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  1. HIV Pathogenesis: Abstracts from the March 2017 Cleveland Immunopathogenesis Consortium Meeting

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    Michael M. Lederman

    2017-06-01

    Full Text Available The Cleveland Immunopathogenesis Consortium (CLIC was launched in March 2004 by a small group of investigators (Ron Bosch, Jason Brenchley,  Steven Deeks, Danny Douek, Zvi Grossman, Robert Kalayjian, Clifford Harding, Michael Lederman, Leonid Margolis, Miguel Quinones, Benigno Rodriguez, Rafick Sekaly, Scott Sieg, and Guido Silvestri who were increasingly persuaded that immune activation was an important driver of HIV pathogenesis. We met around a chalk board and scribbled our models of pathogenesis, designed some experiments then went back home to do them. We met again soon to review our new and unpublished findings that refined and shaped these models. The data presentations were short, informal and heavy on discussion. The model worked well, the consortium was productive and the meetings catalyzed numerous collaborations and scores of high impact papers. The CLIC (less formally, the Bad Boys of Cleveland [1] has been meeting regularly since then. Consortium membership has expanded to include other investigators (some are listed in the presentations below. Whether the goal is to prevent the morbid complications of HIV infection, to understand the determinants of HIV persistence or the factors that protect from acquisition of infection, a more clear understanding of HIV immunopathogenesis is central. Here in this issue of Pathogens and Immunity is a brief summary of the most recent CLIC//BBC meeting held in Cleveland in March 2017.

  2. Serodiagnostic profiles of HIV and HIV pathogenesis in vivo

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    Goudsmit, J.; Lange, J. M.; Smit, L.; Bakker, M.; Klaver, B.; Danner, S. A.; Coutinho, R. A.

    1988-01-01

    Different stages of HIV infection are marked by expression of HIV genes, production of HIV antibodies, formation of antigen/antibody complexes and clearance of such complexes. Transient HIV antigenemia appearing generally 6-8 weeks prior to HIV antibody (HIV-Ab) seroconversion and lasting 3-4 months

  3. HIV Infection of Macrophages: Implications for Pathogenesis and Cure

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    Kiera Leigh Clayton

    2017-05-01

    Full Text Available Although CD4+ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages also contribute. However, investigations of the role of macrophages are often underrepresented at HIV pathogenesis and cure meetings. This was the impetus for a scientific workshop dedicated to this area of study, held in Cambridge, MA in January 2017. The workshop brought together experts in the fields of HIV/SIV immunology/virology, macrophage biology and immunology, and animal models of HIV/SIV infection to facilitate discussions regarding the role of macrophages as a physiologically relevant viral reservoir, and the implications of macrophage infection for HIV pathogenesis and cure strategies. An emerging consensus that infected macrophages likely persist in the setting of combination antiretroviral therapy, driving persistent inflammation and contributing to the viral reservoir, indicate the importance of addressing macrophages as well as CD4+ T cells with future therapeutic strategies.

  4. Polycyclic aromatic hydrocarbons and cytochrome P450 in HIV pathogenesis

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    Rao, P. S. S.; Kumar, Santosh

    2015-01-01

    High prevalence of cigarette smoking in HIV patients is associated with increased HIV pathogenesis and disease progression. While the effect of smoking on the occurrence of lung cancer has been studied extensively, the association between smoking and HIV pathogenesis is poorly studied. We have recently shown the possible role of cytochrome P450 (CYP) in smoking/nicotine-mediated viral replication. In this review, we focus on the potential role of CYP pathway in polycyclic aromatic hydrocarbons (PAH), important constituents of cigarette smoke, mediated HIV pathogenesis. More specifically, we will discuss the role of CYP1A1 and CYP1B1, which are the major PAH-activating CYP enzymes. Our results have shown that treatment with cigarette smoke condensate (CSC) increases viral replication in HIV-infected macrophages. CSC contains PAH, which are known to be activated by CYP1A1 and CYP1B1 into procarcinogens/toxic metabolites. The expression of these CYPs is regulated by aryl hydrocarbon receptors (AHR), the cellular target of PAH, and an important player in various diseases including cancer. We propose that PAH/AHR-mediated CYP pathway is a novel target to develop new interventions for HIV positive smokers. PMID:26082767

  5. HIV-1 Nef in Macrophage-Mediated Disease Pathogenesis

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    Lamers, Susanna L.; Fogel, Gary B.; Singer, Elyse J.; Salemi, Marco; Nolan, David J.; Huysentruyt, Leanne C.; McGrath, Michael S.

    2013-01-01

    Combined anti-retroviral therapy (cART) has significantly reduced the number of AIDS-associated illnesses and changed the course of HIV-1 disease in developed countries. Despite the ability of cART to maintain high CD4+ T-cell counts, a number of macrophage-mediated diseases can still occur in HIV-infected subjects. These diseases include lymphoma, metabolic diseases, and HIV-associated neurological disorders. Within macrophages, the HIV-1 regulatory protein “Nef” can modulate surface receptors, interact with signaling pathways, and promote specific environments that contribute to each of these pathologies. Moreover, genetic variation in Nef may also guide the macrophage response. Herein, we review findings relating to the Nef–macrophage interaction and how this relationship contributes to disease pathogenesis. PMID:23215766

  6. Applications of the FIV Model to Study HIV Pathogenesis

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    Craig Miller

    2018-04-01

    Full Text Available Feline immunodeficiency virus (FIV is a naturally-occurring retrovirus that infects domestic and non-domestic feline species, producing progressive immune depletion that results in an acquired immunodeficiency syndrome (AIDS. Much has been learned about FIV since it was first described in 1987, particularly in regard to its application as a model to study the closely related lentivirus, human immunodeficiency virus (HIV. In particular, FIV and HIV share remarkable structure and sequence organization, utilize parallel modes of receptor-mediated entry, and result in a similar spectrum of immunodeficiency-related diseases due to analogous modes of immune dysfunction. This review summarizes current knowledge of FIV infection kinetics and the mechanisms of immune dysfunction in relation to opportunistic disease, specifically in regard to studying HIV pathogenesis. Furthermore, we present data that highlight changes in the oral microbiota and oral immune system during FIV infection, and outline the potential for the feline model of oral AIDS manifestations to elucidate pathogenic mechanisms of HIV-induced oral disease. Finally, we discuss advances in molecular biology, vaccine development, neurologic dysfunction, and the ability to apply pharmacologic interventions and sophisticated imaging technologies to study experimental and naturally occurring FIV, which provide an excellent, but often overlooked, resource for advancing therapies and the management of HIV/AIDS.

  7. Oligodendrocyte Injury and Pathogenesis of HIV-1-Associated Neurocognitive Disorders

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    Han Liu

    2016-07-01

    Full Text Available Oligodendrocytes wrap neuronal axons to form myelin, an insulating sheath which is essential for nervous impulse conduction along axons. Axonal myelination is highly regulated by neuronal and astrocytic signals and the maintenance of myelin sheaths is a very complex process. Oligodendrocyte damage can cause axonal demyelination and neuronal injury, leading to neurological disorders. Demyelination in the cerebrum may produce cognitive impairment in a variety of neurological disorders, including human immunodeficiency virus type one (HIV-1-associated neurocognitive disorders (HAND. Although the combined antiretroviral therapy has markedly reduced the incidence of HIV-1-associated dementia, a severe form of HAND, milder forms of HAND remain prevalent even when the peripheral viral load is well controlled. HAND manifests as a subcortical dementia with damage in the brain white matter (e.g., corpus callosum, which consists of myelinated axonal fibers. How HIV-1 brain infection causes myelin injury and resultant white matter damage is an interesting area of current HIV research. In this review, we tentatively address recent progress on oligodendrocyte dysregulation and HAND pathogenesis.

  8. 'Omics investigations of HIV and SIV pathogenesis and innate immunity.

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    Palermo, Robert E; Fuller, Deborah H

    2013-01-01

    In the 30 years since the advent of the AIDS epidemic, the biomedical community has put forward a battery of molecular therapies that are based on the accumulated knowledge of a limited number of viral targets. Despite these accomplishments, the community still confronts unanswered foundational questions about HIV infection. What are the cellular or biomolecular processes behind HIV pathogenesis? Can we elucidate the characteristics that distinguish those individuals who are naturally resistant to either infection or disease progression? The discovery of simian immunodeficiency viruses (SIVs) and the ensuing development of in vivo, nonhuman primate (NHP) infection models was a tremendous advance, especially in abetting the exploration of vaccine strategies. And while there have been numerous NHP infection models and vaccine trials performed, fundamental questions remain regarding host-virus interactions and immune correlates of protection. These issues are, perhaps, most starkly illustrated with the appreciation that many species of African nonhuman primates are naturally infected with strains of SIV that do not cause any appreciable disease while replicating to viral loads that match or exceed those seen with pathogenic SIV infections in Asian species of nonhuman primates. The last decade has seen the establishment of high-throughput molecular profiling tools, such as microarrays for transcriptomics, SNP arrays for genome features, and LC-MS techniques for proteins or metabolites. These provide the capacity to interrogate a biological model at a comprehensive, systems level, in contrast to historical approaches that characterized a few genes or proteins in an experiment. These methods have already had revolutionary impacts in understanding human diseases originating within the host genome such as genetic disorders and cancer, and the methods are finding increasing application in the context of infectious disease. We will provide a review of the use of such 'omics

  9. The pathogenesis of HIV infection: stupid may not be so dumb after all

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    Smith Stephen M

    2006-09-01

    Full Text Available Abstract In the mid-1990's, researchers hypothesized, based on new viral load data, that HIV-1 causes CD4+ T-cell depletion by direct cytopathic effect. New data from non-human primate studies has raised doubts about this model of HIV-1 pathogenesis. Despite having high levels of viremia, most SIV infections are well tolerated by their natural hosts. Two recent studies of these models provide information, which may be useful in determining how HIV-1 causes CD4+ T-cell loss. A full understanding of pathogenesis may lead to novel therapies, which preserve the immune system without blocking virus replication.

  10. The involvement of plasmacytoid cells in HIV infection and pathogenesis.

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    Aiello, Alessandra; Giannessi, Flavia; Percario, Zulema A; Affabris, Elisabetta

    2018-04-01

    Plasmacytoid dendritic cells (pDCs) are a unique dendritic cell subset that are specialized in type I interferon (IFN) production. pDCs are key players in the antiviral immune response and serve as bridge between innate and adaptive immunity. Although pDCs do not represent the main reservoir of the Human Immunodeficiency Virus (HIV), they are a crucial subset in HIV infection as they influence viral transmission, target cell infection and antigen presentation. pDCs act as inflammatory and immunosuppressive cells, thus contributing to HIV disease progression. This review provides a state of art analysis of the interactions between HIV and pDCs and their potential roles in HIV transmission, chronic immune activation and immunosuppression. A thorough understanding of the roles of pDCs in HIV infection will help to improve therapeutic strategies to fight HIV infection, and will further increase our knowledge on this important immune cell subset. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. HIV lipodystrophy etiology and pathogenesis. Body composition and metabolic alterations: etiology and pathogenesis.

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    Kotler, Donald P

    2003-04-01

    The results of epidemiologic investigations have clearly indicated that the development of lipodystrophy is multifactorial. Factors related to HIV infection, hormonal influences, mitochondrial dysfunction, cytokine activation related to immune reconstitution, and individual genetic predisposition all have been hypothesized as etiologic. Recent studies suggest that immune dysregulation rather than HIV infection per se may be the predominant factor in the development of lipodystrophy.

  12. Genome-wide association studies on HIV susceptibility, pathogenesis and pharmacogenomics

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    van Manen Daniëlle

    2012-08-01

    Full Text Available Abstract Susceptibility to HIV-1 and the clinical course after infection show a substantial heterogeneity between individuals. Part of this variability can be attributed to host genetic variation. Initial candidate gene studies have revealed interesting host factors that influence HIV infection, replication and pathogenesis. Recently, genome-wide association studies (GWAS were utilized for unbiased searches at a genome-wide level to discover novel genetic factors and pathways involved in HIV-1 infection. This review gives an overview of findings from the GWAS performed on HIV infection, within different cohorts, with variable patient and phenotype selection. Furthermore, novel techniques and strategies in research that might contribute to the complete understanding of virus-host interactions and its role on the pathogenesis of HIV infection are discussed.

  13. Pathogenesis and treatment of HIV-1 infection: recent developments (Y2K update).

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    Dewhurst, S L; da Cruz, R L; Whetter, L

    2000-01-01

    Human immunodeficiency virus type 1 (HIV-1) is the etiologic agent of acquired immunodeficiency syndrome (AIDS). The pathogenesis of HIV-1-induced disease is complex and characterized by the interplay of both viral and host factors, which together determine the outcome of infection. An improved understanding of the pathogenic mechanisms of AIDS, combined with recent insights into the dynamics of viral infection may provide powerful new opportunities for therapeutic intervention against this virus.

  14. The Gut Microbiome and HIV-1 Pathogenesis: A Two Way Street

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    Dillon, Stephanie M.; Frank, Daniel N.; Wilson, Cara C.

    2016-01-01

    HIV-1 infection is associated with substantial damage to the gastrointestinal (GI) tract resulting in structural impairment of the epithelial barrier and a disruption of intestinal homeostasis. The accompanying translocation of microbial products and potentially microbes themselves from the lumen into systemic circulation has been linked to immune activation, inflammation, and HIV-1 disease progression. The importance of microbial translocation in the setting of HIV-1 infection has led to a recent focus on understanding how the communities of microbes that make up the intestinal microbiome are altered during HIV-1 infection and how they interact with mucosal immune cells to contribute to inflammation. This review details the dysbiotic intestinal communities associated with HIV-1 infection and their potential link to HIV-1 pathogenesis. We detail studies that begin to address the mechanisms driving microbiota-associated immune activation and inflammation and the various treatment strategies aimed at correcting dysbiosis and improving the overall health of HIV-1 infected individuals. Finally, we discuss how this relatively new field of research can advance to provide a more comprehensive understanding of the contribution of the gut microbiome to HIV-1 pathogenesis. PMID:27755100

  15. HIV-1 impairs human retinal pigment epithelial barrier function: possible association with the pathogenesis of HIV-associated retinopathy.

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    Tan, Suiyi; Duan, Heng; Xun, Tianrong; Ci, Wei; Qiu, Jiayin; Yu, Fei; Zhao, Xuyan; Wu, Linxuan; Li, Lin; Lu, Lu; Jiang, Shibo; Liu, Shuwen

    2014-07-01

    The breakdown of human retinal pigment epithelial (HRPE) barrier is considered as the etiology of retinopathy, which affects the quality of life of HIV/AIDS patients. Here we demonstrate that HIV-1 could directly impair HRPE barrier function, which leads to the translocation of HIV-1 and bacteria. HRPE cells (D407) were grown to form polarized, confluent monolayers and treated with different HIV-1 infectious clones. A significant increase of monolayer permeability, as measured by trans-epithelial electrical resistance (TEER) and apical-basolateral movements of sodium fluorescein, was observed. Disrupted tightness of HRPE barrier was associated with the downregulation of several tight junction proteins in D407 cells, including ZO-1, Occludin, Claudin-1, Claudin-2, Claudin-3, Claudin-4, and Claudin-5, after exposure to HIV-1, without affecting the viability of cells. HIV-1 gp120 was shown to participate in the alteration of barrier properties, as evidenced by decreased TEER and weakened expression of tight junction proteins in D407 monolayers after exposure to pseudotyped HIV-1, UV-inactivated HIV-1, and free gp120, but not to an envelope (Env)-defective mutant of HIV. Furthermore, exposure to HIV-1 particles could induce the release of pro-inflammatory cytokines in D407, including IL-6 and MCP-1, both of which downregulated the expression of ZO-1 in the HRPE barrier. Disrupted HRPE monolayer allowed translocation of HIV-1 and bacteria across the epithelium. Overall, these findings suggest that HIV-1 may exploit its Env glycoprotein to induce an inflammatory state in HRPE cells, which could result in impairment of HRPE monolayer integrity, allowing virus and bacteria existing in ocular fluids to cross the epithelium and penetrate the HRPE barrier. Our study highlights the role of HIV-1 in the pathogenesis of HIV/AIDS-related retinopathy and suggests potential therapeutic targets for this ocular complication.

  16. The pathogenesis of liver disease in the setting of HIV-hepatitis B virus coinfection.

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    Iser, David M; Lewin, Sharon R

    2009-01-01

    There are many potential reasons for increased liver-related mortality in HIV-hepatitis B virus (HBV) coinfection compared with either infection alone. HIV infects multiple cells in the liver and might potentially alter the life cycle of HBV, although evidence to date is limited. Unique mutations in HBV have been defined in HIV-HBV-coinfected individuals and might directly alter pathogenesis. In addition, an impaired HBV-specific T-cell immune response is likely to be important. The roles of microbial translocation, immune activation and increased hepatic stellate cell activation will be important areas for future study.

  17. Contrasting roles for TLR ligands in HIV-1 pathogenesis.

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    Beda Brichacek

    2010-09-01

    Full Text Available The first line of a host's response to various pathogens is triggered by their engagement of cellular pattern recognition receptors (PRRs. Binding of microbial ligands to these receptors leads to the induction of a variety of cellular factors that alter intracellular and extracellular environment and interfere directly or indirectly with the life cycle of the triggering pathogen. Such changes may also affect any coinfecting microbe. Using ligands to Toll-like receptors (TLRs 5 and 9, we examined their effect on human immunodeficiency virus (HIV-1 replication in lymphoid tissue ex vivo. We found marked differences in the outcomes of such treatment. While flagellin (TLR5 agonist treatment enhanced replication of CC chemokine receptor 5 (CCR 5-tropic and CXC chemokine receptor 4 (CXCR4-tropic HIV-1, treatment with oligodeoxynucleotide (ODN M362 (TLR9 agonist suppressed both viral variants. The differential effects of these TLR ligands on HIV-1 replication correlated with changes in production of CC chemokines CCL3, CCL4, CCL5, and of CXC chemokines CXCL10, and CXCL12 in the ligand-treated HIV-1-infected tissues. The nature and/or magnitude of these changes were dependent on the ligand as well as on the HIV-1 viral strain. Moreover, the tested ligands differed in their ability to induce cellular activation as evaluated by the expression of the cluster of differentiation markers (CD 25, CD38, CD39, CD69, CD154, and human leukocyte antigen D related (HLA-DR as well as of a cell proliferation marker, Ki67, and of CCR5. No significant effect of the ligand treatment was observed on apoptosis and cell death/loss in the treated lymphoid tissue ex vivo. Our results suggest that binding of microbial ligands to TLRs is one of the mechanisms that mediate interactions between coinfected microbes and HIV-1 in human tissues. Thus, the engagement of appropriate TLRs by microbial molecules or their mimetic might become a new strategy for HIV therapy or prevention.

  18. HIV-induced immune activation - pathogenesis and clinical relevance

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    Stellbrink HJ

    2010-01-01

    Full Text Available Abstract This manuscript is communicated by the German AIDS Society (DAIG http://www.daignet.de. It summarizes a series of presentations and discussions during a workshop on immune activation due to HIV infection. The workshop was held on November 22nd 2008 in Hamburg, Germany. It was organized by the ICH Hamburg under the auspices of the German AIDS Society (DAIG e.V..

  19. Understanding HIV infection for the design of a therapeutic vaccine. Part I: Epidemiology and pathogenesis of HIV infection.

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    de Goede, A L; Vulto, A G; Osterhaus, A D M E; Gruters, R A

    2015-03-01

    HIV infection leads to a gradual loss CD4+ T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive life-long adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. Human immunodeficiency virus-associated disruption of mucosal barriers and its role in HIV transmission and pathogenesis of HIV/AIDS disease

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    Tugizov, Sharof

    2016-01-01

    Abstract Oral, intestinal and genital mucosal epithelia have a barrier function to prevent paracellular penetration by viral, bacterial and other pathogens, including human immunodeficiency virus (HIV). HIV can overcome these barriers by disrupting the tight and adherens junctions of mucosal epithelia. HIV-associated disruption of epithelial junctions may also facilitate paracellular penetration and dissemination of other viral pathogens. This review focuses on possible molecular mechanisms of HIV-associated disruption of mucosal epithelial junctions and its role in HIV transmission and pathogenesis of HIV and acquired immune deficiency syndrome (AIDS). PMID:27583187

  1. Interplay of HIV-1 phenotype and neutralizing antibody response in pathogenesis of AIDS.

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    Scarlatti, G; Leitner, T; Hodara, V; Jansson, M; Karlsson, A; Wahlberg, J; Rossi, P; Uhlén, M; Fenyö, E M; Albert, J

    1996-06-01

    A majority of human immunodeficiency virus type 1 (HIV-1) infected individuals display a rapid loss of CD4+ lymphocytes with fast progression towards overt acquired immunodeficiency syndrome (AIDS). However, a small proportion of individuals infected by HIV-1 remain immunologically intact for many years. In order to identify factors that might influence the pathogenesis of HIV-1 infection, 21 Italian mothers and 11 Swedish homosexual men were studied for the presence of autologous neutralizing antibodies in serum, biological phenotype of virus isolates and envelope variable region 3 (V3) sequences. The results were compared to the risk of mother-to-child transmission and progression of the disease. The presence of a neutralizing antibody response to the autologous virus as well as a virus with slow replicative capacity were linked both to low risk of mother-to-child transmission and non-progression of the disease. Patients whose peripheral blood mononuclear cells contained a mutation in the tip of the V3 loop (Arg318 to serine, lysine or leucine) significantly more often had neutralizing antibodies to autologous virus isolates containing arginine at this position. Thus, it appears that the interplay and balance between neutralizing antibody response of the host and the biological phenotype of HIV-1 strongly influence pathogenesis.

  2. Scott S Snyder

    Indian Academy of Sciences (India)

    Home; Journals; Pramana – Journal of Physics. Scott S Snyder. Articles written in Pramana – Journal of Physics. Volume 62 Issue 3 March 2004 pp 565-568 Experimental Particle Physics. Prospects for Higgs search at DØ · Scott S Snyder DØ Collaboration · More Details Abstract Fulltext PDF. The status of the Higgs search ...

  3. Citation for Scott Doney

    Science.gov (United States)

    Glover, David M.; Doney, Scott

    “A man of genius makes no mistakes. His errors are volitional and are the portals of discovery. James Joyce, Ulysses (1922). ”After collaborating with Scott Doney for the past 14 years I know what Joyce meant. When working with someone as bright as Scott it inevitably happens that you just don't understand. And because we're trained skeptics the question immediately arises, ”has our friend and colleague made a mistake?“ But we're wrong; we just didn't see the portal through which people like Scott had already proceeded. Certainly this is what we reserve these awards of ‘outstandingness’ for; those whose insight lead through the portals of discovery”.

  4. Role of transmitted Gag CTL polymorphisms in defining replicative capacity and early HIV-1 pathogenesis.

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    Jessica L Prince

    Full Text Available Initial studies of 88 transmission pairs in the Zambia Emory HIV Research Project cohort demonstrated that the number of transmitted HLA-B associated polymorphisms in Gag, but not Nef, was negatively correlated to set point viral load (VL in the newly infected partners. These results suggested that accumulation of CTL escape mutations in Gag might attenuate viral replication and provide a clinical benefit during early stages of infection. Using a novel approach, we have cloned gag sequences isolated from the earliest seroconversion plasma sample from the acutely infected recipient of 149 epidemiologically linked Zambian transmission pairs into a primary isolate, subtype C proviral vector, MJ4. We determined the replicative capacity (RC of these Gag-MJ4 chimeras by infecting the GXR25 cell line and quantifying virion production in supernatants via a radiolabeled reverse transcriptase assay. We observed a statistically significant positive correlation between RC conferred by the transmitted Gag sequence and set point VL in newly infected individuals (p = 0.02. Furthermore, the RC of Gag-MJ4 chimeras also correlated with the VL of chronically infected donors near the estimated date of infection (p = 0.01, demonstrating that virus replication contributes to VL in both acute and chronic infection. These studies also allowed for the elucidation of novel sites in Gag associated with changes in RC, where rare mutations had the greatest effect on fitness. Although we observed both advantageous and deleterious rare mutations, the latter could point to vulnerable targets in the HIV-1 genome. Importantly, RC correlated significantly (p = 0.029 with the rate of CD4+ T cell decline over the first 3 years of infection in a manner that is partially independent of VL, suggesting that the replication capacity of HIV-1 during the earliest stages of infection is a determinant of pathogenesis beyond what might be expected based on set point VL alone.

  5. Metric Scott analysis

    Czech Academy of Sciences Publication Activity Database

    Ben Yaacov, I.; Doucha, Michal; Nies, A.; Tsankov, T.

    2017-01-01

    Roč. 318, October (2017), s. 46-87 ISSN 0001-8708 Institutional support: RVO:67985840 Keywords : continuous logic * infinitary logic * Scott sentence Subject RIV: BA - General Mathematics OBOR OECD: Pure mathematics Impact factor: 1.373, year: 2016 http://www.sciencedirect.com/science/article/pii/S0001870816309896?via%3Dihub

  6. Pathogenesis of HIV and its implications for serodiagnosis and monitoring of antiviral therapy

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    Goudsmit, J.; Lange, J. M.; Krone, W. J.; Teunissen, M. B.; Epstein, L. G.; Danner, S. A.; van den Berg, H.; Breederveld, C.; Smit, L.; Bakker, M.

    1987-01-01

    Human immunodeficiency virus (HIV) is lymphotropic and neurotropic. In vivo clinical and immunological abnormalities develop in a large proportion of long-term HIV antibody seropositive persons. Different stages of HIV infection are marked by expression of HIV genes, production of HIV antibodies,

  7. The utility of the new generation of humanized mice to study HIV-1 infection: transmission, prevention, pathogenesis, and treatment

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    Rowan Mark R

    2011-08-01

    Full Text Available Abstract Substantial improvements have been made in recent years in the ability to engraft human cells and tissues into immunodeficient mice. The use of human hematopoietic stem cells (HSCs leads to multi-lineage human hematopoiesis accompanied by production of a variety of human immune cell types. Population of murine primary and secondary lymphoid organs with human cells occurs, and long-term engraftment has been achieved. Engrafted cells are capable of producing human innate and adaptive immune responses, making these models the most physiologically relevant humanized animal models to date. New models have been successfully infected by a variety of strains of Human Immunodeficiency Virus Type 1 (HIV-1, accompanied by virus replication in lymphoid and non-lymphoid organs, including the gut-associated lymphoid tissue, the male and female reproductive tracts, and the brain. Multiple forms of virus-induced pathogenesis are present, and human T cell and antibody responses to HIV-1 are detected. These humanized mice are susceptible to a high rate of rectal and vaginal transmission of HIV-1 across an intact epithelium, indicating the potential to study vaccines and microbicides. Antiviral drugs, siRNAs, and hematopoietic stem cell gene therapy strategies have all been shown to be effective at reducing viral load and preventing or reversing helper T cell loss in humanized mice, indicating that they will serve as an important preclinical model to study new therapeutic modalities. HIV-1 has also been shown to evolve in response to selective pressures in humanized mice, thus showing that the model will be useful to study and/or predict viral evolution in response to drug or immune pressures. The purpose of this review is to summarize the findings reported to date on all new humanized mouse models (those transplanted with human HSCs in regards to HIV-1 sexual transmission, pathogenesis, anti-HIV-1 immune responses, viral evolution, pre- and post

  8. Genome-wide association studies on HIV susceptibility, pathogenesis and pharmacogenomics

    NARCIS (Netherlands)

    van Manen, Daniëlle; van 't Wout, Angélique B.; Schuitemaker, Hanneke

    2012-01-01

    Susceptibility to HIV-1 and the clinical course after infection show a substantial heterogeneity between individuals. Part of this variability can be attributed to host genetic variation. Initial candidate gene studies have revealed interesting host factors that influence HIV infection, replication

  9. Novel insights into the effect of CCR5 inhibition on HIV treatment, pathogenesis and cure

    NARCIS (Netherlands)

    Symons, J.

    2014-01-01

    The introduction of combination antiretroviral therapy (cART) in 1996 has significantly reduced HIV related morbidity and mortality in the Western world. Recent advances in antiretroviral treatment have resulted in a life expectancy of effectively treated HIV infected patients, comparable to those

  10. The prevalence and pathogenesis of diabetes mellitus in treated HIV-infection.

    Science.gov (United States)

    Paik, Il Joon; Kotler, Donald P

    2011-06-01

    HIV-associated morbidity and mortality have declined significantly since the introduction of highly active antiretroviral therapy (HAART). These developments have allowed an increased focus on associated adverse metabolic effects, such as dyslipidemia, diabetes mellitus, and insulin resistance, which are risk factors for cardiovascular disease and other adverse outcomes. The pathophysiologic mechanisms underlying the metabolic changes are complicated and not yet fully elucidated due to the difficulty of separating the effects of HIV infection from those of HAART, co-morbidities, or individual patient vulnerabilities. This article reviews studies concerning the prevalence and incidence of diabetes mellitus and HIV, HIV-specific effects on diabetes mellitus complications, and HIV-specific diabetes mellitus treatment considerations. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. HIV-associated neurocognitive disorders: recent advances in pathogenesis, biomarkers, and treatment [version 1; referees: 4 approved

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    Antonia Carroll

    2017-03-01

    Full Text Available HIV-associated neurocognitive disorders (HAND remain prevalent despite plasma viral suppression by antiretroviral agents. In fact, the prevalence of milder subtypes of cognitive impairment is increasing. Neuropsychologic testing remains the “gold standard” of diagnosis; however, this is time consuming and costly in a resource-poor environment. Recently developed screening tools, such as CogState and the revised HIV dementia scale, have very good sensitivity and specificity in the more severe stages of HAND. However, questions remain regarding the utility of, optimal population for, and insensitivity of tests in mild HAND. Recognition of ongoing viral persistence and the inflammatory milieu in the central nervous system (CNS has advanced our understanding of the pathogenesis of HAND and facilitated the development of biomarkers of CNS disease. The importance of the monocyte-macrophage lineage cell and the astrocyte as viral reservoirs, HIV viral proteins, self-perpetuating CNS inflammation, and CCR5 chemokine receptor neurotropism has been identified. Whilst biomarkers demonstrate monocyte activation, inflammation, and neuronal injury, they remain limited in their clinical utility. The improved understanding of pathogenic mechanisms has led to novel approaches to the treatment of HAND; however, despite these advances, the optimal management is still undefined.

  12. Basic science and pathogenesis of ageing with HIV: potential mechanisms and biomarkers.

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    Lagathu, Claire; Cossarizza, Andrea; Béréziat, Véronique; Nasi, Milena; Capeau, Jacqueline; Pinti, Marcello

    2017-06-01

    : The increased prevalence of age-related comorbidities and mortality is worrisome in ageing HIV-infected patients. Here, we aim to analyse the different ageing mechanisms with regard to HIV infection. Ageing results from the time-dependent accumulation of random cellular damage. Epigenetic modifications and mitochondrial DNA haplogroups modulate ageing. In antiretroviral treatment-controlled patients, epigenetic clock appears to be advanced, and some haplogroups are associated with HIV infection severity. Telomere shortening is enhanced in HIV-infected patients because of HIV and some nucleoside analogue reverse transcriptase inhibitors. Mitochondria-related oxidative stress and mitochondrial DNA mutations are increased during ageing and also by some nucleoside analogue reverse transcriptase inhibitors. Overall, increased inflammation or 'inflammageing' is a major driver of ageing and could result from cell senescence with secreted proinflammatory mediators, altered gut microbiota, and coinfections. In HIV-infected patients, the level of inflammation and innate immunity activation is enhanced and related to most comorbidities and to mortality. This status could result, in addition to age, from the virus itself or viral protein released from reservoirs, from HIV-enhanced gut permeability and dysbiosis, from antiretroviral treatment, from frequent cytomegalovirus and hepatitis C virus coinfections, and also from personal and environmental factors, as central fat accumulation or smoking. Adaptive immune activation and immunosenescence are associated with comorbidities and mortality in the general population but are less predictive in HIV-infected patients. Biomarkers to evaluate ageing in HIV-infected patients are required. Numerous systemic or cellular inflammatory, immune activation, oxidative stress, or senescence markers can be tested in serum or peripheral blood mononuclear cells. The novel European Study to Establish Biomarkers of Human Ageing MARK

  13. Understanding HIV infection for the design of a therapeutic vaccine. Part I: Epidemiology and pathogenesis of HIV infection

    NARCIS (Netherlands)

    Goede, A.L. de; Vulto, A.G.; Osterhaus, A.D.; Gruters, R.A.

    2015-01-01

    HIV infection leads to a gradual loss CD4+ T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is

  14. The Th17 Lineage: From Barrier Surfaces Homeostasis to Autoimmunity, Cancer, and HIV-1 Pathogenesis.

    Science.gov (United States)

    Wacleche, Vanessa Sue; Landay, Alan; Routy, Jean-Pierre; Ancuta, Petronela

    2017-10-19

    The T helper 17 (Th17) cells represent a subset of CD4+ T-cells with unique effector functions, developmental plasticity, and stem-cell features. Th17 cells bridge innate and adaptive immunity against fungal and bacterial infections at skin and mucosal barrier surfaces. Although Th17 cells have been extensively studied in the context of autoimmunity, their role in various other pathologies is underexplored and remains an area of open investigation. This review summarizes the history of Th17 cell discovery and the current knowledge relative to the beneficial role of Th17 cells in maintaining mucosal immunity homeostasis. We further discuss the concept of Th17 pathogenicity in the context of autoimmunity, cancer, and HIV infection, and we review the most recent discoveries on molecular mechanisms regulating HIV replication/persistence in pathogenic Th17 cells. Finally, we stress the need for novel fundamental research discovery-based Th17-specific therapeutic interventions to treat pathogenic conditions associated with Th17 abnormalities, including HIV infection.

  15. The Th17 Lineage: From Barrier Surfaces Homeostasis to Autoimmunity, Cancer, and HIV-1 Pathogenesis

    Directory of Open Access Journals (Sweden)

    Vanessa Sue Wacleche

    2017-10-01

    Full Text Available The T helper 17 (Th17 cells represent a subset of CD4+ T-cells with unique effector functions, developmental plasticity, and stem-cell features. Th17 cells bridge innate and adaptive immunity against fungal and bacterial infections at skin and mucosal barrier surfaces. Although Th17 cells have been extensively studied in the context of autoimmunity, their role in various other pathologies is underexplored and remains an area of open investigation. This review summarizes the history of Th17 cell discovery and the current knowledge relative to the beneficial role of Th17 cells in maintaining mucosal immunity homeostasis. We further discuss the concept of Th17 pathogenicity in the context of autoimmunity, cancer, and HIV infection, and we review the most recent discoveries on molecular mechanisms regulating HIV replication/persistence in pathogenic Th17 cells. Finally, we stress the need for novel fundamental research discovery-based Th17-specific therapeutic interventions to treat pathogenic conditions associated with Th17 abnormalities, including HIV infection.

  16. HIV/AIDS in Central Africa: pathogenesis, immunological and medical issues.

    Science.gov (United States)

    Sibanda, Elopy Nimele; Stanczuk, Grazyna; Kasolo, Francis

    2003-11-01

    The estimated worldwide prevalence of human immunodeficiency virus (HIV) infections topped 52.5 million in June 2003, a mere 20 years after the aetiological agent was shown to be a sexually transmissible virus with a predilection for CD4+ T lymphocytes. More than 22 million people have died of the acquired immunodeficiency syndrome (AIDS) and the condition has in one generation become the most devastating and persistent epidemics in recorded history. More than two thirds of the world total of HIV-infected people live in Sub-Saharan Africa. In Central and Southern Africa at least 20% of the adult population is infected. As these adults die, they leave increasing numbers of orphans. Life expectancy at birth declined by 10 years per decade since the late 1980s to 50 years in the late 1990s, and in Botswana it is estimated to be as low as 33 years by 2010. The epidemic is increasing unabated and prospects for a curative or protective vaccine remain remote. The impact on HIV in Africa has been so profound that it influences political, economic, agriculture/food security, social, education, defence, science and health considerations. The medical and in particular immunology communities in Central Africa have the invidious challenge of on the one hand diagnosing the condition, monitoring its impact and contributing to treatment and management efforts. The science and clinical practice of immunology is challenged to find answers to the epidemic, perhaps including a vaccine. In this review we address the peculiarities of the HIV epidemic in Africa, its epidemiology and immunopathogenesis. We address the effect of the epidemic on individual patients, in their homes, workplaces and the knock-on effects on families and friends of the infected. Respective specialists discuss special groups (women, children) that are predominantly seen in Africa. We also discuss the impact of the epidemic on the clinical practice of medicine in general and challenges faced in the introduction of

  17. Blanco White and Walter Scott Blanco white y Walter Scott

    Directory of Open Access Journals (Sweden)

    Fernando DURÁN LÓPEZ

    2011-01-01

    Full Text Available The first edition of Ivanhoe; a romance. By the author of Waverley was published in Edinburgh in 1820. From the beginning of year 1823, José María Blanco White translated several excerpts from Ivanhoe in the numbers 1-3 of the magazine Variedades, owned by the publisher Rudolph Ackermann. in these articles and other later writings, the translator praised Scott as a model for a new way of painting history in a narrative. This paper studies his ideas on Scott’s historical novel, as well as his translation technique, compared with that of José Joaquín de Mora. En 1820 se publicó en Edimburgo la primera edición de Ivanhoe; a romance. By the author of Waverley. Desde comienzos de 1823, en los tres primeros números de su revista Variedades, promovida por el editor Rudolph Ackermann, José María Blanco White tradujo varios fragmentos de Ivanhoe entre grandes elogios. Asimismo, Blanco White tomó a Scott como modelo de referencia de una nueva manera de pintar la historia por medio de la novela en otros varios escritos críticos de años posteriores. El artículo estudia las ideas de Blanco White acerca de la novela histórica de Scott y su técnica como traductor, comparada con la de José Joaquín Mora.

  18. Collaborations Between Scott and Skidmore

    Directory of Open Access Journals (Sweden)

    Alicia Robinson

    2017-04-01

    Full Text Available This essay examines the collaboration between architect and designer George Gilbert Scott and metalworker Francis Skidmore. It compares their metalwork screens at the cathedrals of Hereford, Lichfield, and Salisbury—projects which sometimes overlapped and were all completed in the relatively short time span between 1861 and 1870—within the wider context of Skidmore’s career. While Scott was lauded in his lifetime and has been much studied since, Skidmore has not often been written about, despite having achieved an impressive scale and pace of work in British cathedrals, parish churches, and town halls. This essay therefore shines particular light on Skidmore’s work as designer and maker, and particularly the high profile commissions for these great cathedrals, restored and enhanced with the aesthetics and ambition of the Victorian era.

  19. Scott Brothers Windows and Doors Information Sheet

    Science.gov (United States)

    Scott Brothers Windows and Doors (the Company) is located in Bridgeville, Pennsylvania. The settlement involves renovation activities conducted at property constructed prior to 1978, located in Pittsburgh, Pennsylvania.

  20. Knudsen effects in a Scott effect experiment.

    Science.gov (United States)

    Wells, C. W.; Wood, L. T.; Hildebrandt, A. F.

    1973-01-01

    A thermal torque sometimes observed in Scott effect measurements has been studied experimentally and an explanation for the thermal torque proposed. The magnitude of the thermal torque can be comparable to the Scott torque depending on geometrical and thermal anisotropies. The thermal torque is predicted to decrease with application of an axial magnetic field.

  1. Cocaine modulates HIV-1 integration in primary CD4+ T cells: implications in HIV-1 pathogenesis in drug-abusing patients

    Science.gov (United States)

    Addai, Amma B.; Pandhare, Jui; Paromov, Victor; Mantri, Chinmay K.; Pratap, Siddharth; Dash, Chandravanu

    2015-01-01

    Epidemiologic studies suggest that cocaine abuse worsens HIV-1 disease progression. Increased viral load has been suggested to play a key role for the accelerated HIV disease among cocaine-abusing patients. The goal of this study was to investigate whether cocaine enhances proviral DNA integration as a mechanism to increase viral load. We infected CD4+ T cells that are the primary targets of HIV-1 in vivo and treated the cells with physiologically relevant concentrations of cocaine (1 µM–100 µM). Proviral DNA integration in the host genome was measured by nested qPCR. Our results illustrated that cocaine from 1 µM through 50 µM increased HIV-1 integration in CD4+ T cells in a dose-dependent manner. As integration can be modulated by several early postentry steps of HIV-1 infection, we examined the direct effects of cocaine on viral integration by in vitro integration assays by use of HIV-1 PICs. Our data illustrated that cocaine directly increases viral DNA integration. Furthermore, our MS analysis showed that cocaine is able to enter CD4+ T cells and localize to the nucleus-. In summary, our data provide strong evidence that cocaine can increase HIV-1 integration in CD4+ T cells. Therefore, we hypothesize that increased HIV-1 integration is a novel mechanism by which cocaine enhances viral load and worsens disease progression in drug-abusing HIV-1 patients. PMID:25691383

  2. Role of MRP transporters in regulating antimicrobial drug inefficacy and oxidative stress-induced pathogenesis during HIV-1 and TB infections.

    Science.gov (United States)

    Roy, Upal; Barber, Paul; Tse-Dinh, Yuk-Ching; Batrakova, Elena V; Mondal, Debasis; Nair, Madhavan

    2015-01-01

    Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9) have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function, and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.

  3. Role of MRP Transporters in Regulating Antimicrobial Drug Inefficacy and Oxidative Stress-induced Pathogenesis during HIV-1 and TB Infections

    Directory of Open Access Journals (Sweden)

    Upal eRoy

    2015-09-01

    Full Text Available Multi-Drug Resistance Proteins (MRPs are members of the ATP binding cassette (ABC drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV used in highly active antiretroviral therapy (HAART and antibacterial agents used in Tuberculus Bacilli (TB therapy. Due to their role in efflux of glutathione (GSH conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses their known role in drug-inefficacy in HIV/TB-induced dysfunctions. Currently, nine members of the MRP family (MRP1-MRP9 have been identified, with MRP1 and MRP2 being the most extensively studied. Details of the other members of this family have not been known until recently, but differential expression has been documented in inflammatory tissues. Researchers have found that the distribution, function and reactivity of members of MRP family vary in different types of lymphocytes and macrophages, and are differentially expressed at the basal and apical surfaces of both endothelial and epithelial cells. Therefore, the prime objective of this review is to delineate the role of MRP transporters in HAART and TB therapy and their potential in precipitating cellular dysfunctions manifested in these chronic infectious diseases. We also provide an overview of different available options and novel experimental strategies that are being utilized to overcome the drug resistance and disease pathogenesis mediated by these membrane transporters.

  4. Genetics Home Reference: Aarskog-Scott syndrome

    Science.gov (United States)

    ... A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. Evidence suggests that Aarskog-Scott syndrome is inherited in an autosomal dominant or autosomal recessive pattern in some families, although ...

  5. ASK Talks with W. Scott Cameron

    Science.gov (United States)

    Cameron, W. Scott

    2002-01-01

    This paper presents an interview with Scott Cameron who is the Capital Systems Manager for the Food and Beverage Global Business Unit of Procter and Gamble. He has been managing capital projects and mentoring other project managers for the past 20 years at Procter and Gamble within its Beauty Care, Health Care, Food and Beverage, and Fabric and Home Care Businesses. Scott also has been an Academy Sharing Knowledge (ASK) feature writer since Volume One.

  6. Sir Charles Scott Sherrington (1857–1952)

    Indian Academy of Sciences (India)

    Twentieth century bore witness to remarkable scientists whohave advanced our understanding of the brain. Among them,Sir Charles Scott Sherrington's ideas about the way in whichthe central nervous system operates has continuing relevanceeven today. He received honorary doctorates from twentytwouniversities and ...

  7. Thinking Visually: An Interview with Scott Bennett.

    Science.gov (United States)

    Gamble, Harriet

    2002-01-01

    Presents an interview with Scott Bennett, an artist of abstract art and traditional craft. Focuses on issues such as the role of art in his life, how his art has developed over time, and his process of creating his works of art. Includes directions for a glazing project. (CMK)

  8. Generalization of the Moszkovski-Scott method

    International Nuclear Information System (INIS)

    Balbutsev, E.B.

    1976-01-01

    A constant separation parameter is proposed to be used in the Moszkovski-Scott method for solving the Bethe-Goldstone equation. After such a modification one can apply the method to odd states of relative motion, not only to even ones. Some essential inaccuracies of the original method are eliminated, as well

  9. Interview met professor Joan Wallach Scott

    NARCIS (Netherlands)

    Bijl, Greetje; Tijhoff, Esmeralda

    2012-01-01

    Joan Scott, professor at the School of Social Science in the Institute for Avanced Study in Princeton, New Jersey (USA), was the keynote speaker at the conference 'Uitsluitend emancipatie' in de Beurs van Berlage in Amsterdam in October 2012. An interview on gender, history, feminism and her book

  10. Reframing Michael Scott: Exploring Inappropriate Workplace Communication

    Science.gov (United States)

    Schaefer, Zachary A.

    2010-01-01

    Individuals who work in professional settings interact with others who may exhibit a variety of cultural beliefs and decision-making approaches. Page (2007) argues that cognitive diversity (i.e., how people approach and attempt to solve problems) is a vital asset in effective organizations. Michael Scott, who portrays the inept main character on…

  11. Sir Charles Scott Sherrington (1857–1952)

    Indian Academy of Sciences (India)

    2016-08-26

    Aug 26, 2016 ... Twentieth century bore witness to remarkable scientists whohave advanced our understanding of the brain. Among them,Sir Charles Scott Sherrington's ideas about the way in whichthe central nervous system operates has continuing relevanceeven today. He received honorary doctorates from ...

  12. Astronaut Scott Parazynski during egress training

    Science.gov (United States)

    1994-01-01

    Astronaut Scott E. Parazynski looks at fellow STS-66 mission specialist Joseph R. Tanner, (foreground) during a rehearsal of procedures to be followed during the launch and entry phases of their scheduled November 1994 flight. This rehearsal, held in the crew compartment trainer (CCT) of JSC's Shuttle mockup and integration laboratory, was followed by a training session on emergency egress procedures.

  13. STS-100 Crew Interview: Scott Parazynski

    Science.gov (United States)

    2001-01-01

    STS-100 Mission Specialist Scott Parazynski is seen being interviewed. He answers questions about his inspiration to become an astronaut and his career path. He gives details on the mission's goals and significance, the rendezvous and docking of Endeavour with the International Space Station (ISS), the mission's spacewalks, and installation and capabilities of the Space Station robotic arm, UHF antenna, and Rafaello Logistics Module. Parazynski then discusses his views about space exploration as it becomes an international collaboration.

  14. Generative complexity of Gray-Scott model

    Science.gov (United States)

    Adamatzky, Andrew

    2018-03-01

    In the Gray-Scott reaction-diffusion system one reactant is constantly fed in the system, another reactant is reproduced by consuming the supplied reactant and also converted to an inert product. The rate of feeding one reactant in the system and the rate of removing another reactant from the system determine configurations of concentration profiles: stripes, spots, waves. We calculate the generative complexity-a morphological complexity of concentration profiles grown from a point-wise perturbation of the medium-of the Gray-Scott system for a range of the feeding and removal rates. The morphological complexity is evaluated using Shannon entropy, Simpson diversity, approximation of Lempel-Ziv complexity, and expressivity (Shannon entropy divided by space-filling). We analyse behaviour of the systems with highest values of the generative morphological complexity and show that the Gray-Scott systems expressing highest levels of the complexity are composed of the wave-fragments (similar to wave-fragments in sub-excitable media) and travelling localisations (similar to quasi-dissipative solitons and gliders in Conway's Game of Life).

  15. STS-106 Crew Interviews: Scott D. Altman

    Science.gov (United States)

    2000-01-01

    Live footage of a preflight interview with Pilot Scott D. Altman is seen. The interview addresses many different questions including why Altman became a pilot, the events that led to his interest, his career path through the Navy, and then finally, his selection by NASA as an astronaut. Other interesting information discussed in this one-on-one interview was his work on the movie set of "Top Gun," the highlights of his Navy career, and possible shorter time frame turnarounds for missions. Altman also mentions the scheduled docking with the new International Space Station (ISS) after the arrival of the Zvezda Service Module.

  16. STS-105 Crew Interview: Scott Horowitz

    Science.gov (United States)

    2001-01-01

    STS-105 Commander Scott Horowitz is seen during a prelaunch interview. He answers questions about his inspiration to become an astronaut, his career path, training for the mission, and his role in the mission's activities. He gives details on the mission's goals, which include the transfer of supplies from the Discovery Orbiter to the International Space Station (ISS) and the change-over of the Expedition 2 and Expedition 3 crews (the resident crews of ISS). Horowitz discusses the importance of the ISS in the future of human spaceflight.

  17. STS-82 Pilot Scott Horowitz at SLF

    Science.gov (United States)

    1997-01-01

    STS-82 Pilot Scott J. 'Doc' Horowitz flashes a wide grin for photographers after he lands his T-38 jet at KSCs Shuttle Landing Facility. Horowitz and the other six members of the STS-82 crew came from their home base at Johnson Space Center in Houston, TX, to spend the last few days before launch at KSC. STS-82 is scheduled for liftoff on Feb. 11 during a 65-minute launch window which opens at 3:56 a.m. EST. The 10-day flight aboard the Space Shuttle Discovery will be the second Hubble Space Telescope servicing mission.

  18. STS-103 Crew Interviews: Scott Kelly

    Science.gov (United States)

    1999-01-01

    Live footage of a preflight interview with Pilot Scott J. Kelly is seen. The interview addresses many different questions including why Kelly became an astronaut, the events that led to his interest, any role models that he had, and his inspiration. Other interesting information that this one-on-one interview discusses is an explanation of the why this required mission to service the Hubble Space Telescope must take place at such an early date, replacement of the gyroscopes, transistors, and computers. Also discussed are the Chandra X Ray Astrophysics Facility, and a brief touch on Kelly's responsibility during any of the given four space walks scheduled for this mission.

