceptible to WSSV infection, but the procedure of WSSV infection to both cell types has not yet been carefully investigated. In this study, we analyzed the infection and proliferation of WSSV in crayfish hemocytes as well as HPT cells in detail through transmission electronic microscopy (TEM). The results showed that WSSV could enter both hemocytes and HPT cells through endocytosis, but the production of progeny virus was only achieved in HPT cells. Further investigation demonstrated that although WSSV could transcribe its genes in both cell types, viral genome replication and structural protein expression were unsuccessful in hemocytes, which may be responsible for the failure of progeny production. Therefore, we propose that both hemocytes and HPT cells are susceptible to WSSV infection but only HPT cells are permissive to WSSV replication. These findings will extend our knowledge of the interaction between WSSV and the host immune system.

  17. Inventory model with two rates of production for deteriorating items with permissible delay in payments

    Science.gov (United States)

    Roy, Ajanta; Samanta, G. P.

    2011-08-01

    Goyal (1985) ['Economic Order Quantity Under Conditions of Permissible Delay in Payments', Journal of Operational research Society, 36, 35-38] assumed that unit selling price and unit purchasing price are equal. But in real-life the scenario is different. The purpose of this article is to reflect the real life problem by allowing unit selling price and purchasing price to be unequal. Our model is a continuous production control inventory model for deteriorating items in which two different rates of production are available. The results are illustrated with the help of a numerical example. We discuss the sensitivity of the solution together with the changes of the values of the parameters associated with the model. Our model may be applicable in many manufacturing planning situations where management practices for deterioration are stringent; e.g. the two-production rate will be more profitable than the one-production rate in the manufacture of cold, asthma and allergy medicine. Our proposed model might be applicable to develop a prototype advance planning system for those manufacturers to integrate the management science techniques into commercial planning.

  18. Small Animal Models for Human Metapneumovirus: Cotton Rat is More Permissive than Hamster and Mouse

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    2014-07-01

    Full Text Available Human metapneumovirus (hMPV is the second most prevalent causative agent of pediatric respiratory infections worldwide. Currently, there are no vaccines or antiviral drugs against this virus. One of the major hurdles in hMPV research is the difficulty to identify a robust small animal model to accurately evaluate the efficacy and safety of vaccines and therapeutics. In this study, we compared the replication and pathogenesis of hMPV in BALB/c mice, Syrian golden hamsters, and cotton rats. It was found that BALB/c mice are not permissive for hMPV infection despite the use of a high dose (6.5 log10 PFU of virus for intranasal inoculation. In hamsters, hMPV replicated efficiently in nasal turbinates but demonstrated only limited replication in lungs. In cotton rats, hMPV replicated efficiently in both nasal turbinate and lung when intranasally administered with three different doses (4, 5, and 6 log10 PFU of hMPV. Lungs of cotton rats infected by hMPV developed interstitial pneumonia with mononuclear cells infiltrates and increased lumen exudation. By immunohistochemistry, viral antigens were detected at the luminal surfaces of the bronchial epithelial cells in lungs. Vaccination of cotton rats with hMPV completely protected upper and lower respiratory tract from wildtype challenge. The immunization also elicited elevated serum neutralizing antibody. Collectively, these results demonstrated that cotton rat is a robust small animal model for hMPV infection.

  19. The influence of some blasting techniques on the probability of ignition of firedamp by permissible explosives.

    Science.gov (United States)

    Sanchidrián, J A; López, L M; Segarra, P

    2008-07-15

    The ignition of firedamp by permissible explosives is assessed by means of gallery testing conducted by the Bruceton up-and-down method. Six test series were made in order to analyze the influence of several blasting practices in long-holes coal blasting, namely: use of slotted PVC pipes, detonating cord, salt cartridges and double (top and bottom) initiation. The parameters of the distributions of the probability of ignition are determined by the maximum likelihood method; normal, logistic, lognormal and Weibull distributions have been used. Confidence bands for the probability points are obtained both from the asymptotic standard errors of the parameters and by a bootstrap-like technique. The four distributions used give similar results in a rather ample probability range; discrepancies in the probability points are within 2% and in the confidence limits within 10% in a range of probability [0.1, 0.9] in most of the cases. The use of detonating cord is found to affect significantly the probability of ignition; the double initiation does also have an influence though not statistically significant at a 95% level; the use of salt cartridges, in the amount tested, has little effect in the ignition probability; the use of PVC pipe shows no effect.

  20. Cytokine genes as potential biomarkers for muscle weakness in OPMD

    DEFF Research Database (Denmark)

    Riaz, Muhammad; Raz, Yotam; van der Slujis, Barbara

    2016-01-01

    Molecular biomarkers emerge as an accurate diagnostic tool, but are scarce for myopathies. Lack of outcome measures sensitive to disease onset and symptom severity hamper evaluation of therapeutic developments. Cytokines are circulating immunogenic molecules, and their potential as biomarkers has...... been exploited in the last decade. Cytokines are released from many tissues, including skeletal muscles, but their application to monitor muscle pathology is sparse. We report that the cytokine functional group is altered in the transcriptome of oculopharyngeal muscular dystrophy (OPMD). OPMD...... of these cytokines were highly correlated in controls, but this correlation pattern was disrupted in OPMD. The levels of these 6 cytokines were not altered in expPABPN1 carriers at a pre-symptomatic stage, suggesting that this group of cytokines is a potential biomarker for muscle weakness in OPMD. Correlation...

  1. Ciprofloxacin and ceftriaxone alter cytokine responses, but not Toll-like receptors, to Salmonella infection in vitro.

    Science.gov (United States)

    Anuforom, Olachi; Wallace, Graham R; Buckner, Michelle M C; Piddock, Laura J V

    2016-07-01

    Antibiotics that enhance host natural defences to infection offer an alternative approach to treating infections. However, mechanisms underlying such processes are poorly understood. The aim of this study was to investigate the effects of clinically relevant concentrations of two antibiotics on bacterial interactions with murine macrophages. Adhesion of Salmonella Typhimurium SL1344 to and invasion by Salmonella Typhimurium SL1344 of antibiotic-treated or untreated J774 murine macrophages were measured using a tissue culture infection model. Expression of genes central to the Toll-like receptor (TLR) signalling pathway of macrophages infected with Salmonella was analysed using the RT(2) Profiler PCR Array. Cytokine production was measured by ELISA. Adhesion of Salmonella Typhimurium SL1344 to J774 macrophage monolayers was increased when macrophages were exposed to ciprofloxacin and ceftriaxone, while invasion was decreased by ciprofloxacin. Expression of IL-1β and TNF-α mRNA was greater in SL1344-infected macrophages that had been treated with ciprofloxacin or ceftriaxone than in macrophages exposed to antibiotics alone or SL1344 alone. TLR mRNA was down-regulated by SL1344 infection, a response that was not altered by antibiotic pretreatment. Clinically relevant concentrations of two antibiotics differentially enhanced the response of immune cells and their interaction with bacteria, increasing bacterial adhesion to macrophages and increasing cytokine production. As increased expression of IL-1β fosters apoptosis of Salmonella-infected macrophages and clearance by neutrophils, the immunomodulatory potential of these antibiotics may explain, in part, why these two drugs continue to be used to treat salmonellosis successfully. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Subcellular localization of Aleutian mink disease parvovirus proteins and DNA during permissive infection of Crandell feline kidney cells

    DEFF Research Database (Denmark)

    Oleksiewicz, M.B.; Costello, F.; Huhtanen, M.

    1996-01-01

    Confocal microscopy allowed us to localize viral nonstructural (NS) and capsid (VP) proteins and DNA simultaneously in cells permissively infected with Aleutian mink disease parvovirus (ADV). Early after infection, NS proteins colocalized with viral DNA to form intranuclear inclusions, whereas VP...

  3. 26 CFR 1.9101-1 - Permission to submit information required by certain returns and statements on magnetic tape.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Permission to submit information required by certain returns and statements on magnetic tape. 1.9101-1 Section 1.9101-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Tax Reform Act...

  4. 9 CFR 317.7 - Products for foreign commerce; printing labels in foreign language permissible; other deviations.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Products for foreign commerce; printing labels in foreign language permissible; other deviations. 317.7 Section 317.7 Animals and Animal... DEVICES, AND CONTAINERS General § 317.7 Products for foreign commerce; printing labels in foreign language...

  5. Psychometric Support for a New Measure of Authoritative, Authoritarian, and Permissive Parenting Practices: Cross-Cultural Connections.

    Science.gov (United States)

    Robinson, Clyde C.; And Others

    This study examined the psychometric characteristics of a 62-item parenting questionnaire completed by parents from the United States, Australia, China, and Russia. Factor analyses yielded three global parenting dimensions for each culture which were consistent with D. Baumrind's (1971) authoritative, authoritarian, and permissive typologies. The…

  6. Criteria for permission of radiosterilized products to application in medicine; Zasady dopuszczania wyrobow sterylizowanych radiacyjnie do stosowania w medycynie

    Energy Technology Data Exchange (ETDEWEB)

    Achmatowicz, T. [Instytut Lekow, Warsaw (Poland)

    1997-10-01

    The criteria being used in Poland for permission of radiosterilized medical materials to commercial application result from regulations being in force. The international regulations are also taken into account. The all criteria and procedure needed for any product become accepted for radiosterilization and commercial medical use have been presented and discussed. 1 tab.

  7. 15 CFR 270.323 - Requests for permission to enter and inspect property where building components, materials...

    Science.gov (United States)

    2010-01-01

    ... inspect property where building components, materials, artifacts, and records with respect to a building... Requests for permission to enter and inspect property where building components, materials, artifacts, and... where building components, materials, artifacts, and records with respect to a building failure are...

  8. Trends and countertrends in sexual permissiveness: Three decades of attitude change in the Netherlands 1965-1995

    NARCIS (Netherlands)

    Kraaykamp, G.L.M.

    2002-01-01

    Using longitudinal data from 8 surveys on attitude change in the Netherlands, I tried to clarify trends in sexual permissiveness since the 1960s. In explaining these changes, time-period effects proved most important, whereas cohort replacement appeared to be of minor significance. Hence, changing a

  9. 12 CFR 347.115 - Permissible activities for a foreign branch of an insured state nonmember bank.

    Science.gov (United States)

    2010-01-01

    ... CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING § 347.115 Permissible... documents, if: (1) The guarantee or agreement specifies a maximum monetary liability; and (2) To the extent... applying any legal lending limits. (b) Government obligations. Engage in the following types...

  10. 77 FR 23483 - Notice of Proposals To Engage In or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-04-19

    ... Notice of Proposals To Engage In or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  11. 77 FR 4560 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-01-30

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  12. 78 FR 41929 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-07-12

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  13. 77 FR 46437 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-08-03

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  14. 77 FR 50106 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-08-20

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  15. 77 FR 45352 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-07-31

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y (12 CFR Part 225) to engage de novo, or to acquire or control...

  16. 76 FR 69739 - Notice of Proposals To Engage In or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2011-11-09

    ... Notice of Proposals To Engage In or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  17. 78 FR 52531 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-08-23

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  18. 76 FR 71344 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2011-11-17

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y (12 CFR part 225) to engage de novo, or to acquire or control...

  19. 77 FR 13127 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-03-05

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  20. 77 FR 35387 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-06-13

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  1. 78 FR 24201 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-04-24

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  2. 78 FR 62303 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-10-15

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  3. 77 FR 21100 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-04-09

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C..., Virginia 23261-4528: 1. City Holding Company, Cross Lanes, West Virginia; to acquire 100 percent of...

