WorldWideScience

Sample records for human infectious pathology

  1. [Study of the probable role of the agent of enzootic ovine abortion in infectious human pathology. Preliminary report].

    Science.gov (United States)

    Gnutov, I N; Erokhina, S G

    1980-01-01

    418 workers were surveyed at a meat-packing plant. The presence of complement-fixing antibodies to the causative agent of enzootic abortion of sheep (EAS) was detected in 59 workers (14.27%), brucellosis in 32 workers (7.64%) and Q fever in 5 workers (1.18%). EAS antibodies were found to reach titers of 1 : 10 to 1 : 40 and higher, changing dynamically. The persons found to be seropositive belonged mainly to the workers of the sausage-making, slaughtering, intestinal, subproduct and skin-salting departments, as well as to the workers of the sanitary slaughter-house. Such diseases as acute respiratory infections, pneumonia, arthralgia, arthritis, and in women inflammatory urogenital infections, as well as spontaneous abortions were more frequent among the workers seropositive to the causative agent of EAS than in the control groups. Enzootic halprovial abortion of sheep was suggested to be potentially dangerous for certain groups of workers at the meat-packing plant, but the results of the survey indicate that further research in the fields of the epidemiology, clinical picture and laboratory diagnostics of infectious pathology in persons having contacts with the animals infected with the causative agent of EAS is necessary.

  2. Infectious diseases in paediatric pathology: experience from a developing country.

    Science.gov (United States)

    Peres, Luiz Cesar; Saggioro, Fabiano Pinto; Dias, Leonidas Braga; Alves, Venâncio Avancini Ferreira; Brasil, Roosecelis Araújo; Luiz, Veridiana Ester Dias de Barros; Neder, Luciano; Rosman, Fernando Colonna; Fleury, Raul Negrão; Ura, Somei; Orsi, Ana Tereza; Talhari, Carolina; Ferreira, Luiz Carlos de Lima; Ramos, Simone Gusmão; Rey, Luís Carlos; Martinez-Espinosa, Flor E; Sim, Franklin; Filho, Otilde Es de Satana; Duarte, Maria Irma Seixas; Lambertucci, José Roberto; Chimelli, Leila M Cardão; Rosa, Patrícia Sammarco; Belone, Andrea de Faria Fernandes

    2008-02-01

    Infectious and parasitic diseases have always challenged man. Although many of them are typically seen in some areas of the world and can be adequately managed by just improving socioeconomic status and sanitary conditions, they are still quite prevalent and may sometimes be seen outside their original geographical areas. Human migration due to different reasons, tourism, blood transfusion and solid organ transplantation has created new concerns for health professionals all over the world. If not for diagnostic purposes, at least these tropical and infectious diseases should be largely known because their epidemiology, pathogenesis, host/parasite interaction, inflammatory and reparative responses are quite interesting and teach us about human biology. Curiosity is inherent to pathology practice and so we are compelled to look for things other than tumours or degenerative diseases. This review focuses on infectious and parasitic diseases found in a developing country and brings up-to-date information on diseases caused by viruses (dengue, yellow fever), bacteria (typhoid fever, leprosy), parasites (Chagas' disease, cutaneous and visceral leishmaniasis, amoebiasis, Capillaria hepatica, schistosomiasis, cysticercosis) and caused by fungi (paracoccidioidomycosis, cryptococcosis, histoplasmosis) that may be useful for pathologists when facing somewhat strange cases from developing countries.

  3. Clinical and Pathological Observation on Infectious Serositis of Duck

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    According to clinical and pathological observation in infectious serositis of duck, the main signs of this disease were diarrhoea, breathing with difficulty, head tremble and movement beyond coordination. The pathological changes that had been found in 30 experimental ducks were fibrous pericarditis, hepatitis, and encephalitis. The fibrous serositis, liver fatty degeneration or focus necrosis, nonsuppurative encephalitis and serous-fibrous pneumonia were typical pathological changes of histology.

  4. Metabolic and infectious pathologies in Brazilian medical literature: a review

    Directory of Open Access Journals (Sweden)

    Mauricio Rocha-e-Silva

    2010-06-01

    Full Text Available OBJECTIVE: This review of original reports on metabolic and infectious diseases that were recently published in Brazilian journals is designed to inform the readership of CLINICS about their content. METHODS: I conducted a search in PubMed for original research articles (clinical or basic research recently published (2008-2009 by Brazilian medical and biological periodicals. Papers on metabolic pathologies were retrieved by searching for appropriate keywords such as metabolic syndrome and obesity. Papers on infectious disease were obtained by entering 15 different keywords for the most commonly occurring pathologies. Review articles, editorials, letters to the editor, and case reports were manually excluded. Selected titles were then categorized into appropriate sub-categories. RESULTS: This search produced a total of 123 articles, which filtered down to 72 articles after eliminating editorials, review articles, letters to the Editor and case reports. Reviewed periodicals were Arquivos Brasileiros de Cardiologia, Arquivos Brasileiros de Endocrinologia e Metabologia, Brazilian Journal of Biological and Medical Research, Brazilian Journal of Infectious Diseases, Jornal de Pediatria, Jornal de Pneumologia, Revista da Associação Médica Brasileira, Revista da Escola de Enfermagem da Universidade de São Paulo, and São Paulo Medical Journal. The articles were then briefly summarized.

  5. Metabolic and infectious pathologies in Brazilian medical literature: a review.

    Science.gov (United States)

    Rocha-e-Silva, Mauricio

    2010-06-01

    This review of original reports on metabolic and infectious diseases that were recently published in Brazilian journals is designed to inform the readership of CLINICS about their content. I conducted a search in PubMed for original research articles (clinical or basic research) recently published (2008-2009) by Brazilian medical and biological periodicals. Papers on metabolic pathologies were retrieved by searching for appropriate keywords such as metabolic syndrome and obesity. Papers on infectious disease were obtained by entering 15 different keywords for the most commonly occurring pathologies. Review articles, editorials, letters to the editor, and case reports were manually excluded. Selected titles were then categorized into appropriate sub-categories. This search produced a total of 123 articles, which filtered down to 72 articles after eliminating editorials, review articles, letters to the Editor and case reports. Reviewed periodicals were Arquivos Brasileiros de Cardiologia, Arquivos Brasileiros de Endocrinologia e Metabologia, Brazilian Journal of Biological and Medical Research, Brazilian Journal of Infectious Diseases, Jornal de Pediatria, Jornal de Pneumologia, Revista da Associação Médica Brasileira, Revista da Escola de Enfermagem da Universidade de São Paulo, and São Paulo Medical Journal. The articles were then briefly summarized.

  6. Does biodiversity protect humans against infectious disease?

    Science.gov (United States)

    Wood, Chelsea L; Lafferty, Kevin D; DeLeo, Giulio; Young, Hillary S; Hudson, Peter J; Kuris, Armand M

    2014-04-01

    Control of human infectious disease has been promoted as a valuable ecosystem service arising from the conservation of biodiversity. There are two commonly discussed mechanisms by which biodiversity loss could increase rates of infectious disease in a landscape. First, loss of competitors or predators could facilitate an increase in the abundance of competent reservoir hosts. Second, biodiversity loss could disproportionately affect non-competent, or less competent reservoir hosts, which would otherwise interfere with pathogen transmission to human populations by, for example, wasting the bites of infected vectors. A negative association between biodiversity and disease risk, sometimes called the "dilution effect hypothesis," has been supported for a few disease agents, suggests an exciting win-win outcome for the environment and society, and has become a pervasive topic in the disease ecology literature. Case studies have been assembled to argue that the dilution effect is general across disease agents. Less touted are examples in which elevated biodiversity does not affect or increases infectious disease risk for pathogens of public health concern. In order to assess the likely generality of the dilution effect, we review the association between biodiversity and public health across a broad variety of human disease agents. Overall, we hypothesize that conditions for the dilution effect are unlikely to be met for most important diseases of humans. Biodiversity probably has little net effect on most human infectious diseases but, when it does have an effect, observation and basic logic suggest that biodiversity will be more likely to increase than to decrease infectious disease risk.

  7. Global biogeography of human infectious diseases.

    Science.gov (United States)

    Murray, Kris A; Preston, Nicholas; Allen, Toph; Zambrana-Torrelio, Carlos; Hosseini, Parviez R; Daszak, Peter

    2015-10-13

    The distributions of most infectious agents causing disease in humans are poorly resolved or unknown. However, poorly known and unknown agents contribute to the global burden of disease and will underlie many future disease risks. Existing patterns of infectious disease co-occurrence could thus play a critical role in resolving or anticipating current and future disease threats. We analyzed the global occurrence patterns of 187 human infectious diseases across 225 countries and seven epidemiological classes (human-specific, zoonotic, vector-borne, non-vector-borne, bacterial, viral, and parasitic) to show that human infectious diseases exhibit distinct spatial grouping patterns at a global scale. We demonstrate, using outbreaks of Ebola virus as a test case, that this spatial structuring provides an untapped source of prior information that could be used to tighten the focus of a range of health-related research and management activities at early stages or in data-poor settings, including disease surveillance, outbreak responses, or optimizing pathogen discovery. In examining the correlates of these spatial patterns, among a range of geographic, epidemiological, environmental, and social factors, mammalian biodiversity was the strongest predictor of infectious disease co-occurrence overall and for six of the seven disease classes examined, giving rise to a striking congruence between global pathogeographic and "Wallacean" zoogeographic patterns. This clear biogeographic signal suggests that infectious disease assemblages remain fundamentally constrained in their distributions by ecological barriers to dispersal or establishment, despite the homogenizing forces of globalization. Pathogeography thus provides an overarching context in which other factors promoting infectious disease emergence and spread are set.

  8. Evaluation of pathological changes of natural infectious bursal ...

    African Journals Online (AJOL)

    ADEYEYE

    2017-03-06

    Mar 6, 2017 ... Department of Veterinary Pathology, College of Veterinary Medicine, Michael Okpara University of. Agriculture .... and Scientific Research Ethics. Flock history ..... In the course of embryonic development, precursors of these ...

  9. TUBERCULOSIS AS AN INFECTIOUS PATHOLOGY OF IMMUNE SYSTEM

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    Martynov AV

    2016-09-01

    Full Text Available As a result of years’ research of the many research groups around the world able to understand the reason why it will be impossible to create really effective vaccine for the prevention of tuberculosis infection in the near future. The main reason for the impossibility creating such vaccine is an intracellular nature of tuberculosis. In fact, TB is a pathology of the immune system. Mycobacterium tuberculosis persist within macrophages and thereby inhibit the process of phagocytosis completion and digesting the contents of phagosome. The destruction of the lysosomal membrane inside macrophages is blocked by changing the pH in lysosomes. For the presence of lytic activity for most lysosomal enzymes require need acidic environment. Mycobacteria are also getting into the lysosomes of macrophages start to rapidly hydrolysis for urea by urease to form ammonia. Wherein pH in the medium changes to alkaline, this inactivates enzymes and stabilizes lysosomal membrane. Thus mycobacterium prevent lysosome collapse at inactivated lysosomal enzymes and do not allow them to complete macrophage digestion phase by transition lysosomal to phagosomal stage. Stop phagocytolysis process leads to imbalance of the host immune system. Increasing the number of infected macrophages sensitized to Mycobacterium tuberculosis antigens, leading to constant hyperfunction of cellular immunity, particularly enhanced immune response to cell wall components of mycobacteria, induction high titers of interferon-gamma in response to a stimulus, a sharp jump IL-2 titers and TNF-α , IFN-γ specific activation CD8 + CTL. Need also focus attention on the main differences from the MBT and human BCG, that is well growth in the human body, persists along host life, but does not cause active TB (except in patients with HIV/AIDS. After MBT cell destruction in the environment gets some additional high allergenic antigens, such as 85B, ESAT6, Rv2660c, HyVaC 4 (Ag85B and TB10.4.. These

  10. INFECTIOUS PATHOLOGY OF MOTHER AND ITS INFLUENCE ON THE ANTHROPOMETRIC PARAMETERS OF NEWBORNS

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    Markovsky V. D.

    2014-01-01

    Full Text Available The presence in pregnant woman foci of latent, chronic infection of any localization is an important cause of various complications during pregnancy, childbirth, a wide range of perinatal pathology. The purpose of this study was to reveal the influence of mother infectious diseases on the anthropometric parameters of newborns. The authors set up an experiment on WAG rats on modeling subacute (prolonged peritonitis in females in order to study the influence of this infectiousinflammatory process in the organism of mother on the anthropometric parameters of newborns. The study found that the presence of infectious-inflammatory diseases in mother is not always leads to inflammatory changes in the placenta, but involutive- degenerative and dyscirculatory changes are taking place in all cases. In newborns from mothers with infectious pathology revealed significantly reduced anthropometric parameters in comparison with newborns from healthy mothers. Anthropometric parameters of newborns from mothers with infectious pathology depend on the infective dose (the higher the dose of agent, the less neonatal anthropometric parameters. Negative influence of infectious extragenital pathology of mother on newborn anthropometric parameters requires improving the quality of pregravidal training aimed at early detection and sanitation of foci of infection.

  11. Incorporating pathology in the practice of infectious disease: myths and reality.

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    Guarner, Jeannette

    2014-10-15

    The role pathology plays in establishing or excluding infectious diseases has been established. However, as the practice of pathology has become subspecialized, there is not enough infectious disease specimen volume to have a pathologist dedicated full time to this crosscutting subspecialty. So, what are the myths and realities of a practicing infectious disease pathologist in the hospital setting? Infectious disease clinicians tend to consult pathologists when there are questions regarding terminology used in pathology reports; when there is the need to perform additional studies on formalin-fixed, paraffin-embedded tissues; and when there is an interest in seeing biopsies or resections obtained from patients and in obtaining photographs for presentations. Pathologists consult infectious disease pathologists when there is a need to review diverse inflammatory reactions; for identification of fungi, parasites, or unknown structures; to define the need to use special stains and other techniques in order to identify organisms in tissues that have been formalin fixed; and to help with terminology to be used in reports. This review explores in more detail why and how these consultations occur.

  12. INFECTIOUS DISEASES IN CHILDREN: THE ROLE IN THE OCCURRENCE OF SOMATIC PATHOLOGY

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    L. N. Mazankova

    2013-01-01

    Full Text Available The article examines the relationship of infectious diseases, especially opportunistic and viral infections, with the formation of chronic and physical illness. Scientific meta-analysis of the effect of infections on the start of autoimmune disease, chronic diseases of broncho-pulmonary and cardiovascular system, gastrointestinal tract, urinary and other systems is carried out. Special attention is given to the role of fetal viral infection in the development of congenital malformations and intrauterine pathology. The article discusses the prevention measures taken for controlling certain somatic diseases.

  13. Human Vision Pathology Diagnostics by Photogrammetrics Means

    Science.gov (United States)

    Murynin, A.; Knyaz, V.; Mateev, I.

    2014-06-01

    One of the reasons of such vision pathology as human stereoscopic vision capability dysfunction is an asymmetry of a human face. As a rule, such dysfunctions occur as early as in the babyhood, when diagnostic methods applied for adults are ineffective. Early diagnostics and prophylaxis could help in treatment of such pathology and face 3D modeling is one of the promising ways to solve this problem.

  14. ETHICAL AND LEGAL ASPECTS OF INFECTOLOGY AND VACCINE PROPHYLAXIS. Part 1. Bioethics and social justice in infectious pathology

    Directory of Open Access Journals (Sweden)

    O. I. Kubar

    2011-01-01

    Full Text Available Abstract. The serial materials on the history of establishment and the modern concepts of bioethics in the field of infectious pathology is planned to present in several articles. In the current report problems of forming and compliance of social responsibility are considered. It is demonstrated the universal importance of ethic principles and specificity of their realization in the different stages of combating with infectious diseases. 

  15. Multinational corporations and infectious disease: Embracing human rights management techniques.

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    Salcito, Kendyl; Singer, Burton H; Weiss, Mitchell G; Winkler, Mirko S; Krieger, Gary R; Wielga, Mark; Utzinger, Jürg

    2014-01-01

    Global health institutions have called for governments, international organisations and health practitioners to employ a human rights-based approach to infectious diseases. The motivation for a human rights approach is clear: poverty and inequality create conditions for infectious diseases to thrive, and the diseases, in turn, interact with social-ecological systems to promulgate poverty, inequity and indignity. Governments and intergovernmental organisations should be concerned with the control and elimination of these diseases, as widespread infections delay economic growth and contribute to higher healthcare costs and slower processes for realising universal human rights. These social determinants and economic outcomes associated with infectious diseases should interest multinational companies, partly because they have bearing on corporate productivity and, increasingly, because new global norms impose on companies a responsibility to respect human rights, including the right to health. We reviewed historical and recent developments at the interface of infectious diseases, human rights and multinational corporations. Our investigation was supplemented with field-level insights at corporate capital projects that were developed in areas of high endemicity of infectious diseases, which embraced rights-based disease control strategies. Experience and literature provide a longstanding business case and an emerging social responsibility case for corporations to apply a human rights approach to health programmes at global operations. Indeed, in an increasingly globalised and interconnected world, multinational corporations have an interest, and an important role to play, in advancing rights-based control strategies for infectious diseases. There are new opportunities for governments and international health agencies to enlist corporate business actors in disease control and elimination strategies. Guidance offered by the United Nations in 2011 that is widely embraced

  16. Human genetics of infectious diseases: a unified theory

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    Casanova, Jean-Laurent; Abel, Laurent

    2007-01-01

    Since the early 1950s, the dominant paradigm in the human genetics of infectious diseases postulates that rare monogenic immunodeficiencies confer vulnerability to multiple infectious diseases (one gene, multiple infections), whereas common infections are associated with the polygenic inheritance of multiple susceptibility genes (one infection, multiple genes). Recent studies, since 1996 in particular, have challenged this view. A newly recognised group of primary immunodeficiencies predisposing the individual to a principal or single type of infection is emerging. In parallel, several common infections have been shown to reflect the inheritance of one major susceptibility gene, at least in some populations. This novel causal relationship (one gene, one infection) blurs the distinction between patient-based Mendelian genetics and population-based complex genetics, and provides a unified conceptual frame for exploring the molecular genetic basis of infectious diseases in humans. PMID:17255931

  17. Human prefrontal cortex: evolution, development, and pathology.

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    Teffer, Kate; Semendeferi, Katerina

    2012-01-01

    The prefrontal cortex is critical to many cognitive abilities that are considered particularly human, and forms a large part of a neural system crucial for normal socio-emotional and executive functioning in humans and other primates. In this chapter, we survey the literature regarding prefrontal development and pathology in humans as well as comparative studies of the region in humans and closely related primate species. The prefrontal cortex matures later in development than more caudal regions, and some of its neuronal subpopulations exhibit more complex dendritic arborizations. Comparative work suggests that the human prefrontal cortex differs from that of closely related primate species less in relative size than it does in organization. Specific reorganizational events in neural circuitry may have taken place either as a consequence of adjusting to increases in size or as adaptive responses to specific selection pressures. Living in complex environments has been recognized as a considerable factor in the evolution of primate cognition. Normal frontal lobe development and function are also compromised in several neurological and psychiatric disorders. A phylogenetically recent reorganization of frontal cortical circuitry may have been critical to the emergence of human-specific executive and social-emotional functions, and developmental pathology in these same systems underlies many psychiatric and neurological disorders, including autism and schizophrenia.

  18. The Leeuwenhoek Lecture 2001. Animal origins of human infectious disease.

    Science.gov (United States)

    Weiss, R A

    2001-06-29

    Since time immemorial animals have been a major source of human infectious disease. Certain infections like rabies are recognized as zoonoses caused in each case by direct animal-to-human transmission. Others like measles became independently sustained with the human population so that the causative virus has diverged from its animal progenitor. Recent examples of direct zoonoses are variant Creutzfeldt-Jakob disease arising from bovine spongiform encephalopathy, and the H5N1 avian influenza outbreak in Hong Kong. Epidemics of recent animal origin are the 1918-1919 influenza pandemic, and acquired immune deficiency syndrome caused by human immunodeficiency virus (HIV). Some retroviruses jump into and out of the chromosomal DNA of the host germline, so that they oscillate between being inherited Mendelian traits or infectious agents in different species. Will new procedures like animal-to-human transplants unleash further infections? Do microbes become more virulent upon cross-species transfer? Are animal microbes a threat as biological weapons? Will the vast reservoir of immunodeficient hosts due to the HIV pandemic provide conditions permissive for sporadic zoonoses to take off as human-to-human transmissible diseases? Do human infections now pose a threat to endangered primates? These questions are addressed in this lecture.

  19. Photosensitized inactivation of infectious blood-borne human parasites

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    Judy, Millard M.; Sogandares-Bernal, Franklin M.; Matthews, James Lester

    1995-05-01

    Blood-borne viruses and protozoan parasites that are infectious to humans pose risk world-wide of infection transmission through blood and blood product transfusion. Blood-borne infectious viruses include human immunodeficiency virus (HIV-I), which causes AIDS; hepatitis C virus, which can cause chronic hepatitis; and cytomegalovirus, which can be dangerous to immunocompromised patients, e.g., the newborn, transplant recipients, and AIDS patients. Infectious blood-borne protozoan parasites include Trypanosoma cruzi, which causes Chagas' disease, endemic throughout Central and South America; the Trypanosoma species causing African sleeping sickness endemic in Central Africa; and Plasmodium falciparum, which causes malignant and increasingly drug- resistant human malaria prevalent throughout the tropics. Some researchers have focused on using photosensitizers to inactivate HIV-I and other viruses in whole blood, packed red cells, and platelet concentrates without compromising blood product function. Our group previously has reported photosensitized in vitro inactivation of P. falciparum and the mouse malaria organism Plasmodium berghei in whole blood using hematoporphyrin derivative (HPD) and of T. cruzi using benzoporphyrin derivatives BPDMA and BPDDA, dihematoporphyrin ether (DHE), and hydroxyethylvinyldeuteroporphyrin (HEVD). These results suggest that continued investigation is warranted to evaluate the potential for photosensitized inactivation of blood-borne parasites in blood banking.

  20. Molecular Pathology of Human Prion Diseases

    Directory of Open Access Journals (Sweden)

    2009-03-01

    Full Text Available Prion diseases are fatal neurodegenerative conditions in humans and animals. In this review, we summarize the molecular background of phenotypic variability, relation of prion protein (PrP to other proteins associated with neurodegenerative diseases, and pathogenesis of neuronal vulnerability. PrP exists in different forms that may be present in both diseased and non-diseased brain, however, abundant disease-associated PrP together with tissue pathology characterizes prion diseases and associates with transmissibility. Prion diseases have different etiological background with distinct pathogenesis and phenotype. Mutations of the prion protein gene are associated with genetic forms. The codon 129 polymorphism in combination with the Western blot pattern of PrP after proteinase K digestion serves as a basis for molecular subtyping of sporadic Creutzfeldt-Jakob disease. Tissue damage may result from several parallel, interacting or subsequent pathways that involve cellular systems associated with synapses, protein processing, oxidative stress, autophagy, and apoptosis.

  1. Infectious prion diseases in humans: cannibalism, iatrogenicity and zoonoses.

    Science.gov (United States)

    Haïk, Stéphane; Brandel, Jean-Philippe

    2014-08-01

    In contrast with other neurodegenerative disorders associated to protein misfolding, human prion diseases include infectious forms (also called transmitted forms) such as kuru, iatrogenic Creutzfeldt-Jakob disease and variant Creutzfeldt-Jakob disease. The transmissible agent is thought to be solely composed of the abnormal isoform (PrP(Sc)) of the host-encoded prion protein that accumulated in the central nervous system of affected individuals. Compared to its normal counterpart, PrP(Sc) is β-sheet enriched and aggregated and its propagation is based on an autocatalytic conversion process. Increasing evidence supports the view that conformational variations of PrP(Sc) encoded the biological properties of the various prion strains that have been isolated by transmission studies in experimental models. Infectious forms of human prion diseases played a pivotal role in the emergence of the prion concept and in the characterization of the very unconventional properties of prions. They provide a unique model to understand how prion strains are selected and propagate in humans. Here, we review and discuss how genetic factors interplay with strain properties and route of transmission to influence disease susceptibility, incubation period and phenotypic expression in the light of the kuru epidemics due to ritual endocannibalism, the various series iatrogenic diseases secondary to extractive growth hormone treatment or dura mater graft and the epidemics of variant Creutzfeldt-Jakob disease linked to dietary exposure to the agent of bovine spongiform encephalopathy.

  2. Impact of climate change on human infectious diseases: Empirical evidence and human adaptation.

    Science.gov (United States)

    Wu, Xiaoxu; Lu, Yongmei; Zhou, Sen; Chen, Lifan; Xu, Bing

    2016-01-01

    Climate change refers to long-term shifts in weather conditions and patterns of extreme weather events. It may lead to changes in health threat to human beings, multiplying existing health problems. This review examines the scientific evidences on the impact of climate change on human infectious diseases. It identifies research progress and gaps on how human society may respond to, adapt to, and prepare for the related changes. Based on a survey of related publications between 1990 and 2015, the terms used for literature selection reflect three aspects--the components of infectious diseases, climate variables, and selected infectious diseases. Humans' vulnerability to the potential health impacts by climate change is evident in literature. As an active agent, human beings may control the related health effects that may be effectively controlled through adopting proactive measures, including better understanding of the climate change patterns and of the compound disease-specific health effects, and effective allocation of technologies and resources to promote healthy lifestyles and public awareness. The following adaptation measures are recommended: 1) to go beyond empirical observations of the association between climate change and infectious diseases and develop more scientific explanations, 2) to improve the prediction of spatial-temporal process of climate change and the associated shifts in infectious diseases at various spatial and temporal scales, and 3) to establish locally effective early warning systems for the health effects of predicated climate change.

  3. Human genetics of infectious diseases: between proof of principle and paradigm

    Science.gov (United States)

    Alcaïs, Alexandre; Abel, Laurent; Casanova, Jean-Laurent

    2009-01-01

    The observation that only a fraction of individuals infected by infectious agents develop clinical disease raises fundamental questions about the actual pathogenesis of infectious diseases. Epidemiological and experimental evidence is accumulating to suggest that human genetics plays a major role in this process. As we discuss here, human predisposition to infectious diseases seems to cover a continuous spectrum from monogenic to polygenic inheritance. Although many studies have provided proof of principle that infectious diseases may result from various types of inborn errors of immunity, the genetic determinism of most infectious diseases in most patients remains unclear. However, in the future, studies in human genetics are likely to establish a new paradigm for infectious diseases. PMID:19729848

  4. Malarial birds: modeling infectious human disease in animals.

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    Slater, Leo B

    2005-01-01

    Through the examination of avian malarias as models of infectious human disease, this paper reveals the kinds of claims that scientists and physicians made on the basis of animal models-biological systems in the laboratory and the field-and what characteristics made for congruence between these models and human malaria. The focus is on the period between 1895 and 1945, and on the genesis and trajectory of certain animal models of malaria within specific locations, such as the Johns Hopkins School of Hygiene and Public Health in Baltimore and Bayer (I. G. Farben) in Elberfeld. These exemplars illustrate a diversity of approaches to malaria-as-disease, and the difficulties of framing aspects of this disease complex within an animal or laboratory system. The diversity and nearness to wild types of the birds, protozoan parasites, and mosquitoes that made up these malaria models contributed a great deal to the complexity of the models. Avian malarias, adopted with enthusiasm, were essential to the success of the U.S. antimalarial program during World War II.

  5. Does biodiversity protect humans against infectious disease? Reply

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    Wood, Chelsea L.; Lafferty, Kevin D.; DeLeo, Giulio; Young, Hillary S.; Hudson, Peter J.; Kuris, Armand M.

    2016-01-01

    The dilution effect is the sort of idea that everyone wants to be true. If nature protects humans against infectious disease, imagine the implications: nature's value could be tallied in terms of human suffering avoided. This makes a potent argument for conservation, convincing even to those who would otherwise be disinclined to support conservation initiatives. The appeal of the dilution effect has been recognized by others: “the desire to make the case for conservation has led to broad claims regarding the benefits of nature conservation for human health” (Bauch et al. 2015). Randolph and Dobson (2012) were among the first to critique these claims, making the case that promotion of conservation to reduce Lyme disease risk, although well intentioned, was flawed. Along with Randolph and Dobson's critique, there have been several calls for a more nuanced scientific assessment of the relationship between biodiversity and disease transmission (Dunn 2010, Salkeld et al. 2013, Wood and Lafferty 2013, Young et al. 2013). In response, supporters of the dilution effect have instead increased the scope of their generalizations with review papers, press releases, and, like Levi et al. (2015), letters. These responses have been successful; it is not uncommon to read papers that repeat the assertion that biodiversity generally interferes with disease transmission and that conservation will therefore generally benefit human health. Here, we explain how Levi et al. (2015) and other, similar commentaries use selective interpretation and shifting definitions to argue for the generality of the dilution effect hypothesis.

  6. The Rise of Forensic Pathology in Human Medicine: Lessons for Veterinary Forensic Pathology.

    Science.gov (United States)

    Pollanen, M S

    2016-09-01

    The rise of forensic pathology in human medicine has greatly contributed to the administration of justice, public safety and security, and medical knowledge. However, the evolution of human forensic pathology has been challenging. Veterinary forensic pathologists can learn from some of the lessons that have informed the growth and development of human forensic pathology. Three main observations have emerged in the past decade. First, wrongful convictions tell us to use a truth-seeking stance rather than an a priori "think dirty" stance when investigating obscure death. Second, missed homicides and concealed homicides tell us that training and certification are the beginning of reliable forensic pathology. Third, failure of a sustainable institutional arrangement that fosters a combination of service, research, and teaching will lead to stagnation of knowledge. Forensic pathology of humans and animals will flourish, help protect society, and support justice if we embrace a modern biomedical scientific model for our practice. We must build training programs, contribute to the published literature, and forge strong collaborative institutions.

  7. A preliminary pathological study on human allotransplantation

    Institute of Scientific and Technical Information of China (English)

    WANG Hui-jun 王慧君; DING Yan-qing 丁彦青; PEI Guo-xian 裴国献; GU Li-qiang 顾立强; ZHU Li-jun 朱立军

    2003-01-01

    Objective: To observe the survival of hand allograft under the state of immunosuppression and the pathological changes of rejection in the recovery process.Methods: The biopsies of the skin, nerve, muscle, tendon and bone tissue of hand allografts during different stages from 1 day to 7 months after operation were observed using routine histological technique.Results: No significant changes due to rejection in skin, nerve, muscle and bone tissue were observed.But different degrees of weak rejective changes were found on the wall of blood vessels; in the muscle and nerve the reactions were markedly stronger than those found in skin tissues.Conclusions: The rejection in deep tissues should be monitored in controlling the rejection of hand allograft.

  8. Antimicrobial Human β-Defensins in the Colon and Their Role in Infectious and Non-Infectious Diseases

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    Eduardo R. Cobo

    2013-03-01

    Full Text Available β-defensins are small cationic antimicrobial peptides secreted by diverse cell types including colonic epithelial cells. Human β-defensins form an essential component of the intestinal lumen in innate immunity. The defensive mechanisms of β-defensins include binding to negatively charged microbial membranes that cause cell death and chemoattraction of immune cells. The antimicrobial activity of β-defensin is well reported in vitro against several enteric pathogens and in non-infectious processes such as inflammatory bowel diseases, which alters β-defensin production. However, the role of β-defensin in vivo in its interaction with other immune components in host defense against bacteria, viruses and parasites with more complex membranes is still not well known. This review focuses on the latest findings regarding the role of β-defensin in relevant human infectious and non-infectious diseases of the colonic mucosa. In addition, we summarize the most significant aspects of β-defensin and its antimicrobial role in a variety of disease processes.

  9. Comparison between the diagnostic accuracy of clinico-pathological and molecular tests for feline infectious peritonitis (FIP

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    Angelica Stranieri

    2015-07-01

    Full Text Available The aim of this study was to compare the diagnostic accuracy for feline infectious peritonitis (FIP of conventional clinic-pathological tests with that of molecular tests such as routine PCR and PCR followed by the sequencing of the Spike (S gene. Blood, effusion and tissues specimens were collected from 21 FIP suspected cats. In vivo examination consisted of CBC, serum protein electrophoresis, AGP measurement, cytological and biochemical examination and the evaluation of the ΔTNC on effusions, and of molecular tests such the screening PCR (target: 3’UTR region and the PCR directed towards the S gene followed by the amplification products sequencing in order to detect the aminoacidic substitution recently considered diagnostic for FIP1. These molecular techniques were applied to tissues collected during necropsy, which also allowed forming an FIP group (13 cats and a non-FIP group (5 cats based on histology and immunohistochemistry. The best test on tissues was immunohistochemistry (sens: 92.3%; spec: 100%, while the screening PCR suffered of low specificity (spec: 33.3% and the S gene sequencing showed low sensitivity (sens: 69.2%.On effusions, the best tests resulted screening PCR and cytology (sens and spec: 100% in comparison with the ΔTNC measurement (sens: 85.7 %; spec: 100% and the S gene sequencing (sens: 42.8%; spec: 100%.On blood, the best test resulted AGP measurement (sens: 81.8%; spec: 100%, while serum protein electrophoresis showed a surprisingly low sensitivity (sens: 41.7%. Screening PCR (sens: 55.6%; spec: 100% and S gene sequencing (sens: 33.3%; spec: 100% proved again low accuracy. 

  10. Endogenous production of infectious Inoue-Melnick virus in a human meningioma cell line.

    Science.gov (United States)

    Nishibe, Y; Inoue, Y K; Hollinshead, A C

    1987-11-01

    We investigated continuous production of Inoue-Melnick virus (IMV) in the MG-1 cell line, established from human meningioma. The infectious virus, identified as a type 1 virus, was mostly recovered extracellularly. Assay of MG-1 cells as infective centers indicated that most of the cells were capable of producing infectious virus. By immunofluorescence, more than 90% of the cells were found to have IMV-associated cytoplasmic antigen(s) (IMCA).

  11. The pathology of human spinal cord injury: defining the problems.

    Science.gov (United States)

    Norenberg, Michael D; Smith, Jon; Marcillo, Alex

    2004-04-01

    This article reviews the pathology of human spinal cord injury (SCI), focusing on potential differences between humans and experimental animals, as well as on aspects that may have mechanistic or therapeutic relevance. Importance is placed on astrocyte and microglial reactions. These cells carry out a myriad of functions and we review the evidence that supports their beneficial or detrimental effects. Likewise, vascular responses and the role of inflammation and demyelination in the mechanism of SCI are reviewed. Lastly, schwannosis is discussed, highlighting its high frequency and potential role when designing therapeutic interventions. We anticipate that a better understanding of the pathological responses in the human will be useful to investigators in their studies on the pathogenesis and therapy of SCI.

  12. A comparison between immunofluorescence staining on smears from Membrana nictitans (M3 test), immunohistopathology and routine pathology in cats with suspected feline infectious peritonitis (FIP).

    Science.gov (United States)

    Hök, K

    1991-01-01

    An indirect immunofluorescence method using smears from membrana nictitans (M3 test) to diagnose feline corona virus (FCV) infection was compared with immunohistopathology (using indirect immunofluorescence assay (IFFA) performed on organs (IFO], and routine pathology (RP) in cats with suspected feline infectious peritonitis (FIP). A close correlation between the 2 immunofluorescence methods (IFO and M3) was observed. Although the M3 test requires samples from only 1 organ per animal, both the sensitivity and specificity were high (80%), when compared to IFO (using samples from an average of 5 organs per animal). In 21% of the cats with suspected FIP typical pathological lesions were found. As the M3 test is relatively easy to perform, it could reduce work-load of pathology laboratories and provide valuable data for clinical and epidemiological use.

  13. Dissecting phenotypic traits linked to human resilience to Alzheimer's pathology.

    Science.gov (United States)

    Perez-Nievas, Beatriz G; Stein, Thor D; Tai, Hwan-Ching; Dols-Icardo, Oriol; Scotton, Thomas C; Barroeta-Espar, Isabel; Fernandez-Carballo, Leticia; de Munain, Estibaliz Lopez; Perez, Jesus; Marquie, Marta; Serrano-Pozo, Alberto; Frosch, Mathew P; Lowe, Val; Parisi, Joseph E; Petersen, Ronald C; Ikonomovic, Milos D; López, Oscar L; Klunk, William; Hyman, Bradley T; Gómez-Isla, Teresa

    2013-08-01

    Clinico-pathological correlation studies and positron emission tomography amyloid imaging studies have shown that some individuals can tolerate substantial amounts of Alzheimer's pathology in their brains without experiencing dementia. Few details are known about the neuropathological phenotype of these unique cases that might prove relevant to understanding human resilience to Alzheimer's pathology. We conducted detailed quantitative histopathological and biochemical assessments on brains from non-demented individuals before death whose brains were free of substantial Alzheimer's pathology, non-demented individuals before death but whose post-mortem examination demonstrated significant amounts of Alzheimer's changes ('mismatches'), and demented Alzheimer's cases. Quantification of amyloid-β plaque burden, stereologically-based counts of neurofibrillary tangles, neurons and reactive glia, and morphological analyses of axons were performed in the multimodal association cortex lining the superior temporal sulcus. Levels of synaptic integrity markers, and soluble monomeric and multimeric amyloid-β and tau species were measured. Our results indicate that some individuals can accumulate equivalent loads of amyloid-β plaques and tangles to those found in demented Alzheimer's cases without experiencing dementia. Analyses revealed four main phenotypic differences among these two groups: (i) mismatches had striking preservation of neuron numbers, synaptic markers and axonal geometry compared to demented cases; (ii) demented cases had significantly higher burdens of fibrillar thioflavin-S-positive plaques and of oligomeric amyloid-β deposits reactive to conformer-specific antibody NAB61 than mismatches; (iii) strong and selective accumulation of hyperphosphorylated soluble tau multimers into the synaptic compartment was noted in demented cases compared with controls but not in mismatches; and (iv) the robust glial activation accompanying amyloid-β and tau pathologies in

  14. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  15. Estudio PET/TC en patología inflamatoria-infecciosa PET/CT in infectious and inflammatory pathology

    Directory of Open Access Journals (Sweden)

    Cecilia Carrera

    2012-06-01

    utilidad para el diagnóstico y seguimiento de pacientes con FOD. Cambia la conducta en la vasculitis sin necesidad de realizar una biopsia y es considerado el método Gold Standard. Además, es útil en el monitoreo del tratamiento y seguimiento en la sarcoidosis.Objective. To demonstrate the utility of PET/CT in infectious and inflammatory diseases. Materials and Methods. We evaluated retrospectively five patients with infectious and inflammatory pathology, by PET/CT scan (hybrid SIEMENS-BIOGRAPH 16, Siemens, Erlangen, Germany in the period between january 2009 and may 2011. Results. Case 1: a 68-year-old woman presented with a 6- months duration fever, fatigue, and weight loss. The rheumatologic examination showed a decrease in both radial pulses with no other associated symptoms. She underwent a temporal artery biopsy, which confirmed temporal arteritis. A PET/CT scan showed significant uptake in the thoracic aorta and major branches. Case 2: An 85-year-old patient with fever of unknown origin (FUO was studied suspecting osteomyelitis of the hip, but on the contrary, PET/CT demonstrated an avid enhancement indicative of gluteal cellulitis and pneumonia, ruling out bone infection. Case 3: a 35-year-old woman with evening fever. PET/CT scan showed enlarged multiple FDG-avid mediastinal, axillary and retroperitoneal lymph nodes, as well as diffuse involvement of the spleen with multiple calcifications. Diagnosis of cytomegalovirus infection was confirmed by positive immunoglobulin G and M. Case 4: a 39-year-old patient with HIV-infection presented with hypercalcemia. PET/CT scan showed buttocks silicone implants with associated avid inflammatory process, confirmed by biopsy. Case 5: a 45-year-old female with previous history of breast cancer under follow-up presented in recent CT scans enlarged mediastinal and supraclavicular lymph nodes, as well as diffuse multifocal splenic involvement, all of them avid on PET / CT examination. Sarcoidosis was confirmed by a

  16. Infectious bacterial pathogens, parasites and pathological correlations of sewage pollution as an important threat to farmed fishes in Egypt.

    Science.gov (United States)

    Mahmoud, Mahmoud A; Abdelsalam, Mohamed; Mahdy, Olfat A; El Miniawy, Hala M F; Ahmed, Zakia A M; Osman, Ahmed H; Mohamed, Hussein M H; Khattab, A M; Zaki Ewiss, M A

    2016-12-01

    This paper is a part of a multi-disciplinary research "Application of Decentralized On-Site Water Treatment System in Egypt for Use in Agriculture and Producing Safe Fish and Animal Proteins". The project aimed to investigate the environmental impact of implementing sewage water before and after treatment using the effluent of the on-site decentralized Japanese' Johkasou system, in agriculture and producing fish protein. The aim is to establish such system in Egypt to strengthen the sanitary conditions of water resources. In the present study, the impact of the sewage pollution in some fish farms at El-Fayyum, Port Said and El-Dakahlia governorates in Egypt was carried out. Water and fish (Oreochromis niloticus and Mugil cephalus) samples were collected from private fish farms of such localities. Bacteriological and chemical examination of water samples revealed the existence of coliforms and many other bacterial species of significant human health hazards. The chemical parameters of water showed a marked deviation from normal levels while examination of fish flesh specimens indicated contamination with Streptococcus Sp., Staphylococcus Sp., and Salmonella in all examined localities. Other bacterial isolates of human health importance (Morganella morganii, Pseudomonas cepacia and Enterococcos durans) were identified. The parasitological examination revealed the presence of encysted metacercariae (EMC); Diplostomatidae, Prohemistomatidae and Heterphyidae. Moreover, two protozoan parasites (Mxyoboulus tilapiae and Ichthyophthirius multifilis) were also recorded. The histopathological examination revealed mild tissue reaction in case of bacterial infection and severe pathological lesions in different organs in case of EMC infection. Lamellar hyperplasia and mononuclear cell infiltration in branchial tissue was common findings. In skeletal muscles, atrophy of muscle fibres, myolysis and myophagia were detected.

  17. Domesticated animals and human infectious diseases of zoonotic origins: domestication time matters.

    Science.gov (United States)

    Morand, Serge; McIntyre, K Marie; Baylis, Matthew

    2014-06-01

    The rate of emergence for emerging infectious diseases has increased dramatically over the last century, and research findings have implicated wildlife as an importance source of novel pathogens. However, the role played by domestic animals as amplifiers of pathogens emerging from the wild could also be significant, influencing the human infectious disease transmission cycle. The impact of domestic hosts on human disease emergence should therefore be ascertained. Here, using three independent datasets we showed positive relationships between the time since domestication of the major domesticated mammals and the total number of parasites or infectious diseases they shared with humans. We used network analysis, to better visualize the overall interactions between humans and domestic animals (and amongst animals) and estimate which hosts are potential sources of parasites/pathogens for humans (and for all other hosts) by investigating the network architecture. We used centrality, a measure of the connection amongst each host species (humans and domestic animals) in the network, through the sharing of parasites/pathogens, where a central host (i.e. high value of centrality) is the one that is infected by many parasites/pathogens that infect many other hosts in the network. We showed that domesticated hosts that were associated a long time ago with humans are also the central ones in the network and those that favor parasites/pathogens transmission not only to humans but also to all other domesticated animals. These results urge further investigation of the diversity and origin of the infectious diseases of domesticated animals in their domestication centres and the dispersal routes associated with human activities. Such work may help us to better understand how domesticated animals have bridged the epidemiological gap between humans and wildlife.

  18. Screening-level assays for potentially human-infectious environmental Legionella spp.

    Science.gov (United States)

    In spite of the fact that Legionella species can be isolated from nonclinical settings, there is no standard method to determine whether environmental legionellae may be infectious to humans. In this study, an in vivo murine model of pneumonia and three in vitro proliferation as...

  19. Lyme disease: a unique human model for an infectious etiology of rheumatic disease.

    Science.gov (United States)

    Malawista, S. E.; Steere, A. C.; Hardin, J. A.

    1984-01-01

    Lyme disease is a complex immune-mediated multi-system disorder that is infectious in origin and inflammatory or "rheumatic" in expression. Through its epidemiologic characteristics, large numbers of a seasonally synchronized patient population are readily available for prospective study. Lyme disease has a known clinical onset ("zero time"), marked by the characteristic expanding skin lesion, erythema chronicum migrans, and a clearly defined pre-articular phase. At least some manifestations of the disorder are responsive to antibiotics, and the causative agent--a spirochete--is now known. These advantages make Lyme disease unique as a human model for an infectious etiology of rheumatic disease. PMID:6516449

  20. Infectious Aortitis.

    Science.gov (United States)

    Ramirez, F Daniel; Jamison, Bruce M; Hibbert, Benjamin

    2016-09-28

    Aortitis is broadly divided into infectious and non-infectious etiologies, each with distinct treatment implications. We present the case of a patient who sustained a type A aortic dissection during urgent coronary angiography for acute coronary syndrome. Clinical findings and events during the procedure raised suspicion for an underlying vascular disorder; however, the diagnosis of staphylococcal aortitis was not made until pathological examination of resected tissue. Clues to the diagnosis of infectious aortitis noted throughout the patient's clinical course are detailed as are potential consequences of diagnostic delays and treatment decisions, underscoring the difficulties in recognizing and managing the condition. In addition, we describe a previously unreported complication of cardiac catheterization in the setting of an infectious aortopathy.

  1. Immunohistochemistry of Programmed Cell Death in Archival Human Pathology Specimens

    Directory of Open Access Journals (Sweden)

    Takami Matsuyama

    2012-05-01

    Full Text Available Immunohistochemistry (IHC for detecting key signal molecules involved in programmed cell death (PCD in archival human pathology specimens is fairly well established. Detection of cleaved caspase-3 in lymphocytes in rheumatoid arthritis (RA and gastric surface foveolar glandular epithelia but not in synoviocytes in RA, gastric fundic glandular epithelia, or nasal NK/T-cell lymphoma (NKTCL cells suggests anti-apoptotic mechanisms in cell differentiation and in oncogenesis such as the induction of survivin. Enzymatically pretreated and ultra-super sensitive detection of beclin-1 in synoviocytes in RA and gastric fundic glandular epithelia suggests enhanced autophagy. The deposition of beclin-1 in fibrinoid necrosis in RA and expression of beclin-1 in detached gastric fundic glandular cells suggest that enhanced autophagy undergoes autophagic cell death (ACD. NKTCL exhibited enhanced autophagy through LC3 labeling and showed densely LC3 labeled cell-debris in regions of peculiar necrosis without deposition of beclin-1, indicating massive ACD in NKTCL and the alternative pathway enhancing autophagy following autophagic vesicle nucleation. Autophagy progression was monitored by labeling aggregated mitochondria and cathepsin D. The cell-debris in massive ACD in NKTCL were positive for 8-hydroxydeoxyguanosine, suggesting DNA oxidation occurred in ACD. Immunohistochemical autophagy and PCD analysis in archival human pathology specimens may offer new insights into autophagy in humans.

  2. Natural human mobility patterns and spatial spread of infectious diseases

    CERN Document Server

    Belik, Vitaly; Brockmann, Dirk

    2011-01-01

    We investigate a model for spatial epidemics explicitly taking into account bi-directional movements between base and destination locations on individual mobility networks. We provide a systematic analysis of generic dynamical features of the model on regular and complex metapopulation network topologies and show that significant dynamical differences exist to ordinary reaction-diffusion and effective force of infection models. On a lattice we calculate an expression for the velocity of the propagating epidemic front and find that in contrast to the diffusive systems, our model predicts a saturation of the velocity with increasing traveling rate. Furthermore, we show that a fully stochastic system exhibits a novel threshold for attack ratio of an outbreak absent in diffusion and force of infection models. These insights not only capture natural features of human mobility relevant for the geographical epidemic spread, they may serve as a starting point for modeling important dynamical processes in human and an...

  3. Organosulfur compounds from alliaceae in the prevention of human pathologies.

    Science.gov (United States)

    Tapiero, Haim; Townsend, Danyelle M; Tew, Kenneth D

    2004-04-01

    A strong association between elevated plasma low-density-lipoprotein (LDL) and the development of cardiovascular diseases (CVD) has been established. Oxidation of LDL (Ox-LDL) promotes vascular dysfunction, enhances the production and release of inflammatory mediators such as reactive oxygen species and contribute to the initiation and progression of atherosclerosis. In addition, Ox-LDL enhances the production and release of tumor necrosis factor (TNF-alpha), interleukin (IL)-6, arachidonic acid metabolites and nitric oxide (NO) that are responsible for various human pathologies including cancer. Organosulfur compounds (OSC) from alliaceae modulate the glutathione (GSH) redox cycle and inhibits NFkappa-B activation in human T cells. Furthermore, OSC bioactivities include antioxidant, antibacterial, anticarcinogenic, antiatherogenic, immunostimulatory, and liver protection potential.

  4. Infectious Agents As Markers of Human Migration toward the Amazon Region of Brazil

    Directory of Open Access Journals (Sweden)

    Ricardo Ishak

    2017-08-01

    Full Text Available Infectious agents are common companions of humans and since ancient times they follow human migration on their search for a better place to live. The study of paleomicrobiology was significantly improved in its accuracy of measurement with the constant development of better methods to detect and analyze nucleic acids. Human tissues are constantly used to trace ancient infections and the association of anthropological evidences are important to confirm the microbiological information. Infectious agents which establish human persistent infections are particularly useful to trace human migrations. In the present article, the evidence of infection by viral agents such as human T-lymphotropic virus 1, human T-lymphotropic virus 2, human herpes virus-8, JC virus, and a bacterium, Chlamydia trachomatis, was described using different methodologies for their detection. Their presence was further used as biomarkers associated with anthropological and other relevant information to trace human migration into the Amazon region of Brazil. The approach also evidenced their microbiological origin, emergence, evolution, and spreading. The information obtained confirms much of the archeological information available tracing ancient and more recent human migration into this particular geographical region. In this article, the paleomicrobiological information on the subject was summarized and reviewed.

  5. Muscle Gene Expression Patterns in Human Rotator Cuff Pathology

    Science.gov (United States)

    Choo, Alexander; McCarthy, Meagan; Pichika, Rajeswari; Sato, Eugene J.; Lieber, Richard L.; Schenk, Simon; Lane, John G.; Ward, Samuel R.

    2014-01-01

    Background: Rotator cuff pathology is a common source of shoulder pain with variable etiology and pathoanatomical characteristics. Pathological processes of fatty infiltration, muscle atrophy, and fibrosis have all been invoked as causes for poor outcomes after rotator cuff tear repair. The aims of this study were to measure the expression of key genes associated with adipogenesis, myogenesis, and fibrosis in human rotator cuff muscle after injury and to compare the expression among groups of patients with varied severities of rotator cuff pathology. Methods: Biopsies of the supraspinatus muscle were obtained arthroscopically from twenty-seven patients in the following operative groups: bursitis (n = 10), tendinopathy (n = 7), full-thickness rotator cuff tear (n = 8), and massive rotator cuff tear (n = 2). Quantitative polymerase chain reaction (qPCR) was performed to characterize gene expression pathways involved in myogenesis, adipogenesis, and fibrosis. Results: Patients with a massive tear demonstrated downregulation of the fibrogenic, adipogenic, and myogenic genes, indicating that the muscle was not in a state of active change and may have difficulty responding to stimuli. Patients with a full-thickness tear showed upregulation of fibrotic and adipogenic genes; at the tissue level, these correspond to the pathologies most detrimental to outcomes of surgical repair. Patients with bursitis or tendinopathy still expressed myogenic genes, indicating that the muscle may be attempting to accommodate the mechanical deficiencies induced by the tendon tear. Conclusions: Gene expression in human rotator cuff muscles varied according to tendon injury severity. Patients with bursitis and tendinopathy appeared to be expressing pro-myogenic genes, whereas patients with a full-thickness tear were expressing genes associated with fatty atrophy and fibrosis. In contrast, patients with a massive tear appeared to have downregulation of all gene programs except inhibition of

  6. Modeling physiological and pathological human neurogenesis in the dish

    Directory of Open Access Journals (Sweden)

    Vania eBroccoli

    2014-07-01

    Full Text Available New advances in directing the neuronal differentiation of human embryonic and induced pluripotent stem cells (hPSCs, abbreviation intended to convey both categories of pluripotent stem cells have promoted the development of culture systems capable of modeling early neurogenesis and neural specification at some of their critical milestones. The hPSC-derived neural rosette can be considered the in vitro counterpart of the developing neural tube, since both structures share a virtually equivalent architecture and related functional properties. Epigenetic stimulation methods can modulate the identity of the rosette neural progenitors in order to generate authentic neuronal subtypes, as well as a full spectrum of neural crest derivatives. The intrinsic capacity of induced pluripotent cell-derived neural tissue to self-organize has become fully apparent with the emergence of innovative in vitro systems that are able to shape the neuronal differentiation of hPSCs into organized tissues that develop in three dimensions. However, significant hurdles remain that must be completely solved in order to facilitate the use of hPSCs in modeling (e.g., late-onset disorders or in building therapeutic strategies for cell replacement. In this direction, new procedures have been established to promote the maturation and functionality of hPSC-derived neurons. Meanwhile, new methods to accelerate the aging of in vitro differentiating cells are still in development. hPSC-based technology has matured enough to offer a significant and reliable model system for early and late neurogenesis that could be extremely informative for the study of the physiological and pathological events that occur during this process. Thus, full exploitation of this cellular system can provide a better understanding of the physiological events that shape human brain structures, as well as a solid platform to investigate the pathological mechanisms at the root of human diseases.

  7. Emerging infectious diseases of wildlife--threats to biodiversity and human health.

    Science.gov (United States)

    Daszak, P; Cunningham, A A; Hyatt, A D

    2000-01-21

    Emerging infectious diseases (EIDs) of free-living wild animals can be classified into three major groups on the basis of key epizootiological criteria: (i) EIDs associated with "spill-over" from domestic animals to wildlife populations living in proximity; (ii) EIDs related directly to human intervention, via host or parasite translocations; and (iii) EIDs with no overt human or domestic animal involvement. These phenomena have two major biological implications: first, many wildlife species are reservoirs of pathogens that threaten domestic animal and human health; second, wildlife EIDs pose a substantial threat to the conservation of global biodiversity.

  8. Infectious Chikungunya Virus in the Saliva of Mice, Monkeys and Humans.

    Science.gov (United States)

    Gardner, Joy; Rudd, Penny A; Prow, Natalie A; Belarbi, Essia; Roques, Pierre; Larcher, Thibaut; Gresh, Lionel; Balmaseda, Angel; Harris, Eva; Schroder, Wayne A; Suhrbier, Andreas

    2015-01-01

    Chikungunya virus (CHIKV) is a reemerging, ordinarily mosquito-transmitted, alphavirus that occasionally produces hemorrhagic manifestations, such as nose bleed and bleeding gums, in human patients. Interferon response factor 3 and 7 deficient (IRF3/7-/-) mice, which are deficient for interferon α/β responses, reliably develop hemorrhagic manifestations after CHIKV infection. Here we show that infectious virus was present in the oral cavity of CHIKV infected IRF3/7-/- mice, likely due to hemorrhagic lesions in the olfactory epithelium that allow egress of infected blood into the nasal, and subsequently, oral cavities. In addition, IRF3/7-/- mice were more susceptible to infection with CHIKV via intranasal and oral routes, with IRF3/7-/- mice also able to transmit virus mouse-to-mouse without an arthropod vector. Cynomolgus macaques often show bleeding gums after CHIKV infection, and analysis of saliva from several infected monkeys also revealed the presence of viral RNA and infectious virus. Furthermore, saliva samples collected from several acute CHIKV patients with hemorrhagic manifestations were found to contain viral RNA and infectious virus. Oral fluids can therefore be infectious during acute CHIKV infections, likely due to hemorrhagic manifestations in the oral/nasal cavities.

  9. Assembly of infectious HIV-1 in human epithelial and T-lymphoblastic cell lines.

    Science.gov (United States)

    Grigorov, Boyan; Arcanger, Fabienne; Roingeard, Philippe; Darlix, Jean-Luc; Muriaux, Delphine

    2006-06-16

    The canonical view of the ultimate steps of HIV-1 replication is that virus assembly and budding are taking place at the plasma membrane of infected cells. Surprisingly, recent studies revealed that these steps also occur on endosomal membranes in the interior of infected cells, such as macrophages. This prompted us to revisit the site of HIV-1 assembly in human epithelial-like cells and in infected human T-lymphoblastic cells. To address this question, we investigated the intracellular location of the major viral structural components of HIV-1, namely Gag, Env and the genomic RNA. Using a sub-cellular fractionation method, as well as immuno-confocal and electron microscopy, we show that Gag, the Env glycoproteins and the genomic RNA accumulate in late endosomes that contain infectious HIV-1 particles. In epithelial-like 293T cells, HIV-1 assembles and buds both at the plasma membrane and in endosomes, while in chronically infected human T lymphocytes, viral assembly mostly occurs within the cell where large amounts of infectious virions accumulate in endosomal compartments. In addition, HIV-1 release could be enhanced by ionomycin, a drug stimulating calcium-dependent exocytosis. These results favour the view that newly made Gag molecules associate with the genomic RNA in the cytosol, then viral core complexes can be targeted to late endosomes together with Env, where infectious HIV-1 are made and subsequently released by exocytosis.

  10. The human immune system's response to carcinogenic and other infectious agents transmitted by mosquito vectors.

    Science.gov (United States)

    Johansson, Olle; Ward, Martin

    2017-01-01

    It has been hypothesised that mosquitoes [Diptera: Culicidae] may play more of a role in certain cancers than is currently appreciated. Research links 33 infectious agents to cancer, 27 of which have a presence in mosquitoes, and that, in addition, mosquito saliva downregulates the immune system. The objective of this paper is to review the literature on the immune system and cancer-causing infectious agents, particularly those present in mosquitoes, with a view to establishing whether such infectious agents can, in the long run, defeat the immune system or be defeated by it. Many of the viruses, bacteria and parasites recognised by the International Agency for Research on Cancer (IARC) as carcinogenic and suspected by others as being involved in cancer have evolved numerous complex ways of avoiding, suppressing or altering the immune system's responses. These features, coupled with the multiplicity and variety of serious infectious agents carried by some species of mosquitoes and the adverse effects on the immune system of mosquito saliva, suggest that post-mosquito bite the immune system is likely to be overwhelmed. In such a situation, immunisation strategies offer little chance of cancer prevention, unless a single or limited number of critical infectious agents can be isolated from the 'mosquito' cocktail. If that proves to be impossible cancer prevention will, therefore, if the hypothesis proves to be correct, rest on the twin strategies of environmentally controlling the mosquito population and humans avoiding being bitten. The latter strategy will involve determining the factors that demark those being bitten from those that are not.

  11. Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials.

    Science.gov (United States)

    Warnes, Sarah L; Little, Zoë R; Keevil, C William

    2015-11-10

    The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health. Respiratory viruses are responsible for more deaths globally than any other infectious agent. Animal coronaviruses that "host jump" to humans result in

  12. A High-Resolution Human Contact Network for Infectious Disease Transmission

    CERN Document Server

    Salathé, Marcel; Lee, Jung Woo; Levis, Philip; Feldman, Marcus W; Jones, James H

    2010-01-01

    The most frequent infectious diseases in humans - and those with the highest potential for rapid pandemic spread - are usually transmitted via droplets during close proximity interactions (CPIs). Despite the importance of this transmission route, very little is known about the dynamic patterns of CPIs. Using wireless sensor network technology, we obtained high-resolution data of CPIs during a typical day at an American high school, permitting the reconstruction of the social network relevant for infectious disease transmission. At a 94% coverage, we collected 762,868 CPIs at a maximal distance of 3 meters among 788 individuals. The data revealed a high density network with typical small world properties and a relatively homogenous distribution of both interaction time and interaction partners among subjects. Computer simulations of the spread of an influenza-like disease on the weighted contact graph are in good agreement with absentee data during the most recent influenza season. Analysis of targeted immuniz...

  13. Pathological, immunohistochemical, and molecular findings in commercial laying hens and in backyard chickens naturally infected with the infectious laryngotracheitis virus

    Directory of Open Access Journals (Sweden)

    IS Preis

    2014-12-01

    Full Text Available Seventy-eight chickens from a very high poultry density (approximately eight million region and twelve backyard chickens from neighboring areas were analyzed by histopathology and additional techniques for the presence of the infectious laryngotracheitis virus. The virus distribution was determined in different tissues using immunohistochemistry (IHC and polymerase chain reaction (PCR. The disease was histopathologically diagnosed in 41.0% (32/78 of the commercial layers. Lesions were mainly characterized by syncytial cells with eosinophilic intranuclear inclusion body formed from the hyperplastic epithelium of the upper respiratory tract, primary and secondary bronchi, and conjunctiva. IHC showed 70% (21/30 positive signal in the larynx/trachea and, 53.8% (14/26 in the lungs, either in epithelial cells or syncytia. In the turbinates and paranasal sinuses, 29.6% (8/27 of samples showed positive signal. PCR detected the following gallid herpesvirus 1-positive percentages: conjunctiva 63.2% (31/49, lungs 57.6% (30/52, turbinates and paranasal sinuses 56% (28/50, and larynx/trachea 50% (39/78. IHC showed to be a useful additional tool for definitive ILT diagnosis, especially during the subacute phase of the disease when syncytial cells with intranuclear inclusion bodies are no longer observed. PCR using specific primers from ICP4 gene, generating a product of 237 base pairs, was sensitive for ILT diagnosis, and very useful for rapid detection of GaHV-1 in chickens. Fixed tissues allowing histopatological examination and detection of GaHV-1 by PCR, are a good option in areas where farms are located several hundred kilometers away from a diagnostic center, reducing problems with conservation of fresh samples and the risk of virus spread.

  14. Armed Forces Institute of Pathology Becomes CDC Registered Testing Site for Human Swine Influenza

    Science.gov (United States)

    2010-01-01

    Bethesda, Maryland This impressive course covers general and specialized areas of ana- tomic pathology. An intensive session in inflammatory, infectious ... peritoneal leiomyomatosis, and synovial sarcomas (posi- tive in 5/42, 4/17, and 6/37 cases). Leiomyo- mas colonized by DOG1-positive Cajal cells...and specificity should be recognized. Am J Surg Pathol. 2009 Sep;33(9):1401-8. Feline peripheral nerve sheath tumors: histologic, immunohis

  15. Coupling infectious diseases, human preventive behavior, and networks--a conceptual framework for epidemic modeling.

    Science.gov (United States)

    Mao, Liang; Yang, Yan

    2012-01-01

    Human-disease interactions involve the transmission of infectious diseases among individuals and the practice of preventive behavior by individuals. Both infectious diseases and preventive behavior diffuse simultaneously through human networks and interact with one another, but few existing models have coupled them together. This article proposes a conceptual framework to fill this knowledge gap and illustrates the model establishment. The conceptual model consists of two networks and two diffusion processes. The two networks include: an infection network that transmits diseases and a communication network that channels inter-personal influence regarding preventive behavior. Both networks are composed of same individuals but different types of interactions. This article further introduces modeling approaches to formulize such a framework, including the individual-based modeling approach, network theory, disease transmission models and behavioral models. An illustrative model was implemented to simulate a coupled-diffusion process during an influenza epidemic. The simulation outcomes suggest that the transmission probability of a disease and the structure of infection network have profound effects on the dynamics of coupled-diffusion. The results imply that current models may underestimate disease transmissibility parameters, because human preventive behavior has not been considered. This issue calls for a new interdisciplinary study that incorporates theories from epidemiology, social science, behavioral science, and health psychology. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. Coevolutionary networks: a novel approach to understanding the relationships of humans with the infectious agents

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Tosta

    2001-04-01

    Full Text Available Human organism is interpenetrated by the world of microorganisms, from the conception until the death. This interpenetration involves different levels of interactions between the partners including trophic exchanges, bi-directional cell signaling and gene activation, besides genetic and epigenetic phenomena, and tends towards mutual adaptation and coevolution. Since these processes are critical for the survival of individuals and species, they rely on the existence of a complex organization of adaptive systems aiming at two apparently conflicting purposes: the maintenance of the internal coherence of each partner, and a mutually advantageous coexistence and progressive adaptation between them. Humans possess three adaptive systems: the nervous, the endocrine and the immune system, each internally organized into subsystems functionally connected by intraconnections, to maintain the internal coherence of the system. The three adaptive systems aim at the maintenance of the internal coherence of the organism and are functionally linked by interconnections, in such way that what happens to one is immediately sensed by the others. The different communities of infectious agents that live within the organism are also organized into functional networks. The members of each community are linked by intraconnections, represented by the mutual trophic, metabolic and other influences, while the different infectious communities affect each other through interconnections. Furthermore, by means of its adaptive systems, the organism influences and is influenced by the microbial communities through the existence of transconnections. It is proposed that these highly complex and dynamic networks, involving gene exchange and epigenetic phenomena, represent major coevolutionary forces for humans and microorganisms.

  17. Glycan-functionalized graphene-FETs toward selective detection of human-infectious avian influenza virus

    Science.gov (United States)

    Ono, Takao; Oe, Takeshi; Kanai, Yasushi; Ikuta, Takashi; Ohno, Yasuhide; Maehashi, Kenzo; Inoue, Koichi; Watanabe, Yohei; Nakakita, Shin-ichi; Suzuki, Yasuo; Kawahara, Toshio; Matsumoto, Kazuhiko

    2017-03-01

    There are global concerns about threat of pandemic caused by the human-infectious avian influenza virus. To prevent the oncoming pandemic, it is crucial to analyze the viral affinity to human-type or avian-type sialoglycans with high sensitivity at high speed. Graphene-FET (G-FET) realizes such high-sensitive electrical detection of the targets, owing to graphene’s high carrier mobility. In the present study, G-FET was functionalized using sialoglycans and employed for the selective detection of lectins from Sambucus sieboldiana and Maackia amurensis as alternatives of the human and avian influenza viruses. Glycan-functionalized G-FET selectively monitored the sialoglycan-specific binding reactions at subnanomolar sensitivity.

  18. Infectious hematopoietic necrosis virus (IHNV) outbreak in farmed rainbow trout in Iran: Viral isolation, pathological findings, molecular confirmation, and genetic analysis.

    Science.gov (United States)

    Ahmadivand, Sohrab; Soltani, Mehdi; Mardani, Karim; Shokrpoor, Sara; Hassanzadeh, Reza; Ahmadpoor, Mehran; Rahmati-Holasoo, Hooman; Meshkini, Saeid

    2017-02-02

    Infectious hematopoietic necrosis virus (IHNV) is the etiological agent of a contagious disease (IHN) mainly in salmonid fish. In the present study, we isolated and identified IHNV in trout fry from Iranian trout farms with unexplained high mortality in 2016. The affected fry showed cumulative mortality of 90% with the gross pathological signs including exophthalmia and hemorrhage of the eye, skin darkening, abdominal distension, ulceration of the snout, and the visceral pallor and yellowish fluid in the intestine. Histopathological examination revealed marked necrosis in the anterior kidney, liver and spleen with the intracytoplasmic inclusion bodies in the liver sections. Also, intranuclear inclusion body and marginated chromatin were observable in the hematopoietic cells of the kidney. The homogenates tissues of infected fry induced IHNV-positive cytopathic effects (CPE) in EPC cells and confirmed by RT-PCR reactions and sequencing. Phylogenetic analysis revealed the Iranian IHNV isolates belonged to the European (E) genogroup with 100% identity to some Italian isolates. This is the first report of IHNV infection in farmed trout fry in Iran describing the viral isolation, clinical symptoms, histopathological findings, molecular confirmation, and genetic analysis suggestion of the specific country of origin.

  19. Infectious Achilles Tendinitis After Local Injection of Human Placental Extracts: A Case Report.

    Science.gov (United States)

    Kim, Yoon-Chung; Ahn, Jae Hoon; Kim, Man-Soo

    2015-01-01

    Local injections of corticosteroids or human placental extracts are sometimes used for the treatment of resistant tendinitis or fasciitis. We report a case of infectious Achilles tendinitis complicated by calcaneal osteomyelitis after injection of human placental extracts for the Achilles tendinitis. She was treated with excision of the infected bone and tendon, followed by V-Y lengthening of the proximal portion of the Achilles tendon in a single stage. At 2 years postoperative, she remained symptom free without any signs of recurrence, and the follow-up magnetic resonance imaging scan demonstrated a well-maintained Achilles tendon with normal signal intensity. Copyright © 2015 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  20. A Defective Interfering Influenza RNA Inhibits Infectious Influenza Virus Replication in Human Respiratory Tract Cells: A Potential New Human Antiviral

    Directory of Open Access Journals (Sweden)

    Claire M. Smith

    2016-08-01

    Full Text Available Defective interfering (DI viruses arise during the replication of influenza A virus and contain a non-infective version of the genome that is able to interfere with the production of infectious virus. In this study we hypothesise that a cloned DI influenza A virus RNA may prevent infection of human respiratory epithelial cells with infection by influenza A. The DI RNA (244/PR8 was derived by a natural deletion process from segment 1 of influenza A/PR/8/34 (H1N1; it comprises 395 nucleotides and is packaged in the DI virion in place of a full-length genome segment 1. Given intranasally, 244/PR8 DI virus protects mice and ferrets from clinical influenza caused by a number of different influenza A subtypes and interferes with production of infectious influenza A virus in cells in culture. However, evidence that DI influenza viruses are active in cells of the human respiratory tract is lacking. Here we show that 244/PR8 DI RNA is replicated by an influenza A challenge virus in human lung diploid fibroblasts, bronchial epithelial cells, and primary nasal basal cells, and that the yield of challenge virus is significantly reduced in a dose-dependent manner indicating that DI influenza virus has potential as a human antiviral.

  1. Cutting edge: Human regulatory T cells require IL-35 to mediate suppression and infectious tolerance.

    Science.gov (United States)

    Chaturvedi, Vandana; Collison, Lauren W; Guy, Clifford S; Workman, Creg J; Vignali, Dario A A

    2011-06-15

    Human regulatory T cells (T(reg)) are essential for the maintenance of immune tolerance. However, the mechanisms they use to mediate suppression remain controversial. Although IL-35 has been shown to play an important role in T(reg)-mediated suppression in mice, recent studies have questioned its relevance in human T(reg). In this study, we show that human T(reg) express and require IL-35 for maximal suppressive capacity. Substantial upregulation of EBI3 and IL12A, but not IL10 and TGFB, was observed in activated human T(reg) compared with conventional T cells (T(conv)). Contact-independent T(reg)-mediated suppression was IL-35 dependent and did not require IL-10 or TGF-β. Lastly, human T(reg)-mediated suppression led to the conversion of the suppressed T(conv) into iTr35 cells, an IL-35-induced T(reg) population, in an IL-35-dependent manner. Thus, IL-35 contributes to human T(reg)-mediated suppression, and its conversion of suppressed target T(conv) into IL-35-induced T(reg) may contribute to infectious tolerance.