  19. Professor John Scott, folate and neural tube defects.

    Science.gov (United States)

    Hoffbrand, A Victor

    2014-02-01

    John Scott (1940-2013) was born in Dublin where he was to spend the rest of his career, both as an undergraduate and subsequently Professor of Biochemistry and Nutrition at Trinity College. His research with the talented group of scientists and clinicians that he led has had a substantial impact on our understanding of folate metabolism, mechanisms of its catabolism and deficiency. His research established the leading theory of folate involvement with vitamin B12 in the pathogenesis of vitamin B12 neuropathy. He helped to establish the normal daily intake of folate and the increased requirements needed either in food or as a supplement before and during pregnancy to prevent neural tube defects. He also suggested a dietary supplement of vitamin B12 before and during pregnancy to reduce the risk of neural tube defects. It would be an appropriate epitaph if fortification of food with folic acid became mandatory in the UK and Ireland, as it is in over 70 other countries. © 2013 John Wiley & Sons Ltd.

  20. Astrovirus Pathogenesis

    Directory of Open Access Journals (Sweden)

    Cydney Johnson

    2017-01-01

    Full Text Available Astroviruses are a major cause of diarrhea in the young, elderly, and the immunocompromised. Since the discovery of human astrovirus type 1 (HAstV-1 in 1975, the family Astroviridae has expanded to include two more human clades and numerous mammalian and avian-specific genotypes. Despite this, there is still little known about pathogenesis. The following review highlights the current knowledge of astrovirus pathogenesis, and outlines the critical steps needed to further astrovirus research, including the development of animal models of cell culture systems.

  1. STS-101 Crew Interview / Scott Horowitz

    Science.gov (United States)

    2000-01-01

    Live footage of a preflight interview with Pilot Scott J. Horowitz is seen. The interview addresses many different questions including why Horowitz became an astronaut, the events that led to his interest, any role models that he had, and his inspiration. Other interesting information that this one-on-one interview discusses is the reaction and reasons for the splitting-up of the objectives for STS-101 with STS-106. Horowitz also mentions the scheduled space-walk, docking with the International Space Station (ISS), the new glass cockpit of Atlantis, the repairs of equipment and change of the batteries. Horowitz also discusses his responsibilities during the space-walk, and docking of the spacecraft. He stresses that he will have an added challenge during the space-walk, his inability to see where he needs to place the Extravehicular Activities (EVA) crew.

  2. Mission Specialist Scott Parazynski arrives at KSC

    Science.gov (United States)

    1998-01-01

    STS-95 Mission Specialist Scott E. Parazynski notes the time on his watch upon his late arrival aboard a T-38 jet at the Shuttle Landing Facility. Parazynski's first plane experienced problems at the stop at Tyndall AFB and he had to wait for another jet and pilot to finish the flight to KSC. He joined other crewmembers Mission Commander Curtis L. Brown Jr., Pilot Steven W. Lindsey, Mission Specialist Stephen K. Robinson, Payload Specialist John H. Glenn Jr., senator from Ohio, Mission Specialist Pedro Duque, with the European Space Agency (ESA), and Payload Specialist Chiaki Mukai, with the National Space Development Agency of Japan (NASDA), for final pre-launch preparations. STS-95 is expected to launch at 2 p.m. EST on Oct. 29, last 8 days, 21 hours and 49 minutes, and land at 11:49 a.m. EST on Nov. 7.

  3. Listening in the Silences for Fred Newton Scott

    Science.gov (United States)

    Mastrangelo, Lisa

    2009-01-01

    As part of her recent sabbatical, the author proposed going to the University of Michigan Bentley Archives to do research on Fred Newton Scott, founder and chair of the Department of Rhetoric and teacher from 1889 to 1926 at the University of Michigan. Scott ran the only graduate program in rhetoric and composition in the country between those…

  4. Philip Glass, Scott Walker ja Sigur Ros! / Immo Mihkelson

    Index Scriptorium Estoniae

    Mihkelson, Immo, 1959-

    2007-01-01

    Pimedate Ööde 11. filmifestivali muusikafilme - Austraalia "Glass: Philipi portree 12 osas" (rež. Scott Hicks), Islandi "Sigur Ros kodus" (rež. Dean DeBois), Suurbritannia "Scott Walker: 30 Century Man" (rež. Stephen Kijak)

  5. STS-87 Mission Specialist Winston E. Scott suits up

    Science.gov (United States)

    1997-01-01

    STS-87 Mission Specialist Winston Scott dons his launch and entry suit with the assistance of a suit technician in the Operations and Checkout Building. This is Scotts second space flight. He and the five other crew members will depart shortly for Launch Pad 39B, where the Space Shuttle Columbia awaits liftoff on a 16-day mission to perform microgravity and solar research. Scott is scheduled to perform an extravehicular activity spacewalk with Mission Specialist Takao Doi, Ph.D., of the National Space Development Agency of Japan, during STS-87. He also performed a spacewalk on STS-72.

  6. Relativistic Scott correction in self-generated magnetic fields

    DEFF Research Database (Denmark)

    Erdos, Laszlo; Fournais, Søren; Solovej, Jan Philip

    2012-01-01

    /3}$ and it is unchanged by including the self-generated magnetic field. We prove the first correction term to this energy, the so-called Scott correction of the form $S(\\alpha Z) Z^2$. The current paper extends the result of \\cite{SSS} on the Scott correction for relativistic molecules to include a self......-generated magnetic field. Furthermore, we show that the corresponding Scott correction function $S$, first identified in \\cite{SSS}, is unchanged by including a magnetic field. We also prove new Lieb-Thirring inequalities for the relativistic kinetic energy with magnetic fields....

  7. Pathogenesis of oral FIV infection.

    Directory of Open Access Journals (Sweden)

    Craig Miller

    Full Text Available Feline immunodeficiency virus (FIV is the feline analogue of human immunodeficiency virus (HIV and features many hallmarks of HIV infection and pathogenesis, including the development of concurrent oral lesions. While HIV is typically transmitted via parenteral transmucosal contact, recent studies prove that oral transmission can occur, and that saliva from infected individuals contains significant amounts of HIV RNA and DNA. While it is accepted that FIV is primarily transmitted by biting, few studies have evaluated FIV oral infection kinetics and transmission mechanisms over the last 20 years. Modern quantitative analyses applied to natural FIV oral infection could significantly further our understanding of lentiviral oral disease and transmission. We therefore characterized FIV salivary viral kinetics and antibody secretions to more fully document oral viral pathogenesis. Our results demonstrate that: (i saliva of FIV-infected cats contains infectious virus particles, FIV viral RNA at levels equivalent to circulation, and lower but significant amounts of FIV proviral DNA; (ii the ratio of FIV RNA to DNA is significantly higher in saliva than in circulation; (iii FIV viral load in oral lymphoid tissues (tonsil, lymph nodes is significantly higher than mucosal tissues (buccal mucosa, salivary gland, tongue; (iv salivary IgG antibodies increase significantly over time in FIV-infected cats, while salivary IgA levels remain static; and, (v saliva from naïve Specific Pathogen Free cats inhibits FIV growth in vitro. Collectively, these results suggest that oral lymphoid tissues serve as a site for enhanced FIV replication, resulting in accumulation of FIV particles and FIV-infected cells in saliva. Failure to induce a virus-specific oral mucosal antibody response, and/or viral capability to overcome inhibitory components in saliva may perpetuate chronic oral cavity infection. Based upon these findings, we propose a model of oral FIV pathogenesis

  8. Astronauts Armstrong and Scott arrive at Hickam Field, Hawaii

    Science.gov (United States)

    1966-01-01

    Astronauts Neil A. Armstrong (center), command pilot, and David R. Scott, pilot, arrive at Hickam Field, Hawaii on their way from Naha, Okinawa, to Cape Kennedy, Florida. Astronaut Walter M. Schirra Jr. is at extreme left.

  9. Astronauts Armstrong and Scott during photo session outside KSC

    Science.gov (United States)

    1966-01-01

    Astronauts Neil A. Armstrong (left), command pilot, and David R. Scott, pilot, the Gemini 8 prime crew, during a photo session outside the Kennedy Space Center (KSC) Mission Control Center. They are standing in front of a radar dish.

  10. Awareness Of HIV / AIDS Among Hospital Workers | Ugochukwu ...

    African Journals Online (AJOL)

    Awareness Of HIV / AIDS Among Hospital Workers. ... HIV /AIDS among workers in a teaching Hospital, b) risk of HIV infection among hospital workers ... pathogenesis, prevention, spread and risk of occupational transmission of HIV infection.

  11. Multiparametric Bioinformatics Distinguish the CD4/CD8 Ratio as a Suitable Laboratory Predictor of Combined T Cell Pathogenesis in HIV Infection

    DEFF Research Database (Denmark)

    Buggert, Marcus; Frederiksen, Juliet Wairimu; Noyan, Kajsa

    2014-01-01

    HIV disease progression is characterized by numerous pathological changes of the cellular immune system. Still, the CD4 cell count and viral load represent the laboratory parameters that are most commonly used in the clinic to determine the disease progression. In this study, we conducted an inte...

  12. Wave-splitting in the bistable Gray-Scott model

    DEFF Research Database (Denmark)

    Rasmussen, K.E.; Mazin, W.; Mosekilde, Erik

    1996-01-01

    The Gray-Scott model describes a chemical reaction in which an activator species grows autocatalytically on a continuously fed substrate. For certain feed rates and activator life times the model shows the coexistence of two homogeneous steady states. The blue state, where the activator concentra......The Gray-Scott model describes a chemical reaction in which an activator species grows autocatalytically on a continuously fed substrate. For certain feed rates and activator life times the model shows the coexistence of two homogeneous steady states. The blue state, where the activator...

  13. Theorizing Steampunk in Scott Westerfeld's YA Series Leviathan

    Science.gov (United States)

    Mielke, Tammy L.; LaHaie, Jeanne M.

    2015-01-01

    In this article, we offer an explanation of steampunk and theorize the genre and its functions within Scott Westerfeld's YA series Leviathan. In order to do so, we examine the "cogs" of the genre machine and its use of nostalgic longing for a revised past/future to rebel against present day cultural norms. Critics note that steampunk…

  14. Walter Dill Scott and the Student Personnel Movement

    Science.gov (United States)

    Biddix, J. Patrick; Schwartz, Robert A.

    2012-01-01

    Walter Dill Scott (1869-1955), tenth president of Northwestern University and pioneer of industrial psychology, is an essential architect of student personnel work. This study of his accomplishments, drawing on records from the Northwestern University archives, tells a story about the people he influenced and his involvement in codifying what was…

  15. Scott Morgan Johnson Middle School: Personalization Leads to Unlimited Success

    Science.gov (United States)

    Principal Leadership, 2013

    2013-01-01

    The well-known lyrics may be "The Eyes of Texas Are Upon You," but at Scott Morgan Johnson Middle School in McKinney, TX, it's definitely the "eye of the tiger" that sets the bar for Tiger PRIDE (perseverance, respect, integrity, determination, and excellence). This article describes how those ideals have been infused…

  16. 2015-2016 Expense report for Scott Gilmore | IDRC - International ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    2015-07-13

    2015-2016 Expense report for Scott Gilmore. Total travel expenses: CA$31.46. Download expense report. July 13, 2015 to July 14, 2015. CA$31.46. What we do · Funding · Resources · About IDRC. Knowledge. Innovation. Solutions. Careers · Contact Us · Site map. Sign up now for IDRC news and views sent directly to ...

  17. Nursery Pest Management of Phytolyma lata Walker (Scott) Attack ...

    African Journals Online (AJOL)

    The establishment of plantations of Milicia excelsa has been constrained by the gall-forming psyllid Phytolyma lata Walker (Scott) that causes extensive damage to young plants. We present findings of an experiment aimed at preventing Phytolyma attack on Milicia seedlings in the nursery using chemical control and ...

  18. Astronauts Scott and Armstrong undergoe water egress training

    Science.gov (United States)

    1966-01-01

    Astronauts Neil A. Armstrong (on left), command pilot, and David R. Scott, pilot of the Gemini 8 prime crew, use a boilerplate model of a Gemini spacecraft during water egress training in the Gulf of Mexico. Three Manned Spacecraft Center swimmers assist in the training exercise.

  19. PEOPLE IN PHYSICS: Interview with Scott Durow, Software Engineer, Oxford

    Science.gov (United States)

    Burton, Conducted by Paul

    1998-05-01

    Scott Durow was educated at Bootham School, York. He studied Physics, Mathematics and Chemistry to A-level and went on to Nottingham University to read Medical Physics. After graduating from Nottingham he embarked on his present career as a Software Engineer based in Oxford. He is a musician in his spare time, as a member of a band and playing the French horn.

  20. Scott Fitzgerald: famous writer, alcoholism and probable epilepsy

    Directory of Open Access Journals (Sweden)

    Mariana M. Wolski

    Full Text Available ABSTRACT Scott Fitzgerald, a world-renowned American writer, suffered from various health problems, particularly alcohol dependence, and died suddenly at the age of 44. According to descriptions in A Moveable Feast, by Ernest Hemingway, Fitzgerald had episodes resembling complex partial seizures, raising the possibility of temporal lobe epilepsy.

  1. Astronaut Scott Parazynski in hatch of CCT during training

    Science.gov (United States)

    1994-01-01

    Astronaut Scott E. Parazynski, STS-66 mission specialist, poses near the hatchway of the crew compartment trainer (CCT) (out of frame) in JSC's Shuttle mockup and integration laboratory. Crew members were about to begin a rehearsal of procedures to be followed during the launch and entry phases of their flight. That rehearsal was followed by a training session on emergency egress procedures.

  2. 77 FR 7182 - Scott W. Houghton, M.D.; Decision and Order

    Science.gov (United States)

    2012-02-10

    ... DEPARTMENT OF JUSTICE Drug Enforcement Administration [Docket No. 12-09] Scott W. Houghton, M.D... CFR 0.100(b), I order that DEA Certificate of Registration BH8796077, issued to Scott W. Houghton, M.D., be, and it hereby is, revoked. I further order that any pending application of Scott W. Houghton, M.D...

  3. John Scott Haldane: The father of oxygen therapy

    Directory of Open Access Journals (Sweden)

    K C Sekhar

    2014-01-01

    Full Text Available John Scott Haldane was a versatile genius who solved several problems of great practical significance. His ability to look beyond the laboratory and investigate theory added crucial findings in the field of respiratory physiology. His work on high altitude physiology, diving physiology, oxygen therapy, and carbon monoxide poisoning led to a sea change in clinical medicine and improved safety and reduced mortality and morbidity in many high risk situations.

  4. Cerebrovascular disease associated with Aarskog-Scott syndrome

    Energy Technology Data Exchange (ETDEWEB)

    DiLuna, Michael L.; Amankulor, Nduka M.; Gunel, Murat [Yale University School of Medicine, Department of Neurosurgery, New Haven, CT (United States); Johnson, Michele H. [Yale University School of Medicine, Department of Diagnostic Radiology, New Haven, CT (United States)

    2007-05-15

    Faciogenital dysplasia, also known as Aarskog-Scott syndrome (AAS), is an X-linked dominant congenital disorder characterized by multiple facial, musculoskeletal, dental, neurological and urogenital abnormalities, ocular manifestations, congenital heart defects, low IQ and behavioral problems. Here we describe an unusual presentation of dysplastic carotid artery, basilar artery malformation or occlusion and posterior circulation aneurysm in a 13-year-old male with AAS. (orig.)

  5. Cerebrovascular disease associated with Aarskog-Scott syndrome

    International Nuclear Information System (INIS)

    DiLuna, Michael L.; Amankulor, Nduka M.; Gunel, Murat; Johnson, Michele H.

    2007-01-01

    Faciogenital dysplasia, also known as Aarskog-Scott syndrome (AAS), is an X-linked dominant congenital disorder characterized by multiple facial, musculoskeletal, dental, neurological and urogenital abnormalities, ocular manifestations, congenital heart defects, low IQ and behavioral problems. Here we describe an unusual presentation of dysplastic carotid artery, basilar artery malformation or occlusion and posterior circulation aneurysm in a 13-year-old male with AAS. (orig.)

  6. STS-82 Pilot Scott Horowitz arrives for TCDT

    Science.gov (United States)

    1997-01-01

    STS-82 Pilot Scott J. 'Doc' Horowitz arrives at KSCs Shuttle Landing Facility in a T-38 jet from Houston, TX. Horowitz and the other six crew members are at KSC to participate in the Terminal Countdown Demonstration Test (TCDT), a dress rehearsal for launch. The crew aboard the Space Shuttle Discovery on STS-82 will conduct the second Hubble Space Telescope servicing mission. The 10-day flight is targeted for a Feb. 11 liftoff.

  7. STS-90 Pilot Scott Altman in white room before launch

    Science.gov (United States)

    1998-01-01

    STS-90 Pilot Scott Altman is assisted by NASA and USA closeout crew members immediately preceding launch for the nearly 17-day Neurolab mission. Investigations during the Neurolab mission will focus on the effects of microgravity on the nervous system. Linnehan and six fellow crew members will shortly enter the orbiter at KSC's Launch Pad 39B, where the Space Shuttle Columbia will lift off during a launch window that opens at 2:19 p.m. EDT, April 17.

  8. Aldred scott warthin: Pathologist and teacher par excellence

    Directory of Open Access Journals (Sweden)

    Vineeth G Nair

    2017-01-01

    Full Text Available Born in 1866, Aldred Scott Warthin was a pathologist and teacher of great repute. Even though many know him from his eponyms, the true value of his achievements, and how far he was ahead of his peers, is known to but a few modern day medical students. It was in fact, based on his work, that Henry Lynch came up with his theories on the genetic nature of cancer. He died in 1931 leaving a lot of work unfinished.

  9. On Scott-Phillips' General Account of Communication.

    Science.gov (United States)

    Planer, Ronald J

    2017-12-01

    The purpose of this paper is to critically engage with a recent attempt by Thom Scott-Phillips to offer a general account of communication. As a general account, it is intended to apply equally well to both non-human and human interactions which are prima facie communicative in character. However, so far, Scott-Phillips has provided little detail regarding how his account is supposed to apply to the latter set of cases. After presenting what I take to be the most plausible way of filling in those details, I argue that his account would appear to be too narrow: it (minimally) fails to capture a range of human interactions which strike us as instances of communication. To wit, these are cases in which some but not all of the information an act is designed to convey to a reactor actually reaches that reactor. An alternative account incorporating Scott-Phillips' main insights is then sketched, and it is suggested that this account, or something like it, would accommodate the full range of non-human and human interactions that are intuitively communicative.

  10. STS-82 Pilot Scott J. 'Doc' Horowitz Suit Up

    Science.gov (United States)

    1997-01-01

    STS-82 Pilot Scott J. 'Doc' Horowitz puts on a glove of his launch and entry suit with assistance from a suit technician in the Operations and Checkout Building. This is Horowitz''';s second space flight. He and the six other crew members will depart shortly for Launch Pad 39A, where the Space Shuttle Discovery awaits liftoff on a 10-day mission to service the orbiting Hubble Space Telescope (HST). This will be the second HST servicing mission. Four back-to-back spacewalks are planned.

  11. STS-90 Pilot Scott Altman arrives at KSC for TCDT

    Science.gov (United States)

    1998-01-01

    STS-90 Pilot Scott Altman poses in the cockpit of his T-38 jet trainer aircraft after arriving at the KSC Shuttle Landing Facility along with other members of the crew from NASAs Johnson Space Center to begin Terminal Countdown Demonstration Test (TCDT) activities. The TCDT is held at KSC prior to each Space Shuttle flight to provide crews with the opportunity to participate in simulated countdown activities. Columbia is targeted for launch of STS-90 on April 16 at 2:19 p.m. EST and will be the second mission of 1998. The mission is scheduled to last nearly 17 days.

  12. The gastrointestinal tract and HIV pathogenesis

    African Journals Online (AJOL)

    that the mucosal immune system and the intestinal immune system ..... concentration of ART drugs to infected cells in the GIT, thus allowing the virus to slowly ... enhanced through intramuscular rAd5 injections.13 The activation status of ... Delivery of Human Immunodeficiency Virus Vaccine Vectors to the Intestines Induces.

  13. 77 FR 66469 - CDC/HRSA Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment

    Science.gov (United States)

    2012-11-05

    ... Advisory Committee on HIV, Viral Hepatitis and STD Prevention and Treatment In accordance with section 10(a...--Treatment as Prevention; (2) Ryan White HIV/AIDS Program Client Level Data Update; (3) Viral Hepatitis... Person for More Information: Margie Scott-Cseh, National Center for HIV/AIDS, Viral Hepatitis, STD, and...

  14. Aspm, a Key Element in Medulloblastoma Pathogenesis and a Novel Target for Treatment

    Science.gov (United States)

    2013-10-01

    pathogenesis ( Wechsler -Reya and Scott, 1999; Kenney and Rowitch, 2000; Zurawel et al., 2000; Ellison et al., 2011; Hatten and Roussel, 2011; Roussel...Laboratories, Bar Harbor, ME, USA) to generate Aspm floxed (Aspmf/+) mice. Math-1 cre mice were generously shared by David Rowitch, MD, PhD, UCSF and...Robert Wechsler -Reya, PhD, 10 Sanford-Burnham Medical Research Institute, La Jolla, CA and have been previously described (Matei et al., 2005

  15. Pathogenesis of Parkinson's disease

    OpenAIRE

    Riederer, Peter; Lange, Klaus W.

    1992-01-01

    The importance of genetic aspects, ageing, environmental factors, head trauma, defective mitochondrial respiration, altered iron metabolism, oxidative stress and glutamatergic overactivity of the basal ganglia in the pathogenesis of Parkinson's disease (PD) are considered in this review.

  16. Viral pathogenesis in diagrams

    National Research Council Canada - National Science Library

    Tremblay, Michel; Berthiaume, Laurent; Ackermann, Hans-Wolfgang

    2001-01-01

    .... The 268 diagrams in Viral Pathogenesis in Diagrams were selected from over 800 diagrams of English and French virological literature, including one derived from a famous drawing by Leonardo da Vinci...

  17. Mission Specialist Scott Parazynski arrives late at KSC

    Science.gov (United States)

    1998-01-01

    The T-38 jet aircraft arrives at the Shuttle Landing Facility carrying STS-95 Mission Specialist Scott E. Parazynski (second seat). The pilot is astronaut Kent Rominger. Parazynski's first plane experienced problems at the stop at Tyndall AFB and he had to wait for another jet and pilot to finish the flight to KSC. He joined other crewmembers Mission Commander Curtis L. Brown Jr., Pilot Steven W. Lindsey, Mission Specialist Stephen K. Robinson, Payload Specialist John H. Glenn Jr., senator from Ohio, Mission Specialist Pedro Duque, with the European Space Agency (ESA), and Payload Specialist Chiaki Mukai, with the National Space Development Agency of Japan (NASDA), for final pre-launch preparations. STS-95 is expected to launch at 2 p.m. EST on Oct. 29, last 8 days, 21 hours and 49 minutes, and land at 11:49 a.m. EST on Nov. 7.

  18. STS-90 Pilot Scott Altman is suited up for launch

    Science.gov (United States)

    1998-01-01

    STS-90 Pilot Scott Altman is assisted during suit-up activities by Lockheed Suit Technician Valerie McNeil from Johnson Space Center in KSC's Operations and Checkout Building. Altman and the rest of the STS-90 crew will shortly depart for Launch Pad 39B, where the Space Shuttle Columbia awaits a second liftoff attempt at 2:19 p.m. EDT. His first trip into space, Altman is participating in a life sciences research flight that will focus on the most complex and least understood part of the human body - - the nervous system. Neurolab will examine the effects of spaceflight on the brain, spinal cord, peripheral nerves and sensory organs in the human body.

  19. Mission Specialist Scott Parazynski checks his flight suit

    Science.gov (United States)

    1998-01-01

    STS-95 Mission Specialist Scott E. Parazynski gets help with his flight suit in the Operations and Checkout Building from a suit technician George Brittingham. The final fitting takes place prior to the crew walkout and transport to Launch Pad 39B. Targeted for launch at 2 p.m. EST on Oct. 29, the mission is expected to last 8 days, 21 hours and 49 minutes, and return to KSC at 11:49 a.m. EST on Nov. 7. The STS-95 mission includes research payloads such as the Spartan solar-observing deployable spacecraft, the Hubble Space Telescope Orbital Systems Test Platform, the International Extreme Ultraviolet Hitchhiker, as well as the SPACEHAB single module with experiments on space flight and the aging process.

  20. The Great Kanto earthquake and F. Scott Fitzgerald

    Science.gov (United States)

    Kawakatsu, Hitoshi; Bina, Craig R.

    How many recall the following striking sentence from The Great Gatsby by F. Scott Fitzgerald, which appears on the second page of the novel, where Fitzgerald first introduces Gatsby? “If personality is an unbroken series of successful gestures, then there was something gorgeous about him, some heightened sensitivity to the promises of life, as if he were related to one of those intricate machines that register earthquakes ten thousand miles away.”This line may have failed to focus our attention when we first read the book in our younger days. Now, however, as a Japanese seismologist and an American geophysicist (and student of Japanese culture), we would be greatly remiss for failing to take greater note of this statement. Indeed, as The Great Gatsby was published in 1925, it occurred to us that the earthquake Fitzgerald might have been thinking of was the Great Kanto earthquake, which occurred on September 1, 1923 and devastated the Tokyo metropolitan area.

  1. 78 FR 77791 - Dakota, Minnesota & Eastern Railroad Corporation-Abandonment Exemption-in Scott County, Iowa

    Science.gov (United States)

    2013-12-24

    ... DEPARTMENT OF TRANSPORTATION Surface Transportation Board [Docket No. AB 337 (Sub-No. 7X)] Dakota, Minnesota & Eastern Railroad Corporation--Abandonment Exemption--in Scott County, Iowa Dakota, Minnesota... as Blackhawk Spur, between milepost 0.33+/- and milepost 0.99 +/- in Scott County, Iowa (the Line...

  2. An estimating function approach to inference for inhomogeneous Neyman-Scott processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus Plenge

    “This paper is concerned with inference for a certain class of inhomogeneous Neyman-Scott point processes depending on spatial covariates. Regression parameter estimates obtained from a simple estimating function are shown to be asymptotically normal when the “mother” intensity for the Neyman-Scott...

  3. 78 FR 5854 - Application of Scott Air, LLC for Certificate Authority

    Science.gov (United States)

    2013-01-28

    ... DEPARTMENT OF TRANSPORTATION Office of the Secretary Application of Scott Air, LLC for Certificate Authority AGENCY: Department of Transportation. ACTION: Notice of order to show cause (Order 2013-1-12... to show cause why it should not issue an order finding Scott Air, LLC fit, willing, and able, and...

  4. 78 FR 60929 - Notice of Public Meeting of the Fort Scott Council

    Science.gov (United States)

    2013-10-02

    .... Such requests must be stated prominently at the beginning of the comments. The Trust will make... PRESIDIO TRUST Notice of Public Meeting of the Fort Scott Council AGENCY: The Presidio Trust... Scott Council (Council) will be held from 10 a.m. to 12:30 p.m. on Thursday, October 17, 2013. The...

  5. W. Richard Scott, Institutions and Organizations: Ideas, Interests, and Identities

    DEFF Research Database (Denmark)

    Jakobsen, Michael

    2014-01-01

    Book review of: W. Richard Scott: Institutions and Organizations: Ideas, Interests, and Identities. 4th edition. Thousand Oaks, CA: SAGE Publications, 2014. xiii, 345 pp.......Book review of: W. Richard Scott: Institutions and Organizations: Ideas, Interests, and Identities. 4th edition. Thousand Oaks, CA: SAGE Publications, 2014. xiii, 345 pp....

  6. Executive dysfunctions as part of the behavioural phenotype of Aarskog-Scott syndrome

    NARCIS (Netherlands)

    Egger, J.I.M.; Verhoeven, W.M.A.; Janssen, G.T.L.; Aken, L. van; Hoogeboom, A.J.M.

    2012-01-01

    Introduction Aarskog syndrome (AAS) also called Aarskog-Scott syndrome faciodigitogenital syndrome or faciogenital dysplasia is a genetically heterogeneous developmental disorder, first described in 1970 by the Norwegian pediatrician Dagfin Aarskog and further delineated by Scott in 1971. It is a

  7. Pathogenesis of Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Irena Ciećko-Michalska

    2012-01-01

    Full Text Available Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.

  8. Pathogenesis of Hepatic Encephalopathy

    Science.gov (United States)

    Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

    2012-01-01

    Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

  9. Heroes for the past and present: a century of remembering Amundsen and Scott.

    Science.gov (United States)

    Roberts, Peder

    2011-12-01

    In 1911-1912 Roald Amundsen and Robert Falcon Scott led rival parties in a race to the geographic South Pole. While both parties reached the Pole--Amundsen first--Scott's men died on the return journey. Amundsen became a Norwegian icon through his record-setting travels; Scott became a symbol of courage and devotion to science. The memory of each was invoked at various points during the twentieth century in the context of contemporary Antarctic events. Scott's status as a scientific figure was central to the Scott Polar Research Institute, while Amundsen's lack of scientific legacy became a way for British polar explorers to differentiate themselves from Norwegian contemporaries during the interwar years. After 1945 Scott and Amundsen were again invoked as exemplars of national polar achievement, even as the rise of large-scale science on the continent overshadowed past British and Norwegian achievements. In the present Amundsen and Scott remain wedded to particular values, focused respectively on national achievement and sacrifice in the name of science, while their race has become secondary. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Molecular Pathogenesis of Spondyloarthritis

    DEFF Research Database (Denmark)

    Carlsen, Thomas Gelsing

    This dissertation includes a presentation of knowledge on the molecular pathogenesis of spondyloarthritis achieved through a PhD programme at Aalborg University from 1.12.2011 - 1.12.2014. Work was carried out in the Laboratory of Medical Mass Spectrometry, headed by: Professor Svend Birkelund...

  11. STS-103 Pilot Scott Kelly during TCDT activities

    Science.gov (United States)

    1999-01-01

    STS-103 Pilot Scott J. Kelly is ready to take his turn at driving a small armored personnel carrier that is part of emergency egress training during Terminal Countdown Demonstration Test (TCDT) activities. Behind him (left) is Mission Specialist Jean-Frangois Clervoy of France, who is with the European Space Agency. At right is Mission Specialist Steven L. Smith. The tracked vehicle could be used by the crew in the event of an emergency at the pad during which the crew must make a quick exit from the area. The TCDT also provides simulated countdown exercises and opportunities to inspect the mission payloads in the orbiter's payload bay. STS-103 is a 'call-up' mission due to the need to replace and repair portions of the Hubble Space Telescope. Although Hubble is operating normally and conducting its scientific observations, only three of its six gyroscopes are working properly. Four EVA's are planned to make the necessary repairs and replacements on the telescope. The other STS-103 crew members are Commander Curtis L. Brown Jr. and Mission Specialists C. Michael Foale (Ph.D.), John M. Grunsfeld (Ph.D.), and Claude Nicollier of Switzerland, who also is with the European Space Agency. The mission is targeted for launch Dec. 6 at 2:37 a.m. EST.

  12. Aurora 7 the Mercury space flight of M. Scott Carpenter

    CERN Document Server

    Burgess, Colin

    2016-01-01

    TO A NATION enthralled by the heroic exploits of the Mercury astronauts, the launch of Lt. Cmdr. Scott Carpenter on NASA’s second orbital space flight was a renewed cause for pride, jubilation and celebration. Within hours, that excitement had given way to stunned disbelief and anxiety as shaken broadcasters began preparing the American public for the very real possibility that an American astronaut and his spacecraft may have been lost at sea. In fact, it had been a very close call. Completely out of fuel and forced to manually guide Aurora 7 through the frightening inferno of re-entry, Carpenter brought the Mercury spacecraft down to a safe splashdown in the ocean. In doing so, he controversially overshot the intended landing zone. Despite his efforts, Carpenter’s performance on the MA-7 mission was later derided by powerful figures within NASA. He would never fly into space again. Taking temporary leave of NASA, Carpenter participated in the U.S. Navy’s pioneering Sealab program. For a record 30 days...

  13. The case of Scott Ortiz: a clash between criminal justice and public health

    Directory of Open Access Journals (Sweden)

    Tobia Maria S

    2006-07-01

    Full Text Available Abstract The criminal justice system creates particular challenges for persons with HIV and Hepatitis C, many of whom have a history of injection drug use. The case of Scott Ortiz, taken from public trial and sentencing transcripts, reveals the manner in which incarceration may delay learning of important health problems such as Hepatitis C infection. In addition, the case of Mr. Ortiz suggests the bias in sentencing that a former injection drug user may face. Collaboration between the Montefiore Medical Center residency in Social Medicine and a Bronx legal services agency, Bronx Defenders, yielded the discovery that a decade after diagnosis with HIV and after long term incarceration, Mr. Ortiz was infected with Hepatitis C. Mr. Ortiz only became aware of his advanced Hepatitis C and liver damage during his trial. The second important aspect of this case centers on the justification for lengthy sentence for a burglary conviction. The presiding Judge in Mr. Ortiz's case acknowledged that because of his advanced illness, Mr. Ortiz posed no threat to society as a burglar (the crime for which he was convicted. But the Judge elected to use his discretion to sentence Mr. Ortiz to a term of 15 years to life (as opposed to a minimum of two to four years based on the idea that the public health would be served by preventing Mr. Ortiz from returning to the life of a street addict, sharing dirty needles with others. Mr. Ortiz reports distant injection drug use, no evidence of current or recent drug use was presented during Mr. Ortiz's trial and he reports no injection drug use for over a decade. In this case, bias against a former injection drug user, masquerading as concern for public health, is used to justify a lengthier sentence. Mr. Ortiz's lack of awareness of his Hepatitis C infection despite long term incarceration, combined with the justification for his dramatically increased sentence, provide examples of how persons within the criminal justice

  14. Update on mucormycosis pathogenesis.

    Science.gov (United States)

    Ibrahim, Ashraf S; Kontoyiannis, Dimitrios P

    2013-12-01

    Mucormycosis is an increasingly common fungal infection with unacceptably high mortality. The recent sequencing genome projects of Mucorales and the development of gene manipulation have enabled significant advances in understanding the pathogenesis of mucormycosis. Therefore, we review the pathogenesis of mucormycosis and highlight potential development of novel diagnostic and therapeutic modalities against this lethal disease. Much of the work has been focused on the role of iron uptake in the virulence of Mucorales. Additionally, host receptors and fungal ligands involved in the process of tissue invasion as well as sporangiospore size and sex loci and their contribution to virulence of Mucorales are discussed. Finally, the role of innate and adaptive immunity in protection against Mucorales and new evidence about drug-induced apoptosis in these fungi are discussed. Recent discoveries introduce several potentially novel diagnostic and therapeutic modalities, which are likely to improve management and outcome for mucormycosis. Future preclinical and clinical research is warranted to develop these diagnostic and therapeutic strategies.

  15. Ron Scott d/b/a White Dog Painting Information Sheet

    Science.gov (United States)

    Ron Scott d/b/a White Dog Painting (the Company) is located in Kansas City, Missouri. The settlement involves renovation activities conducted at property constructed prior to 1978, located in Kansas City, Missouri.

  16. Marion duPont Scott Equine Medical Center uses innovative lameness treatment

    OpenAIRE

    Lee, Kate

    2009-01-01

    Virginia Tech's Marion duPont Scott Equine Medical Center is now offering an equine lameness therapy that prevents further degeneration of the affected joint and offers a longer-lasting benefit than traditional steroid treatment.

  17. Eesti tervishoid on tõesti hea. Aitäh, USA! / Scott Abel

    Index Scriptorium Estoniae

    Abel, Scott

    2010-01-01

    Ameeriklane Scott Abel kirjutab, et president Barack Obama tervishoiureform mõjutab arstiabi ka Eestis. Vastukaja artiklile: Turay, Abdul. Kindla individualismi traditsioon // Postimees (2010) 30. märts, lk. 12

  18. An Overview of Justice in Sir Walter Scott Waverley Novels: The Heart of Mid-Lothian

    Directory of Open Access Journals (Sweden)

    Enrique García Díaz

    2014-12-01

    Full Text Available Although Sir Walter Scott is a well-known writer most of his readers know that he became an advocate in 1792, when he was admitted to the bar. Since then Scott and other advocates walked the floor at Parliament House (home of the Faculty of Advocates and the Court of Session waiting to be hired. Scott’s own experiences as a fledgling advocate are echoed in those of Alain Fairford in his novel Redgauntlet (Scott 1824, which provides a vivid picture of Parliament House in the eighteenth century. During his life, Scott combined extensive writing and editing issues with his daily work as Clerk of Session and Sheriff-Depute of Selkirkshire. Walter Scott was not unaware of Justice and Law and The Heart of Mid-Lothian is the novel in which he introduces to the reader the Scottish Legal System during the eighteenth century. However, there are few more examples that I will explain. Aunque Sir Walter Scott es un conocido escritor, la mayoría de sus lectores saben que en 1792 se hizo abogado, cuando fue admitido en el colegio de abogados. Desde entonces Scott y otros abogados rondaron el Parlamento con la esperanza de ser contratados. Las propias experiencias de Scott como un abogado novel se reflejan en las de Alain Fairford en su novela Redgauntlet (Scott 1824, lo que ofrece una vívida imagen del Parlamento (sede de la facultad de Derecho y Tribunal Supremo en el siglo XVIII. Durante su vida, Scott compaginó una profusa actividad como escritor y editor con su trabajo diario como juez en Selkirk. Walter Scott conocía la justicia y el derecho y El corazón de Mid-Lothian es la novela en la presenta al lector el régimen jurídico de Escocia durante el siglo XVIII. Sin embargo, se explicarán algunos otros ejemplos. DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=2543538

  19. The pathogenesis of progressive multifocal leukoencephalopathy.

    Science.gov (United States)

    Berger, Joseph R; Khalili, Kamel

    2011-12-01

    Interest in pathogenesis of progressive multifocal leukoencephalopathy (PML) followed the observation of the high risk for the disease in HIV infection and the recent observation of an association with a variety of newer therapeutic modalities, e.g., natalizumab, an α4β1 integrin inhibitor, and efalizumab, an anti-CD11a monoclonal antibody. Any hypothesis of PML pathogenesis must account for a number of facts. Firstly, the causative agent JC virus is ubiquitously present, yet only a vanishingly small number of infected persons develop the disease. Secondly, disorders of cell-mediated immunity increase the risk of the disease, particularly HIV infection. Impaired innate immunity is not a risk for PML, and antibodies against JC virus are not protective. Thirdly, a latent period of several months appears necessary following the administration of natalizumab and efalizumab before PML develops. Fourthly, restoration of the immune system can arrest the PML. It is possible that infection with JC virus occurs with a form of the virus shed in the urine of as many as 40% of all adults and present in sewage worldwide. Once acquired, perhaps through an oropharyngeal route, it may replicate and disseminate. A neurotropic form of JC virus that replicates in glial tissues causes PML when immunosurveillance is impaired. There are many unanswered questions with respect to PML pathogenesis. How is virus acquired? What tissues are infected? What is the origin of the neurotropic form? When does virus enter brain? What is the role of central nervous system immunosurveillance? The lack of an animal model has made answering these questions challenging. © Discovery Medicine

  20. HIV testing is associated with increased knowledge and reductions ...

    African Journals Online (AJOL)

    HIV testing is associated with increased knowledge and reductions in sexual risk behaviours among men in Cape Town, South Africa. Lori AJ Scott-Sheldon, Michael P Carey, Kate B Carey, Demetria Cain, Leickness C Simbayi, Vuyelwa Mehlomakhulu, Seth C Kalichman ...

  1. Sex Differences in HIV Infection.

    Science.gov (United States)

    Scully, Eileen P

    2018-04-01

    This review will outline the multilevel effects of biological sex on HIV acquisition, pathogenesis, treatment response, and prospects for cure. Potential mechanisms will be discussed along with future research directions. HIV acquisition risk is modified by sex hormones and the vaginal microbiome, with the latter acting through both inflammation and local metabolism of pre-exposure prophylaxis drugs. Female sex associates with enhanced risk for non-AIDS morbidities including cardiovascular and cerebrovascular disease, suggesting different inflammatory profiles in men and women. Data from research on HIV cure points to sex differences in viral reservoir dynamics and a direct role for sex hormones in latency maintenance. Biological sex remains an important variable in determining the risk of HIV infection and subsequent viral pathogenesis, and emerging data suggest sex differences relevant to curative interventions. Recruitment of women in HIV clinical research is a pathway to both optimize care for women and to identify novel therapeutics for use in both men and women.

  2. Molecular Pathogenesis of NASH

    Directory of Open Access Journals (Sweden)

    Alessandra Caligiuri

    2016-09-01

    Full Text Available Nonalcoholic steatohepatitis (NASH is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression.

  3. Under the Radar: The First Woman in Radio Astronomy, Ruby Payne-Scott

    Science.gov (United States)

    Miller Goss, W.

    2012-05-01

    Under the Radar, the First Woman in Radio Astronomy, Ruby Payne-Scott W. Miller Goss, NRAO Socorro NM Ruby Payne-Scott (1912-1981) was an eminent Australian scientist who made major contributions to the WWII radar effort (CSIR) from 1941 to 1945. In late 1945, she pioneered radio astronomy efforts at Dover Heights in Sydney, Australia at a beautiful cliff top overlooking the Tasman Sea. Again at Dover Heights, Payne-Scott carried out the first interferometry in radio astronomy using an Australian Army radar antenna as a radio telescope at sun-rise, 26 January 1946. She continued these ground breaking activities until 1951. Ruby Payne-Scott played a major role in discovering and elucidating the properties of Type III bursts from the sun, the most common of the five classes of transient phenomena from the solar corona. These bursts are one of the most intensively studied forms of radio emission in all of astronomy. She is also one of the inventors of aperture synthesis in radio astronomy. I examine her career at the University of Sydney and her conflicts with the CSIR hierarchy concerning the rights of women in the work place, specifically equal wages and the lack of permanent status for married women. I also explore her membership in the Communist Party of Australia as well as her partially released Australian Scientific Intelligence Organization file. Payne-Scott’s role as a major participant in the flourishing radio astronomy research of the post war era remains a remarkable story. She had a number of strong collaborations with the pioneers of early radio astronomy in Australia: Pawsey, Mills, Christiansen, Bolton and Little. I am currently working on a popular version of the Payne-Scott story; “Making Waves, The Story of Ruby Payne-Scott: Australian Pioneer Radio Astronomer” will be published in 2013 by Springer in the Astronomers’ Universe Series.

  4. The influence of the Scott effect on the determination of q0

    International Nuclear Information System (INIS)

    Kruszewski, A.; Semeniuk, I.

    1975-01-01

    The statistical model for taking into account the Scott effect was constructed. The suggestion that clusters with exceptionally bright first-ranked cluster member possess fainter than average second and third-ranked galaxies is not substantiated by raw observational data. The first-ranked galaxies are brighter and less cluster richness dependent than expected from the statistical model. The bias due to the Scott effect may increase q 0 by up to 0.5 but with proper care it should be possible to take it into account even without employing complicated statistical models. (author)

  5. Kaposi sarcoma herpesvirus pathogenesis

    Science.gov (United States)

    Koch, Sandra; Schulz, Thomas F.

    2017-01-01

    Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis. As it has colonized humans physiologically for many thousand years, cofactors are needed to allow it to unfold its pathogenic potential. In most cases, these include immune defects of genetic, iatrogenic or infectious origin, and inflammation appears to play an important role in disease development. Our much improved understanding of its life cycle and its role in pathogenesis should now allow us to develop new therapeutic strategies directed against key viral proteins or intracellular pathways that are crucial for virus replication or persistence. Likewise, its limited (for a herpesvirus) distribution and transmission should offer an opportunity for the development and use of a vaccine to prevent transmission. This article is part of the themed issue ‘Human oncogenic viruses’. PMID:28893942

  6. Exosomes in Human Immunodeficiency Virus Type I Pathogenesis: Threat or Opportunity?

    Directory of Open Access Journals (Sweden)

    Sin-Yeang Teow

    2016-01-01

    Full Text Available Nanometre-sized vesicles, also known as exosomes, are derived from endosomes of diverse cell types and present in multiple biological fluids. Depending on their cellular origins, the membrane-bound exosomes packed a variety of functional proteins and RNA species. These microvesicles are secreted into the extracellular space to facilitate intercellular communication. Collective findings demonstrated that exosomes from HIV-infected subjects share many commonalities with Human Immunodeficiency Virus Type I (HIV-1 particles in terms of proteomics and lipid profiles. These observations postulated that HIV-resembled exosomes may contribute to HIV pathogenesis. Interestingly, recent reports illustrated that exosomes from body fluids could inhibit HIV infection, which then bring up a new paradigm for HIV/AIDS therapy. Accumulative findings suggested that the cellular origin of exosomes may define their effects towards HIV-1. This review summarizes the two distinctive roles of exosomes in regulating HIV pathogenesis. We also highlighted several additional factors that govern the exosomal functions. Deeper understanding on how exosomes promote or abate HIV infection can significantly contribute to the development of new and potent antiviral therapeutic strategy and vaccine designs.

  7. Pathogenesis of achalasia cardia.

    Science.gov (United States)

    Ghoshal, Uday C; Daschakraborty, Sunil B; Singh, Renu

    2012-06-28

    Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine, resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achalasia). Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down's syndrome and Parkinson's disease. Polymorphisms in genes encoding for nitric oxide synthase, receptors for vasoactive intestinal peptide, interleukin 23 and the ALADIN gene have been reported. However, studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained. Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus.

  8. Pathogenesis of achalasia cardia

    Science.gov (United States)

    Ghoshal, Uday C; Daschakraborty, Sunil B; Singh, Renu

    2012-01-01

    Achalasia cardia is one of the common causes of motor dysphagia. Though the disease was first described more than 300 years ago, exact pathogenesis of this condition still remains enigmatic. Pathophysiologically, achalasia cardia is caused by loss of inhibitory ganglion in the myenteric plexus of the esophagus. In the initial stage, degeneration of inhibitory nerves in the esophagus results in unopposed action of excitatory neurotransmitters such as acetylcholine, resulting in high amplitude non-peristaltic contractions (vigorous achalasia); progressive loss of cholinergic neurons over time results in dilation and low amplitude simultaneous contractions in the esophageal body (classic achalasia). Since the initial description, several studies have attempted to explore initiating agents that may cause the disease, such as viral infection, other environmental factors, autoimmunity, and genetic factors. Though Chagas disease, which mimics achalasia, is caused by an infective agent, available evidence suggests that infection may not be an independent cause of primary achalasia. A genetic basis for achalasia is supported by reports showing occurrence of disease in monozygotic twins, siblings and other first-degree relatives and occurrence in association with other genetic diseases such as Down’s syndrome and Parkinson’s disease. Polymorphisms in genes encoding for nitric oxide synthase, receptors for vasoactive intestinal peptide, interleukin 23 and the ALADIN gene have been reported. However, studies on larger numbers of patients and controls from different ethnic groups are needed before definite conclusions can be obtained. Currently, the disease is believed to be multi-factorial, with autoimmune mechanisms triggered by infection in a genetically predisposed individual leading to degeneration of inhibitory ganglia in the wall of the esophagus. PMID:22791940

  9. Coretta Scott King Award Winner Javaka Steptoe Stands Tall "In Daddy's Arms."

    Science.gov (United States)

    Peck, Jackie; Hendershot, Judy

    1999-01-01

    Offers an interview with artist and author Javaka Steptoe, winner of the Coretta Scott King award for his book "In Daddy's Arms I Am Tall: African Americans Celebrating Fathers." Discusses his background in the arts, the variety of media he uses, how he begins thinking about his illustrations, his work with children's art, and aspects of his work.…

  10. Random attractors for stochastic lattice reversible Gray-Scott systems with additive noise

    Directory of Open Access Journals (Sweden)

    Hongyan Li

    2015-10-01

    Full Text Available In this article, we prove the existence of a random attractor of the stochastic three-component reversible Gray-Scott system on infinite lattice with additive noise. We use a transformation of addition involved with Ornstein-Uhlenbeck process, for proving the pullback absorbing property and the pullback asymptotic compactness of the reaction diffusion system with cubic nonlinearity.

  11. The Pleasures and Lessons of Academic Mythbusting: An Interview with Scott Lilienfeld

    Science.gov (United States)

    Zinn, Tracy E.

    2010-01-01

    Scott O. Lilienfeld is a professor of psychology at Emory University, in Atlanta, Georgia. Dr. Lilienfeld is founder and editor of the journal, "Scientific Review of Mental Health Practice," and is past president of the Society for a Science of Clinical Psychology. He has been a member of 11 journal editorial boards, including the…

  12. "I Have a Dream, Too!": The American Dream in Coretta Scott King Award-Winning Books

    Science.gov (United States)

    Parsons, Linda T.; Castleman, Michele

    2011-01-01

    The Coretta Scott King (CSK) Award, instituted in 1969 and recognized as an official award by the American Library Association (ALA) in 1982, is conferred annually to an African American author and an illustrator for their outstanding contributions to literature about the Black experience for children and young adults. A partial impetus for the…

  13. James Edward Scott: The Leadership Journey of a Senior-Level African American Student Affairs Officer

    Science.gov (United States)

    Willis, Salatha T.