  4. 78 FR 26032 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-05-03

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  5. 78 FR 9391 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-02-08

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  6. 76 FR 67454 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2011-11-01

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  7. 77 FR 56210 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-09-12

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  8. 78 FR 11648 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-02-19

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  9. 78 FR 9051 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-02-07

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  10. 78 FR 29134 - Notice of Proposals to Engage in or to Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-05-17

    ... Notice of Proposals to Engage in or to Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C...., Atlanta, Georgia 30309: 1. HCBF Holding Company, Inc., Fort Pierce, Florida; to acquire 100 percent of...

  11. 78 FR 35271 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-06-12

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  12. 78 FR 1212 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-01-08

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  13. 76 FR 75549 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2011-12-02

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  14. 77 FR 33460 - Notice of Proposals to Engage in or to Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-06-06

    ... Notice of Proposals to Engage in or to Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  15. 77 FR 43285 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-07-24

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  16. 77 FR 61607 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-10-10

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  17. 78 FR 7784 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-02-04

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  18. 77 FR 285 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-01-04

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y (12 CFR part 225) to engage de novo, or to acquire or control...

  19. 78 FR 65312 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-10-31

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  20. 77 FR 73467 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-12-10

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  1. 78 FR 45536 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-07-29

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  2. 78 FR 52768 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-08-26

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  3. 78 FR 61845 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-10-04

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  4. 78 FR 27239 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-05-09

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  5. 77 FR 8258 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-02-14

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  6. 78 FR 30302 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-05-22

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  7. 77 FR 60996 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-10-05

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C..., Virginia 23261-4528: 1. City Holding Company, Cross Lanes, West Virginia; to acquire 100 percent of...

  8. 76 FR 81940 - Notice of Proposals to Engage in or to Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2011-12-29

    ... Notice of Proposals to Engage in or to Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  9. 78 FR 67147 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-11-08

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  10. 77 FR 66464 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-11-05

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  11. 78 FR 70946 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-11-27

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  12. 77 FR 27061 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-05-08

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  13. 77 FR 6564 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-02-08

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  14. 77 FR 7163 - Notice of Proposals to Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-02-10

    ... Notice of Proposals to Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 ] CFR part 225) to engage de novo, or to acquire or...

  15. 78 FR 42524 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-07-16

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  16. 76 FR 68188 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2011-11-03

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  17. 77 FR 36543 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-06-19

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  18. 77 FR 64994 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-10-24

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  19. 77 FR 60119 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-10-02

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  20. 77 FR 14015 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-03-08

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  1. 76 FR 76413 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2011-12-07

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  2. 78 FR 54648 - Notice of Proposals to Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-09-05

    ... Notice of Proposals to Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  3. 78 FR 8534 - Notice of Proposals to Engage in or to Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-02-06

    ... Notice of Proposals to Engage in or to Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  4. 78 FR 33093 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-06-03

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  5. 78 FR 77684 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-12-24

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  6. 77 FR 12304 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-02-29

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y (12 CFR part 225) to engage de novo, or to acquire or control...

  7. 77 FR 1072 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-01-09

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  8. 76 FR 78924 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2011-12-20

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  9. 77 FR 52033 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-08-28

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  10. 77 FR 39494 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-07-03

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  11. 78 FR 77465 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-12-23

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  12. 76 FR 36538 - Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That...

    Science.gov (United States)

    2011-06-22

    ... Notice of Proposals To Engage in Permissible Nonbanking Activities or To Acquire Companies That Are...) to engage de novo, or to acquire or control voting securities or assets of a company, including the... Northern Trust Company and Northern Trust Corporation, both located in Chicago, Illinois; to acquire...

  13. 78 FR 26369 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-05-06

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  14. 78 FR 52915 - Notice of Proposals to Engage In or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2013-08-27

    ... Notice of Proposals to Engage In or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR Part 225) to engage de novo, or to acquire or control...

  15. 76 FR 82298 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2011-12-30

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  16. 77 FR 29348 - Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2012-05-17

    ... Notice of Proposals To Engage in or To Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  17. 76 FR 78658 - Notice of Proposals to Engage in or to Acquire Companies Engaged in Permissible Nonbanking...

    Science.gov (United States)

    2011-12-19

    ... Notice of Proposals to Engage in or to Acquire Companies Engaged in Permissible Nonbanking Activities The companies listed in this notice have given notice under section 4 of the Bank Holding Company Act (12 U.S.C. 1843) (BHC Act) and Regulation Y, (12 CFR part 225) to engage de novo, or to acquire or control...

  18. Prerequisites for cytokine measurements in clinical trials with multiplex immunoassays

    Directory of Open Access Journals (Sweden)

    Rijkers Ger T

    2009-09-01

    Full Text Available Abstract Background Growing knowledge about cellular interactions in the immune system, including the central role of cytokine networks, has lead to new treatments using monoclonal antibodies that block specific components of the immune system. Systemic cytokine concentrations can serve as surrogate outcome parameters of these interventions to study inflammatory pathways operative in patients in vivo. This is now possible due to novel technologies such as multiplex immunoassays (MIA that allows detection of multiple cytokines in a single sample. However, apparently trivial underappreciated processes, (sample handling and storage, interference of endogenous plasma proteins can greatly impact the reliability and reproducibility of cytokine detection. Therefore we set out to investigate several processes that might impact cytokine profiles such as blood collecting tubes, duration of storage, and number of freeze thawing cycles. Results Since under physiological conditions cytokine concentrations normally are low or undetectable we spiked cytokines in the various plasma and serum samples. Overall recoveries ranged between 80-120%. Long time storage showed cytokines are stable for a period up to 2 years of storage at -80°C. After 4 years several cytokines (IL-1α, IL-1β, IL-10, IL-15 and CXCL8 degraded up to 75% or less of baseline values. Furthermore we show that only 2 out of 15 cytokines remained stable after several freeze-thawing cycles. We also demonstrate implementation of an internal control for multiplex cytokine immunoassays. Conclusion All together we show parameters which are essential for measurement of cytokines in the context of clinical trials.

  19. Proinflammatory cytokines oppose opioid induced acute and chronic analgesia

    OpenAIRE

    Hutchinson, Mark R.; Coats, Benjamen D; Lewis, Susannah S.; Zhang, Yingning; Sprunger, David B.; Rezvani, Niloofar; Baker, Eric M.; Jekich, Brian M.; Wieseler, Julie L.; Somogyi, Andrew A; Martin, David; Poole, Stephen; Judd, Charles M.; Steven F. Maier; Watkins, Linda R.

    2008-01-01

    Spinal proinflammatory cytokines are powerful pain-enhancing signals that contribute to pain following peripheral nerve injury (neuropathic pain). Recently, one proinflammatory cytokine, interleukin-1, was also implicated in the loss of analgesia upon repeated morphine exposure (tolerance). In contrast to prior literature, we demonstrate that the action of several spinal proinflammatory cytokines oppose systemic and intrathecal opioid analgesia, causing reduced pain suppression. In vitro morp...

  20. Role of inflammatory cytokines in peripheral nerve injury

    OpenAIRE

    Fregnan, Federica; Muratori, Luisa; Simões, Anabel Rodriguez; Giacobini-Robecchi, Maria Giuseppina; Raimondo, Stefania

    2012-01-01

    Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflamma...

  1. Cytokine Patterns and Endotypes in Acute and Chronic Rhinosinusitis.

    Science.gov (United States)

    Scheckenbach, Kathrin; Wagenmann, Martin

    2016-01-01

    Since rhinosinusitis is an inflammatory disease, cytokines as key regulators of inflammation play a central role in its pathophysiology. In acute rhinosinusitis, several proinflammatory cytokines of different types have been identified. Initial information about the involvement of the inflammasome in rhinosinusitis has been gained, but this area remains open for more detailed research. Although it has been accepted now that chronic rhinosinusitis (CRS) needs to be differentiated into CRS with and without nasal polyps, it has become clear that this distinction is insufficient to clearly define subgroups with uniform pathophysiology and cytokine patterns. While Th1-cytokines are mostly found in CRSsNP and Th2 cytokines in CRSwNP, there is a substantial overlap, and several other cytokines have also been detected. Attempts to identify CRS endotypes based on cytokines are ongoing but not yet generally accepted. Despite the central role of cytokines in rhinosinusitis, no specific cytokine-targeted therapies are currently available, and only very few studies have specifically addressed the effects of such biologicals in rhinosinusitis.

  2. Cytokine ratios in chronic periodontitis and type 2 diabetes mellitus.

    Science.gov (United States)

    Acharya, Anirudh B; Thakur, Srinath; Muddapur, M V; Kulkarni, Raghavendra D

    Chronic periodontitis may influence systemic cytokines in type 2 diabetes. This study aimed to evaluate the cytokine ratios in type 2 diabetes with, and without chronic periodontitis. Gingival status, periodontal, glycemic parameters and serum cytokines were evaluated in participants grouped as healthy, chronic periodontitis, and type 2 diabetes with, and without chronic periodontitis. Cytokine ratios showed significant differences in type 2 diabetes and chronic periodontitis, were highest in participants having both type 2 diabetes and chronic periodontitis, with a statistically significant cut-off point and area under curve by receiver operating characteristic. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  3. Inflammatory cytokines in pediatric obstructive sleep apnea

    Science.gov (United States)

    Huang, Yu-Shu; Guilleminault, Christian; Hwang, Fang-Ming; Cheng, Chuan; Lin, Cheng-Hui; Li, Hsueh-Yu; Lee, Li-Ang

    2016-01-01

    Abstract Pediatric obstructive sleep apnea (OSA) is associated with chronic systemic inflammation and with cognitive impairments. This study aimed to investigate the status of proinflammatory cytokines, particularly interleukin 17 (IL-17) and interleukin 23 (IL-23) and cognition in pediatric OSA. Controls and OSA children participated in the study. Exclusion criteria were adenotonsillectomy, heart, neurological and severe psychiatric diseases, craniofacial syndromes, and obesity. Polysomnogram was followed by serum testing for inflammatory markers and neurocognitive tests such as continuous performance task (CPT) and Wisconsin card sorting test, questionnaires, analyses of plasma high-sensitivity C-reactive protein (HS-CRP), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), IL-17, and IL-23. Seventy-nine, 4 to 12-year-old subjects in 2 groups ended the study: 47 nonobese OSA children (mean age = 7.84 ± 0.56 years, body mass index [BMI] = 16.95 ± 0.47 kg/m2, BMI z-score = 0.15 ± 0.21, and mean apnea–hypopnea index [AHI] = 9.13 ± 1.67 events/h) and 32 healthy control children (mean age = 7.02 ± 0.65 years, with BMI = 16.55 ± 0.58 kg/m2, BMI z-score = −0.12 ± 0.27, and mean AHI = 0.41 ± 0.07 event/h) were enrolled. Serum cytokine analyses showed significantly higher levels of HS-CRP, IL-17, and IL-23 in OSA children (P = 0.002, P = 0.024, and P = 0.047). Regression test showed significant influence of HS-CRP, TNF-α, IL-6, IL-17, and specifically IL-23, with the continuous performance test and Wisconsin card sorting test. OSA children have abnormal levels of IL-17, an interleukin related to T helper 17 cells, a T helper cell involved in development of autoimmunity and inflammation. This high expression level may contribute to the complications of pediatric OSA; we also found a significant influence of inflammatory cytokines, particularly IL-23, on abnormal neurocognitive testing. PMID