  2. Human infectious disease burdens decrease with urbanization but not with biodiversity

    Science.gov (United States)

    Wood, Chelsea L.; McInturff, Alex; Young, Hillary S.; Kim, DoHyung; Lafferty, Kevin D.

    2017-01-01

    nfectious disease burdens vary from country to country and year to year due to ecological and economic drivers. Recently, Murray et al. (Murray CJ et al. 2012 Lancet 380, 2197–2223. (doi:10.1016/S0140-6736(12)61689-4)) estimated country-level morbidity and mortality associated with a variety of factors, including infectious diseases, for the years 1990 and 2010. Unlike other databases that report disease prevalence or count outbreaks per country, Murray et al. report health impacts in per-person disability-adjusted life years (DALYs), allowing comparison across diseases with lethal and sublethal health effects. We investigated the spatial and temporal relationships between DALYs lost to infectious disease and potential demographic, economic, environmental and biotic drivers, for the 60 intermediate-sized countries where data were available and comparable. Most drivers had unique associations with each disease. For example, temperature was positively associated with some diseases and negatively associated with others, perhaps due to differences in disease agent thermal optima, transmission modes and host species identities. Biodiverse countries tended to have high disease burdens, consistent with the expectation that high diversity of potential hosts should support high disease transmission. Contrary to the dilution effect hypothesis, increases in biodiversity over time were not correlated with improvements in human health, and increases in forestation over time were actually associated with increased disease burden. Urbanization and wealth were associated with lower burdens for many diseases, a pattern that could arise from increased access to sanitation and healthcare in cities and increased investment in healthcare. The importance of urbanization and wealth helps to explain why most infectious diseases have become less burdensome over the past three decades, and points to possible levers for further progress in improving global public health.

  3. Postoperative Infectious Morbidities of Cesarean Delivery in Human Immunodeficiency Virus-Infected Women

    Directory of Open Access Journals (Sweden)

    Helen Cavasin

    2009-01-01

    Full Text Available Objective. To compare the infectious complication rates from cesarean delivery of human immunodeficiency virus (HIV-infected women and HIV-negative women. Materials and Methods. A retrospective analysis was performed on data derived from HIV-infected women and HIV-negative women, who underwent cesarean delivery at two teaching hospitals. Main outcome measures were infectious postoperative morbidity. Descriptive, comparison analysis, and multiple logistic regression analysis were performed. Results. One hundred and nineteen HIV-infected women and 264 HIV-negative women delivered by cesarean section and were compared. The HIV-negative women were more likely than the HIV-infected women to deliver by emergent cesarean section (78.0% versus 51.3%, resp., .05. In a multivariate stepwise logistic analysis, emergent cesarean delivery and chorioamnionitis but not HIV infection were associated with increased rate of post-operative endometritis (odds ratio (OR 4.10, 95% confidence interval (95% CI 1.41–11.91, <.01, and OR 3.02, 95% CI 1.13–8.03, <.05, resp.. Conclusion. In our facilities, emergent cesarean delivery and chorioamnionitis but not HIV infection were identified as risk factors for post-operative endometritis.

  4. Infectious Progeny of 2009 A (H1N1) Influenza Virus Replicated in and Released from Human Neutrophils.

    Science.gov (United States)

    Zhang, Zhang; Huang, Tao; Yu, Feiyuan; Liu, Xingmu; Zhao, Conghui; Chen, Xueling; Kelvin, David J; Gu, Jiang

    2015-12-07

    Various reports have indicated that a number of viruses could infect neutrophils, but the multiplication of viruses in neutrophils was abortive. Based on our previous finding that avian influenza viral RNA and proteins were present in the nucleus of infected human neutrophils in vivo, we investigated the possibility of 2009 A (H1N1) influenza viral synthesis in infected neutrophils and possible release of infectious progeny from host cells. In this study we found that human neutrophils in vitro without detectable level of sialic acid expression could be infected by this virus strain. We also show that the infected neutrophils can not only synthesize 2009 A (H1N1) viral mRNA and proteins, but also produce infectious progeny. These findings suggest that infectious progeny of 2009 A (H1N1) influenza virus could be replicated in and released from human neutrophils with possible clinical implications.

  5. Using GPS Technology to Quantify Human Mobility, Dynamic Contacts and Infectious Disease Dynamics in a Resource-Poor Urban Environment: e58802

    National Research Council Canada - National Science Library

    Gonzalo M Vazquez-Prokopec; Donal Bisanzio; Steven T Stoddard; Valerie Paz-Soldan; Amy C Morrison; John P Elder; Jhon Ramirez-Paredes; Eric S Halsey; Tadeusz J Kochel; Thomas W Scott; Uriel Kitron

    2013-01-01

      Empiric quantification of human mobility patterns is paramount for better urban planning, understanding social network structure and responding to infectious disease threats, especially in light...

  6. Using organotypic (raft) epithelial tissue cultures for the biosynthesis and isolation of infectious human papillomaviruses.

    Science.gov (United States)

    Ozbun, Michelle A; Patterson, Nicole A

    2014-08-01

    Papillomaviruses have a strict tropism for epithelial cells, and they are fully reliant on cellular differentiation for completion of their life cycles, resulting in the production of progeny virions. Thus, a permissive environment for full viral replication in vitro-wherein virion morphogenesis occurs under cooperative viral and cellular cues-requires the cultivation of epithelium. Presented in the first section of this unit is a protocol to grow differentiating epithelial tissues that mimic many important morphological and biochemical aspects of normal skin. The technique involves growing epidermal cells atop a dermal equivalent consisting of live fibroblasts and a collagen lattice. Epithelial stratification and differentiation ensues when the keratinocyte-dermal equivalent is placed at the air-liquid interface. The apparent floating nature of the cell-matrix in this method led to the nickname "raft" cultures. The general technique can be applied to normal low passage keratinocytes, to cells stably transfected with papillomavirus genes or genomes, or keratinocytes established from neoplastic lesions. However, infectious papillomavirus particles have only been isolated from organotypic epithelial cultures initiated with cells that maintain oncogenic human papillomavirus genomes in an extrachomosomal replicative form. The second section of this unit is dedicated to a virion isolation method that minimizes aerosol and skin exposure to these human carcinogens. Although the focus of the protocols is on the growth of tissues that yields infectious papillomavirus progeny, this culture system facilitates the investigation of these fastidious viruses during their complex replicative cycles, and raft tissues can be manipulated and harvested at any point during the process. Importantly, a single-step virus growth cycle is achieved in this process, as it is unlikely that progeny virions are released to initiate subsequent rounds of infection.

  7. ["Acute human glanders". Contribution for the scientific history of the Museum of pathological anatomy established in Trieste Hospital].

    Science.gov (United States)

    Braulin, F

    2005-12-01

    The Museum of Pathological Anatomy of the Regina Elena City Hospital of Trieste houses various pathological preparations of infective and contagious diseases, dating back to the early 1900's (ileo-typhus, dysentery, tuberculosis, syphillis, pulmonary plague, etc.) together with their relative diagnostic certificates. These bear witness to the key role of the Hospital's Anatomical Institute (in operation operating since 1872) during the height of the Pasteurian age. In fact, the Institute houses several anatomical-pathological preparations from a fatal clinical case of "acute human glanders". These preparations were correlated by laboratory animal experiments using Strauss' method and emblematically recall the eziological determinism of the new bacteriological science. The preparations served in their day not only as indisputable diagnostic evidence, but can now be considered a promotional metaphor of the scientific mission the Triestine Anatomical Institutés Director, Dr. Enrico Ferrarri (a disciple of Richard Paltauf), endeavored to assign to the Triestine Pathological and Anatomical Institute by strenghthening it with new laboratory methodologies. The establishment of a new "predominant and determining vision" in the international diagnostics of infectious disease was also emerging from the Haspurg city's hospital medicine. Indeed, it was here that in 1907, the brief scientific debate focussing on the cadaver of a coachman who had been infected by a glanders-infected horse was apparently taking place only locally. Yet, it can now be seen as referring to what was happening on the international scale, in a setting that after a century of empiricism and morphologism, was characterized by the progressive penetration of laboratory medicine into clinical-anatomical medicine.

  8. The consequences of human actions on risks for infectious diseases: a review

    Science.gov (United States)

    Lindahl, Johanna F.; Grace, Delia

    2015-01-01

    The human population is growing, requiring more space for food production, and needing more animals to feed it. Emerging infectious diseases are increasing, causing losses in both human and animal lives, as well as large costs to society. Many factors are contributing to disease emergence, including climate change, globalization and urbanization, and most of these factors are to some extent caused by humans. Pathogens may be more or less prone to emergence in themselves, and rapidly mutating viruses are more common among the emerging pathogens. The climate-sensitive vector-borne diseases are likely to be emerging due to climate changes and environmental changes, such as increased irrigation. This review lists the factors within pathogens that make them prone to emergence, and the modes of transmission that are affected. The anthropogenic changes contributing to disease emergence are described, as well as how they directly and indirectly cause either increased numbers of susceptible or exposed individuals, or cause increased infectivity. Many actions may have multiple direct or indirect effects, and it may be difficult to assess what the consequences may be. In addition, most anthropogenic drivers are related to desired activities, such as logging, irrigation, trade, and travelling, which the society is requiring. It is important to research more about the indirect and direct effects of the different actions to understand both the benefits and the risks. PMID:26615822

  9. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    Science.gov (United States)

    Hoehndorf, Robert; Schofield, Paul N.; Gkoutos, Georgios V.

    2015-06-01

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  10. The consequences of human actions on risks for infectious diseases: a review.

    Science.gov (United States)

    Lindahl, Johanna F; Grace, Delia

    2015-01-01

    The human population is growing, requiring more space for food production, and needing more animals to feed it. Emerging infectious diseases are increasing, causing losses in both human and animal lives, as well as large costs to society. Many factors are contributing to disease emergence, including climate change, globalization and urbanization, and most of these factors are to some extent caused by humans. Pathogens may be more or less prone to emergence in themselves, and rapidly mutating viruses are more common among the emerging pathogens. The climate-sensitive vector-borne diseases are likely to be emerging due to climate changes and environmental changes, such as increased irrigation. This review lists the factors within pathogens that make them prone to emergence, and the modes of transmission that are affected. The anthropogenic changes contributing to disease emergence are described, as well as how they directly and indirectly cause either increased numbers of susceptible or exposed individuals, or cause increased infectivity. Many actions may have multiple direct or indirect effects, and it may be difficult to assess what the consequences may be. In addition, most anthropogenic drivers are related to desired activities, such as logging, irrigation, trade, and travelling, which the society is requiring. It is important to research more about the indirect and direct effects of the different actions to understand both the benefits and the risks.

  11. Analysis of the human diseasome using phenotype similarity between common, genetic, and infectious diseases

    KAUST Repository

    Hoehndorf, Robert

    2015-06-08

    Phenotypes are the observable characteristics of an organism arising from its response to the environment. Phenotypes associated with engineered and natural genetic variation are widely recorded using phenotype ontologies in model organisms, as are signs and symptoms of human Mendelian diseases in databases such as OMIM and Orphanet. Exploiting these resources, several computational methods have been developed for integration and analysis of phenotype data to identify the genetic etiology of diseases or suggest plausible interventions. A similar resource would be highly useful not only for rare and Mendelian diseases, but also for common, complex and infectious diseases. We apply a semantic text-mining approach to identify the phenotypes (signs and symptoms) associated with over 6,000 diseases. We evaluate our text-mined phenotypes by demonstrating that they can correctly identify known disease-associated genes in mice and humans with high accuracy. Using a phenotypic similarity measure, we generate a human disease network in which diseases that have similar signs and symptoms cluster together, and we use this network to identify closely related diseases based on common etiological, anatomical as well as physiological underpinnings.

  12. Infectious diseases, IL6 -174G>C polymorphism, and human development.

    Science.gov (United States)

    Napolioni, Valerio; MacMurray, James

    2016-01-01

    Interleukin-6 (IL6) is a pro-inflammatory cytokine that is required for resistance against many pathogens. However, sustained IL6 activity can cause tissue damage in the periphery and brain. Previous studies have shown that populations in disease-endemic regions adapt by selecting the high-producing G-allele at the -174G>C (rs1800795) polymorphism, while others have linked increased IL6 to cognitive impairments. The present study sought to determine whether up-regulation of IL6 by the G-allele at rs1800795 polymorphism in disease-endemic regions was associated with increased cognitive deficits and corollary reductions in social, economic, and political development. We tested these hypotheses in a global sample of 189 nations with World Health Organization ratings for infectious diseases. We also included the Historical Pathogen Prevalence index, a measure of national average intelligence (IQ), and the United Nation Human Development Index (HDI) including per capita income, life expectancy, child mortality, and fertility rate. IL6 -174G>C allele frequencies were obtained from 171,168 individuals spanning 84 nations. The high-producing G-allele frequency was positively correlated with infectious disease ranking (r=0.745, P<0.001) and negatively with IQ (r=-0.524, P<0.001) and HDI (r=-0.671, P<0.001). These robust findings suggest that in regions with a high pathogen burden the need for a strong IL6 response is accompanied by cognitive deficits and reduced HDI ranking. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. A pathology atlas of the human cancer transcriptome.

    Science.gov (United States)

    Uhlen, Mathias; Zhang, Cheng; Lee, Sunjae; Sjöstedt, Evelina; Fagerberg, Linn; Bidkhori, Gholamreza; Benfeitas, Rui; Arif, Muhammad; Liu, Zhengtao; Edfors, Fredrik; Sanli, Kemal; von Feilitzen, Kalle; Oksvold, Per; Lundberg, Emma; Hober, Sophia; Nilsson, Peter; Mattsson, Johanna; Schwenk, Jochen M; Brunnström, Hans; Glimelius, Bengt; Sjöblom, Tobias; Edqvist, Per-Henrik; Djureinovic, Dijana; Micke, Patrick; Lindskog, Cecilia; Mardinoglu, Adil; Ponten, Fredrik

    2017-08-18

    Cancer is one of the leading causes of death, and there is great interest in understanding the underlying molecular mechanisms involved in the pathogenesis and progression of individual tumors. We used systems-level approaches to analyze the genome-wide transcriptome of the protein-coding genes of 17 major cancer types with respect to clinical outcome. A general pattern emerged: Shorter patient survival was associated with up-regulation of genes involved in cell growth and with down-regulation of genes involved in cellular differentiation. Using genome-scale metabolic models, we show that cancer patients have widespread metabolic heterogeneity, highlighting the need for precise and personalized medicine for cancer treatment. All data are presented in an interactive open-access database (www.proteinatlas.org/pathology) to allow genome-wide exploration of the impact of individual proteins on clinical outcomes. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  14. Epigenetic modifications and human pathologies: cancer and CVD.

    Science.gov (United States)

    Duthie, Susan J

    2011-02-01

    Epigenetic changes are inherited alterations in DNA that affect gene expression and function without altering the DNA sequence. DNA methylation is one epigenetic process implicated in human disease that is influenced by diet. DNA methylation involves addition of a 1-C moiety to cytosine groups in DNA. Methylated genes are not transcribed or are transcribed at a reduced rate. Global under-methylation (hypomethylation) and site-specific over-methylation (hypermethylation) are common features of human tumours. DNA hypomethylation, leading to increased expression of specific proto-oncogenes (e.g. genes involved in proliferation or metastasis) can increase the risk of cancer as can hypermethylation and reduced expression of tumour suppressor (TS) genes (e.g. DNA repair genes). DNA methyltransferases (DNMT), together with the methyl donor S-adenosylmethionine (SAM), facilitate DNA methylation. Abnormal DNA methylation is implicated not only in the development of human cancer but also in CVD. Polyphenols, a group of phytochemicals consumed in significant amounts in the human diet, effect risk of cancer. Flavonoids from tea, soft fruits and soya are potent inhibitors of DNMT in vitro, capable of reversing hypermethylation and reactivating TS genes. Folates, a group of water-soluble B vitamins found in high concentration in green leafy vegetables, regulate DNA methylation through their ability to generate SAM. People who habitually consume the lowest level of folate or with the lowest blood folate concentrations have a significantly increased risk of developing several cancers and CVD. This review describes how flavonoids and folates in the human diet alter DNA methylation and may modify the risk of human colon cancer and CVD.

  15. A brief overview of the 33rd Annual STP Symposium on the translational pathology: relevance of toxicologic pathology to human health.

    Science.gov (United States)

    Hoenerhoff, Mark J; Silverman, Lee; Francke, Sabine

    2015-01-01

    The 33rd Society of Toxicologic Pathology's Annual Symposium focused on translational science and the relevance of toxicologic pathology to human health. Toxicologic pathologists work in diverse settings studying changes elicited by pharmacological, chemical, and environmental agents and factors that modify these responses. Regardless of the work setting, society members are dedicated to the integration of toxicologic pathology into hazard identification, risk assessment, and risk communication regarding human and animal exposure to potentially toxic substances. Toxicologic pathologists routinely face not only questions regarding pathological changes related to compound exposure but also questions concerning what translational relevance those lesions and exposures have to a human population or organ system. This symposium provided a basis for the membership to understand the variety of roles the toxicologic pathologist plays in translational science, where our gaps in translational science are, and how we can move forward to better address the challenges in the field translational science in order to continue to positively impact human health.

  16. Cardiovascular pathology in patients with human immune deficiency virus infection

    OpenAIRE

    Valenzuela-Rodríguez, Germán; Fellow of the American College of Physicians

    2013-01-01

    Human immunodeficiency virus (HIV) infection increases both morbidity and mortality by inducing severe immunosupression that generates opportunistic infections. Following use of high active antiretroviral therapy (HAART) in infected patients, infection-related mortality has decreased and both survival and cardiovascular disease have increased. The etiology of cardiovascular disease could be related to either infection itself, proatherogenic conditions associated with antiretroviral therapy or...

  17. Purification of infectious human herpesvirus 6A virions and association of host cell proteins

    Directory of Open Access Journals (Sweden)

    Garoff Henrik

    2007-10-01

    Full Text Available Abstract Background Viruses that are incorporating host cell proteins might trigger autoimmune diseases. It is therefore of interest to identify possible host proteins associated with viruses, especially for enveloped viruses that have been suggested to play a role in autoimmune diseases, like human herpesvirus 6A (HHV-6A in multiple sclerosis (MS. Results We have established a method for rapid and morphology preserving purification of HHV-6A virions, which in combination with parallel analyses with background control material released from mock-infected cells facilitates qualitative and quantitative investigations of the protein content of HHV-6A virions. In our iodixanol gradient purified preparation, we detected high levels of viral DNA by real-time PCR and viral proteins by metabolic labelling, silver staining and western blots. In contrast, the background level of cellular contamination was low in the purified samples as demonstrated by the silver staining and metabolic labelling analyses. Western blot analyses showed that the cellular complement protein CD46, the receptor for HHV-6A, is associated with the purified and infectious virions. Also, the cellular proteins clathrin, ezrin and Tsg101 are associated with intact HHV-6A virions. Conclusion Cellular proteins are associated with HHV-6A virions. The relevance of the association in disease and especially in autoimmunity will be further investigated.

  18. Overview of the "epigenetic end points in toxicologic pathology and relevance to human health" session of the 2014 Society Of Toxicologic Pathology Annual Symposium.

    Science.gov (United States)

    Hoenerhoff, Mark J; Hartke, James

    2015-01-01

    The theme of the Society of Toxicologic Pathology 2014 Annual Symposium was "Translational Pathology: Relevance of Toxicologic Pathology to Human Health." The 5th session focused on epigenetic end points in biology, toxicity, and carcinogenicity, and how those end points are relevant to human exposures. This overview highlights the various presentations in this session, discussing integration of epigenetics end points in toxicologic pathology studies, investigating the role of epigenetics in product safety assessment, epigenetic changes in cancers, methodologies to detect them, and potential therapies, chromatin remodeling in development and disease, and epigenomics and the microbiome. The purpose of this overview is to discuss the application of epigenetics to toxicologic pathology and its utility in preclinical or mechanistic based safety, efficacy, and carcinogenicity studies.

  19. Pathology of Human Pheochromocytoma and Paraganglioma Xenografts in NSG Mice

    Science.gov (United States)

    Powers, James F.; Pacak, Karel; Tischler, Arthur S.

    2016-01-01

    A major impediment to the development of effective treatments for metastatic or unresectable pheochromocytomas and paragangliomas has been the absence of valid models for pre-clinical testing. Attempts to establish cell lines or xenografts from human pheochromocytomas and paragangliomas have previously been unsuccessful. NOD-scid gamma (NSG) mice are a recently developed strain lacking functional B-cells, T-cells and NK cells. We report here that xenografts of primary human paragangliomas will take in NSG mice while maintaining their architectural and immunophenotypic characteristics as expressed in the patients. In contrast to grafts of cell lines and of most common types of primary tumors, the growth rate of grafted paragangliomas is very slow, accurately representing the growth rate of most pheochromocytomas and paragangliomas even in metastases in humans. Although the model is therefore technically challenging, primary patient derived xenografts of paragangliomas in NSG mice provide a potentially valuable new tool that could prove especially valuable for testing treatments aimed at eradicating the small tumor deposits that are often numerous in patients with metastatic paraganglioma. PMID:27709415

  20. Phase transition of the microvascular network architecture in human pathologies.

    Science.gov (United States)

    Bianciardi, Giorgio; Traversi, Claudio; Cattaneo, Ruggero; De Felice, Claudia; Monaco, Annalisa; Tosi, Gianmarco; Parrini, Stefano; Latini, Giuseppe

    2012-01-01

    We have investigated the microvascular pattern in acquired or genetic diseases in humans. The lower gingival and vestibular oral mucosa, as well as the optic nerve head, was chosen to characterize the vascular pattern complexity due to the simple accessibility and visibility Local fractal dimensions, fractal dimension of the minimum path and Lempel-Ziv complexity have been used as operational numerical tools to characterize the microvascular networks. In the normal healthy subjects microvascular networks show nonlinear values corresponding to the complexity of a diffusion limited aggregation (DLA) model, while in several acquired or genetic diseases they are approaching the ones of an invasion percolation model.

  1. [Role of animal gastric Helicobacter species in human gastric pathology].

    Science.gov (United States)

    Pozdeev, O K; Pozdeeva, A O; Pozdnyak, A O; Saifutdinov, R G

    2015-01-01

    Animal Helicobacter species other than Helicobacter pylori are also able to cause human gastritis, gastric ulcers, and MALT lymphomas. Animal Helicobacter species are presented with typical spiral fastidious microorganisms colonizing the gastric mucosa of different animals. Bacteria initially received their provisional name Helicobacter heilmannii, and out of them at least five species colonizing the gastric mucosa of pigs, cats, and dogs were isolated later on. A high proportion of these diseases are shown to be zoonotic. Transmission of pathogens occurs by contact. The factors of bacterial pathogenicity remain little studied.

  2. Human cysticercosis: parasitology, pathology, clinical manifestations and available treatment.

    Science.gov (United States)

    Webbe, G

    1994-10-01

    Human cysticercosis is a global health problem and neurocysticercosis a serious clinical syndrome. The diagnosis of neurocysticercosis can now be made with a high degree of accuracy by scrutiny of clinical signs and symptoms in combination with X-ray, computed tomography or magnetic resonance imaging, serological tests and laboratory examinations. Differential clinical diagnosis with tumor, and vascular and inflammatory conditions, may however, prove difficult in nonendemic areas. The management of cysticercosis has been radically changed by the advent of effective chemotherapy. Both the heterocyclic pyrazinoisoquinoline compound, praziquantel and the benzimidazole carbamate, albendazole, have now been extensively tested and successfully used for treatments of neurocysticercosis, usually in combination with corticosteroids. The definition of appropriate criteria and guidelines for the use of chemotherapy, may however, require further research. Surgical interventions continue to play an important role in certain clinical presentations. Recent advances in immunological research hold realistic promise for the development of a vaccine against Taenia solium.

  3. Gene Expression Analysis of Human Vascular Endothelial Cells Treated by Ouabain in Pathological Concentration

    Institute of Scientific and Technical Information of China (English)

    任延平; 吕卓人

    2004-01-01

    Objectives To study the gene expression of human vascular endothelial cells (HUVEC) treated by ouabain in pathological concentration. Methods The response of endothelial cells to ouabain of 1.8 nmol/L was explored with a complementary DNA microarray representing 8 464 different human genes. Results The results of mRNA profiles analysis indicated that 129 of the genes were differently expressed, 26 were upregulated. Conclusions The pathological role of ouabain on HUVEC may be involved in the controlling of DNA transcription、protein translation、 metabolism and signal transduction.

  4. Trace elements in human physiology and pathology: zinc and metallothioneins.

    Science.gov (United States)

    Tapiero, Haim; Tew, Kenneth D

    2003-11-01

    Zinc is one of the most abundant nutritionally essential elements in the human body. It is found in all body tissues with 85% of the whole body zinc in muscle and bone, 11% in the skin and the liver and the remaining in all the other tissues. In multicellular organisms, virtually all zinc is intracellular, 30-40% is located in the nucleus, 50% in the cytoplasm, organelles and specialized vesicles (for digestive enzymes or hormone storage) and the remainder in the cell membrane. Zinc intake ranges from 107 to 231 micromol/d depending on the source, and human zinc requirement is estimated at 15 mg/d. Zinc has been shown to be essential to the structure and function of a large number of macromolecules and for over 300 enzymic reactions. It has both catalytic and structural roles in enzymes, while in zinc finger motifs, it provides a scaffold that organizes protein sub-domains for the interaction with either DNA or other proteins. It is critical for the function of a number of metalloproteins, inducing members of oxido-reductase, hydrolase ligase, lyase family and has co-activating functions with copper in superoxide dismutase or phospholipase C. The zinc ion (Zn(++)) does not participate in redox reactions, which makes it a stable ion in a biological medium whose potential is in constant flux. Zinc ions are hydrophilic and do not cross cell membranes by passive diffusion. In general, transport has been described as having both saturable and non-saturable components, depending on the Zn(II) concentrations involved. Zinc ions exist primarily in the form of complexes with proteins and nucleic acids and participate in all aspects of intermediary metabolism, transmission and regulation of the expression of genetic information, storage, synthesis and action of peptide hormones and structural maintenance of chromatin and biomembranes.

  5. Integrating pathology into human disease modelling--how to eat the elephant.

    Science.gov (United States)

    Scudamore, Cheryl L

    2014-05-01

    Mouse models are increasingly being used for the study of human disease, and the generation and functional characterisation of new models is underpinned by high-throughput phenotyping consortia such as the International Mouse Phenotyping Consortium. A new study by Adissu and colleagues, published in Disease Models & Mechanisms, demonstrates the usefulness of histopathology in providing corroborative information and uncovering novel phenotypes in genetically modified mice in a high-throughput screen. Although pathology is recognised as a valuable tool to enhance our understanding of animal disease models, it has also been systematically under-resourced. This Editorial aims to highlight ways in which the gap between the usefulness of pathology and its perceived inaccessibility can be addressed by considering pragmatic solutions for planning, resourcing and accessing pathology expertise. The role of funding agencies, academic centres and journals in ensuring that the value of pathology is fully recognised and is adequately supported and funded is also discussed.

  6. Recovery of infectious human immunodeficiency virus type 1 after fusion of defectively infected clones of U-937 cells.

    OpenAIRE

    1991-01-01

    Polyethylene glycol was used to induce polykaryon formation among U-937 cell subclones carrying defective human immunodeficiency virus (HIV) type 1 proviral DNA. Fusion of cells which produced gp120-defective virions (UHC15.7) with cells unable to generate reverse transcriptase (RT) activity (UHC8 and UHC18) yielded polykaryons which made infectious viral progeny that showed normal protein profiles. Southern blot analysis of proviral DNA of cells infected with such fusion-derived virus reveal...

  7. Genomic imprinting and human psychology: cognition, behavior and pathology.

    Science.gov (United States)

    Goos, Lisa M; Ragsdale, Gillian

    2008-01-01

    Imprinted genes expressed in the brain are numerous and it has become clear that they play an important role in nervous system development and function. The significant influence of genomic imprinting during development sets the stage for structural and physiological variations affecting psychological function and behaviour, as well as other physiological systems mediating health and well-being. However, our understanding of the role of imprinted genes in behaviour lags far behind our understanding of their roles in perinatal growth and development. Knowledge of genomic imprinting remains limited among behavioral scientists and clinicians and research regarding the influence of imprinted genes on normal cognitive processes and the most common forms of neuropathology has been limited to date. In this chapter, we will explore how knowledge of genomic imprinting can be used to inform our study of normal human cognitive and behavioral processes as well as their disruption. Behavioural analyses of rare imprinted disorders, such as Prader-Willi and Angelman syndromes, provide insight regarding the phenotypic impact of imprinted genes in the brain, and can be used to guide the study of normal behaviour as well as more common but etiologically complex disorders such as ADHD and autism. Furthermore, hypotheses regarding the evolutionary development of imprinted genes can be used to derive predictions about their role in normal behavioural variation, such as that observed in food-related and social interactions.

  8. Human papillomavirus type 59 immortalized keratinocytes express late viral proteins and infectious virus after calcium stimulation.

    Science.gov (United States)

    Lehr, Elizabeth E; Qadadri, Brahim; Brown, Calla R; Brown, Darron R

    2003-09-30

    Human papillomavirus type 59 (HPV 59) is an oncogenic type related to HPV 18. HPV 59 was recently propagated in the athymic mouse xenograft system. A continuous keratinocyte cell line infected with HPV 59 was created from a foreskin xenograft grown in an athymic mouse. Cells were cultured beyond passage 50. The cells were highly pleomorphic, containing numerous abnormally shaped nuclei and mitotic figures. HPV 59 sequences were detected in the cells by DNA in situ hybridization in a diffuse nuclear distribution. Southern blots were consistent with an episomal state of HPV 59 DNA at approximately 50 copies per cell. Analysis of the cells using a PCR/reverse blot strip assay, which amplifies a portion of the L1 open reading frame, was strongly positive. Differentiation of cells in monolayers was induced by growth in F medium containing 2 mM calcium chloride for 10 days. Cells were harvested as a single tissue-like sheet, and histologic analysis revealed a four-to-six cell-thick layer. Transcripts encoding involucrin, a cornified envelope protein, and the E1/E4 and E1/E4/L1 viral transcripts were detected after several days of growth in F medium containing 2 mM calcium chloride. The E1/E4 and L1 proteins were detected by immunohistochemical analysis, and virus particles were seen in electron micrographs in a subset of differentiated cells. An extract of differentiated cells was prepared by vigorous sonication and was used to infect foreskin fragments. These fragments were implanted into athymic mice. HPV 59 was detected in the foreskin xenografts removed 4 months later by DNA in situ hybridization and PCR/reverse blot assay. Thus, the complete viral growth cycle, including production on infectious virus, was demonstrated in the HPV 59 immortalized cells grown in a simple culture system.

  9. Topography of the Human Papillomavirus Minor Capsid Protein L2 during Vesicular Trafficking of Infectious Entry

    Science.gov (United States)

    DiGiuseppe, Stephen; Keiffer, Timothy R.; Bienkowska-Haba, Malgorzata; Luszczek, Wioleta; Guion, Lucile G. M.; Müller, Martin

    2015-01-01

    ABSTRACT The human papillomavirus (HPV) capsid is composed of the major capsid protein L1 and the minor capsid protein L2. During entry, the HPV capsid undergoes numerous conformational changes that result in endosomal uptake and subsequent trafficking of the L2 protein in complex with the viral DNA to the trans-Golgi network. To facilitate this transport, the L2 protein harbors a number of putative motifs that, if capable of direct interaction, would interact with cytosolic host cell factors. These data imply that a portion of L2 becomes cytosolic during infection. Using a low concentration of digitonin to selectively permeabilize the plasma membrane of infected cells, we mapped the topography of the L2 protein during infection. We observed that epitopes within amino acid residues 64 to 81 and 163 to 170 and a C-terminal tag of HPV16 L2 are exposed on the cytosolic side of intracellular membranes, whereas an epitope within residues 20 to 38, which are upstream of a putative transmembrane region, is luminal. Corroborating these findings, we also found that L2 protein is sensitive to trypsin digestion during infection. These data demonstrate that the majority of the L2 protein becomes accessible on the cytosolic side of intracellular membranes in order to interact with cytosolic factors to facilitate vesicular trafficking. IMPORTANCE In order to complete infectious entry, nonenveloped viruses have to pass cellular membranes. This is often achieved through the viral capsid protein associating with or integrating into intracellular membrane. Here, we determine the topography of HPV L2 protein in the endocytic vesicular compartment, suggesting that L2 becomes a transmembrane protein with a short luminal portion and with the majority facing the cytosolic side for interaction with host cell transport factors. PMID:26246568

  10. The mouse who couldn't stop washing: pathologic grooming in animals and humans.

    Science.gov (United States)

    Feusner, Jamie D; Hembacher, Emily; Phillips, Katharine A

    2009-09-01

    The basic science literature is replete with descriptions of naturally occurring or experimentally induced pathological grooming behaviors in animals, which are widely considered animal models of obsessive-compulsive disorder (OCD). These animal models rely largely on observed similarities between animal behaviors and human OCD behaviors, and on studies of animal pathological grooming disorders that respond to serotonin enhancing drugs. However, current limitations in assessment of complex cognition and affect in animals precludes the field's ability to match the driving primary processes behind observable phenomenology in animal "OCD" with human behavioral disorders. We propose that excessive grooming behaviors in animals may eventually prove to be equally, or possibly more relevant to, other conditions in humans that involve pathological grooming or grooming-like behaviors, such as trichotillomania, body dysmorphic disorder, olfactory reference syndrome, compulsive skin-picking, and onychophagia. Research is needed to better understand pathological grooming behaviors in both humans and animals, as animal models have the potential to elucidate pathogenic mechanisms and inform the treatment of these psychiatric conditions in humans.

  11. Prophylactic antibody treatment and intramuscular immunization reduce infectious human rhinovirus 16 load in the lower respiratory tract of challenged cotton rats

    Directory of Open Access Journals (Sweden)

    Jorge C.G. Blanco

    2014-01-01

    Full Text Available Human rhinoviruses (HRV represent the single most important etiological agents of the common cold and are the most frequent cause of acute respiratory infections in humans. Currently the performance of available animal models for immunization studies using HRV challenge is very limited. The cotton rat (Sigmodon hispidus is a well-recognized model for the study of human respiratory viral infections. In this work we show that, without requiring any genetic modification of either the host or the virus, intranasal infection of cotton rats with HRV16 resulted in measurable isolation of infective virus, lower respiratory tract pathology, mucus production, and expression of interferon-activated genes. Intramuscular immunization with live HRV16 generated robust protective immunity that correlated with high serum levels of neutralizing antibodies. In addition, cotton rats treated prophylactically with hyperimmune anti-HRV16 serum were protected against HRV16 intranasal challenge. Finally, protection by immunization was efficiently transferred from mothers to newborn animals resulting in a substantial reduction of infectious virus loads in the lung following intranasal challenge. Overall, our results demonstrate that the cotton rat provides valuable additional model development options for testing vaccines and prophylactic therapies against rhinovirus infection.

  12. European monitoring systems and data for assessing environmental and climate impacts on human infectious diseases.

    Science.gov (United States)

    Nichols, Gordon L; Andersson, Yvonne; Lindgren, Elisabet; Devaux, Isabelle; Semenza, Jan C

    2014-04-09

    Surveillance is critical to understanding the epidemiology and control of infectious diseases. The growing concern over climate and other drivers that may increase infectious disease threats to future generations has stimulated a review of the surveillance systems and environmental data sources that might be used to assess future health impacts from climate change in Europe. We present an overview of organizations, agencies and institutions that are responsible for infectious disease surveillance in Europe. We describe the surveillance systems, tracking tools, communication channels, information exchange and outputs in light of environmental and climatic drivers of infectious diseases. We discuss environmental and climatic data sets that lend themselves to epidemiological analysis. Many of the environmental data sets have a relatively uniform quality across EU Member States because they are based on satellite measurements or EU funded FP6 or FP7 projects with full EU coverage. Case-reporting systems for surveillance of infectious diseases should include clear and consistent case definitions and reporting formats that are geo-located at an appropriate resolution. This will allow linkage to environmental, social and climatic sources that will enable risk assessments, future threat evaluations, outbreak management and interventions to reduce disease burden.

  13. European Monitoring Systems and Data for Assessing Environmental and Climate Impacts on Human Infectious Diseases

    Directory of Open Access Journals (Sweden)

    Gordon L. Nichols

    2014-04-01

    Full Text Available Surveillance is critical to understanding the epidemiology and control of infectious diseases. The growing concern over climate and other drivers that may increase infectious disease threats to future generations has stimulated a review of the surveillance systems and environmental data sources that might be used to assess future health impacts from climate change in Europe. We present an overview of organizations, agencies and institutions that are responsible for infectious disease surveillance in Europe. We describe the surveillance systems, tracking tools, communication channels, information exchange and outputs in light of environmental and climatic drivers of infectious diseases. We discuss environmental and climatic data sets that lend themselves to epidemiological analysis. Many of the environmental data sets have a relatively uniform quality across EU Member States because they are based on satellite measurements or EU funded FP6 or FP7 projects with full EU coverage. Case-reporting systems for surveillance of infectious diseases should include clear and consistent case definitions and reporting formats that are geo-located at an appropriate resolution. This will allow linkage to environmental, social and climatic sources that will enable risk assessments, future threat evaluations, outbreak management and interventions to reduce disease burden.

  14. Microorganisms human control pathological of aerial transport; Control de microorganismos patogenos humanos de transmision aerea

    Energy Technology Data Exchange (ETDEWEB)

    Pascual, L.; Moreno, C.; Amo, A.; Luz, S.P.; Apraiz, D.; Catalan, V.

    1999-05-01

    The search of methods of display and effective analysis in order to could detect and carry out a recount of human pathological microorganisms of aerial transmission has been one of the fields that more has worried to the micro biologists from beginnings of the XX century. (Author) 14 refs.

  15. Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function.

    Science.gov (United States)

    Sunitha, Balaraju; Gayathri, Narayanappa; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Nalini, Atchayaram; Padmanabhan, Balasundaram; Srinivas Bharath, Muchukunte Mukunda

    2016-07-01

    Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies

  16. Correlative Light and Scanning X-Ray Scattering Microscopy of Healthy and Pathologic Human Bone Sections

    Science.gov (United States)

    Giannini, C.; Siliqi, D.; Bunk, O.; Beraudi, A.; Ladisa, M.; Altamura, D.; Stea, S.; Baruffaldi, F.

    2012-01-01

    Scanning small and wide angle X-ray scattering (scanning SWAXS) experiments were performed on healthy and pathologic human bone sections. Via crystallographic tools the data were transformed into quantitative images and as such compared with circularly polarized light (CPL) microscopy images. SWAXS and CPL images allowed extracting information of the mineral nanocrystalline phase embedded, with and without preferred orientation, in the collagen fibrils, mapping local changes at sub-osteon resolution. This favorable combination has been applied for the first time to biopsies of dwarfism syndrome and Paget's disease to shed light onto the cortical structure of natural bone in healthy and pathologic sections. PMID:22666538

  17. Using GPS technology to quantify human mobility, dynamic contacts and infectious disease dynamics in a resource-poor urban environment.

    Directory of Open Access Journals (Sweden)

    Gonzalo M Vazquez-Prokopec

    Full Text Available Empiric quantification of human mobility patterns is paramount for better urban planning, understanding social network structure and responding to infectious disease threats, especially in light of rapid growth in urbanization and globalization. This need is of particular relevance for developing countries, since they host the majority of the global urban population and are disproportionally affected by the burden of disease. We used Global Positioning System (GPS data-loggers to track the fine-scale (within city mobility patterns of 582 residents from two neighborhoods from the city of Iquitos, Peru. We used ∼2.3 million GPS data-points to quantify age-specific mobility parameters and dynamic co-location networks among all tracked individuals. Geographic space significantly affected human mobility, giving rise to highly local mobility kernels. Most (∼80% movements occurred within 1 km of an individual's home. Potential hourly contacts among individuals were highly irregular and temporally unstructured. Only up to 38% of the tracked participants showed a regular and predictable mobility routine, a sharp contrast to the situation in the developed world. As a case study, we quantified the impact of spatially and temporally unstructured routines on the dynamics of transmission of an influenza-like pathogen within an Iquitos neighborhood. Temporally unstructured daily routines (e.g., not dominated by a single location, such as a workplace, where an individual repeatedly spent significant amount of time increased an epidemic's final size and effective reproduction number by 20% in comparison to scenarios modeling temporally structured contacts. Our findings provide a mechanistic description of the basic rules that shape human mobility within a resource-poor urban center, and contribute to the understanding of the role of fine-scale patterns of individual movement and co-location in infectious disease dynamics. More generally, this study

  18. Using GPS technology to quantify human mobility, dynamic contacts and infectious disease dynamics in a resource-poor urban environment.

    Science.gov (United States)

    Vazquez-Prokopec, Gonzalo M; Bisanzio, Donal; Stoddard, Steven T; Paz-Soldan, Valerie; Morrison, Amy C; Elder, John P; Ramirez-Paredes, Jhon; Halsey, Eric S; Kochel, Tadeusz J; Scott, Thomas W; Kitron, Uriel

    2013-01-01

    Empiric quantification of human mobility patterns is paramount for better urban planning, understanding social network structure and responding to infectious disease threats, especially in light of rapid growth in urbanization and globalization. This need is of particular relevance for developing countries, since they host the majority of the global urban population and are disproportionally affected by the burden of disease. We used Global Positioning System (GPS) data-loggers to track the fine-scale (within city) mobility patterns of 582 residents from two neighborhoods from the city of Iquitos, Peru. We used ∼2.3 million GPS data-points to quantify age-specific mobility parameters and dynamic co-location networks among all tracked individuals. Geographic space significantly affected human mobility, giving rise to highly local mobility kernels. Most (∼80%) movements occurred within 1 km of an individual's home. Potential hourly contacts among individuals were highly irregular and temporally unstructured. Only up to 38% of the tracked participants showed a regular and predictable mobility routine, a sharp contrast to the situation in the developed world. As a case study, we quantified the impact of spatially and temporally unstructured routines on the dynamics of transmission of an influenza-like pathogen within an Iquitos neighborhood. Temporally unstructured daily routines (e.g., not dominated by a single location, such as a workplace, where an individual repeatedly spent significant amount of time) increased an epidemic's final size and effective reproduction number by 20% in comparison to scenarios modeling temporally structured contacts. Our findings provide a mechanistic description of the basic rules that shape human mobility within a resource-poor urban center, and contribute to the understanding of the role of fine-scale patterns of individual movement and co-location in infectious disease dynamics. More generally, this study emphasizes the need for

  19. Acute post-infectious cerebellar ataxia due to co-infection of human herpesvirus-6 and adenovirus mimicking myositis.

    Science.gov (United States)

    Naselli, Aldo; Pala, Giovanna; Cresta, Federico; Finetti, Martina; Biancheri, Roberta; Renna, Salvatore

    2014-11-26

    Acute cerebellar ataxia (ACA) is a relatively common neurological disease in children. Most common types of ACA are acute post-infectious (APCA) and acute disseminated encephalomyelitis (ADEM). Less common but important causes include opsoclonus-myoclonus syndrome (OMS) and acute cerebellitis. Cerebellar neoplasms and acute hydrocephalus are additional causes of paediatric ataxia. APCA is the most common cause of ACA in children, comprising about 30-50% of total cases. This is a report about an immunocompetent 4-yrs-old male affected by APCA, due to co-infection by human herpesvirus-6 (HHV-6) and adenovirus, with symptoms mimicking myositis.

  20. Considerations on the comparative pathology of the vertebrae in Mysticeti and Odontoceti; evidence for the occurrence of discarthrosis, zygarthrosis, infectious spondylitis and spondyloarthritis

    NARCIS (Netherlands)

    Kompanje, E.J.O.

    1999-01-01

    Cleaned skeletons of 658 specimen of 47 species of Odontoceti and 44 skeletons of 10 species of Mysticeti were examined for evidence of pathological changes, especially of the vertebrae. Beside the examination of the cleaned skeletons, 132 spinal columns of seven species of Odontoceti were studied d

  1. Regulatory T-Cells at the Interface between Human Host and Pathogens in Infectious Diseases and Vaccination

    Science.gov (United States)

    Boer, Mardi C.; Joosten, Simone A.; Ottenhoff, Tom H. M.

    2015-01-01

    Regulatory T-cells (Tregs) act at the interface of host and pathogen interactions in human infectious diseases. Tregs are induced by a wide range of pathogens, but distinct effects of Tregs have been demonstrated for different pathogens and in different stages of infection. Moreover, Tregs that are induced by a specific pathogen may non-specifically suppress immunity against other microbes and parasites. Thus, Treg effects need to be assessed not only in homologous but also in heterologous infections and vaccinations. Though Tregs protect the human host against excessive inflammation, they probably also increase the risk of pathogen persistence and chronic disease, and the possibility of disease reactivation later in life. Mycobacterium leprae and Mycobacterium tuberculosis, causing leprosy and tuberculosis, respectively, are among the most ancient microbes known to mankind, and are master manipulators of the immune system toward tolerance and pathogen persistence. The majority of mycobacterial infections occur in settings co-endemic for viral, parasitic, and (other) bacterial coinfections. In this paper, we discuss recent insights in the activation and activity of Tregs in human infectious diseases, with emphasis on early, late, and non-specific effects in disease, coinfections, and vaccination. We highlight mycobacterial infections as important models of modulation of host responses and vaccine-induced immunity by Tregs. PMID:26029205

  2. Serological studies confirm the novel astrovirus HMOAstV-C as a highly prevalent human infectious agent.

    Directory of Open Access Journals (Sweden)

    Peter D Burbelo

    Full Text Available Molecular identification of a microbe is the first step in determining its prevalence of infection and pathogenic potential. Detection of specific adaptive immune responses can provide insights into whether a microbe is a human infectious agent and its epidemiology. Here we characterized human anti-IgG antibody responses by luciferase immunoprecipitation systems (LIPS against two protein fragments derived from the capsid protein of the novel HMOAstV-C astrovirus. While antibodies to the N-terminal fragment were not informative, the C-terminal capsid fragment of HMOAstV-C showed a high frequency of immunoreactivity with serum from healthy blood donors. In contrast, a similar C-terminal capsid fragment from the related HMOAstV-A astrovirus failed to show immunoreactivity. Detailed analysis of adult serum from the United Sates using a standardized threshold demonstrated HMOAstV-C seropositivity in approximately 65% of the samples. Evaluation of serum samples from different pediatric age groups revealed that the prevalence of antibodies in 6-12 month, 1-2 year, 2-5 year and 5-10 year olds was 20%, 23%, 32% and 36%, respectively, indicating rising seroprevalence with age. Additionally, 50% (11/22 of the 0-6 month old children showed anti-HMOAstV-C antibody responses, likely reflecting maternal antibodies. Together these results document human humoral responses to HMOAstV-C and validate LIPS as a facile and effective approach for identifying humoral responses to novel infectious agents.

  3. Correlative Light and Scanning X-Ray Scattering Microscopy of Healthy and Pathologic Human Bone Sections

    OpenAIRE

    Giannini, C.; D. Siliqi; Bunk, O.; Beraudi, A.; Ladisa, M.; Altamura, D.; Stea, S.; Baruffaldi, F.

    2012-01-01

    Scanning small and wide angle X-ray scattering (scanning SWAXS) experiments were performed on healthy and pathologic human bone sections. Via crystallographic tools the data were transformed into quantitative images and as such compared with circularly polarized light (CPL) microscopy images. SWAXS and CPL images allowed extracting information of the mineral nanocrystalline phase embedded, with and without preferred orientation, in the collagen fibrils, mapping local changes at sub-osteon res...

  4. Modeling Viral Infectious Diseases and Development of Antiviral Therapies Using Human Induced Pluripotent Stem Cell-Derived Systems

    Directory of Open Access Journals (Sweden)

    Marta Trevisan

    2015-07-01

    Full Text Available The recent biotechnology breakthrough of cell reprogramming and generation of induced pluripotent stem cells (iPSCs, which has revolutionized the approaches to study the mechanisms of human diseases and to test new drugs, can be exploited to generate patient-specific models for the investigation of host–pathogen interactions and to develop new antimicrobial and antiviral therapies. Applications of iPSC technology to the study of viral infections in humans have included in vitro modeling of viral infections of neural, liver, and cardiac cells; modeling of human genetic susceptibility to severe viral infectious diseases, such as encephalitis and severe influenza; genetic engineering and genome editing of patient-specific iPSC-derived cells to confer antiviral resistance.

  5. Agricultural Applications for Antimicrobials. A Danger to Human Health: An Official Position Statement of the Society of Infectious Diseases Pharmacists.

    Science.gov (United States)

    Aitken, Samuel L; Dilworth, Thomas J; Heil, Emily L; Nailor, Michael D

    2016-04-01

    The use of antibiotics in agriculture, particularly in food-producing animals, is pervasive and represents the overwhelming majority of antibiotic use worldwide. The link between antibiotic use in animals and antibiotic resistance in humans is unequivocal. Transmission can occur by ingesting undercooked meats harboring resistant bacteria, by direct contact of animals by animal handlers, and by various other means. Antibiotics used in aquaculture and antifungals used in horticulture are also an evolving threat to human health. Regulations aimed at decreasing the amount of antibiotics used in food production to limit the development of antibiotic resistance have recently been implemented. However, further action is needed to minimize antibiotic use in agriculture. This article describes the extent of this current problem and serves as the official position of the Society of Infectious Diseases Pharmacists on this urgent threat to human health.

  6. Homo floresiensis contextualized: a geometric morphometric comparative analysis of fossil and pathological human samples.

    Directory of Open Access Journals (Sweden)

    Karen L Baab

    Full Text Available The origin of hominins found on the remote Indonesian island of Flores remains highly contentious. These specimens may represent a new hominin species, Homo floresiensis, descended from a local population of Homo erectus or from an earlier (pre-H. erectus migration of a small-bodied and small-brained hominin out of Africa. Alternatively, some workers suggest that some or all of the specimens recovered from Liang Bua are pathological members of a small-bodied modern human population. Pathological conditions proposed to explain their documented anatomical features include microcephaly, myxoedematous endemic hypothyroidism ("cretinism" and Laron syndrome (primary growth hormone insensitivity. This study evaluates evolutionary and pathological hypotheses through comparative analysis of cranial morphology. Geometric morphometric analyses of landmark data show that the sole Flores cranium (LB1 is clearly distinct from healthy modern humans and from those exhibiting hypothyroidism and Laron syndrome. Modern human microcephalic specimens converge, to some extent, on crania of extinct species of Homo. However in the features that distinguish these two groups, LB1 consistently groups with fossil hominins and is most similar to H. erectus. Our study provides further support for recognizing the Flores hominins as a distinct species, H. floresiensis, whose affinities lie with archaic Homo.

  7. Homo floresiensis contextualized: a geometric morphometric comparative analysis of fossil and pathological human samples.

    Science.gov (United States)

    Baab, Karen L; McNulty, Kieran P; Harvati, Katerina

    2013-01-01

    The origin of hominins found on the remote Indonesian island of Flores remains highly contentious. These specimens may represent a new hominin species, Homo floresiensis, descended from a local population of Homo erectus or from an earlier (pre-H. erectus) migration of a small-bodied and small-brained hominin out of Africa. Alternatively, some workers suggest that some or all of the specimens recovered from Liang Bua are pathological members of a small-bodied modern human population. Pathological conditions proposed to explain their documented anatomical features include microcephaly, myxoedematous endemic hypothyroidism ("cretinism") and Laron syndrome (primary growth hormone insensitivity). This study evaluates evolutionary and pathological hypotheses through comparative analysis of cranial morphology. Geometric morphometric analyses of landmark data show that the sole Flores cranium (LB1) is clearly distinct from healthy modern humans and from those exhibiting hypothyroidism and Laron syndrome. Modern human microcephalic specimens converge, to some extent, on crania of extinct species of Homo. However in the features that distinguish these two groups, LB1 consistently groups with fossil hominins and is most similar to H. erectus. Our study provides further support for recognizing the Flores hominins as a distinct species, H. floresiensis, whose affinities lie with archaic Homo.

  8. Richard Bradley: a unified, living agent theory of the cause of infectious diseases of plants, animals, and humans in the first decades of the 18th century.

    Science.gov (United States)

    Santer, Melvin

    2009-01-01

    During the years 1714 to 1721, Richard Bradley, who was later to become the first Professor of Botany at Cambridge University, proposed a unified, unique, living agent theory of the cause of infectious diseases of plants and animals and the plague of humans. Bradley's agents included microscopic organisms, revealed by the studies of Robert Hooke and Antony van Leeuwenhoek. His theory derived from his experimental studies of plants and their diseases and from microscopic observation of animalcules in different naturally occurring and artificial environments. He concluded that there was a microscopic world of "insects" that lived and reproduced under the appropriate conditions, and that infectious diseases of plants were caused by such "insects." Since there are structural and functional similarities between plants and animals, Bradley concluded that microscopic organisms caused human and animal infectious diseases as well. However, his living agent cause of infectious diseases was not accepted by the contemporary scientific society.

  9. Resource mapping and emergency preparedness to infectious diseases in human and animal populations in Kibaha and Ngorongoro districts, Tanzania

    Directory of Open Access Journals (Sweden)

    E.D. Karimuribo

    2012-06-01

    Full Text Available A rapid situation analysis was conducted in Kibaha and Ngorongoro districts in Tanzania to map resources as well as analysing emergency preparedness to infectious diseases in animal (domestic and wild and human populations. Kibaha was chosen as a district close to a commercial city (Dar es Salaam while Ngorongoro represented a remote, border district with high interactions between humans, domestic and wild animals. In this study, data on resources and personnel as well as emergency preparedness were collected from all wards (n = 22, human health facilities (n = 40 and livestock facilities in the two districts using interview checklists and questionnaires. Descriptive statistics for resources were calculated and mapped by district. Kibaha district had a higher human population density, more health workers, better equipped health facilities and better communication and transport systems. On the other hand, Ngorongoro had a higher population of livestock and more animal health facilities but a poorer ratio of animal health workers to livestock. The average ratio of health personnel to population in catchment areas of the health facilities was 1:147 (range of 1:17−1:1200. The ratio of personnel to human population was significantly higher in Kibaha (1:95 than in Ngorongoro (1:203 district (p = 0 < 0.001. Considering the limited resources available to both human and animal health sectors and their different strengths and weaknesses there are opportunities for greater collaboration and resource-sharing between human and animal health for improved surveillance and emergency-preparedness.

  10. 新生儿病理性黄疸与感染性肺炎相关性研究%The Correlation Study of Neonatal Pathologic Jaundice and Infectious Pneumonia

    Institute of Scientific and Technical Information of China (English)

    丁刚; 张金娥

    2013-01-01

    Objective:To investigate the correlation of neonatal pathologic jaundice and infectious pneumonia. Methods:271 cases of diagnosed neonatal pathologic jaundice in our hospital from January 2012 to June 2012 were taken chest X-ray examination, and analyze its correlation of Neonatal Pathologic Jaundice and Infectious Pneumonia. Results:Among al the cases, 74 cases (27.31%)related to some infectious agents;Among them, 61 cases (22.51%)with Infectious pneumonia, 9 cases (3.32%) with neonatal septicemia, 2 cases with neonatal herpes, accounted for 0.74%,1 case(0.37%) with urinary system infection, 1 cases(0.37%) with intestinal infection.Among al 61 neonatal pneumonia cases, 40 cases(65.57%) with respiratory symptoms, and 21cases(34.43%) without. Conclusion:Infection is the main cause of Neonatal Pathologic Jaundice, and neonatal pneumonia accounted for a large proportion, most of them without typical symptoms, so misdiagnosis and missed analysis easily occurs. Thus, clinical doctors should find the real reasons to eliminate neonatal pneumonia and take anti-infection treatment.%目的:探讨新生儿病理性黄疸与感染性肺炎的相关性。方法:选自2012年1月至2013年6月在我院确诊的新生儿病理性黄疸271例病例进行胸部X线检查。分析病理性黄疸与感染性肺炎的相关性。结果:共271例患儿,与感染因素有关的74例占27.31%。其中合并感染性肺炎61例(22.51%);新生儿败血症9例(3.32%);新生儿脓疱疹2例(0.74%);泌尿系统感染1例(0.37%),肠道感染1例(0.37%)。61例新生儿肺炎其中有呼吸系统症状、体征者40例占65.57%,无呼吸系统症状、体征者21例占34.43%。结论:新生儿病理性黄疸的病因中感染是其主要原因,而感染性肺炎在感染因素中所占权重比较大,部分新生儿肺炎患者症状、体征不明显,如果不拍胸片检查易误诊和漏诊。因此,临床医生对病理性黄疸病人要积

  11. Osler's pathology.

    Science.gov (United States)

    Pai, S A

    2000-12-01

    Sir William Osler, one of the giants of clinical medicine, had his initial training as a pathologist. He was one of the physicians responsible for the impact that autopsies have had on medicine. He also contributed to the development of laboratory medicine. Osler made significant discoveries in anatomic pathology and hematology. His expertise was restricted not just to human pathology, but also to veterinary pathology. His mentors played a fundamental role in his achievements in academics.

  12. A human stem cell model of early Alzheimer's disease pathology in Down syndrome.

    Science.gov (United States)

    Shi, Yichen; Kirwan, Peter; Smith, James; MacLean, Glenn; Orkin, Stuart H; Livesey, Frederick J

    2012-03-07

    Human cellular models of Alzheimer's disease (AD) pathogenesis would enable the investigation of candidate pathogenic mechanisms in AD and the testing and developing of new therapeutic strategies. We report the development of AD pathologies in cortical neurons generated from human induced pluripotent stem (iPS) cells derived from patients with Down syndrome. Adults with Down syndrome (caused by trisomy of chromosome 21) develop early-onset AD, probably due to increased expression of a gene on chromosome 21 that encodes the amyloid precursor protein (APP). We found that cortical neurons generated from iPS cells and embryonic stem cells from Down syndrome patients developed AD pathologies over months in culture, rather than years in vivo. These cortical neurons processed the transmembrane APP protein, resulting in secretion of the pathogenic peptide fragment amyloid-β42 (Aβ42), which formed insoluble intracellular and extracellular amyloid aggregates. Production of Aβ peptides was blocked by a γ-secretase inhibitor. Finally, hyperphosphorylated tau protein, a pathological hallmark of AD, was found to be localized to cell bodies and dendrites in iPS cell-derived cortical neurons from Down syndrome patients, recapitulating later stages of the AD pathogenic process.

  13. Multivariate analysis of the scattering profiles of healthy and pathological human breast tissues

    Energy Technology Data Exchange (ETDEWEB)

    Conceicao, A.L.C.; Antoniassi, M. [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto 14040-901, Sao Paulo (Brazil); Cunha, D.M. [Instituto de Fisica, Universidade Federal de Uberlandia, 38400-902, Uberlandia, Minas Gerais (Brazil); Ribeiro-Silva, A. [Departamento de Patologia, HCFMRP, Universidade de Sao Paulo, Ribeirao Preto 14040-901, Sao Paulo (Brazil); Poletti, M.E., E-mail: poletti@ffclrp.usp.br [Departamento de Fisica e Matematica, FFCLRP, Universidade de Sao Paulo, Ribeirao Preto 14040-901, Sao Paulo (Brazil)

    2011-10-01

    Scattering profiles of 106 healthy and pathological human breast samples were obtained using the angular dispersive X-ray scattering technique (AD-XRD) and synchrotron radiation covering the momentum transfer interval of 0.7 nm{sup -1}{<=}q(=4{pi} sin({theta}/2)/{lambda}){<=}70.5 nm{sup -1}. Multivariate analysis in the form of discriminant analysis was applied over the whole scattering profile curve of each sample in order to build a model for breast tissue classification. The classification results were validated and compared with histological sample classification obtained by microscopy analysis. Finally, the model allows classifying correctly 91.5% of the samples and presented values of 98.5%, 89.7% and 0.90 for sensitivity, specificity and Cohen's {kappa}, respectively, in correctly differentiating between healthy and pathological tissues.

  14. The pathological consequences of impaired genome integrity in humans; disorders of the DNA replication machinery.

    Science.gov (United States)

    O'Driscoll, Mark

    2017-01-01

    Accurate and efficient replication of the human genome occurs in the context of an array of constitutional barriers, including regional topological constraints imposed by chromatin architecture and processes such as transcription, catenation of the helical polymer and spontaneously generated DNA lesions, including base modifications and strand breaks. DNA replication is fundamentally important for tissue development and homeostasis; differentiation programmes are intimately linked with stem cell division. Unsurprisingly, impairments of the DNA replication machinery can have catastrophic consequences for genome stability and cell division. Functional impacts on DNA replication and genome stability have long been known to play roles in malignant transformation through a variety of complex mechanisms, and significant further insights have been gained from studying model organisms in this context. Congenital hypomorphic defects in components of the DNA replication machinery have been and continue to be identified in humans. These disorders present with a wide range of clinical features. Indeed, in some instances, different mutations in the same gene underlie different clinical presentations. Understanding the origin and molecular basis of these features opens a window onto the range of developmental impacts of suboptimal DNA replication and genome instability in humans. Here, I will briefly overview the basic steps involved in DNA replication and the key concepts that have emerged from this area of research, before switching emphasis to the pathological consequences of defects within the DNA replication network; the human disorders. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  15. Humanized Tau Mice with Regionalized Amyloid Exhibit Behavioral Deficits but No Pathological Interaction

    Science.gov (United States)

    Yetman, Michael J.; Fowler, Stephanie W.; Jankowsky, Joanna L.

    2016-01-01

    Alzheimer’s disease (AD) researchers have struggled for decades to draw a causal link between extracellular Aβ aggregation and intraneuronal accumulation of microtubule-associated protein tau. The amyloid cascade hypothesis posits that Aβ deposition promotes tau hyperphosphorylation, tangle formation, cell loss, vascular damage, and dementia. While the genetics of familial AD and the pathological staging of sporadic disease support this sequence of events, attempts to examine the molecular mechanism in transgenic animal models have largely relied on models of other inherited tauopathies as the basis for testing the interaction with Aβ. In an effort to more accurately model the relationship between Aβ and wild-type tau in AD, we intercrossed mice that overproduce human Aβ with a tau substitution model in which all 6 isoforms of the human protein are expressed in animals lacking murine tau. We selected an amyloid model in which pathology was biased towards the entorhinal region so that we could further examine whether the anticipated changes in tau phosphorylation occurred at the site of Aβ deposition or in synaptically connected regions. We found that Aβ and tau had independent effects on locomotion, learning, and memory, but found no behavioral evidence for an interaction between the two transgenes. Moreover, we saw no indication of amyloid-induced changes in the phosphorylation or aggregation of human tau either within the entorhinal area or elsewhere. These findings suggest that robust amyloid pathology within the medial temporal lobe has little effect on the metabolism of wild type human tau in this model. PMID:27070146

  16. Hypertrophy, hyperplasia, and infectious virus in gut-associated lymphoid tissue of mice after oral inoculation with simian-human or bovine-human reassortant rotaviruses.

    Science.gov (United States)

    Moser, C A; Dolfi, D V; Di Vietro, M L; Heaton, P A; Offit, P A; Clark, H F

    2001-04-01

    Oral inoculation of infants with a vaccine that contains simian-human reassortant rotaviruses has been found to be a rare cause of intussusception. Because intussusception can be associated with enlargement of gut-associated lymphoid tissue, we studied the capacity of simian-human and bovine-human reassortant rotaviruses to cause lymphoid hypertrophy and hyperplasia of Peyer's patches (PP) of adult BALB/c mice. Neither hypertrophy nor hyperplasia was detected in PP after oral inoculation with simian-human or bovine-human reassortant rotaviruses. However, infectious virus was detected in PP and mesenteric lymph nodes after oral inoculation with simian, but not bovine, reassortant rotaviruses. Implications of these findings on the pathogenesis of intussusception are discussed.

  17. Plant-made oral vaccines against human infectious diseases-Are we there yet?

    Science.gov (United States)

    Chan, Hui-Ting; Daniell, Henry

    2015-10-01

    Although the plant-made vaccine field started three decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, this goal has not yet been achieved. Plants offer several major advantages in vaccine generation, including low-cost production by eliminating expensive fermentation and purification systems, sterile delivery and cold storage/transportation. Most importantly, oral vaccination using plant-made antigens confers both mucosal (IgA) and systemic (IgG) immunity. Studies in the past 5 years have made significant progress in expressing vaccine antigens in edible leaves (especially lettuce), processing leaves or seeds through lyophilization and achieving antigen stability and efficacy after prolonged storage at ambient temperatures. Bioencapsulation of antigens in plant cells protects them from the digestive system; the fusion of antigens to transmucosal carriers enhances efficiency of their delivery to the immune system and facilitates successful development of plant vaccines as oral boosters. However, the lack of oral priming approaches diminishes these advantages because purified antigens, cold storage/transportation and limited shelf life are still major challenges for priming with adjuvants and for antigen delivery by injection. Yet another challenge is the risk of inducing tolerance without priming the host immune system. Therefore, mechanistic aspects of these two opposing processes (antibody production or suppression) are discussed in this review. In addition, we summarize recent progress made in oral delivery of vaccine antigens expressed in plant cells via the chloroplast or nuclear genomes and potential challenges in achieving immunity against infectious diseases using cold-chain-free vaccine delivery approaches. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  18. Rapid Generation of Human-Like Neutralizing Monoclonal Antibodies in Urgent Preparedness for Influenza Pandemics and Virulent Infectious Diseases.

    Directory of Open Access Journals (Sweden)

    Weixu Meng

    Full Text Available The outbreaks of emerging infectious diseases caused by pathogens such as SARS coronavirus, H5N1, H1N1, and recently H7N9 influenza viruses, have been associated with significant mortality and morbidity in humans. Neutralizing antibodies from individuals who have recovered from an infection confer therapeutic protection to others infected with the same pathogen. However, survivors may not always be available for providing plasma or for the cloning of monoclonal antibodies (mAbs.The genome and the immunoglobulin genes in rhesus macaques and humans are highly homologous; therefore, we investigated whether neutralizing mAbs that are highly homologous to those of humans (human-like could be generated. Using the H5N1 influenza virus as a model, we first immunized rhesus macaques with recombinant adenoviruses carrying a synthetic gene encoding hemagglutinin (HA. Following screening an antibody phage display library derived from the B cells of immunized monkeys, we cloned selected macaque immunoglobulin heavy chain and light chain variable regions into the human IgG constant region, which generated human-macaque chimeric mAbs exhibiting over 97% homology to human antibodies. Selected mAbs demonstrated potent neutralizing activities against three clades (0, 1, 2 of the H5N1 influenza viruses. The in vivo protection experiments demonstrated that the mAbs effectively protected the mice even when administered up to 3 days after infection with H5N1 influenza virus. In particular, mAb 4E6 demonstrated sub-picomolar binding affinity to HA and superior in vivo protection efficacy without the loss of body weight and obvious lung damage. The analysis of the 4E6 escape mutants demonstrated that the 4E6 antibody bound to a conserved epitope region containing two amino acids on the globular head of HA.Our study demonstrated the generation of neutralizing mAbs for potential application in humans in urgent preparedness against outbreaks of new influenza infections or

  19. A Myeloid Progenitor Cell Line Capable of Supporting Human Cytomegalovirus Latency and Reactivation, Resulting in Infectious Progeny

    Science.gov (United States)

    O'Connor, Christine M.

    2012-01-01

    Human cytomegalovirus (HCMV) is a herpesvirus that establishes a lifelong, latent infection within a host. At times when the immune system is compromised, the virus undergoes a lytic reactivation producing infectious progeny. The identification and understanding of the biological mechanisms underlying HCMV latency and reactivation are not completely defined. To this end, we have developed a tractable in vitro model system to investigate these phases of viral infection using a clonal population of myeloid progenitor cells (Kasumi-3 cells). Infection of these cells results in maintenance of the viral genome with restricted viral RNA expression that is reversed with the addition of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, also known as PMA). Additionally, a latent viral transcript (LUNA) is expressed at times where viral lytic transcription is suppressed. Infected Kasumi-3 cells initiate production of infectious virus following TPA treatment, which requires cell-to-cell contact for efficient transfer of virus to other cell types. Importantly, lytically infected fibroblast, endothelial, or epithelial cells can transfer virus to Kasumi-3 cells, which fail to initiate lytic replication until stimulated with TPA. Finally, inflammatory cytokines, in addition to the pharmacological agent TPA, are sufficient for transcription of immediate-early (IE) genes following latent infection. Taken together, our findings argue that the Kasumi-3 cell line is a tractable in vitro model system with which to study HCMV latency and reactivation. PMID:22761372

  20. Integrating gross pathology into teaching of undergraduate medical science students using human cadavers.

    Science.gov (United States)

    Gopalan, Vinod; Dissabandara, Lakal; Nirthanan, Selvanayagam; Forwood, Mark R; Lam, Alfred King-Yin

    2016-09-01

    Human cadavers offer a great opportunity for histopathology students for the learning and teaching of tissue pathology. In this study, we aimed to implement an integrated learning approach by using cadavers to enhance students' knowledge and to develop their skills in gross tissue identification, handling and dissection techniques. A total of 35 students enrolled in the undergraduate medical science program participated in this study. A 3-hour laboratory session was conducted that included an active exploration of cadaveric specimens to identify normal and pathological tissues as well as tissue dissection. The majority of the students strongly agreed that the integration of normal and morbid anatomy improved their understanding of tissue pathology. All the students either agreed or strongly agreed that this laboratory session was useful to improve their tissue dissection and instrument handling skills. Furthermore, students from both cohorts rated the session as very relevant to their learning and recommended that this approach be added to the existing histopathology curriculum. To conclude, an integrated cadaver-based practical session can be used effectively to enhance the learning experience of histopathology science students, as well as improving their manual skills of tissue treatment, instrument handling and dissection.

  1. Third harmonic generation imaging for fast, label-free pathology of human brain tumors.

    Science.gov (United States)

    Kuzmin, N V; Wesseling, P; Hamer, P C de Witt; Noske, D P; Galgano, G D; Mansvelder, H D; Baayen, J C; Groot, M L

    2016-05-01

    In brain tumor surgery, recognition of tumor boundaries is key. However, intraoperative assessment of tumor boundaries by the neurosurgeon is difficult. Therefore, there is an urgent need for tools that provide the neurosurgeon with pathological information during the operation. We show that third harmonic generation (THG) microscopy provides label-free, real-time images of histopathological quality; increased cellularity, nuclear pleomorphism, and rarefaction of neuropil in fresh, unstained human brain tissue could be clearly recognized. We further demonstrate THG images taken with a GRIN objective, as a step toward in situ THG microendoscopy of tumor boundaries. THG imaging is thus a promising tool for optical biopsies.

  2. Third harmonic generation imaging for fast, label-free pathology of human brain tumors

    Science.gov (United States)

    Kuzmin, N. V.; Wesseling, P.; Hamer, P. C. de Witt; Noske, D. P.; Galgano, G. D.; Mansvelder, H. D.; Baayen, J. C.; Groot, M. L.