    2013-01-01

    The purpose of this study was to examine, understand, and describe the life, leadership, and influence of Dr. James Edward Scott on higher education and more specifically student affairs; as one of the most well-known and respected African American male chief student affairs officers in the late 20th and early 21st centuries. Using a qualitative…

  14. Scott Foresman-Addison Wesley Elementary Mathematics. What Works Clearinghouse Intervention Report

    Science.gov (United States)

    What Works Clearinghouse, 2010

    2010-01-01

    "Scott Foresman-Addison Wesley Elementary Mathematics" is a core curriculum for students at all ability levels in prekindergarten through grade 6. The program supports students' understanding of key math concepts and skills and covers a range of mathematical content across grades. The What Works Clearinghouse (WWC) reviewed 12 studies on…

  15. Scott Foresman-Addison Wesley Elementary Mathematics. What Works Clearinghouse Intervention Report. Updated

    Science.gov (United States)

    What Works Clearinghouse, 2013

    2013-01-01

    "Scott Foresman-Addison Wesley Elementary Mathematics" is a core mathematics curriculum for students in prekindergarten through grade 6. The program aims to improve students' understanding of key math concepts through problem-solving instruction, hands-on activities, and math problems that involve reading and writing. The curriculum…

  16. An estimating function approach to inference for inhomogeneous Neyman-Scott processes

    DEFF Research Database (Denmark)

    Waagepetersen, Rasmus

    2007-01-01

    This article is concerned with inference for a certain class of inhomogeneous Neyman-Scott point processes depending on spatial covariates. Regression parameter estimates obtained from a simple estimating function are shown to be asymptotically normal when the "mother" intensity for the Neyman-Sc...

  17. The Paradoxical World of The Great Gatsby by F. Scott Fitzgerald

    OpenAIRE

    ŠANDEROVÁ, Milada

    2015-01-01

    In The Great Gatsby F. Scott Fitzgerald created a world of fundamental contradictions. Whether talking about the way the whole society works, the immense differences among social classes, the characters, or the tension between attributes of a particular character. Therefore, the goal of this bachelor thesis is to analyse the world of this novel as the world built on paradoxes.

  18. Finality regained: A co-algebraic study of Scott-sets and Multisets

    NARCIS (Netherlands)

    D'Agostino, G.; Visser, A.

    1999-01-01

    In this paper we study iterated circular multisets in a coalgebraic frame- work. We will produce two essentially different universes of such sets. The unisets of the first universe will be shown to be precisely the sets of the Scott universe. The unisets of the second universe will be precisely

  19. 78 FR 3479 - Notice of Public Meeting of Fort Scott Council

    Science.gov (United States)

    2013-01-16

    ... submitted on cards that will be provided at the meeting, via mail to Laurie Fox, Presidio Trust, 103... stated prominently at the beginning of the comments. The Trust will make available for public inspection... PRESIDIO TRUST Notice of Public Meeting of Fort Scott Council AGENCY: The Presidio Trust. ACTION...

  20. 76 FR 71611 - Notice of Establishment of the Fort Winfield Scott Advisory Committee

    Science.gov (United States)

    2011-11-18

    ... (``Committee''). The Committee will advise the Executive Director of the Presidio Trust on matters pertaining... of once every three months. Nominations: The Presidio Trust will consider nominations of all... PRESIDIO TRUST Notice of Establishment of the Fort Winfield Scott Advisory Committee AGENCY: The...

  1. Distinguishing different types of inhomogeneity in Neyman-Scott point processes

    Czech Academy of Sciences Publication Activity Database

    Mrkvička, Tomáš

    2014-01-01

    Roč. 16, č. 2 (2014), s. 385-395 ISSN 1387-5841 Institutional support: RVO:60077344 Keywords : clustering * growing clusters * inhomogeneous cluster centers * inhomogeneous point process * location dependent scaling * Neyman-Scott point process Subject RIV: BA - General Mathematics Impact factor: 0.913, year: 2014

  2. Marion duPont Scott Equine Medical Center offers new treatment for lameness

    OpenAIRE

    Musick, Marjorie

    2006-01-01

    The Virginia-Maryland Regional College of Veterinary Medicine's Marion duPont Scott Equine Medical Center has begun offering a new therapy for treating lameness associated with osteoarthritis and cartilage damage in horses, a problem that affects all segments of the equine industry.

  3. 2015-2016 Travel and Hospitality Expense Reports for Scott Gilmore ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Ruxandra Staicu

    Purpose: Board meetings. Date(s):. 2015-07-13 to 2015-07-14. Destination(s):. Ottawa. Airfare: Other. Transportation: $31.46. Accommodation: Meals and. Incidentals: Other: Total: $31.46. Comments: 2015-2016 Travel and Hospitality Expense. Reports for Scott Gilmore, Governor.

  4. Modernity in Two Great American Writers' Vision: Ernest Miller Hemingway and Scott Fitzgerald

    Science.gov (United States)

    Keshmiri, Fahimeh; Darzikola, Shahla Sorkhabi

    2016-01-01

    Scott Fitzgerald and Ernest Hemingway, American memorable novelists have had philosophic ideas about modernity. In fact their idea about existential interests of American, and the effects of American system on society, is mirrored in their creative works. All through his early works, Fitzgerald echoes the existential center of his era. Obviously,…

  5. Conservation assessment for the Siskiyou Mountains salamander and Scott Bar salamander in northern California.

    Energy Technology Data Exchange (ETDEWEB)

    Vinikour, W. S.; LaGory, K. E.; Adduci, J. J.; Environmental Science Division

    2006-10-20

    The purpose of this conservation assessment is to summarize existing knowledge regarding the biology and ecology of the Siskiyou Mountains salamander and Scott Bar salamander, identify threats to the two species, and identify conservation considerations to aid federal management for persistence of the species. The conservation assessment will serve as the basis for a conservation strategy for the species.

  6. Combined Quantification of the Global Proteome, Phosphoproteome, and Proteolytic Cleavage to Characterize Altered Platelet Functions in the Human Scott Syndrome.

    Science.gov (United States)

    Solari, Fiorella A; Mattheij, Nadine J A; Burkhart, Julia M; Swieringa, Frauke; Collins, Peter W; Cosemans, Judith M E M; Sickmann, Albert; Heemskerk, Johan W M; Zahedi, René P

    2016-10-01

    The Scott syndrome is a very rare and likely underdiagnosed bleeding disorder associated with mutations in the gene encoding anoctamin-6. Platelets from Scott patients are impaired in various Ca 2+ -dependent responses, including phosphatidylserine exposure, integrin closure, intracellular protein cleavage, and cytoskeleton-dependent morphological changes. Given the central role of anoctamin-6 in the platelet procoagulant response, we used quantitative proteomics to understand the underlying molecular mechanisms and the complex phenotypic changes in Scott platelets compared with control platelets. Therefore, we applied an iTRAQ-based multi-pronged strategy to quantify changes in (1) the global proteome, (2) the phosphoproteome, and (3) proteolytic events between resting and stimulated Scott and control platelets. Our data indicate a limited number of proteins with decreased (70) or increased (64) expression in Scott platelets, among those we confirmed the absence of anoctamin-6 and the strong up-regulation of aquaporin-1 by parallel reaction monitoring. The quantification of 1566 phosphopeptides revealed major differences between Scott and control platelets after stimulation with thrombin/convulxin or ionomycin. In Scott platelets, phosphorylation levels of proteins regulating cytoskeletal or signaling events were increased. Finally, we quantified 1596 N-terminal peptides in activated Scott and control platelets, 180 of which we identified as calpain-regulated, whereas a distinct set of 23 neo-N termini was caspase-regulated. In Scott platelets, calpain-induced cleavage of cytoskeleton-linked and signaling proteins was downregulated, in accordance with an increased phosphorylation state. Thus, multipronged proteomic profiling of Scott platelets provides detailed insight into their protection against detrimental Ca 2+ -dependent changes that are normally associated with phosphatidylserine exposure. © 2016 by The American Society for Biochemistry and Molecular

  7. Osteoblast role in osteoarthritis pathogenesis.

    Science.gov (United States)

    Maruotti, Nicola; Corrado, Addolorata; Cantatore, Francesco P

    2017-11-01

    Even if osteoarthritis pathogenesis is still poorly understood, numerous evidences suggest that osteoblasts dysregulation plays a key role in osteoarthritis pathogenesis. An abnormal expression of OPG and RANKL has been described in osteoarthritis osteoblasts, which is responsible for abnormal bone remodeling and decreased mineralization. Alterations in genes expression are involved in dysregulation of osteoblast function, bone remodeling, and mineralization, leading to osteoarthritis development. Moreover, osteoblasts produce numerous transcription factors, growth factors, and other proteic molecules which are involved in osteoarthritis pathogenesis. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  8. CD4 T cells mediate both positive and negative regulation of the immune response to HIV infection: complex role of T follicular helper cells and Regulatory T cells in pathogenesis

    Directory of Open Access Journals (Sweden)

    Chansavath ePhetsouphanh

    2015-01-01

    Full Text Available HIV-1 infection results in chronic activation of cells in lymphoid tissue, including T cells, B cells and myeloid lineage cells. The resulting characteristic hyperplasia is an amalgam of proliferating host immune cells in the adaptive response, increased concentrations of innate response mediators due to viral and bacterial products, and homeostatic responses to inflammation. While it is generally thought that CD4 T cells are greatly depleted, in fact, two types of CD4 T cells appear to be increased, namely regulatory T cells (Tregs and T follicular helper cells (Tfh. These cells have opposing roles, but may both be important in the pathogenic process. Whether Tregs are failing in their role to limit lymphocyte activation is unclear, but there is no doubt now that Tfh are associated with B cell hyperplasia and increased germinal centre activity. Antiretroviral therapy (ART may reduce the lymphocyte activation, but not completely, and therefore there is a need for interventions that selectively enhance normal CD4 function without exacerbating Tfh, B cell or Treg dysfunction.

  9. HIV As Trojan Exosome: Immunological Paradox Explained?

    Science.gov (United States)

    Hildreth, James E K

    2017-01-01

    The HIV pandemic is still a major global challenge, despite the widespread availability of antiretroviral drugs. An effective vaccine would be the ideal approach to bringing the pandemic to an end. However, developing an effective HIV vaccine has proven to be an elusive goal. Three major human HIV vaccine trials revealed a strong trend toward greater risk of infection among vaccine recipients versus controls. A similar observation was made in a macaque SIV vaccine study. The mechanism explaining this phenomenon is not known. Here, a model is presented that may explain the troubling results of vaccine studies and an immunological paradox of HIV pathogenesis: preferential infection of HIV-specific T cells. The central hypothesis of this perspective is that as "Trojan exosomes" HIV particles can directly activate HIV-specific T cells enhancing their susceptibility to infection. Understanding the biology of HIV as an exosome may provide insights that enable novel approaches to vaccine development.

  10. Coinfecting viruses as determinants of HIV disease.

    Science.gov (United States)

    Lisco, Andrea; Vanpouille, Christophe; Margolis, Leonid

    2009-02-01

    The human body constitutes a balanced ecosystem of its own cells together with various microbes ("host-microbe ecosystem"). The transmission of HIV-1 and the progression of HIV disease in such an ecosystem are accompanied by de novo infection by other microbes or by activation of microbes that were present in the host in homeostatic equilibrium before HIV-1 infection. In recent years, data have accumulated on the interactions of these coinfecting microbes-viruses in particular-with HIV. Coinfecting viruses generate negative and positive signals that suppress or upregulate HIV-1. We suggest that the signals generated by these viruses may largely affect HIV transmission, pathogenesis, and evolution. The study of the mechanisms of HIV interaction with coinfecting viruses may indicate strategies to suppress positive signals, enhance negative signals, and lead to the development of new and original anti-HIV therapies.

  11. Evaluating safety of concrete gravity dam on weak rock: Scott Dam

    International Nuclear Information System (INIS)

    Goodman, R.E.; Ahlgren, C.S.

    2000-01-01

    Scott Dam is owned and operated by Pacific Gas and Electric Co. (PG and E) as part of the Potter Valley Project. Although it is an unimpressive concrete gravity dam [233 m (765 ft) long with maximum water surface 33.4 m (110 ft) above tail water], the dam has unusually complex and weak foundation rocks; thick condition caused design changes during construction, numerous subsequent special investigations, and several corrections and additions. A main stumbling block to clarification of the dam safety issue for Scott Dam has always been difficulty in characterizing the foundation material. This paper discusses an approach to this problem as well s how the safety of the dam was subsequently confirmed. Following a comprehensive program of research, investigations, and analysis from 1991 to 1997

  12. SCOTT: A time and amplitude digitizer ASIC for PMT signal processing

    Science.gov (United States)

    Ferry, S.; Guilloux, F.; Anvar, S.; Chateau, F.; Delagnes, E.; Gautard, V.; Louis, F.; Monmarthe, E.; Le Provost, H.; Russo, S.; Schuller, J.-P.; Stolarczyk, Th.; Vallage, B.; Zonca, E.; KM3NeT Consortium

    2013-10-01

    SCOTT is an ASIC designed for the readout electronics of photomultiplier tubes developed for KM3NeT, the cubic-kilometer scale neutrino telescope in Mediterranean Sea. To digitize the PMT signals, the multi-time-over-threshold technique is used with up to 16 adjustable thresholds. Digital outputs of discriminators feed a circular sampling memory and a “first in first out” digital memory. A specific study has shown that five specifically chosen thresholds are suited to reach the required timing accuracy. A dedicated method based on the duration of the signal over a given threshold allows an equivalent timing precision at any charge. To verify that the KM3NeT requirements are fulfilled, this method is applied on PMT signals digitized by SCOTT.

  13. Universos ficcionais: o romanesco em Walter Scott e José de Alencar

    Directory of Open Access Journals (Sweden)

    Marcos Roberto Flamínio Peres

    2016-10-01

    Full Text Available Tamanha é a força do romanesco em Walter Scott que ele foi capaz de dar origem a duas linhas de força críticas antagônicas: uma tendendo a situá-lo dentro do conjunto da literatura ocidental, reatualizando arquétipos ancestrais (Frye; outra considerando-o a quintessência do romance histórico por representar momentos cruciais por que passava a sociedade capitalista entre os séculos XVIII e XIX (Lukács. À luz desse pano de fundo teórico contrastivo, este artigo busca analisar Waverley (1814, obra mais influente de Scott, em comparação com As minas de prata (1865-1866, romance mais ambicioso de José de Alencar e que lança mão de estratégias narrativas similares.

  14. Methamphetamine inhibits HIV-1 replication in CD4+ T cells by modulating anti-HIV-1 miRNA expression.

    Science.gov (United States)

    Mantri, Chinmay K; Mantri, Jyoti V; Pandhare, Jui; Dash, Chandravanu

    2014-01-01

    Methamphetamine is the second most frequently used illicit drug in the United States. Methamphetamine abuse is associated with increased risk of HIV-1 acquisition, higher viral loads, and enhanced HIV-1 pathogenesis. Although a direct link between methamphetamine abuse and HIV-1 pathogenesis remains to be established in patients, methamphetamine has been shown to increase HIV-1 replication in macrophages, dendritic cells, and cells of HIV transgenic mice. Intriguingly, the effects of methamphetamine on HIV-1 replication in human CD4(+) T cells that serve as the primary targets of infection in vivo are not clearly understood. Therefore, we examined HIV-1 replication in primary CD4(+) T cells in the presence of methamphetamine in a dose-dependent manner. Our results demonstrate that methamphetamine had a minimal effect on HIV-1 replication at concentrations of 1 to 50 μmol/L. However, at concentrations >100 μmol/L, it inhibited HIV-1 replication in a dose-dependent manner. We also discovered that methamphetamine up-regulated the cellular anti-HIV-1 microRNAs (miR-125b, miR-150, and miR-28-5p) in CD4(+) T cells. Knockdown experiments illustrated that up-regulation of the anti-HIV miRNAs inhibited HIV-1 replication. These results are contrary to the paradigm that methamphetamine accentuates HIV-1 pathogenesis by increasing HIV-1 replication. Therefore, our findings underline the complex interaction between drug use and HIV-1 and necessitate comprehensive understanding of the effects of methamphetamine on HIV-1 pathogenesis. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  15. Rapport de frais de 2015-2016 pour Scott Gilmore | CRDI - Centre ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Accueil · À propos du CRDI · Obligation de rendre compte · Transparence · Déplacements et accueil. Rapport de frais de 2015-2016 pour Scott Gilmore. Total des frais de déplacement : CAD$31.46. Télécharger la version PDF de ce rapport. 13 juillet 2015 au 14 juillet 2015. CAD$31.46. Ce que nous faisons · Financement ...

  16. 2015-2016 Rapports sur les frais de voyage et d'accueil pour Scott ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Ruxandra Staicu

    Réunion du Conseil des gouverneurs. Date(s):. 2015-07-13 à 2015-07-14. Destination(s):. Ottawa. Billet d'avion: Frais de transport au sol ou autrement: 31.46 $. Frais de logement: Repas et frais divers: Autre frais: Total: 31.46 $. Commentaires: 2015-2016 Rapports sur les frais de voyage et d'accueil pour Scott Gilmore, ...

  17. Reliability and validity of the Salford-Scott Nursing Values Questionnaire in Turkish.

    Science.gov (United States)

    Ulusoy, Hatice; Güler, Güngör; Yıldırım, Gülay; Demir, Ecem

    2018-02-01

    Developing professional values among nursing students is important because values are a significant predictor of the quality care that will be provided, the clients' recognition, and consequently the nurses' job satisfaction. The literature analysis showed that there is only one validated tool available in Turkish that examines both the personal and the professional values of nursing students. The aim of this study was to assess the reliability and validity of the Salford-Scott Nursing Values Questionnaire in Turkish. This study was a Turkish linguistic and cultural adaptation of a research tool. Participants and research context: The sample of this study consisted of 627 undergraduate nursing students from different geographical areas of Turkey. Two questionnaires were used for data collection: a socio-demographic form and the Salford-Scott Nursing Values Questionnaire. For the Salford-Scott Nursing Values Questionnaire, construct validity was examined using factor analyses. Ethical considerations: The study was approved by the Cumhuriyet University Faculty of Medicine Research Ethics Board. Students were informed that participation in the study was entirely voluntary and anonymous. Item content validity index ranged from 0.66 to 1.0, and the total content validity index was 0.94. The Kaiser-Meyer-Olkin measure of sampling was 0.870, and Bartlett's test of sphericity was statistically significant (x 2 = 3108.714, p < 0.001). Construct validity was examined using factor analyses and the six factors were identified. Cronbach's alpha was used to assess the internal consistency reliability and the value of 0.834 was obtained. Our analyses showed that the Turkish version of Salford-Scott Nursing Values Questionnaire has high validity and reliability.

  18. Exploring cell apoptosis and senescence to understand and treat cancer: an interview with Scott Lowe

    Directory of Open Access Journals (Sweden)

    2015-11-01

    Full Text Available Scott W. Lowe is currently principal investigator at the Memorial Sloan-Kettering Cancer Center. After beginning his studies in chemical engineering, he decided to take another path and became fascinated by biochemistry, genetics and molecular biology, which ultimately led to an interest in human disease, particularly cancer. During his PhD at the Massachusetts Institute of Technology (MIT, Scott had the opportunity to benefit from the exceptional mentorship of Earl Ruley, David Housman and Tyler Jacks, and contributed to elucidating how the p53 (TP53 tumor suppressor gene limits oncogenic transformation and modulates the cytotoxic response to conventional chemotherapy. This important work earned him a fellowship from the Cold Spring Harbor Laboratory, which helped to launch his independent career. Scott is now a leading scientist in the cancer field and his work has helped to shed light on mechanisms of cell apoptosis and senescence to better understand and treat cancer. In this interview, he talks about this incredible scientific journey.

  19. Exploring cell apoptosis and senescence to understand and treat cancer: an interview with Scott Lowe.

    Science.gov (United States)

    Lowe, Scott; Cifra, Alessandra

    2015-11-01

    Scott W. Lowe is currently principal investigator at the Memorial Sloan-Kettering Cancer Center. After beginning his studies in chemical engineering, he decided to take another path and became fascinated by biochemistry, genetics and molecular biology, which ultimately led to an interest in human disease, particularly cancer. During his PhD at the Massachusetts Institute of Technology (MIT), Scott had the opportunity to benefit from the exceptional mentorship of Earl Ruley, David Housman and Tyler Jacks, and contributed to elucidating how the p53 (TP53) tumor suppressor gene limits oncogenic transformation and modulates the cytotoxic response to conventional chemotherapy. This important work earned him a fellowship from the Cold Spring Harbor Laboratory, which helped to launch his independent career. Scott is now a leading scientist in the cancer field and his work has helped to shed light on mechanisms of cell apoptosis and senescence to better understand and treat cancer. In this interview, he talks about this incredible scientific journey. © 2015. Published by The Company of Biologists Ltd.

  20. Genes contributing to prion pathogenesis

    DEFF Research Database (Denmark)

    Tamgüney, Gültekin; Giles, Kurt; Glidden, David V

    2008-01-01

    incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes...... show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1...

  1. First record of the Calanoid Copepod Pseudodiaptomus serricaudatus (Scott, T. 1894), (Copepoda: Calanoida: Pseudodiaptomidae) in the equatorial Indian ocean.

    Digital Repository Service at National Institute of Oceanography (India)

    Rebello, V.; Narvekar, J.; Gadi, P.; Venenkar, A.; Gauns, M.; PrasannaKumar, S.

    , Pondicherry University, Port Blair, Andaman 3Happy Home Apartment, Near Canara Bank, Fatorda, Margao, Goa-403602 Abstract Pseudodiaptomus serricaudatus (Scott, T. 1894), a planktonic copepod belonging to the family Pseudodiaptomidae, though has...

  2. CYTOMEGALOVIRUS: A REVIEW OF PATHOGENESIS, EPIDEMIOLOGY AND DIAGNOSIS OF INFECTION

    Directory of Open Access Journals (Sweden)

    Sócrates Bezerra de Matos

    2011-05-01

    Full Text Available The cytomegalovirus (CMV is a human β-herpesvirus ubiquitous and has high worldwide prevalence. The transmission occurs through contact with biological fluids, such as: saliva, semen, vaginal secretions, urine and breast milk, as well as transplacental, blood transfusion or organ transplantation. The most CMV infected individuals remains asymptomatic, however, some patients, especially the immunosuppressed, can develop severe infection with serious clinical signs, like the transplant recipients, HIV positive, leukemic or newborn. This review aims, among other things, discuss the pathogenesis and highlight important sites of immunology and diagnosis of CMV infection.

  3. Cytomegalovirus: a review of pathogenesis, epidemiology and diagnosis of infection

    Directory of Open Access Journals (Sweden)

    Sócrates Bezerra de Matos

    2011-01-01

    Full Text Available The cytomegalovirus (CMV is a human β-herpesvirus ubiquitous and has high worldwide prevalence. The transmission occurs through contact with biological fluids, such as: saliva, semen, vaginal secretions, urine and breast milk, as well as trans placental, blood transfusion or organ transplantation. The most CMV infected individuals remains asymptomatic, however, some patients, especially the immunosuppressed, can develop severe infection with serious clinical signs, like the transplant recipients, HIV positive, leukemic or newborn. This review aims, among other things, discuss the pathogenesis and highlight important sites of immunology and diagnosis of CMV infection.

  4. Co-infections and Pathogenesis of KSHV-Associated Malignancies

    Directory of Open Access Journals (Sweden)

    Suhani eThakker

    2016-02-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV, also known as human herpes virus 8 (HHV-8 is one of the several carcinogenic viruses that infect humans. KSHV infection has been implicated in the development of Kaposi’s sarcoma (KS, primary effusion lymphoma (PEL, and multicentric Castleman’s Disease (MCD. While KSHV infection is necessary for the development of KSHV associated malignancies, it is not sufficient to induce tumoriegenesis. Evidently, other co-factors are essential for the progression of KSHV induced malignancies. One of the most important co-factors, necessary for the progression of KSHV induced tumors, is immune suppression that frequently arises during co-infection with HIV and also by other immune suppressants. In this mini-review, we discuss the roles of co-infection with HIV and other pathogens on KSHV infection and pathogenesis.

  5. On the pathogenesis of IDDM

    DEFF Research Database (Denmark)

    Nerup, J; Mandrup-Poulsen, Thomas; Helqvist, S

    1994-01-01

    A model of the pathogenesis of insulin-dependent diabetes mellitus, i.e. the initial phase of beta-cell destruction, is proposed: in a cascade-like fashion efficient antigen presentation, unbalanced cytokine, secretion and poor beta-cell defence result in beta-cell destruction by toxic free...

  6. Pathogenesis of motor neuron disease

    Institute of Scientific and Technical Information of China (English)

    Xuefei Wang

    2006-01-01

    OBJECTIVE: To summarize and analyze the factors and theories related to the attack of motor neuron disease, and comprehensively investigate the pathogenesis of motor neuron disease.DATA SOURCES: A search of Pubmed database was undertaken to identify articles about motor neuron disease published in English from January 1994 to June 2006 by using the keywords of "neurodegenerative diseases". Other literatures were collected by retrieving specific journals and articles.STUDY SELECTION: The data were checked primarily, articles related to the pathogenesis of motor neuron disease were involved, and those obviously irrelated to the articles were excluded.DATA EXTRACTION: Totally 54 articles were collected, 30 of them were involved, and the other 24 were excluded.DATA SYNTHESIS: The pathogenesis of motor neuron disease has multiple factors, and the present related theories included free radical oxidation, excitotoxicity, genetic and immune factors, lack of neurotrophic factor,injury of neurofilament, etc. The studies mainly come from transgenic animal models, cell culture in vitro and patients with familial motor neuron disease, but there are still many restrictions and disadvantages.CONCLUSION: It is necessary to try to find whether there is internal association among different mechanisms,comprehensively investigate the pathogenesis of motor neuron diseases, in order to provide reliable evidence for the clinical treatment.

  7. Biology and pathogenesis of Acanthamoeba

    OpenAIRE

    Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2012-01-01

    Abstract Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and ev...

  8. Michael Scott

    Directory of Open Access Journals (Sweden)

    Ersin Hussein

    2015-04-01

    While Michael has contributed significantly to the field of classics and ancient history by publishing extensively, he has also enjoyed great success in engaging wider audiences with the ancient world. He regularly talks in schools around the country, writes books intended for the popular market as well as articles for national and international newspapers and magazines. Michael's experience in writing and presenting a range of programmes intended for TV and radio audiences has made him a household name. He has written and presented programmes for the National Geographic, History Channel, Nova, and the BBC including Delphi: bellybutton of the ancient world (BBC4; Guilty Pleasures: luxury in the ancient and medieval words (BBC4; Jesus: rise to power (Natural Geographic; Ancient Discoveries (History Channel; Who were the Greeks? (BBC2; The Mystery of the X Tombs (BBC2/Nova; The Greatest Show on Earth (BBC4, in conjunction with the Open University. He has also presented a radio series for BBC Radio 4, Spin the Globe. Michael's most recent programme, Roman Britain from the Air, was aired on ITV in December 2014. In this interview, I talk to him about his engagement with other disciplines within the humanities, his forthcoming book project, and his experiences writing and presenting TV and radio documentaries.

  9. HIV Testing

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... All Collapse All Should I get tested for HIV? CDC recommends that everyone between the ages of ...

  10. Nutritional rickets: pathogenesis and prevention.

    Science.gov (United States)

    Pettifor, John M

    2013-06-01

    Nutritional rickets remains a public health concern in many areas of the world despite cheap and effective means of preventing the disease. The roles of vitamin D deficiency, low dietary calcium intakes and the interrelationships between the two in the pathogenesis of the disease are discussed. It is now recognized that vitamin D deficiency in the pregnant and lactating mother predisposes to the development of rickets in the breastfed infant, and that cultural and social factors are important in the pathogenesis of the disease during the adolescent growth spurt. Prevention of rickets is dependent on the awareness of the medical profession and the general public of the need to ensure adequate intakes of vitamin D in at-risk populations, and of the importance of increasing dietary intakes of calcium using locally available and inexpensive foods in communities in which dietary calcium deficiency rickets is prevalent.

  11. International recognition for ageing research: John Scott Award-2014 to Leonard Hayflick and Paul Moorhead

    OpenAIRE

    Rattan, Suresh

    2014-01-01

    It is with great pleasure and pride that we share the news of the award of the 2014 “City of Philadelphia John Scott Award”, to Dr. Leonard Hayflick and Dr. Paul Moorhead, for their research on ageing. The press release announcing the award states that: “from the first awarded in 1822, the Award is the oldest scientific award in the United States and, as a legacy to Benjamin Franklin, they are in the historic company of past winners who include Marie Curie, Thomas Edison, Jonas Salk, Irving L...

  12. A phyt osociological classification of the vegetation of the Jack Scott Nature Reserve*

    Directory of Open Access Journals (Sweden)

    B. J. Coetzee

    1974-12-01

    Full Text Available The vegetation of the Jack Scott Nature Reserve in the Central Bankenveld Veld Type is classified chiefly by the Braun-Blanquet Table Method. Habitat features, physiognomy, total floristic composition, differentiating species, woody plants and prominent grasses and forbs are presented for each community. Characterizing habitat features, in order of importance for the communities, are: exposure, soil texture, geology, slope, aspect, degree of rockiness and previous ploughing. The classification correlates well with the major physiographic and climatic variation in the Reserve and generally does not cut across main physiognomic types. The communities are potentially homogeneous management units.

  13. Magic neutrino mass matrix and the Bjorken-Harrison-Scott parameterization

    International Nuclear Information System (INIS)

    Lam, C.S.

    2006-01-01

    Observed neutrino mixing can be described by a tribimaximal MNS matrix. The resulting neutrino mass matrix in the basis of a diagonal charged lepton mass matrix is both 2-3 symmetric and magic. By a magic matrix, I mean one whose row sums and column sums are all identical. I study what happens if 2-3 symmetry is broken but the magic symmetry is kept intact. In that case, the mixing matrix is parameterized by a single complex parameter U e3 , in a form discussed recently by Bjorken, Harrison, and Scott

  14. Mafic Materials in Scott Crater? A Test for Lunar Reconnaissance Orbiter

    Science.gov (United States)

    Cooper, Bonnie L.

    2007-01-01

    Clementine 750 nm and multispectral ratio data, along with Lunar Orbiter and radar data, were used to study the crater Scott in the lunar south polar region. The multispectral data provide evidence for mafic materials, impact melts, anorthositic materials, and a small pyroclastic deposit. High-resolution radar data and Lunar Orbiter photography for this area show differences in color and surface texture that correspond with the locations of the hypothesized mafic and anorthositic areas on the crater floor. This region provides a test case for the upcoming Lunar Reconnaissance Orbiter. Verification of the existence of a mafic deposit at this location is relevant to future lunar resource utilization planning.

  15. An assessment of the complications of the Brantley Scott artificial sphincter.

    Science.gov (United States)

    Heathcote, P S; Galloway, N T; Lewis, D C; Stephenson, T P

    1987-08-01

    A Brantley Scott artificial sphincter has been inserted into 95 patients since 1981; more than half of the patients had lower urinary tract neuropathy and most of the others post-TUR incontinence. The main problem with the device has been cuff failure (12), which should be resolved by the new "dipped" cuffs. The major surgical complication has been erosion (10), usually associated with infection. Twenty-four patients had variable degrees of incontinence but the artificial sphincter remains the cornerstone of continence control when other methods have failed or are inappropriate.

  16. Epigenetics and Colorectal Cancer Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bardhan, Kankana; Liu, Kebin, E-mail: Kliu@gru.edu [Department of Biochemistry and Molecular Biology, Medical College of Georgia, and Cancer Center, Georgia Regents University, Augusta, GA 30912 (United States)

    2013-06-05

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.

  17. Epigenetics and colorectal cancer pathogenesis.

    Science.gov (United States)

    Bardhan, Kankana; Liu, Kebin

    2013-06-05

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.

  18. Epigenetics and Colorectal Cancer Pathogenesis

    International Nuclear Information System (INIS)

    Bardhan, Kankana; Liu, Kebin

    2013-01-01

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy

  19. Epigenetics and Colorectal Cancer Pathogenesis

    Directory of Open Access Journals (Sweden)

    Kebin Liu

    2013-06-01

    Full Text Available Colorectal cancer (CRC develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.

  20. Scott Redford: A New Approach to the Permeability of Political Symbolism in Rum Seljuk Turkey

    Directory of Open Access Journals (Sweden)

    Philip Bockholt

    2017-05-01

    Full Text Available As his work transcends what is seen as iconography, from a strictly art history perspective, the choice of Scott Redford for portrayal in this rubric may seem surprising. However, regarding the applicability of iconographical approaches to the wider domain of cultural studies, precisely his adaptation of art history methods, which integrate disparate source material in a quest for meaning, sparked the interest of this issue of META. For most scholars in the field of Islamic history, researching premodern times normally involves reading narrative sources, that is, chronicles. Despite the so-called "documentary turn" taking place in Mamluk and Ottoman Syria, scholars of the Middle East lack the vast array of archival material that is available to their colleagues working on Medieval Europe. Thus, taking into account other types of material generally neglected by historians might be useful (more in the tradition of archaeologists and art historians who do include material culture in general. This article discusses Scott Redford's approach to combining written sources, epigraphy, and archaeological findings of the Seljuks of Rum in 13th century Anatolia in order to gain more insight into the iconography of power in a remote Islamic past.

  1. Making waves the story of Ruby Payne-Scott : Australian pioneer radio astronomer

    CERN Document Server

    Goss, M

    2013-01-01

    This book is an abbreviated, partly re-written version of "Under the Radar - The First Woman in Radio Astronomy: Ruby Payne-Scott." It addresses a general readership interested in historical and sociological aspects of astronomy and presents the biography of Ruby Payne-Scott (1912 – 1981). As the first female radio astronomer (and one of the first people in the world to consider radio astronomy), she made classic contributions to solar radio physics. She also played a major role in the design of the Australian government's Council for Scientific and Industrial Research radars, which were in turn of vital importance in the Southwest Pacific Theatre in World War II. These radars were used by military personnel from Australia, the United States and New Zealand. From a sociological perspective, her career offers many examples of the perils of being a female academic in the first half of the 20th century. Written in an engaging style and complemented by many historical photographs, this book offers fascinating...

  2. La Emulsión de Scott en la Cultura Hispanoamericana.

    Directory of Open Access Journals (Sweden)

    Alfredo Jácome Roca

    2005-06-01

    Varios de los empresarios que fueron pioneros en la industria farmacéutica contaron con algún aceite de hígado de bacalao entre sus primeros productos. En 1876, dos químicos que incursionaron en la industria, llamados Alfred B. Scott y Samuel W. Bowne, empezaron a comerciar en Nueva York la nueva Emulsión de Scott. La fórmula original incluía el aceite de hígado de bacalao –traído de Noruega en grandes cantidades– y los hipofosfitos de lima y soda. No obstante la buena fama que rodeaba sus ingredientes, la comercialización incluyó la propaganda masiva con afirmaciones ciertamente exageradas, que se aprovechaban de la credulidad del público y de la ausencia de mecanismos regulatorios. Se utilizaba tanto el humor como el temor de los parroquianos en postales, almanaques, avisos, que mostraban niños rosados y cachetones. Estos dibujos –y las botellas mismas– hacen actualmente las delicias de los coleccionistas y el negocio de los anticuarios. Una litografía aparecida en 1895 afirma que «la Emulsión de Scott genera vitalidad, carnes, fuerza y la promesa de salud para las personas de todas las edades». Otra estrategia –que aún en tiempos modernos se usa para productos populares– era la de los testimonios de personas que atestiguaban la bondad de la emulsión en su caso concreto. Un aviso que apareció en 1900 en el Greensburg Morning Tribune daba información detallada sobre la escrófula o enfermedad de las linfadenopatías y sobre la consunción, como a la sazón se llamaba a la tuberculosis. «La gente afectada con escrófula a menudo desarrolla consunción; los síntomas más prominentes de la escrófula son la anemia, la secreción de los oídos, las erupciones descamativas, el crecimiento y drenaje de las glándulas del cuello, que pronostican la pronta aparición de la consunción. Todo esto se puede interrumpir, prevenir la consunción y recuperar la salud con el uso precoz de… la Emulsión de Scott». Las niñas que declinaban

  3. HIV: Neuropsychiatric Aspects of Infection and Therapy

    Directory of Open Access Journals (Sweden)

    Rute Alves

    2013-12-01

    Full Text Available Since its recognition in the 80s, HIV infection has reached 65 million people worldwide. The presence of the virus in CNS occurs in most patients, increasingly being identified neuropsychiatric disorders associated with infection and / or treatment with ARV. This article intends to briefly review the neuro-pathogenesis and neuropsychiatric disorders associated with HIV infection and treatment with HAART, as well as its therapeutic approach.

  4. Complications of HIV Disease and Antiretroviral Therapy

    OpenAIRE

    Luetkemeyer, Anne F.; Havlir, Diane V.; Currier, Judith S.

    2010-01-01

    There is growing interest in the pathogenesis, treatment, and prevention of long-term complications of HIV disease and its therapies. Specifically, studies focused on cardiovascular, renal, bone, and fat abnormalities were prominent at the 17th Conference on Retroviruses and Opportunistic Infections. Although enthusiasm about the effectiveness of current antiretroviral therapy remains strong, collectively, the ongoing work in the area of HIV disease and treatment complications appears to refl...

  5. Emotion modelling towards affective pathogenesis.

    Science.gov (United States)

    Bas, James Le

    2009-12-01

    Objective: There is a need in psychiatry for models that integrate pathological states with normal systems. The interaction of arousal and emotion is the focus of an exploration of affective pathogenesis. Method: Given that the explicit causes of affective disorder remain nascent, methods of linking emotion and disorder are evaluated. Results: A network model of emotional families is presented, in which emotions exist as quantal gradients. Morbid emotional states are seen as the activation of distal emotion sites. The phenomenology of affective disorders is described with reference to this model. Recourse is made to non-linear dynamic theory. Conclusions: Metaphoric emotion models have face validity and may prove a useful heuristic.

  6. Molecular pathogenesis of intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Andersen, Jesper Bøje

    2014-01-01

    Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop...... and individualization for precision therapies. Many questions persevere as to the evolutionary process and cellular origin of the initial transforming event, the context of intratumoral plasticity and the causal driver action. Next-generation sequencing has begun to underline the persistent alterations, which may...

  7. Biology and pathogenesis of Acanthamoeba

    Directory of Open Access Journals (Sweden)

    Siddiqui Ruqaiyyah

    2012-01-01

    Full Text Available Abstract Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and evolutionary processes makes it an attractive model organism. There is a significant emphasis on Acanthamoeba as a Trojan horse of other microbes including viral, bacterial, protists and yeast pathogens.

  8. STS-87 Mission Specialists Scott and Doi with EVA coordinator Laws participate in the CEIT for their

    Science.gov (United States)

    1997-01-01

    Participating in the Crew Equipment Integration Test (CEIT) at Kennedy Space Center are STS-87 crew members, assisted by Glenda Laws, extravehicular activity (EVA) coordinator, Johnson Space Center, at left. Next to Laws is Mission Specialist Takao Doi, Ph.D., of the National Space Development Agency of Japan, who is looking on as Mission Specialist Winston Scott gets a hands-on look at some of the equipment. The STS-87 mission will be the fourth United States Microgravity Payload and flight of the Spartan-201 deployable satellite. During the mission, scheduled for a Nov. 19 liftoff from KSC, Dr. Doi and Scott will both perform spacewalks.

  9. Molecular Pathogenesis of Neuromyelitis Optica

    Science.gov (United States)

    Bukhari, Wajih; Barnett, Michael H; Prain, Kerri; Broadley, Simon A

    2012-01-01

    Neuromyelitis optica (NMO) is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG) against aquaporin-4 (AQP4), a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS) when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6) have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies. PMID:23202933

  10. Pathogenesis of Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Beom Jin Lim

    2016-11-01

    Full Text Available Focal segmental glomerulosclerosis (FSGS is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice.

  11. Pathogenesis of varicelloviruses in primates.

    Science.gov (United States)

    Ouwendijk, Werner J D; Verjans, Georges M G M

    2015-01-01

    Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue, simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and, although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  12. Immune Dysfunction and the Pathogenesis of AIDS-associated non-Hodgkin's Lymphoma

    Directory of Open Access Journals (Sweden)

    Martínez-Maza Otoniel

    1998-01-01

    Full Text Available Much has been learned about how HIV-induced immune dysfunction contributes to B cell hyperactivation, and potentially, to the pathogenesis of AIDS-lymphoma. However, further studies are needed to fully understand how HIV infection and immune dysfunction promote B cell hyperactivation and the development/growth of AIDS-lymphoma. In particular, studies are needed to define the role of HHV8 vIL6, IL6 receptor-expression, and lymphocyte surface stimulatory molecules, in promoting B cell hyperactivation or lymphoma cell growth.

  13. Phylogenetic analysis of HIV-1 pol gene: first subgenomic evidence of CRF29-BF among Iranian HIV-1 patients

    Directory of Open Access Journals (Sweden)

    Kazem Baesi

    2014-09-01

    Full Text Available Objective: To identify the dominant subtype among the HIV-1 strains circulation in Iran. Methods: In this cross sectional study 100 HIV positive patients participated. HIV-1 RNA was extracted from plasma. RT nested-PCR was performed and the final products were sequenced and phylogenetically analyzed; reference sequences were downloaded from Los Alamos, aligned with Iranian pol sequences in the study and analyzed by neighbor-joining method. Results: The results of the phylogenetic analysis showed that HIV-1 subtype CRF-35AD was the dominant subtype among HIV-1 infected patients in Iran; this analysis also suggested a new circulating recombinant form that had not previously been identified in Iran: CRF-29BF. Conclusions: The impact of HIV diversity on pathogenesis, transmission and clinical management have been discussed in different studies; therefore, analyses of HIV genetic diversity is required to design effective antiretroviral strategies for different HIV subtypes.

  14. Scott Correction for Large Atoms and Molecules in a Self-Generated Magnetic Field

    DEFF Research Database (Denmark)

    Erdös, Laszlo; Fournais, Søren; Solovej, Jan Philip

    2012-01-01

    constant. We show that, in the simultaneous limit $Z\\to\\infty$, $\\al\\to 0$ such that $\\kappa =Z\\al^2$ is fixed, the ground state energy of the system is given by a two term expansion $c_1Z^{7/3} + c_2(\\kappa) Z^2 + o(Z^2)$. The leading term is given by the non-magnetic Thomas-Fermi theory. Our result shows......We consider a large neutral molecule with total nuclear charge $Z$ in non-relativistic quantum mechanics with a self-generated classical electromagnetic field. To ensure stability, we assume that $Z\\al^2\\le \\kappa_0$ for a sufficiently small $\\kappa_0$, where $\\al$ denotes the fine structure...... that the magnetic field affects only the second (so-called Scott) term in the expansion....

  15. Further developments of the Neyman-Scott clustered point process for modeling rainfall

    Science.gov (United States)

    Cowpertwait, Paul S. P.

    1991-07-01

    This paper provides some useful results for modeling rainfall. It extends work on the Neyman-Scott cluster model for simulating rainfall time series. Several important properties have previously been found for the model, for example, the expectation and variance of the amount of rain captured in an arbitrary time interval (Rodriguez-Iturbe et al., 1987a), In this paper additional properties are derived, such as the probability of an arbitrary interval of any chosen length being dry. In applications this is a desirable property to have, and is often used for fitting stochastic rainfall models to field data. The model is currently being used in rainfall time series research directed toward improving sewage systems in the United Kingdom. To illustrate the model's performance an example is given, where the model is fitted to 10 years of hourly data taken from Blackpool, England.

  16. Pathogenesis of Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627

  17. Richard J. Hill, Picturing Scotland through the Waverley Novels: Walter Scott and the Origins of the Victorian Illustrated Novel.

    Directory of Open Access Journals (Sweden)

    Jacqueline Irene Cannata

    2012-10-01

    Full Text Available Richard J. Hill, Picturing Scotland through the Waverley Novels: Walter Scott and the Origins of the Victorian Illustrated Novel . Farnham, Surrey, and Burlington, VT: Ashgate, 2010. Pp. 236. ISBN 978-0-7546-6806-0. US$99.99.

  18. Case 3724 - Metochus abbreviatus Scott, 1874 (Insecta, Heteroptera): proposed precedence over Rhyparochromus erosus Walker, 1872 (currently Metochus erosus)

    Science.gov (United States)

    The purpose of this application, under Article 23.9.3 of the Code, is to conserve the widely used specific name Metochus abbreviatus Scott, 1874, for a species of rhyparochromid bugs from East Asia. The name is threatened by the senior subjective synonym Metochus erosus (Walker, 1872), which has bee...

  19. Diabetic Cataract—Pathogenesis, Epidemiology and Treatment

    Directory of Open Access Journals (Sweden)

    Andreas Pollreisz

    2010-01-01

    This paper provides an overview of the pathogenesis of diabetic cataract, clinical studies investigating the association between diabetes and cataract development, and current treatment of cataract in diabetics.

  20. Women and HIV

    Science.gov (United States)

    ... Consumer Information by Audience For Women Women and HIV: Get the Facts on HIV Testing, Prevention, and Treatment Share Tweet Linkedin Pin ... How can you lower your chance of HIV? HIV Quick Facts What is HIV? HIV is the ...

  1. 100 years since Scott reached the pole: a century of learning about the physiological demands of Antarctica.

    Science.gov (United States)

    Halsey, Lewis G; Stroud, Mike A

    2012-04-01

    The 1910-1913 Terra Nova Expedition to the Antarctic, led by Captain Robert Falcon Scott, was a venture of science and discovery. It is also a well-known story of heroism and tragedy since his quest to reach the South Pole and conduct research en route, while successful was also fateful. Although Scott and his four companions hauled their sledges to the Pole, they died on their return journey either directly or indirectly from the extreme physiological stresses they experienced. One hundred years on, our understanding of such stresses caused by Antarctic extremes and how the body reacts to severe exercise, malnutrition, hypothermia, high altitude, and sleep deprivation has greatly advanced. On the centenary of Scott's expedition to the bottom of the Earth, there is still controversy surrounding whether the deaths of those five men could have, or should have, been avoided. This paper reviews present-day knowledge related to the physiology of sustained man-hauling in Antarctica and contrasts this with the comparative ignorance about these issues around the turn of the 20th century. It closes by considering whether, with modern understanding about the effects of such a scenario on the human condition, Scott could have prepared and managed his team differently and so survived the epic 1,600-mile journey. The conclusion is that by carrying rations with a different composition of macromolecules, enabling greater calorific intake at similar overall weight, Scott might have secured the lives of some of the party, and it is also possible that enhanced levels of vitamin C in his rations, albeit difficult to achieve in 1911, could have significantly improved their survival chances. Nevertheless, even with today's knowledge, a repeat attempt at his expedition would by no means be bound to succeed.

  2. La Jolie Fille de Perth de Bizet  ou comment trahir et honorer Walter Scott Bizet’s Jolie Fille de Perth or How to Betray and Honour Walter Scott

    Directory of Open Access Journals (Sweden)

    Gilles Couderc

    2011-11-01

    Full Text Available What remains of Walter Scott’s Fair Maid of Perth in Bizet’s 1867 Jolie Fille de Perth, an opera in 4acts on a libretto by Jules Adenis and Vernoy de Saint-Georges? Not much when compared to other Scott-inspired operas. Little historical context or local colour, even in Bizet’s music. Some characters remotely linked to Scott in a libretto that mostly abides by the rules of French opera or opéra-comique of the time and recycles the dramatic ingredients favoured by Saint-Georges, a purveyor of libretti for opera or the ballet second only to Scribe, who engendered such international successes as Flotow’s Martha and Balfe’s Bohemian Girl, whose gipsy, long before his Carmen, haunts Bizet’s “Scottish” opera. Yet the work pays indirect homage to Scott, whose historical novels contributed to the birth of the French “grand opera”, by rewriting scenes or situations drawn from Scott. In spite of borrowing freely from French grand opera and opéra-comique, Bizet here attempts to find his own musical expression and his opera reflects aspects of Second Empire French society and the roles it assigned to women, before the appearance of his revolutionary Carmen on the stage.Que reste t’il du roman de Walter Scott The Fair Maid of Perth dans la Jolie Fille de Perth de Bizet, opéra en 4 actes de 1867 sur un livret de Vernoy de Saint-Georges, vieux routier du théâtre lyrique, et Jules Adenis ? Pas grand-chose par rapport aux opéras inspirés par Scott. Peu d’Ecosse, une absence remarquable de couleur locale ou historique, des personnages vaguement inspirés de Scott pour un livret qui se plie surtout aux règles de l’opéra français et de l’opéra-comique à la manière de Scribe et recycle les ingrédients habituels des livrets de Saint-Georges, père de succès internationaux comme la Martha de Flotow et de la Bohemian Girl de Balfe, dont la figure exotique de la bohémienne, longtemps avant Carmen, hante l’opéra

  3. HIV-Associated Lung Cancer.

    Science.gov (United States)

    Kiderlen, Til R; Siehl, Jan; Hentrich, Marcus

    2017-01-01

    Lung cancer (LC) is one of the most common non-AIDS (acquired immune deficiency syndrome)-defining malignancies. It occurs more frequently in persons living with human immunodeficiency virus (PLWHIV) than in the HIV-negative population. Compared to their HIV-negative counterparts, patients are usually younger and diagnosed at more advanced stages. The pathogenesis of LC in PLWHIV is not fully understood, but immunosuppression in combination with chronic infection and the oncogenic effects of smoking and HIV itself all seem to play a role. Currently, no established preventive screening is available, making smoking cessation the most promising preventive measure. Treatment protocols and standards are the same as for the general population. Notably, immuno-oncology will also become standard of care in a significant subset of HIV-infected patients with LC. As drug interactions and hematological toxicity must be taken into account, a multidisciplinary approach should include a physician experienced in the treatment of HIV. Only limited data is available on novel targeted therapies and checkpoint inhibitors in the setting of HIV. © 2017 S. Karger GmbH, Freiburg.