  4. Leptin–cytokine crosstalk in breast cancer

    Science.gov (United States)

    Newman, Gale; Gonzalez-Perez, Ruben Rene

    2013-01-01

    Despite accumulating evidence suggesting a positive correlation between leptin levels, obesity, post-menopause and breast cancer incidence, our current knowledge on the mechanisms involved in these relationships is still incomplete. Since the cloning of leptin in 1994 and its receptor (OB-R) 1 year later by Friedman’s laboratory (Zhang et al., 1994) and Tartaglia et al. (Tartaglia et al., 1995), respectively, more than 22,000 papers related to leptin functions in several biological systems have been published (Pubmed, 2012). The ob gene product, leptin, is an important circulating signal for the regulation of body weight. Additionally, leptin plays critical roles in the regulation of glucose homeostasis, reproduction, growth and the immune response. Supporting evidence for leptin roles in cancer has been shown in more than 1000 published papers, with almost 300 papers related to breast cancer (Pubmed, 2012). Specific leptin-induced signaling pathways are involved in the increased levels of inflammatory, mitogenic and pro-angiogenic factors in breast cancer. In obesity, a mild inflammatory condition, deregulated secretion of proinflammatory cytokines and adipokines such as IL-1, IL-6, TNF-α and leptin from adipose tissue, inflammatory and cancer cells could contribute to the onset and progression of cancer. We used an in silico software program, Pathway Studio 9, and found 4587 references citing these various interactions. Functional crosstalk between leptin, IL-1 and Notch signaling (NILCO) found in breast cancer cells could represent the integration of developmental, proinflammatory and pro-angiogenic signals critical for leptin-induced breast cancer cell proliferation/migration, tumor angiogenesis and breast cancer stem cells (BCSCs). Remarkably, the inhibition of leptin signaling via leptin peptide receptor antagonists (LPrAs) significantly reduced the establishment and growth of syngeneic, xenograft and carcinogen-induced breast cancer and, simultaneously

  5. Cytokine profile of NALT during acute stress and its possible effect on IgA secretion.

    Science.gov (United States)

    Gutiérrez-Meza, Juan Manuel; Jarillo-Luna, Rosa Adriana; Rivera-Aguilar, Victor; Miliar-García, Angel; Campos-Rodríguez, Rafael

    2017-08-01

    Stress stimuli affect the immune system responses that occur at mucosal membranes, particularly IgA secretion. It has been suggested that acute stress increases the levels of IgA and that sympathetic innervation plays an important role in this process. We herein explore in a murine model how acute stress affects the Th1/Th2/Treg cytokine balance in NALT, and the possible role of glucocorticoids in this effect. Nine-week-old male CD1 mice were divided into three groups: unstressed (control), stressed (subjected to 4h of immobilization), and stressed after pretreatment with a single dose of the corticosterone receptor antagonist RU-486. The parameters evaluated included plasma corticosterone and epinephrine, IgA levels in nasal fluid (by ELISA), the percentage of CD19(+)B220(+)IgA(+) lymphocytes and CD138(+)IgA(+) plasma cells, and the mRNA expression of heavy α chain, J chain and pIgR. Moreover, the gene and protein expression of Th1 cytokines (TNFα, IL-2 and INF-γ), Th2 cytokines (IL-4 and IL-5) and Treg cytokines (IL-10 and TGFβ) were determined in nasal mucosa. The results show that acute stress generated a shift towards the dominance of an anti-inflammatory immune response (Th2 and Treg cytokines), evidenced by a significant rise in the amount of T cells that produce IL4, IL-5 and IL-10. This immune environment may favor IgA biosynthesis by CD138(+)IgA(+) plasma cells, a process mediated mostly by glucocorticoids. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  6. Cytokine Gene Polymorphisms support diagnostic monitoring of Romanian Multiple Myeloma patients

    OpenAIRE

    2011-01-01

    Introduction: cytokines and their receptor genes are very polymorphic. SNPs in the promotor region of the gene may influence the rate of cytokine secretion and may affect the biological activity of the encoded cytokine. A number of cytokines and cytokine receptors have been directly linked to the development of human cancers. The aim of our study was to determine the cytokine gene polymorphism in Romanian multiple myeloma patients. Material and methods: cytokine genotyping was performed in 80...

  7. Parenting Styles and Home Obesogenic Environments

    Directory of Open Access Journals (Sweden)

    Michelle Ihmels

    2012-04-01

    Full Text Available Parenting behaviors are known to have a major impact on childhood obesity but it has proven difficult to isolate the specific mechanism of influence. The present study uses Baumrind’s parenting typologies (authoritative, authoritarian, and permissive to examine associations between parenting styles and parenting practices associated with childhood obesity. Data were collected from a diverse sample of children (n = 182, ages 7–10 in an urban school district in the United States. Parenting behaviors were assessed with the Parenting Styles and Dimension Questionnaire (PSDQ, a 58-item survey that categorizes parenting practices into three styles: authoritative, authoritarian, and permissive. Parent perceptions of the home obesogenic environment were assessed with the Family Nutrition and Physical Activity (FNPA instrument, a simple 10 item instrument that has been shown in previous research to predict risk for overweight. Cluster analyses were used to identify patterns in the PSDQ data and these clusters were related to FNPA scores and measured BMI values in children (using ANCOVA analyses that controlled for parent income and education to examine the impact of parenting styles on risk of overweight/obesity. The FNPA score was positively (and significantly associated with scores on the authoritative parenting scale (r = 0.29 but negatively (and significantly associated with scores on the authoritarian scale (r = −0.22 and permissive scale (r = −0.20. Permissive parenting was significantly associated with BMIz score but this is the only dimension that exhibited a relationship with BMI. A three-cluster solution explained 40.5% of the total variance and clusters were distinguishable by low and high z-scores on different PSDQ sub-dimensions. A cluster characterized as Permissive/Authoritarian (Cluster 2 had significantly lower FNPA scores (more obesogenic than clusters characterized as Authoritative (Cluster 1 or Authoritarian

  8. Parenting styles and home obesogenic environments.

    Science.gov (United States)

    Johnson, Rachel; Welk, Greg; Saint-Maurice, Pedro F; Ihmels, Michelle

    2012-04-01

    Parenting behaviors are known to have a major impact on childhood obesity but it has proven difficult to isolate the specific mechanism of influence. The present study uses Baumrind's parenting typologies (authoritative, authoritarian, and permissive) to examine associations between parenting styles and parenting practices associated with childhood obesity. Data were collected from a diverse sample of children (n = 182, ages 7-10) in an urban school district in the United States. Parenting behaviors were assessed with the Parenting Styles and Dimension Questionnaire (PSDQ), a 58-item survey that categorizes parenting practices into three styles: authoritative, authoritarian, and permissive. Parent perceptions of the home obesogenic environment were assessed with the Family Nutrition and Physical Activity (FNPA) instrument, a simple 10 item instrument that has been shown in previous research to predict risk for overweight. Cluster analyses were used to identify patterns in the PSDQ data and these clusters were related to FNPA scores and measured BMI values in children (using ANCOVA analyses that controlled for parent income and education) to examine the impact of parenting styles on risk of overweight/obesity. The FNPA score was positively (and significantly) associated with scores on the authoritative parenting scale (r = 0.29) but negatively (and significantly) associated with scores on the authoritarian scale (r = -0.22) and permissive scale (r = -0.20). Permissive parenting was significantly associated with BMIz score but this is the only dimension that exhibited a relationship with BMI. A three-cluster solution explained 40.5% of the total variance and clusters were distinguishable by low and high z-scores on different PSDQ sub-dimensions. A cluster characterized as Permissive/Authoritarian (Cluster 2) had significantly lower FNPA scores (more obesogenic) than clusters characterized as Authoritative (Cluster 1) or Authoritarian/Authoritative (Cluster 3) after

  9. Elevated specific peripheral cytokines found in major depressive disorder patients with childhood trauma exposure: a cytokine antibody array analysis.

    Science.gov (United States)

    Lu, Shaojia; Peng, Hongjun; Wang, Lifeng; Vasish, Seewoobudul; Zhang, Yan; Gao, Weijia; Wu, Weiwei; Liao, Mei; Wang, Mi; Tang, Hao; Li, Wenping; Li, Weihui; Li, Zexuan; Zhou, Jiansong; Zhang, Zhijun; Li, Lingjiang

    2013-10-01

    Taking into consideration the previous evidence of revealing the relationship of early life adversity, major depressive disorder (MDD), and stress-linked immunological changes, we recruited 22 MDD patients with childhood trauma exposures (CTE), 21 MDD patients without CTE, and 22 healthy controls without CTE, and then utilized a novel cytokine antibody array methodology to detect potential biomarkers underlying MDD in 120 peripheral cytokines and to evaluate the effect of CTE on cytokine changes in MDD patients. Although 13 cytokines were identified with highly significant differences in expressions between MDD patients and normal controls, this relationship was significantly attenuated and no longer significant after consideration of the effect of CTE in MDD patients. Depressed individuals with CTE (TD patients) were more likely to have higher peripheral levels of those cytokines. Severity of depression was associated with plasma levels of certain increased cytokines; meanwhile, the increased cytokines led to a proper separation of TD patients from normal controls during clustering analyses. Our research outcomes add great strength to the relationship between depression and cytokine changes and suggest that childhood trauma may play a vital role in the co-appearance of cytokine changes and depression.

  10. Cytokine profiles of seventeen cytokines, growth factors and chemokines in cord blood and its relation to perinatal clinical findings.

    Science.gov (United States)

    Takahashi, Naoto; Uehara, Ritei; Kobayashi, Mami; Yada, Yukari; Koike, Yasunori; Kawamata, Ryou; Odaka, Jun; Honma, Yoko; Momoi, Mariko Y

    2010-03-01

    Few papers have investigated the cytokine profiles of multiple cytokines in cord blood. We obtained cord blood samples from 224 infants admitted to our neonatal intensive care unit. Cytokine profiles of 17 cytokines were investigated using cytometric bead array technology. We found a wide variety of cytokines of various levels which ranged from 0.59pg/ml (in Interleukin (IL)-4) to 222.0pg/ml (in macrophage inflammatory protein-1beta. Pro-inflammatory cytokines were highly correlated with each other and with granulocyte-colony stimulating factor and IL-8. On the contrary, IL-5, IL-13, and IL-17 did not show any significant correlation with other cytokines. Several maternal factors were strongly related to several cytokines in cord blood. IL-6, IL-8 and monocyte chemotactic protein-1 were closely related to certain neonatal diseases in preterm neonates. Some cytokines may be regulated independently of each other, while others appear to work as a network affecting physiological and pathological conditions in the fetus.

  11. Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes.

    Science.gov (United States)

    Alnek, Kristi; Kisand, Kalle; Heilman, Kaire; Peet, Aleksandr; Varik, Karin; Uibo, Raivo

    2015-01-01

    The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease.