    2016-01-01

    In brain tumor surgery, recognition of tumor boundaries is key. However, intraoperative assessment of tumor boundaries by the neurosurgeon is difficult. Therefore, there is an urgent need for tools that provide the neurosurgeon with pathological information during the operation. We show that third harmonic generation (THG) microscopy provides label-free, real-time images of histopathological quality; increased cellularity, nuclear pleomorphism, and rarefaction of neuropil in fresh, unstained human brain tissue could be clearly recognized. We further demonstrate THG images taken with a GRIN objective, as a step toward in situ THG microendoscopy of tumor boundaries. THG imaging is thus a promising tool for optical biopsies. PMID:27231629

  3. Development of a human live attenuated West Nile infectious DNA vaccine: conceptual design of the vaccine candidate.

    Science.gov (United States)

    Yamshchikov, Vladimir

    2015-10-01

    West Nile virus has become an important epidemiological problem attracting significant attention of health authorities, mass media, and the public. Although there are promising advancements toward addressing the vaccine need, the perspectives of the commercial availability of the vaccine remain uncertain. To a large extent this is due to lack of a sustained interest for further commercial development of the vaccines already undergoing the preclinical and clinical development, and a predicted insignificant cost effectiveness of mass vaccination. There is a need for a safe, efficacious and cost effective vaccine, which can improve the feasibility of a targeted vaccination program. In the present report, we summarize the background, the rationale, and the choice of the development pathway that we selected for the design of a live attenuated human West Nile vaccine in a novel infectious DNA format.

  4. [Human papillomavirus vaccine. Statement of the Advisory Committee of Immunizations on behalf of the Chilean Infectious Diseases Society. September 2008].

    Science.gov (United States)

    Abarca, Katia; Valenzuela, M Teresa; Vergara, Rodrigo; Luchsinger, Vivian; Muñoz, Alma; Jiménez de la J, Jorge; Ripoll, Erna; O'Ryan, Miguel

    2008-11-01

    This article briefly reviews the epidemiology of human papillomavirus (HPV) infection and associated diseases globally and in Chile, and the scientific information of the licensed HPV vaccines: Gardasil and Cervari. Considering the available information, the Advisory Committee on Immunizations of the Chilean Society of Infectious Diseases recommends vaccination of teenage girls, ideally before initiating sexual activity, i.e., approximately at the age of 12 to 13 years and vaccination of women of any age if they have not started sexual activity. If women are vaccinated after initiating sexual activity, they should be informed of the lower efficacy of immunization if HPV infection has occurred. Education on responsible sexuality and sexually transmitted diseases should be maintained as a priority. Vaccination should be highly considered for inclusion in the National Immunization Program.

  5. Human isolates of Bartonella tamiae induce pathology in experimentally inoculated immunocompetent mice

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    Kosoy Michael Y

    2010-07-01

    Full Text Available Abstract Background Bartonella tamiae, a newly described bacterial species, was isolated from the blood of three hospitalized patients in Thailand. These patients presented with headache, myalgia, anemia, and mild liver function abnormalities. Since B. tamiae was presumed to be the cause of their illness, these isolates were inoculated into immunocompetent mice to determine their relative pathogenicity in inducing manifestations of disease and pathology similar to that observed in humans. Methods Three groups of four Swiss Webster female mice aged 15-18 months were each inoculated with 106-7 colony forming units of one of three B. tamiae isolates [Th239, Th307, and Th339]. A mouse from each experimental group was sampled at 3, 4, 5 and 6 weeks post-inoculation. Two saline inoculated age-matched controls were included in the study. Samples collected at necropsy were evaluated for the presence of B. tamiae DNA, and tissues were formalin-fixed, stained with hematoxylin and eosin, and examined for histopathology. Results Following inoculation with B. tamiae, mice developed ulcerative skin lesions and subcutaneous masses on the lateral thorax, as well as axillary and inguinal lymphadenopathy. B. tamiae DNA was found in subcutaneous masses, lymph node, and liver of inoculated mice. Histopathological changes were observed in tissues of inoculated mice, and severity of lesions correlated with the isolate inoculated, with the most severe pathology induced by B. tamiae Th239. Mice inoculated with Th239 and Th339 demonstrated myocarditis, lymphadenitis with associated vascular necrosis, and granulomatous hepatitis and nephritis with associated hepatocellular and renal necrosis. Mice inoculated with Th307 developed a deep dermatitis and granulomas within the kidneys. Conclusions The three isolates of B. tamiae evaluated in this study induce disease in immunocompetent Swiss Webster mice up to 6 weeks after inoculation. The human patients from whom these

  6. Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease.

    Science.gov (United States)

    Petzold, Axel

    2015-03-10

    This review on the role of glial fibrillary acidic protein (GFAP) as a biomarker for astroglial pathology in neurological diseases provides background to protein synthesis, assembly, function and degeneration. Qualitative and quantitative analytical techniques for the investigation of human tissue and biological fluid samples are discussed including partial lack of parallelism and multiplexing capabilities. Pathological implications are reviewed in view of immunocytochemical, cell-culture and genetic findings. Particular emphasis is given to neurodegeneration related to autoimmune astrocytopathies and to genetic gain of function mutations. The current literature on body fluid levels of GFAP in human disease is summarised and illustrated by disease specific meta-analyses. In addition to the role of GFAP as a diagnostic biomarker for chronic disease, there are important data on the prognostic value for acute conditions. The published evidence permits to classify the dominant GFAP signatures in biological fluids. This classification may serve as a template for supporting diagnostic criteria of autoimmune astrocytopathies, monitoring disease progression in toxic gain of function mutations, clinical treatment trials (secondary outcome and toxicity biomarker) and provide prognostic information in neurocritical care if used within well defined time-frames.

  7. Infectious Arthritis

    Science.gov (United States)

    Most kinds of arthritis cause pain and swelling in your joints. Joints are places where two bones meet, such as your elbow or knee. Infectious arthritis is an infection in the joint. The infection ...

  8. Infectious Diseases

    Science.gov (United States)

    ... people worldwide than any other single cause. Infectious diseases are caused by germs. Germs are tiny living things that are found everywhere - in air, soil and water. You can get infected by touching, eating, drinking ...

  9. Humanized HLA-DR4 mice fed with the protozoan pathogen of oysters Perkinsus marinus (Dermo do not develop noticeable pathology but elicit systemic immunity.

    Directory of Open Access Journals (Sweden)

    Wathsala Wijayalath

    Full Text Available Perkinsus marinus (Phylum Perkinsozoa is a marine protozoan parasite responsible for "Dermo" disease in oysters, which has caused extensive damage to the shellfish industry and estuarine environment. The infection prevalence has been estimated in some areas to be as high as 100%, often causing death of infected oysters within 1-2 years post-infection. Human consumption of the parasites via infected oysters is thus likely to occur, but to our knowledge the effect of oral consumption of P. marinus has not been investigated in humans or other mammals. To address the question we used humanized mice expressing HLA-DR4 molecules and lacking expression of mouse MHC-class II molecules (DR4.EA(0 in such a way that CD4 T cell responses are solely restricted by the human HLA-DR4 molecule. The DR4.EA(0 mice did not develop diarrhea or any detectable pathology in the gastrointestinal tract or lungs following single or repeated feedings with live P. marinus parasites. Furthermore, lymphocyte populations in the gut associated lymphoid tissue and spleen were unaltered in the parasite-fed mice ruling out local or systemic inflammation. Notably, naïve DR4.EA(0 mice had antibodies (IgM and IgG reacting against P. marinus parasites whereas parasite specific T cell responses were undetectable. Feeding with P. marinus boosted the antibody responses and stimulated specific cellular (IFNγ immunity to the oyster parasite. Our data indicate the ability of P. marinus parasites to induce systemic immunity in DR4.EA(0 mice without causing noticeable pathology, and support rationale grounds for using genetically engineered P. marinus as a new oral vaccine platform to induce systemic immunity against infectious agents.

  10. Palaeopathology and genes: investigating the genetics of infectious diseases in excavated human skeletal remains and mummies from past populations.

    Science.gov (United States)

    Anastasiou, Evilena; Mitchell, Piers D

    2013-10-01

    The aim of this paper is to review the use of genetics in palaeomicrobiology, and to highlight the importance of understanding past diseases. Palaeomicrobiology is the study of disease pathogens in skeletal and mummified remains from archaeological contexts. It has revolutionarised our understanding of health in the past by enabling a deeper knowledge of the origins and evolution of many diseases that have shaped us as a species. Bacterial diseases explored include tuberculosis, leprosy, bubonic plague, typhoid, syphilis, endemic and epidemic typhus, trench fever, and Helicobacter pylori. Viral diseases discussed include influenza, hepatitis B, human papilloma virus (HPV), human T-cell lymphotrophic virus (HTLV-1) and human immunodeficiency virus (HIV). Parasitic diseases investigated include malaria, leishmaniasis, Chagas' disease, roundworm, whipworm, pinworm, Chinese liver fluke, fleas and lice. Through a better understanding of disease origins and their evolution, we can place into context how many infectious diseases are changing over time, and so help us estimate how they may change in the future. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Thymic function and T cell parameters in a natural human experimental model of seasonal infectious diseases and nutritional burden

    Directory of Open Access Journals (Sweden)

    Morgan Gareth

    2011-06-01

    Full Text Available Abstract Background The study exploits a natural human experimental model of subsistence farmers experiencing chronic and seasonally modified food shortages and infectious burden. Two seasons existed, one of increased deprivation and infections (Jul-Dec, another of abundance and low infections (Jan-Jun; referred to as the hungry/high infection and harvest/low infection seasons respectively. Prior analysis showed a 10-fold excess in infectious disease associated mortality in young adults born in the hungry/high infection versus harvest/low infection season, and reduced thymic output and T cell counts in infancy. Here we report findings on the role of early life stressors as contributors to the onset of T cell immunological defects in later life. Methods We hypothesised that season of birth effects on thymic function and T cell immunity would be detectable in young adults since Kaplan-Meier survival curves indicated this to be the time of greatest mortality divergence. T cell subset analyses by flow-cytometry, sjTRECs, TCRVβ repertoire and telomere length by PCR, were performed on samples from 60 males (18-23 y selected to represent births in the hungry/high infection and harvest/low infection Results Total lymphocyte counts were normal and did not differ by birth season. CD3+ and CD4+ but not CD8+ counts were lower for those born during the hungry/high infection season. CD8+ telomere length also tended to be shorter. Overall, CD8+ TCRVβ repertoire skewing was observed with 'public' expressions and deletions seen in TCRVβ12/22 and TCRVβ24, respectively but no apparent effect of birth season. Conclusions We conclude that, although thymic function was unchanged, the CD4+ and CD3+ counts, and CD8+ telomere length results suggested that aspects of adult T cell immunity were under the influence of early life stressors. The endemicity of CMV and HBV suggested that chronic infections may modulate immunity through T cell repertoire development. The

  12. DUF1220-domain copy number implicated in human brain-size pathology and evolution.

    Science.gov (United States)

    Dumas, Laura J; O'Bleness, Majesta S; Davis, Jonathan M; Dickens, C Michael; Anderson, Nathan; Keeney, J G; Jackson, Jay; Sikela, Megan; Raznahan, Armin; Giedd, Jay; Rapoport, Judith; Nagamani, Sandesh S C; Erez, Ayelet; Brunetti-Pierri, Nicola; Sugalski, Rachel; Lupski, James R; Fingerlin, Tasha; Cheung, Sau Wai; Sikela, James M

    2012-09-07

    DUF1220 domains show the largest human-lineage-specific increase in copy number of any protein-coding region in the human genome and map primarily to 1q21, where deletions and reciprocal duplications have been associated with microcephaly and macrocephaly, respectively. Given these findings and the high correlation between DUF1220 copy number and brain size across primate lineages (R(2) = 0.98; p = 1.8 × 10(-6)), DUF1220 sequences represent plausible candidates for underlying 1q21-associated brain-size pathologies. To investigate this possibility, we used specialized bioinformatics tools developed for scoring highly duplicated DUF1220 sequences to implement targeted 1q21 array comparative genomic hybridization on individuals (n = 42) with 1q21-associated microcephaly and macrocephaly. We show that of all the 1q21 genes examined (n = 53), DUF1220 copy number shows the strongest association with brain size among individuals with 1q21-associated microcephaly, particularly with respect to the three evolutionarily conserved DUF1220 clades CON1(p = 0.0079), CON2 (p = 0.0134), and CON3 (p = 0.0116). Interestingly, all 1q21 DUF1220-encoding genes belonging to the NBPF family show significant correlations with frontal-occipital-circumference Z scores in the deletion group. In a similar survey of a nondisease population, we show that DUF1220 copy number exhibits the strongest correlation with brain gray-matter volume (CON1, p = 0.0246; and CON2, p = 0.0334). Notably, only DUF1220 sequences are consistently significant in both disease and nondisease populations. Taken together, these data strongly implicate the loss of DUF1220 copy number in the etiology of 1q21-associated microcephaly and support the view that DUF1220 domains function as general effectors of evolutionary, pathological, and normal variation in brain size. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  13. Expression of aquaporin8 in human astrocytomas: Correlation with pathologic grade

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Shu-juan; Wang, Ke-jian; Gan, Sheng-wei; Xu, Jin; Xu, Shi-ye; Sun, Shan-quan, E-mail: sunsq2151@cqmu.edu.cn

    2013-10-11

    Highlights: •AQP8 is mainly distributed in the cytoplasm of human astrocytoma cells. •AQP8 over-expressed in human astrocytomas, especially glioblastoma. •The up-regulation of AQP8 is related to the pathological grade of human astrocytomas. •AQP8 may contribute to the growth and proliferation of astrocytomas. -- Abstract: Aquaporin8 (AQP8), a member of the aquaporin (AQP) protein family, is weakly distributed in mammalian brains. Previous studies on AQP8 have focused mainly on the digestive and the reproductive systems. AQP8 has a pivotal role in keeping the fluid and electrolyte balance. In this study, we investigated the expression changes of AQP8 in 75 cases of human brain astrocytic tumors using immunohistochemistry, Western blotting, and reverse transcription polymerase chain reaction. The results demonstrated that AQP8 was mainly distributed in the cytoplasm of astrocytoma cells. The expression levels and immunoreactive score of AQP8 protein and mRNA increased in low-grade astrocytomas, and further increased in high-grade astrocytomas, especially in glioblastoma. Therefore, AQP8 may contribute to the proliferation of astrocytomas, and may be a biomarker and candidate therapy target for patients with astrocytomas.

  14. Determination of oxidation state of iron in normal and pathologically altered human aortic valves

    Energy Technology Data Exchange (ETDEWEB)

    Czapla-Masztafiak, J. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Kraków (Poland); Lis, G.J.; Gajda, M.; Jasek, E. [Department of Histology, Jagiellonian University Medical College, Kopernika 7, 31-034 Kraków (Poland); Czubek, U. [Department of Coronary Disease, Jagiellonian University Medical College, John Paul II Hospital, Prądnicka 80, 31-202 Kraków (Poland); Bolechała, F. [Department of Forensic Medicine, Jagiellonian University Medical College, Grzegórzecka 16, 31-531 Kraków (Poland); Borca, C. [Swiss Light Source, Paul Scherrer Institute, 5232 Villigen PSI (Switzerland); Kwiatek, W.M. [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Kraków (Poland)

    2015-12-01

    In order to investigate changes in chemical state of iron in normal and pathologically altered human aortic valves X-ray absorption spectroscopy was applied. Since Fe is suspected to play detrimental role in aortic valve stenosis pathogenesis the oxidation state of this element has been determined. The experimental material consisted of 10 μm sections of valves excised during routine surgery and from autopsies. The experiment was performed at the MicroXAS beamline of the SLS synchrotron facility in Villigen (Switzerland). The Fe K-edge XANES spectra obtained from tissue samples were carefully analyzed and compared with the spectra of reference compounds containing iron in various chemical structures. The analysis of absorption edge position and shape of the spectra revealed that both chemical forms of iron are presented in valve tissue but Fe{sup 3+} is the predominant form. Small shift of the absorption edge toward higher energy in the spectra from stenotic valve samples indicates higher content of the Fe{sup 3+} form in pathological tissue. Such a phenomenon suggests the role of Fenton reaction and reactive oxygen species in the etiology of aortic valve stenosis. The comparison of pre-edge regions of XANES spectra for control and stenotic valve tissue confirmed no differences in local symmetry or spin state of iron in analyzed samples.

  15. Integrated optical coherence tomography and optical coherence microscopy imaging of human pathology

    Science.gov (United States)

    Lee, Hsiang-Chieh; Zhou, Chao; Wang, Yihong; Aquirre, Aaron D.; Tsai, Tsung-Han; Cohen, David W.; Connolly, James L.; Fujimoto, James G.

    2010-02-01

    Excisional biopsy is the current gold standard for disease diagnosis; however, it requires a relatively long processing time and it may also suffer from unacceptable false negative rates due to sampling errors. Optical coherence tomography (OCT) is a promising imaging technique that provide real-time, high resolution and three-dimensional (3D) images of tissue morphology. Optical coherence microscopy (OCM) is an extension of OCT, combining both the coherence gating and the confocal gating techniques. OCM imaging achieves cellular resolution with deeper imaging depth compared to confocal microscopy. An integrated OCT/OCM imaging system can provide co-registered multiscale imaging of tissue morphology. 3D-OCT provides architectural information with a large field of view and can be used to find regions of interest; while OCM provides high magnification to enable cellular imaging. The integrated OCT/OCM system has an axial resolution of kidney (19), were imaged with OCT and OCM within 2 to 6 hours after excision. The images were compared with H & E histology to identify characteristic features useful for disease diagnosis. The feasibility of visualizing human pathology using integrated OCT/OCM was demonstrated in the pathology laboratory settings.

  16. Photoacoustic spectroscopy of the expired air at a human respiratory pathology

    Science.gov (United States)

    Ageev, B. G.; Kapitanov, V. A.; Ponomarev, Yu. N.; Nikiforova, O. Yu.; Karapuzikov, A. I.; Sherstov, I. V.; Volkova, L. I.; Djakova, E. Yu.; Kapilevich, L. V.; Kapitanova, D. V.; Kistenev, Yu. V.; Smotrova, N. A.; Fokin, V. A.; Plohotin, A. V.; Berendeeva, T. A.

    2006-12-01

    There are about 600 volatile compounds in air expired by man, including molecules-biomarkers of endogenous (produced in organism) origin, the specificity of generation and excretion mechanisms of which is sufficient for studies of both normal and pathologic processes. The goal of this work is analysis of the human-expired air by means of the intracavity laser photoacoustic sensor intended for detection of air gas admixtures having the absorption bands in the wavelength spectral range 9.2 - 10.8 μm. The sensor principle of operation is based on the photoacoustic effect caused by gas absorption of the CO II laser radiation. Measurements were conducted with a test group consisting of 100 persons and a group of patients (60 persons) affected by different bronchopulnionary pathologies. The state of health of each group members was determined from questioning data. The spectral absorption dependences were normalized to referent points and then investigated in respect to a qualitative coincidence. The typical results are presented below.

  17. Human movement variability, nonlinear dynamics, and pathology: is there a connection?

    Science.gov (United States)

    Stergiou, Nicholas; Decker, Leslie M

    2011-10-01

    Fields studying movement generation, including robotics, psychology, cognitive science, and neuroscience utilize concepts and tools related to the pervasiveness of variability in biological systems. The concept of variability and the measures for nonlinear dynamics used to evaluate this concept open new vistas for research in movement dysfunction of many types. This review describes innovations in the exploration of variability and their potential importance in understanding human movement. Far from being a source of error, evidence supports the presence of an optimal state of variability for healthy and functional movement. This variability has a particular organization and is characterized by a chaotic structure. Deviations from this state can lead to biological systems that are either overly rigid and robotic or noisy and unstable. Both situations result in systems that are less adaptable to perturbations, such as those associated with unhealthy pathological states or absence of skillfulness.

  18. Diffuse Optical Characterization of the Healthy Human Thyroid Tissue and Two Pathological Case Studies.

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    Claus Lindner

    Full Text Available The in vivo optical and hemodynamic properties of the healthy (n = 22 and pathological (n = 2 human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS and diffuse correlation spectroscopy (DCS system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (μa, μs' at three wavelengths (690, 785 and 830 nm to derive total hemoglobin concentration (THC and oxygen saturation (StO2. DCS measured the microvascular blood flow index (BFI. Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 μM to 144.8 μM, showing a 25-44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s, while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%, yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 μM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening.

  19. Expression of the TGF-beta1 system in human testicular pathologies

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    Puigdomenech Elisa

    2010-12-01

    Full Text Available Abstract Background In non-obstructive azoospermia, histological patterns of Sertoli cell-only Syndrome (SCO and hypospermatogenesis (H are commonly found. In these pathologies, Leydig cell hyperplasia (LCH is detected in some patients. Since TGF-β1 is involved in cellular proliferation/development, the aim of this work was to analyze the expression of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5, and the co-receptor endoglin in human biopsies from patients with idiopathic infertility. Methods Specific immunostaining of TGF-β1, its receptors TGFBRII, TGFBRI (ALK-1 and ALK-5, co-receptor endoglin and Smads proteins, were carried out in testicular biopsies from normal and infertile men with SCO or H. Gene expression of TGF-β1 system were made in biopsies from infertile patients with semi-quantitative and quantitative PCR. Results Immunohistochemical studies revealed that TGF-β1 and its specific receptors are present in Leydig cells in biopsies from normal tissue or patients with SCO or H with or without LCH. Smad proteins, which are involved in TGF-β1 signaling, are also detected in both their phosphorylated (activated and dephosphorylated form in all samples TGF-β1, ALK-1 and endoglin gene expression are stronger in human biopsies with LCH than in those with SCO or H. Neither TGFBRII nor ALK-5 gene expression showed significant differences between pathologies. A significant correlation between ALK-1 and endoglin expression was observed. Conclusions In conclusion, the high levels of mRNA and protein expression of the TGF-β1 system in patients with LCH, particularly ALK1 and its correlation with endoglin, suggest that these proteins acting in concert might be, at least in part, committed actors in the Leydig cell hyperplasia.

  20. Propagation of alpha-synuclein pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

    Science.gov (United States)

    Uchihara, Toshiki; Giasson, Benoit I

    2016-01-01

    Progressive aggregation of alpha-synuclein (αS) through formation of amorphous pale bodies to mature Lewy bodies or in neuronal processes as Lewy neurites may be the consequence of conformational protein changes and accumulations, which structurally represents "molecular template". Focal initiation and subsequent spread along anatomically connected structures embody "structural template". To investigate the hypothesis that both processes might be closely associated and involved in the progression of αS pathology, which can be observed in human brains, αS amyloidogenic precursors termed "seeds" were experimentally injected into the brain or peripheral nervous system of animals. Although these studies showed that αS amyloidogenic seeds can induce αS pathology, which can spread in the nervous system, the findings are still not unequivocal in demonstrating predominant transsynaptic or intraneuronal spreads either in anterograde or retrograde directions. Interpretation of some of these studies is further complicated by other concurrent aberrant processes including neuroimmune activation, injury responses and/or general perturbation of proteostasis. In human brain, αS deposition and neuronal degeneration are accentuated in distal axon/synapse. Hyperbranching of axons is an anatomical commonality of Lewy-prone systems, providing a structural basis for abundance in distal axons and synaptic terminals. This neuroanatomical feature also can contribute to such distal accentuation of vulnerability in neuronal demise and the formation of αS inclusion pathology. Although retrograde progression of αS aggregation in hyperbranching axons may be a consistent feature of Lewy pathology, the regional distribution and gradient of Lewy pathology are not necessarily compatible with a predictable pattern such as upward progression from lower brainstem to cerebral cortex. Furthermore, "focal Lewy body disease" with the specific isolated involvement of autonomic, olfactory or cardiac

  1. Morphological characterization of the nasopalatine region in human fetuses and its association to pathologies

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    Saulo Gabriel Moreira FALCI

    2013-06-01

    Full Text Available The nasopalatine region is composed of structures such as the vomeronasal organ and nasopalatine duct. The nasopalatine duct may provide the communication of the mouth to the nasal cavity in human fetuses and can be obliterated in an adult human. Knowledge on the development of the nasopalatine region and nasopalatine duct in humans is necessary for understanding the morphology and etiopathogenesis of lesions that occur in this region. Objective The aim of the present study was to describe the morphological aspects of the nasopalatine region in human fetuses and correlate these aspects with the development of pathologies in this region. Material and Methods Five human fetuses with no facial or palatine abnormalities were used for the acquisition of specimens from the nasopalatine region. After demineralization, the specimens were histologically processed. Histological cuts were stained with methylene blue to orient the cutting plane and hematoxylin-eosin for the descriptive histological analysis. Results The age of the fetuses was 8.00, 8.25, 9.00 and 9.25 weeks, and it was not possible to determine the age in the last one. The incisive canal was observed in all specimens as an opening delimited laterally by the periosteum and connecting oral and nasal cavity. The nasopalatine duct is an epithelial structure with the greatest morphological variation, with either unilateral or bilateral occurrence and total patent, partial patent and islet forms. The vomeronasal organ is a bilateral epithelized structure located alongside the nasal septum above the incisive canal in all the fetuses. Conclusions The incisive canal, nasopalatine duct and vomeronasal organ are distinct anatomic structures. The development of nasopalatine duct cysts may occur in all forms of the nasopalatine duct.

  2. Will the damage be done before we feel the heat? Infectious disease emergence and human response.

    Science.gov (United States)

    Kock, R A

    2013-12-01

    The global political economy is facing extreme challenges against a backdrop of large-scale expansion of human and domestic animal populations and related impacts on the biosphere. Significant global socio-ecological changes have occurred in the period of a single lifetime, driven by increased technology and access to physical and biological resources through open markets and globalization. Current resource consumption rates are not sustainable and ecological tipping points are being reached and one of the indicators of these may be a changing balance between hosts and pathogens. A period of extraordinary progress in reducing infection risk and disease impact on humans and domestic animals in the 20th Century is reversing in the 21st, but not always and not everywhere. Drivers for this shift are discussed in terms of demographics, agroecology, biodiversity decline and loss of resilience in ecosystems, climate change and increasing interconnectedness between species globally. Causality of disease emergence remains highly speculative, but patterns and data are emerging to commend a precautionary approach, while reassessing our global political, social and economic systems.

  3. IgA 型感染后肾小球肾炎的临床病理与预后研究%Pathologic and prognostic investigation of IgA dominant post infectious glomerulonephritis

    Institute of Scientific and Technical Information of China (English)

    吴智慧; 唐小铁; 王艳娥; 李力

    2014-01-01

    目的:观察IgA型感染后肾小球肾炎( PIGN)的临床与病理特征,及其与金黄色葡萄球菌感染及潜在糖尿病的相关性。方法回顾性分析IgA型PIGN患者25例,均进行肾组织活检,分析其在光镜病理、免疫荧光显微镜和电子显微镜下变化特点,总结其临床结局。结果所有患者在发病时均为临床金黄色葡萄球菌感染其中MSSA感染11例,MRSA感染14例。肾活检显示:急性期PIGN 6例,表现为弥漫性增生性肾小球肾炎,恢复期或亚急性期显示系膜细胞增生。免疫荧光显示IgA沉积。超微结构分析表明局灶性上皮下驼峰状电子致密物沉积。25例均使用抗生素治疗12例联合应用甲泼尼龙治疗,血液透析依赖8例。其中16例出院,完全缓解6例,部分缓解10例;9例持续住院,死亡5例。结论 IgA型与金黄色葡萄球菌感染有关。诊断主要依靠IgA的免疫荧光染色和存在毛细血管内增殖,电镜检查示上皮下电子致密沉积。%Objective To determine the clinical and pathologic features of IgA dominant post infectious glomerulone -phritis ( PIGN ) , including its association with staphylococcal infections , underlying diabetes , frequency of progression to ESRD, and its pathologic spectrum on renal biopsy .Methods We retrospectively reviewed 25 renal biopsy of PIGN for the past 5 years, and analyzed the pathologic results of light microscopy , immunofluorescence microscopy and electron microsco-py.Their clinical outcomes were also summarized .Results All patients at the onset of clinical are S .aureus infections, among them, MSSA infection were 11 cases, MRSA infection in 14 cases.Renal biopsy showed that:acute phase PIGN 6 ca-ses with diffuse proliferative glomerulonephritis , recovery or subacute phase display mesangial cell proliferation .Immunofluo-rescence showed IgA deposition .Ultrastructural analysis showed that subcutaneous hump-shaped electron dense deposits

  4. Zika Virus Strains Potentially Display Different Infectious Profiles in Human Neural Cells

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    Yannick Simonin

    2016-10-01

    Full Text Available The recent Zika virus (ZIKV epidemic has highlighted the poor knowledge on its physiopathology. Recent studies showed that ZIKV of the Asian lineage, responsible for this international outbreak, causes neuropathology in vitro and in vivo. However, two African lineages exist and the virus is currently found circulating in Africa. The original African strain was also suggested to be neurovirulent but its laboratory usage has been criticized due to its multiple passages. In this study, we compared the French Polynesian (Asian ZIKV strain to an African strain isolated in Central African Republic and show a difference in infectivity and cellular response between both strains in human neural stem cells and astrocytes. Consistently, this African strain led to a higher infection rate and viral production, as well as stronger cell death and anti-viral response. Our results highlight the need to better characterize the physiopathology and predict neurological impairment associated with African ZIKV.

  5. Nuclear Factor kappa B is required for the production of infectious human herpesvirus 8 virions

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    Negin N Blattman

    2014-04-01

    Full Text Available Human herpesvirus 8 (HHV8 infection leads to potent activation of nuclear factor kappa B (NFB in primary and transformed cells. We used recombinant HHV8 (rKSHV.219 expressing green fluorescent protein under the constitutive cellular promoter elongation factor 2 and red fluorescent protein under an early HHV8 lytic gene promoter T1.1, to monitor replication during infection of human foreskin fibroblasts (HF, noting changes in NFB activity. In primary HF, NFB levels do not affect HHV8 ability to establish infection or maintain latency. Furthermore, there was no effect on the percent of cells undergoing reactivation from latency, and there were similar numbers of released and cell associated HHV8 viral particles following reactivation in the presence of inhibitors. Reactivation of HHV8 in latently infected HF in the presence of NFB inhibitors resulted in production of viral particles that did not efficiently establish infection, due to deficiencies in binding and/or entry into normally permissive cells. Exogenous expression of glycoprotein M, an envelope protein involved in viral binding and entry was able to partially overcome the deficiency induced by NFB inhibitors. Our data indicate that in primary cells, NFB is not required for infection, establishment of latency, or entry into the lytic cycle, but is required for the expression of virion associated genes involved in the initial steps of virion infectivity. These studies suggest that strategies to inhibit NFB may prevent HHV8 spread and should be considered as a potential therapeutic target for preventing HHV8 associated diseases.

  6. Production of infectious ferret hepatitis E virus in a human hepatocarcinoma cell line PLC/PRF/5.

    Science.gov (United States)

    Li, Tian-Cheng; Yoshizaki, Sayaka; Yang, Tingting; Kataoka, Michiyo; Nakamura, Tomofumi; Ami, Yasushi; Yuriko, Suzaki; Takeda, Naokazu; Wakita, Takaji

    2016-02-02

    A strain of ferret hepatitis E virus (HEV), sF4370, isolated from an imported ferret was used to inoculate a human hepatocarcinoma cell line, PLC/PRF/5. The virus genome and capsid protein were detected in the cell culture supernatant. Immunofluorescence microscopy indicated that the capsid protein was located in the cytoplasm. The virus particles were purified from the culture supernatant by sucrose gradient ultracentrifugation. The capsid protein with molecular mass of ∼72 kDa was detected in fractions with density of 1.150-1.162 g/cm(3), and particles of ferret HEV was associated with cell membrane. The virus recovered from the supernatant was serially passaged with PLC/PRF/5 cells and had the ability to infect ferrets by oral inoculation, indicating that the ferret HEV grown in PLC/PRF/5 was infectious. The establishment of ferret HEV cell culture system might be useful to understand the life cycle, mechanism of infection and replication of ferret HEV.

  7. The carrying pigeons of the cell: exosomes and their role in infectious diseases caused by human pathogens.

    Science.gov (United States)

    Fleming, Adam; Sampey, Gavin; Chung, Myung-Chul; Bailey, Charles; van Hoek, Monique L; Kashanchi, Fatah; Hakami, Ramin M

    2014-07-01

    Exosomes have recently been classified as the newest family members of 'bioactive vesicles' that function to promote intercellular communication. Long ignored and thought to be only a mechanism by which cellular waste is removed, exosomes have garnered a huge amount of interest in recent years as their critical functions in maintaining homeostasis through intercellular communication and also in different types of diseases have been demonstrated. Many groundbreaking studies of exosome functions have been performed in the cancer field and the infectious disease areas of study, revealing the importance and also the fascinating complexity of exosomal packaging, targeting, and functions. Selective packaging of exosomes in response to the type of infection, exosomal modulation of the immune response and host signaling pathways, exosomal regulation of pathogen spread, and effects of exosomes on the degree of pathogenesis have all been well documented. In this review, we provide a synthesis of the current understanding of the role of exosomes during infections caused by human pathogens and discuss the implications of these findings for a better understanding of pathogenic mechanisms and future therapeutic and diagnostic applications.

  8. Immortalized pathological human myoblasts: towards a universal tool for the study of neuromuscular disorders

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    Mamchaoui Kamel

    2011-11-01

    Full Text Available Abstract Background Investigations into both the pathophysiology and therapeutic targets in muscle dystrophies have been hampered by the limited proliferative capacity of human myoblasts. Isolation of reliable and stable immortalized cell lines from patient biopsies is a powerful tool for investigating pathological mechanisms, including those associated with muscle aging, and for developing innovative gene-based, cell-based or pharmacological biotherapies. Methods Using transduction with both telomerase-expressing and cyclin-dependent kinase 4-expressing vectors, we were able to generate a battery of immortalized human muscle stem-cell lines from patients with various neuromuscular disorders. Results The immortalized human cell lines from patients with Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, oculopharyngeal muscular dystrophy, congenital muscular dystrophy, and limb-girdle muscular dystrophy type 2B had greatly increased proliferative capacity, and maintained their potential to differentiate both in vitro and in vivo after transplantation into regenerating muscle of immunodeficient mice. Conclusions Dystrophic cellular models are required as a supplement to animal models to assess cellular mechanisms, such as signaling defects, or to perform high-throughput screening for therapeutic molecules. These investigations have been conducted for many years on cells derived from animals, and would greatly benefit from having human cell models with prolonged proliferative capacity. Furthermore, the possibility to assess in vivo the regenerative capacity of these cells extends their potential use. The innovative cellular tools derived from several different neuromuscular diseases as described in this report will allow investigation of the pathophysiology of these disorders and assessment of new therapeutic strategies.

  9. The immunology and inflammatory responses of human melanocytes in infectious diseases.

    Science.gov (United States)

    Gasque, Philippe; Jaffar-Bandjee, Marie Christine

    2015-10-01

    Melanin is a canonical and major defense molecule in invertebrates but its role in mammalian immunity remains unexplored. In contrast, several recent studies have highlighted the emerging innate immune activities of human melanin-producing cells which can sense and respond to bacterial and viral infections. Indeed, the skin is a major portal of entry for pathogens such as arboviruses (Chikungunya, Dengue) and bacteria (mycobacterium leprae, Leptospira spirochetes). Melanocytes of the epidermis could contribute to the phagocytosis of these invading pathogens and to present antigens to competent immune cells. Melanocytes are known to produce key cytokines such as IL-1β, IL6 and TNF-α as well as chemokines. These molecules will subsequently alert macrophages, neutrophils, fibroblasts and keratinocytes through unique crosstalk mechanisms. The infection and the inflammatory responses will control melanocyte's immune and metabolic functions and could contribute to skin manifestations (rash, hyper or de-pigmentation, epidermolysis and psoriasis-like lesions). This review will address the potential role of melanocytes in immunity, inflammation and infection of the skin in health and diseases.

  10. Anal study in immunocompetent women with human papillomavirus related lower genital tract pathology.

    Science.gov (United States)

    Donaire, Concepción; Reillo, Marcos; Martínez-Escoriza, Juan C; López-Fernández, José A

    2017-04-01

    To estimate the prevalence of anal dysplasia in immunocompetent women with cervical intraepithelial dysplasia. We did a prospective cohort study, in which we enrolled 166 women with gynecological pathology related to human papilloma virus (HPV) infection. All patients underwent an anal cytology and HPV detection. Statistical analysis with a 95% confidence interval was used for prevalence calculations. A Χ2 test and Fisher's exact one were used to determine differences between groups of qualitative variables. Differences between normally distributed and non-normally distributed groups in quantitative variables were accounted for using Student's t-test or Mann-Whitney's U test, respectively. Out of the 166 patients studied, high risk HPV in the anal canal was detected in 107 (64.46%) cases. The most prevalent genotype observed was non 16/18 high risk HPV, present in 54 (50.47%) patients. There was no a significant association with smoking, use of condom, anal intercourse, or anal benign pathology. However, a significant correlation between the presence of high risk HPV in the anal canal and the antecedent of condylomas was observed (p=0.047) (CI95%: 1.00%-12.58%). Women with cervical intraepithelial neoplasia (CIN) grade 1 had a significantly increased presence of high risk HPV in the anal canal (p=0.044). Out of the 166 women, 6 (3.61%) had abnormal anal cytology results, and were referred to high-resolution anoscopy. Anal biopsy was performed in these six cases. In 2 patients the biopsy reported low-grade Anal Intraepithelial Neoplasia: 1.20% (0.15%-4.28%). Women with cervical intraepithelial dysplasia have 1.20% prevalence of anal intraepithelial neoplasia, so that it does not seem necessary to screen this population. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. The human rhinovirus: human-pathological impact, mechanisms of antirhinoviral agents, and strategies for their discovery.

    Science.gov (United States)

    Rollinger, Judith M; Schmidtke, Michaela

    2011-01-01

    As the major etiological agent of the common cold, human rhinoviruses (HRV) cause millions of lost working and school days annually. Moreover, clinical studies proved an association between harmless upper respiratory tract infections and more severe diseases e.g. sinusitis, asthma, and chronic obstructive pulmonary disease. Both the medicinal and socio-economic impact of HRV infections and the lack of antiviral drugs substantiate the need for intensive antiviral research. A common structural feature of the approximately 100 HRV serotypes is the icosahedrally shaped capsid formed by 60 identical copies of viral capsid proteins VP1-4. The capsid protects the single-stranded, positive sense RNA genome of about 7,400 bases in length. Both structural as well as nonstructural proteins produced during the viral life cycle have been identified as potential targets for blocking viral replication at the step of attachment, entry, uncoating, RNA and protein synthesis by synthetic or natural compounds. Moreover, interferon and phytoceuticals were shown to protect host cells. Most of the known inhibitors of HRV replication were discovered as a result of empirical or semi-empirical screening in cell culture. Structure-activity relationship studies are used for hit optimization and lead structure discovery. The increasing structural insight and molecular understanding of viral proteins on the one hand and the advent of innovative computer-assisted technologies on the other hand have facilitated a rationalized access for the discovery of small chemical entities with antirhinoviral (anti-HRV) activity. This review will (i) summarize existing structural knowledge about HRV, (ii) focus on mechanisms of anti-HRV agents from synthetic and natural origin, and (iii) demonstrate strategies for efficient lead structure discovery.

  12. Animal Ownership and Touching Enrich the Context of Social Contacts Relevant to the Spread of Human Infectious Diseases.

    Science.gov (United States)

    Kifle, Yimer Wasihun; Goeyvaerts, Nele; Van Kerckhove, Kim; Willem, Lander; Kucharski, Adam; Faes, Christel; Leirs, Herwig; Hens, Niel; Beutels, Philippe

    2015-01-01

    Many human infectious diseases originate from animals or are transmitted through animal vectors. We aimed to identify factors that are predictive of ownership and touching of animals, assess whether animal ownership influences social contact behavior, and estimate the probability of a major zoonotic outbreak should a transmissible influenza-like pathogen be present in animals, all in the setting of a densely populated European country. A diary-based social contact survey (n = 1768) was conducted in Flanders, Belgium, from September 2010 until February 2011. Many participants touched pets (46%), poultry (2%) or livestock (2%) on a randomly assigned day, and a large proportion of participants owned such animals (51%, 15% and 5%, respectively). Logistic regression models indicated that larger households are more likely to own an animal and, unsurprisingly, that animal owners are more likely to touch animals. We observed a significant effect of age on animal ownership and touching. The total number of social contacts during a randomly assigned day was modeled using weighted-negative binomial regression. Apart from age, household size and day type (weekend versus weekday and regular versus holiday period), animal ownership was positively associated with the total number of social contacts during the weekend. Assuming that animal ownership and/or touching are at-risk events, we demonstrate a method to estimate the outbreak potential of zoonoses. We show that in Belgium animal-human interactions involving young children (0-9 years) and adults (25-54 years) have the highest potential to cause a major zoonotic outbreak.

  13. Simulating Nationwide Pandemics: Applying the Multi-scale Epidemiologic Simulation and Analysis System to Human Infectious Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Dombroski, M; Melius, C; Edmunds, T; Banks, L E; Bates, T; Wheeler, R

    2008-09-24

    This study uses the Multi-scale Epidemiologic Simulation and Analysis (MESA) system developed for foreign animal diseases to assess consequences of nationwide human infectious disease outbreaks. A literature review identified the state of the art in both small-scale regional models and large-scale nationwide models and characterized key aspects of a nationwide epidemiological model. The MESA system offers computational advantages over existing epidemiological models and enables a broader array of stochastic analyses of model runs to be conducted because of those computational advantages. However, it has only been demonstrated on foreign animal diseases. This paper applied the MESA modeling methodology to human epidemiology. The methodology divided 2000 US Census data at the census tract level into school-bound children, work-bound workers, elderly, and stay at home individuals. The model simulated mixing among these groups by incorporating schools, workplaces, households, and long-distance travel via airports. A baseline scenario with fixed input parameters was run for a nationwide influenza outbreak using relatively simple social distancing countermeasures. Analysis from the baseline scenario showed one of three possible results: (1) the outbreak burned itself out before it had a chance to spread regionally, (2) the outbreak spread regionally and lasted a relatively long time, although constrained geography enabled it to eventually be contained without affecting a disproportionately large number of people, or (3) the outbreak spread through air travel and lasted a long time with unconstrained geography, becoming a nationwide pandemic. These results are consistent with empirical influenza outbreak data. The results showed that simply scaling up a regional small-scale model is unlikely to account for all the complex variables and their interactions involved in a nationwide outbreak. There are several limitations of the methodology that should be explored in future

  14. Animal Ownership and Touching Enrich the Context of Social Contacts Relevant to the Spread of Human Infectious Diseases

    Science.gov (United States)

    Kifle, Yimer Wasihun; Goeyvaerts, Nele; Van Kerckhove, Kim; Willem, Lander; Faes, Christel; Leirs, Herwig; Hens, Niel; Beutels, Philippe

    2015-01-01

    Many human infectious diseases originate from animals or are transmitted through animal vectors. We aimed to identify factors that are predictive of ownership and touching of animals, assess whether animal ownership influences social contact behavior, and estimate the probability of a major zoonotic outbreak should a transmissible influenza-like pathogen be present in animals, all in the setting of a densely populated European country. A diary-based social contact survey (n = 1768) was conducted in Flanders, Belgium, from September 2010 until February 2011. Many participants touched pets (46%), poultry (2%) or livestock (2%) on a randomly assigned day, and a large proportion of participants owned such animals (51%, 15% and 5%, respectively). Logistic regression models indicated that larger households are more likely to own an animal and, unsurprisingly, that animal owners are more likely to touch animals. We observed a significant effect of age on animal ownership and touching. The total number of social contacts during a randomly assigned day was modeled using weighted-negative binomial regression. Apart from age, household size and day type (weekend versus weekday and regular versus holiday period), animal ownership was positively associated with the total number of social contacts during the weekend. Assuming that animal ownership and/or touching are at-risk events, we demonstrate a method to estimate the outbreak potential of zoonoses. We show that in Belgium animal-human interactions involving young children (0–9 years) and adults (25–54 years) have the highest potential to cause a major zoonotic outbreak. PMID:26193480

  15. Chlamydophila pneumoniae derived from inclusions late in the infectious cycle induce aponecrosis in human aortic endothelial cells

    Directory of Open Access Journals (Sweden)

    Groscurth Peter

    2008-02-01

    Full Text Available Abstract Background Atherosclerosis is still the leading cause of death in the western world. Besides known risk factors studies demonstrating Chlamydophila pneumoniae (C. pneumoniae to be implicated in the progression of the disease, little is known about C. pneumoniae infection dynamics. We investigated whether C. pneumoniae induce cell death of human aortic endothelial cells, a cell type involved in the initiation of atherosclerosis, and whether chlamydial spots derive from inclusions. Results Lactate dehydrogenase release revealed host cell death to be dependent on the amounts of Chlamydia used for infection. The morphology of lysed human aortic endothelial cells showed DNA strand breaks simultaneously with cell membrane damage exclusively in cells carrying Chlamydia as spots. Further ultrastructural analysis revealed additional organelle dilation, leading to the definition as aponecrotic cell death of endothelial cells. Exclusive staining of the metabolic active pathogens by chlamydial heat shock protein 60 labelling and ceramide incorporation demonstrated that the bacteria responsible for the induction of aponecrosis had resided in former inclusions. Furthermore, a strong pro-inflammatory molecule, high mobility group box protein 1, was shown to be released from aponecrotic host cells. Conclusion From the data it can be concluded that aponecrosis inducing C. pneumoniae stem from inclusions, since metabolically active bacterial spots are strongly associated with aponecrosis late in the infectious cycle in vascular endothelial cells and metabolic activity was exclusively located inside of inclusions in intact cells. Vice versa initial spot-like infection with metabolically inert bacteria does not have an effect on cell death induction. Hence, C. pneumoniae infection can contribute to atherosclerosis by initial endothelial damage.

  16. Human neural stem cells alleviate Alzheimer-like pathology in a mouse model.

    Science.gov (United States)

    Lee, Il-Shin; Jung, Kwangsoo; Kim, Il-Sun; Lee, Haejin; Kim, Miri; Yun, Seokhwan; Hwang, Kyujin; Shin, Jeong Eun; Park, Kook In

    2015-08-21

    Alzheimer's disease (AD) is an inexorable neurodegenerative disease that commonly occurs in the elderly. The cognitive impairment caused by AD is associated with abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, which are accompanied by inflammation. Neural stem cells (NSCs) are self-renewing, multipotential cells that differentiate into distinct neural cells. When transplanted into a diseased brain, NSCs repair and replace injured tissues after migration toward and engraftment within lesions. We investigated the therapeutic effects in an AD mouse model of human NSCs (hNSCs) that derived from an aborted human fetal telencephalon at 13 weeks of gestation. Cells were transplanted into the cerebral lateral ventricles of neuron-specific enolase promoter-controlled APPsw-expressing (NSE/APPsw) transgenic mice at 13 months of age. Implanted cells extensively migrated and engrafted, and some differentiated into neuronal and glial cells, although most hNSCs remained immature. The hNSC transplantation improved spatial memory in these mice, which also showed decreased tau phosphorylation and Aβ42 levels and attenuated microgliosis and astrogliosis. The hNSC transplantation reduced tau phosphorylation via Trk-dependent Akt/GSK3β signaling, down-regulated Aβ production through an Akt/GSK3β signaling-mediated decrease in BACE1, and decreased expression of inflammatory mediators through deactivation of microglia that was mediated by cell-to-cell contact, secretion of anti-inflammatory factors generated from hNSCs, or both. The hNSC transplantation also facilitated synaptic plasticity and anti-apoptotic function via trophic supplies. Furthermore, the safety and feasibility of hNSC transplantation are supported. These findings demonstrate the hNSC transplantation modulates diverse AD pathologies and rescue impaired memory via multiple mechanisms in an AD model. Thus, our data provide tangible preclinical evidence that human NSC transplantation could be a

  17. A functionally significant polymorphism in ID3 is associated with human coronary pathology.

    Directory of Open Access Journals (Sweden)

    Ani Manichaikul

    Full Text Available We previously identified association between the ID3 SNP rs11574 and carotid intima-media thickness in the Diabetes Heart Study, a predominantly White diabetic population. The nonsynonymous SNP rs11574 results in an amino acid substitution in the C-terminal region of ID3, attenuating the dominant negative function of ID3 as an inhibitor of basic HLH factor E12-mediated transcription. In the current investigation, we characterize the association between the functionally significant polymorphism in ID3, rs11574, with human coronary pathology.The Multi-Ethnic Study of Atherosclerosis (MESA is a longitudinal study of subclinical cardiovascular disease, including non-Hispanic White (n = 2,588, African American (n = 2,560 and Hispanic (n = 2,130 participants with data on coronary artery calcium (CAC. The Coronary Assessment in Virginia cohort (CAVA included 71 patients aged 30-80 years, undergoing a medically necessary cardiac catheterization and intravascular ultrasound (IVUS at the University of Virginia. ID3 SNP rs11574 risk allele was associated with the presence of CAC in MESA Whites (P = 0.017. In addition, the risk allele was associated with greater atheroma burden and stenosis in the CAVA cohort (P = 0.003, P = 0.04 respectively. The risk allele remained predictive of atheroma burden in multivariate analysis (Model 1: covariates age, gender, and LDL, regression coefficient = 9.578, SE = 3.657, p = 0.0110; Model 2: covariates Model 1, presence of hypertension, presence of diabetes, regression coefficient = 8.389, SE = 4.788, p = 0.0163.We present additional cohorts that demonstrate association of ID3 SNP rs11574 directly with human coronary artery pathology as measured by CAC and IVUS: one a multiethnic, relatively healthy population with low levels of diabetes and the second a predominantly White population with a higher incidence of T2DM referred for cardiac catheterization.

  18. Pathological cyclic strain-induced apoptosis in human periodontal ligament cells through the RhoGDIα/caspase-3/PARP pathway.

    Directory of Open Access Journals (Sweden)

    Li Wang

    Full Text Available AIM: Human periodontal ligament (PDL cells incur changes in morphology and express proteins in response to cyclic strain. However, it is not clear whether cyclic strain, especially excessive cyclic strain, induces PDL cell apoptosis and if so, what mechanism(s are responsible. The aim of the present study was to elucidate the molecular mechanisms by which pathological levels of cyclic strain induce human PDL cell apoptosis. MATERIALS AND METHODS: Human PDL cells were obtained from healthy premolar tissue. After three to five passages in culture, the cells were subjected to 20% cyclic strain at a frequency of 0.1 Hz for 6 or 24 h using an FX-5000T system. Morphological changes of the cells were assessed by inverted phase-contrast microscopy, and apoptosis was detected by fluorescein isothiocyanate (FITC-conjugated annexin V and propidium iodide staining followed by flow cytometry. Protein expression was evaluated by Western blot analysis. RESULTS: The number of apoptotic human PDL cells increased in a time-dependent manner in response to pathological cyclic strain. The stretched cells were oriented parallel to each another with their long axes perpendicular to the strain force vector. Cleaved caspase-3 and poly-ADP-ribose polymerase (PARP protein levels increased in response to pathological cyclic strain over time, while Rho GDP dissociation inhibitor alpha (RhoGDIα decreased. Furthermore, knock-down of RhoGDIα by targeted siRNA transfection increased stretch-induced apoptosis and upregulated cleaved caspase-3 and PARP protein levels. Inhibition of caspase-3 prevented stretch-induced apoptosis, but did not change RhoGDIα protein levels. CONCLUSION: The overall results suggest that pathological-level cyclic strain not only influenced morphology but also induced apoptosis in human PDL cells through the RhoGDIα/caspase-3/PARP pathway. Our findings provide novel insight into the mechanism of apoptosis induced by pathological cyclic strain in

  19. Procurement of Human Tissues for Research Banking in the Surgical Pathology Laboratory: Prioritization Practices at Washington University Medical Center

    Science.gov (United States)

    Chernock, Rebecca D.; Leach, Tracey A.; Kahn, Ajaz A.; Yip, James H.; Rossi, Joan; Pfeifer, John D.

    2011-01-01

    Academic hospitals and medical schools with research tissue repositories often derive many of their internal human specimen acquisitions from their site's surgical pathology service. Typically, such acquisitions come from appropriately consented tissue discards sampled from surgical resections. Because the practice of surgical pathology has patient care as its primary mission, competing needs for tissue inevitably arise, with the requirement to preserve adequate tissue for clinical diagnosis being paramount. A set of best-practice gross pathology guidelines are summarized here, focused on the decision for tissue banking at the time specimens are macroscopically evaluated. These reflect our collective experience at Washington University School of Medicine, and are written from the point of view of our site biorepository. The involvement of trained pathology personnel in such procurements is very important. These guidelines reflect both good surgical pathology practice (including the pathologic features characteristic of various anatomic sites) and the typical objectives of research biorepositories. The guidelines should be helpful to tissue bank directors, and others charged with the procurement of tissues for general research purposes. We believe that appreciation of these principles will facilitate the partnership between surgical pathologists and biorepository directors, and promote both good patient care and strategic, value-added banking procurements. PMID:23386925

  20. The ferric yersiniabactin uptake receptor FyuA is required for efficient biofilm formation by urinary tract infectious Escherichia coli in human urine

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Ferrieres, Lionel; Klemm, Per

    2008-01-01

    Urinary tract infection (UTI) is the most common infection in patients with indwelling urinary catheters, and bacterial biofilm formation is a major problem in this type of infection. Escherichia coli is responsible for the large majority of UTIs. Free iron is strictly limited in the human urinary...... tract and there is fierce competition between the host and infectious bacteria for this essential metal. Urinary tract infectious E coli have highly efficient mechanisms of iron acquisition, one of which is the yersiniabactin system. The fyuA gene, encoding the yersiniabactin receptor, is one...... of the most upregulated genes in biofilm; it was upregulated 63-fold in the E coli UTI strain VR50. FyuA was found to be highly important for biofilm formation in iron-poor environments such as human urine. Mutants in fyuA show aberrant biofilm formation and the cells become filamentous; a VR50fyuA mutant...

  1. [Hyaluronic acid (hyaluronan) levels in pathological human saphenous veins. Effects of procyanidol oligomers].

    Science.gov (United States)

    Drubaix, I; Maraval, M; Robert, L; Robert, A M

    1997-01-01

    We investigated the hyaluronan content in the pathologic human venous wall using an ELSA assay with hyaluronectin according to the method of Delpech et al. The mean hyaluronan content in the 74 fragments from 12 venous walls studied was 596 +/- 528 ng/mg dry weight. These 12 venous walls could be separated in 3 distinct groups according to their hyaluronan content, low (277 +/- 141 ng/mg dry weight), moderate (552 +/- 361 ng/m dry weight) or high (1299 +/- 568 ng/mg dry weight). The differences between these groups are significant (p < 0.001). The presence of a veino-lymphatic oedema was generally associated with a high hyaluronan level (in 65% of cases). The 3H-glucosamine incorporation in cultured venous wall explants showed a 35% increase (p < 0.002) in varicosis as compared with the non or less modified segments of the vein and a 29% (p < 0.001) increase in presence of a veino-lymphatic oedema. The addition of 1 mg/ml of PCO (Procyanidolic Oligomers) to the culture media induced near to 20% decrease of the 3H-glucosamine incorporation and a 34% decrease of the hyaluronan content. Our results confirm the role of local overproduction of hyaluronan in the establishment of oedema and the potential effect of PCO to counteract it.

  2. Wavelet analysis of hemispheroid flow separation toward understanding human vocal fold pathologies

    Science.gov (United States)

    Plesniak, Daniel H.; Carr, Ian A.; Bulusu, Kartik V.; Plesniak, Michael W.

    2014-11-01

    Physiological flows observed in human vocal fold pathologies, such as polyps and nodules, can be modeled by flow over a wall-mounted protuberance. The experimental investigation of flow separation over a surface-mounted hemispheroid was performed using particle image velocimetry (PIV) and measurements of surface pressure in a low-speed wind tunnel. This study builds on the hypothesis that the signatures of vortical structures associated with flow separation are imprinted on the surface pressure distributions. Wavelet decomposition methods in one- and two-dimensions were utilized to elucidate the flow behavior. First, a complex Gaussian wavelet was used for the reconstruction of surface pressure time series from static pressure measurements acquired from ports upstream, downstream, and on the surface of the hemispheroid. This was followed by the application of a novel continuous wavelet transform algorithm (PIVlet 1.2) using a 2D-Ricker wavelet for coherent structure detection on instantaneous PIV-data. The goal of this study is to correlate phase shifts in surface pressure with Strouhal numbers associated with the vortex shedding. Ultimately, the wavelet-based analytical framework will be aimed at addressing pulsatile flows. This material is based in part upon work supported by the National Science Foundation under Grant Number CBET-1236351, and GW Center for Biomimetics and Bioinspired Engineering (COBRE).

  3. Mining the human genome after Association for Molecular Pathology v. Myriad Genetics.

    Science.gov (United States)

    Evans, Barbara J

    2014-07-01

    The Supreme Court's recent decision in Association for Molecular Pathology v. Myriad Genetics portrays the human genome as a product of nature. This frames medical genetics as an extractive industry that mines a natural resource to produce valuable goods and services. Natural resource law offers insights into problems medical geneticists can expect after this decision and suggests possible solutions. Increased competition among clinical laboratories offers various benefits but threatens to increase fragmentation of genetic data resources, potentially causing waste in the form of lost opportunities to discover the clinical significance of particular gene variants. The solution lies in addressing legal barriers to appropriate data sharing. Sustainable discovery in the field of medical genetics can best be achieved through voluntary data sharing rather than command-and-control tactics, but voluntary mechanisms must be conceived broadly to include market-based approaches as well as donative and publicly funded data commons. The recently revised Health Insurance Portability and Accountability Act Privacy Rule offers an improved--but still imperfect--framework for market-oriented data sharing. This article explores strategies for addressing the Privacy Rule's remaining defects. America is close to having a legal framework that can reward innovators, protect privacy, and promote needed data sharing to advance medical genetics.

  4. Evolutionary developmental pathology and anthropology: A new field linking development, comparative anatomy, human evolution, morphological variations and defects, and medicine.

    Science.gov (United States)

    Diogo, Rui; Smith, Christopher M; Ziermann, Janine M

    2015-11-01

    We introduce a new subfield of the recently created field of Evolutionary-Developmental-Anthropology (Evo-Devo-Anth): Evolutionary-Developmental-Pathology-and-Anthropology (Evo-Devo-P'Anth). This subfield combines experimental and developmental studies of nonhuman model organisms, biological anthropology, chordate comparative anatomy and evolution, and the study of normal and pathological human development. Instead of focusing on other organisms to try to better understand human development, evolution, anatomy, and pathology, it places humans as the central case study, i.e., as truly model organism themselves. We summarize the results of our recent Evo-Devo-P'Anth studies and discuss long-standing questions in each of the broader biological fields combined in this subfield, paying special attention to the links between: (1) Human anomalies and variations, nonpentadactyly, homeotic transformations, and "nearest neighbor" vs. "find and seek" muscle-skeleton associations in limb+facial muscles vs. other head muscles; (2) Developmental constraints, the notion of "phylotypic stage," internalism vs. externalism, and the "logic of monsters" vs. "lack of homeostasis" views about human birth defects; (3) Human evolution, reversions, atavisms, paedomorphosis, and peromorphosis; (4) Scala naturae, Haeckelian recapitulation, von Baer's laws, and parallelism between phylogeny and development, here formally defined as "Phylo-Devo parallelism"; and (5) Patau, Edwards, and Down syndrome (trisomies 13, 18, 21), atavisms, apoptosis, heart malformations, and medical implications.

  5. Brain-derived neurotrophic factor expression predicts adverse pathological & clinical outcomes in human breast cancer

    Directory of Open Access Journals (Sweden)

    Mokbel Kefah

    2011-07-01

    Full Text Available Abstract Introduction Brain-derived neurotrophic factor (BDNF has established physiological roles in the development and function of the vertebrate nervous system. BDNF has also been implicated in several human malignancies, including breast cancer (BC. However, the precise biological role of BDNF and its utility as a novel biomarker have yet to be determined. The objective of this study was to determine the mRNA and protein expression of BDNF in a cohort of women with BC. Expression levels were compared with normal background tissues and evaluated against established pathological parameters and clinical outcome over a 10 year follow-up period. Methods BC tissues (n = 127 and normal tissues (n = 33 underwent RNA extraction and reverse transcription, BDNF transcript levels were determined using real-time quantitative PCR. BDNF protein expression in mammary tissues was assessed with standard immuno-histochemical methodology. Expression levels were analyzed against tumour size, grade, nodal involvement, TNM stage, Nottingham Prognostic Index (NPI and clinical outcome over a 10 year follow-up period. Results Immuno-histochemical staining revealed substantially greater BDNF expression within neoplastic cells, compared to normal mammary epithelial cells. Significantly higher mRNA transcript levels were found in the BC specimens compared to background tissues (p = 0.007. The expression of BDNF mRNA was demonstrated to increase with increasing NPI; NPI-1 vs. NPI-2 (p = 0.009. Increased BDNF transcript levels were found to be significantly associated with nodal positivity (p = 0.047. Compared to patients who remained disease free, higher BDNF expression was significantly associated with local recurrence (LR (p = 0.0014, death from BC (p = 0.018 and poor prognosis overall (p = 0.013. After a median follow up of 10 years, higher BDNF expression levels were significantly associated with reduced overall survival (OS (106 vs. 136 months, p = 0.006. BDNF

  6. A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes

    DEFF Research Database (Denmark)

    Hansen, Kasper Lage; Hansen, Niclas Tue; Karlberg, Erik, Olof, Linnart

    2008-01-01

    Heritable diseases are caused by germ-line mutations that, despite tissuewide presence, often lead to tissue-specific pathology. Here, we make a systematic analysis of the link between tissue-specific gene expression and pathological manifestations in many human diseases and cancers. Diseases were...... to be overexpressed in the normal tissues where defects cause pathology. In contrast, cancer genes and complexes were not overexpressed in the tissues from which the tumors emanate. We specifically identified a complex involved in XY sex reversal that is testis-specific and down-regulated in ovaries. We also...... identified complexes in Parkinson disease, cardiomyopathies, and muscular dystrophy syndromes that are similarly tissue specific. Our method represents a conceptual scaffold for organism-spanning analyses and reveals an extensive list of tissue-specific draft molecular pathways, both known and unexpected...

  7. Brain burdens of aluminum, iron, and copper and their relationships with amyloid-β pathology in 60 human brains.

    Science.gov (United States)

    Exley, Christopher; House, Emily; Polwart, Anthony; Esiri, Margaret M

    2012-01-01

    The deposition in the brain of amyloid-β as beta sheet conformers associated with senile plaques and vasculature is frequently observed in Alzheimer’s disease. While metals, primarily aluminum, iron, zinc, and copper, have been implicated in amyloid-β deposition in vivo, there are few data specifically relating brain metal burden with extent of amyloid pathologies in human brains. Herein brain tissue content of aluminum, iron, and copper are compared with burdens of amyloid-β, as senile plaques and as congophilic amyloid angiopathy, in 60 aged human brains. Significant observations were strong negative correlations between brain copper burden and the degree of severity of both senile plaque and congophilic amyloid angiopathy pathologies with the relationship with the former reaching statistical significance. While we did not have access to the dementia status of the majority of the 60 brain donors, this knowledge for just 4 donors allowed us to speculate that diagnosis of dementia might be predicted by a combination of amyloid pathology and a ratio of the brain burden of copper to the brain burden of aluminum. Taking into account only those donor brains with either senile plaque scores ≥4 and/or congophilic amyloid angiopathy scores ≥12, a Cu:Al ratio of <20 would predict that at least 39 of the 60 donors would have been diagnosed as suffering from dementia. Future research should test the hypothesis that, in individuals with moderate to severe amyloid pathology, low brain copper is a predisposition to developing dementia.

  8. Age-associated and cell-type-specific neurofibrillary pathology in transgenic mice expressing the human midsized neurofilament subunit.

    Science.gov (United States)

    Vickers, J C; Morrison, J H; Friedrich, V L; Elder, G A; Perl, D P; Katz, R N; Lazzarini, R A

    1994-09-01

    Alterations in neurofilaments are a common occurrence in neurons of the human nervous system during aging and diseases associated with aging. Such pathologic changes may be attributed to species-specific properties of human neurofilaments as well as cell-type-specific regulation of this element of the cytoskeleton. The development of transgenic animals containing human neurofilament subunits offers an opportunity to study the effects of aging and other experimental conditions on the human-specific form of these proteins in a rodent model. The present study shows that mice from the transgenic line NF(M)27, which express the human midsized neurofilament subunit at low levels (2-25% of the endogenous NF-M), develop neurofilamentous accumulations in specific subgroups of neurons that are age dependent, affecting 78% of transgenic mice over 12 months of age. Similar accumulations do not occur in age-matched, wild-type littermates or in 3-month-old transgenic mice. In 12-month-old transgenic mice, somatic neurofilament accumulations resembling neurofibrillary tangles were present predominantly in layers III and V of the neocortex, as well as in select subpopulations of subcortical neurons. Intraperikaryal, spherical neurofilamentous accumulations were particularly abundant in cell bodies in layer II of the neocortex, and neurofilament-containing distentions of Purkinje cell proximal axons occurred in the cerebellum. These pathological accumulations contained mouse as well as human NF subunits, but could be distinguished by their content of phosphorylation-dependent NF epitopes. These cytoskeletal alterations closely resemble the cell-type-specific alterations in neurofilaments that occur during normal human aging and in diseases associated with aging, indicating that these transgenic animals may serve as models of some aspects of the pathologic features of human neurodegenerative diseases.

  9. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease

    DEFF Research Database (Denmark)

    Wolf, Heike; Damme, Markus; Stroobants, Stijn;

    2016-01-01

    Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fuc...... demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model may be utilized to establish diagnostic and therapeutic strategies for fucosidosis....

  10. Intracellular Aβ pathology and early cognitive impairments in a transgenic rat overexpressing human amyloid precursor protein: a multidimensional study.

    Science.gov (United States)

    Iulita, M Florencia; Allard, Simon; Richter, Luise; Munter, Lisa-Marie; Ducatenzeiler, Adriana; Weise, Christoph; Do Carmo, Sonia; Klein, William L; Multhaup, Gerhard; Cuello, A Claudio

    2014-06-05

    Numerous studies have implicated the abnormal accumulation of intraneuronal amyloid-β (Aβ) as an important contributor to Alzheimer's disease (AD) pathology, capable of triggering neuroinflammation, tau hyperphosphorylation and cognitive deficits. However, the occurrence and pathological relevance of intracellular Aβ remain a matter of controversial debate. In this study, we have used a multidimensional approach including high-magnification and super-resolution microscopy, cerebro-spinal fluid (CSF) mass spectrometry analysis and ELISA to investigate the Aβ pathology and its associated cognitive impairments, in a novel transgenic rat model overexpressing human APP. Our microscopy studies with quantitative co-localization analysis revealed the presence of intraneuronal Aβ in transgenic rats, with an immunological signal that was clearly distinguished from that of the amyloid precursor protein (APP) and its C-terminal fragments (CTFs). The early intraneuronal pathology was accompanied by a significant elevation of soluble Aβ42 peptides that paralleled the presence and progression of early cognitive deficits, several months prior to amyloid plaque deposition. Aβ38, Aβ39, Aβ40 and Aβ42 peptides were detected in the rat CSF by MALDI-MS analysis even at the plaque-free stages; suggesting that a combination of intracellular and soluble extracellular Aβ may be responsible for impairing cognition at early time points. Taken together, our results demonstrate that the intraneuronal development of AD-like amyloid pathology includes a mixture of molecular species (Aβ, APP and CTFs) of which a considerable component is Aβ; and that the early presence of these species within neurons has deleterious effects in the CNS, even before the development of full-blown AD-like pathology.

  11. Enfermedades infecciosas emergentes: interacción entre el mundo microbiano y las sociedades humanas (Emergent infectious diseases: interaction between the microbial world and human societies

    Directory of Open Access Journals (Sweden)

    Fernando García

    2008-09-01

    Full Text Available En este artículo se analizan dos facetas importantes de las enfermedades infecciosas emergentes. Por un lado, las características de los microorganismos que las causan, por otro, las características del ser humano que promueven o contribuyen al surgimiento de las enfermedades infecciosas. Desde el punto de vista microbiano, se pueden identificar tres aspectos fundamentales. Primero, los patógenos emergentes son predominantemente virales, seguidos por los bacterianos. Numéricamente los virus ARN dominan, constituyendo el 37% de todos los patógenos emergentes. Los virus ARN predominan entre los virus patógenos emergentes que aparentemente entraron en las poblaciones humanas en las últimas décadas, como VIH y el coronavirus asociado al SARS. Segundo, los patógenos emergentes no se asocian a un único tipo de hospedero, sino que usualmente tienen amplio rango de hospederos que incluye varios órdenes de especies de mamíferos y no mamíferos. En efecto, la mayoría de las infecciones emergentes son de origen zoonótico. Tercero, los patógenos emergentes tienen un cierto grado de flexibilidad biológica que les permite aprovecharse de nuevas oportunidades epidemiológicas para ingresar a las poblaciones humanas. Las enfermedades infecciosas no son un problema reciente sino que han estado "emergiendo" a lo largo de la historia de la humanidad y es posible identificar, al menos, cuatro transiciones históricas. La última de esas transiciones es la globalización actual. Muchos factores antropogénicos inciden en el surgimiento de las enfermedades infecciosas emergentes, incluyendo eventos sociales, comportamiento humano, cambios ambientales, políticas en salud pública, procedimientos médicos y otros.In this review, 2 relevant aspects of emerging infectious diseases are analyzed: the characteristics of the microorganisms causing such infections and the human facts that promote or contribute to emerging infectious diseases. Three important

  12. Vasculitis and infectious diseases.

    Science.gov (United States)

    Satta, R; Biondi, G

    2015-04-01

    Vasculitis usually presents without a well-known underline cause (idiopathic vasculitis), nevertheless, it is sometimes possible to find out one or more causative agents (secondary vasculitis). Nowadays, thanks to the increasing amount of precise diagnostic tools, a piece of idiopathic vasculitis is reclassified as associated with probable etiology, which can be set off by several factors, such as infections. Infections are considered to be the most common cause of secondary vasculitis. Virtually, every infectious agent can trigger a vasculitis by different mechanisms which can be divided in two main categories: direct and indirect. In the former, infectious agents destroy directly the vascular wall leading, eventually, to a subsequent inflammatory response. In the latter, indirect form, they stimulate an immune response against blood vessels. Different infectious agents are able to directly damage the vascular wall. Among these, it is possible to recognize Staphylococcus spp, Streptococcus spp, Salmonella spp, Treponema spp, Rickettsia spp, Cytomegalovirus, Herpes Simplex Virus 1 and 2, and many others which have a peculiar tropism for endothelial cells. Conversely, another group of microbial agents, such as Mycobacterium tuberculosis, Mycobacterium leprae, Hepatits B Virus, Human Immunodeficiency Virus and others, trigger vasculitis in the indirect way. This is due to the fact that they can share epitopes with the host or modify self-antigens, thus leading to a cross-self reaction of the immune system. These mechanism, in turn, leads to immunological responses classified as type I-IV by Gell-Coombs. Nevertheless, it is difficult to strictly separate the direct and indirect forms, because most infectious agents can cause vasculitis in both ways (mixed forms). This paper will analyze the link between infectious agents and vasculitis, focusing on direct and indirect secondary vasculitis, and on a group of probable infection-related idiopathic vasculitis, and finally

  13. Pathological alterations typical of human Tay-Sachs disease, in the retina of a deep-sea fish

    Science.gov (United States)

    Fishelson, L.; Delarea, Yacov; Galil, Bella S.