  4. Pathogenesis of ovarian cancer: current perspectives | Chesang ...

    African Journals Online (AJOL)

    Objective: To present a review of current knowledge of the pathogenesis of ovarian cancer and its clinical implications. Data Source: Extensive literature search was conducted to identify relevant studies. Study Selection: Studies in the English language about or related to pathogenesis of ovarian cancer were selected.

  5. Achondroplasia: Development, pathogenesis, and therapy.

    Science.gov (United States)

    Ornitz, David M; Legeai-Mallet, Laurence

    2017-04-01

    Autosomal dominant mutations in fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include hypochondroplasia (Hch), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD). FGFR3 is expressed in chondrocytes and mature osteoblasts where it functions to regulate bone growth. Analysis of the mutations in FGFR3 revealed increased signaling through a combination of mechanisms that include stabilization of the receptor, enhanced dimerization, and enhanced tyrosine kinase activity. Paradoxically, increased FGFR3 signaling profoundly suppresses proliferation and maturation of growth plate chondrocytes resulting in decreased growth plate size, reduced trabecular bone volume, and resulting decreased bone elongation. In this review, we discuss the molecular mechanisms that regulate growth plate chondrocytes, the pathogenesis of Ach, and therapeutic approaches that are being evaluated to improve endochondral bone growth in people with Ach and related conditions. Developmental Dynamics 246:291-309, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Hand osteoarthritis: diagnosis, pathogenesis, treatment

    Directory of Open Access Journals (Sweden)

    R. M. Balabanova

    2018-01-01

    Full Text Available Due to the development of synovitis, early-stage hand osteoarthritis (HOA mimics hand joint injury in rheumatoid arthritis (RA. However, the topography of synovitis is diverse in these diseases:  distal interphalangeal and thumb joints are involved in the process in HOA. In the latter, tests are negative for immunological markers  (anti-cyclic citrullinated peptide antibodies, which is typical of RA.  The differences between HOA and RA are prominent, as evidenced  by hand X-rays and magnetic resonance imaging. Investigations  suggest that cytokine profile imbalance is implicated in the  pathogenesis of osteoarthritis, which brings it closer to RA. However, therapy for HOA has not been practically developed; there are only a few works on the use of disease-modifying antirheumatic drugs and  biological agents in these patients. It is necessary to work out Russian guidelines for the treatment of HOA.

  7. The Pathogenesis of Lupus Nephritis

    Science.gov (United States)

    Lech, Maciej

    2013-01-01

    Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies. PMID:23929771

  8. Molecular Pathogenesis of MALT Lymphoma

    Directory of Open Access Journals (Sweden)

    Katharina Troppan

    2015-01-01

    Full Text Available Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT, also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis.

  9. HIV-1 Latency in Monocytes/Macrophages

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2014-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

  10. Betydning af hiv for knogletæthed

    DEFF Research Database (Denmark)

    Wessman, Maria; Weis, Nina; Katzenstein, Terese L

    2017-01-01

    The life expectancy in well-treated HIV-infected persons approaches that of the general population, but HIV-infected persons have a greater incidence of fractures and osteoporosis. A decrease in bone mineral density is observed primarily during the first 1-2 years of antiretroviral therapy. Dual X......-ray absorptiometry scan should be considered in HIV-infected men ≥ 50 years and postmenopausal women. In case of osteoporosis, bisphosphonate treatment should follow guidelines for the general population. Future research should focus on pathogenesis and prevention of bone density loss in HIV....

  11. The significance of HIV to bone mineral density

    DEFF Research Database (Denmark)

    Wessman, Maria; Weis, Nina; Katzenstein, Terese L

    2017-01-01

    The life expectancy in well-treated HIV-infected persons approaches that of the general population, but HIV-infected persons have a greater incidence of fractures and osteoporosis. A decrease in bone mineral density is observed primarily during the first 1-2 years of antiretroviral therapy. Dual X......-ray absorptiometry scan should be considered in HIV-infected men ≥ 50 years and postmenopausal women. In case of osteoporosis, bisphosphonate treatment should follow guidelines for the general population. Future research should focus on pathogenesis and prevention of bone density loss in HIV....

  12. Pathogenesis of Proteus mirabilis Infection

    Science.gov (United States)

    Armbruster, Chelsie E.; Mobley, Harry L. T.; Pearson, Melanie M.

    2017-01-01

    Proteus mirabilis, a Gram-negative rod-shaped bacterium most noted for its swarming motility and urease activity, frequently causes catheter-associated urinary tract infections (CAUTI) that are often polymicrobial. These infections may be accompanied by urolithiasis, development of bladder or kidney stones due to alkalinization of urine from urease-catalyzed urea hydrolysis. Adherence of the bacterium to epithelial and catheter surfaces is mediated by 17 different fimbriae, most notably MR/P fimbriae. Repressors of motility are often encoded by these fimbrial operons. Motility is mediated by flagella encoded on a single contiguous 54 kb chromosomal sequence. On agar plates, P. mirabilis undergoes a morphological conversion to a filamentous swarmer cell expressing hundreds of flagella. When swarms from different strains meet, a line of demarcation, a “Dienes line”, develops due to the killing action of each strain’s type VI secretion system. During infection, histological damage is caused by cytotoxins including hemolysin and a variety of proteases, some autotransported. The pathogenesis of infection, including assessment of individual genes or global screens for virulence or fitness factors has been assessed in murine models of ascending UTI or CAUTI using both single-species and polymicrobial models. Global gene expression studies carried out in culture and in the murine model have revealed the unique metabolism of this bacterium. Vaccines, using MR/P fimbria and its adhesin, MrpH, have been shown to be efficacious in the murine model. A comprehensive review of factors associated with urinary tract infection is presented, encompassing both historical perspectives and current advances. PMID:29424333

  13. The Quest for Success and Power in F. Scott Fitzgerald's Novel The Beautiful and Damned

    Directory of Open Access Journals (Sweden)

    Ala Eddin Sadeq

    2017-02-01

    Full Text Available This study aims at investigating the concepts of success and power, as depicted by F. Scott Fitzgerald in The Beautiful and Damned (2009. Cultural change motivates individuals to work harder to achieve success, which in turn makes them influential. The study reveals that the concepts of success and power are controversial, as their means vary from one theorist to another.  Waldo Emerson, for example, believes that success is connected to happiness.  He, therefore, lists down features that characterize successful people. To succeed, one must learn to follow their desires, an argument that is expounded by the ideology of the American Dream.  Friedrich Nietzsche, however, explains that individuals are motivated to lead due to the fact that power brings about the superman. To achieve the status of the superman, Nietzsche believes that individuals develop the will to power and are able to influence others (Nietzsche, 1968. Fitzgerald, on the other hand, makes it clear that power leads to liberty. The novel provides a deep analysis of the quest for power and success. The main characters are Gloria, Joseph, and Anthony who helps to demonstrate the quest for success and power. Richard Caramel is also a character whose role explains the pursuit of true happiness. He is depicted as powerful because he influences the society through his writings. He has a strong determination to be a writer, which motivates him to work hard and to seek further success.

  14. 1995 Emerging Leaders in Healthcare. The new leaders: Gita Budd, Colene Daniel, Elizabeth Gallup, Scott Wordelman.

    Science.gov (United States)

    Southwick, K

    1995-01-01

    Fierce pressures for cost containment. Demands for quality improvements. The drive toward patient-centered care. The push for community involvement. Insistent voices of payers, patients, consumers, physicians. Accumulated tensions amid the chaos of change. Balancing all of these demands while inspiring and encouraging the professionals and other workers within the healthcare organization requires a high level of leadership ability. One that insists on the best from everyone involved in a healthcare system--from physicians to staff, nurses to social workers. And then strives for more. The four young executives who are this year's Emerging Leaders in Healthcare have all pushed their systems beyond traditional boundaries into new territory, helping their patients, their employees, their physicians, and their communities rise to new levels of achievement. At the same time, these leaders emphasize teamwork and consensus-style management, so that their co-workers feel like they're participating in the changes, not being victimized by them. Gita Budd, Colene Daniel, Elizabeth Gallup, and Scott Wordelman are winners of the 1995 award from The Healthcare Forum and Korn/Ferry International that honors ¿dynamic, decisive young leaders (under 40) with the proven ability to nurture the growth of the industry.¿ Korn/Ferry International and The Healthcare Forum are proud to present 1995's Emerging Leaders.

  15. Deviations of the lepton mapping matrix form the harrison-perkins-scott form

    International Nuclear Information System (INIS)

    Friedberg, R.; Lee, T.D.

    2010-01-01

    We propose a simple set of hypotheses governing the deviations of the leptonic mapping matrix from the Harrison-Perkins-Scott (HPS) form. These deviations are supposed to arise entirely from a perturbation of the mass matrix in the charged lepton sector. The perturbing matrix is assumed to be purely imaginary (thus maximally T-violating) and to have a strength in energy scale no greater (but perhaps smaller) than the muon mass. As we shall show,it then follows that the absolute value of the mapping matrix elements pertaining to the tau lepton deviate by no more than O((m μ /m τ ) 2 ) ≅ 3.5 x 10 -3 from their HPS values. Assuming that(m μ /m τ ) 2 can be neglected, we derive two simple constraints on the four parameters θ12, θ23, θ31, and δ of the mapping matrix. These constraints are independent of the details of the imaginary T-violating perturbation of the charged lepton mass matrix. We also show that the e and μ parts of the mapping matrix have a definite form governed by two parameters α and β; any deviation of order m μ /m τ can be accommodated by adjusting these two parameters. (authors)

  16. STS-103 Pilot Scott Kelly and MS John Grunsfeld try on oxygen masks

    Science.gov (United States)

    1999-01-01

    In the bunker at Launch Pad 39B, STS-103 Pilot Scott J. Kelly (left) and Mission Specialist John M. Grunsfeld (Ph.D.) (right) try on oxygen masks during Terminal Countdown Demonstration Test (TCDT) activities. The TCDT provides the crew with emergency egress training, opportunities to inspect their mission payloads in the orbiter's payload bay, and simulated countdown exercises. Other crew members taking part are Commander Curtis L. Brown Jr. and Mission Specialists Steven L. Smith, C. Michael Foale (Ph.D.), and Jean-Frangois Clervoy of France and Claude Nicollier of Switzerland, who are with the European Space Agency. STS-103 is a 'call-up' mission due to the need to replace and repair portions of the Hubble Space Telescope, including the gyroscopes that allow the telescope to point at stars, galaxies and planets. The STS-103 crew will be replacing a Fine Guidance Sensor, an older computer with a new enhanced model, an older data tape recorder with a solid-state digital recorder, a failed spare transmitter with a new one, and degraded insulation on the telescope with new thermal insulation. The crew will also install a Battery Voltage/Temperature Improvement Kit to protect the spacecraft batteries from overcharging and overheating when the telescope goes into a safe mode. Four EVA's are planned to make the necessary repairs and replacements on the telescope. The mission is targeted for launch Dec. 6 at 2:37 a.m. EST.

  17. ROBERT VENTURI, DENISE SCOTT BROWN Y STEVEN IZENOUR: LEARNING FROM LAS VEGAS

    Directory of Open Access Journals (Sweden)

    Ignacio Senra Fernández-Miranda

    2013-05-01

    Full Text Available RESUMEN Poco tiene que ver la edición original de 1972 de Learning from las Vegas, the forgotten symbolism of the architectural form, con la edición revisada de 1977, que fue traducida al español y publicada por Gustavo Gili en 1978. El gran formato del libro original (38x28cm se justificaba por la importancia del material gráfico desplegado, un ejercicio de análisis que aspiraba a descubrir nuevas técnicas de representación capaces de reproducir una realidad tan compleja sensorialmente como la de la ciudad de las Vegas. La drástica transformación, impulsada por los propios autores, suponía un abaratamiento y por tanto una mayor difusión del libro, pero sobretodo trataba de acabar con el conflicto entre su crítica al diseño Bauhaus y el diseño Bauhaus tardío del libro original, como señaló la propia Denise Scott Brown en el prologo de la edición revisada de 1977.

  18. Review of behavioral health integration in primary care at Baylor Scott and White Healthcare, Central Region.

    Science.gov (United States)

    Jolly, John B; Fluet, Norman R; Reis, Michael D; Stern, Charles H; Thompson, Alexander W; Jolly, Gillian A

    2016-04-01

    The integration of behavioral health services in primary care has been referred to in many ways, but ultimately refers to common structures and processes. Behavioral health is integrated into primary care because it increases the effectiveness and efficiency of providing care and reduces costs in the care of primary care patients. Reimbursement is one factor, if not the main factor, that determines the level of integration that can be achieved. The federal health reform agenda supports changes that will eventually permit behavioral health to be fully integrated and will allow the health of the population to be the primary target of intervention. In an effort to develop more integrated services at Baylor Scott and White Healthcare, models of integration are reviewed and the advantages and disadvantages of each model are discussed. Recommendations to increase integration include adopting a disease management model with care management, planned guideline-based stepped care, follow-up, and treatment monitoring. Population-based interventions can be completed at the pace of the development of alternative reimbursement methods. The program should be based upon patient-centered medical home standards, and research is needed throughout the program development process.

  19. Studies on the presence and spatial distribution of anthropogenic pollutants in the glacial basin of Scott Glacier in the face of climate change (Fiord Bellsund, Spitsbergen)

    Science.gov (United States)

    Lehmann, Sara; Kociuba, Waldemar; Franczak, Łukasz; Gajek, Grzegorz; Łeczyński, Leszek; Kozak, Katarzyna; Szopińska, Małgorzata; Ruman, Marek; Polkowska, Żaneta

    2014-10-01

    The study area covered the NW part of the Wedel Jarlsberg Land (SW part of the Svalbard Archipelago). The primary study object was the catchment of the Scott Glacier in the vicinity of the Research Station of of Maria Curie-Skłodowska University in Lublin - Calypsobyen. The Scott River catchment (of glacial hydrological regime) has an area of approximately 10 km2, 40% of which is occupied by the valley Scott Glacier in the phase of strong recession. The present study concerns the determination of physical and chemical parameters (pH, conductivity, TOC) and concentrations of pollutants (phenols, aldehydes).

  20. Frequency and site mapping of HIV-1/SIVcpz, HIV- 2/SIVsmm and ...

    African Journals Online (AJOL)

    Administrator

    2007-05-16

    May 16, 2007 ... Other issues of safety are dependant upon choice of enzyme gene deli- very, and although various ex vivo and in vivo gene transfer techniques exist, we believe that a recom-binant. HIV viral vector whose pathogenesis gene, NEF has been removed to render it impotent, could offer a more targeted delivery ...

  1. Staphylococcus aureus nasal colonization in HIV-seropositive and HIV-seronegative drug users

    NARCIS (Netherlands)

    K.A. Holbrook; R.S. Klein; D. Hartel; D.A. Elliott; T. B. Barsky; L. H. Rothschild; F. D. Lowy

    1997-01-01

    textabstractNasal colonization plays an important role in the pathogenesis of Staphylococcus aureus infections. To identify characteristics associated with colonization, we studied a cross-section of a well-described cohort of HIV-seropositive and -seronegative active and former drug users

  2. STS-87 Mission Specialist Scott poses in his launch and entry spacesuit at LC 39B during TCDT

    Science.gov (United States)

    1997-01-01

    STS-87 Mission Specialist Winston Scott poses in his orange launch and entry spacesuit with NASA suit technicians at Launch Pad 39B during Terminal Countdown Demonstration Test (TCDT) activities. The crew of the STS-87 mission is scheduled for launch Nov. 19 aboard the Space Shuttle Columbia. Scott will be performing an extravehicular activity (EVA) spacewalk during the mission. The TCDT is held at KSC prior to each Space Shuttle flight providing the crew of each mission opportunities to participate in simulated countdown activities. The TCDT ends with a mock launch countdown culminating in a simulated main engine cut-off. The crew also spends time undergoing emergency egress training exercises at the pad and has an opportunity to view and inspect the payloads in the orbiter's payload bay.

  3. No Absolutism Here: Harm Predicts Moral Judgment 30× Better Than Disgust-Commentary on Scott, Inbar, & Rozin (2016).

    Science.gov (United States)

    Gray, Kurt; Schein, Chelsea

    2016-05-01

    Moral absolutism is the idea that people's moral judgments are insensitive to considerations of harm. Scott, Inbar, and Rozin (2016, this issue) claim that most moral opponents to genetically modified organisms are absolutely opposed-motivated by disgust and not harm. Yet there is no evidence for moral absolutism in their data. Perceived risk/harm is the most significant predictor of moral judgments for "absolutists," accounting for 30 times more variance than disgust. Reanalyses suggest that disgust is not even a significant predictor of the moral judgments of absolutists once accounting for perceived harm and anger. Instead of revealing actual moral absolutism, Scott et al. find only empty absolutism: hypothetical, forecasted, self-reported moral absolutism. Strikingly, the moral judgments of so-called absolutists are somewhat more sensitive to consequentialist concerns than those of nonabsolutists. Mediation reanalyses reveal that moral judgments are most proximally predicted by harm and not disgust, consistent with dyadic morality. © The Author(s) 2016.

  4. HIV-related neuropathy: current perspectives

    Directory of Open Access Journals (Sweden)

    Schütz SG

    2013-09-01

    Full Text Available Sonja G Schütz, Jessica Robinson-Papp Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA Abstract: Distal symmetric polyneuropathy (DSP related to human immunodeficiency virus (HIV is one of the most common neurologic complications of HIV, possibly affecting as many as 50% of all individuals infected with HIV. Two potentially neurotoxic mechanisms have been proposed to play a crucial role in the pathogenesis of HIV DSP: neurotoxicity resulting from the virus and its products; as well as adverse neurotoxic effects of medications used in the treatment of HIV. Clinically, HIV DSP is characterized by a combination of signs and symptoms that include decreased deep tendon reflexes at the ankles and decreased sensation in the distal extremities as well as paresthesias, dysesthesias, and pain in a symmetric stocking–glove distribution. These symptoms are generally static or slowly progressive over time, and depending on the severity, may interfere significantly with the patient's daily activities. In addition to the clinical picture, nerve conduction studies and skin biopsies are often pursued to support the diagnosis of HIV DSP. Anticonvulsants, antidepressants, topical agents, and nonspecific analgesics may help relieve neuropathic pain. Specifically, gabapentin, lamotrigine, pregabalin, amitriptyline, duloxetine, and high-dose topical capsaicin patches have been used in research and clinical practice. Further research is needed to elucidate the pathogenesis of HIV DSP, thus facilitating the development of novel treatment strategies. This review discusses the epidemiology, pathophysiology, clinical findings, diagnosis, and management of DSP in the setting of HIV. Keywords: neuropathy, human immunodeficiency virus, acquired immunodeficiency syndrome, AIDS, distal symmetric polyneuropathy, DSP, pain

  5. An Odyssey to Viral Pathogenesis.

    Science.gov (United States)

    Oldstone, Michael B A

    2016-05-23

    polishing by Karl Habel (a superb senior virologist who left the National Institutes of Health and came to Scripps), and the gifted postdoctoral fellows who joined my laboratory over four decades form the log of my scientific voyage. The strong friendships and collaborations developed with other young but growing experimentalists like Bernie Fields and Abner Notkins are the fabric of the tale I will weave and were pivotal in the establishment of viral pathogenesis as a discipline.

  6. Current understanding in pathogenesis of atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Tess McPherson

    2016-01-01

    Full Text Available There have been advances in our understanding of the complex pathogenesis of atopic eczema over the past few decades. This article examines the multiple factors which are implicated in this process.

  7. Pathogenesis of Dengue Vaccine Viruses in Mosquitoes.

    Science.gov (United States)

    1980-01-01

    1973). Sabin (1948) showed that attenuated dpngiie, passed through mosquitoes, did not revert to pathogenicity frnr man. -7- Thus even if the vaccine ...AD-A138 518 PATHOGENESIS OF DENGUE VACCINE YIRUSES IN MOSQUITOES 1/ (U) YALE UNIV NEW HAVEN CONN SCHOOL OF MEDICINE B J BEATY ET AL. 9i JAN 80 DRND7...34 ’ UNCLASSIFIED 0{) AD 0Pathogenesis of dengue vaccine viruses in mosquitoes -First Annual Report Barry I. Beaty, Ph.D. Thomas H. G

  8. The Italian validation of the Salford-Scott Nursing Values Questionnaire.

    Science.gov (United States)

    Mecugni, Daniela; Albinelli, Patrizia; Pellegrin, Joellemarie; Finotto, Stefano

    2015-03-01

    To properly direct nursing training and to improve the professional practice to become more effective, it is important to understand students' values. Literature review has shown that there have been changes in students' values in the last 20 years. In contemporary students, a general decrease in altruism has been observed, but also a larger appreciation for honesty toward patients has been declared. The analyzed literature did not find validated tools available in Italian that explore personal and professional values of nursing students. This study was an Italian linguistic and cultural adaptation of a research tool. The authors aimed to validate, for the Italian context, the Salford-Scott Nursing Values Questionnaire, enhanced by Johnson to explore the nursing profession's values. The Beaton Model was used as well as Valmi's. These models require five phases, with the goal of producing a pre-final version of the instrument for it to then be administered to a sample of the target and expert population. The study was approved by the Council of the Nursing Degree University course of the Modena and Reggio Emilia University, Reggio Emilia site, and the identity of the subjects was protected at every moment of the testing. Face validation was achieved since the clarity percentile for each item was 100%. Content validity was also reached, measured from the content validity index and the scale validity index. The study has confirmed the reliability of the instrument's internal consistence with a value of Cronbach's alpha on 0.95 of total of items. The reliability of the test-retest confirms the stability of the instrument in time (r = 0.908; p = 0.01). The study concludes that the instrument is ready to be administered to the target population, a sample group of nursing students. © The Author(s) 2014.

  9. Spermiogenesis and sperm ultrastructure in Calicotyle affinis Scott, 1911 (Platyhelminthes, Monogenea, Monopisthocotylea, Monocotylidae

    Directory of Open Access Journals (Sweden)

    Bruňanská M.

    2017-12-01

    Full Text Available Spermatological characteristics of Calicotyle affinis Scott, 1911, an endoparasitic monocotylid monogenean from the cloaca of a holocephalan fish Chimaera monstrosa L, have been investigated by means of transmission electron microscopy for the first time. Spermiogenesis exhibits features basically similar to those of the congeneric Calicotyle kroyeri and Calicotyle australiensis, but there are some new findings with respect to the formation and fine structure of the spermatozoon including the remarkable complex end-piece (EP. Morphogenesis of the EP, which is located at the anterior (proximal region of the late spermatid, includes two stages: (1 the centriolar region is continuous with a cytoplasmic mass of the zone of differentiation, the electron-dense surface of the spermatid undergoes significant changes in the sculpturing and the inner core of developing spermatid is electron-lucent; (2 after central fusion of the arching membranes a definitive structure of the EP is subsequently evolved, finally comprising 3 – 4 electron-dense discs attached to a central common electron-lucent column. The EP is considered as a synapomorphy of the genera Calicotyle + Dictyocotyle. The mature spermatozoon of C. affinis comprises the EP, two parallel axonemes of almost equal lengths with the 9 + “1” trepaxonematan pattern, mitochondrion, nucleus, and a reduced number of parallel cortical microtubules (1 – 3. The posterior (distal extremity of the mature spematozoon contains a single tapering axoneme. Ultrastructural characteristics of the mature spermatozoon of C. affinis coincide mostly with those of congeneric C. australiensis. Variations of the spermatological characters within the genus Calicotyle, between Calicotyle and enigmatic Dictyocotyle as well as other monocotylid monogeneans are discussed.

  10. Hedonism And Materialism As Negative Effects Of Social Changes In American Society Potrayed In The Novel This Side Of Paradise Written By F. Scott Fitzgerald

    OpenAIRE

    Elysia, Irene Nyssa

    2015-01-01

    Judul skripsi ini adalah ‘HEDONISM AND MATERIALISM AS NEGATIVE EFFECTS OF SOCIAL CHANGES IN AMERICAN SOCIETY POTRAYED IN THE NOVEL THIS SIDE OF PARADISE WRITTEN BY F. SCOTT FITZGERALD’. Sesuai dengan judulnya, skripsi ini membahas tentang fenomena hedonisme dan materialisme yang terjadi di Amerika pada awal tahun 1920an, sebagai dampak negatif dari Perang Dunia I. Fenomena ini dapat dibuktikan dari gambaran yang dipaparkan oleh Scott melalui novel ini, yaitu tentang kondisi masyarakat terutam...

  11. Chemokines, lymphocytes, and HIV

    Directory of Open Access Journals (Sweden)

    Farber J.M.

    1998-01-01

    Full Text Available Chemokines are members of a family of more than 30 human cytokines whose best-described activities are as chemotactic factors for leukocytes and that are presumed to be important in leukocyte recruitment and trafficking. While many chemokines can act on lymphocytes, the roles of chemokines and their receptors in lymphocyte biology are poorly understood. The recent discoveries that chemokines can suppress infection by HIV-1 and that chemokine receptors serve, along with CD4, as obligate co-receptors for HIV-1 entry have lent urgency to studies on the relationships between chemokines and lymphocytes. My laboratory has characterized Mig and Crg-2/IP-10, chemokines that are induced by IFN-g and that specifically target lymphocytes, particularly activated T cells. We have demonstrated that the genes for these chemokines are widely expressed during experimental infections in mice with protozoan and viral pathogens, but that the patterns of mig and crg-2 expression differed, suggesting non-redundant roles in vivo. Our related studies to identify new chemokine receptors from activated lymphocytes resulted in the cloning of STRL22 and STRL33. We and others have shown that STRL22 is a receptor for the CC chemokine MIP-3a, and STRL22 has been re-named CCR6. Although STRL33 remains an orphan receptor, we have shown that it can function as a co-receptor for HIV-1 envelope glycoproteins, and that it is active with a broader range of HIV-1 envelope glycoproteins than the major co-receptors described to date. The ability of STRL33 to function with a wide variety of envelope glycoproteins may become particularly important if therapies are instituted to block other specific co-receptors. We presume that investigations into the roles of chemokines and their receptors in lymphocyte biology will provide information important for understanding the pathogenesis of AIDS and for manipulating immune and inflammatory responses for clinical benefit

  12. HIV infection and OTC supplements: do they really have an impact?

    African Journals Online (AJOL)

    Repro

    treatment of chronic diseases. HIV infection and OTC supplements: do they really have an impact? ... the pathogenesis of HIV-related disease ... venous glycyrrhizin has been used in Japan to ... ulcers) but this would not have much effect on ...

  13. Cognitive impairment and MRI-findings in patients with HIV on antiretroviral treatment

    NARCIS (Netherlands)

    Su, T.

    2017-01-01

    With combination antiretroviral therapy (cART), human immunodeficiency virus (HIV) associated morbidity and mortality has decreased remarkably. Although life expectancy has increased, the frequently reported milder forms of HIV-associated cognitive impairment remain a concern and its pathogenesis is

  14. Virological Mechanisms in the Coinfection between HIV and HCV

    Directory of Open Access Journals (Sweden)

    Maria Carla Liberto

    2015-01-01

    Full Text Available Due to shared transmission routes, coinfection with Hepatitis C Virus (HCV is common in patients infected by Human Immunodeficiency Virus (HIV. The immune-pathogenesis of liver disease in HIV/HCV coinfected patients is a multifactorial process. Several studies demonstrated that HIV worsens the course of HCV infection, increasing the risk of cirrhosis and hepatocellular carcinoma. Also, HCV might increase immunological defects due to HIV and risk of comorbidities. A specific cross-talk among HIV and HCV proteins in coinfected patients modulates the natural history, the immune responses, and the life cycle of both viruses. These effects are mediated by immune mechanisms and by a cross-talk between the two viruses which could interfere with host defense mechanisms. In this review, we focus on some virological/immunological mechanisms of the pathogenetic interactions between HIV and HCV in the human host.

  15. Purinergic Receptors: Key Mediators of HIV-1 infection and inflammation

    Directory of Open Access Journals (Sweden)

    Talia H Swartz

    2015-11-01

    Full Text Available Human immunodeficiency virus (HIV-1 causes a chronic infection that afflicts more than 38 million individuals worldwide. While the infection can be suppressed with potent anti-retroviral therapies, individuals infected with HIV have elevated levels of inflammation as indicated by increased T cell activation, soluble biomarkers, and associated morbidity and mortality. A single mechanism linking HIV pathogenesis to this inflammation has yet to be identified. Purinergic receptors are known to mediate inflammation and have been shown to be required for HIV-1 infection at the level of HIV-1 membrane fusion. Here we review the literature on the role of purinergic receptors in HIV-1 infection and associated inflammation and describe a role for these receptors as potential therapeutic targets.

  16. HIV Prevention

    Centers for Disease Control (CDC) Podcasts

    2012-02-01

    Dr. Kevin Fenton, Director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, talks about steps people can take to protect their health from HIV.  Created: 2/1/2012 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 2/1/2012.

  17. Animal models of papillomavirus pathogenesis.

    Science.gov (United States)

    Campo, M Saveria

    2002-11-01

    Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less

  18. Trichomonas vaginalis Pathogenesis: a Narrative Review

    Directory of Open Access Journals (Sweden)

    Zahra Arab-Mazar

    2015-07-01

    Full Text Available In the latest articles which were published during 2013-2014, Trichomonas vaginalis (T. vaginalis was mentioned as a neglected sexual transmission disease (STD, while the exact mechanism of its pathogenesis has not been cleared yet. Although trichomonasiasis is easy curable, there is concern that resistance to drug are increasing. This common infection as concerning the important public health implications needs more research to be done for understanding the diagnosis, treatment, immunology and pathogenesis. In this review we searched all valuable and relevant information considering the pathogenesis of T. vaginalis. We referred to the information databases of Medline, PubMed, Scopus and Google scholar. The used keywords were the combinations of T. vaginalis and words associated with pathogenicity. This review discusses the host-parasite interaction and pathogenicity of this parasite.

  19. Pathogenesis Concept Of Extracranial Dissections In Iran

    Directory of Open Access Journals (Sweden)

    Kavian Ghandehari

    2017-02-01

    Full Text Available Background: Dissection of Extracranial Internal Carotid Artery (EICA and Extracranial Vertebral Artery (EVA is an amportant cause of brain infarction with miscellaneous etiologies around the world. Methods: A prospective observational clinical study was conducted in Ghaem Hospital, Mashhad, Iran between 2008-2016. Diagnosis of brain infarction and TIA was made by stroke neurologist. Detection of EICA and EVA dissections were made by performing CT angiography  and MR angiography  or DSA in the suspected patients. Demographic features, clinical manifestations, territorial involvement, pathophysiology and pathogenesis of dissections were assessed in all of the patients. Pathogenesis of dissections was classified as Idiopathic, Trumatic, Postural and Genetic categories. Results: Twenty eight patients (21 males, 7 females were admitted with extracranial arterial dissection. Mean age of males and females with dissection was 39.81± 4.2 and 35.71±6.1 years respectively. Influence of gender on age of the patients was not significant, p>0.05. Among patients with extracranial dissection only 3.6% had atherosclerosis risk factors and 96.4% had no other cause for brain infarction. 100% of extracranial dissections in males occured in carotid territory, while 28.6% of females had dissection in the EVA. The influence of gender in territory of dissection was significant, p<0.05. Idiopathic dissections and genetic susceptibility was found in 10.7% and 3.6% of extracranial dissections respectively. 53.5% of the patienrs had trumatic pathogenesis for extracranial dissections and 32.1% developed dissection due to special neck  postures. Important details in pathophysiology and pathogenesis of extracranial dissections will be presented in the lecture. Conclusion: Stroke patients with extracranial dissections have characteristic demographic and  territorial involvement. Trumatic pathogenesis is the most frequent cause of dissection in Iran followed by neck

  20. Bordetella pertussis pathogenesis: current and future challenges

    Science.gov (United States)

    Melvin, Jeffrey A.; Scheller, Erich V.; Miller, Jeff F.; Cotter, Peggy A.

    2014-01-01

    Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. We also discuss the changing epidemiology of pertussis and the challenges of vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies. PMID:24608338

  1. Scott y Zelda Fitzgerald y el psicoanálisis: la construcción de "Suave es la noche"

    OpenAIRE

    Esteve Díaz, Nuria

    2016-01-01

    Esta tesis aporta una investigación original que pretende analizar la novela Suave es la noche (Tender is the Night, 1934) del escritor norteamericano Francis Scott Key Fitzgerald desde la perspectiva de las humanidades médicas y de manera particular, de las relaciones entre medicina y literatura. En Suave es la noche existen amplias referencias médicas y conceptos psicoanalíticos relacionados con la psiquiatría europea de finales del siglo XIX y comienzos del XX, por lo que cobra especial in...

  2. Possible Mafic Patches in Scott Crater Highlight the Need for Resource Exploration on the Lunar South Polar Region

    Science.gov (United States)

    Cooper, Bonnie L.

    2007-01-01

    Possible areas of mafic material on the rim and floor of Scott crater (82.1 deg S, 48.5 deg E) are suggested by analysis of shadow-masked Clementine false-color-ratio images. Mafic materials common in mare and pyroclastic materials can produce more oxygen than can highlands materials, and mafic materials close to the south pole may be important for propellant production for a future lunar mission. If the dark patches are confirmed as mafic materials, this finding would suggest that other mafic patches may exist, even closer to the poles, which were originally mapped as purely anorthositic.

  3. La diaspora americana in Europa: il caso degli espatriati in Tender is the Night di F. Scott Fitzgerald

    Directory of Open Access Journals (Sweden)

    Elisa A. Pantaleo

    2015-11-01

    Full Text Available From 1921 to 1930, F. Scott Fitzgerald travelled to Europe four times, and he spent almost four years in France and one year in Switzerland. While living abroad in the multicultural environment of Paris and of the French Riviera, his attitude towards Europe underwent a major change. Tender is the Night marks a significant transition from the narrow nationalism of Fitzgerald’s first travel correspondence to an increased sensitivity towards European otherness. The cultural encounter with Europe – that in the novel is rendered through an hybridization of the language and the characters –helped the author to reinterpret his identity in a cosmopolitan perspective.

  4. Aging with HIV-1 Infection: Motor Functions, Cognition, and Attention--A Comparison with Parkinson's Disease.

    Science.gov (United States)

    DeVaughn, S; Müller-Oehring, E M; Markey, B; Brontë-Stewart, H M; Schulte, T

    2015-12-01

    Recent advances in highly active anti-retroviral therapy (HAART) in their various combinations have dramatically increased the life expectancies of HIV-infected persons. People diagnosed with HIV are living beyond the age of 50 but are experiencing the cumulative effects of HIV infection and aging on brain function. In HIV-infected aging individuals, the potential synergy between immunosenescence and HIV viral loads increases susceptibility to HIV-related brain injury and functional brain network degradation similar to that seen in Parkinson's disease (PD), the second most common neurodegenerative disorder in the aging population. Although there are clear diagnostic differences in the primary pathology of both diseases, i.e., death of dopamine-generating cells in the substantia nigra in PD and neuroinflammation in HIV, neurotoxicity to dopaminergic terminals in the basal ganglia (BG) has been implied in the pathogenesis of HIV and neuroinflammation in the pathogenesis of PD. Similar to PD, HIV infection affects structures of the BG, which are part of interconnected circuits including mesocorticolimbic pathways linking brainstem nuclei to BG and cortices subserving attention, cognitive control, and motor functions. The present review discusses the combined effects of aging and neuroinflammation in HIV individuals on cognition and motor function in comparison with age-related neurodegenerative processes in PD. Despite the many challenges, some HIV patients manage to age successfully, most likely by redistribution of neural network resources to enhance function, as occurs in healthy elderly; such compensation could be curtailed by emerging PD.

  5. Altered structural brain changes and neurocognitive performance in pediatric HIV

    Directory of Open Access Journals (Sweden)

    Santosh K. Yadav

    2017-01-01

    Full Text Available Pediatric HIV patients often suffer with neurodevelopmental delay and subsequently cognitive impairment. While tissue injury in cortical and subcortical regions in the brain of adult HIV patients has been well reported there is sparse knowledge about these changes in perinatally HIV infected pediatric patients. We analyzed cortical thickness, subcortical volume, structural connectivity, and neurocognitive functions in pediatric HIV patients and compared with those of pediatric healthy controls. With informed consent, 34 perinatally infected pediatric HIV patients and 32 age and gender matched pediatric healthy controls underwent neurocognitive assessment and brain magnetic resonance imaging (MRI on a 3 T clinical scanner. Altered cortical thickness, subcortical volumes, and abnormal neuropsychological test scores were observed in pediatric HIV patients. The structural network connectivity analysis depicted lower connection strengths, lower clustering coefficients, and higher path length in pediatric HIV patients than healthy controls. The network betweenness and network hubs in cortico-limbic regions were distorted in pediatric HIV patients. The findings suggest that altered cortical and subcortical structures and regional brain connectivity in pediatric HIV patients may contribute to deficits in their neurocognitive functions. Further, longitudinal studies are required for better understanding of the effect of HIV pathogenesis on brain structural changes throughout the brain development process under standard ART treatment.

  6. Thai dental practitioners' knowledge and attitudes regarding patients with HIV.

    Science.gov (United States)

    Rungsiyanont, Sorasun; Lam-Ubol, Aroonwan; Vacharotayangul, Piamkamon; Sappayatosok, Kraisorn

    2013-09-01

    To investigate the knowledge and attitudes of Thai dental practitioners regarding patients with HIV, a cross-sectional study using self-administered questionnaires was conducted. The questionnaires requested demographic information and included questions evaluating the knowledge and attitude of dental practitioners towards HIV. The results were analyzed using Scheffe method for multiple comparisons at the 95 percent confidence level. Out of 1,200 questionnaires sent, 446 questionnaires were returned (response rate 37.2 percent). The subjects included final (sixth)-year dental students (11.9 percent), general dentists (29.1 percent), specialist dentists (15.5 percent), dental hygienists (30.5 percent), and dental assistants (13 percent). More than 80 percent of the dental practitioners correctly answered the questions testing their basic knowledge of HIV such as routes of transmission and common opportunistic infections. However, knowledge about HIV pathogenesis, complications, and advances in HIV management was lacking. Dental hygienists and dental assistants had statistically significant lower scores in knowledge about HIV than other groups. Sixty-seven percent of dental practitioners said they feel worried when treating patients with HIV, and 20.4 percent said they would deny treatment for patients with HIV if possible. While knowledge about HIV may be adequate among dental practitioners in Thailand, greater effort should be put into emphasizing positive attitudes towards patients with HIV.

  7. Latest animal models for anti-HIV drug discovery.

    Science.gov (United States)

    Sliva, Katja

    2015-02-01

    HIV research is limited by the fact that lentiviruses are highly species specific. The need for appropriate models to promote research has led to the development of many elaborate surrogate animal models. This review looks at the history of animal models for HIV research. Although natural animal lentivirus infections and chimeric viruses such as chimera between HIV and simian immunodeficiency virus and simian-tropic HIV are briefly discussed, the main focus is on small animal models, including the complex design of the 'humanized' mouse. The review also traces the historic evolution and milestones as well as depicting current models and future prospects for HIV research. HIV research is a complex and challenging task that is highly manpower-, money- and time-consuming. Besides factors such as hypervariability and latency, the lack of appropriate animal models that exhibit and recapitulate the entire infectious process of HIV, is one of the reasons behind the failure to eliminate the lentivirus from the human population. This obstacle has led to the exploitation and further development of many sophisticated surrogate animal models for HIV research. While there is no animal model that perfectly mirrors and mimics HIV infections in humans, there are a variety of host species and viruses that complement each other. Combining the insights from each model, and critically comparing the results obtained with data from human clinical trials should help expand our understanding of HIV pathogenesis and drive future drug development.

  8. Insights in the pathogenesis of Dobermann hepatitis

    NARCIS (Netherlands)

    Mandigers, Paulus Justinus Johannes

    2005-01-01

    The pathogenesis of Dobermann hepatitis has been under debate for several years. In this thesis two hypotheses were formulated and discussed. Hypothesis 1: In Dobermann dogs exists an autosomal genetic error in metabolism that leads to an abnormal copper metabolism which results in an increased

  9. Pathogenesis of helicobacter pylori infection involves interaction ...

    African Journals Online (AJOL)

    It is now clear that both bacterial virulence factors and host susceptibility play key roles in disease pathogenesis. The nature and levels of these interactions between these major factors has been found to determine the spectrum of clinical outcomes of the infection with this important bacterium. Virulence factors include the ...

  10. Mitochondrial Contribution to Parkinson's Disease Pathogenesis

    Directory of Open Access Journals (Sweden)

    Anthony H. V. Schapira

    2011-01-01

    Full Text Available The identification of the etiologies and pathogenesis of Parkinson's disease (PD should play an important role in enabling the development of novel treatment strategies to prevent or slow the progression of the disease. The last few years have seen enormous progress in this respect. Abnormalities of mitochondrial function and increased free radical mediated damage were described in post mortem PD brain before the first gene mutations causing familial PD were published. Several genetic causes are now known to induce loss of dopaminergic cells and parkinsonism, and study of the mechanisms by which these mutations produce this effect has provided important insights into the pathogenesis of PD and confirmed mitochondrial dysfunction and oxidative stress pathways as central to PD pathogenesis. Abnormalities of protein metabolism including protein mis-folding and aggregation are also crucial to the pathology of PD. Genetic causes of PD have specifically highlighted the importance of mitochondrial dysfunction to PD: PINK1, parkin, DJ-1 and most recently alpha-synuclein proteins have been shown to localise to mitochondria and influence function. The turnover of mitochondria by autophagy (mitophagy has also become a focus of attention. This review summarises recent discoveries in the contribution of mitochondrial abnormalities to PD etiology and pathogenesis.

  11. Frontoethmoidal encephaloceles, a study of their pathogenesis

    NARCIS (Netherlands)

    Hoving, Eelco; Vermeij-Keers, C

    1997-01-01

    A prospective clinical study of 30 patients with frontoethmoidal encephaloceles was performed in order to find support for a proposed theory concerning its pathogenesis, based on a previously performed embryological study and relevant findings in the literature. According to this proposed theory the

  12. Immunological pathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Seung Hoon Lee

    2018-01-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory state of the gastrointestinal tract and can be classified into 2 main clinical phenomena: Crohn's disease (CD and ulcerative colitis (UC. The pathogenesis of IBD, including CD and UC, involves the presence of pathogenic factors such as abnormal gut microbiota, immune response dysregulation, environmental changes, and gene variants. Although many investigations have tried to identify novel pathogenic factors associated with IBD that are related to environmental, genetic, microbial, and immune response factors, a full understanding of IBD pathogenesis is unclear. Thus, IBD treatment is far from optimal, and patient outcomes can be unsatisfactory. As result of massive studying on IBD, T helper 17 (Th17 cells and innate lymphoid cells (ILCs are investigated on their effects on IBD. A recent study of the plasticity of Th17 cells focused primarily on colitis. ILCs also emerging as novel cell family, which play a role in the pathogenesis of IBD. IBD immunopathogenesis is key to understanding the causes of IBD and can lead to the development of IBD therapies. The aim of this review is to explain the pathogenesis of IBD, with a focus on immunological factors and therapies.

  13. Pathogenesis of bovine spongiform encephalopathy in sheep

    NARCIS (Netherlands)

    Keulen, van L.J.M.; Vromans, M.E.W.; Dolstra, C.H.; Bossers, A.; Zijderveld, van F.G.

    2008-01-01

    The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrPSc) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrPSc was

  14. Osteonecrosis. Part 1. Risk factors and pathogenesis

    Directory of Open Access Journals (Sweden)

    Ekaterina Valeriyevna Ilyinykh

    2013-01-01

    Full Text Available The paper considers different risk factors for osteonecrosis (ON and some aspects of its pathogenesis: impairments in the differentiation of stromal cells, the vascular provision of intraand extravasal genesis, the quality of proper bone tissue due to generalized or local osteoporosis, intravascular coagulation factors contributing to microthrombogenesis. The basic types of ON are identified.

  15. Tryptophan-induced pathogenesis of breast cancer

    African Journals Online (AJOL)

    Aims: To investigate the pathogenesis of breast cancer through targeted metabolomics of amino acids ... Furthermore, the biological function of tryptophan was determined through determining the influence ... profiling all the small molecules in the biosamples (e.g., .... is a promising therapeutic agent for pancreatic cancer7.

  16. HIV/AIDS Coinfection

    Science.gov (United States)

    ... Coinfection Hepatitis C Coinfection HIV/AIDS Coinfection HIV/AIDS Coinfection Approximately 10% of the HIV-infected population ... Control and Prevention website to learn about HIV/AIDS and Viral Hepatitis guidelines and resources. Home About ...

  17. HIV/AIDS

    Science.gov (United States)

    HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV most ...

  18. HIV and Immunizations

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV and Immunizations Last Reviewed: February 6, 2018 Key ...

  19. HIV Medication Adherence

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV Medication Adherence Last Reviewed: January 17, 2018 Key ...

  20. HIV and AIDS

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español HIV and AIDS KidsHealth / For Kids / HIV and AIDS ... actually the virus that causes the disease AIDS. HIV Hurts the Immune System People who are HIV ...

  1. HIV Treatment: The Basics

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV Treatment Home Understanding HIV/AIDS Fact Sheets HIV ... 4 p.m. ET) Send us an email HIV Treatment: The Basics Last Reviewed: March 22, 2018 ...

  2. HIV and Pregnancy

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG HIV and Pregnancy Home For Patients Search FAQs HIV ... HIV and Pregnancy FAQ113, July 2017 PDF Format HIV and Pregnancy Pregnancy What is human immunodeficiency virus ( ...

  3. HIV and Cardiovascular Disease

    Science.gov (United States)

    ... Select a Language: Fact Sheet 652 HIV and Cardiovascular Disease HIV AND CARDIOVASCULAR DISEASE WHY SHOULD PEOPLE WITH HIV CARE ABOUT CVD? ... OF CVD? WHAT ABOUT CHANGING MEDICATIONS? HIV AND CARDIOVASCULAR DISEASE Cardiovascular disease (CVD) includes a group of problems ...

  4. Hepatitis E: Molecular Virology and Pathogenesis

    Science.gov (United States)

    Panda, Subrat K.; Varma, Satya P.K.

    2013-01-01

    Hepatitis E virus is a single, positive-sense, capped and poly A tailed RNA virus classified under the family Hepeviridae. Enteric transmission, acute self-limiting hepatitis, frequent epidemic and sporadic occurrence, high mortality in affected pregnants are hallmarks of hepatitis E infection. Lack of an efficient culture system and resulting reductionist approaches for the study of replication and pathogenesis of HEV made it to be a less understood agent. Early studies on animal models, sub-genomic expression of open reading frames (ORF) and infectious cDNA clones have helped in elucidating the genome organization, important stages in HEV replication and pathogenesis. The genome contains three ORF's and three untranslated regions (UTR). The 5′ distal ORF, ORF1 is translated by host ribosomes in a cap dependent manner to form the non-structural polyprotein including the viral replicase. HEV replicates via a negative-sense RNA intermediate which helps in the formation of the positive-sense genomic RNA and a single bi-cistronic sub-genomic RNA. The 3′ distal ORF's including the major structural protein pORF2 and the multifunctional host interacting protein pORF3 are translated from the sub-genomic RNA. Pathogenesis in HEV infections is not well articulated, and remains a concern due to the many aspects like host dependent and genotype specific variations. Animal HEV, zoonosis, chronicity in immunosuppressed patients, and rapid decompensation in affected chronic liver diseased patients warrants detailed investigation of the underlying pathogenesis. Recent advances about structure, entry, egress and functional characterization of ORF1 domains has furthered our understanding about HEV. This article is an effort to review our present understanding about molecular biology and pathogenesis of HEV. PMID:25755485

  5. Dynamics of the Davydov–Scott soliton with location or velocity mismatch of its high-frequency component

    Energy Technology Data Exchange (ETDEWEB)

    Blyakhman, L.G.; Gromov, E.M.; Onosova, I.V.; Tyutin, V.V., E-mail: vtyutin@hse.ru

    2017-05-03

    The dynamics of a two-component Davydov–Scott (DS) soliton with a small mismatch of the initial location or velocity of the high-frequency (HF) component was investigated within the framework of the Zakharov-type system of two coupled equations for the HF and low-frequency (LF) fields. In this system, the HF field is described by the linear Schrödinger equation with the potential generated by the LF component varying in time and space. The LF component in this system is described by the Korteweg–de Vries equation with a term of quadratic influence of the HF field on the LF field. The frequency of the DS soliton's component oscillation was found analytically using the balance equation. The perturbed DS soliton was shown to be stable. The analytical results were confirmed by numerical simulations. - Highlights: • The dynamics of the Davydov–Scott soliton with initial location or velocity mismatch of the HF component was investigated. • The study was performed within the framework of coupled linear Schrödinger and KdV equations for the HF and LF fields. • Analytical and numerical approaches were used. • The frequency of the DS soliton component oscillation was found. • Stability of the perturbed DS solitons was demonstrated.

  6. Adapting Scott and Bruce's General Decision-Making Style Inventory to Patient Decision Making in Provider Choice.

    Science.gov (United States)

    Fischer, Sophia; Soyez, Katja; Gurtner, Sebastian

    2015-05-01

    Research testing the concept of decision-making styles in specific contexts such as health care-related choices is missing. Therefore, we examine the contextuality of Scott and Bruce's (1995) General Decision-Making Style Inventory with respect to patient choice situations. Scott and Bruce's scale was adapted for use as a patient decision-making style inventory. In total, 388 German patients who underwent elective joint surgery responded to a questionnaire about their provider choice. Confirmatory factor analyses within 2 independent samples assessed factorial structure, reliability, and validity of the scale. The final 4-dimensional, 13-item patient decision-making style inventory showed satisfactory psychometric properties. Data analyses supported reliability and construct validity. Besides the intuitive, dependent, and avoidant style, a new subdimension, called "comparative" decision-making style, emerged that originated from the rational dimension of the general model. This research provides evidence for the contextuality of decision-making style to specific choice situations. Using a limited set of indicators, this report proposes the patient decision-making style inventory as valid and feasible tool to assess patients' decision propensities. © The Author(s) 2015.