  12. Role of secreted conjunctival mucosal cytokine and chemokine proteins in different stages of trachomatous disease.

    Directory of Open Access Journals (Sweden)

    Troy A Skwor

    Full Text Available BACKGROUND: Chlamydia trachomatis is responsible for trachoma, the primary cause of preventable blindness worldwide. Plans to eradicate trachoma using the World Health Organization's SAFE program (Surgery, Antibiotics, Facial Cleanliness and Environment Improvement have resulted in recurrence of infection and disease following cessation of treatment in many endemic countries, suggesting the need for a vaccine to control infection and trachomatous disease. Vaccine development requires, in part, knowledge of the mucosal host immune responses in both healthy and trachomatous conjuctivae-an area of research that remains insufficiently studied. METHODOLOGY/PRINCIPAL FINDINGS: We characterized 25 secreted cytokines and chemokines from the conjunctival mucosa of individuals residing in a trachoma endemic region of Nepal using Luminex X100 multiplexing technology. Immunomodulating effects of concurrent C. trachomatis infection were also examined. We found that proinflammatory cytokines IL-1beta (r = 0.259, P = 0.001 and TNFalpha (r = 0.168, P<0.05 were significantly associated with trachomatous disease and concurrent C. trachomatis infection compared with age and sex matched controls from the same region who did not have trachoma. In support of these findings, anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra was negatively associated with chronic scarring trachoma (r = -0.249, P = 0.001. Additional cytokines (Th1, IL-12p40 [r = -0.212, P<0.01], and Th2, IL-4 and IL-13 [r = -0.165 and -0.189, respectively, P<0.05 for both] were negatively associated with chronic scarring trachoma, suggesting a protective role. Conversely, a pathogenic role for the Th3/Tr1 cytokine IL-10 (r = 0.180, P<0.05 was evident with increased levels for all trachoma grades. New risk factors for chronic scarring trachoma included IL-6 and IL-15 (r = 0.259 and 0.292, respectively, P<0.005 for both with increased levels for concurrent C. trachomatis infections (r = 0.206, P

  13. Mesenchymal stem cell derived hematopoietic cells are permissive to HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Mondal Debasis

    2011-01-01

    Full Text Available Abstract Background Tissue resident mesenchymal stem cells (MSCs are multipotent, self-renewing cells known for their differentiation potential into cells of mesenchymal lineage. The ability of single cell clones isolated from adipose tissue resident MSCs (ASCs to differentiate into cells of hematopoietic lineage has been previously demonstrated. In the present study, we investigated if the hematopoietic differentiated (HD cells derived from ASCs could productively be infected with HIV-1. Results HD cells were generated by differentiating clonally expanded cultures of adherent subsets of ASCs (CD90+, CD105+, CD45-, and CD34-. Transcriptome analysis revealed that HD cells acquire a number of elements that increase their susceptibility for HIV-1 infection, including HIV-1 receptor/co-receptor and other key cellular cofactors. HIV-1 infected HD cells (HD-HIV showed elevated p24 protein and gag and tat gene expression, implying a high and productive infection. HD-HIV cells showed decreased CD4, but significant increase in the expression of CCR5, CXCR4, Nef-associated factor HCK, and Vpu-associated factor BTRC. HIV-1 restricting factors like APOBEC3F and TRIM5 also showed up regulation. HIV-1 infection increased apoptosis and cell cycle regulatory genes in HD cells. Although undifferentiated ASCs failed to show productive infection, HIV-1 exposure increased the expression of several hematopoietic lineage associated genes such as c-Kit, MMD2, and IL-10. Conclusions Considering the presence of profuse amounts of ASCs in different tissues, these findings suggest the possible role that could be played by HD cells derived from ASCs in HIV-1 infection. The undifferentiated ASCs were non-permissive to HIV-1 infection; however, HIV-1 exposure increased the expression of some hematopoietic lineage related genes. The findings relate the importance of ASCs in HIV-1 research and facilitate the understanding of the disease process and management strategies.

  14. Proteasome-independent degradation of HIV-1 in naturally non-permissive human placental trophoblast cells

    Directory of Open Access Journals (Sweden)

    Barré-Sinoussi Françoise

    2009-05-01

    Full Text Available Abstract Background The human placenta-derived cell line BeWo has been demonstrated to be restrictive to cell-free HIV-1 infection. BeWo cells are however permissive to infection by VSV-G pseudotyped HIV-1, which enters cells by a receptor-independent mechanism, and to infection by HIV-1 via a cell-to-cell route. Results Here we analysed viral entry in wild type BeWo (CCR5+, CXCR4+ and BeWo-CD4+ (CD4+, CCR5+, CXCR4+ cells. We report that HIV-1 internalisation is not restricted in either cell line. Levels of internalised p24 antigen between VSV-G HIV-1 pseudotypes and R5 or X4 virions were comparable. We next analysed the fate of internalised virions; X4 and R5 HIV-1 virions were less stable over time in BeWo cells than VSV-G HIV-1 pseudotypes. We then investigated the role of the proteasome in restricting cell-free HIV-1 infection in BeWo cells using proteasome inhibitors. We observed an increase in the levels of VSV-G pseudotyped HIV-1 infection in proteasome-inhibitor treated cells, but the infection by R5-Env or X4-Env pseudotyped virions remains restricted. Conclusion Collectively these results suggest that cell-free HIV-1 infection encounters a surface block leading to a non-productive entry route, which either actively targets incoming virions for non-proteasomal degradation, and impedes their release into the cytoplasm, or causes the inactivation of mechanisms essential for viral replication.

  15. Permissibility of Multifetal Pregnancy Reduction from The Shiite Point of View

    Science.gov (United States)

    Zabihi Bidgoli, Atefeh; Ardbili, Faezeh Azimzadeh

    2017-01-01

    Background Advancements in medical technology have significantly increased the possibility of successful infertility treatment. Medical interventions in the initial process of pregnancy that intend to increase the chances of pregnancy create the risk of multifetal pregnancies for both mothers and fetuses. Physicians attempt to reduce the numbers of fetuses in order to decrease this risk and guarantee the continuation of pregnancy. The aim of this paper is to understand the Shiite instruction in terms of the risks multifetal pregnancies have for fetuses and if it is permissible to reduce the numbers of fetuses. An affirmative answer will lead to the development of Islamic criteria for reduction of the number of embryos. Materials and Methods This analytical-descriptive research gathered relevant data as a literature search. We reviewed a number of Islamic resources that pertained to the fetus; after a description of the fundamentals and definitions, we subsequently analyzed juridical texts. The order of reduction was inevitably determined by taking into consideration the rules that governed the abortion provisions or general juridical rules. We also investigated the UK law as a comparison to the Shiite perspective. Results The primary ordinance states that termination of an embryo is not permitted and is considered taboo. However, fetal reductions that occur in emergency situations where there is no option or ordinary indication are permitted before the time of ensoulment. The goal of reduction can be chosen from different ways. Conclusion According to Shiite sources, fetal reduction is permitted. Defective fetuses are the criteria for selective reduction. If none are defective, the criteria are possibility and facility. But if the possibility of selection is equally for more than one fetus, the criterion is importance (for example one fetus is healthier). PMID:28042419

  16. Alternative mechanisms of telomere lengthening: Permissive mutations, DNA repair proteins and tumorigenic progression

    Energy Technology Data Exchange (ETDEWEB)

    Gocha, April Renee Sandy; Harris, Julia [Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine, Columbus, OH 43210 (United States); Groden, Joanna, E-mail: joanna.groden@osumc.edu [Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University College of Medicine, Columbus, OH 43210 (United States)

    2013-03-15

    Highlights: ► Neoplastic cells maintain telomeres by telomerase or ALT. ► Genetic mutations in p53, ATRX, DAXX or H3F3A may activate ALT. ► Many DNA repair proteins are involved in ALT. ► Tumor progression is favored by telomerase expression. - Abstract: Telomeres protect chromosome termini to maintain genomic stability and regulate cellular lifespan. Maintenance of telomere length is required for neoplastic cells after the acquisition of mutations that deregulate cell cycle control and increase cellular proliferation, and can occur through expression of the enzyme telomerase or in a telomerase-independent manner termed alternative lengthening of telomeres (ALT). The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are unknown, although cellular origin may favor one or the other mechanisms. ALT pathways are incompletely understood to date; however, recent publications have increasingly broadened our understanding of how ALT is activated, how it proceeds, and how it influences tumor growth. Specific mutational events influence ALT activation, as mutations in genes that suppress recombination and/or alterations in the regulation of telomerase expression are associated with ALT. Once engaged, ALT uses DNA repair proteins to maintain telomeres in the absence of telomerase; experiments that manipulate the expression of specific proteins in cells using ALT are illuminating some of its mechanisms. Furthermore, ALT may influence tumor growth, as experimental and clinical data suggest that telomerase expression may favor tumor progression. This review summarizes recent findings in mammalian cells and models, as well as clinical data, that identify the genetic mutations permissive to ALT, the DNA repair proteins involved in ALT mechanisms and the importance of telomere maintenance mechanisms for tumor progression. A comprehensive understanding of the mechanisms that permit tumor cell immortalization will be important for identifying

  17. Development of mouse hepatocyte lines permissive for hepatitis C virus (HCV.

    Directory of Open Access Journals (Sweden)

    Hussein Hassan Aly

    Full Text Available The lack of a suitable small animal model for the analysis of hepatitis C virus (HCV infection has hampered elucidation of the HCV life cycle and the development of both protective and therapeutic strategies against HCV infection. Human and mouse harbor a comparable system for antiviral type I interferon (IFN induction and amplification, which regulates viral infection and replication. Using hepatocytes from knockout (ko mice, we determined the critical step of the IFN-inducing/amplification pathways regulating HCV replication in mouse. The results infer that interferon-beta promoter stimulator (IPS-1 or interferon A receptor (IFNAR were a crucial barrier to HCV replication in mouse hepatocytes. Although both IFNARko and IPS-1ko hepatocytes showed a reduced induction of type I interferons in response to viral infection, only IPS-1-/- cells circumvented cell death from HCV cytopathic effect and significantly improved J6JFH1 replication, suggesting IPS-1 to be a key player regulating HCV replication in mouse hepatocytes. We then established mouse hepatocyte lines lacking IPS-1 or IFNAR through immortalization with SV40T antigen. Expression of human (hCD81 on these hepatocyte lines rendered both lines HCVcc-permissive. We also found that the chimeric J6JFH1 construct, having the structure region from J6 isolate enhanced HCV replication in mouse hepatocytes rather than the full length original JFH1 construct, a new finding that suggests the possible role of the HCV structural region in HCV replication. This is the first report on the entry and replication of HCV infectious particles in mouse hepatocytes. These mouse hepatocyte lines will facilitate establishing a mouse HCV infection model with multifarious applications.