    Micrographs of retinas from the deep-sea fish Cataetyx laticeps revealed visual cells containing membranous whorls in the ellipsoids of the inner segments resulting from stretching and modifications of the mitochondria membranes and their cristae. These pathological structures seem to be homologous to the whorls observed in retinas of human carriers of Tay-Sachs disease. This disease, a genetic disorder, is found in humans and some mammals. Our findings in fish suggest that the gene responsible can be found throughout the vertebrate evolutionary tree, possibly dormant in most taxa.

  14. Primary stromal cells isolated from human various histological/pathological prostate have different phenotypes and tumor promotion role

    Institute of Scientific and Technical Information of China (English)

    WANG Xiao-hai; ZHAO Fu-jun; HAN Bang-min; JIANG Qi; WANG Yong-chuan; WU Jian-hong; TANG Yue-qing; ZHANG Yue-ping; XIA Shu-jie

    2011-01-01

    Background Prostate stromal cells are known to regulate epithelial growth as well as support and maintain epithelial function. However, how stromal cells regulate epithelial cells and what differences among various histological/pathological prostate stromal cells in prostate cancer progression still remain unclear. This study aimed to investigate the different phenotypes of human various histological/pathological prostate stromal cells, and their role in tumor promotion.Methods The different phenotypes of the human normal prostatic peripheral zonal primary stromal cells (NPPF),transitional zonal primary stromal cells (NPTF), and prostate cancer associated primary stromal cells (CAF) were examined with growth curves and Annexin V-fluorescein isothiocyanate (FITC) assay. The different effects on prostate cancer cell line C4-2B by NPPF, NPTF, and CAF were examined with MTT assay and Annexin V-FITC assay. The gene expression of different histological/pathological prostate stromal cells was profiled by microarray and hierarchical cluster analysis.Results The growth rate of NPPF, NPTF and CAF gradually increased, followed by decreasing apoptosis. In vitro stromal-C4-2B cell line co-culture models, the proliferation and apoptosis of C4-2B cell line were differently affected by human various histological/pathological prostate stromal cells. CAF showed the most powerful effect to C4-2B cell line,as opposed to a weakest effect of NPTF. Microarray and hierarchical cluster analysis showed that the differentially expressed genes of CAF and NPPF were less than NPPF and NPTF, or CAF and NPTF. This was consistent with clinical observations that prostate cancer mostly derived from the peripheral zone and does not usually occur in the transitional zone.Conclusion NPPF, NPTF and CAF possess extremely different biological characteristics and gene expression, which may play an important role in genesis and development of prostate cancer.

  15. Small interference RNA profiling reveals the essential role of human membrane trafficking genes in mediating the infectious entry of dengue virus

    Directory of Open Access Journals (Sweden)

    Chu Justin

    2010-02-01

    Full Text Available Abstract Background Dengue virus (DENV is the causative agent of Dengue fever and the life-threatening Dengue Haemorrhagic fever or Dengue shock syndrome. In the absence of anti-viral agents or vaccine, there is an urgent need to develop an effective anti-viral strategy against this medically important viral pathogen. The initial interplay between DENV and the host cells may represent one of the potential anti-viral targeting sites. Currently the involvements of human membrane trafficking host genes or factors that mediate the infectious cellular entry of dengue virus are not well defined. Results In this study, we have used a targeted small interfering RNA (siRNA library to identify and profile key cellular genes involved in processes of endocytosis, cytoskeletal dynamics and endosome trafficking that are important and essential for DENV infection. The infectious entry of DENV into Huh7 cells was shown to be potently inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis. The important role of clathrin-mediated endocytosis was confirmed by the expression of well-characterized dominant-negative mutants of genes in this pathway and by using the clathrin endocytosis inhibitor chlorpromazine. Furthermore, DENV infection was shown to be sensitive to the disruption of human genes in regulating the early to late endosomal trafficking as well as the endosomal acidic pH. The importance and involvement of both actin and microtubule dynamics in mediating the infectious entry of DENV was also revealed in this study. Conclusions Together, the findings from this study have provided a detail profiling of the human membrane trafficking cellular genes and the mechanistic insight into the interplay of these host genes with DENV to initiate an infection, hence broadening our understanding on the entry pathway of this medically important viral pathogen. These data may also provide a new potential avenue for development of anti

  16. Third harmonic generation imaging for fast, label-free pathology of human brain tumors

    NARCIS (Netherlands)

    Kuzmin, N. V.; Wesseling, P.; Hamer, P. C de Witt; Noske, D. P.; Galgano, G. D.; Mansvelder, H. D.; Baayen, J. C.; Groot, M. L.

    In brain tumor surgery, recognition of tumor boundaries is key. However, intraoperative assessment of tumor boundaries by the neurosurgeon is difficult. Therefore, there is an urgent need for tools that provide the neurosurgeon with pathological information during the operation. We show that third

  17. Third harmonic generation imaging for fast, label-free pathology of human brain tumors

    NARCIS (Netherlands)

    Kuzmin, N.V.; Wesseling, P.; Hamer, P.C.; Noske, D.P.; Galgano, G.D.; Mansvelder, H.D.; Baayen, J.C.; Groot, M.L.

    2016-01-01

    In brain tumor surgery, recognition of tumor boundaries is key. However, intraoperative assessment of tumor boundaries by the neurosurgeon is difficult. Therefore, there is an urgent need for tools that provide the neurosurgeon with pathological information during the operation. We show that third

  18. 75 FR 7487 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-02-19

    ... HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases... personal privacy. Name of Committee: National Institute of Allergy and Infectious Diseases Special Emphasis...: National Institute of Allergy and Infectious Diseases Special Emphasis Panel; Human Immune...

  19. Relation of Cystatin C and Cathepsin B Expression to the Pathological Grade and Invasion of Human Gliomas

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To explore the relation of cystatin C and cathepsin B expression to the pathological grade and invasion of human gliomas.METHODS A immunohistochemical method was used to detect the expression of cystatin C and cathepsin B in 57 glioma samples.RESULTS The expression of cystatin C in high-grade (Grade Ⅲ~Ⅳ )gliomas was significantly weaker than that in low-grade(Grade Ⅰ~Ⅱ, P=0.0001).On the other hand, the expression of cathepsin B in high-grade gliomas was significantly stronger than that in low-grade (P=0.0001). Cystatin C expression correlated inversely with cathepsin B expression in gliomas (P=0.01).CONCLUSION Cystatin C and cathepsin B expression is related to the pathological grade and invasion of gliomas. Combining detection of cystatin C and cathepsin B expressions might provide significant information for clinical assessment of maglignant phenotypes and invasion of gliomas.

  20. Efeitos da eritropoetina recombinante humana em recém-nascidos pré-termo com doenças infecciosas Effects of recombinant human erythropoietin in preterm newborns with infectious diseases

    Directory of Open Access Journals (Sweden)

    Iara Flávia de Vasconcelos P. Aguiar

    2007-02-01

    Full Text Available OBJETIVO: Analisar os efeitos da eritropoetina recombinante humana (rHuEpo em recém-nascidos pré-termo com doenças infecciosas graves. MÉTODOS: Foi realizado um estudo controlado, não randomizado, em 34 recém-nascidos com diagnóstico de patologias infecciosas graves, peso de nascimento igual ou inferior a 1500 g, idade gestacional inferior a 35 semanas e estabilidade clínica. Os recém-nascidos designados para o tratamento com rHuEpo receberam a eritropoetina ß na dose de 400 UI/kg, duas vezes por semana, por via subcutânea. A suplementação oral com ferro foi iniciada quando os níveis de ferritina sérica foram inferiores a 60 mcg/L. O estudo foi realizado durante seis semanas ou até a alta hospitalar do paciente. Foram avaliados a eritropoese, o número de transfusões, o número de neutrófilos, a contagem de plaquetas e os episódios de novas infecções durante o tratamento com o hormônio. RESULTADOS: Houve aumento significativo do número de reticulócitos no grupo tratado; entretanto, não houve impacto sobre o número ou volume de transfusões. Não foram observadas alterações no número de neutrófilos ou plaquetas. CONCLUSÃO: O uso de rHuEpo em RNPT com doenças infecciosas, na dose de 800 UI/Kg/semana, foi efetivo para induzir eritropoese, sem ocorrerem alterações significativas sobre o número de neutrófilos ou plaquetas. Essa estratégia, associada ao controle rigoroso do volume de sangue retirado para exames, poderá ser benéfica na prevenção da anemia em RNPT com infecção grave.OBJECTIVE: To study the effects of recombinant human erythropoietin (rHuEpo in preterm newborns (PTNs with serious infectious diseases. METHODS: A not randomized case-control study was carried out in 34 preterm newborns with diagnosis of serious infectious pathologies, gestational age up to 35 weeks, birth weight less than 1500 g and clinical stability. Newborns selected for treatment with rHuEpo received 400 U/kg erythropoietin

  1. [Recognition of commensal microflora by pattern recognition receptors in human physiology and pathology].

    Science.gov (United States)

    Bondarenko, V M; Likhoded, V G

    2012-01-01

    Contemporary data on the interaction of commensal microflora and Toll-like pattern recognition receptors are presented. These receptors recognize normal intestine microflora in physiological conditions, and this interaction is necessary for the maintenance of homeostasis and damage reparation of the intestine, for the induction of heat shock cytoprotective proteins. As a side effect in disruption of immunologic tolerance and misbalance of protective immunological mechanisms, multiorgan pathologic changes of organs and tissues may develop, including chronic inflammation processes of various localization.

  2. Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.

    Directory of Open Access Journals (Sweden)

    Silvia Zucchini

    Full Text Available The microRNAs (miRNAs are small size non-coding RNAs that regulate expression of target mRNAs at post-transcriptional level. miRNAs differentially expressed under pathological conditions may help identifying mechanisms underlying the disease and may represent biomarkers with prognostic value. However, this kind of studies are difficult in the brain because of the cellular heterogeneity of the tissue and of the limited access to fresh tissue. Here, we focused on a pathology affecting specific cells in a subpopulation of epileptic brains (hippocampal granule cells, an approach that bypasses the above problems. All patients underwent surgery for intractable temporal lobe epilepsy and had hippocampal sclerosis associated with no granule cell pathology in half of the cases and with type-2 granule cell pathology (granule cell layer dispersion or bilamination in the other half. The expression of more than 1000 miRNAs was examined in the laser-microdissected dentate granule cell layer. Twelve miRNAs were differentially expressed in the two groups. One of these, miR487a, was confirmed to be expressed at highly differential levels in an extended cohort of patients, using RT-qPCR. Bioinformatics searches and RT-qPCR verification identified ANTXR1 as a possible target of miR487a. ANTXR1 may be directly implicated in granule cell dispersion because it is an adhesion molecule that favors cell spreading. Thus, miR487a could be the first identified element of a miRNA signature that may be useful for prognostic evaluation of post-surgical epilepsy and may drive mechanistic studies leading to the identification of therapeutic targets.

  3. Infectious haematopoietic necrosis virus: Chapter 2

    Science.gov (United States)

    Leong, Jo-Ann; Kurath, Gael

    2017-01-01

    Infectious haematopoietic necrosis virus (IHNV) is a Rhabdovirus that causes significant disease in Pacific salmon (Oncorhynchus spp.), Atlantic salmon (Salmo salar), and rainbow and steelhead trout (O. mykiss). IHNV causes necrosis of the haematopoietic tissues, and consequently it was named infectious haematopoietic necrosis. This virus is waterborne and may transmit horizontally and vertically through virus associated with seminal and ovarian fluids. The clinical signs of disease and diagnosis; pathology; pathophysiology; and control strategies against IHNV are discussed.

  4. 特异性人免疫球蛋白与传染性疾病的防治%Specific human immunoglobulin in prevention and treatment of infectious diseases

    Institute of Scientific and Technical Information of China (English)

    马玉媛; 向思龙; 王卓; 吕茂民; 章金刚

    2015-01-01

    特异性人免疫球蛋白是指针对某一特定病原体或生物毒素等的一类高免疫球蛋白制剂,是血液制品的重要品种,多用于预防和治疗一些发病率高、感染后果严重、无特效治疗方法的病原体感染,在传染性疾病的防治中具有其他药物不可比拟的优点。国外特异性人免疫球蛋白上市品种较多,而国内由于技术瓶颈约束、经济效益有限等原因,新型特异性人免疫球蛋白的研发进展缓慢。该文对多种特异性人免疫球蛋白及其对于传染病的防治作用进行了综述。%The specific human immunoglobulin is a hyperimmune globulin against a particular pathogen or biotoxin .It′s an important variety in plasma derivatives .Specific human immunoglobulin is usually used to prevent and treat pathogen in -fections with high morbidity , severe outcomes and no efficient treatment available .Thus it has unique advantages in preven-tion and management of infectious diseases .A variety of specific human immunoglobulins have been licensed abroad , but the development of new specific human immunoglobulins is slow in China due to technical constraints , limited economic benefits or for other reasons .Here we reviewed some specific human immunoglobulins and their preventive and therapeutic effect on infectious diseases .

  5. Contiguous spinal metastasis mimicking infectious spondylodiscitis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Chul Min; Lee, Seung Hun [Dept. of Radiology, Hanyang University Hospital, Seoul (Korea, Republic of); Bae, Ji Yoon [Dept. of Pathology, National Police Hospital, Seoul (Korea, Republic of)

    2015-12-15

    Differential diagnosis between spinal metastasis and infectious spondylodiscitis is one of the occasional challenges in daily clinical practice. We encountered an unusual case of spinal metastasis in a 75-year-old female breast cancer patient that mimicked infectious spondylodiscitis. Magnetic resonance imaging (MRI) showed diffuse bone marrow infiltrations with paraspinal soft tissue infiltrative changes in 5 contiguous cervical vertebrae without significant compression fracture or cortical destruction. These MRI findings made it difficult to differentiate between spinal metastasis and infectious spondylodiscitis. Infectious spondylodiscitis such as tuberculous spondylodiscitis was regarded as the more appropriate diagnosis due to the continuous involvement of > 5 cervical vertebrae. The patient's clinical presentation also supported the presumptive diagnosis of infectious spondylodiscitis rather than spinal metastasis. Intravenous antibiotics were administered, but clinical symptoms worsened despite treatment. After pathologic confirmation by computed tomography-guided biopsy, we were able to confirm a final diagnosis of spinal metastasis.

  6. INFECTIOUS DISEASE

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    3.1 Viral disease2004310 One-step simultaneous detection of G-genotype of human group a rotaviruses by multiplex RT-PCR. TANG Shaowen (唐少文) , et al. Dept Epidemiol, Tongji Med Coll Huozhong Univ Sci & Technol, Wuhan 430030. Chin J Lab Med 2004; 27 (4):234-236

  7. The clinical assessment, treatment, and prevention of lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the Infectious Diseases Society of America.

    Science.gov (United States)

    Wormser, Gary P; Dattwyler, Raymond J; Shapiro, Eugene D; Halperin, John J; Steere, Allen C; Klempner, Mark S; Krause, Peter J; Bakken, Johan S; Strle, Franc; Stanek, Gerold; Bockenstedt, Linda; Fish, Durland; Dumler, J Stephen; Nadelman, Robert B

    2006-11-01

    Evidence-based guidelines for the management of patients with Lyme disease, human granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis), and babesiosis were prepared by an expert panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 31[Suppl 1]:1-14). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. For each of these Ixodes tickborne infections, information is provided about prevention, epidemiology, clinical manifestations, diagnosis, and treatment. Tables list the doses and durations of antimicrobial therapy recommended for treatment and prevention of Lyme disease and provide a partial list of therapies to be avoided. A definition of post-Lyme disease syndrome is proposed.

  8. Effects of age and pathology on shear wave speed of the human rotator cuff.

    Science.gov (United States)

    Baumer, Timothy G; Dischler, Jack; Davis, Leah; Labyed, Yassin; Siegal, Daniel S; van Holsbeeck, Marnix; Moutzouros, Vasilios; Bey, Michael J

    2017-06-28

    Rotator cuff tears are common and often repaired surgically, but post-operative repair tissue healing, and shoulder function can be unpredictable. Tear chronicity is believed to influence clinical outcomes, but conventional clinical approaches for assessing tear chronicity are subjective. Shear wave elastography (SWE) is a promising technique for assessing soft tissue via estimates of shear wave speed (SWS), but this technique has not been used extensively on the rotator cuff. Specifically, the effects of age and pathology on rotator cuff SWS are not well known. The objectives of this study were to assess the association between SWS and age in healthy, asymptomatic subjects, and to compare measures of SWS between patients with a rotator cuff tear and healthy, asymptomatic subjects. SWE images of the supraspinatus muscle and intramuscular tendon were acquired from 19 asymptomatic subjects and 11 patients with a rotator cuff tear. Images were acquired with the supraspinatus under passive and active (i.e., minimal activation) conditions. Mean SWS was positively associated with age in the supraspinatus muscle and tendon under passive and active conditions (p ≤ 0.049). Compared to asymptomatic subjects, patients had a lower mean SWS in their muscle and tendon under active conditions (p ≤ 0.024), but no differences were detected under passive conditions (p ≥ 0.783). These findings identify the influences of age and pathology on SWS in the rotator cuff. These preliminary findings are an important step toward evaluating the clinical utility of SWE for assessing rotator cuff pathology. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  9. Structural Features of Human Memapsin 2 (β-Secretase) and Their Biological and Pathological Implications

    Institute of Scientific and Technical Information of China (English)

    Lin HONG; Xiangyuan HE; Xiangping HUANG; Wanpin CHANG; Jordan TANG

    2004-01-01

    Memapsin 2 (β-secretase) is the membrane-anchored aspartic protease that initiates the cleavage of β-amyloid precursor protein (APP) leading to the production of amyloid-β (Aβ), a major factor in the pathogenesis of Alzheimer's disease (AD). Since memapsin 2 is a major target for the development of inhibitor drugs for AD, it has been intensively studied during the past five years. Here we discuss the structural features of the catalytic/specificity apparatus, transmembrane domain, cytosolic domain and the implications of these features in the physiological and pathological roles of this protease.

  10. Red cell alloimmunization and infectious marker status (human immunodeficiency virus, hepatitis B virus and hepatitis C virus in multiply transfused thalassemia patients of North India

    Directory of Open Access Journals (Sweden)

    Raj Nath Makroo

    2013-01-01

    Full Text Available Background: Patients with thalassemia major are largely transfusion dependent and are thus exposed to a variety of risks such as transmission of infectious diseases, iron overload and alloimmunization. This study was performed to determine the prevalence of human immune deficiency virus (HIV, hepatitis B virus (HBV, hepatitis C virus (HCV and red cell antibodies among multiple-transfused thalassemic patients in and around the national capital region. Materials and Methods: The Department of Transfusion Medicine, Indraprastha Apollo Hospitals, conducted this study in collaboration with the National Thalassemia Welfare Society over a period of 1 year starting February2011. Blood samples from the patients were tested for blood group, red cell alloantibody/ies, anti-HIV, anti-HCV and hepatitis B surface antigen (HBsAg by ELISA and for the respective viral ribonucleic acid (RNA or deoxyribonucleic acid (DNA by nucleic acid testing (NAT. Results: A total of 462 thalassemics which consists of 290 males and 172 females were tested. The overall alloimmunization rate was 4.1% and anti-Kell was the most common antibody identified. Thirteen cases (2.8% were positive for HBsAg by ELISA, 107 (23.1% were reactive for anti HCV and 11 (2.38% for anti HIV antibodies. Further screening and discriminatory assays by NAT confirmed the presence of HBV DNA in 11 cases, HIV RNA in 7 cases and HCV RNA in 48 cases. Conclusion: In spite of advances in Immunohematology and infectious marker testing in recent years, the rates of alloimmunization and infectious marker positivity remains high among multiply transfused patients like thalassemics. Provision of safe and adequate blood supply to these patients is a key to improving their quality-of-life and longevity.

  11. The global one health paradigm: challenges and opportunities for tackling infectious diseases at the human, animal, and environment interface in low-resource settings.

    Directory of Open Access Journals (Sweden)

    Wondwossen A Gebreyes

    Full Text Available Zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. Today, approximately 75% of newly emerging infectious diseases (EIDs are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. These interrelated driving forces make it difficult to predict and to prevent zoonotic EIDs. Although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic EIDs remain a major global concern, and such threats are expanding, especially in less developed regions. The current Ebola epidemic in West Africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a One Health approach. The complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of Global One Health in low-resource settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec Global Consortium launched the International Congress on Pathogens at the Human-Animal Interface (ICOPHAI in order to address important challenges and needs for capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011 and the second congress (Porto de Galinhas, Brazil, 2013 were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. In addition to strong scientific reports in eight thematic areas that necessitate One Health implementation, the congress identified four key capacity-building needs: (1 development of adequate science-based risk management policies, (2 skilled-personnel capacity building, (3 accredited veterinary and public health diagnostic laboratories with a shared database, and (4 improved use of existing natural resources and implementation. The aim of this review is to

  12. The global one health paradigm: challenges and opportunities for tackling infectious diseases at the human, animal, and environment interface in low-resource settings.

    Science.gov (United States)

    Gebreyes, Wondwossen A; Dupouy-Camet, Jean; Newport, Melanie J; Oliveira, Celso J B; Schlesinger, Larry S; Saif, Yehia M; Kariuki, Samuel; Saif, Linda J; Saville, William; Wittum, Thomas; Hoet, Armando; Quessy, Sylvain; Kazwala, Rudovick; Tekola, Berhe; Shryock, Thomas; Bisesi, Michael; Patchanee, Prapas; Boonmar, Sumalee; King, Lonnie J

    2014-01-01

    Zoonotic infectious diseases have been an important concern to humankind for more than 10,000 years. Today, approximately 75% of newly emerging infectious diseases (EIDs) are zoonoses that result from various anthropogenic, genetic, ecologic, socioeconomic, and climatic factors. These interrelated driving forces make it difficult to predict and to prevent zoonotic EIDs. Although significant improvements in environmental and medical surveillance, clinical diagnostic methods, and medical practices have been achieved in the recent years, zoonotic EIDs remain a major global concern, and such threats are expanding, especially in less developed regions. The current Ebola epidemic in West Africa is an extreme stark reminder of the role animal reservoirs play in public health and reinforces the urgent need for globally operationalizing a One Health approach. The complex nature of zoonotic diseases and the limited resources in developing countries are a reminder that the need for implementation of Global One Health in low-resource settings is crucial. The Veterinary Public Health and Biotechnology (VPH-Biotec) Global Consortium launched the International Congress on Pathogens at the Human-Animal Interface (ICOPHAI) in order to address important challenges and needs for capacity building. The inaugural ICOPHAI (Addis Ababa, Ethiopia, 2011) and the second congress (Porto de Galinhas, Brazil, 2013) were unique opportunities to share and discuss issues related to zoonotic infectious diseases worldwide. In addition to strong scientific reports in eight thematic areas that necessitate One Health implementation, the congress identified four key capacity-building needs: (1) development of adequate science-based risk management policies, (2) skilled-personnel capacity building, (3) accredited veterinary and public health diagnostic laboratories with a shared database, and (4) improved use of existing natural resources and implementation. The aim of this review is to highlight

  13. Absorption spectra and light penetration depth of normal and pathologically altered human skin

    Science.gov (United States)

    Barun, V. V.; Ivanov, A. P.; Volotovskaya, A. V.; Ulashchik, V. S.

    2007-05-01

    A three-layered skin model (stratum corneum, epidermis, and dermis) and engineering formulas for radiative transfer theory are used to study absorption spectra and light penetration depths of normal and pathologically altered skin. The formulas include small-angle and asymptotic approximations and a layer-addition method. These characteristics are calculated for wavelengths used for low-intensity laser therapy. We examined several pathologies such as vitiligo, edema, erythematosus lupus, and subcutaneous wound, for which the bulk concentrations of melanin and blood vessels or tissue structure (for subcutaneous wound) change compared with normal skin. The penetration depth spectrum is very similar to the inverted blood absorption spectrum. In other words, the depth is minimal at blood absorption maxima. The calculated absorption spectra enable the power and irradiation wavelength providing the required light effect to be selected. Relationships between the penetration depth and the diffuse reflectance coefficient of skin (unambiguously expressed through the absorption coefficient) are analyzed at different wavelengths. This makes it possible to find relationships between the light fields inside and outside the tissue.

  14. Interests of the PET with 18-F.D.G. in infectious pathology: about a case of systemic candidiasis; Interets de la TEP au 18-FDG en pathologie infectieuse: a propos d'un cas de candidose systemique

    Energy Technology Data Exchange (ETDEWEB)

    Avet, J.; Granjon, D.; Prevot, N.; Isnardi, V.; Dubois, F. [Service de medecine nucleaire, CHU de Saint-etienne, (France); Stephan, J.L.; Berger, C. [service de pediatrie, CHU de Saint-etienne, (France)

    2009-05-15

    We report the interest of the PET with {sup 18}F-F.D.G. in the extension evaluation of injuries and in the therapy decision for a patient suffering of a systemic candida. Conclusions: In spite of a lack of recommendations, because of its great sensitivity for the deep infectious centres detection, the PET with {sup 18}F-F.D.G. can bring useful information to the management and follow up of the systemic infections. (N.C.)

  15. Ex vivo imaging of human thyroid pathology using integrated optical coherence tomography and optical coherence microscopy

    Science.gov (United States)

    Zhou, Chao; Wang, Yihong; Aguirre, Aaron D.; Tsai, Tsung-Han; Cohen, David W.; Connolly, James L.; Fujimoto, James G.

    2010-01-01

    We evaluate the feasibility of optical coherence tomography (OCT) and optical coherence microscopy (OCM) for imaging of benign and malignant thyroid lesions ex vivo using intrinsic optical contrast. 34 thyroid gland specimens are imaged from 17 patients, covering a spectrum of pathology ranging from normal thyroid to benign disease/neoplasms (multinodular colloid goiter, Hashimoto's thyroiditis, and follicular adenoma) and malignant thyroid tumors (papillary carcinoma and medullary carcinoma). Imaging is performed using an integrated OCT and OCM system, with sections. Characteristic features that suggest malignant lesions, such as complex papillary architecture, microfollicules, psammomatous calcifications, or replacement of normal follicular architecture with sheets/nests of tumor cells, can be identified from OCT and OCM images and are clearly differentiable from normal or benign thyroid tissues. With further development of needle-based imaging probes, OCT and OCM could be promising techniques to use for the screening of thyroid nodules and to improve the diagnostic specificity of fine needle aspiration evaluation.

  16. Role of Histological Findings and Pathologic Diagnosis for Detection of Human Papillomavirus Infection in Men

    Science.gov (United States)

    Vyas, Nikki S.; Pierce Campbell, Christine M.; Mathew, Rahel; Abrahamsen, Martha; Van der Kooi, Kaisa; Jukic, Drazen M.; Stoler, Mark H.; Villa, Luisa L.; da Silva, Roberto Carvalho; Lazcano-Ponce, Eduardo; Quiterio, Manuel; Salmeron, Jorge; Sirak, Bradley A.; Ingles, Donna J.; Giuliano, Anna R.; Messina, Jane L.

    2016-01-01

    Early HPV infection in males is difficult to detect clinically and pathologically. This study assessed histopathology in diagnosing male genital HPV. External genital lesions (n = 352) were biopsied, diagnosed by a dermatopathologist, and HPV genotyped. A subset (n = 167) was diagnosed independently by a second dermatopathologist and also re-evaluated in detail, tabulating the presence of a set of histopathologic characteristics related to HPV infection. Cases that received discrepant diagnoses or HPV-related diagnoses were evaluated by a third dermatopathologist (n = 163). Across dermatopathologists, three-way concordance was fair (k = 0.30). Pairwise concordance for condyloma was fair to good (k = 0.30–0.67) and poor to moderate for penile intraepithelial neoplasia (k = −0.05 to 0.42). Diagnoses were 44–47% sensitive and 65–72% specific for HPV 6/ 11-containing lesions, and 20–37% sensitive and 98–99% specific for HPV 16/18. Presence of HPV 6/ 11 was 75–79% sensitive and 35% specific for predicting pathologic diagnosis of condyloma. For diagnosis of penile intraepithelial neoplasia, HPV 16/18 was 95–96% specific but only 40–64% sensitive. Rounded papillomatosis, hypergranulosis, and dilated vessels were significantly (P<0.05) associated with HPV 6/11. Dysplasia was significantly (P= 0.001) associated with HPV 16/18. Dermatopathologists’ diagnoses of early male genital HPV-related lesions appear discordant with low sensitivity, while genotyping may overestimate clinically significant HPV-related disease. Rounded papillomatosis, hypergranulosis, and dilated vessels may help establish diagnosis of early condyloma. PMID:25945468

  17. Role of histological findings and pathologic diagnosis for detection of human papillomavirus infection in men.

    Science.gov (United States)

    Vyas, Nikki S; Pierce Campbell, Christine M; Mathew, Rahel; Abrahamsen, Martha; Van der Kooi, Kaisa; Jukic, Drazen M; Stoler, Mark H; Villa, Luisa L; da Silva, Roberto Carvalho; Lazcano-Ponce, Eduardo; Quiterio, Manuel; Salmeron, Jorge; Sirak, Bradley A; Ingles, Donna J; Giuliano, Anna R; Messina, Jane L

    2015-10-01

    Early HPV infection in males is difficult to detect clinically and pathologically. This study assessed histopathology in diagnosing male genital HPV. External genital lesions (n = 352) were biopsied, diagnosed by a dermatopathologist, and HPV genotyped. A subset (n = 167) was diagnosed independently by a second dermatopathologist and also re-evaluated in detail, tabulating the presence of a set of histopathologic characteristics related to HPV infection. Cases that received discrepant diagnoses or HPV-related diagnoses were evaluated by a third dermatopathologist (n = 163). Across dermatopathologists, three-way concordance was fair (k = 0.30). Pairwise concordance for condyloma was fair to good (k = 0.30-0.67) and poor to moderate for penile intraepithelial neoplasia (k = -0.05 to 0.42). Diagnoses were 44-47% sensitive and 65-72% specific for HPV 6/11-containing lesions, and 20-37% sensitive and 98-99% specific for HPV 16/18. Presence of HPV 6/11 was 75-79% sensitive and 35% specific for predicting pathologic diagnosis of condyloma. For diagnosis of penile intraepithelial neoplasia, HPV 16/18 was 95-96% specific but only 40-64% sensitive. Rounded papillomatosis, hypergranulosis, and dilated vessels were significantly (P < 0.05) associated with HPV 6/11. Dysplasia was significantly (P = 0.001) associated with HPV 16/18. Dermatopathologists' diagnoses of early male genital HPV-related lesions appear discordant with low sensitivity, while genotyping may overestimate clinically significant HPV-related disease. Rounded papillomatosis, hypergranulosis, and dilated vessels may help establish diagnosis of early condyloma.

  18. Diagnostic vitrectomy for infectious uveitis

    Science.gov (United States)

    Jeroudi, Abdallah; Yeh, Steven

    2014-01-01

    The identification of an infectious or noninfectious uveitis syndrome is important to determine the range of therapeutic and prognostic implications of that disease entity. Diagnostic dilemmas arise with atypical history, atypical clinical presentations, inconclusive diagnostic workup, and persistent or worsened inflammation despite appropriate immunosuppression. More invasive intraocular testing is indicated in these situations particularly in infectious uveitis where a delay in treatment may result in worsening of the patient’s disease and a poor visual outcome. Laboratory analysis of vitreous fluid via diagnostic pars plana vitrectomy is an important technique in the diagnostic armamentarium, but the most important aspects of sample collection include rapid processing, close coordination with an ophthalmic pathology laboratory, and directed testing on this limited collected sample. Culture and staining has utility in bacterial, fungal, and nocardial infection. Polymerase chain reaction (PCR) analysis has shown promising results for bacterial endophthalmitis and infection with mycobacterium tuberculosis whereas PCR testing for viral retinitides and ocular toxoplasmosis has a more established role. Antibody testing is appropriate for toxoplasmosis and toxocariasis, and may be complementary to PCR for viral retinitis. Masquerade syndromes represent neoplastic conditions that clinically appear as infectious or inflammatory conditions and should be considered as part of the differential diagnosis. Diagnostic vitrectomy and chorioretinal biopsy are thus critical tools for the management of patients in whom an infectious etiology of uveitis is suspected. PMID:24613892

  19. Mitigating Infectious Disease Outbreaks

    Science.gov (United States)

    Davey, Victoria

    The emergence of new, transmissible infections poses a significant threat to human populations. As the 2009 novel influenza A/H1N1 pandemic and the 2014-2015 Ebola epidemic demonstrate, we have observed the effects of rapid spread of illness in non-immune populations and experienced disturbing uncertainty about future potential for human suffering and societal disruption. Clinical and epidemiologic characteristics of a newly emerged infectious organism are usually gathered in retrospect as the outbreak evolves and affects populations. Knowledge of potential effects of outbreaks and epidemics and most importantly, mitigation at community, regional, national and global levels is needed to inform policy that will prepare and protect people. Study of possible outcomes of evolving epidemics and application of mitigation strategies is not possible in observational or experimental research designs, but computational modeling allows conduct of `virtual' experiments. Results of well-designed computer simulations can aid in the selection and implementation of strategies that limit illness and death, and maintain systems of healthcare and other critical resources that are vital to public protection. Mitigating Infectious Disease Outbreaks.

  20. Interrelationships of food safety and plant pathology: the life cycle of human pathogens on plants.

    Science.gov (United States)

    Barak, Jeri D; Schroeder, Brenda K

    2012-01-01

    Bacterial food-borne pathogens use plants as vectors between animal hosts, all the while following the life cycle script of plant-associated bacteria. Similar to phytobacteria, Salmonella, pathogenic Escherichia coli, and cross-domain pathogens have a foothold in agricultural production areas. The commonality of environmental contamination translates to contact with plants. Because of the chronic absence of kill steps against human pathogens for fresh produce, arrival on plants leads to persistence and the risk of human illness. Significant research progress is revealing mechanisms used by human pathogens to colonize plants and important biological interactions between and among bacteria in planta. These findings articulate the difficulty of eliminating or reducing the pathogen from plants. The plant itself may be an untapped key to clean produce. This review highlights the life of human pathogens outside an animal host, focusing on the role of plants, and illustrates areas that are ripe for future investigation.

  1. Identification of "pathologs" (disease-related genes from the RIKEN mouse cDNA dataset using human curation plus FACTS, a new biological information extraction system

    Directory of Open Access Journals (Sweden)

    Socha Luis A

    2004-04-01

    Full Text Available Abstract Background A major goal in the post-genomic era is to identify and characterise disease susceptibility genes and to apply this knowledge to disease prevention and treatment. Rodents and humans have remarkably similar genomes and share closely related biochemical, physiological and pathological pathways. In this work we utilised the latest information on the mouse transcriptome as revealed by the RIKEN FANTOM2 project to identify novel human disease-related candidate genes. We define a new term "patholog" to mean a homolog of a human disease-related gene encoding a product (transcript, anti-sense or protein potentially relevant to disease. Rather than just focus on Mendelian inheritance, we applied the analysis to all potential pathologs regardless of their inheritance pattern. Results Bioinformatic analysis and human curation of 60,770 RIKEN full-length mouse cDNA clones produced 2,578 sequences that showed similarity (70–85% identity to known human-disease genes. Using a newly developed biological information extraction and annotation tool (FACTS in parallel with human expert analysis of 17,051 MEDLINE scientific abstracts we identified 182 novel potential pathologs. Of these, 36 were identified by computational tools only, 49 by human expert analysis only and 97 by both methods. These pathologs were related to neoplastic (53%, hereditary (24%, immunological (5%, cardio-vascular (4%, or other (14%, disorders. Conclusions Large scale genome projects continue to produce a vast amount of data with potential application to the study of human disease. For this potential to be realised we need intelligent strategies for data categorisation and the ability to link sequence data with relevant literature. This paper demonstrates the power of combining human expert annotation with FACTS, a newly developed bioinformatics tool, to identify novel pathologs from within large-scale mouse transcript datasets.

  2. Delayed loss of hearing after hearing preservation cochlear implantation: Human temporal bone pathology and implications for etiology.

    Science.gov (United States)

    Quesnel, Alicia M; Nakajima, Hideko Heidi; Rosowski, John J; Hansen, Marlan R; Gantz, Bruce J; Nadol, Joseph B

    2016-03-01

    After initially successful preservation of residual hearing with cochlear implantation, some patients experience subsequent delayed hearing loss. The etiology of such delayed hearing loss is unknown. Human temporal bone pathology is critically important in investigating the etiology, and directing future efforts to maximize long term hearing preservation in cochlear implant patients. Here we present the temporal bone pathology from a patient implanted during life with an Iowa/Nucleus Hybrid S8 implant, with initially preserved residual hearing and subsequent hearing loss. Both temporal bones were removed for histologic processing and evaluated. Complete clinical and audiologic records were available. He had bilateral symmetric high frequency severe to profound hearing loss prior to implantation. Since he was implanted unilaterally, the unimplanted ear was presumed to be representative of the pre-implantation pathology related to his hearing loss. The implanted and contralateral unimplanted temporal bones both showed complete degeneration of inner hair cells and outer hair cells in the basal half of the cochleae, and only mild patchy loss of inner hair cells and outer hair cells in the apical half. The total spiral ganglion neuron counts were similar in both ears: 15,138 (56% of normal for age) in the unimplanted right ear and 13,722 (51% of normal for age) in the implanted left ear. In the basal turn of the implanted left cochlea, loose fibrous tissue and new bone formation filled the scala tympani, and part of the scala vestibuli. Delayed loss of initially preserved hearing after cochlear implantation was not explained by additional post-implantation degeneration of hair cells or spiral ganglion neurons in this patient. Decreased compliance at the round window and increased damping in the scala tympani due to intracochlear fibrosis and new bone formation might explain part of the post-implantation hearing loss. Reduction of the inflammatory and immune response to

  3. Dental caries: an infectious and transmissible disease.

    Science.gov (United States)

    Caufield, Page W; Li, Yihong; Dasanayake, Ananda

    2005-05-01

    By definition, dental caries is an infectious and transmissible disease because it is caused by bacteria colonizing the tooth surfaces. Unlike most infectious diseases affecting humans, caries is the result of an imbalance of the indigenous oral biota rather than a nonindigenous, exogenous pathogen. The introduction of refined sugar into modern society's diet has tipped the balance from health to disease. New insight into the natural history of the leading cariogenic bacteria, the mutans streptococci, may contribute ways to control or prevent this infectious disease. Here, we use the host-parasite model as a platform for viewing the pathogenicity of the caries process in contrast to other infectious diseases.

  4. Development of Pathological Diagnostics of Human Kidney Cancer by Multiple Staining Using New Fluorescent Fluolid Dyes

    Directory of Open Access Journals (Sweden)

    Dilibaier Wuxiuer

    2014-01-01

    Full Text Available New fluorescent Fluolid dyes have advantages over others such as stability against heat, dryness, and excess light. Here, we performed simultaneous immunostaining of renal tumors, clear cell renal cell carcinoma (RCC, papillary RCC, chromophobe RCC, acquired cystic disease-associated RCC (ACD-RCC, and renal angiomyolipoma (AML, with primary antibodies against Kank1, cytokeratin 7 (CK7, and CD10, which were detected with secondary antibodies labeled with Fluolid-Orange, Fluolid-Green, and Alexa Fluor 647, respectively. Kank1 was stained in normal renal tubules, papillary RCC, and ACD-RCC, and weakly or negatively in all other tumors. CK7 was positive in normal renal tubules, papillary RCC, and ACD-RCC. In contrast, CD10 was expressed in renal tubules and clear cell RCC, papillary RCC, AML, and AC-RCC, and weakly in chromophobe RCC. These results may contribute to differentiating renal tumors and subtypes of RCCs. We also examined the stability of fluorescence and found that fluorescent images of Fluolid dyes were identical between a tissue section and the same section after it was stored for almost three years at room temperature. This indicates that tissue sections can be stored at room temperature for a relatively long time after they are stained with multiple fluorescent markers, which could open a door for pathological diagnostics.

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

    Directory of Open Access Journals (Sweden)

    Karoly Toth

    2015-03-01

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

  6. Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.

    Science.gov (United States)

    Yahagi, Kazuyuki; Kolodgie, Frank D; Lutter, Christoph; Mori, Hiroyoshi; Romero, Maria E; Finn, Aloke V; Virmani, Renu

    2017-02-01

    The continuing increase in the prevalence of diabetes mellitus in the general population is predicted to result in a higher incidence of cardiovascular disease. Although the mechanisms of diabetes mellitus-associated progression of atherosclerosis are not fully understood, at clinical and pathological levels, there is an appreciation of increased disease burden and higher levels of arterial calcification in these subjects. Plaques within the coronary arteries of patients with diabetes mellitus generally exhibit larger necrotic cores and significantly greater inflammation consisting mainly of macrophages and T lymphocytes relative to patients without diabetes mellitus. Moreover, there is a higher incidence of healed plaque ruptures and positive remodeling in hearts from subjects with type 1 diabetes mellitus and type 2 diabetes mellitus, suggesting a more active atherogenic process. Lesion calcification in the coronary, carotid, and other arterial beds is also more extensive. Although the role of coronary artery calcification in identifying cardiovascular disease and predicting its outcome is undeniable, our understanding of how key hormonal and physiological alterations associated with diabetes mellitus such as insulin resistance and hyperglycemia influence the process of vascular calcification continues to grow. Important drivers of atherosclerotic calcification in diabetes mellitus include oxidative stress, endothelial dysfunction, alterations in mineral metabolism, increased inflammatory cytokine production, and release of osteoprogenitor cells from the marrow into the circulation. Our review will focus on the pathophysiology of type 1 diabetes mellitus- and type 2 diabetes mellitus-associated vascular disease with particular focus on coronary and carotid atherosclerotic calcification.

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

    Science.gov (United States)

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

    2015-03-23

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

  8. [Physiology and pathology of bactericidal activity in human polymorphonuclear neutrophils (author's transl)].

    Science.gov (United States)

    Hakim, J

    1980-09-13

    Blood polymorphonuclear neutrophils defend man against aggressions from pathogens. Under the combined influence of granulocytic and non-granulocytic factors, the defensive process develops by steps: the neutrophil moves towards the pathogenic organism which, one reached, is engulfed and killed. The killing systems of the cell are either oxygen-dependent or independent. the oxygen-dependent system is triggered off by stimulation of the cell membrane and involves various reactions, including cyanide-resistant oxygen consumption, production of activated oxygen, oxygen peroxide and halogenisation of the pathogen membrane. Impairment of the killing activity requires quantitative assessment of its various components in the presence of autologous or control serum with the view of: determining the origin (granulocytic or non-granulocytic) of the impairment, and identifying the step in oxygen metabolism that is affected. In the vast majority of non-granulocytic insufficiencies the cause lies in defective opsonins. In granulocytic insufficiencies, global failure of the system indicates chromic granulomatous disease, a syndrome that is now being dismembered. Defective halogenisation should lead to testing for deficiency of myeloperoxidase or abnormal degranulation. The non oxygen-independent bactericidal system, although highly effective in vitro, appears to be less important in vivo than the oxygen-dependent system. Little is known of its pathology.

  9. Concordance of gene expression in human protein complexes reveals tissue specificity and pathology

    DEFF Research Database (Denmark)

    Börnigen, Daniela; Pers, Tune Hannes; Thorrez, Lieven

    2013-01-01

    Disease-causing variants in human genes usually lead to phenotypes specific to only a few tissues. Here, we present a method for predicting tissue specificity based on quantitative deregulation of protein complexes. The underlying assumption is that the degree of coordinated expression among...... proteins in a complex within a given tissue may pinpoint tissues that will be affected by a mutation in the complex and coordinated expression may reveal the complex to be active in the tissue. We identified known disease genes and their protein complex partners in a high-quality human interactome. Each...... susceptibility gene's tissue involvement was ranked based on coordinated expression with its interaction partners in a non-disease global map of human tissue-specific expression. The approach demonstrated high overall area under the curve (0.78) and was very successfully benchmarked against a random model...

  10. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology

    Directory of Open Access Journals (Sweden)

    Srikanth Mairpady Shambat

    2015-11-01

    Full Text Available Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL, and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a

  11. Modelling staphylococcal pneumonia in a human 3D lung tissue model system delineates toxin-mediated pathology.

    Science.gov (United States)

    Mairpady Shambat, Srikanth; Chen, Puran; Nguyen Hoang, Anh Thu; Bergsten, Helena; Vandenesch, Francois; Siemens, Nikolai; Lina, Gerard; Monk, Ian R; Foster, Timothy J; Arakere, Gayathri; Svensson, Mattias; Norrby-Teglund, Anna

    2015-11-01

    Staphylococcus aureus necrotizing pneumonia is recognized as a toxin-mediated disease, yet the tissue-destructive events remain elusive, partly as a result of lack of mechanistic studies in human lung tissue. In this study, a three-dimensional (3D) tissue model composed of human lung epithelial cells and fibroblasts was used to delineate the role of specific staphylococcal exotoxins in tissue pathology associated with severe pneumonia. To this end, the models were exposed to the mixture of exotoxins produced by S. aureus strains isolated from patients with varying severity of lung infection, namely necrotizing pneumonia or lung empyema, or to purified toxins. The necrotizing pneumonia strains secreted high levels of α-toxin and Panton-Valentine leukocidin (PVL), and triggered high cytotoxicity, inflammation, necrosis and loss of E-cadherin from the lung epithelium. In contrast, the lung empyema strain produced moderate levels of PVL, but negligible amounts of α-toxin, and triggered limited tissue damage. α-toxin had a direct damaging effect on the epithelium, as verified using toxin-deficient mutants and pure α-toxin. Moreover, PVL contributed to pathology through the lysis of neutrophils. A combination of α-toxin and PVL resulted in the most severe epithelial injury. In addition, toxin-induced release of pro-inflammatory mediators from lung tissue models resulted in enhanced neutrophil migration. Using a collection of 31 strains from patients with staphylococcal pneumonia revealed that strains producing high levels of α-toxin and PVL were cytotoxic and associated with fatal outcome. Also, the strains that produced the highest toxin levels induced significantly greater epithelial disruption. Of importance, toxin-mediated lung epithelium destruction could be inhibited by polyspecific intravenous immunoglobulin containing antibodies against α-toxin and PVL. This study introduces a novel model system for study of staphylococcal pneumonia in a human setting. The

  12. Recognition memory and the medial temporal lobe: from monkey research to human pathology.

    Science.gov (United States)

    Meunier, M; Barbeau, E

    2013-01-01

    This review provides a historical overview of decades of research on recognition memory, the process that allows both humans and animals to tell familiar from novel items. The emphasis is put on how monkey research improved our understanding of the medial temporal lobe (MTL) role and how tasks designed for monkeys influenced research in humans. The story starts in the early 1950s. Back then, memory was not a fashionable scientific topic. It was viewed as a function of the whole brain and not of specialized brain areas. All that changed in 1957-1958 when Brenda Milner, a neuropsychologist from Montreal, described patient H.M. He forgot all events as he lived them despite a fully preserved intelligence. He had received a MTL resection to relieve epilepsy. H.M. (1926-2008) would become the most influential patient in brain science. Which structures among those included in H.M.'s large lesion were important for recognition memory could not be evaluated in humans. It was gradually understood only after the successful development of a monkey model of human amnesia by Mishkin in 1978. Selective lesions and two behavioral tasks, delayed nonmatching-to-sample and visual paired comparison, were used to distinguish the contribution of the hippocampus from that of adjacent cortical areas. Driven by findings in non-human primates, human research on recognition memory is now trying to solve the question of whether the different structures composing MTL contributes to familiarity and recollection, the two possible forms taken by recognition. We described in particular two French patients, FRG and JMG, whose deficits support the currently dominant model attributing to the perirhinal cortex a critical role in recognition memory. Research on recognition memory has implications for the clinician as it may help understanding the cognitive deficits observed in different diseases. An illustration of such approach, linking basic and applied research, is provided for Alzheimer's disease.

  13. Extreme weather events and infectious disease outbreaks

    OpenAIRE

    McMichael, Anthony J.

    2015-01-01

    Human-driven climatic changes will fundamentally influence patterns of human health, including infectious disease clusters and epidemics following extreme weather events. Extreme weather events are projected to increase further with the advance of human-driven climate change. Both recent and historical experiences indicate that infectious disease outbreaks very often follow extreme weather events, as microbes, vectors and reservoir animal hosts exploit the disrupted social and environmental c...

  14. 75 FR 3472 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-01-21

    ... HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases... of Allergy and Infectious Diseases Special Emphasis Panel; NIAID Clinical Trial Planning (R34) Grants..., Allergy, Immunology, and Transplantation Research; 93.856, Microbiology and Infectious Diseases...

  15. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease.

    Science.gov (United States)

    Wolf, Heike; Damme, Markus; Stroobants, Stijn; D'Hooge, Rudi; Beck, Hans Christian; Hermans-Borgmeyer, Irm; Lüllmann-Rauch, Renate; Dierks, Thomas; Lübke, Torben

    2016-09-01

    Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1) was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6)-GlcNAc(β1-N)-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS). On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis.

  16. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease

    Directory of Open Access Journals (Sweden)

    Heike Wolf

    2016-09-01

    Full Text Available Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1 was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6-GlcNAc(β1-N-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS. On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis.

  17. Localization and quantitation of the chromosome 6-encoded dystrophin-related protein in normal and pathological human muscle.

    Science.gov (United States)

    Karpati, G; Carpenter, S; Morris, G E; Davies, K E; Guerin, C; Holland, P

    1993-03-01

    A dystrophin-related protein (DRP) encoded by a gene on chromosome 6 was studied in 14 normal and 79 pathological human skeletal muscle biopsies, as well as in cultured myotubes by light microscopic immunocytochemistry and quantitative immunoblots. In normal muscle immunoreactive DRP was present at the postjunctional surface membrane, at the surface of satellite cells, in the walls of blood vessels, in Schwann cells and in perineurium of intramuscular nerves. All of this produced a weak signal on immunoblots. In Duchenne/Becker dystrophy (DMD/BMD) and in polymyositis (PM) or dermatomyositis (DM) DRP was present throughout the extrajunctional surface membrane of extra- and intrafusal muscle fibers, particularly regenerating ones. This produced a 15-17-fold increase of DRP over normal in DMD/BMD and 4-10-fold increase over normal in PM and DM on immunoblots. In other pathological muscles, DRP localization pattern and quantity was about the same as in normals. Dystrophin-related protein was present in about the same amounts and distribution in normal and DMD cultured myoblasts and myotubes. The molecular stimulus for the marked upregulation of DRP in DMD/BMD and in the inflammatory myopathies is not known. In DMD/BMD the diffuse sarcolemmal DRP may partially compensate for dystrophin deficiency.

  18. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease

    Science.gov (United States)

    Wolf, Heike; Stroobants, Stijn; D'Hooge, Rudi; Hermans-Borgmeyer, Irm; Lüllmann-Rauch, Renate; Dierks, Thomas; Lübke, Torben

    2016-01-01

    ABSTRACT Fucosidosis is a rare lysosomal storage disorder caused by the inherited deficiency of the lysosomal hydrolase α-L-fucosidase, which leads to an impaired degradation of fucosylated glycoconjugates. Here, we report the generation of a fucosidosis mouse model, in which the gene for lysosomal α-L-fucosidase (Fuca1) was disrupted by gene targeting. Homozygous knockout mice completely lack α-L-fucosidase activity in all tested organs leading to highly elevated amounts of the core-fucosylated glycoasparagine Fuc(α1,6)-GlcNAc(β1-N)-Asn and, to a lesser extent, other fucosylated glycoasparagines, which all were also partially excreted in urine. Lysosomal storage pathology was observed in many visceral organs, such as in the liver, kidney, spleen and bladder, as well as in the central nervous system (CNS). On the cellular level, storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage material. In the CNS, cellular alterations included enlargement of the lysosomal compartment in various cell types, accumulation of secondary storage material and neuroinflammation, as well as a progressive loss of Purkinje cells combined with astrogliosis leading to psychomotor and memory deficits. Our results demonstrate that this new fucosidosis mouse model resembles the human disease and thus will help to unravel underlying pathological processes. Moreover, this model could be utilized to establish diagnostic and therapeutic strategies for fucosidosis. PMID:27491075

  19. [Pathomorphology of lung changes caused by gramoxone poisoning. Human pathologic and animal experimental studies].

    Science.gov (United States)

    Vadnay, I; Haraszti, A

    1988-01-01

    An account is given in this paper of changes caused by Gramoxone, a week killer, to the human lung as well as to experimental material. The process of damage was found to depend on the amount of toxic substance involved and on the route of uptake. Fibrosis, eventually, is the greatest danger. Intraperitoneal application leads to squamous epithelium metaplasia in the lung.

  20. Study of OH● Radicals in Human Serum Blood of Healthy Individuals and Those with Pathological Schizophrenia

    Directory of Open Access Journals (Sweden)

    Wolfgang Linert

    2011-01-01

    Full Text Available The human body is constantly under attack from free radicals that occur as part of normal cell metabolism, and by exposure to environmental factors such as UV light, cigarette smoke, environmental pollutants and gamma radiation. The resulting “Reactive Oxygen Species” (ROS circulate freely in the body with access to all organs and tissues, which can have serious repercussions throughout the body. The body possesses a number of mechanisms both to control the production of ROS and to cope with free radicals in order to limit or repair damage to tissues. Overproduction of ROS or insufficient defense mechanisms leads to a dangerous disbalance in the organism. Thereby several pathomechanisms implicated in over 100 human diseases, e.g., cardiovascular disease, cancer, diabetes mellitus, physiological disease, aging, etc., can be induced. Thus, a detailed investigation on the quantity of oxygen radicals, such as hydroxyl radicals (OH● in human serum blood, and its possible correlation with antioxidant therapy effects, is highly topical. The subject of this study was the influence of schizophrenia on the amount of OH● in human serum blood. The radicals were detected by fluorimetry, using terephthalic acid as a chemical trap. For all experiments the serum blood of healthy people was used as a control group.

  1. Equine Infectious Anemia

    OpenAIRE

    Hoopes, Karl H.

    2017-01-01

    This fact sheet gives information on equine infectious anemia, a blood-borne infectious viral disease of horses, donkeys, and mules. It describes transmission, clinical disease, diagnosis and control.

  2. Equine Infectious Anemia

    OpenAIRE

    Hoopes, Karl H.

    2017-01-01

    This fact sheet gives information on equine infectious anemia, a blood-borne infectious viral disease of horses, donkeys, and mules. It describes transmission, clinical disease, diagnosis and control.

  3. Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

    Directory of Open Access Journals (Sweden)

    Laura A. Runck

    2014-04-01

    Full Text Available Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations

  4. Immune genes are associated with human glioblastoma pathology and patient survival

    Directory of Open Access Journals (Sweden)

    Vauléon Elodie

    2012-09-01

    Full Text Available Abstract Background Glioblastoma (GBM is the most common and lethal primary brain tumor in adults. Several recent transcriptomic studies in GBM have identified different signatures involving immune genes associated with GBM pathology, overall survival (OS or response to treatment. Methods In order to clarify the immune signatures found in GBM, we performed a co-expression network analysis that grouped 791 immune-associated genes (IA genes in large clusters using a combined dataset of 161 GBM specimens from published databases. We next studied IA genes associated with patient survival using 3 different statistical methods. We then developed a 6-IA gene risk predictor which stratified patients into two groups with statistically significantly different survivals. We validated this risk predictor on two other Affymetrix data series, on a local Agilent data series, and using RT-Q-PCR on a local series of GBM patients treated by standard chemo-radiation therapy. Results The co-expression network analysis of the immune genes disclosed 6 powerful modules identifying innate immune system and natural killer cells, myeloid cells and cytokine signatures. Two of these modules were significantly enriched in genes associated with OS. We also found 108 IA genes linked to the immune system significantly associated with OS in GBM patients. The 6-IA gene risk predictor successfully distinguished two groups of GBM patients with significantly different survival (OS low risk: 22.3 months versus high risk: 7.3 months; p  Conclusions This study demonstrates the immune signatures found in previous GBM genomic analyses and suggests the involvement of immune cells in GBM biology. The robust 6-IA gene risk predictor should be helpful in establishing prognosis in GBM patients, in particular in those with a proneural GBM subtype, and even in the well-known good prognosis group of patients with methylated MGMT promoter-bearing tumors.

  5. Comparative analysis of antibiotic resistance and phylogenetic group patterns in human and porcine urinary tract infectious Escherichia coli

    DEFF Research Database (Denmark)

    Hancock, Viktoria; Nielsen, E.M.; Krag, L.

    2009-01-01

    to relatively benign asymptomatic bacteriuria strains. Here we analyse a spectrum of porcine and human UTI E. coli strains with respect to their antibiotic resistance patterns and their phylogenetic groups, determined by multiplex PCR. The clonal profiles of the strains differed profoundly; whereas human...... strains predominantly belonged to clonal types B2 and D, these were not seen among the porcine strains, which all belonged to the E. coli clonal groups A and B1. Contrary to the human strains, the majority of the porcine strains were multidrug resistant. The distinct profiles of the porcine strains...... suggest selective pressure due to extensive antibiotic use....

  6. [Globalization and infectious diseases].

    Science.gov (United States)

    Mirski, Tomasz; Bartoszcze, Michał; Bielawska-Drózd, Agata

    2011-01-01

    Globalization is a phenomenon characteristic of present times. It can be considered in various aspects: economic, environmental changes, demographic changes, as well as the development of new technologies. All these aspects of globalization have a definite influence on the emergence and spread of infectious diseases. Economic aspects ofglobalization are mainly the trade development, including food trade, which has an impact on the spread of food-borne diseases. The environmental changes caused by intensive development of industry, as a result of globalization, which in turn affects human health. The demographic changes are mainly people migration between countries and rural and urban areas, which essentially favors the global spread of many infectious diseases. While technological advances prevents the spread of infections, for example through better access to information, it may also increase the risk, for example through to create opportunities to travel into more world regions, including the endemic regions for various diseases. The phenomenon ofglobalization is also closely associated with the threat of terrorism, including bioterrorism. It forces the governments of many countries to develop effective programs to protect and fight against this threat.

  7. Study of OH● Radicals in Human Serum Blood of Healthy Individuals and Those with Pathological Schizophrenia

    OpenAIRE

    2011-01-01

    The human body is constantly under attack from free radicals that occur as part of normal cell metabolism, and by exposure to environmental factors such as UV light, cigarette smoke, environmental pollutants and gamma radiation. The resulting “Reactive Oxygen Species” (ROS) circulate freely in the body with access to all organs and tissues, which can have serious repercussions throughout the body. The body possesses a number of mechanisms both to control the production of ROS and to cope with...

  8. Electron Pathways through Erythrocyte Plasma Membrane in Human Physiology and Pathology: Potential Redox Biomarker?

    Directory of Open Access Journals (Sweden)

    Elena Matteucci

    2007-01-01

    Full Text Available Erythrocytes are involved in the transport of oxygen and carbon dioxide in the body. Since pH is the influential factor in the Bohr-Haldane effect, pHi is actively maintained via secondary active transports Na+/H+ exchange and HC3 -/Cl- anion exchanger. Because of the redox properties of the iron, hemoglobin generates reactive oxygen species and thus, the human erythrocyte is constantly exposed to oxidative damage. Although the adult erythrocyte lacks protein synthesis and cannot restore damaged proteins, it is equipped with high activity of protective enzymes. Redox changes in the cell initiate various signalling pathways. Plasma membrane oxido-reductases (PMORs are transmembrane electron transport systems that have been found in the membranes of all cells and have been extensively characterized in the human erythrocyte. Erythrocyte PMORs transfer reducing equivalents from intracellular reductants to extracellular oxidants, thus their most important role seems to be to enable the cell respond to changes in intra- and extra-cellular redox environments.So far the activity of erythrocyte PMORs in disease states has not been systematically investigated. This review summarizes present knowledge on erythrocyte electron transfer activity in humans (health, type 1 diabetes, diabetic nephropathy, and chronic uremia and hypothesizes an integrated model of the functional organization of erythrocyte plasma membrane where electron pathways work in parallel with transport metabolons to maintain redox homeostasis.

  9. MRI-based glomerular morphology and pathology in whole human kidneys.

    Science.gov (United States)

    Beeman, Scott C; Cullen-McEwen, Luise A; Puelles, Victor G; Zhang, Min; Wu, Teresa; Baldelomar, Edwin J; Dowling, John; Charlton, Jennifer R; Forbes, Michael S; Ng, Amanda; Wu, Qi-zhu; Armitage, James A; Egan, Gary F; Bertram, John F; Bennett, Kevin M

    2014-06-01

    Nephron number (N(glom)) and size (V(glom)) are correlated with risk for chronic cardiovascular and kidney disease and may be predictive of renal allograft viability. Unfortunately, there are no techniques to assess N(glom) and V(glom) in intact kidneys. This work demonstrates the use of cationized ferritin (CF) as a magnetic resonance imaging (MRI) contrast agent to measure N(glom) and V(glom) in viable human kidneys donated to science. The kidneys were obtained from patients with varying levels of cardiovascular and renal disease. CF was intravenously injected into three viable human kidneys. A fourth control kidney was perfused with saline. After fixation, immunofluorescence and electron microscopy confirmed binding of CF to the glomerulus. The intact kidneys were imaged with three-dimensional MRI and CF-labeled glomeruli appeared as punctate spots. Custom software identified, counted, and measured the apparent volumes of CF-labeled glomeruli, with an ~6% false positive rate. These measurements were comparable to stereological estimates. The MRI-based technique yielded a novel whole kidney distribution of glomerular volumes. Histopathology demonstrated that the distribution of CF-labeled glomeruli may be predictive of glomerular and vascular disease. Variations in CF distribution were quantified using image texture analyses, which be a useful marker of glomerular sclerosis. This is the first report of direct measurement of glomerular number and volume in intact human kidneys.

  10. Electron Pathways through Erythrocyte Plasma Membrane in Human Physiology and Pathology: Potential Redox Biomarker?

    Science.gov (United States)

    Matteucci, Elena; Giampietro, Ottavio

    2007-09-17

    Erythrocytes are involved in the transport of oxygen and carbon dioxide in the body. Since pH is the influential factor in the Bohr-Haldane effect, pHi is actively maintained via secondary active transports Na(+)/H(+) exchange and HC(3) (-)/Cl(-) anion exchanger. Because of the redox properties of the iron, hemoglobin generates reactive oxygen species and thus, the human erythrocyte is constantly exposed to oxidative damage. Although the adult erythrocyte lacks protein synthesis and cannot restore damaged proteins, it is equipped with high activity of protective enzymes. Redox changes in the cell initiate various signalling pathways. Plasma membrane oxido-reductases (PMORs) are transmembrane electron transport systems that have been found in the membranes of all cells and have been extensively characterized in the human erythrocyte. Erythrocyte PMORs transfer reducing equivalents from intracellular reductants to extracellular oxidants, thus their most important role seems to be to enable the cell respond to changes in intra- and extra-cellular redox environments.So far the activity of erythrocyte PMORs in disease states has not been systematically investigated. This review summarizes present knowledge on erythrocyte electron transfer activity in humans (health, type 1 diabetes, diabetic nephropathy, and chronic uremia) and hypothesizes an integrated model of the functional organization of erythrocyte plasma membrane where electron pathways work in parallel with transport metabolons to maintain redox homeostasis.

  11. Pathological implications of Cx43 down-regulation in human colon cancer.

    Science.gov (United States)

    Ismail, Rehana; Rashid, Rabiya; Andrabi, Khurshid; Parray, Fazl Q; Besina, Syed; Shah, Mohd Amin; Ul Hussain, Mahboob

    2014-01-01

    Connexin 43 is an important gap junction protein in vertebrates and is known for its tumor suppressive properties. Cx43 is abundantly expressed in the human intestinal epithelial cells and muscularis mucosae. To explore the role of Cx43 in the genesis of human colon cancer, we performed the expression analysis of Cx43 in 80 cases of histopathologically confirmed and clinically diagnosed human colon cancer samples and adjacent control tissue and assessed correlations with clinicopathological variables. Western blotting using anti-Cx43 antibody indicated that the expression of Cx43 was significantly down regulated (75%) in the cancer samples as compared to the adjacent control samples. Moreover, immunohistochemical analysis of the tissue samples confirmed the down regulation of the Cx43 in the intestinal epithelial cells. Cx43 down regulation showed significant association (pcancer. Our data demonstrated that loss of Cx43 may be an important event in colon carcinogenesis and tumor progression, providing significant insights about the tumor suppressive properties of the Cx43 and its potential as a diagnostic marker for colon cancer.

  12. [Genomic medicine and infectious diseases].

    Science.gov (United States)

    Fellay, Jacques

    2014-05-07

    Relentless progress in our knowledge of the nature and functional consequences of human genetic variation allows for a better understanding of the protracted battle between pathogens and their human hosts. Multiple polymorphisms have been identified that impact our response to infections or to anti-infective drugs, and some of them are already used in the clinic. However, to make personalized medicine a reality in infectious diseases, a sustained effort is needed not only in research but also in genomic education.

  13. Human leukocyte antigen class II transgenic mouse model unmasks the significant extrahepatic pathology in toxic shock syndrome.

    Science.gov (United States)

    Tilahun, Ashenafi Y; Marietta, Eric V; Wu, Tsung-Teh; Patel, Robin; David, Chella S; Rajagopalan, Govindarajan

    2011-06-01

    Among the exotoxins produced by Staphylococcus aureus and Streptococcus pyogenes, the superantigens (SAgs) are the most potent T-cell activators known to date. SAgs are implicated in several serious diseases including toxic shock syndrome (TSS), Kawasaki disease, and sepsis. However, the immunopathogenesis of TSS and other diseases involving SAgs are still not completely understood. The commonly used conventional laboratory mouse strains do not respond robustly to SAgs in vivo. Therefore, they must be artificially rendered susceptible to TSS by using sensitizing agents such as d-galactosamine (d-galN), which skews the disease exclusively to the liver and, hence, is not representative of the disease in humans. SAg-induced TSS was characterized using transgenic mice expressing HLA class II molecules that are extremely susceptible to TSS without d-galN. HLA-DR3 transgenic mice recapitulated TSS in humans with extensive multiple-organ inflammation affecting the lung, liver, kidneys, heart, and small intestines. Heavy infiltration with T lymphocytes (both CD4(+) and CD8+), neutrophils, and macrophages was noted. In particular, the pathologic changes in the small intestines were extensive and accompanied by significantly altered absorptive functions of the enterocytes. In contrast to massive liver failure alone in the d-galN sensitization model of TSS, findings of the present study suggest that gut dysfunction might be a key pathogenic event that leads to high morbidity and mortality in humans with TSS.

  14. Optical pathology of human brain metastasis of lung cancer using combined resonance Raman and spatial frequency spectroscopies

    Science.gov (United States)

    Zhou, Yan; Liu, Cheng-hui; Pu, Yang; Cheng, Gangge; Zhou, Lixin; Chen, Jun; Zhu, Ke; Alfano, Robert R.

    2016-03-01

    Raman spectroscopy has become widely used for diagnostic purpose of breast, lung and brain cancers. This report introduced a new approach based on spatial frequency spectra analysis of the underlying tissue structure at different stages of brain tumor. Combined spatial frequency spectroscopy (SFS), Resonance Raman (RR) spectroscopic method is used to discriminate human brain metastasis of lung cancer from normal tissues for the first time. A total number of thirty-one label-free micrographic images of normal and metastatic brain cancer tissues obtained from a confocal micro- Raman spectroscopic system synchronously with examined RR spectra of the corresponding samples were collected from the identical site of tissue. The difference of the randomness of tissue structures between the micrograph images of metastatic brain tumor tissues and normal tissues can be recognized by analyzing spatial frequency. By fitting the distribution of the spatial frequency spectra of human brain tissues as a Gaussian function, the standard deviation, σ, can be obtained, which was used to generate a criterion to differentiate human brain cancerous tissues from the normal ones using Support Vector Machine (SVM) classifier. This SFS-SVM analysis on micrograph images presents good results with sensitivity (85%), specificity (75%) in comparison with gold standard reports of pathology and immunology. The dual-modal advantages of SFS combined with RR spectroscopy method may open a new way in the neuropathology applications.

  15. RET/PTC Translocations and Clinico-Pathological Features in Human Papillary Thyroid Carcinoma.

    Science.gov (United States)

    Romei, Cristina; Elisei, Rossella

    2012-01-01

    Thyroid carcinoma is the most frequent endocrine cancer accounting for 5-10% of thyroid nodules. Papillary histotype (PTC) is the most prevalent form accounting for 80% of all thyroid carcinoma. Although much is known about its epidemiology, pathogenesis, clinical, and biological behavior, the only documented risk factor for PTC is the ionizing radiation exposure. Rearrangements of the Rearranged during Transfection (RET) proto-oncogene are found in PTC and have been shown to play a pathogenic role. The first RET rearrangement, named RET/PTC, was discovered in 1987. This rearrangement constitutively activates the transcription of the RET tyrosine-kinase domain in follicular cell, thus triggering the signaling along the MAPK pathway and an uncontrolled proliferation. Up to now, 13 different types of RET/PTC rearrangements have been reported but the two most common are RET/PTC1 and RET/PTC3. Ionizing radiations are responsible for the generation of RET/PTC rearrangements, as supported by in vitro studies and by the evidence that RET/PTC, and particularly RET/PTC3, are highly prevalent in radiation induced PTC. However, many thyroid tumors without any history of radiation exposure harbor similar RET rearrangements. The overall prevalence of RET/PTC rearrangements varies from 20 to 70% of PTCs and they are more frequent in childhood than in adulthood thyroid cancer. Controversial data have been reported on the relationship between RET/PTC rearrangements and the PTC prognosis. RET/PTC3 is usually associated with a more aggressive phenotype and in particular with a greater tumor size, the solid variant, and a more advanced stage at diagnosis which are all poor prognostic factors. In contrast, RET/PTC1 rearrangement does not correlate with any clinical-pathological characteristics of PTC. Moreover, the RET protein and mRNA expression level did not show any correlation with the outcome of patients with PTC and no correlation between RET/PTC rearrangements and the

  16. Normal aging in rats and pathological aging in human Alzheimer's disease decrease FAAH activity: modulation by cannabinoid agonists.