  7. Environmental Assessment of the Gering-Stegall 115-kV Transmission Line Consolidation Project, Scotts Bluff County, Nebraska

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-05-01

    The Department of Energy (DOE), Western Area Power Administration (Western) proposes to consolidate segments of two transmission lines near the Gering Substation in Gering, Nebraska. The transmission lines are both located in Scotts Bluff County, Nebraska. The transmission lines are both located in Scotts Bluff County, Nebraska, within the city of Gering. Presently, there are three parallel 115-kilovolt (kV) transmission lines on separate rights-of-way (ROW) that terminate at the Gering Substation. The project would include dismantling the Archer-Gering wood-pole transmission line and rebuilding the remaining two lines on single-pole steel double circuit structures. The project would consolidate the Gering-Stegall North and Gering-Stegall South 115-kV transmission lines on to one ROW for a 1.33-mile segment between the Gering Substation and a point west of the Gering Landfill. All existing wood-pole H-frame structures would be removed, and the Gering-Stegall North and South ROWs abandoned. Western is responsible for the design, construction, operation, and maintenance of the line. Western prepared an environmental assessment (EA) that analyzed the potential environmental impacts of the proposed construction, operation, and maintenance of the 115-kV transmission line consolidation. Based on the analyses in the EA, the DOE finds that the proposed action is not a major Federal action significantly affecting the quality of the human environment, within the meaning of the National Environmental Policy Act of 1969 (NEPA).

  8. Environmental Assessment of the Gering-Stegall 115-kV Transmission Line Consolidation Project, Scotts Bluff County, Nebraska

    International Nuclear Information System (INIS)

    1995-05-01

    The Department of Energy (DOE), Western Area Power Administration (Western) proposes to consolidate segments of two transmission lines near the Gering Substation in Gering, Nebraska. The transmission lines are both located in Scotts Bluff County, Nebraska. The transmission lines are both located in Scotts Bluff County, Nebraska, within the city of Gering. Presently, there are three parallel 115-kilovolt (kV) transmission lines on separate rights-of-way (ROW) that terminate at the Gering Substation. The project would include dismantling the Archer-Gering wood-pole transmission line and rebuilding the remaining two lines on single-pole steel double circuit structures. The project would consolidate the Gering-Stegall North and Gering-Stegall South 115-kV transmission lines on to one ROW for a 1.33-mile segment between the Gering Substation and a point west of the Gering Landfill. All existing wood-pole H-frame structures would be removed, and the Gering-Stegall North and South ROWs abandoned. Western is responsible for the design, construction, operation, and maintenance of the line. Western prepared an environmental assessment (EA) that analyzed the potential environmental impacts of the proposed construction, operation, and maintenance of the 115-kV transmission line consolidation. Based on the analyses in the EA, the DOE finds that the proposed action is not a major Federal action significantly affecting the quality of the human environment, within the meaning of the National Environmental Policy Act of 1969 (NEPA)

  9. HIV/AIDS - Multiple Languages

    Science.gov (United States)

    ... HIV - Newly diagnosed with HIV, part 5 - English MP3 Children and HIV - Newly diagnosed with HIV, part 5 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 Children and HIV - Newly diagnosed with HIV, part ...

  10. Basic HIV/AIDS Statistics

    Science.gov (United States)

    ... HIV Syndicated Content Website Feedback HIV/AIDS Basic Statistics Recommend on Facebook Tweet Share Compartir HIV and ... HIV. Interested in learning more about CDC's HIV statistics? Terms, Definitions, and Calculations Used in CDC HIV ...

  11. Innate immune recognition and activation during HIV infection

    Directory of Open Access Journals (Sweden)

    Larsen Carsten S

    2010-06-01

    Full Text Available Abstract The pathogenesis of HIV infection, and in particular the development of immunodeficiency, remains incompletely understood. Whichever intricate molecular mechanisms are at play between HIV and the host, it is evident that the organism is incapable of restricting and eradicating the invading pathogen. Both innate and adaptive immune responses are raised, but they appear to be insufficient or too late to eliminate the virus. Moreover, the picture is complicated by the fact that the very same cells and responses aimed at eliminating the virus seem to play deleterious roles by driving ongoing immune activation and progressive immunodeficiency. Whereas much knowledge exists on the role of adaptive immunity during HIV infection, it has only recently been appreciated that the innate immune response also plays an important part in HIV pathogenesis. In this review, we present current knowledge on innate immune recognition and activation during HIV infection based on studies in cell culture, non-human primates, and HIV-infected individuals, and discuss the implications for the understanding of HIV immunopathogenesis.

  12. Living with HIV

    Science.gov (United States)

    ... Abroad Treatment Basic Statistics Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Syndicated Content Website Feedback HIV/AIDS Living With HIV Language: English (US) Español (Spanish) Recommend on Facebook ...

  13. HIV Risk and Prevention

    Science.gov (United States)

    ... Prevention VIH En Español Get Tested Find an HIV testing site near you. Enter ZIP code or city Follow HIV/AIDS CDC HIV CDC HIV/AIDS See RSS | ... Email Updates on HIV Syndicated Content Website Feedback HIV Risk and Prevention Recommend on Facebook Tweet Share ...

  14. Glycosylation in HIV-1 envelope glycoprotein and its biological implications

    KAUST Repository

    Ho, Yung Shwen

    2013-08-01

    Glycosylation of HIV-1 envelope proteins (Env gp120/gp41) plays a vital role in viral evasion from the host immune response, which occurs through the masking of key neutralization epitopes and the presentation of the Env glycosylation as \\'self\\' to the host immune system. Env glycosylation is generally conserved, yet its continual evolution plays an important role in modulating viral infectivity and Env immunogenicity. Thus, it is believed that Env glycosylation, which is a vital part of the HIV-1 architecture, also controls intra- and inter-clade genetic variations. Discerning intra- and inter-clade glycosylation variations could therefore yield important information for understanding the molecular and biological differences between HIV clades and may assist in effectively designing Env-based immunogens and in clearly understanding HIV vaccines. This review provides an in-depth perspective of various aspects of Env glycosylation in the context of HIV-1 pathogenesis. © 2013 Future Medicine Ltd.

  15. Role of Endogenous Peptides and Enzymes in the Pathogenesis of ...

    African Journals Online (AJOL)

    1. Michael LS. Relationship between pancreatitis and lung diseases. Respiration Physiology 2001; 128(1): 13–. 16. 2. Scott FG, Yang J, Kathryn B, Krista H, Heather CPK. Epling-Burnette, Yanhua P, James N, Michel MM. Acute Pancreatitis Induces FasL Gene Expression and Apoptosis in the Liver. J Surg Res 2004; 122(2):.

  16. Theories on the Pathogenesis of Endometriosis

    Directory of Open Access Journals (Sweden)

    Samer Sourial

    2014-01-01

    Full Text Available Endometriosis is a common, chronic inflammatory disease defined by the presence of extrauterine endometrial tissue. The aetiology of endometriosis is complex and multifactorial, where several not fully confirmed theories describe its pathogenesis. This review examines existing theories on the initiation and propagation of different types of endometriotic lesions, as well as critically appraises the myriad of biologically relevant evidence that support or oppose each of the proposed theories. The current literature suggests that stem cells, dysfunctional immune response, genetic predisposition, and aberrant peritoneal environment may all be involved in the establishment and propagation of endometriotic lesions. An orchestrated scientific and clinical effort is needed to consider all factors involved in the pathogenesis of this multifaceted disease and to propose novel therapeutic targets to reach effective treatments for this distressing condition.

  17. Helicobacter pylori virulence and cancer pathogenesis.

    Science.gov (United States)

    Yamaoka, Yoshio; Graham, David Y

    2014-06-01

    Helicobacter pylori is human gastric pathogen that causes chronic and progressive gastric mucosal inflammation and is responsible for the gastric inflammation-associated diseases, gastric cancer and peptic ulcer disease. Specific outcomes reflect the interplay between host-, environmental- and bacterial-specific factors. Progress in understanding putative virulence factors in disease pathogenesis has been limited and many false leads have consumed scarce resources. Few in vitro-in vivo correlations or translational applications have proved clinically relevant. Reported virulence factor-related outcomes reflect differences in relative risk of disease rather than specificity for any specific outcome. Studies of individual virulence factor associations have provided conflicting results. Since virulence factors are linked, studies of groups of putative virulence factors are needed to provide clinically useful information. Here, the authors discuss the progress made in understanding the role of H. pylori virulence factors CagA, vacuolating cytotoxin, OipA and DupA in disease pathogenesis and provide suggestions for future studies.

  18. NEW DEVELOPMENTS IN THE PATHOGENESIS OF PREECLAMPSIA

    OpenAIRE

    Naljayan, Mihran V.; Karumanchi, S. Ananth

    2013-01-01

    Preeclampsia affecting 3-5% of all pregnancies is a major cause of maternal and perinatal morbidity and mortality worldwide. This disorder is characterized by a constellation of signs and symptoms, most notably new onset hypertension and proteinuria during the last trimester of pregnancy. In this review, the molecular mechanisms of preeclampsia with an emphasis on the role of circulating anti-angiogenic proteins in the pathogenesis of preeclampsia and its complications will be discussed.

  19. Osmotin, a Pathogenesis-Related Protein

    Czech Academy of Sciences Publication Activity Database

    Viktorová, J.; Krásný, Lukáš; Kamlar, M.; Nováková, M.; Macková, M.; Macek, T.

    2012-01-01

    Roč. 13, č. 7 (2012), s. 672-681 ISSN 1389-2037 Grant - others:GA ČR(CZ) GAP501/11/1654; GA ČR(CZ) GA522/09/1693 Program:GA; GA Institutional support: RVO:61388971 Keywords : osmotin * pathogenesis-related proteins * antifungal activity Subject RIV: CE - Biochemistry Impact factor: 2.326, year: 2012

  20. Mid-Atlantic Microbial Pathogenesis Meeting

    Science.gov (United States)

    2005-12-01

    rheumatic fever, yet little is understood about the regulation of streptococcal genes involved in disease processes and survival in the host. Genome...of brucellosis, a disease that is characterized by abortion and infertility in ruminant animals and undulant fever in humans. In the natural hosts...were presented at this session. 15. SUBJECT TERMS bacteria, pathogenesis, microbiology, virulence, disease 16. SECURITY CLASSIFICATION OF: 17

  1. Patients with discordant responses to antiretroviral therapy have impaired killing of HIV-infected T cells.

    Directory of Open Access Journals (Sweden)

    Sekar Natesampillai

    2010-11-01

    Full Text Available In medicine, understanding the pathophysiologic basis of exceptional circumstances has led to an enhanced understanding of biology. We have studied the circumstance of HIV-infected patients in whom antiretroviral therapy results in immunologic benefit, despite virologic failure. In such patients, two protease mutations, I54V and V82A, occur more frequently. Expressing HIV protease containing these mutations resulted in less cell death, caspase activation, and nuclear fragmentation than wild type (WT HIV protease or HIV protease containing other mutations. The impaired induction of cell death was also associated with impaired cleavage of procaspase 8, a requisite event for HIV protease mediated cell death. Primary CD4 T cells expressing I54V or V82A protease underwent less cell death than with WT or other mutant proteases. Human T cells infected with HIV containing these mutations underwent less cell death and less Casp8p41 production than WT or HIV containing other protease mutations, despite similar degrees of viral replication. The reductions in cell death occurred both within infected cells, as well as in uninfected bystander cells. These data indicate that single point mutations within HIV protease which are selected in vivo can significantly impact the ability of HIV to kill CD4 T cells, while not impacting viral replication. Therefore, HIV protease regulates both HIV replication as well as HIV induced T cell depletion, the hallmark of HIV pathogenesis.

  2. [Anatomy and pathogenesis of diverticular disease].

    Science.gov (United States)

    Wedel, T; Böttner, M

    2014-04-01

    Although diverticular disease is one of the most frequent gastrointestinal disorders the pathogenesis is not yet sufficiently clarified. The aim is to define the anatomy and pathogenesis of diverticular disease considering the risk factors and description of structural and functional alterations of the bowel wall. This article gives an appraisal of the literature, presentation and evaluation of classical etiological factors, analysis and discussion of novel pathogenetic concepts. Colonic diverticulosis is defined as an acquired out-pouching of multiple and initially asymptomatic pseudodiverticula through muscular gaps in the colon wall. Diverticular disease is characterized by diverticular bleeding and/or inflammatory processes (diverticulitis) with corresponding complications (e.g. abscess formation, fistula, covered and open perforation, peritonitis and stenosis). Risk factors for diverticular disease include increasing age, genetic predisposition, congenital connective tissue diseases, low fiber diet, high meat consumption and pronounced overweight. Alterations of connective tissue cause a weakening of preformed exit sites of diverticula and rigidity of the bowel wall with reduced flexibility. It is assumed that intestinal innervation disorders and structural alterations of the musculature induce abnormal contractile patterns with increased intraluminal pressure, thereby promoting the development of diverticula. Moreover, an increased release of pain-mediating neurotransmitters is considered to be responsible for persistent pain in chronic diverticular disease. According to the present data the pathogenesis of diverticular disease cannot be attributed to a single factor but should be considered as a multifactorial event.

  3. Modern concepts of pathogenesis of ichthyosis

    Directory of Open Access Journals (Sweden)

    Світлана Володимирівна Дмитренко

    2015-06-01

    Full Text Available The modern concepts of ichthyosis are rather ambiguous and need more precise definition. The modern conception of pathogenesis of ichthysosis is offered and considered in this article.Aim. An aim is to analyze received data of our researches about molecular disturbances of keratin on the background of ichthyosis and the current data on the pathogenesis of disease.Materials and methods. An analysis of the results of research in 70 patients with ichthyosis by the methods of the flow cytometry, immunohistochemistry and by immunologic methods is presented in an article.Results. Authors revealed molecular, immunologic and immunohistochemical changes that realizes the disturbance of keratinization on the background of this disease. The model of pathogenesis of the various manifestations of gene mutations that causes ichthyosis is proposed and it can be taken into account when elaborating the new directions of therapy.Conclusions. Gene mutations that cause ichthyosis realizes on the background of disturbance of the cell cycle causing cornification and disturb the local and general immune reactions that summarily lead to the clinical presentations of disease. 

  4. HIV Vaccine for Prevention and Cure, A Mission Possible.

    Science.gov (United States)

    Lu, Da-Yong; Wu, Hong-Ying; Ding, Jian; Sastry, Nagendra; Lu, Ting-Ren

    2016-01-01

    HIV/AIDS was once a highly deadly infective disease that killed the global people of a million annually two decades ago. While we are enjoying the HIV therapeutic advances (mostly important from HAART invention), one obvious drawback is still unresolved-unable to clearance all HIV from infected human bodies. As a result, a series of different therapeutic attempts have been proposed based on present knowledge of different features of HIV-induced pathogenesis and human mortalities. Facing this shortcoming, innovative designs and update of HIV vaccines and other types of HIV therapeutic inventions can be a final solution for completely HIV clearance and infection managements in human beings. Owing to these scientific and medical significances, several experimental and clinical attempts have to be made. Among these attempts, part of them (updating HIV vaccine developments and clinical routines) are quite promising and noteworthy. In this article, we offer the general information of this attempt and discuss it separately, especially on the respects of HIV vaccine strategic innovations.

  5. From wasting to obesity, changes in nutritional concerns in HIV/AIDS.

    Science.gov (United States)

    Mankal, Pavan K; Kotler, Donald P

    2014-09-01

    Optimal nutrition is an important part of human immunodeficiency virus (HIV) care; to support the immune system, limit HIV-associated complications as well as maintain better quality of life and survival. The presentation and nature of malnutrition in patients with HIV has changed dramatically over the past 30 years from predominantly a wasting syndrome to lipodystrophy and, now, frailty. Nevertheless, we continue to see all 3 presentations in patient care today. The pathogenesis of poor nutrition in HIV-infected patients depends on caloric intake, intestinal nutrient absorption/translocation, and resting energy expenditure, which are features seen in all chronic diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Oxidized lipoproteins are associated with markers of inflammation and immune activation in HIV-1 infection

    Science.gov (United States)

    Kelesidis, T; Jackson, N; McComsey, GA; Wang, X; Elashoff, D; Dube, MP; Brown, TT; Yang, OO; Stein, JH; Currier, JS

    2016-01-01

    Objective The pathogenesis of immune dysfunction in chronic HIV-1 infection is unclear, and a potential role for oxidized lipids has been suggested. We hypothesize that both oxidized low- and high-density lipoproteins (HDLox, LDLox) contribute to HIV-1 related immune dysfunction. Study In the AIDS Clinical Trials Group (ACTG) A5260, 234 HIV-infected antiretroviral therapy (ART)-naïve participants were randomized to receive tenofovir-emtricitabine plus protease inhibitors or raltegravir and had HIV-1 RNA lipoproteins may contribute to persistent immune activation on ART. PMID:27603288

  7. PORTER S FIVE FORCES MODEL SCOTT MORTON S FIVE FORCES MODEL BAKOS TREACY MODEL ANALYZES STRATEGIC INFORMATION SYSTEMS MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Indra Gamayanto

    2004-01-01

    Full Text Available Wollongong City Council (WCC is one of the most progressive and innovative local government organizations in Australia. Wollongong City Council use Information Technology to gain the competitive advantage and to face a global economy in the future. Porter's Five Force model is one of the models that can be using at Wollongong City Council because porter's five Forces model has strength in relationship between buyer and suppliers (Bargaining power of suppliers and bargaining power of buyers. Other model such as Scott Morton's Five Forces model has strength to analyze the social impact factor, so to gain competitive advantage in the future and have a good IT/IS strategic planning; this model can be use also. Bakos & Treacy model almost the same as Porter's model but Bakos & Treacy model can also be applying into Wollongong City Council to improve the capability in Transforming organization, efficiency, and effectiveness.

  8. Absence of a Scott correction for the total binding energy of noninteracting fermions in a smooth potential well

    International Nuclear Information System (INIS)

    Huxtable, B.D.

    1988-01-01

    It is shown, for V in a particular class of smooth functions, that the total binding energy, E(Z), of Z noninteracting Fermions in the potential well Z 4/3 V(Z 1/3 X) obeys E(Z) = c TF (V)Z 7/3 + O(Z 5/3 ) as Z → ∞. Here c TF (V) is the coefficient predicted by Thomas-Fermi theory. This result is consistent with the conjectured Scott correction, which occurs at order Z 2 , to the total binding energy of an atomic number Z. This correction is thought to arise only because V(x)∼ - |x| -1 near x = 0 in the atomic problem, and so V is not a smooth function

  9. Transcriptome analysis of monocyte-HIV interactions

    Directory of Open Access Journals (Sweden)

    Tran Huyen

    2010-06-01

    Full Text Available Abstract Background During HIV infection and/or antiretroviral therapy (ART, monocytes and macrophages exhibit a wide range of dysfunctions which contribute significantly to HIV pathogenesis and therapy-associated complications. Nevertheless, the molecular components which contribute to these dysfunctions remain elusive. We therefore applied a parallel approach of genome-wide microarray analysis and focused gene expression profiling on monocytes from patients in different stages of HIV infection and/or ART to further characterise these dysfunctions. Results Processes involved in apoptosis, cell cycle, lipid metabolism, proteasome function, protein trafficking and transcriptional regulation were identified as areas of monocyte dysfunction during HIV infection. Individual genes potentially contributing to these monocyte dysfunctions included several novel factors. One of these is the adipocytokine NAMPT/visfatin, which we show to be capable of inhibiting HIV at an early step in its life cycle. Roughly half of all genes identified were restored to control levels under ART, while the others represented a persistent dysregulation. Additionally, several candidate biomarkers (in particular CCL1 and CYP2C19 for the development of the abacavir hypersensitivity reaction were suggested. Conclusions Previously described areas of monocyte dysfunction during HIV infection were confirmed, and novel themes were identified. Furthermore, individual genes associated with these dysfunctions and with ART-associated disorders were pinpointed. These genes form a useful basis for further functional studies concerning the contribution of monocytes/macrophages to HIV pathogenesis. One such gene, NAMPT/visfatin, represents a possible novel restriction factor for HIV. Background Both macrophages and T lymphocyte subsets express the CD4 receptor and either the CXCR4 and/or the CCR5 coreceptor which confer susceptibility to infection with the Human Immunodeficiency Virus

  10. A análise de redes na sociologia e nos estudos sobre grupos econômicos: entrevista com John Scott

    Directory of Open Access Journals (Sweden)

    Rodolfo Palazzo Dias

    2017-07-01

    Full Text Available Com o objetivo de tornar mais acessível ao público brasileiro a área de Análise de Redes Sociais (ARS, Em Tese realizou uma entrevista com Jonh Scott, renomado autor dessa área.

  11. Runoff Variability in the Scott River (SW Spitsbergen in Summer Seasons 2012–2013 in Comparison with the Period 1986–2009

    Directory of Open Access Journals (Sweden)

    Franczak Łukasz

    2016-09-01

    Full Text Available River runoff variability in the Scott River catchment in the summer seasons 2012 and 2013 has been presented in comparison to the multiannual river runoff in 1986–2009. Both in particular seasons and in the analysed multiannual, high variability of discharge rate was recorded. In the research periods 2012–2013, a total of 11 952 water stages and 20 flow rates were measured in the analysed cross-section for the determination of 83 daylong discharges. The mean multiannual discharge of the Scott River amounted to 0.96 m3·s−1. The value corresponds to a specific runoff of 94.6 dm3·s−1·km2, and the runoff layer 937 mm. The maximum values of daily discharge amounted to 5.07 m3·s−1, and the minimum values to 0.002 m3·s−1. The highest runoff occurs in the second and third decade of July, and in the first and second decade of August. The regime of the river is determined by a group of factors, and particularly meteorological conditions affecting the intensity of ablation, and consequently river runoff volume. We found a significant correlation (0.60 in 2012 and 0.67 in 2013 between the air temperature and the Scott River discharge related to the Scott Glacier ice melt.

  12. The Third Turn toward the Social: Nancy Welch's "Living Room," Tony Scott's "Dangerous Writing," and Rhetoric and Composition's Turn toward Grassroots Political Activism

    Science.gov (United States)

    Kinney, Kelly; Girshin, Thomas; Bowlin, Barrett

    2013-01-01

    This review essay examines recent texts by Nancy Welch and Tony Scott, both of which use embodied activism as a starting point for their inquiries. Taken together, these works point to a distinct shift in composition studies' turn toward the social, one that calls on workers both within and outside the academy to actively engage in grassroots…

  13. In vitro modeling of HIV proviral activity in microglia.

    Science.gov (United States)

    Campbell, Lee A; Richie, Christopher T; Zhang, Yajun; Heathward, Emily J; Coke, Lamarque M; Park, Emily Y; Harvey, Brandon K

    2017-12-01

    Microglia, the resident macrophages of the brain, play a key role in the pathogenesis of HIV-associated neurocognitive disorders (HAND) due to their productive infection by HIV. This results in the release of neurotoxic viral proteins and pro-inflammatory compounds which negatively affect the functionality of surrounding neurons. Because models of HIV infection within the brain are limited, we aimed to create a novel microglia cell line with an integrated HIV provirus capable of recreating several hallmarks of HIV infection. We utilized clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing technology and integrated a modified HIV provirus into CHME-5 immortalized microglia to create HIV-NanoLuc CHME-5. In the modified provirus, the Gag-Pol region is replaced with the coding region for NanoLuciferase (NanoLuc), which allows for the rapid assay of HIV long terminal repeat activity using a luminescent substrate, while still containing the necessary genetic material to produce established neurotoxic viral proteins (e.g. tat, nef, gp120). We confirmed that HIV-NanoLuc CHME-5 microglia express NanoLuc, along with the HIV viral protein Nef. We subsequently exposed these cells to a battery of experiments to modulate the activity of the provirus. Proviral activity was enhanced by treating the cells with pro-inflammatory factors lipopolysaccharide (LPS) and tumor necrosis factor alpha and by overexpressing the viral regulatory protein Tat. Conversely, genetic modification of the toll-like receptor-4 gene by CRISPR/Cas9 reduced LPS-mediated proviral activation, and pharmacological application of NF-κB inhibitor sulfasalazine similarly diminished proviral activity. Overall, these data suggest that HIV-NanoLuc CHME-5 may be a useful tool in the study of HIV-mediated neuropathology and proviral regulation. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  14. Pathogenesis of Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    A. M. Golubev

    2012-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS is a common complication of many diseases. Its polyetiological pattern determines the specific features of lung morphological changes and the clinical course of ARDS. Objective: to analyze the pathogenesis of ARDS in the context of the general pathological processes underlying its development. Material and methods. More than 200 lungs from the people who had died from severe concomitant injury or ARDS-complicated pneumonia were investigated. More than 150 rat experiments simulated various types of lung injury: ventilator-induced lung injury with different ventilation parameters; reperfusion injuries (systemic circulation blockade due to 12-minute vascular fascicle ligation, followed by the recovery of cardiac performance and breathing; microcirculatory disorder (injection of a thromboplastin solution into the jugular vein; blood loss; betaine-pepsin aspiration; and closed chest injury. Different parts of the right and left lungs were histologically examined 1 and 3 hours and 1 and 3 days after initiation of the experiment. Lung pieces were fixed in 10% neutral formalin solution and embedded in paraffin. Histological sections were stained with hematoxylin and eosin and using the van Gieson and Weigert procedures; the Schiff test was used. Results. The influence of aggression factors (trauma, blood loss, aspiration, infection, etc. results in damage to the lung and particularly air-blood barrier structures (endothelium, alveolar epithelium, their basement membrane. In turn the alteration of cellular and extracellular structures is followed by the increased permeability of hemomicrocirculatory bed vessels, leading to the development of non-cardiogenic (interstitial, alveolar pulmonary edema that is a central component in the pathogenesis of ARDS. Conclusion. The diagnosis of the early manifestations of ARDS must account for the nature of an aggression factor, the signs confirming the alteration of the lung

  15. Get Tested for HIV

    Science.gov (United States)

    ... AIDS: What is HIV/AIDS? Women and HIV/AIDS Next section ... Tested? Why do I need to get tested for HIV? The only way to know if you have HIV is to get tested. Many people with HIV don’t have any symptoms. In the United States, about 1 in 7 ...

  16. Physiology and pathogenesis of gastroesophageal reflux disease.

    Science.gov (United States)

    Mikami, Dean J; Murayama, Kenric M

    2015-06-01

    Gastroesophageal reflux disease (GERD) is one of the most common problems treated by primary care physicians. Almost 20% of the population in the United States experiences occasional regurgitation, heartburn, or retrosternal pain because of GERD. Reflux disease is complex, and the physiology and pathogenesis are still incompletely understood. However, abnormalities of any one or a combination of the three physiologic processes, namely, esophageal motility, lower esophageal sphincter function, and gastric motility or emptying, can lead to GERD. There are many diagnostic and therapeutic approaches to GERD today, but more studies are needed to better understand this complex disease process. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Pathogenesis and treatment of diabetic glomerulopathy

    International Nuclear Information System (INIS)

    Marre, M.; Le Jeune, J.J.

    1995-01-01

    Diabetic glomerulopathy is the consequence, at the glomerular level, of diabetes. Diagnosis is based on the association of proteinuria, arterial hypertension and an early reduction of glomerular filtration in a diabetic patient, generally insulin-dependent. Diabetic glomerulopathy is a complication of type I diabetes, which begins in childhood or adolescence, but can also be discovered in type II diabetes. A definite diagnosis requires histological evidences ; glomerular clearance measurements ( 125 I-iodothalamate or 51 Cr-EDTA) yield important information concerning glomerular filtration. The authors subsequently address pathogenesis and therapeutic regimens, and they report on the particularities of this condition in type II diabetes. (authors). 30 refs., 2 tabs

  18. Molecular pathogenesis and mechanisms of thyroid cancer

    Science.gov (United States)

    Xing, Mingzhao

    2013-01-01

    Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. PMID:23429735

  19. Polycystic Kidney Disease: Pathogenesis and Potential Therapies

    Science.gov (United States)

    Takiar, Vinita; Caplan, Michael J.

    2011-01-01

    Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent, inherited condition for which there is currently no effective specific clinical therapy. The disease is characterized by the progressive development of fluid-filled cysts derived from renal tubular epithelial cells which gradually compress the parenchyma and compromise renal function. Current interests in the field focus on understanding and exploiting signaling mechanisms underlying disease pathogenesis as well as delineating the role of the primary cilium in cystogenesis. This review highlights the pathogenetic pathways underlying renal cyst formation as well as novel therapeutic targets for the treatment of PKD. PMID:21146605

  20. Urinary Tract Infection: Pathogenesis and Outlook.

    Science.gov (United States)

    McLellan, Lisa K; Hunstad, David A

    2016-11-01

    The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Urinary Tract Infection: Pathogenesis and Outlook

    Science.gov (United States)

    McLellan, Lisa K.; Hunstad, David A.

    2016-01-01

    The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities. PMID:27692880

  2. The pathogenesis of Ebola hemorrhagic fever.

    Science.gov (United States)

    Takada, A; Kawaoka, Y

    2001-10-01

    Ebola virus causes lethal hemorrhagic disease in humans, yet there are still no satisfactory biological explanations to account for its extreme virulence. This review focuses on recent findings relevant to understanding the pathogenesis of Ebola virus infection and developing vaccines and effective therapy. The available data suggest that the envelope glycoprotein and the interaction of some viral proteins with the immune system are likely to play important roles in the extraordinary pathogenicity of this virus. There are also indications that genetically engineered vaccines, including plasmid DNA and viral vectors expressing Ebola virus proteins, and passive transfer of neutralizing antibodies could be feasible options for the control of Ebola virus-associated disease.

  3. The Role of the spv Genes in Salmonella Pathogenesis

    Directory of Open Access Journals (Sweden)

    Donald G. Guiney

    2011-06-01

    Full Text Available Salmonella strains cause three main types of diseases in people: gastroenteritis, enteric (typhoid fever, and non-typhoid extra-intestinal disease with bacteremia. Genetic analysis indicates that each clinical syndrome requires distinct sets of virulence genes, and Salmonella isolates differ in their constellation of virulence traits. The spv locus is strongly associated with strains that cause non-typhoid bacteremia, but are not present in typhoid strains. The spv region contains three genes required for the virulence phenotype in mice: the positive transcriptional regulator spvR and two structural genes spvB and spvC. SpvB and SpvC are translocated into the host cell by the SPI-2 type-three secretion system. SpvB prevents actin polymerization by ADP-ribosylation of actin monomers, while SpvC has phosphothreonine lyase activity and has been shown to inhibit MAP kinase signaling. The exact mechanisms by which SpvB and SpvC act in concert to enhance virulence are still unclear. SpvB exhibits a cytotoxic effect on host cells and is required for delayed cell death by apoptosis following intracellular infection. Strains isolated from systemic infections of immune compromised patients, particularly HIV patients, usually carry the spv locus, strongly suggesting that CD4 T cells are required to control disease due to Salmonella that are spv positive. This association is not seen with typhoid fever, indicating that the pathogenesis and immunology of typhoid have fundamental differences from the syndrome of non-typhoid bacteremia.

  4. Creatine protects against mitochondrial dysfunction associated with HIV-1 Tat-induced neuronal injury

    Science.gov (United States)

    Stevens, Patrick R.; Gawryluk, Jeremy W.; Hui, Liang; Chen, Xuesong; Geiger, Jonathan D.

    2015-01-01

    HIV-1 infected individuals are living longer but experiencing a prevalence rate of over 50% for HIV-1 associated neurocognitive disorders (HAND) for which no effective treatment is available. Viral and cellular factors secreted by HIV-1 infected cells leads to neuronal injury and HIV-1 Tat continues to be implicated in the pathogenesis of HAND. Here we tested the hypothesis that creatine protected against HIV-1 Tat-induced neuronal injury by preventing mitochondrial bioenergetic crisis and/or redox catastrophe. Creatine blocked HIV-1 Tat1-72-induced increases in neuron cell death and synaptic area loss. Creatine protected against HIV-1 Tat-induced decreases in ATP. Creatine and creatine plus HIV-1 Tat increased cellular levels of creatine, and creatine plus HIV-1 Tat further decreased ratios of phosphocreatine to creatine observed with creatine or HIV-1 Tat treatments alone. Additionally, creatine protected against HIV-1 Tat-induced mitochondrial hypopolarization and HIV-1 Tat-induced mitochondrial permeability transition pore opening. Thus, creatine may be a useful adjunctive therapy against HAND. PMID:25613139

  5. Understanding HIV infection for the design of a therapeutic vaccine. Part II: Vaccination strategies for HIV.

    Science.gov (United States)

    de Goede, A L; Vulto, A G; Osterhaus, A D M E; Gruters, R A

    2015-05-01

    HIV infection leads to a gradual loss CD4(+) T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive lifelong adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore, there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies. Copyright © 2014. Published by Elsevier Masson SAS.

  6. The effect of HIV infection and HCV viremia on inflammatory mediators and hepatic injury-The Women's Interagency HIV Study.

    Directory of Open Access Journals (Sweden)

    Sheila M Keating

    Full Text Available Hepatitis C virus infection induces inflammation and while it is believed that HIV co-infection enhances this response, HIV control may reduce inflammation and liver fibrosis in resolved or viremic HCV infection. Measurement of systemic biomarkers in co-infection could help define the mechanism of inflammation on fibrosis and determine if HIV control reduces liver pathology. A nested case-control study was performed to explore the relationship of systemic biomarkers of inflammation with liver fibrosis in HCV viremic and/or seropositive women with and without HIV infection. Serum cytokines, chemokines, growth factors and cell adhesion molecules were measured in HIV uninfected (HIV-, n = 18, ART-treated HIV-controlled (ARTc, n = 20, uncontrolled on anti-retroviral therapy (ARTuc, n = 21 and elite HIV controllers (Elite, n = 20. All were HCV seroreactive and had either resolved (HCV RNA-; <50IU/mL or had chronic HCV infection (HCV RNA+. In HCV and HIV groups, aspartate aminotransferase to platelet ratio (APRI was measured and compared to serum cytokines, chemokines, growth factors and cell adhesion molecules. APRI correlated with sVCAM, sICAM, IL-10, and IP-10 levels and inversely correlated with EGF, IL-17, TGF-α and MMP-9 levels. Collectively, all HCV RNA+ subjects had higher sVCAM, sICAM and IP-10 compared to HCV RNA-. In the ART-treated HCV RNA+ groups, TNF-α, GRO, IP-10, MCP-1 and MDC were higher than HIV-, Elite or both. In ARTuc, FGF-2, MPO, soluble E-selectin, MMP-9, IL-17, GM-CSF and TGF-α are lower than HIV-, Elite or both. Differential expression of soluble markers may reveal mechanisms of pathogenesis or possibly reduction of fibrosis in HCV/HIV co-infection.

  7. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids- ... HIV, STD, and TB Prevention. About HIV/AIDS. ( https://www.cdc.gov/actagainstaids/basics/whatishiv.html ). Atlanta, ...

  8. Retroviruses As Myeloid Cell Riders: What Natural Human Siglec-1 “Knockouts” Tell Us About Pathogenesis

    Directory of Open Access Journals (Sweden)

    Javier Martinez-Picado

    2017-11-01

    Full Text Available Myeloid cells initiate immune responses and are crucial to control infections. In the case of retroviruses, however, myeloid cells also promote pathogenesis by enabling viral dissemination; a process extensively studied in vitro using human immunodeficiency virus type 1 (HIV-1. This viral hijacking mechanism does not rely on productive myeloid cell infection but requires HIV-1 capture via Siglec-1/CD169, a receptor expressed on myeloid cells that facilitates the infection of bystander target cells. Murine retroviruses are also recognized by Siglec-1, and this interaction is required for robust retroviral infection in vivo. Yet, the relative contribution of Siglec-1-mediated viral dissemination to HIV-1 disease progression remains unclear. The identification of human null individuals lacking working copies of a particular gene enables studying how this loss affects disease progression. Moreover, it can reveal novel antiviral targets whose blockade might be therapeutically effective and safe, since finding null individuals in natura uncovers dispensable functions. We previously described a loss-of-function variant in SIGLEC-1. Analysis of a large cohort of HIV-1-infected individuals identified homozygous and heterozygous subjects, whose cells were functionally null or partially defective for Siglec-1 activity in HIV-1 capture and transmission ex vivo. Nonetheless, analysis of the effect of Siglec-1 truncation on progression to AIDS was not conclusive due to the limited cohort size, the lack of complete clinical records, and the restriction to study only off-therapy periods. Here, we review how the study of loss-of-function variants might serve to illuminate the role of myeloid cells in viral pathogenesis in vivo and the challenges ahead.

  9. Transport proteins promoting Escherichia coli pathogenesis

    Science.gov (United States)

    Tang, Fengyi; Saier, Milton H.

    2014-01-01

    Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex receptors and high-affinity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, different from those of extracellular pathogens. The results presented in this report provide information about transport systems relevant to various types of E. coli pathogenesis that can be exploited in future basic and applied studies. PMID:24747185

  10. Transport proteins promoting Escherichia coli pathogenesis.

    Science.gov (United States)

    Tang, Fengyi; Saier, Milton H

    2014-01-01

    Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex receptors and high-affinity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, different from those of extracellular pathogens. The results presented in this report provide information about transport systems relevant to various types of E. coli pathogenesis that can be exploited in future basic and applied studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Channelopathy Pathogenesis in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Galina eSchmunk

    2013-11-01

    Full Text Available Autism spectrum disorder (ASD is a syndrome that affects normal brain development and is characterized by impaired social interaction as well as verbal and non-verbal communication and by repetitive, stereotypic behavior. ASD is a complex disorder arising from a combination of multiple genetic and environmental factors that are independent from racial, ethnic and socioeconomical status. The high heritability of ASD suggests a strong genetic basis for the disorder. Furthermore, a mounting body of evidence implies a role of various ion channel gene defects (channelopathies in the pathogenesis of autism. Indeed, recent genome-wide association, and whole exome- and whole- genome resequencing studies linked polymorphisms and rare variants in calcium, sodium and potassium channels and their subunits with susceptibility to ASD, much as they do with bipolar disorder, schizophrenia and other neuropsychiatric disorders, and animal models with these genetic variations recapitulate endophenotypes considered to be correlates of autistic behavior seen in patients. An ion flux across the membrane regulates a variety of cell functions, from generation of action potentials to gene expression and cell morphology, thus it is not surprising that channelopathies have profound effects on brain functions. In the present work, we summarize existing evidence for the role of ion channel gene defects in the pathogenesis of autism with a focus on calcium signaling and its downstream effects.

  12. Pathogenesis and treatment modalities of localized scleroderma.

    Science.gov (United States)

    Valančienė, Greta; Jasaitienė, Daiva; Valiukevičienė, Skaidra

    2010-01-01

    Localized scleroderma is a chronic inflammatory disease primarily of the dermis and subcutaneous fat that ultimately leads to a scar-like sclerosis of connective tissue. The disorder manifests as various plaques of different shape and size with signs of skin inflammation, sclerosis, and atrophy. This is a relatively rare inflammatory disease characterized by a chronic course, unknown etiology, and insufficiently clear pathogenesis. Many factors may influence its appearance: trauma, genetic factors, disorders of the immune system or hormone metabolism, viral infections, toxic substances or pharmaceutical agents, neurogenic factors, and Borrelia burgdorferi infection. Various therapeutic modalities are being used for the treatment of localized scleroderma. There is no precise treatment scheme for this disease. A majority of patients can be successfully treated with topical pharmaceutical agents and phototherapy, but some of them with progressive, disseminated, and causing disability localized scleroderma are in need of systemic treatment. The aim of this article is not only to dispute about the clinical and morphological characteristics of localized scleroderma, but also to present the newest generalized data about the possible origin, pathogenesis, and treatment modalities of this disease.

  13. Penile cancer: epidemiology, pathogenesis and prevention.

    Science.gov (United States)

    Bleeker, M C G; Heideman, D A M; Snijders, P J F; Horenblas, S; Dillner, J; Meijer, C J L M

    2009-04-01

    Penile cancer is a disease with a high morbidity and mortality. Its prevalence is relatively rare, but the highest in some developing countries. Insight into its precursor lesions, pathogenesis and risk factors offers options to prevent this potentially mutilating disease. This review presents an overview of the different histologically and clinically identified precursor lesions of penile cancer and discusses the molecular pathogenesis, including the role of HPV in penile cancer development. A systematic review of the literature evaluating penile carcinogenesis, risk factors and molecular mechanisms involved. Careful monitoring of men with lichen sclerosis, genital Bowen's disease, erythroplasia of Queyrat and bowenoid papulosis seems useful, thereby offering early recognition of penile cancer and, subsequently, conservative therapeutic options. Special attention is given to flat penile lesions, which contain high numbers of HPV. Their role in HPV transmission to sexual partners is highlighted, but their potential to transform as a precursor lesion into penile cancer has been unsatisfactorily explored. Further research should not only focus on HPV mediated pathogenic pathways but also on the non-HPV related molecular and genetic factors that play a role in penile cancer development. Options for prevention of penile cancer include (neonatal) circumcision, limitation of penile HPV infections (either by prophylactic vaccination or condom use), prevention of phimosis, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation and hygienic measures.

  14. Hypothalamic pathogenesis of type 2 diabetes.

    Science.gov (United States)

    Koshiyama, Hiroyuki; Hamamoto, Yoshiyuki; Honjo, Sachiko; Wada, Yoshiharu; Lkeda, Hiroki

    2006-01-01

    There have recently been increasing experimental and clinical evidences suggesting that hypothalamic dysregulation may be one of the underlying mechanisms of abnormal glucose metabolism. First, increased hypothalamic-pituitary-adrenal axis activity induced by uncontrollable excess stress may cause diabetes mellitus as well as dyslipidemia, visceral obesity, and osteoporosis with some resemblance to Cushing's disease. Second, several molecules are known to be expressed both in pancreas and hypothalamus; adenosine triphosphate-sensitive potassium channels, malonyl-CoA, glucokinase, and AMP-activated protein kinase. Those molecules appear to form an integrated hypothalamic system, which may sense hypothalamic fuel status, especially glucose level, and inhibit action of insulin on hepatic gluconeogenesis, thereby forming a brain-liver circuit. Third, hypothalamic resistance to insulin as an adiposity signal may be involved in pathogenesis of peripheral insulin resistance. The results with mice with a neuron-specific disruption of the insulin receptor gene or those lacking insulin receptor substrate 2 in hypothalamus supported this possibility. Finally, it has very recently been suggested that dysregulation of clock genes in hypothalamus may cause abnormal glucose metabolism. Taken together, it is plausible that some hypothalamic abnormality may underlie at least some portion of type 2 diabetes or insulin resistance in humans, and this viewpoint of hypothalamic pathogenesis of type 2 diabetes may lead to the development of new drugs for type 2 diabetes.

  15. Current questions in HIV-associated lung cancer.

    Science.gov (United States)

    Shcherba, Marina; Shuter, Jonathan; Haigentz, Missak

    2013-09-01

    In this review, we explore current questions regarding risk factors contributing to frequent and early onset of lung cancer among populations with HIV infection, treatment, and outcomes of lung cancer in HIV-infected patients as well as challenges in a newly evolving era of lung cancer screening. Lung cancer, seen in three-fold excess in HIV-infected populations, has become the most common non-AIDS defining malignancy in the highly active antiretroviral therapy era. HIV-associated lung cancer appears to be associated with young age at diagnosis, cigarette smoking, advanced stage at presentation, and a more aggressive clinical course. There is no unified explanation for these observations, and aside from traditional risk factors, HIV-related immunosuppression and biological differences might play a role. In addition to smoking cessation interventions, screening and early cancer detection in HIV-infected populations are of high clinical importance, although evidence supporting lung cancer screening in this particularly high-risk subset is currently lacking, as are prospective studies of lung cancer therapy. There is an urgent need for prospective clinical trials in HIV-associated lung cancer to improve understanding of lung cancer pathogenesis and to optimize patient care. Several clinical trials are in progress to address questions in cancer biology, screening, and treatment for this significant cause of mortality in persons with HIV infection.

  16. Measuring and managing cognitive impairment in HIV.

    Science.gov (United States)

    Nightingale, Sam; Winston, Alan

    2017-06-01

    : Cognitive impairment remains a frequently reported complaint in HIV-positive patients despite virologically suppressive antiretroviral therapy. Rates of cognitive impairment in antiretroviral treated HIV-positive cohorts vary and strongly depend on definitions utilized.The underlying pathogenesis is likely to be multifactorial and includes immune activation, neuroinflammation, antiretroviral neurotoxicity, the presence of noninfectious comorbidities such as vascular disease and depression and patient lifestyle factors such as recreational drug use.Contributing factors to cognitive impairment may change over time with ageing HIV-positive populations. Cerebrovascular disease and neurodegenerative causes of cognitive impairment may become more common with advancing age; how these factors interact with HIV-associated cognitive impairment is not yet known.Cerebrospinal fluid HIV RNA escape may occur in up to 10% of patients undergoing lumbar puncture clinically and can be associated with compartmentalized and resistant virus.Changes in antiretroviral therapy in patients with cognitive impairment should be based on current and historic resistance profiles of cerebrospinal fluid and plasma virus, or on potential antiretroviral drug neurotoxicity. Whether and how antiretroviral therapy should be changed in the absence of these factors is not known and requires study in adequately powered randomized trials in carefully selected clinical cohorts.

  17. Research progress of HIV-associated myelopathy

    Directory of Open Access Journals (Sweden)

    Kun HONG

    2016-08-01

    Full Text Available The wide usage of highly active antiretroviral therapy (HAART leads to reduction of the occurence rate of focal or diffuse neurological damage caused by human immunodeficiency virus (HIV infection, which prominently improves the living quality of HIV-infected patients. Despite this progress, about 70% of HIV-infected patients develop neurological complications. Although neurological disease typically occurs in the advanced stage of the disease or after severe damage of immune functions, it may also occur during early stage of the infection. HIV-associated myelopathy is a common complication of immunodeficiency syndrome and its typical pathological appearence is vacuolar degeneration. In many patients the clinical manifestations of vacuolar myelopathy are in fact limited to non-specific sphincter or sexual dysfunction, and may remain completely asymptomatic. Even when motor and sensory symptoms become evident, the diagnosis is often complicated by a concomitant peripheral neuropathy. The purpose of this study is to summarize pathogenesis, clinical manifestations, pathological features, diagnosis and treatment of HIV-associated myelopathy. DOI: 10.3969/j.issn.1672-6731.2016.08.004

  18. Asymptomatic HIV infection

    Science.gov (United States)

    ... of HIV/AIDS during which there are no symptoms of HIV infection. During this phase, the immune system in someone with HIV slowly weakens, but the person has no symptoms. How long this phase lasts depends on how ...

  19. HIV and Pulmonary Hypertension

    Science.gov (United States)

    ... What do I need to know about pulmonary hypertension in connection with HIV? Although pulmonary hypertension and ... Should an HIV patient be tested for pulmonary hypertension? HIV patients know that medical supervision is critical ...

  20. EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment.

    Science.gov (United States)

    Gu, Chao-Jiang; Borjabad, Alejandra; Hadas, Eran; Kelschenbach, Jennifer; Kim, Boe-Hyun; Chao, Wei; Arancio, Ottavio; Suh, Jin; Polsky, Bruce; McMillan, JoEllyn; Edagwa, Benson; Gendelman, Howard E; Potash, Mary Jane; Volsky, David J

    2018-06-01

    Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI. EcoHIV established latent reservoirs in CD4+ T lymphocytes in chronically-infected mice but could be induced by epigenetic modulators ex vivo and in mice. In contrast, macrophages expressed EcoHIV constitutively in mice for up to 16 months; murine leukemia virus (MLV), the donor of gp80 envelope in EcoHIV, did not infect macrophages. Both EcoHIV and MLV were found in brain tissue of infected mice but only EcoHIV induced NCI. Murine HIV-NCI was prevented by antiretroviral prophylaxis but once established neither persistent EcoHIV infection in mice nor NCI could be reversed by long-acting antiretroviral therapy. EcoHIV-infected, athymic mice were more permissive to virus replication in macrophages than were wild-type mice, suffered cognitive dysfunction, as well as increased numbers of monocytes and macrophages infiltrating the brain. Our results suggest an important role of HIV expressing macrophages in HIV neuropathogenesis in hosts with suppressed HIV replication.

  1. Future directions in the treatment of HIV-HBV coinfection.

    Science.gov (United States)

    Iser, David M; Lewin, Sharon R

    2009-07-01

    Liver disease is a major cause of mortality in individuals with HIV-HBV coinfection. The pathogenesis of liver disease in this setting is unknown, but is likely to involve drug toxicity, infection of hepatic cells with both HIV and HBV, and an altered immune response to HBV. The availability of therapeutic agents that target both HIV and HBV replication enable dual viral suppression, and assessment of chronic hepatitis B is important prior to commencement of antiretroviral therapy. Greater importance is now placed on HBV DNA levels and staging of liver fibrosis, either by liver biopsy or noninvasive measurement, such as transient elastography, since significant liver fibrosis may exist in the presence of normal liver function tests. Earlier treatment of both HIV and HBV is now generally advocated and treatment is usually lifelong.

  2. Rhesus macaque and chimpanzee DC-SIGN act as HIV/SIV gp120 trans-receptors, similar to human DC-SIGN

    NARCIS (Netherlands)

    Geijtenbeek, T. B.; Koopman, G.; van Duijnhoven, G. C.; van Vliet, S. J.; van Schijndel, A. C.; Engering, A.; Heeney, J. L.; van Kooyk, Y.