  18. Ganciclovir inhibits human adenovirus replication and pathogenicity in permissive immunosuppressed Syrian hamsters.

    Science.gov (United States)

    Ying, Baoling; Tollefson, Ann E; Spencer, Jacqueline F; Balakrishnan, Lata; Dewhurst, Stephen; Capella, Cristina; Buller, R Mark L; Toth, Karoly; Wold, William S M

    2014-12-01

    Adenovirus infections of immunocompromised patients can develop into deadly multiorgan or systemic disease. The virus is especially threatening for pediatric allogeneic hematopoietic stem cell transplant recipients; according to some studies, 10% or more of these patients succumb to disease resulting from adenovirus infection. At present, there is no drug approved for the treatment or prevention of adenovirus infections. Compounds that are approved to treat other virus infections are used off-label to combat adenovirus, but only anecdotal evidence of the efficacy of these drugs exists. Ganciclovir, a drug approved for the treatment of herpesvirus infection, was previously reported to be effective against human adenoviruses in vitro. To model adenovirus infections in immunocompromised humans, we examined ganciclovir's efficacy in immunosuppressed Syrian hamsters intravenously infected with type 5 human adenovirus (Ad5). This animal model is permissive for Ad5 replication, and the animals develop symptoms similar to those seen in humans. We demonstrate that ganciclovir suppresses Ad5 replication in the liver of infected hamsters and that it mitigates the consequences of Ad5 infections in these animals when administered prophylactically or therapeutically. We show that ganciclovir inhibits Ad5 DNA synthesis and late gene expression. The mechanism of action for the drug is not clear; preliminary data suggest that it exerts its antiadenoviral effect by directly inhibiting the adenoviral DNA polymerase. While more extensive studies are required, we believe that ganciclovir is a promising drug candidate to treat adenovirus infections. Brincidofovir, a drug with proven activity against Ad5, was used as a positive control in the prophylactic experiment.

  19. Permissibility of Multifetal Pregnancy Reduction from The Shiite Point of View.

    Science.gov (United States)

    Zabihi Bidgoli, Atefeh; Ardbili, Faezeh Azimzadeh

    2017-01-01

    Advancements in medical technology have significantly increased the possibility of successful infertility treatment. Medical interventions in the initial process of pregnancy that intend to increase the chances of pregnancy create the risk of multifetal pregnancies for both mothers and fetuses. Physicians attempt to reduce the numbers of fetuses in order to decrease this risk and guarantee the continuation of pregnancy. The aim of this paper is to understand the Shiite instruction in terms of the risks multifetal pregnancies have for fetuses and if it is permissible to reduce the numbers of fetuses. An affirmative answer will lead to the development of Islamic criteria for reduction of the number of embryos. This analytical-descriptive research gathered relevant data as a literature search. We reviewed a number of Islamic resources that pertained to the fetus; after a description of the fundamentals and definitions, we subsequently analyzed juridical texts. The order of reduction was inevitably determined by taking into consideration the rules that governed the abortion provisions or general juridical rules. We also investigated the UK law as a comparison to the Shiite perspective. The primary ordinance states that termination of an embryo is not permitted and is considered taboo. However, fetal reductions that occur in emergency situations where there is no option or ordinary indication are permitted before the time of ensoulment. The goal of reduction can be chosen from different ways. According to Shiite sources, fetal reduction is permitted. Defective fetuses are the criteria for selective reduction. If none are defective, the criteria are possibility and facility. But if the possibility of selection is equally for more than one fetus, the criterion is importance (for example one fetus is healthier).

  20. Permissibility of Multifetal Pregnancy Reduction from The Shiite Point of View

    Directory of Open Access Journals (Sweden)

    Atefeh Zabihi Bidgoli

    2016-11-01

    Full Text Available Background: Advancements in medical technology have significantly increased the possibility of successful infertility treatment. Medical interventions in the initial process of pregnancy that intend to increase the chances of pregnancy create the risk of multifetal pregnancies for both mothers and fetuses. Physicians attempt to reduce the numbers of fetuses in order to decrease this risk and guarantee the continuation of pregnancy. The aim of this paper is to understand the Shiite instruction in terms of the risks multifetal pregnancies have for fetuses and if it is permissible to reduce the numbers of fetuses. An affirmative answer will lead to the development of Islamic criteria for reduction of the number of embryos. Materials and Methods: This analytical-descriptive research gathered relevant data as a literature search. We reviewed a number of Islamic resources that pertained to the fetus; after a description of the fundamentals and definitions, we subsequently analyzed juridical texts. The order of reduction was inevitably determined by taking into consideration the rules that governed the abortion provisions or general juridical rules. We also investigated the UK law as a comparison to the Shiite perspective. Results: The primary ordinance states that termination of an embryo is not permitted and is considered taboo. However, fetal reductions that occur in emergency situations where there is no option or ordinary indication are permitted before the time of ensoulment. The goal of reduction can be chosen from different ways. Conclusion: According to Shiite sources, fetal reduction is permitted. Defective fetuses are the criteria for selective reduction. If none are defective, the criteria are possibility and facility. But if the possibility of selection is equally for more than one fetus, the criterion is importance (for example one fetus is healthier.

  1. Permissiveness of bovine epithelial cells from lung, intestine, placenta and udder for infection with Coxiella burnetii.

    Science.gov (United States)

    Sobotta, Katharina; Bonkowski, Katharina; Liebler-Tenorio, Elisabeth; Germon, Pierre; Rainard, Pascal; Hambruch, Nina; Pfarrer, Christiane; Jacobsen, Ilse D; Menge, Christian

    2017-04-12

    Ruminants are the main source of human infections with the obligate intracellular bacterium Coxiella (C.) burnetii. Infected animals shed high numbers of C. burnetii by milk, feces, and birth products. In goats, shedding by the latter route coincides with C. burnetii replication in epithelial (trophoblast) cells of the placenta, which led us to hypothesize that epithelial cells are generally implicated in replication and shedding of C. burnetii. We therefore aimed at analyzing the interactions of C. burnetii with epithelial cells of the bovine host (1) at the entry site (lung epithelium) which govern host immune responses and (2) in epithelial cells of gut, udder and placenta decisive for the quantity of pathogen excretion. Epithelial cell lines [PS (udder), FKD-R 971 (small intestine), BCEC (maternal placenta), F3 (fetal placenta), BEL-26 (lung)] were inoculated with C. burnetii strains Nine Mile I (NMI) and NMII at different cultivation conditions. The cell lines exhibited different permissiveness for C. burnetii. While maintaining cell viability, udder cells allowed the highest replication rates with formation of large cell-filling Coxiella containing vacuoles. Intestinal cells showed an enhanced susceptibility to invasion but supported C. burnetii replication only at intermediate levels. Lung and placental cells also internalized the bacteria but in strikingly smaller numbers. In any of the epithelial cells, both Coxiella strains failed to trigger a substantial IL-1β, IL-6 and TNF-α response. Epithelial cells, with mammary epithelial cells in particular, may therefore serve as a niche for C. burnetii replication in vivo without alerting the host's immune response.

  2. Pivotal Advance: Th-1 cytokines inhibit, and Th-2 cytokines promote fibrocyte differentiation

    OpenAIRE

    Shao, Diane D.; Suresh, Rahul; Vakil, Varsha; Gomer, Richard H.; Pilling, Darrell

    2008-01-01

    CD14+ peripheral blood monocytes can differentiate into fibroblast-like cells called fibrocytes, which are associated with and are at least partially responsible for wound healing and fibrosis in multiple organ systems. Signals regulating fibrocyte differentiation are poorly understood. In this study, we find that when added to human PBMCs cultured in serum-free medium, the profibrotic cytokines IL-4 and IL-13 promote fibrocyte differentiation without inducing fibrocyte or fibrocyte precursor...

  3. Pivotal Advance: Th-1 cytokines inhibit, and Th-2 cytokines promote fibrocyte differentiation.

    Science.gov (United States)

    Shao, Diane D; Suresh, Rahul; Vakil, Varsha; Gomer, Richard H; Pilling, Darrell

    2008-06-01

    CD14+ peripheral blood monocytes can differentiate into fibroblast-like cells called fibrocytes, which are associated with and are at least partially responsible for wound healing and fibrosis in multiple organ systems. Signals regulating fibrocyte differentiation are poorly understood. In this study, we find that when added to human PBMCs cultured in serum-free medium, the profibrotic cytokines IL-4 and IL-13 promote fibrocyte differentiation without inducing fibrocyte or fibrocyte precursor proliferation. We also find that the potent, antifibrotic cytokines IFN-gamma and IL-12 inhibit fibrocyte differentiation. In our culture system, IL-1beta, IL-3, IL-6, IL-7, IL-16, GM-CSF, M-CSF, fetal liver tyrosine kinase 3, insulin growth factor 1, vascular endothelial growth factor, and TNF-alpha had no significant effect on fibrocyte differentiation. IL-4, IL-13, and IFN-gamma act directly on monocytes to regulate fibrocyte differentiation, and IL-12 acts indirectly, possibly through CD16-positive NK cells. We previously identified the plasma protein serum amyloid P (SAP) as a potent inhibitor of fibrocyte differentiation. When added together, the fibrocyte-inhibitory activity of SAP dominates the profibrocyte activities of IL-4 and IL-13. The profibrocyte activities of IL-4 and IL-13 and the fibrocyte-inhibitory activities of IFN-gamma and IL-12 counteract each other in a concentration-dependent manner. These results indicate that the complex mix of cytokines and plasma proteins present in inflammatory lesions, wounds, and fibrosis will influence fibrocyte differentiation.

  4. Measuring Cytokine Concentrations Using Magnetic Spectroscopy of Nanoparticle Brownian Relaxation

    Science.gov (United States)

    Khurshid, Hafsa; Shi, Yipeng; Weaver, John

    The magnetic particle spectroscopy is a newly developed non-invasive technique for obtaining information about the nanoparticles' micro environment. In this technique the nanoparticles' magnetization, induced by an alternating magnetic field at various applied frequencies, is processed to analyze rotational freedom of nanoparticles. By analyzing average rotational freedom, it is possible to measure the nanoparticle's relaxation time, and hence get an estimate of the temperature and viscosity of the medium. In molecular concentration sensing, the rotational freedom indicates the number of nanoparticles that are bound by a selected analyte. We have developed microscopic nanoparticles probes to measure the concentration of selected molecules. The nanoparticles are targeted to bind the selected molecule and the resulting reduction in rotational freedom can be quantified remotely. Previously, sensitivity measurements has been reported to be of the factor of 200. However, with our newer perpendicular field setup (US Patent Application Serial No 61/721,378), it possible to sense cytokine concentrations as low as 5 Pico-Molar in-vitro. The excellent sensitivity of this apparatus is due to isolation of the drive field from the signal so the output can be amplified to a higher level. Dartmouth College.

  5. Cytokine expression & TGF-beta signaling in cervical cancer

    NARCIS (Netherlands)

    Kloth, Judith Nathalie

    2009-01-01

    Immune surveillance is of utmost importance in preventing cervical carcinogenesis. Cytokines play a central role in directing and fine tuning the immune response. In cancer, cytokines can either be involved in stimulating the anti-tumor immune response or in tumor growth and progression. The studies

  6. Cytokines in crevicular fluid and orthodontic tooth movement

    NARCIS (Netherlands)

    Ren, Yijin; Vissink, Arjan

    2008-01-01

    This review aimed to evaluate studies on cytokines in the gingival crevicular fluid (GCF) during orthodontic treatment, summarizing the regulation patterns of the most commonly studied cytokines and exploring their clinical implications. To achieve this, a number of key databases were searched using

  7. Characterization and potential clinical applications of autoantibodies against cytokines

    DEFF Research Database (Denmark)

    de Lemos Rieper, Carina; Galle, Pia; Hansen, Morten Bagge

    2009-01-01

    Autoantibodies recognizing cytokines arise in certain patients during the course of therapy with recombinant cytokines, although they may arise spontaneously as well. They are typically high avidity and in vitro neutralizing IgG antibodies present in picomolar to nanomolar concentrations. Methodo...