    Science.gov (United States)

    Pascual, A C; Martín-Moreno, A M; Giusto, N M; de Ceballos, M L; Pasquaré, S J

    2014-12-01

    Anandamide is an endocannabinoid involved in several physiological functions including neuroprotection. Anandamide is synthesized on demand and its endogenous level is regulated through its degradation, where fatty acid amide hydrolase plays a major role. The aim of this study was to characterize anandamide breakdown in physiological and pathological aging and its regulation by CB1 and CB2 receptor agonists. Fatty acid amide hydrolase activity was analyzed in an independent cohort of human cortical membrane samples from control and Alzheimer's disease patients, and in membrane and synaptosomes from adult and aged rat cerebral cortex. Our results demonstrate that fatty acid amide hydrolase activity decreases in the frontal cortex from human patients with Alzheimer's disease and this effect is mimicked by Aβ(1-40) peptide. This activity increases and decreases in aged rat cerebrocortical membranes and synaptosomes, respectively. Also, while the presence of JWH-133, a CB2 selective agonist, slightly increases anandamide hydrolysis in human controls, it decreases this activity in adults and aged rat cerebrocortical membranes and synaptosomes. In the presence of WIN55,212-2, a mixed CB1/CB2 agonist, anandamide hydrolysis increases in Alzheimer's disease patients but decreases in human controls as well as in adult and aged rat cerebrocortical membranes and synaptosomes. Although a similar profile is observed in fatty acid amide hydrolase activity between aged rat synaptic endings and human Alzheimer's disease brains, it is differently modulated by CB1/CB2 agonists. This modulation leads to a reduced availability of anandamide in Alzheimer's disease and to an increased availability of this endocannabinoid in aging.

  17. Capsid proteins from human immunodeficiency virus type 1 and simian immunodeficiency virus SIVmac can coassemble into mature cores of infectious viruses.

    Science.gov (United States)

    Chen, Jianbo; Pathak, Vinay K; Peng, Weiqun; Hu, Wei-Shau

    2008-09-01

    We have recently shown that the Gag polyproteins from human immunodeficiency virus type 1 (HIV-1) and HIV-2 can coassemble and functionally complement each other. During virion maturation, the Gag polyproteins undergo proteolytic cleavage to release mature proteins including capsid (CA), which refolds and forms the outer shell of a cone-shaped mature core. Less than one-half of the CA proteins present within the HIV-1 virion are required to form the mature core. Therefore, it is unclear whether the mature core in virions containing both HIV-1 and HIV-2 Gag consists of CA proteins from a single virus or from both viruses. To determine whether CA proteins from two different viruses can coassemble into mature cores of infectious viruses, we exploited the specificity of the tripartite motif 5alpha protein from the rhesus monkey (rhTRIM5alpha) for cores containing HIV-1 CA (hCA) but not the simian immunodeficiency virus SIV(mac) CA protein (sCA). If hCA and sCA cannot coassemble into the same core when equal amounts of sCA and hCA are coexpressed, the infectivities of such virus preparations in cells should be inhibited less than twofold by rhTRIM5alpha. However, if hCA and sCA can coassemble into the same core structure to form a mixed core, rhTRIM5alpha would be able to recognize such cores and significantly restrict virus infectivity. We examined the restriction phenotypes of viruses containing both hCA and sCA. Our results indicate that hCA and sCA can coassemble into the same mature core to produce infectious virus. To our knowledge, this is the first demonstration of functional coassembly of heterologous CA protein into the retroviral core.

  18. Production of infectious human immunodeficiency virus type 1 does not require depletion of APOBEC3G from virus-producing cells

    Directory of Open Access Journals (Sweden)

    Goila-Gaur Ritu

    2004-09-01

    Full Text Available Abstract Background The human immunodeficiency virus Vif protein overcomes the inhibitory activity of the APOBEC3G cytidine deaminase by prohibiting its packaging into virions. Inhibition of APOBEC3G encapsidation is paralleled by a reduction of its intracellular level presumably caused by the Vif-induced proteasome-dependent degradation of APOBEC3G. Results In this report we employed confocal microscopy to study the effects of Vif on the expression of APOBEC3G on a single cell level. HeLa cells dually transfected with Vif and APOBEC3G expression vectors revealed efficient co-expression of the two proteins. Under optimal staining conditions approximately 80% of the transfected cells scored double-positive for Vif and APOBEC3G. However, the proportion of double-positive cells observed in identical cultures varied dependent on the fixation protocol and on the choice of antibodies used ranging from as low as 40% to as high as 80% of transfected cells. Importantly, single-positive cells expressing either Vif or APOBEC3G were observed both with wild type Vif and a biologically inactive Vif variant. Thus, the lack of APOBEC3G in some Vif-expressing cells cannot be attributed to Vif-induced degradation of APOBEC3G. These findings are consistent with our results from immunoblot analyses that revealed only moderate effects of Vif on the APOBEC3G steady state levels. Of note, viruses produced under such conditions were fully infectious demonstrating that the Vif protein used in our analyses was both functional and expressed at saturating levels. Conclusions Our results suggest that Vif and APOBEC3G can be efficiently co-expressed. Thus, depletion of APOBEC3G from Vif expressing cells as suggested previously is not a universal property of Vif and thus is not imperative for the production of infectious virions.

  19. Inhibitory effect of human telomerase antisense oligodeoxyribonucleotides on the growth of gastric cancer cell lines in variant tumor pathological subtype

    Institute of Scientific and Technical Information of China (English)

    Jing Ye; Yun-Lin Wu; Shu Zhang; Zi Chen; Li-Xia Guo; Ruo-Yu Zhou; Hong Xie

    2005-01-01

    AIM: To investigate the inhibitory effect of specialized human telomerase antisense oligodeoxyribonucleotides on the growth of well (MKN-28), moderately (SGC-7901)and poorly (MKN-45) differentiated gastric cancer cell lines under specific conditions and its inhibition mechanism,and to observe the correlation between the growth inhibition ratio and the tumor pathologic subtype of gastric cancer cells.METHODS: Telomerase activity in three gastric cancer cell lines of variant tumor pathologic subtype was determined by modified TRAP assay before and after the specialized human telomerase antisense oligodeoxyribonucleotides were dealt with under specific conditions. Effect of antisense oligomer under specific conditions of the growth and viability of gastric cancer cell lines was explored by using trypan blue dye exclusion assay, and cell apoptosis was detected by cell morphology observation, flow cytometry and TUNEL assay.RESULTS: Telomerase activity was detected in well,moderately and poorly differentiated gastric cancer cell lines (the quantification expression of telomerase activity was 43.7TPG, 56.5TPG, 76.7TPG, respectively).Telomerase activity was controlled to 30.2TPG, 36.3TPG and 35.2TPG for MKN-28, SGC-7901 and MKN-45 cell lines respectively after treatment with human telomerase antisense oligomers at the concentration of 5 μmol/L, and was entirely inhibited at 10 μmol/L, against the template region of telomerase RNA component, whereas no inhibition effect was detected in missense oligomers (P<0.05). After treatment with antisense oligomers at different concentrations under specific conditions for 96 h, significant growth inhibition effects were found in MKN-45 and SGC-7901gastric cancer cell lines (the inhibition ratio was 40.89%and 71.28%), but not in MKN-28 cell lines (15.86%). The ratio of inactive SGC-7901 cells increased according to the prolongation of treatment from 48 to 96 h. Missense oligomers could not lead to the same effect (P<0

  20. Motorcycle accidents in forensic pathology. Human factors, and injury and crash tipologies

    Directory of Open Access Journals (Sweden)

    Annalisa Lanino

    2008-10-01

    Full Text Available The aim of this study is to investigate the association between the main human factors, related to motorcycle accidents, and the accident configuration and the lesive pattern. The present study considers the 200 two-wheel crashes occurred in Italy in the Province of Pavia between 1999 and 2001. For all cases a revision of the injured people’s interviews and their clinical records has been made. All the accidents of the survey have been examined considering the traumatic lesion abscribed to the accident to assess a direct causal link between human factors and the crash tipology and the injury pattern. Chi-square test was used to evaluate the relationship between the variables and a logistic regression was performed to evaluate the association of injury severity with some variables supposed to be predictive factors. Frontal-lateral impact collisions are about 6 times more likely to be caused by a traffic scan error of the other vehicle driver (no rider than other types of crashes (OR= 5,8; p < 0,0001; IC 95%: 2,875-11,736. Contusions-abrasions show the highest percentages in motorcyclists with no coverage worn (p < 0,001 and riders with no clothing have a higher risk to be severely injured than riders with coverage, but it is not statistically significant. Instead, there is not a statistical significant association between: rider’s gender, rider’s age, riding experience and accident configuration; damaged region of the helmet and cranium injury severity.

  1. Circulating microRNAs as Potential Biomarkers of Infectious Disease

    Science.gov (United States)

    Correia, Carolina N.; Nalpas, Nicolas C.; McLoughlin, Kirsten E.; Browne, John A.; Gordon, Stephen V.; MacHugh, David E.; Shaughnessy, Ronan G.

    2017-01-01

    microRNAs (miRNAs) are a class of small non-coding endogenous RNA molecules that regulate a wide range of biological processes by post-transcriptionally regulating gene expression. Thousands of these molecules have been discovered to date, and multiple miRNAs have been shown to coordinately fine-tune cellular processes key to organismal development, homeostasis, neurobiology, immunobiology, and control of infection. The fundamental regulatory role of miRNAs in a variety of biological processes suggests that differential expression of these transcripts may be exploited as a novel source of molecular biomarkers for many different disease pathologies or abnormalities. This has been emphasized by the recent discovery of remarkably stable miRNAs in mammalian biofluids, which may originate from intracellular processes elsewhere in the body. The potential of circulating miRNAs as biomarkers of disease has mainly been demonstrated for various types of cancer. More recently, however, attention has focused on the use of circulating miRNAs as diagnostic/prognostic biomarkers of infectious disease; for example, human tuberculosis caused by infection with Mycobacterium tuberculosis, sepsis caused by multiple infectious agents, and viral hepatitis. Here, we review these developments and discuss prospects and challenges for translating circulating miRNA into novel diagnostics for infectious disease. PMID:28261201

  2. Reconstructing the emergence of a lethal infectious disease of wildlife supports a key role for spread through translocations by humans

    Science.gov (United States)

    Cunningham, Andrew A.; Langton, Tom E. S.

    2016-01-01

    There have been few reconstructions of wildlife disease emergences, despite their extensive impact on biodiversity and human health. This is in large part attributable to the lack of structured and robust spatio-temporal datasets. We overcame logistical problems of obtaining suitable information by using data from a citizen science project and formulating spatio-temporal models of the spread of a wildlife pathogen (genus Ranavirus, infecting amphibians). We evaluated three main hypotheses for the rapid increase in disease reports in the UK: that outbreaks were being reported more frequently, that climate change had altered the interaction between hosts and a previously widespread pathogen, and that disease was emerging due to spatial spread of a novel pathogen. Our analysis characterized localized spread from nearby ponds, consistent with amphibian dispersal, but also revealed a highly significant trend for elevated rates of additional outbreaks in localities with higher human population density—pointing to human activities in also spreading the virus. Phylogenetic analyses of pathogen genomes support the inference of at least two independent introductions into the UK. Together these results point strongly to humans repeatedly translocating ranaviruses into the UK from other countries and between UK ponds, and therefore suggest potential control measures. PMID:27683363

  3. The apelinergic system: the role played in human physiology and pathology and potential therapeutic applications.

    Science.gov (United States)

    Ladeiras-Lopes, Ricardo; Ferreira-Martins, João; Leite-Moreira, Adelino F

    2008-05-01

    Apelin is a recently discovered peptide, identified as an endogenous ligand of receptor APJ. Apelin and receptor APJ are expressed in a wide variety of tissues including heart, brain, kidneys and lungs. Their interaction may have relevant pathophysiologic effects in those tissues. In fact, the last decade has been rich in illustrating the possible roles played by apelin in human physiology, namely as a regulating peptide of cardiovascular, hypothalamus-hypophysis, gastrointestinal, and immune systems. The possible involvement of apelin in the pathogenesis of high prevalence conditions and comorbidities - such as hypertension, heart failure, and Diabetes Mellitus Type 2 (T2DM) - rank it as a likely therapeutic target to be investigated in the future. The present paper is an overview of apelin physiologic effects and presents the possible role played by this peptide in the pathogenesis of a number of conditions as well as the therapeutic implications that might, therefore, be investigated.

  4. The fuzzy coat of pathological human Tau fibrils is a two-layered polyelectrolyte brush.

    Science.gov (United States)

    Wegmann, Susanne; Medalsy, Izhar D; Mandelkow, Eckhard; Müller, Daniel J

    2013-01-22

    The structure and properties of amyloid-like Tau fibrils accumulating in neurodegenerative diseases have been debated for decades. Although the core of Tau fibrils assembles from short β-strands, the properties of the much longer unstructured Tau domains protruding from the fibril core remain largely obscure. Applying immunogold transmission EM, and force-volume atomic force microscopy (AFM), we imaged human Tau fibrils at high resolution and simultaneously mapped their mechanical and adhesive properties. Tau fibrils showed a ≈ 16-nm-thick fuzzy coat that resembles a two-layered polyelectrolyte brush, which is formed by the unstructured short C-terminal and long N-terminal Tau domains. The mechanical and adhesive properties of the fuzzy coat are modulated by electrolytes and pH, and thus by the cellular environment. These unique properties of the fuzzy coat help in understanding how Tau fibrils disturb cellular interactions and accumulate in neurofibrillary tangles.

  5. A network biology approach to understanding the importance of chameleon proteins in human physiology and pathology.

    Science.gov (United States)

    Bahramali, Golnaz; Goliaei, Bahram; Minuchehr, Zarrin; Marashi, Sayed-Amir

    2017-02-01

    Chameleon proteins are proteins which include sequences that can adopt α-helix-β-strand (HE-chameleon) or α-helix-coil (HC-chameleon) or β-strand-coil (CE-chameleon) structures to operate their crucial biological functions. In this study, using a network-based approach, we examined the chameleon proteins to give a better knowledge on these proteins. We focused on proteins with identical chameleon sequences with more than or equal to seven residues long in different PDB entries, which adopt HE-chameleon, HC-chameleon, and CE-chameleon structures in the same protein. One hundred and ninety-one human chameleon proteins were identified via our in-house program. Then, protein-protein interaction (PPI) networks, Gene ontology (GO) enrichment, disease network, and pathway enrichment analyses were performed for our derived data set. We discovered that there are chameleon sequences which reside in protein-protein interaction regions between two proteins critical for their dual function. Analysis of the PPI networks for chameleon proteins introduced five hub proteins, namely TP53, EGFR, HSP90AA1, PPARA, and HIF1A, which were presented in four PPI clusters. The outcomes demonstrate that the chameleon regions are in critical domains of these proteins and are important in the development and treatment of human cancers. The present report is the first network-based functional study of chameleon proteins using computational approaches and might provide a new perspective for understanding the mechanisms of diseases helping us in developing new medical therapies along with discovering new proteins with chameleon properties which are highly important in cancer.

  6. Abnormal mitochondrial transport and morphology as early pathological changes in human models of spinal muscular atrophy

    Directory of Open Access Journals (Sweden)

    Chong-Chong Xu

    2016-01-01

    Full Text Available Spinal muscular atrophy (SMA, characterized by specific degeneration of spinal motor neurons, is caused by mutations in the survival of motor neuron 1, telomeric (SMN1 gene and subsequent decreased levels of functional SMN. How the deficiency of SMN, a ubiquitously expressed protein, leads to spinal motor neuron-specific degeneration in individuals affected by SMA remains unknown. In this study, we examined the role of SMN in mitochondrial axonal transport and morphology in human motor neurons by generating SMA type 1 patient-specific induced pluripotent stem cells (iPSCs and differentiating these cells into spinal motor neurons. The initial specification of spinal motor neurons was not affected, but these SMA spinal motor neurons specifically degenerated following long-term culture. Moreover, at an early stage in SMA spinal motor neurons, but not in SMA forebrain neurons, the number of mitochondria, mitochondrial area and mitochondrial transport were significantly reduced in axons. Knocking down of SMN expression led to similar mitochondrial defects in spinal motor neurons derived from human embryonic stem cells, confirming that SMN deficiency results in impaired mitochondrial dynamics. Finally, the application of N-acetylcysteine (NAC mitigated the impairment in mitochondrial transport and morphology and rescued motor neuron degeneration in SMA long-term cultures. Furthermore, NAC ameliorated the reduction in mitochondrial membrane potential in SMA spinal motor neurons, suggesting that NAC might rescue apoptosis and motor neuron degeneration by improving mitochondrial health. Overall, our data demonstrate that SMN deficiency results in abnormal mitochondrial transport and morphology and a subsequent reduction in mitochondrial health, which are implicated in the specific degeneration of spinal motor neurons in SMA.

  7. Abnormal mitochondrial transport and morphology as early pathological changes in human models of spinal muscular atrophy.

    Science.gov (United States)

    Xu, Chong-Chong; Denton, Kyle R; Wang, Zhi-Bo; Zhang, Xiaoqing; Li, Xue-Jun

    2016-01-01

    Spinal muscular atrophy (SMA), characterized by specific degeneration of spinal motor neurons, is caused by mutations in the survival of motor neuron 1, telomeric (SMN1) gene and subsequent decreased levels of functional SMN. How the deficiency of SMN, a ubiquitously expressed protein, leads to spinal motor neuron-specific degeneration in individuals affected by SMA remains unknown. In this study, we examined the role of SMN in mitochondrial axonal transport and morphology in human motor neurons by generating SMA type 1 patient-specific induced pluripotent stem cells (iPSCs) and differentiating these cells into spinal motor neurons. The initial specification of spinal motor neurons was not affected, but these SMA spinal motor neurons specifically degenerated following long-term culture. Moreover, at an early stage in SMA spinal motor neurons, but not in SMA forebrain neurons, the number of mitochondria, mitochondrial area and mitochondrial transport were significantly reduced in axons. Knocking down of SMN expression led to similar mitochondrial defects in spinal motor neurons derived from human embryonic stem cells, confirming that SMN deficiency results in impaired mitochondrial dynamics. Finally, the application of N-acetylcysteine (NAC) mitigated the impairment in mitochondrial transport and morphology and rescued motor neuron degeneration in SMA long-term cultures. Furthermore, NAC ameliorated the reduction in mitochondrial membrane potential in SMA spinal motor neurons, suggesting that NAC might rescue apoptosis and motor neuron degeneration by improving mitochondrial health. Overall, our data demonstrate that SMN deficiency results in abnormal mitochondrial transport and morphology and a subsequent reduction in mitochondrial health, which are implicated in the specific degeneration of spinal motor neurons in SMA.

  8. Anti-infective activities of lactobacillus strains in the human intestinal microbiota: from probiotics to gastrointestinal anti-infectious biotherapeutic agents.

    Science.gov (United States)

    Liévin-Le Moal, Vanessa; Servin, Alain L

    2014-04-01

    A vast and diverse array of microbial species displaying great phylogenic, genomic, and metabolic diversity have colonized the gastrointestinal tract. Resident microbes play a beneficial role by regulating the intestinal immune system, stimulating the maturation of host tissues, and playing a variety of roles in nutrition and in host resistance to gastric and enteric bacterial pathogens. The mechanisms by which the resident microbial species combat gastrointestinal pathogens are complex and include competitive metabolic interactions and the production of antimicrobial molecules. The human intestinal microbiota is a source from which Lactobacillus probiotic strains have often been isolated. Only six probiotic Lactobacillus strains isolated from human intestinal microbiota, i.e., L. rhamnosus GG, L. casei Shirota YIT9029, L. casei DN-114 001, L. johnsonii NCC 533, L. acidophilus LB, and L. reuteri DSM 17938, have been well characterized with regard to their potential antimicrobial effects against the major gastric and enteric bacterial pathogens and rotavirus. In this review, we describe the current knowledge concerning the experimental antibacterial activities, including antibiotic-like and cell-regulating activities, and therapeutic effects demonstrated in well-conducted, placebo-controlled, randomized clinical trials of these probiotic Lactobacillus strains. What is known about the antimicrobial activities supported by the molecules secreted by such probiotic Lactobacillus strains suggests that they constitute a promising new source for the development of innovative anti-infectious agents that act luminally and intracellularly in the gastrointestinal tract.

  9. Two rare human mitofusin 2 mutations alter mitochondrial dynamics and induce retinal and cardiac pathology in Drosophila.

    Directory of Open Access Journals (Sweden)

    William H Eschenbacher

    Full Text Available Mitochondrial fusion is essential to organelle homeostasis and organ health. Inexplicably, loss of function mutations of mitofusin 2 (Mfn2 specifically affect neurological tissue, causing Charcot Marie Tooth syndrome (CMT and atypical optic atrophy. As CMT-linked Mfn2 mutations are predominantly within the GTPase domain, we postulated that Mfn2 mutations in other functional domains might affect non-neurological tissues. Here, we defined in vitro and in vivo consequences of rare human mutations in the poorly characterized Mfn2 HR1 domain. Human exome sequencing data identified 4 rare non-synonymous Mfn2 HR1 domain mutations, two bioinformatically predicted as damaging. Recombinant expression of these (Mfn2 M393I and R400Q in Mfn2-null murine embryonic fibroblasts (MEFs revealed incomplete rescue of characteristic mitochondrial fragmentation, compared to wild-type human Mfn2 (hMfn2; Mfn2 400Q uniquely induced mitochondrial fragmentation in normal MEFs. To compare Mfn2 mutation effects in neurological and non-neurological tissues in vivo, hMfn2 and the two mutants were expressed in Drosophila eyes or heart tubes made deficient in endogenous fly mitofusin (dMfn through organ-specific RNAi expression. The two mutants induced similar Drosophila eye phenotypes: small eyes and an inability to rescue the eye pathology induced by suppression of dMfn. In contrast, Mfn2 400Q induced more severe cardiomyocyte mitochondrial fragmentation and cardiac phenotypes than Mfn2 393I, including heart tube dilation, depressed fractional shortening, and progressively impaired negative geotaxis. These data reveal a central functional role for Mfn2 HR1 domains, describe organ-specific effects of two Mfn2 HR1 mutations, and strongly support prospective studies of Mfn2 400Q in heritable human heart disease of unknown genetic etiology.

  10. [Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II)].

    Science.gov (United States)

    Toledano, A; Álvarez, M I; López-Rodríguez, A B; Toledano-Díaz, A; Fernández-Verdecia, C I

    2014-01-01

    In the ageing process there are some species of non-human primates which can show some of the defining characteristics of the Alzheimer's disease (AD) of man, both in neuropathological changes and cognitive-behavioural symptoms. The study of these species is of prime importance to understand AD and develop therapies to combat this neurodegenerative disease. In this second part of the study, these AD features are discussed in the most important non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet -Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and M. arctoides) and experimental models (lesional, neurotoxic, pharmacological, immunological, etc.) non-human primates. In all these models cerebral amyloid neuropathology can occur in senility, although with different levels of incidence (100% in vervets;Alzheimer's) senility in these species are difficult to establish due to the lack of cognitive-behavioural studies in the many groups analysed, as well as the controversy in the results of these studies when they were carried out. However, in some macaques, a correlation between a high degree of functional brain impairment and a large number of neuropathological changes ("possible AD") has been found. In some non-human primates, such as the macaque, the existence of a possible continuum between "normal" ageing process, "normal" ageing with no deep neuropathological and cognitive-behavioural changes, and "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other cases, such as the Caribbean vervet, neuropathological changes are constant and quite marked, but its impact on cognition and behaviour does not seem to be very important. This does assume the possible existence in the human senile physiological regression of a stable phase without dementia even if neuropathological changes appeared. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  11. Human and animal health in Europe: the view from the European Academies Science Advisory Council (EASAC on challenges in infectious disease

    Directory of Open Access Journals (Sweden)

    Fears Robin

    2012-06-01

    Full Text Available For the last seven years, the European Academies Science Advisory Council (EASAC has conducted a series of projects defining and clarifying priorities for European policy in infectious disease. Both human and animal populations are increasingly threatened by emerging and re-emerging infections, including zoonoses, partly attributable to the impact of environmental change on the distributions of pathogens, hosts and vectors. Among the key challenges to be faced are the impact of climate change, the increase of antibiotic resistance and the need to develop novel global surveillance and early warning systems worldwide. Multidisciplinary approaches are required to build the new interfaces between human and animal medicine (One Health, with new connections between epidemiological and environmental data for surveillance, communication and risk assessment. This multidisciplinarity involves integration between microbiology, immunology, genetics and genomics, entomology, ecology and the social sciences, among other disciplines. Improved understanding of patterns of both human and animal disease also requires commitment to standardisation of surveillance methodologies and better analysis, co-ordination and use of the data collected. There must be sustained support for fundamental research, for example to explore how pathogens cross the species barrier, encouragement for industry innovation in developing diagnostics, therapeutics and vaccines, and the increased use of scientific evidence to inform coherent strategic development across different policy-making functions and to support international leadership. Our paper is intended as an introduction to some of the issues for building collaboration between human and animal medicine, to be discussed in greater detail in the other contributions to this Issue....

  12. Cosmology and Particle Physics/Human evolution and infectious disease/Cognitive evolution (1 page - 3 subjects)

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    Carroll, Sean; Hauser, Marc D

    2007-01-01

    "On the theoretical side, particle phenomenologists will continue to develop physics beyond the Standard Model; string theorists are connecting ore strongly to cosmology and astrophysics/With the recent advent of whole-genome sequencing and increasingly complete surveys of genetic variation, we are now routinely studying 500 thousand variations at a time, enabling complete genome wide surveys in many human populations and in specific disease populations./The most exciting developments today sit at the intersection between science and philosophy.

  13. The Role of Laminin α4 in Human Umbilical Vein Endothelial Cells and Pathological Mechanism of Preeclampsia.

    Science.gov (United States)

    Shan, Nan; Zhang, Xuemei; Xiao, Xiaoqiu; Zhang, Hua; Chen, Ying; Luo, Xin; Liu, Xiru; Zhuang, Baimei; Peng, Wei; Qi, Hongbo

    2015-08-01

    Preeclampsia (PE) is associated with defective placental angiogenesis and poor placentation. Laminins are the main noncollagenous glycoproteins in basement membranes, and laminin α4 (LAMA4) promotes the migration, proliferation, and survival of various cells. The primary purpose of this study is to investigate the role of LAMA4 in human umbilical vein endothelial cells (HUVECs) function during the development of PE. We found expression levels of LAMA4 in human PE placentas were significantly lower compared to the control placentas. The LAMA4 small-interfering RNA transfection and hypoxia-reoxygenation (H/R) intervention reduced the migratory and tube formation abilities of HUVECs. The mitogen-activated protein kinase (MAPK) signaling pathways interacted with LAMA4 expression and H/Rexposure led to MAPK pathways activation in HUVECs. We demonstrated that LAMA4 is very crucial in promoting the functions of endothelial cells. Oxidative stress plays a vital role in controlling expression of LAMA4 through MAPK signaling pathways, which suggests a possible pathological mechanism of PE.

  14. Structure of FGFR3 transmembrane domain dimer: implications for signaling and human pathologies.

    Science.gov (United States)

    Bocharov, Eduard V; Lesovoy, Dmitry M; Goncharuk, Sergey A; Goncharuk, Marina V; Hristova, Kalina; Arseniev, Alexander S

    2013-11-05

    Fibroblast growth factor receptor 3 (FGFR3) transduces biochemical signals via lateral dimerization in the plasma membrane, and plays an important role in human development and disease. Eight different pathogenic mutations, implicated in cancers and growth disorders, have been identified in the FGFR3 transmembrane segment. Here, we describe the dimerization of the FGFR3 transmembrane domain in membrane-mimicking DPC/SDS (9/1) micelles. In the solved NMR structure, the two transmembrane helices pack into a symmetric left-handed dimer, with intermolecular stacking interactions occurring in the dimer central region. Some pathogenic mutations fall within the helix-helix interface, whereas others are located within a putative alternative interface. This implies that although the observed dimer structure is important for FGFR3 signaling, the mechanism of FGFR3-mediated transduction across the membrane is complex. We propose an FGFR3 signaling mechanism that is based on the solved structure, available structures of isolated soluble FGFR domains, and published biochemical and biophysical data.

  15. Antimycotic effect of the essential oil of Aloysia triphylla against Candida species obtained from human pathologies.

    Science.gov (United States)

    Oliva, María de las Mercedes; Carezzano, María Evangelina; Gallucci, Mauro Nicolás; Demo, Mirta Susana

    2011-07-01

    The research of alternative substances to treat infections caused by Candida species is a need. Aromatic plants have the ability to produce secondary metabolites, such as essential oils (EO). The antimicrobial properties of Aloysia triphylla (L'Her.) Britton (cedrón) EO has been previously described. The aims of this work were to determine the antimicrobial activity and the effect on the cell structure of the EO of A. triphylla against Candida sp isolated from human illnesses. The EO was obtained by hydrodistillation of A. triphylla leaves. The minimum inhibitory concentration (MIC) was performed with microdilution method and the minimum fungicidal concentration (MFC) was determined. A. triphylla EO's showed antifungal activity against all yeast: C. albicans, C. dubliniensis, C. glabrata, C. krusei, C. guillermondii, C. parapsilosis and C. tropicalis which were resistant to fluconazol (150 mg/mL). The range of MIC values was from: 35 to 140 microg/mL and the MFC: 1842 to 2300 microg/mL. The time of killing at the MFC against C. albicans (3 x 10(5) UFC/mL) was 140 min. The dates of OD620 and OD260 suggest lysis and loss of absorbing material, respectively. The HROM shows distortion in morphology and shape of the cell, with large vacuoles in the cytoplasm. These studies clearly show that A. triphylla EO is a promising alternative for the treatment of candidiasis.

  16. Genotypes of human papilloma virus in Sudanese women with cervical pathology

    Directory of Open Access Journals (Sweden)

    Tobi Khater

    2010-12-01

    Full Text Available Abstract Background Knowledge of the distribution of human papillomavirus (HPV genotypes among women with cervical lesion and in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. There is no published data concerning HPV and cervical abnormalities in Sudan. This study aimed to define the prevalence of HPV and its subtypes in the cervical smears of women presenting with gynecological complains at Omdurman Military Hospital, Sudan. During the period between March 2003 and April 2004, 135 cervical smears collected from these women, were screened using cytological techniques, and analysed by PCR for (beta-globin and HPV DNA using gel electrophoresis and ELISA. Results Of these 135 smears, there were 94 (69.3% negative, 22 (16.3% positive for inflammation, 12(8.9 mild dyskaryosis, 5 (3.7 moderate dyskaryosis and 2 (1.8 severe dyskaryosis. There were 60.7% ß. globin positive samples for HPV indicating DNA integrity. HPV DNA was identified in three samples (2.2% by gel electrophoresis and. was positive in four samples (2.9% as single and multiple infections by PCR-ELISA. The high risk HPV types 16 and 58 were identified in one sample as a mixed infection. The low risk HPV types 40 and 42 were also found as a mixed infection in another patient. HPV types 58 and 42 were identified in the other two patients. Conclusion HPV type distribution in Sudan appears to differ from that in other countries. The HPV genotypes identified were not associated with cancer.

  17. E- and N-Cadherin Distribution in Developing and Functional Human Teeth under Normal and Pathological Conditions

    Science.gov (United States)

    Heymann, Robert; About, Imad; Lendahl, Urban; Franquin, Jean-Claude; Öbrink, Björn; Mitsiadis, Thimios A.

    2002-01-01

    Cadherins are calcium-dependent cell adhesion molecules involved in the regulation of various biological processes such as cell recognition, intercellular communication, cell fate, cell polarity, boundary formation, and morphogenesis. Although previous studies have shown E-cadherin expression during rodent or human odontogenesis, there is no equivalent study available on N-cadherin expression in dental tissues. Here we examined and compared the expression patterns of E- and N-cadherins in both embryonic and adult (healthy, injured, carious) human teeth. Both proteins were expressed in the developing teeth during the cap and bell stages. E-cadherin expression in dental epithelium followed an apical-coronal gradient that was opposite to that observed for N-cadherin. E-cadherin was distributed in proliferating cells of the inner and outer enamel epithelia but not in differentiated cells such as ameloblasts, whereas N-cadherin expression was up-regulated in differentiated epithelial cells. By contrast to E-cadherin, N-cadherin was also expressed in mesenchymal cells that differentiate into odontoblasts and produce the hard tissue matrix of dentin. Although N-cadherin was not detected in permanent intact teeth, it was re-expressed during dentin repair processes in odontoblasts surrounding carious or traumatic sites. Similarly, N-cadherin re-expression was seen in vitro, in cultured primary pulp cells that differentiate into odontoblast-like cells. Taken together these results suggest that E- and N-cadherins may play a role during human tooth development and, moreover, indicate that N-cadherin is important for odontoblast function in normal development and under pathological conditions. PMID:12057916

  18. Non-Infectious Meningitis

    Science.gov (United States)

    ... 13 Chapter 14 Annex Viral Meningitis Fungal Meningitis Parasitic ... How it Spreads Non–infectious meningitis causes include: Cancers Systemic lupus erythematosus (lupus) Certain drugs Head injury ...

  19. The bovine model for elucidating the role of γδ T cells in controlling infectious diseases of importance to cattle and humans.

    Science.gov (United States)

    Baldwin, Cynthia L; Telfer, Janice C

    2015-07-01

    There are several instances of co-investigation and related discoveries and achievements in bovine and human immunology; perhaps most interesting is the development of the BCG vaccine, the tuberculin skin test and the more recent interferon-gamma test that were developed first in cattle to prevent and diagnosis bovine tuberculosis and then applied to humans. There are also a number of immune-physiological traits that ruminant share with humans including the development of their immune systems in utero which increases the utility of cattle as a model for human immunology. These are reviewed here with a particular focus on the use of cattle to unravel γδ T cell biology. Based on the sheer number of γδ T cells in this γδ T cell high species, it is reasonable to expect γδ T cells to play an important role in protective immune responses. For that reason alone cattle may provide good models for elucidating at least some of the roles γδ T cells play in protective immunity in all species. This includes fundamental research on γδ T cells as well as the responses of ruminant γδ T cells to a variety of infectious disease situations including to protozoan and bacterial pathogens. The role that pattern recognition receptors (PRR) play in the activation of γδ T cells may be unique relative to αβ T cells. Here we focus on that of the γδ T cell specific family of molecules known as WC1 or T19 in ruminants, which are part of the CD163 scavenger receptor cysteine rich (SRCR) family that includes SCART1 and SCART2 expressed on murine γδ T cells. We review the evidence for WC1 being a PRR as well as an activating co-receptor and the role that γδ T cells bearing these receptors play in immunity to leptospirosis and tuberculosis. This includes the generation of memory responses to vaccines, thereby continuing the tradition of co-discovery between cattle and humans.

  20. Pathology in Greece.

    Science.gov (United States)

    Sakellariou, S; Patsouris, E

    2015-11-01

    Pathology is the field of medicine that studies diseases. Ancient Greece hosted some of the earliest societies that laid the structural foundations of pathology. Initially, knowledge was based on observations but later on the key elements of pathology were established based on the dissection of animals and the autopsy of human cadavers. Christianized Greece under Ottoman rule (1453-1821) was not conducive to the development of pathology. After liberation, however, a series of events took place that paved the way for the establishment and further development of the specialty. The appointment in 1849 of two Professors of Pathology at the Medical School of Athens for didactical purposes proved to be the most important step in fostering the field of pathology in modern Greece. Presently in Greece there are seven university departments and 74 pathology laboratories in public hospitals, employing 415 specialized pathologists and 90 residents. The First Department of Pathology at the Medical School of Athens University is the oldest (1849) and largest in Greece, encompassing most pathology subspecialties.

  1. High-definition Fourier Transform Infrared (FT-IR) spectroscopic imaging of human tissue sections towards improving pathology.

    Science.gov (United States)

    Sreedhar, Hari; Varma, Vishal K; Nguyen, Peter L; Davidson, Bennett; Akkina, Sanjeev; Guzman, Grace; Setty, Suman; Kajdacsy-Balla, Andre; Walsh, Michael J

    2015-01-21

    High-definition Fourier Transform Infrared (FT-IR) spectroscopic imaging is an emerging approach to obtain detailed images that have associated biochemical information. FT-IR imaging of tissue is based on the principle that different regions of the mid-infrared are absorbed by different chemical bonds (e.g., C=O, C-H, N-H) within cells or tissue that can then be related to the presence and composition of biomolecules (e.g., lipids, DNA, glycogen, protein, collagen). In an FT-IR image, every pixel within the image comprises an entire Infrared (IR) spectrum that can give information on the biochemical status of the cells that can then be exploited for cell-type or disease-type classification. In this paper, we show: how to obtain IR images from human tissues using an FT-IR system, how to modify existing instrumentation to allow for high-definition imaging capabilities, and how to visualize FT-IR images. We then present some applications of FT-IR for pathology using the liver and kidney as examples. FT-IR imaging holds exciting applications in providing a novel route to obtain biochemical information from cells and tissue in an entirely label-free non-perturbing route towards giving new insight into biomolecular changes as part of disease processes. Additionally, this biochemical information can potentially allow for objective and automated analysis of certain aspects of disease diagnosis.

  2. Astrocyte pathology in a human neural stem cell model of frontotemporal dementia caused by mutant TAU protein

    Science.gov (United States)

    Hallmann, Anna-Lena; Araúzo-Bravo, Marcos J.; Mavrommatis, Lampros; Ehrlich, Marc; Röpke, Albrecht; Brockhaus, Johannes; Missler, Markus; Sterneckert, Jared; Schöler, Hans R.; Kuhlmann, Tanja; Zaehres, Holm; Hargus, Gunnar

    2017-01-01

    Astroglial pathology is seen in various neurodegenerative diseases including frontotemporal dementia (FTD), which can be caused by mutations in the gene encoding the microtubule-associated protein TAU (MAPT). Here, we applied a stem cell model of FTD to examine if FTD astrocytes carry an intrinsic propensity to degeneration and to determine if they can induce non-cell-autonomous effects in neighboring neurons. We utilized CRISPR/Cas9 genome editing in human induced pluripotent stem (iPS) cell-derived neural progenitor cells (NPCs) to repair the FTD-associated N279K MAPT mutation. While astrocytic differentiation was not impaired in FTD NPCs derived from one patient carrying the N279K MAPT mutation, FTD astrocytes appeared larger, expressed increased levels of 4R-TAU isoforms, demonstrated increased vulnerability to oxidative stress and elevated protein ubiquitination and exhibited disease-associated changes in transcriptome profiles when compared to astrocytes derived from one control individual and to the isogenic control. Interestingly, co-culture experiments with FTD astrocytes revealed increased oxidative stress and robust changes in whole genome expression in previously healthy neurons. Our study highlights the utility of iPS cell-derived NPCs to elucidate the role of astrocytes in the pathogenesis of FTD. PMID:28256506

  3. The presence and absence of lymphatic vessels in the adult human intervertebral disc: relation to disc pathology

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    Kliskey, Karolina; Williams, Kelly; Yu, J.; Urban, Jill; Athanasou, Nick [University of Oxford, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Science, Oxford (United Kingdom); Jackson, David [Weatherall Institute of Molecular Medicine, Human Immunology Unit, Oxford (United Kingdom)

    2009-12-15

    Although the normal adult human intervertebral disc is considered to be avascular, vascularised cellular fibrous tissue can be found in pathological conditions involving the disc such as disc herniation. Whether lymphatics vessels form a component of this reparative tissue is not known as the presence or absence of lymphatics in herniated and normal disc tissue is not known. We examined spinal tissues and discectomy specimens for the presence of lymphatics. The examination used immunohistochemistry to identify the specific lymphatic endothelial cell markers, podoplanin and LYVE1. Lymphatic vessels were not found in the nucleus pulposus or annulus fibrosus of intact, non-herniated lumbar and thoracic discs but were present in the surrounding ligaments. Ingrowth of fibrous tissue was seen in 73% of herniated disc specimens of which 36% contained LYVE1+/podoplanin + lymphatic vessels. Lymphatic vessels were not seen in the sacrum and coccyx or biopsies of four sacrococcygeal chordomas, but they were noted in surrounding extra-osseous fat and fibrous tissue at the edge of the infiltrating tumour. Our findings indicate that lymphatic vessels are not present in the normal adult intervertebral disc but that, when there is extrusion of disc material into surrounding soft tissue, there is ingrowth of reparative fibrous tissue containing lymphatic vessels. Our findings also indicate that chordoma, a tumour of notochordal origin, spreads to regional lymph nodes via lymphatics in para-spinal soft tissues. (orig.)

  4. The Role of Gap Junction Channels During Physiologic and Pathologic Conditions of the Human Central Nervous System

    Science.gov (United States)

    Basilio, Daniel; Sáez, Juan C.; Orellana, Juan A.; Raine, Cedric S.; Bukauskas, Feliksas; Bennett, Michael V. L.; Berman, Joan W.

    2013-01-01

    Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP3, and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system. PMID:22438035

  5. The role of gap junction channels during physiologic and pathologic conditions of the human central nervous system.

    Science.gov (United States)

    Eugenin, Eliseo A; Basilio, Daniel; Sáez, Juan C; Orellana, Juan A; Raine, Cedric S; Bukauskas, Feliksas; Bennett, Michael V L; Berman, Joan W

    2012-09-01

    Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP(3), and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system.

  6. [Pathological jealousy].

    Science.gov (United States)

    Zacher, A

    2004-10-28

    Pathological jealousy can make life unbearable for all concerned. The proximity of this condition to obsessive-compulsive phenomena has given rise to the notion that it might respond to substances of proven value in the treatment of obsessive-compulsive disorders. This case history exemplifies the successful treatment of pathological jealousy with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. The substance not only proved to be a successful antidepressant, but also effectively mitigated the anguish of the patient's pathological jealousy. On the basis of these findings, fluoxetine--as also other SSRIs--should always be considered as a possible effective pharmacological strategy for the treatment of pathological jealousy.

  7. Pathological changes in acute experimental toxoplasmosis with Toxoplasma gondii strains obtained from human cases of congenital disease.

    Science.gov (United States)

    Pinheiro, Breno Veloso; Noviello, Maria de Lourdes Meirelles; Cunha, Mariana Maciel; Tavares, Alice Thomaz; Carneiro, Ana Carolina Aguiar Vasconcelos; Arantes, Rosa Maria Esteves; Vitor, Ricardo Wagner Almeida

    2015-09-01

    There is a lack of studies using Toxoplasma gondii strains isolated from human patients. Here, we present a pathological study of three strains obtained from human cases of congenital toxoplasmosis in Brazil using inbred mice after oral infection with 10 tissue cysts. Multiplex-nested PCR-RFLP of eleven loci revealed atypical genotypes commonly found in Brazil: toxodb #8 for TgCTBr5 and TgCTBr16 strains and toxodb #11 for the TgCTBr9 strain. BALB/c and C57BL/6 mice were evaluated for survival and histological changes during the acute phase of the disease. All mice inoculated with the non-virulent TgCTBR5 strain survived after 30 days, although irreversible tissue damage was found. In contrast, no mice were resistant to infection with the highly virulent TgCTBR9 strain. The TgCTBr16 strain resulted in 80% survival in mice. However, this strain presented low infectivity, especially by the oral route of infection. Despite being identified with the same genotype, TgCTBr5 and TgCTBr16 strains showed biological differences. Histopathologic analysis revealed liver and lungs to be the most affected organs, and the pattern of tissue injury was similar to that found in mice inoculated perorally with strains belonging to clonal genotypes. However, there was a variation in the intensity of ileum lesions according to T. gondii strain and mouse lineage. C57BL/6 mice showed higher susceptibility than BALB/c for histological lesions. Taken together, these results revealed that the pathogenesis of T. gondii strains belonging to atypical genotypes can induce similar tissue damage to those from clonal genotypes, although intrinsic aspects of the strains seem critical to the induction of ileitis in the infected host.

  8. Mitochondrial network complexity and pathological decrease in complex I activity are tightly correlated in isolated human complex I deficiency.

    Science.gov (United States)

    Koopman, Werner J H; Visch, Henk-Jan; Verkaart, Sjoerd; van den Heuvel, Lambertus W P J; Smeitink, Jan A M; Willems, Peter H G M

    2005-10-01

    Complex I (NADH:ubiquinone oxidoreductase) is the largest multisubunit assembly of the oxidative phosphorylation system, and its malfunction is associated with a wide variety of clinical syndromes ranging from highly progressive, often early lethal, encephalopathies to neurodegenerative disorders in adult life. The changes in mitochondrial structure and function that are at the basis of the clinical symptoms are poorly understood. Video-rate confocal microscopy of cells pulse-loaded with mitochondria-specific rhodamine 123 followed by automated analysis of form factor (combined measure of length and degree of branching), aspect ratio (measure of length), and number of revealed marked differences between primary cultures of skin fibroblasts from 13 patients with an isolated complex I deficiency. These differences were independent of the affected subunit, but plotting of the activity of complex I, normalized to that of complex IV, against the ratio of either form factor or aspect ratio to number revealed a linear relationship. Relatively small reductions in activity appeared to be associated with an increase in form factor and never with a decrease in number, whereas relatively large reductions occurred in association with a decrease in form factor and/or an increase in number. These results demonstrate that complex I activity and mitochondrial structure are tightly coupled in human isolated complex I deficiency. To further prove the relationship between aberrations in mitochondrial morphology and pathological condition, fibroblasts from two patients with a different mutation but a highly fragmented mitochondrial phenotype were fused. Full restoration of the mitochondrial network demonstrated that this change in mitochondrial morphology was indeed associated with human complex I deficiency.

  9. Are PrP(C)s involved in some human myelin diseases? Relating experimental studies to human pathology.

    Science.gov (United States)

    Veber, Daniela; Scalabrino, Giuseppe

    2015-12-15

    We have experimentally demonstrated that cobalamin (Cbl) deficiency increases normal cellular prion (PrP(C)) levels in rat spinal cord (SC) and cerebrospinal fluid (CSF), and decreases PrP(C)-mRNA levels in rat SC. Repeated intracerebroventricular administrations of anti-octapeptide repeat-PrP(C)-region antibodies to Cbl-deficient (Cbl-D) rats prevent SC myelin lesions, and the administrations of PrP(C)s to otherwise normal rats cause SC white matter lesions similar to those induced by Cbl deficiency. Cbl positively regulates SC PrP(C) synthesis in rat by stimulating the local synthesis of epidermal growth factor (EGF), which also induces the local synthesis of PrP(C)-mRNAs, and downregulating the local synthesis of tumor necrosis factor(TNF)-α, thus preventing local PrP(C) overproduction. We have clinically demonstrated that PrP(C) levels are increased in the CSF of patients with subacute combined degeneration (SCD), unchanged in the CSF of patients with Alzheimer's disease and amyotrophic lateral sclerosis, and decreased in the CSF and SC of patients with multiple sclerosis (MS), regardless of its clinical course. We conclude that SCD (human and experimental) is a neurological disease due to excess PrP(C) without conformational change and aggregation, that the increase in PrP(C) levels in SCD and Cbl-D polyneuropathy and their decrease in MS CNS make them antipodian myelin diseases in terms of quantitative PrP(C) abnormalities, and that these abnormalities are related to myelin damage in the former, and impede myelin repair in the latter.

  10. SIGNIFICANCE OF UROGENITAL INFECTIONS IN PATHOLOGY OF PREGNANCY AND DELIVERY IN EXPERIMENTS

    Directory of Open Access Journals (Sweden)

    I. M. Arshba

    2011-01-01

    Full Text Available Abstract. Development of adequate models in laboratory animals is highly important to detect etiological links between urogenital tract pathology and chlamydia, mycoplasma and ureaplasma bacteria. These model systems can be very useful to find solutions in combating with urogenital tract diseases. One of the obligatory conditions to use monkeys in development of experimental models of infectious and somatic human diseases is knowledge of spontaneous pathology in primates. The present study has shown high frequency of urogenital infections bacteria in the urogenital tract of healthy and sick monkeys.

  11. [Infectious diseases research].

    Science.gov (United States)

    Carratalà, Jordi; Alcamí, José; Cordero, Elisa; Miró, José M; Ramos, José Manuel

    2008-12-01

    There has been a significant increase in research activity into infectious diseases in Spain in the last few years. The Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) currently has ten study groups, with the cooperation of infectious diseases specialists and microbiologists from different centres, with significant research activity. The program of Redes Temáticas de Investigación Cooperativa en Salud (Special Topics Cooperative Health Research Networks) is an appropriate framework for the strategic coordination of research groups from the Spanish autonomous communities. The Spanish Network for Research in Infectious Diseases (REIPI) and the Network for Research in AIDS (RIS) integrate investigators in Infectious Diseases from multiple groups, which continuously perform important research projects. Research using different experimental models in infectious diseases, in numerous institutions, is an important activity in our country. The analysis of the recent scientific production in Infectious Diseases shows that Spain has a good position in the context of the European Union. The research activity in Infectious Diseases carried out in our country is a great opportunity for the training of specialists in this area of knowledge.

  12. Global Climate Change and Infectious Diseases

    Directory of Open Access Journals (Sweden)

    EK Shuman

    2010-12-01

    Full Text Available Climate change is occurring as a result of warming of the earth’s atmosphere due to human activity generating excess amounts of greenhouse gases. Because of its potential impact on the hydrologic cycle and severe weather events, climate change is expected to have an enormous effect on human health, including on the burden and distribution of many infectious diseases. The infectious diseases that will be most affected by climate change include those that are spread by insect vectors and by contaminated water. The burden of adverse health effects due to these infectious diseases will fall primarily on developing countries, while it is the developed countries that are primarily responsible for climate change. It is up to governments and individuals to take the lead in halting climate change, and we must increase our understanding of the ecology of infectious diseases in order to protect vulnerable populations.

  13. Infectious diseases in the 21st century.

    Science.gov (United States)

    Kumate, J

    1997-01-01

    Infecto-contagious diseases in the twenty-first century with respect to precedent will see themselves deprived of smallpox, dracunculiasis and very probably of paralyzing poliomyelitis. Vaccination-preventable diseases, such as measles, whooping cough, diphtheria, tetanus, rabies, some forms of meningitis, yellow fever and episodes of disseminated tuberculosis will greatly diminish in their rates of morbi-lethality; the elimination of some, and the eradication of measles, are expected. Other diseases such as diarrhea (including cholera), geo-helminthiasis, some severe respiratory tract infections and the majority of vector-transmitted infectious diseases will decrease due to improvements in potable water services, drainage, sanitary food control, living quarters, and individual and community anti-vector action. Leprosy, onchocerciasis and several parasitoses will be controlled by the available antimicrobial drugs. Infectious diseases will continue to be an important health problem due to: Reduction in the immunocompetence resulting from the aging of the population, chemotherapies necessary for neoplasms, and autoimmune pathology and the survival of persons with primary immunodeficiencies; lifestyles prone to infectious pathology, such as mega-city urbanization, children in day care centers, industrialized foods, intravenous drug addiction, sexual liberation, global commerce, and tourism; antibiotic-multiresistant microbial flora; environmental disturbances as a result of global warming, deforestation, the settling of virgin areas, dams, the large-scale use of pesticides, fertilizers and antimicrobials, and natural/social disasters generators of poverty, violence and deprivation will result in emergence or re-emergence of infectious diseases already controlled in the past.

  14. The large-scale functional connectivity correlates of consciousness and arousal during the healthy and pathological human sleep cycle.

    Science.gov (United States)

    Tagliazucchi, Enzo; van Someren, Eus J W

    2017-06-12

    Advances in neuroimaging have greatly improved our understanding of human sleep from a systems neuroscience perspective. However, cognition and awareness are reduced during sleep, hindering the applicability of standard task-based paradigms. Methods recently developed to study spontaneous brain activity fluctuations have proven useful to overcome this limitation. In this review, we focus on the concept of functional connectivity (FC, i.e. statistical covariance between brain activity signals) and its application to functional magnetic resonance imaging (fMRI) data acquired during sleep. We discuss how FC analyses of endogenous brain activity during sleep have contributed towards revealing the large-scale neural networks associated with arousal and conscious awareness. We argue that the neuroimaging of deep sleep can be used to evaluate the predictions of theories of consciousness; at the same time, we highlight some apparent limitations of deep sleep as an experimental model of unconsciousness. In resting state fMRI experiments, the onset of sleep can be regarded as the object of interest but also as an undesirable confound. We discuss a series of articles contributing towards the disambiguation of wakefulness from sleep on the basis of fMRI-derived dynamic FC, and then outline a plan for the development of more general and data-driven sleep classifiers. To complement our review of studies investigating the brain systems of arousal and consciousness during healthy sleep, we then turn to pathological and abnormal sleep patterns. We review the current literature on sleep deprivation studies and sleep disorders, adopting the critical stance that lack of independent vigilance monitoring during fMRI experiments is liable for false positives related to atypical sleep propensity in clinical and sleep-deprived populations. Finally, we discuss multimodal neuroimaging as a promising future direction to achieve a better understanding of the large-scale FC of the brain during

  15. Trichohyalin-like 1 protein, a member of fused S100 proteins, is expressed in normal and pathologic human skin

    Energy Technology Data Exchange (ETDEWEB)

    Yamakoshi, Takako [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Makino, Teruhiko, E-mail: tmakino@med.u-toyama.ac.jp [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Ur Rehman, Mati; Yoshihisa, Yoko [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Sugimori, Michiya [Department of Integrative Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan); Shimizu, Tadamichi, E-mail: shimizut@med.u-toyama.ac.jp [Department of Dermatology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama 930-0194 (Japan)

    2013-03-01

    Highlights: ► Trichohyalin-like 1 protein is a member of the fused-type S100 protein gene family. ► Specific antibodies against the C-terminus of the TCHHL1 protein were generated. ► TCHHL1 proteins were expressed in the basal layer of the normal epidermis. ► TCHHL1 proteins were strongly expressed in tumor nests of BCC and SCC. ► The expression of TCHHL1 proteins increased in epidermis of psoriasis vulgaris. - Abstract: Trichohyalin-like 1 (TCHHL1) protein is a novel member of the fused-type S100 protein gene family. The deduced amino acid sequence of TCHHL1 contains an EF-hand domain in the N-terminus, one trans-membrane domain and a nuclear localization signal. We generated specific antibodies against the C-terminus of the TCHHL1 protein and examined the expression of TCHHL1 proteins in normal and pathological human skin. An immunohistochemical study showed that TCHHL1 proteins were expressed in the basal layer of the normal epidermis. In addition, signals of TCHHL1 proteins were observed around the nuclei of cultured growing keratinocytes. Accordingly, TCHHL1 mRNA has been detected in normal skin and cultured growing keratinocytes. Furthermore, TCHHL1 proteins were strongly expressed in the peripheral areas of tumor nests in basal cell carcinomas and squamous cell carcinomas. A dramatic increase in the number of Ki67 positive cells was observed in TCHHL1-expressing areas. The expression of TCHHL1 proteins also increased in non-cancerous hyperproliferative epidermal tissues such as those of psoriasis vulgaris and lichen planus. These findings highlight the possibility that TCHHL1 proteins are expressed in growing keratinocytes of the epidermis and might be associated with the proliferation of keratinocytes.

  16. Generation of human single-chain variable fragment antibodies specific to dengue virus non-structural protein 1 that interfere with the virus infectious cycle.

    Science.gov (United States)

    Poungpair, Ornnuthchar; Bangphoomi, Kunan; Chaowalit, Prapaipit; Sawasdee, Nunghathai; Saokaew, Nichapatr; Choowongkomon, Kiattawee; Chaicumpa, Wanpen; Yenchitsomanus, Pa-thai

    2014-01-01

    Severe forms of dengue virus (DENV) infection frequently cause high case fatality rate. Currently, there is no effective vaccine against the infection. Clinical cases are given only palliative treatment as specific anti-DENV immunotherapy is not available and it is urgently required. In this study, human single-chain variable fragment (HuScFv) antibodies that bound specifically to the conserved non-structural protein-1 (NS1) of DENV and interfered with the virus replication cycle were produced by using phage display technology. Recombinant NS1 (rNS1) of DENV serotype 2 (DENV2) was used as antigen in phage bio-panning to select phage clones that displayed HuScFv from antibody phage display library. HuScFv from two phagemid transformed E. coli clones, i.e., clones 11 and 13, bound to the rNS1 as well as native NS1 in both secreted and intracellular forms. Culture fluids of the HuScFv11/HuScFv13 exposed DENV2 infected cells had significant reduction of the infectious viral particles, implying that the antibody fragments affected the virus morphogenesis or release. HuScFv epitope mapping by phage mimotope searching revealed that HuScFv11 bound to amino acids 1-14 of NS1, while the HuScFv13 bound to conformational epitope at the C-terminal portion of the NS1. Although the functions of the epitopes and the molecular mechanism of the HuScFv11 and HuScFv13 require further investigations, these small antibodies have high potential for development as anti-DENV biomolecules.

  17. 运用人性化护理内涵解决传染病护理中的伦理冲突%Humane Care Connotation to Resolve Ethical Conflicts in Nursing for Infectious Diseases

    Institute of Scientific and Technical Information of China (English)

    潘孟侠; 崔玉新; 于瀛

    2015-01-01

    目的:探讨人性化护理解决传染病护理中伦理冲突的效果。方法收集100例传染病患者,分为两组,各50例。对照组使用常规护理,观察组使用人性化护理,比较伦理冲突发生率。结果对照组患者伦理冲突发生率高于观察组患者。结论人性化护理能够降低传染病护理过程中的伦理冲突发生率。%Objective To investigate the humane care and treatment of infectious diseases to resolve ethical conflicts in effect. Methods Col ected 100 cases of patients with infectious diseases,divided into two groups,each of 50 cases. The control group using conventional care,humane care was used in the observation group,comparing the incidence of ethical conflicts. Results The rate of ethical conflict in the control group was significantly higher than the observation group. Conclusion Humane care and treatment wil reduce the incidence rate of ethical conflicts significantly in the process of nursing for infectious diseases.

  18. Pathological concentration of zinc dramatically accelerates abnormal aggregation of full-length human Tau and thereby significantly increases Tau toxicity in neuronal cells.

    Science.gov (United States)

    Hu, Ji-Ying; Zhang, De-Lin; Liu, Xiao-Ling; Li, Xue-Shou; Cheng, Xiao-Qing; Chen, Jie; Du, Hai-Ning; Liang, Yi

    2017-02-01

    A pathological hallmark of Alzheimer disease and other tauopathies is the formation of neurofibrillary tangles mainly composed of bundles of fibrils formed by microtubule-associated protein Tau. Here we study the effects of Zn(2+) on abnormal aggregation and cytotoxicity of a pathological mutant ΔK280 of full-length human Tau. As revealed by Congo red binding assays, transmission electron microscopy, immunofluorescence, Western blot, and immunogold electron microscopy, pathological concentration of Zn(2+) dramatically accelerates the fibrillization of ΔK280 both in vitro and in SH-SY5Y neuroblastoma cells. As evidenced by annexin V-FITC apoptosis detection assay and MTT reduction assay, pathological concentration of Zn(2+) remarkably enhances ΔK280 fibrillization-induced apoptosis and toxicity in SH-SY5Y cells. Substitution of Cys-291 and Cys-322 with Ala, however, essentially eliminates such enhancing effects of Zn(2+) on the fibrillization and the consequent cytotoxicity of ΔK280. Furthermore, Zn(2+) is co-localized with and highly enriched in amyloid fibrils formed by ΔK280 in SH-SY5Y cells. The results from isothermal titration calorimetry show that Zn(2+) binds to full-length human Tau by interacting with Cys-291 and Cys-322, forming a 1:1 Zn(2+)-Tau complex. Our data demonstrate that zinc dramatically accelerates abnormal aggregation of human Tau and significantly increases Tau toxicity in neuronal cells mainly via bridging Cys-291 and Cys-322. Our findings could explain how pathological zinc regulates Tau aggregation and toxicity associated with Alzheimer disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Infectious abortions in swine

    Directory of Open Access Journals (Sweden)

    Vakanjac Slobodanka

    2003-01-01

    Full Text Available Abortions in pigs can be caused by infectious or non-infectious factors About 38% of all diagnosed abortions in pigs were caused by infectious agents. Consequences of infection can be early embryonal deaths or abortions which occur after the 40th day following conception. Causes of abortions include different species of viruses (parvoviruses, enteroviruses pseudorabies viruses, PRRS or bacteria (Brucella, Leptospira, and others. A precise diagnosis is imperative for therapy and prevention of abortions in pigs, and it is necessary to apply measures to prevent reproductive disorders in pigs.

  20. Oral pathology.

    Science.gov (United States)

    Niemiec, Brook A

    2008-05-01

    Oral disease is exceedingly common in small animal patients. In addition, there is a very wide variety of pathologies that are encountered within the oral cavity. These conditions often cause significant pain and/or localized and systemic infection; however, the majority of these conditions have little to no obvious clinical signs. Therefore, diagnosis is not typically made until late in the disease course. Knowledge of these diseases will better equip the practitioner to effectively treat them. This article covers the more common forms of oral pathology in the dog and cat, excluding periodontal disease, which is covered in its own chapter. The various pathologies are presented in graphic form, and the etiology, clinical signs, recommended diagnostic tests, and treatment options are discussed. Pathologies that are covered include: persistent deciduous teeth, fractured teeth, intrinsically stained teeth, feline tooth resorption, caries, oral neoplasia, eosinophilic granuloma complex, lymphoplasmacytic gingivostomatitis, enamel hypoplasia, and "missing" teeth.

  1. Pathology Milestones

    Directory of Open Access Journals (Sweden)

    J. Stacey Klutts MD, PhD

    2015-10-01

    Full Text Available All Accreditation Council for Graduate Medical Education accredited pathology residency training programs are now required to evaluate residents using the new Pathology Milestones assessment tool. Similar to implementation of the 6 Accreditation Council for Graduate Medical Education competencies a decade ago, there have been challenges in implementation of the new milestones for many residency programs. The pathology department at the University of Iowa has implemented a process that divides the labor of the task in rating residents while also maintaining consistency in the process. The process is described in detail, and some initial trends in milestone evaluation are described and discussed. Our experience indicates that thoughtful implementation of the Pathology Milestones can provide programs with valuable information that can inform curricular changes.

  2. Links between Evolution, Development, Human Anatomy, Pathology, and Medicine, with A Proposition of A Re-defined Anatomical Position and Notes on Constraints and Morphological "Imperfections".

    Science.gov (United States)

    Diogo, Rui; Molnar, Julia

    2016-06-01

    Surprisingly the oldest formal discipline in medicine (anatomy) has not yet felt the full impact of evolutionary developmental biology. In medical anatomy courses and textbooks, the human body is still too often described as though it is a "perfect machine." In fact, the study of human anatomy predates evolutionary theory; therefore, many of its conventions continue to be outdated, making it difficult to study, understand, and treat the human body, and to compare it with that of other, nonbipedal animals, including other primates. Moreover, such an erroneous view of our anatomy as "perfect" can be used to fuel nonevolutionary ideologies such as intelligent design. In the section An Evolutionary and Developmental Approach to Human Anatomical Position of this paper, we propose the redefinition of the "human standard anatomical position" used in textbooks to be consistent with human evolutionary and developmental history. This redefined position also simplifies, for students and practitioners of the health professions, the study and learning of embryonic muscle groups (each group including muscles derived from the same/ontogenetically closely related primordium/primordia) and joint movements and highlights the topological correspondence between the upper and lower limbs. Section Evolutionary and Developmental Constraints, "Imperfections" and Sports Pathologies continues the theme by describing examples of apparently "illogical" characteristics of the human body that only make sense when one understands the developmental and evolutionary constraints that have accumulated over millions of years. We focus, in particular, on musculoskeletal functional problems and sports pathologies to emphasize the links with pathology and medicine. These examples demonstrate how incorporating evolutionary theory into anatomy education can be helpful for medical students, teachers, researchers, and physicians, as well as for anatomists, functional morphologists, and evolutionary and

  3. Infectious Agents and Cancer

    African Journals Online (AJOL)

    these agents on subsequent risk of cancer. There are currently ... tween genetic and environmental factors (that include infectious agents) .... opment of gastric adenocarcinoma and gastric lym- phoma. However .... Lung cancer i. Skin cancers ...

  4. Pathology of thyroid in acquired immunodeficiency syndrome

    Directory of Open Access Journals (Sweden)

    Dhaneshwar Namdeorao Lanjewar

    2016-01-01

    Full Text Available Background: The course of human immunodeficiency virus infection and the acquired immunodeficiency syndrome can be complicated by a variety of endocrine abnormalities, including abnormalities of thyroid gland. Materials and Methods: This study was designed to understand the spectrum of pathology of thyroid in Indian patients with AIDS. The present study describes the findings of retrospective autopsy findings of 158 patients with AIDS which revealed infectious diseases from a time period before the use of highly active antiretroviral regimen. Results: A wide range of bacterial, fungal, and viral infections were observed. Tuberculosis was recorded in 14 (09% patients, Cryptococcus neoformans in 11 (7% patients and cytomegalovirus in 3 (2% patients. Hashimoto's thyroiditis and lymphocytic thyroiditis were seen in 02 (01% patients each. One patient had dual infection comprising of tuberculosis and cytomegalovirus infection. The other microscopic findings observed were goiter (2 patients, interstitial fibrosis in thyroid (7 patients, and calcification in thyroid (8 patients. Conclusions: Abnormalities of thyroid are uncommon findings in patients with HIV infection however several case reports of thyroid involvement by infectious agents and neoplasm are described in these patients; hence patients with HIV infection should be closely followed up for development of goiter or abnormalities of thyroid functions.

  5. Gordon Wilson Lecture: Infectious Disease Causes of Cancer: Opportunities for Prevention and Treatment.

    Science.gov (United States)

    Howley, Peter M

    2015-01-01

    The role of infectious agents in cancer is generally underappreciated. However, approximately 20% of human cancers are caused by infectious agents and as such they rank second only to tobacco as a potentially preventable cause in humans. Specific viruses, parasites, and bacteria have been linked to specific human cancers. The infectious etiology for these specific cancers provides opportunities for prevention and treatment.

  6. Infectious bovine keratoconjunctivitis (pinkeye)

    OpenAIRE

    Angelos, JA

    2015-01-01

    Copyright © 2015 Elsevier Inc. All rights reserved. As is the case for controlling other infectious livestock diseases, the most successful efforts to control infectious bovine keratoconjunctivitis (IBK) will include consideration of the host, the environment, herd management, and ongoing surveillance even after the immediate crisis has passed. Research over many years has led to the discovery of a variety of antibiotic treatments and antibiotic regimens that can be effective against IBK. The...

  7. Pathology and first report of natural infections of the eye trematode Philophthalmus lachrymosus Braun, 1902 (Digenea, Philophthalmidae in a non-human mammalian host

    Directory of Open Access Journals (Sweden)

    Roberto Magalhães Pinto

    2005-10-01

    Full Text Available The avian eye trematode Philophthalmus lachrymosus Braun, 1902 is for the first time referred naturally occurring in a non-human mammalian host. Previously, natural infections with P. lachrymosus and other species of Philophthalmus have been occasionally reported from man, with few data on experimental infections of non-human mammals. Results presented here are related to the report of two cases of philophthalmosis due to natural infections of wild Brazilian capybaras, Hydrochaeris hydrochaeris L., 1766 with P. lachrymosus and associated pathology. Clinical signs, gross and microscopic lesions as well as new morphometric data on the parasite are presented.

  8. Helicobacter pylori lipopolysaccharide:Biological activities in vitro and in vivo, pathological correlation to human chronic gastritis and peptic ulcer

    Institute of Scientific and Technical Information of China (English)

    Yi-Hui Luo; Jie Yan; Ya-Fei Mao

    2004-01-01

    AIM: To determine the biological activity of Helicobacter pylori (Hpylori) lipopolysaccharide (H-LPS) and understand pathological correlation between H-LPS and human chronic gastritis and peptic ulcer.METHODS: H-LPS of a clinical Hpylori strain and LPS of Escherichia coli strain O55:B5 (E-LPS) were extracted by phenol-water method. Biological activities of H-LPS and E-LPS were detected by limulus lysate assay, pyrogen assay,blood pressure test and PBMC induction test in rabbits,cytotoxicity test in NIH 3T3 fibroblast cells and lethality test in NIH mice. By using self-prepared rabbit anti-H-LPS serum as the first antibody and commercial HRP-labeled sheep anti-rabbit sera as the second antibody, H-LPS in biopsy specimens from 126 patients with chronic gastritis (68 cases) or gastric ulcer (58 cases) were examined by immunohistochemistry.RESULTS: Fibroblast cytotoxicity and mouse lethality of H-LPS were weaker than those of E-LPS. But the ability of coagulating limulus lysate of the two LPSs was similar (+/0.5 ng/mL). At 0.5 h after H-LPS injection, the blood pressures of the 3 rabbits rapidly declined. At 1.0 h after H-LPS injection, the blood pressures in 2 of the 3 rabbits fell to zero causing death of the 2 animals. For the other one rabbit in the same group, its blood pressure gradually elevated. At 0.5 h after E-LPS injection, the blood pressures of the three rabbits also quickly declined and then maintained at low level for approximately 1.0 h. At 0.5 h after injection with H-LPS or E-LPS, PBMC numbers of the rabbits showed a remarkable increase. The total positivity rate of H-LPS from 126 biopsy specimens was 60.3%(76/126). H-LPS positivity rate in the biopsy specimens from chronic gastritis (50/68, 73.5%) was significantly higher than that from gastric ulcer (26/58, 44.8%) (X2=10.77,P<0.01). H-LPS positivity rates in biopsy specimens from chronic superficial gastritis (38/48, 79.2%) and chronic active gastritis (9/10, 90.0%) were significantly higher than

  9. Digital pathology

    CERN Document Server

    Sucaet, Yves

    2014-01-01

    Digital pathology has experienced exponential growth, in terms of its technology and applications, since its inception just over a decade ago. Though it has yet to be approved for primary diagnostics, its values as a teaching tool, facilitator of second opinions and quality assurance reviews and research are becoming, if not already, undeniable. It also offers the hope of providing pathology consultant and educational services to under-served areas, including regions of the world that could not possibly sustain this level of services otherwise. And this is just the beginning, as its adoption b

  10. A mouse model for fucosidosis recapitulates storage pathology and neurological features of the milder form of the human disease

    DEFF Research Database (Denmark)

    Wolf, Heike; Damme, Markus; Stroobants, Stijn

    2016-01-01

    were also partially excreted with the urine. Lysosomal storage pathology was observed in many visceral organs like liver, kidney, spleen and bladder as well as in the CNS. On the cellular level storage was characterized by membrane-limited cytoplasmic vacuoles primarily containing water-soluble storage...

  11. Human embryonic stem cell-derived pancreatic endoderm alleviates diabetic pathology and improves reproductive outcome in C57BL/KsJ-Lep(db/+) gestational diabetes mellitus mice.