    2001-01-01

    Dendritic cells (DC) have been implicated in the pathogenesis of both human and simian immunodeficiency viruses (HIV and SIV, respectively). The DC-specific HIV-1 trans-receptor DC-SIGN is thought to be essential for viral dissemination by DC. Abundant expression in lymphoid tissues also implies a

  3. OsteOpaenia and OsteOnecrOsis in HiV infectiOn: repOrt Of tWO ...

    African Journals Online (AJOL)

    diseases and aroused interest in the interaction of HiV and aging the pathogenesis of the .... prolonged use of corticosteroids in patient case report. 1, with HiV viral ... calcium deposition. this would help rationalise the selection of protease ...

  4. Innate immunity in the pathogenesis of psoriasis.

    LENUS (Irish Health Repository)

    Sweeney, Cheryl M

    2011-12-01

    Psoriasis is a common, immune-mediated inflammatory skin disorder. T helper(h)1 and Th17 lymphocytes contribute to the pathogenesis of psoriasis through the release of inflammatory cytokines that promote further recruitment of immune cells, keratinocyte proliferation and sustained inflammation. The innate immune system is the first line of defence against infection and plays a crucial role in the initiation of the adaptive immune response. The presence of innate immune cells and their products in psoriatic skin plaques suggests a role for innate immunity in this disease. In addition, the innate immune system can direct the development of pathogenic Th cells in psoriasis. In this article, we will summarise the role of the innate immune system in psoriasis with particular emphasis on the role of cytokines, signalling pathways and cells of the innate immune system.

  5. The role of EBV in MS pathogenesis

    DEFF Research Database (Denmark)

    Christensen, Tove

    2006-01-01

    Environmental factors operate on a background of genetic susceptibility in the pathogenesis of MS. Human herpesviruses, notably Epstein-Barr virus (EBV), and human endogenous retroviruses are factors associated with MS. EBV association is found in epidemiological surveys where late EBV infection...... confers a higher risk of MS, and EBV reactivation also appears to be linked to disease activity in early MS. MS patients have elevated anti-EBV antibody responses, both in serum and cerebrospinal fluid. Molecular mimicry is found between certain EBV and myelin epitopes in the cell-mediated immune response....... EBV cannot stand alone as a causal factor of MS, but is likely to play an indirect role as an activator of the underlying disease process....

  6. Protein misfolding disorders: pathogenesis and intervention

    DEFF Research Database (Denmark)

    Gregersen, Niels

    2006-01-01

    of the functional structure of cellular proteins. Aberrant proteins, the result of production errors, inherited or acquired amino acid substitutions or damage, especially oxidative modifications, can in many cases not fold correctly and will be trapped in misfolded conformations. To rid the cell of misfolded...... be accompanied by a gain-of-function pathogenesis, which in many cases determines the pathological and clinical features. Examples are Parkinson and Huntington diseases. Although a number of strategies have been tried to decrease the amounts of accumulated and aggregated proteins, a likely future strategy seems......Newly synthesized proteins in the living cell must go through a folding process to attain their functional structure. To achieve this in an efficient fashion, all organisms, including humans, have evolved a large set of molecular chaperones that assist the folding as well as the maintenance...

  7. Psoriatic arthritis: from pathogenesis to therapy.

    LENUS (Irish Health Repository)

    Fitzgerald, Oliver

    2012-02-01

    Psoriatic arthritis is a multigenic autoimmune disease that involves synovial tissue, entheseal sites and skin, and that may result in significant joint damage. Although there are no diagnostic tests for psoriatic arthritis, research has identified consistent features that help to distinguish the condition from other common rheumatic diseases. Comparison of HLA-B and HLA-C regions in psoriatic arthritis with those in psoriasis without joint involvement demonstrates significant differences, such that psoriatic arthritis cannot be viewed simply as a subset of genetically homogeneous psoriasis. T-cell receptor phenotypic studies have failed to identify antigen-driven clones, and an alternative hypothesis for CD8 stimulation involving innate immune signals is proposed. Finally, imaging studies have highlighted entheseal involvement in psoriatic arthritis, and it is possible that entheseal-derived antigens may trigger an immune response that is critically involved in disease pathogenesis.

  8. Foodborne Campylobacter: Infections, Metabolism, Pathogenesis and Reservoirs

    Directory of Open Access Journals (Sweden)

    Sharon V. R. Epps

    2013-11-01

    Full Text Available Campylobacter species are a leading cause of bacterial-derived foodborne illnesses worldwide. The emergence of this bacterial group as a significant causative agent of human disease and their propensity to carry antibiotic resistance elements that allows them to resist antibacterial therapy make them a serious public health threat. Campylobacter jejuni and Campylobacter coli are considered to be the most important enteropathogens of this genus and their ability to colonize and survive in a wide variety of animal species and habitats make them extremely difficult to control. This article reviews the historical and emerging importance of this bacterial group and addresses aspects of the human infections they cause, their metabolism and pathogenesis, and their natural reservoirs in order to address the need for appropriate food safety regulations and interventions.

  9. Origin and pathogenesis of antiphospholipid antibodies

    Directory of Open Access Journals (Sweden)

    C.M. Celli

    1998-06-01

    Full Text Available Antiphospholipid antibodies (aPL are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus, infectious (syphilis, AIDS and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias. Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.

  10. Actinic Keratosis Pathogenesis Update and New Patents.

    Science.gov (United States)

    Cantisani, Carmen; Paolino, Giovanni; Melis, Marcello; Faina, Valentina; Romaniello, Federico; Didona, Dario; Cardone, Michele; Calvieri, Stefano

    2016-01-01

    Actinic keratosis is a common premalignant skin lesion. Because of its increasing incidence, several efforts have been made to earlier detectection and to improve knowledge on photocarcinogenic pathways of keratinocytes. As a consequence, recently new discoveries have been done in this field. Starting from our previous review on actinic keratosis, we reviewed the literature focusing on pathogenesis and new patents in order to highlight the most recent progresses in diagnosis and therapeutic approach. Although several efforts have been done in the field of photodamaged skin, new upgrades in diagnosis and therapy are needed to detect superficial actinic keratosis earlier, to improve the disease free survival of patient and to better treat the field cancerization.

  11. Etiology and pathogenesis of antisperm antibody

    Directory of Open Access Journals (Sweden)

    farhad Shahsavar

    2011-06-01

    Full Text Available Antisperm antibodies (ASA occur in men and women and may significantly impair fertility. In this case, the testis is an immunologically privileged site where germ cell antigens are protected from autoimmune attack. However, due to disruption of the blood-testis barrier occurring from testicular injury, or as a consequence of trauma to the epididymis or vas deferens many testicular proteins get autoantigenic during immunological challenges resulting in the formation of ASA in the blood serum, seminal plasma or located on the sperm membrane. ASA have also been reported to be associated with inflammation, cryptorchidism, varicocele and surgical intervention in the genital organs. ASA may interfere with different sperm functions, which are essential for the fertilization process.This review article will help to increase our understanding of the specific mechanisms that elicit the autoimmune response to sperm and of the pathogenesis of ASA that leads to an antibody-mediated infertility.

  12. MicroRNA involvement in glioblastoma pathogenesis

    International Nuclear Information System (INIS)

    Novakova, Jana; Slaby, Ondrej; Vyzula, Rostislav; Michalek, Jaroslav

    2009-01-01

    MicroRNAs are endogenously expressed regulatory noncoding RNAs. Altered expression levels of several microRNAs have been observed in glioblastomas. Functions and direct mRNA targets for these microRNAs have been relatively well studied over the last years. According to these data, it is now evident, that impairment of microRNA regulatory network is one of the key mechanisms in glioblastoma pathogenesis. MicroRNA deregulation is involved in processes such as cell proliferation, apoptosis, cell cycle regulation, invasion, glioma stem cell behavior, and angiogenesis. In this review, we summarize the current knowledge of miRNA functions in glioblastoma with an emphasis on its significance in glioblastoma oncogenic signaling and its potential to serve as a disease biomarker and a novel therapeutic target in oncology.

  13. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

  14. Thrombocytopenia in leukemia: Pathogenesis and prognosis.

    Science.gov (United States)

    Shahrabi, Saeid; Behzad, Masumeh Maleki; Jaseb, Kaveh; Saki, Najmaldin

    2018-02-20

    Leukemias, a heterogeneous group of hematological disorders, are characterized by ineffective hematopoiesis and morphologic abnormalities of hematopoietic cells. Thrombocytopenia is a common problem among leukemia types that can lead to hemorrhagic complications in patients. The purpose of this review article is to identify the conditions associated with the incidence of thrombocytopenia in leukemias. It can be stated that although translocations have been considered responsible for this complication in many studies, other factors such as bone marrow failure, genes polymorphism, a mutation in some transcription factors, and the adverse effects of treatment could be associated with pathogenesis and poor prognosis of thrombocytopenia in leukemias. Considering the importance of thrombocytopenia in leukemias, it is hoped that the recognition of risk factors increasing the incidence of this complication in leukemic patients would be useful for prevention and treatment of this disorder.

  15. Pathogenesis of Graves' disease and therapeutic implications

    International Nuclear Information System (INIS)

    Seif, F.J.

    1997-01-01

    Graves' disease presents itself clinically mainly as hyperthyroidism and infiltrative ophthalmopathy and to a minimal extent also as dermopathy and acropachy. Autoimmune processes are the basic pathogenesis. Stimulating antibodies against the TSH receptor cause hyperthyroidism. Autoantibodies and autoreactive T lymphocytes against primarily thyroidal antigens cross-react with similar antigens of the eye muscles and orbital connective tissue, thus spreading the disease from the thyroid to the eyes. The therapeutic goal comprises not only the treatment of hyperthyroidism, but also the induction of a steady immuntolerance in order to minimize the irreversible damage to the eye. The therapeutic armamentarium is formed by antithyroid drugs, glucocorticoids, retrobulbar radition and thyroid ablation, either by nearly total thyroidectomy or by radioiodine. The different indications for both ablative procedures are discussed. (orig.) [de

  16. STUDIES ON THE PATHOGENESIS OF FEVER

    Science.gov (United States)

    Atkins, Elisha; Wood, W. Barry

    1955-01-01

    Further studies have been made of a pyrogenic substance which appears in the circulation of rabbits during the course of experimental fever induced by injection of typhoid vaccine. With the use of a passive transfer method and pyrogen-tolerant recipients, the biological properties of this substance have been differentiated from those of the uncleared vaccine in the circulation. The newly identified factor resembles leucocytic pyrogen in the rapidity with which it produces fever and in its failure to exhibit cross-tolerance with bacterial pyrogen. This striking similarity of properties suggests that the circulating factor is of endogenous origin and may arise from cell injury. A close correlation between its presence in the circulation and the existence of fever has been demonstrated. The possible relationship of these findings to the pathogenesis of fever is evident. PMID:13271667

  17. Feline Coronaviruses: Pathogenesis of Feline Infectious Peritonitis.

    Science.gov (United States)

    Tekes, G; Thiel, H-J

    2016-01-01

    Feline infectious peritonitis (FIP) belongs to the few animal virus diseases in which, in the course of a generally harmless persistent infection, a virus acquires a small number of mutations that fundamentally change its pathogenicity, invariably resulting in a fatal outcome. The causative agent of this deadly disease, feline infectious peritonitis virus (FIPV), arises from feline enteric coronavirus (FECV). The review summarizes our current knowledge of the genome and proteome of feline coronaviruses (FCoVs), focusing on the viral surface (spike) protein S and the five accessory proteins. We also review the current classification of FCoVs into distinct serotypes and biotypes, cellular receptors of FCoVs and their presumed role in viral virulence, and discuss other aspects of FIPV-induced pathogenesis. Our current knowledge of genetic differences between FECVs and FIPVs has been mainly based on comparative sequence analyses that revealed "discriminatory" mutations that are present in FIPVs but not in FECVs. Most of these mutations result in amino acid substitutions in the S protein and these may have a critical role in the switch from FECV to FIPV. In most cases, the precise roles of these mutations in the molecular pathogenesis of FIP have not been tested experimentally in the natural host, mainly due to the lack of suitable experimental tools including genetically engineered virus mutants. We discuss the recent progress in the development of FCoV reverse genetics systems suitable to generate recombinant field viruses containing appropriate mutations for in vivo studies. © 2016 Elsevier Inc. All rights reserved.

  18. Some aspects of periodontitis pathogenesis in children

    Directory of Open Access Journals (Sweden)

    Shcherbina I.N.

    2013-12-01

    Full Text Available Inflammatory processes in the tissues surrounding tooth root are frequent enough and develop as the direct complication of caries. As acute periodontitis is manifested with grinding toothache and violation of ph¬y¬sio¬logical act of chewing, symptoms of general intoxication, the continuous sluggish chronic periodontitis is harmful and dangerous to the organism as well. It forms the state of chronic оdontogenetic intoxication and chroneosepsis with wrong functioning of some internal organs and body systems. The like complications can cause significant disturbance to the function of kidneys, liver, heart, joints and their treatment without ablating focus of inflammation is often in- effective; this must be taken into account by doctors-interns. However, scanning of the oral cavity by conservative means has its difficulties mostly because of ignoring pathogenesis of such inflammation. That is why activity of ferments of blood dehydrogenases from the periapical tissues of the teeth affected with the chronic periodontitis was studied. The level of succinate dehydrogenase and alpha-glycerophosphate degydrogenase of lymphocytes of 110 schoolchildren aged 13-17 years old was studied. The main group of examined individuals included those of infected with tuber¬culousis – 50 individuals, and the control group (60 individuals – clinically healthy ones without tuberculousis desease. All schoolchildren had 1 or 2 teeth affected with chronic periodontitis of the apical localization. The researchers found that a significant inhibition of activity of succinate dehydrogenase and alpha-glycerophosphate degydrogenase ferments occurs in the inflammatory periodontal tissues, which indicates to local immunity decline, and as a consequence, pathogenic bacteria activation. In people infected with tuberculousis these violations were more developed. Such features of periodontitis pathogenesis must be taken into account when providing a combined treatment.

  19. Perinatally acquired HIV infection in adolescents from sub-Saharan Africa: a review of emerging challenges.

    Science.gov (United States)

    Lowenthal, Elizabeth D; Bakeera-Kitaka, Sabrina; Marukutira, Tafireyi; Chapman, Jennifer; Goldrath, Kathryn; Ferrand, Rashida A

    2014-07-01

    Worldwide, more than three million children are infected with HIV, 90% of whom live in sub-Saharan Africa. As the HIV epidemic matures and antiretroviral treatment is scaled up, children with HIV are reaching adolescence in large numbers. The growing population of adolescents with perinatally acquired HIV infection living within this region presents not only unprecedented challenges but also opportunities to learn about the pathogenesis of HIV infection. In this Review, we discuss the changing epidemiology of paediatric HIV and the particular features of HIV infection in adolescents in sub-Saharan Africa. Longstanding HIV infection acquired when the immune system is not developed results in distinctive chronic clinical complications that cause severe morbidity. As well as dealing with chronic illness, HIV-infected adolescents have to confront psychosocial issues, maintain adherence to drugs, and learn to negotiate sexual relationships, while undergoing rapid physical and psychological development. Context-specific strategies for early identification of HIV infection in children and prompt linkage to care need to be developed. Clinical HIV care should integrate age-appropriate sexual and reproductive health and psychological, educational, and social services. Health-care workers will need to be trained to recognise and manage the needs of these young people so that the increasing numbers of children surviving to adolescence can access quality care beyond specialist services at low-level health-care facilities. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Research advances in the pathogenesis of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    WANG Hu

    2017-04-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has been developing rapidly in recent years and has become one of the most common liver diseases. However, its pathogenesis remains unclear, and there are no widely accepted therapeutic regimens. NAFLD has a complex pathogenesis with multiple factors involved, including insulin resistance, oxidative stress, bile acid metabolic disorders, and autophagy. This article reviews the pathogenesis of NAFLD in order to provide a reference for further research and clinical treatment in the future.

  1. Molecular HIV screening.

    Science.gov (United States)

    Bourlet, Thomas; Memmi, Meriam; Saoudin, Henia; Pozzetto, Bruno

    2013-09-01

    Nuclear acid testing is more and more used for the diagnosis of infectious diseases. This paper focuses on the use of molecular tools for HIV screening. The term 'screening' will be used under the meaning of first-line HIV molecular techniques performed on a routine basis, which excludes HIV molecular tests designed to confirm or infirm a newly discovered HIV-seropositive patient or other molecular tests performed for the follow-up of HIV-infected patients. The following items are developed successively: i) presentation of the variety of molecular tools used for molecular HIV screening, ii) use of HIV molecular tools for the screening of blood products, iii) use of HIV molecular tools for the screening of organs and tissue from human origin, iv) use of HIV molecular tools in medically assisted procreation and v) use of HIV molecular tools in neonates from HIV-infected mothers.

  2. Information geometric analysis of phase transitions in complex patterns: the case of the Gray-Scott reaction–diffusion model

    International Nuclear Information System (INIS)

    Har-Shemesh, Omri; Quax, Rick; Hoekstra, Alfons G; Sloot, Peter M A

    2016-01-01

    The Fisher–Rao metric from information geometry is related to phase transition phenomena in classical statistical mechanics. Several studies propose to extend the use of information geometry to study more general phase transitions in complex systems. However, it is unclear whether the Fisher–Rao metric does indeed detect these more general transitions, especially in the absence of a statistical model. In this paper we study the transitions between patterns in the Gray-Scott reaction–diffusion model using Fisher information. We describe the system by a probability density function that represents the size distribution of blobs in the patterns and compute its Fisher information with respect to changing the two rate parameters of the underlying model. We estimate the distribution non-parametrically so that we do not assume any statistical model. The resulting Fisher map can be interpreted as a phase-map of the different patterns. Lines with high Fisher information can be considered as boundaries between regions of parameter space where patterns with similar characteristics appear. These lines of high Fisher information can be interpreted as phase transitions between complex patterns. (paper: disordered systems, classical and quantum)

  3. Multi-time-over-threshold technique for photomultiplier signal processing: Description and characterization of the SCOTT ASIC

    International Nuclear Information System (INIS)

    Ferry, S.; Guilloux, F.; Anvar, S.; Chateau, F.; Delagnes, E.; Gautard, V.; Louis, F.; Monmarthe, E.; Le Provost, H.; Russo, S.; Schuller, J.-P.; Stolarczyk, Th.; Vallage, B.; Zonca, E.

    2012-01-01

    KM3NeT aims to build a cubic-kilometer scale neutrino telescope in the Mediterranean Sea based on a 3D array of photomultiplier tubes. A dedicated ASIC, named SCOTT, has been developed for the readout electronics of the PMTs: it uses up to 16 adjustable thresholds to digitize the signals with the multi-time-over-threshold technique. Digital outputs of discriminators feed a circular sampling memory and a “first in first out” digital memory for derandomization. At the end of the data processing, the ASIC produces a digital waveform sampled at 800 MHz. A specific study was carried out to process PMT data and has showed that five specifically chosen thresholds are suited to reach the required timing precision. A dedicated method based on the duration of the signal over a given threshold allows an equivalent timing precision at any charge. A charge estimator using the information from the thresholds allows a charge determination within less than 20% up to 60 pe.

  4. Multi-time-over-threshold technique for photomultiplier signal processing: Description and characterization of the SCOTT ASIC

    Science.gov (United States)

    Ferry, S.; Guilloux, F.; Anvar, S.; Chateau, F.; Delagnes, E.; Gautard, V.; Louis, F.; Monmarthe, E.; Le Provost, H.; Russo, S.; Schuller, J.-P.; Stolarczyk, Th.; Vallage, B.; Zonca, E.; Representing the KM3NeT Consortium

    2012-12-01

    KM3NeT aims to build a cubic-kilometer scale neutrino telescope in the Mediterranean Sea based on a 3D array of photomultiplier tubes. A dedicated ASIC, named SCOTT, has been developed for the readout electronics of the PMTs: it uses up to 16 adjustable thresholds to digitize the signals with the multi-time-over-threshold technique. Digital outputs of discriminators feed a circular sampling memory and a “first in first out” digital memory for derandomization. At the end of the data processing, the ASIC produces a digital waveform sampled at 800 MHz. A specific study was carried out to process PMT data and has showed that five specifically chosen thresholds are suited to reach the required timing precision. A dedicated method based on the duration of the signal over a given threshold allows an equivalent timing precision at any charge. A charge estimator using the information from the thresholds allows a charge determination within less than 20% up to 60 pe.

  5. Aarskog-Scott syndrome: clinical update and report of nine novel mutations of the FGD1 gene.

    Science.gov (United States)

    Orrico, A; Galli, L; Faivre, L; Clayton-Smith, J; Azzarello-Burri, S M; Hertz, J M; Jacquemont, S; Taurisano, R; Arroyo Carrera, I; Tarantino, E; Devriendt, K; Melis, D; Thelle, T; Meinhardt, U; Sorrentino, V

    2010-02-01

    Mutations in the FGD1 gene have been shown to cause Aarskog-Scott syndrome (AAS), or facio-digito-genital dysplasia (OMIM#305400), an X-linked disorder characterized by distinctive genital and skeletal developmental abnormalities with a broad spectrum of clinical phenotypes. To date, 20 distinct mutations have been reported, but little phenotypic data are available on patients with molecularly confirmed AAS. In the present study, we report on our experience of screening for mutations in the FGD1 gene in a cohort of 60 European patients with a clinically suspected diagnosis of AAS. We identified nine novel mutations in 11 patients (detection rate of 18.33%), including three missense mutations (p.R402Q; p.S558W; p.K748E), four truncating mutations (p.Y530X; p.R656X; c.806delC; c.1620delC), one in-frame deletion (c.2020_2022delGAG) and the first reported splice site mutation (c.1935+3A>C). A recurrent mutation (p.R656X) was detected in three independent families. We did not find any evidence for phenotype-genotype correlations between type and position of mutations and clinical features. In addition to the well-established phenotypic features of AAS, other clinical features are also reported and discussed. Copyright 2010 Wiley-Liss, Inc.

  6. Osteonecrosis en pacientes infectados por HIV Osteonecrosis in HIV-infected patients

    Directory of Open Access Journals (Sweden)

    Edgardo G. Bottaro

    2004-08-01

    Full Text Available Según la literatura, la osteonecrosis tiene una mayor incidencia en los pacientes infectados con HIV que en la población general. Ello sería resultado de la confluencia de factores de riesgo clásicos y de otros propios de esta población o más prevalentes en ella, como el tratamiento con inhibidores de proteasa, la dislipemia producto de su consumo, la presencia de anticuerpos anticardiolipina séricos, la hipercoagulabilidad, la restauración inmune y las vasculitis. Presentamos una serie de 13 pacientes infectados con HIV con osteonecrosis. El motivo de consulta fue dolor en grandes articulaciones. Cuatro eran alcoholistas, 8 tabaquistas y 9 tenían dislipemia. Once habían recibido esteroides en algún momento de la vida aunque sólo uno estaba recibiéndolos al momento del inicio del dolor. En 2 se detectaron anticuerpos anticardiolipina séricos. Doce tenían sida y recibían tratamiento antirretroviral de alta eficacia (11 con inhibidores de proteasa. Ellos lograron una adecuada recuperación inmunológica. Consideramos necesario incluir la osteonecrosis como diagnóstico diferencial de artralgia persistente en pacientes infectados con HIV e investigar infección por HIV en todo paciente con osteonecrosis sin claros factores predisponentes.Osteonecrosis, also known as avascular necrosis, is chiefly characterized by death of bone caused by vascular compromise. The true incidence of osteonecrosis in HIV-infected patients is not well known and the pathogenesis remains undefined. Hypothetical risk factors peculiar to HIV-infected individuals that might play a role in the pathogenesis of osteonecrosis include the introduction of protease inhibitors and resulting hyperlipidemia, the presence of anticardiolipin antibodies in serum leading to a hypercoagulable state, immune recovery and vasculitis. Hereby we present a series of 13 HIV-infected patients with osteonecrosis. The most common symptom upon presentation was arthralgia. The majority

  7. TNF and TNF Receptor Superfamily Members in HIV infection: New Cellular Targets for Therapy?

    Directory of Open Access Journals (Sweden)

    Amit Kumar

    2013-01-01

    Full Text Available Tumor necrosis factor (TNF and TNF receptors (TNFR superfamily members are engaged in diverse cellular phenomena such as cellular proliferation, morphogenesis, apoptosis, inflammation, and immune regulation. Their role in regulating viral infections has been well documented. Viruses have evolved with numerous strategies to interfere with TNF-mediated signaling indicating the importance of TNF and TNFR superfamily in viral pathogenesis. Recent research reports suggest that TNF and TNFRs play an important role in the pathogenesis of HIV. TNFR signaling modulates HIV replication and HIV proteins interfere with TNF/TNFR pathways. Since immune activation and inflammation are the hallmark of HIV infection, the use of TNF inhibitors can have significant impact on HIV disease progression. In this review, we will describe how HIV infection is modulated by signaling mediated through members of TNF and TNFR superfamily and in turn how these latter could be targeted by HIV proteins. Finally, we will discuss the emerging therapeutics options based on modulation of TNF activity that could ultimately lead to the cure of HIV-infected patients.

  8. Participation in HIV research: the importance of clinic contact factors.

    Science.gov (United States)

    Worthington, Catherine A; Gill, M John

    2008-08-01

    Recruiting minority populations living with HIV to many types of clinic-based HIV research is a concern. This study examined an expanded range of predictors of HIV research participation (clinic contact, clinical, and personal characteristics) to investigate observed ethnocultural differences in HIV research participation. Research participation was defined as participation in any of diagnostic, pathogenesis, drug trial or survey research. Logistic regression modeling was used to predict research participation of 657 eligible patients (93% of the patient population) who began care between January 1997 and the end of September 2003 at a regional outpatient HIV care program in Calgary, Canada. Approximately one third (32%) were non-white, including 18% Aboriginal, 9% black, 4% Asian, and 1% Hispanic individuals. Twenty-nine percent (187/657) of the patients participated in at least one study of any kind. Multivariate analysis indicated that the strongest predictors of any research participation (including diagnostic, pathogenesis, drug trial, or survey studies) are clinical (including nadir CD4 count [odds ratio {OR} = 0.132, p percentage of appointments kept [OR = 1.022, p service use shown by these groups that may influence research participation. To attract under researched populations, attention should shift from the "who" of research participation to the "how" of clinical interactions.

  9. Pathogenesis and role of nuclear medicine

    International Nuclear Information System (INIS)

    Freedman, P. N; Korowlay, N. A

    2002-01-01

    The means by which replication of viruses takes place is explained, as it helps in the understanding of how viruses spread in the blood and how antiretroviral drugs work. The most important viruses, from a health care workers point of view, are hepatitis B and C and human immunodefiency virus (HIV). Whether nuclear medicine has a role to play in the diagnosis of these viruses, and the oportunistic infections that go with them, is debatable. Several radiopharmaceuticals are extremely sensitive for infection and tumor imaging but lack specificity. Patients' treatment is often not based on the outcome of the investigation but rather on preset protocols. AIDS patients are put on prophylactic antibiotic treatment as protection against infections such as toxoplasmosis and pneumocystis carinii pneumonia and there is a poor prognosis for AIDS patients with tumors (Au)

  10. Peripheral blood mononuclear cells HIV DNA levels impact intermittently on neurocognition.

    Directory of Open Access Journals (Sweden)

    Lucette A Cysique

    Full Text Available To determine the contribution of peripheral blood mononuclear cells' (PBMCs HIV DNA levels to HIV-associated dementia (HAD and non-demented HIV-associated neurocognitive disorders (HAND in chronically HIV-infected adults with long-term viral suppression on combined antiretroviral treatment (cART.Eighty adults with chronic HIV infection on cART (>97% with plasma and CSF HIV RNA <50 copies/mL were enrolled into a prospective observational cohort and underwent assessments of neurocognition and pre-morbid cognitive ability at two visits 18 months apart. HIV DNA in PBMCs was measured by real-time PCR at the same time-points.At baseline, 46% had non-demented HAND; 7.5% had HAD. Neurocognitive decline occurred in 14% and was more likely in those with HAD (p<.03. Low pre-morbid cognitive ability was uniquely associated with HAD (p<.05. Log10 HIV DNA copies were stable between study visits (2.26 vs. 2.22 per 106 PBMC. Baseline HIV DNA levels were higher in those with lower pre-morbid cognitive ability (p<.04, and higher in those with no ART treatment during HIV infection 1st year (p = .03. Baseline HIV DNA was not associated with overall neurocognition. However, % ln HIV DNA change was associated with decline in semantic fluency in unadjusted and adjusted analyses (p = .01-.03, and motor-coordination (p = .02-.12 to a lesser extent.PBMC HIV DNA plays a role in HAD pathogenesis, and this is moderated by pre-morbid cognitive ability in the context of long-term viral suppression. While the HIV DNA levels in PBMC are not associated with current non-demented HAND, increasing HIV DNA levels were associated with a decline in neurocognitive functions associated with HAND progression.

  11. Latent M. tuberculosis infection--pathogenesis, diagnosis, treatment and prevention strategies.

    Science.gov (United States)

    Druszczyńska, Magdalena; Kowalewicz-Kulbat, Magdalena; Fol, Marek; Włodarczyk, Marcin; Rudnicka, Wiesława

    2012-01-01

    One third of the earths population is infected with Mycobacterium tuberculosis (Mtb), but only 5-10% of the infected individuals develop active tuberculosis (TB) over their lifetime. The remaining 90-95% stay healthy and are called latently infected individuals. They are the biggest reservoir of the tubercle bacilli and identifying the cases of latent TB is a part of the global plan of TB control. From the clinical point of view detection of latent TB infections (LTBI) in individuals with the highest active TB risk including cases of HIV infection, autoimmune inflammatory diseases or cancer, is a priority. This review summarizes the recent findings in the pathogenesis of latent TB, its diagnosis, treatment and prevention.

  12. True Grit: In Tracking down the Real Story of a Legendary Hero of the Old West, Vaunda Micheaux Nelson also Nabbed the Coretta Scott King Award

    Science.gov (United States)

    Fleishhacker, Joy

    2010-01-01

    When Vaunda Micheaux Nelson donned a black Stetson to become the biographer of Deputy U.S. Marshal Bass Reeves, she had no idea that her square-shooting book about an unsung African-American hero of the Old West would win over a posse of fans and earn her the prestigious 2010 Coretta Scott King (CSK) Author Award. "Bad News for Outlaws"…

  13. Features of ozone intraannual variability in polar regions based on ozone sounding data obtained at the Resolute and Amundsen-Scott stations

    Energy Technology Data Exchange (ETDEWEB)

    Gruzdev, A.N.; Sitnov, S.A. (AN SSSR, Institut Fiziki Atmosfery, Moscow (USSR))

    1991-04-01

    Ozone sounding data obtained at the Resolute and Amundsen-Scott stations are used to analyze ozone intraannual variability in Southern and Northern polar regions. For the Arctic, in particular, features associated with winter stratospheric warmings, stratospheric-tropospheric exchange, and the isolated evolution of surface ozone are noted. Correlative connections between ozone and temperature making it possible to concretize ozone variability mechanisms are analyzed. 31 refs.

  14. HIV Structural Database

    Science.gov (United States)

    SRD 102 HIV Structural Database (Web, free access)   The HIV Protease Structural Database is an archive of experimentally determined 3-D structures of Human Immunodeficiency Virus 1 (HIV-1), Human Immunodeficiency Virus 2 (HIV-2) and Simian Immunodeficiency Virus (SIV) Proteases and their complexes with inhibitors or products of substrate cleavage.

  15. HIV Viral Load

    Science.gov (United States)

    ... PF4 Antibody Hepatitis A Testing Hepatitis B Testing Hepatitis C Testing HER2/neu Herpes Testing High-sensitivity C-reactive Protein (hs-CRP) Histamine Histone Antibody HIV Antibody and HIV Antigen (p24) HIV Antiretroviral Drug Resistance Testing, Genotypic HIV Viral Load HLA Testing HLA- ...

  16. National HIV Testing Day

    Centers for Disease Control (CDC) Podcasts

    Dr. Kevin A. Fenton, Director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, discusses National HIV Testing Day, an annual observance which raises awareness of the importance of knowing one's HIV status and encourages at-risk individuals to get an HIV test.

  17. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

    In this podcast, CDC’s Dr. Steve Nesheim discusses perinatal HIV transmission, including the importance of preventing HIV among women, preconception care, and timely HIV testing of the mother. Dr. Nesheim also introduces the revised curriculum Eliminating Perinatal HIV Transmission intended for faculty of OB/GYN and pediatric residents and nurse midwifery students.

  18. Molecular Mechanisms of Liver Fibrosis in HIV/HCV Coinfection

    Directory of Open Access Journals (Sweden)

    Claudio M. Mastroianni

    2014-05-01

    Full Text Available Chronic hepatitis C virus (HCV infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV. Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV.

  19. HAART in HIV/AIDS Treatments: Future Trends.

    Science.gov (United States)

    Lu, Da-Yong; Wu, Hong-Ying; Yarla, Nagendra Sastry; Xu, Bin; Ding, Jian; Lu, Ting-Ren

    2018-01-01

    AIDS (acquired immune deficient syndrome) is a deadly human viral infectious disease caused by HIV (human immune-deficient virus) infection. Almost every AIDS patient losses his/her life before mid 1990s. AIDS was once the 1st disease killer in US (1993). After one decade hard work, antiviral drug cocktails-high active anti-retroviral therapy (HAART) have been invented for almost all HIV infection treatments. Due to the invention of HAART, 80-90% HIV/AIDS patients still effectively response to HAART for deadly AIDS episode controls and life saving. Yet, this type of HIV therapeutics is incurable. HIV/AIDS patients need to take HAART medications regularly and even life-long. To counteract this therapeutic drawback, more revolutionary efforts (different angles of therapeutic modes/attempts) are urgently needed. In this article, the major progresses and drawbacks of HIV/AIDS chemotherapy (HAART) to HIV/AIDS patients have been discussed. Future trends (updating pathogenesis study, next generations of drug developments, new drug target discovery, different scientific disciplinary and so on) are highlighted. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  20. Controlling Listeria monocytogenes Scott A on Surfaces of Fully Cooked Turkey Deli Product Using Organic Acid-Containing Marinades as Postlethality Dips.

    Science.gov (United States)

    Casco, Gerardo; Johnson, Jennifer L; Taylor, T Matthew; Gaytán, Carlos N; Brashears, Mindy M; Alvarado, Christine Z

    2015-01-01

    This study evaluated the efficacy of organic acids applied singly or in combination as postlethality dips to sliced uncured turkey deli loaves to inhibit the growth of Listeria monocytogenes (Lm) Scott A. Treatments consisted of sodium lactate (SL; 3.6%), potassium lactate (PL; 3.6%), sodium citrate (SC; 0.75%), a combination of SL and sodium diacetate (SDA; 0.25%), and a combination of SL/PL/SDA, alongside appropriate negative and positive controls. Products were inoculated with 10(4)-10(5) CFU/mL streptomycin-resistant (1500 μg/mL) Lm Scott A prior to treatment. Products were then stored at ~4°C and sampled at 0, 7, 14, 21, 28, 42, and 56 d. The SL/SDA combination applied to turkey slices extended the lag phase through 21 days of refrigerated storage. Numbers of Lm Scott A rose by 0.7 log10 CFU/g through the 56 d storage period. The application of the SL/PL/SDA treatment to turkey product surfaces extended the lag phase through 42 d, with pathogen numbers declining after 21 d. Combination organic acid dips prolonged the lag phase for 2 to 6 wk on turkey product surfaces and can be useful as antimicrobial agents for Lm control on postlethality exposed sliced deli products.

  1. Demonstrating concepts of pathogenesis using effectors of Phytophthora infestans

    Science.gov (United States)

    Pathogenesis, or how pathogens cause disease, is an important concept in plant pathology. The study of pathogenesis in plant pathology has rapidly expanded and is now a significant portion of plant pathology research (especially research at the molecular level of host-pathogen interaction). With the...

  2. Aetio-pathogenesis of breast cancer | Abdulkareem | Nigerian ...

    African Journals Online (AJOL)

    This is a literature review on the aetiology and pathogenesis of breast cancer, which is the most common cancer worldwide, and the second leading cause of cancer death, especially in Western countries. Several aetiological factors have been implicated in its pathogenesis, and include age, genetics, family history, diet, ...

  3. Tryptophan-induced pathogenesis of breast cancer | Cao | African ...

    African Journals Online (AJOL)

    Background: The pathogenesis of breast cancer remains unclear. Aims: To investigate the pathogenesis of breast cancer through targeted metabolomics of amino acids components in serum of patients with breast cancer. Methods: Patients with breast cancers were enrolled in our hospital between year January 1st, 2013 ...

  4. Pathogenesis of Nervous and Mental Diseases in Children.

    Science.gov (United States)

    Harms, Ernest, Ed.

    Major pathogenic sources of mental diseases in children and a classification of these diseases are considered. Contributions include the following: pathogenesis of mental diseases in childhood by Ernest Harms, organ inferiority and psychiatric disorders by Bernard Shulman and Howard Klapman, pathogenesis of neurological disorders by George Gold,…

  5. National HIV Testing Day

    Centers for Disease Control (CDC) Podcasts

    2011-06-09

    Dr. Kevin A. Fenton, Director of CDC's National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, discusses National HIV Testing Day, an annual observance which raises awareness of the importance of knowing one's HIV status and encourages at-risk individuals to get an HIV test.  Created: 6/9/2011 by National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention (NCHHSTP).   Date Released: 6/9/2011.

  6. Eliminating Perinatal HIV Transmission

    Centers for Disease Control (CDC) Podcasts

    2012-11-26

    In this podcast, CDC’s Dr. Steve Nesheim discusses perinatal HIV transmission, including the importance of preventing HIV among women, preconception care, and timely HIV testing of the mother. Dr. Nesheim also introduces the revised curriculum Eliminating Perinatal HIV Transmission intended for faculty of OB/GYN and pediatric residents and nurse midwifery students.  Created: 11/26/2012 by Division of HIV/AIDS Prevention.   Date Released: 11/26/2012.

  7. [Transthyretin: it's miracle function and pathogenesis].

    Science.gov (United States)

    Ando, Yukio

    2009-03-01

    Transthyretin (TTR) was previously called prealbumin because the band it formed on agarose gel electrophoresis at pH 8.6 was at the prealbumin position. However, it has been well documented that TTR of rodents does not show a prealbumin position on electrophoresis. Now, its name describes its function, binding to retinol binding protein (RBP) and T4. The serum concentration of the protein is 20-40 mg/dl, and TTR forms a tetramer. The plasma half life of the protein is 1.9 days. TTR is synthesized by the liver, retina, pancreas, and choroid plexus. In cerebro-spinal fluid (CSF), it is the second most abundant protein, and is considered as an important protein in the pathogenesis of Alzheimer's disease, depression, and lead intoxication. In addition, TTR is a tryptophan-rich protein, it is used as one of the nutrition assessment proteins, it acts as an anti acute phase protein, and its plasma concentration decreases during inflammation and bacterial infection. Since TTR is a highly amyloidogenic protein because it contains a beta-sheet structure, it becomes a precursor protein in familial amyloidotic polyneuropathy(FAP). Moreover, TTR plays important roles in various CNS disorders, diabetes melitus, and lipid metabolism.

  8. Misbehaving macrophages in the pathogenesis of psoriasis.

    Science.gov (United States)

    Clark, Rachael A; Kupper, Thomas S

    2006-08-01

    Psoriasis is a chronic inflammatory skin disease unique to humans. In this issue of the JCI, 2 studies of very different mouse models of psoriasis both report that macrophages play a key role in inducing psoriasis-like skin disease. Psoriasis is clearly a polygenic, inherited disease of uncontrolled cutaneous inflammation. The debate that currently rages in the field is whether psoriasis is a disease of autoreactive T cells or whether it reflects an intrinsic defect within the skin--or both. However, these questions have proven difficult to dissect using molecular genetic tools. In the current studies, the authors have used 2 different animal models to address the role of macrophages in disease pathogenesis: Wang et al. use a mouse model in which inflammation is T cell dependent, whereas the model used by Stratis et al. is T cell independent (see the related articles beginning on pages 2105 and 2094, respectively). Strikingly, both groups report an important contribution by macrophages, implying that macrophages can contribute to both epithelial-based and T cell-mediated pathways of inflammation.

  9. Canine neosporosis: perspectives on pathogenesis and management

    Directory of Open Access Journals (Sweden)

    Silva RC

    2016-04-01

    Full Text Available Rodrigo C Silva,1 Gustavo P Machado2 1Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA; 2Department of Internal Medicine and Surgery of Small Animals, Dr Munhoz Veterinary Hospital, Itápolis, Brazil Abstract: Canine neosporosis is a worldwide disease caused by the obligate intracellular parasite protozoan Neospora caninum, manifesting mainly neurological symptoms. N. caninum has a heteroxenous life cycle and affects a wide range of warm-blooded animals. The domestic and wild canids are the definitive host of the parasite. They shed oocysts after ingestion of tissue cysts from infected intermediate hosts (ovine, equine, bovine, canine, and many other species, containing bradyzoites, or oocyst-contaminated water and food. The presence of dogs in farms is considered a risk factor for production animals. A wide range of diagnostic methods are currently available, but the most used is serology, ie, indirect fluorescent antibody test specific to the antibody detection in blood serum samples. No vaccine is available, but control strategies should be focused on the vertical and horizontal transmission of the parasite, ie, avoid feeding dogs with raw or undercooked meat, and taking care with water for human and animal consumption. No medicines to control the transplacental transmission are available yet. Keywords: neosporosis, Neospora caninum, pathogenesis, management, dogs

  10. Fibromyalgia Pathogenesis and Treatment Options Update.

    Science.gov (United States)

    Chinn, Steven; Caldwell, William; Gritsenko, Karina

    2016-04-01

    This review article presents and summarizes up-to-date literature on the clinical manifestations, diagnosis, pathophysiological mechanisms, and treatment options for fibromyalgia patients. First, the most recent diagnostic criteria for fibromyalgia, as put forth by the American College of Rheumatology will be summarized. Clinical features, including chronic widespread pain, hyperalgesia, mood disorders, anxiety, and disturbed sleep patterns will be explored in-depth. The pathogenesis and pathophysiology of fibromyalgia involves alterations in multiple ascending and descending central nervous system pathways, as well as peripheral pathways, leading to heightened pain sensitivity. Risk factors have been studied extensively, and the most recent research focuses on various genetic influences and the contributions of stress and poor sleep. Lastly, the discussion in this article focuses on treatment options for fibromyalgia; some have been mainstay options for many years. Pharmacological agents include tricyclic antidepressants, anti-epileptic drugs, selective serotonin reuptake inhibitors, norepinephrine/serotonin reuptake inhibitors, as well as some investigational agents. The evidence behind non-pharmacologic treatments, including massage therapy, exercise, and acupuncture, are discussed.

  11. Achondroplasia: pathogenesis and implications for future treatment.

    Science.gov (United States)

    Laederich, Melanie B; Horton, William A

    2010-08-01

    Although the genetic defect underlying achondroplasia has been known for over a decade, no effective therapies to stimulate bone growth have emerged. Here we review the recent literature and summarize the molecular mechanisms underlying disease pathology and examine their potential as therapeutic targets. Currently used preclinical models are discussed in the context of recent advances with a special focus on C-type natriuretic peptide. Research on the mutation in Fibroblast Growth Factor Receptor 3 (FGFR3) that causes achondroplasia suggests that disease results from increased signal transduction from the mutant receptor. Thus, current therapeutic strategies have focused on reducing signals emanating from FGFR3. First-generation therapies directly targeting FGFR3, such as kinase inhibitors and neutralizing antibodies, designed for targeting FGFR3 in cancer, are still in the preclinical phase and have yet to translate into the management of achondroplasia. Counteracting signal transduction pathways downstream of FGFR3 holds promise with the discovery that administration of C-type natriuretic peptide to achondroplastic mice ameliorates their clinical phenotype. However, more research into long-term effectiveness and safety of this strategy is needed. Direct targeting of therapeutic agents to growth plate cartilage may enhance efficacy and minimize side effects of these and future therapies. Current research into the pathogenesis of achondroplasia has expanded our understanding of the mechanisms of FGFR3-induced disease and has increased the number of approaches that we may use to potentially correct it. Further research is needed to validate these approaches in preclinical models of achondroplasia.

  12. Celiac disease: Prevalence, diagnosis, pathogenesis and treatment

    Science.gov (United States)

    Gujral, Naiyana; Freeman, Hugh J; Thomson, Alan BR

    2012-01-01

    Celiac disease (CD) is one of the most common diseases, resulting from both environmental (gluten) and genetic factors [human leukocyte antigen (HLA) and non-HLA genes]. The prevalence of CD has been estimated to approximate 0.5%-1% in different parts of the world. However, the population with diabetes, autoimmune disorder or relatives of CD individuals have even higher risk for the development of CD, at least in part, because of shared HLA typing. Gliadin gains access to the basal surface of the epithelium, and interact directly with the immune system, via both trans- and para-cellular routes. From a diagnostic perspective, symptoms may be viewed as either “typical” or “atypical”. In both positive serological screening results suggestive of CD, should lead to small bowel biopsy followed by a favourable clinical and serological response to the gluten-free diet (GFD) to confirm the diagnosis. Positive anti-tissue transglutaminase antibody or anti-endomysial antibody during the clinical course helps to confirm the diagnosis of CD because of their over 99% specificities when small bowel villous atrophy is present on biopsy. Currently, the only treatment available for CD individuals is a strict life-long GFD. A greater understanding of the pathogenesis of CD allows alternative future CD treatments to hydrolyse toxic gliadin peptide, prevent toxic gliadin peptide absorption, blockage of selective deamidation of specific glutamine residues by tissue, restore immune tolerance towards gluten, modulation of immune response to dietary gliadin, and restoration of intestinal architecture. PMID:23155333

  13. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  14. Premature ovarian insufficiency: Pathogenesis and management

    Directory of Open Access Journals (Sweden)

    Anna J Fenton

    2015-01-01

    Full Text Available The term premature ovarian insufficiency (POI describes a continuum of declining ovarian function in a young woman, resulting in an earlier than average menopause. It is a term that reflects the variable nature of the condition and is substantially less emotive than the formerly used "premature ovarian failure" which signaled a single event in time. Contrary to the decline in the age of menarche seen over the last 3-4 decades there has been no similar change in the age of menopause. In developed nations, the average age for cessation of menstrual cycles is 50-52 years. The age is younger among women from developing nations. Much has been written about POI despite a lack of good data on the incidence of this condition. It is believed that 1% of women under the age of 40 years and 0.1% under the age of 30 years will develop POI. Research is increasingly providing information about the pathogenesis and treatments are being developed to better preserve ovarian function during cancer treatment and to improve fertility options. This narrative review summarizes the current literature to provide an approach to best practice management of POI.

  15. β-Cell Autophagy in Diabetes Pathogenesis.

    Science.gov (United States)

    Marasco, Michelle R; Linnemann, Amelia K

    2018-05-01

    Nearly 100 years have passed since Frederick Banting and Charles Best first discovered and purified insulin. Their discovery and subsequent improvements revolutionized the treatment of diabetes, and the field continues to move at an ever-faster pace with respect to unique treatments for both type 1 and type 2 diabetes. Despite these advances, we still do not fully understand how apoptosis of the insulin-producing β-cells is triggered, presenting a challenge in the development of preventative measures. In recent years, the process of autophagy has generated substantial interest in this realm due to discoveries highlighting its clear role in the maintenance of cellular homeostasis. As a result, the number of studies focused on islet and β-cell autophagy has increased substantially in recent years. In this review, we will discuss what is currently known regarding the role of β-cell autophagy in type 1 and type 2 diabetes pathogenesis, with an emphasis on new and exciting developments over the past 5 years. Further, we will discuss how these discoveries might be translated into unique treatments in the coming years.

  16. The Pathogenesis of Ebola Virus Disease.

    Science.gov (United States)

    Baseler, Laura; Chertow, Daniel S; Johnson, Karl M; Feldmann, Heinz; Morens, David M

    2017-01-24

    For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.

  17. Molecular Diagnostic and Pathogenesis of Hereditary Hemochromatosis

    Directory of Open Access Journals (Sweden)

    Paulo C. J. L. Santos

    2012-02-01

    Full Text Available Hereditary hemochromatosis (HH is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin pigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.Cys282Tyr or p.Cys282Tyr/p.His63Asp compound heterozygosity. In addition to HFE gene, mutations in the genes that encode hemojuvelin (HJV, hepcidin (HAMP, transferrin receptor 2 (TFR2 and ferroportin (SLC40A1 have been associated with regulation of iron homeostasis and development of HH. The aim of this review was to identify the main gene mutations involved in the pathogenesis of type 1, 2, 3 and 4 HH and their genetic testing indication. HFE testing for the two main mutations (p.Cys282Tyr and p.His63Asp should be performed in all patients with primary iron overload and unexplained increased transferrin saturation and/or serum ferritin values. The evaluation of the HJV p.Gly320Val mutation must be the molecular test of choice in suspected patients with juvenile hemochromatosis with less than 30 years and cardiac or endocrine manifestations. In conclusion, HH is an example that genetic testing can, in addition to performing the differential diagnostic with secondary iron overload, lead to more adequate and faster treatment.