  8. Cytokine Levels in the Serum of Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Giulio Kleiner

    2013-01-01

    Full Text Available Growing knowledge about the cytokine network response has led to a better comprehension of mechanisms of pathologies and to the development of new treatments with biological drugs, able to block specific molecules of the immune response. Indeed, when the cytokine production is deregulated, diseases often occur. The understanding of the physiological mechanism of the cytokine network would be useful to better comprehend pathological conditions. Moreover, since the immune system and response change their properties with development, differences in patients' age should be taken into account, both in physiological and in pathological conditions. In this study, we analyzed the profile of 48 cytokines and chemokines in the serum of healthy subjects, comparing adults (≥18 years with young children and children (1–6 and 7–17 years. We found that a certain number of cytokines were not being produced in healthy subjects; others showed a constant serum level amongst the groups. Certain cytokines exhibited a downward or an upward trend with increasing age. The remaining cytokines were up- or downregulated in the group of the children with respect to the other groups. In conclusion, we drew some kinds of guidelines about the physiological production of cytokines and chemokines, underling the difference caused by aging.

  9. Cytokine levels in the serum of healthy subjects.

    Science.gov (United States)

    Kleiner, Giulio; Marcuzzi, Annalisa; Zanin, Valentina; Monasta, Lorenzo; Zauli, Giorgio

    2013-01-01

    Growing knowledge about the cytokine network response has led to a better comprehension of mechanisms of pathologies and to the development of new treatments with biological drugs, able to block specific molecules of the immune response. Indeed, when the cytokine production is deregulated, diseases often occur. The understanding of the physiological mechanism of the cytokine network would be useful to better comprehend pathological conditions. Moreover, since the immune system and response change their properties with development, differences in patients' age should be taken into account, both in physiological and in pathological conditions. In this study, we analyzed the profile of 48 cytokines and chemokines in the serum of healthy subjects, comparing adults (≥18 years) with young children and children (1-6 and 7-17 years). We found that a certain number of cytokines were not being produced in healthy subjects; others showed a constant serum level amongst the groups. Certain cytokines exhibited a downward or an upward trend with increasing age. The remaining cytokines were up- or downregulated in the group of the children with respect to the other groups. In conclusion, we drew some kinds of guidelines about the physiological production of cytokines and chemokines, underling the difference caused by aging.

  10. The role of cytokines in ultraviolet-B induced immunosuppression

    NARCIS (Netherlands)

    Boonstra, A.; Savelkoul, H.F.J.

    1997-01-01

    Summary : Cytokines play an important role in the mechanisms resulting in ultraviolet B-induced immunosuppression. They play a crucial role in the induction of local as well as systemic immunomodulatory events. Ultraviolet B irradiation directly induces the release of cytokines in the epidermis, res

  11. Cytokines in crevicular fluid and orthodontic tooth movement

    NARCIS (Netherlands)

    Ren, Yijin; Vissink, Arjan

    This review aimed to evaluate studies on cytokines in the gingival crevicular fluid (GCF) during orthodontic treatment, summarizing the regulation patterns of the most commonly studied cytokines and exploring their clinical implications. To achieve this, a number of key databases were searched using

  12. Inflammatory cytokines and risk of coronary heart disease

    DEFF Research Database (Denmark)

    Kaptoge, Stephen; Seshasai, Sreenivasa Rao Kondapally; Gao, Pei

    2014-01-01

    Because low-grade inflammation may play a role in the pathogenesis of coronary heart disease (CHD), and pro-inflammatory cytokines govern inflammatory cascades, this study aimed to assess the associations of several pro-inflammatory cytokines and CHD risk in a new prospective study, including meta...

  13. Cytokines: abnormalities in major depression and implications for pharmacological treatment.

    LENUS (Irish Health Repository)

    O'Brien, Sinead M

    2012-02-03

    The role of cytokines in depression was first considered when the cytokine interferon resulted in "sickness behaviour", the symptoms of which are similar to those of major depression. The latter is associated with an increase in pro-inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). These cytokines are potent modulators of corticotropin-releasing hormone (CRH) which produces heightened hypothalamic-pituitary-adrenal axis (HPA) activity characterized by increases in ACTH and cortisol, both of which are reported elevated in major depression. Antidepressant treatment has immunomodulatory effects with increases in the production of IL-10, which is an anti-inflammatory cytokine. This review based on a Medline search from 1980-2003, focuses on the evidence available of cytokine changes in acute stress, chronic stress and major depression. It examines the effects of antidepressant treatment on immune parameters in both animal models and clinical trials. We suggest that future antidepressants may target the immune system by either blocking the actions of pro-inflammatory cytokines or increasing the production of anti-inflammatory cytokines.

  14. Anti-cytokine therapies in T1D

    DEFF Research Database (Denmark)

    Nepom, Gerald T; Ehlers, Mario; Mandrup-Poulsen, Thomas

    2013-01-01

    selective cytokine blockade as a component of preventative or interventional immunotherapy. The rationale and status of inhibitory therapy directed against IL-1, TNF, IL-12, IL-23, and IL-6 are discussed, towards a goal of using cytokine inhibition as a therapeutic platform to establish an in vivo milieu...

  15. Cytokines and the Risk of Preterm Delivery in Twin Pregnancies

    DEFF Research Database (Denmark)

    Rode, Line; Klein, Katharina; Larsen, Helle

    2012-01-01

    To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment.......To estimate the association between cytokine levels in twin pregnancies and risk of spontaneous preterm delivery, including the effect of progesterone treatment....

  16. Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies

    Directory of Open Access Journals (Sweden)

    David Barrera

    2015-08-01

    Full Text Available Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

  17. Class I Cytokine Receptors: Structure and function in the Membrane

    DEFF Research Database (Denmark)

    Bugge, Katrine Østergaard

    ample material of high quality for structural studies with NMR spectroscopy of several class I cytokine receptor TMDs. Furthermore, the structure of a class I cytokine receptor TMD in DHPC micelles was solved with solution-state NMR spectroscopy. Additionally, since structural studies of intact proteins...

  18. Autophagy modulates the Mycobacterium tuberculosis-induced cytokine response

    NARCIS (Netherlands)

    Kleinnijenhuis, J.; Oosting, M.; Plantinga, T.S.; Meer, J.W.M. van der; Joosten, L.A.B.; Crevel, R. van; Netea, M.G.

    2011-01-01

    Both autophagy and pro-inflammatory cytokines are involved in the host defence against mycobacteria, but little is known regarding the effect of autophagy on Mycobacterium tuberculosis (MTB)-induced cytokine production. In the present study, we assessed the effect of autophagy on production of monoc

  19. Cytokines in lethal graft-versus-host disease

    NARCIS (Netherlands)

    Knulst, A.C.; Bril-Bazuin, C.; Tibbe, G.J.M.; Oudenaren, van A.; Savelkoul, H.F.J.; Benner, R.

    1992-01-01

    Graft-versus-host disease (GVHD) is caused by donor T lymphocytes that recognize foreign antigens on host tissues. This leads to T cell activation, which involves a cascade of events including the transcription of genes for cytokines and their receptors and the production of cytokines. One of the fi

  20. Role of inflammatory cytokines in peripheral nerve injury

    Institute of Scientific and Technical Information of China (English)

    Federica Fregnan; Luisa Muratori; Anabel Rodriguez Sim(o)es; Maria Giuseppina Giacobini-Robecchi; Stefania Raimondo

    2012-01-01

    Inflammatory events occurring in the distal part of an injured peripheral nerve have,nowadays,a great resonance.Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery.The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration.Cytokines can be divided into pro-and anti-inflammatory cytokines that upregutate and downregulate,respectively,the production of inflammatory mediators.While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages,anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines,thus determining the end of the process.In this review,we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration.In particular,we focus on interleukin-1,interleukin-2,interleukin-6,tumor necrosis factor-β,interleukin-10 and transforming growth factor-β.

  1. Vitamin D and Inflammatory Cytokines in Healthy and Preeclamptic Pregnancies.

    Science.gov (United States)

    Barrera, David; Díaz, Lorenza; Noyola-Martínez, Nancy; Halhali, Ali

    2015-08-04

    Preeclampsia is a pregnancy disease characterized by hypertension and proteinuria. Among several disorders, the imbalance of inflammatory cytokines and the alteration of vitamin D metabolism have been reported in preeclampsia. The effects of calcitriol upon inflammatory cytokines has been demonstrated. In healthy pregnant women there is a shift toward a Th2 cytokine profile, which is necessary for an adequate pregnancy outcome. As compared with normal pregnancy, high pro-inflammatory and low anti-inflammatory cytokine levels have been observed in preeclamptic women. Preeclampsia has been associated with low calcitriol levels and vitamin D deficiency is correlated with a higher risk of the development of this disease. It has been demonstrated that placenta is a source as well as the target of calcitriol and cytokines and placental dysfunction has been associated with preeclampsia. Therefore, the present manuscript includes a review about serum calcitriol levels in non-pregnant, pregnant, and preeclamptic women as well as a review on the fetoplacental vitamin D metabolism in healthy and preeclamptic pregnancies. In addition, circulating and fetoplacental inflammatory cytokines in healthy and preeclamptic pregnancies are reviewed. Finally, the effects of calcitriol upon placental pro-inflammatory cytokines are also explored. In conclusion, maternal and placental calcitriol levels are low in preeclampsia which may explain, at least in part, high pro-inflammatory cytokine levels in this disease.

  2. Spironolactone inhibits production of proinflammatory cytokines by human mononuclear cells

    DEFF Research Database (Denmark)

    Hansen, Peter Riis; Rieneck, Klaus; Bendtzen, Klaus

    2004-01-01

    The mineralocorticoid receptor antagonist spironolactone (SPIR) reduces the mortality and morbidity in patients with congestive heart failure (CHF). Overexpression of proinflammatory cytokines contribute to the development and progression of CHF.......The mineralocorticoid receptor antagonist spironolactone (SPIR) reduces the mortality and morbidity in patients with congestive heart failure (CHF). Overexpression of proinflammatory cytokines contribute to the development and progression of CHF....

  3. Peripheral blood neutrophil cytokine hyper-reactivity in chronic periodontitis.

    Science.gov (United States)

    Ling, Martin R; Chapple, Iain L C; Matthews, John B

    2015-10-01

    Pro-inflammatory cytokine release (IL-8, IL-6, TNF-α, IL-1β) by peripheral blood neutrophils, isolated from periodontitis patients (before/after therapy) and matched controls, was determined after 18 h culture in the presence/absence of Escherichia coli LPS, opsonised Staphylococcus aureus, heat-killed Fusobacterium nucleatum and Porphyromonas gingivalis. All cultures demonstrated differences in the amounts of each cytokine detected (P IL-6 > TNF-α = IL-1β). Median cytokine release from unstimulated patient neutrophils was consistently, but non-significantly, higher than from control cells. Stimulated cytokine release from untreated patient neutrophils was also consistently higher than from control cells. This hyper-reactivity was significant for all tested cytokines when data for all stimuli were combined (P TNF-α), opsonised S. aureus (IL-8, TNF-α, IL-1β) and P. gingivalis (IL-8, IL-1β). Cytokine production by patient neutrophils did not reduce following successful non-surgical periodontal therapy and, except for responses to F. nucleatum, the cytokine hyper-reactivity detected pre-therapy was retained. These data demonstrate that chronic periodontitis is characterised by neutrophils that constitutively exhibit cytokine hyper-reactivity, the effects of which could modulate local and systemic inflammatory-immune responses and influence the risk and severity of periodontitis-associated systemic inflammatory diseases.