    Science.gov (United States)

    Xing, Baoheng; Wang, Lili; Li, Qin; Cao, Yalei; Dong, Xiujuan; Liang, Jun; Wu, Xiaohua

    2015-07-01

    Gestational diabetes mellitus is a condition commonly encountered during mid to late pregnancy with pathologic manifestations including hyperglycemia, hyperinsulinemia, insulin resistance, and fetal maldevelopment. The cause of gestational diabetes mellitus can be attributed to both genetic and environmental factors, hence complicating its diagnosis and treatment. Pancreatic progenitors derived from human embryonic stem cells were shown to be able to effectively treat diabetes in mice. In this study, we have developed a system of treating diabetes using human embryonic stem cell-derived pancreatic endoderm in a mouse model of gestational diabetes mellitus. Human embryonic stem cells were differentiated in vitro into pancreatic endoderm, which were then transplanted into db/+ mice suffering from gestational diabetes mellitus. The transplant greatly improved glucose metabolism and reproductive outcome of the females compared with the control groups. Our findings support the feasibility of using differentiated human embryonic stem cells for treating gestational diabetes mellitus patients.

  12. Cardiac fibroblast-derived extracellular matrix (biomatrix) as a model for the studies of cardiac primitive cell biological properties in normal and pathological adult human heart.

    Science.gov (United States)

    Castaldo, Clotilde; Di Meglio, Franca; Miraglia, Rita; Sacco, Anna Maria; Romano, Veronica; Bancone, Ciro; Della Corte, Alessandro; Montagnani, Stefania; Nurzynska, Daria

    2013-01-01

    Cardiac tissue regeneration is guided by stem cells and their microenvironment. It has been recently described that both cardiac stem/primitive cells and extracellular matrix (ECM) change in pathological conditions. This study describes the method for the production of ECM typical of adult human heart in the normal and pathological conditions (ischemic heart disease) and highlights the potential use of cardiac fibroblast-derived ECM for in vitro studies of the interactions between ECM components and cardiac primitive cells responsible for tissue regeneration. Fibroblasts isolated from adult human normal and pathological heart with ischemic cardiomyopathy were cultured to obtain extracellular matrix (biomatrix), composed of typical extracellular matrix proteins, such as collagen and fibronectin, and matricellular proteins, laminin, and tenascin. After decellularization, this substrate was used to assess biological properties of cardiac primitive cells: proliferation and migration were stimulated by biomatrix from normal heart, while both types of biomatrix protected cardiac primitive cells from apoptosis. Our model can be used for studies of cell-matrix interactions and help to determine the biochemical cues that regulate cardiac primitive cell biological properties and guide cardiac tissue regeneration.

  13. Cardiac Fibroblast-Derived Extracellular Matrix (Biomatrix as a Model for the Studies of Cardiac Primitive Cell Biological Properties in Normal and Pathological Adult Human Heart

    Directory of Open Access Journals (Sweden)

    Clotilde Castaldo

    2013-01-01

    Full Text Available Cardiac tissue regeneration is guided by stem cells and their microenvironment. It has been recently described that both cardiac stem/primitive cells and extracellular matrix (ECM change in pathological conditions. This study describes the method for the production of ECM typical of adult human heart in the normal and pathological conditions (ischemic heart disease and highlights the potential use of cardiac fibroblast-derived ECM for in vitro studies of the interactions between ECM components and cardiac primitive cells responsible for tissue regeneration. Fibroblasts isolated from adult human normal and pathological heart with ischemic cardiomyopathy were cultured to obtain extracellular matrix (biomatrix, composed of typical extracellular matrix proteins, such as collagen and fibronectin, and matricellular proteins, laminin, and tenascin. After decellularization, this substrate was used to assess biological properties of cardiac primitive cells: proliferation and migration were stimulated by biomatrix from normal heart, while both types of biomatrix protected cardiac primitive cells from apoptosis. Our model can be used for studies of cell-matrix interactions and help to determine the biochemical cues that regulate cardiac primitive cell biological properties and guide cardiac tissue regeneration.

  14. Extreme weather events and infectious disease outbreaks.

    Science.gov (United States)

    McMichael, Anthony J

    2015-01-01

    Human-driven climatic changes will fundamentally influence patterns of human health, including infectious disease clusters and epidemics following extreme weather events. Extreme weather events are projected to increase further with the advance of human-driven climate change. Both recent and historical experiences indicate that infectious disease outbreaks very often follow extreme weather events, as microbes, vectors and reservoir animal hosts exploit the disrupted social and environmental conditions of extreme weather events. This review article examines infectious disease risks associated with extreme weather events; it draws on recent experiences including Hurricane Katrina in 2005 and the 2010 Pakistan mega-floods, and historical examples from previous centuries of epidemics and 'pestilence' associated with extreme weather disasters and climatic changes. A fuller understanding of climatic change, the precursors and triggers of extreme weather events and health consequences is needed in order to anticipate and respond to the infectious disease risks associated with human-driven climate change. Post-event risks to human health can be constrained, nonetheless, by reducing background rates of persistent infection, preparatory action such as coordinated disease surveillance and vaccination coverage, and strengthened disaster response. In the face of changing climate and weather conditions, it is critically important to think in ecological terms about the determinants of health, disease and death in human populations.

  15. Emergent infectious uveitis

    Directory of Open Access Journals (Sweden)

    Khairallah Moncef

    2009-01-01

    Full Text Available Infectious causes should always be considered in all patients with uveitis and it should be ruled out first. The differential diagnosis includes multiple well-known diseases including herpes, syphilis, toxoplasmosis, tuberculosis, bartonellosis, Lyme disease, and others. However, clinicians should be aware of emerging infectious agents as potential causes of systemic illness and also intraocular inflammation. Air travel, immigration, and globalization of business have overturned traditional pattern of geographic distribution of infectious diseases, and therefore one should work locally but think globally, though it is not possible always. This review recapitulates the systemic and ocular mainfestations of several emergent infectious diseases relevant to the ophthalmologist including Rickettsioses, West Nile virus infection, Rift valley fever, dengue fever, and chikungunya. Retinitis, chorioretinitis, retinal vasculitis, and optic nerve involvement have been associated with these emergent infectious diseases. The diagnosis of any of these infections is usually based on pattern of uveitis, systemic symptoms and signs, and specific epidemiological data and confirmed by detection of specific antibody in serum. A systematic ocular examination, showing fairly typical fundus findings, may help in establishing an early clinical diagnosis, which allows prompt, appropriate management.

  16. Inguinoscrotal pathology

    Science.gov (United States)

    Guerra, Luis; Leonard, Michael

    2017-01-01

    Infants, children, and adolescents with inguinoscrotal pathology comprise a significant proportion of emergency department and outpatient visits. Visits to the emergency department primarily comprise individuals presenting with scrotal pain due to testicular torsion or torsion of the testicular appendages. At such time, immediate urological consultation is sought. Outpatient visits comprise those individuals with undescended testes, hydroceles, and varicoceles. Rare, but important problems, such as pediatric testicular tumours, may also present in the office setting. Many of these outpatient visits are to primary care physicians, who should have an appreciation of the timing and need for referral. The purpose of this review is to familiarize the general urologist and primary care physician with these varied pathologies and give insight into their assessment and management. Some of these same conditions are seen in adult patients, but there are some significant differences in their management in the pediatric group. In addition, the utility of imaging studies, such as ultrasound, are discussed within each pathological entity. It is hoped that this overview will assist our general urology and primary care colleagues in patient management for diverse inguinoscrotal pathologies. PMID:28265317

  17. Infectious bovine keratoconjunctivitis (pinkeye).

    Science.gov (United States)

    Angelos, John A

    2015-03-01

    As is the case for controlling other infectious livestock diseases, the most successful efforts to control infectious bovine keratoconjunctivitis (IBK) will include consideration of the host, the environment, herd management, and ongoing surveillance even after the immediate crisis has passed. Research over many years has led to the discovery of a variety of antibiotic treatments and antibiotic regimens that can be effective against IBK. The discoveries of Mor bovoculi and reports of IBK associated with Mycoplasma spp without concurrent Mor bovis or Mor bovoculi have raised new questions into the roles that other organisms may play in IBK pathogenesis.

  18. [Proteomics in infectious diseases].

    Science.gov (United States)

    Quero, Sara; Párraga-Niño, Noemí; García-Núñez, Marian; Sabrià, Miquel

    2016-04-01

    Infectious diseases have a high incidence in the population, causing a major impact on global health. In vitro culture of microorganisms is the first technique applied for infection diagnosis which is laborious and time consuming. In recent decades, efforts have been focused on the applicability of "Omics" sciences, highlighting the progress provided by proteomic techniques in the field of infectious diseases. This review describes the management, processing and analysis of biological samples for proteomic research. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  19. Enumeration of the colony-forming units–fibroblast from mouse and human bone marrow in normal and pathological conditions

    OpenAIRE

    Kuznetsov, Sergei A; Mankani, Mahesh H.; Bianco, Paolo; Robey, Pamela G.

    2008-01-01

    Bone marrow stromal cell populations, containing a subset of multipotential skeletal stem cells, are increasingly contemplated for use in tissue engineering and stem cell therapy, whereas their involvement in the pathogenetic mechanisms of skeletal disorders is far less recognized. We compared the concentrations of stromal clonogenic cells, colony forming units–fibroblast (CFU-Fs), in norm and pathology. Initially, culture conditions were optimized by demonstrating that fetal bovine serum hea...

  20. Homing of regulatory T cells to human skin is important for the prevention of alloimmune-mediated pathology in an in vivo cellular therapy model.

    Directory of Open Access Journals (Sweden)

    Fadi Issa

    Full Text Available Regulatory T cell (Treg therapy for immune modulation is a promising therapeutic strategy for the treatment and prevention of autoimmune disease and graft-versus-host disease (GvHD after bone marrow transplantation. However, Treg are heterogeneous and express a variety of chemokine receptor molecules. The optimal subpopulation of Treg for therapeutic use may vary according to the pathological target. Indeed, clinical trials of Treg for the prevention of GvHD where the skin is a major target of the anti-host response have employed Treg derived from a variety of different sources. We postulated that for the effective treatment of GvHD-related skin pathology, Treg must be able to migrate to skin in order to regulate local alloimmune responses efficiently. To test the hypothesis that different populations of Treg display distinct efficacy in vivo based on their expression of tissue-specific homing molecules, we evaluated the activity of human Treg derived from two disparate sources in a model of human skin transplantation. Treg were derived from adult blood or cord blood and expanded in vitro. While Treg from both sources displayed similar in vitro suppressive efficacy, they exhibited marked differences in the expression of skin homing molecules. Importantly, only adult-derived Treg were able to prevent alloimmune-mediated human skin destruction in vivo, by virtue of their improved migration to skin. The presence of Treg within the skin was sufficient to prevent its alloimmune-mediated destruction. Additionally, Treg expressing the skin homing cutaneous lymphocyte antigen (CLA were more efficient at preventing skin destruction than their CLA-deficient counterparts. Our findings highlight the importance of the careful selection of an effective subpopulation of Treg for clinical use according to the pathology of interest.

  1. Eosinophilia in Infectious Diseases.

    Science.gov (United States)

    O'Connell, Elise M; Nutman, Thomas B

    2015-08-01

    In determining the etiology of eosinophilia, it is necessary to consider the type of patient, including previous travel and exposure history, comorbidities, and symptoms. In this review, we discuss the approach to the patient with eosinophilia from an infectious diseases perspective based on symptom complexes. Published by Elsevier Inc.

  2. Feline infectious peritonitis: still an enigma?

    Science.gov (United States)

    Kipar, A; Meli, M L

    2014-03-01

    Feline infectious peritonitis (FIP) is one of the most important fatal infectious diseases of cats, the pathogenesis of which has not yet been fully revealed. The present review focuses on the biology of feline coronavirus (FCoV) infection and the pathogenesis and pathological features of FIP. Recent studies have revealed functions of many viral proteins, differing receptor specificity for type I and type II FCoV, and genomic differences between feline enteric coronaviruses (FECVs) and FIP viruses (FIPVs). FECV and FIP also exhibit functional differences, since FECVs replicate mainly in intestinal epithelium and are shed in feces, and FIPVs replicate efficiently in monocytes and induce systemic disease. Thus, key events in the pathogenesis of FIP are systemic infection with FIPV, effective and sustainable viral replication in monocytes, and activation of infected monocytes. The host's genetics and immune system also play important roles. It is the activation of monocytes and macrophages that directly leads to the pathologic features of FIP, including vasculitis, body cavity effusions, and fibrinous and granulomatous inflammatory lesions. Advances have been made in the clinical diagnosis of FIP, based on the clinical pathologic findings, serologic testing, and detection of virus using molecular (polymerase chain reaction) or antibody-based methods. Nevertheless, the clinical diagnosis remains challenging in particular in the dry form of FIP, which is partly due to the incomplete understanding of infection biology and pathogenesis in FIP. So, while much progress has been made, many aspects of FIP pathogenesis still remain an enigma.

  3. 77 FR 5035 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-02-01

    ... HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases... personal privacy. Name of Committee: National Institute of Allergy and Infectious Diseases Special Emphasis... . (Catalogue of Federal Domestic Assistance Program Nos. 93.855, Allergy, Immunology, and...

  4. 78 FR 9404 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2013-02-08

    ... HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases... personal privacy. Name of Committee: National Institute of Allergy and Infectious Diseases Special Emphasis... of Federal Domestic Assistance Program Nos. 93.855, Allergy, Immunology, and Transplantation...

  5. 75 FR 22817 - Emerging Infectious Diseases: Evaluation to Implementation for Transfusion and Transplantation...

    Science.gov (United States)

    2010-04-30

    ... HUMAN SERVICES Food and Drug Administration Emerging Infectious Diseases: Evaluation to Implementation.... The Food and Drug Administration (FDA) is announcing two public workshops entitled ``Emerging... of risk from, and prioritization of response to, emerging infectious diseases relevant to blood...

  6. The homozygote VCP(R¹⁵⁵H/R¹⁵⁵H mouse model exhibits accelerated human VCP-associated disease pathology.

    Directory of Open Access Journals (Sweden)

    Angèle Nalbandian

    Full Text Available Valosin containing protein (VCP mutations are the cause of hereditary inclusion body myopathy, Paget's disease of bone, frontotemporal dementia (IBMPFD. VCP gene mutations have also been linked to 2% of isolated familial amyotrophic lateral sclerosis (ALS. VCP is at the intersection of disrupted ubiquitin proteasome and autophagy pathways, mechanisms responsible for the intracellular protein degradation and abnormal pathology seen in muscle, brain and spinal cord. We have developed the homozygous knock-in VCP mouse (VCP(R155H/R155H model carrying the common R155H mutations, which develops many clinical features typical of the VCP-associated human diseases. Homozygote VCP(R155H/R155H mice typically survive less than 21 days, exhibit weakness and myopathic changes on EMG. MicroCT imaging of the bones reveal non-symmetrical radiolucencies of the proximal tibiae and bone, highly suggestive of PDB. The VCP(R155H/R155H mice manifest prominent muscle, heart, brain and spinal cord pathology, including striking mitochondrial abnormalities, in addition to disrupted autophagy and ubiquitin pathologies. The VCP(R155H/R155H homozygous mouse thus represents an accelerated model of VCP disease and can be utilized to elucidate the intricate molecular mechanisms involved in the pathogenesis of VCP-associated neurodegenerative diseases and for the development of novel therapeutic strategies.

  7. Infectious uveitis in Virginia

    Directory of Open Access Journals (Sweden)

    Engelhard SB

    2015-08-01

    Full Text Available Stephanie B Engelhard,1 Zeina Haddad,1 Asima Bajwa,1 James Patrie,2 Wenjun Xin,2 Ashvini K Reddy1 1Department of Ophthalmology, 2Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA Purpose: To report the causes, clinical features, and outcomes of infectious uveitis in patients managed in a mid-Atlantic tertiary care center.Methods: Retrospective, observational study of infectious uveitis patients seen at the University of Virginia from 1984 to 2014.Results: Seventy-seven of 491 patients (15.7% were diagnosed with infectious uveitis (mean age 58 years, 71.4% female, 76.6% Caucasian. The mean follow-up was 5 years. Anterior uveitis was the most common anatomic classification (39 patients, 50.6% followed by panuveitis (20 patients, 26.0% and posterior uveitis (18 patients, 23.4%. The most common infectious etiology was herpetic anterior uveitis (37 patients, 48.1% followed by toxoplasma uveitis (14 patients, 18.2%. The most prevalent viral pathogen was varicella-zoster virus (21 patients, 27.3% followed by herpes simplex virus (20 patients, 26.0%. Acute retinal necrosis (ARN was diagnosed in 14 patients (18.2%. Aqueous humor yielded an etiologic diagnosis in seven (50% of ARN patients, four of whom tested positive for cytomegalovirus and three for varicella-zoster virus. On presentation, 43 patients (55.8% had a visual acuity (VA better than 20/40 and 17 (22.1% had a VA worse than 20/200. VA at the final follow-up was better than 20/40 in 39 patients (50.6% and worse than 20/200 in 22 patients (28.6%. In all, 16 (20.8% and 10 (13.0% patients required cataract and vitrectomy surgery, respectively. A total of 14 patients (18.2% were on glaucoma topical treatment and four (5.2% required glaucoma surgery.Conclusion: The most common type of infectious uveitis seen over the study period was herpetic anterior uveitis secondary to varicella-zoster virus or herpes simplex virus, found to be most prevalent in patients

  8. Cidofovir treatment improves the pathology caused by the growth of human papillomavirus-positive cervical carcinoma xenografts in athymic nude mice.

    Science.gov (United States)

    De Schutter, Tim; Andrei, Graciela; Topalis, Dimitri; Duraffour, Sophie; Mitera, Tania; Naesens, Lieve; van den Oord, Joost; Matthys, Patrick; Snoeck, Robert

    2013-02-28

    Cidofovir has shown antiproliferative effects against human papillomavirus (HPV)-positive cells and successfully suppressed the growth of HPV-positive xenografts in athymic nude mice. The present study evaluated the effect of cidofovir on several disease parameters in this animal model. Intratumoral administration of cidofovir resulted in a beneficial effect on body weight gain, a reduction in splenomegaly, a partial restoration of tryptophan catabolism, and diminished the inflammatory state induced by the xenografts. Administration of cidofovir to tumor-free animals did not have a direct effect on these parameters. Beyond suppressing tumor growth, intratumoral treatment with cidofovir ameliorated the pathology associated with HPV-tumor growth.

  9. Climate change and infectious diseases in the Arctic

    DEFF Research Database (Denmark)

    Parkinson, Alan J; Evengard, Birgitta; Semenza, Jan C

    2014-01-01

    distribution of a range of infectious diseases. Many infectious diseases are climate sensitive, where their emergence in a region is dependent on climate-related ecological changes. Most are zoonotic diseases, and can be spread between humans and animals by arthropod vectors, water, soil, wild or domestic...

  10. Progressive Motor Neuron Pathology and the Role of Astrocytes in a Human Stem Cell Model of VCP-Related ALS

    Directory of Open Access Journals (Sweden)

    Claire E. Hall

    2017-05-01

    Full Text Available Motor neurons (MNs and astrocytes (ACs are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS, but their interaction and the sequence of molecular events leading to MN death remain unresolved. Here, we optimized directed differentiation of induced pluripotent stem cells (iPSCs into highly enriched (> 85% functional populations of spinal cord MNs and ACs. We identify significantly increased cytoplasmic TDP-43 and ER stress as primary pathogenic events in patient-specific valosin-containing protein (VCP-mutant MNs, with secondary mitochondrial dysfunction and oxidative stress. Cumulatively, these cellular stresses result in synaptic pathology and cell death in VCP-mutant MNs. We additionally identify a cell-autonomous VCP-mutant AC survival phenotype, which is not attributable to the same molecular pathology occurring in VCP-mutant MNs. Finally, through iterative co-culture experiments, we uncover non-cell-autonomous effects of VCP-mutant ACs on both control and mutant MNs. This work elucidates molecular events and cellular interplay that could guide future therapeutic strategies in ALS.

  11. Morphological and chemical studies of pathological human and mice brain at the subcellular level: correlation between light, electron, and nanosims microscopies.

    Science.gov (United States)

    Quintana, Carmen; Wu, Ting-Di; Delatour, Benoit; Dhenain, Marc; Guerquin-Kern, Jean Luc; Croisy, Alain

    2007-04-01

    Neurodegenerative diseases induce morphological and chemical alterations in well-characterized regions of the brain. Understanding their pathological processes requires the use of methods that assess both morphological and chemical alterations in the tissues. In the past, microprobe approaches such as scanning electron microscopy combined with an X-ray spectrometer, Proton induced X-ray emission, secondary ion mass spectrometry (SIMS), and laser microprobe mass analysis have been used for the study of pathological human brain with limited success. At the present, new SIMS instruments have been developed, such as the NanoSIMS-50 ion microprobe, that allow the simultaneous identification of five elements with high sensitivity, at subcellular spatial resolution (about 50-100 nm with the Cs(+) source and about 150-200 nm with O(-) source). Working in scanning mode, 2D distribution of five elements (elemental maps) can be obtained, thus providing their exact colocalization. The analysis can be performed on semithin or ultrathin embedded sections. The possibility of using transmission electron microscopy and SIMS on the same ultrathin sections allows the correlation between structural and analytical observations at subcellular and ultrastructural level to be established. Our observations on pathological brain areas allow us to establish that the NanoSIMS-50 ion microprobe is a highly useful instrument for the imaging of the morphological and chemical alterations that take place in these brain areas. In the human brain our results put forward the subcellular distribution of iron-ferritin-hemosiderin in the hippocampus of Alzheimer disease patients. In the thalamus of transgenic mice, our results have shown the presence of Ca-Fe mineralized amyloid deposits.

  12. A Simple Method for Establishing Adherent Ex Vivo Explant Cultures from Human Eye Pathologies for Use in Subsequent Calcium Imaging and Inflammatory Studies

    Directory of Open Access Journals (Sweden)

    Sofija Andjelic

    2014-01-01

    Full Text Available A novel, simple, and reproducible method for cultivating pathological tissues obtained from human eyes during surgery was developed using viscoelastic material as a tissue adherent to facilitate cell attachment and expansion and calcium imaging of cultured cells challenged by mechanical and acetylcholine (ACh stimulation as well as inflammatory studies. Anterior lens capsule-lens epithelial cells (aLC-LECs from cataract surgery and proliferative diabetic retinopathy (PDR fibrovascular epiretinal membranes (fvERMs from human eyes were used in the study. We hereby show calcium signaling in aLC-LECs by mechanical and acetylcholine (ACh stimulation and indicate presence of ACh receptors in these cells. Furthermore, an ex vivo study model was established for measuring the inflammatory response in fvERMs and aLC-LECs upon TNFα treatment.

  13. Biodiversity loss and infectious diseases: chapter 5

    Science.gov (United States)

    Lafferty, Kevin D.

    2014-01-01

    When conservation biologists think about infectious diseases, their thoughts are mostly negative. Infectious diseases have been associated with the extinction and endangerment of some species, though this is rare, and other factors like habitat loss and poorly regulated harvest still are the overwhelming drivers of endangerment. Parasites are pervasive and play important roles as natural enemies on par with top predators, from regulating population abundances to maintaining species diversity. Sometimes, parasites themselves can be endangered. However, it seems unlikely that humans will miss extinct parasites. Parasites are often sensitive to habitat loss and degradation, making them positive indicators of ecosystem “health”. Conservation biologists need to carefully consider infectious diseases when planning conservation actions. This can include minimizing the movement of domestic and invasive species, vaccination, and culling.

  14. Inflammatory, vascular, and infectious myelopathies in children.

    Science.gov (United States)

    Verhey, Leonard H; Banwell, Brenda L

    2013-01-01

    Acute nontraumatic myelopathies of childhood include inflammatory, infectious, and vascular etiologies. Inflammatory immune-mediated disorders of the spinal cord can be categorized as idiopathic isolated transverse myelitis, neuromyelitis optica, and multiple sclerosis. In recent years, human T-cell lymphotropic virus type 1, West Nile virus, enterovirus-71, and Lyme disease have been increasingly recognized as infectious etiologies of myelopathy, and poliomyelitis remains an important etiology in world regions where vaccination programs have not been universally available. Vascular etiologies include vasculopathies (systemic lupus erythematosus, small vessel primary angiitis of the central nervous system), arteriovenous malformations, and spinal cord infarction (fibrocartilaginous embolism, diffuse hypoxic ischemia-mediated infarction). Vascular myelopathies are less common than inflammatory and infectious myelopathies, but are more likely to lead to devastating clinical deficits. Current therapeutic strategies include acute anti-inflammatory treatment and rehabilitation. Stem cell transplantation, nerve graft implantation, and stimulation of endogenous repair mechanisms represent promising strategies for spinal cord repair.

  15. Sapronosis: a distinctive type of infectious agent

    Science.gov (United States)

    Kuris, Armand M.; Lafferty, Kevin D.; Sokolow, Susanne H.

    2014-01-01

    Sapronotic disease agents have evolutionary and epidemiological properties unlike other infectious organisms. Their essential saprophagic existence prevents coevolution, and no host–parasite virulence trade-off can evolve. However, the host may evolve defenses. Models of pathogens show that sapronoses, lacking a threshold of transmission, cannot regulate host populations, although they can reduce host abundance and even extirpate their hosts. Immunocompromised hosts are relatively susceptible to sapronoses. Some particularly important sapronoses, such as cholera and anthrax, can sustain an epidemic in a host population. However, these microbes ultimately persist as saprophages. One-third of human infectious disease agents are sapronotic, including nearly all fungal diseases. Recognition that an infectious disease is sapronotic illuminates a need for effective environmental control strategies.

  16. 76 FR 39041 - Infectious Diseases

    Science.gov (United States)

    2011-07-05

    ... Occupational Safety and Health Administration 29 CFR Part 1910 RIN 1218-AC46 Infectious Diseases AGENCY... exposure to infectious diseases. OSHA plans to use the information gathered at these meetings to explore... your request to: (781) 674-7200, and label it ``Attention: OSHA Infectious Diseases Stakeholder...

  17. [CHRONIC DIARRHEA OF INFECTIOUS ETIOLOGY

    Science.gov (United States)

    Farfán F G, Gustavo

    1997-01-01

    Chronic Diarrhea syndrome is due to several causes. In LatinAmericen countries, infectious and parasitic etiology is frequent. Withinthese infections, the following has been determined: parasitic and enterobacterial agents, overpopulation of bacteria syndrome in the upper small bowel (SOBIA, abbreviation for Síndrome de Sobrepoblación Bacteriana del Intestino Delgado Alto), intestinal TBC, and AIDS. In these processes, the precipitating factor may be unique or multifactor; or there could also exist a tendency towards pathologies for these infections. There has been evidence of SOBIA cases without associated factor in Latin American countries. A study made in Peru shows SOBIA cases in 30 percent of chronic diarrhea.In chronic diarrhea cases, and even more, in those diarrheas of infectiousetiology, a complete study should be made, considering the several factorsthat generate diarrhea in a same one case, such as the mechanisms ofimmunodeficiency, neurological, endocrinemetabolic, and others associated with intestinal infections. This approach will be helpful to make a complete diagnosis and apply timely treatment.

  18. Predicting global variation in infectious disease severity

    DEFF Research Database (Denmark)

    Jensen, Per Moestrup; de Fine Licht, Henrik Hjarvard

    2016-01-01

    Background and objectives: Understanding the underlying causes for the variation in case-fatality-ratios (CFR) is important for assessing the mechanism governing global disparity in the burden of infectious diseases. Variation in CFR is likely to be driven by factors such as population genetics...... to their biology. We suggest that the overall result reflects an interaction between the forces driving demographic change and the virulence of human-to-human transmitted diseases....

  19. Protein misfolding cyclic amplification of infectious prions.

    Science.gov (United States)

    Morales, Rodrigo; Duran-Aniotz, Claudia; Diaz-Espinoza, Rodrigo; Camacho, Manuel V; Soto, Claudio

    2012-06-28

    Prions are proteinaceous infectious agents responsible for the transmission of prion diseases. The lack of a procedure for cultivating prions in the laboratory has been a major limitation to the study of the unorthodox nature of this infectious agent and the molecular mechanism by which the normal prion protein (PrP(C)) is converted into the abnormal isoform (PrP(Sc)). Protein misfolding cyclic amplification (PMCA), described in detail in this protocol, is a simple, fast and efficient methodology to mimic prion replication in the test tube. PMCA involves incubating materials containing minute amounts of infectious prions with an excess of PrP(C) and boosting the conversion by cycles of sonication to fragment the converting units, thereby leading to accelerated prion replication. PMCA is able to detect the equivalent of a single molecule of infectious PrP(Sc) and propagate prions that maintain high infectivity, strain properties and species specificity. A single PMCA assay takes little more than 3 d to replicate a large amount of prions, which could take years in an in vivo situation. Since its invention 10 years ago, PMCA has helped to answer fundamental questions about this intriguing infectious agent and has been broadly applied in research areas that include the food industry, blood bank safety and human and veterinary disease diagnosis.

  20. A comprehensive infectious disease management system.

    Science.gov (United States)

    Marcu, Alex; Farley, John D

    2009-01-01

    An efficient electronic management system is now an essential tool for the successful management and monitoring of those affected by communicable infectious diseases (Human Immunodeficiency Virus - HIV, hepatitis C - HEP C) during the course of the treatment. The current methods which depend heavily on manual collecting, compiling and disseminating treatment information are labor-intensive and time consuming. Clinics specialized in the treatment of infectious diseases use a mix of electronic systems that fail to interact with each other, result in data duplication, and do not support treatment of the patient as a whole. The purpose of the Infectious Disease Management System is to reduce the administrative overhead associated with data collection and analysis while providing correlation abilities and decision support in accordance with defined treatment guidelines. This Infectious Disease Management System was developed to: Ensure cost effectiveness by means of low software licensing costs, Introduce a centralized mechanism of collecting and monitoring all infectious disease management data, Automate electronic retrieval of laboratory findings, Introduce a decision support mechanism as per treatment guidelines, Seamlessly integrate of application modules, Provide comprehensive reporting capabilities, Maintain a high level of user friendliness.

  1. Wetlands and infectious diseases

    OpenAIRE

    Robert H. Zimmerman

    2001-01-01

    There is a historical association between wetlands and infectious disease that has led to the modification of wetlands to prevent disease. At the same time there has been the development of water resources projects that increase the risk of disease. The demand for more water development projects and the increased pressure to make natural wetlands economically beneficial creates the need for an ecological approach to wetland management and health assessment. The environmental and health intera...

  2. The large-scale functional connectivity correlates of consciousness and arousal during the healthy and pathological human sleep cycle

    NARCIS (Netherlands)

    Tagliazucchi, E.; van Someren, Eus J W

    2017-01-01

    Advances in neuroimaging have greatly improved our understanding of human sleep from a systems neuroscience perspective. However, cognition and awareness are reduced during sleep, hindering the applicability of standard task-based paradigms. Methods recently developed to study spontaneous brain

  3. Ultrastructural characteristics of novel epithelial cell types identified in human pathologic liver specimens with chronic ductular reaction.

    OpenAIRE

    De Vos, R; Desmet, V

    1992-01-01

    Previous immunohistochemical studies on human liver biopsies with chronic ductular reaction revealed the presence of "small cells" with bile-duct type cytokeratin profile in the periportal area. This study identified similar cells by electron microscopy. The authors studied 13 human liver specimens with various liver diseases, but all characterized by chronic ductular reaction. In all specimens, variable numbers of "small cells" with common epithelial characteristics were identified in the pe...

  4. The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features

    Science.gov (United States)

    Fan, Shengtao; Cai, Hongzhi; Xu, Xingli; Feng, Min; Wang, Lichun; Liao, Yun; Zhang, Ying; He, Zhanlong; Yang, Fengmei; Yu, Wenhai; Wang, Jingjing; Zhou, Jumin; Li, Qihan

    2017-01-01

    As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1) causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1. Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post-infection, and viral latency-associated transcript (LAT) mRNA was found in the trigeminal ganglia (TG) on day 365 post-infection. Neutralization testing and enzyme-linked immunospot (ELISpot) detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues. PMID:28146109

  5. STUDY ON ORGANIZATIONAL PATHOLOGY AND IMPLICATIONS ON HUMAN RESOURCES JOB SATISFACTION, ALSO ON THE EMPLOYMENT OF THE LABOR MARKET

    Directory of Open Access Journals (Sweden)

    Diana-Elena, SERB

    2014-11-01

    Full Text Available People need to face the demands resulting induced neurotic styles of their leaders. The result is lower morale, affect behavior, dissatisfaction at work. This paper aims to present the point of view of theoretical and practical implications of failures in the organization on job satisfaction of employees. The practical part of this article is the analysis of statistically labor employment level , and a marketing research field, a survey using questionnaire as the main instrument. The main objectives during the research aims: knowledge labor employment in Romania, identify employee satisfaction on labor relations between managers and subordinates, knowledge of the involvement of the manager in providing a suitable work environment, to determine the extent the problems arising in the workplace creates dissatisfaction which ultimately rebounds on return. The main results drawn as a result of research carried out show that existing pathology in an organization is felt on one side by the employee the aggression and persecution has implications for morale, and on the other hand these disturbances are felt at employment in that workplace, stress employees resign and this leads to higher unemployment.

  6. The SIRT 3 Expression Profile is Associated with Pathological and Clinical Outcomes in Human Breast Cancer Patients

    Directory of Open Access Journals (Sweden)

    Shaozhong He

    2014-11-01

    Full Text Available Aims: To investigate the association of Sirtuin 3 (SIRT 3 expression between the clinical characteristics and prognosis in breast cancer patients. Methods: 308 female patients with histologically confirmed breast cancer were enrolled in this study. The SIRT 3 expressions in tumor samples were detected. All the patients were followed up overall survival time (OS and disease-free survival (DFS time. Results: SIRT 3 expression was significantly correlated with clinical characteristics including lymph node metastasis, pathological grade and tumor size of breast cancer. SIRT 3 expression status also affected the DFS and OS of breast cancer. Patients with high expression of SIRT 3 had shorter DFS and OS than those with low expression. Univariate and multivariate Cox analyses confirmed that high SIRT 3 expression predicted a poor prognosis in breast cancer patient. In vitro study revealed that the SIRT 3 knockdown by small interfering RNA technique dramatically reduced the proliferation, migration and invasion of breast cancer cell lines. Conclusion: Our results suggest that SIRT 3 may serve as a marker for clinical feature and prognosis for breast cancer.

  7. The Use of Human Adipose-Derived Stem Cells in the Treatment of Physiological and Pathological Vulvar Dystrophies

    Directory of Open Access Journals (Sweden)

    Maria Giuseppina Onesti

    2016-01-01

    Full Text Available “Vulvar dystrophy” is characterized by chronic alterations of vulvar trophism, occurring in both physiological (menopause and pathological (lichen sclerosus, vulvar graft-versus-host disease conditions. Associated symptoms are itching, burning, dyspareunia and vaginal dryness. Current treatments often do not imply a complete remission of symptoms. Adipose-Derived Stem Cells (ADSCs injection represents a valid alternative therapy to enhance trophism and tone of dystrophic tissues. We evaluated efficacy of ADSCs-based therapy in the dystrophic areas. From February to April 2013 we enrolled 8 patients with vulvar dystrophy. A biopsy specimen was performed before and after treatment. Digital photographs were taken at baseline and during the follow-up. Pain was detected with Visual Analogue Scale and sexual function was evaluated with Female Sexual Function Index. All patients received 2 treatments in 3 months. Follow-up was at 1 week , 1 and 3 months, and 1 and 2 years. We obtained a significant vulvar trophism enhancement in all patients, who reported pain reduction and sexual function improvement. Objective exam with speculum was easy to perform after treatment. We believe ADSCs-based therapy finds its application in the treatment of vulvar dystrophies, since ADSCs could induce increased vascularization due to their angiogenic properties and tissue trophism improvement thanks to their eutrophic effect.

  8. SteatoNet: the first integrated human metabolic model with multi-layered regulation to investigate liver-associated pathologies.

    Directory of Open Access Journals (Sweden)

    Adviti Naik

    2014-12-01

    Full Text Available Current state-of-the-art mathematical models to investigate complex biological processes, in particular liver-associated pathologies, have limited expansiveness, flexibility, representation of integrated regulation and rely on the availability of detailed kinetic data. We generated the SteatoNet, a multi-pathway, multi-tissue model and in silico platform to investigate hepatic metabolism and its associated deregulations. SteatoNet is based on object-oriented modelling, an approach most commonly applied in automotive and process industries, whereby individual objects correspond to functional entities. Objects were compiled to feature two novel hepatic modelling aspects: the interaction of hepatic metabolic pathways with extra-hepatic tissues and the inclusion of transcriptional and post-transcriptional regulation. SteatoNet identification at normalised steady state circumvents the need for constraining kinetic parameters. Validation and identification of flux disturbances that have been proven experimentally in liver patients and animal models highlights the ability of SteatoNet to effectively describe biological behaviour. SteatoNet identifies crucial pathway branches (transport of glucose, lipids and ketone bodies where changes in flux distribution drive the healthy liver towards hepatic steatosis, the primary stage of non-alcoholic fatty liver disease. Cholesterol metabolism and its transcription regulators are highlighted as novel steatosis factors. SteatoNet thus serves as an intuitive in silico platform to identify systemic changes associated with complex hepatic metabolic disorders.

  9. Role of the Yes and Csk tyrosine kinases in the development of a pathological state in the human retina.

    Science.gov (United States)

    Baranova, Lyudmila; Emelyanova, Valentina; Volotovski, Igor

    2010-07-01

    Amplification and a cloning of fragments of genes of human retina tyrosine kinases, the nucleotide sequences of which feature a high homology to the gene families of the Yes and Csk tyrosine kinases, and a cloning of the complete coding sequence of the cDNA of the Csk tyrosine kinase gene of the human lymphocytes have been carried out. It has been established that this sequence contains 1,624 bp and encodes a protein that, with a 99% homology, corresponds to the human tyrosine kinase. A comparative analysis of the nucleotide sequences of the full-size cDNA of the Csk tyrosine kinase of the lymphocytes of healthy donors and of patients with an eye choroidal melanoma has shown that a risk of development of an eye choroidal melanoma can be estimated by the frequency of occurrence of a mutant allele in the 10th exon.

  10. Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions

    Energy Technology Data Exchange (ETDEWEB)

    Tusscher, K H W J Ten; Panfilov, A V [Department of Theoretical Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht (Netherlands)

    2006-12-07

    In this paper, we formulate a model for human ventricular cells that is efficient enough for whole organ arrhythmia simulations yet detailed enough to capture the effects of cell level processes such as current blocks and channelopathies. The model is obtained from our detailed human ventricular cell model by using mathematical techniques to reduce the number of variables from 19 to nine. We carefully compare our full and reduced model at the single cell, cable and 2D tissue level and show that the reduced model has a very similar behaviour. Importantly, the new model correctly produces the effects of current blocks and channelopathies on AP and spiral wave behaviour, processes at the core of current day arrhythmia research. The new model is well over four times more efficient than the full model. We conclude that the new model can be used for efficient simulations of the effects of current changes on arrhythmias in the human heart.

  11. Cell model for efficient simulation of wave propagation in human ventricular tissue under normal and pathological conditions

    Science.gov (United States)

    Ten Tusscher, K. H. W. J.; Panfilov, A. V.

    2006-12-01

    In this paper, we formulate a model for human ventricular cells that is efficient enough for whole organ arrhythmia simulations yet detailed enough to capture the effects of cell level processes such as current blocks and channelopathies. The model is obtained from our detailed human ventricular cell model by using mathematical techniques to reduce the number of variables from 19 to nine. We carefully compare our full and reduced model at the single cell, cable and 2D tissue level and show that the reduced model has a very similar behaviour. Importantly, the new model correctly produces the effects of current blocks and channelopathies on AP and spiral wave behaviour, processes at the core of current day arrhythmia research. The new model is well over four times more efficient than the full model. We conclude that the new model can be used for efficient simulations of the effects of current changes on arrhythmias in the human heart.

  12. Human cytomegalovirus-encoded miR-US4-1 promotes cell apoptosis and benefits discharge of infectious virus particles via down-regulation of glutaminyl-tRNA synthetase, QARS in HCMV-infected HELF cells

    Indian Academy of Sciences (India)

    Yaozhong Shao; Ying Qi; Yujing Huang; Zhongyang Liu; Yanping Ma; Xin Guo; Shujuan Jiang; Zhengrong Sun; Qiang Ruan

    2016-06-01

    Human cytomegalovirus (HCMV) can cause congenital diseases and opportunistic infections in immunocompromised individuals. Its functional proteins and microRNAs (miRNAs) facilitate efficient viral propagation by altering host cell behaviour. Identification of functional target genes of miRNAs is an important step in studies on HCMV pathogenesis. In this study, Glutaminyl-tRNA Synthetase (QARS), which could regulate signal transduction pathways for cellular apoptosis, was identified as a direct target of hcmv-miR-US4-1. Apoptosis assay revealed that as silence of QARS by ectopic expression of hcmv-miR-US4-1 and specific small interference RNA of QARS can promote cell apoptosis in HCMV-infected HELF cells. Moreover, viral growth curve assays showed that hcmv-miR-US4-1 benefits the discharge of infectious virus particles. However, silence of hcmv-miR-US4-1 by its specific inhibitor overturned these effects. These results imply that hcmv-miR-US4-1 might have the same effects during HCMV nature infection. In general, hcmv-miR-US4-1 may involve in promoting cell apoptosis and benefiting discharge of infectious virus particles via down-regulation of QARS in HCMV-infected HELF cells.

  13. Gene expression profiling suggests a pathological role of human bone marrow-derived mesenchymal stem cells in aging-related skeletal diseases.

    Science.gov (United States)

    Jiang, Shih Sheng; Chen, Chung-Hsing; Tseng, Kuo-Yun; Tsai, Fang-Yu; Wang, Ming Jen; Chang, I-Shou; Lin, Jiunn-Liang; Lin, Shankung

    2011-07-01

    Aging is associated with bone loss and degenerative joint diseases, in which the aging of bone marrow-derived mesenchymal stem cell (bmMSC)[1] may play an important role. In this study, we analyzed the gene expression profiles of bmMSC from 14 donors between 36 and 74 years old, and obtained age-associated genes (in the background of osteoarthritis) and osteoarthritis-associated genes (in the background of old age). Pathway analysis of these genes suggests that alterations in glycobiology might play an important role in the aging of human bmMSC. On the other hand, antigen presentation and signaling of immune cells were the top pathways enriched by osteoarthritis-associated genes, suggesting that alteration in immunology of bmMSC might be involved in the pathogenesis of osteoarthritis. Most intriguingly, we found significant age-associated differential expression of HEXA, HEXB, CTSK, SULF1, ADAMTS5, SPP1, COL8A2, GPNMB, TNFAIP6, and RPL29; those genes have been implicated in the bone loss and the pathology of osteoporosis and osteoarthritis in aging. Collectively, our results suggest a pathological role of bmMSC in aging-related skeletal diseases, and suggest the possibility that alteration in the immunology of bmMSC might also play an important role in the etiology of adult-onset osteoarthritis.

  14. Distinct Renal Pathology and a Chemotactic Phenotype after Enterohemorrhagic Escherichia coli Shiga Toxins in Non-Human Primate Models of Hemolytic Uremic Syndrome

    Science.gov (United States)

    Stearns-Kurosawa, Deborah J.; Oh, Sun-Young; Cherla, Rama P.; Lee, Moo-Seung; Tesh, Vernon L.; Papin, James; Henderson, Joel; Kurosawa, Shinichiro

    2014-01-01

    Enterohemorrhagic Escherichia coli cause approximately 1.5 million infections globally with 176,000 cases occurring in the United States annually from ingesting contaminated food, most frequently E. coli O157:H7 in ground beef or fresh produce. In severe cases, the painful prodromal hemorrhagic colitis is complicated by potentially lethal hemolytic uremic syndrome (HUS), particularly in children. Bacterial Shiga-like toxins (Stx1, Stx2) are primarily responsible for HUS and the kidney and neurologic damage that ensue. Small animal models are hampered by the inability to reproduce HUS with thrombotic microangiopathy, hemolytic anemia, and acute kidney injury. Earlier, we showed that nonhuman primates (Papio) recapitulated clinical HUS after Stx challenge and that novel therapeutic intervention rescued the animals. Here, we present detailed light and electron microscopic pathology examination of the kidneys from these Stx studies. Stx1 challenge resulted in more severe glomerular endothelial injury, whereas the glomerular injury after Stx2 also included prominent mesangiolysis and an eosinophilic inflammatory infiltration. Both toxins induced glomerular platelet-rich thrombi, interstitial hemorrhage, and tubular injury. Analysis of kidney and other organs for inflammation biomarkers showed a striking chemotactic profile, with extremely high mRNA levels for IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1α and elevated urine chemokines at 48 hours after challenge. These observations give unique insight into the pathologic consequences of each toxin in a near human setting and present potential pathways for therapeutic intervention. PMID:23402998

  15. Retinal Angiogenesis Effects of TGF-β1 and Paracrine Factors Secreted From Human Placental Stem Cells in Response to a Pathological Environment.

    Science.gov (United States)

    Kim, Kyung-Sul; Park, Ji-Min; Kong, TaeHo; Kim, Chul; Bae, Sang-Hun; Kim, Han Wool; Moon, Jisook

    2016-01-01

    Abnormal angiogenesis is a primary cause of many eye diseases, including diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity. Mesenchymal stem cells (MSCs) are currently being investigated as a treatment for several such retinal diseases based on their neuroprotective and angiogenic potentials. In this study, we evaluated the role of systemically injected human placental amniotic membrane-derived MSCs (AMSCs) on pathological neovascularization of proliferative retinopathy. We determined that AMSCs secrete higher levels of transforming growth factor-β (TGF-β1) than other MSCs, and the secreted TGF-β1 directly suppresses the proliferation of endothelial cells under pathological conditions in vitro. Moreover, in a mouse model of oxygen-induced retinopathy, intraperitoneally injected AMSCs migrated into the retina and suppressed excessive neovascularization of the vasculature via expression of TGF-β1, and the antineovascular effect of AMSCs was blocked by treatment with TGF-β1 siRNA. These findings are the first to demonstrate that TGF-β1 secreted from AMSCs is one of the key factors to suppress retinal neovascularization in proliferative retinopathy and further elucidate the therapeutic function of AMSCs for the treatment of retinal neovascular diseases.

  16. 77 FR 297 - National Institute of Allergy And Infectious Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-01-04

    ... HUMAN SERVICES National Institutes of Health National Institute of Allergy And Infectious Diseases... personal privacy. Name of Committee: National Institute of Allergy and Infectious Diseases Special Emphasis....nih.gov . Name of Committee: National Institute of Allergy and Infectious Diseases Special...

  17. Propidium monoazide reverse transcription PCR and RT-qPCR for detecting infectious enterovirus and norovirus

    Science.gov (United States)

    Presently there is no established cell line or small animal model that allows for the detection of infectious human norovirus. Current methods based on RT-PCR and RT-qPCR detect both infectious and non-infectious virus and thus the conclusions that may be drawn regarding the publ...

  18. INFECTIOUS MYXOMATOSIS OF RABBITS

    Science.gov (United States)

    Rivers, T. M.

    1930-01-01

    The virus of infectious myxomatosis of rabbits (Sanarelli) induces multiple lesions in the skin, lymph glands, tunica vaginalis,epididymis, testicle, spleen, and lungs. Growth and destruction of cells in the epidermis overlying the myxomatous masses leads to the formation of vesicles. Cytoplasmic inclusions are found in affected epidermal cells. Occasionally, similar inclusions are seen in other involved epithelial cells. The nature of the inclusions is an open question. In the myxomatous masses situated in the subcutaneous and other tissues, evidences of alteration and growth of certain cells are observed. PMID:19869741

  19. [Equine Infectious Anemia (EIA)].

    Science.gov (United States)

    Kaiser, A; Meier, H P; Straub, R; Gerber, V

    2009-04-01

    Equine Infectious Anemia (EIA) is a reportable, eradicable epizootic disease caused by the equine lentivirus of the retrovirus family which affects equids only and occurs worldwide. The virus is transmitted by blood, mainly by sanguivorous insects. The main symptoms of the disease are pyrexia, apathy, loss of body condition and weight, anemia, edema and petechia. However, infected horses can also be inapparent carriers without any overt signs. The disease is diagnosed by serological tests like the Coggins test and ELISA tests. Presently, Switzerland is offi cially free from EIA. However, Switzerland is permanently at risk of introducing the virus as cases of EIA have recently been reported in different European countries.

  20. [Infectious colitis. Endoscopy].

    Science.gov (United States)

    Dive, C

    1986-11-01

    Colon and rectum localizations of an disease or a parasitosis depend essentially on the nature of the pathogenous agent and the host resistance. Acute enterocolitis is secondary to enterotoxinogenous germs (such as cholera vibrio), invasive germs (such as shigella), penetrating germs (such as salmonella); viruses are seldom concerned. Parasitic colitis include mostly amibiasis and bilharziosis. Infectious and parasitic enterocolitis may be transmitted sexually. On the other hand, certain venereal diseases have intestinal manifestations. Finally, in AIDS, timely gastro-intestinal infections develop. The diagnosis rests on endoscopy, histological examination and biological and parasitological samplings.

  1. Globalization and infectious diseases.

    Science.gov (United States)

    Frenk, Julio; Gómez-Dantés, Octavio; Knaul, Felicia M

    2011-09-01

    This article discusses the nature of the health challenges created by globalization and proposes new forms of international cooperation to confront them. The discussion of global health challenges includes both the transfer of health risks, with an emphasis on infectious diseases, and the international dissemination of health opportunities, including the transfer of knowledge and technology. The authors argue that the health-related challenges and opportunities of an increasingly interdependent world demand new forms of international cooperation. The authors suggest the promotion of 3 elements that, in their essence, contain the idea of collaboration: exchange, evidence, and empathy.

  2. Feline infectious peritonitis.

    Science.gov (United States)

    Goodson, Teresa; Randell, Susan; Moore, Lisa

    2009-10-01

    Feline infectious peritonitis (FIP) frequently results in death in cats. It is caused by a mutated, highly contagious coronavirus, and it is more common in indoor cats in multicat households. A complex interaction between the coronavirus and the feline immune system causes disseminated vasculitis, which is the hallmark of FIP. New tests are being developed, but the antemortem diagnosis of FIP continues to be difficult and frustrating. Current treatments are crude and involve supportive care and immunosuppression. Minimizing exposure is the best method of preventing infection.

  3. Evidence from human and animal studies: Pathological roles of CD8+ T cells in autoimmune peripheral neuropathies

    Directory of Open Access Journals (Sweden)

    Mu eYang

    2015-10-01

    Full Text Available Autoimmune peripheral neuropathies such as Guillain Barre Syndrome (GBS and chronic inflammatory demyelinating polyneuropathy (CIDP affect millions of people worldwide. Despite significant advances in understanding the pathology, the molecular and cellular mechanisms of immune-mediated neuropathies remain elusive. T lymphocytes definitely play an important role in disease pathogenesis and CD4+ T cells have been the main area of research for decades. This is partly due to the fact that the most frequent animal model to study autoimmune peripheral neuropathy is experimental allergic neuritis (EAN. As it is induced commonly by immunization with peripheral nerve proteins, EAN is driven mainly by CD4+ T cells. However, similarly to what has been reported for patients suffering from multiple sclerosis, a significant body of evidence indicate that CD8+ T cells may play a pathogenic role in GBS and CIDP disease development and/or progression. Here, we summarize clinical studies pertaining to the presence and potential role of CD8+ T cells in autoimmune peripheral neuropathy. We also discuss the findings from our most recent studies using a transgenic mouse line (L31 mice in which the T cell co-stimulator molecule B7.2 (CD86 is constitutively expressed in antigen presenting cells of the nervous tissues. L31 mice spontaneously develop peripheral neuropathy, and CD8+ T cells are found accumulating in peripheral nerves of symptomatic animals. Interestingly, depletion of CD4+ T cells accelerates disease onset and increases disease prevalence. Finally, we point out some unanswered questions for future research to dissect the critical roles of CD8+ T cells in autoimmune peripheral neuropathies.

  4. 42 CFR 493.853 - Condition: Pathology.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Pathology. 493.853 Section 493.853 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.853 Condition: Pathology. The specialty of pathology includes, for purposes...

  5. Computer treatment of the contents of some elements in the normal and pathologically altered human colon mucosa tissues obtained by INAA

    Energy Technology Data Exchange (ETDEWEB)

    Draskovic, R.J.; Bozanic, M.; Bozanic, V.; Bohus, T. (Institut za Nuklearne Nauke Boris Kidric, Belgrade (Yugoslavia))

    1984-11-01

    Distribution of some elements (Cr, Fe, Co, Sb, Sc and Zn) in normal and pathologically altered human colon mucosa tissues were investigated by INAA. The following tissues were analyzed: normal colon mucosa, colitis chronica, colitis ulcerosa, adenoma tubulare and adenocarcinoma (diagnoses were previously confirmed clinically and histopathologically). The values of contents of the elements in these tissues (Csub(x) in nkg/g) are treated by specific computer functional programs. Regression functions of these parameters were found for the altered tissues in comparison to the normal, as well as specific functional correlations of the Csub(x)/Csub(y) relations for pairs of investigated elements. The functions which characterize these relations for the investigated colon mucosa tissue were also determined.

  6. Alpha-1-antitrypsin deficiency: from genoma to liver disease. PiZ mouse as model for the development of liver pathology in human.

    Science.gov (United States)

    Giovannoni, Isabella; Callea, Francesco; Stefanelli, Marta; Mariani, Riccardo; Santorelli, Filippo M; Francalanci, Paola

    2015-01-01

    Homozygous individuals with alpha-1-antitrypsin deficiency (AATD) type PiZ have an increased risk of chronic liver disease and hepatocellular carcinoma (HCC). It is noteworthy that HCCs are composed by hepatocytes without accumulation of AAT, but the reason for this remains unclear. The aim of this study was to determine liver pathology in PiZ mice, focusing the attention on the distribution of AAT globules in normal liver, regenerative foci and neoplastic nodules. Liver of 79 PiZ mice and 18 wild type (Wt) was histologically analysed for steatosis, clear cell foci, hyperplasia and neoplasia. The expression of human-AAT transgene and murine AAT, in non-neoplastic liver and in hyperplastic/neoplastic nodules was tested by qPCR and qRT-PCR. RT-PCR was used to study expression of hepatic markers: albumin, α-foetoprotein, transthyretin, AAT, glucose-6-phospate, tyrosine aminotransferase. Liver pathology was seen more frequently in PiZ (47/79) than in Wt (5/18) and its development was age related. In older PiZ mice (18-24 m), livers showed malignant tumours (HCC and angiosarcoma) (17/50), hyperplastic nodules (28/50), non-specific changes (33/50), whereas only 9/50 were normal. Both human-AATZ DNA and mRNA showed no differences between tumours/nodules and normal liver, while murine-AAT mRNA was reduced in tumours/nodules. Accumulation of AAT is associated with an increased risk of liver nodules. The presence of globule-devoid hepatocytes and the reduced expression of murine-AAT mRNA in hyperplastic and neoplastic nodules suggest that these hepatic lesions in AATD could originate from proliferating dedifferentiated cells, lacking AAT storage and becoming capable of AFP re-expression. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Studies on Infectious Mononucleosis

    Science.gov (United States)

    Joncas, J.; Chagnon, A.; Pavilanis, V.

    1966-01-01

    Viral studies were carried out on throat swabs, rectal swabs and washed white blood cells from 27 cases of infectious mononucleosis (positive Paul-Bunnell-David-sohn test), and from 22 controls. Four cytopathic agents were isolated in the test group, two of which were readily subcultured for at least three successive passages. Three cytopathic agents were recovered in the control group, two of which have been identified as adenovirus type 5 and adenovirus type 3. The unidentified agents tested so far are sensitive to ether and to pH 3. The results of acridine-orange staining and the immunofluorescence technique, using a conjugated control serum and two conjugated convalescent infectious mononucleosis sera, indicate that the isolated agent or agents in the test group are RNA-type agents with a cytoplasmic cycle of development. The overall results of this study lead the authors to suspect a respiratory syncytial-like myxovirus as the as yet unidentified agent which they recovered. ImagesFig. 1aFig. 1bFig. 1cFig. 1dFig. 2aFig. 2bFig. 2cFig. 2dFig. 3aFig. 3bFig. 3cFig. 3dFig. 3eFig. 3f PMID:4952899

  8. Ultrastructural characteristics of novel epithelial cell types identified in human pathologic liver specimens with chronic ductular reaction.

    Science.gov (United States)

    De Vos, R; Desmet, V

    1992-06-01

    Previous immunohistochemical studies on human liver biopsies with chronic ductular reaction revealed the presence of "small cells" with bile-duct type cytokeratin profile in the periportal area. This study identified similar cells by electron microscopy. The authors studied 13 human liver specimens with various liver diseases, but all characterized by chronic ductular reaction. In all specimens, variable numbers of "small cells" with common epithelial characteristics were identified in the periportal area. They could be classified into three types. Type I cells showed an oval cell shape and oval nucleus, early or established formation of junctional complexes with adjacent cells, a full assortment of cytoplasmic organelles, and bundles of tonofilaments. Type II cells showed features of bile-duct cell differentiation, including lateral interdigitations, apical microvilli, basal pinocytotic vacuoles, and basement membrane formation. In contrast, type III cells displayed additional features indicating hepatocellular differentiation, such as a more prominent nucleus, formation of a hemicanaliculus, and glycogen rosettes. It is concluded that these small cells of epithelial nature display variable differentiation characteristics of either bile-duct type cells or hepatocytes. These findings support the existence of bipotential progenitor epithelial cells in human liver. They may have implications for liver regeneration and carcinogenesis.

  9. Cidofovir and brincidofovir reduce the pathology caused by systemic infection with human type 5 adenovirus in immunosuppressed Syrian hamsters, while ribavirin is largely ineffective in this model.

    Science.gov (United States)

    Tollefson, Ann E; Spencer, Jacqueline F; Ying, Baoling; Buller, R Mark L; Wold, William S M; Toth, Karoly

    2014-12-01

    There are no drugs approved specifically to treat disseminated adenovirus (Ad) infections in humans. Cidofovir is active against Ad in cell culture, and it is used frequently in the clinic with disseminated infection in pediatric transplant patients; however, controlled clinical studies have not been conducted to prove the anti-Ad efficacy of cidofovir. Brincidofovir, a lipid-linked derivative of cidofovir, which has strong activity against Ad in cell culture and in animal models, is a promising new drug currently in clinical trials. Ribavirin, which has modest activity against some Ad types in cell culture, has been used in the clinic against disseminated Ad, but the efficacy of ribavirin is unknown. In the current study, we have examined the activity of cidofovir, brincidofovir, and ribavirin against disseminated Ad5 infection in the immunosuppressed Syrian hamster model. Hamsters are immunosuppressed by treatment with cyclophosphamide, then infected intravenously with Ad5, leading to disseminated Ad5 infection, especially in the liver. We found that cidofovir and brincidofovir have excellent activity against Ad5 pathology and replication in the liver, even when administered therapeutically starting at 3 days post-challenge with Ad5. Ribavirin did not have anti-Ad5 activity in our model. Our data support the use of cidofovir and brincidofovir in humans for the treatment of disseminated Ad infections in humans.

  10. Possible Roles of Proinflammatory and Chemoattractive Cytokines Produced by Human Fetal Membrane Cells in the Pathology of Adverse Pregnancy Outcomes Associated with Influenza Virus Infection

    Directory of Open Access Journals (Sweden)

    Noboru Uchide

    2012-01-01

    Full Text Available Pregnant women are at an increased risk of influenza-associated adverse outcomes, such as premature delivery, based on data from the latest pandemic with a novel influenza A (H1N1 virus in 2009-2010. It has been suggested that the transplacental transmission of influenza viruses is rarely detected in humans. A series of our study has demonstrated that influenza virus infection induced apoptosis in primary cultured human fetal membrane chorion cells, from which a factor with monocyte differentiation-inducing (MDI activity was secreted. Proinflammatory cytokines, such as interleukin (IL-6, tumor necrosis factor (TNF-α, and interferon (IFN-β, were identified as a member of the MDI factor. Influenza virus infection induced the mRNA expression of not only the proinflammatory cytokines but also chemoattractive cytokines, such as monocyte chemoattractant protein (MCP-1, regulated on activation, normal T-cell expressed and secreted (RANTES, macrophage inflammatory protein (MIP-1β, IL-8, growth-regulated oncogene (GRO-α, GRO-β, epithelial cell-derived neutrophil-activating protein (ENA-78, and interferon inducible protein (IP-10 in cultured chorion cells. These cytokines are postulated to associate with human parturition. This paper, therefore, reviews (1 lessons from pandemic H1N1 2009 in pregnancy, (2 production of proinflammatory and chemoattractive cytokines by human fetal membranes and their functions in gestational tissues, and (3 possible roles of cytokines produced by human fetal membranes in the pathology of adverse pregnancy outcomes associated with influenza virus infection.

  11. Climate change-related migration and infectious disease.

    Science.gov (United States)

    McMichael, Celia

    2015-01-01

    Anthropogenic climate change will have significant impacts on both human migration and population health, including infectious disease. It will amplify and alter migration pathways, and will contribute to the changing ecology and transmission dynamics of infectious disease. However there has been limited consideration of the intersections between migration and health in the context of a changing climate. This article argues that climate-change related migration - in conjunction with other drivers of migration - will contribute to changing profiles of infectious disease. It considers infectious disease risks for different climate-related migration pathways, including: forced displacement, slow-onset migration particularly to urban-poor areas, planned resettlement, and labor migration associated with climate change adaptation initiatives. Migration can reduce vulnerability to climate change, but it is critical to better understand and respond to health impacts - including infectious diseases - for migrant populations and host communities.

  12. Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells.

    Science.gov (United States)

    Bursomanno, Sara; Beli, Petra; Khan, Asif M; Minocherhomji, Sheroy; Wagner, Sebastian A; Bekker-Jensen, Simon; Mailand, Niels; Choudhary, Chunaram; Hickson, Ian D; Liu, Ying

    2015-01-01

    SUMOylation is a form of post-translational modification involving covalent attachment of SUMO (Small Ubiquitin-like Modifier) polypeptides to specific lysine residues in the target protein. In human cells, there are four SUMO proteins, SUMO1-4, with SUMO2 and SUMO3 forming a closely related subfamily. SUMO2/3, in contrast to SUMO1, are predominantly involved in the cellular response to certain stresses, including heat shock. Substantial evidence from studies in yeast has shown that SUMOylation plays an important role in the regulation of DNA replication and repair. Here, we report a proteomic analysis of proteins modified by SUMO2 in response to DNA replication stress in S phase in human cells. We have identified a panel of 22 SUMO2 targets with increased SUMOylation during DNA replication stress, many of which play key functions within the DNA replication machinery and/or in the cellular response to DNA damage. Interestingly, POLD3 was found modified most significantly in response to a low dose aphidicolin treatment protocol that promotes common fragile site (CFS) breakage. POLD3 is the human ortholog of POL32 in budding yeast, and has been shown to act during break-induced recombinational repair. We have also shown that deficiency of POLD3 leads to an increase in RPA-bound ssDNA when cells are under replication stress, suggesting that POLD3 plays a role in the cellular response to DNA replication stress. Considering that DNA replication stress is a source of genome instability, and that excessive replication stress is a hallmark of pre-neoplastic and tumor cells, our characterization of SUMO2 targets during a perturbed S-phase should provide a valuable resource for future functional studies in the fields of DNA metabolism and cancer biology.

  13. Progress and Challenges in Infectious Disease Cartography.

    Science.gov (United States)

    Kraemer, Moritz U G; Hay, Simon I; Pigott, David M; Smith, David L; Wint, G R William; Golding, Nick

    2016-01-01

    Quantitatively mapping the spatial distributions of infectious diseases is key to both investigating their epidemiology and identifying populations at risk of infection. Important advances in data quality and methodologies have allowed for better investigation of disease risk and its association with environmental factors. However, incorporating dynamic human behavioural processes in disease mapping remains challenging. For example, connectivity among human populations, a key driver of pathogen dispersal, has increased sharply over the past century, along with the availability of data derived from mobile phones and other dynamic data sources. Future work must be targeted towards the rapid updating and dissemination of appropriately designed disease maps to guide the public health community in reducing the global burden of infectious disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. [Research of keratinophiles in the soil and their effects on human cutaneous pathology in the Lyons area].

    Science.gov (United States)

    Coudert, J; Michel-Brun, J; Mojon, M; Pichot, J

    1979-01-01

    Between 1967 and 1977, the systematic research of keratinophiles of the ground in a radius of 30--50 km around Lyon, has shown the ubiquitarian predominance of Microsporum nanum, which is probably the most ancient occupant of the ground. The most intensive areas of human and animal occupation in the Rhodanian tract show the predominance of Microsporum gypseum, which is scarcely found in man. Sporadic localizations, tightly limites, bound to cirulcation axes and international gathering, let us detect Microsporum cookei, Trichophyton verrucosum, Trichophyton mentagrophytes, Chrysosporium keratinophilum, and Keratinomyces ajelloi. However, in the last years, a progressive extension of recently imported kinds and a decrease in native kinds appears to have occurred.

  15. Pseudothrombocytopenia associated with infectious mononucleosis.

    Science.gov (United States)

    Hsieh, A T; Chao, T Y; Chen, Y C

    2003-01-01

    A 22-year-old man was hospitalized for assessment of thrombocytopenia and fever. Examination showed that he had infectious mononucleosis and moderately severe thrombocytopenia that was asymptomatic. Examination of blood smears revealed that the thrombocytopenia was caused by the clumping of platelets. We made a diagnosis of ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia after excluding other infectious mononucleosis-related mechanisms of thrombocytopenia. When the patient recovered from infectious mononucleosis 2 months later, his thrombocytopenia improved, and no platelet clumping in peripheral blood smears was noted. Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia should always be considered as a possible cause of reported low platelet counts, even in patients with infectious mononucleosis and splenomegaly.

  16. Identification of Phylogenetic Position in the Chlamydiaceae Family for Chlamydia Strains Released from Monkeys and Humans with Chlamydial Pathology

    Directory of Open Access Journals (Sweden)

    Alexander Karaulov

    2010-01-01

    Full Text Available Based on the results of the comparative analysis concerning relatedness and evolutional difference of the 16S–23S nucleotide sequences of the middle ribosomal cluster and 23S rRNA I domain, and based on identification of phylogenetic position for Chlamydophila pneumoniae and Chlamydia trichomatis strains released from monkeys, relatedness of the above stated isolates with similar strains released from humans and with strains having nucleotide sequences presented in the GenBank electronic database has been detected for the first time ever. Position of these isolates in the Chlamydiaceae family phylogenetic tree has been identified. The evolutional position of the investigated original Chlamydia and Chlamydophila strains close to analogous strains from the Gen-Bank electronic database has been demonstrated. Differences in the 16S–23S nucleotide sequence of the middle ribosomal cluster and 23S rRNA I domain of plasmid and nonplasmid Chlamydia trachomatis strains released from humans and monkeys relative to different genotype groups (group B-B, Ba, D, Da, E, L1, L2, L2a; intermediate group-F, G, Ga have been revealed for the first time ever. Abnormality in incA chromosomal gene expression resulting in Chlamydia life development cycle disorder, and decrease of Chlamydia virulence can be related to probable changes in the nucleotide sequence of the gene under consideration

  17. BASE OF SKULL ANATOMY AND DIFFERENT PATHOLOGIES IN CROSS SECTIONAL IMAGING

    OpenAIRE

    Hashem Sharifian

    2012-01-01

    Purpose: The aim of this study is to improvethe radiologic knowledge of skull base anatomy and pathologies. Content: Skull base is composed of multiple complex bones and soft tissues. So many pathologies as tumoral, infectious and traumatic can involve it. With a brief discussion of the anatomy, we review various pathologic conditions in this region.

  18. [Methods and methodology of pathology].

    Science.gov (United States)

    Lushnikov, E F

    2016-01-01

    The lecture gives the state-of-the-art of the methodology of human pathology that is an area of the scientific and practice activity of specialists to produce and systematize objective knowledge of pathology and to use the knowledge in clinical medicine. It considers the objects and subjects of an investigation, materials and methods of a pathologist, and the results of his/her work.

  19. The effect of global warming on infectious diseases.

    Science.gov (United States)

    Kurane, Ichiro

    2010-12-01

    Global warming has various effects on human health. The main indirect effects are on infectious diseases. Although the effects on infectious diseases will be detected worldwide, the degree and types of the effect are different, depending on the location of the respective countries and socioeconomical situations. Among infectious diseases, water- and foodborne infectious diseases and vector-borne infectious diseases are two main categories that are forecasted to be most affected. The effect on vector-borne infectious diseases such as malaria and dengue fever is mainly because of the expansion of the infested areas of vector mosquitoes and increase in the number and feeding activity of infected mosquitoes. There will be increase in the number of cases with water- and foodborne diarrhoeal diseases. Even with the strongest mitigation procedures, global warming cannot be avoided for decades. Therefore, implementation of adaptation measures to the effect of global warming is the most practical action we can take. It is generally accepted that the impacts of global warming on infectious diseases have not been apparent at this point yet in East Asia. However, these impacts will appear in one form or another if global warming continues to progress in future. Further research on the impacts of global warming on infectious diseases and on future prospects should be conducted.

  20. Proteome-wide analysis of SUMO2 targets in response to pathological DNA replication stress in human cells

    DEFF Research Database (Denmark)

    Bursomanno, Sara; Beli, Petra; Khan, Asif M;

    2015-01-01

    SUMOylation is a form of post-translational modification involving covalent attachment of SUMO (Small Ubiquitin-like Modifier) polypeptides to specific lysine residues in the target protein. In human cells, there are four SUMO proteins, SUMO1-4, with SUMO2 and SUMO3 forming a closely related...... subfamily. SUMO2/3, in contrast to SUMO1, are predominantly involved in the cellular response to certain stresses, including heat shock. Substantial evidence from studies in yeast has shown that SUMOylation plays an important role in the regulation of DNA replication and repair. Here, we report a proteomic...... repair. We have also shown that deficiency of POLD3 leads to an increase in RPA-bound ssDNA when cells are under replication stress, suggesting that POLD3 plays a role in the cellular response to DNA replication stress. Considering that DNA replication stress is a source of genome instability...

  1. Sports: The Infectious Hazards.

    Science.gov (United States)

    Minooee, Arezou; Wang, Jeff; Gupta, Geeta K

    2015-10-01

    Although the medical complications of sports are usually traumatic in nature, infectious hazards also arise. While blood-borne pathogens such as HIV, hepatitis B, and hepatitis C, cause significant illness, the risk of acquiring these agents during sporting activities is minimal. Skin infections are more commonplace, arising from a variety of microbial agents including bacterial, fungal, and viral pathogens. Sports involving water contact can lead to enteric infections, eye infections, or disseminated infections such as leptospirosis. Mumps, measles, and influenza are vaccine-preventable diseases that have been transmitted during sporting events, both in players and in spectators. Prevention is the key to many of these infections. Players should be vaccinated and should not participate in sports if their infection can be spread by contact, airborne, or droplet transmission.