  18. Pathogenesis of bovine spongiform encephalopathy in sheep.

    Science.gov (United States)

    van Keulen, L J M; Vromans, M E W; Dolstra, C H; Bossers, A; van Zijderveld, F G

    2008-01-01

    The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrP(Sc)) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrP(Sc) was detected after 6 months in the tonsil and the ileal Peyer's patches. At 9 months postinfection, PrP(Sc) accumulation involved all gut-associated lymphoid tissues and lymph nodes as well as the spleen. At this time point, PrP(Sc) accumulation in the peripheral neural tissues was first seen in the enteric nervous system of the caudal jejunum and ileum and in the coeliac-mesenteric ganglion. In the central nervous system, PrP(Sc) was first detected in the dorsal motor nucleus of the nervus Vagus in the medulla oblongata and in the intermediolateral column in the spinal cord segments T7-L1. At subsequent time points, PrP(Sc) was seen to spread within the lymphoid system to also involve all non-gut-associated lymphoid tissues. In the enteric nervous system, further spread of PrP(Sc) involved the neural plexi along the entire gastrointestinal tract and in the CNS the complete neuraxis. These findings indicate a spread of the BSE agent in sheep from the enteric nervous system through parasympathetic and sympathetic nerves to the medulla oblongata and the spinal cord.

  19. Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines.

    Science.gov (United States)

    Phipps, Elizabeth; Prasanna, Devika; Brima, Wunnie; Jim, Belinda

    2016-06-06

    Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after. Copyright © 2016 by the American Society of Nephrology.

  20. Large granular lymphocytic leukaemia pathogenesis and management.

    Science.gov (United States)

    Dearden, Claire

    2011-02-01

    The WHO classification recognises three distinct disorders of large granular lymphocytes: T-cell large granular lymphocytic leukaemia (T-LGL), chronic lymphoproliferative disorders of NK-cells (CLPD-NK) and agressive NK-cell leukaemia. Despite the different cell of origin, there is considerable overlap between T-LGL and CLPD-NK in terms of clinical presentation and therapy. Many patients are asymptomatic and do not require treatment. Therapy, with immunosuppressant agents such as low dose methotrexate or ciclosporin, is usually indicated to correct cytopenias. In contrast, aggressive NK-cell leukaemia and the rare CD56(+) aggressive T-LGL leukaemia follow a fulminant clinical course, affect younger individuals and require more intensive combination chemotherapy followed by allogeneic stem cell transplant in eligible patients. The relative rarity of these disorders means that there have been few clinical trials to inform management. However, there is now considerable interest in the pathogenesis of the chronic LGL leukaemias and this has stimulated early trials to evaluate novel agents which target the dysregulated apoptotic pathways characteristic of this disease. © 2010 Blackwell Publishing Ltd.

  1. Pathogenesis of trypanosome infections in cattle

    International Nuclear Information System (INIS)

    Murray, M.; Morrison, W.I.; Emery, D.L.; Akol, G.W.O.; Masake, R.A.; Moloo, S.K.

    1980-01-01

    The potential application of radioisotopes are not discussed in this review of trypanosome pathogenesis in cattle. Initially, structural changes in the lymphoid system are characterized by marked proliferation and germinal centre formation, whereas in long-standing infections the lymphoid organs become depleted. These changes appear associated with immunodepression. Anaemia dominates the clinical disease syndrome in bovine trypanosomiasis. It develops with the onset of parasitaemia and is largely haemolytic, resulting from increased red blood cell destruction by phagocytosis. Several factors may be involved in this process including haemolysins produced by the trypanosome, immunological mechanisms, fever, disseminated intravascular coagulation and an expanded and active mononuclear phagocytic system. During this phase of the disease, cattle respond well to chemotherapy. However, in later phases of the disease, when trypanosomes cannot be detected, the anaemia sometimes persists and animals do not respond to treatment. Concerning the underlying mechanisms responsible for the anaemia, continued red cell destruction combined with some dyshaemopoiesis, associated with a defect in iron metabolism, appears responsible. Widespread tissue degeneration occurs. Organs particularly severely affected include the heart. Death in bovine trypanosomiasis is presumably due to a combination of anaemia, microcirculatory disturbances and myocardial damage. The factors incriminated in tissue damage probably vary with the species of trypanosome involved, although under natural field conditions it is common to find T. congolense, T. vivax and T. brucei in one animal. Likely pathogenic mechanisms in bovine include anoxia as a result of anaemia, microcirculatory disorders and hypersensitivity reactions

  2. Pathogenesis and prognosis of bilateral thalamic infarction

    International Nuclear Information System (INIS)

    Nakase, Taizen; Ogura, Naoko; Maeda, Tetsuya; Yamazaki, Takashi; Kameda, Tomoaki; Sato, Yuichi; Nagata, Ken

    2008-01-01

    Only a few reports have discussed the detailed clinical symptoms and pathogenesis of bilateral thalamic infarction. The thalamus is composed of different functional nuclei and supplied by vessels containing several variations from the main arteries, leading to difficulty in the precise evaluation of bilateral thalamic infarction. In the present study, we assessed the prognosis of bilateral thalamic infarction based on the distribution of stroke lesions. From among the consecutive ischemic stroke patients admitted to hospital between April 2001 and March 2005, cases of acute bilateral thalamic infarction were selected for this study (n=9; 65.1±13.6 y.o.). The stroke lesions and vascular abnormalities were investigated by magnetic resonance imaging and magnetic resonance angiography on admission. Outcome was evaluated from the modified Rankin scale (mRS) at discharge. Good outcome patients (mRS 0-2; n=5) showed memory disturbance, cognitive impairment and hypersomnia. On the other hand, quadriplegia, oculomotor disturbance and bulbar palsy were observed in the poor outcome patients (mRS≥4; n=4). The critical features of a poor outcome were the age at onset (72.0±15.3 vs. 58.2±11.9 y.o.), inclusion of brainstem lesions and total occlusion of the basilar artery. In conclusion, older age at onset and/or basilar artery occlusion may be critical factors for predicting a poor outcome in bilateral thalamic infarction cases. (author)

  3. New Insights into the Pathogenesis of Pancreatitis

    Science.gov (United States)

    Sah, Raghuwansh P.; Dawra, Rajinder K.; Saluja, Ashok K.

    2014-01-01

    Purpose of review In this article, we review important advances in our understanding of the mechanisms of pancreatitis. Recent Findings The relative contribution of intra-pancreatic trypsinogen activation and NFκB activation, the two major early independent cellular events in the etiology of pancreatitis, have been investigated using novel genetic models. Trypsinogen activation has traditionally held the spotlight for many decades as it is believed to be the central pathogenic event of pancreatitis However, recent experimental evidence points to the role of trypsin activation in early acinar cell damage but not in the inflammatory response of acute pancreatitis through NFκB activation. Further, chronic pancreatitis in the caerulein model develops independently of typsinogen activation. Sustained activation of the NFκB pathway, but not persistent intra-acinar expression of active trypsin, was shown to result in chronic pancreatitis. Calcineurin-NFAT signaling was shown to mediate downstream effects of pathologic rise in intracellular calcium. IL-6 was identified as a key cytokine mediating pancreatitis-associated lung injury. Summary Recent advances challenge the long-believed trypsin-centered understanding of pancreatitis. It is becoming increasingly clear that activation of intense inflammatory signaling mechanisms in acinar cells is crucial to the pathogenesis of pancreatitis, which may explain the strong systemic inflammatory response in pancreatitis. PMID:23892538

  4. Hemophagocytic Lymphohistiocytosis in Children: Pathogenesis and Treatment

    Science.gov (United States)

    Ishii, Eiichi

    2016-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder in children that is characterized by persistent fever, splenomegaly with cytopenia, hypertriglyceridemia, and hypofibrinogenemia. Increased levels of various cytokines and soluble interleukin-2 receptor are biological markers of HLH. HLH can be classified into two major forms: primary and secondary. Familial hemophagocytic lymphohistiocytosis (FHL), a type of primary HLH, is an autosomal recessive disorder that typically occurs in infancy and can be classified into five different subtypes (FHL types 1–5). In Japan, >80% of patients with FHL have either PRF1 (FHL type 2) or UNC13D (FHL type 3) defects. FHL is considered to be a disorder of T-cell function because the activity of NK cells or cytotoxic T lymphocytes as target cells is usually impaired. Moreover, Epstein–Barr virus-associated HLH (EBV-HLH) is considered a major subtype of secondary HLH. Any genetic background could have an effect on the pathogenesis of secondary HLH because EBV-HLH is considered to be particularly prevalent in Asian countries. For primary HLH, hematopoietic stem cell transplantation is the only accepted curative therapy, although cord blood transplantation with a reduced-conditioning regimen has been used with superior outcomes. For secondary HLH, including EBV-HLH, immunochemotherapy based on the HLH-2004 protocol has been used. In the near future, the entire mechanism of HLH should be clarified to establish less toxic therapies, including cell therapy and gene targeting therapy. PMID:27242976

  5. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    International Nuclear Information System (INIS)

    Nandy, Debashis; Mukhopadhyay, Debabrata

    2011-01-01

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

  6. Road Bridges and Culverts, MDTA Culverts, Culverts on John F. Kennedy Highway (I95), Baltimore Harbor Tunnel Throughway, Francis Scott Key Bridge, Bay bridge, Nice Bridge, Published in 2010, 1:1200 (1in=100ft) scale, Maryland Transportation Authority.

    Data.gov (United States)

    NSGIC State | GIS Inventory — Road Bridges and Culverts dataset current as of 2010. MDTA Culverts, Culverts on John F. Kennedy Highway (I95), Baltimore Harbor Tunnel Throughway, Francis Scott Key...

  7. Care of HIV-exposed and HIV-infected neonates

    African Journals Online (AJOL)

    However, further reduction in MTCT may be possible if newborns at high risk of acquiring HIV ... infants of breastfeeding mothers with newly diagnosed HIV infection, dual NVP/ .... birth HIV DNA PCR testing for HIV-exposed low birth weight.

  8. Side Effects of HIV Medicines: HIV and Diabetes

    Science.gov (United States)

    ... Children and Adolescents HIV and Women HIV and Gay and Bisexual Men HIV and Older Adults HIV ... throughout the body. A hormone called insulin helps move the glucose into the cells. Once in the ...

  9. Interferon-inducible protein 10 (IP-10) is associated with viremia of early HIV-1 infection in Korean patients.

    Science.gov (United States)

    Lee, SoYong; Chung, Yoon-Seok; Yoon, Cheol-Hee; Shin, YoungHyun; Kim, SeungHyun; Choi, Byeong-Sun; Kim, Sung Soon

    2015-05-01

    Cytokines/chemokines play key roles in modulating disease progression in human immunodeficiency virus (HIV) infection. Although it is known that early HIV-1 infection is associated with increased production of proinflammatory cytokines, the relationship between cytokine levels and HIV-1 pathogenesis is not clear. The concentrations of 18 cytokines/chemokines in 30 HIV-1 negative and 208 HIV-1 positive plasma samples from Korean patients were measured by the Luminex system. Early HIV-1 infection was classified according to the Fiebig stage (FS) based on the characteristics of the patients infected with HIV-1. Concentrations of interleukin-12 (IL-12), interferon-inducible protein-10 (IP-10), macrophage inflammatory protein-1α (MIP-1α) and regulated upon activation, normal T cells expressed and secreted (RANTES) were increased significantly during the early stage of HIV-1 infection (FS II-IV) compared with the HIV-1-negative group. Of these cytokines, an elevated level of IP-10 was the only factor to be correlated positively with a higher viral load during the early stages of HIV-1 infection (FS II-IV) in Koreans (R = 0.52, P IP-10 may be an indicator for HIV-1 viremia and associated closely with viral replication in patients with early HIV-1 infection. © 2015 Wiley Periodicals, Inc.

  10. Macrophage Resistance to HIV-1 Infection Is Enhanced by the Neuropeptides VIP and PACAP

    Science.gov (United States)

    Temerozo, Jairo R.; Joaquim, Rafael; Regis, Eduardo G.; Savino, Wilson; Bou-Habib, Dumith Chequer

    2013-01-01

    It is well established that host factors can modulate HIV-1 replication in macrophages, critical cells in the pathogenesis of HIV-1 infection due to their ability to continuously produce virus. The neuropeptides VIP and PACAP induce well-characterized effects on macrophages through binding to the G protein-coupled receptors VPAC1, VPAC2 and PAC1, but their influence on HIV-1 production by these cells has not been established. Here, we describe that VIP and PACAP reduce macrophage production of HIV-1, acting in a synergistic or additive manner to decrease viral growth. Using receptor antagonists, we detected that the HIV-1 inhibition promoted by VIP is dependent on its ligation to VPAC1/2, whereas PACAP decreases HIV-1 growth via activation of the VPAC1/2 and PAC1 receptors. Specific agonists of VPAC2 or PAC1 decrease macrophage production of HIV-1, whereas sole activation of VPAC1 enhances viral growth. However, the combination of specific agonists mimicking the receptor preference of the natural neuropeptides reproduces the ability of VIP and PACAP to increase macrophage resistance to HIV-1 replication. VIP and PACAP up-regulated macrophage secretion of the β-chemokines CCL3 and CCL5 and the cytokine IL-10, whose neutralization reversed the neuropeptide-induced inhibition of HIV-1 replication. Our results suggest that VIP and PACAP and the receptors VPAC2 and PAC1 could be used as targets for developing alternative therapeutic strategies for HIV-1 infection. PMID:23818986

  11. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors associated with ... Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) is the ...

  12. Global HIV/AIDS Epidemic

    Science.gov (United States)

    ... Policy The Global HIV/AIDS Epidemic The Global HIV/AIDS Epidemic Published: Nov 29, 2017 Facebook Twitter ... 2001-FY 2018 Request The Global Response to HIV/AIDS International efforts to combat HIV began in ...

  13. HIV/AIDS in Women

    Science.gov (United States)

    HIV stands for human immunodeficiency virus. It harms your immune system by destroying the white blood cells ... It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. HIV often ...

  14. HIV / AIDS: An Unequal Burden

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV / AIDS: An Unequal Burden Past Issues / Summer 2009 ... high-risk category, emphasizes Dr. Cargill. Photo: iStock HIV and Pregnancy Are there ways to help HIV- ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... contracting or transmitting HIV/AIDS or other infectious diseases. Research Reports: HIV/AIDS : Explores the link between drug misuse and HIV/AIDS, populations most at risk, trends in HIV/AIDS, and ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... help us Send the Message . Get the Facts What are HIV and AIDS? HIV (human immunodeficiency virus) ... hiv-aids-101/statistics/ . Reference Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, National ...

  17. Gastrointestinal viral load and enteroendocrine cell number are associated with altered survival in HIV-1 infected individuals.

    Directory of Open Access Journals (Sweden)

    Guido van Marle

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS. The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to immunodeficiency, HIV-1 infection also directly causes gastrointestinal (GI dysfunction, also known as HIV enteropathy. This enteropathy can manifest itself as many pathological changes in the GI tract. The objective of this study was to determine the association of gut HIV-1 infection markers with long-term survival in a cohort of men who have sex with men (MSM enrolled pre-HAART (Highly Active Antiretroviral Therapy. We examined survival over 15-years in a cohort of 42 HIV-infected cases: In addition to CD4+ T cell counts and HIV-1 plasma viral load, multiple gut compartment (duodenum and colon biopsies were taken by endoscopy every 6 months during the initial 3-year period. HIV-1 was cultured from tissues and phenotyped and viral loads in the gut tissues were determined. Moreover, the tissues were subjected to an extensive assessment of enteroendocrine cell distribution and pathology. The collected data was used for survival analyses, which showed that patients with higher gut tissue viral load levels had a significantly worse survival prognosis. Moreover, lower numbers of serotonin (duodenum and somatostatin (duodenum and colon immunoreactive cell counts in the gut tissues of patients was associated with significant lower survival prognosis. Our study, suggested that HIV-1 pathogenesis and survival prognosis is associated with altered enteroendocrine cell numbers, which could point to a potential role for enteroendocrine function in HIV infection and pathogenesis.

  18. Living with HIV/AIDS - Multiple Languages

    Science.gov (United States)

    ... HIV - Newly diagnosed with HIV, part 5 - English MP3 Children and HIV - Newly diagnosed with HIV, part 5 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 Children and HIV - Newly diagnosed with HIV, part ...

  19. The pathogenesis of malaria: a new perspective.

    Science.gov (United States)

    Mawson, Anthony R

    2013-04-01

    With 3·3 billion people at risk of infection, malaria remains one of the world's most significant health problems. Increasing resistance of the main causative parasite to currently available drugs has created an urgent need to elucidate the pathogenesis of the disease in order to develop new treatments. A possible clue to such an understanding is that the malaria parasite Plasmodium falciparum selectively absorbs vitamin A from the host and appears to use it for its metabolism; serum vitamin A levels are also reduced in children with malaria. Although vitamin A is essential in low concentration for numerous biological functions, higher concentrations are cytotoxic and pro-oxidant, and potentially toxic quantities of the vitamin are stored in the liver. During their life cycle in the host the parasites remain in the liver for several days before invading the red blood cells (RBCs). The hypothesis proposed is that the parasites emerge from the liver packed with vitamin A and use retinoic acid (RA), the main biologically active metabolite of vitamin A, as a cell membrane destabilizer to invade the RBCs throughout the body. The characteristic hemolysis and anemia of malaria and other symptoms of the disease may thus be manifestations of an endogenous form of vitamin A intoxication associated with high concentrations of RA but low concentrations of retinol (ROL). Retinoic acid released from the parasites may also affect the fetus and cause preterm birth and fetal growth restriction (FGR) as a function of the membranolytic and growth inhibitory effects of these compounds, respectively. Subject to testing, the hypothesis suggests that parasite vitamin A metabolism could become a new target for the treatment and prevention of malaria.

  20. Pathogenesis of diverticulosis and diverticular disease.

    Science.gov (United States)

    Walker, Marjorie M; Harris, Angela K

    2017-06-01

    Diverticulosis is defined by the presence of diverticula due to herniation of mucosa and muscularis mucosa through the muscularis propria at sites of vascular penetration in the colon and is asymptomatic in the vast majority affected. There are global differences of distribution, in Western industrialized societies, the most common site is in the left colon, but in Asia right sided diverticulosis predominates. Whilst present in 17.5% of a general population and 42% of all comers at endoscopy it is seen in 71% of those aged ≥80 years. Diverticular disease is defined as clinically significant and symptomatic diverticulosis, which may have an absence of macroscopically overt colitis and in true diverticulitis there is macroscopic inflammation of diverticula with related acute or chronic complications. Whilst overall, diverticulitis affects only 4% of those with diverticulosis, in younger patients (aged 40-49 years) this peaks at 11%. Diverticulosis is one of the most common chronic diseases, yet research in this field on pathogenesis has lagged behind other common conditions such as diabetes mellitus. However, in the last decade there have been major advances in taxonomy that can be used to relate to patients' outcome and treatment in both medicine and surgery. It has been shown there is an association with age, diet, drugs and smoking. Genetic studies have shown a familial association and a specific gene, TNFSF 15 may predict severity of disease. The role of the microbiome has been explored and microbial and metabolomic signatures are also important in predicting disease severity. That diverticulosis is a chronic disease is shown by mucosal pathology with subtle chronic inflammation present in those with asymptomatic diverticulosis and inflammation may lead to muscular hypertrophy, enteric nerve remodeling with disordered motility. The diverticulitis quality of life instrument shows that this condition impacts markedly on patients' well-being and prevention and

  1. Obesity Pathogenesis: An Endocrine Society Scientific Statement.

    Science.gov (United States)

    Schwartz, Michael W; Seeley, Randy J; Zeltser, Lori M; Drewnowski, Adam; Ravussin, Eric; Redman, Leanne M; Leibel, Rudolph L

    2017-08-01

    Obesity is among the most common and costly chronic disorders worldwide. Estimates suggest that in the United States obesity affects one-third of adults, accounts for up to one-third of total mortality, is concentrated among lower income groups, and increasingly affects children as well as adults. A lack of effective options for long-term weight reduction magnifies the enormity of this problem; individuals who successfully complete behavioral and dietary weight-loss programs eventually regain most of the lost weight. We included evidence from basic science, clinical, and epidemiological literature to assess current knowledge regarding mechanisms underlying excess body-fat accumulation, the biological defense of excess fat mass, and the tendency for lost weight to be regained. A major area of emphasis is the science of energy homeostasis, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time. Growing evidence suggests that obesity is a disorder of the energy homeostasis system, rather than simply arising from the passive accumulation of excess weight. We need to elucidate the mechanisms underlying this "upward setting" or "resetting" of the defended level of body-fat mass, whether inherited or acquired. The ongoing study of how genetic, developmental, and environmental forces affect the energy homeostasis system will help us better understand these mechanisms and are therefore a major focus of this statement. The scientific goal is to elucidate obesity pathogenesis so as to better inform treatment, public policy, advocacy, and awareness of obesity in ways that ultimately diminish its public health and economic consequences. Copyright © 2017 Endocrine Society.

  2. [Evolution of pathogenesis of atherosclerosis in phylogenesis].

    Science.gov (United States)

    Titov, V N

    2014-01-01

    The first atherosclerosis pandemics developed in phylogenesis when animals went out of the ocean, the second coincided with mutations of proteins that transferred zero-cholesterol esters, the third (present-day pandemics) results from disturbed biological function of trophology, abnormally high content of saturated fatty acids and their trans-forms in food, and blockade of bioavailability of polyenic FA (PNFA) for cells. The blood pool of ligand-free lipoproteins, phylogenetically early macrophages are only partly utilized in intima giving rise to atheromatosis. When active absorption of w-3 and w-6 PNFA is blocked, the cells synthesize by way of compensation non-physiological w-9 eicosanoids which creates the basis of pathogenesis of atherosclerosis, pathology ofautocrine regulation, and paracrine humoral regulation of cell communities and the body. A rise in the frequency of non-infectious diseases above 5-7% is regarded as pathology of biological functions and reactions. Non-physiological environmental effects should be neutralized by normalization of tropholgy function, exotrophic biological reaction. Metabolic pandemics may have two outcomes. First: (a) effective reduction to a minimum of infavourable environmental effects, i.e. normalization of the nutritive function, (b) matching it with possibilities of lipoproteins, (c) reduction of morbidity and mortality from atherosclerosis. Second: man continues to develop as in phylogenesis and adapts himself to nonphysiological nutrition. Mortality from infarction and stroke will remain high during the next 40-50 thousand years. Increased content of w-3 PNFA in food without reduction of NAF with blockade of bioavailability will further facilitate atheromatosis. Man should rely on physiological nutrition, there is no reason to rely on hypolipidemic agents. Otherwise, the second outcome awaits the mankind. Tertium non datum.

  3. Editorial | Scott | Ergonomics SA

    African Journals Online (AJOL)

    Ergonomics SA. Journal Home · ABOUT THIS JOURNAL · Advanced Search · Current Issue · Archives · Journal Home > Vol 23, No 1 (2011) >. Log in or Register to get access to full text downloads. Username, Password, Remember me, or Register. DOWNLOAD FULL TEXT Open Access DOWNLOAD FULL TEXT ...

  4. FLOODPLAIN, SCOTT COUNTY, IOWA

    Data.gov (United States)

    Federal Emergency Management Agency, Department of Homeland Security — The Floodplain Mapping/Redelineation study deliverables depict and quantify the flood risks for the study area. The primary risk classifications used are the...

  5. Comorbidities as risk factors of chronic kidney disease in HIV-infected persons

    Directory of Open Access Journals (Sweden)

    Zofia Marchewka

    2015-12-01

    Full Text Available Significant survival prolongation in HIV-infected patients due to effective antiretroviral therapy is connected with increasing prevalence of chronic non-infective diseases in this population, among them chronic kidney disease. The pathogenesis of kidney disease in the setting of HIV includes conditions specific for HIV infection: direct effect of the virus, stage of immunodeficiency and drug toxicity. Chronic comorbidities, such as diabetes mellitus, hypertension, and hyperlipidemia, are additional significant risk factors of kidney disease. In HIV-infected individuals some distinct features of these conditions are observed, which are partly related to the virus and antiretroviral therapy. The article summarizes the effect of comorbidities on kidney function in HIV-infected persons.

  6. [Comorbidities as risk factors of chronic kidney disease in HIV-infected persons].

    Science.gov (United States)

    Marchewka, Zofia; Szymczak, Aleksandra; Knysz, Brygida

    2015-12-16

    Significant survival prolongation in HIV-infected patients due to effective antiretroviral therapy is connected with increasing prevalence of chronic non-infective diseases in this population, among them chronic kidney disease. The pathogenesis of kidney disease in the setting of HIV includes conditions specific for HIV infection: direct effect of the virus, stage of immunodeficiency and drug toxicity. Chronic comorbidities, such as diabetes mellitus, hypertension, and hyperlipidemia, are additional significant risk factors of kidney disease. In HIV-infected individuals some distinct features of these conditions are observed, which are partly related to the virus and antiretroviral therapy. The article summarizes the effect of comorbidities on kidney function in HIV-infected persons.

  7. Novel host restriction factors implicated in HIV-1 replication.

    Science.gov (United States)

    Ghimire, Dibya; Rai, Madhu; Gaur, Ritu

    2018-04-01

    Human immunodeficiency virus-1 (HIV-1) is known to interact with multiple host cellular proteins during its replication in the target cell. While many of these host cellular proteins facilitate viral replication, a number of them are reported to inhibit HIV-1 replication at various stages of its life cycle. These host cellular proteins, which are known as restriction factors, constitute an integral part of the host's first line of defence against the viral pathogen. Since the discovery of apolipoprotein B mRNA-editing enzyme 3G (APOBEC3G) as an HIV-1 restriction factor, several human proteins have been identified that exhibit anti-HIV-1 restriction. While each restriction factor employs a distinct mechanism of inhibition, the HIV-1 virus has equally evolved complex counter strategies to neutralize their inhibitory effect. APOBEC3G, tetherin, sterile alpha motif and histidine-aspartate domain 1 (SAMHD1), and trim-5α are some of the best known HIV-1 restriction factors that have been studied in great detail. Recently, six novel restriction factors were discovered that exhibit significant antiviral activity: endoplasmic reticulum α1,2-mannosidase I (ERManI), translocator protein (TSPO), guanylate-binding protein 5 (GBP5), serine incorporator (SERINC3/5) and zinc-finger antiviral protein (ZAP). The focus of this review is to discuss the antiviral mechanism of action of these six restriction factors and provide insights into the probable counter-evasion strategies employed by the HIV-1 virus. The recent discovery of new restriction factors substantiates the complex host-pathogen interactions occurring during HIV-1 pathogenesis and makes it imperative that further investigations are conducted to elucidate the molecular basis of HIV-1 replication.

  8. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity...

  9. Stepping toward a Macaque Model of HIV-1 Induced AIDS

    Directory of Open Access Journals (Sweden)

    Jason T. Kimata

    2014-09-01

    Full Text Available HIV-1 exhibits a narrow host range, hindering the development of a robust animal model of pathogenesis. Past studies have demonstrated that the restricted host range of HIV-1 may be largely due to the inability of the virus to antagonize and evade effector molecules of the interferon response in other species. They have also guided the engineering of HIV-1 clones that can replicate in CD4 T-cells of Asian macaque species. However, while replication of these viruses in macaque hosts is persistent, it has been limited and without progression to AIDS. In a new study, Hatziioannou et al., demonstrate for the first time that adapted macaque-tropic HIV-1 can persistently replicate at high levels in pigtailed macaques (Macaca nemestrina, but only if CD8 T-cells are depleted at the time of inoculation. The infection causes rapid disease and recapitulates several aspects of AIDS in humans. Additionally, the virus undergoes genetic changes to further escape innate immunity in association with disease progression. Here, the importance of these findings is discussed, as they relate to pathogenesis and model development.

  10. Reflections on the pathogenesis of Down syndrome.

    Science.gov (United States)

    Opitz, J M; Gilbert-Barness, E F

    1990-01-01

    Present efforts to identify, isolate, and characterize in molecular terms the "consensus" segment of 21q sufficient to cause most of the major and some of the most characteristic minor manifestations of Down syndrome will soon provide answers to many questions. However, we think that a reductionist approach to explain the Down syndrome phenotype in a "linear" manner from the DNA sequence of the segment will be doomed to failure from the outset because of the open, complex, nonlinear, hierarchical nature of morphogenetic systems. Neo-Darwinism is under strong attack; most genetic changes accumulated over time may very well be of neutral effect, and detailed studies in several related groups of vertebrate species has shown that molecular and organismal evolution are largely independent of one another. It has been pointed out recently that biology lacks a theory of ontogenetic and phylogenetic development, and that a purely "genocentric" view of biology at the expense of the complexly hierarchical intrinsic epigenetic attributes of developmental systems is "out of focus with respect to ... biological organization and morphogenesis," and may be "a residue of nineteenth century romantic idealism." Down syndrome impresses us as a paradigm of increased developmental variability due to a deceleration of the rate of development (neoteny) with many anomalies of incomplete morphogenesis (vestigia), atavisms, increased morphometric variability with many decreased means, increased variances, and increased fluctuating asymmetry. These abnormalities, together with highly increased risk of prenatal death and postnatal morbidity, impaired growth, and abnormal CNS and gonadal structure and function characteristic of most aneuploidy syndromes, suggest to us that the pathogenesis of Down syndrome is best viewed in terms of the mechanisms of speciation. Transgenic experiment involving sequential or overlapping pieces of "the consensus segment" on distal 21q22.1-22.3 may help decide to

  11. Aetiology and pathogenesis of alcoholic liver disease.

    Science.gov (United States)

    Lieber, C S

    1993-09-01

    carcinogens and even nutritional factors such as vitamin A. Ethanol causes not only vitamin A depletion but it also enhances its hepatotoxicity. Furthermore, induction of the microsomal pathway contributes to increased acetaldehyde generation, with formation of protein adducts, resulting in antibody production, enzyme inactivation and decreased DNA repair; it is also associated with a striking impairment of the capacity of the liver to utilize oxygen. Moreover, acetaldehyde promotes glutathione depletion, free-radical mediated toxicity and lipid peroxidation. In addition, acetaldehyde affects hepatic collagen synthesis: both in vivo and in vitro (in cultured myofibroblasts and lipocytes), ethanol and its metabolite acetaldehyde were found to increase collagen accumulation and mRNA levels for collagen. This new understanding of the pathogenesis of alcoholic liver disease may eventually improve therapy with drugs and nutrients.

  12. Role of perfumes in pathogenesis of autism.

    Science.gov (United States)

    Bagasra, Omar; Golkar, Zhabiz; Garcia, Miranda; Rice, Lakya N; Pace, Donald Gene

    2013-06-01

    Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system and underdeveloped olfactory bulb (OB) has been associated with the disorder. It has been reported that the number of children who have ASD has increased considerably since the early 1990 s. In developed countries, it is now reported that 1-1.5% of children have ASD, and in the US it is estimated that one in 88 children suffer from ASD. Currently, there is no known cause for ASD. During the last three decades, the most commonly accepted paradigm about autism is that it is a genetically inherited disease. The recent trio analyses, in which both biological parents and the autistic child's exomes are sequenced, do not support this paradigm. On the other hand, the environmental factors that may induce genetic mutations in vitro have not been clearly identified, and there is little irrefutable evidence that pesticides, water born chemicals, or food preservatives play critical roles in inducing the genetic mutations associated with known intellectual deficiencies that have been linked to autism spectrum disorder (ASD). Here, we hypothesize and provide scientific evidence that ASD is the result of exposure to perfumes and cosmetics. The highly mutagenic, neurotoxic, and neuromodulatory chemicals found in perfumes are often overlooked and ignored as a result of a giant loophole in the Federal Fair Packaging and Labeling Act of 1973, which explicitly exempts fragrance producers from having to disclose perfume ingredients on product labels. We hypothesize that perfumes and cosmetics may be important factors in the pathogenesis of ASD. Synthetic perfumes have gained global utility not only as perfumes but also as essential chemicals in detergents

  13. Modifier genes: Moving from pathogenesis to therapy.

    Science.gov (United States)

    McCabe, Edward R B

    2017-09-01

    This commentary will focus on how we can use our knowledge about the complexity of human disease and its pathogenesis to identify novel approaches to therapy. We know that even for single gene Mendelian disorders, patients with identical mutations often have different presentations and outcomes. This lack of genotype-phenotype correlation led us and others to examine the roles of modifier genes in the context of biological networks. These investigations have utilized vertebrate and invertebrate model organisms. Since one of the goals of research on modifier genes and networks is to identify novel therapeutic targets, the challenges to patient access and compliance because of the high costs of medications for rare genetic diseases must be recognized. A recent article explored protective modifiers, including plastin 3 (PLS3) and coronin 1C (CORO1C), in spinal muscular atrophy (SMA). SMA is an autosomal recessive deficit of survival motor neuron protein (SMN) caused by mutations in SMN1. However, the severity of SMA is determined primarily by the number of SMN2 copies, and this results in significant phenotypic variability. PLS3 was upregulated in siblings who were asymptomatic compared with those who had SMA2 or SMA3, but identical homozygous SMN1 deletions and equal numbers of SMN2 copies. CORO1C was identified by interrogation of the PLS3 interactome. Overexpression of these proteins rescued endocytosis in SMA models. In addition, antisense RNA for upregulation of SMN2 protein expression is being developed as another way of modifying the SMA phenotype. These investigations suggest the practical application of protective modifiers to rescue SMA phenotypes. Other examples of the potential therapeutic value of novel protective modifiers will be discussed, including in Duchenne muscular dystrophy and glycerol kinase deficiency. This work shows that while we live in an exciting era of genomic sequencing, a functional understanding of biology, the impact of its

  14. PET brain imaging in HIV-associated neurocognitive disorders (HAND) in the era of combination antiretroviral therapy

    Energy Technology Data Exchange (ETDEWEB)

    Vera, Jaime H. [Brighton and Sussex Medical School, Department of Infection and Global Health, Brighton (United Kingdom); Brighton and Sussex University Hospitals NHS Trust, HIV Department, Brighton (United Kingdom); Ridha, Basil [Brighton and Sussex University Hospitals NHS Trust, Neurology Department, Brighton (United Kingdom); Gilleece, Yvonne; Amlani, Aliza [Brighton and Sussex University Hospitals NHS Trust, HIV Department, Brighton (United Kingdom); Thorburn, Patrick; Dizdarevic, Sabina [Brighton and Sussex University Hospitals NHS Trust, Imaging and Nuclear Medicine Department, Brighton (United Kingdom); Brighton and Sussex Medical School, Clinical Imaging Science Centre, Brighton (United Kingdom)

    2017-05-15

    Effective combination antiretroviral therapy (cART) has lead to a significant reduction in the prevalence and incidence of central nervous system (CNS) HIV-associated brain disease, particularly CNS opportunistic infections and HIV encephalitis. Despite this, cognitive deficits in people living with HIV, also known as HIV-associated neurocognitive disorders (HAND) have become more prevalent in recent years. The pathogenesis of HAND is likely to be multifactorial, however recent evidence suggests that brain microglial activation is the most likely pathogenic mechanism. Recent developments in positron emission tomography (PET) brain neuroimaging using novel brain radioligands targeting a variety of physiological changes in the brains of HIV-positive individuals have improved our understanding of the mechanisms associated with the development of HAND. This review will highlight recent PET brain neuroimaging studies in the cART era, focusing on physiological and neurochemical changes associated with HAND in people living with HIV. (orig.)

  15. PET brain imaging in HIV-associated neurocognitive disorders (HAND) in the era of combination antiretroviral therapy

    International Nuclear Information System (INIS)

    Vera, Jaime H.; Ridha, Basil; Gilleece, Yvonne; Amlani, Aliza; Thorburn, Patrick; Dizdarevic, Sabina

    2017-01-01

    Effective combination antiretroviral therapy (cART) has lead to a significant reduction in the prevalence and incidence of central nervous system (CNS) HIV-associated brain disease, particularly CNS opportunistic infections and HIV encephalitis. Despite this, cognitive deficits in people living with HIV, also known as HIV-associated neurocognitive disorders (HAND) have become more prevalent in recent years. The pathogenesis of HAND is likely to be multifactorial, however recent evidence suggests that brain microglial activation is the most likely pathogenic mechanism. Recent developments in positron emission tomography (PET) brain neuroimaging using novel brain radioligands targeting a variety of physiological changes in the brains of HIV-positive individuals have improved our understanding of the mechanisms associated with the development of HAND. This review will highlight recent PET brain neuroimaging studies in the cART era, focusing on physiological and neurochemical changes associated with HAND in people living with HIV. (orig.)

  16. Regulatory T Cells As Potential Targets for HIV Cure Research

    Science.gov (United States)

    Kleinman, Adam J.; Sivanandham, Ranjit; Pandrea, Ivona; Chougnet, Claire A.; Apetrei, Cristian

    2018-01-01

    T regulatory cells (Tregs) are a key component of the immune system, which maintain a delicate balance between overactive responses and immunosuppression. As such, Treg deficiencies are linked to autoimmune disorders and alter the immune control of pathogens. In HIV infection, Tregs play major roles, both beneficial and detrimental. They regulate the immune system such that inflammation and spread of virus through activated T cells is suppressed. However, suppression of immune activation also limits viral clearance and promotes reservoir formation. Tregs can be directly targeted by HIV, thereby harboring a fraction of the viral reservoir. The vital role of Tregs in the pathogenesis and control of HIV makes them a subject of interest for manipulation in the search of an HIV cure. Here, we discuss the origin and generation, homeostasis, and functions of Tregs, particularly their roles and effects in HIV infection. We also present various Treg manipulation strategies, including Treg depletion techniques and interventions that alter Treg function, which may be used in different cure strategies, to simultaneously boost HIV-specific immune responses and induce reactivation of the latent virus.

  17. Dopamine receptor activation increases HIV entry into primary human macrophages.

    Directory of Open Access Journals (Sweden)

    Peter J Gaskill

    Full Text Available Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers.

  18. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    Science.gov (United States)

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  19. Nucleolar protein trafficking in response to HIV-1 Tat: rewiring the nucleolus.

    Science.gov (United States)

    Jarboui, Mohamed Ali; Bidoia, Carlo; Woods, Elena; Roe, Barbara; Wynne, Kieran; Elia, Giuliano; Hall, William W; Gautier, Virginie W

    2012-01-01

    The trans-activator Tat protein is a viral regulatory protein essential for HIV-1 replication. Tat trafficks to the nucleoplasm and the nucleolus. The nucleolus, a highly dynamic and structured membrane-less sub-nuclear compartment, is the site of rRNA and ribosome biogenesis and is involved in numerous cellular functions including transcriptional regulation, cell cycle control and viral infection. Importantly, transient nucleolar trafficking of both Tat and HIV-1 viral transcripts are critical in HIV-1 replication, however, the role(s) of the nucleolus in HIV-1 replication remains unclear. To better understand how the interaction of Tat with the nucleolar machinery contributes to HIV-1 pathogenesis, we investigated the quantitative changes in the composition of the nucleolar proteome of Jurkat T-cells stably expressing HIV-1 Tat fused to a TAP tag. Using an organellar proteomic approach based on mass spectrometry, coupled with Stable Isotope Labelling in Cell culture (SILAC), we quantified 520 proteins, including 49 proteins showing significant changes in abundance in Jurkat T-cell nucleolus upon Tat expression. Numerous proteins exhibiting a fold change were well characterised Tat interactors and/or known to be critical for HIV-1 replication. This suggests that the spatial control and subcellular compartimentaliation of these cellular cofactors by Tat provide an additional layer of control for regulating cellular machinery involved in HIV-1 pathogenesis. Pathway analysis and network reconstruction revealed that Tat expression specifically resulted in the nucleolar enrichment of proteins collectively participating in ribosomal biogenesis, protein homeostasis, metabolic pathways including glycolytic, pentose phosphate, nucleotides and amino acids biosynthetic pathways, stress response, T-cell signaling pathways and genome integrity. We present here the first differential profiling of the nucleolar proteome of T-cells expressing HIV-1 Tat. We discuss how these

  20. mTOR as a multifunctional therapeutic target in HIV infection

    DEFF Research Database (Denmark)

    Nicoletti, Ferdinando; Fagone, Paolo; Meroni, PierLuigi

    2011-01-01

    Patients undergoing long-term highly active antiretroviral therapy treatment are probably at a higher risk of various HIV-related complications. Hyperactivation of The mammalian target of rapamycin (mTOR) has been found to contribute to dysregulated apoptosis and autophagy which determine CD4(+)-T......-cell loss, impaired function of innate immunity and development of neurocognitive disorders. Dysregulated mTOR activation has also been shown to play a key part in the development of nephropathy and in the pathogenesis of HIV-associated malignancies. These studies strongly support a multifunctional key role...... for mTOR in the pathogenesis of HIV-related disorders and suggest that specific mTOR inhibitors could represent a novel approach for the prevention and treatment of these pathologies....

  1. Necroptosis takes place in human immunodeficiency virus type-1 (HIV-1-infected CD4+ T lymphocytes.

    Directory of Open Access Journals (Sweden)

    Ting Pan

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 infection is characterized by progressive depletion of CD4+ T lymphocytes and dysfunction of the immune system. The numbers of CD4+ T lymphocytes in the human body are maintained constantly by homeostatic mechanisms that failed during HIV-1 infection, resulting in progressive loss of CD4+ T cells mainly via apoptosis. Recently, a non-apoptotic form of necrotic programmed cell death, named necroptosis, has been investigated in many biological and pathological processes. We then determine whether HIV-1-infected cells also undergo necroptosis. In this report, we demonstrate that HIV-1 not only induces apoptosis, but also mediates necroptosis in the infected primary CD4+ T lymphocytes and CD4+ T-cell lines. Necroptosis-dependent cytopathic effects are significantly increased in HIV-1-infected Jurkat cells that is lack of Fas-associated protein-containing death domain (FADD, indicating that necroptosis occurs as an alternative cell death mechanism in the absence of apoptosis. Unlike apoptosis, necroptosis mainly occurs in HIV-infected cells and spares bystander damage. Treatment with necrostatin-1(Nec-1, a RIP1 inhibitor that specifically blocks the necroptosis pathway, potently restrains HIV-1-induced cytopathic effect and interestingly, inhibits the formation of HIV-induced syncytia in CD4+ T-cell lines. This suggests that syncytia formation is mediated, at least partially, by necroptosis-related processes. Furthermore, we also found that the HIV-1 infection-augmented tumor necrosis factor-alpha (TNF-α plays a key role in inducing necroptosis and HIV-1 Envelope and Tat proteins function as its co-factors. Taken together,necroptosis can function as an alternative cell death pathway in lieu of apoptosis during HIV-1 infection, thereby also contributing to HIV-1-induced cytopathic effects. Our results reveal that in addition to apoptosis, necroptosis also plays an important role in HIV-1-induced pathogenesis.

  2. Oral candidiasis: pathogenesis, clinical presentation, diagnosis and treatment strategies.

    Science.gov (United States)

    Lalla, Rajesh V; Patton, Lauren L; Dongari-Bagtzoglou, Anna

    2013-04-01

    Oral candidiasis is a clinical fungal infection that is the most common opportunistic infection affecting the human oral cavity. This article reviews the pathogenesis, clinical presentations, diagnosis and treatmentstrategies for oral candidiasis.

  3. The Roles of Environmental Pollutants in the Pathogenesis and ...

    African Journals Online (AJOL)

    ADOWIE PERE

    Toxic chemicals in pollutants may destroy or cause mutation ... Keywords: Diabetes, Pathogenesis, Pancreas, Mutation, Insulin, Blood vessel. INTRODUCTION. Diabetes is a chronic disease that occurs either when .... alter insulin metabolism.

  4. [Morphology and pathogenesis of visceral manifestations of chronic alcoholism].

    Science.gov (United States)

    Lebedev, S P

    1982-01-01

    Chronic alcoholism is accompanied by systemic involvement of the internal organs. Clinico-morphological forms of chronic alcoholism are distinguished on the basis of the prevailing organ pathology, Morphological data are presented, and pathogenesis of the lesions of the liver, heart, pancreas, and kidneys in patients with chronic alcoholism is analysed. The hepatic form may present alcoholic dystrophy, hepatitis or cirrhosis which are stages of progressing hepatopathy. The toxic and metabolic effect of ethanol is important in the pathogenesis of liver lesion. The cardiac form is characterized by the development of alcoholic myocardiodystrophy. In addition to the toxic influence of ethanol, hormonal and electrolyte changes and microcirculatory disorders play a role in its pathogenesis. Chronic calcifying pancreatitis in chronic alcoholism is associated with the effect of ethanol on the mediatory system. The renal form any present necronephrosis, hepatorenal syndrome, glomerulonephritis or pyelonephritis. Their pathogenesis is determined by toxicity of ethanol, circulation of immune complexes in the blood, or immunosuppression.

  5. Tubuloreticular structures in different types of myositis: implications for pathogenesis

    NARCIS (Netherlands)

    Bronner, Irene M.; Hoogendijk, Jessica E.; Veldman, Henk; Ramkema, Marja; van den Bergh Weerman, Marius A.; Rozemuller, Annemieke J. M.; de Visser, Marianne

    2008-01-01

    In dermatomyositis (DM) there is strong histopathological evidence of a microvascular pathogenesis, including endothelial microtubular inclusions. In nonspecific myositis, perimysial and perivascular infiltrates in the muscle biopsy similar to DM are found. Microtubular inclusions in endothelial

  6. Tubuloreticular structures in different types of myositis: Implications for pathogenesis

    NARCIS (Netherlands)

    Bronner, I.M.; Hoogendijk, J.E.; Veldman, H.; Ramkema, M; Weerman, M.A.V.; Rozemuller, A.J.M.; Visser, M.

    2008-01-01

    In dermatomyositis (DM) there is strong histopathological evidence of a microvascular pathogenesis, including endothelial microtubular inclusions. In nonspecific myositis, perimysial and perivascular infiltrates in the muscle biopsy similar to DM are found. Microtubular inclusions in endothelial

  7. Current insights in sepsis: from pathogenesis to new treatment targets

    NARCIS (Netherlands)

    Wiersinga, W. Joost

    2011-01-01

    Sepsis continues to be a leading cause of ICU death. This review summarizes current knowledge on sepsis pathogenesis and new therapeutical strategies. Although systemic inflammatory response syndrome predominates in early sepsis, the compensatory anti-inflammatory response syndrome causes

  8. HIV and Hepatitis C

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV and Opportunistic Infections, Coinfections, and Conditions Home Understanding ... 4 p.m. ET) Send us an email HIV and Hepatitis C Last Reviewed: July 25, 2017 ...

  9. HIV/AIDS Basics

    Science.gov (United States)

    ... Partner Spotlight Awareness Days Get Tested Find an HIV testing site near you. Enter ZIP code or ... AIDS Get Email Updates on AAA Anonymous Feedback HIV/AIDS Media Infographics Syndicated Content Podcasts Slide Sets ...

  10. HIV and Tuberculosis (TB)

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV and Opportunistic Infections, Coinfections, and Conditions Home Understanding ... 4 p.m. ET) Send us an email HIV and Tuberculosis (TB) Last Reviewed: June 14, 2018 ...

  11. HIV and Hepatitis B

    Science.gov (United States)

    ... AIDS Drugs Clinical Trials Apps skip to content HIV and Opportunistic Infections, Coinfections, and Conditions Home Understanding ... 4 p.m. ET) Send us an email HIV and Hepatitis B Last Reviewed: July 24, 2017 ...

  12. Thrombocytopenia in HIV

    African Journals Online (AJOL)

    2007-06-15

    infected community and can severely hamper thrombopoietin production, due to liver damage. HIV and platelets. Thrombocytopenia in HIV was first described in 1982. The prevalence is more or less 40%, depending on which ...

  13. HIV Resistance Testing

    Science.gov (United States)

    ... 14, 2016 Select a Language: Fact Sheet 126 HIV Resistance Testing WHAT IS RESISTANCE? HOW DOES RESISTANCE ... ARVs. If you miss doses of your medications, HIV will multiply more easily. More mutations will occur. ...

  14. HIV: Treatment and Comorbidity

    NARCIS (Netherlands)

    C. Rokx (Casper)

    2016-01-01

    markdownabstractClinicians worldwide strive to improve HIV care for their patients. Antiretroviral therapy prevents HIV related mortality and is lifelong. A clinical evaluation of these treatment strategies is necessary to identify strategies that may jeopardize treatment effectiveness and patient

  15. Testing for HIV

    Science.gov (United States)

    ... Medical Devices Radiation-Emitting Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability (Biologics) HIV Home Test Kits Testing for HIV Share Tweet Linkedin Pin it More ...

  16. Pregnancy and HIV

    Science.gov (United States)

    ... 17, 2014 Select a Language: Fact Sheet 611 Pregnancy and HIV HOW DO BABIES GET AIDS? HOW CAN WE ... doses due to nausea and vomiting during early pregnancy, giving HIV a chance to develop resistance The risk of ...

  17. Engineering Cellular Resistance to HIV-1 Infection In Vivo Using a Dual Therapeutic Lentiviral Vector

    Directory of Open Access Journals (Sweden)

    Bryan P Burke

    2015-01-01

    Full Text Available We described earlier a dual-combination anti-HIV type 1 (HIV-1 lentiviral vector (LVsh5/C46 that downregulates CCR5 expression of transduced cells via RNAi and inhibits HIV-1 fusion via cell surface expression of cell membrane-anchored C46 antiviral peptide. This combinatorial approach has two points of inhibition for R5-tropic HIV-1 and is also active against X4-tropic HIV-1. Here, we utilize the humanized bone marrow, liver, thymus (BLT mouse model to characterize the in vivo efficacy of LVsh5/C46 (Cal-1 vector to engineer cellular resistance to HIV-1 pathogenesis. Human CD34+ hematopoietic stem/progenitor cells (HSPC either nonmodified or transduced with LVsh5/C46 vector were transplanted to generate control and treatment groups, respectively. Control and experimental groups displayed similar engraftment and multilineage hematopoietic differentiation that included robust CD4+ T-cell development. Splenocytes isolated from the treatment group were resistant to both R5- and X4-tropic HIV-1 during ex vivo challenge experiments. Treatment group animals challenged with R5-tropic HIV-1 displayed significant protection of CD4+ T-cells and reduced viral load within peripheral blood and lymphoid tissues up to 14 weeks postinfection. Gene-marking and transgene expression were confirmed stable at 26 weeks post-transplantation. These data strongly support the use of LVsh5/C46 lentiviral vector in gene and cell therapeutic applications for inhibition of HIV-1 infection.