  4. The cytokines cardiotrophin-like cytokine/cytokine-like factor-1 (CLC/CLF) and ciliary neurotrophic factor (CNTF) differ in their receptor specificities.

    Science.gov (United States)

    Tormo, Aurélie Jeanne; Letellier, Marie-Claude; Lissilaa, Rami; Batraville, Laurie-Anne; Sharma, Mukut; Ferlin, Walter; Elson, Greg; Crabé, Sandrine; Gauchat, Jean-François

    2012-12-01

    Ciliary neurotrophic factor (CNTF) and cardiotrophin-like cytokine (CLC) are two cytokines with neurotrophic and immunomodulatory activities. CNTF is a cytoplasmic factor believed to be released upon cellular damage, while CLC requires interaction with a soluble cytokine receptor, cytokine-like factor 1 (CLF), to be efficiently secreted. Both cytokines activate a receptor complex comprising the cytokine binding CNTF receptor α (CNTFRα) and two signaling chains namely, leukemia inhibitory factor receptor β (LIFRβ) and gp130. Human CNTF can recruit and activate an alternative receptor in which CNTFRα is substituted by IL-6Rα. As both CNTF and CLC have immune-regulatory activities in mice, we compared their ability to recruit mouse receptors comprising both gp130 and LIFRβ signaling chains and either IL-6Rα or IL-11Rα which, unlike CNTFRα, are expressed by immune cells. Our results indicate that 1) mouse CNTF, like its human homologue, can activate cells expressing gp130/LIFRβ with either CNTFRα or IL-6Rα and, 2) CLC/CLF is more restricted in its specificity in that it activates only the tripartite CNTFR. Several gp130 signaling cytokines influence T helper cell differentiation. We therefore investigated the effect of CNTF on CD4 T cell cytokine production. We observed that CNTF increased the number of IFN-γ producing CD4 T cells. As IFN-γ is considered a mediator of the therapeutic effect of IFN-β in multiple sclerosis, induction of IFN-γ by CNTF may contribute to the beneficial immunomodulatory effect of CNTF in mouse multiple sclerosis models. Together, our results indicate that CNTF activates the same tripartite receptors in mouse and human cells and further validate rodent models for pre-clinical investigation of CNTF and CNTF derivatives. Furthermore, CNTF and CLC/CLF differ in their receptor specificities. The receptor α chain involved in the immunomodulatory effects of CLC/CLF remains to be identified.

  5. Unique Cytokine Signature in the Plasma of Patients with Fibromyalgia

    Directory of Open Access Journals (Sweden)

    Jamie Sturgill

    2014-01-01

    Full Text Available Fibromyalgia (FMS is a chronic pain syndrome with a complex but poorly understood pathogenesis affecting approximately 10 million adults in the United States. The lack of a clear etiology of FMS has limited the effective diagnosis and treatment of this debilitating condition. The objective of this secondary data analysis was to examine plasma cytokine levels in women with FMS using the Bio-Plex Human Cytokine 17-plex Assay. Post hoc analysis of plasma cytokine levels was performed to evaluate patterns that were not specified a priori. Upon examination, patients with FMS exhibited a marked reduction in TH2 cytokines such as IL-4, IL-5, and IL-13. The finding of this pattern of altered cytokine milieu not only supports the role of inflammation in FMS but also may lead to more definitive diagnostic tools for clinicians treating FMS. The TH2 suppression provides strong evidence of immune dysregulation in patients with FMS.

  6. [Role of cytokines in the central nervous system].

    Science.gov (United States)

    Benavides, J; Toulmond, S

    1993-01-01

    Cytokines were first characterized as high-molecular weight modulators of the immune response. However they also play an important role in the CNS. Thus, some cytokines could influence the synaptic transmission or modulate the neuronal and glial growth during brain development or after brain injury. Activated glial cells appear to be the major cytokines producing cells. Some of these cytokines are glial cells mitogens, whilst others have a direct neurotrophic activity. These effects seem to be mediated by receptors similar to those of neurotrophic factors. Cytokines might be crucial factors in the evolution of different acute or chronic neuropathological processes such as ischemia, brain trauma, multiple sclerosis and Alzheimer's disease. Control of their effect on brain cells could allow prevention of brain damage observed in such pathologies.

  7. The inflammatory cytokines: molecular biomarkers for major depressive disorder?

    Science.gov (United States)

    Martin, Charlotte; Tansey, Katherine E; Schalkwyk, Leonard C; Powell, Timothy R

    2015-01-01

    Cytokines are pleotropic cell signaling proteins that, in addition to their role as inflammatory mediators, also affect neurotransmitter systems, brain functionality and mood. Here we explore the potential utility of cytokine biomarkers for major depressive disorder. Specifically, we explore how genetic, transcriptomic and proteomic information relating to the cytokines might act as biomarkers, aiding clinical diagnosis and treatment selection processes. We advise future studies to investigate whether cytokine biomarkers might differentiate major depressive disorder patients from other patient groups with overlapping clinical characteristics. Furthermore, we invite future pharmacogenetic studies to investigate whether early antidepressant-induced changes to cytokine mRNA or protein levels precede behavioral changes and act as longer-term predictors of clinical antidepressant response.

  8. Role of IL-38 and Its Related Cytokines in Inflammation

    Directory of Open Access Journals (Sweden)

    Xianli Yuan

    2015-01-01

    Full Text Available Interleukin- (IL- 38 is a recently discovered cytokine and is the tenth member of the IL-1 cytokine family. IL-38 shares structural features with IL-1 receptor antagonist (IL-1Ra and IL-36Ra. IL-36R is the specific receptor of IL-38, a partial receptor antagonist of IL-36. IL-38 inhibits the production of T-cell cytokines IL-17 and IL-22. IL-38 also inhibits the production of IL-8 induced by IL-36γ, thus inhibiting inflammatory responses. IL-38-related cytokines, including IL-1Ra and IL-36Ra, are involved in the regulation of inflammation and immune responses. The study of IL-38 and IL-38-related cytokines might provide new insights for developing anti-inflammatory treatments in the near future.

  9. The role of cytokines in immunological tolerance: potential for therapy.

    Science.gov (United States)

    Harber, M; Sundstedt, A; Wraith, D

    2000-11-27

    Current immunosuppression protocols, although often effective, are nonspecific and therefore hazardous. Consequently, immunological tolerance that is antigen specific and does not globally depress the patient's immune system has become one of the Holy Grails of immunology. Since the discovery that cytokines have immunomodulatory effects, extensive research has investigated the potential of these molecules to induce and maintain specific immunological tolerance in the context of transplantation, allergy and autoimmunity. In this article, we review the possible mechanisms by which cytokines can modulate the immune response and the animal models that frequently confound the theory that a single cytokine, or group of cytokines, can induce tolerance in a predictable manner. Finally, we discuss the role of cytokines at a paracrine level, particularly in the context of inducing and maintaining antigen-specific, regulatory T cells with the clinical potential to suppress specific immune responses.

  10. The role of cytokines in immune changes induced by spaceflight

    Science.gov (United States)

    Sonnenfeld, G.; Miller, E. S.

    1993-01-01

    It has become apparent that spaceflight alters many immune responses. Among the regulatory components of the immune response that have been shown to be affected by spaceflight is the cytokine network. Spaceflight, as well as model systems of spaceflight, have been shown to affect the production and action of various cytokines including interferons, interleukins, colony stimulating factors, and tumor necrosis factors. These changes have been shown not to involve a general shutdown of the cytokine network but, rather, to involve selective alterations of specific cytokine functions by spaceflight. The full breadth of changes in cytokines induced by spaceflight, as well as mechanisms, duration, adaptation, reversibility, and significance to resistance to infection and neoplastic diseases, remains to be established.

  11. Securing the User's Work Environment

    Science.gov (United States)

    Cardo, Nicholas P.

    2004-01-01

    High performance computing at the Numerical Aerospace Simulation Facility at NASA Ames Research Center includes C90's, J90's and Origin 2000's. Not only is it necessary to protect these systems from outside attacks, but also to provide a safe working environment on the systems. With the right tools, security anomalies in the user s work environment can be deleted and corrected. Validating proper ownership of files against user s permissions, will reduce the risk of inadvertent data compromise. The detection of extraneous directories and files hidden amongst user home directories is important for identifying potential compromises. The first runs of these utilities detected over 350,000 files with problems. With periodic scans, automated correction of problems takes only minutes. Tools for detecting these types of problems as well as their development techniques will be discussed with emphasis on consistency, portability and efficiency for both UNICOS and IRIX.

  12. Infection and upregulation of proinflammatory cytokines in human brain vascular pericytes by human cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Alcendor Donald J

    2012-05-01

    Full Text Available Abstract Background Congenital human cytomegalovirus (HCMV infections can result in CNS abnormalities in newborn babies including vision loss, mental retardation, motor deficits, seizures, and hearing loss. Brain pericytes play an essential role in the development and function of the blood–brain barrier yet their unique role in HCMV dissemination and neuropathlogy has not been reported. Methods Primary human brain vascular pericytes were exposed to a primary clinical isolate of HCMV designated ‘SBCMV’. Infectivity was analyzed by microscopy, immunofluorescence, Western blot, and qRT-PCR. Microarrays were performed to identify proinflammatory cytokines upregulated after SBCMV exposure, and the results validated by real-time quantitative polymerase chain reaction (qPCR methodology. In situ cytokine expression of pericytes after exposure to HCMV was examined by ELISA and in vivo evidence of HCMV infection of brain pericytes was shown by dual-labeled immunohistochemistry. Results HCMV-infected human brain vascular pericytes as evidenced by several markers. Using a clinical isolate of HCMV (SBCMV, microscopy of infected pericytes showed virion production and typical cytomegalic cytopathology. This finding was confirmed by the expression of major immediate early and late virion proteins and by the presence of HCMV mRNA. Brain pericytes were fully permissive for CMV lytic replication after 72 to 96 hours in culture compared to human astrocytes or human brain microvascular endothelial cells (BMVEC. However, temporal transcriptional expression of pp65 virion protein after SBCMV infection was lower than that seen with the HCMV Towne laboratory strain. Using RT-PCR and dual-labeled immunofluorescence, proinflammatory cytokines CXCL8/IL-8, CXCL11/ITAC, and CCL5/Rantes were upregulated in SBCMV-infected cells, as were tumor necrosis factor-alpha (TNF-alpha, interleukin-1 beta (IL-1beta, and interleukin-6 (IL-6. Pericytes exposed to SBCMV elicited

  13. Tracking the fate of antigen-specific versus cytokine-activated natural killer cells after cytomegalovirus infection.

    Science.gov (United States)

    Nabekura, Tsukasa; Lanier, Lewis L

    2016-11-14

    Natural killer (NK) cells provide important host defense and can generate long-lived memory NK cells. Here, by using novel transgenic mice carrying inducible Cre expressed under the control of Ncr1 gene, we demonstrated that two distinct long-lived NK cell subsets differentiate in a mouse model of cytomegalovirus (MCMV) infection. NK cells expressing the MCMV-specific Ly49H receptor differentiated into memory NK cells by an activating signaling through Ly49H and Ly49H(-) NK cells differentiated into cytokine-activated NK cells by exposure to inflammatory cytokines during infection. Interleukin-12 is indispensable for optimal generation of both antigen-specific memory NK cells and cytokine-activated NK cells. MCMV-specific memory NK cells show enhanced effector function and augmented antitumor activity in vivo as compared with cytokine-activated NK cells, whereas cytokine-activated NK cells exhibited a more robust response to IL-15 and persisted better in an MCMV-free environment. These findings reveal that NK cells are capable of differentiation into distinct long-lived subsets with different functional properties. © 2016 Nabekura and Lanier.