  2. Clinical pathology of amphibians: a review.

    Science.gov (United States)

    Forzán, María J; Heatley, Jill; Russell, Karen E; Horney, Barbara

    2017-03-01

    Amphibian declines and extinctions have worsened in the last 2 decades. Partly because one of the main causes of the declines is infectious disease, veterinary professionals have increasingly become involved in amphibian research, captive husbandry, and management. Health evaluation of amphibians, free-living or captive, can benefit from employing the tools of clinical pathology, something that is commonly used in veterinary medicine of other vertebrates. The present review compiles what is known of amphibian clinical pathology emphasizing knowledge that may assist with the interpretation of laboratory results, provides diagnostic recommendations for common amphibian diseases, and includes RIs for a few amphibian species estimated based on peer-reviewed studies. We hope to encourage the incorporation of clinical pathology in amphibian practice and research, and to highlight the importance of applying veterinary medicine principles in furthering our knowledge of amphibian pathophysiology. © 2017 American Society for Veterinary Clinical Pathology.

  3. A curated transcriptome dataset collection to investigate the development and differentiation of the human placenta and its associated pathologies [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Alexandra K. Marr

    2016-05-01

    Full Text Available Compendia of large-scale datasets made available in public repositories provide a precious opportunity to discover new biomedical phenomena and to fill gaps in our current knowledge. In order to foster novel insights it is necessary to ensure that these data are made readily accessible to research investigators in an interpretable format. Here we make a curated, public, collection of transcriptome datasets relevant to human placenta biology available for further analysis and interpretation via an interactive data browsing interface. We identified and retrieved a total of 24 datasets encompassing 759 transcriptome profiles associated with the development of the human placenta and associated pathologies from the NCBI Gene Expression Omnibus (GEO and present them in a custom web-based application designed for interactive query and visualization of integrated large-scale datasets (http://placentalendocrinology.gxbsidra.org/dm3/landing.gsp. We also performed quality control checks using relevant biological markers. Multiple sample groupings and rank lists were subsequently created to facilitate data query and interpretation. Via this interface, users can create web-links to customized graphical views which may be inserted into manuscripts for further dissemination, or e-mailed to collaborators for discussion. The tool also enables users to browse a single gene across different projects, providing a mechanism for  developing new perspectives on the role of a molecule of interest across multiple biological states. The dataset collection we created here is available at: http://placentalendocrinology.gxbsidra.org/dm3.

  4. Violence, mental illness, and the brain - A brief history of psychosurgery: Part 3 - From deep brain stimulation to amygdalotomy for violent behavior, seizures, and pathological aggression in humans.

    Science.gov (United States)

    Faria, Miguel A

    2013-01-01

    In the final installment to this three-part, essay-editorial on psychosurgery, we relate the history of deep brain stimulation (DBS) in humans and glimpse the phenomenal body of work conducted by Dr. Jose Delgado at Yale University from the 1950s to the 1970s. The inception of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1974-1978) is briefly discussed as it pertains to the "determination of the Secretary of Health, Education and Welfare regarding the recommendations and guidelines on psychosurgery." The controversial work - namely recording of brain activity, DBS, and amygdalotomy for intractable psychomotor seizures in patients with uncontrolled violence - conducted by Drs. Vernon H. Mark and Frank Ervin is recounted. This final chapter recapitulates advances in neuroscience and neuroradiology in the evaluation of violent individuals and ends with a brief discussion of the problem of uncontrolled rage and "pathologic aggression" in today's modern society - as violence persists, and in response, we move toward authoritarianism, with less freedom and even less dignity.

  5. Human breast cancer in vitro: matching histo-pathology with small-angle x-ray scattering and diffraction enhanced x-ray imaging

    Science.gov (United States)

    Fernández, Manuel; Keyriläinen, Jani; Serimaa, Ritva; Torkkeli, Mika; Karjalainen-Lindsberg, Marja-Liisa; Leidenius, Marjut; von Smitten, Karl; Tenhunen, Mikko; Fiedler, Stefan; Bravin, Alberto; Weiss, Thomas M.; Suortti, Pekka

    2005-07-01

    Twenty-eight human breast tumour specimens were studied with small-angle x-ray scattering (SAXS), and 10 of those were imaged by the diffraction enhanced x-ray imaging (DEI) technique. The sample diameter was 20 mm and the thickness 1 mm. Two examples of ductal carcinoma are illustrated by histology images, DEI, and maps of the collagen d-spacing and scattered intensity in the Porod regime, which characterize the SAXS patterns from collagen-rich regions of the samples. Histo-pathology reveals the cancer-invaded regions, and the maps of the SAXS parameters show that in these regions the scattering signal differs significantly from scattering by the surrounding tissue, indicating a degradation of the collagen structure in the invaded regions. The DEI images show the borders between collagen and adipose tissue and provide a co-ordinate system for tissue mapping by SAXS. In addition, degradation of the collagen structure in an invaded region is revealed by fading contrast of the DEI refraction image. The 28 samples include fresh, defrosted tissue and formalin-fixed tissue. The d-values with their standard deviations are given. In the fresh samples there is a systematic 0.76% increase of the d-value in the invaded regions, averaged over 11 samples. Only intra-sample comparisons are made for the formalin-fixed samples, and with a long fixation time, the difference in the d-value stabilizes at about 0.7%. The correspondence between the DEI images, the SAXS maps and the histo-pathology suggests that definitive information on tumour growth and malignancy is obtained by combining these x-ray methods.

  6. Administrations of human adult ischemia-tolerant mesenchymal stem cells and factors reduce amyloid beta pathology in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Harach, Taoufiq; Jammes, Fabien; Muller, Charles; Duthilleul, Nicolas; Cheatham, Victoria; Zufferey, Valentin; Cheatham, David; Lukasheva, Yelizaveta A; Lasser, Theo; Bolmont, Tristan

    2017-03-01

    The impact of human adult ischemia-tolerant mesenchymal stem cells (hMSCs) and factors (stem cell factors) on cerebral amyloid beta (Aβ) pathology was investigated in a mouse model of Alzheimer's disease (AD). To this end, hMSCs were administered intravenously to APPPS1 transgenic mice that normally develop cerebral Aβ. Quantitative reverse transcriptase polymerase chain reaction biodistribution revealed that intravenously delivered hMSCs were readily detected in APPPS1 brains 1 hour following administration, and dropped to negligible levels after 1 week. Notably, intravenously injected hMSCs that migrated to the brain region were localized in the cerebrovasculature, but they also could be observed in the brain parenchyma particularly in the hippocampus, as revealed by immunohistochemistry. A single hMSC injection markedly reduced soluble cerebral Aβ levels in APPPS1 mice after 1 week, although increasing several Aβ-degrading enzymes and modulating a panel of cerebral cytokines, suggesting an amyloid-degrading and anti-inflammatory impact of hMSCs. Furthermore, 10 weeks of hMSC treatment significantly reduced cerebral Aβ plaques and neuroinflammation in APPPS1 mice, without increasing cerebral amyloid angiopathy or microhemorrhages. Notably, a repeated intranasal delivery of soluble factors secreted by hMSCs in culture, in the absence of intravenous hMSC injection, was also sufficient to diminish cerebral amyloidosis in the mice. In conclusion, this preclinical study strongly underlines that cerebral amyloidosis is amenable to therapeutic intervention based on peripheral applications of hMSC or hMSC factors, paving the way for a novel therapy for Aβ amyloidosis and associated pathologies observed in AD. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Chorionic gonadotropin and its receptor are both expressed in human retina, possible implications in normal and pathological conditions.

    Directory of Open Access Journals (Sweden)

    Sladjana Dukic-Stefanovic

    Full Text Available Extra-gonadal role of gonadotropins has been re-evaluated over the last 20 years. In addition to pituitary secretion of luteinizing hormone (LH and follicle stimulating hormone (FSH, the CNS has been clearly identified as a source of hCG acting locally to influence behaviour. Here we demonstrated that human retina is producing this gonadotropin that acts as a neuroactive molecule. Müller glial and retinal pigmented epithelial (RPE cells are producing hCG that may affects neighbour cells expressing its receptor, namely cone photoreceptors. It was previously described that amacrine and retinal ganglion (RGC cells are targets of the gonadotropin releasing hormone that control the secretion of all gonadotropins. Therefore our findings suggest that a complex neuroendocrine circuit exists in the retina, involving hCG secreting cells (glial and RPE, hCG targets (photoreceptors and hCG-release controlling cells (amacrine and RGC. The exact physiological functions of this circuit have still to be identified, but the proliferation of photoreceptor-derived tumor induced by hCG demonstrated the need to control this neuroendocrine loop.

  8. A crystallographic study of human NONO (p54(nrb)): overcoming pathological problems with purification, data collection and noncrystallographic symmetry.

    Science.gov (United States)

    Knott, Gavin J; Panjikar, Santosh; Thorn, Andrea; Fox, Archa H; Conte, Maria R; Lee, Mihwa; Bond, Charles S

    2016-06-01

    Non-POU domain-containing octamer-binding protein (NONO, a.k.a. p54(nrb)) is a central player in nuclear gene regulation with rapidly emerging medical significance. NONO is a member of the highly conserved Drosophila behaviour/human splicing (DBHS) protein family, a dynamic family of obligatory dimeric nuclear regulatory mediators. However, work with the NONO homodimer has been limited by rapid irreversible sample aggregation. Here, it is reported that L-proline stabilizes purified NONO homodimers, enabling good-quality solution small-angle X-ray structure determination and crystallization. NONO crystallized in the apparent space group P21 with a unique axis (b) of 408.9 Å and with evidence of twinning, as indicated by the cumulative intensity distribution L statistic, suggesting the possibility of space group P1. Structure solution by molecular replacement shows a superhelical arrangement of six NONO homodimers (or 12 in P1) oriented parallel to the long axis, resulting in extensive noncrystallographic symmetry. Further analysis revealed that the crystal was not twinned, but the collected data suffered from highly overlapping reflections that obscured the L-test. Optimized data collection on a new crystal using higher energy X-rays, a smaller beam width and an increased sample-to-detector distance produced non-overlapping reflections to 2.6 Å resolution. The steps taken to analyse and overcome this series of practical difficulties and to produce a biologically informative structure are discussed.

  9. Reversal of Alzheimer's-like pathology and behavior in human APP transgenic mice by mutation of Asp664.

    Science.gov (United States)

    Galvan, Veronica; Gorostiza, Olivia F; Banwait, Surita; Ataie, Marina; Logvinova, Anna V; Sitaraman, Sandhya; Carlson, Elaine; Sagi, Sarah A; Chevallier, Nathalie; Jin, Kunlin; Greenberg, David A; Bredesen, Dale E

    2006-05-02

    The deficits characteristic of Alzheimer's disease (AD) are believed to result, at least in part, from the neurotoxic effects of beta-amyloid peptides, a set of 39-43 amino acid fragments derived proteolytically from beta-amyloid precursor protein (APP). APP also is cleaved intracytoplasmically at Asp-664 to generate a second cytotoxic peptide, APP-C31, but whether this C-terminal processing of APP plays a role in the pathogenesis of AD is unknown. Therefore, we compared elements of the Alzheimer's phenotype in transgenic mice modeling AD with vs. without a functional Asp-664 caspase cleavage site. Surprisingly, whereas beta-amyloid production and plaque formation were unaltered, synaptic loss, astrogliosis, dentate gyral atrophy, increased neuronal precursor proliferation, and behavioral abnormalities were completely prevented by a mutation at Asp-664. These results suggest that Asp-664 plays a critical role in the generation of Alzheimer-related pathophysiological and behavioral changes in human APP transgenic mice, possibly as a cleavage site or via protein-protein interactions.

  10. Topographic maps of human motor cortex in normal and pathological conditions: mirror movements, amputations and spinal cord injuries.

    Science.gov (United States)

    Cohen, L G; Bandinelli, S; Topka, H R; Fuhr, P; Roth, B J; Hallett, M

    1991-01-01

    We studied motor evoked potentials to transcranial magnetic stimulation in patients with unilateral upper limb amputations, complete T10-T12 spinal cord transection, and congenital mirror movements and in controls. Different muscles in the trunk and upper and lower extremities were evaluated at rest. In controls, muscles could be activated with stimulation of regions several centimeters wide. These areas overlapped extensively when muscles studied were from the same limb and shifted positions abruptly when muscles were from different limbs. Distal muscles were easier to activate than proximal muscles and normally evidenced exclusively a contralateral representation. Congenital defects in motor control in patients with mirror movements resulted in marked derangement of the map of outputs of distal hand muscles with enlarged and ipsilateral representations. Peripheral lesions, either acquired (amputations) or congenital (congenital absence of a limb), resulted in plastic reorganization of motor outputs targeting muscles immediately proximal to the stump. Central nervous system lesions (i.e., spinal cord injury producing paraplegia) also resulted in enlargement of the map of outputs targeting muscles proximal to the lesion. These results indicate that magnetic stimulation is a useful non-invasive tool for exploring plastic changes in human motor pathways following different types of injury.

  11. Pathologic approach to spinal cord infections.

    Science.gov (United States)

    Tihan, Tarik

    2015-05-01

    The pathologic evaluation of spinal cord infections requires comprehensive clinical, radiological, and laboratory correlation, because the histologic findings in acute, chronic, or granulomatous infections rarely provide clues for the specific cause. This brief review focuses on the pathologic mechanisms as well as practical issues in the diagnosis and reporting of infections of the spinal cord. Examples are provided of the common infectious agents and methods for their diagnosis. By necessity, discussion is restricted to the infections of the medulla spinalis proper and its meninges, and not bone or soft tissue infections.

  12. Infectious Diseases in Day Care.

    Science.gov (United States)

    Sleator, Esther K.

    Discussed in this publication are infectious illnesses for which children attending day care appear to be at special risk. Also covered are the common cold, some infectious disease problems receiving media attention, and some other annoying but not serious diseases, such as head lice, pinworms, and contagious skin conditions. Causes,…

  13. Curriculum Guidelines for Pathology and Oral Pathology.

    Science.gov (United States)

    Journal of Dental Education, 1985

    1985-01-01

    Guidelines for dental school pathology courses describe the interrelationships of general, systemic, and oral pathology; primary educational goals; prerequisites; a core curriculum outline and behavioral objectives for each type of pathology. Notes on sequencing, faculty, facilities, and occupational hazards are included. (MSE)

  14. The pathology of severe dengue in multiple organs of human fatal cases: histopathology, ultrastructure and virus replication.

    Directory of Open Access Journals (Sweden)

    Tiago F Póvoa

    Full Text Available Dengue is a public health problem, with several gaps in understanding its pathogenesis. Studies based on human fatal cases are extremely important and may clarify some of these gaps. In this work, we analyzed lesions in different organs of four dengue fatal cases, occurred in Brazil. Tissues were prepared for visualization in optical and electron microscopy, with damages quantification. As expected, we observed in all studied organ lesions characteristic of severe dengue, such as hemorrhage and edema, although other injuries were also detected. Cases presented necrotic areas in the liver and diffuse macro and microsteatosis, which were more accentuated in case 1, who also had obesity. The lung was the most affected organ, with hyaline membrane formation associated with mononuclear infiltrates in patients with pre-existing diseases such as diabetes and obesity (cases 1 and 2, respectively. These cases had also extensive acute tubular necrosis in the kidney. Infection induced destruction of cardiac fibers in most cases, with absence of nucleus and loss of striations, suggesting myocarditis. Spleens revealed significant destruction of the germinal centers and atrophy of lymphoid follicles, which may be associated to decrease of T cell number. Circulatory disturbs were reinforced by the presence of megakaryocytes in alveolar spaces, thrombus formation in glomerular capillaries and loss of endothelium in several tissues. Besides histopathological and ultrastructural observations, virus replication were investigated by detection of dengue antigens, especially the non-structural 3 protein (NS3, and confirmed by the presence of virus RNA negative strand (in situ hybridization, with second staining for identification of some cells. Results showed that dengue had broader tropism comparing to what was described before in literature, replicating in hepatocytes, type II pneumocytes and cardiac fibers, as well as in resident and circulating monocytes

  15. The pathology of severe dengue in multiple organs of human fatal cases: histopathology, ultrastructure and virus replication.

    Science.gov (United States)

    Póvoa, Tiago F; Alves, Ada M B; Oliveira, Carlos A B; Nuovo, Gerard J; Chagas, Vera L A; Paes, Marciano V

    2014-01-01

    Dengue is a public health problem, with several gaps in understanding its pathogenesis. Studies based on human fatal cases are extremely important and may clarify some of these gaps. In this work, we analyzed lesions in different organs of four dengue fatal cases, occurred in Brazil. Tissues were prepared for visualization in optical and electron microscopy, with damages quantification. As expected, we observed in all studied organ lesions characteristic of severe dengue, such as hemorrhage and edema, although other injuries were also detected. Cases presented necrotic areas in the liver and diffuse macro and microsteatosis, which were more accentuated in case 1, who also had obesity. The lung was the most affected organ, with hyaline membrane formation associated with mononuclear infiltrates in patients with pre-existing diseases such as diabetes and obesity (cases 1 and 2, respectively). These cases had also extensive acute tubular necrosis in the kidney. Infection induced destruction of cardiac fibers in most cases, with absence of nucleus and loss of striations, suggesting myocarditis. Spleens revealed significant destruction of the germinal centers and atrophy of lymphoid follicles, which may be associated to decrease of T cell number. Circulatory disturbs were reinforced by the presence of megakaryocytes in alveolar spaces, thrombus formation in glomerular capillaries and loss of endothelium in several tissues. Besides histopathological and ultrastructural observations, virus replication were investigated by detection of dengue antigens, especially the non-structural 3 protein (NS3), and confirmed by the presence of virus RNA negative strand (in situ hybridization), with second staining for identification of some cells. Results showed that dengue had broader tropism comparing to what was described before in literature, replicating in hepatocytes, type II pneumocytes and cardiac fibers, as well as in resident and circulating monocytes/macrophages and

  16. Epidemiological data of different human papillomavirus genotypes in cervical specimens of HIV-1-infected women without history of cervical pathology.

    Science.gov (United States)

    Videla, Sebastian; Darwich, Laila; Cañadas, Maria Paz; Paredes, Roger; Tarrats, Antoni; Castella, Eva; Llatjos, Mariona; Bofill, Margarita; Clotet, Bonaventura; Sirera, Guillem

    2009-02-01

    To study the epidemiology of different human papillomavirus (HPV) genotypes in cervical samples of HIV-1-infected women with normal Papanicolau smears. : Retrospective analysis of a prospective cohort. We selected HIV-1-infected women with 2 consecutive normal Papanicolau smears at baseline and at least 1 baseline and 1 follow-up cervical sample. HPV infection was assessed by second-generation hybrid capture (HC-2) and multiplex polymerase chain reaction (mPCR). HPV genotypes were determined by mPCR. From a cohort of 139 women followed up to 4 years, 93 women meeting the inclusion criteria were analyzed. The mean period between samples was 20 months (range, 6-44 months). HPV baseline prevalence was 63% [59/93; 95% confidence interval (CI), 53% to 73%] using polymerase chain reaction and 41% (38/93; 95% CI, 31% to 51%) using HC-2, P = 0.007 (kappa, 0.45; P = 0.001). The most prevalent high oncogenic risk genotypes (HR-HPV) were HPV-16 (28%), HPV-33 (18%), HPV-52 (12%), HPV-58 (11%), and HPV-39 (11%). Infection with multiple HPV genotypes was detected in >40% of women. HPV infection persisted at follow-up in 86% (51/59; 95% CI, 77% to 95%) by polymerase chain reaction and 76% (29/38; 95% CI, 62% to 90%) by HC-2. HPV infection persisted in 55% of women with samples available beyond 3 years. The actuarial probabilities of clearance and incidence of HPV infection at 36 months were 16% and 45%, respectively. HPV infection is highly prevalent and persistent among HIV-1-infected women with normal Papanicolau smears. HR-HPV genotypes other than HPV-16 (HPV-33, HPV-52) are frequently detected in HIV-infected women. mPCR provides better surveillance of HPV infection than HC-2 methods.

  17. The Pathology of Severe Dengue in Multiple Organs of Human Fatal Cases: Histopathology, Ultrastructure and Virus Replication

    Science.gov (United States)

    Póvoa, Tiago F.; Alves, Ada M. B.; Oliveira, Carlos A. B.; Nuovo, Gerard J.; Chagas, Vera L. A.; Paes, Marciano V.

    2014-01-01

    Dengue is a public health problem, with several gaps in understanding its pathogenesis. Studies based on human fatal cases are extremely important and may clarify some of these gaps. In this work, we analyzed lesions in different organs of four dengue fatal cases, occurred in Brazil. Tissues were prepared for visualization in optical and electron microscopy, with damages quantification. As expected, we observed in all studied organ lesions characteristic of severe dengue, such as hemorrhage and edema, although other injuries were also detected. Cases presented necrotic areas in the liver and diffuse macro and microsteatosis, which were more accentuated in case 1, who also had obesity. The lung was the most affected organ, with hyaline membrane formation associated with mononuclear infiltrates in patients with pre-existing diseases such as diabetes and obesity (cases 1 and 2, respectively). These cases had also extensive acute tubular necrosis in the kidney. Infection induced destruction of cardiac fibers in most cases, with absence of nucleus and loss of striations, suggesting myocarditis. Spleens revealed significant destruction of the germinal centers and atrophy of lymphoid follicles, which may be associated to decrease of T cell number. Circulatory disturbs were reinforced by the presence of megakaryocytes in alveolar spaces, thrombus formation in glomerular capillaries and loss of endothelium in several tissues. Besides histopathological and ultrastructural observations, virus replication were investigated by detection of dengue antigens, especially the non-structural 3 protein (NS3), and confirmed by the presence of virus RNA negative strand (in situ hybridization), with second staining for identification of some cells. Results showed that dengue had broader tropism comparing to what was described before in literature, replicating in hepatocytes, type II pneumocytes and cardiac fibers, as well as in resident and circulating monocytes/macrophages and

  18. Multiple sclerosis after infectious mononucleosis

    DEFF Research Database (Denmark)

    Nielsen, Trine Rasmussen; Rostgaard, Klaus; Nielsen, Nete Munk

    2007-01-01

    , and attained age to the risk of developing multiple sclerosis after infectious mononucleosis. DESIGN: Cohort study using persons tested serologically for infectious mononucleosis at Statens Serum Institut, the Danish Civil Registration System, the Danish National Hospital Discharge Register, and the Danish......: A total of 104 cases of multiple sclerosis were observed during 556,703 person-years of follow-up, corresponding to a standardized incidence ratio of 2.27 (95% confidence interval, 1.87-2.75). The risk of multiple sclerosis was persistently increased for more than 30 years after infectious mononucleosis...... and uniformly distributed across all investigated strata of sex and age. The relative risk of multiple sclerosis did not vary by presumed severity of infectious mononucleosis. CONCLUSIONS: The risk of multiple sclerosis is increased in persons with prior infectious mononucleosis, regardless of sex, age...

  19. Regulation of Inflammatory Pathways in Cancer and Infectious Disease of the Cervix

    Directory of Open Access Journals (Sweden)

    Anthonio Adefuye

    2012-01-01

    Full Text Available Cervical cancer is one of the leading gynaecological malignancies worldwide. It is an infectious disease of the cervix, associated with human papillomavirus infection (HPV, infection with bacterial agents such as Chlamydia trachomatis and Neisseria gonorrhoea as well as human immunodeficiency virus (HIV. Furthermore, it is an AIDS-defining disease with an accelerated mortality in HIV-infected women with cervical cancer. With the introduction of robust vaccination strategies against HPV in the developed world, it is anticipated that the incidence of cervical cancer will decrease in the coming years. However, vaccination has limited benefit for women already infected with high-risk HPV, and alternative therapeutic intervention strategies are needed for these women. Many pathological disorders, including cervical cancer, are characterised by the exacerbated activation and maintenance of inflammatory pathways which are considered to be regulated by infectious agents. In cervical cancer, hyperactivation of these inflammatory pathways and regulation of immune infiltrate into tissues can potentially play a role not only in tumorigenesis but also in HIV infection. In this paper we will discuss the contribution of inflammatory pathways to cervical cancer progression and HIV infection and the role of HIV in cervical cancer progression.

  20. New technologies in predicting, preventing and controlling emerging infectious diseases

    OpenAIRE

    Christaki, Eirini

    2015-01-01

    Surveillance of emerging infectious diseases is vital for the early identification of public health threats. Emergence of novel infections is linked to human factors such as population density, travel and trade and ecological factors like climate change and agricultural practices. A wealth of new technologies is becoming increasingly available for the rapid molecular identification of pathogens but also for the more accurate monitoring of infectious disease activity. Web-based surveillance to...

  1. Epidemiology of cancers of infectious origin and prevention strategies

    OpenAIRE

    Flora, S; LA MAESTRA, S.

    2015-01-01

    Summary Infectious and parasitic diseases represent the third cause of cancer worldwide. A number of infectious and parasitic agents have been suspected or recognized to be associated with human cancers, including DNA viruses, such as papillomaviruses (several HPV types), herpesviruses (EBV and KSHV), polyomaviruses (SV40, MCV, BK, and JCV), and hepadnaviruses (HBV); RNA viruses, such as flaviviruses (HCV), defective viruses (HDV), and retroviruses (HTLV-I, HTLV-II, HIV-1, HIV-2,HERV-K, and X...

  2. Parasites and other infectious agents in marine finfish and shellfish species posing a hazard to human health (ToR b)

    DEFF Research Database (Denmark)

    Alfjorden, A.; Podolska, M.; Karaseva, T.

    2015-01-01

    , but are not limited to, larval stages of the nematodes Anisakis simplex and Pseudoterranova decipiens. For them the risk to human health may occur in two ways: gastrointestinal infections with the possibility of sub-sequent peritonitis or the involvement of other sites in the body. Infections may also lead...

  3. Infectious laryngotracheitis: a review

    Directory of Open Access Journals (Sweden)

    H Hidalgo

    2003-12-01

    Full Text Available Infectious laryngotracheitis (ILT herpesvirus continues to cause outbreaks of respiratory disease in chickens world-wide. Sporadic cases of ILT occur in all classes of birds, including hobby/show/game chickens, broilers, heavy breeders, and commercial laying hens. These epornitics of ILT tend to occur where there are large populations of naïve, unvaccinated birds, i.e., in concentrated areas of broiler production. ILT virus can be transmitted through (a chickens with acute upper respiratory tract disease, (b latently infected "carrier" fowls, and (c fomites and contaminated persons. Chicken flocks which are endemic infected with ILT virus occur only in some regions of countries or even in particular multiple-age production farms. In these cases modified live vaccines are actually used, even though these biological products, as well as wild ILTV strains, can establish latent infections. In the case of heavy breeders and laying hens, which are typically vaccinated against ILT, sporadic cases are often related to errors in vaccine application and to biosecurity failures.

  4. The prostaglandin F synthase activity of the human aldose reductase AKR1B1 brings new lenses to look at pathologic conditions.

    Directory of Open Access Journals (Sweden)

    Eva eBresson

    2012-05-01

    Full Text Available Prostaglandins are important regulators of female reproductive functions to which aldose reductases exhibiting hydroxysteroid dehydrogenase activity also contribute. Our work on the regulation of reproductive function by prostaglandins (PGs, lead us to the discovery that AKR1B5 and later AKR1B1 were highly efficient and physiologically relevant PGF synthases. PGE2 and PGF2α are the main prostanoids produced in the human endometrium and proper balance in their relative production is important for normal menstruation and optimal fertility. Recent evidence suggests that PGE2 and PGF2α may constitute a functional dyad with physiological relevance at least as important as the prostacyclin-thromboxane dyad in the vascular system. We have recently reported that AKR1B1 was expressed and modulated in association with PGF2α production in response to IL-1β in the human endometrium. In the present study, we show that the human AKR1B1 (gene ID: 231 also known as ALDR1 or ALR2 is a functional PGF2α synthase in different models of living cells and tissues. Using human endometrial cells, prostate and vascular smooth muscle cells, cardiomyocytes and endothelial cells we demonstrate that IL-1β is able to up regulate COX-2 and AKR1B1 proteins as well as PGF2α production under normal glucose concentrations. We show that the promoter activity of AKR1B1 gene is increased by IL-1β particularly around the multiple stress response region (MSRR containing two putative antioxidant response elements (ARE adjacent to TonE and AP1.We also show that AKR1B1 is able to regulate PGE2 production through PGF2α acting on its FP receptor and that aldose reductase inhibitors (ARIs like alrestatin, statil (ponalrestat and EBPC exhibit distinct and characteristic inhibition of PGF2α production in different cell models. The PGF synthase activity of AKR1B1 represents a new and important target to regulate ischemic and inflammatory responses associated with several human

  5. Biochemical studies on equine infectious anaemia.

    Science.gov (United States)

    Palomba, E; Martone, F; Meduri, A; Vaccaro, A; Damiani, N

    1976-01-01

    A description is given of an outbreak of equine infectious anaemia (E.I.A.) in Campania [at Naples and Aversa (Caserta)]; it was diagnosed by clinical, pathological and serological examinations (Coggins test). Using the serum of 45 horses with E.I.A. and 11 healthy horses (controls), numerous investigations were carried out on: enzymes, intrinsic coagulation factors, lipids and other substances. The results obtained were very interesting and show that in this disease there are significant increases in many enzymes (LDH, LAP, gamma-GT, CPK, PK and ALD) and copper. Insignificant increases were found in other enzymes (SDH, GLDH, MDH, ICDH, AIP, lysozyme, cholinesterase, GOT and GPT) and also intrinsic coagulation factors, lipid substances (total cholesterol, esterified cholesterol, triglycerides) and glucose. LDH-1-isoenzyme remains unchanged, whilst AcP decreases slightly.

  6. Protein Misfolding Cyclic Amplification of Infectious Prions.

    Science.gov (United States)

    Moda, Fabio

    2017-01-01

    Transmissible spongiform encephalopathies, or prion diseases, are a group of incurable disorders caused by the accumulation of an abnormally folded prion protein (PrP(Sc)) in the brain. According to the "protein-only" hypothesis, PrP(Sc) is the infectious agent able to propagate the disease by acting as a template for the conversion of the correctly folded prion protein (PrP(C)) into the pathological isoform. Recently, the mechanism of PrP(C) conversion has been mimicked in vitro using an innovative technique named protein misfolding cyclic amplification (PMCA). This technology represents a great tool for studying diverse aspects of prion biology in the field of basic research and diagnosis. Moreover, PMCA can be expanded for the study of the misfolding process associated to other neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and frontotemporal lobar degeneration. © 2017 Elsevier Inc. All rights reserved.

  7. MRI evaluation of infectious and non-infectious synovitis: preliminary studies in a rabbit model

    Energy Technology Data Exchange (ETDEWEB)

    Strouse, P.J.; DiPietro, M.A.; Teo, E.L.H.J. [Section of Pediatric Radiology, University of Michigan Health System, Ann Arbor, MI (United States); Londy, F. [Division of Magnetic Resonance Imaging, Department of Radiology, University of Michigan Health System, Ann Arbor, MI (United States); Chrisp, C.E. [Unit of Laboratory Animal Medicine, University of Michigan Health System, Ann Arbor, MI (United States); Doi, K. [Division of Musculoskeletal Radiology, University of Michigan Health System, Ann Arbor, MI (United States)

    1999-05-01

    Background. Literature on magnetic resonance imaging (MR) evaluation of inflammatory joint effusions is sparse. Objective. To describe an animal model for studying infectious and non-infectious joint effusions with magnetic resonance imaging. Materials and methods. Ten rabbit knees with septic arthritis and four with talc synovitis were imaged with MR. Contralateral knees injected with saline served as controls. Fat saturation T2-weighted and gadolinium-enhanced T1-weighted images were assessed for joint effusion, and periarticular and adjacent intraosseous increased signal or enhancement. Each knee was cultured and underwent pathologic examination. Results. Both Staphylococcus aureus and talc produced effusions in all knees. The degree of periarticular signal and enhancement was greater in infected knees than talc-injected knees. No abnormal enhancement was seen within bone. Pathologic examination showed a greater degree of inflammation and joint destruction in the infected knees, but no evidence of osteomyelitis. Conclusion. A greater degree of abnormal signal and enhancement seen on MR suggests a more vigorous inflammatory process, as seen with septic arthritis. In spite of advanced septic arthritis, no enhancement was evident within bone, suggesting that enhancement within bone is not an expected finding in isolated septic arthritis and should raise concern for osteomyelitis. (orig.) With 3 figs., 15 refs.

  8. Decreased agonist-stimulated mitochondrial ATP production caused by a pathological reduction in endoplasmic reticulum calcium content in human complex I deficiency.

    Science.gov (United States)

    Visch, Henk-Jan; Koopman, Werner J H; Leusink, Anouk; van Emst-de Vries, Sjenet E; van den Heuvel, Lambertus W P J; Willems, Peter H G M; Smeitink, Jan A M

    2006-01-01

    Although a large number of mutations causing malfunction of complex I (NADH:ubiquinone oxidoreductase) of the OXPHOS system is now known, their cell biological consequences remain obscure. We previously showed that the bradykinin (Bk)-induced increase in mitochondrial [ATP] ([ATP](M)) is significantly reduced in primary skin fibroblasts from a patient with an isolated complex I deficiency. The present work addresses the mechanism(s) underlying this impaired response. Luminometry of fibroblasts from 6 healthy subjects and 14 genetically characterized patients expressing mitochondria targeted luciferase revealed that the Bk-induced increase in [ATP](M) was significantly, but to a variable degree, decreased in 10 patients. The same variation was observed for the increases in mitochondrial [Ca(2+)] ([Ca(2+)](M)), measured with mitochondria targeted aequorin, and cytosolic [Ca(2+)] ([Ca(2+)](C)), measured with fura-2, and for the Ca(2+) content of the endoplasmic reticulum (ER), calculated from the increase in [Ca(2+)](C) evoked by thapsigargin, an inhibitor of the ER Ca(2+) ATPase. Regression analysis revealed that the increase in [ATP](M) was directly proportional to the increases in [Ca(2+)](C) and [Ca(2+)](M) and to the ER Ca(2+) content. Our findings provide evidence that a pathological reduction in ER Ca(2+) content is the direct cause of the impaired Bk-induced increase in [ATP](M) in human complex I deficiency.

  9. Detection of human papilomavirus types 16 and 18 in pathologic samples from patients with cervical cancer by PCR and RFLP methods

    Directory of Open Access Journals (Sweden)

    Parviz Maleknejad

    2006-05-01

    Full Text Available Infection with human papiloma virus (HPV is the most frequent sexually transmitted disease worldwide. HPV types 16, 18, 31 and 33 are considered as the most important types in the cervical cancer.This study was undertaken on 64 samples of archival cervical carcinoma pathologic to assess the rate of HPV infection (HPV16,18 in cervical carcinoma among Iranian patients. HPV DNA was detected by polymerase chain reaction (PCR and typing by restriction fragment length polymorphism (RFLP analysis.The total prevalence of HPV in this study (HPV16,18 for all cases was 59.4% (38/64. HPV type 16 was the most common one (22/64, 34% followed by HPV type 18 (16/64, 25%. On the basis of the rate of HPV (16,18 which were detected in squamous cell carcinoma and adenocarcinoma,only women with HPV18 infection showed a statistically significant risk for development of cervical cancer (P=0.019 while P value for HPV16 was 0.47 .

  10. Infectious Diseases in the Homeless

    Centers for Disease Control (CDC) Podcasts

    2008-08-26

    In this podcast, Ted Pestorius speaks with Dr. Marian McDonald, Associate Director for Minority and Women’s Health at CDC about an article in September 2008 issue of Emerging Infectious Diseases on infectious diseases in the homeless. There are an estimated 100 million homeless people worldwide today, and this number is likely to grow. The homeless population is vulnerable to many diseases, including HIV, hepatitis, and tuberculosis. Dr. McDonald discusses why this population is so vulnerable.  Created: 8/26/2008 by Emerging Infectious Diseases.   Date Released: 8/27/2008.

  11. Prevention of infectious tick-borne diseases in humans: Comparative studies of the repellency of different dodecanoic acid-formulations against Ixodes ricinus ticks (Acari: Ixodidae

    Directory of Open Access Journals (Sweden)

    Dautel Hans

    2008-04-01

    Full Text Available Abstract Background Ticks of the species Ixodes ricinus are the main vectors of Lyme Borreliosis and Tick-borne Encephalitis – two rapidly emerging diseases in Europe. Repellents provide a practical means of protection against tick bites and can therefore minimize the transmission of tick-borne diseases. We developed and tested seven different dodecanoic acid (DDA-formulations for their efficacy in repelling host-seeking nymphs of I. ricinus by laboratory screening. The ultimately selected formulation was then used for comparative investigations of commercially available tick repellents in humans. Methods Laboratory screening tests were performed using the Moving-object (MO bioassay. All test formulations contained 10% of the naturally occurring active substance DDA and differed only in terms of the quantitative and qualitative composition of inactive ingredients and fragrances. The test procedure used in the human bioassays is a modification of an assay described by the U.S. Environmental Protection Agency and recommended for regulatory affairs. Repellency was computed using the equation: R = 100 - NR/N × 100, where NR is the number of non-repelled ticks, and N is the respective number of control ticks. All investigations were conducted in a controlled laboratory environment offering standardized test conditions. Results All test formulations strongly repelled nymphs of I. ricinus (100-81% protection as shown by the MO-bioassay. The majority of ticks dropped off the treated surface of the heated rotating drum that served as the attractant (1 mg/cm2 repellent applied. The 10% DDA-based formulation, that produced the best results in laboratory screening, was as effective as the coconut oil-based reference product. The mean protection time of both preparations was generally similar and averaged 8 hours. Repellency investigations in humans showed that the most effective 10% DDA-based formulation (~1.67 mg/cm2 applied strongly avoided the

  12. Horizontal transmission of malignancy: in-vivo fusion of human lymphomas with hamster stroma produces tumors retaining human genes and lymphoid pathology.

    Directory of Open Access Journals (Sweden)

    David M Goldenberg

    Full Text Available We report the in-vivo fusion of two Hodgkin lymphomas with golden hamster cheek pouch cells, resulting in serially-transplanted (over 5-6 years GW-532 and GW-584 heterosynkaryon tumor cells displaying both human and hamster DNA (by FISH, lymphoma-like morphology, aggressive metastasis, and retention of 7 human genes (CD74, CXCR4, CD19, CD20, CD71, CD79b, and VIM out of 24 tested by PCR. The prevalence of B-cell restricted genes (CD19, CD20, and CD79b suggests that this uniform population may be the clonal initiating (malignant cells of Hodgkin lymphoma, despite their not showing translation to their respective proteins by immunohistochemical analysis. This is believed to be the first report of in-vivo cell-cell fusion of human lymphoma and rodent host cells, and may be a method to disclose genes regulating both organoid and metastasis signatures, suggesting that the horizontal transfer of tumor DNA to adjacent stromal cells may be implicated in tumor heterogeneity and progression. The B-cell gene signature of the hybrid xenografts suggests that Hodgkin lymphoma, or its initiating cells, is a B-cell malignancy.

  13. Northwestern profiling of potential translation-regulatory proteins in human breast epithelial cells and malignant breast tissues: evidence for pathological activation of the IGF1R IRES.

    Science.gov (United States)

    Blume, Scott W; Jackson, Nateka L; Frost, Andra R; Grizzle, William E; Shcherbakov, Oleg D; Choi, Hyoungsoo; Meng, Zheng

    2010-06-01

    . Most importantly, we are able to assess the RNA-binding activities of these putative translation-regulatory proteins in primary human breast surgical specimens, and begin to discern positive correlations between individual ITAFs and the malignant phenotype. Together with our previous findings, these new data provide further evidence that pathological dysregulation of IGF1R translational control may contribute to development and progression of human breast cancer, and breast metastasis in particular.

  14. The Danish Pathology Register

    DEFF Research Database (Denmark)

    Bjerregaard, Beth; Larsen, Ole B

    2011-01-01

    The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established.......The National Board of Health, Denmark in 1997 published guidelines for reporting of pathology data and the Danish Pathology Register (DPR) was established....

  15. Illumination from light-emitting diodes (LEDs) disrupts pathological cytokines expression and activates relevant signal pathways in primary human retinal pigment epithelial cells.

    Science.gov (United States)

    Shen, Ye; Xie, Chen; Gu, Yangshun; Li, Xiuyi; Tong, Jianping

    2016-04-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the aged people. The latest systemic review of epidemiological investigations revealed that excessive light exposure increases the risk of AMD. With the drastically increasing use of high-energy light-emitting diodes (LEDs) light in our domestic environment nowadays, it is supposed to pose a potential oxidative threat to ocular health. Retinal pigment epithelium (RPE) is the major ocular source of pathological cytokines, which regulate local inflammation and angiogenesis. We hypothesized that high-energy LED light might disrupt the pathological cytokine expression of retinal pigment epithelium (RPE), contributing to the pathogenesis of AMD. Primary human RPE cells were isolated from eyecups of normal eye donors and seeded into plate wells for growing to confluence. Two widely used multichromatic white light-emitting diodes (LEDs) with correlated color temperatures (CCTs) of 2954 and 7378 K were used in this experiment. The confluent primary RPE cells were under white LEDs light exposure until 24 h. VEGF-A, IL-6, IL-8 and MCP-1 proteins and mRNAs were measured using an ELISA kit and RT-PCR, respectively. Activation of mitogen-activated protein kinases (MAPKs), Akt, Janus kinase (JAK)2 and Nuclear factor (NF)-κB signal pathways after LEDs illumination were evaluated by western blotting analysis. The level of reactive oxygen species (ROS) using chloromethyl- 2',7'-dichlorodihydrofluorescein diacetate. Inhibitors of relevant signal pathways and anti-oxidants were added to the primary RPE cells before LEDs illumination to evaluate their biological functions. We found that 7378 K light, but not 2954 K upregulated the VEGF-A, IL-6, IL-8 and downregulated MCP-1 proteins and mRNAs levels in a time-dependent manner. In parallel, initial activation of MAPKs and NF-κB signal pathways were also observed after 7378 K light exposure. Mechanistically, antioxidants for eliminating reactive oxygen

  16. Coronavirus avian infectious bronchitis virus

    National Research Council Canada - National Science Library

    Cavanagh, Dave

    2007-01-01

    Infectious bronchitis virus (IBV), the coronavirus of the chicken (Gallus gallus), is one of the foremost causes of economic loss within the poultry industry, affecting the performance of both meat-type and egg-laying birds...

  17. Infectious Agents Trigger Trophic Cascades.

    Science.gov (United States)

    Buck, Julia C; Ripple, William J

    2017-09-01

    Most demonstrated trophic cascades originate with predators, but infectious agents can also cause top-down indirect effects in ecosystems. Here we synthesize the literature on trophic cascades initiated by infectious agents including parasitoids, pathogens, parasitic castrators, macroparasites, and trophically transmitted parasites. Like predators, infectious agents can cause density-mediated and trait-mediated indirect effects through their direct consumptive and nonconsumptive effects respectively. Unlike most predators, however, infectious agents are not fully and immediately lethal to their victims, so their consumptive effects can also trigger trait-mediated indirect effects. We find that the frequency of trophic cascades reported for different consumer types scales with consumer lethality. Furthermore, we emphasize the value of uniting predator-prey and parasite-host theory under a general consumer-resource framework. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. New technologies in predicting, preventing and controlling emerging infectious diseases.

    Science.gov (United States)

    Christaki, Eirini

    2015-01-01

    Surveillance of emerging infectious diseases is vital for the early identification of public health threats. Emergence of novel infections is linked to human factors such as population density, travel and trade and ecological factors like climate change and agricultural practices. A wealth of new technologies is becoming increasingly available for the rapid molecular identification of pathogens but also for the more accurate monitoring of infectious disease activity. Web-based surveillance tools and epidemic intelligence methods, used by all major public health institutions, are intended to facilitate risk assessment and timely outbreak detection. In this review, we present new methods for regional and global infectious disease surveillance and advances in epidemic modeling aimed to predict and prevent future infectious diseases threats.

  19. Subspecialty surgical pathologist′s performances as triage pathologists on a telepathology-enabled quality assurance surgical pathology service: A human factors study

    Directory of Open Access Journals (Sweden)

    Beth L. Braunhut

    2014-01-01

    Full Text Available Background: The case triage practice workflow model was used to manage incoming cases on a telepathology-enabled surgical pathology quality assurance (QA service. Maximizing efficiency of workflow and the use of pathologist time requires detailed information on factors that influence telepathologists′ decision-making on a surgical pathology QA service, which was gathered and analyzed in this study. Materials and Methods: Surgical pathology report reviews and telepathology service logs were audited, for 1862 consecutive telepathology QA cases accrued from a single Arizona rural hospital over a 51 month period. Ten university faculty telepathologists served as the case readers. Each telepathologist had an area of subspecialty surgical pathology expertise (i.e. gastrointestinal pathology, dermatopathology, etc. but functioned largely as a general surgical pathologist while on this telepathology-enabled QA service. They handled all incoming cases during their individual 1-h telepathology sessions, regardless of the nature of the organ systems represented in the real-time incoming stream of outside surgical pathology cases. Results: The 10 participating telepathologists′ postAmerican Board of pathology examination experience ranged from 3 to 36 years. This is a surrogate for age. About 91% of incoming cases were immediately signed out regardless of the subspecialty surgical pathologists′ area of surgical pathology expertise. One hundred and seventy cases (9.13% were deferred. Case concurrence rates with the provisional surgical pathology diagnosis of the referring pathologist, for incoming cases, averaged 94.3%, but ranged from 88.46% to 100% for individual telepathologists. Telepathology case deferral rates, for second opinions or immunohistochemistry, ranged from 4.79% to 21.26%. Differences in concordance rates and deferral rates among telepathologists, for incoming cases, were significant but did not correlate with years of experience as a

  20. Forensic Pathology Education in Pathology Residency

    Science.gov (United States)

    Ross, Wayne K.; Domen, Ronald E.

    2017-01-01

    Forensic pathology is a fundamental part of anatomic pathology training during pathology residency. However, the lack of information on forensic teaching suggests the highly variable nature of forensic education. A survey of pathology residency program directors was performed to determine key aspects of their respective forensic rotations and curriculum. A total of 38.3% of programs from across the country responded, and the survey results show 5.6% don’t require a forensic pathology rotation. In those that do, most forensic pathology rotations are 4 weeks long, are done at a medical examiner’s office, and require set prerequisites. A total of 21.1% of responding programs have residents who are not receiving documented evaluations for this rotation. While 39.6% of programs have a defined forensics curriculum, as many as 15% do not. Furthermore, nearly 43% of programs place no limit on counting forensic autopsies when applying for pathology board examinations. Our survey confirmed the inconsistent nature of forensic pathology training in resident education. Additionally, our curriculum was reorganized to create a more robust educational experience. A pre- and post-forensic lecture quiz and Resident In-Service Examination scores were analyzed to determine our curriculum’s impact and effectiveness. Analysis of our pre- and post-lecture quiz showed an improved overall average as well as an increase in Resident In-Service Examination scores, indicating improved general forensic pathology knowledge. Using this knowledge, along with changes in our curriculum, we generated a number of recommendations for improving forensic pathology education in pathology residency. PMID:28913415

  1. Follicular Dendritic Cells Retain Infectious HIV in Cycling Endosomes.

    Directory of Open Access Journals (Sweden)

    Balthasar A Heesters

    2015-12-01

    Full Text Available Despite the success of antiretroviral therapy (ART, it does not cure Human Immunodeficiency Virus (HIV and discontinuation results in viral rebound. Follicular dendritic cells (FDC are in direct contact with CD4+ T cells and they retain intact antigen for prolonged periods. We found that human FDC isolated from patients on ART retain infectious HIV within a non-degradative cycling compartment and transmit infectious virus to uninfected CD4 T cells in vitro. Importantly, treatment of the HIV+ FDC with a soluble complement receptor 2 purges the FDC of HIV virions and prevents viral transmission in vitro. Our results provide an explanation for how FDC can retain infectious HIV for extended periods and suggest a therapeutic strategy to achieve cure in HIV-infected humans.

  2. Development of pathology in Turkey

    Directory of Open Access Journals (Sweden)

    Gökhan GEDİKOĞLU

    2007-05-01

    Full Text Available Autospy is an important tool for the development of pathology as a science. In western civilisation dissection of human body became widespread with Renaissance, in contrast in the Ottoman Empire first dissection was not performed until the 19th century. Mustafa Behçet Efendi, head physician of the Empire, was one of the Ottoman physician who suggested the importance of dissection in the medical education. The first dissection was however performed by Charles Ambroise Bernard, a foreign physician who had been invited to help establishing a new medical school; “Mekteb-i Tıbbiye-i Adliye-i Şâhâne”, in 1843. The first modern medical schools called “Tıphane” and “Cerrahhane-i Amire” which were founded in 1827, did not have pathology courses. Pathology courses began in “Mekteb-i Tıbbiye-i Adliyei Şâhâne”. Dr. Hamdi Suat (Aknar, educated in anatomic pathology in Germany, was the first pathologist who established the modern pathology in Turkey in “İstanbul Darülfünun” medical school. In 1933 “Darülfünün” was closed and İstanbul University was built and the “University Reform Commission” invited many scientists escaping from Nazi government to study in İstanbul University. Dr. Philipp Schwartz had an important role both in the invitation of these scientists and establishment of the pathology department in İstanbul University. Practical courses were increased, clinicopathologic courses were organized for the first time and a lot of autopsies were performed, as high as 1000 autopsy per year, by Dr. Philipp Schwartz. More progress has takes place in Turkey over the years since pathology was first established. Today Turkey has many pathology departments which keep up with the worldwide advances in the field.

  3. Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design

    Energy Technology Data Exchange (ETDEWEB)

    Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain

    2016-01-15

    Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E{sub 138}K and K{sub 279}M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use. - Highlights: • Further attenuation of a WN vaccine precursor is outlined. • Effect of SA14-14-2 attenuating mutations is tested. • Mechanism of attenuation is proposed and illustrated. • The need for additional attenuating mutations is justified.

  4. Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design.

    Science.gov (United States)

    Yamshchikov, Vladimir; Manuvakhova, Marina; Rodriguez, Efrain

    2016-01-01

    Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E138K and K279M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use.

  5. Targeting the human parasite Leishmania donovani: discovery of a new promising anti-infectious pharmacophore in 3-nitroimidazo[1,2-a]pyridine series.

    Science.gov (United States)

    Castera-Ducros, Caroline; Paloque, Lucie; Verhaeghe, Pierre; Casanova, Magali; Cantelli, Christophe; Hutter, Sébastien; Tanguy, Floriane; Laget, Michèle; Remusat, Vincent; Cohen, Anita; Crozet, Maxime D; Rathelot, Pascal; Azas, Nadine; Vanelle, Patrice

    2013-11-15

    We report herein the discovery of antileishmanial molecules based on the imidazo[1,2-a]pyridine ring. In vitro screenings of imidazopyridines belonging to our chemical library, toward the promastigotes stage of Leishmania donovani, J774A.1 murine and HepG2 human cells, permitted to identify three selective hit-compounds (12, 20 and 28). New derivatives were then synthesized to allow structure-activity and -toxicity relationships analyses, enabling to characterize a lead-compound (44) displaying both a high potency (IC50=1.8 μM) and a good selectivity index, in comparison with three antileishmanial reference drug-compounds (amphotericin B, miltefosine and pentamidine). Moreover, lead-compound 44 also exhibits good in vitro activity against the intracellular amastigote stage of L. donovani. Thus, the 6-halo-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridine scaffold appears as a new promising selective antileishmanial pharmacophore, especially when substituted at position 8 by a bromine atom.

  6. Gray matter pathology and multiple sclerosis.

    Science.gov (United States)

    Wegner, Christiane; Stadelmann, Christine

    2009-09-01

    Gray matter demyelination is frequent and extensive in most patients with multiple sclerosis (MS) and has recently received much attention in neuropathologic and imaging studies. Gray matter lesions show distinct pathologic features that make their detection difficult with conventional imaging techniques. Thus, despite their high prevalence, their impact on clinical symptoms has not been defined well so far. This review focuses on recent information from pathologic and imaging studies and summarizes our current knowledge on cortical pathology derived from human and experimental studies.

  7. Factors influencing the seasonal patterns of infectious diseases

    Directory of Open Access Journals (Sweden)

    Auda Fares

    2013-01-01

    Full Text Available The recognition of seasonal patterns in infectious disease occurrence dates back at least as far as the hippocratic era, but the mechanisms underlying these fluctuations remain poorly understood. Many classes of mechanistic hypotheses have been proposed to explain seasonality of various directly transmitted diseases, including at least the following; human activity, seasonal variability in human immune system function, seasonal variations in vitamin D levels, seasonality of melatonin, and pathogen infectivity. In this short paper will briefly discuss the role of these factors in the seasonal patterns of infectious diseases.

  8. Pathological Gambling in Parkinson's Disease

    DEFF Research Database (Denmark)

    Callesen, Mette Buhl; Linnet, Jakob; Thomsen, Kristine Rømer

    Pathological Gambling in Parkinson’s Disease Mette Buhl Callesen, Jakob Linnet, Kristine Rømer Thomsen, Albert Gjedde, Arne Møller PET Center, Aarhus University Hospital and Center of Functionally Integrative Neuroscience, Aarhus University.   The neurotransmitter dopamine is central to many...... aspects of human functioning, e.g., reward, learning, and addiction, including Pathological Gambling (PG), and its loss is key to Parkinson’s Disease (PD). PD is a neurodegenrative disorder caused by progressive loss of dopamine-producing cells in the midbrain [1]. One type of treatment of PD symptoms...

  9. IDBD: infectious disease biomarker database.

    Science.gov (United States)

    Yang, In Seok; Ryu, Chunsun; Cho, Ki Joon; Kim, Jin Kwang; Ong, Swee Hoe; Mitchell, Wayne P; Kim, Bong Su; Oh, Hee-Bok; Kim, Kyung Hyun

    2008-01-01

    Biomarkers enable early diagnosis, guide molecularly targeted therapy and monitor the activity and therapeutic responses across a variety of diseases. Despite intensified interest and research, however, the overall rate of development of novel biomarkers has been falling. Moreover, no solution is yet available that efficiently retrieves and processes biomarker information pertaining to infectious diseases. Infectious Disease Biomarker Database (IDBD) is one of the first efforts to build an easily accessible and comprehensive literature-derived database covering known infectious disease biomarkers. IDBD is a community annotation database, utilizing collaborative Web 2.0 features, providing a convenient user interface to input and revise data online. It allows users to link infectious diseases or pathogens to protein, gene or carbohydrate biomarkers through the use of search tools. It supports various types of data searches and application tools to analyze sequence and structure features of potential and validated biomarkers. Currently, IDBD integrates 611 biomarkers for 66 infectious diseases and 70 pathogens. It is publicly accessible at http://biomarker.cdc.go.kr and http://biomarker.korea.ac.kr.

  10. DIFFERENTIAL DIAGNOSTICS OF INFECTIOUS EXANTHEMAS IN CHILDREN

    OpenAIRE

    D. Yu. Ovsyannikov

    2015-01-01

    The lecture is devoted to the problem of differential diagnosis of infectious exanthemas in children. Information about differential-diagnostic sings of infectious and non-infectious exanthemas is present. Differential diagnosis is proposed on the basis of morphological elements identified in objective research. Presents possible infectious and non-infectious causes of rashes which are characterized by different primary (spot, papula, blister, knob, knot, bubble, abscess, bladder) and seconda...

  11. DIFFERENTIAL DIAGNOSTICS OF INFECTIOUS EXANTHEMAS IN CHILDREN

    Directory of Open Access Journals (Sweden)

    D. Yu. Ovsyannikov

    2015-01-01

    Full Text Available The lecture is devoted to the problem of differential diagnosis of infectious exanthemas in children. Information about differential-diagnostic sings of infectious and non-infectious exanthemas is present. Differential diagnosis is proposed on the basis of morphological elements identified in objective research. Presents possible infectious and non-infectious causes of rashes which are characterized by different primary (spot, papula, blister, knob, knot, bubble, abscess, bladder and secondary (scale, erosion, ulcer morphological elements.

  12. 人松果体组织结构的退行性变化及其意义%Degenerative pathological change of human pineal body and its significance

    Institute of Scientific and Technical Information of China (English)

    申新华; 马超; 李文婷; 王乃利; 鲍双振; 王保芝

    2012-01-01

    Objective:To study the size, amount, distribution of brain sands and other morphology features in the human pineal body. Methods: Micro-and ultra-structure of 43 pineal bodies from human cadaver was observed under a light microscope, scanning-and transmission electron microscope. Results: The human pineal body was mainly composed of two elements of parenchyma and interstitium. The pineal parenchyma consisted of many pinealocytes and a few neurogliocytes. The pineal interstitium was made up of connective tissues through which the blood vessels and nerve fibers went The brain sands usually clustered together and formed large plaques in the central part of the pineal body. The number and size of brain sands varied individually. In the samples from aged people, we observed an increase in the number and size of brain sands together with proliferation of connective tissues in the interstitium. However, the pinealocytes of parenchyma decreased with aging. In addition, granulovacuolar degeneration was also seen in the pinealocytes. Conclusion: These degenerative pathological changes observed in the human pineal body may lead to progressive degradation of its neuroendo-crine function.%目的:观察人松果体的细微和超微结构,探讨松果体内脑砂的形态特点、大小、多少及分布规律.方法:取人尸体的松果体,光镜、扫描和透射电镜观察其结构特征.结果:松果体主要由实质和间质两种成分构成;松果体实质由松果体细胞和神经胶质细胞组成,间质为结缔组织和穿行其中的神经和血管.脑砂多分布于松果体的中央部,常聚集形成较大的斑块.脑砂的大小、多少个体差异较大.变化趋势为随着年龄的增加,松果体内脑砂增多、增大,并伴有间质成分的结缔组织增生;然而,松果体实质成分减少;而且,在大量的松果体细胞内,可观察到颗粒空泡样变性.结论:松果体组织结构出现的退行性变化,可造成松果体神经内分泌功能的进行性减退.

  13. Pathology of the parathyroid glands in hyperparathyroidism.

    Science.gov (United States)

    Baloch, Zubair W; LiVolsi, Virginia A

    2013-08-01

    This paper reviews the embryology, histology and pathology of the human parathyroid glands. It emphasizes those pathologic lesions which are found in the setting of clinical hyperparathyroidism. Also discussed are certain molecular features of hyperfunctioning parathyroid glands. The difficulties encountered in parathyroid FNA are reviewed and illustrated.

  14. Infectious Disease, Endangerment, and Extinction

    Directory of Open Access Journals (Sweden)

    Ross D. E. MacPhee

    2013-01-01

    Full Text Available Infectious disease, especially virulent infectious disease, is commonly regarded as a cause of fluctuation or decline in biological populations. However, it is not generally considered as a primary factor in causing the actual endangerment or extinction of species. We review here the known historical examples in which disease has, or has been assumed to have had, a major deleterious impact on animal species, including extinction, and highlight some recent cases in which disease is the chief suspect in causing the outright endangerment of particular species. We conclude that the role of disease in historical extinctions at the population or species level may have been underestimated. Recent methodological breakthroughs may lead to a better understanding of the past and present roles of infectious disease in influencing population fitness and other parameters.

  15. The infectious etiology of Alzheimer's Disease.

    Science.gov (United States)

    Sochocka, Marta; Zwolińska, Katarzyna; Leszek, Jerzy

    2017-03-13

    Inflammation is a part of the first line of defense of the body against invasive pathogens, and plays a crucial role in tissue regeneration and repair. A proper inflammatory response ensures the suitable resolution of inflammation and elimination of harmful stimuli, but when the inflammatory reactions are inappropriate it can lead to damage of the surrounding normal cells. The relationship between infections and Alzheimer's Disease (AD) etiology, especially late-onset AD (LOAD) has been continuously debated over the past three decades. It is suggested that chronic viral, bacterial and fungal infections might be causative factors for the inflammatory pathway for AD. Emerging evidence supports the hypothesis of the role of neurotropic viruses from the Herpesviridae family, especially Human herpesvirus 1 (HHV-1), Cytomegalovirus (CMV), and Human herpesvirus 2 (HHV-2), in AD neuropathology. Recent investigations also indicate the association between Hepatitis C virus (HCV) infection and dementia. Among bacteria special attention is focused on spirochetes family and on periodontal pathogens such as Porphyromonas gingivalis or Treponema denticola that could cause chronic periodontitis and possibly contribute to the clinical onset of AD. This review discusses whether infections could be a causative factor that promotes the progression of AD and summarizes recent investigations associating infectious agents and chronic inflammation with AD. Preventive and therapeutic approaches to AD in the context of an infectious etiology of the disease are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Conservation, biodiversity and infectious disease: scientific evidence and policy implications

    Science.gov (United States)

    Young, Hillary S.; Wood, Chelsea L.; Kilpatrick, A. Marm; Lafferty, Kevin D.; Nunn, Charles L.; Vincent, Jeffrey R.

    2017-01-01

    Habitat destruction and infectious disease are dual threats to nature and people. The potential to simultaneously advance conservation and human health has attracted considerable scientific and popular interest; in particular, many authors have justified conservation action by pointing out potential public health benefits . One major focus of this debate—that biodiversity conservation often decreases infectious disease transmission via the dilution effect—remains contentious. Studies that test for a dilution effect often find a negative association between a diversity metric and a disease risk metric, but how such associations should inform conservation policy remains unclear for several reasons. For one, diversity and infection risk have many definitions, making it possible to identify measures that conform to expectations. Furthermore, the premise that habitat destruction consistently reduces biodiversity is in question, and disturbance or conservation can affect disease in many ways other than through biodiversity change. To date, few studies have examined the broader set of mechanisms by which anthropogenic disturbance or conservation might increase or decrease infectious disease risk to human populations. Due to interconnections between biodiversity change, economics and human behaviour, moving from ecological theory to policy action requires understanding how social and economic factors affect conservation.This Theme Issue arose from a meeting aimed at synthesizing current theory and data on ‘biodiversity, conservation and infectious disease’ (4–6 May 2015). Ecologists, evolutionary biologists, economists, epidemiologists, veterinary scientists, public health professionals, and conservation biologists from around the world discussed the latest research on the ecological and socio-economic links between conservation, biodiversity and infectious disease, and the open questions and controversies in these areas. By combining ecological understanding

  17. Emerging Infectious Diseases Cover Art

    Centers for Disease Control (CDC) Podcasts

    2017-07-26

    Byron Breedlove, managing editor of the EID Journal, discusses his approach to cover art.  Created: 7/26/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 7/26/2017.

  18. 75 FR 24835 - Infectious Diseases

    Science.gov (United States)

    2010-05-06

    ... healthcare and social assistance sector as a whole had 16.5 million employees.\\1\\ Healthcare workplaces can... that dealt with the negative impact of non-compliance with hand hygiene on the transmission of... on occupationally-acquired infectious diseases (e.g., Federal, State, provider network, or...

  19. 75 FR 7283 - Board of Scientific Counselors, Coordinating Center for Infectious Diseases, (BSC, CCID)

    Science.gov (United States)

    2010-02-18

    ... National Center for Emerging and Zoonotic Infectious Diseases. 6. Plan the May meeting. Written comments... HUMAN SERVICES Centers for Disease Control and Prevention Board of Scientific Counselors, Coordinating Center for Infectious Diseases, (BSC, CCID) In accordance with section 10(a)(2) of the Federal...

  20. 77 FR 298 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meeting

    Science.gov (United States)

    2012-01-04

    ... HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases... personal privacy. Name of Committee: National Institute of Allergy and Infectious Diseases Special Emphasis..., ec17w@nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.855, Allergy, Immunology,...

  1. 77 FR 298 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2012-01-04

    ... HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases... personal privacy. Name of Committee: National Institute of Allergy and Infectious Diseases Special Emphasis...@niaid.nih.gov . (Catalogue of Federal Domestic Assistance Program Nos. 93.855, Allergy, Immunology,...

  2. 75 FR 7488 - National Institute of Allergy and Infectious Diseases; Notice of Closed Meetings

    Science.gov (United States)

    2010-02-19

    ... HUMAN SERVICES National Institutes of Health National Institute of Allergy and Infectious Diseases... personal privacy. Name of Committee: National Institute of Allergy and Infectious Diseases Special Emphasis..., Bethesda, MD 20892. 301-402-1464. eb237e@nih.gov . Name of Committee: National Institute of Allergy...

  3. The Characteristics of Herpes Simplex Virus Type 1 Infection in Rhesus Macaques and the Associated Pathological Features

    Directory of Open Access Journals (Sweden)

    Shengtao Fan

    2017-01-01

    Full Text Available As one of the major pathogens for human herpetic diseases, herpes simplex virus type 1 (HSV1 causes herpes labialis, genital herpes and herpetic encephalitis. Our aim here was to investigate the infectious process of HSV1 in rhesus macaques and the pathological features induced during this infection. Clinical symptoms that manifested in the rhesus macaque during HSV1 infection included vesicular lesions and their pathological features. Viral distribution in the nervous tissues and associated pathologic changes indicated the typical systematic pathological processes associated with viral distribution of HSV1.Interestingly, vesicular lesions recurred in oral skin or in mucosa associated with virus shedding in macaques within four to five months post‐infection,and viral latency‐associated transcript (LAT mRNA was found in the trigeminal ganglia (TGon day 365 post‐infection. Neutralization testing and enzyme‐linked immunospot (ELISpot detection of specific T cell responses confirmed the specific immunity induced by HSV1 infection. Thus, rhesus macaques could serve as an infectious model for HSV1 due to their typical clinical symptoms and the pathological recurrence associated with viral latency in nervous tissues.

  4. The preparation of an infectious full-length cDNA clone of Saffold virus

    OpenAIRE

    Okuwa Takako; Shimizu Hiroyuki; Asif Naeem; Hosomi Takushi; Himeda Toshiki; Muraki Yasushi; Ohara Yoshiro

    2011-01-01

    Abstract The pathogenicity of Saffold virus (SAFV) among humans still remains unclear, although it was identified as a novel human cardiovirus in 2007. In order to encourage the molecular pathogenetic studies of SAFV, we generated an infectious cDNA clone of SAFV type 3 (SAFV-3). The present study demonstrated that the synthesis of the full-length infectious RNA by T7 RNA polymerase was terminated by a homologous sequence motif with the human preproparathyroid hormone (PTH) signal in the SAFV...

  5. Infectious exposure in the first years of life and risk of central nervous system tumours in children: analysis of birth order, childcare attendance and seasonality of birth

    DEFF Research Database (Denmark)

    Schmidt, L S; Kamper-Jørgensen, M; Schmiegelow, K

    2010-01-01

    An infective, mostly viral basis has been found in different human cancers. To test the hypothesis of a possible infectious aetiology for central nervous system (CNS) tumours in children, we investigated the associations with proxy measures of exposure to infectious disease.......An infective, mostly viral basis has been found in different human cancers. To test the hypothesis of a possible infectious aetiology for central nervous system (CNS) tumours in children, we investigated the associations with proxy measures of exposure to infectious disease....

  6. Application of Molecular Pathology in Endocrine Pathology.

    Science.gov (United States)

    Linke, Ebru Serinsoz; Tezel, Gaye Güler

    2015-01-01

    Rapid growth in knowledge of cell and molecular biology led to the increased usage of molecular techniques in anatomical pathology. This is also due to the advances achieved in the techniques introduced in the last few years which are less laborious as compared to the techniques used at the beginning of the "molecular era". The initial assays were also very expensive and were not performed except for selected centers. Moreover, the clinicians were not sure how to make use of the accumulating molecular information. That situation has also changed and molecular techniques are being performed in a wide variety of medical settings which also has a reflection on the endocrine system pathology among other organ systems. This review will provide an update of genetic changes observed in different endocrine system pathologies and their diagnostic, therapeutic and prognostic values.

  7. Transcriptomic analysis of responses to infectious salmon anemia virus infection in macrophage-like cells

    Science.gov (United States)

    The aquatic orthomyxovirus infectious salmon anemia virus (ISAV) is an important pathogen for salmonid aquaculture, however little is known about protective and pathological host responses to infection. We have investigated intracellular responses during cytopathic ISAV infection in the macrophage-l...

  8. A New Catalog of Microbiological Tools for Women's Infectious Disease Research.

    Science.gov (United States)

    Lewis, Amanda L; Lewis, Warren G

    2016-09-29

    Genitourinary infections pose serious health risks. But, little is known about how genitourinary bacteria attach, maintain colonization, compete for resources, and cause pathology. In this issue, we introduce a new set of 62 genitourinary reference strains of bacteria and their genomes to spur experimental research on infectious diseases that impact women.

  9. A Review of the Comparative Anatomy, Histology, Physiology and Pathology of the Nasal Cavity of Rats, Mice, Dogs and Non-human Primates. Relevance to Inhalation Toxicology and Human Health Risk Assessment.

    Science.gov (United States)

    Chamanza, R; Wright, J A

    2015-11-01

    There are many significant differences in the structural and functional anatomy of the nasal cavity of man and laboratory animals. Some of the differences may be responsible for the species-specific nasal lesions that are often observed in response to inhaled toxicants. This paper reviews the comparative anatomy, physiology and pathology of the nasal cavity of the rat, mouse, dog, monkey and man, highlighting factors that may influence the distribution of nasal lesions. Gross anatomical variations such as turbinate structure, folds or grooves on nasal walls, or presence or absence of accessory structures, may influence nasal airflow and species-specific uptake and deposition of inhaled material. In addition, interspecies variations in the morphological and biochemical composition and distribution of the nasal epithelium may affect the local tissue susceptibility and play a role in the development of species-specific nasal lesions. It is concluded that, while the nasal cavity of the monkey might be more similar to that of man, each laboratory animal species provides a model that responds in a characteristic and species-specific manner. Therefore for human risk assessment, careful consideration must be given to the anatomical differences between a given animal model and man.