  18. The HCV and HIV coinfected patient: what have we learned about pathophysiology?

    Science.gov (United States)

    Talal, Andrew H; Canchis, P Wilfredo; Jacobson, Ira

    2002-02-01

    Hepatitis C virus (HCV) infection is an important problem in individuals who are also infected with HIV. HCV infection is very common in HIV-infected individuals, occurring in approximately one quarter to one third of this group, presumably as a consequence of shared routes of transmission related to virologic and pathogenic aspects of the viral infections. Although both are single-stranded RNA viruses and share similar epidemiologic properties, there are many important differences. Although the quantity of HIV RNA in plasma is an important prognostic determinant of HIV infection, this has not been shown with HCV. A direct relationship is apparent between HIV-related destruction of CD4 cells and the clinical consequences of the disease resulting from immunodeficiency. The pathogenesis of HCV, which occurs as a consequence of hepatic fibrosis, is much more complex. The hepatic stellate cell, the major producer of the extracellular matrix protein, is the main contributor to hepatic fibrosis, but the mechanism by which HCV induces hepatic fibrosis remains unclear. Treatment of HCV is increasingly important in HIV-infected patients due to improved HIV-associated morbidity and mortality and due to the frequency with which HCV occurs in patients with HIV-HCV coinfection. Timing of treatment initiation, management of side effects, and possible effects of anti-HCV therapy on HIV are among the issues that need consideration. Also, because several issues concerning HCV are unique to coinfected patients, further research is needed to determine optimal management of HCV in this setting.

  19. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Science.gov (United States)

    Verma, Meghna; Erwin, Samantha; Abedi, Vida; Hontecillas, Raquel; Hoops, Stefan; Leber, Andrew; Bassaganya-Riera, Josep; Ciupe, Stanca M

    2017-01-01

    Human immunodeficiency virus (HIV)-infected patients are at an increased risk of co-infection with human papilloma virus (HPV), and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1) cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  20. Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa.

    Directory of Open Access Journals (Sweden)

    Meghna Verma

    Full Text Available Human immunodeficiency virus (HIV-infected patients are at an increased risk of co-infection with human papilloma virus (HPV, and subsequent malignancies such as oral cancer. To determine the role of HIV-associated immune suppression on HPV persistence and pathogenesis, and to investigate the mechanisms underlying the modulation of HPV infection and oral cancer by HIV, we developed a mathematical model of HIV/HPV co-infection. Our model captures known immunological and molecular features such as impaired HPV-specific effector T helper 1 (Th1 cell responses, and enhanced HPV infection due to HIV. We used the model to determine HPV prognosis in the presence of HIV infection, and identified conditions under which HIV infection alters HPV persistence in the oral mucosa system. The model predicts that conditions leading to HPV persistence during HIV/HPV co-infection are the permissive immune environment created by HIV and molecular interactions between the two viruses. The model also determines when HPV infection continues to persist in the short run in a co-infected patient undergoing antiretroviral therapy. Lastly, the model predicts that, under efficacious antiretroviral treatment, HPV infections will decrease in the long run due to the restoration of CD4+ T cell numbers and protective immune responses.

  1. Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis

    Science.gov (United States)

    2015-08-01

    exposure to the HFD or LFD, obese mice weighed significantly greater than lean mice (p=0.003, Table 1). There was no effect of HFD on non- fasted blood...AWARD NUMBER: W81XWH-13-1-0164 TITLE: Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis PRINCIPAL INVESTIGATOR: Victoria Bae...31 May 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Obesity Exposure Across the Lifespan on Ovarian Cancer Pathogenesis 5b. GRANT NUMBER

  2. ROLE OF MAGNESIUM IN HEADACHE PATHOGENESIS IN CHILDREN AND ADOLESCENTS

    Directory of Open Access Journals (Sweden)

    E. S. Akarachkova

    2013-01-01

    Full Text Available Article is dedicated to the problem of headache in children. This pathology is being found more frequently in pediatric and children’s neurologic practice. The authors examine headache pathogenesis from the position of magnesium deficiency. Analysis of results of the modern studies on magnesium deficiency and its correction in patients with headache indicates that magnesium metabolism may play an important role both in pathogenesis of different headache types and in its treatment and prevention.

  3. Signaling Pathways in Pathogenesis of Diamond Blackfan Anemia

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-12-1-0590 TITLE: SIGNALING PATHWAYS IN PATHOGENESIS OF DIAMOND BLACKFAN ANEMIA PRINCIPAL INVESTIGATOR: KATHLEEN M...SUBTITLE 5a. CONTRACT NUMBER W81XWH-12-1-0590 SIGNALING PATHWAYS IN PATHOGENESIS OF DIAMOND BLACKFAN ANEMIA 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Unlimited 13. SUPPLEMENTARY NOTES None 14. ABSTRACT: Diamond Blackfan Anemia (DBA) is a disorder that results in pure red cell aplasia, congenital

  4. Studies on the molecular pathogenesis of radiation pulmonary fibrosis

    International Nuclear Information System (INIS)

    Li Yang

    2003-01-01

    Radiation pulmonary fibrosis (RPF) is a frequent side effect of thoracic radiotherapy for breast neoplasm and total body irradiation before bone marrow transplantation. Studies on its pathogenesis have arrived at molecular level. Many cytokines, adhesion molecules and vasoactive substances all play important role in the course of RPF. Moreover, there exists genetic loci that has relation with RPF. Furthermore, studies on the molecular pathogenesis of RPF have provided new ideas and new measures for the precaution and therapy of RPF

  5. The application of business models to medical research: interviews with two founders of directed-philanthropy foundations. Interview with Scott Johnson and Don Listwin by Kathryn A. Phillips.

    Science.gov (United States)

    Scott, Johnson; Listwin, Don

    2007-01-01

    A new trend in research funding has emerged: directed philanthropy, in which the donor plays an active, hands-on role in managing the research by applying a "business model." Although such efforts now represent only a small portion of foundation funding, they have potentially far-reaching implications because (1) the approach of using a business model is being applied more broadly and (2) the success or failure of these efforts may portend the fate of larger translational efforts. The author conducted interviews with Scott Johnson of the Myelin Repair Foundation and Don Listwin of the Canary Foundation in the fall of 2006.

  6. The transcriptome of HIV-1 infected intestinal CD4+ T cells exposed to enteric bacteria.

    Directory of Open Access Journals (Sweden)

    Alyson C Yoder

    2017-02-01

    Full Text Available Global transcriptome studies can help pinpoint key cellular pathways exploited by viruses to replicate and cause pathogenesis. Previous data showed that laboratory-adapted HIV-1 triggers significant gene expression changes in CD4+ T cell lines and mitogen-activated CD4+ T cells from peripheral blood. However, HIV-1 primarily targets mucosal compartments during acute infection in vivo. Moreover, early HIV-1 infection causes extensive depletion of CD4+ T cells in the gastrointestinal tract that herald persistent inflammation due to the translocation of enteric microbes to the systemic circulation. Here, we profiled the transcriptome of primary intestinal CD4+ T cells infected ex vivo with transmitted/founder (TF HIV-1. Infections were performed in the presence or absence of Prevotella stercorea, a gut microbe enriched in the mucosa of HIV-1-infected individuals that enhanced both TF HIV-1 replication and CD4+ T cell death ex vivo. In the absence of bacteria, HIV-1 triggered a cellular shutdown response involving the downregulation of HIV-1 reactome genes, while perturbing genes linked to OX40, PPAR and FOXO3 signaling. However, in the presence of bacteria, HIV-1 did not perturb these gene sets or pathways. Instead, HIV-1 enhanced granzyme expression and Th17 cell function, inhibited G1/S cell cycle checkpoint genes and triggered downstream cell death pathways in microbe-exposed gut CD4+ T cells. To gain insights on these differential effects, we profiled the gene expression landscape of HIV-1-uninfected gut CD4+ T cells exposed to bacteria. Microbial exposure upregulated genes involved in cellular proliferation, MAPK activation, Th17 cell differentiation and type I interferon signaling. Our findings reveal that microbial exposure influenced how HIV-1 altered the gut CD4+ T cell transcriptome, with potential consequences for HIV-1 susceptibility, cell survival and inflammation. The HIV-1- and microbe-altered pathways unraveled here may serve as a

  7. The HIV Airway

    African Journals Online (AJOL)

    Adele

    dren living with HIV/AIDS. Annual national antenatal surveil- lance shows an HIV prevalence of 26.5% among pregnant women. Anaesthetists are confronted with an increasing number of HIV infected patients, presenting for both emergency and elective sur- gery. They range from having asymptomatic infection to end stage.

  8. HIV/AIDS

    Science.gov (United States)

    ... Key populations are groups who are at increased risk of HIV irrespective of epidemic type or local context. They include: men who have sex with men, ... HIV testing and counselling; HIV treatment and care; risk-reduction ... management of STIs, tuberculosis and viral hepatitis. Elimination of ...

  9. HIV Antibody Test

    Science.gov (United States)

    ... 65 in the case of the USPSTF) and pregnant women be screened for HIV at least once. The CDC and American College ... to make sure she is not infected with HIV before getting pregnant may opt to get tested (see Pregnancy: HIV .) ...

  10. Genetic Variation of HIV: Viral Load and Genotypic Diversity in Relation to Viral Pathogenesis and Treatment

    Science.gov (United States)

    1993-07-20

    1985) 50. Pang, S., Nature 343:85-89., (1990) 51. Goff, S.P. Cancer Cells 2:172-178., (1990) 52. Kulkosky, J., and A.M. Skalka. AIDS. 3:839-851...0 Z MAMA -0341 10/25 11 705 64 0 N ADFR-O 194 05/10 If 703 387 0 N BECH-0171 03109 11 678 5% 0 N MALE-0264 07/26 Ii1 644 3138 0 N ROJO-0331 11/29 11...or III RIPH 0179 1060 40.800 39 0 0 HI{D) 1099 623 36.000 0 0 0 ATKA 0361 760 9.400 0 0 0 HOJU 0143 720 36.900 0 0 0 MAMA 0341 706 113.400 31 0 0 ADFR

  11. Point mutations associated with HIV-1 drug resistance, evasion of the immune response and AIDS pathogenesis

    CSIR Research Space (South Africa)

    Khati, M

    2012-03-01

    Full Text Available RNA and Vpr, respectively pol Protease (PR) gag/pol cleavage pol Reverse Transcriptase (RT) Reverse transcription pol RNase H RNase H activity pol Integrase (IN) DNA provirus integration env Env (gp120 and gp41) gp120 binds CD4 receptor and CXCR4.../CCR5 co-receptors , gp41 mediates fusion tat Tat Viral transcription activator rev Rev RNA transport, stability and utilization factor (phosphoprotein) vif Vif Promotes virion maturation and infectivity vpr Vpr Promotes nuclear localization...

  12. HIV antibodies for treatment of HIV infection.

    Science.gov (United States)

    Margolis, David M; Koup, Richard A; Ferrari, Guido

    2017-01-01

    The bar is high to improve on current combination antiretroviral therapy (ART), now highly effective, safe, and simple. However, antibodies that bind the HIV envelope are able to uniquely target the virus as it seeks to enter new target cells, or as it is expressed from previously infected cells. Furthermore, the use of antibodies against HIV as a therapeutic may offer advantages. Antibodies can have long half-lives, and are being considered as partners for long-acting antiretrovirals for use in therapy or prevention of HIV infection. Early studies in animal models and in clinical trials suggest that such antibodies can have antiviral activity but, as with small-molecule antiretrovirals, the issues of viral escape and resistance will have to be addressed. Most promising, however, are the unique properties of anti-HIV antibodies: the potential ability to opsonize viral particles, to direct antibody-dependent cellular cytotoxicity (ADCC) against actively infected cells, and ultimately the ability to direct the clearance of HIV-infected cells by effector cells of the immune system. These distinctive activities suggest that HIV antibodies and their derivatives may play an important role in the next frontier of HIV therapeutics, the effort to develop treatments that could lead to an HIV cure. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

  13. Decoding noises in HIV computational genotyping.

    Science.gov (United States)

    Jia, MingRui; Shaw, Timothy; Zhang, Xing; Liu, Dong; Shen, Ye; Ezeamama, Amara E; Yang, Chunfu; Zhang, Ming

    2017-11-01

    Lack of a consistent and reliable genotyping system can critically impede HIV genomic research on pathogenesis, fitness, virulence, drug resistance, and genomic-based healthcare and treatment. At present, mis-genotyping, i.e., background noises in molecular genotyping, and its impact on epidemic surveillance is unknown. For the first time, we present a comprehensive assessment of HIV genotyping quality. HIV sequence data were retrieved from worldwide published records, and subjected to a systematic genotyping assessment pipeline. Results showed that mis-genotyped cases occurred at 4.6% globally, with some regional and high-risk population heterogeneities. Results also revealed a consistent mis-genotyping pattern in gp120 in all studied populations except the group of men who have sex with men. Our study also suggests novel virus diversities in the mis-genotyped cases. Finally, this study reemphasizes the importance of implementing a standardized genotyping pipeline to avoid genotyping disparity and to advance our understanding of virus evolution in various epidemiological settings. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Scotts Valley Energy Office and Human Capacity Building that will provide energy-efficiency services and develop sustainable renewable energy projects.

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Temashio [Scotts Valley Band of Pomo Indians

    2013-06-28

    The primary goal of this project is to develop a Scotts Valley Energy Development Office (SVEDO). This office will further support the mission of the Tribe's existing leadership position as the DOE Tribal Multi-County Weatherization Energy Program (TMCWEP) in creating jobs and providing tribal homes and buildings with weatherization assistance to increase energy efficiency, occupant comfort and improved indoor air quality. This office will also spearhead efforts to move the Tribe towards its further strategic energy goals of implementing renewable energy systems through specific training, resource evaluation, feasibility planning, and implementation. Human capacity building and continuing operations are two key elements of the SVEDO objectives. Therefore, the project will 1) train and employ additional Tribal members in energy efficiency, conservation and renewable resource analyses and implementation; 2) purchase materials and equipment required to implement the strategic priorities as developed by the Scotts Valley Tribe which specifically include implementing energy conservation measures and alternative energy strategies to reduce energy costs for the Tribe and its members; and 3) obtain a dedicated office and storage space for ongoing SVEDO operations.

  15. Tryptophan Metabolism and Its Relationship with Depression and Cognitive Impairment among HIV-infected Individuals

    Directory of Open Access Journals (Sweden)

    Michael R. Keegan

    2016-01-01

    Full Text Available Objective Cognitive impairment (CI and major depressive disorder (MDD remain prevalent in treated HIV-1 disease; however, the pathogenesis remains elusive. A possible contributing mechanism is immune-mediated degradation of tryptophan (TRP via the kynurenine (KYN pathway, resulting in decreased production of serotonin and accumulation of TRP degradation products. We explored the association of these biochemical pathways and their relationship with CI and MDD in HIV-positive (HIV+ individuals. Methods In a cross-sectional analysis, concentrations of neopterin (NEO, tumor necrosis factor-alpha, TRP, KYN, KYN/TRP ratio, phenylalanine (PHE, tyrosine (TYR, PHE/TYR ratio, and nitrite were assessed in the cerebrospinal fluid (CSF and plasma of HIV+( n = 91 and HIV-negative (HIV- individuals ( n = 66. CI and MDD were assessed via a comprehensive neuropsychological test battery. A Global Deficit Score ≥0.5 was defined as CI. Nonparametric statistical analyses included Kruskal–Wallis and Mann–Whitney U tests, and multivariate logistic regression. Results Following Bonferroni correction, NEO concentrations were found to be greater in CSF and TRP concentration was found to be lower in the plasma of HIV+ versus HIV– individuals, including a subgroup of aviremic (defined as HIV-1 RNA <50 cps/mL HIV+ participants receiving antiretroviral therapy ( n = 44. There was a nonsignificant trend toward higher KYN/TRP ratios in plasma in the HIV+ group ( P = 0.027; Bonferroni corrected α = 0.0027. In a logistic regression model, lower KYN/TRP ratios in plasma were associated with CI and MDD in the overall HIV+ group ( P = 0.038 and P = 0.063, respectively and the aviremic subgroup ( P = 0.066 and P = 0.027, respectively, though this observation was not statistically significant following Bonferroni correction (Bonferroni corrected α = 0.0031. Conclusions We observed a trend toward lower KYN/TRP ratios in aviremic HIV+ patients with CI and MDD.

  16. Drug delivery strategies and systems for HIV/AIDS pre-exposure prophylaxis and treatment.

    Science.gov (United States)

    Nelson, Antoinette G; Zhang, Xiaoping; Ganapathi, Usha; Szekely, Zoltan; Flexner, Charles W; Owen, Andrew; Sinko, Patrick J

    2015-12-10

    The year 2016 will mark an important milestone - the 35th anniversary of the first reported cases of HIV/AIDS. Antiretroviral Therapy (ART) including Highly Active Antiretroviral Therapy (HAART) drug regimens is widely considered to be one of the greatest achievements in therapeutic drug research having transformed HIV infection into a chronically managed disease. Unfortunately, the lack of widespread preventive measures and the inability to eradicate HIV from infected cells highlight the significant challenges remaining today. Moving forward there are at least three high priority goals for anti-HIV drug delivery (DD) research: (1) to prevent new HIV infections from occurring, (2) to facilitate a functional cure, i.e., when HIV is present but the body controls it without drugs and (3) to eradicate established infection. Pre-exposure Prophylaxis (PrEP) represents a significant step forward in preventing the establishment of chronic HIV infection. However, the ultimate success of PrEP will depend on achieving sustained antiretroviral (ARV) tissue concentrations and will require strict patient adherence to the regimen. While first generation long acting/extended release (LA/ER) DD Systems (DDS) currently in development show considerable promise, significant DD treatment and prevention challenges persist. First, there is a critical need to improve cell specificity through targeting in order to selectively achieve efficacious drug concentrations in HIV reservoir sites to control/eradicate HIV as well as mitigate systemic side effects. In addition, approaches for reducing cellular efflux and metabolism of ARV drugs to prolong effective concentrations in target cells need to be developed. Finally, given the current understanding of HIV pathogenesis, next generation anti-HIV DDS need to address selective DD to the gut mucosa and lymph nodes. The current review focuses on the DDS technologies, critical challenges, opportunities, strategies, and approaches by which novel

  17. Gene expression patterns associated with neurological disease in human HIV infection.

    Directory of Open Access Journals (Sweden)

    Pietro Paolo Sanna

    Full Text Available The pathogenesis and nosology of HIV-associated neurological disease (HAND remain incompletely understood. Here, to provide new insight into the molecular events leading to neurocognitive impairments (NCI in HIV infection, we analyzed pathway dysregulations in gene expression profiles of HIV-infected patients with or without NCI and HIV encephalitis (HIVE and control subjects. The Gene Set Enrichment Analysis (GSEA algorithm was used for pathway analyses in conjunction with the Molecular Signatures Database collection of canonical pathways (MSigDb. We analyzed pathway dysregulations in gene expression profiles of patients from the National NeuroAIDS Tissue Consortium (NNTC, which consists of samples from 3 different brain regions, including white matter, basal ganglia and frontal cortex of HIV-infected and control patients. While HIVE is characterized by widespread, uncontrolled inflammation and tissue damage, substantial gene expression evidence of induction of interferon (IFN, cytokines and tissue injury is apparent in all brain regions studied, even in the absence of NCI. Various degrees of white matter changes were present in all HIV-infected subjects and were the primary manifestation in patients with NCI in the absence of HIVE. In particular, NCI in patients without HIVE in the NNTC sample is associated with white matter expression of chemokines, cytokines and β-defensins, without significant activation of IFN. Altogether, the results identified distinct pathways differentially regulated over the course of neurological disease in HIV infection and provide a new perspective on the dynamics of pathogenic processes in the course of HIV neurological disease in humans. These results also demonstrate the power of the systems biology analyses and indicate that the establishment of larger human gene expression profile datasets will have the potential to provide novel mechanistic insight into the pathogenesis of neurological disease in HIV

  18. Inefficient HIV-1 trans infection of CD4+ T cells by macrophages from HIV-1 nonprogressors is associated with altered membrane cholesterol and DC-SIGN.

    Science.gov (United States)

    DeLucia, Diana C; Rinaldo, Charles R; Rappocciolo, Giovanna

    2018-04-11

    Professional antigen presenting cells (APC: myeloid dendritic cells (DC) and macrophages (MΦ); B lymphocytes) mediate highly efficient HIV-1 infection of CD4 + T cells, termed trans infection, that could contribute to HIV-1 pathogenesis. We have previously shown that lower cholesterol content in DC and B lymphocytes is associated with a lack of HIV-1 trans infection in HIV-1 infected nonprogressors (NP). Here we assessed whether HIV-1 trans infection mediated by another major APC, MΦ, is deficient in NP due to altered cholesterol metabolism. When comparing healthy HIV-1 seronegatives (SN), rapid progressors (PR), and NP, we found that monocyte-derived MΦ from NP did not mediate HIV-1 trans infection of autologous CD4 + T cells, in contrast to efficient trans infection mediated by SN and PR MΦ. MΦ trans infection efficiency was directly associated with the number of DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN)-expressing MΦ. Significantly fewer NP MΦ expressed DC-SIGN. Unesterified (free) cholesterol in MΦ cell membranes and lipid rafting was significantly lower in NP than PR, as well as virus internalization in early endosomes. Furthermore, simvastatin (SIMV), decreased the subpopulation of DC-SIGN + MΦ, as well as MΦ cis and trans infection. Notably, SIMV decreased cell membrane cholesterol and led to lipid raft dissociation, effectively mimicking the incompetent APC trans infection environment characteristic of NP. Our data support that DC-SIGN and membrane cholesterol are central to MΦ trans infection, and a lack of these limits HIV-1 disease progression. Targeting the ability of MΦ to drive HIV-1 dissemination in trans could enhance HIV-1 therapeutic strategies. IMPORTANCE Despite the success of combination anti-retroviral therapy, neither a vaccine nor a cure for HIV infection has been developed, demonstrating a need for novel prophylactic and therapeutic strategies. Here we show that efficiency of macrophage (M

  19. Correlates of HIV infection among people visiting public HIV ...

    African Journals Online (AJOL)

    Correlates of HIV infection among people visiting public HIV counseling and testing clinics in Mpumalanga, ... Background: HIV voluntary counselling and testing (VCT) reduces high-risk sexual behaviour. ... AJOL African Journals Online.

  20. HIV/AIDS in Women - Multiple Languages

    Science.gov (United States)

    ... medicines and women - HIV medicines, part 7 - English MP3 HIV medicines and women - HIV medicines, part 7 - 简体中文 (Chinese, Simplified (Mandarin dialect)) MP3 HIV medicines and women - HIV medicines, part 7 - ...

  1. Acute mucosal pathogenesis of feline immunodeficiency virus is independent of viral dose in vaginally infected cats

    Directory of Open Access Journals (Sweden)

    Egan Erin A

    2010-01-01

    Full Text Available Abstract Background The mucosal pathogenesis of HIV has been shown to be an important feature of infection and disease progression. HIV-1 infection causes depletion of intestinal lamina propria CD4+ T cells (LPL, therefore, intestinal CD4+ T cell preservation may be a useful correlate of protection in evaluating vaccine candidates. Vaccine studies employing the cat/FIV and macaque/SIV models frequently use high doses of parenterally administered challenge virus to ensure high plasma viremia in control animals. However, it is unclear if loss of mucosal T cells would occur regardless of initial viral inoculum dose. The objective of this study was to determine the acute effect of viral dose on mucosal leukocytes and associated innate and adaptive immune responses. Results Cats were vaginally inoculated with a high, middle or low dose of cell-associated and cell-free FIV. PBMC, serum and plasma were assessed every two weeks with tissues assessed eight weeks following infection. We found that irrespective of mucosally administered viral dose, FIV infection was induced in all cats. However, viremia was present in only half of the cats, and viral dose was unrelated to the development of viremia. Importantly, regardless of viral dose, all cats experienced significant losses of intestinal CD4+ LPL and CD8+ intraepithelial lymphocytes (IEL. Innate immune responses by CD56+CD3- NK cells correlated with aviremia and apparent occult infection but did not protect mucosal T cells. CD4+ and CD8+ T cells in viremic cats were more likely to produce cytokines in response to Gag stimulation, whereas aviremic cats T cells tended to produce cytokines in response to Env stimulation. However, while cell-mediated immune responses in aviremic cats may have helped reduce viral replication, they could not be correlated to the levels of viremia. Robust production of anti-FIV antibodies was positively correlated with the magnitude of viremia. Conclusions Our results indicate

  2. Genetic architecture of HIV-1 genes circulating in north India & their functional implications.

    Science.gov (United States)

    Neogi, Ujjwal; Sood, Vikas; Ronsard, Larence; Singh, Jyotsna; Lata, Sneh; Ramachandran, V G; Das, S; Wanchu, Ajay; Banerjea, Akhil C

    2011-12-01

    This review presents data on genetic and functional analysis of some of the HIV-1 genes derived from HIV-1 infected individuals from north India (Delhi, Punjab and Chandigarh). We found evidence of novel B/C recombinants in HIV-1 LTR region showing relatedness to China/Myanmar with 3 copies of Nfκb sites; B/C/D mosaic genomes for HIV-1 Vpr and novel B/C Tat. We reported appearance of a complex recombinant form CRF_02AG of HIV-1 envelope sequences which is predominantly found in Central/Western Africa. Also one Indian HIV-1 envelope subtype C sequence suggested exclusive CXCR4 co-receptor usage. This extensive recombination, which is observed in about 10 per cent HIV-1 infected individuals in the Vpr genes, resulted in remarkably altered functions when compared with prototype subtype B Vpr. The Vpu C was found to be more potent in causing apoptosis when compared with Vpu B when analyzed for subG1 DNA content. The functional implications of these changes as well as in other genes of HIV-1 are discussed in detail with possible implications for subtype-specific pathogenesis highlighted.

  3. Viremic long-term nonprogressive HIV-1 infection is not associated with abnormalities in known Nef functions

    NARCIS (Netherlands)

    Heigele, Anke; Camerini, David; van't Wout, Angélique B.; Kirchhoff, Frank

    2014-01-01

    A small minority of HIV-1-infected individuals show low levels of immune activation and do not develop immunodeficiency despite high viral loads. Since the accessory viral Nef protein modulates T cell activation and plays a key role in the pathogenesis of AIDS, we investigated whether specific

  4. Tackling HIV Persistence: Pharmacological versus CRISPR-Based Shock Strategies.

    Science.gov (United States)

    Darcis, Gilles; Das, Atze T; Berkhout, Ben

    2018-03-29

    Jan Svoboda studied aspects of viral latency, in particular with respect to disease induction by avian RNA tumor viruses, which were later renamed as part of the extended retrovirus family. The course of retroviral pathogenesis is intrinsically linked to their unique property of integrating the DNA copy of the retroviral genome into that of the host cell, thus forming the provirus. Retroviral latency has recently become of major clinical interest to allow a better understanding of why we can effectively block the human immunodeficiency virus type 1 (HIV-1) in infected individuals with antiviral drugs, yet never reach a cure. We will discuss HIV-1 latency and its direct consequence-the formation of long-lasting HIV-1 reservoirs. We next focus on one of the most explored strategies in tackling HIV-1 reservoirs-the "shock and kill" strategy-which describes the broadly explored pharmacological way of kicking the latent provirus, with subsequent killing of the virus-producing cell by the immune system. We furthermore present how the clustered regularly interspaced palindromic repeats (CRISPR) and associated protein (Cas) system can be harnessed to reach the same objective by reactivating HIV-1 gene expression from latency. We will review the benefits and drawbacks of these different cure strategies.

  5. Positron emission tomography in patients suffering from HIV-1 infection

    Energy Technology Data Exchange (ETDEWEB)

    Sathekge, Mike [University Hospital of Pretoria, Department of Nuclear Medicine, Pretoria (South Africa); Goethals, Ingeborg; Wiele, Christophe van de [University Hospital Ghent, Department of Nuclear Medicine, Ghent (Belgium); Maes, Alex [AZ Groening, Department of Nuclear Medicine, Kortrijk (Belgium)

    2009-07-15

    This paper reviews currently available PET studies performed either to improve our understanding of the pathogenesis of HIV-1 infection or to assess the value of PET imaging in the clinical decision making of patients infected with HIV-1 presenting with AIDS-related opportunistic infections and malignancies. FDG PET has shown that HIV-1 infection progresses by distinct anatomical steps, with involvement of the upper torso preceding involvement of the lower part of the torso, and that the degree of FDG uptake relates to viral load. The former finding suggests that lymphoid tissues are engaged in a predictable sequence and that diffusible mediators of activation might be important targets for vaccine or therapeutic intervention strategies. In lipodystrophic HIV-infected patients, limited available data support the hypothesis that stavudine-related lipodystrophy is associated with increased glucose uptake by adipose tissue as a result of the metabolic stress of adipose tissue in response to highly active antiretroviral treatment (HAART). Finally, in early AIDS-related dementia complex (ADC), striatal hypermetabolism is observed, whereas progressive ADC is characterized by a decrease in subcortical and cortical metabolism. In the clinical setting, PET has been shown to allow the differentiation of AIDS-related opportunistic infections and malignancies, and to allow monitoring of side effects of HAART. However, in patients suffering from HIV infection and presenting with extracerebral lymphoma or other human malignancies, knowledge of viraemia is essential when interpreting FDG PET imaging. (orig.)

  6. Positron emission tomography in patients suffering from HIV-1 infection

    International Nuclear Information System (INIS)

    Sathekge, Mike; Goethals, Ingeborg; Wiele, Christophe van de; Maes, Alex

    2009-01-01

    This paper reviews currently available PET studies performed either to improve our understanding of the pathogenesis of HIV-1 infection or to assess the value of PET imaging in the clinical decision making of patients infected with HIV-1 presenting with AIDS-related opportunistic infections and malignancies. FDG PET has shown that HIV-1 infection progresses by distinct anatomical steps, with involvement of the upper torso preceding involvement of the lower part of the torso, and that the degree of FDG uptake relates to viral load. The former finding suggests that lymphoid tissues are engaged in a predictable sequence and that diffusible mediators of activation might be important targets for vaccine or therapeutic intervention strategies. In lipodystrophic HIV-infected patients, limited available data support the hypothesis that stavudine-related lipodystrophy is associated with increased glucose uptake by adipose tissue as a result of the metabolic stress of adipose tissue in response to highly active antiretroviral treatment (HAART). Finally, in early AIDS-related dementia complex (ADC), striatal hypermetabolism is observed, whereas progressive ADC is characterized by a decrease in subcortical and cortical metabolism. In the clinical setting, PET has been shown to allow the differentiation of AIDS-related opportunistic infections and malignancies, and to allow monitoring of side effects of HAART. However, in patients suffering from HIV infection and presenting with extracerebral lymphoma or other human malignancies, knowledge of viraemia is essential when interpreting FDG PET imaging. (orig.)

  7. Emmprin and KSHV: new partners in viral cancer pathogenesis.

    Science.gov (United States)

    Dai, Lu; Bai, Lihua; Lu, Ying; Xu, Zengguang; Reiss, Krys; Del Valle, Luis; Kaleeba, Johnan; Toole, Bryan P; Parsons, Chris; Qin, Zhiqiang

    2013-09-01

    Emmprin (CD147; basigin) is a multifunctional glycoprotein expressed at higher levels by cancer cells and stromal cells in the tumor microenvironment. Through direct effects within tumor cells and promotion of tumor-stroma interactions, emmprin participates in induction of tumor cell invasiveness, angiogenesis, metastasis and chemoresistance. Although its contribution to cancer progression has been widely studied, the role of emmprin in viral oncogenesis still remains largely unclear, and only a small body of available literature implicates emmprin-associated mechanisms in viral pathogenesis and tumorigenesis. We summarize these data in this review, focusing on the role of emmprin in pathogenesis associated with the Kaposi sarcoma-associated herpesvirus (KSHV), a common etiology for cancers arising in the setting of immune suppression. We also discuss future directions for mechanistic studies exploring roles for emmprin in viral cancer pathogenesis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Case Report: HIV test misdiagnosis

    African Journals Online (AJOL)

    Case Study: HIV test misdiagnosis 124. Case Report: HIV ... A positive rapid HIV test does not require ... 3 College of Medicine - Johns Hopkins Research Project, Blantyre,. Malawi ... test results: a pilot study of three community testing sites.

  9. HIV/AIDS and Alcohol

    Science.gov (United States)

    ... Psychiatric Disorders Other Substance Abuse HIV/AIDS HIV/AIDS Human immunodeficiency virus (HIV) targets the body’s immune ... and often leads to acquired immune deficiency syndrome (AIDS). The U.S. CDC reported that in 2015, 39, ...

  10. Living with HIV/AIDS

    Science.gov (United States)

    ... destroying the white blood cells that fight infection. AIDS stands for acquired immunodeficiency syndrome. It is the final stage of infection with HIV. Not everyone with HIV develops AIDS. Infection with HIV is serious. But thanks to ...

  11. HIV, AIDS, and the Future

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues HIV / AIDS HIV, AIDS, and the Future Past Issues / Summer 2009 ... turn Javascript on. Photo: The NAMES Project Foundation HIV and AIDS are a global catastrophe. While advances ...

  12. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... hiv-aids-101/statistics/ . Reference Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, National ... not just injection) can put a person at risk for getting HIV. Drug and alcohol intoxication affect ...

  13. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... What are HIV and AIDS? HIV (human immunodeficiency virus) is the virus that causes AIDS (acquired immune deficiency syndrome). AIDS ... but no cure, at the present time. The virus (HIV) and the disease it causes (AIDS) are ...

  14. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the Link - Drugs and HIV Learn the Link - Drugs and HIV Email Facebook Twitter 2005 –Ongoing Behaviors ... GA: CDC, DHHS. Retrieved November 2017. How are Drug Misuse and HIV Related? Drug misuse and addiction ...

  15. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... Consequences of Drug Misuse Hepatitis (Viral) HIV/AIDS Mental Health Military Opioid Overdose Reversal with Naloxone (Narcan, ... hiv-aids-101/statistics/ . Reference Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention, National ...

  16. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... can suppress the virus and prevent or decrease symptoms of illness. To learn about current statistics of HIV in the United States, please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids-101/statistics/ . ...

  17. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... please visit: https://www.aids.gov/hiv-aids-basics/hiv-aids-101/statistics/ . Reference Centers for Disease ... About HIV/AIDS. ( https://www.cdc.gov/actagainstaids/basics/whatishiv.html ). Atlanta, GA: CDC, DHHS. Retrieved November ...

  18. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... causes (AIDS) are often linked and referred to as "HIV/AIDS." HIV can be transferred between people ... years, HIV is no longer a death sentence, as it was when the epidemic began. This is ...

  19. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... of HIV infection in the United States. Drugs can change the way the brain works, disrupting the ... linked and referred to as "HIV/AIDS." HIV can be transferred between people if an infected person's ...

  20. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... the spread of HIV infection in the United States. Drugs can change the way the brain works, ... about current statistics of HIV in the United States, please visit: https://www.aids.gov/hiv-aids- ...

  1. Drugs + HIV, Learn the Link

    Medline Plus

    Full Text Available ... in the spread of HIV infection in the United States. Drugs can change the way the brain works, ... learn about current statistics of HIV in the United States, please visit: https://www.aids.gov/hiv-aids- ...

  2. Clinical epidemiology of bocavirus, rhinovirus, two polyomaviruses and four coronaviruses in HIV-infected and HIV-uninfected South African children.

    Directory of Open Access Journals (Sweden)

    Marta C Nunes

    Full Text Available Advances in molecular diagnostics have implicated newly-discovered respiratory viruses in the pathogenesis of pneumonia. We aimed to determine the prevalence and clinical characteristics of human bocavirus (hBoV, human rhinovirus (hRV, polyomavirus-WU (WUPyV and -KI (KIPyV and human coronaviruses (CoV-OC43, -NL63, -HKU1 and -229E among children hospitalized with lower respiratory tract infections (LRTI.Multiplex real-time reverse-transcriptase polymerase chain reaction was undertaken on archived nasopharyngeal aspirates from HIV-infected and -uninfected children (<2 years age hospitalized for LRTI, who had been previously investigated for respiratory syncytial virus, human metapneumovirus, parainfluenza I-III, adenovirus and influenza A/B.At least one of these viruses were identified in 274 (53.0% of 517 and in 509 (54.0% of 943 LRTI-episodes in HIV-infected and -uninfected children, respectively. Human rhinovirus was the most prevalent in HIV-infected (31.7% and -uninfected children (32.0%, followed by CoV-OC43 (12.2% and hBoV (9.5% in HIV-infected; and by hBoV (13.3% and WUPyV (11.9% in HIV-uninfected children. Polyomavirus-KI (8.9% vs. 4.8%; p = 0.002 and CoV-OC43 (12.2% vs. 3.6%; p<0.001 were more prevalent in HIV-infected than -uninfected children. Combined with previously-tested viruses, respiratory viruses were identified in 60.9% of HIV-infected and 78.3% of HIV-uninfected children. The newly tested viruses were detected at high frequency in association with other respiratory viruses, including previously-investigated viruses (22.8% in HIV-infected and 28.5% in HIV-uninfected children.We established that combined with previously-investigated viruses, at least one respiratory virus was identified in the majority of HIV-infected and HIV-uninfected children hospitalized for LRTI. The high frequency of viral co-infections illustrates the complexities in attributing causality to specific viruses in the aetiology of LRTI and may indicate a

  3. Harnessing the Power of Emotion for Social Change: Review of Numbers and Nerves: Information, Emotion, and Meaning in a World of Data by Scott Slovic and Paul Slovic (2015

    Directory of Open Access Journals (Sweden)

    Anne M.W. Kelly

    2017-01-01

    Full Text Available Scott Slovic and Paul Slovic (Eds.. Numbers and Nerves: Information, Emotion, and Meaning in a World of Data (Corvallis, OR: Oregon State University Press, 2015. 272 pp. ISBN 978-0-87071-776-5. Literature and environment professor Scott Slovic, and his father, psychologist Paul Slovic, editors of this collection of essays and interviews, describe and demonstrate the psychological effects which hamper our ability to comprehend and respond appropriately to large numerical data. The collection then offers a brief survey of art works which, by first appealing to viewers’ emotions, can potentially move the viewer to a better understanding of numbers.

  4. Multiple sclerosis pathogenesis: missing pieces of an old puzzle.

    Science.gov (United States)

    Rahmanzadeh, Reza; Brück, Wolfgang; Minagar, Alireza; Sahraian, Mohammad Ali

    2018-06-08

    Traditionally, multiple sclerosis (MS) was considered to be a CD4 T cell-mediated CNS autoimmunity, compatible with experimental autoimmune encephalitis model, which can be characterized by focal lesions in the white matter. However, studies of recent decades revealed several missing pieces of MS puzzle and showed that MS pathogenesis is more complex than the traditional view and may include the following: a primary degenerative process (e.g. oligodendroglial pathology), generalized abnormality of normal-appearing brain tissue, pronounced gray matter pathology, involvement of innate immunity, and CD8 T cells and B cells. Here, we review these findings and discuss their implications in MS pathogenesis.

  5. Modern views on the epidemiology, etiology and pathogenesis of gynecomastia

    Directory of Open Access Journals (Sweden)

    Yu. N. Yashina

    2014-01-01

    Full Text Available The review deals with one of the pressing andrological issues – gynecomastia, its etiology and pathogenesis. Based on the current epidemiological and experimental data, most common etiological factors of gynecomastia were investigated. A multiple-valued role of various causes of gynecomastia in several age-groups was revealed. Literature data show that gynecomastia may be a manifestation of various diseases: endocrine, genetic, systematic. As well as that, gynecomastia may occur in patients with oncological diseases. However, gynecomastia can be an iatrogenic complication. Currently, we continue to make insights to the problem of gynecomastia in order to be able to classify its etiological factors and determine its basic pathogenesis pathways.

  6. The Paradox of Feline Coronavirus Pathogenesis: A Review

    Directory of Open Access Journals (Sweden)

    Luciana Wanderley Myrrha

    2011-01-01

    Full Text Available Feline coronavirus (FCoV is an enveloped single-stranded RNA virus, of the family Coronaviridae and the order Nidovirales. FCoV is an important pathogen of wild and domestic cats and can cause a mild or apparently symptomless enteric infection, especially in kittens. FCoV is also associated with a lethal, systemic disease known as feline infectious peritonitis (FIP. Although the precise cause of FIP pathogenesis remains unclear, some hypotheses have been suggested. In this review we present results from different FCoV studies and attempt to elucidate existing theories on the pathogenesis of FCoV infection.

  7. [Current concepts in pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Romanowska-Dixon, Bożena

    2014-01-01

    Age-related macular degeneration is the leading cause of central blindness in elderly population of the western world. The pathogenesis of this disease, likely multifactorial, is not well known, although a number of theories have been put forward, including oxidative stress, genetic interactions, hemodynamic imbalance, immune and inflammatory processes. The understanding of age-related macular degeneration pathogenesis will give rise to new approaches in prevention and treatment of the early and late stages of both atrophic and neovascular age-related macular degeneration.

  8. Systematic approach to understanding the pathogenesis of systemic sclerosis.

    Science.gov (United States)

    Zuo, Xiaoxia; Zhang, Lihua; Luo, Hui; Li, Yisha; Zhu, Honglin

    2017-10-01

    Systemic sclerosis (SSc) is a complex heterogeneous autoimmune disease. Progressive organ fibrosis is a major contributor to SSc mortality. Despite extensive efforts, the underlying mechanism of SSc remains unclear. Efforts to understand the pathogenesis of SSc have included genomics, epigenetics, transcriptomic, proteomic and metabolomic studies in the last decade. This review focuses on recent studies in SSc research based on multi-omics. The combination of these technologies can help us understand the pathogenesis of SSc. This review aims to provide important information for disease identification, therapeutic targets and potential biomarkers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Travelling with HIV

    DEFF Research Database (Denmark)

    Nielsen, Ulla S; Jensen-Fangel, Søren; Pedersen, Gitte

    2014-01-01

    BACKGROUND: We aimed to describe travel patterns, extent of professional pre-travel advice and health problems encountered during travel among HIV-infected individuals. METHODS: During a six-month period a questionnaire was handed out to 2821 adult HIV-infected individuals attending any...... of the eight Danish medical HIV care centers. RESULTS: A total of 763 individuals responded. During the previous two years 49% had travelled outside Europe; 18% had travelled less and 30% were more cautious when choosing travel destination than before the HIV diagnosis. Pre-travel advice was sought by only 38......%, and travel insurance was taken out by 86%. However, 29%/74% did not inform the advisor/the insurance company about their HIV status. Nearly all patients on highly active antiretroviral therapy (HAART) were adherent, but 58% worried about carrying HIV-medicine and 19% tried to hide it. Only 19% experienced...

  10. Parenting and HIV.

    Science.gov (United States)

    Rochat, Tamsen; Netsi, Elena; Redinger, Stephanie; Stein, Alan

    2017-06-01

    With the widespread use of antiretroviral therapy and successful prevention of mother-to-child transmission the development of HIV-negative children with HIV-positive parents has become an important focus. There is considerable evidence that children's developmental risk is heightened because a parental HIV-diagnosis is associated with a range of potential problems such as depression, stigma and financial difficulties. Up to a third of children in sub-Saharan Africa (SSA) are cared for by an HIV-positive parent or caregiver. We review the mechanisms by which HIV affects parenting including its negative effects on parental responsiveness in the early years of parenting and parental avoidant coping styles and parenting deficits in the later years. We describe low-cost parenting interventions suited for low resourced HIV endemic settings. Copyright © 2017. Published by Elsevier Ltd.

  11. HIV and Neurocognitive Dysfunction

    OpenAIRE

    Spudich, Serena

    2013-01-01

    The spectrum of HIV-associated neurocognitive disorder (HAND) has been dramatically altered in the setting of widely available effective antiretroviral therapy (ART). Once culminating in dementia in many individuals infected with HIV, HAND now typically manifests as more subtle, though still morbid, forms of cognitive impairment in persons surviving long-term with treated HIV infection. Despite the substantial improvement in severity of this disorder, the fact that neurologic injury persists ...

  12. Pregnancy and HIV infection

    OpenAIRE

    Mete Sucu; Cihan Cetin; Mehmet Ozsurmeli; Ghanim Khatib; Ceren Cetin; Cuneyt Evruke

    2016-01-01

    The management of Human Immunodeficiency Virus (HIV) infection is progressing rapidly. In developed countries, the perinatal transmission rates have decreased from 20-30% to 1-2% with the use of antiretroviral therapy and cesarean section. Interventions for the prevention of prenatal transmission has made the prenatal care of pregnant patients with HIV infection more complex. Rapid development of standard care and continuing increase in the distribution of HIV infection has required clinician...

  13. Paediatric HIV infection.

    Science.gov (United States)

    Scarlatti, G

    1996-09-28

    By the year 2000 there will be six million pregnant women and five to ten million children infected with HIV-1. Intervention strategies have been planned and in some instances already started. A timely and cost-effective strategy needs to take into account that most HIV-1 infected individuals reside in developing countries. Further studies are needed on immunological and virological factors affecting HIV-1 transmission from mother to child, on differential disease progression in affected children, and on transient infection.

  14. Language and HIV communication

    Directory of Open Access Journals (Sweden)

    Lynn VA

    2017-09-01

    Full Text Available Vickie A LynnDepartment of Community and Family Health, College of Public Health, University of South Florida, Tampa, FL, USAI am writing to comment on Kontomanolis et al’s recent article entitled “The social stigma of HIV-AIDS: society’s role”.1 Although I applaud the authors for writing about this important topic and I wholeheartedly agree that HIV-related stigma is devastating to women living with HIV, I want to point out that using stigmatizing language when writing an article about HIV-related stigma is counterproductive.View the original paper by Kontomanolis and colleagues.

  15. Role of tumour necrosis factor in pathogenesis of radicular cyst

    International Nuclear Information System (INIS)

    Qureshi, W.U.R.; Idris, M.; Khan, S.A.

    2011-01-01

    Background: The radicular cyst is very common odontogenic cyst of the jaws, which is usually associated with a tooth with necrotic pulp. The cyst formation requires proliferation of the epithelial rest cells of Malassez present in the periodontal ligament. Proliferation of epithelial rest cells of Malassez is an essential event in the Pathogenesis of radicular cyst. The wall of the cyst contains epithelial cells, macrophages, fibroblasts and other cells. TNF is one of inflammatory mediators, which is produced by macrophages and monocytes. This study was carried out to investigate the role of tumour necrosis factor in the pathogenesis of radicular cyst, which is by far the commonest cystic lesion of the jaws. Methods: Explants from 20 radicular cysts were cultured in vitro to grow the epithelial cells. However, the cultures were rapidly contaminated with fibroblasts and it was impossible to grow the epithelial cells separately. Therefore, the proliferative effect of Tumour Necrosis Factor (TNF) was studied on mammalian epithelial cells. Results: TNF at low concentration had a proliferative effect on the epithelial cells, which may play some role in pathogenesis of radicular cyst. Conclusion: TNF stimulated the epithelial cell proliferation in low concentration and inhibit the proliferation in higher concentrations. These two effects may have some implications in the pathogenesis of radicular cyst. (author)

  16. The potential implication of eosinophil activation in the pathogenesis ...

    African Journals Online (AJOL)

    Ehab

    The potential implication of eosinophil activation in the pathogenesis of childhood asthma. INTRODUCTION. Asthma is recognized as an eosinophil mediated inflammation of the airways1. Eosinophils are major contributors to the damage in the airways of asthmatic patients which when activated, degranulate and release ...

  17. Tick-borne encephalitis: Pathogenesis and clinical implications

    Czech Academy of Sciences Publication Activity Database

    Růžek, Daniel; Dobler, G.; Mantke, O. D.

    2010-01-01

    Roč. 8, č. 4 (2010), s. 223-232 ISSN 1477-8939 R&D Projects: GA ČR GPP302/10/P438; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Tick-borne encephalitis * Tick-borne encephalitis virus * Pathogenesis * Clinical data Subject RIV: EE - Microbiology, Virology

  18. Molecular cloning and characterization of pathogenesis-related ...

    African Journals Online (AJOL)

    We described the cloning and characterization of pathogenesis-related protein 5 gene in maize, named ZmPR5 (GenBank Accession Number: HM230665). Molecular and bioinformatic analyses of ZmPR5 revealed an open reading frame (ORF) of 525 bp, encoding a protein of 175 amino acids (aa) and a deduced ...

  19. [AETIOLOGY AND PATHOGENESIS GASTRO-DUODENALES ULCERATIVE LESIONS IN ELDERLY].

    Science.gov (United States)

    Chernekhovskaya, N E; Povalayev, A V; Layshenko, G A

    2015-01-01

    In review today conceptions of view to aetiology and pathogenesis gastro-duodenales ulcerative lesions in elderly. Atherosclerosis, ischemic disease of the heart and hypertension are reasons of acute ulcers and erosions in elderly. The breaking of microcirculation are very importance.

  20. Extrahepatic manifestations of cholestatic liver diseases: pathogenesis and therapy

    NARCIS (Netherlands)

    Pusl, Thomas; Beuers, Ulrich

    2005-01-01

    Pruritus, fatigue, and metabolic bone disease are frequent complications of cholestatic liver diseases, which can be quite distressing for the patient and can considerably reduce the quality of life. The molecular pathogenesis of these extrahepatic manifestations of cholestasis is poorly understood,