  14. Citoquinas en tuberculosis Cytokines in tuberculosis

    Directory of Open Access Journals (Sweden)

    Jaime I. Rodríguez

    1997-04-01

    Full Text Available La tuberculosis continúa siendo un modelo inmunológico para estudiar las infecciones intracelulares. Entenderlos complejos mecanismos de interacción de la micobacteria con el sistema inmune del hospedero permitirá un manejo más racional de los fenómenos clínicos que se presentan en la enfermedad. Las citoquinas desempeñan un papel fundamental tanto en el desarrollo de los mecanismos de inmunidad protectora como en el daño tisular presente en esta enfermedad. La estimulación in vitro de linfocitos de sujetos sanos tuberculino positivos con antígenos específicos induce preferencial mente un patrón de citoquinas tipo I (1'IL-2, 1'IFN-y, ~IL-4, ~IL-5, mientras que en la mayoría de los pacientes no se presenta este patrón. Las citoquinas tipo I conducen a la activación de los macrófagos que a su vez inhiben la replicación de las micobacterias. En el ratón, los macrófagos activados inhiben la micobacteria por medio del óxido nítrico; en los humanos la producción de óxido nítrico por los macrófagos no está plenamente demostrada. Recientemente se ha demostrado que la infección con M. tuberculosis puede inducir apoptosis en los macrófagos infectados. La apoptosis depende de la producción del Factor de Necrosis Tumoral a y de óxido nítrico. Paradójicamente, ellipoarabinomanán manosilado (ManLAM presente en la pared de las micobacterias inhibe la apoptosis. Estos hallazgos muestran un nuevo fenómeno en la interacción micobacteriamacrófago el cual debe estar finamente regulado tanto en el microorganismo como en el hospedero. Tuberculosis continues to be a model to study the immunological aspects of intracellular infections. A better understanding of the mycobacteria.host interaction would allow a more rational approach to the clinical problems of this disease. Cytokines playa key role in the development of protective immunity as well as in the tissue injury that occurs during the disease. In vitro stimulation with

  15. H pylori seropositivity and cytokine gene polymorphisms

    Institute of Scientific and Technical Information of China (English)

    Yasuaki Saijo; Eiji Yoshioka; Tomonori Fukui; Mariko Kawaharada; Fumihiro Sata; Hirokazu Sato; Reiko Kishi

    2007-01-01

    AIM: To investigate whether the pro- and antiinflammatory cytokine gene polymorphisms, IL1B-511C/T,IL1B-31C/T, IL6-634C/G, TNF-1031T/C, TNF-857C/T, and IL10-1082A/G, interact with smoking and drinking habits to influence infection with H pylori.METHODS: The subjects were 410 Japanese transit company employees. C-reactive protein and conventional cardiovascular risk factors were evaluated. Serum anti-H pylori antibodies were measured. The genotypes of IL1B-511C/T, IL1B-31C/T, IL6-634C/G, TNF-1031T/C,TNF-857C/T, and IL10-1082A/G polymorphisms were determined by allelic discrimination using fluorogenic probes and a 5'nuclease assay.RESULTS: In gender- and age-adjusted logistic analyses,the subjects with TNF-857T/T had a significantly lower odds ratio (OR) for H pylori seropositivity (reference -857C/C; OR = 0.15, 95% CI: 0.03-0.59, P = 0.007).After stratification according to smoking and drinking status, among never-smokers, the subjects with IL1B-511C/T had a significantly lower OR (reference -511C/C;OR = 0.30, 95% CI: 0.10-0.90, P = 0.032). Among drinkers in the 1-5 times/wk category, the subjects with IL1B-511T/T had a significantly lower OR (reference C/C; OR = 0.38, 95% CI: 0.16-0.95, P = 0.039), and the subjects with IL1B-31C/T and T/T had a significantly higher OR (reference C/C; C/T: OR = 2.59, 95% CI, P =0.042: 1.04-6.47; C/C: OR = 3.17, 95% CI: 1.23-8.14,P = 0.017). Among current smokers, the subjects with IL6-634C/G had a significantly higher OR (reference C/C;OR = 2.28, 95% CI: 1.13-4.58, P = 0.021). However,the interactions terms between the aforementioned genotypes and lifestyles were not statistically significant.CONCLUSION: Contrary to previous findings, the results herein suggest that the TNF-857T/T genotype may be protective against chronic infection with H pylori. Drinking and smoking habits may influence the effect of cytokine gene polymorphisms. Further studies are required to clarify the effects of the pro- and anti-inflammatory cytokine

  16. Permissive tolerance of the patent ductus arteriosus may increase the risk of Chronic Lung Disease

    Directory of Open Access Journals (Sweden)

    Kaempf JW

    2013-03-01

    Full Text Available Joseph W Kaempf,1 Robert Huston,2 YingXing Wu,1 Andrew J Kaempf,1 Lian Wang,1 Gary Grunkemeier,1 Rebecca Mischel,2 Howard Cohen,3 Bret Freitag41Providence St Vincent Medical Center, Portland, OR, 2Randall Children’s Hospital at Legacy Emanuel, Portland, OR, 3Salem Hospital, Salem, OR, 4Legacy Salmon Creek Hospital, Vancouver, WA, USAPurpose: Because early closure therapies of the patent ductus arteriosus (PDA have not been shown to confer benefit to premature infants, the authors’ four neonatal intensive care units adopted a less aggressive PDA management protocol.Study design: A before–after investigation in infants with PDAs born 501–1500 g. Era 1 (January 2005 to December 2007 featured traditional management with indomethacin and/or surgical ligation used early to close PDAs; Era 2 (January 2008 to June 2009 featured fluid restriction and watchful waiting for PDA closure, limiting indomethacin or surgical ligation to only those infants with large PDAs needing significant respiratory support.Results: Era 2 infants (n = 129, mean ± standard deviation 27 ± 2 weeks received less and later indomethacin and less Day 1–28 total fluids as compared to Era 1 infants (n = 240, mean ± standard deviation 27 ± 2 weeks. The Chronic Lung Disease (CLD rate was higher in Era 2 (48% versus 34%, P < 0.01 as was the combined outcome of Death after Day 7 or CLD (57% versus 42%, P < 0.01. Multiple regression analysis showed Era 2 birth was a predictor of CLD. However, Poisson regression analysis determined the predictors of all seven major Vermont Oxford Network morbidities were earlier gestational age, lower birth weight, and male gender, not the era of birth. Significantly more infants were discharged home with PDAs in Era 2.Conclusion: Permissive tolerance of PDAs may increase the risk of CLD and Death after Day 7 or CLD but is not associated with significant changes in other Vermont Oxford Network morbidities.Keywords: premature infant

  17. Keratinocytes under Fire of Proinflammatory Cytokines: Bona Fide Innate Immune Cells Involved in the Physiopathology of Chronic Atopic Dermatitis and Psoriasis

    Science.gov (United States)

    Bernard, François-Xavier; Morel, Franck; Camus, Magalie; Pedretti, Nathalie; Barrault, Christine; Garnier, Julien; Lecron, Jean-Claude

    2012-01-01

    Cutaneous homeostasis and defenses are maintained by permanent cross-talk among particular epidermal keratinocytes and immune cells residing or recruited in the skin, through the production of cytokines. If required, a coordinated inflammatory response is triggered, relayed by specific cytokines. Due to numerous reasons, troubles in the resolution of this phenomenon could generate a cytokine-mediated vicious circle, promoting skin chronic inflammation, the most common being atopic dermatitis and psoriasis. In this paper, we discuss the biological effects of cytokine on keratinocytes, more particularly on specific or shared cytokines involved in atopic dermatitis or psoriasis. We report and discuss monolayer or 3D in vitro models of keratinocytes stimulated by specific sets of cytokines to mimic atopic dermatitis or psoriasis. IL-22, TNFa, IL-4, and IL-13 combination is able to mimic an “atopic dermatitis like” state. In psoriasis lesions, over expression of IL-17 is observed whereas IL-4 and IL-13 were not detected; the replacement of IL-4 and IL-13 by IL-17 from this mix is able to mimic in vitro a “psoriasis like” status on keratinocytes. We conclude that specific cytokine environment deregulation plays a central role on skin morphology and innate immunity, moving towards specific pathologies and opening the way to new therapeutic strategies. PMID:23193414

  18. Keratinocytes under Fire of Proinflammatory Cytokines: Bona Fide Innate Immune Cells Involved in the Physiopathology of Chronic Atopic Dermatitis and Psoriasis

    Directory of Open Access Journals (Sweden)

    François-Xavier Bernard

    2012-01-01

    Full Text Available Cutaneous homeostasis and defenses are maintained by permanent cross-talk among particular epidermal keratinocytes and immune cells residing or recruited in the skin, through the production of cytokines. If required, a coordinated inflammatory response is triggered, relayed by specific cytokines. Due to numerous reasons, troubles in the resolution of this phenomenon could generate a cytokine-mediated vicious circle, promoting skin chronic inflammation, the most common being atopic dermatitis and psoriasis. In this paper, we discuss the biological effects of cytokine on keratinocytes, more particularly on specific or shared cytokines involved in atopic dermatitis or psoriasis. We report and discuss monolayer or 3D in vitro models of keratinocytes stimulated by specific sets of cytokines to mimic atopic dermatitis or psoriasis. IL-22, TNFa, IL-4, and IL-13 combination is able to mimic an “atopic dermatitis like” state. In psoriasis lesions, over expression of IL-17 is observed whereas IL-4 and IL-13 were not detected; the replacement of IL-4 and IL-13 by IL-17 from this mix is able to mimic in vitro a “psoriasis like” status on keratinocytes. We conclude that specific cytokine environment deregulation plays a central role on skin morphology and innate immunity, moving towards specific pathologies and opening the way to new therapeutic strategies.

  19. Operational Reconnaissance for the Anti-Access /Area Denial environment

    Science.gov (United States)

    2015-04-01

    computational power equivalent to two supercomputers.20 This impressive analytical capacity gives the pilot a coherent, real -time understanding of...performing Operational Reconnaissance in Anti-Access/Area Denial (A2/AD) environments. Contested battlespace is radically different from the permissive...AD environment. After gaining access to this airspace, fighters can use a variety of sensors to provide commanders with a real -time understanding of

  20. Inventory model with cash flow oriented and time-dependent holding cost under permissible delay in payments

    Directory of Open Access Journals (Sweden)

    Tripathi R.P.

    2013-01-01

    Full Text Available This study develops an inventory model for determining an optimal ordering policy for non-deteriorating items and time-dependent holding cost with delayed payments permitted by the supplier under inflation and time-discounting. The discounted cash flows approach is applied to study the problem analysis. Mathematical models have been derived under two different situations i.e. case I: The permissible delay period is less than cycle time for settling the account and case II: The permissible delay period is greater than or equal to cycle time for settling the account. An algorithm is used to obtain minimum total present value of the costs over the time horizon H. Finally, numerical example and sensitivity analysis demonstrate the applicability of the proposed model. The main purpose of this paper is to investigate the optimal cycle time and optimal payment time for an item so that annual total relevant cost is minimized.