  10. Lacrimal Duct Occlusion Is Associated with Infectious Keratitis

    Science.gov (United States)

    Li, Guigang; Guo, Jingmin; Liu, Rong; Hu, Weikun; Xu, Lingjuan; Wang, Juan; Cai, Subo; Zhang, Hong; Zhu, Yingting

    2016-01-01

    Background: To explore the prevalence of lacrimal duct obstruction in patients with infectious keratitis, and the necessity of lacrimal duct dredge in the treatment of human infectious keratitis. Methodology/Principle Findings: The design is prospective, non-control case series. Thirty-one eyes from twenty-eight continuous patients with infectious keratitis were included in this study. The presence/absence of lacrimal duct obstruction was determined by the lacrimal duct irrigation test. The diagnosis of infectious keratitis was made based on clinical manifestations, cornea scraping microscopic examination and bacterial/fungus culture. Diagnosis of viral keratitis was set up based on the recurrent history, deep neovascularization and typical outlook of the cornea scar. The treatment of keratitis included drugs, eye drops or surgery, while treatment of chronic dacryocystitis was lacrimal duct dredging with supporting tube implantation surgery. In the thirty-one eyes with infectious keratitis, fifteen suffered from fungal keratitis (48%), two bacterial keratitis (6%), and fourteen viral keratitis (45%). Eleven eyes (35%) from ten patients with infectious keratitis also suffered from lacrimal duct obstruction. In those cases, six eyes also suffered from lower canalicular obstruction, three nasolacrimal duct obstruction and chronic dacryocystitis, one a combination of upper and lower canalicular obstruction, one upper canalicular obstruction. After local and systemic applications of anti-bacterial, anti-viral, anti-fungal and anti-inflammatory drugs, twenty-eight eyes (90%) recovered within three weeks, while the ulceration of three patients required the lacrimal duct dredging and supporting tube implantation surgery for the healing. Conclusions: Herein, we first report that the prevalence of infectious keratitis is closely correlated to the occurrence of lacrimal duct obstruction. When both confirmed, simultaneous treatment of keratitis and lacrimal duct obstruction

  11. Therapeutic and lesional aspects of feline infectious peritonitis

    Directory of Open Access Journals (Sweden)

    Adrian C. Stancu

    2013-05-01

    Full Text Available The prevalence of feline infectious peritonitis (FIP can not be assessed on the basis of serological surveys because positive serological reagents rate does not correlate with disease rates. In units with more cats and numerous movements (input - output, the proportion of positive serological reagents is very high, and could reach, in some countries or regions at 50-75-100%, while among cats scattered nearhomes reactants rate positive to VPIF is well below 50%. Research conducted aimed at treating and determining evolutionary form of FIP based on pathological lesions in dead cats.

  12. Global climate change and infectious diseases

    Energy Technology Data Exchange (ETDEWEB)

    Shope, R. (Yale Univ. School of Medicine, New Haven, CT (United States))

    1991-12-01

    The effects of global climate change on infectious diseases are hypothetical until more is known about the degree of change in temperature and humidity that will occur. Diseases most likely to increase in their distribution and severity have three-factor (agent, vector, and human being) and four-factor (plus vertebrate reservoir host) ecology. Aedes aegypti and Aedes albopictus mosquitoes may move northward and have more rapid metamorphosis with global warming. These mosquitoes transmit dengue virus, and Aedes aegypti transmits yellow fever virus. The faster metamorphosis and a shorter extrinsic incubation of dengue and yellow fever viruses could lead to epidemics in North America. Vibrio cholera is harbored persistently in the estuaries of the U.S. Gulf Coast. Over the past 200 years, cholera has become pandemic seven times with spread from Asia to Europe, Africa, and North America. Global warming may lead to changes in water ecology that could enhance similar spread of cholera in North America. Some other infectious diseases such as LaCrosse encephalitis and Lyme disease are caused by agents closely dependent on the integrity of their environment. These diseases may become less prominent with global warming because of anticipated modification of their habitats. Ecological studies will help as to understand more fully the possible consequences of global warming. New and more effective methods for control of vectors will be needed. 12 refs., 1 tab.

  13. Handheld computing in pathology

    Directory of Open Access Journals (Sweden)

    Seung Park

    2012-01-01

    Full Text Available Handheld computing has had many applications in medicine, but relatively few in pathology. Most reported uses of handhelds in pathology have been limited to experimental endeavors in telemedicine or education. With recent advances in handheld hardware and software, along with concurrent advances in whole-slide imaging (WSI, new opportunities and challenges have presented themselves. This review addresses the current state of handheld hardware and software, provides a history of handheld devices in medicine focusing on pathology, and presents future use cases for such handhelds in pathology.

  14. Handheld computing in pathology

    Science.gov (United States)

    Park, Seung; Parwani, Anil; Satyanarayanan, Mahadev; Pantanowitz, Liron

    2012-01-01

    Handheld computing has had many applications in medicine, but relatively few in pathology. Most reported uses of handhelds in pathology have been limited to experimental endeavors in telemedicine or education. With recent advances in handheld hardware and software, along with concurrent advances in whole-slide imaging (WSI), new opportunities and challenges have presented themselves. This review addresses the current state of handheld hardware and software, provides a history of handheld devices in medicine focusing on pathology, and presents future use cases for such handhelds in pathology. PMID:22616027

  15. Infectious diseases following natural disasters: prevention and control measures.

    Science.gov (United States)

    Kouadio, Isidore K; Aljunid, Syed; Kamigaki, Taro; Hammad, Karen; Oshitani, Hitoshi

    2012-01-01

    Natural disasters may lead to infectious disease outbreaks when they result in substantial population displacement and exacerbate synergic risk factors (change in the environment, in human conditions and in the vulnerability to existing pathogens) for disease transmission. We reviewed risk factors and potential infectious diseases resulting from prolonged secondary effects of major natural disasters that occurred from 2000 to 2011. Natural disasters including floods, tsunamis, earthquakes, tropical cyclones (e.g., hurricanes and typhoons) and tornadoes have been secondarily described with the following infectious diseases including diarrheal diseases, acute respiratory infections, malaria, leptospirosis, measles, dengue fever, viral hepatitis, typhoid fever, meningitis, as well as tetanus and cutaneous mucormycosis. Risk assessment is essential in post-disaster situations and the rapid implementation of control measures through re-establishment and improvement of primary healthcare delivery should be given high priority, especially in the absence of pre-disaster surveillance data.

  16. Infectious diseases and global warming: Tracking disease incidence rates globally

    Energy Technology Data Exchange (ETDEWEB)

    Low, N.C. [Low and Associates Actuary, Cerritos, CA (United States)

    1995-09-01

    Given the increasing importance of impact of global warming on public health, there is no global database system to monitor infectious disease and disease in general, and to which global data of climate change and environmental factors, such as temperature, greenhouse gases, and human activities, e.g., coastal development, deforestation, can be calibrated, investigated and correlated. The author proposes the diseases incidence rates be adopted as the basic global measure of morbidity of infectious diseases. The importance of a correctly chosen measure of morbidity of disease is presented. The importance of choosing disease incidence rates as the measure of morbidity and the mathematical foundation of which are discussed. The author further proposes the establishment of a global database system to track the incidence rates of infectious diseases. Only such a global system can be used to calibrate and correlate other globally tracked climatic, greenhouse gases and environmental data. The infrastructure and data sources for building such a global database is discussed.

  17. Evaluación de la respuesta clínico-patológica e inmune humoral en crías de trucha arco iris (Oncorhynchus mykiss infectadas experimentalmente con el virus de la Necrosis Pancreática Infecciosa (IPNV Evaluation of the clinical-pathological and humoral immune response in rainbow trout fry (Oncorhynchus mykiss experimentally infected with Infectious Pancreatic Necrosis Virus (IPNV

    Directory of Open Access Journals (Sweden)

    LF Vega

    2011-01-01

    Full Text Available Se realizó un estudio para obtener información acerca de la relación existente entre el cuadro clínico-patológico desarrollado en crías de trucha arco iris (Oncorhynchus mykiss infectadas con el virus de la necrosis pancreática infecciosa (IPNV y el nivel de inmunoglobulina M (IgM en suero sanguíneo. Los parámetros fueron determinados hasta 45 días postinfección (dpi en peces inoculados por vía intraperitoneal (IP con 1X10(4 TCDI de IPNV o únicamente inoculados con Medio Mínimo Esencial (MEM y en un grupo control no inoculado. Los peces infectados presentaron los signos característicos de necrosis pancreática (IPN a partir de 19 dpi, alcanzando una mortalidad acumulada de 70%, con evidente emaciación de animales sobrevivientes; asimismo, el nivel de IgM en suero sanguíneo se incrementó progresivamente hasta alcanzar su punto máximo a 31 dpi; los hallazgos histopatológicos más significativos fueron: incremento de centros de melanomacrófagos en riñón, necrosis pancreática y enteritis catarral. El aislamiento viral fue posible únicamente en peces infectados a partir del día 3 y hasta los 45 dpi (P > 0,5. Los resultados observados sugieren que aunque los animales infectados con IPNV pueden desarrollar una respuesta inmune humoral caracterizada por incremento de IgM, ésta es insuficiente para desarrollar protección, ya que al mismo tiempo que se incrementa el nivel de IgM, también aumenta el título viral, acompañado de signos clínicos y lesiones histopatológicas típicas de la enfermedad.The aim of this study was to assess the relationship between the clinical-pathologic process in rainbow trout fry (Oncorhynchus mykiss infected with infectious pancreatic necrosis virus (IPNV and the immunoglobulin M (IgM levels in blood serum. Parameters were evaluated up to 45 days post infection (dpi in fish intraperitoneally inoculated (IP with 1X10(4 TCDI of IPNV, with minimal essential medium (MEM and in the control group

  18. Infectious pathogens and bronchiolitis outcomes.

    Science.gov (United States)

    Hasegawa, Kohei; Mansbach, Jonathan M; Camargo, Carlos A

    2014-07-01

    Bronchiolitis is a common early childhood illness and an important cause of morbidity, it is the number one cause of hospitalization among US infants. Bronchiolitis is also an active area of research, and recent studies have advanced our understanding of this illness. Although it has long been the conventional wisdom that the infectious etiology of bronchiolitis does not affect outcomes, a growing number of studies have linked specific pathogens of bronchiolitis (e.g., rhinovirus) to short- and long-term outcomes, such as future risk of developing asthma. The authors review the advent of molecular diagnostic techniques that have demonstrated diverse pathogens in bronchiolitis, and they review recent studies on the complex link between infectious pathogens of bronchiolitis and the development of childhood asthma.

  19. Infectious Diseases in Sub-Saharan Immigrants to Spain.

    Science.gov (United States)

    Serre Delcor, Núria; Maruri, Begoña Treviño; Arandes, Antoni Soriano; Guiu, Isabel Claveria; Essadik, Hakima Ouaarab; Soley, Mateu Espasa; Romero, Israel Molina; Ascaso, Carlos

    2016-04-01

    Immigrants may be carriers of infectious diseases because of the prevalence of these diseases in their country of origin, exposure during migration, or conditions during resettlement, with this prevalence being particularly high in sub-Saharan Africans. We performed a retrospective review of 180 sub-Saharan immigrants screened for infectious diseases at an International Health Center from January 2009 to December 2012. At least one pathogenic infectious disease was diagnosed in 72.8% patients: 60.6% latent tuberculosis infection, 36.8% intestinal parasites (intestinal protozoa or helminths), 28.1% helminths, 14.8% hepatitis B surface antigen positive, 1.2% anti-hepatitis C virus positive, 1.2% human immunodeficiency virus-positive, and 1.2% malaria. Coinfections were present in 28.4%. There was significant association between eosinophilia (absolute count or percentage) or hyper-IgE and the presence of helminths (P< 0.001). Relative eosinophilia and hyper-IgE were better indicators of helminth infection than absolute eosinophilia, particularly for schistosomiasis and strongyloidiasis. We found a high prevalence of infectious diseases in sub-Saharan immigrants, which could lead to severe health problems (in the absence of prompt treatment), representing a high cost to the public health system and possible transmission in the host country. Accurate screening and tailored protocols for infectious diseases are recommended in sub-Saharan immigrants.

  20. Radiological-Pathological Correlations Following Blast-Related Traumatic Brain Injury in the Whole Human Brain Using ex Vivo Diffusion Tensor Imaging

    Science.gov (United States)

    2014-01-01

    injuries caused by non-blast related trauma (e.g. falls, motor vehicle accidents, etc.), post - mortem pathological analyses have revealed that...issues: 1) Selection of control cases: we will select only young, otherwise healthy patients who died from non-head trauma and had a short post - mortem ...20 Oppenheimer, D. R. (1968). "Microscopic lesions in the brain following head injury." J Neurol Neurosurg Psychiatry 31(4): 299-306. http

  1. Acute tonsillitis at infectious patients

    Directory of Open Access Journals (Sweden)

    Y. P. Finogeev

    2011-01-01

    Full Text Available We examined 1824 patients with diphtheria treated in Clinical Infectious Diseases Hospital Botkin (St. Petersburg in 1993 – 1994, and more than 500 patients referred to the clinic with a diagnosis of «angina». Based on published data and our own research observations investigated the etiology of acute tonsillitis. Bacterial tonsillitis should be treated with antibiotics, and this is important aetiological interpretation of these diseases. Streptococcal tonsillitis should always be a sore throat syndrome as a diagnostic sign of support. For other forms of lymphoma lesion of the tonsils should not be defined as «angina», and called «tonsillitis». Аngina as β-hemolytic streptococcus group A infection is recognized as the leader in the development of rheumatic fever. On the basis of a large clinical material briefly analyzed the clinical manifestations of various forms of diphtheria with membranous tonsillitis. Also presented with a syndrome of infectious diseases as tonsillitis, therapeutic and surgical «mask» of infectious diseases.

  2. Human Dirofilaria repens Infection in Romania: A Case Report

    Directory of Open Access Journals (Sweden)

    Ioana Popescu

    2012-01-01

    Full Text Available Human dirofilariasis is a zoonotic infectious disease caused by the filarial nematodes of dogs Dirofilaria repens and Dirofilaria immitis. Depending on the species involved, human infections usually manifest as one cutaneous or visceral larva migrans that forms a painless nodule in the later course of disease. Dirofilariae are endemic in the Mediterranean, particularly in Italy. They are considered as emerging pathogens currently increasing their geographical range. We present one of the few known cases of human dirofilariasis caused by D. repens in Romania. The patient developed unusual and severe clinical manifestations that mimicked pathological conditions like cellulitis or deep venous thrombosis.

  3. Hip joint pathology

    DEFF Research Database (Denmark)

    Tijssen, M; van Cingel, R E H; de Visser, E

    2016-01-01

    The purpose of this retrospective cohort study was to (a) describe the clinical presentation of femoroacetabular impingement (FAI) and hip labral pathology; (b) describe the accuracy of patient history and physical tests for FAI and labral pathology as confirmed by hip arthroscopy. Patients (18-6...

  4. Updates in ophthalmic pathology.

    Science.gov (United States)

    Mendoza, Pia R; Grossniklaus, Hans E

    2017-05-01

    Ophthalmic pathology has a long history and rich heritage in the field of ophthalmology. This review article highlights updates in ophthalmic pathology that have developed significantly through the years because of the efforts of committed individuals and the confluence of technology such as molecular biology and digital pathology. This is an exciting period in the history of ocular pathology, with cutting-edge techniques paving the way for new developments in diagnostics, therapeutics, and research. Collaborations between ocular oncologists and pathologists allow for improved and comprehensive patient care. Ophthalmic pathology continues to be a relevant specialty that is important in the understanding and clinical management of ocular disease, education of eye care providers, and overall advancement of the field.

  5. Simulating City-level Airborne Infectious Diseases

    CERN Document Server

    Shan, Mei; Yifan, Zhu; Zhenghu, Zu; Tao, Zheng; Boukhanovsky, A V; Sloot, P M A

    2012-01-01

    With the exponential growth in the world population and the constant increase in human mobility, the danger of outbreaks of epidemics is rising. Especially in high density urban areas such as public transport and transfer points, where people come in close proximity of each other, we observe a dramatic increase in the transmission of airborne viruses and related pathogens. It is essential to have a good understanding of the `transmission highways' in such areas, in order to prevent or to predict the spreading of infectious diseases. The approach we take is to combine as much information as is possible, from all relevant sources and integrate this in a simulation environment that allows for scenario testing and decision support. In this paper we lay out a novel approach to study Urban Airborne Disease spreading by combining traffic information, with geo-spatial data, infection dynamics and spreading characteristics.

  6. Ribonucleoprotein of avian infectious bronchitis virus.

    Science.gov (United States)

    Davies, H A; Dourmashkin, R R; Macnaughton, M R

    1981-03-01

    The ribonucleoprotein (RNP) of avian infectious bronchitis virus (IBV) was examined by electron microscopy after shadowing with carbon/platinum. Linear RNP strands up to 6.7 microns in length, from three IVB strains, were sensitive to both pancreatic RNase and to proteases. These strands were obtained from spontaneously disrupted complete particles but not from disrupted incomplete particles that lacked RNP. They were also released from Nonidet P40-disrupted particles and could be isolated on sucrose density gradients at a density of 1.27 g/ml. In some cases, helical RNP complexes associated with virus particles were observed that were similar to RNPs of human coronavirus strain 229E and mouse hepatitis virus strain 3.

  7. Eight challenges in modelling infectious livestock diseases

    Directory of Open Access Journals (Sweden)

    E. Brooks-Pollock

    2015-03-01

    Full Text Available The transmission of infectious diseases of livestock does not differ in principle from disease transmission in any other animals, apart from that the aim of control is ultimately economic, with the influence of social, political and welfare constraints often poorly defined. Modelling of livestock diseases suffers simultaneously from a wealth and a lack of data. On the one hand, the ability to conduct transmission experiments, detailed within-host studies and track individual animals between geocoded locations make livestock diseases a particularly rich potential source of realistic data for illuminating biological mechanisms of transmission and conducting explicit analyses of contact networks. On the other hand, scarcity of funding, as compared to human diseases, often results in incomplete and partial data for many livestock diseases and regions of the world. In this overview of challenges in livestock disease modelling, we highlight eight areas unique to livestock that, if addressed, would mark major progress in the area.

  8. Managed care and the infectious diseases specialist.

    Science.gov (United States)

    Tice, A D; Slama, T G; Berman, S; Braun, P; Burke, J P; Cherney, A; Gross, P A; Harris, P; Reid-Hatton, M; Hoffman, R; Joseph, P; Lawton, S; Massanari, R M; Miller, Z I; Osheroff, W J; Poretz, D; Shalowitz, M; Simmons, B; Turner, J P; Wade, B; Nolet, B R

    1996-08-01

    There is growing demand to contain health care costs and to reassess the value of medical services. The traditional hospital, academic, and research roles of the infectious disease (ID) specialist are threatened, yet there is an increasing need for expertise because of growing antimicrobial resistance and emerging pathogens. Opportunities exist to develop and expand services for the care of patients infected with human immunodeficiency virus and in infection control, epidemiology, outcomes research, outpatient intravenous therapy, and resource management. It is important for ID physicians to appreciate the principles involved in managed care and the areas in which ID services can be valuable. To be effective, physicians need to know about tools such as practice guidelines, physician profiling, outcomes monitoring, computerized information management, risk sharing, networking, and marketing, as well as related legal issues. With a positive attitude toward learning, application, and leadership, ID physicians can redefine their role and expand their services through managed care.

  9. Proactive strategies to avoid infectious disease.

    Science.gov (United States)

    Stevenson, Richard J; Case, Trevor I; Oaten, Megan J

    2011-12-12

    Infectious disease exerts a large selective pressure on all organisms. One response to this has been for animals to evolve energetically costly immune systems to counter infection, while another--the focus of this theme issue--has been the evolution of proactive strategies primarily to avoid infection. These strategies can be grouped into three types, all of which demonstrate varying levels of interaction with the immune system. The first concerns maternal strategies that function to promote the immunocompetence of their offspring. The second type of strategy influences mate selection, guiding the selection of a healthy mate and one who differs maximally from the self in their complement of antigen-coding genes. The third strategy involves two classes of behaviour. One relates to the capacity of the organisms to learn associations between cues indicative of pathogen threat and immune responses. The other relates to prevention and even treatment of infection through behaviours such as avoidance, grooming, quarantine, medicine and care of the sick. In humans, disease avoidance is based upon cognition and especially the emotion of disgust. Human disease avoidance is not without its costs. There is a propensity to reject healthy individuals who just appear sick--stigmatization--and the system may malfunction, resulting in various forms of psychopathology. Pathogen threat also appears to have been a highly significant and unrecognized force in shaping human culture so as to minimize infection threats. This cultural shaping process--moralization--can be co-opted to promote human health.

  10. Pathological Gambling in Parkinson's Disease

    DEFF Research Database (Denmark)

    Callesen, Mette Buhl; Linnet, Jakob; Thomsen, Kristine Rømer

    Pathological Gambling in Parkinson’s Disease Mette Buhl Callesen, Jakob Linnet, Kristine Rømer Thomsen, Albert Gjedde, Arne Møller PET Center, Aarhus University Hospital and Center of Functionally Integrative Neuroscience, Aarhus University.   The neurotransmitter dopamine is central to many...... aspects of human functioning, e.g., reward, learning, and addiction, including Pathological Gambling (PG), and its loss is key to Parkinson’s Disease (PD). PD is a neurodegenrative disorder caused by progressive loss of dopamine-producing cells in the midbrain [1]. One type of treatment of PD symptoms...... is medication that binds to dopamine receptors in the brain, i.e., dopamine agonists [1]. Unfortunately, for some PD patients a very serious side effect to this specific kind of treatment is developing PG. PG is an Impulse Control Disorder characterized by recurrent maladaptive behavior associated with personal...

  11. Mechanistic Differences Leading to Infectious and Sterile Inflammation.

    Science.gov (United States)

    Behnia, Faranak; Sheller, Samantha; Menon, Ramkumar

    2016-05-01

    Inflammation is a physiologic component of pregnancy and parturition. Overwhelming intrauterine inflammatory load promotes quiescent feto-maternal tissues into a contractile phenotype. Like inflammation, oxidative stress is an inevitable component of both pregnancy and parturition. Pathologic activation of host innate immune response to adverse pregnancy conditions can lead to premature activation of inflammatory and oxidative stress. Inflammation and oxidative stress markers seen with both sterile and infectious inflammation are often similar; therefore, it is difficult to understand causality of conditions like spontaneous preterm birth. This review demonstrates potential mechanistic pathways of activation of sterile and infectious inflammation. We demonstrate the activation of two unique pathways of inflammation by factors that are well-documented proxies for oxidative stress (cigarette smoke extract) and infection (lipopolysaccharide). Sterile inflammation seen after exposure to an oxidative stress inducer is due to cellular elemental damage resulting in p38 mitogen-activated protein kinase (MAPK) induced cellular senescence. Infectious inflammation is through activation of transcription factor NF-κB and independent of oxidative stress-associated damages and p38 MAPK-induced senescence. Understanding the differences in the inflammatory pathway activation by various risk factors is important to design better screening, diagnostic and intervention strategies to reduce the risks of adverse pregnancy outcomes.

  12. [Pathology- a new revival].

    Science.gov (United States)

    Barshack, Iris

    2013-06-01

    The field of pathology has undergone considerable change in recent years. The editor and editorial board of this journal are to be commended for their decision to devote a special issue to the field of pathology. Pathology deals with the characterization, investigation, and diagnosis of disease and disease processes and as such, has Long been considered one of the foundations of medicine. It is a rich and multi-faceted field which has retained its breadth of scope in the face of ever-increasing specialization and sub-specialization in medicine. In addition to its classic roles in autopsy, case description, and the diagnosis of pathoLogic processes, new and innovative spheres of activity are becoming integral to the field, especially in the realm of molecular pathology. Pathology is a Leading player in the new age of "personalized cancer therapy", where pathologists are responsible not only for diagnosing disease in the tissue, but also for conducting additional tests which may predict its response to specific drug therapies. In this context, moLecular pathology has become essential to the field both in the provision of cLinical service and research. To fully implement this trend, we are witness to the rise of tissue collection and tissue banking initiatives for both diagnostic and research purposes. A national tissue banking project in Israel has recently received considerable attention.

  13. Key points in the presentation of the infectious bursal disease

    Directory of Open Access Journals (Sweden)

    Javier Andrés Jaimes-Olaya

    2009-06-01

    Full Text Available The infectious bursal disease or Gumboro disease is an immunosuppressive pathology of birds, which has great importance in the poultry industry due to large economic losses that it produces not only for its direct effect, but because of the susceptibility to secondary infections, interference with commercial vaccines, reducing the effective use of them. The disease is produced by the infectious bursal disease virus (IBDV, which is an RNA genome birnavirus, with high capacity for mutation, so the agent is continually evolving. The pathology has three types of clinical presentation: a subclinical form, a mild or moderate clinical form and a severe clinical form. However, the type of manifestation is determined mainly by three factors: the age of birds at the time of infection, the type of strain or acting or genetic variability of it, and the immunity degree. In this article, we discuss each of these factors and their importance in the presentation of the disease. These elements are vital in order to establish effective prevention and control programs.

  14. Investigative modalities in infectious keratitis

    Directory of Open Access Journals (Sweden)

    Gupta Noopur

    2008-01-01

    Full Text Available Standard recommended guidelines for diagnosis of infectious keratitis do exist. Based on an extensive Medline literature search, the various investigative modalities available for aiding the diagnosis of microbial keratitis have been reviewed and described briefly. Preferred practice patterns have been outlined and the importance of routine pre-treatment cultures in the primary management of infectious keratitis has been highlighted. Corneal scraping, tear samples and corneal biopsy are few of the specimens needed to carry out the investigative procedures for diagnosis and for initiating therapy in cases of microbial keratitis. In bacterial, fungal and amoebic keratitis, microscopic examination of smears is essential for rapid diagnosis. Potassium hydroxide (KOH wet mount, Gram′s stain and Giemsa stain are widely used and are important for clinicians to start empirical therapy before microbial culture results are available. The usefulness of performing corneal cultures in all cases of suspected infectious keratitis has been well established. In cases of suspected viral keratitis, therapy can be initiated on clinical judgment alone. If a viral culture is needed, scrapings should directly be inoculated into the viral transport media. In vivo confocal microscopy is a useful adjunct to slit lamp bio-microscopy for supplementing diagnosis in most cases and establishing early diagnosis in many cases of non-responding fungal and amoebic keratitis. This is a non-invasive, high resolution technique which allows rapid detection of Acanthamoeba cysts and trophozoites and fungal hyphae in the cornea long before laboratory cultures give conclusive results. Other new modalities for detection of microbial keratitis include molecular diagnostic techniques like polymerase chain reaction, and genetic finger printing by pulsed field gel electrophoresis.

  15. [Gunshot wounds: forensic pathology].

    Science.gov (United States)

    Lorin de la Grandmaison, Geoffroy

    2012-02-01

    Gunshot wounds are among the most complex traumatic lesions encountered in forensic pathology. At the time of autopsy, careful scrutiny of the wounds is essential for correct interpretation of the lesions. Complementary pathological analysis has many interests: differentiation between entrance and exit wounds, estimation of firing distance, differentiation between vital and post mortem wounds and wounds dating. In case of multiple headshots, neuropathological examination can provide arguments for or against suicide. Sampling of gunshot wounds at autopsy must be systematic. Pathological data should be confronted respectively to autopsy and death scene investigation data and also ballistic studies. Forensic pathologist must be aware of the limits of optic microscopy.

  16. Contribution of Human Lung Parenchyma and Leukocyte Influx to Oxidative Stress and Immune System-Mediated Pathology following Nipah Virus Infection.

    Science.gov (United States)

    Escaffre, Olivier; Saito, Tais B; Juelich, Terry L; Ikegami, Tetsuro; Smith, Jennifer K; Perez, David D; Atkins, Colm; Levine, Corri B; Huante, Matthew B; Nusbaum, Rebecca J; Endsley, Janice J; Freiberg, Alexander N; Rockx, Barry

    2017-08-01

    Nipah virus (NiV) is a zoonotic emerging paramyxovirus that can cause fatal respiratory illness or encephalitis in humans. Despite many efforts, the molecular mechanisms of NiV-induced acute lung injury (ALI) remain unclear. We previously showed that NiV replicates to high titers in human lung grafts in NOD-SCID/γ mice, resulting in a robust inflammatory response. Interestingly, these mice can undergo human immune system reconstitution by the bone marrow, liver, and thymus (BLT) reconstitution method, in addition to lung tissue engraftment, giving altogether a realistic model to study human respiratory viral infections. Here, we characterized NiV Bangladesh strain (NiV-B) infection of human lung grafts from human immune system-reconstituted mice in order to identify the overall effect of immune cells on NiV pathogenesis of the lung. We show that NiV-B replicated to high titers in human lung grafts and caused similar cytopathic effects irrespective of the presence of human leukocytes in mice. However, the human immune system interfered with virus spread across lung grafts, responded to infection by leukocyte migration to small airways and alveoli of the lung grafts, and accelerated oxidative stress in lung grafts. In addition, the presence of human leukocytes increased the expression of cytokines and chemokines that regulate inflammatory influx to sites of infection and tissue damage. These results advance our understanding of how the immune system limits NiV dissemination and contributes to ALI and inform efforts to identify therapeutic targets.IMPORTANCE Nipah virus (NiV) is an emerging paramyxovirus that can cause a lethal respiratory and neurological disease in humans. Only limited data are available on NiV pathogenesis in the human lung, and the relative contribution of the innate immune response and NiV to acute lung injury (ALI) is still unknown. Using human lung grafts in a human immune system-reconstituted mouse model, we showed that the NiV Bangladesh

  17. Global climate and infectious disease: The cholera paradigm

    Energy Technology Data Exchange (ETDEWEB)

    Colwell, R.R. [Univ. of Maryland Biotechnology Inst., College Park, MD (United States)

    1996-12-20

    Historically, infectious diseases have had a profound effect on human populations, including their evolution and cultural development. Despite significant advances in medical science, infectious diseases continue to impact human populations in many parts of the world. Emerging diseases are considered to be those infections that either are newly appearing in the population or are rapidly increasing in incidence or expanding in geographic range. Emergence of disease is not a simple phenomenon, mainly because infectious diseases are dynamic. Most new infections are not caused by truly new pathogens but are microorganisms (viruses, bacteria, fungi, protozoa, and helminths) that find a new way to enter a susceptible host and are newly recognized because of recently developed, sensitive techniques. Human activities drive emergence of disease and a variety of social, economic, political, climatic, technological, and environmental factors can shape the pattern of a disease and influence its emergence into populations. For example, travel affects emergence of disease, and human migrations have been the main source of epidemics throughout history. Trade caravans, religious pilgrimage, and military campaigns facilitated the spread of plague, smallpox, and cholera. Global travel is a fact of modern life and, equally so, the continued evolution of microorganisms; therefore, new infections will continue to emerge, and known infections will change in distribution, frequency, and severity. 88 refs., 1 fig.

  18. Infectious Risks of Traveling Abroad.

    Science.gov (United States)

    Chen, Lin H; Blair, Barbra M

    2015-08-01

    A popular leisure activity, international travel can be associated with some infections. The most common travel-related illnesses appear to be gastrointestinal, dermatologic, respiratory, and systemic febrile syndromes. The pretravel medical consultation includes immunizations, malaria chemoprophylaxis, self-treatment for traveler's diarrhea, and advice on the prevention of a myriad of other infectious causes including dengue, chikungunya, rickettsiosis, leptospirosis, schistosomiasis, and strongyloidiasis. Travel to locations experiencing outbreaks such as Ebola virus disease, Middle East respiratory syndrome, avian influenza, and chikungunya call for specific alerts on preventive strategies. After travel, evaluation of an ill traveler must explore details of exposure, including destinations visited; activities; ingestion of contaminated food or drinks; contact with vectors, animals, fresh water, or blood and body fluids; and other potential exposures. Knowledge of the geographic distribution of infectious diseases is important in generating the differential diagnoses and testing accordingly. Empiric treatment is sometimes necessary when suspicion of a certain diagnosis is strong and confirmatory tests are delayed or lacking, particularly for infections that are rapidly progressive (for example, malaria) or for which timing of testing is prolonged (such as leptospirosis).

  19. Infectious bovine keratoconjunctivitis: a review.

    Science.gov (United States)

    Brown, M H; Brightman, A H; Fenwick, B W; Rider, M A

    1998-01-01

    The economic impact of infectious bovine keratoconjunctivitis (IBK) warrants continued investigation of the mechanisms by which Moraxella bovis survives on and colonizes the corneal surface. Virulent strains of M bovis produce hemolysin and exhibit different plasmid profiles than nonvirulent strains. Interactions among host, environment, vector, season, and concurrent infection influence the prevalence of IBK. Mycoplasma sp. or infectious bovine rhinotracheitis virus may enhance or hasten the disease process. The manifestations of IBK may range from mild conjunctivitis to severe ulceration, corneal perforation, and blindness. Treatment of IBK is dictated by economic considerations, intended animal use, and feasibility of administration. Antibiotic therapy is aimed at achieving drug concentrations in tears to meet or exceed the minimum inhibitory concentration for prolonged periods. At present, IBK is not a preventable disease. Affected animals must be separated from the herd and vector control vigorously instituted. Carrier animals must be identified and removed from the herd. Vaccination trials have been unsuccessful because of pili antigen cross-reactivity, variable strains, and uncontrolled environmental factors. Recent investigations have determined that M bovis may utilize host iron sources via iron-repressible outer membrane proteins and siderophores for growth. Elucidation of normal defense mechanisms of the bovine eye may lead to new strategies to enhance the immune response against M bovis.

  20. Determinants of pathologic mineralization.

    Science.gov (United States)

    Kirsch, Thorsten

    2008-01-01

    Physiologic mineralization is necessary for the formation of skeletal tissues and for their appropriate functions during adulthood. Mineralization has to be controlled and restricted to specific regions. If the mineralization process occurs in regions that normally do not mineralize, there can be severe consequences (pathologic or ectopic mineralization). Recent findings have indicated that physiologic and pathologic mineralization events are initiated by matrix vesicles, membrane-enclosed particles released from the plasma membranes of mineralization-competent cells. The understanding of how these vesicles are released from the plasma membrane and initiate the mineralization process may provide novel therapeutic strategies to prevent pathologic mineralization. In addition, other regulators (activators and inhibitors) of physiologic mineralization have been identified and characterized, and there is evidence that the same factors also contribute to the regulation of pathologic mineralization. Finally, programmed cell death (apoptosis) may be a contributor to physiologic mineralization and if occurring after tissue injury may induce pathologic mineralization and mineralization-related differentiation events in the injured and surrounding areas. This review describes how the understanding of mechanisms and factors regulating physiologic mineralization can be used to develop new therapeutic strategies to prevent pathologic or ectopic mineralization events.

  1. The practice of infectious diseases in the 1990s: the Canadian experience.

    Science.gov (United States)

    Schlech, W F

    1995-02-01

    A survey of the members of the Canadian Infectious Disease Society was carried out to determine the content of an infectious diseases consultative practice in the 1990s. Respondents were asked to identify all new inpatient, outpatient, and telephone consultations during a 1-week period in 1990. Consultations were categorized by the infectious disease syndrome of the patient and by the microorganism that was identified. Bacterial infections were the most common cause of inpatient consultations, while viral infections were more common in outpatients. Consultations for parasitic infections were primarily for Pneumocystis carinii pneumonia related to infection with the human immunodeficiency virus (HIV). "Newer" infectious disease syndromes such as chronic fatigue syndrome, toxic shock syndrome, and Lyme disease were all represented in the responses for the 1-week study period. The significant impact of HIV infection on the overall consultative load suggests that there will be a continuing need for newly trained infectious disease consultants into the 21st century.

  2. Synthetic Biology-Based Point-of-Care Diagnostics for Infectious Disease.

    Science.gov (United States)

    Wei, Ting-Yen; Cheng, Chao-Min

    2016-09-22

    Infectious diseases outpace all other causes of death in low-income countries, posing global health risks, laying stress on healthcare systems and societies, and taking an avoidable human toll. One solution to this crisis is early diagnosis of infectious disease, which represents a powerful way to optimize treatment, increase patient survival rate, and decrease healthcare costs. However, conventional early diagnosis methods take a long time to generate results, lack accuracy, and are known to seriously underperform with regard to fungal and viral infections. Synthetic biology offers a fast and highly accurate alternative to conventional infectious disease diagnosis. In this review, we outline obstacles to infectious disease diagnostics and discuss two emerging alternatives: synthetic viral diagnostic systems and biosensors. We argue that these synthetic biology-based approaches may overcome diagnostic obstacles in infectious disease and improve health outcomes.

  3. Sources of potentially infectious human microsporidia: molecular characterisation of microsporidia isolates from exotic birds in the Czech Republic, prevalence study and importance of birds in epidemiology of the human microsporidial infections.

    Science.gov (United States)

    Kasicková, D; Sak, B; Kvác, M; Ditrich, O

    2009-10-28

    A total of 287 faecal specimens of captive exotic birds from the orders Psittaciformes, Passeriformes and Columbiformes were randomly collected from Bohemian pet stores, avian breeders and avian keepers and were screened for the presence of human pathogenic microsporidia by polymerase chain reaction (PCR). Microsporidial DNA was identified in 115 faecal samples (40.1%). Single-species infection was detected in 36 birds (12.5%) for Enterocytozoon bieneusi, 36 birds (12.5%) for Encephalitozoon cuniculi and 18 birds (6.3%) for Encephalitozoon hellem. No Encephalitozoon intestinalis positive samples were identified. Moreover, co-infections were detected in 25 birds: E. bieneusi together with E. cuniculi in 14 animals (4.9%) or E. hellem in 11 cases (3.8%). E. hellem was present in 1A (5.2%) and three (0.3%) genotypes, E. cuniculi in I (2.4%), II (8.0%) and III (0.7%) genotypes and E. bieneusi in A (8.4%) and EbpA (10.8%) genotypes. Several of these genotypes have never been recorded in birds before. The results of this report suggest the low host specificity of E. bieneusi, E. hellem and E. cuniculi and describe 44 new avian hosts.

  4. Unmet Diagnostic Needs in Infectious Disease

    Science.gov (United States)

    Blaschke, Anne J.; Hersh, Adam L.; Beekmann, Susan E.; Ince, Dilek; Polgreen, Philip M.; Hanson, Kimberly E.

    2014-01-01

    Accurate diagnosis is critical to providing appropriate care in infectious diseases. New technologies for infectious disease diagnostics are emerging, but gaps remain in test development and availability. The Emerging Infections Network surveyed Infectious Diseases physicians to assess unmet diagnostic needs. Responses reflected the urgent need to identify drug-resistant infections and highlighted the potential for early diagnosis to improve antibiotic stewardship. Information gained from this survey can help inform recommendations for new diagnostic test development in the future. PMID:25456043

  5. Infectious Disease Clinical Research Program (IDCRP)

    Data.gov (United States)

    Federal Laboratory Consortium — Our mission is to conduct infectious disease clinical research of importance to the military through a unique, adaptive, and collaborative network, to inform health...

  6. DIAGNOSTIC SIGNIFICATION OF ICTERIC IN INFECTIOUS DISEASES

    Directory of Open Access Journals (Sweden)

    T. Ya. Chernobrovkina

    2017-01-01

    Full Text Available The differential diagnosis of infectious diseases for general practitioners is always a difficult process. The spectrum of clinical entities when jaundice may develop is unusually wide. First of all doctor must exclude or confirm infectious nature of the jaundice, which is dictated primarily by epidemiological rules. This report contains clinical and epidemiological characteristics of key diseases causing jaundice syndrome. Authors conducted analysis based on the data of the 18th department of the Moscow Infectious Hospital № 1 for the years 2014-2015 and revealed how common infectious diseases causing jaundice syndrome are.

  7. What Is a Pediatric Infectious Diseases Specialist?

    Science.gov (United States)

    ... are recurrent Respiratory infections Bone and joint infections Tuberculosis (TB) Acquired Immunodeficiency syndrome (AIDS) Hepatitis Meningitis Where Can I Find A Pediatric Infectious Diseases ...

  8. Forecasting infectious disease emergence subject to seasonal forcing.

    Science.gov (United States)

    Miller, Paige B; O'Dea, Eamon B; Rohani, Pejman; Drake, John M

    2017-09-06

    Despite high vaccination coverage, many childhood infections pose a growing threat to human populations. Accurate disease forecasting would be of tremendous value to public health. Forecasting disease emergence using early warning signals (EWS) is possible in non-seasonal models of infectious diseases. Here, we assessed whether EWS also anticipate disease emergence in seasonal models. We simulated the dynamics of an immunizing infectious pathogen approaching the tipping point to disease endemicity. To explore the effect of seasonality on the reliability of early warning statistics, we varied the amplitude of fluctuations around the average transmission. We proposed and analyzed two new early warning signals based on the wavelet spectrum. We measured the reliability of the early warning signals depending on the strength of their trend preceding the tipping point and then calculated the Area Under the Curve (AUC) statistic. Early warning signals were reliable when disease transmission was subject to seasonal forcing. Wavelet-based early warning signals were as reliable as other conventional early warning signals. We found that removing seasonal trends, prior to analysis, did not improve early warning statistics uniformly. Early warning signals anticipate the onset of critical transitions for infectious diseases which are subject to seasonal forcing. Wavelet-based early warning statistics can also be used to forecast infectious disease.

  9. Cardiac imaging in infectious endocarditis

    DEFF Research Database (Denmark)

    Bruun, Niels Eske; Habib, Gilbert; Thuny, Franck;

    2014-01-01

    Infectious endocarditis remains both a diagnostic and a treatment challenge. A positive outcome depends on a rapid diagnosis, accurate risk stratification, and a thorough follow-up. Imaging plays a key role in each of these steps and echocardiography remains the cornerstone of the methods in use....... The technique of both transthoracic echocardiography and transoesophageal echocardiography has been markedly improved across the last decades and most recently three-dimensional real-time echocardiography has been introduced in the management of endocarditis patients. Echocardiography depicts structural changes...... with conventional CT (SPECT/CT). Of these methods, (18)F-FDG PET-CT carries the best promise for a future role in endocarditis. But there are distinct limitations with both SPECT/CT and (18)F-FDG PET-CT which should not be neglected. MRI and spiral CT are methods primarily used in the search for extra cardial...

  10. Eponyms in forensic pathology.

    Science.gov (United States)

    Nečas, Pavel; Hejna, Petr

    2012-12-01

    The phenomenon of eponymous terms in forensic pathology is described in this paper. The authors analyzed representative textbooks (monographs) dealing with forensic pathology in both English and German and identified several eponymous terms. The paper aims to present to the reader the most important eponymous terms in forensic pathology. Included in the paper are the following terms: Beckwith's Sign, Casper's Rule, Krönlein's Shot, Lichtenberg's Figures, Nysten's Law, Paltauf's Spots, Puppe's Rule, Sehrt's Sign, Simon's Sign, Sveshnikov's Sign, Tardieu's Spots, Wischnewski Spots, Wydler's Sign. The spread of eponymous terms throughout various languages is mentioned. The linguistic basis of such terms as well as their advantages and disadvantages in specialist fields, and indeed in even wider circles, is discussed. The authors state that the main function of these terms is to facilitate the open flow of unambiguous information among scholars. Eponymous terms in forensic pathology are characteristic for the German speaking countries and for all countries influenced by the German school of forensic pathology. Their usage in the Anglo-Saxon world is much less widespread, meaning they do not occur very often in English monographs and textbooks.

  11. VCP associated inclusion body myopathy and paget disease of bone knock-in mouse model exhibits tissue pathology typical of human disease.

    Directory of Open Access Journals (Sweden)

    Mallikarjun Badadani

    Full Text Available Dominant mutations in the valosin containing protein (VCP gene cause inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia (IBMPFD. We have generated a knock-in mouse model with the common R155H mutation. Mice demonstrate progressive muscle weakness starting approximately at the age of 6 months. Histology of mutant muscle showed progressive vacuolization of myofibrils and centrally located nuclei, and immunostaining shows progressive cytoplasmic accumulation of TDP-43 and ubiquitin-positive inclusion bodies in quadriceps myofibrils and brain. Increased LC3-II staining of muscle sections representing increased number of autophagosomes suggested impaired autophagy. Increased apoptosis was demonstrated by elevated caspase-3 activity and increased TUNEL-positive nuclei. X-ray microtomography (uCT images show radiolucency of distal femurs and proximal tibiae in knock-in mice and uCT morphometrics shows decreased trabecular pattern and increased cortical wall thickness. Bone histology and bone marrow derived macrophage cultures in these mice revealed increased osteoclastogenesis observed by TRAP staining suggestive of Paget bone disease. The VCP(R155H/+ knock-in mice replicate the muscle, bone and brain pathology of inclusion body myopathy, thus representing a useful model for preclinical studies.

  12. Prognostic value of stromal and epithelial periostin expression in human prostate cancer: correlation with clinical pathological features and the risk of biochemical relapse or death

    Directory of Open Access Journals (Sweden)

    Nuzzo Pier Vitale

    2012-12-01

    Full Text Available Abstract Background The purpose of the present study was to evaluate the prognostic value of POSTN expression following prostatectomy. Methods Periostin (POSTN expression in prostate cancer (PCa and in normal specimens was evaluated in 90 patients by an immuno-reactive score(IRS based on the intensity of immunostaining and on the quantity of stained cells. The t-test was applied to compare IRS values in cancer specimens to values in normal specimens. Pearson’s test was used to correlate POSTN expression to clinical pathologic features. PSA progression-free and survival curves were constructed by the Kaplan–Meier method and compared using the log-rank test. Multi-parametric models were constructed according to the Cox technique adding all the covariates predicting for either PSA progression or death into the models after univariate analysis. Results Both stromal and epithelial POSTN expression were significantly increased in tumor tissues. In particular, we found stromal expression to be significantly higher than epithelial expression as compared to normal tissues (p Conclusions Although requiring further validation through larger studies, our findings show that POSTN might represent a novel prognostic marker for PCa.

  13. MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis

    Science.gov (United States)

    Lecca, Davide; Marangon, Davide; Coppolino, Giusy T.; Méndez, Aida Menéndez; Finardi, Annamaria; Costa, Gloria Dalla; Martinelli, Vittorio; Furlan, Roberto; Abbracchio, Maria P.

    2016-01-01

    In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS). Here, we identify miR-125a-3p, a developmentally regulated miRNA, as a new actor of oligodendroglial maturation, that, in the mammalian CNS regulates the expression of myelin genes by simultaneously acting on several of its already validated targets. In cultured OPCs, over-expression of miR-125a-3p by mimic treatment impairs while its inhibition with an antago-miR stimulates oligodendroglial maturation. Moreover, we show that miR-125a-3p levels are abnormally high in the cerebrospinal fluid of MS patients bearing active demyelinating lesions, suggesting that its pathological upregulation may contribute to MS development, at least in part by blockade of OPC differentiation leading to impaired repair of demyelinated lesions. PMID:27698367

  14. Understanding neuropsychiatric diseases, analysing the peptide sharing between infectious agents and the language-associated NMDA 2A protein

    Directory of Open Access Journals (Sweden)

    Guglielmo eLucchese

    2016-04-01

    Full Text Available Language disorders and infections may occur together and often concur, to a different extent and via different modalities, in characterizing brain pathologies such as schizophrenia, autism, epilepsies, bipolar disorders, frontotemporal neurodegeneration, and encephalitis, inter alia. The biological mechanism(s that might channel language dysfunctions and infections into etiological pathways connected to neuropathologic sequelae are unclear. Searching for molecular link(s between language disorders and infections, the present study explores the language-associated NMDA 2A subunit for peptide sharing with pathogens that have been described in concomitance of neuropsychiatric diseases. It was found that a vast peptide commonality links the human glutamate ionotropic receptor NMDA 2A subunit to infectious agents. Such a link expands to and interfaces with neuropsychiatric disorders in light of the specific allocation of NMDA 2A gene expression in brain areas related to language functions. The data hint at a possible pathologic scenario based on anti-pathogen immune responses crossreacting with NMDA 2A in the brain.

  15. Scavenging nucleic acid debris to combat autoimmunity and infectious disease

    Science.gov (United States)

    Holl, Eda K.; Shumansky, Kara L.; Borst, Luke B.; Burnette, Angela D.; Sample, Christopher J.; Ramsburg, Elizabeth A.; Sullenger, Bruce A.

    2016-08-01

    Nucleic acid-containing debris released from dead and dying cells can be recognized as damage-associated molecular patterns (DAMPs) or pattern-associated molecular patterns (PAMPs) by the innate immune system. Inappropriate activation of the innate immune response can engender pathological inflammation and autoimmune disease. To combat such diseases, major efforts have been made to therapeutically target the pattern recognition receptors (PRRs) such as the Toll-like receptors (TLRs) that recognize such DAMPs and PAMPs, or the downstream effector molecules they engender, to limit inflammation. Unfortunately, such strategies can limit the ability of the immune system to combat infection. Previously, we demonstrated that nucleic acid-binding polymers can act as molecular scavengers and limit the ability of artificial nucleic acid ligands to activate PRRs. Herein, we demonstrate that nucleic acid scavengers (NASs) can limit pathological inflammation and nucleic acid-associated autoimmunity in lupus-prone mice. Moreover, we observe that such NASs do not limit an animal’s ability to combat viral infection, but rather their administration improves survival when animals are challenged with lethal doses of influenza. These results indicate that molecules that scavenge extracellular nucleic acid debris represent potentially safer agents to control pathological inflammation associated with a wide range of autoimmune and infectious diseases.

  16. 25 CFR 140.26 - Infectious plants.

    Science.gov (United States)

    2010-04-01

    ... 25 Indians 1 2010-04-01 2010-04-01 false Infectious plants. 140.26 Section 140.26 Indians BUREAU... Infectious plants. Traders shall not introduce into, sell, or spread within Indian reservations any plant, plant product, seed, or any type of vegetation, which is infested, or infected or which might act as...

  17. Atypical Pyoderma Gangrenosum Mimicking an Infectious Process

    Directory of Open Access Journals (Sweden)

    Derek To

    2014-01-01

    Full Text Available We present a patient with atypical pyoderma gangrenosum (APG, which involved the patient’s arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics.

  18. Atypical pyoderma gangrenosum mimicking an infectious process.

    Science.gov (United States)

    To, Derek; Wong, Aaron; Montessori, Valentina

    2014-01-01

    We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics.

  19. An Interdisciplinary Perspective: Infectious Diseases and History.

    Science.gov (United States)

    Turco, Jenifer; Byrd, Melanie

    2001-01-01

    Introduces the course "Infectious Diseases and History" which is designed for freshman and sophomore students. Aims to teach about infectious diseases, develop skills of using libraries and computer resources, and develop oral and written communication skills. Focuses on tuberculosis as an example of an instructional approach and…

  20. Empowering African genomics for infectious disease control.

    Science.gov (United States)

    Folarin, Onikepe A; Happi, Anise N; Happi, Christian T

    2014-11-07

    At present, African scientists can only participate minimally in the genomics revolution that is transforming the understanding, surveillance and clinical treatment of infectious diseases. We discuss new initiatives to equip African scientists with knowledge of cutting-edge genomics tools, and build a sustainable critical mass of well-trained African infectious diseases genomics scientists.

  1. Emerging Infectious Disease Journal Cover Art

    Centers for Disease Control (CDC) Podcasts

    2012-04-04

    Polyxeni Potter discusses the art used on the covers of the Emerging Infectious Diseases journal.  Created: 4/4/2012 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 4/5/2012.

  2. Breeding against infectious diseases in animals

    NARCIS (Netherlands)

    Rashidi, H.

    2016-01-01

    Infectious diseases in farm animals are of major concern because of animal welfare, production costs, and public health. Farms undergo huge economic losses due to infectious disease. The costs of infections in farm animals are mainly due to production losses, treatment of infected animals, and

  3. Expression of human A53T alpha-synuclein in the rat substantia nigra using a novel AAV1/2 vector produces a rapidly evolving pathology with protein aggregation, dystrophic neurite architecture and nigrostriatal degeneration with potential to model the pathology of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Sun Xuan

    2010-10-01

    Full Text Available Abstract Background The pathological hallmarks of Parkinson's disease (PD include the presence of alpha-synuclein (α-syn rich Lewy bodies and neurites and the loss of dopaminergic (DA neurons of the substantia nigra (SN. Animal models of PD based on viral vector-mediated over-expression of α-syn have been developed and show evidence of DA toxicity to varying degrees depending on the type of virus used, its concentration, and the serotype of vector employed. To date these models have been variable, difficult to reproduce, and slow in their evolution to achieve a desired phenotype, hindering their use as a model for testing novel therapeutics. To address these issues we have taken a novel vector in this context, that can be prepared in high titer and which possesses an ability to produce neuronally-directed expression, with expression dynamics optimised to provide a rapid rise in gene product expression. Thus, in the current study, we have used a high titer chimeric AAV1/2 vector, to express human A53T α-syn, an empty vector control (EV, or green fluorescent protein (GFP, the latter to control for the possibility that high levels of protein in themselves might contribute to damage. Results We show that following a single 2 μl injection into the rat SN there is near complete coverage of the structure and expression of A53T α-syn or GFP appears throughout the striatum. Within 3 weeks of SN delivery of their respective vectors, aggregations of insoluble α-syn were observed in SN DA neurons. The numbers of DA neurons in the SN were significantly reduced by expression of A53T α-syn (52%, and to a lesser extent by GFP (24%, compared to EV controls (both P P Conclusions In the current implementation of the model, we recapitulate the primary pathological hallmarks of PD, although a proportion of the SN damage may relate to general protein overload and may not be specific for A53T α-syn. Future studies will thus be required to optimise the dose of

  4. prM-antibody renders immature West Nile virus infectious in vivo.

    Science.gov (United States)

    Colpitts, Tonya M; Rodenhuis-Zybert, Izabela; Moesker, Bastiaan; Wang, Penghua; Fikrig, Erol; Smit, Jolanda M

    2011-10-01

    West Nile virus (WNV) is a member of the family Flaviviridae and is a neurotropic pathogen responsible for severe human disease. Flavivirus-infected cells release virus particles that contain variable numbers of precursor membrane (prM) protein molecules at the viral surface. Consequently, antibodies are produced against the prM protein. These antibodies have been shown to activate the infectious potential of fully immature flavivirus particles in vitro. Here, we provide in vivo proof that prM antibodies render immature WNV infectious. Infection with antibody-opsonized immature WNV particles caused disease and death of mice, and infectious WNV was found in the brains and sera.

  5. Human apolipoprotein E4 worsens acute axonal pathology but not amyloid-β immunoreactivity after traumatic brain injury in 3xTG-AD mice.

    Science.gov (United States)

    Bennett, Rachel E; Esparza, Thomas J; Lewis, Hal A; Kim, Eddie; Mac Donald, Christine L; Sullivan, Patrick M; Brody, David L

    2013-05-01

    Apolipoprotein E4 (APOE4) genotype is a risk factor for poor outcome after traumatic brain injury (TBI), particularly in young patients, but the underlying mechanisms are not known. By analogy to effects of APOE4 on the risk of Alzheimer disease (AD), the APOE genotype may influence β-amyloid (Aβ) and tau deposition after TBI. To test this hypothesis, we crossed 3xTG-AD transgenic mice carrying 3 human familial AD mutations (PS1(M146V), tauP(301)L, and APP(SWE)) to human ApoE2-, ApoE3-, and ApoE4-targeted replacement mice. Six- to 8-month-old 3xTG-ApoE mice were assayed by quantitative immunohistochemistry for amyloid precursor protein (APP), Aβ(1-40) (Aβ40), Aβ(1-42) (Aβ42), total human tau, and phospho-serine 199 (pS199) tau at 24 hours after moderate controlled cortical impact. There were increased numbers of APP-immunoreactive axonal varicosities in 3xTG-ApoE4 mice versus the other genotypes. This finding was repeated in a separate cohort of ApoE4-targeted replacement mice without human transgenes compared with ApoE3 and ApoE2 mice. There were no differences between genotypes in the extent of intra-axonal Aβ40 and Aβ42; none of the mice had extracellular Aβ deposition. Regardless of injury status, 3xTG-ApoE4 mice had more total human tau accumulation in both somatodendritic and intra-axonal compartments than other genotypes. These results suggest that the APOE4 genotype may have a primary effect on the severity of axonal injury in acute TBI.

  6. Serum and peritoneal fluid concentrations of soluble human leukocyte antigen, tumor necrosis factor alpha and interleukin 10 in patients with selected ovarian pathologies.

    Science.gov (United States)

    Sipak-Szmigiel, Olimpia; Włodarski, Piotr; Ronin-Walknowska, Elżbieta; Niedzielski, Andrzej; Karakiewicz, Beata; Słuczanowska-Głąbowska, Sylwia; Laszczyńska, Maria; Malinowski, Witold

    2017-04-04

    Although immune system plays a key role in the pathogenesis of both endometriosis and ovarian cancer, its function is different. Therefore, we hypothesized, that selected immune parameters can serve as diagnostic markers of these two conditions. The aim of this study was to compare serum and peritoneal fluid concentrations of sHLA-G, IL-10 and TNF-alpha in women with selected ovarian pathologies: benign serous cysts, endometrioma and malignant tumors. Clinical significance of using them for diagnostic purposes in women with serous ovarian cysts, endometriosis, and ovarian cancer, which in the future may improve the early diagnosis of ovarian diseases. The study included women treated surgically for benign serous ovarian cysts, ovarian endometrioma and serous ovarian adenocarcinomas. Peripheral blood and peritoneal fluid samples were obtained intraoperatively. Patients with benign serous cysts, endometrioma and ovarian malignancies did not differ significantly in terms of their serum and peritoneal fluid concentrations of sHLA-G. Ovarian cancer patients presented with significantly higher median serum concentrations of IL-10 and TNF-alpha than other study subjects. Median concentrations of IL-10 and TNF-alpha in peritoneal fluid turned out to be the highest in ovarian cancer patients, followed by women with endometrioma and subjects with benign serous cysts. All these intergroup differences were statistically significant. Irrespective of the group, median concentrations of sHLA-G, IL-10 and TNF-alpha in peritoneal fluid were higher than serum levels of these markers. Elevated serum and peritoneal fluid concentrations of IL-10 and TNF-alpha distinguish ovarian malignancies and endometriomas from benign serous ovarian cysts. In contrast to endometriosis, ovarian malignancies are characterized by elevated peritoneal fluid concentrations of IL-10 and TNF-alpha, elevated serum concentrations of IL-10 and low serum levels of TNF-alpha. Serum and peritoneal fluid

  7. Pathological Gambling Subtypes

    Science.gov (United States)

    Vachon, David D.; Bagby, R. Michael

    2009-01-01

    Although pathological gambling (PG) is regarded in the 4th edition of the "Diagnostic and Statistical Manual of Mental Disorders" (American Psychiatric Association, 1994) as a unitary diagnostic construct, it is likely composed of distinct subtypes. In the current report, the authors used cluster analyses of personality traits with a…

  8. Next-Generation Pathology.

    Science.gov (United States)

    Caie, Peter D; Harrison, David J

    2016-01-01

    The field of pathology is rapidly transforming from a semiquantitative and empirical science toward a big data discipline. Large data sets from across multiple omics fields may now be extracted from a patient's tissue sample. Tissue is, however, complex, heterogeneous, and prone to artifact. A reductionist view of tissue and disease progression, which does not take this complexity into account, may lead to single biomarkers failing in clinical trials. The integration of standardized multi-omics big data and the retention of valuable information on spatial heterogeneity are imperative to model complex disease mechanisms. Mathematical modeling through systems pathology approaches is the ideal medium to distill the significant information from these large, multi-parametric, and hierarchical data sets. Systems pathology may also predict the dynamical response of disease progression or response to therapy regimens from a static tissue sample. Next-generation pathology will incorporate big data with systems medicine in order to personalize clinical practice for both prognostic and predictive patient care.

  9. Pathological Gambling: Psychiatric Models

    Science.gov (United States)

    Westphal, James R.

    2008-01-01

    Three psychiatric conceptual models: addictive, obsessive-compulsive spectrum and mood spectrum disorder have been proposed for pathological gambling. The objectives of this paper are to (1) evaluate the evidence base from the most recent reviews of each model, (2) update the evidence through 2007 and (3) summarize the status of the evidence for…

  10. Immunogenetics and the Pathological Mechanisms of Human T-Cell Leukemia Virus Type 1- (HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP

    Directory of Open Access Journals (Sweden)

    Mineki Saito

    2010-01-01

    Full Text Available Human T-cell leukemia virus type 1 (HTLV-1 is a replication-competent human retrovirus associated with two distinct types of disease only in a minority of infected individuals: the malignancy known as adult T-cell leukemia (ATL and a chronic inflammatory central nervous system disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP. Although the factors that cause these different manifestations of HTLV-1 infection are not fully understood, accumulating evidence suggests that complex virus-host interactions play an important role in determining the risk of HAM/TSP. This review focuses on the role of the immune response in controlling or limiting viral persistence in HAM/TSP patients, and the reason why some HTLV-1-infected people develop HAM/TSP whereas the majority remains asymptomatic carriers of the virus.

  11. Hearing impairment and ear pathology in Nepal.

    Science.gov (United States)

    Little, P; Bridges, A; Guragain, R; Friedman, D; Prasad, R; Weir, N

    1993-05-01

    A stratified random cluster sample of 15,845 subjects was performed in two regions of Nepal to determine the prevalence and main causes of hearing impairment (the most common disability) and the prevalence of ear disease. Subjects reporting current ear pain, or ear discharge, or hearing impairment on direct questioning by a Nepali health worker (primary screening failed), had otoscopy and audiometry (using the Liverpool Field Audiometer) performed, and a questionnaire administered relating to past history. In every fifth house subjects who passed the primary screening (1,716 subjects) were examined to assess the false negative rate of screening. An estimated 16.6 per cent of the study population have hearing impairment (either ear worse than 30 dB hearing threshold level (HTL) 1.0-4.0 kHz, or 50 dB HTL 0.5 kHz), and 7.4 per cent ear drum pathology, equivalent to respectively 2.71 and 1.48 million people extrapolated to the whole of Nepal. Most hearing impairment in the school age group (55.2 per cent) is associated with otitis media or its sequelae. Probably at least 14 per cent of sensorineural deafness is preventable (7 per cent infectious disease, 3.9 per cent trauma, 0.8 per cent noise exposure, 1 per cent cretinism, and 1 per cent abnormal pregnancy or labour). Most individuals reporting current ear pathology (61 per cent) had never attended a health post, and of those receiving ear drop treatment, 84 per cent still had serious pathology. Of subjects who reported ear drop treatment at any time, 31 per cent still had serious pathology. The use of traditional remedies was prevalent.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Trains of Thought in Treating Infectious Atypical Pneumonia with Integrative Chinese and Western Medicine Approach

    Institute of Scientific and Technical Information of China (English)

    林琳

    2003-01-01

    @@ Infectious atypical pneumonia (also called severe acute respiratory syndrome, SARS by WHO) is a new type of infectious disease, whose disease condition is fierce and ferocious, rapid in changing, seriously threatened human health and life. The author has treated around 200 SARS patients in Guangzhou and Hong Kong with integrative Chinese and western medicine (ICWM) approach from January 2003till present. Now I would like to make a comment on ICWM in treating SARS.

  13. Generation of Cholinergic and Dopaminergic Interneurons from Human Pluripotent Stem Cells as a Relevant Tool for In Vitro Modeling of Neurological Disorders Pathology and Therapy

    Directory of Open Access Journals (Sweden)

    Anna Ochalek

    2016-01-01

    Full Text Available The cellular and molecular bases of neurological diseases have been studied for decades; however, the underlying mechanisms are not yet fully elucidated. Compared with other disorders, diseases of the nervous system have been very difficult to study mainly due to the inaccessibility of the human brain and live neurons in vivo or in vitro and difficulties in examination of human postmortem brain tissue. Despite the availability of various genetically engineered animal models, these systems are still not adequate enough due to species variation and differences in genetic background. Human induced pluripotent stem cells (hiPSCs reprogrammed from patient somatic cells possess the potential to differentiate into any cell type, including neural progenitor cells and postmitotic neurons; thus, they open a new area to in vitro modeling of neurological diseases and their potential treatment. Currently, many protocols for generation of various neuronal subtypes are being developed; however, most of them still require further optimization. Here, we highlight accomplishments made in the generation of dopaminergic and cholinergic neurons, the two subtypes most affected in Alzheimer’s and Parkinson’s diseases and indirectly affected in Huntington’s disease. Furthermore, we discuss the potential role of hiPSC-derived neurons in the modeling and treatment of neurological diseases related to dopaminergic and cholinergic system dysfunction.

  14. MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer's Disease (AD)-Novel and Unique Pathological Features.

    Science.gov (United States)

    Zhao, Yuhai; Pogue, Aileen I; Lukiw, Walter J

    2015-12-17

    Of the approximately ~2.65 × 10³ mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset-about 35-40-are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs) for productive miRNA-mRNA interactions and the down-regulation of gene expression. In this article we will: (i) consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer's disease (AD) and related forms of chronic neurodegeneration; and (ii) highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-κB-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS.

  15. Interference of infectious bursal disease virus on antibody production against Newcastle disease and infectious bronchitis virus

    Directory of Open Access Journals (Sweden)

    WM Cardoso

    2006-09-01

    Full Text Available This work has the objective of verifying the interference of infectious bursal disease virus in the antibody production against Newcastle disease virus and infectious bronchitis virus. The experiment was carried out with 640 day-old-chicks from a 42 weeks old hen flock. The birds were separated into eight experimental groups (n=80/group and were submitted to different combinations of vaccinations, with live vaccines, to Newcastle disease, avian infectious bronchitis, and infectious bursal disease with diverse combinations of days of vaccination. We verified that the utilization of polyvalent vaccinal programs have a different efficacy comparing to monovalent vaccinations when Newcastle disease, infectious bronchitis, and infectious bursal disease vaccinations are applied. This way, the use of vaccinations to infectious bursal disease in polyvalent vaccinal programs is desirable due to improvement of NDV response with the presence of IBV by the probable reduction of interference of IBV under NDV.

  16. First case of infectious endocarditis caused by Parvimonas micra.

    Science.gov (United States)

    Gomez, Carlos A; Gerber, Daniel A; Zambrano, Eduardo; Banaei, Niaz; Deresinski, Stan; Blackburn, Brian G

    2015-12-01

    P. micra is an anaerobic Gram-positive cocci, and a known commensal organism of the human oral cavity and gastrointestinal tract. Although it has been classically described in association with endodontic disease and peritonsillar infection, recent reports have highlighted the role of P. micra as the primary pathogen in the setting of invasive infections. In its most recent taxonomic classification, P. micra has never been reported causing infectious endocarditis in humans. Here, we describe a 71 year-old man who developed severe native valve endocarditis complicated by aortic valvular destruction and perivalvular abscess, requiring emergent surgical intervention. Molecular sequencing enabled identification of P. micra.

  17. Resident microbiota affect Bordetella pertussis infectious dose and host specificity.

    Science.gov (United States)

    Weyrich, Laura S; Feaga, Heather A; Park, Jihye; Muse, Sarah J; Safi, Chetan Y; Rolin, Olivier Y; Young, Sarah E; Harvill, Eric T

    2014-03-01

    Before contacting host tissues, invading pathogens directly or indirectly interact with host microbiota, but the effects of such interactions on the initial stages of infection are poorly understood. Bordetella pertussis is highly infectious among humans but requires large doses to colonize rodents, unlike a closely related zoonotic pathogen, Bordetella bronchiseptica, raising important questions about the contributions of bacterial competition to initial colonization and host selection. We observed that <100 colony-forming units (CFU) of B. bronchiseptica efficiently infected mice and displaced culturable host microbiota, whereas 10 000 CFU of B. pertussis were required to colonize murine nasal cavities and did not displace host microorganisms. Bacteria isolated from murine nasal cavities but not those from the human lower respiratory tract limited B. pertussis growth in vitro, indicating that interspecies competition may limit B. pertussis colonization of mice. Further, a broad-spectrum antibiotic treatment delivered before B. pertussis inoculation reduced the infectious dose to <100 CFU, and reintroduction of single Staphylococcus or Klebsiella species was sufficient to inhibit B. pertussis colonization of antibiotic-treated mice. Together, these results reveal that resident microorganisms can prevent B. pertussis colonization and influence host specificity, and they provide rationale for manipulating microbiomes to create more-accurate animal models of infectious diseases.

  18. The impact of infection on population health: results of the Ontario burden of infectious diseases study.

    Directory of Open Access Journals (Sweden)

    Jeffrey C Kwong

    Full Text Available BACKGROUND: Evidence-based priority setting is increasingly important for rationally distributing scarce health resources and for guiding future health research. We sought to quantify the contribution of a wide range of infectious diseases to the overall infectious disease burden in a high-income setting. METHODOLOGY/PRINCIPAL FINDINGS: We used health-adjusted life years (HALYs, a composite measure comprising premature mortality and reduced functioning due to disease, to estimate the burden of 51 infectious diseases and associated syndromes in Ontario using 2005-2007 data. Deaths were estimated from vital statistics data and disease incidence was estimated from reportable disease, healthcare utilization, and cancer registry data, supplemented by local modeling studies and national and international epidemiologic studies. The 51 infectious agents and associated syndromes accounted for 729 lost HALYs, 44.2 deaths, and 58,987 incident cases per 100,000 population annually. The most burdensome infectious agents were: hepatitis C virus, Streptococcus pneumoniae, Escherichia coli, human papillomavirus, hepatitis B virus, human immunodeficiency virus, Staphylococcus aureus, influenza virus, Clostridium difficile, and rhinovirus. The top five, ten, and 20 pathogens accounted for 46%, 67%, and 75% of the total infectious disease burden, respectively. Marked sex-specific differences in disease burden were observed for some pathogens. The main limitations of this study were the exclusion of certain infectious diseases due to data availability issues, not considering the impact of co-infections and co-morbidity, and the inability to assess the burden of milder infections that do not result in healthcare utilization. CONCLUSIONS/SIGNIFICANCE: Infectious diseases continue to cause a substantial health burden in high-income settings such as Ontario. Most of this burden is attributable to a relatively small number of infectious agents, for which many effective

  19. Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome

    Science.gov (United States)

    Meteyer, Carol U.; Barber, Daniel; Mandl, Judith N.

    2012-01-01

    White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS), which was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology.

  20. Pathology in euthermic bats with white nose syndrome suggests a natural manifestation of immune reconstitution inflammatory syndrome.

    Science.gov (United States)

    Meteyer, Carol U; Barber, Daniel; Mandl, Judith N

    2012-11-15

    White nose syndrome, caused by Geomyces destructans, has killed more than 5 million cave hibernating bats in eastern North America. During hibernation, the lack of inflammatory cell recruitment at the site of fungal infection and erosion is consistent with a temperature-induced inhibition of immune cell trafficking. This immune suppression allows G. destructans to colonize and erode the skin of wings, ears and muzzle of bat hosts unchecked. Yet, paradoxically, within weeks of emergence from hibernation an intense neutrophilic inflammatory response to G. destructans is generated, causing severe pathology that can contribute to death. We hypothesize that the sudden reversal of immune suppression in bats upon the return to euthermia leads to a form of immune reconstitution inflammatory syndrome (IRIS). IRIS was first described in HIV-infected humans with low helper T lymphocyte counts and bacterial or fungal opportunistic infections. IRIS is a paradoxical and rapid worsening of symptoms in immune compromised humans upon restoration of immunity in the face of an ongoing infectious process. In humans with HIV, the restoration of adaptive immunity following suppression of HIV replication with anti-retroviral therapy (ART) can trigger severe immune-mediated tissue damage that can result in death. We propose that the sudden restoration of immune responses in bats infected with G. destructans results in an IRIS-like dysregulated immune response that causes the post-emergent pathology.